A study into the vaccine’s effectiveness, published in eBioMedicine, was led by experts from the Sydney Infectious Diseases Institute at University of Sydney, the Centenary Institute and the Monash Institute of Pharmaceutical Science (MIPS) at Monash University.

Currently the only approved vaccine for TB is the century-old Bacillus Calmette-Guerin (BCG) vaccine, which is widely used despite its effectiveness in adults being inconsistent.

The study found that the new mRNA vaccine was successful in triggering an immune defence response that helped to reduce TB numbers in infected mice. In addition, the researchers discovered that for mice that had received the BCG vaccine, a booster dose of the new mRNA vaccine significantly improved their long-term protection.

The vaccine used mRNA technology, which is where genetic instructions are used to trigger an immune response in the body, as opposed to using a weakened or deadened version of a virus.

Senior author Professor Jamie Triccas, Deputy Director of the Sydney Infectious Diseases Institute, said: “Our findings demonstrate that an mRNA vaccine can induce potent, pathogen-specific immune responses that target TB, a disease that has long evaded effective vaccine development. This represents a major advance in TB vaccine research and provides a strong rationale for further clinical development.”

TB is the leading cause of infectious mortality worldwide, responsible for approximately 1.3 million deaths annually, with a particular prevalence in countries such as India, Indonesia, Vietnam and Pakistan.

The researchers hope that the mRNA vaccine will ultimately be more effective and consistent than the BCG when used in humans. This is because, unlike protein-based or live-attenuated vaccines (those that contain a weakened version of a pathogen), mRNA vaccines allow for rapid adaptation, making them an attractive option for global TB control efforts.

Dr Claudio Counoupas, co-lead author from the Centenary Institute’s Centre for Infection & Immunity, highlighted the vaccine’s potential impact: “mRNA vaccines offer a scalable, cost-effective, and adaptable platform that can be rapidly deployed against infectious diseases. This study is an important step in demonstrating that mRNA technology is not just for COVID-19 but could be a game-changer for bacterial diseases like TB.”

Professor Colin Pouton from Monash University, a key contributor to the study, explained: “The success of mRNA vaccines in the COVID-19 pandemic underscored their ability to generate strong immune responses. Our study provides the evidence that this platform can be harnessed for TB, potentially improving protection and durability of immunity in a way that traditional vaccines cannot.”

Following the study’s promising results, the research team is now looking to advance the vaccine to clinical trials.

“Our next goal is to refine the formulation and assess its efficacy in larger models before moving to human studies,” said Professor Triccas. “Given the global burden of TB and the limitations of current vaccines, we believe this platform could provide a new pathway toward eradicating this disease.”

The researchers found that engaging in as little as 35 minutes of moderate to vigorous physical activity per week, compared to zero minutes per week, was associated with a 41% lower risk of developing dementia over an average four-year follow-up period. Even for frail older adults — those at elevated risk of adverse health outcomes — greater activity was associated with lower dementia risks.

The researchers found dementia risk decreased with higher amounts of physical activity. Dementia risks were 60% lower in participants in the 35 to 69.9 minutes of physical activity/week category; 63% lower in the 70 to 139.9 minutes/week category; and 69% lower in the 140 and over minutes/week category.

For their analysis, the researchers analyzed a dataset covering nearly 90,000 adults living in the U.K. who wore smart-watch-type activity trackers.

The study was published online January 15 in the Journal of the American Medical Directors Association.

“Our findings suggest that increasing physical activity, even as little as five minutes per day, can reduce dementia risk in older adults,” says study lead author Amal Wanigatunga, PhD, MPH, assistant professor in the Bloomberg School’s Department of Epidemiology. Wanigatunga is also a core faculty member at the Johns Hopkins Center on Aging and Health and has a joint appointment at the Johns Hopkins University School of Medicine. “This adds to a growing body of evidence that some exercise is better than nothing, especially with regard to an aging-related disorder that affects the brain that currently has no cure.”

Dementia, usually from Alzheimer’s disease, is one of the most common conditions of old age. It is estimated to affect about seven million people in the U.S., including about a third of those who are 85 years or older. Although the risk of dementia rises with age, studies in recent years have suggested that dementia is somewhat preventable, within a normal lifespan, by lifestyle changes that include better control of cholesterol, blood pressure and blood sugar, and being more active.

The minimum amount of activity needed to reduce dementia risk meaningfully isn’t yet clear. For many older individuals, especially frail ones, the high amounts of exercise recommended in official guidelines are unattainable and may discourage any exercise at all. Both the U.S. Department of Health and Human Services and the U.K. National Health System recommendthat adults get at least 150 minutes of moderate intensity exercise per week, an average of 20 minutes per day.

For their study, Wanigatunga analyzed data on British adults generated as part of the UK Biobank project, a long-running, ongoing study of approximately 500,000 individuals. The dataset for the new study covered 89,667 adults, mostly in their 50s and older, who used wrist-worn accelerometers to track their physical activity for a week during the period from February 2013 to December 2015. Follow-up of their health status extended for an average of 4.4 years, through November 2021, during which 735 of the participants were diagnosed with dementia.

The analysis compared individuals whose trackers showed some weekly moderate to vigorous physical activity to those whose trackers showed none and accounted for age and other medical conditions. The associations between higher activity and lower dementia risk were striking. Participants in the lowest activity category, ranging from one to 34.9 minutes per week, had an apparent risk reduction of about 41%.

When the researchers took into account participants who met their definitions of frailty or “pre-frailty,” they found that the association between more activity and less dementia was essentially unchanged.

“This suggests that even frail or nearly frail older adults might be able to reduce their dementia risk through low-dose exercise,” Wanigatunga says.

Wanigatunga notes that the study was not a clinical trial that established causation indicating that exercise reduces dementia risk, but its findings are consistent with that hypothesis. To check the possibility that their findings reflected undiagnosed dementia leading to lower physical activity, the researchers repeated their analysis but excluded dementia diagnoses in the first two years of follow-up. The association between more activity and lower dementia risk remained robust.

Wanigatunga and his colleagues recommend that future clinical trial-type studies investigate low-dose exercise as an important initial step towards increasing physical activity as a dementia-preventing strategy.

Funding for the study was provided by the National Institute on Aging (K01 AG076967, R01 AG075883).

The study, published Jan. 30 in the Journal of Antimicrobial Chemotherapy, adds to growing evidence that lenacapavir may be a powerful new tool in the global anti-HIV drug arsenal. Approximately, 1.5 million people are living with HIV in Uganda.

“Our data shows that only 1.6% of the individuals studied are living with HIV strains that have any known lenacapavir-associated resistance mutations,” said senior author Dr. Guinevere Lee, assistant professor of virology in medicine at Weill Cornell Medicine. “That’s important because it shows lenacapavir is likely to be effective against strains of HIV circulating in East Africa.”

Since the 1990s, HIV drug combinations targeting different steps in the virus’ life cycle have been able to reduce virus load in patients to nearly undetectable levels. But drug resistance is a growing concern as the virus has evolved ways to thwart existing therapies. Lenacapavir, however, is the first drug to disrupt the protective capsid layer surrounding HIV’s genetic material (RNA), blocking the virus’s ability to reproduce and be transmitted from person to person.

Treatment twice a year with lenacapavir has been effective in patients who have never been treated and those with HIV strains that are resistant to other drugs. Last year, clinical trials showed that lenacapavir injections were 100% effective in preventing HIV infection among women in sub-Saharan Africa, who were HIV-negative.

However, little information was available about pre-existing resistance to lenacapavir in less well-studied HIV-1 strains like subtype A1 and D, which are more common in Eastern and Southern Africa. HIV-1 subtype B strains, which predominantly affect Europe and the United States, rarely have pre-existing mutations that would cause lenacapavir drug resistance.

Dr. Lee and her colleagues at Mbarara University of Science and Technology in Uganda and Massachusetts General Hospital in Boston helped fill that gap. They sequenced the capsid proteins from HIV-1 subtypes A1 and D from 546 Ugandan patients, who had never used antiretroviral therapy before. This approach allowed the investigators to examine naturally circulating viral variants.

They found that none of the patients had genetic mutations that would lead to major lenacapavir resistance. Only nine participants had minor lenacapavir resistance mutations that could partially reduce the effectiveness, but not enough to cause full resistance to the drug.

“Our study supports lenacapavir’s potential efficacy in this region. As lenacapavir is rolled out in East Africa, further studies will need to monitor for the emergence of drug-resistant strains,” Dr. Lee said. “It is important that we ensure HIV research reaches understudied communities where unique viral strains circulate.”

Intoxicated offenders commit around half the 1.4 million violent incidents reported annually in England and Wales, and alcohol is the drug most likely to be found in perpetrators and victims of violent crime.

A study, led by the University of Portsmouth, conducted experiments to explore how alcohol consumption affects face memory.

Thirty-eight participants, all of whom had normal or corrected to normal vision, consumed either alcoholic or non-alcoholic drinks before viewing videos of unfamiliar female faces. The following day, they were asked to describe these faces.

Those who drank alcohol had more difficulty accurately recalling internal facial features compared to the sober participants, but they could still remember external features like hairstyles. Interestingly, whether or not the models’ hair was tied back or worn loose did not influence recall accuracy.

The paper, published in the journal Memory, says this suggests that alcohol narrows attention to more noticeable external features, while impairing memory for the defining internal facial features that are crucial for suspect identification.

Lead author Dr Alistair Harvey, a Visiting Researcher at the University of Portsmouth’s Department of Psychology, said: “Given that many crimes occur in bars and nightclubs where witnesses may have been drinking, these findings have important implications for law enforcement.

“Getting accurate perpetrator descriptions from witnesses is crucial for locating and identifying suspects — especially during line-ups.”

The study builds on previous research by Dr Harvey and his colleague Danny Tomlinson, which found drunk people are only able to concentrate on external facial features — such as hair and face shape — and not internal features like the eyes and mouth.

“There is a phenomenon known as alcohol myopia, which results in attentional shortsightedness when consuming alcohol,” explained Dr Harvey.

“We suspected this could have an impact on how well people can identify perpetrators of crimes they witness while drunk, and wanted to put it to the test.”

The study’s authors recommend that police and forensic interviewers take these findings into account when questioning witnesses and developing suspect descriptions.

They also suggest further research — with a larger group of participants — to explore how different interviewing techniques might mitigate alcohol’s impact on memory recall.

Dr Sarah Bayless from the University of Winchester’s Department of Psychology, said: “The study underscores the importance of gathering multiple witness accounts and using additional evidence, such as CCTV footage, when investigating crimes.

“Given that intoxicated individuals are frequently present at crime scenes — whether as victims, witnesses, or perpetrators — understanding the effects of alcohol on memory is critical.”

A new study, led by UC San Francisco researchers, found that older, healthy volunteers, with lower concentrations of B12, but still in the normal range, showed signs of neurological and cognitive deficiency. These levels were associated with more damage to the brain’s white matter — the nerve fibers that enable communication between areas of the brain — and test scores associated with slower cognitive and visual processing speeds, compared to those with higher B12.

The study published in Annals of Neurology on Feb. 10.

The researchers led by senior author Ari J. Green, MD, of the UCSF Departments of Neurology and Ophthalmology and the Weill Institute for Neurosciences, said that the results raise questions about current B12 requirements and suggest the recommendations need updating.

“Previous studies that defined healthy amounts of B12 may have missed subtle functional manifestations of high or low levels that can affect people without causing overt symptoms,” said Green, noting that clear deficiencies of the vitamin are commonly associated with a type of anemia. “Revisiting the definition of B12 deficiency to incorporate functional biomarkers could lead to earlier intervention and prevention of cognitive decline.”

Lower B12 correlates with slower processing speeds, brain lesions

In the study, researchers enrolled 231 healthy participants without dementia or mild cognitive impairment, whose average age was 71. They were recruited through the Brain Aging Network for Cognitive Health (BrANCH) study at UCSF.

Their blood B12 amounts averaged 414.8 pmol/L, well above the U.S. minimum of 148 pmol/L. Adjusted for factors like age, sex, education and cardiovascular risks, researchers looked at the biologically active component of B12, which provides a more accurate measure of the amount of the vitamin that the body can utilize. In cognitive testing, participants with lower active B12 were found to have slower processing speed, relating to subtle cognitive decline. Its impact was amplified by older age. They also showed significant delays responding to visual stimuli, indicating slower visual processing speeds and general slower brain conductivity.

MRIs revealed a higher volume of lesions in the participants’ white matter, which may be associated with cognitive decline, dementia or stroke.

While the study volunteers were older adults, who may have a specific vulnerability to lower levels of B12, co-first author Alexandra Beaudry-Richard, MSc, said that these lower levels could “impact cognition to a greater extent than what we previously thought, and may affect a much larger proportion of the population than we realize.” Beaudry-Richard is currently completing her doctorate in research and medicine at the UCSF Department of Neurology and the Department of Microbiology and Immunology at the University of Ottawa.

“In addition to redefining B12 deficiency, clinicians should consider supplementation in older patients with neurological symptoms even if their levels are within normal limits,” she said. “Ultimately, we need to invest in more research about the underlying biology of B12 insufficiency, since it may be a preventable cause of cognitive decline.”

MRI provides detailed images of the human body and is essential for diagnosing various medical conditions, from neurological disorders to musculoskeletal injuries. For in-depth interpretation of MRI images, the organs, muscles and bones in the images are outlined or marked, which is known as segmenting.

“MRI images have traditionally been manually segmented, which is a time-consuming process that requires intensive effort by radiologists and is subject to inter-reader variability,” said Jakob Wasserthal, Ph.D., Radiology Department research scientist at University Hospital Basel in Basel, Switzerland. “Automated systems can potentially reduce radiologist’s workload, minimize human errors and provide more consistent and reproducible results.”

Dr. Wasserthal and colleagues built an open-source automated segmentation tool called the TotalSegmentator MRI based on nnU-Net, a self-configuring framework that has set new standards in medical image segmentation. It adapts to any new dataset with minimal user intervention, automatically adjusting its architecture, preprocessing, and training strategies to optimize performance. A similar model for CT (TotalSegmentator CT) is being used by over 300,000 users worldwide to process over 100,000 CT images daily.

In the retrospective study, the researchers trained TotalSegmentator MRI to provide sequence-independent segmentations of major anatomic structures using a randomly sampled dataset of 616 MRI and 527 CT exams.

The training set included segmentations of 80 anatomic structures typically used for measuring volume, characterizing disease, surgical planning and opportunistic screening.

“Our innovation was creating a large data set,” Dr. Wasserthal said. “We used a lot more data and segmented many more organs, bones and muscles than has been previously done. Our model also works across different MRI scanners and image acquisition settings.”

To evaluate the model’s performance, Dice scores — which measure how similar two sets of data are — were calculated between predicted segmentations and radiologist reference standards for segmentations. The model performed well across the 80 structures with a Dice score of 0.839 on an internal MRI test set. It also significantly outperformed two publicly available segmentation models (0.862 versus 0.838 and 0.560) and matched the performance of TotalSegmentator CT.

“To our knowledge, our model is the only one that can automatically segment the highest number of structures on MRIs of any sequence,” he said. “It’s a tool that helps improve radiologists’ work, makes measurements more precise and enables other measurements to be done that would have taken too much time to do manually.”

In addition to research and AI product development, Dr. Wasserthal said the model could potentially be used clinically for treatment planning, monitoring disease progression, and opportunistic screening.

The Lancet Global Health Commission report details for the first time how future investment in strengthening medical oxygen systems could have a huge impact by saving millions of lives and improving pandemic preparedness.

Almost 400 million children and adults require medical oxygen every year. More than five billion people, 60 per cent of the world’s population, don’t have access to safe and affordable medical oxygen services.

The Commission, co-chaired by Makerere University in Uganda, the International Centre for Diarrheal Disease Research (icddr,b) in Bangladesh, Murdoch Children’s Research Institute (MCRI) in Australia, Karolinska Institute in Sweden and the Every Breath Counts Coalition in the US was launched in 2022 against the backdrop of the COVID-19 pandemic. The Commission was tasked with submitting actionable recommendations for governments, industry, global health agencies, donors and the healthcare workforce.

MCRI Dr Hamish Graham said the COVID-19 pandemic had put a spotlight on the longstanding global inequities in accessing medical oxygen.

“Oxygen is required at every level of the healthcare system for children and adults with a wide range of acute and chronic conditions,” he said. Previous efforts, including the major investments in response to the COVID-19 pandemic, largely focused on the delivery of equipment to produce more oxygen, neglecting the supporting systems and people required to ensure it was distributed, maintained, and used safely and effectively.”

Dr Graham said channelling investments into national oxygen plans and bolstering health systems, including wider use of pulse oximeters (a small device that measures how much oxygen is in the blood), would help solve the medical oxygen crisis.

“We urgently need to make high-quality, pulse oximeters more affordable and widely accessible,” he said. Pulse oximeters are available in 54 per cent of general and 83 per cent of tertiary hospitals in low- and middle-income countries, with frequent shortages and equipment breakdowns.

“Concerningly, in these countries the devices are performed for only 20 per cent of patients presenting to general hospitals and almost never for those at primary healthcare facilities. We see the greatest inequities in small and rural government health facilities and across Sub-Saharan Africa.”

Dr Graham said the importance of medical oxygen must also be recognised and integrated into broader national strategies and pandemic preparedness and response planning.

“Governments should bring together public and private sector partners with a stake in medical oxygen delivery, including health, education, industry, energy and transport to design a system and set up a governance structure that supports the new Global Oxygen Alliance (GO₂AL) and replenishing The Global Fund with a strong oxygen access mandate,” he said.

Key findings from the report published in The Lancet Global Health include:

• The global need for medical oxygen is high. Every year, 374 million children and adults need medical oxygen, including 364 million patients with acute medical and surgical conditions and nine million patients with long-term oxygen needs due to chronic obstructive pulmonary disease.
• Global access to oxygen is highly inequitable with huge gaps in coverage despite pandemic-related investments. Less than one in three people in low- and middle-income countries who need oxygen for acute medical or surgical conditions receives it.

• Costs to fill the oxygen gap are large but represent a highly cost-effective investment that will have wide reaching impacts. Closing the large acute medical and surgical oxygen access gap in low- and middle-income countries requires an additional $US6.8 billion annually.

• National Medical Oxygen Plans are essential to facilitate investment and effectively coordinate service delivery. Less than 30 countries have developed National Oxygen Plans to date but all governments are encouraged to have one by 2030.

• Oxygen systems must be designed to suit the context, include operational costs, and be affordable to all patients. There is no one-size-fits-all national medical oxygen system. Governments should define priorities and optimise their systems to suit local conditions.

• Pulse oximetry is the gateway to safe, quality, affordable oxygen care and needs to be integrated in clinical guidelines, education and all levels of the healthcare system. Pulse oximetry measures should be routinely assessed in patients at all levels of health care.

• A need for closer collaboration between the medical oxygen industry, national governments and global health agencies. Companies should adopt specific oxygen access targets and publish progress while global health agencies should regularly assess oxygen industry progress similar to how the pharmaceutical industry operates.

• Accurate and timely data on oxygen systems is essential for effective decision making and oxygen service access. New toolssuch as the 10 Oxygen Coverage Indicators and a national Access to Medical Oxygen Scorecard (ATMO₂S) would help governments to both plan their national oxygen systems and report progress implementing the WHO Oxygen Resolution.

The report comes after it was announced MCRI would partner with 12 countries in the Pacific and Southeast Asia under a $10 million initiative to improve child and adolescent health across the region.

The Australian Government has awarded MCRI a strategic grant as part of its Partnerships for a Healthy Region Initiative.

The three-year funding will be used to establish the ReALiSE program — the Regional Alliance for Learning in Systems for Equitable Child and Adolescent Health — which will strengthen resilience in public health systems and engage with youth leaders and local communities to improve the health of all young people.

Blocking lymphangiogenesis to limit the risk of metastasis? The idea seemed promising but turned out to be disappointing. ”While it is true that lymphatic vessels promote metastasis, they are also essential for transporting immune cells and activating the anti-tumour immune response,” explains Stéphanie Hugues, a full professor in the Department of Pathology and Immunology and at the Geneva Centre for Inflammation Research in UNIGE Faculty of Medicine, who led this research. ”Their role is therefore more complex than we imagined, which is why we wanted to understand how the cells that make them up respond to the tumour microenvironment in order to influence the immune response.”

An enzyme that blocks the tumour’s defences

The research team measured the gene expression of lymphatic endothelial cells, the cells that make up the wall of lymphatic vessels, in melanoma and in healthy mouse skin. They detected an over-expression of an enzyme called CH25H in the lymphatic endothelial cells associated with the tumours, a result they confirmed in human beings: the more lymphatic vessels the melanomas contained, the more this enzyme was over-expressed. ”What’s more, patients with high levels of this enzyme had a better prognosis, an effect that was even more pronounced in those treated with a particular type of immunotherapy, the immune checkpoint inhibitors,” explains Stéphanie Hugues.

This enzyme’s function is to convert cholesterol into 25-hydroxycholesterol, a cholesterol metabolite important in antiviral immunity. In melanoma, this enzyme seems to also have an impact on the immune system, probably by undermining the tumour’s defence mechanisms. Indeed, the tumour microenvironment naturally produces factors that inhibit the activation of immune cells. However, 25-hydroxycholesterol prevents this inhibition, and therefore enables better activation of anti-tumour immunity.

The multiple roles of lymphatic cells

Prof Hugues’ team then deleted this enzyme in mouse lymphatic endothelial cells. Its absence led to a sharp drop in 25- hydroxycholesterol levels in the melanoma tumours, followed by a suppression of immune activity leading to a much less effective fight against the disease. In contrast, mice vaccinated with tumour antigens showed a clear increase in the expression of the CH25H enzyme and in the production of 25-hydroxycholesterol, leading to better activation of the immune cells. This is consistent with clinical observations: in patients undergoing immunotherapy, the level of expression of this enzyme gives an indication of the response to treatment. ”Our discovery could therefore provide a biomarker for predicting the success of immunotherapy, enabling treatments to be adjusted according to the specific characteristics of each patient,” adds Stéphanie Hugues.

Lymphatic vessels have long been regarded as simple transport routes. ”Our work clearly shows the much more complex role of the cells that make them up. Highly malleable, they respond to the tumour microenvironment and to modulations by the immune system. The stroma is therefore not just a scaffold for the tumour but constitutes a highly complex microworld with both beneficial and pathological roles. We therefore recommend not targeting lymphangiogenesis as a whole but modulating specific functions to fight the disease more effectively,” conclude the authors.

Most cases are caused by a genetic mutation; Dravet syndrome in particular is most often caused by variants in the sodium channel gene SCN1A.

Recent research from Michigan Medicine takes aim at another variant in SCN1B, which causes an even more severe form of DEE.

Mice without the SCN1B gene experience seizures and 100 percent mortality just three weeks after birth.

Using mouse models, the investigative team, led by Chunling Chen, M.D., and Yukun Yuan, M.D., Ph.D., in the lab of Lori Isom, Ph.D., of the Department of Pharmacology at the Medical School, tested a gene therapy to replace SCN1B to increase the expression of beta-1 protein, which is necessary for the regulation of sodium channels in the brain.

Administering the therapy to newborn mice increased their survival, reduced the severity of their seizures and restored brain neuron excitability.

The team notes that different forms of SCN1B gene expression may result in different outcomes for the therapy.

However, the proof-of-concept is the first step toward a gene replacement therapy for SCN1B-linked developmental and epileptic encephalopathy.

The research, published in Nature Biomedical Engineering, is a major advance in neuronal recording and may help bring scientists a step closer to drawing a detailed synaptic connection map of the brain.

Higher-order brain functions are believed to be derived from the ways brain cells, or neurons, are connected. Neuron-to-neuron contact points are called synapses, and scientists seek to draw synaptic connection maps that show not only which neurons connect to which other neurons, but also how strong each connection is. While electron microscopy has been used with great success to make visual maps of synaptic connections, these images lack information on connection strengths and thus the ultimate function of the neuronal network.

In contrast, a patch-clamp electrode, the gold standard in neuronal recording, can effectively get inside an individual neuron to record a faint synaptic signal with high sensitivity, and thus can find a synaptic connection and tell its strength. Scientists have long tried to apply such high-sensitivity intracellular recording to a large number of neurons in parallel, in order to measure and characterize a large number of synaptic signals and thus draw a map annotated with connection strengths. But they have seldom gotten further than obtaining intracellular access from a handful of neurons at once.

The researchers, led by Donhee Ham, the John A. and Elizabeth S. Armstrong Professor of Engineering and Applied Sciences at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), developed an array of 4,096 microhole electrodes on a silicon chip, which performed massively parallel intracellular recording of rat neurons cultured on the chip. From these unprecedented recording data that abounded with synaptic signals, they extracted over 70,000 synaptic connections from about 2,000 neurons.

The work builds on the team’s 2020 breakthrough device — an array of 4,096 vertical nanoneedle electrodes sticking out of a silicon chip of the same integrated circuit design. On this previous device, a neuron could wrap around a needle to allow intracellular recording, which was parallelized through the large number of electrodes. In the best case, they could extract about 300 synaptic connections from the recording data — still blowing well past what patch-clamp recording can reach.

With the basic premise in hand, the team suspected they could do better. Co-lead authors Jun Wang and Woo-Bin Jung from the Ham group at SEAS led the design and fabrication of the microhole electrode array on the silicon chip, the electrophysiological recording and the data analysis.

They operated the chip to gently open up cells with small current injections through the electrodes in order to parallelize their intracellular recording. Postdoctoral researcher Wang said the microhole design is similar to the patch-clamp electrode, which is essentially an electrode-housing glass pipette with a hole at the end.

“Not only do microhole electrodes better couple to the interiors of neurons than the vertical nanoneedle electrodes, but they are also much easier to fabricate. This accessibility is another important feature of our work,” Wang said.

The new design exceeded the team’s expectations. On average, more than 3,600 microhole electrodes out of the total 4,096 — that is, 90 percent — were intracellularly coupled to neurons on top. The number of synaptic connections the team extracted from such unprecedented network-wide intracellular recording data bloomed to 70,000 plausible synaptic connections, compared with about 300 with their previous nanoneedle electrode array. The quality of the recording data was also better, which allowed the team to categorize each synaptic connection based on its characteristics and strengths.

“The integrated electronics in the silicon chip plays as equally an important role as the microhole electrode, providing gentle currents in an elaborate way to obtain intracellular access, and recording at the same time the intracellular signals,” said Jung, a former postdoctoral researcher and now a faculty member at Pohang University of Science and Technology in South Korea.

“One of the biggest challenges, after we succeeded in the massively parallel intracellular recording, was how to analyze the overwhelming amount of data,” Ham said. “We have since come a long way to gain insight into synaptic connections from them. We are now working toward a newer design that can be deployed in a live brain.”

Paper co-authors include Rona S. Gertner of the Department of Chemistry and Chemical Biology, and Hongkun Park, the Mark Hyman, Jr. Professor of Chemistry and Professor of Physics.

The research was supported by the Samsung Advanced Institute of Technology of Samsung Electronics.

The paper published in PLOS Biology today found that a fungus called Beauveria bassiana was able to make the fly’s innate immune system trigger a process that kills neurons and glia in the brain, leading to more than half of flies dying after seven days compared to half of control samples living for nearly 50 days.

In experiments conducted by a team of academics from the University of Birmingham, fruit flies were exposed to B.bassiana in infection chambers. After three days exposure, the fungus had penetrated the blood-brain barrier and had made its way into the central brain.

The scientists found that the fungus is able to trick the fly’s immune system agents called Toll receptors to release two different responses. The Toll-1 receptor triggered the release of antimicrobial peptides (AMPs) as expected, which attack and try to kill pathogens. However, the fungus also provoked Toll-1 to trigger the production of another molecule called Sarm, which suppresses the immune response and kills brain cells instead.

Alicia Hidalgo, Professor of Neurogenetics at the University of Birmingham and corresponding author of the study said:

“We have shown a process for how fungi have evolved to trick the immune system to get into the brain. The fungus is detected by the receptor that does a normal process to induce innate immunity, but in the brain this can also trigger an immune-evasion pathway that induces cell death in the host brain instead.

“The key antagonist in the immune process is Sarm, a so-called master of destruction, that is causing cell death in the brain. The ability of B. bassiana to trick the fruit fly immune system into activating the master of destruction Sarm and killcells enables spores to beat the blood-brain barrier and start feeding on brain cells.”

Dr Deepanshu Singh, who worked on the study for their PhD carried out at the University of Birmingham, and is now a post-doc at the University of Manchester, said:

“From an evolutionary perspective, these findings highlight the ongoing arms race between hosts and pathogens, where hosts enhance their immune mechanisms while pathogens evolve new strategies to evade immunity.

“It is important to stress that B. bassiana cannot affect humans. Some fungi have co-evolved with the host, so they will infect only particular hosts. B. bassiana infects multiple insect species, but not mammals. However, in principle, this study shows that other fungal infections could affect the human brain in analogous ways.”

Some electronic textiles, or e-textiles, have sensors that can monitor the wearer’s heart rate, blood pressure and movement, or can connect via Bluetooth to mobile apps that control temperature. Yet, even with technological advances, users can still be injured by these products. Older people are especially prone to heat-related injuries because of decreased heat sensitivity, and residents of nursing homes and assisted living communities are vulnerable because their temperatures cannot always be easily or frequently monitored by healthcare providers. Jeanne Tan and collaborators believed they could improve e-textile safety by combining AI-driven systems with thermochromic yarn to create a fabric that warms the user without overheating and provides immediate temperature readings for easy monitoring.

The researchers created an intelligent heating jacket from their new e-textile containing heat-generating, silver-coated yarn and two types of thermochromic yarn. The silver-coated yarn warms the garment with less bulk and more flexibility than traditionally used carbon fiber. The AI-based temperature control system incorporated into the jacket was trained on 50 subjects with a range of ages, genders and body types who identified their ideal heat settings in environments with varying temperatures, humidities and wind speeds. The color-changing yarns added a safety feature to the jacket, with one yarn transitioning from purple to pink to indicate a heating temperature above 86 degrees Fahrenheit (30 degrees Celsius) to allow for easy temperature monitoring during the day. In dark environments, the other, polymeric optical fiber yarn gave off a blue, yellow or red glow to indicate temperatures of 86 F (30 C), 104 F (40 C) and 122 F (50 C), respectively.

In a demonstration, the thermochromic and optical fiber yarns in the jacket accurately indicated heating temperature, and the jacket’s AI component predicted a comfortable temperature and provided consistent heating for the wearer, even when the environment changed. In the future, the team says their e-textile technology could be used in various applications, from heated car seats and furniture to spacesuits.

The authors acknowledge funding from the Laboratory for Artificial Intelligence in Design under InnoHK Research Clusters, Hong Kong Special Administrative Region.

The research shows that a higher concentration of copper in some pads is associated with increased harmful effects on sensitive cells from people’s lungs, as a result of particles being breathed in.

Exposure to pollution generated by cars, vans and lorries has long been linked to an increased risk of lung and heart disease. However, while past attention has mainly concentrated on exhaust emissions, particles are also released into the air from tyre, road and brake pad wear — emissions which are largely unregulated by legislation.

These ‘non-exhaust’ pollution sources are now responsible for the majority of vehicle particulate matter (PM) emissions in the UK and parts of Europe, with brake dust being the main contributor.

Lead author of the study, Dr James Parkin, explains that a move to electric cars is bringing the problem into sharper focus: “People generally associate pollution from cars as being from exhaust pipes and think of electric vehicles as having zero emissions. However, EVs still produce particulate matter due to friction and wear of the road, tyres, and brakes.

“We wanted to understand how different types of chemical composition of pads affect the toxicity of the particles emitted and what this might mean for the health of individuals.”

The scientists undertook an in-depth study examining the effects on lung health of PM from four different types of brake pad with differing chemical compositions; low metallic, semi-metallic, non-asbestos organic and hybrid-ceramic. The researchers were particularly interested in the smallest particles, of PM2.5 and below (often referred to as fine PM) — 30 times smaller than the diameter of a human hair.

These tiny particles can make their way beyond the upper airways and deeper into the delicate lung air sacs, which enable the exchange of oxygen and carbon dioxide to and from the blood stream. Fine PM from a variety of different sources is associated with over four million premature deaths per year worldwide.

Brake pad particulate matter was collected using specialist equipment. In the laboratory, the Southampton team used samples of cells from the lining of the lung and exposed them to the fine particulate matter to measure its effects, such as oxidative stress, inflammation, or the death of cells.

Results showed that of the four types of brake pads, non-asbestos organic pads were the most potent in terms of inducing inflammation and other markers of toxicity, and more toxic to human lung cells than diesel exhaust particles. Ceramic pads were the second most toxic. Importantly, both non-asbestos organic and ceramic pads contain high concentrations of copper, and later experiments to remove this copper found the PM became less toxic.

The findings, published in the journal Particle and Fibre Toxicology, suggest that a reduction of copper content in brake pads could help mitigate some of the harmful effects of vehicle particulate matter. Air pollution, including from cars, has been linked to a range of conditions, such as asthma, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, dementia and idiopathic pulmonary fibrosis (scarring of the lung).

Project supervisor Professor Matthew Loxham comments: “This research has important implications for health and future policy because as we switch from diesel and petrol-powered cars to electric vehicles, non-exhaust particle emissions will remain. Non-exhaust emissions could increase over time due to electric vehicles being heavier than combustion engine vehicles and creating greater friction.”

The researchers highlight that while electric vehicles emit no exhaust emissions they aren’t emission-free and that health effects from vehicle emissions won’t necessarily be completely removed once the fleet is fully electrified. They suggest that current legislation, which focuses on PM exhaust emissions, may be inadequate to fully mitigate the health effects of vehicles in the future.

“Intermittent fasting is known to have benefits, including boosting metabolism and helping with weight loss and heart disease. But until now, its potential side effects weren’t well understood,” says Alexander Bartelt, the Else Kröner Fresenius Professor and Chair of Translational Nutritional Medicine at TUM. In a recently published study, the team shows that intermittent fasting during adolescence could have long-term negative effects on metabolism.

Fasting improves metabolism in older mice, but not in the young

The researchers studied three groups of mice: adolescent, adult, and older animals. The mice remained without food for one day and were fed normally on two days. After ten weeks, insulin sensitivity improved in both the adult and older mice, meaning that their metabolism responded better to insulin produced by the pancreas. This is key to regulating blood sugar levels and preventing conditions like type 2 diabetes.

However, the adolescent mice showed a troubling decline in their beta cell function, the insulin-producing cells of the pancreas. Insufficient insulin production is linked to diabetes and disrupted metabolism. “Intermittent fasting is usually thought to benefit beta cells, so we were surprised to find that young mice produced less insulin after the extended fasting,” explains Leonardo Matta from Helmholtz Munich, one of the study’s lead authors.

Defective beta cells resemble those of type 1 diabetes patients

The researchers used the latest single-cell sequencing to uncover the cause of the beta cell impairment. By examining the blueprint of the pancreas, the team found that the beta cells in the younger mice failed to mature properly. “At some point, the cells in the adolescent mice stopped developing and produced less insulin,” says Peter Weber from Helmholtz Munich, also a lead author. Older mice, whose beta cells were already mature before the fasting began, remained unaffected.

The team compared their mouse findings to data from human tissues. They found that patients with type 1 diabetes, where beta cells are destroyed by an autoimmune response, showed similar signs of impaired cell maturation. This suggests that the findings from the mouse study could also be relevant to humans. “Our study confirms that intermittent fasting is beneficial for adults, but it might come with risks for children and teenagers,” says Stephan Herzig, a professor at TUM and director of the Institute for Diabetes and Cancer at Helmholtz Munich. “The next step is digging deeper into the molecular mechanisms underlying these observations. If we better understand how to promote healthy beta cell development, it will open new avenues for treating diabetes by restoring insulin production.”

When mice are full and eat sugar, these nerve cells not only release signaling molecues that stimulate satiety, but also one of the body’s own opiate: ß-endorphin. This acts on other nerve cells with opiate receptors and triggers a feeling of reward, that causes the mice to eat sugar even beyond fullness. This opioid pathway in the brain was specifically activated when the mice ate additional sugar, but not when they ate normal or fatty food. When the researchers blocked this pathway, the mice refrained from eating additional sugar. This effect was only observed in full animals. In hungry mice, the inhibition of ß-endorphin release had no effect.

Interestingly, this mechanism was already activated when the mice perceived the sugar before eating it. In addition, the opiate was also released in the brains of mice that had never eaten sugar before. As soon as the first sugar solution entered the mice’s mouths, ß-endorphin was released in the “dessert stomach region,” which was further strengthened by additional sugar consumption.

What happens in humans?

The scientists also carried out brain scans on volunteers who received a sugar solution through a tube. They found that the same region of the brain reacted to the sugar in humans. In this region, as in mice, there are many opiate receptors close to satiety neurons.

“From an evolutionary perspective, this makes sense: sugar is rare in nature, but provides quick energy. The brain is programmed to control the intake of sugar whenever it is available,” explains Henning Fenselau, research group leader at the Max Planck Institute for Metabolism Research and head of the study.

Relevance for the treatment of obesity

The research group’s findings could also be important for the treatment of obesity. “There are already drugs that block opiate receptors in the brain, but the weight loss is less than with appetite-suppressant injections. We believe that a combination with them or with other therapies could be very useful. However, we need to investigate this further,” says Fenselau.

“Our study provides unique evidence about the potential benefit of yogurt,” said corresponding author Shuji Ogino, MD, PhD, the chief of the Program in Molecular Pathological Epidemiology in the Department of Pathology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. Ogino is also an American Cancer Society Professor, a Professor at Harvard T.H. Chan School of Public Health, and an Affiliate Member of the Broad Institute of MIT and Harvard. “My lab’s approach is to try to link long-term diets and other exposures to a possible key difference in tissue, such as the presence or absence of a particular species of bacteria. This kind of detective work can increase the strength of evidence connecting diet to health outcomes.”

Ogino and colleagues — team OPTISTIMISTICC — are funded by Cancer Research UK through Cancer Grand Challenges, a research initiative co-founded by Cancer Research UK and the National Cancer Institute in the United States. OPTIMISTICC aims to transform the understanding of how the microbiome contributes to disease development, progression and response to treatment. As part of this, Ogino’s team aims to define the risk factors and environmental exposures that individuals encounter through life which are behind the rise of early-onset colorectal cancer and ultimately develop strategies to reduce the burden of this type of cancer.

To conduct their study, the researchers used data from two U.S.-wide prospective cohort studies known as the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). The studies have followed more than 100,000 female registered nurses and 51,000 male health professionals, respectively. Participants have been followed since 1976 for the NHS and 1986 for HFPS, answering repeated questionnaires about lifestyle factors and disease outcomes, including questions about average daily intake of plain and flavored yogurt, as well as other dairy products. The researchers also assessed tissue samples for participants with confirmed cases of colorectal cancer, measuring the amount of Bifidobacterium DNA in tumor tissue.

The researchers found 3,079 documented cases of colorectal cancer in the two study populations. Information on Bifidobacterium content was available in 1,121 colorectal cancer cases. Among those, 346 cases (31%) were Bifidobacterium-positive, and 775 cases (69%) were Bifidobacterium-negative. The researchers did not observe a significant association between long-term yogurt intake and overall colorectal cancer incidence, but they did see an association in Bifidobacterium-positive tumors, with a 20 percent lower rate of incidence for participants who consumed two or more servings of yogurt a week. This lower rate was driven by lower incidence of Bifidobacterium-positive proximal colon cancer — a type of colorectal cancer that occurs in the right side of the colon. Studies have found that patients with proximal colon cancer have worse survival outcomes than patients with distal cancers.

“It has long been believed that yogurt and other fermented milk products are beneficial for gastrointestinal health,” said co-senior author Tomotaka Ugai, MD, PhD, of the Department of Pathology at the Brigham and the Department of Epidemiology at the Harvard T.H. Chan School of Public Health. “Our new findings suggest that this protective effect may be specific for Bifidobacterium-positive tumors.”

The researchers hypothesize that long-term yogurt intake may reduce risk of proximal colon cancer by changing the gut microbiome, including Bifidobacterium, but they note that further research that brings together both basic science and population health studies is needed to draw a definitive conclusion.

“This paper adds to the growing evidence that illustrates the connection between diet, the gut microbiome, and risk of colorectal cancer,” said co-author Andrew T Chan, MD, chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system and co-lead for Cancer Grand Challenges team PROSPECT addressing causes of cancer in young adults. “It provides an additional avenue for us to investigate the specific role of these factors in the risk of colorectal cancer among young people.”

Surgeons routinely use stainless steel or titanium, which stay in the body forever, can cause discomfort and may require follow-up surgeries. A new zinc alloy, designed by Monash biomedical engineers, could solve these problems by being mechanically strong but gentle enough to degrade safely over time while supporting optimal healing.

A study published today in Nature shows the research team’s innovative approach to making the zinc alloy as strong as permanent steel implants and more durable than other biodegradable options like magnesium-based implants.

Lead researcher, Professor Jian-feng Nie, from the Department of Materials Science and Engineering, said the innovative material had the potential to transform orthopaedic care by reducing complications, minimising the need for additional surgeries, and offering a sustainable alternative to permanent metallic implants.

“Our zinc alloy material could revolutionise orthopaedic care — opening the door to safer, smaller implants that not only enhance patient comfort but also promote better healing outcomes by minimising disruption to surrounding tissues,” Professor Nie said.

“An implant that never disappears will always be a risk to the patient. On the other hand, one that degrades too fast won’t allow adequate time for the bones to heal. With our zinc alloy material, we can achieve the optimal balance between strength and controlled degradation of the implant to promote better healing.”

The research shows that by engineering the size and orientation of the material’s grains, the zinc alloy can bend and adapt in unique ways to accommodate the shapes of its neighbouring tissues.

“This made it not only stronger but more flexible, offering a game-changing alternative for orthopaedics,” Professor Nie said.

The research is paving the way for a new start-up to be launched out of Monash University with a focus on developing next-generation biodegradable implants.

More than two-thirds of those who work after age 50 say that working boosts their physical health, mental health, and/or their overall wellbeing, according to a new report from the University of Michigan National Poll on Healthy Aging.

Nearly half (46%) of those who work say that having a sense of purpose is a very important reason for doing so. The same percentage strongly agrees that working keeps their brain sharp.

Those who were still working past age 65 were more likely to report that work has very positive impacts on their health and well-being, and to strongly agree that working keeps their brain sharp.

Overall, 18% of poll respondents aged 65 and older said they work full- or part-time for an employer or are self-employed, compared with 63% of those aged 50 to 64. Of all those age 50 and over who are working, 69% said their work is all in-person, with the rest divided among those who work fully remotely or partially so. And 88% of those who work say they feel satisfied (45% very, 43% somewhat) with their job.

But the poll also spotlights the barriers to working faced by older adults and reveals that some experience negative effects.

Among people aged 50 and over who work, 33% say their job has a negative effect on their physical health, and 29% say it has a negative effect on their mental health. Among working adults who say their mental health is fair or poor, 22% say they can’t take time off from work for health-related appointments, compared with 7% of those reporting better mental health.

The poll is based at the U-M Institute for Healthcare Policy and Innovation, and supported by AARP and Michigan Medicine, U-M’s academic medical center.

“Our perceptions of working after age 65 have changed over time, and these data suggest that most older adults who are still able to work after the traditional retirement age derive health-related benefits from doing so,” said poll director Jeffrey Kullgren, M.D., M.P.H., M.S., a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M. “As we learn more about how loneliness, lack of social connection and isolation intertwine with physical and mental health in older adults, the role of work is important to consider.”

In addition to the national poll report, the team compiled data for Michigan adults aged 50 and older compared with those in other states; an interactive data visualization is available at https://michmed.org/geZ3B. 

“Americans are living and working longer than ever before, with nearly 38 million older adults in the workforce today — more than two and a half times the number from 40 years ago,” said Carly Roszkowski, vice president of financial resilience at AARP. “This poll reinforces what we hear from older workers every day — that work provides more than just a paycheck. It offers purpose, connection and cognitive benefits. But barriers like age discrimination stand in the way.” 

Barriers to work and negative experiences

The poll asked about barriers to work, both among those who work and among those who don’t currently work but also aren’t retired. The latter group includes 24% of people aged 50 to 64 and 5% of people aged 65 and over.

Overall, 39% of all non-retired older adults — whether they work for pay or not — cited at least one barrier to working. Many cited multiple barriers. The percentage reporting at least one barrier was very high — more than 80% — among those who aren’t working but aren’t retired.

Barriers included disability, chronic illness or poor health (29% of all non-retired older adults), lack of training, skills or experience (13%), limited transportation options (11%), caregiving for an adult (8%), caregiving for a child or grandchild (5%) or a prior conviction or legal action (3%).

The poll also asked all adults aged 50 and up who had worked in the past five years about their experiences related to work. Of this group, 26% thought their skills weren’t being fully utilized, 25% said the pay was too low to be worth their time, and 20% said their health insurance didn’t cover their needs. In addition, 13% felt their job was too physically demanding and 11% said they experienced age discrimination at work.

Other findings:

Very important reasons for working, among those 50 and older who work:

• Financial stability: 78%
• Save for retirement: 65%
• Access to health insurance: 59%
• Contribute to society: 26%

Impacts of work on health, among those 50 and older who work:

• Very positive impact on physical health (32% age 65+ vs. 14% age 50-64)
• Very positive impact on mental health (41% age 65+ vs. 20% age 50-64)
• Very positive impact on well-being (39% age 65+ vs. 21% age 50-64)

Percent of older adults who work who strongly agree with specific benefits of working:

• Helps keep their brain sharp (57% age 65+ vs. 43% age 50 to 64)
• Helps maintain social connections (37% age 65+, 28% age 50-64)
• Helps stay focused (40% age 65+, 28% age 50-64)

The poll findings come from a nationally representative survey conducted by NORC at the University of Chicago for IHPI and administered online and via phone in August 2024 among 3,486 adults ages 50 to 94 across the U.S. The sample was subsequently weighted to reflect the U.S. population. Read past National Poll on Healthy Aging reports and about the poll methodology.

Vimentin is a type III intermediate filament (IF) protein normally expressed in cells that develop into connective tissue, blood vessels, and lymphatic tissue (mesenchymal cells). Despite being widely studied, its role in tumour growth and progression remains unexplored.

A team of researchers at Queen Mary University of London have discovered how a small change in the vimentin protein can make breast cancer more aggressive. By modifying a specific amino acid cysteine to serine residue at position 328 in vimentin, they discovered that this mutation disrupted the protein’s interaction with the cell’s structural network. Remarkably, the mutated vimentin induced aggressive cancer-like behaviour in breast cancer cells, including faster cell growth, migration, and invasion accompanied by reduced cell adhesion. RNA-sequencing further revealed that the presence of mutant vimentin was associated with upregulation of a non-coding RNA called XIST, suggesting a potential link between this mutation and gene expression changes that drive cancer progression.

Researchers also found that mutant vimentin made breast cancer cells grow without depending on the hormone oestrogen when injected into immuno-compromised mice. The tumours in these mice showed high expression of cancer stem cell markers CD56 and CD20, suggesting a role for mutant vimentin in driving cancer stem cell-like behaviour that is often associated with tumour progression, therapeutic resistance and recurrence.

Senior author Ahmad Waseem, Professor of Molecular and Cellular Oral Biology at the Institute of Dentistry, Queen Mary University of London, said: “Our study has discovered a molecular interaction that, when disrupted, causes breast cancer cells to behave like cancer stem cells. Additionally, we identified a potential biomarker that could help detect these stem-like cells in breast cancer tissues. This discovery represents an important step towards understanding how breast cancer develops and spreads, with potential implications for early diagnosis, prognosis, and targeted treatment strategies.” The lead author, Dr Saima Usman (HEC Fellow), did her PhD with Professor Waseem on this project.

Co-author Andrew Yeudall, Professor of Oral Biology in the Dental College of Georgia at Augusta University, said: “The study will open new avenues for our understanding of cancer stem cell behaviour. For several years, Professor Waseem and I have been interested in studying the cancer-related roles of vimentin, which is induced in almost all later-stage tumours that have spread to other sites in the body and can be difficult to treat. We used MCF-7, a model breast epithelial cell line, partly because it is devoid of vimentin which therefore makes it easier to define functions related to specific vimentin mutations. Our observation that the cells became more aggressive, and that stem cell markers were induced, may unlock the door to new therapeutic approaches for breast and other cancers.”

The study analysed data from nearly 400,000 births in Western Australia and found that higher exposure to fine particulate air pollution (PM2.5) and biothermal stress (a measure that combines air temperature, radiant temperature, relative humidity, wind speed, and human physiology) was associated with pregnancies lasting beyond 41 weeks.

Lead author Dr Sylvester Dodzi Nyadanu from Curtin’s School of Population Health said while climate exposure has long been linked to preterm births, this is the first study to examine its impact on prolonged pregnancies.

“We know that being ‘born too soon’ — preterm birth — has well-documented health risks, but little attention has been given to the risks associated with being ‘born too late’,” Dr Nyadanu said.

“Our findings show that exposure to air pollution and biothermal stress during pregnancy increases the likelihood of prolonged pregnancies, particularly among mothers over 35 years old, first-time mothers, those living in urban areas, and those with complicated pregnancies.

“Environmental stressors, including climate-related exposures during pregnancy, have been associated with maternal stress response and subsequent disruptions in endocrine and inflammatory activities, which increase towards the end of pregnancy. This can either shorten gestation, leading to preterm birth, or lengthen gestation, resulting in prolonged pregnancy in some cases.”

Dr Nyadanu said prolonged pregnancy can have serious health implications for both mother and baby, including the need for medical interventions such as labour induction or caesarean sections, increased risk of stillbirth, birth complications, child mortality, early childhood behavioural and emotional problems, and emotional impacts on families.

“With climate change driving more frequent extreme weather events and worsening air quality, it is essential that we recognise the potential impacts on maternal and child health,” Dr Nyadanu said.

“Healthcare providers, policymakers and pregnant women — particularly those in vulnerable groups — must consider climate-related exposures when assessing pregnancy risks and planning interventions.

“This study highlights the need for targeted policies and preventative measures to reduce climate-related health risks, including better air quality regulations and public health initiatives aimed at protecting expectant mothers and children from extreme climatic conditions.”

The cerebrospinal fluid biomarker test correlates with the severity of cognitive decline, independent of other factors, including brain amyloid deposition, thereby opening doors for early-stage disease diagnosis and intervention.

Since amyloid-beta pathology often precedes tau abnormalities in Alzheimer’s disease, most biomarker efforts have focused on early detection of amyloid-beta changes. However, the clumping of tau protein into well-ordered structures referred to by pathologists as “neurofibrillary tangles” is a more defining event for Alzheimer’s disease as it is more strongly associated with the cognitive changes seen in affected people.

“Our test identifies very early stages of tau tangle formation — up to a decade before any tau clumps can show up on a brain scan,” said senior author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt. “Early detection is key to more successful therapies for Alzheimer’s disease since trials show that patients with little-to-no quantifiable insoluble tau tangles are more likely to benefit from new treatments than those with a significant degree of tau brain deposits.”

Since many elderly people who have amyloid-beta plaques in their brains will never go on to develop cognitive symptoms of Alzheimer’s disease during their lifetime, the widely adopted diagnostics framework developed by the Alzheimer’s Association specifies the three neuropathological pillars necessary to diagnose the disease — combined presence of tau and amyloid-beta pathology and neurodegeneration. In a quest for early and accessible biomarkers for Alzheimer’s disease, Karikari’s earlier work showed that a brain-specific form of tau, called BD-tau, can be measured in blood and reliably indicate the presence of Alzheimer’s disease-specific neurodegeneration. Several years prior, Karikari showed that specific forms of phosphorylated tau, p-tau181, p-tau217 and p-tau212, in the blood can predict the presence of brain amyloid-beta without the need for costly and time-consuming brain imaging.

But these tools largely detect amyloid pathology, so the issue of early detection of tau still looms large. While tau-PET remains a reliable and accurate predictor of tau burden in the brain, the test’s utility is limited by availability, low resolution, high cost, labor and sensitivity. At present, tau-PET scans can pick up the signal from neurofibrillary tangles only when a large number are present in the brain, at which point the degree of brain pathology has become pronounced and is not easily reversible.

In this latest research, using the tools of biochemistry and molecular biology, Karikari and team identified a core region of the tau protein that is necessary for neurofibrillary tangle formation. Detecting sites within that core region of 111 amino acids, a sequence they call tau_258-368,can identify clumping-prone tau proteins and help initiate further diagnostics and early treatment. In particular, the two new phosphorylation sites, p-tau-262 and p-tau-356, can accurately inform the status of early-stage tau aggregation that, with an appropriate intervention, could potentially be reversed.

“Amyloid-beta is a kindling, and tau is a matchstick. A large percentage of people who have brain amyloid-beta deposits will never develop dementia. But once the tau tangles light up on a brain scan, it may be too late to put out the fire and their cognitive health can quickly deteriorate,” said Karikari. “Early detection of tangle-prone tau could identify the individuals who are likely to develop Alzheimer’s-associated cognitive decline and could be helped with new generation therapies.”

Other authors of this research are Eric Abrahamson, Ph.D., Xuemei Zeng, Ph.D., Anuradha Sehrawat, Ph.D., Yijun Chen, M.S., Tharick Pascoal, M.D., Ph.D., and Milos Ikonomovic, M.D., all of Pitt; Tohidul Islam, Ph.D., Przemys?aw Kac, M.S., Hlin Kvartsberg, Ph.D., Maria Olsson, B.S., Emma Sjons, B.S., Fernando Gonzalez-Ortiz, M.D., M.S., Henrik Zetterberg, M.D., Ph.D., and Kaj Blennow, M.D., Ph.D., all of University of Gothenburg, Sweden; Emily Hill, Ph.D., Ivana Del Popolo, M.S., Abbie Richardson, M.S., Victoria Mitchell, M.S., and Mark Wall, Ph.D., all of the University of Warwick, UK; Stijn Servaes, Ph.D., Joseph Therriault, Ph.D., Cécile Tissot, Ph.D., Nesrine Rahmouni, M.S., and Pedro Rosa-Neto, M.D., Ph.D., all of McGill University, Canada; Denis Smirnov, Ph.D., and Douglas Galasko, M.D., both of University of California, San Diego; Tammaryn Lashley, Ph.D., of University College London, UK.

This study was supported by, among others, the National Institute on Aging (grants R01AG083874, U24AG082930, P30AG066468, RF1AG052525-01A1, R01AG053952, R37AG023651, RF1AG025516, R01AG073267, R01AG075336, R01AG072641, P01AG14449, and P01AG025204, among others), the Swedish Research Council (grant 2021-03244), the Alzheimer’s Association (grant AARF-21-850325), the Swedish Alzheimer Foundation, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Emil and Wera Cornells Foundation and a professorial endowment fund from the Department of Psychiatry, University of Pittsburgh.

In reality, research has shown that human bodily responses and cognitive shifts affect each other in both directions. We feel sorry because we cry, but also cry when feeling sorry. So how then for our primate cousins? To date, their connections have remained largely unexplored.

Now a team of researchers at Kyoto University has led a study on six Japanese macaques living in KyotoU’s Center for the Evolutionary Origins of Human Behavior, in Aichi prefecture. The researchers focused on self-scratching — a bodily response linked to negative emotions like anxiety and fear — and its relationship to pessimistic judgment bias, which is the tendency to expect a negative outcome when faced with ambiguous information.

By presenting the monkeys with a white rewarding button and a black non-rewarding button, together with a gray ambiguous button, the researchers were able to estimate each monkey’s degree of pessimism. They also videoed the monkeys to identify the timing of self-scratching, analyzing the relationship between self-scratching and pessimism.

“Bodily responses associated with negative emotions can predict subsequent cognitive pessimism,” says corresponding author Sakumi Iki, “but not the other way around.”

In other words, the monkeys were more likely to make pessimistic judgments — avoiding the gray button — immediately after self-scratching, yet making a pessimistic judgment did not necessarily lead to self-scratching. This stands in contrast to humans, for whom evidence suggests a pessimistic way of thinking can cause bodily responses. That this influence did not appear in the macaques suggests that their emotional bodily responses may precede cognitive changes.

From an evolutionary standpoint, the coping strategy of first addressing immediate needs through bodily responses and then engaging in cognitive information processing is probably adaptive for dealing with challenges in natural habitats. Thus, this mechanism might have existed long before humans and macaques diverged, pointing to an evolutionarily conserved system.

“In humans, the relationship between mind and body may have evolved in a distinctive way, influenced by our use of language and advanced introspection,” adds Iki.

“But it might be observable in monkeys if different bodily reactions or cognitive processes are examined.”

Future research involving a wider range of primates and other animals could shed more light on the evolutionary origins of human emotions, and deepen our understanding of the connection between the mind and the body.

New research led by the Lippincott-Schwartz Lab shows that a network of subcellular structures similar to those responsible for propagating molecular signals that make muscles contract are also responsible for transmitting signals in the brain that may facilitate learning and memory.

“Einstein said that when he uses his brain, it is like he is using a muscle, and in that respect, there is some parallel here,” says Janelia Senior Group Leader Jennifer Lippincott-Schwartz. “The same machinery is operating in both cases but with different readouts.”

The first clue about the possible connection between brain and muscle cells came when Janelia scientists noticed something strange about the endoplasmic reticulum, or ER — the membranous sheets and folds inside cells that are crucial for many cellular functions.

Lorena Benedetti, a research scientist in the Lippincott-Schwartz Lab, was tracking molecules at high resolution along the surface of the ER in mammalian neurons when she saw that the molecules were tracing a repeating, ladder-like pattern along the entire length of the dendrites — the branch-like extensions on brain cells that receive incoming signals.

Around the same time, Senior Group Leader Stephan Saalfeld alerted Lippincott-Schwartz to high-resolution 3D electron microscopy images of neurons in the fly brain where the ER was also forming regularly spaced, transversal structures.

The ER normally appears like a huge, dynamic net, so as soon as Lippincott-Schwartz saw the structures, she knew her lab needed to figure out what they were for.

“In science, structure is function,” says Lippincott-Schwartz, who also heads Janelia’s 4D Cellular Physiology research area. “This is an unusual, beautiful structure that we are seeing throughout the whole dendrite, so we just had this feeling that it must have some important function.”

The researchers, led by Benedetti, started by looking at the only other area of the body known to have similar, ladder-like ER structures: muscle tissue. In muscle cells, the ER and the plasma membrane — the outer membrane of the cell — meet at periodic contact sites, an arrangement controlled by a molecule called junctophilin.

Using high-resolution imaging, the researchers discovered that dendrites also contain a form of junctophilin that controls contact sites between their ER and plasma membrane. Further, the team found that the same molecular machinery controlling calcium release at muscle cells’ contact sites — where calcium drives muscle contraction — was also present at dendrite contact sites — where calcium regulates neuronal signaling.

Because of these clues, the researchers had a hunch that the molecular machinery at the dendritic contact sites must also be important for transmitting calcium signals, which cells use to communicate. They suspected that the contact sites along the dendrites might act like a repeater on a telegraph machine: receiving, amplifying, and propagating signals over long distances. In neurons, this could explain how signals received at specific sites on dendrites are relayed to the cell body hundreds of micrometers away.

“How that information travels over long distances and how the calcium signal gets specifically amplified was not known,” says Benedetti. “We thought that ER could play that role, and that these regularly distributed contact sites are spatially and temporally localized amplifiers: they can receive this calcium signal, locally amplify this calcium signal, and relay this calcium signal over a distance.”

The researchers found that this process is triggered when a neuronal signal causes calcium to enter the dendrite through voltage-gated ion channel proteins, which are positioned at the contact sites. Although this initial calcium signal dissipates quickly, it triggers the release of additional calcium from the ER at the contact site.

This influx of calcium at the contact site attracts and activates a kinase called CaMKII, a protein known to be important in memory. CaMKII alters the plasma membrane’s biochemical properties, changing the strength of the signal that is passed down the plasma membrane.

This process continues from contact site to contact site all along the dendrite to the cell body, where the neuron decides how it will communicate with other neurons.

The new research reveals a novel mechanism for signal transmission in brain cells and helps answer an open question in neuroscience about how intracellular signals travel over long distances in neurons, enabling information received at specific sites on dendrites to be processed in the brain.

It also sheds light on the molecular mechanisms underlying synaptic plasticity — the strengthening or weakening of neuronal connections that enables learning and memory. Figuring out this process at the molecular level could increase understanding of how the brain works normally and in diseases where these processes go awry, like Alzheimer’s.

“We are showing that a structure — a beautiful structure — operating at a level of subcellular organization is having a huge effect on the way the entire neuronal system is operating vis-à-vis calcium signaling,” Lippincott-Schwartz says. “This is a great example of how, in doing science, if you see a beautiful structure, it can take you into a whole new world.”

Searching for subtypes of immune cells seen only in the most serious, grade 4 brain tumors, called glioblastomas, and using a recently developed technology called spatial genomics, the researchers found that glioblastoma stem cells were co-localized with a type of immunosuppressive cell called myeloid-derived suppressor cell (MDSC), and that these two cells symbiotically feed off of each other to promote tumor growth and aggressiveness. A description of the work was published Jan. 17 in the journal Science. “Tumor stem cells represent only 5% to 10% of the tumor, but they’re the critical cells that are renewing and generating the rest of the tumor and are essentially responsible for the aggressiveness of the tumor,” says senior study author Drew Pardoll, M.D., Ph.D., the Martin D. Abeloff Professor of Cancer Research , co-director of the Mark Foundation Center for Advanced Genomics and Imaging, and director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy. “We found that the myeloid-derived suppressor cells and tumor stem cells literally were in the same place — a region described by pathologists in the 1980s as the pseudopalisading region. There was a very intimate connection.”

To better characterize the cellular components of brain cancer, investigators performed single-cell RNA sequencing on tissue samples from 33 types of brain tumors spanning from low to high grade, finding two populations of MDSCs in IDH-WT glioblastoma. Then, using a technique called spatial transcriptomics to look at patterns of gene expression of over 750,000 immune cells and more than 350,000 tumor and associated cells in these samples, they found MDSCs were co-located with the tumor stem cells.

“Glioblastoma is a highly aggressive brain tumor with remarkable ability to evade the immune system, which has made immune-based therapies largely ineffective to this point,” said first and co-corresponding author, Christina Jackson, M.D., an assistant professor of neurosurgery at the Perelman School of Medicine at the University of Pennsylvania, who was at Johns Hopkins at the time the research was conducted. “Our study revealed a distinct subset of immune cells, known as myeloid-derived suppressor cells that promote glioblastoma growth, providing new insights into how the tumor interacts with the immune system. By identifying these cells and their role, we hope to uncover new therapeutic targets andlay the groundwork for more effective treatments.”

In their studies, investigators discovered that the two types of cells were feeding each other in the brain tumors. Tumor stem cells were producing chemical signals called chemokines that attracted the MDSCs, and making growth factors and activation factors for the MDSCs. In turn, the MDSCs were producing growth factors for the tumor cells.

The researchers were able to further ascertain what specific molecules tumor stem cells were producing to attract and activate MDSCs. Two of the key ones identified by the team were IL (interleukin)-6 and IL-8, which play a role in inflammatory responses, and for which MDSCs have receptors.

“IL-8 is one of the major attractants to bring the MDSCs to the tumor, and IL-6 is one of the major activators of the MDSCs,” Pardoll says.

On the flip side, the team found that MDSCs secreted a growth factor called fibroblast growth factor 11 (FGF11) to feed the stem cells, a molecule never before known to be involved in brain or other cancers.

Along the way, Jackson, Pardoll and colleagues found that tumors with a mutation in the IDH1 gene, which are less aggressive, had almost no MDSCs and far fewer cancer stem cells. This led them to look across all brain cancers at the correlation between MDSC infiltration and survival. Using the National Cancer Institute’s Cancer Genome Atlas (TCGA) database of cancer samples, they indeed found that very tight correlation — the fewer cancer stem cells and fewer MDSCs a person had in their tumors, the better they did.

While additional studies are needed to further understand these cellular interactions, the work is exciting in that it suggests additional potential targets to block in treatment of these aggressive brain tumors, Pardoll says. For example, Jamie Spangler, Ph.D., an associate professor of biomedical engineering at Johns Hopkins, has developed an investigational bispecific antibody that binds to the receptors for IL-6 and IL-8, blocking their signaling.

Study co-authors were Christopher Cherry, Sadhana Bom, Arbor Dykema, Rulin Wang, Elizabeth Thompson, Ming Zhang, Runzhe Li, Zhicheng Ji, Wenpin Hou, Wentao Zhan, Hao Zhang, John Choi, Ajay Vaghasia, Landon Hansen, Kate Jones, Fausto Rodriguez, Jon Weingart, Calixto-Hope Lucas, Jonathan Powell, Jennifer Elisseeff, Srinivasan Yegnasubramanian, Chetan Bettegowda and Hongkai Ji of Johns Hopkins. Other researchers contributing to the work were from Stanford University School of Medicine in California.

The research was supported by the National Institutes of Health (grants #F32NS108580, #R01HG010889, R01HG009518, RA37CA230400, U07CA230691), the Neurosurgery Research Education Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy, the Mark Foundation for Cancer Research, a Burroughs Wellcome Career Award for Medical Scientists, the Commonwealth Foundation, the Maryland Cigarette Restitution Fund and the NIH Pioneer Award.

Bettegowda is a consultant for Bionaut Labs, Privo Technologies, Haystack Oncology and Depuy-Synthes. He also is a co-founder of OrisDx and Belay Diagnostics. Yegnasubramanian has received grant support through Johns Hopkins from Bristol Myers Squibb and Janssen and grants and personal fees from Cepheid. He is a co-founder of Digital Harmonic and Brahm Astra Therapeutics. Elisseeff is founder of Aegeria Soft Tissue. Powell is an employee of Calico but was not when this research was performed. Pardoll is a consultant for Amgen, Arcturus Therapeutics, ATengen, Bristol Myers Squibb, Compugen, Dragonfly Therapeutics, Immunomic Therapeutics, Normunity, PathAI, RAPT Therapeutics, Regeneron, Takeda Pharmaceuticals and Tizona. He has received grant support through Bristol Myers Squibb, Compugen, Enara Bio and Immunomic Therapeutics, and owns stock in Dracen Pharmaceuticals, Dragonfly Therapeutics, Enara Bio, RAPT Therapeutics and Tizona. Pardoll is on the board of directors of Clasp Therapeutics and Dracen Pharmaceuticals and has patent royalties with Bristol Myers Squibb and Immunomic Therapeutics. These relationships are managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

Mitochondrial defects, however, are associated with the development of diseases such as type 2 diabetes. Patients who suffer from this disorder are unable to produce enough insulin or use the insulin produced by their pancreas to keep their blood sugar at normal levels.

Several studies have shown that insulin-producing pancreatic β-cells of patients with diabetes have abnormal mitochondria and are unable to generate energy. Yet, these studies were unable to explain why the cells behaved this way.

In a study published in Science, researchers at the University of Michigan used mice to show that dysfunctional mitochondria trigger a response that affects the maturation and function of β-cells.

“We wanted to determine which pathways are important for maintaining proper mitochondrial function,” said Emily M. Walker, Ph.D, a research assistant professor of internal medicine and first author of the study.

To do so, the team damaged three components that are essential for mitochondrial function: their DNA, a pathway used to get rid of damaged mitochondria, and one that maintains a healthy pool of mitochondria in the cell.

“In all three cases, the exact same stress response was turned on, which caused β-cells to become immature, stop making enough insulin, and essentially stop being β-cells,” Walker said.

“Our results demonstrate that the mitochondria can send signals to the nucleus and change the fate of the cell.”

The researchers also confirmed their findings in human pancreatic islet cells.

Mitochondrial dysfunction affects several types of cells

Their results prompted the team to expand their search into other cells that are affected during diabetes.

“Diabetes is a multi-system disease — you gain weight, your liver produces too much sugar and your muscles are affected. That’s why we wanted to look at other tissues as well,” said Scott A. Soleimanpour, M.D., director of the Michigan Diabetes Research Center and senior author of the study.

The team repeated their mouse experiments in liver cells and fat-storing cells and saw that the same stress response was turned on. Both cell types were unable to mature and function properly.

“Although we haven’t tested all possible cell types, we believe that our results could be applicable to all the different tissues that are affected by diabetes,” Soleimanpour said.

Reversing mitochondrial damage could help cure diabetes

Regardless of the cell type, the researchers found that damage to the mitochondria did not cause cell death.

This observation brought up the possibility that if they could reverse the damage, the cells would function normally.

To do so, they used a drug called ISRIB that blocked the stress response. They found that after four weeks, the β-cells regained their ability to control glucose levels in mice.

“Losing your β-cells is the most direct path to getting type 2 diabetes. Through our study we now have an explanation for what might be happening and how we can intervene and fix the root cause,” Soleimanpour said.

The team is working on further dissecting the cellular pathways that are disrupted and hope that they will be able to replicate their results in cell samples from diabetic patients.

The Ray Laboratory, led by Department of Biological Sciences Professor and Associate Chair David Ray, as part of a study on bat genomes published by the scientific journal Nature, helped identify the components of a genome in a specific species of bats that have shown more genetic adaptations in their immune systems than other animals.

The study revealed that a gene common in some bats can reduce the production of the SARS-CoV-2 virus by up to 90%, which could help lead to new medical approaches to combating viral diseases.

“Bats have an amazing ability to resist some of the worst effects of viral infection that make us so vulnerable to certain diseases,” Ray said. “While we get very sick, the bats barely blink an eye when exposed to the same pathogens.”

Ray said his laboratory aided in the annotation of the genome assemblies in the bats. Genome annotation is how scientists characterize all component parts of the genome — the genes, regulatory sequences and non-coding and coding regions. The Texas Tech lab identified the transposable element (TE) regions of the assemblies, where bits of DNA can create new copies of themselves and introduce variations within the genome.

Ray said bats have a unique TE repertoire among mammals, presenting a potentially powerful way to generate new genetic pathways to deal with pathogens like the coronavirus.

“If every individual of a species was genetically identical, they would all have the same risk associated with infection — if one dies, they all die,” Ray said. “TEs are a great way for organisms to generate genetic diversity in the species, allowing some individuals to survive better in the face of environmental pressures like viral diseases.”

This study is part of a larger international project called Bat1K, which is attempting to sequence and assemble the genomes of every living bat species, numbering around 1,500, according to Ray. It was led by the Senckenberg Research Institute and Natural History Museum in Frankfurt, Germany.

Michael Hiller, a professor of comparative genomics at the Goethe University and a member of the Senckenberg Institute is one of the main investigators in the study. He and Ray are both members of the executive board for the Bat1K consortium, and their relationship provided the perfect opportunity for Ray’s lab to collaborate with the international scientific community.

The lab studies genomes and genome evolution with an emphasis on TEs. Their past studies have included genome research on bats and other mammals, crocodiles and various insects. The lab has worked with entities in the past such as the National Science Foundation, the U.S. Department of Agriculture, the state of Texas and the Texas Department of Wildlife and Fisheries.

Researchers in this recent study paid particular attention to the ISG15 gene, which is associated with a severe course of COVID-19 in humans. Bats are known to carry numerous viruses, including those transmissible to humans, but do not show any symptoms of disease when infected.

The ISG15 gene from the bats, the study showed, is able to reduce production of the SARS CoV-2 virus by 80-90%. By contrast, the ISG15 gene from a human genome showed no antiviral effect in this study.

“Thus, the ISG15 gene is likely one of several factors that contribute to viral disease resistance in bats,” Hiller said. “These promising results can be used as a basis for further experimental studies, which are necessary to decipher the unique adaptations of the bats’ immune system.”

These results give hope to stroke patients worldwide who may not be able to access clot-dissolving medications within the approved time window, which in China is within 4.5 hours, said the trial’s principal investigator Min Lou, M.D., Ph.D., a professor at the Second Affiliated Hospital of Zhejiang University’s School of Medicine in China.

In the U.S., alteplase is approved to treat stroke within three hours of symptom onset and is recommended for use up to 4.5 hours for select patients. Other research has indicated it may also work well in some patients 4.5 to 9 hours after stroke onset.

The American Heart Association/American Stroke Association 2019 Guidelines for the Early Management of Patients with Acute Ischemic Stroke note that IV alteplase within 4.5 hours of stroke onset is the standard of care for most ischemic stroke patients in the United States.

Researchers enrolled 372 stroke patients whose symptoms began 4.5 hours to 24 hours earlier. They used widely available CT perfusion imaging (advanced brain scanning) to confirm that these patients still had brain tissue that could recover with treatment. Participants were randomly split into two groups — one group received the clot-busting medication alteplase, while the other received standard stroke care of antiplatelet therapy at the discretion of the investigator, based on the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2018. Functional recovery was assessed at 90 days.

“We believe these findings mean more people may return to normal or near-normal lives after a stroke, even if they receive treatment later than originally thought beneficial,” Lou said. “This method of treatment could become the new standard, especially in hospitals that use CT perfusion imaging. This technology helps health care professionals see how blood flows in different parts of the brain after an ischemic stroke. This could extend treatment eligibility to millions more patients across the globe.”

The study found:

• 40% of participants treated with alteplase had little to no disability after 90 days, compared to 26% of those who received standard care — a 54% higher chance of functional recovery.
• Less than 3% of participants in either group received rescue mechanical clot removal as an additional treatment.
• Rates of death were the same (10.8%) for both groups.
• The risk of brain bleeding was higher among those who received alteplase than among participants who did not (3.8% vs. 0.5%), but researchers believe this is a manageable risk.

“We also need to look more closely at how safe and effective other clot-dissolving medications, like tenecteplase, are when given after a stroke, especially beyond the usual time frames. It’s also important to learn if our findings apply to other groups of people, especially in areas with different stroke risks and health care resources,” Lou explained.

Study limitations include the that both participants and researcher knew which treatment was being given, which could have introduced bias, and results may not be generalizable to patients outside of China.

Study design, background and details:

• The study enrolled 372 stroke patients in a multicenter, prospective, randomized trial at 26 stroke centers in China.
• The patient’s average age was 72 years, and 43% were women.
• The trial used widely available CT perfusion imaging software to gauge salvageable brain tissue, making the findings more applicable to real-world clinical settings.
• Enrolled patients were assigned to the alteplase group or a standard medical treatment group.
• The primary outcome was a score of 0 or 1 on the modified Rankin scale, which scores disability from 0 (no symptoms) to 6 (death) at 90 days.

“It’s the first study, as far as we know, to evaluate the effectiveness of mental health counseling for veterinary trainees,” said Kerry Karaffa, PhD, a licensed psychologist at the Mizzou College of Veterinary Medicine. “Through our study on embedded counseling models, we found only one in three veterinary mental health practitioners were collecting outcome data with their clients. Data is important to evaluate whether what we’re doing is working. If students know that there are good outcomes associated with counseling, they may be more likely to seek help.”

For the study, Karaffa partnered with fellow Mizzou psychologists Tiffany Sanford-Martens, PhD, and Anne Meyer, PhD. Together, the trio conducted an archival analysis of client data from 437 Mizzou doctor of veterinary medicine students, veterinary interns and veterinary residents who participated in embedded counseling services between 2016 and 2024.

The researchers found veterinary trainees who took advantage of embedded counseling services reported improvements in psychological distress on every scale of the Counseling Center Assessment of Psychological Symptoms-62 including depression, anxiety, academic distress, eating concerns and substance use. The study also identified several issues veterinary trainees may be navigating alongside mental health challenges, including financial stress, chronic health problems and histories of traumatic experiences.

“These data suggest embedded counseling programs may enable veterinary students to manage their personal and academic challenges more effectively during their training,” Karaffa said.

Expanding the impact: lessons for veterinary medicine and beyond

In addition to evaluating the effectiveness of embedded counseling services in the Mizzou CVM, the study also explored how veterinary trainees’ experiences and needs compared to other college students seeking counseling services. The team found that veterinary trainees were not notably different on most metrics — reinforcing the idea that counseling services may play a crucial role in supporting students’ mental health, regardless of their field of training.

Karaffa said the insights gained from veterinary medicine could be applied more broadly, leading to better care for all students and a deeper understanding for mental health providers. He also encourages other embedded counseling providers to incorporate clinical progress monitoring into their practices to enhance services and inform key decisions.

“This approach would help us track mental health trends, refine our practices, adapt outreach programs and demonstrate the effectiveness of embedded services to stakeholders,” he said. “It could also ultimately promote help-seeking and guide decisions on funding and resource allocation.”

“Client Characteristics and the Effectiveness of Embedded Counseling Services in a College of Veterinary Medicine” was published in the Journal of Veterinary Medical Education.

The research team, led by Dr Sara Mederos and Professor Sonja Hofer, mapped out how the brain learns to suppress responses to perceived threats that prove harmless over time.

“Humans are born with instinctive fear reactions, such as responses to loud noises or fast-approaching objects,” explains Dr Mederos, Research Fellow in the Hofer Lab at SWC. “However, we can override these instinctive responses through experience — like children learning to enjoy fireworks rather than fear their loud bangs. We wanted to understand the brain mechanisms that underlie such forms of learning.”

Using an innovative experimental approach, the team studied mice presented with an overhead expanding shadow that mimicked an approaching aerial predator. Initially, the mice sought shelter when encountering this visual threat. However, with repeated exposure and no actual danger, the mice learned to remain calm instead of escaping, providing researchers with a model to study the suppression of fear responses.

Based on previous work in the Hofer Lab, the team knew that an area of the brain called the ventrolateral geniculate nucleus (vLGN) could suppress fear reactions when active and was able to track knowledge of previous experience of threat. The vLGN also receives strong input from visual areas in the cerebral cortex, and so the researchers explored whether this neural pathway had a role in learning not to fear a visual threat.

The study revealed two key components in this learning process: (1) specific regions of the visual cortex proved essential for the learning process, and (2) a brain structure called the ventrolateral geniculate nucleus (vLGN) stores these learning-induced memories.

“We found that animals failed to learn to suppress their fear responses when specific cortical visual areas where inactivated. However, once the animals had already learned to stop escaping, the cerebral cortex was no longer necessary,” explained Dr Mederos.

“Our results challenge traditional views about learning and memory,” notes Professor Hofer, senior author of the study. “While the cerebral cortex has long been considered the brain’s primary centre for learning, memory and behavioural flexibility, we found the subcortical vLGN and not the visual cortex actually stores these crucial memories. This neural pathway can provide a link between cognitive neocortical processes and ‘hard-wired’ brainstem-mediated behaviours, enabling animals to adapt instinctive behaviours.”

The researchers also uncovered the cellular and molecular mechanisms behind this process. Learning occurs through increased neural activity in specific vLGN neurons, triggered by the release of endocannabinoids — brain-internal messenger molecules known to regulate mood and memory. This release decreases inhibitory input to vLGN neurons, resulting in heightened activity in this brain area when the visual threat stimulus is encountered, which suppresses fear responses.

The implications of this discovery extend beyond the laboratory. “Our findings could also help advance our understanding of what is going wrong in the brain when fear response regulation is impaired in conditions such as phobias, anxiety and PTSD. While instinctive fear reactions to predators may be less relevant for modern humans, the brain pathway we discovered exists in humans too,” explains Professor Hofer. “This could open new avenues for treating fear disorders by targeting vLGN circuits or localised endocannabinoid systems.”

The research team is now planning to collaborate with clinical researchers to study these brain circuits in humans, with the hope of someday developing new, targeted treatments for maladaptive fear responses and anxiety disorders.

This research was funded by the Sainsbury Wellcome Centre core grant from the Gatsby Charity Foundation and Wellcome (090843/F/09/Z); a Wellcome Investigator Award (219561/Z/19/Z); an EMBO postdoctoral fellowship (EMBO ALTF 327-2021) and a Wellcome Early Career Award (225708/Z/22/Z).

Scientists discovered that even brief exposure to high concentrations of PM may impair a person’s ability to focus on tasks, avoid distractions, and behave in a socially acceptable manner.

Researchers exposed study participants to either high levels of air pollution — using candle smoke — or clean air, testing cognitive abilities before and four hours after exposure. The tests measured working memory, selective attention, emotion recognition, psychomotor speed, and sustained attention.

Publishing their findings today (6 Feb) in Nature Communications, researchers from the Universities of Birmingham and Manchester reveal that selective attention and emotion recognition were negatively affected by air pollution — regardless of whether subjects breathed normally or only through their mouths.

The experts suggest that inflammation caused by pollution may be responsible for these deficits noting that while selective attention and emotion recognition were affected, working memory was not. This indicates that some brain functions are more resilient to short-term pollution exposure.

Co-author Dr Thomas Faherty, from the University of Birmingham, commented: “Our study provides compelling evidence that even short-term exposure to particulate matter can have immediate negative effects on brain functions essential for daily activities, such as doing the weekly supermarket shop.”

Co-author Professor Francis Pope, from the University of Birmingham, commented: “Poor air quality undermines intellectual development and worker productivity, with significant societal and economic implications in a high-tech world reliant on cognitive excellence.

“Reduced productivity impacts economic growth, further highlighting the urgent need for stricter air quality regulations and public health measures to combat the harmful effects of pollution on brain health, particularly in highly polluted urban areas.”

Cognitive functioning encompasses a diverse array of mental processes crucial for everyday tasks. Selective attention, for example, helps decision-making and goal-directed behaviour, such as prioritising items on your shopping list in the supermarket, while ignoring other products and resisting impulse buys.

Working memory serves as a temporary workspace for holding and manipulating information, vital for tasks requiring simultaneous processing and storage, essential for tasks that require multitasking, such as planning a schedule or juggling multiple conversations.

Socio-emotional cognition, which involves detecting and interpreting emotions in oneself and others, helps guide socially acceptable behaviour. Although these are separate cognitive skills, they work together to enable the successful completion of tasks both at work in other aspects of life.

Overall, the study highlights the need for further research to understand the pathways through which air pollution affects cognitive functions and to explore the long-term impacts, especially on vulnerable populations like children and older adults.

Co-author Professor Gordon McFiggans, from the University of Manchester, commented: “This study shows the importance of understanding the impacts of air pollution on cognitive function and the need to study the influences of different sources of pollution on brain health in vulnerable older members of society.”

The study is the first to experimentally manipulate inhalation routes of PM air pollution, providing valuable insights into how different pathways affect cognitive functions. Researchers emphasise the need for further investigation into long-term impacts and potential protective measures.

Globally, air pollution is the leading environmental risk factor to human health, increasing premature mortality. The detrimental impacts of poor air quality on cardiovascular and respiratory systems are widely acknowledged, with links to neurodegenerative conditions such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease.

PM_2.5 is the air pollutant most responsible for human health effects with some 4.2 million deaths attributed to this size of particle alone in 2015. The World Health Organization (WHO) recommends that 24-hour and annual limits are below 15 μg m^?3 and 5 μg m^?3 respectively.

The prevalence of mental health disorders has been rising over the years. According to the latest nationwide study, 1 in 7 people in Singapore has experienced a mental health disorder, which includes depressive and anxiety disorders[1]. In 2019, mental health disorders were one of the top four leading causes of disease burden in Singapore[2].

The research team thus set out to investigate the role microbes play in anxious behaviour. In pre-clinical studies, the scientists observed that in a germ-free environment, those which were not exposed to live microbes, showed significantly more anxiety-related behaviour than those with typical resident live microbes.

Further investigation revealed that the increased anxiety was associated with heightened activity in a brain region involved in processing emotions such as fear and anxiety, the basolateral amygdala (BLA). This was further identified to be related to specialised proteins within brain cells known as the calcium dependent SK2 channels, associated with anxiety behaviour. In conditions when the body and brain are exposed to live microbe metabolites, the SK2 channels act like a clutch, thus preventing neurons from becoming overly excited and firing too frequently.

Associate Professor Shawn Je from Duke-NUS’ Neuroscience and Behavioural Disorders Programme and one of the lead authors, explained:

“Our findings reveal the specific and intricate neural process that link microbes to mental health. Those without any live microbes showed higher levels of anxious behavior than those with live bacteria. Essentially, the lack of these microbes disrupted the way their brains functioned, particularly in areas that control fear and anxiety, leading to anxious behavior.”

To better understand the role of microbes in this process, the researchers introduced live microbes into germ-free mice[3]. This reduced the elevated neuronal activity in the basolateral amygdala and thus SK2 channel activity. As a result, the mice showed significantly less anxiety-related behavior — their emotional responses became like those exposed to microbes.

The researchers also tried treatment with indoles, microbial metabolites produced by certain microbes. When the germ-free mice were given indoles, they showed reduced activity in the basolateral amygdala and displayed less anxiety-related behaviour. This demonstrated that our indigenous microbes produce metabolites, which suggest a direct link between our microbiota and maintaining mental balance.

Professor Sven Pettersson from the Department of Research, National Neuroscience Institute of Singapore, who is also a lead author of the study, said:

“Establishing hunger signals and controlling hunger is an evolutionarily conserved defence mechanism. The physiological switch at birth, can therefore, be viewed as a first major wave of anxiety exposure for the newborn, which simply says, “If you don’t eat, you will die.” Additionally, birth is associated with exposure to breast milk, known to contain microbes that can produce molecules known as indoles. Indoles are known to be secreted in plants when they are exposed to stress or malnutrition (draught) and in this paper we report a similar mechanism in which indoles can regulate anxiety levels in mammals. That is, different levels of circulating microbial plasma indoles in the blood may reflect different sensitivity and vulnerability to stressful situations and therefore variable risk of experiencing anxiety-related situations.”

The implications of these observations are multiple: for example, it opens for the therapeutic potential of targeting the gut-brain axis to treat anxiety-related disorders by restoring the microbe composition through dietary supplementation with indoles or by introducing indole-producing gut microbes as probiotics. “In other words, it opens for tailor-made therapies in line with 21st-century precision medicine. Studies such as this illustrate the close hereditary relationship that exists between our indigenous microbes and the higher complexity of life,” concludes Pettersson.

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, said:

“Our findings underscore the deep evolutionary links between microbes, nutrition and brain function. This has huge potential for people suffering from stress-related conditions, such as sleep disorders or those unable to tolerate standard psychiatric medications. It’s a reminder that mental health is not just in the brain-it’s in the gut too.”

The team now hopes to explore clinical trials to determine whether indole-based probiotics or supplements can be effectively used in humans as a natural anxiety treatment. If successful, this could mark the beginning of a new era in mental health care — one where gut microbes help keep our minds at ease.

[1] Institute of Mental Health, Singapore Mental Health study

[2] Ministry of Health 28 October 2020 Global Burden of Disease 2019 Study Findings https://www.moh.gov.sg/news-highlights/details/global-burden- of-disease-2019-study-findings

[3] The study was conducted according to the National Advisory Committee for Laboratory Animal Research (NACLAR) guidelines.

Many malignant cancers overexpress a protein called P-cadherin, which is embedded in the cell membrane. Because cancer cells have a lot of P-cadherin sticking out of their surface, the protein has been targeted for drug development.

Monoclonal antibodies against P-cadherin can carry a drug payload to the cancer cells. It has not been clear, though, exactly how the antibodies attach to P-cadherin or how they get inside the cancer cell once attached.

Bin Xie and Shipeng Xu, graduate students in biophysics and biomedical engineering at the University of California, Davis, with Professor Sanjeevi Sivasankar, carried out a series of experiments to study binding of antibody CQY684 to P-cadherin in detail.

P-cadherin is embedded in the cell membrane as a dimer, or matched pair, with P-cadherin on the surface of an adjacent cell. This dimer can exist in two conformations: a more open, “strand-swap” dimer and a cross-shaped, X-dimer.

The researchers found that when the anti-cancer antibody binds to P-cadherin, it locks it into the X-dimer form. The stable X-form then triggers a chemical signal that causes that patch of membrane to be pinched off and sucked into the cell as a tiny bubble. The whole P-cadherin/antibody/drug complex is then sent to a structure called the lysosome to be broken down.

“Our results establish an outside-in signaling mechanism that provides fundamental insights into how cells regulate adhesion,” the authors wrote. Understanding the binding targets for antibodies against cadherin could help design drugs that exploit this pathway to find and destroy cancer cells.

Staying active is a key part of cancer survivorship care and research. Physical activity can help reduce the negative effects of cancer and its treatments, while also empowering survivors to live fulfilling lives. It offers many benefits, such as better heart and lung health, improved physical function, healthier body composition, reduced stress, and a higher quality of life. However, despite the widespread guidelines, many cancer survivors — between 53% and 83% — do not meet the recommended levels of physical activity.

The lead to the study, published in Healthcare, ran from September, 2023 to January, 2024 and included 23 participants: 18 cancer survivors and five family members or friends without a history of cancer. The cancer survivors, mostly women aged 47 to 76, had various types of cancer, including breast and hematological cancers. Many had undergone surgeries, chemotherapy and radiation therapy before joining the program. The participants without a history of cancer were all men, with a median age of 58 years.

The study found that the program was appealing and accessible. Recruitment was successful, with 95.5% of cancer survivors and 77.8% of participants without a history of cancer who expressed interest joining the program. Retention rates were also strong: 85.7% of cancer survivors completed the program, exceeding the target of 75%. Overall, 82.1% of participants stayed in the study until the end, with an adherence rate of 85.2% for attending the recommended sessions.

Participants in Project Rally reported significant increases in physical activity. Cancer survivors, on average, increased their weekly moderate-to-strenuous physical activity by over 80 minutes, including more strenuous exercise. The program also helped increase social support, with cancer survivors reporting more companionship involving their physical activity.

In addition to increased physical activity, participants also showed improvements in physical strength and endurance. Participants enjoyed the social aspects of the program, which included group activities and the opportunity to learn pickleball together. Many cited making new friends and increasing their physical activity as key benefits of participation. Participants also appreciated the support and encouragement provided by the YMCA coach.

“This study shows that pickleball is not only fun, but it can also be a powerful tool for improving the physical and emotional well-being of cancer survivors,” said Nathan Parker, Ph.D., a researcher in the Department of Health Outcomes and Behavior at Moffitt and lead author of the study. “The success of Project Rally highlights how community-based programs can provide a meaningful way for cancer survivors to stay active, build connections and improve their overall quality of life. The YMCA has been an outstanding research partner, and we’re excited about the potential to expand this program and help even more survivors.”

The pilot study’s positive results are just the beginning for Project Rally. The program’s design, which uses pickleball to promote fitness and social connection, has the potential to grow and serve more cancer survivors. The study’s findings show that such community-based programs can help cancer survivors increase physical activity and improve their overall health.

With plans to expand the program to more locations and offer additional sessions, Project Rally aims to reach a broader audience and help more cancer survivors improve their quality of life through physical activity.

This study was funded by a seed grant from the Moffitt Cancer Center Office of Community Outreach, Engagement, and Equity’s Support for Community Organization Research Engagement (COEE-SCORE) initiative.

Neurodegenerative diseases, including Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), result from the progressive decline of brain and nervous system functions, primarily due to aging. Chronic neuroinflammation, a key driver of these disorders, arises from the intricate interactions between cerebral blood vessels and neural cells, where the BBB plays a pivotal regulatory role. However, existing BBB models have been unable to replicate the complex three-dimensional 3D structure of cerebral blood vessels, posing significant challenges for research and drug development.

To address these limitations, the research team developed a cerebrovascular-specific bioink using “decellularized extracellular matrix” (CBVdECM), derived from porcine brain and blood vessels. Additionally, the team applied 3D bioprinting technology to construct a tubular vascular model that precisely replicates the anatomical structure and function of the human BBB.

A key feature of this model is the spontaneous formation of a dual-layered structure without external stimuli. When “HBMEC (human brain microvascular endothelial cells)” and “HBVP (human brain vascular pericytes)” were incorporated into the CBVdECM bioink and printed, the endothelial cells self-assembled into the inner vascular wall, while pericytes formed a surrounding layer. This resulted in the creation of a dual-layered structure that closely resembles the architecture of actual blood vessels.

Further, the research team successfully replicated the arrangement and organization process of “tight junction proteins,” a component typically absent in conventional 2D models. Additionally, BBB permeability and inflammatory responses were observed following exposure to inflammation-inducing substances (TNF-α and IL-1β). This approach enabled the precise modeling of neuroinflammatory mechanisms, yielding critical insights into the role of BBB dysfunction and inflammation in the pathophysiology of neurodegenerative diseases.

Professor Sun Ha Paek of Seoul National University Hospital commented, “This study provides a crucial platform for investigating the pathological mechanisms of neuroinflammation and developing novel therapeutic strategies.” Professor Jinah Jang of POSTECH added, “We aim to integrate additional cell types, such as glial cells, neurons, and immune cells, to refine methods for quantifying inflammatory responses and permeability, while also expanding to patient-specific disease models.”

This research was supported by Ministry of Trade, Industry & Energy and the Korea Planning & Evaluation Institute of Industrial Technology’s Industrial Technology Alchemist Project, as well as the National Research Foundation of Korea’s University-Focused Research Institute Support Program.

“In our analysis focusing on Los Angeles County, unexpected traffic delays beyond the usual congestion led to a 1% increase in fast food visits. That might not sound like a lot, but it’s equivalent to 1.2 million more fast food visits per year in LA County alone. We describe our results as being modest but meaningful in terms of potential for changing unhealthy food choices,” said study author Becca Taylor, assistant professor in the Department of Agricultural and Consumer Economics, part of the College of Agricultural, Consumer and Environmental Sciences at Illinois.

Taylor and her co-authors had access to daily highway traffic patterns over more than two years in Los Angeles, along with data showing how many cell phone users entered fast-food restaurants in the same time period. With these data, the team created a computational model showing a causal link between unexpected traffic slow-downs and fast food visits.

This pattern held at various time scales, including 24-hour cycles and by the hour throughout a given day. When analyzed by the day, traffic delays of just 30 seconds per mile were enough to spike fast-food visits by 1%.

“It might not be intuitive to imagine what a 30-second delay per mile feels like,” Taylor said. “I think of it as the difference between 10 a.m. traffic and 5 p.m. traffic.”

When the researchers broke the day into hour-long segments, they found a significantly greater number of fast food visits when traffic delays hit during the evening rush hour. At the same time, grocery store visits declined slightly.

“If there’s traffic between 5 and 7 p.m., which happens to be right around the evening meal time, we see an increase in fast food visits,” Taylor said. “Drivers have to make a decision about whether to go home and cook something, stop at the grocery store first, or just get fast food.”

Considering every major city has both traffic and fast food restaurants lining highway feeder roads, it’s not a stretch to extrapolate the pattern beyond Los Angeles. Taylor and her co-authors say the link between traffic and unhealthy food choices is just one more reason policymakers around the country and the globe should prioritize infrastructure reforms to ease congestion.

“Our results contribute to the literature suggesting time constraints are really important to the food choices people make. Any policies aimed at loosening time constraints — and traffic is essentially lost time — could help battle unhealthy eating,” Taylor said. “That could mean improvements in infrastructure to mitigate traffic congestion, expanding public transport availability, and potentially increasing work from home opportunities.”

Fatty liver, also called hepatic steatosis, is the most common liver disease worldwide, and occurs when excess fat builds up in liver cells. It can lead to inflammation, scarring (cirrhosis), and an increased risk of cancer and liver failure.

“We think of air pollution as being harmful to people’s lungs, but it has a broader impact on health including on the liver,” said lead author Professor Hui Chen from the University of Technology Sydney (UTS).

“The liver is critical for metabolism. It clears toxins, regulates blood sugar, and produces essential vitamins and proteins, among many other functions. If the liver isn’t functioning properly, it can leave people feeling tired and unwell due to disrupted metabolism,” said Professor Chen.

“When we inhale air pollution, the very tiny particles known as PM2.5 enter the bloodstream through the lungs. The liver, which filters toxins from the blood, then accumulates these substances, which can include heavy metals such as arsenic, lead, nickel and zinc.”

World-leading liver specialist Professor Jacob George, Director of the Storr Liver Centre at The Westmead Institute for Medical Research, studies the causes of liver diseases and cancer, and is a co-author on the study.

“Around one in three Australian adults has fatty liver disease, and it is more common in those who are overweight or have diabetes,” said Professor George.

“Lifestyle factors such as a bad diet, lack of exercise and excessive alcohol contribute to the development of fatty liver, however this research suggests that your environment, particularly exposure to traffic air pollution, may also be a contributing factor,” said Professor Chen.

The study, Prolonged exposure to low-dose traffic-derived PM2.5 causes fatty liver disorder in mice, was recently published in the Journal of Environmental Sciences.

The researchers exposed mice to a dose (10 micrograms daily of traffic-derived PM2.5 particles) that reflects typical human exposure in Sydney, collected from a major road in Sydney.

Signs of inflammation and fibrosis, or scarring, as well as changes to liver sugars and fats, were measured at four, eight and 12 weeks.

“The effect was cumulative. At four weeks we didn’t see much change, but by eight weeks there was disruption to the normal metabolic function of the liver and by 12 weeks we could see significant changes,” said first author Dr Min Feng, a medical doctor and PhD candidate in the UTS Faculty of Science.

Exposure to air pollution particles caused more immune cells to gather in the liver and it increased inflammation. It also led to more scar tissue forming.

The liver’s fat processing went up, and potentially harmful fats like triglycerides, diacylglycerols, and ceramides also increased. At the same time, the liver stored less sugar for energy.

The researchers discovered changes in 64 specific functional proteins in the liver, many linked to conditions like fatty liver disease, immune system dysfunction, and processes linked to cancer.

“Previous research has shown that exposure to heavily polluted air is associated with liver disorders, however this study reveals even low levels can cause harm. It suggests there is no safe level of exposure to traffic-derived air pollution,” said Professor Chen.

“To minimise exposure to traffic-derived air pollution, avoid peak hour traffic, take less congested routes when walking or cycling or consider wearing a mask, and keep car windows closed with air recirculation mode on while driving in heavy traffic,” she said.

Amniotic fluid is the vital fluid that surrounds and protects a fetus during pregnancy. In addition to providing much-needed cushion and protection for the fetus, it also aids in development of vital organs — especially the lungs, digestive tract and skin — and stabilizes the temperature inside the womb.

The new study, published in the journal Research and Practice in Thrombosis and Haemostasis, found that the addition of amniotic fluid to plasma — the liquid portion of blood — improves the blood’s ability to thicken and clot, which is a critical and likely a protective function throughout pregnancy and during delivery for both the birthing parent and the baby.

The mechanism of amniotic fluid’s role in fetal development is not well understood and is understudied: The OHSU study is one of the first to identify how the features and properties of amniotic fluid change over time, especially those properties that play a role in thickening the blood, and how those changes can affect how maternal blood coagulates. If a pregnant person’s blood does not clot properly, it can create life-threatening complications for the fetus and birthing parent, including excessive bleeding during pregnancy and delivery.

“We have always known that amniotic fluid is very important for fetal development and growth, but we don’t know much about it beyond that,” said the study’s corresponding author Jamie Lo, M.D., M.C.R., associate professor of obstetrics and gynecology (maternal-fetal medicine) in the OHSU School of Medicine, and Division of Reproductive & Developmental Sciences at the Oregon National Primate Research Center, or ONPRC. “We examined amniotic fluid across the pregnancy and found that indeed the composition and proteins in the amniotic fluid do change to match the growing needs of the developing baby.”

This discovery prompted Lo and her team to work with scientists in the Department of Biomedical Engineering at OHSU to take a deeper dive into the potential protective factors of amniotic fluid, and consider potential regenerative and therapeutic uses that could be developed down the road.

The research involved a multidisciplinary team including Lo, Chih Jen Yang, M.D., Lyndsey Shorey-Kendrick, Ph.D., Joseph Shatzel, M.D. M.C.R., Brian Scottoline, M.D., Ph.D., and Owen McCarty, Ph.D.

Researchers analyzed the properties of amniotic fluid obtained by amniocentesis, a prenatal test that involves sampling a small amount of amniotic fluid to examine the health of the pregnancy, from both human and non-human primates at gestational-age matched timepoints. The findings showed that amniotic fluid increases blood clotting through key fatty acids and proteins that change each trimester and help regulate coagulation.

With the untapped potential for amniotic fluid to aid in diagnosing and treating various prenatal conditions, researchers are now collaborating with Sanjay Malhotra, Ph.D., professor of cell, developmental and cancer biology in the OHSU School of Medicine, to target disorders of pregnancy — including disorders that affect the blood and blood-forming organs — that could benefit from the protective properties of proteins and other compounds within amniotic fluid.

The team is also working with OHSU’s Fetal Care Program to collect unique amniotic fluid samples, including pregnancies undergoing in-utero repair surgeries for neural tube defects, such as spina bifida. The hope is that through studying amniotic fluid from these pregnancies, it may be possible to determine if there are any unique developmental elements that may be targeted for future interventions to improve health outcomes.

Researchers are eager to learn more about the potential uses of amniotic fluid components and how they might be harnessed to improve prenatal and maternal health.

“Babies born prematurely miss out on critical weeks developing within amniotic fluid,” said the study’s co-senior author Brian Scottoline, M.D., Ph.D., professor of pediatrics (neonatology), OHSU School of Medicine. “But if we have a better understanding of amniotic fluid, how it develops and what properties are valuable for what functions, that opens up many new possibilities for creating new therapies.”

“Through our research, our team is learning that amniotic fluid may be a critical precursor to breast milk — almost like ‘pre-term’ milk for a fetus in utero. With that analogy, could we eventually develop a formula that’s fit for preterm babies that mimics amniotic fluid, aiding in growth and development and protecting babies from complications of being born prematurely?” Lo added. “This is really the tip of the iceberg for what’s possible.”

Nanoflowers are tiny, self-assembling structures. But their large surface area provides plenty of space to attach drug molecules, making the flowers particularly suitable for delivering medications. For their bandage blooms, Fatemeh Ahmadpoor, Pier Francesco Ferrari and colleagues chose copper(II) phosphate and tannic acid because of the antibiotic and anti-inflammatory properties of both reagents.

After growing their flowers in a saline solution, the researchers attached the bioinspired structures onto strips of electrospun nanofiber fabric. In tests, the nanoflower-coated bandages inactivated a broad spectrum of cultured bacteria (including E. coli, Pseudomonas aeruginosa and Staphylococcus aureus) and their antibiotic-resistant biofilms, scavenged reactive oxygen species, and didn’t damage lab-grown human cells.

Ahmadpoor and Ferrari say these nanoflower-coated bandages represent a breakthrough advancement by providing a natural, cost-effective and highly efficient solution for combating infections and accelerating wound healing, with the potential to redefine treatment standards.

The authors acknowledge funding from the Italian Ministry of University and Research.

Skateboarders develop the skill to tune into the noise of urban surfaces. They both hear and feel noise and this means images and videos alone are a poor insight into the sport. They use sound to verify the success of their manoeuvres, judge the veracity and capacity of surfaces for use and as a social cue. For some the sensory overload of skateboarding is therapeutic and it helps them connect with others skating nearby.

But the research also shows there is a “skatesound paradox” — skateboarders are aware of the negative impacts of the sound they make on some people nearby and alter their behaviour in some circumstances to counteract this.

Skateboarders who took part in the research described the sound of the sport as both unpleasant and lovely. For some it was a critical part of the experience, and a therapeutic sensory aid to those who identified as neurodiverse.

The findings demonstrate how the visually spectacular sport has a rich sensory world not accessible by just watching the sport. Skateboarders actually hear and feel what they are doing, and through skatesound can understand and appreciate what others are doing.

Dr Paul O’Connor, from the University of Exeter, interviewed 18 adult skateboarders aged between 19 and 51. Participants had an average of 12 years skateboarding experience. The most novice skateboarder aged 22 had only three years of experience, in contrast to a 44-year-old participant who has been skateboarding for 36 years. Seven of the participants were from the UK, three from the USA, three from France, two from Canada, and one from Sweden and Germany.

The research also identifies how skatesound was an inclusive experience for some who may feel marginalised or uninspired by more rigid and institutionalised sports. Three of the participants wore hearing aids, however only one used hearing aids while skateboarding. Four participants also reported some diagnosis that placed them on a sensory spectrum related to either autism or ADHD, or a combination of the two.

Dr O’Connor said: “Skateboarders spoke of their love for the sound of skateboarding yet also described it as noisy and abrasive. Many of the respondents described the challenging sound of skateboarding in evocative sensory terms, such as ‘clattering’ ‘the sound of drills and angle grinders’, ‘an irritant’, the sound of ‘beer bottle on beer bottle’, of ‘bone on concrete’, ‘rolling, rough, smooth tickling in my ear’, and ‘rough and in your face. Loud in the best way’.

“This meant they sometimes chose not to skate near homes, or noisy tunnels, or felt overwhelmed by the claustrophobic monotonous soundscape of skateparks.

“Skateboarders know that their sound is unpleasant. But they also recognise its importance. Next time you are frustrated by the noise of skateboarders practicing their skills in the local neighbourhood, remind yourself that they know they are noisy. You might also remind yourself that they are likely in the throes of deep sensory learning, a meditative calming of the modern malady of the wandering mind, and above all bonding with friends.”

One very accomplished skateboarder, Alfie said tuning into the rhythm and flow of skatesound had enabled him to become a more empathetic person. He spoke of how his sensory engagement with skateboarding had helped him deal with anxiety, find pleasure, and become more self-aware of his neurodiversity.

Roughly half of the participants were against skateboarding while listening to music through headphones while skateboarding because it was anti-social and because the sport is a communal activity. Gavin felt so strongly about this that he would approach people wearing headphones while skateboarding and ask them to remove their headphones and come join in the session with him and his friends, to engage socially. Eddy said he couldn’t imagine skateboarding with ear buds in because of the danger.

Dr O’Connor said: “Those who did chose to listen to headphones had manifold reasons for doing so. Some, like 22-year-old Andy, simply wanted music to accentuate his focus and stoke, while Fiona used headphones as a social barrier when she was the only female skateboarder on the session and wanted to enhance her confidence. In contrast Steph used headphones to battle the sensory overload of skatesound that was particularly prevalent in indoor skateparks.”

The research, carried out with colleagues Professor Brian Glenney and Dr Max Boutin, also used elements of the Boutin’s texturologies art installation. This interactive art allows people to experience the sensory world of skateboarding through video, sound, and haptic platforms. The experience highlights how the skateboard is not merely a toy or sports object but can also be an ear beneath the feet.

Published in Science Immunology, the study revealed that the endurance of these stem-like T cells is fuelled by a protein called ID3, expressed by a gene of the same name. These ID3+ T cells have a unique ability to self-renew and resist exhaustion, giving them the power to sustain immune responses far longer than other T cells that don’t express ID3.

The University of Melbourne’s Catarina Gago da Graça, PhD Candidate at the Doherty Institute, said the research highlights how ID3+ T cells hold the key to overcoming one of the biggest challenges in treating chronic diseases — immune exhaustion.

“ID3+ T cells have the remarkable ability to resist burnout and maintain a powerful immune response over time, making them particularly effective in the face of chronic infections or cancer,” said and co-first author Gago da Graça.

The research also found that certain signals in the body could increase the number of ID3+ T cells, paving the way for improved treatments like CAR T cell therapy. While CAR T therapy has been transformative in treating certain cancers, its effectiveness can wane over time due to T cell exhaustion.

Professor Ricky Johnstone, Executive Director Cancer Research at Peter Mac and co-lead author of the study, said enhancing ID3 activity could strengthen the endurance of these cells, making therapies more effective and long-lasting.

“We discovered that ID3+ T cell formation could be promoted by specific inflammatory cues, potentially offering new strategies to boost the number of immune cells that excel at fighting cancer in patients,” said Professor Johnstone.

“This could lead to better treatments for cancer patients and improve clinical immunotherapy outcomes.”

The University of Melbourne’s Dr Daniel Utzschneider, Laboratory Head at the Doherty Institute, said the findings could lead to advancements in immunotherapy treatments and the development of vaccines that provide long-lasting protection.

“Exhausted immune cells remain one of the biggest challenges in treating chronic diseases,” said Dr Utzschneider.

“This research provides a roadmap for how we might reinvigorate the immune system to improve health outcomes for people living with cancer or chronic infections like HIV or hepatitis B and C, thanks to these stem-like T cells, the immune system’s secret power.”

This research is the result of a collaborative effort between the Doherty Institute, Peter Mac, La Trobe University, Northwestern University (USA), the Olivia Newton-John Cancer Research Institute, the University of Birmingham (UK) and the University of Melbourne.

MIT chemists have now come up with a new way to determine those 3D genome structures, using generative artificial intelligence. Their technique can predict thousands of structures in just minutes, making it much speedier than existing experimental methods for analyzing the structures.

Using this technique, researchers could more easily study how the 3D organization of the genome affects individual cells’ gene expression patterns and functions.

“Our goal was to try to predict the three-dimensional genome structure from the underlying DNA sequence,” says Bin Zhang, an associate professor of chemistry and the senior author of the study. “Now that we can do that, which puts this technique on par with the cutting-edge experimental techniques, it can really open up a lot of interesting opportunities.”

MIT graduate students Greg Schuette and Zhuohan Lao are the lead authors of the paper, which appears today in Science Advances.

From sequence to structure

Inside the cell nucleus, DNA and proteins form a complex called chromatin, which has several levels of organization, allowing cells to cram 2 meters of DNA into a nucleus that is only one-hundredth of a millimeter in diameter. Long strands of DNA wind around proteins called histones, giving rise to a structure somewhat like beads on a string.

Chemical tags known as epigenetic modifications can be attached to DNA at specific locations, and these tags, which vary by cell type, affect the folding of the chromatin and the accessibility of nearby genes. These differences in chromatin conformation help determine which genes are expressed in different cell types, or at different times within a given cell.

Over the past 20 years, scientists have developed experimental techniques for determining chromatin structures. One widely used technique, known as Hi-C, works by linking together neighboring DNA strands in the cell’s nucleus. Researchers can then determine which segments are located near each other by shredding the DNA into many tiny pieces and sequencing it.

This method can be used on large populations of cells to calculate an average structure for a section of chromatin, or on single cells to determine structures within that specific cell. However, Hi-C and similar techniques are labor-intensive, and it can take about a week to generate data from one cell.

To overcome those limitations, Zhang and his students developed a model that takes advantage of recent advances in generative AI to create a fast, accurate way to predict chromatin structures in single cells. The AI model that they designed can quickly analyze DNA sequences and predict the chromatin structures that those sequences might produce in a cell.

“Deep learning is really good at pattern recognition,” Zhang says. “It allows us to analyze very long DNA segments, thousands of base pairs, and figure out what is the important information encoded in those DNA base pairs.”

ChromoGen, the model that the researchers created, has two components. The first component, a deep learning model taught to “read” the genome, analyzes the information encoded in the underlying DNA sequence and chromatin accessibility data, the latter of which is widely available and cell type-specific.

The second component is a generative AI model that predicts physically accurate chromatin conformations, having been trained on more than 11 million chromatin conformations. These data were generated from experiments using Dip-C (a variant of Hi-C) on 16 cells from a line of human B lymphocytes.

When integrated, the first component informs the generative model how the cell type-specific environment influences the formation of different chromatin structures, and this scheme effectively captures sequence-structure relationships. For each sequence, the researchers use their model to generate many possible structures. That’s because DNA is a very disordered molecule, so a single DNA sequence can give rise to many different possible conformations.

“A major complicating factor of predicting the structure of the genome is that there isn’t a single solution that we’re aiming for. There’s a distribution of structures, no matter what portion of the genome you’re looking at. Predicting that very complicated, high-dimensional statistical distribution is something that is incredibly challenging to do,” Schuette says.

Rapid analysis

Once trained, the model can generate predictions on a much faster timescale than Hi-C or other experimental techniques.

“Whereas you might spend six months running experiments to get a few dozen structures in a given cell type, you can generate a thousand structures in a particular region with our model in 20 minutes on just one GPU,” Schuette says.

After training their model, the researchers used it to generate structure predictions for more than 2,000 DNA sequences, then compared them to the experimentally determined structures for those sequences. They found that the structures generated by the model were the same or very similar to those seen in the experimental data.

“We typically look at hundreds or thousands of conformations for each sequence, and that gives you a reasonable representation of the diversity of the structures that a particular region can have,” Zhang says. “If you repeat your experiment multiple times, in different cells, you will very likely end up with a very different conformation. That’s what our model is trying to predict.”

The researchers also found that the model could make accurate predictions for data from cell types other than the one it was trained on. This suggests that the model could be useful for analyzing how chromatin structures differ between cell types, and how those differences affect their function. The model could also be used to explore different chromatin states that can exist within a single cell, and how those changes affect gene expression.

Another possible application would be to explore how mutations in a particular DNA sequence change the chromatin conformation, which could shed light on how such mutations may cause disease.

“There are a lot of interesting questions that I think we can address with this type of model,” Zhang says.

The researchers have made all of their data and the model available to others who wish to use it.

The research was funded by the National Institutes of Health.

In the most comprehensive systematic review and meta-analysis of its kind, University of South Australia researchers have taken a deep dive into the effects of cold-water immersion on health and wellbeing.

Analysing data from 11 studies with 3177 participants, researchers found that cold-water immersion may lower stress, improve sleep quality, and boost quality of life.

UniSA researcher Tara Cain says the study reveals time-dependant and nuanced effects on health and wellbeing measures.

“Cold-water immersion has been extensively researched and used in sporting contexts to help athletes recover, but despite its growing popularity among health and wellbeing circles, little is known about its effects on the general population,” Cain says.

“In this study, we noted a range of time-dependant results. Firstly, we found that cold-water immersion could reduce stress levels, but for only about 12 hours post exposure.

“We also noted that participants who took 20, 60, or 90 second cold showers reported slightly higher quality of life scores. But again, after three months these effects had faded.

“Benefits may be gained from cold showers as well, with one study reporting that participants who took regular cold showers experiencing a 29% reduction in sickness absence.

“We also found some links to cold-water immersion and better sleep outcomes, but the data was restricted to males, so its broader application is limited.

“And while there have been many claims that cold-water immersion experiences can boost your immunity and mood, we found very little evidence to support these claims.”

Cold-water immersion involves immersing the body partially or fully in cold water, in temperatures typically ranging from 10-15 degrees Celsius, and in this study, data was only included if exposure was at or above chest level, and for a minimum time of 30 seconds. It included cold showers, ice baths and cold plunges.

Co-researcher, UniSA’s Dr Ben Singh says the study also showed that cold-water immersion caused a temporary increase in inflammation.

“At first glance this seems contradictory, as we know that ice baths are regularly used by elite athletes to reduce inflammation and muscle soreness after exercise,” Dr Singh says.

“The immediate spike in inflammation is the body’s reaction to the cold as a stressor. It helps the body adapt and recover and is similar to how exercise causes muscle damage before making muscles stronger, which is why athletes use it despite the short-term increase.

“Knowing this, people with pre-existing health conditions should take extra care if participating in cold-water immersion experiences as the initial inflammation could have detrimental health impacts.”

Researchers say that while the findings highlight the potential benefits of cold-water immersion, they also underscore the highly time-dependent and contextual nature of its effects.

“Whether you are an elite athlete or everyday wellness seeker — it’s important to understand the effects of what you put your body through,” Cain says.

“Right now, there isn’t enough high-quality research to say exactly who benefits most or what the ideal approach is to cold-water immersion. More long-term studies, among more diverse populations, are needed to understand its lasting effects and practical applications.”

“A recent global health report revealed that oral diseases — such as untreated tooth decay and gum disease — affected 3.5 billion people in 2022, making them the most widespread health conditions,” said study lead author Souvik Sen, M.D., M. S., M.P.H, chair of the Department of Neurology, Prisma Health Richland Hospital and the University of South Carolina School of Medicine in Columbia, South Carolina. “We aimed to determine which oral hygiene behavior — dental flossing, brushing or regular dentist visits — has the greatest impact on stroke prevention.”

The Atherosclerosis Risk in Communities (ARIC) study, one of the first large-scale investigations of this kind in the U.S., assessed the home use of dental floss through a structured questionnaire of more than 6,000 people. Among those who reported flossing, 4,092 had not experienced a stroke, and 4,050 had not been diagnosed with an irregular heartbeat known as atrial fibrillation (AFib).

Participants were asked about their status regarding high blood pressure, diabetes, high cholesterol, smoking, body mass index, education, regular brushing and dentist visits. During the 25 years of follow-up, 434 participants were identified as having strokes, of which 147 were larger artery brain clots, 97 were heart-driven clots and 95 were hardening of the smaller arteries. Additionally, 1,291 participants were noted to have experienced AFib.

The analysis found:

• Flossing was associated with a 22% lower risk of ischemic stroke, 44% lower risk of cardioembolic stroke (blood clots traveling from the heart) and 12% lower risk of AFib.
• The associated lower risk was independent of regular brushing and routine dental visits or other oral hygiene behaviors.
• Increasing the frequency of flossing had a greater chance of stroke risk reduction.
• Flossing was also associated with a lower chance of cavities and periodontal disease.

Researchers were surprised by the reduction of irregular heartbeats, or AFib. AFib is the most common form of irregular heartbeat. It can lead to stroke, heart failure or other cardiovascular complications. More than 12 million people are projected to have AFib in the United States by 2030, according to the American Heart Association’s 2025 Heart Disease and Stroke Statistics.

“Oral health behaviors are linked to inflammation and artery hardening. Flossing may reduce stroke risk by lowering oral infections and inflammation and encouraging other healthy habits,” Sen said. “Many people have expressed that dental care is costly. Flossing is a healthy habit that is easy to adopt, affordable and accessible everywhere.”

Study limitations include that data were based on answers to a questionnaire, and the 25-year follow-up appears to have focused on stroke and heart outcomes only. There was no follow-up concerning flossing or other oral behaviors over the years, Sen said.

“This study offers more insights into the specific dental health behaviors that may be linked to stroke risks and potential risk reduction. With further research, dental health practices could possibly be incorporated into the “Life’s Essential 8″ risk factors, which include diet, physical activity, nicotine exposure, sleep, body mass index, blood pressure, blood glucose and blood lipids,” said Daniel T. Lackland, Dr.P.H., FAHA, American Heart Association EPI and Stroke Council member and professor of epidemiology and director of the Division of Translational Neurosciences and Population Studies in the department of neurology at the Medical University of South Carolina in Charleston. Lackland was not involved in this study.

Study background, and details:

• The study began in 1987 and is ongoing.
• Of the 6,258 participants, 82% were self-reported white adults and 18% Black adults. Their average age was 62 years and 55% were women.
• Potential participants were excluded if they had total tooth loss, dental implants, heart disease, organ transplant, artificial joints, implanted heart valve or stent or major surgery.

Cutaneous lupus erythematosus is a common manifestation of systemic lupus erythematosus.

The condition is characterized by rashes on various parts of the body including the face and scalp, hair loss and scarring of the skin.

The rashes are caused by inflammation from the immune system fighting the body.

The standard treatment for cutaneous lupus erythematosus is using immunosuppressants and biologic drugs to reduce inflammation.

While the medications can be helpful, many patients with systemic lupus erythematosus already take a high number of drugs and are looking for other treatment methods other than pills.

J. Michelle Kahlenberg, M.D., Ph.D., a professor of internal medicine in the Division of Rheumatology at University of Michigan Health led a team of researchers looking at one of these alternatives, a topical treatment called mupirocin.

This trial was based on Kahlenberg’s previous discovery that cutaneous lupus rashes are often colonized with a common skin bacteria, Staphyloccous areus, also known asstaph, and contributes to inflammation in the rashes.

Mupirocin kills this type of bacteria.

The study randomly selected systemic lupus erythematosus patients currently experiencing cutaneous lupus erythematosus flares to treat their skin lesions with mupirocin or with an inactive control, petrolatum jelly.

Samples from the nose and lesional skin were used to determine baseline and post treatment Staphylococcus abundance and microbial community profiles.

Paired samples collected prior to treatment with the topical solution and seven days after treatment showed decreases in lesional staphylococcus aureusin the mupirocin treated samples.

Importantly, the reduction in staph also was accompanied by a reduction in inflammatory signals, including interferon-driven gene expression, in the lesions.

“In addition to decreasing the inflammation by decreasing lesional staphylococcus aureus, the mupirocin treatment also lowered skin monocyte levels, which are important in driving cutaneous lupus,” said Kahlenberg.

Mupirocin is a prescription treatment, and while this early study showed signs of decreasing inflammation, the study wasn’t designed to see if it can decrease the rash of cutaneous lupus erythematosus.

“Additional larger studies are needed to determine whether topical antibiotics will be helpful to make rashes go away,” Kahlenberg said.

“However, this is an exciting first step to show that there may be additional treatments that can improve inflammation beyond our usual immunosuppressant and biologic drugs.”

A team of researchers led by Celia Romero, a graduate student in clinical psychology, along with associate professor Lynn Perry, professor Michael Alessandri, and former University professor Lucina Uddin, explored the role of bilingualism in 112 children, including typically developing children and children with autism, between the ages of 7 to 12 years old. Overall, they found that children who spoke two or more languages often had stronger executive functioning skills. This means they are able to control impulses and to switch between different tasks more easily than children who only spoke one language.

“We discovered that multilingualism is associated with improvements in executive function, which in turn is associated with improvements in autism symptoms,” Perry said. “There were hints of this in the literature before, but it was exciting to see how far reaching those differences were in this research.”

Published in the journal Autism Research, the results are significant because executive functioning skills are a key challenge for children on the spectrum but are important for all kids to thrive in school and later in the workplace. Yet, the team found the benefits of speaking more than one language were not limited to children with autism.

Key features of autism include social communication difficulties and restrictive and repetitive behaviors, as well as difficulty with executive function skills. These are mental processes that help us plan, focus, remember instructions, and manage multiple tasks effectively. While executive function skills develop and improve across the lifespan, individuals with autism often struggle with executive functioning, impacting their ability to manage daily tasks and adapt to new situations.

The study also looked at the impact of multilingualism on core symptoms of autism, including perspective taking, restricted and repetitive behaviors, and social communication.

“We also found that multilingual children have enhanced perspective taking skills, or the ability to understand someone else’s thoughts or point of view,” Romero added.

An idea called joint activation from the field of neuroscience can help explain the results. Prior research suggests that the bilingual brain has two languages constantly active and competing. As a result, the daily experience of shifting between these languages is associated with enhanced executive control. This concept is also known as the “bilingual advantage” and is a topic of much debate.

“If you have to juggle two languages, you have to suppress one in order to use the other. That’s the idea, that inhibition — or the ability to stop yourself from doing something — might be bolstered by knowing two languages,” said Uddin, now a professor at the University of California, Los Angeles, and director of the Brain Connectivity and Cognition Laboratory.

Romero realized she wanted to explore this topic while working in Uddin’s neuroscience lab on campus that was doing brain imaging research on children with autism. She noticed that some bilingual families did not speak to their child in their native language because they thought it may be too challenging and harmful for their child to learn more than one language.

“I started investigating this to let families know there’s no detriment for their child to learn another language, whether or not they have a neurodevelopmental disorder,” she said. “We know this through research, but often it takes time to translate that to families, so I hope this study helps address that.”

In his work as executive director of the University’s Center for Autism and Related Disabilities, Alessandri said this question often comes up with parents.

“It is wonderful to have sound research supporting our general recommendation to not restrict language exposures to children in multilingual homes,” Alessandri said. “This will surely bring a sense of relief to many of our families living with loved ones with autism.”

Romero and Perry are now doing further research with preschool children to see if bilingualism also has an impact on kids’ peer interactions, which are crucial for children’s social and cognitive development. And at UCLA, Uddin is currently conducting a large follow-up study to further investigate the impact of multilingualism on brain and cognitive development in children with autism.

But lately, incredibly complex AI models have begun outperforming their simpler counterparts. Consider AlphaFold for predicting protein structures, or ChatGPT and its competitors for generating humanlike text.

A new paper in PNAS argues that by relying too much on parsimony in modeling, scientists make mistakes and miss opportunities.

First author and SFI Complexity Postdoctoral Fellow Marina Dubova says overreliance on parsimony is historical.

“Scientists need a tool to guide how they build models of the world. Parsimony was historically adopted as an easy tool to use. Since then, it’s not been questioned enough. Educational programs teach parsimony as a key principle in scientific theory and model building. Most research tries to justify why parsimony is good, but those justifications haven’t stood the test of time,” she says.

Dubova recently ran a computational simulation showing that random experiments generated better models than did scientific experiments chosen based on previous assumptions.

Now Dubova, a cognitive scientist, is probing one of the biggest scientific assumptions of all: avoiding complex models.

“Relying on parsimony alone as our guiding principle limits what we can learn about the world and potentially drives us in wrong directions,” says Dubova. “Parsimony and complexity are complementary tools. Scientists need to use evidence, judgment, and context-specific demands to determine whether a more parsimonious or complex model suits their research goals.”

Dubova and co-authors discuss findings that suggest misapplied parsimony can make models biased and lead to bad predictions. For example, simple models for interpreting live brain scans often read periodic back-and-forth patterns when, in fact, brain activity is changing slowly over time. Leaving out key characteristics (like patient age) from a model evaluating untested new drugs could lead to poor predictions of who will and won’t respond well.

By contrast, complex models can be more flexible and accurate, as new approaches in climate change research have shown. Often in science, each lab develops its own model for making predictions about the phenomenon of interest, and the field eventually converges on the most parsimonious model that best fits the data. However, climate scientists have found that when they combine dozens of sometimes contradictory models from different labs into one ensemble, climate forecasts get better at predicting actual real-world phenomena.

“Even when these climate models are incompatible, scientists decide to employ them all because they know each one is capturing some aspect of the world. The literature suggests that using them together helps us better predict the reality around us,” she says. “Could this approach inspire completely new understandings of what climate is, without us as scientists trying to impose our preference for just one simple explanation?”

Dubova hopes that the paper will kickstart new research into when scientific modelers should choose parsimony or complexity.

“We could target individual cells and explore how this affected their ability to stay healthy and functional,” says Chiara Musumeci, researcher at the Laboratory of Organic Electronics, LOE, at Linköping University.

The brain is controlled by electrical signals that are converted into chemical substances in the communication between the brain cells. It has long been known that different parts of the brain can be stimulated with the help of electricity. But methods are often imprecise and affect large parts of the brain. Sometimes, metal electrodes are needed to hit the right part of the brain, which entails a risk that the hard electrode instead damages the brain tissue, causing inflammation or scarring.

A solution for treating specific parts of the brain could involve conductive plastics, also known as polymers.

“The goal is to combine biological systems with electrodes, specifically using organic conductive polymers. As polymers are soft and conformable and can transport both electricity and ions, they are preferable to conventional electrodes,” says Chiara Musumeci.

Together with researchers at Karolinska Institutet, the research team at Campus Norrköping has succeeded in anchoring the conductive plastic to individual living cell membranes. This opens up for future precise treatments of neurological diseases.

“At the moment, our results are rather general, which is a good thing, as our future research can explore what types of diseases this important tool would be suitable for. But more research is needed before we can say anything with any certainty,” says Alex Bersellini Farinotti, researcher at Karolinska Institutet.

Previous attempts to anchor organic electronics at the cell surface have been made, but with genetically modified cells that make the membranes more receptive. In their present study, the researchers have not used genetically modified cells and yet managed to achieve a tight coupling without affecting the cell’s other functions. This is the first time this has been done.

To succeed, the researchers used a two-step process where an anchor molecule is first used to create an attachment point in the cell membrane. At the other end of the molecule is a structure where the polymer electrode itself can attach.

The next step in the research is to get a more evenly distributed and stable anchoring over the membrane and to see how the polymer coupling behaves over time. Hanne Biesmans is a doctoral student at LOE and believes that there is great potential but also many challenges left to solve.

“We have taken a big step forward now. But we can’t say with any certainty that it will work in living tissue. This is basic research, where we are now trying to figure out the way forward.”

An emerging area of research is the evolutionarily conserved transfer of mitochondria between cells. Yet researchers have lacked unique and universally accepted terms and practices to describe such transfers. Absent an agreed nomenclature and standard practices, different researchers may use different methods and terminology to describe the same event, or they may employ the same term that actually describe two different processes.

“Over the past few years, we have come to understand that mitochondria can be transferred from one cell to another, and that isolated mitochondria can be transplanted like an organ transplant,” said Keshav K. Singh, Ph.D., professor in the University of Alabama at Birmingham Department of Genetics. “Though the origins of mitochondria transfer are unclear, it has been observed in evolutionarily diverse eukaryotes, including yeast, mollusks, fish and rodents, as well as human cells. We are just beginning to understand how alterations in this process contribute to disease pathogenesis and how to harness mitochondria transfer and transplantation biology to develop new therapies.”

In 2024, Singh and Jonathan Brestoff, M.D., Ph.D., Washington University School of Medicine, Saint Louis, Missouri, set up an international consortium on mitochondria transfer and transplantation and led an international team of 31 researchers to develop consensus and recommendations about how to advance the field by providing common terminology and characterizations for the transfer or transplantation of mitochondria. Their consensus paper, “Recommendations for mitochondria transfer and transplantation nomenclature and characterization,” is published in the journal Nature Metabolism.

The paper begins with a brief history of the field — some foundational early discoveries, recent studies of mitochondrial transfer and development of therapeutic approaches, including cell engineering and clinical trials for children requiring extracorporeal membrane oxygenation.

The paper defines types of mitochondria transfer and mitochondria transplantation, and when both the donor and acceptor cell types are established in vivo, that defines a mitochondria transfer axis. The paper reviews methods to define mitochondria transfer, including mitochondria reporter proteins and dyes, methods to enforce transfer, and discussion of the fate of mitochondria after cell entry. Mechanism-based nomenclature is roughly grouped into contact-dependent mitochondria transfer, where the donor cell and recipient cell touch each other, and contact-independent mitochondria transfer.

The recommendations also review therapeutic approaches of mitochondria transplantation, including the definition of transplants; the types, durability, degree of engraftment and heterogeneity of transplants; cell engineering using extracellular mitochondria; and drugs that affect mitochondria transfer. Extracellular mitochondria are common in humans — for example there are about 3 billion to 12 billion extracellular mitochondria in a unit of blood platelets, a blood product that is routinely and safely transfused to patients intravenously.

The paper concludes that “the goal of this proposed nomenclature is to reduce the confusion that can be caused by the introduction of different names for similar processes or extracellular mitochondria subsets as this field has evolved. We recognize that mitochondria transfer and transplantation are very active areas of research and that it is possible that new findings and insights may necessitate updates to the proposed nomenclature.”

Singh has a long-standing interest in mitochondria. He was founding editor-in-chief of the journal Mitochondrion and the founder of the Society for Mitochondria Research and Medicine. In 2007 and 2009, his laboratory showed that isolated mouse mitochondria can be transferred to human cells by co-incubation, providing a proof of principle for transfer of mitochondria by diffusion, and that xeno-transplanted platelet mitochondria from an African American woman who suffered aggressive breast cancer at young age was able to recapitulate aggressiveness of breast cancer in mice. At that time, these findings were not appreciated by the field, Singh says.

Research into ageing is producing an overwhelming amount of data, making it difficult to determine which interventions — such as new medicines, dietary changes, or exercise routines — are safe and effective. This study investigated how AI can analyse data more efficiently and accurately, by proposing a comprehensive set of standards for AI systems to ensure they deliver accurate, reliable, and understandable evaluations through their ability to analyse complex biological data.

The researchers identified eight critical requirements for effective AI-based evaluations:

1. Correctness of the evaluation results. Data quality will be assessed for accuracy.
2. Usefulness and comprehensiveness.
3. Interpretability and explainability of the evaluation results. Clarity and conciseness of the results and the given explanations.
4. Specific consideration of causal mechanisms affected by the intervention.
5. Consideration of data in a holistic context:
   1. Efficacy and toxicity, and evidence for the existence of a large therapeutic window;
   2. Analyses in an “interdisciplinary” setting.
6. Enabling reproducibility, standardisation, and harmonisation of the analyses (and of the reporting).
7. Specific emphasis on diverse longitudinal large-scale data.
8. Specific emphasis on results that relate to known mechanisms of ageing.

Telling LLMs about these requirements as part of the prompting improved the quality of the recommendations they produced.

Professor Brian Kennedy from the Department of Biochemistry & Physiology, and Healthy Longevity Translational Research Programme at NUS Medicine, who co-led the study, said, “We tested AI methods using real-world examples such as medicines and dietary supplements. We found that by following specific guidelines, AI can provide more accurate and detailed insights. For instance, when analysing rapamycin, a drug often studied for its potential to promote healthy ageing, the AI not only evaluated its efficacy but also provided context-specific explanations and caveats, such as possible side effects.”

“The study’s findings could have far-reaching effects,” added Professor Georg Fuellen, Director, Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, who co-led the study, “For healthcare, telling the AI about the critical requirements of a good response can enable it to find more effective treatments and make them safer to use. Generally, AI tools could design better clinical trials and help tailor health recommendations to each person. This research is a major step toward using AI to improve health outcomes for everyone, especially as they age.”

Moving forward, the team is now focusing on a large-scale study of how to best prompt AI models for longevity-related intervention advice, to evaluate their accuracy and reliability for a wide array of carefully designed benchmarks, that is, curated, high-quality data. The validation of such AI systems is specifically important because the longevity interventions may then be implemented by a large number of healthy people. Prospective studies will need to demonstrate that AI-based evaluations can accurately predict successful outcomes in human trials, paving the way for safer and more effective health interventions.

The team hopes to use their findings to make health and longevity interventions more precise and accessible, and ultimately improve the quality and duration of life. Collaboration between researchers, clinicians, and policymakers will be essential to establish robust regulatory frameworks, ensuring the safe and effective use of AI-driven evaluations.

“Nearly all premalignant cervical lesions and cervical cancers are caused by HPV infection, with HPV16 implicated in the majority of cases,” said Refika Yigit, MD, principal investigator and oncological gynecologist at University Medical Centre Groningen in the Netherlands.

In those with grade 3 cervical intraepithelial neoplasia (CIN3), cells are already on the path toward malignancy. If left untreated, approximately one-third of these cases progress to cervical cancer within 10 years and roughly half within 30 years, Yigit explained.

“The main purpose of our trial was to investigate whether our therapeutic vaccine — Vvax001 — could offer a potential alternative treatment to the standard-of-care loop excision, which is frequently associated with complications,” Yigit added.

The Vvax001 vaccine is a modified version of the Semliki Forest virus that cannot replicate and produces the oncogenic E6 and E7 proteins that are expressed exclusively by HPV16-infected cells.

In the phase II trial, 18 patients with HPV16-positive CIN3 received three doses of Vvax001 three weeks apart, and then were routinely monitored via colposcopy before a final colposcopy-guided biopsy at 19 weeks post-immunization.

Nine of the 18 patients experienced regression — six to low-grade dysplasia and three with complete regressions and no signs of dysplasia. Lesion size was significantly reduced in all but one of the patients, and these reductions were evident within a month of finishing vaccination. The nine patients whose disease did not regress received loop excision surgery, though no residual disease was found in four of these patients, suggesting the additional time to surgery might have allowed for full lesion eradication, according to the authors.

“To the best of our knowledge, this response rate makes Vvax001 one of the most effective therapeutic vaccines for HPV16-associated CIN3 lesions reported to date,” said Yigit. “If confirmed in a larger trial, our results could mean that at least half of the patients with CIN3 might be able to omit surgery and avoid all its possible side effects and complications.”

In the standard-of-care setting, HPV clearance is linked to lower risk of recurrence, and Yigit said her team expects the same here. Ten of the 16 patients evaluated cleared HPV16, including all nine of those whose disease regressed. Two patients whose disease did not regress also cleared HPV16; however, their lesions harbored other HPV strains.

After a median follow-up of 20 months, none of the patients had recurrences.

Limitations of the study include limited follow-up time, small sample size, and lack of a control group for spontaneous regression due to ethical concerns.

This study was supported by the Dutch Cancer Society (KWF) and ViciniVax. 

Sepsis is one of the most frequent causes of death worldwide, according to the World Health Organization (WHO), killing 11 million people each year. It’s characterized by runaway inflammation, usually sparked by an infection. It can lead to shock, multiple organ failure, and death if treatment is not rapid enough or effective.

But recent research has shown that it isn’t actually the infection that causes the spiraling inflammation: it’s the cells caught up in it. Even if those cells aren’t infected, they act as if they are, and die. As they die, they send out messages to other cells. Those messages somehow cause the recipient cells to die. If scientists understood what caused this deadly message chain, they might be able to stop it. And that could help heal sepsis.

The deadly message mystery may now be solved. It appears that the “messages” are a byproduct of the cells trying to stay alive, UConn School of Medicine researchers report in Cell.

The process starts with cells that really are infected. To prevent the infection from spreading, those cells destroy themselves by sending a protein called gasdermin-D to their surface. Several gasdermin-D proteins will link together to create a round pore on the cell, like a hole punched in a balloon. The cell’s contents leak out, the cell collapses, and dies.

But the collapse isn’t inevitable. Sometimes cells can act quickly and eject the section of their surface membrane with the gasdermin-D pore. The cell then zips the membrane closed and survives. The ejected membrane forms a little bubble, called a vesicle, that just happens to carry the deadly gasdermin-D pore. The vesicle floats around, and when it encounters a cell nearby, that deadly gasdermin-D pore punches into the healthy nearby cell’s membrane and causes that cell to spill and die.

“When a dying cell releases these vesicles, they can transplant these pores to a neighboring cell’s surface, which leads to the neighboring cell’s death,” says Vijay Rathinam, an immunologist in the UConn School of Medicine. In other words, the deadly messages are a side effect of cells just trying to save themselves. A group of dying cells can release enough gasdermin-D vesicles to kill a considerable number of nearby cells. That spreading message of death fuels the spiraling inflammation of sepsis.

Rathinam and his colleagues are now looking for a way to damp down the deadly gasdermin-D vesicles. If successful, it could lead to a treatment for inflammatory diseases like sepsis.

This study led by Skylar Wright, an MD/PhD student in the Rathinam lab, was done in collaboration with the laboratories of Drs. Jianbin Ruan, Beiyan Zhou, Sivapriya Kailasan Vanaja of UConn Health and Dr. Katia Cosentino of University of Osnabrück, Germany. This project was funded by grants from the National Institutes of Health to Dr. Rathinam.

AML, which affects four out of 100,000 patients in the U.S. every year, according to the National Cancer Institute, is a type of cancer that first attacks the bone marrow before moving to infect the blood. The current treatment plan includes targeted chemotherapy followed by a stem cell transplant. Unfortunately, up to 40% of these patients relapse after transplant and have a median survival of six months. At that stage, the only hope for remission is through immunotherapy.

Led by Elham Azizi, associate professor of biomedical engineering at Columbia Engineering, the research explores how coordinated immune networks in leukemia bone marrow microenvironments influence responses to cellular therapy, raising the question: why do some patients benefit from immunotherapy while others do not? The current treatment for relapsed AML, donor lymphocyte infusion (DLI) — a therapy involving donor immune cells — has a 5-year survival rate of only 24%, according to research conducted by Pfizer.

This new study finds that a unique population of T cells found in patients who are responding to DLI might be the key. These cells fight leukemia by boosting the immune response. Additionally, the study shows that patients with a healthier, more active and diverse immune environment in the bone marrow are better able to support these cells and their cancer-fighting abilities.

Utilizing the team’s proprietary computational DIISCO approach, the researchers discovered key interactions between the unique T cell population and other immune cells may lead to patient remission. They also traced these T cells back to the donor product. However, it was discovered that the donor’s immune cell composition has little to no effect on the patient’s success. In fact, the success of this treatment is determined by the patient’s immune environment. DIISCO is a machine learning method used to analyze how cell interactions change over time with a focus on cancer and immune cells profiled in clinical specimens.

The study’s findings can lead to new intervention options such as improving the immune environment before starting the standard DLI treatment and exploring combinations of immunotherapies. This will help patients who don’t typically respond well to find a personalized option that works for them.

“This research exemplifies the power of combining computational and experimental methods through close collaboration to answer complex biological questions and uncover unexpected insights,” said Azizi, who is a member of the Irving Institute for Cancer Dynamics, the Herbert Irving Comprehensive Cancer Center, and Columbia’s Data Science Institute. “Our findings not only shed light on mechanisms underlying successful immunotherapy response in leukemia, but also provide a roadmap for developing effective treatments guided by innovative machine learning tools.”

“Seeing our findings validated through functional experiments is incredibly exciting and offers real hope for improving cancer immunotherapy,” said Cameron Park, a PhD student in the Azizi lab, who co-led this study with Katie Maurer at the Catherine Wu Lab at Dana Farber-Cancer Institute. Park was also a co-developer of the DIISCO algorithm.

In this particular research’s future, the team plans to explore interventions that enhance the effectiveness of DLI while focusing on modulating the tumor microenvironment. Although exciting, much more work has to be done before the team can head to clinical trials with the hope to improve outcomes for patients with relapsed AML.

The findings, presented today at the American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Annual Symposium and published in Nature Medicine, demonstrated a 60.9% overall response rate (ORR) with the three-drug combination compared to 40% with the standard-of-care (SOC) treatment — chemotherapy with or without bevacizumab. In the experimental arm, 68.7% of patients had a duration of response of at least six months, compared to 34.1% of patients in the SOC arm.

Data from this multi-institutional collaboration across 28 countries supported the accelerated approval of this combination by the Food and Drug Administration (FDA) in Dec. 2024, providing an effective new first-line treatment option for patients with BRAF V600E-mutant mCRC.

“Chemotherapy has had limited efficacy as a first-line treatment in controlling the aggressive tumor growth we see in patients with this mutation,” said co-principal investigator Scott Kopetz, M.D., Ph.D., professor of Gastrointestinal Medical Oncology and associate vice president of Translational Integration at MD Anderson. “This new regimen highlights the importance of combining dual-targeted therapy with chemotherapy to improve patient outcomes in the first-line setting, and the durable responses are a significant development as we work to improve quality of life for these patients.”

More than 150,000 people are diagnosed with colorectal cancer each year, making it the fourth most common cancer in the U.S., according to the National Cancer Institute. BRAF mutations occur in approximately 8-12% of cases and are associated with aggressive tumor growth, low efficacy from SOC treatments and a poor prognosis, with a median overall survival less than 12 months. Previously, there were no first-line targeted therapies approved for patients with BRAF V600E-mutant mCRC.

The BREAKWATER trial was one of the first studies to utilize the FDA’s Project FrontRunner, an initiative to encourage the evaluation of therapies in earlier clinical settings for advanced cancers rather than after patients received numerous previous treatments.

The trial enrolled patients who were at least 16 years of age with previously untreated BRAF V600E-mutant mCRC. Patients were randomized equally to one of three treatment arms: SOC chemotherapy with or without bevacizumab; a dual combination of encorafenib plus cetuximab; or a triple combination of encorafenib, cetuximab and mFOLFOX6.

When researchers analyzed patient subgroups on the trial, the triple combination showed benefits across important groups, including patients with cancer spread to three or more organs and those with liver metastases.

“These results support this combination as a new first-line standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer,” Kopetz said. “It also highlights the importance of swiftly identifying molecular subtypes of colorectal cancer at diagnosis to optimize treatment strategies for our patients.”

The safety profile of this combination was consistent with the known safety profile of each respective drug. No new safety signals were identified. The most common adverse reactions included nausea, rash, fatigue, vomiting, abdominal pain, diarrhea and decreased appetite, all of which were reported in at least 25% of patients and were similar between arms.

Final calculations of progression-free survival and overall survival will be formally assessed in the next phase of the trial. Future analyses of this trial may shed light on predictive biomarkers for this combination therapy.

The study was sponsored by Pfizer Inc., and Kopetz disclosed consulting for Pfizer and receiving research funding from the company.

Visual information has long been proven to affect balance—for example, strobe lights and swirling images can cause instability—but a new study published in PLOS ONE shows that sounds can also be a disruptive factor for those who have vestibular hypofunction, a vestibular system disorder resulting in impaired balance.

“People with vestibular hypofunction have difficulty in places like busy streets or train stations where the overwhelming visual information may cause them to lose balance or be anxious or dizzy,” says lead author Anat Lubetzky, associate professor of physical therapy at NYU Steinhardt School of Culture, Education, and Human Development. “Sounds are not typically considered during physical therapy, making our findings particularly relevant for future interventions.”

The researchers conducted an experiment with 69 participants divided into two groups: healthy controls and individuals with unilateral vestibular hypofunction (affecting one ear).

Participants wore a virtual reality headset that simulated the experience of being in a New York City subway. As they experienced the sights and sounds of the “subway,” they stood on a platform that measured their body movement (known as sway), while the headset recorded their head movement, two indicators of balance. Participants were provided with different subway scenarios: static or moving visuals paired with silence, white noise, or recorded subway sounds.

The results revealed that for the group with vestibular hypofunction, the moving visuals accompanied by audio (either white noise or subway sounds) resulted in the greatest amount of sway. This sway was evident by the body’s forward and backward movements, as well as head movements left to right, and head tilts upward and downward. Audio conditions did not affect the balance of the healthy individuals.

“What we’ve learned is that sound should be included as part of both the assessment of balance and intervention programs,” says Lubetzky.  “Because balance training is known to be task-specific, ideally, these should be real sounds related to patients’ typical environments and combined with salient and increasingly challenging visual cues. Portable virtual headsets are a promising tool for both assessing and treating balance problems.”

Funding for this study was provided by a grant from the National Institute on Deafness and Other Communication Disorders (R21DC018101), resources from the Icahn School of Medicine at Mount Sinai, and a grant from the National Center for Advancing Translational Science (UL1TR004419).

Drug delivery systems often face two critical challenges: poor solubility and inefficient delivery within the body. Many drugs do not dissolve well, making it difficult for them to reach their intended targets. Furthermore, current delivery systems waste a significant portion of the drug during preparation — only 5-10% of the drug is successfully loaded, leading to less effective treatments.

Peptide Helpers

The research team has developed a novel solution by designing peptides — short strings of amino acids — to bind with specific drugs and create therapeutic nanoparticles. These nanoparticles are primarily composed of the drug, with a thin peptide coating that improves solubility, enhances stability in the body, and optimizes delivery to targeted areas. Remarkably, this approach achieves drug loadings of up to 98%, a dramatic improvement over traditional methods.

By using a combination of computer models and laboratory tests, new drug/peptide nanoparticles where identified. They subsequently demonstrated remarkable results in leukemia models. The nanoparticles were more effective at shrinking tumors compared to the drugs alone. Additionally, their high efficiency allows for lower doses of drugs, potentially reducing the side effects.

“Peptides, which are designed molecules made from the same building blocks as the proteins in our body, are extremely versatile,” said Co-Principal Investigator Rein Ulijn, director of the Nanoscience Initiative at CUNY ASRC and a chemistry professor at Hunter College. “We thought they could be useful in solving two big problems seen in many drugs: poor solubility and inefficient delivery. By designing a peptide that binds the drug while enhancing its solubility, we were able to create nanoparticles with very high loading.”

Customizable Technology

This innovation holds significant potential because peptides can be customized to enhance the effectiveness of various drugs. Given the vast range of possible interactions in peptide design, it may be feasible to tailor peptides for specific drugs, extending their applicability beyond cancer treatments.

“This breakthrough enables the development of better precision medicines,” said Co-Principal Investigator Daniel Heller,head of the Cancer Nanomedicine Laboratory at Memorial Sloan Kettering Cancer Center’s Molecular Pharmacology Program. “Using specially designed peptides, we can build nanomedicines that make existing drugs more effective and less toxic and even enable the development of drugs that might not be able to work without these nanoparticles.”

Naxhije “Gia” Berisha, a former CUNY Graduate Center Ph.D. student who performed much of the experimental work, highlighted the potential of the peptide approach: “We used experimental testing to identify promising peptides and computational modeling to analyze their interactions with therapeutic molecules,” she said “It’s incredible to see how simple variations in peptide sequence could match specific drugs. This suggests there may be a peptide match for every drug, potentially revolutionizing the way medicines are delivered.”

Looking Ahead

The research team is now adopting lab automation methods to further refine and accelerate the peptide-drug matching process. Their next steps include verifying the approach’s potential in a wider range of diseases. If successful, this innovation could lead to more effective treatments, reduced side effects, and significant cost savings in drug development.

A study, published in Aging Cell, a journal focused on the biology of aging, indicates that therapies targeting this insulin action may be developed to offset or even prevent dementia progression.

“We believe this work is important because it suggests exercise may work to improve cognition and memory by improving the abilities of insulin to act on the brain,” said Steven Malin, an associate professor in the Department of Kinesiology and Health in the Rutgers School of Arts and Sciences and lead author of the study.

Conducted in collaboration with the National Institutes of Health’s National Institute on Aging, the researchers focused on the role of neuronal extracellular vesicles, specialized cells released by the brain.

Extracellular vesicles, once dismissed by researchers as “cell dust,” have in the past 15 years grown exponentially in recognition as important players in the microscopic world of the human body, facilitating transport of key molecules such as proteins between cells. For this study, the scientists targeted vesicles produced in the brain that ferry several proteins involved in insulin sensitivity — one of which is called Akt.

Insulin sensitivity is a measure of how well the body responds to insulin, a hormone that controls blood sugar levels. People with high insulin sensitivity can use blood glucose more effectively in the body, such as in its muscles, which reduces blood sugar. People with diabetes, with its key symptom of low insulin sensitivity or insulin resistance, have brain cells that are less responsive to insulin. This can have negative impacts on cognition.

Researchers were able to study the vesicles by isolating them in the blood of participants in an experimental study. The trial, conducted over two weeks, included a group of 21 volunteers who had an average age of 60 and had prediabetes. Over the course of the study, they engaged in 12 individual, supervised, 60-minute exercise sessions of moderate to high intensity. The participants ingested a glucose drink before and after training. Researchers then collected blood samples before and during the drink from the participants at the start and end of exercise training.

The blood samples showed that the number of neuronal vesicles carrying proteins involved in insulin sensitivity increased after each training, with Akt being most notable.

“We showed for the first time that exercise impacts insulin signaling from neuronal extracellular vesicles in relation to clinical improvements in blood sugar,” Malin said. “And we use these neuronal extracellular vesicles as an indicator of brain insulin sensitivity.”

Exercise, therefore, is potentially able to improve the brain’s capacity to respond to insulin for neuronal function, he said.

Insulin is a hormone increasingly recognized to regulate cognition, the mental process of acquiring knowledge through thought, experience and the senses. Prediabetes is a serious health condition that occurs when blood sugar levels are higher than normal but not high enough to be diagnosed as Type 2 diabetes. Those with prediabetes run the risk of having insufficient levels of insulin in their bodies, particularly the brain, which increases the chances of developing diseases of dementia such as Alzheimer’s, Malin said.

Insulin also plays a crucial role in memory formation, recall, processing speed and the functioning of synapses, structures that allow brain cells to communicate with one another.

“If insulin is insufficient in the brain, that means not only will brain cells become potentially dysfunctional, but also they may fail to interact with each other properly,” Malin said. “It’s like playing the game telephone with a friend. At some point the message gets lost when the brain becomes insulin resistant.”

Exercise has long been believed to improve cognition, but the mechanisms involved have been unclear. Past studies have uncovered evidence that high blood sugar contributes to a decrease in the brain’s ability to recall information and learn new information.

Malin said that insulin, which is produced by the pancreas and travels to the brain to perform its functions, plays a central role in promoting brain blood flow and neuronal functioning for cognition.

“Our work suggests that therapies that target brain insulin action may be able to ward off dementia,” Malin said.

In a new study, Malin and his colleagues are examining whether a single bout of exercise can enhance the ability of intranasal insulin to support cognitive health in aging adults with obesity by measuring brain blood flow and neuronal extracellular vesicles. Their future plans are to conduct a long-term exercise training study that assesses brain insulin sensitivity improvements in relation to cognition in older adults.

Other Rutgers scientists on the study included Michal Beeri, director of the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center at Rutgers Robert Wood Johnson Medical School; and Daniel Battillo, a doctoral candidate in the kinesiology and applied physiology graduate program. Scientists from the National Institute of Health’s National Institute on Aging involved in the study included Dimitrios Kapogiannis, Maja Mustapic and Francheska Delgado-Peraza.

In recent years, immunotherapies have had significant success in the treatment and cure of a wide range of cancers. However, for some patients, these agents are still not sufficiently effective. As part of a preclinical study, Maria Sibilia, Head of the Center for Cancer Research at the Medical University of Vienna, therefore investigated the effects of a combination immunotherapy consisting of systemic administration of the tissue hormone interferon (IFN)-I and local imiquimod therapy. Imiquimod is an active substance that activates the innate receptors TLR7/8 and used to treat basal cell carcinomas. The researchers employed various preclinical mouse tumor models of melanoma and breast cancer. What both tumors have in common is that they are accessible to local therapy and often form distant metastases.

Effective for local tumors and distant metastases

Immunotherapies use the body’s own immune system to fight cancer cells. Plasmacytoid dendritic cells (pDCs), which are activated by Imiquimod via TLR7/8, play an important role in this process. The study showed that oral imiquimod stimulates pDCs to produce the tissue hormone IFN-I. This sensitized other dendritic cells and macrophages in the tumor environment to topical imiquimod therapy, which inhibited the formation of new blood vessels via the cytokine IL12 leading to the death of tumor cells. The combination immunotherapy not only had an effect on the treated tumors, but also on distant metastases. It reduced the formation of new metastases thus preventing tumor relapses and increasing the sensitivity of melanomas to checkpoint inhibitors.

“These findings illustrate that the combination of systemic treatment with imiquimod or IFN-I and topical therapy with imiquimod has the potential to expand treatment options for patients and improve therapy outcomes in locally accessible tumors such as melanoma or breast cancer,” emphasizes Maria Sibilia. “Topical treatment of the primary tumor with imiquimod is essential for this combination therapy with systemic IFN-I to be effective at the treated site and also to clear distant metastases,” adds Philipp Novoszel, MedUni Vienna, one of the first authors of the study.

The results suggest that this therapeutic strategy has the potential to improve treatment outcomes in superficial and thus locally accessible tumors such as melanoma and breast cancer — on the one hand through therapy-associated cancer cell death at the locally treated tumors, but also through the induction of a T cell-induced anti-tumor immune response at distant metastases, which is further enhanced by checkpoint inhibitors.

“Our aim is to continue developing immunotherapeutic strategies in order to improve the long-term prospects for patients who are not yet responding well to these agents,” says Maria Sibilia, who is also Deputy Head of the Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna.

“As systemic interferon is a well-known cancer therapy and dendritic cells are activated in a similar way to our preclinical models, we believe that the new combination therapy can show an effect in patients,” adds Martina Sanlorenzo, dermato-oncologist at MedUni Vienna and co-first author of the study.

The researchers found that the inflammation severity shown by CD45-PET correlates with both microscopic tissue analysis and clinical symptoms. They also developed a human CD45-PET probe and demonstrated its ability to detect human immune cells in a humanized mouse model. Furthermore, in animal models of graft-versus-host disease — a serious condition following bone marrow transplants — the human CD45-PET probe showed potential for early detection and precise localization of the disease, which can manifest in various body parts. The team is now working toward initiating clinical trials to validate their human CD45-PET probe.

Inflammation is a sign that the immune system is actively defending the body against disease. However, prolonged and excessive inflammation can become pathological and is a key factor in many chronic diseases, such as cardiovascular diseases, cancer, and diabetes, which collectively contribute to a significant portion of global mortality. Currently, there are no non-invasive tools to reliably detect and pinpoint inflamed areas within the body. The developed CD45-PET probe is the first to identify inflammation generally and with high sensitivity through whole-body imaging. Once validated in humans, this tool could have immediate clinical applications, guiding the selection of anti-inflammatory treatments, monitoring responses to anti-inflammatory medications and cancer immunotherapies, and aiding in the diagnosis of conditions with known inflammatory underpinnings.

Dana-Farber Cancer Institute, Parker Institute for Cancer Immunotherapy, Harvard Medical School, the National Institutes of Health, National Institute of Allergy and Infectious Disease, Brigham and Women’s Hospital Heart and Vascular Center.

“This is a surface where pathogens can sneak in,” says La Jolla Institute for Immunology (LJI) Assistant Professor Miguel Reina-Campos, Ph.D. “That’s a massive challenge for the immune system.”

So how do immune cells keep the gut safe? New research led by scientists at LJI, UC San Diego, and the Allen Institute for Immunology shows that pathogen-fighting immune cells called tissue-resident memory CD8 T cells (T_RM cells) go through a surprising transformation — and relocation — as they fight infections in the small intestine.

In fact, these cells literally rise up higher in the tissue to fight infections before pathogens can spread to deeper, more vulnerable areas.

“The tissue in the gut has evolved to provide signals to immune cell infiltrates — to put immune cells in specific places so they have a better ability to stop pathogens,” says Reina-Campos, who served as first author of the new Nature study alongside co-first author Alexander Monell of UC San Diego and co-senior authors Maximilian Heeg, M.D., and Ananda W. Goldrath, Ph.D., of the Allen Institute for Immunology and UC San Diego.

The new findings add to the growing body of evidence that immune cells adapt to protect specific tissues. Reina-Campos thinks these “tissue-resident” immune cells may be key players in future cancer immunotherapies that target tumors in specific organs.

T cells on the move

Reina-Campos and his colleagues investigated the formation of T_RM cells in the small intestine. The team harnessed a cutting-edge technology called spatial transcriptomics to track these cells in both human and mouse tissue samples.

Their work showed that the small intestine holds two types of T_RM cells. These cells are split between the tiny, finger-like “villi” structures that line the small intestine or the “crypts” between the protruding villi.

The researchers found that progenitor-like T_RM cells live closer to the crypts between the villi. On the other hand, differentiated T_RM occupy more exposed regions at the top of the villi. “Differentiated immune cells are more exposed at the top of the villi, and that’s where they have a better ability to protect you from infections,” says Reina-Campos.

Meanwhile, a reserve population of progenitor-like T_RM cells continues to lie low in the crypts. “These cells can replenish the pool of effector T cells, so the immune system keeps them as back-ups in the deeper parts of the tissue,” adds Reina-Campos.

What keeps these populations organized and in check?

To spy on these important immune cells within their natural habitat, Reina-Campos and colleagues used a new technology — called spatial transcriptomics — to observe millions of messenger RNA molecules simultaneously at subcellular resolution.

“For the first time, we were able to capture the formation of immunological memory in space and time,” says Reina-Campos.

Looking at small intestines after a viral infection, the scientists found that the gut releases chemical signals to instruct immune cells where to go and what to do. “This study offers a new resource for finding signals that position immune residents to strengthen our gut immunity,” says Reina-Campos.

Checkmate for disease?

Reina-Campos credits his mentor, Goldrath, as well as Heeg’s and Monell’s expertise for making this study possible. As Reina-Campos explains, Heeg and Monell developed new computational approaches to make sense of the massive amounts of data captured through spatial transcriptomics.

“It’s led to a breakthrough in our ability to look at hundreds to thousands of genes simultaneously in intact tissues,” says Reina-Campos. “With this study, we’ve opened up a new path for discovery.”

Reina-Campos compares the battle between immune cells and pathogens to a chess match.

“To be a chess grandmaster, you need to know not only about the pieces: the bishops, pawns, rooks, etc, but also how they move in concert on the chessboard,” he says.

For a long time, scientists have studied the chess pieces — by analyzing cells extracted from tissue — but they haven’t gotten a good look at the chess match itself. “We don’t know as much about how the chessboard works — and we know even less about the rules that apply to our chess pieces as they move across the board,” says Reina-Campos.

The new study gives researchers a detailed look at how immune cells interact with each other and their cellular gameboard.

Reina-Campos says the new finding should guide future research into how immune cells develop and move through other organs with different tissue structures, such as the kidneys and lungs — and how immune cells might fight tumors in these organs.

Researchers have identified a key pathway that links how neurons send signals to each other, or synaptic activity, to the expression of genes necessary for long-term changes in the brain, providing crucial insights into the molecular processes underlying memory formation.

“These findings illuminate a critical mechanism that connects local synaptic activity to the broader gene expression changes necessary for learning and memory,” said Mark Dell’Acqua, professor of pharmacology at the University of Colorado Anschutz Medical Campus and senior author of the study. “This paper is mainly a basic science finding of a fundamental process of what nerve cells do. Understanding this relay system not only enhances our knowledge of brain function but could also better inform therapeutic treatments for cognitive disorders.”

The nucleus where the genes that modify neuron function are controlled is a long distance away from where neurons receive input from their synapses, which are located in distant dendrites that extend like branches from the trunk of a tree. This research focuses on the cAMP-response element binding protein (CREB), a transcription factor known to regulate genes vital for dynamic changes at synapses which is essential for neuronal communication. Despite CREB’s well-documented role in supporting learning and memory, the exact mechanisms leading to CREB activation during neuronal activity remain unclear.

Using advanced microscopy techniques, graduate student Katlin Zent in Dr. Dell’Acqua’s research group revealed a crucial relay mechanism involving the activation of receptors and ion channels generating calcium signals that rapidly communicates from synapses in remote dendrite branches to the nucleus in the neuron cell body.

“Going forward, this research will enable us to better examine the way these pathways are utilized in different disease states,” said Dell’Acqua. “We could see exactly what parts of this new mechanism are interfered with and where, giving us a better idea of how this pathway affecting learning and memory is impacted. This research highlights potential targets for interventions aimed at conditions like Alzheimer’s disease and other memory-related disorders.”

These nano-sized motors are highly programmable and can be designed for use in molecular computation, diagnostics, and transport. Despite their genius, DNA-nanoparticle motors don’t have the speed of their biological counterparts, the motor protein, which is where the issue lies. This is where researchers come in to analyze, optimize, and rebuild a faster artificial motor using single-particle tracking experiment and geometry-based kinetic simulation.

“Natural motor proteins play essential roles in biological processes, with a speed of 10-1000 nm/s. Until now, artificial molecular motors have struggled to approach these speeds, with most conventional designs achieving less than 1 nm/s,” said Takanori Harashima, researcher and first author of the study.

Researchers published their work in Nature Communications on January 16th, 2025, featuring a proposed solution to the most pressing issue of speed: switching the bottleneck.

The experiment and simulation revealed that binding of RNase H is the bottleneck in which the entire process is slowed. RNase H is an enzyme involved in genome maintenance, and breaks down RNA in RNA/DNA hybrids in the motor. The slower RNase H binding occurs, the longer the pauses in motion, which is what leads to a slower overall processing time. By increasing the concentration of RNase H, the speed was markedly improved, showing a decrease in pause lengths from 70 seconds to around 0.2 seconds.

However, increasing motor speed came at the cost of processivity (the number of steps before detachment) and run-length (the distance the motor travels before detachment). Researchers found that this trade-off between speed and processivity/run-length could be improved by a larger DNA/RNA hybridization rate, bringing the simulated performance closer to that of a motor protein.

The engineered motor, with redesigned DNA/RNA sequences and a 3.8-fold increase in hybridization rate, achieved a speed of 30 nm/s, 200 processivity, and a 3 μm run-length. These results demonstrate that the DNA-nanoparticle motor is now comparable to a motor protein in performance.

“Ultimately, we aim to develop artificial molecular motors that surpass natural motor proteins in performance,” said Harashima. These artificial motors can be very useful in molecular computations based on the motion of the motor, not to mention their merit in the diagnosis of infections or disease-related molecules with a high sensitivity.

The experiment and simulation done in this study provide an encouraging outlook for the future of DNA-nanoparticle and related artificial motors and their ability to measure up to motor proteins as well as their applications in nanotechnology.

Takanori Harashima, Akihiro Otomo, and Ryota Iino of the Institute for Molecular Science at National Institutes of Natural Sciences and the Graduate Institute for Advanced Studies at SOKENDAI contributed to this research.

This work was supported by JSPS KAKENHI, Grants-in-Aid for Transformative Research Areas (A) (Publicly Offered Research) “Materials Science of Meso-Hierarchy” (24H01732) and “Molecular Cybernetics” (23H04434), Grant-in-Aid for Scientific Research on Innovative Areas “Molecular Engine” (18H05424), Grant-in-Aid for Early-Career Scientists (23K13645), JST ACT-X “Life and Information” (MJAX24LE), and Tsugawa foundation Research Grant for FY2023.

Psoriasis is a hereditary, chronic skin condition that can also result in inflammation of the joints. In Sweden, almost 300,000 people live with some form of the condition. Chronic inflammatory bowel diseases (IBD), especially Crohn’s disease, are more common in patients with psoriasis than in the rest of the population.

“Previous research has also shown that people with psoriasis have more gastrointestinal problems than the general population. However we didn’t know much about why this is the case. With our study, we can now show that people with psoriasis often have invisible inflammation in their small intestines, with an increased risk of what’s called leaky gut,” says Maria Lampinen, researcher at Uppsala University.

Pro-inflammatory activity in the gut

The study involved 18 patients with psoriasis and 15 healthy controls as subjects. None of the participants had been diagnosed with gastrointestinal diseases. Samples were taken from both their small and large bowel. The researchers then studied different types of immune cells in the mucous membrane.

“It turned out that psoriasis sufferers had higher numbers of certain types of immune cells in their small intestine, and the cells showed signs of pro-inflammatory activity. Interestingly, we found the same type of immune cells in skin flare-ups from psoriasis patients, suggesting that the inflammation of the skin may have an impact on the gut, or vice versa.

Increased propensity for leaky gut

Normally, the intestinal mucosa act as a protective barrier that also allows nutrients and water to pass through it. In some autoimmune diseases, the intestinal barrier may function poorly. This is called having a leaky gut, and leads to bacteria and harmful substances leaking through the intestinal barrier and causing inflammation. This can also cause more widespread inflammation when these substances are spread via the bloodstream.

Half of the psoriasis patients in the study had increased intestinal barrier permeability or leaky gut. These same patients also reported more gastrointestinal symptoms such as abdominal pain and bloating than patients with a normal intestinal barrier. They also had elevated levels of inflammatory substances in their intestines.

“Given that the psoriasis patients in our study had relatively mild skin disease and showed no visible intestinal inflammation in a gastroscopy, they had surprisingly clear changes in their small intestine compared to healthy controls. These changes could explain why psoriasis sufferers often have gastrointestinal problems, and an increased risk of developing Crohn’s disease.

Important research for these patients

The Psoriasisförbundet (the Swedish Psoriasis Association) member magazine published an article about this study. Following its publication, Maria Lampinen received many e-mails from people who recognised this phenomenon.

“They wanted to know more about the link between the gut and the skin because they recognised that symptoms from their gut and skin were often linked. So it feels like this research is needed and is important for the patients themselves. A greater understanding of gastrointestinal problems in psoriasis patients can help the healthcare system to pay more attention to the link between the gut and the skin in patients with psoriasis, and in the long term it could also lead to better treatment of these problems.

The study was funded by the Psoriasis Association’s managed funds and Hudfonden (the Skin Foundation), among others.

“Although past evidence showing causal links between modelling and getting rewarded for violence had an immediate impact on aggressive behavior in 4-year-old children, few studies have investigated long-term risks with antisocial behavior. We studied such risks in mid-adolescence, explained Pagani, who is also a researcher at the Centre de recherche Azrieli du CHU Sainte-Justine. It was ideal to study this question with typically developing middle-class children because, as a population, they have the lowest chances of engaging in aggression and behavior harmful to others.”

Close to 2,000 children

In all, Pagani and her team looked at 963 girls and 982 boys born between the springs of 1997 and 1998 who were enrolled in the Quebec Longitudinal Study of Child Development. Parents reported the frequency of their child’s exposure to violent television content at ages 3.5 and 4.5 years old. Boys and girls then self-reported on several aspects of antisocial behavior at age 15.

The study defines screen violence as anything “characterized by physical aggression, verbal aggression, and relational aggression […] depicting situations that intentionally attempt or cause harm to others.” Children, the study says “are attracted to fast-paced, stimulating violent content, which often features appealing characters like superheroes who commit and are rewarded for aggressive acts, thus increasing the likelihood of exposure.”

The researchers then conducted analyses to examine whether exposure to violent television content at ages 3.5 and 4.5 years predicted later antisocial behavior eleven years later.

The researcher added, “We statistically took into account alternative child and family factors that could have explained our results, to be as close as possible to the truth in the relationships we were looking at.”

Boys stand out

At age 15, for boys only, preschool violent televiewing predicted increases in antisocial behavior. Being exposed to violent content in early childhood predicted later aggressive behaviors such as hitting or beating another person, with the intention of obtaining something, stealing, with or without any apparent reason.

Risks also included threats, insults, and gang fight involvement. The use of weapons is also among the behavioral outcomes predicted by exposure to childhood television violence in this study. No effects were found for girls, which was not surprising given that boys are generally more exposed to such content.

Pagani concluded, “Our study provides compelling evidence that early childhood exposure to media violence can have serious, long-lasting consequences, particularly for boys. This underscore the urgent need for public health initiatives that targets campaigns to inform parents and communities about the long-term risks and empower them to make informed choices about young children’s screen content exposure.”

The entire team of students from Université de Montréal and researchers from the United States and Italy established that, “Parents and communities can play a crucial role in limiting future problems by carefully avoiding young children’s exposure to violent media content.”

“Rotavirus alone accounts for one-quarter of all cases of severe pediatric acute gastroenteritis, which typically presents with watery diarrhea, vomiting, fever and abdominal pain. Currently, nearly 500,000 children worldwide die from this condition every year,” said corresponding author Dr. Joseph Hyser, associate professor of molecular virology and microbiology, as well as part of the Alkek Center for Metagenomic and Microbiome Research and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. “Although oral rehydration therapy and live-attenuated rotavirus vaccines have helped reduce the burden of rotavirus acute gastroenteritis in children worldwide, there is still room for improvement.”

In the current study, Hyser and his colleagues looked deeper into how functions of NSP4 during rotavirus infection contribute to disease severity in hopes of finding a novel approach to treat or prevent the disease. In a previous study, the researchers discovered that rotavirus triggers aberrant calcium signals known as ‘intercellular calcium waves’ that radiate from infected cells to neighboring uninfected cells and that inhibition of these signals lessened disease severity.

“The results indicated that it was likely that calcium waves contributed to rotavirus replication and virulence; however, it was not clear how the virus triggered this signal,” Hyser said. “We already had evidence that placed NSP4 at the top of the list of viral proteins that could be involved in triggering calcium waves.”

Working with existing human and porcine virulent and attenuated rotavirus strains, as well as novel genetic recombinant strains generated by a reverse genetics system, the team examined the role of NSP4 in the induction of calcium waves and its connection to disease severity using a range of experimental models, including cells grown in the lab, intestinal organoid cultures and animal models.

The researchers found that the ability of rotavirus to generate calcium waves was fully attributable to NSP4, such that expression of NSP4 in cells, even in the absence of rotavirus infection, generated calcium waves indistinguishable from a native infection.

Importantly NSP4 from attenuated rotaviruses, which cause milder or no disease, induced fewer calcium waves than NSP4 from virulent strains and inserting the attenuated NSP4 into a virulent rotavirus strain both decreased the number of calcium waves it produced and decreased its ability to cause diarrhea in an animal model.

“We found that the ability of rotavirus to generate calcium waves goes hand in hand with NSP4, expression of NSP4 alone is sufficient to generate calcium waves, and multiple aspects of rotavirus disease severity correlated with the ability to generate calcium waves,” Hyser said.

Furthermore, calcium waves also triggered an immune response, implicating calcium dysregulation as a means of viral recognition.

“Altogether, the evidence suggested that NSP4 seemed to be involved in inducing calcium waves linked to both rotavirus disease severity and host cell responses to this aberrant level of calcium signaling,” Hyser said.

The findings may apply beyond rotavirus to other viruses carrying proteins similar to NSP4 that could be involved in disrupting calcium signaling.

Other contributors to this work include J. Thomas Gebert, Francesca J. Scribano, Kristen A. Engevik, Ethan M. Huleatt, Michael R. Eledge, Lauren E. Dorn, Asha A. Philip, Takahiro Kawagishi, Harry B. Greenberg and John T. Patton. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Indiana University and Stanford University School of Medicine.

The study was supported by National Institutes of Health grants (NICH R01AI158683, R01DK115507, NIH S10OD028480, NIH F30DK131828, NIH F31DK132942, NIH F32DK130288 and NIH T32DK007664) and the McNair Foundation M.D./Ph.D. Scholars Program.

The bacteria is a sure sign of fecal contamination, which is washed into waterways from farm fields or sewage systems by rain. The microbes are also dangerous — exposure to E. coli can lead to illness, hospitalization and even death.

Still, as many beachgoers know, it’s not uncommon for E. coli to temporarily shut down lakes and other recreational waters across the U.S. Now, research led by the University of Michigan shows that communities of color in Texas face pronounced risks of E. coli exposure in nearby waters following storms that dump abnormally high amounts of rain.

“E. coli is the leading cause of water quality impairments in the United States, and exposure to this pollution is not evenly distributed. We’re also seeing that extreme precipitation has a disproportionate effect on E. coli pollution,” said lead author Xiaofeng Liu, a postdoctoral researcher at the U-M School for Environment and Sustainability and a Schmidt AI in Science fellow at the Michigan Institute for Data and AI in Society.

Liu and colleagues worked with E.coli, climate, environmental and socioeconomic data available for the state of Texas between 2001 and 2021. Using computational models, the team could spot when and where the extreme rainfall had the greatest impact on E. coli levels, while uncovering associations between these impacts and socioeconomic factors.

The patterns were complex, but a couple of clear results emerged.

Communities in the north and east with higher percentages of Black residents had higher concentrations of E. coli flushed into their recreational waters by extreme rain in winter.

Predominantly Latino communities — where the majority of residents were of Latin American descent — in the southern and western parts of the state experienced outsize E. coli increases following intense storms in September.

“This is a complicated issue. The communities live in these places all the time, but the rainfall impact is different in different seasons,” Liu said.

There are numerous social, historical, geological and meteorological variables at play for understanding this seasonality and location dependence, which are not all captured by available data, she says.

Still, when coupled with the team’s computational analysis, there is enough data to identify when and where contamination is most likely to occur. And with that knowledge, people can start looking for opportunities to prevent or combat the influx of E. coli.

“This can inform local governments and environmental agencies and help develop targeted policies and targeted water management practices to help these impacted communities,” Liu said.

This work, published in the journal of Science of the Total Environment, was part of a larger project looking at water quality issues and their relationship to social factors.

That project also yielded another recent report — led by Runzi Wang, assistant professor at the University of California, Davis — looking at E. coli levels and trends throughout Texas. That report showed that not only did Black and Latino communities tend to reside near water with higher concentrations of E. coli, so did economically disadvantaged communities.

Liu and her colleagues did not observe a similar correlation between income level and extreme rainfall impacts on E. coli concentrations during their investigation. But they did find that lower-income areas were more likely to experience an increase in extreme rainfall intensity heading forward.

“The regions with this increasing trend also tended to have higher percentages of lower-income residents,” Liu said. “So even though there isn’t a correlation now, climate variability could amplify the effect for lower-income communities in the future.”

The team focused their initial study on Texas because E. coli is a serious and known problem. About a third of the streams in Texas are polluted by bacteria, Liu said, but the state also has a robust monitoring system.

Because of that, the team could validate their methods while also performing useful analysis. The researchers now plan to extend their work to other locations in the U.S.

“With this study, we wanted to demonstrate our framework to connect surface water quality with social factors,” Liu said. “Our model is definitely applicable to other regions.”

The study, published Jan. 2 in Nature Immunology, may lead to therapies that target the earliest stages of cancer. The findings bolster the idea that the inflammasome has a dual role — it promotes inflammation associated with poor outcomes in late cancer stages, but early on, it can help prevent cells from becoming cancerous in the first place.

“What was striking was that the innate immune system, which includes the inflammasome, has a role beyond infection,” said Dr. Julie Magarian Blander, the Gladys and Roland Harriman Professor of Immunology in Medicine and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “We found that it functions in maintaining homeostasis in the tissue, keeping an eye on whether stem cells are proliferating too much. By doing so, it prevents cells from becoming cancerous and this activity is independent of inflammation.”

The co-first authors of the study are Dr. Andrew Kent, an assistant professor of medicine-hematology at the University of Colorado School of Medicine and Dr. Kristel Joy Yee Mon, a postdoctoral associate in Dr. Blander’s lab.

Origin Story

By the time patients typically go to the doctor with cancer symptoms, tumors have already formed. As a result, very little is known about cancer’s beginnings.

To get a better understanding of how the disease takes hold, Dr. Blander and her colleagues chose to study a mouse model of B-cell lymphoma called Eµ-myc, which has a mutation in the Myc oncogene. These mice have a long delay before tumors develop, giving researchers a chance to observe what happens early on in cancer. Because B-cell lymphoma develops in a type of white blood cell, the team examined their precursors, called hematopoietic stem cells, in the mice.

Genetically disrupting inflammasome activity in the Eµ-myc mice greatly accelerated stem cell proliferation and tumor development. The investigators were surprised to find that stem cells in control mice that lacked the inflammasome also proliferated at a fast pace compared with wild-type mice, suggesting that the complex has an important role in healthy cells, too. The team found that without the inflammasome, the stem cells have high levels of the protein Ras, which is another oncogene product. This protein can work together with mutant Myc to drive cancer, so the inflammasome’s normal job of keeping Ras in check delays tumorigenesis.

Ground zero for the protective activity was not the hematopoietic stem cells themselves, but the bone marrow stroma, a collection of many cell types surrounding and nurturing the stem cells.

Higher levels of soluble tumor necrosis factor (TNF) receptors were found in the stroma of control mice compared with the inflammasome-deficient mice. “It turned out that TNF receptors were being shed from stem cells in control mice, and they were being retained on stem cells from inflammasome-deficient mice. Higher TNF receptor levels lead to increased stem cell proliferation. Maintaining a healthy level of TNF receptors becomes important for these stem cells to maintain homeostatic control of proliferation,” said Dr. Blander. “We think that the inflammasome in the stroma is orchestrating something where it’s cleaving TNF receptors, shaving them off the stem cells.”

Next steps

Next, the team will test for the inflammasome’s protective effects in other tissues. In addition, they will determine which of the stromal cell types is responsible for the activity, and which molecules the inflammasome is using to suppress cell growth.

Ultimately, the researchers hope that the study will lay the groundwork for a therapeutic that would stave off cancer. “A therapy could target the inflammasome, but it should be directed only to the inflammation side of its activity that is associated with tumor progression,” said Dr. Blander, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “You want to protect the inflammasome’s beneficial function of delaying tumorigenesis.”

A study published in the Proceedings of the National Academy of Sciences outlines this novel approach. Presenting a mathematical model, SFI Complexity Postdoctoral Fellow Kaleda Denton with colleagues at Stanford University — former SFI Post-baccalaureate Fellow Elisa Heinrich Mora, SFI External Professor Marcus Feldman, and Michael Palmer — expand on previous research to offer a more realistic representation of how conformist and anti-conformist biases shape the transmission of cultural traits through a population.

“The idea behind this research was to come up with a better way to mathematically represent how individuals make decisions in the real world,” says Denton. “If we can do that, we can then scale things up to see what would happen in a population of 10,000 people over the long run.”

Traditional models of conformity often assume individuals gravitate toward the average or “mean” trait in a population. This concept works well if the most popular traits are near this mean, which may be the case for, say, working hours or food portion sizes. However, the mean is a poor indicator of popularity in other cases; for example, if most people fall on either the far left or far right of a political spectrum, but the mean lies in the center.

To address this gap, the authors designed a model that incorporates trait clustering. In this model, individuals conform by adopting traits that are more clustered together (e.g., variations of a far-left political belief) rather than the mean trait in the population (e.g., the centrist view). Anti-conformists, on the other hand, deliberately distance themselves from the traits of their peers, creating polarization.

Using computer simulations, the team analyzed how traits spread across populations over multiple generations. Conformity often led to groups clustering around specific traits, but not necessarily the average. Anti-conformity created a starkly different pattern: a U-shaped distribution, with individuals clustering at the extremes and leaving the middle sparsely populated.

One significant finding was that populations rarely converge to a single trait unless the unrealistic assumption of perfect behavioral copying is imposed. Instead, even small variations in how individuals interpret or adopt traits result in persistent diversity.

“These outcomes align with what we observe in the real world, where cultural practices and ideologies don’t simply average out but instead maintain significant variation,” Denton says.

The research also challenges the notion that conformity always leads to homogeneity. The model shows that under certain conditions, conformity can sustain diversity, while anti-conformity amplifies polarization.

Denton sees broad implications for the study. “This framework could help explain voting behavior, social media trends, or even how people estimate values in group settings,” she says. “It offers a way to understand how individual decisions aggregate into societal patterns, whether that’s consensus-building or polarization.” This model can be tested on real-world data in future studies.

“We’re excited to see if this framework works in different scenarios,” Denton said. “The ultimate goal is to understand how individual choices influence entire populations over time.

Researchers from the Max Planck Institute for Astronomy in Germany were also involved in the study. The findings are published in the journal Nature Astronomy.

“The Large Binocular Telescope Interferometer can be considered the first extremely large telescope, so it’s very exciting to prove this is possible,” said Jacob Isbell, a postdoctoral research associate at the U of A Steward Observatory and lead author of the Nature Astronomy paper.

Every galaxy has a supermassive black hole at the center. Some of them are considered active while others are inactive, depending on how quickly material is falling onto them, Isbell said. There’s a disk around the black hole that glows more brightly the more material there is. If this accretion disk glows brightly enough, it’s called an active supermassive black hole. The AGN that exists in galaxy NGC 1068, which neighbors the Milky Way, is one of the nearest ones that is considered active.

The Large Binocular Telescope is located on Mount Graham northeast of Tucson. It operates its two 8.4-meter mirrors independently, essentially functioning as two separate telescopes mounted side by side. The Large Binocular Telescope Interferometer combines the light from both mirrors, allowing for much higher resolution observations than would be possible with each mirror on its own. This imaging technique has been successfully used in the past to study volcanoes on the surface of Jupiter’s moon Io. The Jupiter results encouraged the researchers to use the interferometer to look at an AGN.

“The AGN within the galaxy NGC 1068 is especially bright, so it was the perfect opportunity to test this method,” Isbell said. “These are the highest resolution direct images of an AGN taken so far.”

The Large Binocular Interferometer Team is led by Steve Ertel, associate astronomer of Steward Observatory. Through the interferometer, the team was able to observe several cosmic phenomena going on simultaneously in the AGN.

The bright disk around the supermassive black hole releases a lot of light, which pushes dust away like many tiny sails, a phenomenon known as radiation pressure. The images revealed a dusty, outflowing wind caused by radiation pressure. Simultaneously, farther out, there was a lot of material that was way brighter than it should have been, considering it was illuminated only by the bright accretion disk. By comparing the new images to past observations, the researchers were able to tie this finding to a radio jet that’s blasting through the galaxy, hitting and heating up clouds of molecular gas and dust. Radio jet feedback is the interaction between powerful jets of radiation and particles emitted from supermassive black holes and their surrounding environment.

Direct imaging with extremely large telescopes such as the Larger Binocular Telescope Interferometer and the upcoming 83.5 feet Giant Magellan Telescope located in Chile makes it possible to distinguish feedback from the radio jet and dusty wind simultaneously. Previously, the various processes were blended due to low resolution, but now it is possible to view their individual impact, Isbell said.

The study shows that the environments of AGN can be complex, and the new findings help better understand AGN’s interaction with their host galaxies.

“This type of imaging can be used on any astronomical object,” Isbell said. “We’ve already started looking at disks around stars or very large, evolved stars, which have dusty envelopes around them.”

A team of researchers from universities, health departments, and agricultural agencies from across the Northeast conducted a meta-analysis of data on how many blacklegged ticks there are and how many of them have the potential to pass pathogens responsible for Lyme disease and three other tick-borne diseases in the Northeast from 1989 to 2021, including in Connecticut, New York, New Hampshire, Vermont, and Maine.

Data was collected in Maine starting in 1989, while most of the other states began data collection in the mid- 2000s. Massachusetts and Rhode Island were not represented in the study due to either unavailable or insufficient data.

Lyme disease was first discovered in Lyme, Conn, in 1975. Its symptoms can vary depending on the stage and severity of the disease but can include a rash, fever, chills, fatigue, muscle or joint aches, and swollen lymph nodes. If left untreated, prolonged and more severe symptoms may develop.

Lyme disease is caused by a bacteria calledBorrelia burgdorferi. Some but not all, white-footed mice, chipmunks, birds, squirrels, and other small animals carry the bacteria in their blood, making them “competent” hosts. Blacklegged ticks are not born infected with the Lyme disease bacteria. But when a blacklegged tick feeds on an infected host, the tick can get the bacteria that causes Lyme disease and then potentially spread it to humans through its bite. Other animals, like white-tailed deer, are “incompetent hosts,” so while they are a food source for blacklegged ticks, they do not transmit the Lyme disease bacteria.

Blacklegged ticks typically consume three blood meals over the course of a two-year life cycle: after they hatch into larvae in the midsummer of their first year; as nymphs during the following late spring, often in May or June; and as adults that fall, most likely between September and November.

In general, ticks must be attached to a person for at least 24 hours to transmit the Lyme disease bacteria. So even though adult blacklegged ticks are more likely to carry the bacteria than younger ticks, because they are bigger, about the size of a sesame seed, there is particular concern about the younger ticks or nymphs, which are only about the size of a poppy seed, making them difficult to spot.

“While the bacteria responsible for Lyme disease has a complicated chain of transmission, our results show the relative abundance of blacklegged ticks, and just how many of them are carrying disease-causing pathogens throughout the Northeast,” says lead author Lucas Price, who was a postdoctoral fellow in geography at Dartmouth at the time of the study and is now a wildlife biologist at the Interior Department’s Bureau of Land Management.

The researchers analyzed the abundance of blacklegged ticks and the presence of Lyme disease bacteria and other pathogens so that they could determine how blacklegged ticks and the pathogens they carry are changing in time and space.

“Contrary to the well-documented spread of blacklegged ticks and Lyme disease over the past 30 years, we found very small changes in the abundance of blacklegged ticks, but think this is likely because we usually don’t start sampling a location for blacklegged ticks until they’re already established,” says senior author Jonathan Winter, an associate professor of geography and director of the Applied Hydroclimatology Group at Dartmouth. However, we did find an increase in the percentage of blacklegged ticks that carry the Lyme disease bacteria.”

These findings underscore advice from the Centers for Disease Control and Prevention and health professionals, who recommend a range of tick bite prevention measures, including conducting full-body tick checks after spending time outdoors in regions where pathogen-carrying ticks are present. While much of the data were already available publicly prior to the study, the team made the surveys consistent across states, creating one of the most comprehensive tick abundance and pathogen prevalence datasets in the United States, and establishing a baseline that can be used in the future.

The researchers have another study underway examining the relationship between climate change and the prevalence of blacklegged ticks and Lyme disease in the Northeast.

Joseph Savage, a graduate student in the Ecology, Evolution, Environment & Society program at Dartmouth, also contributed to the study.

A study involving over 600 fully vaccinated children in South Africa found those who were undernourished had substantially lower levels of antibodies against measles.

Researchers from McGill University, UC Berkeley School of Public Health and the University of Pretoria tracked the children’s growth over time as an indicator of undernutrition and measured their antibody levels through blood tests. Children who were stunted around age three had an average of 24-per-cent-lower measles antibody levels by age five compared to their typical-sized peers.

The findings, published in Vaccine, suggest that undernutrition may affect the duration of vaccine protection.

This indicates that addressing child hunger could be a key piece of the puzzle in preventing viral outbreaks, said senior author Jonathan Chevrier, an Associate Professor in McGill’s Department of Epidemiology, Biostatistics and Occupational Health and Canada Research Chair in Global Environmental Health and Epidemiology.

A growing threat worldwide

Measles is a highly contagious viral infection that causes symptoms such as a rash, fever and cough, and can lead to severe complications, especially in young children. The disease is a threat in regions where it was once under control, including Canada, which in 2024 reported its highest number of cases in nearly a decade.

“Global measles cases declined from 2000 to 2016, but the trend reversed in 2018, driven in part by under-vaccination and the impact of the pandemic. Measles is now making a strong comeback in many parts of the world despite being preventable with vaccination and adequate immunity,” said co-author Brian Ward, Professor in McGill’s Department of Medicine.

“We need to vaccinate children against infectious diseases that are preventable and ensure they are protected,” said first author Brenda Eskenazi, Professor Emerita of Public Health at the University of California, Berkeley. “This is especially important now, given that many known diseases are expected to spread with climate change.”

About 22 per cent of children under age five worldwide — approximately 148 million — were stunted in 2022, Chevrier added, with the highest rates in Asia and sub-Saharan Africa.

The team plans to monitor the children in the study as they grow older to understand whether the effects of early-life undernutrition persist.

This study was funded by the U.S. National Institute of Environmental Health Sciences and the Canadian Institutes of Health Research.

“Most people don’t realize how often they rely on touch instead of vision — typing, walking, picking up a flimsy cup of water,” said Charles Greenspon, PhD, a neuroscientist at the University of Chicago. “If you can’t feel, you have to constantly watch your hand while doing anything, and you still risk spilling, crushing or dropping objects.”

Greenspon and his research collaborators recently published papers in Nature Biomedical Engineering and Science documenting major progress on a technology designed to address precisely this problem: direct, carefully timed electrical stimulation of the brain that can recreate tactile feedback to give nuanced “feeling” to prosthetic hands.

The science of restoring sensation

These new studies build on years of collaboration among scientists and engineers at UChicago, the University of Pittsburgh, Northwestern University, Case Western Reserve University and Blackrock Neurotech. Together they are designing, building, implementing and refining brain-computer interfaces (BCIs) and robotic prosthetic arms aimed at restoring both motor control and sensation in people who have lost significant limb function.

On the UChicago side, the research was led by neuroscientist Sliman Bensmaia, PhD, until his unexpected passing in 2023.

The researchers’ approach to prosthetic sensation involves placing tiny electrode arrays in the parts of the brain responsible for moving and feeling the hand. On one side, a participant can move a robotic arm by simply thinking about movement, and on the other side, sensors on that robotic limb can trigger pulses of electrical activity called intracortical microstimulation (ICMS) in the part of the brain dedicated to touch.

For about a decade, Greenspon explained, this stimulation of the touch center could only provide a simple sense of contact in different places on the hand.

“We could evoke the feeling that you were touching something, but it was mostly just an on/off signal, and often it was pretty weak and difficult to tell where on the hand contact occurred,” he said.

The newly published results mark important milestones in moving past these limitations.

Advancing understanding of artificial touch

In the first study, published in Nature Biomedical Engineering, Greenspon and his colleagues focused on ensuring that electrically evoked touch sensations are stable, accurately localized and strong enough to be useful for everyday tasks.

By delivering short pulses to individual electrodes in participants’ touch centers and having them report where and how strongly they felt each sensation, the researchers created detailed “maps” of brain areas that corresponded to specific parts of the hand. The testing revealed that when two closely spaced electrodes are stimulated together, participants feel a stronger, clearer touch, which can improve their ability to locate and gauge pressure on the correct part of the hand.

The researchers also conducted exhaustive tests to confirm that the same electrode consistently creates a sensation corresponding to a specific location.

“If I stimulate an electrode on day one and a participant feels it on their thumb, we can test that same electrode on day 100, day 1,000, even many years later, and they still feel it in roughly the same spot,” said Greenspon, who was the lead author on this paper.

From a practical standpoint, any clinical device would need to be stable enough for a patient to rely on it in everyday life. An electrode that continually shifts its “touch location” or produces inconsistent sensations would be frustrating and require frequent recalibration. By contrast, the long-term consistency this study revealed could allow prosthetic users to develop confidence in their motor control and sense of touch, much as they would in their natural limbs.

Adding feelings of movement and shapes

The complementary Science paper went a step further to make artificial touch even more immersive and intuitive. The project was led by first author Giacomo Valle, PhD, a former postdoctoral fellow at UChicago who is now continuing his bionics research at Chalmers University of Technology in Sweden.

“Two electrodes next to each other in the brain don’t create sensations that ’tile’ the hand in neat little patches with one-to-one correspondence; instead, the sensory locations overlap,” explained Greenspon, who shared senior authorship of this paper with Bensmaia.

The researchers decided to test whether they could use this overlapping nature to create sensations that could let users feel the boundaries of an object or the motion of something sliding along their skin. After identifying pairs or clusters of electrodes whose “touch zones” overlapped, the scientists activated them in carefully orchestrated patterns to generate sensations that progressed across the sensory map.

Participants described feeling a gentle gliding touch passing smoothly over their fingers, despite the stimulus being delivered in small, discrete steps. The scientists attribute this result to the brain’s remarkable ability to stitch together sensory inputs and interpret them as coherent, moving experiences by “filling in” gaps in perception.

The approach of sequentially activating electrodes also significantly improved participants’ ability to distinguish complex tactile shapes and respond to changes in the objects they touched. They could sometimes identify letters of the alphabet electrically “traced” on their fingertips, and they could use a bionic arm to steady a steering wheel when it began to slip through the hand.

These advancements help move bionic feedback closer to the precise, complex, adaptive abilities of natural touch, paving the way for prosthetics that enable confident handling of everyday objects and responses to shifting stimuli.

The future of neuroprosthetics

The researchers hope that as electrode designs and surgical methods continue to improve, the coverage across the hand will become even finer, enabling more lifelike feedback.

“We hope to integrate the results of these two studies into our robotics systems, where we have already shown that even simple stimulation strategies can improve people’s abilities to control robotic arms with their brains,” said co-author Robert Gaunt, PhD, associate professor of physical medicine and rehabilitation and lead of the stimulation work at the University of Pittsburgh.

Greenspon emphasized that the motivation behind this work is to enhance independence and quality of life for people living with limb loss or paralysis.

“We all care about the people in our lives who get injured and lose the use of a limb — this research is for them,” he said. “This is how we restore touch to people. It’s the forefront of restorative neurotechnology, and we’re working to expand the approach to other regions of the brain.”

The approach also holds promise for people with other types of sensory loss. In fact, the group has also collaborated with surgeons and obstetricians at UChicago on the Bionic Breast Project, which aims to produce an implantable device that can restore the sense of touch after mastectomy.

Although many challenges remain, these latest studies offer evidence that the path to restoring touch is becoming clearer. With each new set of findings, researchers come closer to a future in which a prosthetic body part is not just a functional tool, but a way to experience the world.

The parent perspective led Cooper on a scientific quest that began four years ago — and continues today — to study the half-billion nerve cells in the bowel wall that are part of the enteric nervous system and how Batten disease affects their function. His new work shows enteric neurons in two mouse models of Batten disease degenerate in the bowel, paralleling neurodegeneration long known to occur in brain and spinal cord.

Cooper’s prior research also showed that supplying the missing enzyme to the brain in mouse or sheep Batten disease models via enzyme replacement therapy slowed cellular degeneration. Now his latest study has found that gene therapy in mice produced the same protective effect in the bowel. This genetic treatment reduced bowel symptoms and extended the lifespan of the mice by preventing enteric neuron degeneration.

The findings, published Jan. 15 in Science Translational Medicine, may one day lead to new treatments for Batten disease as well as for other neurodegenerative disorders with gastrointestinal symptoms.

“We believe our studies in mice have demonstrated a novel and highly promising way to successfully treat GI conditions with gene therapy,” said Cooper, the study’s co-senior author. “Importantly, we also established that the GI issues were not secondary to the neurological changes in the brain or spinal cord caused by the disease, but happen in the bowel itself.”

Patient-driven research

Batten disease refers to a group of inherited nervous system disorders in which a child lacks a crucial enzyme that breaks down and recycles cellular waste. Also known as neuronal ceroid lipofuscinosis, the disease is named after the accumulated material inside the cells. Not having these enzymes causes progressive brain damage that leads to death. Cooper and his colleagues are exploring exactly how this happens.

The exact number of kids with Batten disease remains unknown; however, some researchers have estimated it affects around three out of every 100,000 children in the U.S.

Two of Tracy VanHoutan’s children had the disease. The father met Cooper in 2009 at a rare disease conference in Hamburg, Germany, after his son, Noah, was diagnosed with a form of Batten disease. VanHoutan had traveled more than 4,000 miles from his home in Chicago to find scientists who might help his 5-year-old-boy, suffering from this extremely rare and understudied disease.

The two clicked immediately. They began speaking regularly. Together, they grieved when Noah died in 2016, just before his 12th birthday. And again, less than two years later, in December 2018, when VanHoutan’s daughter, Laine, died from the disease at age 12.

VanHoutan, who has become an accomplished advocate for rare disease research, invited Cooper to speak at patient-advocacy meetings, some of which were organized through Noah’s Hope-Hope4Bridget Foundation, the nonprofit he founded after his son’s diagnosis. During one of those meetings, Cooper asked parents about the day-to-day issues their children experienced.

Severe constipation, they told him. You might want to investigate it, they suggested.

“And Dr. Cooper listened,” VanHoutan said. “Dr. Cooper is a special scientist because he seeks out patients and their families. It doesn’t matter how old the patient is, he will get on their level and ask and answer questions in a relatable manner. He’ll talk to the parents but also the siblings and grandparents. He wants to know all perspectives.”

Motivated by what he learned from the families, Cooper turned his attention to the nervous system in the gut. Collaborating with Cooper is Robert O. Heuckeroth, MD, PhD, a pediatric gastroenterologist at Children’s Hospital of Philadelphia and a professor of pediatrics and of cell and developmental biology at the University of Pennsylvania. Heuckeroth completed his graduate and medical training at WashU Medicine where he first became interested in the nervous system of the bowel.

Together, the scientists discovered that while Batten disease ravages nerve cells in the brain and spinal cord, it also kills neurons that are part of the GI tract’s enteric nervous system.

Their research on Batten disease in mouse models and in colon tissue from children who died of Batten disease showed that nerve cell degeneration in the bowel occurs in parallel with events in the brain, following a similar pattern and timeline. About half of the nerve cells normally present die in Batten mice as the disease progresses, causing problems with bowel motility.

The basis for treating these diseases is to introduce a working copy the defective gene. This is supplied by a gene therapy virus that instructs cells to make this missing enzyme, secreting it to treat nearby cells. Giving gene therapy to newborn mice with Batten disease prevented the loss of many nerve cells in the bowel and prevented related problems with bowel function. The mice treated by gene therapy also lived significantly longer than untreated Batten disease mice.

The researchers have begun to apply their findings to other forms of Batten disease and similar neurodegenerative conditions in children such as the mucopolysaccharidoses, another group of rare inherited diseases caused by enzyme deficiencies that thwart a cell’s ability to break down material. Symptoms include GI distress, cognitive and developmental decline, skeletal and joint issues, vision impairment and physical deformities, among others.

“Our reasoning is that if nerve cells in the brain die because they’re missing a key enzyme, then there’s a high probability nerve cells in other organ systems could also die,” Cooper explained. “And given that a person has half a billion nerve cells in their bowels, about as many as in the spinal cord, it was important to determine if this occurs, opening up a whole new perspective on these diseases.”

Heuckeroth, a leading expert in the enteric nervous system whom Cooper fondly calls his “co-pilot” in research, added that damage to the enteric nervous system can profoundly impair bowel function, causing debilitating symptoms such as vomiting, distension, constipation, abdominal pain, malnutrition and a predisposition to bowel inflammation, sepsis and death.

“The enteric nervous system controls most aspects of bowel function,” said Heuckeroth. “We believe this work shows for the first time that a serious disease of the enteric nervous system can be treated by gene therapy, at least in mice.”

Cooper and Heuckeroth noted that future studies will focus on providing simultaneous gene therapy to both the brain and bowel, which they think is necessary for optimal outcomes.

“Red meat is high in saturated fat and has been shown in previous studies to increase the risk of type 2 diabetes and heart disease, which are both linked to reduced brain health,” said study author Dong Wang, MD, ScD, of Brigham and Women’s Hospital in Boston. “Our study found processed red meat may increase the risk of cognitive decline and dementia, but the good news is that it also found that replacing it with healthier alternatives, like nuts, fish and poultry, may reduce a person’s risk.”

To examine the risk of dementia, researchers included a group of 133,771 people with an average age of 49 who did not have dementia at the start of the study. They were followed up to 43 years. Of this group, 11,173 people developed dementia.

Participants completed a food diary every two to four years, listing what they ate and how often.

Researchers defined processed red meat as bacon, hot dogs, sausages, salami, bologna and other processed meat products. They defined unprocessed red meat as beef, pork, lamb and hamburger. A serving of red meat is three ounces, about the size of a deck of cards.

Researchers calculated how much red meat participants ate on average per day.

For processed red meat, they divided participants into three groups. The low group ate an average of fewer than 0.10 servings per day; the medium group ate between 0.10 and 0.24 servings per day; and the high group, 0.25 or more servings per day.

After adjusting for factors such as age, sex and other risk factors for cognitive decline, researchers found that participants in the high group had a 13% higher risk of developing dementia compared to those in the low group.

For unprocessed red meat, researchers compared people who ate an average of less than one half serving per day to people who ate one or more servings per day and did not find a difference in dementia risk.

To measure subjective cognitive decline, researchers looked at a different group of 43,966 participants with an average age of 78. Subjective cognitive decline is when a person reports memory and thinking problems before any decline is large enough to show up on standard tests.

The subjective cognitive decline group took surveys rating their own memory and thinking skills twice during the study.

After adjusting for factors such as age, sex and other risk factors for cognitive decline, researchers found that participants who ate an average of 0.25 servings or more per day of processed red meat had a 14% higher risk of subjective cognitive decline compared to those who ate an average of fewer than 0.10 servings per day.

They also found people who ate one or more servings of unprocessed red meat per day had a 16% higher risk of subjective cognitive decline compared to people who ate less than a half serving per day.

To measure objective cognitive function, researchers looked at a different group of 17,458 female participants with an average age of 74. Objective cognitive function is how well your brain works to remember, think and solve problems.

This group took memory and thinking tests four times during the study.

After adjusting for factors such as age, sex and other risk factors for cognitive decline, researchers found that eating higher processed red meat was associated with faster brain aging in global cognition with 1.61 years with each additional serving per day and in verbal memory with 1.69 years with each additional serving per day.

Finally, researchers found that replacing one serving per day of processed red meat with one serving per day of nuts and legumes was associated with a 19% lower risk of dementia and 1.37 fewer years of cognitive aging. Making the same substitution for fish was associated with a 28% lower risk of dementia and replacing with chicken was associated with a 16% lower risk of dementia.

“Reducing how much red meat a person eats and replacing it with other protein sources and plant-based options could be included in dietary guidelines to promote cognitive health,” said Wang. “More research is needed to assess our findings in more diverse groups.”

A limitation of the study was that it primarily looked at white health care professionals, so the results might not be the same for other race, ethnic and non-binary sex and gender populations.

The study was supported by the National Institutes of Health.

In a paper published recently in Nature Communications, the UC Irvine scientists describe their construction of complementary, internal, ion-gated, organic electrochemical transistors that are more amenable chemically, biologically and electronically to living tissues than rigid, silicon-based technologies. The medical device based on these transistors can function in sensitive parts of the body and conform to organ structures even as they grow.

“Advanced electronics have been in development for several decades now, so there is a large repository of available circuit designs. The problem is that most of these transistor and amplifier technologies are not compatible with our physiology,” said co-author Dion Khodagholy, Henry Samueli Faculty Excellence Professor in UC Irvine’s Department of Electrical Engineering and Computer Science. “For our innovation, we used organic polymer materials that are inherently closer to us biologically, and we designed it to interact with ions, because the language of the brain and body is ionic, not electronic.”

In standard bioelectronics, complementary transistors have been composed of different materials to account for different polarities of signals, which, in addition to being unyielding and cumbersome, present the risk of toxicity when implanted in sensitive areas. The team of researchers from UC Irvine and Columbia University worked around this problem by creating its transistors in an asymmetric fashion that enables them to be operated using a single, biocompatible material.

“A transistor is like a simple valve that controls the flow of current. In our transistors, the physical process that controls this modulation is governed by the electrochemical doping and de-doping of the channel,” said first author Duncan Wisniewski, Columbia University Ph.D. candidate during the project who is now a visiting scholar in the UC Irvine Department of Electrical Engineering and Computer Science. “By designing devices with asymmetrical contacts, we can control the doping location in the channel and switch the focus from negative potential to positive potential. This design approach allows us to make a complementary device using a single material.”

He added that arraying transistors into a smaller, single-polymer material greatly simplifies the fabrication process, enabling large-scale manufacturing and opportunities to expand the technology beyond the original neurological application to almost any biopotential processes.

Khodagholy, who heads the UC Irvine Translational Neuroelectronics Laboratory, which recently moved to Irvine from Columbia University, said that his team’s work has the added benefit of scalability: “You can make different device sizes and still maintain this complementarity, and you can even change the material, which makes this innovation applicable in multiple situations.”

Another advantage highlighted in the Nature Communications paper is that the device can be implanted in a developing animal and withstand transitions in tissue structures as the organism grows, something that is not possible with hard, silicon-based implants.

“This characteristic will make the device particularly useful in pediatric applications,” said co-author Jennifer Gelinas, UC Irvine associate professor of anatomy and neurobiology as well as pediatrics, who’s also a physician at Children’s Hospital of Orange County.

“We demonstrated our ability to create robust complementary, integrated circuits that are capable of high-quality acquisition and processing of biological signals,” Khodagholy said. Complementary, internal, ion-gated, organic electrochemical transistors “will substantially broaden the application of bioelectronics to devices that have traditionally relied on bulky, nonbiocompatible components.”

Joining Khodagholy, Gelinas and Wisniewski on this project were Claudia Cea, Liang Ma, Alexander Ranschaert, Onni Rauhala and Zifang Zhao of Columbia University. The work was supported by the National Institutes of Health and the National Science Foundation.

Previous studies showed that a protein called PIN1 helps cancers initiate and progress, but its exact role in tumor development has remained unclear. Now, cancer biologists at the Salk Institute have discovered that PIN1 is a significant driver of bladder cancer and revealed that it works by triggering the synthesis of cholesterol — a membrane lipid essential for cancer cells to grow.

After mapping out the molecular pathway between PIN1 and cholesterol, the researchers developed an effective treatment regimen that largely halted tumor growth in their mouse model of cancer. The therapy consists of two drugs: a PIN1 inhibitor called sulfopin, an experimental drug not yet tested in humans, and simvastatin, a statin that is already used in humans for lowering cholesterol levels to reduce the risk of cardiovascular disease.

The findings were published in Cancer Discovery, a journal of the American Association for Cancer Research, on January 14, 2025.

“We’re excited to be the first to identify PIN1’s role in bladder cancer and to describe the mechanism it uses to drive tumor growth,” says senior author Tony Hunter, American Cancer Society professor and holder of the Renato Dulbecco Chair at Salk. “Given the high costs, morbidity, and mortality rates for bladder cancer, we’re especially thrilled to discover that targeting the cholesterol pathway with this therapeutic combination was so effective in suppressing bladder tumor growth in mice, and we hope to see this approach explored in a future clinical trial, once a PIN1 inhibitor is approved for clinical use.”

Bladder cancer is one of the most diagnosed cancers worldwide and the fourth most common cancer among men. It poses a serious threat to public health, as most cases result in either expensive, lifelong treatment, or rapid progression and mortality.

Hunter’s lab had originally discovered PIN1 in 1996 as a part of its work on phosphorylation, a process in which phosphate molecules are tacked onto proteins to change their structure and function. The lab showed that PIN1 is an enzyme that can recognize a protein when a phosphate is added to the amino acid serine while it’s next to the amino acid proline. PIN1 then changes that protein’s shape.

Phosphorylation of proteins at serine residues next to prolines is known to be a major signaling mechanism controlling cell proliferation and malignant transformation, and its dysregulation causes human cancers. PIN1 can target these phosphorylated areas and instigate structural and functional changes to the protein. Still, it’s been unclear exactly how this PIN1 activity contributes to tumor formation or which proteins PIN1 might be interacting with in bladder cancer cells.

In search of answers, the team compared normal human bladder cells with bladder cancercells, in culture dishes and implanted in mice.

First, they demonstrated that PIN1 expression was higher in bladder cancer cells — specifically in the specialized tissue layer that lines the inside of the urinary tract, called the urothelium. Then, they used genetic scissors to eliminate the PIN1 gene in the cancer cells. Without PIN1, they saw fewer cancerous cells develop, and those that did develop migrated less aggressively within and beyond the urothelium.

These findings indicated that PIN1 was contributing to the development of bladder cancer, but how?

The researchers returned to the cells that were missing PIN1 and looked to see if any other biological processes had been altered. Surprisingly, they found that one of the most affected pathways was the cholesterol synthesis pathway, mediated by a protein called SREBP2. Without PIN1, the bladder cells contained much lower levels of cholesterol.

“Cancer cells need a lot of cholesterol to accomplish their trademark excess growth,” says first author Xue Wang, a postdoctoral researcher in Hunter’s lab. “Our findings show that PIN1 plays an important role in cholesterol production, and removing it leads to lower cholesterol and therefore less out-of-control tumor growth.”

Through a series of experiments, the researchers confirmed that PIN1 was working with the SREBP2 protein to stimulate cholesterol production. Removing PIN1 effectively put a lid on the cancer’s fuel supply, but reinstating PIN1 reversed those anti-cancer effects. Without intervention, the high level of PIN1 in bladder cancer assists in tumor growth and metastasis.

How can we stop PIN1? One obvious answer is to inhibit the protein itself, but it’s also possible to inhibit an enzyme in the cholesterol pathway that PIN1 stimulates. One class of drugs, called statins, is already very widely used to control cholesterol levels. Statins work by blocking a protein in the cholesterol biosynthesis pathway called HMGCR. The idea was to attack the cholesterol pathway from two angles by combining simvastatin, a widely prescribed statin, to block HMGCR, and sulfopin to disable PIN1 and prevent its activation of SREBP2, thus drastically reducing the ability of the bladder cancer cells to make cholesterol.

When the researchers treated the mice with bladder cancer tumors with the PIN1 inhibitor sulfopin and the HMGCR inhibitor simvastatin, they found the combination suppressed cancer cell proliferation and tumor growth — importantly, the two worked better in tandem than as individual treatments.

“This is likely just one of many roles that PIN1 plays in cancers,” says Hunter. “What’s exciting about this discovery, though, is that statins are already in human use to prevent cardiovascular disease, and our work suggests an opportunity to use statins in combination with other drugs for bladder cancer therapy. And beyond this, we’ll continue to study whether PIN1 plays a similar role in other cancers, so our findings can hopefully improve lives regardless of cancer type.”

Not only did the team confirm PIN1’s role in bladder cancer progression, they also connected PIN1 to cholesterol biosynthesis and created viable treatment solutions to improve treatment outcomes.

Other authors include Yuan Sui and Jill Meisenhelder of Salk, Derrick Lee of UC San Diego, and Haibo Xu of Shenzhen University in China.

The work was supported by the National Institutes of Health (CCSG P30CA023100, CCSG CA014159, 5 R35 CA242443) and a Pioneer Fund Postdoctoral Scholar Award.

In gene therapy, a person’s faulty genes are either replaced or modified to treat or prevent disease. With roughly two dozen products on the market and hundreds of clinical trials in progress or planned, the treatment is hailed as a revolutionary method for targeting the root genetic causes of diseases ranging from sickle cell to cancer.

Some gene therapy treatments use modified adeno-associated viruses (AAVs) to deliver therapeutic genetic material into a patient’s cells. These AAVs are engineered to target specific cell types. Then their infectious genetic material is replaced with the therapeutic genetic material, and they are administered to the patient.

Correctly measuring AAV vectors, as they are called, is critical to their safety and efficacy.

In a recently released study, researchers at the National Institute of Standards and Technology, the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), and the U.S. Pharmacopeia (USP) recruited six industry labs in the United States and Europe to measure sample AAV vectors.

The labs were asked to quantify the concentration of genetic material and viral particles in the vectors. They used four measurement techniques and reported their results back to the study’s authors.

Of the four measurement methods deployed, polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) had the lowest accuracy and precision. By accuracy, researchers mean how close the measurement is to the correct value. Precision refers to whether the method produces consistently similar results.

PCR-ELISA’s imprecision led the study’s authors to conclude that the method had “poor reproducibility.” Its results could not be reliably replicated both within the same lab and at different labs.

The method “should not be used for quantitative [measurements of AAV vectors] without further method development and harmonization,” they added.

PCR-ELISA is actually two separate tools combined into one. PCR is used to quantify genetic material, and ELISA measures the proteins that make up the viral shell. Both tests have been around for decades, and there are dozens of versions of each currently sold on the market.

As a result, there are subtle but important differences in the ways PCR-ELISA is manufactured and used, NIST chemical engineer Wyatt N. Vreeland said. Everyone may think they are doing the same thing when conducting a PCR-ELISA test, he said, but they often aren’t.

“It’s like a recipe for the same chocolate cake,” said Vreeland, who was the principal investigator on the study. “You can give someone the same ingredients, but when you use different equipment to make them or bake them in different ovens, the cakes don’t turn out the same.”

Here’s what the study found about the other three methods:

• SEC-MALS (size exclusion chromatography with multi-angle light scattering and tandem UV/Vis and/or refractive index) was the most accurate and precise of the methods tested.
• SV-AUC (sedimentation velocity-analytical ultracentrifugation) with UV/Vis and/or Rayleigh interference optics was less accurate and precise than SEC-MALS, which surprised the researchers since SV-AUC is considered the “gold standard” for AAV vector measurement. However, SV-AUC was better than SEC-MALS in creating a detailed “map” of the distribution of the genetic and viral particles in the AAV vector. The study suggested that “SEC-MALS could be implemented as a general method with [SV-AUC] being used for more complete analysis as necessary.”
• A260/A280 dual wavelength ultraviolet spectrophotometry, which measures the absorption of ultraviolet light by a sample, has significant limitations compared with other methods. It cannot distinguish between partially filled or overfilled AAV vectors. Additionally, AAV protein particles are too large for the equipment to handle without producing errors. These issues with spectrophotometry are well documented, and the technique is generally not relied upon for highly accurate measurements.

The study did not draw conclusions about past, ongoing or future gene therapy research that relied upon these methods for measuring AAV vectors. It also did not make any policy or regulatory recommendations.

In future work, researchers at NIST, USP and NIIMBL, a NIST-supported public-private partnership to support biopharmaceutical manufacturing, plan to develop standard operating procedures (SOPs) for the SV-AUC. SOPs are a detailed, written set of instructions for a specific technology or methodology. The scientists believe having widely accepted SOPs for SV-AUC will improve its reproducibility performance to the same level as that of SEC-MALS, for which there are already SOPs.

“All the different methods we tested have their limitations and uncertainties,” said Vreeland. “What’s important is that you understand what your measurement technique can and cannot tell you.”

The study, led by Luiz Bertassoni, D.D.S., Ph.D., founding director of the Knight Cancer Precision Biofabrication Hub and a professor at the OHSU Knight Cancer Institute and the OHSU School of Dentistry, shows that perivascular cells sense changes in nearby tissues and send signals that disrupt blood vessel function, worsening disease progression.

Nearly a decade ago, Bertassoni and his team developed a method to 3D print blood vessels in the lab — a breakthrough recognized as one of the top scientific discoveries of the year by Discover magazine. Since then, they’ve focused on engineering blood vessels that better mimic those in the human body to study more complex diseases.

“Historically, endothelial cells lining blood vessels have been considered the main contributors of vascular disease,” Bertassoni said. “Our findings represent a paradigm shift, showing how perivascular cells, instead, act as important sentinels. They detect changes in tissues and coordinating vascular responses. This opens the door to entirely new treatment strategies.”

Cristiane Miranda Franca, D.D.S., Ph.D., the study’s lead author, is an assistant professor in the OHSU School of Dentistry and holds appointments with the OHSU Knight Cancer Precision Biofabrication Hub and Knight Cancer Institute’s Cancer Early Detection Advanced Research Center, or CEDAR.

“The applications of this research are wide,” she said. “We’ve shown for the first time how perivascular cells trigger inflammation and signal blood vessel changes when surrounding tissues are altered.”

The study used an innovative “blood vessel on-a-chip” model developed by Christopher Chen, M.D., Ph.D., and his team from Boston University and the Wyss Institute at Harvard, who are collaborators on this project. By replicating conditions like tissue stiffening and scarring — common in aging, chronic diseases and cancer — the researchers discovered that perivascular cells drive blood vessel leakage and distortion, worsening inflammation and disease.

Learn more: OHSU Knight Cancer Institute offers the latest treatments, technologies, hundreds of research studies and clinical trials

“When we removed perivascular cells, blood vessels essentially failed to respond to tissue changes,” Franca said.

The findings shed light on the relationship between the extracellular matrix, blood vessel function and disease progression. Perivascular cells could become targets for therapies aimed at restoring normal vascular function and reducing the progression of various diseases such as fibrosis, diabetes and cancer.

Importantly, the research also holds promise for cancer prevention and early intervention. Early detection and treatment of changes in these cells could help stop tumors before they grow.

“If we intervene early, we might prevent precancerous lesions from advancing to full-blown cancer,” Bertassoni said. “This could revolutionize how we approach cancer prevention and treatment.”

In addition to Bertassoni and Franca, OHSU co-authors include Maria Elisa Lima Verde, Ph.D., Alice Correa Silva-Sousa, D.D.S., Ph.D., Amin Mansoorifar, Ph.D., Avathamsa Athirasala, M.S., Ramesh Subbiah, Ph.D., Anthony Tahayeri, B.S., Mauricio Sousa, D.D.S., M.S., Ph.D., May Anny Fraga, D.D.S., M.S., Rahul Visalakshan, Ph.D., Aaron Doe, M.S., Keith Beadle, B.S., and McKenna Finley, B.A. Co-authors also include Emilios Dimitriadis, Ph.D., with the National Institute of Biomedical Imaging and Bioengineering; Jennifer Bays, Ph.D., and Marina Uroz, Ph.D., with Boston University; and Kenneth Yamada, M.D., Ph.D., with the National Institute of Dental and Craniofacial Research of the National Institutes of Health.

In this study, researchers aimed to understand how CAR T cells with different signaling domains work at the molecular and cellular levels to lay the foundation for designing CAR molecules that maximize antitumor activity beyond B cell malignancies.

“We looked at two different types of CAR T cells. The first, CD28.ζ-CART cells, are like sprinters. They kill cancer cells quickly and efficiently, but their activity is short-lived. The second, 4-1BB.ζ-CART cells, are like marathon runners. They kill cancer cells consistently over a long period,” said senior author Dr. Nabil Ahmed, professor of pediatrics — hematology and oncology at Baylor and Texas Children’s. “We need to understand what’s happening at the molecular level so we can engineer CAR T cells to adapt their killing behavior to target hard-to-treat malignancies, such as solid tumors.” Ahmed also is a member of the Center for Cell and Gene Therapy and the Dan L Duncan Comprehensive Cancer Center.

Led by first author Dr. Ahmed Gad, postdoctoral associate in Ahmed’s lab, the research team examined molecular dynamics at the immune synapse. The team biopsied the CAR T cell immunological synapse by isolating the membrane lipid rafts — cholesterol-rich molecules on the cell surface where most molecular interactions between cells take place.

They found that CD28.ζ-CAR molecules shuttle through the immune synapse quickly, working within minutes to kill cancer cells. This enabled fast CAR T cell recovery and a mastery of “serial killing” of cancer cells. In contrast, researchers found that 4-1BB.ζ-CAR molecules linger in the lipid rafts and immune synapse. The 4-1BB.ζ-CAR T cells multiply and work together, resulting in sustained “collaborative” killing of tumor cells.

“Observing the distinct pattern of dynamics between single molecules helps us understand the big picture of how these products work,” Gad said. “Next, we are studying how to dynamically adapt these CAR T cells at the synapse level to make them more effective.”

“Tumors are very sophisticated. We need to adapt our tools to the biology of the disease. This may involve using multiple tools that work in different ways at different stages,” Ahmed added.

Other authors who contributed to this work include Jessica S. Morris, Lea Godret-Miertschin, Melisa J. Montalvo, Sybrina S. Kerr, Harrison Berger, Jessica C.H. Lee, Amr M. Saadeldin, Mohammad Abu-Arja, Shuo Xu, Spyridoula Vasileiou, Rebecca M. Brock, Kristen Fousek, Mohamed F. Sheha, Madhuwanti Srinivasan, Yongshuai Li, Arash Saeedi, Kandice Levental, Ann M. Leen, Maksim Mamonkin, Alexandre Carisey, Navin Varadarajan, Meenakshi Hegde, Sujith K. Joseph, Ilya Levental and Malini Mukherjee. They are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children’s Hospital, Center for Cell and Gene Therapy, the Dan L Duncan Comprehensive Cancer Center, the University of Houston, and the University of Virginia.

This work was supported by the National Institutes of Health U54 Moonshot Grant, the National Cancer Institute, the Cancer Prevention and Research Institute of Texas, the Be Brooks Brave Fund St. Baldrick’s Foundation Fellowship, Stand Up To Cancer, the St. Baldrick’s Pediatric Cancer Dream Team Translational Research Grant, Triumph Over Kids Cancer Foundation, the Alex Moll Family Fund, and The Faris Foundation.

“Criteria for better identifying DLB exists in research settings, but we wanted to pull research studies together to establish something applicable for clinical settings,” says Ece Bayram, MD, PhD, assistant professor of neurology at the University of Colorado Anschutz Medical Campus and study lead author. “By pooling information from available publications, we were able to establish a cognitive profile that can differentiate DLB from Alzheimer’s before the dementia stage hits, which could better help inform the direction of care for people with these diseases.”

Researchers were able to identify consistencies in cognitive symptoms among people with DLB compared to people with Alzheimer’s in a meta-analysis of pre-dementia stage diagnoses. At the pre-dementia stage, people with DLB demonstrated more diminished attention, processing speed and executive function as well as better immediate recall and memory compared to people with Alzheimer’s.

“Identifying cognitive profiles gave us the outcome necessary to suggest guidelines that practitioners could easily be trained in to better tailor plans of care,” says Bayram. “Furthermore, providing framework for clinical assessment versus biomarker testing means more accessibility for practitioners. It is easier and cheaper to train in providing cognitive assessments than administering imaging or invasive biomarker tests,” says Bayram.

Researchers say identifying the form of dementia early can guide future planning for both the person with dementia and their care partners, and ease disease by providing proper symptomatic treatment. People with DLB, for instance, are reactive to certain types of commonly prescribed medications for psychosis, such as haloperidol, that tend to worsen their condition. Dr. Bayram says, overall, this study provides a promising step in advancing dementia prevention and care.

“We are seeing more and more treatment trials that are focused on disease modification for both Alzheimer’s and Lewy body diseases. Having validated clinical criteria to diagnose DLB before dementia hits means we can prevent it from happening instead of reacting to it after significant loss in the brain has occurred. These types of clinical assessments provide opportunities for everyone to receive care even without access to a specialty center.”

UC Riverside scientists have now discovered a chemical that plants produce when they’re stressed prevents biofilm from forming. The breakthrough offers potential advances in healthcare as well as preventing equipment corrosion in industrial settings.

“In simple terms, biofilms are communities of microorganisms, like bacteria or fungi, that stick together and form a protective layer on surfaces,” said Katayoon Dehesh, distinguished professor of molecular biochemistry at UCR, and corresponding author of a study about the discovery.

“You’ve probably seen them as the slimy layer on river rocks or the plaque on your teeth. While they’re a natural part of many ecosystems, biofilms can cause big problems.”

The study, published in the journal Nature Communications, highlights the importance of a particular metabolite, which is a molecule produced during life-sustaining chemical reactions inside plants, as well as bacteria and even some parasites, like the one that causes malaria.

In plants, this metabolite, MEcPP, plays a critical role not only in producing essential compounds but also in stress signaling. For example, when a plant is damaged in some way and too much oxygen enters its cells, it accumulates MEcPP. This molecule then triggers protective responses within the plant. The researchers discovered that this same molecule has a surprising effect on bacteria like E. coli: it disrupts biofilm development by interfering with its ability to attach to surfaces.

In medical settings, biofilms grow on devices like catheters, stents, or implants, making infections harder to treat because the microbes in biofilms are highly resistant to antibiotics. In industrial contexts, they clog pipes, contaminate food processing equipment, and cause corrosion.

“By preventing the early stages of biofilm development, this molecule offers real potential to improve outcomes in any industries reliant on clean surfaces,” Dehesh said.

Bacteria rely on hair-like structures called fimbriae to anchor themselves to surfaces, a critical step in biofilm initiation. Fimbriae help bacteria latch onto medical implants, pipes, or even teeth, where they secrete a protective matrix that shields them from antibiotics and cleaning agents. Without fimbriae, biofilm formation cannot begin.

“Biofilms are like fortresses for bacteria,” said Jingzhe Guo, UCR project scientist and first author of the paper. “By disrupting the initial phase of attachment, MEcPP essentially disarms the bacteria’s ability to establish these fortresses.”

Through genetic screenings of more than 9,000 bacterial mutants, the research team identified a key gene called fimE, which acts as an “off switch” for fimbriae production. MEcPP enhances the activity of this gene and increases the expression of fimE. This, in turn, prevents the bacteria from producing fimbriae and forming biofilms.

“Our discovery could inspire biofilm prevention strategies across a wide range of industries,” Guo said. “From cleaner water systems to better dental care products, the possibilities are immense.”

Biofilms are not only a medical concern but also a costly problem in industrial settings. They contribute to clogged pipelines, corroded machinery, and contamination in food processing facilities. Traditional methods for managing biofilms often rely on harsh chemicals or expensive treatments, which can be harmful to the environment or ineffective over time as bacteria adapt.

“This study is a testament to the unexpected connections between plant biology and microbiology,” Guo said. “It’s thrilling to think a molecule that plants use to signal stress might one day help humans combat bacterial threats.”

People who have limited access to air conditioning may be at higher risk of seeking emergency care for health problems following exposure to wildfire smoke, according to a new study led by Boston University School of Public Health (BUSPH).

Posted online ahead of publication in the journal Environmental Research: Health, the study found that exposure to fine particle matter (PM2.5) from wildfire smoke in California is associated with higher rates of emergency department visits for all causes, non-accidental causes, and respiratory disease. This risk varied by age and race, but was especially high for individuals who lived in areas with lower availability of air conditioning.

The findings come at a critical time, as firefighters in Southern California continue to battle multiple wildfires that have been blazing in and around Los Angeles County since Tuesday, January 7 — including the Palisades fire, which is likely the largest and most destructive wildfire in the county’s history. Health experts are urging residents who are not under evacuation orders and can safely remain in their homes to turn on air conditioners and/or air purifiers if they have access to these devices.

Despite this guidance — and the growing threat of more frequent and intense wildfires due to worsening climate change — very little research has examined how the health effects of wildfire smoke exposure may differ based on individuals’ access to air conditioning. Understanding this relationship can inform policies and interventions that mitigate barriers to air conditioners and protect vulnerable populations from the consequences of inhaling PM2.5 and other harmful pollutants from this smoke, which can permeate the air from hundreds or thousands of miles away.

“Depending on the type of system and filter used, air conditioning may modify the impact of smoke exposure on human health,” says study lead and corresponding author Dr. Jennifer Stowell, research scientist in climate and health at BUSPH, noting that the analysis only addressed the likelihood of access to air conditioning, rather than air conditioning types or actual usage. “Studies like these will become more and more relevant as wildfire exposure increases. California is, perhaps, the best example of this in the US, with bigger fires and longer fire seasons. An important next step will be to identify ways to better characterize access to air conditioning.”

For the study, Dr. Stowell and colleagues from BUSPH, Boston University College of Arts & Sciences (CAS), and the Health Effects Institute utilized a nationwide dataset of healthcare claims to assess more than 50,000 emergency department visits during the 2012-2019 California wildfire seasons, which occurred from May to November each year. They quantified the adverse health effects from PM2.5 exposure among all study participants, as well as subgroups of participants.

Consistent with prior research, wildfire smoke exposure was most strongly associated with emergency department visits for respiratory issues, but not cardiovascular-related complications. These visits were generally higher among children under 10 years old, adults between 20-74 years old, and among the Black population, although also elevated among White, Hispanic, and Asian/Pacific Islander populations.

People living in areas with lower availability of air conditioning had a 22-percent greater risk of visiting the emergency department for respiratory conditions associated with wildfire smoke exposure. Greater insight into air conditioning use as a pollutant-filtering tool and the barriers that certain populations face in accessing these cooling systems is critical, as wildfires are expected to occur more regularly in the Wildland-Urban Interface (WUI) — areas where human activity is in close contact with sources of dry fuel. This is exactly what is happening now in LA County, Dr. Stowell says, as the fires destroy thousands of homes and businesses near vegetation.

“WUI fires are particularly concerning due to the burning of human-made structures and the additional toxic chemicals and particulates that can be found in their smoke plume,” says Dr. Stowell. “The current fires in LA are out-of-season fires driven by severe Santa Ana winds coming from the mountains. As climate change continues, the temperature differentials between land and sea will grow and, potentially, drive stronger and stronger late-season or out-of-season wind events.”

So how may residential air conditioners help dispel PM2.5 from homes? The filters in these cooling systems can remove particulate matter, although certain filters are more effective at filtering particulate matter than others. “HEPA filters can remove the majority of particles greater than 0.3 µm, but they are significantly more expensive than fiberglass air filters, which only remove larger particles and may allow high amounts of fine particulate matter to penetrate indoors,” Dr. Stowell says. “Generic pleated air filters are also fairly efficient at filtering out most particulate matter.”

Air conditioning systems with a Minimum Efficiency Reporting Value (MERV) rating of seven or higher are thought to be the most efficient at removing particulate matter from outdoor air, but are also more expensive.

The study findings indicate a need for stronger policy measures that can reduce the health risks associated with wildfire smoke exposure.

“Many homeowners do not understand the differences between MERV ratings and how these might impact your health,” Dr. Stowell says. “Policymakers should consider delivering better information to the public — such as the types and ratings of filters that perform better — especially for those who reside in smoke-prone regions.”

Given that marginalized populations appear to be disproportionately burdened by the health effects of wildfire smoke exposure, economic assistance should also be considered, she says, particularly for low-income populations residing in smoke-prone regions. “Considering the current fires in CA, local and state governments should heighten their responses to these events and develop plans and policies to reduce exposure before the fires occur,” Dr. Stowell says.

The study’s senior author is Dr. Gregory Wellenius, professor of environmental health and director of the Center for Climate and Health at BUSPH. The study was coauthored by Dr. Ian Sue Wing, professor of earth and environment at CAS; Dr. Yasmin Romitti, staff scientist at the Health Effects Institute, and Dr. Patrick Kinney, Beverly Brown Professor of Urban Health at BUSPH.

Researchers have used computational approaches including AI to analyse the gut microbiome composition of over 12,000 people across 45 countries from their stool samples. They found that a person’s microbiome ‘signature’ can predict whether a person’s gut is likely to be colonised by Enterobacteriaceae. The results are consistent across different states of health and geographic locations.

The researchers identified 135 gut microbe species that are commonly found in the absence of Enterobacteriaceae, likely protecting against infection.

Notable amongst the protective gut species are a group of bacteria called Faecalibacterium, which produce beneficial compounds called short-chain fatty acids by breaking down fibre in the foods we eat. This seems to protect against infection by a range of disease-causing Enterobacteriaceae bugs.

The researchers suggest that eating more fibre in our diet will support the growth of good bacteria — and crowd out the bad ones to significantly reduce the risk of illness.

In contrast, taking probiotics — which don’t directly change the environment in the gut — is less likely to affect the likelihood of Enterobacteriaceae infection.

The results are published today in the journal Nature Microbiology.

“Our results suggest that what we eat is potentially very important in controlling the likelihood of infection with a range of bacteria, including E.coli and Klebsiella pneumoniae, because this changes our gut environment to make it more hostile to invaders,” said Dr Alexandre Almeida, a researcher at the University of Cambridge’s Department of Veterinary Medicine and senior author of the paper.

He added: “By eating fibre in foods like vegetables, beans and whole grains, we can provide the raw material for our gut bacteria to produce short chain fatty acids — compounds that can protect us from these pathogenic bugs.”

Klebsiella pneumonia can cause pneumonia, meningitis and other infections. The alarming global rise in antibiotic resistance to this bacterial pathogen has led scientists to look for new ways of keeping it, and other similar infectious bacteria, under control.

“With higher rates of antibiotic resistance there are fewer treatment options available to us. The best approach now is to prevent infections occurring in the first place, and we can do this by reducing the opportunities for these disease-causing bacteria to thrive in our gut,” said Almeida.

A new understanding of gut microbe interactions

Earlier research to understand interactions between the different bacteria in our gut has used mouse models. But some of these new results are at odds with previous findings.

The new study revealed that 172 species of gut microbe can coexist with disease-causing Enterobacteriaceae bugs. Many of these species are functionally similar to the bugs: they need the same nutrients to survive. Previously it was thought that competition for resources would stop the disease-causing bacteria from getting established in the gut.

This has important implications for treatment: taking probiotics that compete for the same nutrients with the bad bacteria to try and starve them out isn’t going to work. The researchers say that it will be more beneficial to change the environment in the gut, for instance through diet, to reduce the risk of infection with Enterobacteriaceae.

“This study highlights the importance of studying pathogens not as isolated entities, but in the context of their surrounding gut microbiome,” said Dr Qi Yin, a visiting researcher at the University of Cambridge’s Department of Veterinary Medicine and first author of the report.

The in-built safety mechanisms circumvent the possibility of an accidental self-infection with weakened mycobacteria, offering a safe and effective way to combat the disease that was named as the deadliest of 2024 by the World Health Organization.

“Although the idea of intravenous vaccination with a live vaccine may sound scary, it was very effective in our previous studies in non-human primates. Here, we focused on the safety aspect of IV vaccination and used a strain of mycobacteria that kills itself once administered to the animals. To our surprise, it was equal or slightly better than the regular TB vaccine in protecting monkeys against infection, providing sterilizing immunity in almost all animals,” said JoAnne Flynn, Ph.D., distinguished professor and chair of microbiology and molecular genetics at Pitt. “The live-attenuated form of the mycobacteria does not need to be alive for very long to provide outstanding protection and with this strain there is essentially no chance for a vaccine-derived infection, even in an immunocompromised host.”

Despite the ongoing global public health burden of TB, safe and effective protection strategies against the infection are lacking. Bacillus Calmette-Guérin (BCG) vaccine — named for its developers — contains inactivated mycobacteria that infect cattle and remains the only vaccination strategy against the infection in humans. Injected into the skin, it provides only partial protection against TB in young children and no protection in adults.

To develop a more universally effective vaccination approach, Flynn partnered with colleagues at Cornell University. In Flynn’s earlier work in macaque monkeys with collaborators at the National Institutes of Health, researchers saw a 100,000-fold reduction in bacterial burden in the lungs of animals who were given the BCG vaccine intravenously compared with the standard intradermal route. Nine out of 10 animals showed no inflammation in their lungs.

To improve the safety of IV BCG delivery in the new study, researchers engineered two built-in mechanisms that instruct the BCG particles to dissolve either upon exposure to the antibiotic doxycycline or when chronic doxycycline treatment is stopped. Mouse experiments showed that the BCG vaccine containing this dual safety switch protects the animals against TB comparable to a standard BCG vaccination but has the added benefit of faster elimination and safety, even for mice that were immunocompromised.

In macaque monkeys, the updated self-destructing BCG vaccine caused an even stronger immune response and better protection against TB than a standard IV BCG injection. None of the monkeys that received the updated BCG vaccine had any detectable level of lung inflammation eight weeks after being infected with live Mycobacterium tuberculosis. In addition, six out of eight monkeys had no traces of recoverable live M. tuberculosis compared to two out of eight monkeys that received the standard BCG intravenously.

Despite the additional challenges of clinical testing required for expanding the use of the updated BCG vaccine in humans, researchers are optimistic.

“We hope that this ‘kill switch’ BCG strain could limit safety concerns over intravenous vaccine administration and provide an option for a safer and more effective vaccination route for individuals who are immunocompromised,” Flynn said.

The other senior authors of this research are Dirk Schnappinger, Ph.D., and Sabine Ehrt, Ph.D. of Weill Cornell Medicine. Other authors of this research are Alexander Smith, Ph.D., Pauline Maiello, M.S., H. Jacob Borish, Ph.D., Caylin Winchell, Ph.D., Andrew Simonson, Ph.D., Philana Ling Lin, M.D., Mark Rodgers, M.S., Daniel Fillmore and Jennifer Sakal, all of Pitt; and Hongwei Su, Ph.D., Joshua Wallach, Yao Liu, Ph.D., Kan Lin, Ph.D., Valerie Vinette, Ph.D., all of Weill Cornell Medicine.

Oral cancer is an increasingly prevalent disease worldwide, with over 300,000 new cases diagnosed each year. Among oral cancers, tongue cancer (TC) is the most common type and often carries a poor prognosis. Surgery combined with chemoradiotherapy is one of the main lines of treatment for high-risk cases of TC. However, recurrence rates are high since the tumors can reestablish themselves from only a few surviving cells. A few surviving cells are referred to as minimal residual disease (MRD).

Understanding the mechanisms behind MRD formation is paramount to improving treatment outcomes in TC and many other forms of cancer. To study it, scientists often rely on cancer cell lines as preclinical models, which serve as a convenient tool to test drugs and analyze the roles of genes and proteins. However, cancer cell lines are quite difficult to establish from primary cancer tissues and do not accurately reflect cancer characteristics. This makes comparisons of tumor characteristics between patients challenging.

Against this backdrop, a research team led by Professor Toshiaki Ohteki from Institute of Science Tokyo, Japan, adopted a different approach to shed light on MRD in TC. Instead of trying to establish cancer cell lines, they built a large-scale library of tongue cancer organoids (TCOs) from surgery samples of 28 patients. Organoids are three-dimensional tissue models that mimic organs. As explained in their paper, which was published in Developmental Cell on November 5, 2024, the team sought to have this library accurately represent the diversity that exists in TC from patient to patient and use it to identify promising treatment avenues.

Organoids allow scientists to replicate the biology of cancer in a controlled lab setting. The team built the TCO library by obtaining tissue samples from 28 untreated patients with TC of different ages and stages of the disease. They used these organoids to conduct comprehensive and comparative analyses, such as functional, genetic/epigenetic, histopathologic characterization, and drug-sensitivity tests.

Their experiments revealed new insights into the mechanisms of chemoresistance, namely MRD formation. By treating the TCOs with cisplatin, a key drug in chemotherapy, the researchers found that chemo-resistant TCOs showed a dormant-like state that resembled embryonic diapause — a temporary pause that sometimes occurs during embryo development.

Taking a deeper look, the research team found that chemo-resistant TCOs rely on the activation of autophagy (or ‘internal recycling’) and cholesterol biosynthesis pathways to survive. “Inhibiting these pathways with specific inhibitors converted the chemo-resistant TCOs into chemo-sensitive TCOs. Conversely, autophagy activation with appropriate inhibitors conferred chemo-resistance on the chemo-sensitive TCOs,” highlights Ohteki, “Given that a comparative analysis of our unique TCO library provided insights into the molecular basis of MRD formation, this library may offer an important resource for discovering effective drug targets and biomarkers for chemo-resistant TC cells, thereby helping in the development of personalized medicine,” concludes Ohteki.

Intuition and past research suggest that whether people deem someone trustworthy depends on that person’s past behavior and reputation for betrayal. But now, new work from psychologists at UCLA and Oklahoma State University is helping to explain why people might nevertheless trust certain cheaters and other betrayers.

When we benefit from someone’s betrayal, we tend to still regard that person as inherently trustworthy, the psychologists reported in a study published in Evolution and Human Behavior. Their experiments found that, although subjects tended to regard people who betrayed others as generally less trustworthy, when a person’s betrayal benefited the subject, that person was still thought to be worthy of trust.

At question is the role concepts like “trustworthiness” play in our relationships. According to the research team, inferences about someone’s trustworthiness are used for making adaptive choices — that is, choices that benefit us. So, while people might be attuned to whether someone has betrayed others in the past, the researchers predicted that people would also be attuned to certain relationship-based factors that impact how that person is viewed/trusted.

“Making decisions about whom to trust based only on whether that person has betrayed someone else might not be the best way to determine whether or not I can trust someone,” said study co-author and UCLA professor of psychology Jaimie Krems.

“Sure, if someone betrays other people, that could be a valuable cue that they might betray me — but not always. For example, think about that friend who always tells you other friends’ secrets but doesn’t share yours. This friend is betraying other people but enriching you with information,” Krems added.

This was the researchers’ main contention: The mind should be attuned to whether someone has a reputation for betrayal, yes, but also to how someone’s betrayal affects you.

The researchers designed experiments to test whether people deemed targets more trustworthy when the targets avoided betrayal — but also when the betrayal had different impacts on the subject.

In one series of experiments, participants were randomly assigned to read one of three vignettes describing their interaction with a target. The first experiment involved sharing secrets among friends, while the second involved romantic infidelity. The third described an interaction in the context of international relations, with participants acting as CIA agents attempting to cultivate a French official as a source.

The targets exhibited one of three behaviors: they did not betray anyone when they had the opportunity; they betrayed another person to the participant or betrayed the participant to someone else. For example, some targets did not share a secret, others shared a secret about someone else with the participant, and still others shared the participant’s secret with a third party. After reading the vignettes, participants rated the target’s trustworthiness on a 7-point scale with questions such as, “I would trust the target to keep my secrets.”

As intuition would predict, across all types of relationships, participants regarded targets as more trustworthy if they did not betray anyone and less trustworthy if they did. But people who betrayed were not all deemed equally untrustworthy. When betrayal benefited the participants, they still considered the target trustworthy. This pattern was largely consistent across friendships, romantic relationships and professional relationships.

The findings upheld the researchers’ hypothesis that judgments of trustworthiness are partly a reflection of the person’s disposition and idiosyncratic factors specific to the participant and the person at hand.

The findings show that while people might start with lofty ideals when it comes to trusting people, what they do in practice is often based more on self-interest.

The research was funded by the National Science Foundation.

Key takeaways

• Both intuition and past research suggest that whether people deem someone trustworthy depends on that person’s past behavior and reputation for betrayal.
• In a series of experiments, psychologists found that subjects regarded those who previously exhibited that behavior as less trustworthy. However, when the betrayal benefited them or had no effect on them, participants regarded the betrayer as trustworthy.
• This pattern was largely consistent across the types of relationships studied: friendships, romantic relationships and professional relationships.

A new study from a University of Notre Dame expert on the future of work finds that robot use is associated with increased employment and employee retention, improved productivity and a higher quality of care. The research has important implications for the workplace and the long-term care industry.

Yong Suk Lee, associate professor of technology, economy and global affairs at Notre Dame’s Keough School of Global Affairs, was the lead author for the study, published in Labour Economics. Most studies of robots in the workplace have focused on manufacturing and the industrial sector, but Lee’s research broke new ground by analyzing long-term care — and by looking at the different types of robots used in this setting. Researchers drew on surveys of Japanese nursing homes taken in 2020 and 2022.

“Our research focused on Japan because it is a super-aging society that provides a good example of what the future could entail elsewhere — a declining population, a growing share of senior citizens and a declining share of working-age people,” Lee said. “We need to be ready for this new reality.”

In 2022, for instance, more than 57 million U.S. residents were 65 or older, according to the National Council on Aging. The Census Bureau forecasts that by 2050, this number will grow to 88.5 million.

The impact on workers

In a future where there are more senior citizens requiring care, using robots in a targeted fashion could benefit workers and patients alike, Lee said. The study analyzed three types of robots that are increasingly used in assisted living facilities:

• Transfer robots, which nurses use to lift, move and rotate patients in beds and around rooms.

• Mobility robots, which patients use to move around and to bathe.

• Monitoring and communication robots, which include technologies such as computer vision and bed sensors that can monitor patient data such as movement and share it with care providers.

“We found that robot adoption complements care workers by reducing quit rates,” Lee said. “This is important because turnover is a big concern in nursing homes. Workers typically experience a great deal of physical pain, particularly in their knees and back. The work is hard and the pay is low. So robot use was associated with employee retention.”

While robot use was associated with an overall employment increase, Lee said, the trend seems to have helped some workers more than others: It was associated with an increased demand for part-time, less experienced employees and with less demand for more experienced workers.

Improving patient care

Patients benefited in facilities that have used robots, according to the study. The nursing homes that Lee’s team studied reported a decrease in the use of patient restraints and in the pressure ulcers or bedsores that nursing home residents commonly suffer, largely because of a lack of mobility. Both metrics are widely used in the long-term care industry to measure patient outcomes, Lee said.

By removing the physical strain associated with certain tasks, Lee said, robots may have made room for care workers to focus on tasks better suited for human beings.

“Robots can improve productivity by shifting the tasks performed by care workers to those involving human touch, empathy and dexterity,” Lee said. “Ultimately, robots can help workers provide a higher level of patient care.”

“This research provides critical insights into how societies can successfully navigate the challenges of caring for aging populations”

The future of work

Lee co-authored the study with Toshiaki Iizuka from the University of Tokyo and Karen Eggleston from Stanford University. The study received funding from Stanford’s Shorenstein Asia-Pacific Research Center, Stanford’s Freeman Spogli Institute for International Studies Japan Fund and the Japan Society for the Promotion of Science, as well as the Keough School’s Liu Institute for Asia and Asian Studies and Kellogg Institute for International Studies.

This latest research fits into Lee’s ongoing work to examine how new technologies, including artificial intelligence and robotics, affect inequality and the future of work. Lee serves as program chair in technology ethics for the Institute for Ethics and the Common Good, a key element of the Notre Dame Ethics Initiative. He is also a faculty affiliate of the Keough School’s McKenna Center for Human Development and Global Business and a faculty fellow of the school’s Kellogg Institute for International Studies, Pulte Institute for Global Development and Liu Institute for Asia and Asian Studies.

“This research provides critical insights into how societies can successfully navigate the challenges of caring for aging populations,” Lee said. “It will help inform the work of the long-term care industry and help us better understand how technologies impact workers and patients.”

The same is now possible in gene editing. Rather than employ separate tools for editing genes and regulating their expression, these distinct goals can now be combined into a single tool that can simultaneously and independently address different genetic diseases in the same cell.

Merging Gene Editing and Regulation

In a new paper in Nature Communications, researchers in the Center for Precision Engineering for Health (CPE4H) at the University of Pennsylvania School of Engineering and Applied Science (Penn Engineering) describe minimal versatile genetic perturbation technology (mvGPT).

Capable of precisely editing genes, activating gene expression and repressing genes all at the same time, the technology opens new doors to treating genetic diseases and investigating the fundamental mechanisms of how our DNA functions.

“Not all genetic diseases are solely caused by errors in the genetic code itself,” says Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and in Bioengineering (BE) and the paper’s senior author. “In some cases, diseases with genetic components — like type I diabetes — are due to how much or little certain genes are expressed.”

One Tool, Multiple Functions

In the past, addressing multiple, unrelated genetic abnormalities at once — by, say, editing one gene and suppressing another — would have required multiple distinct tools. “We wanted to build a single platform that could precisely and efficiently edit DNA as well as upregulate and downregulate gene expression,” says Tyler Daniel, a doctoral student in the Gao Lab and one of the paper’s co-first authors.

The platform works by combining an improved “Prime Editor,” capable of modifying DNA sequences, with previously invented technologies for increasing and decreasing the expression of genes. “All these functions are orthogonal,” says Daniel. “They can happen independently of each other at the same time.”

“This level of precision for modifying DNA sequences and gene expression was not previously possible,” he continues. “Each task functions independently. It’s as if we took a car with a faulty navigation system and fixed the bug in that system while simultaneously turning up the volume on the stereo and turning down the air conditioning.”

The Power of Precision Editing

The team tested mvGPT on human liver cells with a mutation causing Wilson’s disease, successfully editing out the mutation while also upregulating a gene linked to type I diabetes treatment and suppressing another associated with transthyretin amyloidosis. In multiple tests, mvGPT achieved all three tasks with high precision, demonstrating its ability to target multiple genetic conditions simultaneously.

Because mvGPT takes up less space than three separate tools, the system is also easier to transport into cells. The researchers showed that mvGPT can be delivered by multiple means, including strands of mRNA and viruses used to deliver genetic editing tools.

“When you have a single tool that can accomplish all of these things at the same time,” says Gao, “you make the process so much simpler, because there’s less machinery you have to deliver to the cell.”

Moving Towards a Greater Impact

Now that the technology has shown promise in human cells, the researchers plan to test mvGPT in animal models, and against other diseases with genetic components, including cardiovascular diseases. “The more advanced our tools become,” continues Gao, “the more we can do to treat genetic diseases.”

This study was conducted at the University of Pennsylvania School of Engineering and Applied Science and supported by the National Science Foundation (CBET-2143626) and the National Institutes of Health (HL157714).

Additional co-authors include co-first authors Qichen Yuan and Hongzhi Zeng of Rice University; Emmanuel C. Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M. Abramson and Boyang Zhang, also of Rice University; and Qingzhuo Liu, Yongjie Yang and Yong Xu of Baylor College of Medicine.

A research team co-led by Prof. Dr. Claudine Kraft from the CIBSS Cluster of Excellence at the University of Freiburg and Dr. Florian Wilfling from the Max Planck Institute of Biophysics in Frankfurt has now discovered the conditions necessary for autophagy to start. They were also able to artificially create these conditions and thus trigger the degradation of otherwise non-degradable molecules in yeast cells. Targeting autophagy in this way is a promising approach for promoting the degradation of aggregates that can otherwise form plaques in neurodegenerative diseases such as Alzheimer’s, as well as to improve the efficacy of cancer treatments. The study has been published in the scientific journal Nature Cell Biology.

Weak molecular interactions essential for autophagy to begin

In order for the degradation of cellular components through autophagy to occur, they must first be recognised as waste. This is done by receptor and other adapter molecules. However, it was previously unknown how exactly these molecules trigger the subsequent steps. “We have now been able to show that the receptors must bind weakly to the material to be disposed of for autophagy to start,” explains Kraft. “If they bind too strongly, the process is not triggered.”

What initially sounds counterintuitive could be explained by the researchers with the help of computer simulations and experiments on living yeast cells and human cells in cell culture: the weak binding causes the receptors to remain mobile and form random clusters. “When the point of critical concentration has been reached, phase separation occurs: the adapter molecules come together and form a droplet, similar to oil in water,” explains Wilfling. “Such a liquid accumulation has different physical properties than the individual molecules serving as a flexible platform for all other molecules involved in autophagy.”

The process can be controlled artificially

To test their hypothesis, the researchers introduced virus particles into yeast cells that the cells are normally unable to break down. By modifying the virus particles so that autophagy receptors could weakly bind to them, the researchers were able to trigger the degradation of the viral protein. However, if they modified the surface so that the receptors bound strongly to it, no degradation took place. “This result is promising because it shows that we can specifically intervene in the autophagy of cargo molecules of living cells,” summarise both Kraft and Wilfling.

The study was funded by the German Research Foundation (EXC-2189; SFB 1381; SFB 1177; 450216812; 409673687; GRK 2606;) by the European Research Council under the Horizon 2020 programme (ERC 769065), the Max Planck Society and by the European Union (ERC 101041982).

A recent study analyzing data from the National Survey on Drug Use and Health (NSDUH) found that past-year recreational ketamine use among adults has increased dramatically since 2015, including significant shifts in associations with depression and sociodemographic characteristics such as race, age and education status. Ketamine use has shown promise in clinical trials therapy for several mental illnesses, including treatment-resistant depression, and the new research suggests that ongoing monitoring of recreational use trends is crucial to balancing these clinical benefits against the risk of unmonitored recreational use.

Previously, early pregnancy care was provided through separate appointments for ultrasound, risk assessment and patient education. This new integrated approach allows patients who are under 14 weeks pregnant to receive comprehensive care during a single visit. This includes ultrasound-based pregnancy dating, immediate assessment of pregnancy viability, risk evaluation and on-site counseling — all based on real-time ultrasound results.

“Our study demonstrates that the use of point-of-care ultrasound provides meaningful benefit to the patients we serve by addressing early pregnancy problems at the time they are identified,” said Allison Newman, MD, an assistant professor at the U of M Medical School and family medicine physician with M Health Fairview. “POCUS in early pregnancy helps clinicians more efficiently and accurately diagnose problems without compromising the quality of needed first trimester assessments — saving time, money and stress for patients.”

The research team introduced this integrated approach at M Health Fairview Clinic — Bethesda in fall 2022, allowing the clinic to quickly identify high-risk cases and offer timely intervention for issues such as miscarriage or abnormal pregnancies. They found:

• The clinic saw an 81% reduction in emergency visits, urgent clinic appointments and first-trimester phone inquiries for non-miscarrying patients.
• Clinic implementation led to more timely diagnosis of abnormal pregnancies and improved education and support for all patients, including those who experience miscarriage.
• For miscarriage cases, the time from initial concern to diagnosis decreased from an average of 5.8 days to 1.7 days.

Suggested next steps include rolling out the process more widely within other family medicine practices and performing a wider study across multiple sites.

“Glucarpidase is unique because it’s one of the very few potential antidotes available to counteract the high rates of toxicity caused by chemotherapy,” said first author Shruti Gupta, MD, an associate physician in the Division of Renal Medicine at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system. Gupta is also the director of Onconephrology at BWH and Dana-Farber Cancer Institute. “Even though glucarpidase was approved by the FDA in 2012, our study is the first to provide a comprehensive assessment of its potential clinical benefits.”

Due to its ability to penetrate the blood-brain barrier, MTX is one of the most common chemotherapeutic agents used worldwide for cancers involving the central nervous system. However, high doses of MTX (defined as doses ≥ 500 g/m²) often cause severe complications such as AKI, liver toxicity, and neutropenia (i.e., low white blood cell count). Glucarpidase converts MTX in the blood into inactive metabolites within 15 minutes of its administration. Despite its potent biochemical effects, no study has examined whether these effects translate into clinical benefit. Due to this evidence gap, there is widespread variation in the use of glucarpidase.

The study, funded by BTG International Inc., a SERB Pharmaceuticals Company, addresses this knowledge gap. The researchers used detailed data from multiple cancer centers to mimic the conditions of a randomized clinical trial — a research method known as a target trial emulation. This approach can estimate the outcomes of a full clinical trial without the costs, timescale, and biases inherent in clinical trials, especially for relatively rare events in a specific patient population.

“Target trial emulation is a way to effectively analyze real-world data and to draw causal inferences from it, especially when clinical trials are unavailable and would be impractical to perform,” said senior author David E. Leaf, MD, director of clinical and translational research in acute kidney injury at BWH’s Division of Renal Medicine. “We worked with dozens of our collaborators across 28 sites to extract granular data from medical records — all by manual chart review — which allowed us to account for key variables in our models. This allowed us to have a high degree of confidence in our findings.”

The authors evaluated data collected between 2000 and 2022 from 708 patients with MTX-induced AKI, including 209 who received glucarpidase within four days following MTX exposure and 499 who did not. They compared kidney recovery for the two groups at the time of hospital discharge, based on changes in serum creatinine levels. The investigators also examined the speed of kidney recovery as well as the incidence of other adverse events, such as liver toxicity and neutropenia.

The analysis revealed that glucarpidase treatment was associated with a 2.7-fold increase in the chances of kidney recovery compared with no glucarpidase. Patients who received glucarpidase also had faster kidney recovery and a lower risk of severe neutropenia or liver toxicity compared to those who did not receive it.

The authors hope that their findings will encourage doctors to use glucarpidase for patients with kidney toxicity from MTX.

“FDA approval is only the first step. If people aren’t using the drug, then patients aren’t benefiting from it,” said Leaf. “Our findings offer clinicians evidence-based data supporting glucarpidase.”

Authorship: In addition to Gupta and Leaf, Mass General Brigham authors include Sarah A. Kaunfer, Shobana Krishnamurthy, Rafia Ali, Osman A. Yilmam, Sophia L. Wells, Jessica L. Ortega, Olivia L. Green-Lingren, Jian Ni, and Meghan E. Sise.

In the elderly, however, excessive filtration cannot be detected due to age-related GFR decline. To accurately assess GFR, Osaka Metropolitan University researchers have come up with a new calculation method.

The group led by Dr. Akihiro Tsuda, a lecturer at the Graduate School of Medicine, assessed 180 kidney transplant donor candidates to define a new formula for determining the threshold value for hyperfiltration based on age and GFR values.

Among other findings, the conventional method of correcting for body surface area in obese patients was determined to be inaccurate as excessive filtration cannot be detected. The researchers suggest calculating GFR without the correction but by taking into account the decline in the filtration rate due to aging.

“Since hyperfiltration is a precursor to diabetic nephropathy, we hope that using this new formula will more accurately diagnose the condition, leading to early detection and treatment,” stated Dr. Tsuda.

The findings were published in Hypertension Research.

Metastases are the dangerous offshoots of tumors that spread to vital organs such as the liver, lungs or brain and are usually difficult to treat. Even though the prognosis for breast cancer patients has improved significantly in recent decades, metastatic breast cancer still poses a major challenge, as the metastases often only respond temporarily to treatment.

Breast cancer metastases are initiated by cancer cells that detach from the primary tumor and migrate to other organs via the bloodstream. These circulating cancer cells (CTCs) are extremely rare and hide among the billions of blood cells. Andreas Trumpp, Head of a research division at the DKFZ and Director of HI-STEM, had already demonstrated several years ago that only a few of the circulating tumor cells are capable of forming a new metastasis in another organ. These mostly therapy-resistant “germ cells” of metastases are very rare, difficult to isolate and could not be multiplied in the laboratory until now. “This makes it difficult to develop targeted new therapies that directly attack the metastasis-initiating cells. However, if we understand how these cells survive the initial therapy and what drives their resistance, we could tackle the formation of breast cancer metastases at the root and perhaps one day even prevent them,” explains the first author of the paper, Roberto Würth from Trumpp’s lab.

Andreas Trumpp’s team has succeeded for the first time in multiplying CTCs from blood samples of breast cancer patients and growing them as stable tumor organoids in the culture dish. Until now, this always required a detour, namely the complex and lengthy propagation of CTCs in immunodeficient mice. In order to understand how tumor cells become resistant to therapies, researchers need tumor material from different time points in the course of the disease. In contrast to surgical removal of tissue samples (biopsies), blood samples are simple and can be taken several times.

The three-dimensional and patient-specific mini-tumors can be cultivated from blood samples several times during the course of the disease and are ideally suited for investigating the molecular mechanisms that enable tumors to survive despite therapy. Preclinical tests on the efficacy of already available cancer drugs can also be carried out quickly and on a large scale on organoids in the culture dish.

In the clinical registry trial CATCH at the NCT Heidelberg, the genetic diversity of patients’ breast cancer cells is analyzed. Thanks to the successful cultivation of the organoids, Trumpp’s interdisciplinary research team, in close collaboration with the experts of the CATCH trial, was able to identify a key signaling pathway that ensures the growth and survival of breast cancer CTCs in the blood. The protein NRG1 (neuregulin 1) acts like a vital “fuel.” It binds to the HER3 receptor on the cancer cells and, together with the HER2 receptor, activates signaling pathways that ensure the growth and survival of the cells. What is also exciting is that even if this fuel runs out or the receptors are blocked by drugs, the cells find new tricks. An alternative signaling pathway, controlled by FGFR1 (fibroblast growth factor receptor 1), steps in and ensures growth and survival.

“With the help of such ‘bypasses’, tumors react to external influences, for example to targeted therapies against HER2. This is a crucial mechanism in the development of therapy resistance,” explains Roberto Würth. But there are ways out: the researchers used organoids to show that a combined blockade of both signaling pathways (NRG1-HER2/3 and FGFR) can effectively stop the proliferation of tumor cells and induce cell death.

Andreas Trumpp summarizes: “The possibility of cultivating CTCs from the blood of breast cancer patients as tumor organoids in the laboratory at different time points is a decisive breakthrough. This makes it much easier to investigate how tumor cells become resistant to therapies. On this basis, we can develop new treatments that may also specifically kill resistant tumor cells. Another conceivable approach is to adapt existing therapies in such a way that the development of resistance and metastases is reduced or even prevented from the outset. As the organoids are specific to each patient, this method is suitable for identifying or developing customized therapies that are optimally tailored to the respective diseases.” Before the method can be used to treat breast cancer patients, it must first be tested in clinical trials.

*The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH was founded in 2008 as a public-private partnership between the DKFZ and the Dietmar Hopp Foundation

** The National Center for Tumor Diseases (NCT) Heidelberg is a long-term cooperation between the German Cancer Research Center, the University Hospital and the University of Heidelberg.

“We often assume that mutations in cancer genes are bad news, but that’s not the whole story,” says lead researcher Francesca Ciccarelli, Professor of Cancer Genomics at Queen Mary University of London’s Barts Cancer Institute and Principal Group Leader at the Francis Crick Institute, where the experimental work in this study took place. “The context is crucial. These results support a paradigm shift in how we think about the effect of mutations in cancer.”

This research was funded by Cancer Research UK and the experimental work in this study took place at the Francis Crick Institute.

A new understanding of oesophageal cancer risk

Just 12% of patients with oesophageal cancer in England survive their disease for 10 years or more. The UK has one of the world’s highest incidences of a subtype called oesophageal adenocarcinoma, and cases continue to increase. This cancer type develops from a condition called Barrett’s oesophagus, in which the cells lining the oesophagus become abnormal. However, only around 1% of people with Barrett’s go on to develop cancer each year. In the new study, the research team sought to better understand why some cases of Barrett’s lead to cancer, while others do not, to support better prediction and treatment of oesophageal adenocarcinoma.

The team analysed a large gene sequencing dataset from more than 1,000 people with oesophageal adenocarcinoma and more than 350 people with Barrett’s oesophagus, including samples from the OCCAMS consortium*. They found that defects in a gene called CDKN2A were more common in people with Barrett’s oesophagus who never progressed to cancer. This finding was unexpected, as CDKN2A is commonly lost in various cancers and is well-known as a tumour suppressor gene — a molecular safeguard that stops cancer from forming.

The research showed that if normal cells in our oesophagus lose CDKN2A, it helps promote the development of Barrett’s oesophagus. However, it also protects cells against the loss of another key gene encoding p53 — a critical tumour suppressor often dubbed the ‘guardian of the genome’. Loss of p53 strongly drives the progression of disease from Barrett’s to cancer.

The team found that potentially cancerous cells that lost both CDKN2A and p53 were weakened and unable to compete with other cells around them, preventing cancer from taking root. In contrast, if cancer cells lose CDKN2A after the disease has had time to develop, it promotes a more aggressive disease and worse outcomes for patients.

A gene with two faces

Professor Ciccarelli likens the dual role of CDKN2A to the ancient Roman god of transitions Janus, after whom January is named. Janus has two faces — one looking to the past and one to the future.

“It can be tempting to look at cancer mutations as good or bad, black or white. But like Janus, they can have multiple faces — a dual nature,” she explains. “We’re increasingly learning that we all accumulate mutations as an inevitable part of aging. Our findings challenge the simplistic perception that these mutations are ticking time bombs and show that, in some cases, they can even be protective.”

The findings could have significant implications for how we assess cancer risk. They suggest that if a person with Barrett’s oesophagus has an early CDKN2A mutation but no mutations in p53, it could indicate that their condition is less likely to progress to cancer. On the other hand, later in the disease, CDKN2A mutations may signal a poor prognosis. Further research is needed to determine how to best apply this new knowledge to benefit patients in the clinic.

Science Engagement Manager at Cancer Research UK, Dr Nisharnthi Duggan, said: “Survival for oesophageal cancer has improved since the 1970s, but it’s still one of the most challenging cancers to treat. This is largely because it’s often diagnosed at advanced stages, when treatments are less likely to be successful.

“Funding research like this is critical to advancing our understanding and improving outcomes for people affected by the disease. It shows the importance of discovery science in unravelling the complexities of cancer, so we can identify new ways to prevent, detect and treat it.”

Tuberculosis (TB), one of the leading infectious killers in Brazil and other low- and middle-income countries, is closely linked to poverty. “We know that TB is driven by poverty, but until now, the effects of cash transfers on disease outcomes among the most vulnerable populations had not been fully analysed,” says the coordinator of the study, Davide Rasella, head of the Health Impact Assessment and Evaluation group at ISGlobal and collaborating professor of the Institute of Collective Health.

Rasella and his colleagues in Brazil analysed data, including ethnic and socioeconomic conditions, from 54.5 million low-income Brazilians between 2004 and 2015. They compared TB incidence (number of new cases), mortality (number of deaths in the population) and case fatality rate (how many people who have the disease die) among people who received BFP support (23.9 million) or not (30.6 million). In total, there were 159,777 new TB diagnoses and 7,993 TB deaths in the cohort under study.

Stronger effects among indigenous and extremely poor people

The results show a large decrease in TB cases and deaths among those benefiting from cash transfers. The decrease was of over 50% in extremely poor people and more than 60% among the indigenous populations. Although the program reduced TB cases across all groups, its effect was smaller in those who were less poor, and there was no significant reduction in TB deaths in that group. The TB case fatality rate (i.e. how deadly the disease is in those affected) was also lower among Bolsa Família beneficiaries compared to non-beneficiaries, although the difference between the two groups was not statistically significant.

The reason behind the BFP’s effect on TB outcomes is not a mystery. “We know that the program improves access to food, both in quantity and quality, which reduces food insecurity and malnutrition- a major risk factor for TB- and strengthens people’s immune defences as a result. It also reduces barriers to accessing healthcare,” says Gabriela Jesus, co-first author of the study along with Priscila Pinto, both from FIOCRUZ.

Global implications

Expanding the BFP can help Brazil address the worrying increase in TB cases among vulnerable populations following the COVID-19 pandemic. But the implications of these findings extend beyond Brazil.

“Our study has far-reaching implications for policy-making in all countries with a high burden of TB,” says Rasella. The message is clear: social protection programmes not only help reduce poverty and malnutrition, but can also play a crucial role in achieving the targets of the END-TB strategy and those of the Sustainable Development Goals.

Researchers from the UK and China drew this conclusion after studying proteins from blood samples taken from over 42,000 adults recruited to the UK Biobank. Their findings are published today in the journal Nature Human Behaviour.

Social relationships play an important role in our wellbeing. Evidence increasingly demonstrates that both social isolation and loneliness are linked to poorer health and an early death. Despite this evidence, however, the underlying mechanisms through which social relationships impact health remain elusive.

One way to explore biological mechanisms is to look at proteins circulating in the blood. Proteins are molecules produced by our genes and are essential for helping our bodies function properly. They can also serve as useful drug targets, allowing researchers to develop new treatments to tackle diseases.

A team led by scientists at the University of Cambridge, UK, and Fudan University, China, examined the ‘proteomes’ — the suite of proteins — in blood samples donated by over 42,000 adults aged 40-69 years who are taking part in the UK Biobank. This allowed them to see which proteins were present in higher levels among people who were socially isolated or lonely, and how these proteins were connected to poorer health.

The team calculated social isolation and loneliness scores for individuals. Social isolation is an objective measure based on, for example, whether someone lives alone, how frequently they have contact with others socially, and whether they take part in social activities. Loneliness, on the other hand, is a subjective measure based on whether an individual feels lonely.

When they analysed the proteomes and adjusted for factors such as age, sex and socioeconomic background, the team found 175 proteins associated with social isolation and 26 proteins associated with loneliness (though there was substantial overlap, with approximately 85% of the proteins associated with loneliness being shared with social isolation). Many of these proteins are produced in response to inflammation, viral infection and as part of our immune responses, as well as having been linked to cardiovascular disease, type 2 diabetes, stroke, and early death.

The team then used a statistical technique known as Mendelian randomization to explore the causal relationship between social isolation and loneliness on the one hand, and proteins on the other. Using this approach, they identified five proteins whose abundance was caused by loneliness.

Dr Chun Shen from the Department of Clinical Neurosciences at the University of Cambridge and the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, said: “We know that social isolation and loneliness are linked to poorer health, but we’ve never understood why. Our work has highlighted a number of proteins that appear to play a key role in this relationship, with levels of some proteins in particular increasing as a direct consequence of loneliness.

Professor Jianfeng Feng from the University of Warwick said: “There are more than 100,000 proteins and many of their variants in the human body. AI and high throughput proteomics can help us pinpoint some key proteins in prevention, diagnosis, treatment and prognosis in many human diseases and revolutionise the traditional view of human health.

“The proteins we’ve identified give us clues to the biology underpinning poor health among people who are socially isolated or lonely, highlighting why social relationships play such an important part in keeping us healthy.”

One of the proteins produced in higher levels as a result of loneliness was ADM. Previous studies have shown that this protein plays a role in responding to stress and in regulating stress hormones and social hormones such as oxytocin — the so-called ‘love hormone’ — which can reduce stress and improve mood.

The team found a strong association between ADM and the volume of the insula, a brain hub for interoception, our ability to sense what’s happening inside our body — the greater the ADM levels, the smaller the volume of this region. Higher ADM levels were also linked to lower volume of the left caudate, a region involved in emotional, reward, and social processes. In addition, higher levels of ADM were linked to increased risk of early death.

Another of the proteins, ASGR1, is associated with higher cholesterol and an increased risk of cardiovascular disease, while other identified proteins play roles in the development of insulin resistance, atherosclerosis (‘furring’ of the arteries) and cancer progression, for example.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “These findings drive home the importance of social contact in keeping us well. More and more people of all ages are reporting feeling lonely. That’s why the World Health Organization has described social isolation and loneliness as a ‘global public health concern’. We need to find ways to tackle this growing problem and keep people connected to help them stay healthy.”

The research was supported by the National Natural Sciences Foundation of China, China Postdoctoral Science Foundation, Shanghai Rising-Star Program, National Key R&D Program of China, Shanghai Municipal Science and Technology Major Project, 111 Project, Shanghai Center for Brain Science and Brain-Inspired Technology, and Zhangjiang Lab.

After its discovery, which revolutionized oncology and earned a 2018 Nobel Prize, researchers developed new drugs to block PD-1 and unleash the body’s immune system to fight cancer. Yet treatments leveraging PD-1 are only effective in a small fraction of cancer patients, highlighting the need for a deeper understanding of how PD-1 works. Much of our current knowledge of PD-1’s functions comes from studies in mice, grounded on the assumption that rodent and human biology operate similarly.

Researchers in UC San Diego’s School of Biological Sciences and School of Medicine have now discovered that this assumption may be flawed. In a comprehensive assessment of PD-1 that featured novel biochemical analyses, animal modeling and a new evolutionary roadmap tracing PD-1 back millions of years, the UC San Diego scientists and their colleagues at the Chinese Academy of Sciences found that PD-1 in mice is significantly weaker than the human version.

The study, led by assistant project scientist Takeya Masubuchi, revealed several previously unknown PD-1 characteristics, including a “motif” — a specific sequence of amino acids — that is vastly different in rodents and humans.

“Our work uncovers unexpected species-specific features of PD-1 with implications for developing better pre-clinical models for PD-1,” said Associate Professor Enfu Hui of the School of Biological Sciences, Department of Cell and Developmental Biology, and a senior author of the paper. “We found a motif in PD-1 that’s present in most mammals, including humans, but is surprisingly missing in rodents, making rodent PD-1 uniquely weaker.”

The results of the study are published January 3, 2025, in the journal Science Immunology.

“Although many proteins in mice and humans have similar sequences, receptors in the immune system often show greater differences,” said Masubuchi. “Our study shows that these sequence differences can lead to functional variations of immune checkpoint receptors across species.”

Furthering their analysis, the researchers tested the impact of PD-1 humanization in mice — replacing mouse PD-1 with the human version — through co-senior author Professor Jack Bui’s laboratory in the Department of Pathology. They found that PD-1 humanization disrupted the ability of immune cells (T cells) to combat tumors.

“This study shows that as science progresses we need to have a rigorous understanding of the model systems that we use to develop medicines and drugs,” said Bui. “Finding that rodents might be outliers in terms of PD-1 activity forces us to rethink how to deploy medicines to people. If we’ve been testing medicines in rodents and they’re really outliers, we might need better model systems.”

To trace the PD-1 human-rodent differences over time, the researchers collaborated with co-senior author Professor Zhengting Zou and his Chinese Academy of Sciences colleagues. They discovered evidence of a major dip in ancestral rodent PD-1 activity around 66 million years ago after the Cretaceous-Paleogene (K-Pg) mass extinction event, which wiped out the (non-avian) dinosaurs. The analysis showed that the rodent PD-1 is uniquely weak among all vertebrates. The weakening may be attributed to special ecological adaptations to escape the effects of rodent-specific pathogens.

“The rodent ancestors survived the extinction event but their immune receptor activities or landscape might have been altered as a consequence of adaptation to new environmental challenges,” said Hui.

Future studies will assess the impact of PD-1 on the anti-tumor activity of T cells in a humanized context across various tumor types.

Background

Clozapine is currently the only antipsychotic drug approved by the Food and Drug Administration (FDA) of the United States for treatment-resistant schizophrenia. It is widely known for its high efficacy in reducing symptoms, relapse rate, and all-cause mortality in schizophrenia and is widely regarded as a drug of last resort. Recent Finnish and American studies suggested that clozapine may be associated with a significantly increased risk of blood cancer. However, owing to data restrictions and study design, the additional number of blood cancer cases associated with prior clozapine exposure could not be estimated and remained unclear. The clinical significance of this risk, therefore, had yet to be determined.

Research methods and findings

The research team utilised territory-wide electronic health records from the Hospital Authority of Hong Kong to comb through 400,000 patient records to construct a retrospective cohort of approximately 10,000 patients diagnosed with schizophrenia between 2001 and 2022 and followed up for a median of seven years since their drug initiation. The team’s observations of the patients showed the following:

• The absolute risk of blood cancer is very rare: In the cohort of 10,000 patients followed over a period of about seven years, only 39 developed blood cancer. After statistical adjustment, the study estimated that there were fewer than six cases of blood cancer per 10,000 patients using clozapine for one year.
• Consistent with Western studies: The weighted incidence rate ratio of blood cancer in clozapine users versus controls was estimated at 2.22, suggesting that there is a slight association. This observation is consistent with the findings of previous Finnish and American case-control studies.
• No risk for other cancers: No association was observed for other cancer types.

Significance of the study

‘In response to Western studies suggesting a potential risk of blood cancer after clozapine use, this study provides reliable evidence for patients and healthcare professionals supporting the safety of the drug. The current blood monitoring measures are very comprehensive. Patients do not need to be overly concerned about the risk of blood cancer caused by clozapine given the rarity of its occurrence demonstrated in this study. Clinicians should weigh the risks and benefits of the drug, taking into account the rarity of the association between clozapine and blood cancer, and make appropriate arrangements according to patients’ needs,’ said Professor Francisco Lai Tsz-tsun, the project leader and Assistant Professor in both the Department of Pharmacology and Pharmacy and the Department of Family Medicine and Primary Care under the School of Clinical Medicine of HKUMed.

‘Because of the readily linked and longitudinally available data across all public healthcare facilities in Hong Kong, we were able to come up with a better study design than those in other countries,’ said Professor Lai. ‘This enabled us to make immediate use of big data to better address clinically meaningful healthcare issues than researchers in many other countries, highlighting the key strengths of Hong Kong’s healthcare big data and its potential application in drug safety monitoring.’

The research team is currently re-examining a wide range of potential adverse effects of other psychotropic drugs, especially cancer risks, and their overall long-term safety and effectiveness. ‘Ultimately, through our joint interdisciplinary efforts, we hope to better inform day-to-day clinical decisions and make medication use in patients with mental illness much safer and more effective,’ Professor Lai added.

“Ovarian tumours are common and are often detected by chance,” says Professor Elisabeth Epstein at the Department of Clinical Science and Education, Södersjukhuset (Stockholm South General Hospital), at Karolinska Institutet and senior consultant at the hospital’s Department of Obstetrics and Gynecology. “There is a serious shortage of ultrasound experts in many parts of the world, which has raised concerns of unnecessary interventions and delayed cancer diagnoses. We therefor wanted to find out if AI can complement human experts.”

AI outperforms experts

The researchers have developed and validated neural network models able to differentiate between benign and malignant ovarian lesions, having trained and tested the AI on over 17,000 ultrasound images from 3,652 patients across 20 hospitals in eight countries. They then compared the models’ diagnostic capacity with a large group of experts and less experienced ultrasound examiners.

The results showed that the AI models outperformed both expert and non-expert examiners at identifying ovarian cancer, achieving an accuracy rate of 86.3 per cent, compared to 82.6 per cent and 77.7 per cent for the expert and non-expert examiners respectively.

“This suggests that neural network models can offer valuable support in the diagnosis of ovarian cancer, especially in difficult-to-diagnose cases and in settings where there’s a shortage of ultrasound experts,” says Professor Epstein.

Reducing the need for expert referrals

The AI models can also reduce the need for expert referrals. In a simulated triage situation, the AI support cut the number of referrals by 63 per cent and the misdiagnosis rate by 18 per cent. This can lead to faster and more cost-effective care for patients with ovarian lesions.

Despite the promising results, the researchers stress that further studies are needed before the full potential of the neural network models and their clinical limitations are fully understood.

“With continued research and development, AI-based tools can be an integral part of tomorrow’s healthcare, relieving experts and optimising hospital resources, but we need to make sure that they can be adapted to different clinical environments and patient groups,” says Filip Christiansen, doctoral student in Professor Epstein’s research group at Karolinska Institutet and joint first author with Emir Konuk at the KTH Royal Institute of Technology.

Evaluating the safety of the AI support

The researchers are now conducting prospective clinical studies at Södersjukhuset to evaluate the everyday clinical safety and usefulness of the AI tool. Future research will also include a randomised multicentre study to examine its effect on patient management and healthcare costs.

The study was conducted in close collaboration with researchers at the KTH Royal Institute of Technology and was financed by grants from the Swedish Research Council, the Swedish Cancer Society, the Stockholm Regional Council, the Cancer Research Funds of Radiumhemmet and the Wallenberg AI, Autonomous Systems and Software Program (WASP).

Elisabeth Epstein, Filip Christiansen and three co-authors have applied for a patent through the company Intelligyn for methods of computer-supported diagnostics. Elisabeth Epstein, Filip Christiansen and Kevin Smith, researcher at the KTH Royal Institute of Technology, also own shares in Intelligyn, for which Professor Epstein is an unsalaried manager.

Key findings

• Sensitive cells: Scientists discovered dozens of specific cell types, mostly glial cells, known as brain support cells, that underwent significant gene expression changes with age. Those strongly affected included microglia and border-associated macrophages, oligodendrocytes, tanycytes, and ependymal cells.
• Inflammation and neuron protection: In aging brains, genes associated with inflammation increased in activity while those related to neuronal structure and function decreased.
• Aging hot spot: Scientists discovered a specific hot spot combining both the decrease in neuronal function and the increase in inflammation in the hypothalamus. The most significant gene expression changes were found in cell types near the third ventricle of the hypothalamus, including tanycytes, ependymal cells, and neurons known for their role in food intake, energy homeostasis, metabolism, and how our bodies use nutrients. This points to a possible connection between diet, lifestyle factors, brain aging, and changes that can influence our susceptibility to age-related brain disorders.

“Our hypothesis is that those cell types are getting less efficient at integrating signals from our environment or from things that we’re consuming,” said Kelly Jin, Ph.D., a scientist at the Allen Institute for Brain Science and lead author of the study. “And that loss of efficiency somehow contributes to what we know as aging in the rest of our body. I think that’s pretty amazing, and I think it’s remarkable that we’re able to find those very specific changes with the methods that we’re using.”

To conduct the study, funded by the National Institutes of Health (NIH), researchers used cutting-edge single-cell RNA sequencing and advanced brain-mapping tools developed through NIH’s The BRAIN Initiative® to map over 1.2 million brain cells from young (two months old) and aged (18 months old) mice across 16 broad brain regions. The aged mice are what scientists consider to be the equivalent of a late middle-aged human. Mouse brains share many similarities with human brains in terms of structure, function, genes, and cell types.

“Aging is the most important risk factor for Alzheimer’s disease and many other devastating brain disorders. These results provide a highly detailed map for which brain cells may be most affected by aging,” said Richard J. Hodes, M.D., director of NIH’s National Institute on Aging. “This new map may fundamentally alter the way scientists think about how aging affects the brain and also provides a guide for developing new treatments for aging-related brain diseases.”

A path toward new therapies

Understanding this hot spot in the hypothalamus makes it a focal point for future study. Along with knowing which cells to specifically target, this could lead to the development of age-related therapeutics, helping to preserve function and prevent neurodegenerative disease.

“We want to develop tools that can target those cell types,” said Hongkui Zeng, Ph.D., executive vice president and director of the Allen Institute for Brain Science. “If we improve the function of those cells, will we be able to delay the aging process?”

The latest findings also align with past studies that link aging to metabolic changes as well as research suggesting that intermittent fasting, balanced diet, or calorie restriction can influence or perhaps increase life span.

“It’s not something we directly tested in this study,” said Jin. “But to me, it points to the potential players involved in the process, which I think is a huge deal because this is a very specific, rare population of neurons that express very specific genes that people can develop tools for to target and further study.”

Future brain aging research

This study lays the groundwork for new strategies in diet and therapeutic approaches aimed at maintaining brain health into old age, along with more research on the complexities of advanced aging in the brain. As scientists further explore these connections, research may unlock more specific dietary or drug interventions to combat or slow aging on a cellular level.

“The important thing about our study is that we found the key players — the real key players — and the biological substrates for this process,” said Zeng. “Putting the pieces of this puzzle together, you have to find the right players. It’s a beautiful example of why you need to study the brain and the body at this kind of cell type-specific level. Otherwise, changes happening in specific cell types could be averaged out and undetected if you mix different types of cells together.”

This study was funded by NIH grants R01AG066027 and U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The new approach uses samples from infected humans to allow real-time monitoring of pathogens circulating in human populations, and enable vaccine-evading bugs to be quickly and automatically identified. This could inform the development of vaccines that are more effective in preventing disease.

The approach can also quickly detect emerging variants with resistance to antibiotics. This could inform the choice of treatment for people who become infected — and try to limit the spread of the disease.

It uses genetic sequencing data to provide information on the genetic changes underlying the emergence of new variants. This is important to help understand why different variants spread differently in human populations.

There are very few systems in place to keep watch for emerging variants of infectious diseases, apart from the established COVID and influenza surveillance programmes. The technique is a major advance on the existing approach to these diseases, which has relied on groups of experts to decide when a circulating bacteria or virus has changed enough to be designated a new variant.

By creating ‘family trees’, the new approach identifies new variants automatically based on how much a pathogen has changed genetically, and how easily it spreads in the human population — removing the need to convene experts to do this.

It can be used for a broad range of viruses and bacteria and only a small number of samples, taken from infected people, are needed to reveal the variants circulating in a population. This makes it particularly valuable for resource-poor settings.

The report is published today in the journal Nature.

“Our new method provides a way to show, surprisingly quickly, whether there are new transmissible variants of pathogens circulating in populations — and it can be used for a huge range of bacteria and viruses,” said Dr Noémie Lefrancq, first author of the report, who carried out the work at the University of Cambridge’s Department of Genetics.

Lefrancq, who is now based at ETH Zurich, added: “We can even use it to start predicting how new variants are going to take over, which means decisions can quickly be made about how to respond.”

“Our method provides a completely objective way of spotting new strains of disease-causing bugs, by analysing their genetics and how they’re spreading in the population. This means we can rapidly and effectively spot the emergence of new highly transmissible strains,” said Professor Julian Parkhill, a researcher in the University of Cambridge’s Department of Veterinary Medicine who was involved in the study.

Testing the technique

The researchers used their new technique to analyse samples of Bordetella pertussis, the bacteria that causes whooping cough. Many countries are currently experiencing their worst whooping cough outbreaks of the last 25 years. It immediately identified three new variants circulating in the population that had been previously undetected.

“The novel method proves very timely for the agent of whooping cough, which warrants reinforced surveillance, given its current comeback in many countries and the worrying emergence of antimicrobial resistant lineages,” said Professor Sylvain Brisse, Head of the National Reference Center for whooping cough at Institut Pasteur, who provided bioresources and expertise on Bordetella pertussis genomic analyses and epidemiology.

In a second test, they analysed samples of Mycobacterium tuberculosis, the bacteria that causes Tuberculosis. It showed that two variants with resistance to antibiotics are spreading.

“The approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible,” said Professor Henrik Salje in the University of Cambridge’s Department of Genetics, senior author of the report.

He added: “If we see a rapid expansion of an antibiotic-resistant variant, then we could change the antibiotic that’s being prescribed to people infected by it, to try and limit the spread of that variant.”

The researchers say this work is an important piece in the larger jigsaw of any public health response to infectious disease.

A constant threat

Bacteria and viruses that cause disease are constantly evolving to be better and faster at spreading between us. During the COVID pandemic, this led to the emergence of new strains: the original Wuhan strain spread rapidly but was later overtaken by other variants, including Omicron, which evolved from the original and were better at spreading. Underlying this evolution are changes in the genetic make-up of the pathogens.

Pathogens evolve through genetic changes that make them better at spreading. Scientists are particularly worried about genetic changes that allow pathogens to evade our immune system and cause disease despite us being vaccinated against them.

“This work has the potential to become an integral part of infectious disease surveillance systems around the world, and the insights it provides could completely change the way governments respond,” said Salje.

Bone defects, which arise from various causes such as trauma, infection, and congenital abnormalities, are becoming increasingly common in aging societies. Conventional treatments often involve bone grafts combined with serum or bioadhesives to fill the defect. However, existing injectable hydrogels face challenges such as difficulty in maintaining their shape within the body and limited adhesive strength. Moreover, traditional methods using bone grafts with adhesive materials often fail to achieve simultaneous “bone regeneration” and “adhesion.”

The POSTECH team has introduced a novel system that addresses these limitations. This new hydrogel system employs visible light — safe for the human body — to facilitate cross-linking, where the main components of the hydrogel bond and harden, and to simultaneously boost mineralization where bone-building minerals like calcium and phosphate form within the hydrogel. While earlier studies have explored the use of light in similar applications, they encountered issues such as requiring separate preparation and mixing of bone grafts and adhesive materials, as well as weak bonding of the main components, which often degraded over time.

The newly developed hydrogel precursor comprises alginate (natural polysaccharide derived from brown algae), RGD peptide-containing mussel adhesive protein, calcium ions, phosphonodiols, and a photoinitiator. The coacervate-based formulation, which is immiscible in water, ensures that the hydrogel retains its shape and position after injection into the body. Upon visible light irradiation, cross-linking occurs, and amorphous calcium phosphate, which functions as a bone graft material, is simultaneously formed. This eliminates the need for separate bone grafts or adhesives, enabling the hydrogel to provide both bone regeneration and adhesion.

In experiments using animal models with femoral bone defects, the hydrogel was successfully injected, adhered accurately, and effectively delivered components essential for bone regeneration.

Professor Cha commented, “The injectable hydrogel system for bone regeneration developed by our research team represents an innovative alternative to conventional complex treatments for bone diseases and will greatly advance bone tissue regeneration technology.”

This research was supported by the Ministry of Health and Welfare’s Dental Medical Technology Research and Development Project and the Integrated End-to-End Medical Device R&D Project.

The study, conducted by a research team at the Johns Hopkins Transplant Research Center, was published today in the Journal of the American Medical Association (JAMA). It parallels earlier work done at the center to better understand how the immune systems of people who are immunocompromised respond to vaccines against SARS-CoV-2, the virus that causes COVID-19.

RSV is a contagious pathogen that causes infections of the respiratory tract. It is most commonly seen in infants and young children, but poses a threat to all age groups and may lead to more serious respiratory illnesses, such as pneumonia, in the elderly and those who are immunocompromised.

“We found that on average, older adults who are immunocompromised developed fewer antibodies against RSV following vaccination as compared with the very strong responses for healthy people over age 60 seen in the clinical trials used to validate the vaccines,” says study lead author Andrew Karaba, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine. “Additionally, antibody levels in people who are immunocompromised were highly variable, with some study participants showing strong increases in immunity because of the vaccines while others barely responded.”

The researchers used an ongoing, Johns Hopkins Medicine-led national study — the Emerging Pathogens of Concern in Immunocompromised Persons (EPOC) — to follow 38 people (between ages 64 and 72) who self-reported that they are immunocompromised and received either the RSVPreF3-AS01 (also known as Arexvy) or RSVpreF (also known as Abrysvo) vaccine. The study group was evenly split between males and females, with 82% being solid organ transplant recipients and 74% taking two or more immunosuppressive medications.

The two vaccines induce the immune system to target a critical protein on the surface of RSV, the F protein, in its pre-infection form, known as pre-fusion F. High levels of antibodies against pre-fusion F, particularly those that neutralize and block RSV from entering cells, are a major contributor in preventing RSV infections. Although most people are infected by RSV many times in their lives, natural infections do not lead to a sufficient level of virus-neutralizing, anti-pre-fusion F antibodies to prevent reinfections, and perhaps, prevent serious illness.

Both RSV vaccines were designed to solve that shortcoming, and in fact, they have been shown to successfully generate large amounts of pre-fusion F antibodies in trials with healthy adults. So why, the authors of the JAMA study asked, do immune responses to the vaccines vary in people who are immunocompromised?

“We suspected that a fundamental difference in the two vaccines — the presence or absence of an immune-stimulating chemical called an adjuvant — might play a role in the variance in immunity, so we looked at that,” says study senior author William Werbel, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine.

Arexvy contains an adjuvant while Abrysvo does not.

“When we compared the antibody responses between those study participants who received Arexvy with those who got Abrysvo, we found that the group receiving the adjuvanted vaccine tended to have higher levels of RSV-neutralizing, anti-pre-fusion F antibodies,” says Werbel. “So, adjuvant-enhanced vaccines as a means of improving immune response in people who are immunocompromised merits further investigation in larger, more comprehensive studies.”

However, both Karaba and Werbel point out that this study does not suggest RSV vaccines will not reduce RSV disease in people who are immunocompromised.

The U.S. Centers for Disease Control and Prevention (CDC) currently recommends that everyone 75 and older receive a single dose of an RSV vaccine, as well as people 60 or older in groups at high risk of infection by the virus — including people who are immunocompromised.

“As with our previous work with COVID-19 vaccines [which led to recommendation that people who are immunocompromised getting additional vaccine doses to improve protection], we look forward to additional research on RSV vaccine responses that will provide guidance for optimized timing and vaccine selection for people who are immunocompromised,” says Karaba.

Along with Karaba and Werbel, the other members of the research team from Johns Hopkins Medicine are Prasanthy Balasubramanian, Sc.M.; Camille Hage, M.D.; Isabella Sengsouk; and Aaron Tobian, M.D., Ph.D. The study co-author from the New York University Grossman School of Medicine is Dorry Segev, M.D., Ph.D., formerly with Johns Hopkins Medicine.

The work was supported by National Institute of Allergy and Infectious Diseases grants 3U01A11338897-04S1, K08A1156021 and K23A1157893; and subaward 3UM1AI109565 from the COVID Protection After Transplant Data Coordinating Center, Immune Tolerance Network at the Benaroya Research Institute at the Virginia Mason Medical Center.

Karaba reports receiving consulting fees from Hologic Inc. and speaking fees from PRIME Education. Werbel reports receiving consulting fees from the CDC/Infectious Diseases Society of America and AstraZeneca; and advisory board fees from AstraZeneca and Novavax. Segev reports receiving consulting fees from AstraZeneca, CareDx, Moderna Therapeutics, Novavax, Regeneron and Springer Publishing; and speaker fees and honoraria from AstraZeneca, CareDx, Houston Methodist, Northwell Health, Optum Health Education, Sanofi and WebMD.

“This adds to some emerging evidence that an individual’s brain structure, alongside their unique genetics, environmental exposures, and interactions among these factors, may impact their level of risk and resilience for substance use and addiction,” said Nora Volkow M.D., director of NIDA. “Understanding the complex interplay between the factors that contribute and that protect against drug use is crucial for informing effective prevention interventions and providing support for those who may be most vulnerable.”

Among the 3,460 adolescents who initiated substances before age 15, most (90.2%) reported trying alcohol, with considerable overlap with nicotine and/or cannabis use; 61.5% and 52.4% of kids initiating nicotine and cannabis, respectively, also reported initiating alcohol. Substance initiation was associated with a variety of brain-wide (global) as well as more regional structural differences primarily involving the cortex, some of which were substance-specific. While these data could someday help inform clinical prevention strategies, the researchers emphasize that brain structure alone cannot predict substance use during adolescence, and that these data should not be used as a diagnostic tool.

The study, published in JAMA Network Open, used data from the Adolescent Brain Cognitive Development Study,(ABCD Study), the largest longitudinal study of brain development and health in children and adolescents in the United States, which is supported by the NIH’s National Institute on Drug Abuse (NIDA) and nine other institutes, centers, and offices.

Using data from the ABCD Study, researchers from Washington University in St. Louis assessed MRI scans taken of 9,804 children across the U.S. when they were ages 9 to 11 — at “baseline” — and followed the participants over three years to determine whether certain aspects of brain structure captured in the baseline MRIs were associated with early substance initiation. They monitored for alcohol, nicotine, and/or cannabis use, the most common substances used in early adolescence, as well as use of other illicit substances. The researchers compared MRIs of 3,460 participants who reported substance initiation before age 15 from 2016 to 2021 to those who did not (6,344).

They assessed both global and regional differences in brain structure, looking at measures like volume, thickness, depth of brain folds, and surface area, primarily in the brain cortex. The cortex is the outermost layer of the brain, tightly packed with neurons and responsible for many higher-level processes, including learning, sensation, memory, language, emotion, and decision-making. Specific characteristics and differences in these structures — measured by thickness, surface area, and volume — have been linked to variability in cognitive abilities and neurological conditions.

The researchers identified five brain structural differences at the global level between those who reported substance initiation before the age of 15 and those who did not. These included greater total brain volume and greater subcortical volume in those who indicated substance initiation. An additional 39 brain structure differences were found at the regional level, with approximately 56% of the regional variation involving cortical thickness. Some brain structural differences also appeared unique to the type of substance used.

In a post-hoc analysis, the researchers found that many of these brain differences still held even after removing those participants who reported substance initiation prior to collection of their baseline MRIs. The resulting comparison was between those who did not report any substance use initiation and a subgroup of 1,203 participants in the substance use initiation group who did not have any substance use experience when their MRIs were first captured. The results of this secondary analysis suggest that some of these brain structural differences may exist prior to any substance use, challenging the interpretation that such differences are only driven by substance exposure and pointing to an area for further investigation.

While some of the brain regions where differences were identified have been linked to sensation-seeking and impulsivity, the researchers note that more work is needed to delineate how these structural differences may translate to differences in brain function or behaviors. They also emphasize that the interplay between genetics, environment, brain structure, the prenatal environment, and behavior influence affect behaviors.

Another recent analysis of data from the ABCD study conducted by the University of Michigan demonstrates this interplay, showing that patterns of functional brain connectivity in early adolescence could predict substance use initiation in youth, and that these trajectories were likely influenced by exposure to pollution.

Future studies will be crucial to determine how initial brain structure differences may change as children age and with continued substance use or development of substance use disorder.

“Through the ABCD study, we have a robust and large database of longitudinal data to go beyond previous neuroimaging research to understand the bidirectional relationship between brain structure and substance use,” said Alex Miller, Ph.D., the study’s corresponding author and an assistant professor of psychiatry at Indiana University. “The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward.”

The findings, published Dec. 30 in the journal Nature Communications, could lead to novel approaches for treating alcohol use disorder.

“We know a lot less about what drives alcohol drinking behavior in females because most studies of alcohol use have been done in males,” said senior author Dr. Kristen Pleil, an associate professor of pharmacology. Yet females, too, overindulge and are more susceptible to the negative health effects of alcohol than males.

Recent studies indicate that, during the pandemic lockdown, women increased their heavy alcohol consumption more than men. That behavior has important consequences for women’s health, said Dr. Pleil, “because many studies show this pattern of drinking enhances alcohol’s harmful effects.” Indeed, women had many more alcohol-related hospital visits and complications than men during and since the pandemic.

Peak Levels of Estrogen Associated with Increased Alcohol Consumption

In a 2021 study, Dr. Pleil and her team showed that a specific subpopulation of neurons in a brain region called the bed nucleus of the stria terminalis (BNST) were more excitable in female mice than in males. This enhanced activity correlated with their binge drinking behavior.

But what makes this neural circuit more excitable in females? “Estrogen has such powerful effects on so many behaviors, particularly in females,” Dr. Pleil said. “So, it makes sense that it would also modulate drinking.”

To assess estrogen’s potential involvement, the researchers, including first author Dr. Lia Zallar, who was a graduate student in the Pleil lab at the time of the research, began by monitoring the hormone levels throughout estrous cycle of female mice. Then, they served up the alcohol. They found that when a female has a high level of circulating estrogen, she drinks much more than on days when her estrogen is low.

That enhanced bingeing behavior was reflected in heightened activity in those same neurons in the BNST. “When a female takes her first sip from the bottle containing alcohol, those neurons go crazy,” Dr. Pleil said. “And if she’s in a high-estrogen state, they go even crazier.” That extra boost of neural activity means the mice hit the bottle even harder, particularly within the first 30 minutes after the alcohol was made available, a behavior Dr. Pleil refers to as “front-loading.”

Surprising Discovery: Cell-surface Receptors Allow Estrogen to Act Fast

Although the researchers suspected estrogen would have an effect on drinking, they were surprised by its mechanism of action. This steroid hormone typically regulates behaviors by binding to receptors that then travel to the nucleus, where they alter the activity of specific genes — a process that could take hours. However, Dr. Pleil and her team realized that something else must be happening when estrogen infused directly into the BNST excited the neurons and triggered binge drinking within minutes.

So, the researchers tested estrogen that had been doctored so it could not enter cells and bind to nuclear receptors — a feat of chemical engineering performed by Dr. Jacob Geri, assistant professor of pharmacology at Weill Cornell Medicine. They determined that when estrogen promotes bingeing, the hormone is binding to receptors on the neurons’ surface, where it directly modulates cell-cell communication.

“We believe this is the first time that anybody has shown that during a normal estrous cycle, endogenous estrogen made by the ovaries can use such a rapid mechanism to control behavior,” Dr. Pleil said. That rapid action drives the front-loading of alcohol when estrogen is high.

The team identified the estrogen receptor that mediates this effect and determined that it is expressed in the excited BNST neurons and in neurons from other brain regions that excite them. The researchers are now investigating the signaling mechanisms for this effect, and they will also examine whether the same system regulates drinking in males.

“All of the infrastructure is there in males, too: the estrogen receptors and the basic circuit organization,” Dr. Pleil said. The only difference will be the source of the estrogen, which in males without an ovarian source relies on local conversion of testosterone to estrogen in the brain.

Inhibiting the enzyme that synthesizes estrogens could offer a novel treatment for selectively reducing alcohol consumption when hormone levels surge. An FDA-approved version of such an inhibitor is currently used to treat women with estrogen-sensitive cancers.

“Combining this drug with compounds that modulate the downstream effects of the chemicals produced by the BNST neurons could potentially provide a new, targeted approach for treating alcohol use disorder,” Dr. Pleil said.

The findings are among the first to portray the landscape of hospitals participating in this rapidly growing care model, said Dr. Hashem Zikry, a participant in the National Clinician Scholars Program at UCLA and lead author on the paper, which will be published in the peer-reviewed JAMA.

“If CMS’ goal is to continue to expand hospital-at-home, these findings suggest that different incentives or outreach may be needed for smaller, rural, and non-teaching hospitals,” Zikry said.

Established in November 2020, the CMS program allows hospitals to deliver care for acute medical illness to patients in their own homes in lieu of a traditional hospital admission.

“Imagine, for example, a 70-year-old who needs treatment for pneumonia,” Zikry said. “Instead of being admitted to the brick-and-mortar hospital, hospital-at-home allows this patient to get the same resources, such as antibiotics and vital sign monitoring, in her own home.” An initial motivation for promoting hospital-at-home was to lessen capacity strain on hospitals — a problem that was exposed and exacerbated by the Covid-19 pandemic. “Many hospitals are operating at 100% capacity almost all the time,” said Zikry, “so anything that might free up beds and mitigate that capacity crisis is tremendously appealing to heath systems.”

Initially scheduled to expire in December 2022, Congress extended the hospital-at-home waiver program through the end of 2024 and recently introduced legislation to extend it for another five years. Early participants in the CMS program tended to be large, urban, not-for-profit, academic hospitals. In light of the current proposal to extend the waiver, Zikry and coauthors were curious to see whether participation continued to grow after the initial 2022 extension and whether the characteristics of participating hospitals had changed over time.

The researchers conducted a cross-sectional analysis of short-term acute care hospitals in the United States and used the 2022 American Hospital Association Annual Survey to obtain data on hospital characteristics. They compared hospitals that applied for the waiver between November 2020 and December 2022 (pre-extension hospitals) and those that applied afterward (post-extension). Of about 3,000 hospitals included in the study, 299 obtained the waiver, with 249 of them pre-extension and 50 post-extension.

The study found that adoption of the waiver remained concentrated among large, urban, not-for-profit, and academic hospitals. The characteristics of post-extension hospitals were similar to pre-extension hospitals, although the former were somewhat smaller and demonstrated regional differences.

Among their findings:

• Geographically, 49 (98%) post-extension and 226 (91%) pre-extension hospitals were in metropolitan areas
• Post-extension facilities were most often located in the northeastern (16 hospitals, for 31%) or western U.S (10, for 20%), compared with 30 (12%) and 26 (10%) pre-extension hospitals, respectively. In the south, 19 (38%) were post-extension and 143 (57%) pre-extension
• Of the post-extension facilities, 24 (48%) had 100 to 299 beds and 20 (40%) had more than 300 beds, compared with 86 (35%) and 126 (51%) pre-extension, respectively
• Non-profits comprised 46 (92%) post-extension and 201 (81%) pre-extension hospitals
• Among academic hospitals, 27 (54%) were minor teaching hospitals and 11 (22%) were major teaching hospitals post-extension, compared with 137 (55%) and 64 (26%) pre-extension, respectively.

There are multiple implications of this research, according to Zikry. For one, if CMS wants to expand the reach of hospital-at-home, more work must be done to incorporate smaller, rural, and non-teaching hospitals. The data is clear that these types of hospitals are not seeking to create these programs on their own, potentially because of the resources involved in creating and sustaining their operation until they scale.

Moreover, additional research is needed to understand the practical implications and tradeoffs of hospital-at-home.

“Resources are being poured into these programs around the country,” Zikry said, “yet we still don’t have a comprehensive understanding of how the programs are functioning on the ground.”

Many questions remain, he said.: “Are family members of these patients acting as unpaid caregivers during these admissions? Could these patients do just as well in other care settings? Do patients actually prefer to be at home? And are health systems leveraging this program equitably?”

Study co-authors are Dr. David Schriger of UCLA and Dr. Austin Kilaru of the University of Pennsylvania.

Microglia, often dubbed the brain’s first responders, are now recognized as a significant causal cell type in Alzheimer’s pathology. However, these cells play a double-edged role: some protect brain health, while others worsen neurodegeneration. Understanding the functional differences between these microglial populations has been a research focus for Pinar Ayata, the study’s principal investigator and a professor with the CUNY ASRC Neuroscience Initiative and the CUNY Graduate Center’s Biology and Biochemistry programs.

“We set out to answer what are the harmful microglia in Alzheimer’s disease and how can we therapeutically target them,” said Ayata. “We pinpointed a novel neurodegenerative microglia phenotype in Alzheimer’s disease characterized by a stress-related signaling pathway.”

The research team discovered that activation of this stress pathway, known as the integrated stress response (ISR), prompts microglia to produce and release toxic lipids. These lipids damage neurons and oligodendrocyte progenitor cells — two cell types essential for brain function and most impacted in Alzheimer’s disease. Blocking this stress response or the lipid synthesis pathway reversed symptoms of Alzheimer’s disease in preclinical models.

Key Findings

• Dark Microglia and Alzheimer‘s Disease: Using electron microscopy, the researchers identified an accumulation of “dark microglia,” a subset of microglia associated with cellular stress and neurodegeneration, in postmortem brain tissues from Alzheimer’s patients. These cells were present at twice the levels seen in healthy-aged individuals.
• Toxic Lipid Secretion: The ISR pathway in microglia was shown to drive the synthesis and release of harmful lipids that contribute to synapse loss, a hallmark of Alzheimer’s disease.
• Therapeutic Potential: In mouse models, inhibiting ISR activation or lipid synthesis prevented synapse loss and accumulation of neurodegenerative tau proteins, offering a promising pathway for therapeutic intervention.

“These findings reveal a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer’s disease,” said the study’s co-lead author Anna Flury, a member of Ayata’s lab and a Ph.D. student with the CUNY Graduate Center’s Biology Program. “Targeting this pathway may open up new avenues for treatment by either halting the toxic lipid production or preventing the activation of harmful microglial phenotypes.”

Implications for Alzheimer’s Patients This research underscores the potential of developing drugs that target specific microglial populations or their stress-induced mechanisms. “Such treatments could significantly slow or even reverse the progression of Alzheimer’s disease, offering hope to millions of patients and their families,” explained co-lead author Leen Aljayousi, a member of Ayata’s lab and a Ph.D. student with the CUNY Graduate Center’s Biology Program.

The study represents a major leap forward in understanding the cellular underpinnings of Alzheimer’s and emphasizes the importance of microglial health in maintaining overall brain function.

Interactions between proteins play a significant role in biological processes, including those involved in disease. The team behind the SIMPL2 platform designed it to optimize researchers’ ability to measure protein-protein interactions for targeted drug therapies. While protein-protein interactions have previously been considered ‘undruggable’ using small molecules, the platform addresses this challenge by facilitating the measurement of these interactions — improving our understanding of the types of molecules needed to control them.

“Many methods have been developed to measure interactions between proteins, especially more recently as the significance of protein interactions in disease has become more apparent,” said Zhong Yao, first author on the study and senior research associate of U of T’s Donnelly Centre for Cellular and Biomolecular Research. “However, all of these methods have shortcomings, including high costs and complicated procedures that delay results. The biggest advantages of our SIMPL2 platform are that it produces more reliable measurements and is comparatively cheaper to use.”

The study was published recently in the journal Molecular Systems Biology.

Yao started working on the protein interaction measurement problem while developing the original SIMPL (Split-Intein Medicated Protein Ligation) system. SIMPL2 is an update of SIMPL that involves the use of the split luciferase enzyme for detection of protein interactions through luminescence. In addition to improving identification of interactions, the entire measurement process occurs through one medium: liquid. This simplifies the process considerably by reducing the number of steps required to carry out measurements.

“One of the issues with SIMPL was that we had to use an additional process, called ELISA, to identify the proteins spliced by the SIMPL platform,” said Yao. “It was a painful process that made an otherwise effective technology more complicated and expensive to use than it needed to be. SIMPL2 only requires one step, which can be performed manually, or it can be automated for even more efficiency in high-throughput studies.”

To test the new platform’s sensitivity and applicability, the research team used it to measure interactions between proteins affected by modulators. Protein modulators include molecules that inhibit interactions between proteins, those that facilitate protein interactions and those that facilitate the degradation of target proteins. SIMPL2 was found to perform well in identifying these interactions, even in cases where the interactions were weak.

While quantum computers and AI have made it easier to design small molecules for drug therapies, this has led to a need to develop much faster methods for validating the efficacy of new drugs. SIMPL2 can meet that need, as it can be used to test interactions between new molecules and their target proteins in cultured human cells. It is also capable of keeping apace with the rate at which new molecules are being designed.

“We designed SIMPL2 to be a universal method for studying protein interactions that is rapid and inexpensive, as well as highly sensitive,” said Igor Stagljar, principal investigator on the study and professor of biochemistry at U of T’s Temerty Faculty of Medicine. “Now that we have optimized the platform, our next step is to use it to study interactions that play key roles in diseases, like cancer, to learn how to develop drug therapies. This work will involve the use of quantum computers and AI in collaboration with Alán Aspuru-Guzik’s lab at U of T and Insilico Medicine, a global leader in generative AI drug discovery.”

This research was supported by FACIT and Ontario Genomics.

Changes in these spin states can be detected using optically detected magnetic resonance (ODMR), which measures fluorescence changes under microwave radiation. NDs with NV centers are biocompatible and can be designed to interact with specific biological molecules, making them valuable tools for biological sensing. However, NDs used for bioimaging generally exhibit lower spin quality compared to bulk diamonds, resulting in reduced sensitivity and accuracy in measurements.

In a recent breakthrough, scientists from Okayama University in Japan developed nanodiamond sensors bright enough for bioimaging, with spin properties comparable to those of bulk diamonds. The study, published in ACS Nano, on 16 December 2024, was led by Research Professor Masazumi Fujiwara from Okayama University, in collaboration with Sumitomo Electric Company and the National Institutes for Quantum Science and Technology.

“This is the first demonstration of quantum-grade NDs with exceptionally high-quality spins, a long-awaited breakthrough in the field. These NDs possess properties that have been highly sought after for quantum biosensing and other advanced applications,” says Prof. Fujiwara.

Current ND sensors for bioimaging face two main limitations: high concentrations of spin impurities, which disrupt NV spin states, and surface spin noise, which destabilizes the spin states more rapidly. To overcome these challenges, the researchers focused on producing high-quality diamonds with very few impurities. They grew single-crystal diamonds enriched with 99.99% ¹²C carbon atoms and then introduced a controlled amount of nitrogen (30-60 parts per million) to create an NV center with about 1 part per million. The diamonds were crushed into NDs and suspended in water.

The resulting NDs had a mean size of 277 nanometers and contained 0.6-1.3 parts per million of negatively charged NV centers. They displayed strong fluorescence, achieving a photon count rate of 1500 kHz, making them suitable for bioimaging applications. These NDs also showed enhanced spin properties compared to commercially available larger NDs. They required 10-20 times less microwave power to achieve a 3% ODMR contrast, had reduced peak splitting, and demonstrated significantly longer spin relaxation times (T₁ = 0.68 ms, T₂ = 3.2 µs), which were 6 to 11 times longer than those of type-Ib NDs. These improvements indicate that the NDs possess stable quantum states, which can be accurately detected and measured with low microwave radiation, minimizing the risk of microwave-induced toxicity in cells.

To evaluate their potential for biological sensing, the researchers introduced NDs into HeLa cells and measured the spin properties using ODMR experiments. The NDs were bright enough for clear visibility and produced narrow, reliable spectra despite some impact from Brownian motion (random ND movement within cells). Furthermore, the NDs were capable of detecting small temperature changes. At temperatures around 300 K and 308 K, the NDs exhibited distinct oscillation frequencies, demonstrating a temperature sensitivity of 0.28 K/√Hz, superior to bare type-Ib NDs.

With these advanced sensing capabilities, the sensor has potential for diverse applications, from biological sensing of cells for early disease detection to monitoring battery health and enhancing thermal management and performance for energy-efficient electronic devices. “These advancements have the potential to transform healthcare, technology, and environmental management, improving quality of life and providing sustainable solutions for future challenges,” says Prof. Fujiwara.

“With many current drugs to prevent migraine, it takes time to find the right dosage for the individual and it can take weeks or even months for it to be most effective,” said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in the Bronx, New York, and a Fellow of the American Academy of Neurology. “Some people give up and stop taking the drugs before they reach this point. Plus, many people experience side effects with current treatments. Developing a drug that works both effectively and quickly is critical.”

In the study, people taking the drug atogepant were less likely to have a migraine on the first day of taking the drug compared to those taking a placebo. They also had fewer migraines per week during each of the first four weeks of the study and fewer migraines during the study overall than those taking a placebo.

For this study, researchers looked at the data from three trials on the safety and effectiveness of atogepant over 12 weeks to focus on how rapidly improvements appeared. The ADVANCE trial, which enrolled people with episodic migraine, had 222 people taking the drug and 214 taking placebo. The ELEVATE trial, which enrolled people with episodic migraine who had previously not responded well to other oral preventive treatments, had 151 on the drug and 154 on placebo. The PROGRESS trial, which enrolled people with chronic migraine, had 256 on the drug and 246 on placebo.

People with episodic migraine experience up to 14 migraine days per month. People with chronic migraine experience at least 15 days with headache per month, with at least eight days being characteristic of migraine.

On the first day of the study, 12% of those taking the drug in the first trial, the ADVANCE trial had a migraine, compared to 25% of those taking placebo. In the second trial, the ELEVATE trial, the numbers were 15% and 26%. For the third trial, the PROGRESS trial, the numbers were 51% and 61%.

When researchers adjusted for other factors that could affect the rate of migraine, they found that people taking the drug were 61% less likely to have a migraine in the first trial, 47% less likely in the second trial, and 37% less likely in the third trial.

For the first two trials, the people taking atogepant had an average of one fewer day with migraine per week, compared to an average of less than one-half day fewer per week for those taking the placebo. For the third trial, average migraine days per week declined by about 1.5 days for those taking the drug compared to about one day for those taking the placebo.

The people taking atogepant also showed improvement on assessments of how much migraine impaired their activities and their overall quality of life compared to people taking the placebo.

“Migraine is the second-leading cause of disability in the overall population and the leading cause of disability in young women, with people reporting negative effects on their relationships, parenting, career and finances,” Lipton said. “Having a treatment that can act quickly and effectively addresses a key need.”

A limitation of the study is that it involved mostly female and white participants, so the results may not apply to the overall population.

The study was supported by AbbVie, the maker of atogepant.

Tonsillitis is a common reason for visits to the doctor and prescriptions of antibiotics in primary care. To determine whether a patient needs antibiotics, doctors use the so-called Centor Criteria for tonsillitis. The criteria include fever, tender and swollen lymph nodes in the angles of the jaw and inspection of the tonsils.

However, it has been unclear how well these criteria can be assessed during digital healthcare consultations compared to traditional in-person consultations. This lack of scientific evidence has become a growing concern as digital healthcare consultations become more common.

Digital vs physical assessment

The current study, published in the journal Infectious Diseases, examines whether digital assessments are as reliable as physical examinations in determining whether antibiotic treatment is warranted. The study includes 189 patients who sought care at healthcare clinics and urgent care clinics in Region Västra Götaland, Sweden, between January 2020 and October 2023.

Each patient in the study underwent two assessments: a digital medical assessment via video and a physical examination conducted by another doctor. The results show that digital healthcare consultations are not sufficient to assess some of the most important criteria, such as tonsil inspection and lymph node examination.

Digital not safe enough

One of the driving forces behind the study is Patrycja Woldan-Gradalska, a PhD student at Sahlgrenska Academy at the University of Gothenburg and a Resident Physician at Sätila Healthcare Clinic.

“Our study shows that although digital healthcare consultations are convenient for many patients, they are not reliable enough to assess tonsillitis. To ensure a correct diagnosis and treatment, it is still important to conduct a physical examination,” she says.

The authors are active in community medicine and public health at Sahlgrenska Academy at the University of Gothenburg and at Region Västra Götaland’s FoUUI primary and community healthcare, a support resource for research, education, development and innovation.

Viruses are uniquely designed to encapsulate genetic material within spherical protein shells, enabling them to replicate and invade host cells, often causing disease. Inspired by these complex structures, researchers have been exploring artificial proteins modeled after viruses. These “nanocages” mimic viral behavior, effectively delivering therapeutic genes to target cells. However, existing nanocages face significant challenges: their small size restricts the amount of genetic material they can carry, and their simple designs fall short of replicating the multifunctionality of natural viral proteins.

To address these limitations, the research team used AI-driven computational design. While most viruses display symmetrical structures, they also feature subtle asymmetries. Leveraging AI, the team recreated these nuanced characteristics and successfully designed nanocages in tetrahedral, octahedral, and icosahedral shapes for the first time.

The resulting nanostructures are composed of four types of artificial proteins, forming intricate architectures with six distinct protein-protein interfaces. Among these, the icosahedral structure, measuring up to 75 nanometers in diameter, stands out for its ability to hold three times more genetic material than conventional gene delivery vectors, such as adeno-associated viruses (AAV), marking a significant advancement in gene therapy.

Electron microscopy confirmed the AI-designed nanocages achieved precise symmetrical structures as intended. Functional experiments further demonstrated their ability to effectively deliver therapeutic payloads to target cells, paving the way for practical medical applications.

“Advancements in AI have opened the door to a new era where we can design and assemble artificial proteins to meet humanity’s needs,” said Professor Sangmin Lee. “We hope this research not only accelerates the development of gene therapies but also drives breakthroughs in next-generation vaccines and other biomedical innovations.”

Professor Lee previously worked as a postdoctoral researcher in Professor Baker’s laboratory at the University of Washington for nearly three years, from February 2021 to late 2023, before joining POSTECH in January 2024.

This study was supported by the Republic of Korea’s Ministry of Science and ICT under the Outstanding Young Scientist Program, the Nano and Material Technology Development Program, and the Global Frontier Research Program, with additional funding provided by the Howard Hughes Medical Institute (HHMI) in the United States.

New research in Psychological Science reveals that lifelong singles have lower scores on life satisfaction measures and different personality traits compared to partnered people, findings that point to the need for both helpful networks and ways to create such networks that are better catered to single people.

“When there are differences, they might be especially important in elderly people who face more health issues and financial issues,” said Julia Stern, one of the lead authors and a senior researcher at the University of Bremen in Germany, in an interview with APS. “They need more help, and the help is usually the partner.”

Stern and colleagues compared single people and partnered individuals on life satisfaction ratings and the Big Five personality traits (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism). The study used a survey of more than 77,000 Europeans over the age of 50 and was the first of its kind to look across cultures and at people who had been single their entire lives. The findings revealed that, in addition to lower life satisfaction scores, lifelong singles are less extraverted, less conscientious, and less open to experience, compared to partnered people.

Previous studies used different definitions of being single, sometimes considering only current status and other times drawing the line at having never married or, alternatively, at never living with a partner. But people who have been in a serious relationship in the past — even if it has ended — might have different personality traits than those who have never been that committed. To investigate this, Stern and colleagues grouped respondents by the different definitions: currently partnered, never living with a partner, never married, or never being in any long-term relationship. People who had never been in a serious long-term relationship scored lower on extraversion, openness, and life satisfaction than those who were currently single but had lived with a partner or been married in the past. All singles scored lower on these measures than people in current relationships.

Although this study cannot definitively decipher if personality differences are due to selection — people with certain personality types may be more likely to start relationships — or socialization — long-term relationships could change personalities — the evidence points to the former. Stern said that changes to personality from being in a relationship are small and temporary. For instance, although an extraverted person beginning a new relationship may be keen to stay in with their partner, eventually their extraversion comes back.

“It’s more likely you have these selection effects: For example, people who are more extraverted are more likely to enter a relationship,” Stern said. But she warned that the results are average effects and not necessarily descriptive of everyone; of course, there are single extraverts and introverts in committed relationships.

For singles, living in a society where marriage is the expectation may affect their life satisfaction. Because the large sample included people from 27 European countries, the researchers were able to ask whether there were any cultural differences. In countries with higher marriage rates (such as southern European countries), singlehood resulted in even lower life satisfaction scores, but the effects were small. The religiosity of the country did not seem to matter, however.

When comparing across gender and age, single women scored higher on life satisfaction than single men, and older people tended to be happier with their singlehood status than middle-aged singles. Stern speculated that, with the era of their peers getting married and starting families behind them, older singles may accept their circumstances and be happier.

Singles may grow happier with age, but their lower scores compared to partnered people are still worrying. Previous research has shown life satisfaction and particular personality traits (including extraversion and conscientiousness) can predict health and mortality, emphasizing the need to find ways to promote the well-being of older singles.

“There are differences between people who stay single their entire lives and people who get partnered, and for me this means that we have to take extra care of these people,” Stern said. She suggested developing new kinds of programs to prevent loneliness that take these personality traits into consideration and help older singles meet like-minded people. “If they have people who care for them or look out for them regularly, this might help.”

PolyP and magnesium are involved in many biological processes. Thus, the findings could lead to new methods for tuning cellular responses, which could have impactful applications in translational medicine.

The ensuing study, published in Nature Communications on October 26, 2024, reveals a delicate “Goldilocks” zone — a specific magnesium concentration range — where DNA wraps around polyP-magnesium ion condensates. Similar to a thin eggshell covering a liquid-like interior, this seemingly simple structure may help cells organize and protect their genetic material.

This work began as a collaboration between co-senior authors Associate Professor Lisa Racki, PhD, and Professor Ashok Deniz, PhD, both in the Department of Integrative Structural and Computational Biology at Scripps Research. Racki had been studying these structures in bacterial cells, while Deniz’s next-door lab was exploring the physical chemistry of biomolecular condensates for the past decade. Collaboration, they realized, was the only way to unlock these ancient interactions.

“We knew that DNA was in close proximity to the magnesium-rich polyP condensates in cells, but we were totally surprised by the beautiful spheres of DNA that lit up under the microscope,” says Racki.

“Being molecular detectives, seeing these structures raised exciting questions for us about the physics and mathematics of the DNA shells and whether they influenced the polyP condensates,” adds Deniz.

Their microscopy images revealed that DNA wraps itself around a condensate, creating a thin eggshell-like barrier. This shell could affect molecule transportation and also slow down fusion: the process where two condensates merge into one. Without DNA shells, polyP-magnesium ion condensates readily fused — like how oil drops and vinegar fuse in a salad dressing bottle when shook.

However, careful examination showed that fusion overall slowed to varying extents, depending on DNA length. Longer DNA, the researchers suspected, caused greater entanglement on condensate surfaces — similar to how long hair tangles more than short hair.

DNA is more than 1,000 times thinner in diameter than condensates, making molecular details hard to visualize. Fortunately, infrastructure to capture such imaging has been developed by two other faculty members at Scripps Research: Assistant Professor Danielle Grotjahn, PhD, and Scripps Fellow Donghyun Raphael Park, PhD.

Teaming with Park, with help from Grotjahn, the researchers used cryo-electron tomography to closely examine the condensate surfaces. Using electrons instead of light, this technique captures three-dimensional, high-resolution images of samples that were rapidly frozen to preserve their structures. The new images revealed that DNA forms filaments protruding from condensate surfaces, resembling tangled hairs.

Another crucial discovery: DNA shell formation only occurred within a specific magnesium concentration range — too much or too little, and the shell wouldn’t materialize. This “Goldilocks” effect highlights how cells can regulate condensate structure, size and function simply by tuning control parameters.

“Although we think of cellular interfaces as boundaries, they also create a new landscape by providing a surface for molecules to organize,” notes Racki. “DNA may not actually be a tangled mess at the surface and is instead organized by these condensates.”

In this context, Deniz and Racki are particularly interested in understanding DNA supercoiling — how DNA twists like a spring to fit inside cells.

“Cells have to manage their DNA curls,” explains Racki. “Interestingly, the mathematics of DNA supercoiling results in ‘action-at-a-distance’ effects — like how twisting a rope can create coils far from where you’re holding it.”

The researchers suspect that DNA interactions with polyP condensates in cells might propagate local changes in DNA supercoiling over long distances, resulting in broader changes in gene expression and cell function. Investigating this effect is one of the team’s next goals.

“We’re excited by the prospects of leveraging these discoveries to develop new tools for cellular control — potentially simpler, more cost-effective approaches to manage biomatter for biomedicine,” says Deniz.

In addition to Deniz, Racki, Grotjahn and Park, authors of the study, “Reentrant DNA shells tune polyphosphate condensate size,” include co-first authors Ravi Chawla and Jenna K. A. Tom, and Tumara Boyd, Nicholas H. Tu and Tanxi Bai of Scripps Research.

This work was supported by funding from the National Institutes of Health (NIGMS Grant R35 GM130375, Grant DP2-GM-739-140918 and S10OD032467), Scripps Research start-up funds, a Postdoctoral Fellowship from the American Heart Association (Award #903967) and the Pew Scholars Program.

This could enable medics to identify sooner any decline in lung function.

The scan method has enabled the team, led by researchers at Newcastle University, UK, to see how air moves in and out of the lungs as people take a breath in patients with asthma, chronic obstructive pulmonary disease (COPD), and patients who have received a lung transplant.

Publishing two complementary papers in Radiology and JHLT Open, the team explain how they use a special gas, called perfluoropropane, that can be seen on an MRI scanner. The gas can be safely breathed in and out by patients, and then scans taken to look at where in the lungs the gas has reached.

The project lead, Professor Pete Thelwallis Professor of Magnetic Resonance Physics and Director of the Centre for In Vivo Imaging at Newcastle University. He said; “Our scans show where there is patchy ventilation in patients with lung disease, and show us which parts of the lung improve with treatment. For example, when we scan a patient as they use their asthma medication, we can see how much of their lungs and which parts of their lung are better able to move air in and out with each breath.”

Using the new scanning method, the team are able to reveal the parts of the lung that air doesn’t reach properly during breathing. By measuring how much of the lung is well-ventilated and how much is poorly ventilated, experts can make an assessment of the effects of a patient’s respiratory disease, and they can locate and visualise the lung regions with ventilation defects.

Demonstrating that the scans work in patients with asthma or COPD, the team comprising experts from across Universities and NHS Trusts in Newcastle and Sheffield publish the first paper in Radiology.

The new scanning technique allows the team to quantify the degree of improvement in ventilation when patients have a treatment, in this case a widely used inhaler, the bronchodilator, salbutamol. This shows that the imaging methods could be valuable in clinical trials of new treatments of lung disease.

Use in lung transplants

A further study, published in JHLT Open, examined patients who had previously received a lung transplant for very severe lung disease at the Newcastle upon Tyne Hospitals NHS Foundation Trust. It demonstrates how the team further developed the imaging method to provide lung function measurements which could be used to better support lung transplant recipients in the future. The sensitivity of the measurement means medics can spot early changes in lung function allowing them to identify lung problems earlier and so provide better care for patients.

In research studies, the team scanned transplant recipients’ lungs over multiple breaths in and out, collecting MRI pictures that show how the air containing the gas reached different areas of the lung. The team scanned those who either had normal lung function or who were experiencing chronic rejection after lung transplant, which is a common issue in lung transplant recipients as their immune system attacks the donor lungs. In those with chronic rejection, the scans showed poorer movement of air to the edges of the lungs, most likely due to damage in the very small breathing tubes (airways) in the lung, a feature typical of chronic rejection also known as chronic lung allograft dysfunction.

Professor Andrew Fisher, Professor of Respiratory Transplant Medicine at Newcastle Hospitals NHS Foundation Trust and Newcastle University, UK, co-author of the study said; “We hope this new type of scan might allow us to see changes in the transplant lungs earlier and before signs of damage are present in the usual blowing tests. This would allow any treatment to be started earlier and help protect the transplanted lungs from further damage.”

The team say there is potential for this scan method to be used in the clinical management of lung transplant recipients and other lung diseases in the future, bringing a sensitive measurement that may spot early changes in lung function that enable better management of these conditions.

This work on lung imaging has been funded by the Medical Research Council and by The Rosetrees Trust.

KAIST (represented by President Kwang Hyung Lee) announced on the 20th of December that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering has developed a groundbreaking technology that can treat colon cancer by converting cancer cells into a state resembling normal colon cells without killing them, thus avoiding side effects.

The research team focused on the observation that during the oncogenesis process, normal cells regress along their differentiation trajectory. Building on this insight, they developed a technology to create a digital twin of the gene network associated with the differentiation trajectory of normal cells.

Through simulation analysis, the team systematically identified master molecular switches that induce normal cell differentiation. When these switches were applied to colon cancer cells, the cancer cells reverted to a normal-like state, a result confirmed through molecular and cellular experiments as well as animal studies.

This research demonstrates that cancer cell reversion can be systematically achieved by analyzing and utilizing the digital twin of the cancer cell gene network, rather than relying on serendipitous discoveries. The findings hold significant promise for developing reversible cancer therapies that can be applied to various types of cancer.

Professor Kwang-Hyun Cho remarked, “The fact that cancer cells can be converted back to normal cells is an astonishing phenomenon. This study proves that such reversion can be systematically induced.”

He further emphasized, “This research introduces the novel concept of reversible cancer therapy by reverting cancer cells to normal cells. It also develops foundational technology for identifying targets for cancer reversion through the systematic analysis of normal cell differentiation trajectories.”

The study was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-Career Researcher Program and Basic Research Laboratory Program. The research findings have been transferred to BioRevert Inc., where they will be used for the development of practical cancer reversion therapies.

Over half of U.S. adults (52%) think the vaccine given to pregnant individuals to protect their infants from RSV (respiratory syncytial virus) is effective, up from 42% in October 2023, soon after the Centers for Disease Control and Prevention (CDC) recommended the vaccine. And 61% say the RSV vaccine for adults age 60 and older is effective, up from 54% in October 2023.

The rise in perceived effectiveness for the RSV vaccine comes even though there has been no sign to date of a dreaded “tripledemic,” the wave of flu, Covid-19, and RSV illnesses that filled emergency rooms in the fall and winter of 2022-23 and may have resulted in over 100,000 U.S. deaths. As of Dec. 20, 2024, the CDC reports overall moderate levels of acute respiratory illness, though flu season is underway with levels increasing across the country, Covid-19 activity is increasing from low levels in some areas of the country, and RSV activity is high and increasing in most U.S. areas, especially in young children.

The rise also comes as several of president-elect Donald Trump’s nominees for leading policy-making health positions have cast doubt on the efficacy and safety of vaccines, notably Health and Human Services Secretary nominee Robert F. Kennedy Jr., who has said “no vaccine” is safe and effective, and CDC chief nominee Dave Weldon, who, like Kennedy, has promoted the disproven link between vaccines and autism.

The APPC survey findings are based on a nationally representative panel survey of 1,771 U.S. adults fielded from Nov. 14-24, 2024, and has a margin of error of ± 3.3 percentage points. For more on the survey, see the end of this news release or the topline.

Vaccine hesitancy may have plateaued

The past several years have shown evidence of increased vaccine hesitancy. However, by several measures in the November survey, including the RSV findings noted above, public acceptance of vaccination has risen slightly or held steady:

• 86% of respondents say the measles, mumps, and rubella vaccine (MMR) is safe, up from 81% in October 2023. The rebound brings it back toward the 88% who perceived it as safe in August 2022.
• 83% say the flu vaccine is safe, unchanged from October 2023.
• 65% say the Covid-19 vaccine is safe, unchanged from last fall.
• The perceived effectiveness of a variety of other vaccines is unchanged from October 2023.
• Over three-quarters of the public would recommend various vaccines, when appropriate, to members of their families and households.

In addition, despite continuing attacks on the safety and efficacy of certain vaccines by some politicians, 9 in 10 respondents say it is important for parents to get their children vaccinated: 72% say it is very or extremely important and 19% say it is somewhat important. Only 10% say it is not at all or not very important that parents get their children vaccinated.

Flu vaccine vs. Covid-19

In the survey, U.S. adults view the seasonal flu shot as more effective at reducing the risk of getting a severe case of the flu this season (75%) than the Covid booster is at reducing the risk of getting a severe case of Covid this season (55%). There’s been a significant increase in understanding that the flu shot doesn’t necessarily prevent a person who is exposed to the flu from getting sick but it does make the infection less severe (54%, up from 48% in October 2023). Fewer people say they are unsure what effect a flu shot has on a person who is later exposed to someone with the flu (14%, down from 20%).

The November data show that fewer people have received or plan to receive the Covid booster, as compared with the flu shot:

• Just over half of survey respondents (51%) either got the seasonal flu shot (40%) or say they are very likely to (11%) get it, compared with 38% who either got the latest Covid-19 booster (29%) or say they are very likely to (9%).
• The most common reason people select to explain why they have received the Covid booster and the flu shot is to protect themselves against catching that illness (82% and 78%, respectively).
• More people report getting the flu shot because they “get it every year” (76%) than those who report getting the Covid booster because they “get one every time a new booster comes out” (51%).
• 68% know they can get a Covid booster and a flu shot in the same visit to a health care clinic or pharmacy, unchanged from October 2023, though there’s a significant increase in the number who report that this is definitely true (44%, up from 38% in October 2023).

Flu knowledge

• Most people (80%) know the effectiveness of the seasonal flu shot varies year to year.
• Although most people (69%) see this year’s flu vaccine as effective at reducing the risk of getting the flu (unchanged from October 2023), more people think it is ineffective this fall (20%) than last fall (15%).
  • In fact, early reports suggest that this seasonal flu vaccine may be less effective than last year’s: Based on reports from five South American countries, the CDC has said the effectiveness of the seasonal flu vaccine at cutting the risk of hospitalization among high-risk groups appears to be 35%, lower than the 51.9% seen in those countries last flu season, according to WebMD.
• 69% know that there is value in getting a flu shot after November, but 19% are unsure.
• Most people (80%) know it is possible to spread the flu to others even if you have no symptoms, up from 76% in January of 2023. (The CDC says that some “people can be infected with influenza viruses and have no symptoms but may still be able to spread the virus to their close contacts.”)
• Most (71%) know that the flu shot is the best defense against seasonal flu.
• However, only 42% believe that everyone 6 months of age and older should get a flu shot, unchanged from last year.

Beliefs in vaccine effectiveness and safety

Longstanding vaccines such as the MMR, polio, and Tdap (tetanus, diphtheria, and pertussis) vaccines are usually top-rated by the public in effectiveness, safety, and in recommendations that others get the vaccines. Newer vaccines such as the Covid-19 vaccine or those for which public health advice has recently changed — such as the CDC recommendation that adults 50 and older get a vaccine against pneumonia — are less familiar and often lower-rated by the public.

Recommending vaccines. Here are the public’s views on recommending vaccines to others:

• MMR vaccine: 90% would be likely to recommend an MMR vaccine for a child in their household who is either between the ages of 12-15 months or 4 to 6 years old.
• Polio vaccine: 88% would be likely to recommend a polio vaccine to a child in their household of 2 to 6 months old.
• Tdap vaccine: 85% would be likely to recommend a Tdap vaccine to a child in their household of 11-12 years old or an adult in their family.
• Shingles vaccine: 82% would be likely to recommend a shingles vaccine to someone age 50+ in their family.
• HPV vaccine: 79% would be likely to recommend an HPV (human papillomavirus) vaccine for a child aged 11 or 12 years old in their household.
• Pneumonia vaccine: 77% would be likely to recommend a pneumonia vaccine to a person aged 50 or older in their family, down from 84% who were likely to recommend it to someone 65 or older in their family in April 2022. The CDC recommended lowering the age for the vaccine on Oct. 23, 2024, weeks before this survey was fielded.

Vaccine safety. Public views on vaccine safety:

• MMR: 86% say the MMR vaccine is safe, up from 81% in October 2023 (as noted above)
• Flu: 83% say the flu vaccine is safe, unchanged
• Covid-19: 65% say the Covid-19 vaccine is safe, unchanged from October 2023 but lower than 73% in August 2022.

Vaccine effectiveness. Public views on vaccine effectiveness are stable with the exception of RSV, which rose as noted above. The following percentages saw these vaccines as effective. Comparisons are to October 2023, if this question was asked then:

• MMR: 86% see the vaccine as effective (unchanged)
• Polio: 85%
• Tdap: 80%
• Flu: 75% (unchanged)
• Shingles: 74% (unchanged)
• Pneumonia: 71% (unchanged)
• HPV: 65% (unchanged)
• Covid-19: 65% (unchanged)
• RSV for adults 60 and older: 61%, up from 54% in October 2023
• RSV for pregnant individuals: 52%, up from 42% in October 2023

APPC’s Annenberg Science and Public Health knowledge survey

The survey data come from the 22^nd wave of a nationally representative panel of 1,771 U.S. adults conducted for the Annenberg Public Policy Center by SSRS, an independent market research company. Most have been empaneled since April 2021. To account for attrition, small replenishment samples have been added over time using a random probability sampling design. The most recent replenishment, in September 2024, added 360 respondents to the sample. This wave of the Annenberg Science and Public Health Knowledge (ASAPH) survey was fielded Nov. 14-24, 2024. The margin of sampling error (MOE) is ± 3.3 percentage points at the 95% confidence level. All figures are rounded to the nearest whole number and may not add to 100%. Combined subcategories may not add to totals in the topline and text due to rounding.

People with Parkinson’s disease report that tremors worsen during stressful situations. ‘Tremors act as a sort of barometer for stress; you see this in all people with Parkinson’s’, says neurologist Rick Helmich from Radboud university medical center. The commonly used drug levodopa usually helps with tremors, but it tends to be less effective during stress, when tremors are often at their worst. Helmich and his team wanted to investigate whether a medication targeting the stress system could help and how this effect of stress on tremors works in the brain.

Mathematical calculations

The medication in question, propranolol, is a beta-blocker that inhibits the action of stress hormones. It was developed for high blood pressure and heart arrhythmias, has been around for a long time, and is already used as a standard treatment for essential tremor — a condition in which people experience tremors without other neurological symptoms. There were already indications that propranolol might reduce tremors in Parkinson’s, but until now, no thorough research has explored its potential effects.

Helmich and his team studied 27 people with Parkinson’s who experienced tremors. They were given propranolol on one day and a placebo on another day. A device on their hands measured the intensity of their tremors, while an MRI scan mapped brain activity. This was done both at rest and during a task involving stressful mathematical calculations. The stress response was measured by pupil size and heart rate, both of which increased during the calculations. As expected, without medication, tremors worsened during stress.

Amplifier

The study showed that propranolol reduced tremors both at rest and during stress. The MRI scans revealed how this works: after taking the medication, the brain circuit responsible for tremors showed less activity. Helmich explains: ‘We know that abnormalities in systems like the dopamine system cause tremors. Based on our study, we now think that the stress hormone noradrenaline acts as an amplifier, which increases tremor intensity in the brain’s movement area. Propranolol inhibits this amplifying effect and thus reduces symptoms.’

It surprised the researchers that propranolol also worked to reduce tremors at rest. ‘Apparently, our stress system is occasionally active, even at rest’, says researcher Anouk van der Heide. ‘This changes how alert someone is and leads to spontaneous fluctuations in tremors. We previously thought that the stress hormone system was only active under stress, but apparently, that’s too simplistic. It also plays a role at rest.’

Mindfulness

Helmich already prescribes propranolol for some Parkinson’s patients. ‘The most effective medication for Parkinson’s is levodopa. It not only helps with tremors but also with other symptoms, so that’s what we start with’, Helmich explains. ‘However, in about forty percent of patients, it is not effective against tremors. In that case, we first increase the dose, but if that doesn’t work, propranolol is an option. However, we must be cautious about side effects, such as low blood pressure.’

In addition to medication studies, Helmich’s team is also exploring lifestyle changes that could help with Parkinson’s. ‘It doesn’t take much to trigger a stress response, causing people to tremble more. Even something as simple as wondering: did I lock the front door? can set it off. We are currently investigating whether mindfulness can positively influence the stress system.’

The application in live mice shows the improved efficiency of the tool, called SPLICER, over the current standard in gene editing technology, as well as the potential for application in other diseases, the researchers said. Led by Pablo Perez-Pinera, a professor of bioengineering at the U. of I., the researchers published their findings in the journal Nature Communications.

SPLICER uses a gene editing approach called exon skipping, which is of particular interest for health conditions caused by mutations that produce misfolded or toxic proteins, such as Duchenne’s muscular dystrophy or Huntington’s disease.

“DNA contains the instructions to build everything that is responsible for how cells function. So it’s like a book of recipes that contains very detailed instructions for cooking,” Perez-Pinera said. “But there are large regions of DNA that don’t code for anything. It’s like, you start the recipe for a turkey dinner, and then you hit a note that says, ‘continued on page 10.’ After page 10, it’s ‘continued on page 25.’ The pages between are gibberish.

“But say on one of the recipe pages — in genetics, an exon — there is a typo that makes the turkey inedible, or even poisonous. If we cannot correct the typo directly, we could amend the note before it to send you to the next page, skipping over the page with the error, so that at the end you could make an edible turkey. Though you might lose out on the gravy that was on the skipped page, you’d still have dinner. In the same way, if we can skip the piece of the gene with the toxic mutation, the resulting protein could still have enough function to perform its critical roles.”

SPLICER builds upon the popular CRISPR-Cas9 gene editing platform — with key changes. CRISPR-Cas9 systems require a specific DNA sequence to latch on, limiting which genes could be edited. SPLICER uses newer Cas9 enzymes that do not need that sequence, opening up the door to new targets like the Alzheimer’s-related gene that the Illinois group focused on.

“Another problem we address in our work is precision in what gets skipped,” said graduate student Angelo Miskalis, a co-first author of the paper. “With current exon-skipping techniques, sometimes not all of the exon gets skipped, so there’s still part of the sequence we don’t want expressed. In the cookbook analogy, it’s like trying to skip a page, but the new page starts in the middle of a sentence, and now the recipe doesn’t make sense. We wanted to prevent that.”

There are two key sequence areas surrounding an exon that tell the cellular machinery which parts of a gene to use for making proteins: one at the beginning and one at the end. While most exon-skipping tools target only one sequence, SPLICER edits both the starting and ending sequences. As a result, the targeted exons are skipped over more efficiently, Miskalis said.

The Illinois group chose to target an Alzheimer’s gene for the first demonstration of SPLICER’s therapeutic abilities because while the target gene has been well-studied, efficient exon skipping has remained elusive in living organisms. The researchers targeted a specific exon coding for an amino acid sequence within a protein that gets cleaved to form amyloid-beta, which accumulates to form plaques on neurons in the brain as the disease progresses.

In cultured neurons, SPLICER reduced the formation of amyloid-beta efficiently. When analyzing the DNA and RNA output of mouse brains, the researchers found that the targeted exon was decreased by 25% in the SPLICER-treated mice, with no evidence of off-target effects.

“When we originally tried to target this exon with older techniques, it didn’t work,” said graduate student Shraddha Shirguppe, also a co-first author of the study. “Combining the newer base editors with dual splice editing skipped the exon at a much better rate than we were previously able to with any of the available methods. We were able to show that not only could it skip the whole exon better, it reduced the protein that produces the plaque in these cells.”

“Exon skipping only works if the resulting protein is still functional, so it can’t treat every disease with a genetic basis. That’s the overall limitation of the approach,” Perez-Pinera said. “But for diseases like Alzheimer’s, Parkinson’s, Huntington’s or Duchenne’s muscular dystrophy, this approach holds a lot of potential. The immediate next step is to look at the safety of removing the targeted exons in these diseases, and make sure we aren’t creating a new protein that is toxic or missing a key function. We would also need to do longer term animal studies and see if the disease progresses over time.”

At Illinois, Perez-Pinera also is affiliated with the department of Molecular and Integrative Physiology, the Carle Illinois College of Medicine, the Cancer Center at Illinois and the Carl R. Woese Institute for Genomic Biology. U. of I. Bioengineering professors Sergei Maslov and Thomas Gaj were coauthors of the paper. The National Institutes of Health, the Muscular Dystrophy Association, the American Heart Association, the Parkinson’s Disease Foundation and the Simons Foundation supported this work.

This work was supported by the National Institutes of Health grants 1U01NS122102, 1R01NS123556, 1R01GM141296, 1R01GM127497, T32EB019944 and 1R01GM131272.

Typically, experts seeking answers to questions about care need to pore over hundreds of medical charts. But new research shows that large language models — AI tools that can find patterns in complex written language — may be able to take over this busywork and that their findings could have practical uses. For instance, AI tools could monitor patients’ charts for mentions of hazardous interactions between drugs or could help doctors identify patients who will respond well or poorly to specific treatments.

The AI tool, described in a study that published online Dec. 19 in Pediatrics, was designed to figure out from medical records if children with attention deficit hyperactivity disorder received appropriate follow-up care after being prescribed new medications.

“This model enables us to identify some gaps in ADHD management,” said the study’s lead author, Yair Bannett, MD, assistant professor of pediatrics.

The study’s senior author is Heidi Feldman, MD, the Ballinger-Swindells Endowed Professor in Developmental and Behavioral Pediatrics.

The research team used the tool’s insights to pinpoint tactics that could improve how doctors follow up with ADHD patients and their families, Bannett noted, adding that the power of such AI tools could be applied to many aspects of medical care.

A slog for a human, a breeze for AI

Electronic medical records contain information such as lab results or blood pressure measurements in a format that’s easy for computers to compare among many patients. But everything else — about 80% of the information in any medical record — is in the notes that physicians write about the patient’s care.

Although these notes are handy for the next human who reads a patient’s chart, their freeform sentences are challenging to analyze en masse. This less-organized information must be categorized before it can be used for research, typically by a person who reads the notes looking for specific details. The new study looked at whether researchers could employ artificial intelligence for that task instead.

The study used medical records from 1,201 children who were 6 to 11 years old, were patients at 11 pediatric primary care practices in the same health care network, and had a prescription for at least one ADHD medication. Such medications can have disruptive side effects, such as suppressing a child’s appetite, so it is important for doctors to inquire about side effects when patients are first using the drugs and adjust dosages as necessary.

The team trained an existing large language model to read doctors’ notes, looking for whether children or their parents were asked about side effects in the first three months of taking a new drug. The model was trained on a set of 501 notes that researchers reviewed. The researchers counted any note that mentioned either the presence or absence of side effects (e.g., either “reduced appetite” or “no weight loss”) as indicating that follow-up had happened, while notes with no mention of side effects were counted as meaning follow-up hadn’t occurred.

These human-reviewed notes were used as what’s known in AI as “ground truth” for the model: The research team used 411 of the notes to teach the model what an inquiry about side effects looked like, and the remaining 90 notes to verify that the model could accurately find such inquiries. They then manually reviewed an additional 363 notes and tested the model’s performance again, finding that it classified about 90% of the notes correctly.

Once the large language model was working well, the researchers used it to quickly evaluate all 15,628 of the notes in the patients’ charts, a task that would have taken more than seven months of full-time work without AI.

From analysis to better care

From the AI analysis, the researchers picked up information they would not have detected otherwise. For instance, the AI saw that some of the pediatric practices frequently asked about drug side effects during phone conversations with patients’ parents, while other practices did not.

“That is something you would never be able to detect if you didn’t deploy this model on 16,000 notes the way we did, because no human will sit and do that,” Bannett said.

The AI also found that pediatricians asked follow-up questions about certain medications less often. Kids with ADHD can be prescribed stimulants or, less commonly, non-stimulant medications such as some types of anti-anxiety drugs. Doctors were less likely to ask about the latter category of drugs.

The finding offers an example of the limits of what AI can do, Bannett said: It could detect a pattern in patient records but not explain why the pattern was there.

“We really had to talk to pediatricians to understand this,” he said, noting that pediatricians told him they had more experience managing the side effects of the stimulants.

The AI tool may have missed some inquiries about medication side effects in its analysis, the researchers said, because some conversations about side effects may not have been recorded in patients’ electronic medical records, and some patients received specialty care — such as with a psychiatrist — that was not tracked in the medical records used in this study. The AI tool also misclassified a few physician notes on side effects of prescriptions for other conditions, such as acne medication.

Guiding the AI

As scientists build more AI tools for medical research, they need to consider what the tools do well and what they do poorly, Bannett said. Some tasks, such as sorting through thousands of medical records, are ideal for an appropriately trained AI tool.

Others, such as understanding the ethical pitfalls of the medical landscape, will require careful human thought, he said. An editorial that Bannett and colleagues recently published in Hospital Pediatrics explains some of the potential problems and how they might be addressed.

“These AI models are trained on existing health care data, and we know from many studies over the years that there are disparities in health care,” Bannett said. Researchers need to think through how to mitigate such biases both as they build AI tools and when they put them to work, he said, adding that with the right cautions in place, he is excited about the potential of AI to help doctors do their jobs better.

“Each patient has their own experience, and the clinician has their knowledge base, but with AI, I can put at your fingertips the knowledge from large populations,” he said. For instance, AI might eventually help doctors predict based on a patient’s age, race or ethnicity, genetic profile, and combination of diagnoses whether the individual is likely to have a bad side effect from a specific drug, he said. “That can help doctors make personalized decisions about medical management.”

The research was supported by the Stanford Maternal and Child Health Research Institute and the National Institute of Mental Health (grant K23MH128455).

Chagas disease, caused by the parasite Trypanosoma cruzi, affects about 7 to 8 million people worldwide, mainly in Latin America. The parasite can be transmitted by triatomine bugs, via food, blood transfusions and organ donations, as well as from mother to child during pregnancy and birth. Chagas disease has two phases: In the acute phase in the first 2 months, symptoms are mild or absent, though some may have fever, headache or swelling at the bite site. Decades later, in the chronic phase, up to a third of infected individuals develop cardiovascular, digestive and/or neurological problems. Advanced cases can lead to heart complications such as arrhythmias and sudden death. Chagas disease is categorized as a neglected tropical disease (NTD) by the World Health Organization (WHO).

2,000 to 4,000 people in Switzerland affected

A review published yesterday in the Swiss Medical Weekly now sheds light on the prevalence, challenges and management of Chagas disease. The study found that an estimated 2,000 to 4,000 people are affected by this tropical disease. While most of the cases stem from migration, the study also shows that Chagas disease can be transmitted in Switzerland through mother-child transmission during pregnancy and childbirth. The vector — the triatomine bug — is not present in Europe. “A major problem of Chagas disease is that it is often underdiagnosed, particularly in non-endemic regions,” said Pablo Martinez de Salazar, Senior Scientific Collaborator at Swiss TPH, and last author of the study. “Indeed, many cases remain undiagnosed or undetected for years, potentially resulting in severe cardiac or digestive complications if untreated.” Factors such as limited awareness among healthcare professionals, absence of nationwide screening programmes and barriers to healthcare access — especially for undocumented migrants -, contribute to this underdiagnosis.

Establishment of the Swiss Chagas Network

To address these issues, the study team established the Swiss Chagas Network to eliminate Chagas disease as a public health problem through coordinated measures. The network aims to interrupt transmission and to provide adequate clinical management to people living with Chagas disease in Switzerland. Key priorities include integrating screening into prenatal and paediatric care for early detection and preventing mother-to-child transmission during pregnancy and childbirth. In line with international guidelines, the Swiss Society for Gynaecology and Obstetrics recently issued an expert letter on Screening, prevention and treatment of congenital Chagas disease.

“Systematic screening in Latin American migrants, with a focus on women of reproductive age, pregnant women and children, will be critical,” said Mar Velarde, Scientific Collaborator at Swiss TPH and co-author of the paper. “If appropriate measures are put in place, Switzerland will be well positioned to achieve the targets of the WHO road map for neglected tropical diseases by 2030 and could become a blueprint for other countries.” The road map sets out global targets to prevent, control, eliminate and eradicate different NTDs by 2030.

About the study

The study was led by Swiss TPH in collaboration with WHO, Unisanté, the University of Lausanne, the School of Health Sciences (HESAV), the University of Applied Sciences and Arts Western Switzerland (HES-SO), the University of Zurich, the University of Basel, the Geneva University Hospital, and the University of Geneva. The coordination of the study was supported by the R. Geigy Foundation.

Swiss TPH expertise in Chagas disease

Swiss TPH has a long tradition of work pertaining to neglected tropical diseases, from basic research to training, diagnosis, treatment and elimination efforts. With regards to Chagas disease, Swiss TPH is involved in drug discovery, drug development, epidemiology, diagnosis, control and elimination.

“When viruses infect cells, they usually create specialized compartments — replication factories — where they form new viruses that infect more cells causing the disease,” said first author Dr. Soni Kaundal, postdoctoral associate in the Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology at Baylor in the lab of Dr. B.V. Venkataram Prasad, corresponding author of the work. “However, little is known about norovirus’s replication factories.

Increasing evidence shows that some replication factories typically are not separated from their surroundings by a membrane. Instead, they are biomolecular condensates, structures resembling a bubble formed by liquid-liquid phase separation. These condensates selectively incorporate proteins and other materials needed for viral replication. Liquid-like condensates as replication factories have been extensively studied in other viruses, including the rabies and measles viruses. In this study the researchers investigated whether norovirus forms biomolecular condensates that serve as replication hubs.

“We knew that these condensates are often initiated by a single viral protein capable of binding genetic material, having a flexible region and forming oligomers, molecules made of small numbers of repeating units,” Kaundal said.

The team began their investigation by applying bioinformatic analysis to identify norovirus proteins that would present the characteristics most likely leading to the formation of liquid condensates.

“Working with the human norovirus pandemic strain GII.4, the one responsible for causing most cases of gastroenteritis around the world, we found that the RNA-dependent RNA polymerase has the highest propensity to form biomolecular condensates,” Kaundal said. “This protein has a flexible region, can form oligomers, binds RNA, the norovirus’s genetic material, and plays an essential role during viral replication making copies of the viral RNA. All these characteristics prompted us to experimentally test whether the GII.4 RNA polymerase drives the formation of biomolecular condensates conducive to viral replication.”

“Our experimental studies show that GII.4 RNA polymerase indeed forms highly dynamic liquid-like condensates at physiologically relevant conditions in the lab and that the flexible region of this protein is critical for this process,” said Prasad, professor of molecular virology and microbiology and Alvin Romansky Chair in Biochemistryat Baylor. Prasad also is a member of Baylor’s Dan L Duncan Comprehensive Cancer Center. “Furthermore, the condensates are highly dynamic structures: several can merge forming a larger structure or they can divide into smaller ones; they also move inside the cell, exchanging materials with their surroundings.”

Next, the researchers investigated whether these liquid-like condensates are also formed in human norovirus-infected human intestinal cells. Until recently, studying how norovirus replicates inside cells has been difficult because researchers lacked an effective biological system in which to grow the virus in the lab. But in 2016, the lab of Dr. Mary Estes at Baylor and colleagues succeeded at cultivating human norovirus strains in human intestinal enteroid cultures.

Also known as mini-guts, these cultures are a laboratory model of the human gastrointestinal tract that recapitulates its cellular complexity, diversity and physiology. Human enteroids mimic strain-specific host-virus infection patterns, making them an ideal system to dissect human norovirus infection, as in the current study, to identify strain-specific growth requirements and develop and test treatments and vaccines.

“We showed that liquid-like condensates are formed in human norovirus-infected human intestinal enteroid cultures as well as in the HEK293T human cell line grown in the lab. We propose that these condensates are replication hubs for human norovirus, an elegant solution to the puzzling question of how ribosome-assisted translation of the viral genome is segregated from its replication by the viral polymerase in positive-strand RNA viruses,” Prasad said. “Our bioinformatics analysis also showed that the RNA polymerases of almost all the norovirus strains have a high propensity to form these replication factories, suggesting that this may be a common phenomenon of most noroviruses.”

“This is a remarkable paper, and I was glad we could validate the findings in virus-infected cells using our human intestinal enteroids cultivation system for human norovirus,” said Estes, Distinguished Service Professor and Cullen Foundation Endowed Chair of molecular virology and microbiology at Baylor. Estes also is the co-director of the Gastrointestinal Experimental Model Systems core at the Texas Medical Center Digestive Diseases Center and a member of Baylor’s Dan L Duncan Comprehensive Cancer Center.

The findings not only provide new insight into human norovirus replication but also open new targets for designing antivirals for human norovirus infections, which remain a serious threat in children and immunocompromised patients.

Other contributors to this work include Ramakrishnan Anish, B. Vijayalakshmi Ayyar, Sreejesh Shanker, Gundeep Kaur, Sue E. Crawford, Jeroen Pollet and Fabio Stossi. The authors are affiliated with Baylor College of Medicine and the University of Texas, MD Anderson Cancer Center.

Support for this project was provided by NIH grant P01 AI057788, Robert Welch Foundation grant Q1279, the Center for Advanced Microscopy and Image Informatics (Cancer Prevention and Research Institute of Texas (CPRIT) grant RP170719), the Integrated Microscopy Core at Baylor College of Medicine (NIH grants: DK56338, CA125123, ES030285 and S10OD030414), and CPRIT grant RR160029.

Led by Texas A&M University graduate students Samere Zade of the biomedical engineering department and Ting-Ching Wang of the chemical engineering department, an article released by the Lele Lab has uncovered new details about the mechanism behind cancer progression.

Published in Nature Communications, the article explores the influence the mechanical stiffening of the tumor cell’s environment may have on the structure and function of the nucleus.

“Cancer has proven to be a difficult disease to treat. It is extremely complex and the molecular mechanisms that enable tumor progression are not understood,” said Dr. Tanmay Lele, joint faculty in the biomedical engineering and chemical engineering departments. “Our findings shed new light into how the stiffening of tumor tissue can promote tumor cell proliferation.”

In the article, researchers reveal that when a cell is faced with a stiff environment, the nuclear lamina — scaffolding that helps the nucleus keep its shape and structure — becomes unwrinkled and taut as the cell spreads on the stiff surface. This spreading causes yes-associated protein (YAP), the protein that regulates the multiplication of cells, to move to the nucleus.

That localization can cause increased cell proliferation, which may explain the rapid growth of cancer cells in stiff environments.

“The ability of stiff matrices to influence nuclear tension and regulate YAP localization could help explain how tumors become more aggressive and perhaps even resistant to treatment in stiffened tissues,” Zade said.

These findings build on Lele’s previous discovery that the cell nucleus behaves like a liquid droplet. In that work, researchers found that a protein in the nuclear lamina called lamin A/C helps maintain the nucleus’ surface tension. In the most recent study, it was found that reducing the levels of lamin A/C decreases the localization of YAP, in turn decreasing rapid cell proliferation.

“The protein lamin A/C plays a key role here — reducing it made cells less responsive to environmental stiffness, particularly affecting the localization of a key regulatory protein (YAP) to the nucleus,” Zade explained.

Although seemingly complex and specialized, Zade and Lele believe the broader implications of their discovery may guide future treatments for cancer.

“Uncovering how matrix stiffness drives nuclear changes and regulates key pathways, like YAP signaling, opens the door to developing therapies that target these mechanical pathways,” Zade explained. “Drugs or treatments could be designed to soften the tumor environment, disrupting the physical cues that help cancer cells thrive. Lamin A/C and related nuclear mechanics could become targets for cancer treatments.”

Moving forward, the Lele Lab aims to investigate the extent to which their discoveries apply to tumors derived from patients.

For this work, the Lele Lab was funded by the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and the National Science Foundation. Funding for this research is administered by the Texas A&M Engineering Experiment Station, the official research agency for Texas A&M Engineering.

According to the Centers for Disease Control and Prevention, heart failure affects nearly 7 million U.S. adults and is responsible for 14% of deaths per year. There is no cure for heart failure, though medications can slow its progression. The only treatment for advanced heart failure, other than a transplant, is pump replacement through an artificial heart, called a left ventricular assist device, which can help the heart pump blood.

“Skeletal muscle has a significant ability to regenerate after injury. If you’re playing soccer and you tear a muscle, you need to rest it, and it heals,” said Hesham Sadek, MD, PhD, director of the Sarver Heart Center and chief of the Division of Cardiology at the U of A College of Medicine — Tucson’s Department of Medicine. “When a heart muscle is injured, it doesn’t grow back. We have nothing to reverse heart muscle loss.”

Sadek led a collaboration between international experts to investigate whether heart muscles can regenerate. The study was funded through a grant awarded to Sadek by the Leducq Foundation Transatlantic Networks of Excellence Program, which brings together American and European investigators to tackle big problems.

The project began with tissue from artificial heart patients provided by colleagues at the University of Utah Health and School of Medicine led by Stavros Drakos, MD, PhD, a pioneer in left ventricular assist device-mediated recovery.

Jonas Frisén, MD, PhD, and Olaf Bergmann, MD, PhD, of the Karolinska Institute in Stockholm, led teams in Sweden and Germany and used their own innovative method of carbon dating human heart tissue to track whether these samples contained newly generated cells.

The investigators found that patients with artificial hearts regenerated muscle cells at more than six times the rate of healthy hearts.

“This is the strongest evidence we have, so far, that human heart muscle cells can actually regenerate, which really is exciting, because it solidifies the notion that there is an intrinsic capacity of the human heart to regenerate,” Sadek said. “It also strongly supports the hypothesis that the inability of the heart muscle to ‘rest’ is a major driver of the heart’s lost ability to regenerate shortly after birth. It may be possible to target the molecular pathways involved in cell division to enhance the heart’s ability to regenerate.”

Finding better ways to treat heart failure is a top priority for Sadek and the Sarver Heart Center. This study builds on Sadek’s prior research into rest and heart muscle regeneration.

In 2011, Sadek published a paper in Science showing that while heart muscle cells actively divide in utero, they stop dividing shortly after birth to devote their energy to pumping blood through the body nonstop, with no time for breaks.

In 2014, he published evidence of cell division in patients with artificial hearts, hinting that their heart muscle cells might have been regenerating.

These findings, combined with other research teams’ observations that a minority of artificial heart patients could have their devices removed after experiencing a reversal of symptoms, led him to wonder if the artificial heart provides cardiac muscles the equivalent of bedrest in a person recovering from a soccer injury.

“The pump pushes blood into the aorta, bypassing the heart,” he said. “The heart is essentially resting.”

Sadek’s previous studies indicated that this rest might be beneficial for the heart muscle cells, but he needed to design an experiment to determine whether patients with artificial hearts were actually regenerating muscles.

“Irrefutable evidence of heart muscle regeneration has never been shown before in humans,” he said. “This study provided direct evidence.”

Next, Sadek wants to figure out why only about 25% of patients are “responders” to artificial hearts, meaning that their cardiac muscle regenerates.

“It’s not clear why some patients respond and some don’t, but it’s very clear that the ones who respond have the ability to regenerate heart muscle,” he said. “The exciting part now is to determine how we can make everyone a responder, because if you can, you can essentially cure heart failure. The beauty of this is that a mechanical heart is not a therapy we hope to deliver to our patients in the future — these devices are tried and true, and we’ve been using them for years.”

The findings, reported in Nature Communications, also solve a decades-long scientific puzzle that’s prevented drugmakers from successfully using azole antifungal drugs to treat visceral leishmaniasis, or VL.

About 30 years ago, scientists discovered the two species of single-cell parasites that cause VL, Leishmania donovani and Leishmania infantum, made the same lipid sterol, called ergosterol, as fungi proven susceptible to azoles antifungals. These azoles antifungals target a crucial enzyme for sterol biosynthesis, called CYP51.

While not fungi, both Leishmania species have biochemical similarities to fungi in their plasma membrane, where ergosterol helps maintain cellular integrity and supports a host of biological functions, much as cholesterol does in humans.

“People looked into the sterol profile of the parasites and discovered they primarily have ergosterol,” said study corresponding author Michael Zhuo Wang, professor of pharmaceutical chemistry at the University of Kansas School of Pharmacy. “This sterol is the main component of their plasma-membrane sterols. A similar case can be observed in fungi. Fungal organisms also have a high amount of ergosterol in their membranes. There was an original instinct to use antifungal azoles to try to block that pathway.”

However, scientists were unable to effectively use antifungals against VL.

“In the research lab and some of the clinical trials, some azoles worked a little bit, and some other azoles didn’t work at all,” Wang said. “I eventually focused on this sterol pathway a scientific question — if this parasite also uses ergosterol, you’d think all the antifungal azoles would work against this parasite.”

Along these lines, Wang started his independent research career as part of a group at the University of North Carolina-Chapel Hill called the Consortium for Parasitic Drug Development.

“We were interested in developing new drugs against neglected tropical diseases,” he said. “One of these diseases is leishmaniasis. The other one is the African sleeping sickness. Leishmaniasis, spread by a sandfly vector in warmer climates, can cause really devastating infection of internal organs such as the liver and the spleen, as well as the bone marrow.”

In his new scholarly paper, Wang and his collaborators have largely solved that longstanding scientific question. They show the parasites that cause leishmaniasis are vulnerable via a different pathway for biosynthesis of their ergosterol, known as the CYP5122A1 enzyme. Therefore, azole antifungals targeting the CYP5122A1 enzyme as well as the traditional CYP51 pathway should be much more effective at treating leishmaniasis.

“So those azoles don’t work very well against leishmania unless you have an azole that also inhibits the new pathway, the CYP5122A1,” Wang said. “Then, all of a sudden, they’re much more active against leishmania. That’s the main discovery in this study — we figured out the true drug target in leishmania. You really need to hit this new enzyme, 22A1, in order to stop the parasites.”

Wang’s lab at KU demonstrated the CYP5122A1 gene encodes an essential sterol C4-methyl oxidase in the leishmania parasite, through extensive biochemical characterization.

“This involved defining its biochemical function — what this enzyme does in terms of sterol biosynthesis,” he said. “We pinned down its biochemical function, clarifying its role in the ergosterol biosynthesis pathway.”

Already, the researchers are publishing follow-up scholarship and discovery based on their new breakthrough in understanding the sterol synthesis pathway in the parasites. They said drugmakers and researchers should be developing therapies that target CYP5122A1. These should prove more effective at helping people survive leishmaniasis, Wang said.

“This tells us how we should repurpose these existing antifungal azoles through screening against this new target,” said the KU researcher. “The ones that actually inhibit this new target should have a better chance to work against leishmania infection.”

Wang’s co-authors at the KU School of Pharmacy were doctoral students Yiru Jin and Mei Feng, who served as lead authors, and doctoral student Lingli Qin as co-author in the Department of Pharmaceutical Chemistry; Director Chamani Perera and doctoral student Indeewara Munasinghe from KU’s Synthetic Chemical Biology Core Laboratory; Philip Gao, director of KU’s Protein Production Group; and Judy Qiju Wu, associate teaching professor of pharmacy practice.

The KU researchers were joined by Kai Zhang, Somrita Basu, Yu Ning, Robert Madden, Hannah Burks and Salma Waheed Sheikh from Texas Tech University; and Karl Werbovetz, Arline Joachim, Junan Li and April Joice from The Ohio State University.

This study was supported in part by the U.S. National Institute of Allergy and Infectious Diseases, the U.S. Department of Defense and the KU Centers of Biomedical Research Excellence (COBRE).

ASD, which affects more males than females, encompasses a group of neurodevelopmental conditions that result in challenges related to communication, social understanding and behaviour. While DDX53, located on the X chromosome, is known to play a role in brain development and function, it was not previously definitively associated with autism.

In the study published today, researchers from The Hospital for Sick Children (SickKids) in Canada and the Istituto Giannina Gaslini in Italy clinically tested 10 individuals with ASD from 8 different families and found that variants in the DDX53 gene were maternally inherited and present in these individuals. Notably, the majority were male, highlighting the gene’s potential role in the male predominance observed in ASD.

“By pinpointing DDX53 as a key player, particularly in males, we can better understand the biological mechanisms at play and improve diagnostic accuracy for individuals and their families,” says senior author Dr. Stephen Scherer, Senior Scientist, Genetics & Genome Biology and Chief of Research at SickKids, and Director of the McLaughlin Centre at the University of Toronto.

“Identifying this new gene as a confirmed contributor to ASD underscores the complexity of autism and the need for comprehensive genetic analysis.”

At the same location on the X chromosome, the researchers found evidence that another gene, PTCHD1-AS, might be involved in autism. The study highlights a case where a boy and his mother, both with autism with little support needs, had a specific gene deletion involving the DDX53 gene and parts of PTCHD1-AS.

The study cohort was assembled through an international collaborative effort, involving several renowned clinical and research institutions from Canada, Italy and the U.S. Further analysis of large autism research databases, including Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, identified 26 more individuals with ASD who had similar rare DDX53 variants to the study participants.

“This gene has long eluded us, not previously linked to any neuropsychiatric condition. Our findings support a direct link between DDX53 and autism, which is not only crucial for future clinical genetic testing, but its discovery suggests that the pathway it affects is related to the behavioural traits of autism, opening a whole new area of exploration,” says lead author Dr. Marcello Scala, researcher in Medical Genetics at the Istituto Giannina Gaslini, affiliated with the University of Genoa (Department of Neuroscience).

In another paper published today in the same journal, Scherer and lead author Dr. Marla Mendes, a research fellow at SickKids, identified 59 genetic variants on the X chromosome significantly associated with ASD. The variants were found in genes linked to autism, including PTCHD1-AS (near to DDX53), DMD, HDAC8, PCDH11X, and PCDH19 beside novel ASD-linked candidates ASB11 and ASB9. Additionally, the FGF13 gene was highlighted as being related to ASD, with sex-specific differences, adding more evidence to the role of sex chromosomes in the condition.

“These findings provide new insights into the biology of the X chromosome in ASD, providing additional evidence for the involvement of certain genes like DDX53 and FGF13, and suggesting they should be investigated further,” says Scherer.

The team notes that the absence of a similar gene like DDX53 in commonly used mouse models may require future researchers to reconsider how they study ASD. Since it lacks a functional equivalent in these models, findings in DDX53 cannot be easily replicated.

“Insights from this study could significantly influence the design and interpretation of autism research, particularly in developing new models. Identifying these variants is an important step towards developing more precise diagnostics and therapeutics for patients and families with ASD,” says Scherer.

Scherer also added “both studies provide even more evidence that complex neurobehavioral conditions like autism can sometimes have simple biologic (genetic) underpinnings.”

The study was funded by the University of Toronto McLaughlin Centre, Autism Speaks, Autism Speaks Canada, Ontario Brain Institute, the Italian Ministry for Education, University and Research and SickKids Foundation. Additional funding was provided by National Institutes of Health and the California Center for Rare Diseases at UCLA.

The hippocampus plays a crucial role in memory formation, learning and emotional regulation. Hippocampal neuroinflammation occurs in a range of diseases and disorders such as Alzheimer’s, Multiple Sclerosis and Depression.

People with these diseases often experience common symptoms such as apathy, difficulty with daily activities and changes to food preferences. These symptoms also tend to be more severe in women than in men.

“While inflammation in the hippocampus is not solely responsible for behaviour changes, it likely triggers wider brain activity that influences behaviour,” said study co-author Dr Laura Bradfield, Director of the Brain and Behaviour Lab at the University of Technology Sydney (UTS).

“This research suggests that treatments targeting hippocampal neuroinflammation could help reduce cognitive and behavioural symptoms in these diseases and improve brain health, especially in women,” she said.

The study, “Hippocampal neuroinflammation induced by lipopolysaccharide causes sex-specific disruptions in action selection, food approach memories, and neuronal activation,” was published in the journal Brain Behavior and Immunity.

Researchers induced inflammation by exposing mouse hippocampal cell cultures in the lab to lipopolysaccharide, a bacterial toxin that elicits a strong immune response.

They found the toxin only activated neurons in the presence of other types of brain cells such as microglia and astrocytes. This highlights the complex interaction between different cell types during inflammation.

To examine behaviour, the researchers injected lipopolysaccharide directly into the hippocampus of mice and observed their activity and food-seeking behaviours.

They discovered that neuroinflammation increased movement and activity levels in both sexes but had a more pronounced effect on food-seeking behaviours in females.

Lead author Dr Kiruthika Ganesan, who recently completed her PhD at UTS, said the study underscores the importance of considering sex-specific effects when developing treatments for neurological diseases.

“These findings provide fresh insights into how neuroinflammation affects brain function, potentially paving the way for new therapies that address the behavioural and cognitive symptoms of a range of diseases,” she said.

“We hope that future research will focus on understanding the mechanisms behind these sex-specific effects, including the influence of hormones such as estrogen, and their implications for brain health.”

Prior research has revealed a tendency of people to blame AI for various moral transgressions, such as in cases of an autonomous vehicle hitting a pedestrian or decisions that caused medical or military harm. Additional research suggests that people tend to assign more blame to AIs perceived to be capable of awareness, thinking, and planning. People may be more likely to attribute such capacities to AIs they perceive as having human-like minds that can experience conscious feelings.

On the basis of that earlier research, Joo hypothesized that AIs perceived as having human-like minds may receive a greater share of blame for a given moral transgression.

To test this idea, Joo conducted several experiments in which participants were presented with various real-world instances of moral transgressions involving AIs — such as racist auto-tagging of photos — and were asked questions to evaluate their mind perception of the AI involved, as well as the extent to which they assigned blame to the AI, its programmer, the company behind it, or the government. In some cases, AI mind perception was manipulated by describing a name, age, height, and hobby for the AI.

Across the experiments, participants tended to assign considerably more blame to an AI when they perceived it as having a more human-like mind. In these cases, when participants were asked to distribute relative blame, they tended to assign less blame to the involved company. But when asked to rate the level of blame independently for each agent, there was no reduction in blame assigned to the company.

These findings suggest that AI mind perception is a critical factor contributing to blame attribution for transgressions involving AI. Additionally, Joo raises concerns about the potentially harmful consequences of misusing AIs as scapegoats and calls for further research on AI blame attribution.

The author adds: “Can AIs be held accountable for moral transgressions? This research shows that perceiving AI as human-like increases blame toward AI while reducing blame on human stakeholders, raising concerns about using AI as a moral scapegoat.”

According to the researchers, “there is no doubt that excessive alcohol consumption has serious health consequences. However, the effects of moderate and responsible wine consumption are still the subject of debate in the scientific community. The results of this study and others should help to place moderate wine consumption in its rightful place as an element of the Mediterranean diet, considered to be the healthiest in the world.” ​​​​​​​

The principal authors of the study are the researcher Inés Domínguez, from the UB’s Faculty of Pharmacy and Food Sciences and the Nutrition and Food Safety Research Institute (INSA); Professor Ramon Estruch, from the UB’s Faculty of Medicine and Health Sciences and IDIBAPS; Rosa María Lamuela, professor and ICREA Academia, and member of INSA, and Professor Miguel Ángel Martínez, from the University of Navarra (UNAV); all members of CIBEROBN.

​​​​​​​Controversy over the effects of wine

Today, there is much controversy about the health effects of moderate consumption of alcoholic beverages in general and wine in particular. Ramon Estruch stresses that “part of this debate is due to conflicting results of studies that have pointed to a protective effect of wine, while others have found no such effect.” These differences could be explained by possible errors in wine consumption records. “Epidemiological studies assessing the role of wine in the rate of cardiovascular events are often based on self-reported information on wine consumption. These are reliable data, but subject to measurement errors due to inaccurate recall or biased perceptions about the social desirability of drinking alcoholic beverages,” he explains. In response to this problem, the researchers in this study measured wine consumption by means of food intake frequency surveys, which they confirmed with an objective biomarker: the concentration found in urine of tartaric acid, a molecule produced mainly in grapes and rarely synthesized by other plant species.

While excessive alcohol consumption has serious health consequences, a new multicentre study provides new evidence that drinking between half a glass of wine and a full glass of wine a day could help reduce the risk of heart problems.

A reduction from 38% to 50%

Using this methodology, the study analysed wine consumption and cardiovascular outcomes in a cohort of PREDIMED patients. In total, 1,232 participants were evaluated, including 685 who had a cardiovascular event (cardiovascular death, myocardial infarction, stroke or heart failure) and 625 who were randomly selected.

Analysis of the data shows that light wine consumption (between one glass per week and less than half a glass per day) reduces the risk of having a cardiovascular complication by 38%, but this reduction reaches 50% when consumption is moderate (between half a glass and one glass per day). However, when consumption exceeds one drink per day, the protective effect disappears. The researchers also warn that “when we talk about moderate wine consumption, it is always with meals, never between meals.”

More studies to confirm the results ​​​​​​​

Despite these conclusions, Inés Domínguez points out that “the observational design of the study limits the ability to establish causality,” and the experts point out that more research is needed: “The results of cohort studies should always be confirmed for greater certainty.” In this regard, they point to two potential avenues for action. The first would involve the design of randomized nutritional intervention studies, by randomly assigning participants to groups with different wine consumption. “These are very expensive studies to conduct. There is one underway now, but the results will still take four to five years,” they add. The second would be to study the mechanisms of these protective effects of wine on the cardiovascular system, such as research on the anti-inflammatory power of wine polyphenols — such as resveratrol and other phenolic compounds. “Knowing the mechanisms gives a lot of plausibility to the results of epidemiological cohort studies,” they conclude.​​​​

Surprisingly, the organoids were still healthy when they returned from orbit a month later, but the cells had matured faster compared to identical organoids grown on Earth — they were closer to becoming adult neurons and were beginning to show signs of specialization. The results, which could shed light on potential neurological effects of space travel, were published on October 23, 2024, in Stem Cells Translational Medicine.

“The fact that these cells survived in space was a big surprise,” says co-senior author Jeanne Loring, PhD, professor emeritus in the Department of Molecular Medicine and founding director of the Center for Regenerative Medicine at Scripps Research. “This lays the groundwork for future experiments in space, in which we can include other parts of the brain that are affected by neurodegenerative disease.”

On Earth, the team used stem cells to create organoids consisting of either cortical or dopaminergic neurons, which are the neuronal populations impacted in multiple sclerosis and Parkinson’s disease — diseases that Loring has studied for decades. Some organoids also included microglia, a type of immune cell that is resident within the brain, to examine the impact of microgravity on inflammation.

Organoids are usually grown in a nutrient-rich liquid medium that must be changed regularly to ensure that the cells have adequate nutrition, and to remove waste products. To avoid the need for lab work on the ISS, the team pioneered a method for growing smaller-than-usual organoids in cryovials — small, airtight vials that were originally designed for deep freezing.

The organoids were prepared in labs at the Kennedy Space Station and traveled to the ISS in a miniature incubator. After a month in orbit, they returned to Earth, where the team showed that they were healthy and intact.

To examine how the space environment impacts cellular functions, the team compared the cells’ RNA expression patterns — a measure of gene activity — to identical “ground control” organoids that had remained on Earth. Surprisingly, they found that the organoids grown in microgravity had higher levels of genes associated with maturity and lower levels of genes associated with proliferation compared to the ground controls, meaning that the cells exposed to microgravity developed faster and replicated less than those on Earth.

“We discovered that in both types of organoids, the gene expression profile was characteristic of an older stage of development than the ones that were on ground,” says Loring. “In microgravity, they developed faster, but it’s really important to know these were not adult neurons, so this doesn’t tell us anything about aging.”

The team also noted that, contrary to their hypothesis, there was less inflammation and lower expression of stress-related genes in organoids grown in microgravity, but more research is needed to determine why.

Loring speculates that microgravity conditions may more closely mirror the conditions experienced by cells within the brain compared to organoids grown under conventional lab conditions and in the presence of gravity.

“The characteristics of microgravity are probably also at work in people’s brains, because there’s no convection in microgravity — in other words, things don’t move,” says Loring. “I think that in space, these organoids are more like the brain because they’re not getting flushed with a whole bunch of culture medium or oxygen. They’re very independent; they form something like a brainlet, a microcosm of the brain.”

The paper describes the team’s first space mission, but since then, they have sent four more missions to the ISS. With each one, they’ve replicated the conditions from the first mission and added additional experiments.

“The next thing we plan to do is to study the part of the brain that’s most affected by Alzheimer’s disease,” says Loring. “We also want to know whether there are differences in the way neurons connect with each other in space. With these kinds of studies, you can’t rely on earlier work to predict what the result would be because there is no earlier work. We’re on the ground floor, so to speak; in the sky, but on the ground floor.”

This work was supported by funding from the National Stem Cell Foundation.

Researchers from the University of Nottingham’s Schools of Psychology and Medicine conducted detailed interviews with employees from a range of professions and found that the cognitive and affective effort associated with constant connectivity and high work pace driven by the digital workplace is detrimental to employee wellbeing. The results have been published today in Frontiers in Organizational Psychology.

This new paper is the final part of a research project exploring the ‘dark side effects’ of digital working which include stress, overload, anxiety and fear of missing out. The results highlight an overarching theme of ‘digital workplace technology intensity’ as a result of digital workplace job demands.

The findings in this latest paper indicate a sense of burden associated with working digitally which surfaced for most participants in perceptions of overload and feelings of being overwhelmed by the proliferation of messages, applications and meetings in the digital workplace. Fear of missing out on important information and contact with colleagues also contributed to stress and strain for digital workers, as did hassles encountered when using digital technologies.

Elizabeth Marsh, ESRC PhD student from the School of Psychology led the qualitative study and said: “Digital workplaces benefit both organisations and employees, for example by enabling collaborative and flexible work. However, what we have found in our research is that there is a potential dark side to digital working, where employees can feel fatigue and strain due to being overburdened by the demands and intensity of the digital work environment. A sense of pressure to be constantly connected and keeping up with messages can make it hard to

psychologically detach from work.”

Fourteen employees were interviewed in detail and asked about their perceptions and experiences of digital workplace job demands and impacts to their health. In the analysis, the researchers explore potential underlying psychological, technological and organisational factors that may influence ways in which employees experience the digital workplace job demands.

Participants’ dark side experiences were particularly shaped by a pervasive and constant state of connectivity in the digital workplace, termed “hyperconnectivity.” These experiences contributed to a sense of pressure to be available and the erosion of work-life boundaries. The evidence also indicates that this hyperconnectivity has become the norm among workers post-pandemic.

Comments from interviewees included:

“[It’s] just more difficult to leave it behind when it’s all online and you can kind of jump on and do work at any time of the day or night.”

“You kind of feel like you have to be there all the time. You have to be a little green light.”

“It’s that pressure to respond […] I’ve received an e-mail, I’ve gotta do this quickly because if not, someone might think “What is she doing from home?”

Elizabeth adds: “The findings underline the need for both researchers and professionals to identify, understand and mitigate the digital workplace job demands to protect the well-being of digital workers.”

The research makes practical suggestions for employers which include helping workers improve their digital skills and empowering them to manage boundaries in the digital workplace. The findings could also be used by technology departments to consider how to improve usability and accessibility of the digital workplace, as well as reining in the proliferation of applications. Understanding employees’ needs and preferences for digital working is important to inform such work.

Dr Alexa Spence, Professor of Psychology adds: “This research extends the Job Demands-Resources literature by clarifying digital workplace job demands including hyperconnectivity and overload. It also contributes a novel construct of digital workplace technology intensity which adds new insight on the causes of technostress in the digital workplace. In doing so, it highlights the potential health impacts, both mental and physical, of digital work.”

The research was funded by ESRC-MGS (Economic and Social Research Council — Midland Graduate School).

In a paper published in the journal Neuroscience of Consciousness psychology researchers from the University of Technology Sydney (UTS) worked with 54 participants to examine the effects of surveillance on an essential function of human sensory perception — the ability to detect another person’s gaze.

Lead author, Associate Professor of neuroscience and behaviour Kiley Seymour, said previous research has established the effects on conscious behaviour when people know they are being watched, but the new study provided the first direct evidence that being watched also has an involuntary response.

“We know CCTV changes our behaviour, and that’s the main driver for retailers and others wanting to deploy such technology to prevent unwanted behaviour,” Associate Professor Seymour said.

“However, we show it’s not only overt behaviour that changes — our brain changes the way it processes information.

“We found direct evidence that being conspicuously monitored via CCTV markedly impacts a hardwired and involuntary function of human sensory perception — the ability to consciously detect a face.

“It’s a mechanism that evolved for us to detect other agents and potential threats in our environment, such as predators and other humans, and it seems to be enhanced when we’re being watched on CCTV.

“Our surveilled participants became hyper aware of face stimuli almost a second faster than the control group. This perceptual enhancement also occurred without participants realising it.”

Associate Professor Seymour said that given the increasing level of surveillance in society and the ongoing debates around privacy reform, the study’s findings suggested the need for closer examination of the effects of surveillance on mental processes and on public health more broadly.

“We had a surprising yet unsettling finding that despite participants reporting little concern or preoccupation with being monitored, its effects on basic social processing were marked, highly significant and imperceptible to the participants.

“The ability to rapidly detect faces is of critical importance to human social interactions. Information conveyed in faces, such as gaze direction, enables us to construct models of other people’s minds and to use this information to predict behaviour.

“We see hyper-sensitivity to eye gaze in mental health conditions like psychosis and social anxiety disorder where individuals hold irrational beliefs or preoccupations with the idea of being watched.

“Whilst this investigation was specifically focussed on unconscious social processes, future investigations should explore effects on the limbic system more broadly, which would have more general implications for public mental health and the importance of privacy.”

Parents of children ages three to five were most likely to say they use threats to address misbehavior — with a fourth threatening their child with no Santa or gifts — according to the University of Michigan Health C.S. Mott Children’s Hospital National Poll on Children’s Health.

Many parents have also threatened to leave an activity or place, take away toys or not get dessert while nearly half of parents polled have used bribes.

“Discipline helps young children learn what behaviors are safe and appropriate and can play a crucial role in helping them learn the difference between right and wrong,” said Mott pediatrician and Mott Poll co-director Susan Woolford, M.D.

“Empty threats, however, undermine trust and credibility and aren’t usually effective. Positive reinforcement and consistent discipline are more likely to shape long term behavior.”

Consistency is key

While half of parents rate themselves as very consistent in disciplining their child, many admit struggling with consistency, according to the nationally representative report based on 725 responses from parents with at least one child ages one to five surveyed in August.

Top challenges include a child being too young to understand, strategies not always working and parents trying to prevent a public tantrum.

Nearly a fourth of parents also say they get too irritated when their child misbehaves, react before remembering their strategies or are too tired to be consistent.

“It can be difficult to have a consistent approach to discipline without consideration and planning — and even then, consistency can be difficult, especially when parents are tired, distracted, or feeling overwhelmed,” Woolford said.

“It’s important for parents to plan ahead and be on the same page with discipline strategies to provide a foundation for understanding expectations and prevent sending mixed signals about boundaries.”

Parents may need guidance finding the best discipline strategies

Parents weren’t always sure whether their discipline strategies worked, with about two fifths saying they’re very effective and three in five believing they’re somewhat effective.

Most parents polled also reported getting input about discipline strategies from several sources, with many turning to the child’s other parent, talking with family and friends or using parenting books, articles and social media.

Meanwhile, less than a fifth of parents have discussed discipline with a healthcare provider and one in eight parents say they haven’t thought about their discipline strategies.

Some parents polled also admitted using discipline strategies that aren’t recommended by experts, with two in five sometimes spanking — which evidence suggests may lead to defiance and be linked to increased aggression in preschoolers and school aged children.

“Parents should avoid the temptation to rely on tactics that might yield short-term compliance but have negative effects later on,” Woolford said.

“Discipline strategies should be appropriate for the child’s age and developmental level.”

For children ages one to two, for example, distraction and redirection are often most effective, Woolford says, noting that children this young are exploring their environment and willful misbehavior is rare. Parents of children in this age group polled were also more likely to redirect behavior as a strategy.

But after age two, children understand their actions can cause a reaction from others and may increasingly test that out. Parents of children ages three to five polled were more likely to use warnings, speak firmly, and give timeouts.

During these preschool ages, Woolford says, strategies should emphasize logical consequences to misbehavior. For instance, if a child spills a drink out of anger, an appropriate punishment would be to have them clean up the mess while an unrelated punishment will be less effective.

“Consequences should be immediate, so the child understands the connection with their misbehavior,” she said.

She adds that since children respond differently to various discipline methods, parents should try to be flexible.

“As children grow, their responses to discipline will also change, so parents should adapt their strategies and stay open to new approaches,” she said.

“Balancing correction with positive reinforcement — like praise and rewards — helps children build self-esteem while learning from their mistakes.”

Cancer immunotherapy has revolutionised treatment for patients, whereby the body’s own immune system is harnessed to destroy cancer cells.

Typically, several molecules restrain the ability of T cells to target cancer cells and developing approaches to limit this restraining effect can lead to improved effectiveness of cancer immunotherapy.

Research published in Science Immunology has determined the structure of how an inhibitory molecule, LAG3, interacts with its main ligand and provides a new targeted approach to improving the effectiveness of immunotherapy for certain forms of cancer.

The publication is the first to show the crystal structure of a human LAG-3/HLA-II complex and provides a better foundation for development of blocking LAG-3 therapeutics.

Led by Professor Jamie Rossjohn at Monash University’s Biomedicine Discovery Institute (BDI), in Melbourne, Australia, in collaboration with Immutep, this research resolves how the human LAG-3 receptor binds to HLA II molecules.

First author Dr Jan Petersen said: “The way the PD-1 and CTLA-4 immune checkpoint molecules bind to their respective ligands has been resolved for many years.

“However, the resolution of the interface between another important checkpoint molecule, LAG-3, and its main ligands, HLA-II molecules, has remained elusive.

“Solved using data collected at the Australian Synchrotron, a structure of a LAG-3/HLA-II complex provides a structural foundation to harness rationally for future development of antibodies and small molecule therapeutics designed to block LAG-3 activity.”

Dr Frédéric Triebel, Immutep’s CSO, added: “These findings add to the strong foundation of our work with Professor Rossjohn and his team to develop a deeper understanding of the structure and function of the LAG-3 immune control mechanism, particularly as it relates to our anti-LAG-3 small molecule program.”

The study, which was published Dec. 13 in the print edition of the journal Patterns and featured on the journal’s cover, describes a computer program named PlacentaVision that can analyze a simple photograph of the placenta to detect abnormalities associated with infection and neonatal sepsis, a life-threatening condition that affects millions of newborns globally.

“Placenta is one of the most common specimens that we see in the lab,” said study co-author Dr. Jeffery Goldstein, director of perinatal pathology and an associate professor of pathology at Northwestern University Feinberg School of Medicine. “When the neonatal intensive care unit is treating a sick kid, even a few minutes can make a difference in medical decision making. With a diagnosis from these photographs, we can have an answer days earlier than we would in our normal process.”

Northwestern provided the largest set of images for the study, and Goldstein led the development and troubleshooting of the algorithms.

Alison D. Gernand, contact principal investigator on the project, conceived the original idea for this tool through her global health work, particularly with pregnancies where women deliver in their homes due to lack of health care resources.

“Discarding the placenta without examination is a common but often overlooked problem,” said Gernand, associate professor in the Penn State College of Health and Human Development (HHD) Department of Nutritional Sciences. “It is a missed opportunity to identify concerns and provide early intervention that can reduce complications and improve outcomes for both the mother and the baby.”

Why early examination of the placenta matters

The placenta plays a vital role in the health of both the pregnant individual and baby during pregnancy, yet it is often not thoroughly examined at birth, especially in areas with limited medical resources.

“This research could save lives and improve health outcomes,” said Yimu Pan, a doctoral candidate in the informatics program from the College of Information Sciences and Technology (IST) and lead author on the study. “It could make placental examination more accessible, benefitting research and care for future pregnancies, especially for mothers and babies at higher risk of complications.”

Early identification of placental infection through tools like PlacentaVision might enable clinicians to take prompt actions, such as administering antibiotics to the mother or baby and closely monitoring the newborn for signs of infection, the scientists said.

PlacentaVision is intended for use across a range of medical demographics, according to the researchers.

“In low-resource areas — places where hospitals don’t have pathology labs or specialists — this tool could help doctors quickly spot issues like infections from a placenta,” Pan said. “In well-equipped hospitals, the tool may eventually help doctors determine which placentas need further, detailed examination, making the process more efficient and ensuring the most important cases are prioritized.”

“Before such a tool can be deployed globally, core technical obstacles we faced were to make the model flexible enough to handle various diagnoses related to the placenta and to ensure that the tool can be robust enough to handle various delivery conditions, including variation in lighting conditions, imaging quality and clinical settings” said James Z. Wang, distinguished professor in the College of IST at Penn State and one of the principal investigators on the study. “Our AI tool needs to maintain accuracy even when many training images come from a well-equipped urban hospital. Ensuring that PlacentaVision can handle a wide range of real-world conditions was essential.”

How the tool learned how to analyze pictures of placentas

The researchers used cross-modal contrastive learning, an AI method for aligning and understanding relationship between different types of data — in this case, visual (images) and textual (pathological reports) — to teach a computer program how to analyze pictures of placentas. They gathered a large, diverse dataset of placental images and pathological reports spanning a 12-year period, studied how these images relate to health outcomes and built a model that could make predictions based on new images. The team also developed various image alteration strategies to simulate different photo-taking conditions so the model’s resilience can be evaluated properly.

The result was PlacentaCLIP+, a robust machine-learning model that can analyze photos of placentas to detect health risks with high accuracy. It was validated cross-nationally to confirm consistent performance across populations.

According to the researchers, PlacentaVision is designed to be easy to use, potentially working through a smartphone app or integrated into medical record software so doctors can get quick answers after delivery.

Next step: A user-friendly app for medical staff

“Our next steps include developing a user-friendly mobile app that can be used by medical professionals — with minimal training — in clinics or hospitals with low resources,” Pan said. “The user-friendly app would allow doctors and nurses to photograph placentas and get immediate feedback and improve care.”

The researchers plan to make the tool even smarter by including more types of placental features and adding clinical data to improve predictions while also contributing to research on long-term health. They’ll also test the tool in different hospitals to ensure it works in a variety of settings.

“This tool has the potential to transform how placentas are examined after birth, especially in parts of the world where these exams are rarely done,” Gernand said. “This innovation promises greater accessibility in both low- and high-resource settings. With further refinement, it has the potential to transform neonatal and maternal care by enabling early, personalized interventions that prevent severe health outcomes and improve the lives of mothers and infants worldwide.”

This research was supported by the National Institutes of Health National Institute of Biomedical Imaging and Bioengineering (grant R01EB030130). The team used supercomputing resources from the National Science Foundation-funded Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) program.

In a study published in Nature Communications, Lewis Zhichang Shi, M.D., Ph.D., and University of Alabama at Birmingham colleagues show, for the first time, how HIF1α in T cells is key for induction of interferon gamma, or IFN-γ, in that hypoxic environment. The cytokine IFN-γ is known to be essential to induce the tumor-killing capacity of T cells. Additionally, an alternative metabolism called glycolysis, which is able to produce energy in human cells when no oxygen is present, is similarly known to be required for IFN-γ induction in T cells.

“Intriguingly, under normal oxygen levels in the body, called normoxia, IFN-g induction and glycolysis in T cells are not mediated by HIF1α, a primary regulator of glycolysis, but by its widely regarded downstream target LDHa, as reported in an early study by another group,” said Shi, a professor in the UAB Department of Radiation Oncology. “However, it has been unknown, under hypoxia, whether and how HIF1α regulates IFN-γ induction and glycolysis in T cells.”

The UAB researchers found that HIF1α-glycolysis is indispensable for IFN-γ induction in hypoxic T cells. HIF1α is a subunit of HIF, or hypoxia-inducible factor, that is known to play a crucial role in orchestrating cellular responses to hypoxia.

Shi and colleagues showed this key role for HIF1α in hypoxia by combining genetic mouse models, metabolic flux analysis using ¹³C-labeled glucose tracing assays and a Seahorse analyzer, as well as pharmacological approaches.

In both human and mouse T cells that were activated under hypoxia, they found that the deletion of HIF1α from the T cells prevented the metabolic reprogramming shift from catabolic metabolism to anabolic metabolism, of which anaerobic glycolysis is a major component; the deletion also suppressed the induction of IFN-γ. Additionally, pharmacologic inhibition of T cell glycolysis under hypoxia prevented induction of IFN-γ. Conversely, stabilization of HIF1α by knocking out a negative regulator of HIF1α increased IFN-γ under hypoxic conditions.

With regard to defense against cancer, the researchers found that hypoxic T cells deleted for HIF1α were less able to kill tumor cells in vitro. In vivo, tumor-bearing mice that had the HIF1α-deleted in T cells did not respond to ICB therapy.

The researchers then showed a way to overcome that resistance to ICB therapy. Elucidation of the mechanistic function of the HIF1α deletion showed that loss of HIF1α greatly diminished glycolytic activity in hypoxic T cells, resulting in depleted intracellular acetyl-CoA and attenuated activation-induced cell death, or AICD. Restoration of intracellular acetyl-CoA by supplementing growth media with acetate reengaged AICD and rescued IFN-γ production for hypoxic Hif1α-deletion T cells.

Shi and colleagues then demonstrated, in living mice, that acetate supplementation was an effective strategy to bypass ICB resistance in tumor-bearing mice with specific deletion of HIF1α in T cells. When Hif1α-deletion tumor-bearing mice were given acetate supplementation followed by combination ICB therapy, the mice had significant improvement in ICB therapy, as seen by potent suppression of tumor growth and greatly reduced tumor weights.

“TILs and tumor cells utilize the same metabolic pathways for their growth and function, and co-live in the metabolically harsh tumor-microenvironments characterized by hypoxia and poor nutrition, placing them in a fierce metabolic tug-of-war,” Shi said. “How to tilt this metabolic battle to favor TILs would be key, and we showed that acetate supplementation restored IFN-γ production in Hif1α-deletion-TILs and overcame ICB resistance derived from HIF1α loss in T cells.”

“Our study, together with an early report by others, compellingly shows that the impaired HIF1α function in T cells is a major T cell-intrinsic mechanism of therapeutic resistance to ICBs, like anti-CTLA-4 and anti-PD-1/L1,” Shi said.

Co-authors with Shi in the study, “HIF1α-regulated glycolysis promotes activation-induced cell death and IFN-γ induction in hypoxic T cells,” are Hongxing Shen, Oluwagbemiga A. Ojo, Haitao Ding, Chuan Xing, Abdelrahman Yassin, Vivian Y. Shi, Zach Lewis, Ewa Podgorska and James A. Bonner, UAB Department of Radiation Oncology; Logan J. Mullen, University of Alaska Fairbanks, Fairbanks, Alaska; M. Iqbal Hossain and Shaida A. Andrabi, UAB Department of Pharmacology and Toxicology; and Maciek R. Antoniewicz, University of Michigan, Ann Arbor, Michigan.

Support came from UAB; the O’Neal Comprehensive Cancer Center at UAB; National Institutes of Health grants CA230475-01A1, CA25972101A1 and CA279849-01A1; V Foundation Scholar Award V2018-023; Department of Defense-Congressionally Directed Medical Research Programs grant ME210108; and Cancer Research Institute CLIP Grant CRI4342.

At UAB Radiation Oncology and Pharmacology and Toxicology are departments in the Marnix E. Heersink School of Medicine. Shi is a scientist in the O’Neal Comprehensive Cancer Center and holds the Koikos-Petelos-Jones-Bragg ROAR Endowed Professorship for Cancer Research.

The findings, published in the Journal of Clinical Oncology, show that a diet low in omega-6 and high in omega-3 fatty acids, combined with fish oil supplements, significantly reduced the growth rate of prostate cancer cells in men with early-stage disease.

“This is an important step toward understanding how diet can potentially influence prostate cancer outcomes,” said Dr. William Aronson, Professor of Urology at the David Geffen School of Medicine at UCLA and first author of the study. “Many men are interested in lifestyle changes, including diet, to help manage their cancer and prevent the progression of their disease. Our findings suggest that something as simple as adjusting your diet could potentially slow cancer growth and extend the time before more aggressive interventions are needed.”

Many men with low-risk prostate cancer choose active surveillance over immediate treatment, however, within five years, about 50% of these men eventually need to undergo therapy with either surgery or radiation. Because of this, patients are eager to find ways to delay the need for treatment, including through dietary changes or supplements. However, specific dietary guidelines in this area have yet to be established. While other clinical trials have looked at increasing vegetable intake and healthy diet patterns, none have found a significant impact on slowing cancer progression.

To determine whether diet or supplements can play a role in managing prostate cancer, the UCLA-led team conducted a prospective clinical trial, called CAPFISH-3, that included 100 men with low risk or favorable intermediate risk prostate cancer who chose active surveillance. Participants were randomly assigned to either continue their normal diet or follow a low omega-6, high omega-3 diet, supplemented with fish oil, for one year.

Participants in the intervention arm received dietary personalized counseling by a registered dietician nutritionist, either in-person, through telehealth or by phone. Patients were guided on healthier, lower fat alternatives for high fat/high calorie foods (such as using olive oil or lemon and vinegar for salad dressing), and on reducing consumption of foods with higher omega-6 content (such as, chips, cookies, mayonnaise and other fried or processed foods). The goal was to create a favorable balance of their intake of omega-6 and omega-3 fats and make participants feel empowered to control how they change their behavior. They were also given fish oil capsules for extra omega-3s. The control group did not get any dietary counseling or take fish oil capsules.

The researchers tracked changes in a biomarker called the Ki-67 index, which indicates how fast cancer cells are multiplying — a key predictor of cancer progression, metastasis and survival.

Same site biopsies were obtained at the start of the study and again after the one-year mark, using an image fusion device that helps track and locate the cancer sites.

Results showed that the low omega-6, omega-3 rich diet and fish oil group had a 15% decrease in the Ki-67 index, while the control group saw a 24% increase.

“This significant difference suggests that the dietary changes may help slow cancer growth, potentially delaying or even preventing the need for more aggressive treatments,” said Aronson, who is also the Chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center and member of the UCLA Health Jonsson Comprehensive Cancer Center.

While the results are promising, researchers did not find any differences in other cancer growth markers, such as Gleason grade, which are commonly used to track prostate cancer progression.

The investigators caution that further research is necessary to confirm the long-term benefits of omega-3 fatty acids and lowering omega-6 in managing prostate cancer. The findings support further, larger trials to explore the long-term impact of dietary changes on cancer progression, treatment outcomes and survival rates in men on active surveillance.

The study’s senior author is Dr. Susanne Henning, adjunct professor emerita and former director of the nutritional biomarker laboratory at the Center for Human Nutrition at UCLA. Other UCLA co-authors are Tristan Grogan, Dr. Pei Liang, Patricia Jardack, Amana Liddell, Claudia Perez, Dr. David Elashoff, Dr. Jonathan Said and Dr. Leonard Marks.

The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein and the Seafood Industry Research Fund.

Cisplatin and carboplatin — which have been approved for more than 30 years — are widely used to treat a variety of cancers, including lung, head and neck, breast, bladder, ovarian, uterine, and testicular cancers. When the FDA announced a shortage of cisplatin in February 2023, followed by a shortage of carboplatin in April 2023, it drew attention to the ongoing challenge of generic drug shortages, and prompted major national oncology societies to recommend best practices for priority use and alternative medicines.

“At the time, national surveys showed that most cancer centers in the US were reporting shortages of these platinum chemotherapies, but it wasn’t clear how the shortages were actually affecting patients,” said lead author Jacob B. Reibel, MD, a third-year fellow in Hematology-Oncology. “When we looked at the data on prescribing practices over the shortage period, compared to the previous year, we found that although reporting of the shortages was widespread, it didn’t affect as many patients as we had feared.”

Reibel, senior author Ronac Mamtani, MD, section chief of Genitourinary Cancers, and colleagues, analyzed data from 11,797 adults across the U.S. with advanced solid cancers for which platinum chemotherapy is recommended as the first line of therapy and who began treatment during the one-year period before or during the platinum chemotherapy shortage. Because cisplatin and carboplatin were prioritized for patients with curable cancers during the shortage, the researchers expected that patients with advanced cancers would be most affected by drug availability.

From February 2023 through January 2024, there was a 2.7 percent decrease in platinum chemotherapy use compared to the previous year. This translates into 137 fewer patients in this advanced cancer cohort receiving platinum chemotherapy than expected, and the researchers estimate about 1,000 patients affected overall in the US, based on the rates observed in the study. At the peak of the shortage in June 2023, the decrease was 15.1 percent compared to the previous year. With a median follow-up time of 7.6 months after beginning treatment, there was no difference in mortality compared to the previous year.

Alternative therapies help mitigate the crisis, but are not first choice

The researchers hypothesized that the limited impact on mortality was likely due to the use of effective alternative medications recommended by medical societies, such as immune checkpoint inhibitors, targeted therapy or other forms of chemotherapy. The study did not assess the potential drawbacks of alternative medications, including the financial burden of more expensive non-generic alternatives and side effects of different drugs.

“We always want to prioritize the best treatments that we have for patients, and platinum chemotherapies just happen to also be very cost-effective because they’re generic and have been around for decades,” Mamtani said. “While the alternative options may be effective, we want to be able to provide the ‘standard-of-care’ medications to any patient in need. Even one hundred patients who can’t get the preferred chemotherapy for their cancer type due to supply chain issues is far too many.”

The FDA listed the cisplatin shortage as resolved at the end of June 2024 and carboplatin remains on the shortage list, though the research team found prescribing levels have returned to normal.

The study was funded by the National Institutes of Health (T32CA009679).

More than half of all people with type 2 diabetes have steatotic (or fatty) liver disease, but most do not realise it since liver disease rarely causes any symptoms in the earlier stages. Over time, liver fibrosis can develop. This is a type of scarring of the liver that can lead to cirrhosis or liver cancer in some patients. International guidelines recommend screening for liver fibrosis in people at increased risk of it, including patients with type 2 diabetes.

“Unfortunately, severe liver disease is often detected late when the prognosis is poor,” says Hannes Hagström, adjunct professor at the Department of Medicine, Huddinge, Karolinska Institutet and consultant in hepatology at the Karolinska University Hospital. “Since there is now an approved treatment for steatotic liver disease with fibrosis, it would be good to be able to screen diabetic patients for liver fibrosis and thus prevent severe disease.”

In Sweden, retina scanning (fundus photography) is an established screening programme to detect eye damage in people with type 2 diabetes. In a new study, Hannes Hagström and his research colleagues investigated whether it would be possible to simultaneously screen for liver fibrosis using elastography. This ultrasound-based technique is painless and takes 5 to 10 minutes to perform.

“This would allow us to kill two birds with one stone and easily detect liver fibrosis in this patient group before it develops into cirrhosis or liver cancer,” says Hannes Hagström. “Our study shows that many patients with type 2 diabetes are willing to undergo such combined screening.”

The researchers asked more than 1,300 patients with type 2 diabetes who underwent retina scanning whether they would also consider having their liver examined by elastography. More than 1,000 people, 77 per cent of the study participants, said yes.

15.8 per cent of patients who had their livers examined by elastography had findings suggestive of liver fibrosis, whereas 5.0 per cent had findings suggestive of advanced liver fibrosis or cirrhosis. However, on repeat examination and reassessment, these figures were lower; 7.4 per cent and 2.9 per cent respectively.

“It shows that the method gives many false positives, partly because many people were probably not fasting as instructed at the first examination,” says Hannes Hagström. “The next step will be to conduct health economic analyses to see if the combined screening strategy for eye and liver disease is beneficial,” he concludes.

The study was conducted in collaboration with the eye clinic Capio Ögon Stockholm Globen. It was mainly funded by the pharmaceutical companies Gilead Sciences and Pfizer, and Region Stockholm.

Hannes Hagström’s research group has received research funding from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer. He has also been a consultant or served on advisory committees for Astra Zeneca, Bristol Myers-Squibb, MSD and Novo Nordisk, and has served on review committees for Arrowhead, Boehringer Ingelheim, KOWA and GW Pharma.

The study, published in the American Journal of Epidemiology, showed a strong connection between place and activity by studying about 11,000 twins, which helps control for family influences and genetic factors. The researchers found that each 1% increase in an area’s “walkability” resulted in 0.42% increase in neighborhood walking. When scaled up, that means a 55% increase in the walkability of the surrounding neighborhood would result in about 23% more walking — or about 19 minutes a week for every resident living in that area.

In terms of public health, that can add up to a big difference for the highly sedentary U.S. populace, according to study lead author Glen Duncan, a Washington State University nutrition and exercise physiology professor.

“We have so many people in the U.S. population who don’t get sufficient activity. If we could shift the percentage of the population that just took on more plain old walking, we would see real health benefits,” said Duncan, who is also the director of the Washington State Twin Registry.

For the study, neighborhoods were deemed walkable based on an index that assesses the density of people, roads and desirable places to walk to, such as stores, parks, restaurants and coffee shops. The twin pairs in the study lived in all parts of the U.S., but the more walkable neighborhoods were typically found in urban areas.

Seattle’s Capitol Hill area is a good example of a walkable neighborhood, Duncan said, given its profusion of shops and restaurants, as well as access to public transportation such as buses and a light rail station. On the other side, more suburban or rural areas tend to be less walkable as they require driving to access things like grocery stores or other amenities.

The study analyzed data from surveys of 5,477 pairs of twins taken from 2009 to 2020 which included information about where they lived and number of minutes walked in a typical week, whether for recreation, exercise or simply to get from one place to the other. The analysis revealed that those who lived in areas considered more walkable actually did walk more.

The researchers also looked at whether an area’s walkability increased transit use, but few study participants used public transit. However, living in a walkable neighborhood reduced the chance of having no transit use at all by 32%.

Living in a walkable area didn’t appear to have an effect on more vigorous exercise, but the authors note that this kind of exercise, which includes running and lifting weights, isn’t limited to the neighborhood environment. For example, a person could go for a vigorous bike ride that would take them well outside the boundaries of their neighborhood.

Regardless, Duncan emphasized that walking is a great and easy way to improve health. It also counts toward the widely recommended 150 minutes a week of physical activity.

“You don’t have to spend loads of money on fitness clothing and the best gear. Walking is a very natural thing. You just lace on some shoes and head out the door,” he said.

In addition to Duncan, co-authors on this study include researchers from the University of Washington, University of Southern California, University of Virginia, Columbia University and WSU.

For years, scientists have looked to a critical piece of immune system machinery — known as the interferon pathway — for answers. There, when our cells sense an infection, they release a protein known as interferon, which warns other cells to fight the virus.

Studies show that when this signaling goes awry and leads the body to under or overreact, people are more likely to develop severe or Long COVID. Glitches in this pathway have also been implicated in autoimmune diseases and cancer.

But little is known about what, precisely, drives these immunological misfires.

A new CU Boulder study, published Dec. 12 in the journal Cell, sheds light on the subject by identifying what the authors describe as an “immune system tuning dial,” which originated as a bug in the genetic code tens of millions of years ago.

“We’ve discovered that there is an entire class of under-appreciated protein variants that can have an immense impact on our immune function,” said senior author Ed Chuong, an assistant professor in the Department of Molecular, Cellular and Developmental Biology and the BioFrontiers Institute.

His lab demonstrated that one particular variant of a protein called IFNAR2 acts like a tuning dial to regulate interferon signaling.

“If we can manipulate this dial to turn the immune system up or down it could have broad therapeutic applications, from infection to autoimmune disorders to cancer.”

How evolution turned a bug into a feature

Chuong studies transposons, bits of DNA that infiltrated primate cells as many as 70 million years ago and now make up more than half of the human genome.

Some transposons, known as endogenous retroviruses, got there via ancient viruses. When reawakened, these genetic parasites can help cancer survive and thrive. Others, like the ones explored in the new paper, emerged from the genome itself, like random bugs popping up in a computer program’s source code.

“If you think of a gene as a sentence, a transposon is like a word that jumps into the sentence, making the instructions for the cell slightly different,” explained first author Giulia Pasquesi, a postdoctoral researcher in Chuong’s lab.

Cells normally suppress these bugs, ensuring only the correct version of the gene is spurred into action, so scientists have long viewed them as inert ‘junk DNA’.

Pasquesi set out to challenge this assumption, looking for gene variants formed by transposons that were actually important for human immune function.

When she analyzed state-of-the-art genetic sequencing data from human tissues and cells, she found 125 instances across 99 genes.

A break in the antenna

Pasquesi and Chuong focused on a variant of interferon receptor 2 (IFNAR2) — a critical protein which acts like a cellular antenna for interferon, turning on other genes that fight off infection and cancer. They found that the new “short” variant could sense interferon, but it was missing parts required to transmit the signal.

Surprisingly, it was present in all cells, and often more abundant than the normal protein suggesting it played an important role in immunity.

They followed up with laboratory studies using cells with different combinations of the two IFNAR2 varieties. They exposed them to immune challenges, including viral infections, finding that the short variant acted as a “decoy” that interferes with normal IFNAR2 signaling. When they removed the short variant from the genome, cells became much more sensitive to interferon, with stronger immune responses against viruses including SARS-CoV-2 and dengue virus.

The findings suggest that the balance between IFNAR2 variants acts as a “tuning dial” for controlling the strength of immune signaling, and this can vary from person to person. Individuals who express abnormally high levels of the variant might be more susceptible to severe infections, while people expressing low levels may have chronic inflammation, autoimmune issues like psoriasis or irritable bowel syndrome, or Long COVID.

“Different individuals are well known to exhibit differences in their immune responses, but the reasons why are still poorly understood. We’ve uncovered a new control dial that could be behind some of this variation,” said Chuong.

The team has filed for a provisional patent and begun developing and testing compounds to therapeutically target the dial.

Bigger picture, they believe that the story of IFNAR2 is the tip of the iceberg, and many other immune functions may be regulated by these long-ignored genomic hitchhikers.

“Our findings suggest that looking into the dark corners of the genome is key to making new discoveries to improve human health,” said Chuong.

“The increase in early-onset colorectal cancer is a global phenomenon,” said Dr. Hyuna Sung, senior principal scientist, cancer surveillance research at the American Cancer Society and lead author of the study. “Previous studies have shown this rise in predominately high-income Western countries, but now, it is documented in various economies and regions worldwide.”

The primary study objective was to examine contemporary CRC incidence trends in young versus older adults using data through 2017 from 50 countries/territories. Data were compiled using the Cancer Incidence in Five Continents Plus and trends were examined for age-standardized incidence rates of CRC ranging from 1943-2017. Temporal trends were visualized and quantified by age at diagnosis (25-49 years and 50-74 years). Average annual percentage changes (AAPC) were estimated for the last 10 years of data.

During the past decade, incidence rates of early-onset CRC (25-49 years) were stable in 23 countries, but increased in 27 countries, with the greatest annual increases in New Zealand (4.0%), Chile (4.0%) and Puerto Rico (3.8%). Fourteen of the 27 countries/territories showed either stable (Puerto Rico, Argentina, Norway, France, Ireland) or decreasing rates (Israel, Canada, the USA, England, Germany, Scotland, Slovenia, Australia, and New Zealand) in older adults. The rise in early-onset CRC was faster among men than women in Chile, Puerto Rico, Argentina, Ecuador, Thailand, Sweden, Israel, and Croatia, while young women experienced faster increases in England, Norway, Australia, Türkiye, Costa Rica, and Scotland. For the remaining 13 countries with increasing trends in both age groups, the annual percentage increase in young compared to older adults was larger in Chile, Japan, Sweden, the Netherlands, Croatia, and Finland, smaller in Thailand, Martinique, Denmark, Costa Rica, and similar in Türkiye, Ecuador, and Belarus. For the last five years, the incidence rate of early-onset CRC was highest in Australia, Puerto Rico, New Zealand, the U.S., and the Republic of Korea (14 to 17 per 100,000) and lowest in Uganda and India (4 per 100,000).

“The global scope of this concerning trend highlights the need for innovative tools to prevent and control cancers linked to dietary habits, physical inactivity, and excess body weight. Ongoing efforts are essential to identify the additional factors behind these trends and to develop effective prevention strategies tailored to younger generations and local resources worldwide,” added Sung. “Raising awareness of the trend and the distinct symptoms of early-onset colorectal cancer (e.g., rectal bleeding, abdominal pain, altered bowel habits, and unexplained weight loss) among young people and primary care providers can help reduce delays in diagnosis and decrease mortality.”

“This flagship study reveals that increasing rates of early onset bowel cancer, affecting adults aged 25-49, is a global issue. Concerningly, this research has revealed for the first time ever that rates are rising more sharply in England than in many other countries around the world,” said Michelle Mitchell, chief executive of Cancer Research UK.”A cancer diagnosis at any age has a huge impact on patients and their families — so while it’s important to note that rates in younger adults are still very low compared to people over 50, we need to understand what’s causing this trend in younger people. More research is needed — like team PROSPECT, a global Cancer Grand Challenges team who has been awarded £20m to uncover the causes of bowel cancer in younger adults, and strategies to prevent it.”

Other ACS researchers contributing to the study include Rebecca Siegel, Chenxi Jiang, and senior author Dr. Ahmedin Jemal. Yin Cao, an associate professor of surgery and of medicine at Washington University School of Medicine in St. Louis and a research member of Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University Medicine, is a contributing author.

But a study in Scientific Reports highlights a hidden challenge of using AI in medical imaging research — the phenomenon of highly accurate yet potentially misleading results known as “shortcut learning.”

The researchers analyzed more than 25,000 knee X-rays from the National Institutes of Health-funded Osteoarthritis Initiative and found that AI models can “predict” unrelated and implausible traits such as whether patients abstained from eating refried beans or beer. While these predictions have no medical basis, the models achieved surprising levels of accuracy by exploiting subtle and unintended patterns in the data.

“While AI has the potential to transform medical imaging, we must be cautious,” says the study’s senior author, Dr. Peter Schilling, an orthopaedic surgeon at Dartmouth Health’s Dartmouth Hitchcock Medical Center and an assistant professor of orthopaedics in Dartmouth’s Geisel School of Medicine.

“These models can see patterns humans cannot, but not all patterns they identify are meaningful or reliable,” Schilling says. “It’s crucial to recognize these risks to prevent misleading conclusions and ensure scientific integrity.”

The researchers examined how AI algorithms often rely on confounding variables — such as differences in X-ray equipment or clinical site markers — to make predictions rather than medically meaningful features. Attempts to eliminate these biases were only marginally successful — the AI models would just “learn” other hidden data patterns.

“This goes beyond bias from clues of race or gender,” says Brandon Hill, a co-author of the study and a machine learning scientist at Dartmouth Hitchcock. “We found the algorithm could even learn to predict the year an X-ray was taken. It’s pernicious — when you prevent it from learning one of these elements, it will instead learn another it previously ignored. This danger can lead to some really dodgy claims, and researchers need to be aware of how readily this happens when using this technique.”

The findings underscore the need for rigorous evaluation standards in AI-based medical research. Overreliance on standard algorithms without deeper scrutiny could lead to erroneous clinical insights and treatment pathways.

“The burden of proof just goes way up when it comes to using models for the discovery of new patterns in medicine,” Hill says. “Part of the problem is our own bias. It is incredibly easy to fall into the trap of presuming that the model ‘sees’ the same way we do. In the end, it doesn’t.”

“AI is almost like dealing with an alien intelligence,” Hill continues. “You want to say the model is ‘cheating,’ but that anthropomorphizes the technology. It learned a way to solve the task given to it, but not necessarily how a person would. It doesn’t have logic or reasoning as we typically understand it.”

Schilling, Hill, and study co-author Frances Koback, a third-year medical student in Dartmouth’s Geisel School, conducted the study in collaboration with the Veterans Affairs Medical Center in White River Junction, Vt.

This study found that certain social factors that influence health are associated with lower odds of children receiving CPR, application of automated external defibrillators (AEDs) and surviving after experiencing a cardiac arrest. These factors include socioeconomic or poverty status, education level and minority racial makeup.

“This may be due in part to a lack of education on how to administer CPR and AED,” said emergency pediatrics doctor and study author Dr. Mary Bernardin. “The areas with highest educational attainment had the highest odds of performing CPR and using AEDs.”

While several studies show that social factors affect care for adults experiencing cardiac arrests, few focused on children and had small data groups. This study is the largest of its kind, having analyzed 21,137 data entries across 54 states and territories in the United States.

Bystanders performed CPR on children in about 62% of cases and used AEDs in about 23% of cases. Only 21% of children survived, and survival was lowest in communities with lower education levels, higher rates of poverty and high racial or ethnic minority prevalence.

The most common cause for a pediatric cardiac arrest involved an acute, traumatic event. When discussing factors that impact patient outcomes, Bernadin says it is imperative to address firearm injuries, which is the most common cause of death among children in the United States.

“Children of racial or ethnic minorities have suffered the majority of firearm injuries for decades,” Bernardin said. “Implementing interventions or community prevention of gun violence could save the lives of children most at risk.”

In addition, building educational programs may help those most at risk of seeing or experiencing a pediatric cardiac arrest. These programs would offer CPR and AED training as well as targeted interventions.

Dr. Mary Bernardin is an assistant professor of emergency medicine and pediatrics at the MU School of Medicine and a pediatric emergency medicine doctor at MU Health Care. She is the medical director of Emergency Medical Services for Children, the assistant medical director of Pediatric Emergency Medicine, and the director of Pediatric Emergency Medicine Education.

Researchers from Imperial College London, working with the company MakeSense Technology and the charity Bravo Victor, have developed a shape-changing device called Shape that helps people with visual impairment navigate through haptic perception — the way people understand information about objects through touch. The device, which looks like a torch, bends to indicate where a person needs to move and straightens when the user is facing the correct direction.

In a study published in Nature Scientific Reports, researchers tested how well people with visual impairment were able to locate targets in a 3D virtual reality (VR) space using Shape and vibration feedback technology — which is commonly used to help visually impaired people navigate. Sighted individuals were also recruited for the study to locate the targets in the VR space using only their natural vision.

Dr Ad Spiers, lead researcher for the study, from Imperial’s Department of Electrical and Electronic Engineering, said: “The exciting thing about this study is we’ve managed to demonstrate that Shape can help people with visual impairment perform a navigation task as well as sighted people. This is something that we haven’t seen before with other navigation devices.

“Shape is unusual because it uses our ability to understand information through touch in a way that goes beyond vibration. Humans have an innate ability to feel and interpret shapes through our hands, with very little concentration. Exploiting this allows us to create a device that is simple to learn and isn’t tiring to use.”

The study compared the results of 10 participants with visual impairment and 10 sighted participants, testing their ability to locate targets as quickly as possible in a controlled indoor environment, measuring the time taken to locate virtual targets and the efficiency in locating these targets.

The trial found that there was no significant difference in the performance between visually impaired participants using Shape and sighted participants using only natural vision. It also found that participants with visual impairment located targets significantly faster using Shape than with vibration technology. Feedback showed that participants with visual impairment preferred using Shape to vibration technology.

It is hoped that the device, which is believed to be the most advanced of its kind, could be the future of navigation technology for visual impairment, as the Shape device has notable advantages over current tools used to guide people with visual impairment.

Dr Robert Quinn, CEO of MakeSense Technology, said: “The impressive results from this study demonstrate the enormous potential of this technology to make life changing improvements in mobility for people with visual impairment.

“Building upon the research described in this paper, MakeSense is developing a blind wayfinding product which leverages the latest advancements in spatial artificial intelligence and computer vision without the need for interpretive training. We are aiming for our first product to be available from the end of 2025.”

Currently, individuals with visual impairment most commonly use aids such as white canes or guide dogs. While guide dogs are often effective, they require expensive expert training and can cost thousands of pounds per year to keep. White canes enable navigation through a process of elimination by telling users where not to go, rather than where they should go. This process limits a user’s ability to navigate freely in complex environments.

Recent developments with technology have tended to focus on using auditory interfaces, which give audio cues such as “turn left at the next corner,” or vibration feedback, which alerts a user through vibration patterns that indicate where to move.

Auditory interfaces can prevent people from hearing important warning sounds of imminent hazards and can dampen users’ ability to engage fully with the world. Vibration feedback can lead to numbness after prolonged periods of use and studies have shown users can become quickly irritated and distracted by frequent vibration sensations.

In order to test the performance of Shape against vibration technology and natural sight in a controlled environment, the researchers designed a simulation of real-world navigation that reduced the possibility of significant variation between experiments.

In a real-world navigation scenario, it is expected that there would be significant variation in conditions due to changes in weather and the presence of other pedestrians or objects. It is also expected that there will often be multiple potential target options in a real-world scenario rather than the single targets which were presented individually in the experiment.

Further research is needed to understand how the Shape device performs in more variable real-world scenarios.

The Shape device was developed working with MakeSense Technology, a startup company which was co-founded at Imperial by Dr Robert Quinn — an Imperial PhD graduate in Mechanical Engineering. The company received support in its early stages from Imperial’s thriving entrepreneurial ecosystem, which aims to develop innovative solutions with the potential to change the world for better.

Following the completion of the Shape study, MakeSense has worked on developing the technology further to be used for real-world outdoor navigation. It is hoped that the device could be ready for practical use in real-world environments in the coming years.

The research published in Nature Scientific Reports was supported by funding from Innovate UK’s SMART Grant, which was awarded to MakeSense Technology Ltd, Bravo Victor, and Imperial College London.

CTE, a progressive neurodegenerative disease often linked to contact sports, has long been characterized by tau protein accumulation in the brain, and computer models have suggested that the base of the folds of the cortex experience the greatest strain when a human brain is rotated rapidly. This study is the first to measure patterns of brain degeneration in CTE, and shows that repetitive head impacts are linked to loss of cells, shrinkage, and tau pathology buildup within the folds of the brain. Regional brain atrophy is also prominent in the frontal, hippocampal, hypothalamic, mammillary body, and thalamic areas of the brain.

The study analyzed brain samples from 185 athletes with histories of contact sports and 52 non-athlete controls. Additional key findings include:

• Significant cortical thinning and reduced neuronal density in the brain folds within the frontal cortex, especially in advanced CTE stages.

• A strong association between the duration of contact sports exposure and cortical thinning, indicating a potential cumulative effect of head impacts.

• Evidence that neuronal loss is mediated by tau protein accumulation, while cortical thinning also involves tau-independent mechanisms.

• Synaptic protein changes suggesting a dynamic process of damage and repair in CTE-affected brains.

“The cortical sulcus appears uniquely vulnerable to head impacts, with pronounced neurodegenerative changes occurring in these regions,” said corresponding author Thor Stein, MD, PhD, a neuropathologist at VA and Bedford Healthcare Systems and associate professor of pathology & laboratory medicine at the school. “These findings have significant implications for understanding how CTE progresses and identifying potential biomarkers for early detection.”

This research underscores the need for protective measures in contact sports and offers new insights into the role of neurodegeneration in cognitive and behavioral symptoms of CTE.

And some older adults — especially those dealing with major physical health or mental health issues — still have much higher rates of loneliness and social isolation than others.

The new findings, from a review of six years of data from the National Poll on Healthy Aging (https://www.healthyagingpoll.org/), are published in JAMA by a team from the University of Michigan Institute for Healthcare Policy and Innovation.

Starting in 2018, and most recently earlier this year, the poll asked older adults nationwide how often they’d felt they lacked companionship (the subjective feeling of being alone, or loneliness), and felt isolated from others (the experience of social isolation). The poll is supported by AARP and Michigan Medicine, U-M’s academic medical center.

The latest data show that in 2024, 33% of older adults felt lonely some of the time or often in the past year, about the same as the rate in 2018 (34%). During the years in between, as many as 42% of older adults had this level of loneliness.

Similarly, 29% of older adults said they felt isolated some of the time or often in 2024, just above the rate of 27% seen in 2018. During the early months of the COVID-19 pandemic, 56% of older adults said they had experienced this level of isolation, but the rate has declined each year since.

“At the surface, this might seem like great news, that we’re back to where we were before COVID-19 struck. But that baseline was not good, and it was especially bad for some groups of older adults, who continue to have very high rates of loneliness and social isolation,” said Preeti Malani, M.D., MSJ, the study’s lead author and a professor of internal medicine at the U-M Medical School. “One of the biggest differences now is that we have greater recognition of the impact of loneliness and isolation on health especially as we age.” Malani serves as senior advisor to the poll, which she directed from 2017 to 2022.

The groups of older adults with the highest rates of loneliness in 2024 were:

• Those who said their mental health is fair or poor: 75% (in 2018, it was 74%)
• Those who said their physical health is fair or poor: 53% (up from 50% in 2018)
• Those who were not working or received disability income (does not include retirees): 52% (up from 38% in 2018)

The groups with the highest rates of social isolation in 2024 were:

• Those who said their mental health is fair or poor: 77% (up slightly from 79% in 2018)
• Those who said their physical health is fair or poor: 52% (up from 43% in 2018)
• Those who were not working or received disability income (does not include retirees): 50% (up from 36% in 2018)

These rates for 2024 are double, or even more, the rates of loneliness and isolation seen among older adults who said their physical health or mental health were excellent, very good or good, or those who were working or retired.

“These trends make it clear: clinicians should see loneliness and isolation as a key factor in their patients’ lives, especially those with serious physical or mental health conditions,” says poll director Jeffrey Kullgren, M.D., M.P.H., M.S., an associate professor of internal medicine at U-M and primary care clinician at the VA Ann Arbor Healthcare System.

“We should consider screening our patients for these issues and connecting them with resources in their communities, whether that’s a senior center, Veterans’ groups, volunteering opportunities, or services offered by an Area Agency on Aging or other community organizations,” he said.

Other key findings:

In general, adults age 50 to 64 were more likely than those age 65 to 80 to say they felt lonely or isolated across all poll years, and rates had not dropped back to pre-pandemic rates for those age 50 to 64 in 2024.

Similarly, those with household incomes below $60,000, and those who live alone, were more likely to say they sometimes or often felt lonely or isolated than those with higher incomes or those living with others, a finding that was consistent across most years. However, rates in 2024 for those who live alone were lower than for those who live with others.

More about loneliness and isolation in older adults:

The new study builds upon the evidence collected by U.S. Surgeon General Vivek Murthy, M.D., M.B.A. and his team and published in an official advisory in May 2023.

The AARP Foundation has created an initiative called Connect2Affect, offering resources to help older adults combat social isolation and loneliness for themselves and others: https://connect2affect.org/

Malani and colleagues published a Patient Page in JAMA on social isolation in May 2024; it’s available for free (https://jamanetwork.com/journals/jama/fullarticle/2819153) and is designed for clinicians to share with patients.

About the poll:

The data in the new JAMA paper come from six fieldings of the NPHA from 2018 to 2024, most of which asked older adults to report how often they felt a lack of companionship or felt isolated from others in the past year. The poll fielded in June 2020 asked participants to reflect on the past three months. The poll is not longitudinal — each fielding’s sample was unique. poll sample ranged in size from 2,033 to 2,563 and the organization that administers the poll changed once, beginning in 2022. More details about NPHA methodology are at: https://www.healthyagingpoll.org/survey-methods

Read NPHA reports on loneliness and isolation among older adults here: https://www.healthyagingpoll.org/national-reports

In addition to Malani and Kullgren, the authors of the new JAMA research letter are poll team members Erica Solway, Ph.D., M.S.W., M.P.H., Matthias Kirch, M.S., Dianne Singer, M.P.H., and J. Scott Roberts, Ph.D. Malani is a deputy editor at JAMA but was not involved in the review process for the article.

Current strains of the bovine (cow) H5N1 virus are not known to be transmissible among people; however, infections have occurred in people exposed to infected wild birds, poultry, dairy cows and other mammals. As part of pandemic preparedness efforts, researchers have monitored the H5N1 virus for years to understand viral genetic mutations that occur in nature and what impact they may have on transmissibility.

Influenza viruses attach to cells with a surface viral protein called hemagglutinin (HA). The HA latches on to sugar (glycan) molecule receptors on cells to cause infection. Avian (bird) influenza viruses — like H5N1 — have not infected people often because the human upper respiratory tract lacks the avian-type cell receptors found in birds. Scientists are concerned that viruses could evolve to recognize human-type cell receptors in the upper airways and acquire the ability to infect people and spread between them.

Scientists at Scripps Research used the H5N1 strain isolated from the first U.S. human infection with the bovine strain 2.3.4.4b (A/Texas/37/2024) to test how mutations in the HA gene sequence affected the binding of that protein with avian versus human-type cell receptors. The researchers introduced several mutations into the viral HA protein that had been observed to occur naturally in the past and found that one mutation, called Q226L, improved the ability of the protein to attach to receptors typically found on human cells, especially when an additional mutation was present. Importantly, the researchers introduced the genetic mutations only into the HA surface protein and did not create or conduct experiments with a whole, infectious virus.

The experimental finding with the Q226L mutation alone does not mean HPAI H5N1 is on the verge of causing a widespread pandemic, the authors note. Other genetic mutations would likely be required for the virus to transmit among people. In the setting of a growing number of H5N1 human cases resulting from direct contact with infected animals, the findings stress the importance of continued efforts at outbreak control and continued genomic surveillance to monitor for the emergence of HPAI H5N1 genetic changes and maintain public health preparedness.

The research was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), through its Centers of Excellence for Influenza Research and Response program.

The findings, which have been published in the journal Parasitology, present some of the earliest evidenceof schistosomiasis outside its endemic region of Africa.

“Many of the parasites we see today have been around for centuries. One of our goals in infectious disease studies is to understand where in the world people had these parasites in the past and how their epidemiology has changed through time,” says Marissa Ledger, a post-doctoral fellow at McMaster’s Ancient DNA Centre, who led the research.

Schistosomiasis is caused by Schistosoma mansoni, a water-borne parasitic flatworm that can burrow into the skin, move through the bloodstream and establish itself in the intestines. There it reproduces and releases eggs, which are passed through human waste. Ledger discovered a preserved egg in the contents of a 15^th-century latrine in present-day Belgium, thousands of kilometers away from its endemic region.

The latrine had been uncovered in an excavation in 1996, but its artifacts and organic remains were only recently examined as part of a larger research project at Ghent University focused on the many foreign communities living and trading in medieval Bruges and its former harbor towns.

Researchers say the latrine came from a house known as the Spanish nation house, the administrative seat and meeting place of the Castilian merchant community. The parasite in question is likely associated with one of these Spanish traders who facilitated the import of African commodities like gold dust, ivory and various spices. There’s also evidence they were involved in the early Atlantic slave trade.

The combination of this rich historical record with the archaeological and parasitological data is quite unique and helps us better understand human migration and disease transmission in the past and underscores the historical significance of this Belgian-Canadian collaboration.

“Our findings speak to the complexity of medieval urban life and how interconnected this world was centuries ago. It not only provides novel insight into daily life of people in medieval Bruges but also shows how the city, known as an international hub for people, goods and ideas, inevitably also facilitated the spread of diseases through its strong maritime trade networks,” says Maxime Poulain, archaeologist at Ghent University.

It also demonstrates the importance of analyzing organic remains from these types of archaeological finding, as it can provide information on the health, hygiene and mobility of populations.

Ledger plans to analyze the genetics of the parasite to understand how its makeup compares to that of its modern counterparts.

“Understanding these parasites over a broader time frame provides more information on how they are impacted by factors like migration. Even in the past as people were migrating over these long distances, they were still very effectively moving infectious diseases across long distances. That’s incredibly useful to know.”

“Tell me why: The missing w in episodic memory’s what, where and when” appears in a special issue of Cognitive, Affective & Behavioral Neuroscience focusing on individual differences in memory modulation. Authors Fernanda Morales-Calva, a graduate student in psychological sciences at Rice, and Stephanie Leal, an adjunct assistant professor of psychological sciences, examined existing research to create a comprehensive analysis of the “three Ws” of memory — what, where and when we remember — to answer the central question of why people remember.

Specifically, the researchers explore how emotional significance, personal relevance and individual differences shape memory retention. Unlike experimental studies, this review gathers and interprets existing findings to advance the understanding of episodic memory.

The review categorizes memory research into three primary domains centered on what, where and when people remember. Morales-Calva and Leal found that memories are often shaped by emotional content, personal significance, repetition and attention. For example, individuals are more likely to remember events with deep emotional resonance or details on which they actively focus.

However, what we remember is also influenced by factors such as where the event happened. What is known as spatial memory is often studied in animals, and the researchers said it is also an important aspect of what we remember that applies to human experiences. New environments command greater attention and therefore foster stronger memories when compared to familiar, routine settings.

Finally, the researchers said when the event occurs makes a difference in what people remember. How individuals sequence events and recognize transitions between them plays a critical role in memories. Specific events are often compartmentalized into distinct episodes and therefore can be easier for individuals to recall.

In addition to the what, where and when of memory, Morales-Calva said individual circumstances, including cultural, personal and cognitive differences, can have a significant impact in shaping how individuals remember.

“Memory is not a one-size-fits-all phenomenon,” Morales-Calva said. “What’s memorable for one person might be entirely forgettable for another depending on their unique background and cognitive priorities.”

The researchers said that examining why we remember certain experiences over others can have significant implications for both clinical and everyday settings. For instance, professional memory assessments often rely on standardized tests developed in specific cultural contexts, which have the potential to overlook critical individual differences, the researchers said. Such tests may yield skewed results when applied in diverse populations, highlighting the need for more tailored approaches.

As the global population ages and memory impairments become increasingly prevalent, understanding the specific factors that shape memory could inform interventions for conditions like dementia and cognitive decline, the researchers said.

“This review highlights the importance of considering subjectivity and context in memory research,” Leal said. “By accounting for these variables, we can develop more accurate diagnostic tools and effective interventions.”

The authors argue that complexity of memory can be better understood when the researchers incorporate individual differences into experimental designs. By doing so, they say they hope to bridge gaps between laboratory findings and real-world applications to foster a deeper understanding of the human experience.

The CAST/EiJ mouse, part of a research panel including eight genetically diverse mouse strains, stands out for its severe response to SARS-CoV-2 infection, including beta, omicron, and delta variants. While other strains either recovered or showed mild symptoms, the CAST mice displayed acute illness, highlighting their unique susceptibility to the virus.

“Although most mice strains have negligible symptoms from infection with SARS-CoV-2 variants, CAST mice exhibit a lethal response, making them an invaluable resource for studying the virus’s impact and testing next-generation therapies,” said Nadia Rosenthal, scientific director and professor at JAX, and one of the senior authors of the study.

Originally collected on the island of Castania and brought to JAX in 1971, CAST mice were bred at JAX to maintain a genetically pure line, creating a model as true to the mouse genome as possible. This characteristic makes them an ideal model for investigating severe COVID-19 symptoms on a clean genetic background.

These mice not only carry high viral loads in the lungs but also display severe lung damage, mirroring the kind of hyperinflammatory response seen in human patients with severe COVID-19. This unique strain offers researchers a model that closely parallels the human response to the virus without brain infection — an issue in previous models of COVID-19.

Initial trials using antiviral treatments have shown promising results, boosting survival rates in CAST mice and sparking hope for their role in developing therapies for future coronavirus outbreaks. As new variants continue to emerge, the CAST mouse model stands ready to accelerate a response, providing insights that could ultimately save lives.

Diversity in mouse models offers new perspectives

The study explored eight genetically diverse mouse strains, including A/J, B6J, CAST, 129S1, NSG, NZO, PWK, and WSB, encompassing traits like type 1 and type 2 diabetes susceptibility, obesity, and leanness. These diverse genetic backgrounds enabled the team to uncover differences in virus susceptibility.

Rosenthal and Candice Baker, director of research projects at JAX and first author of the study, started with all eight strains of mice and found the CAST mouse stood out as a highly susceptible mouse for Sars-CoV-2 infection. While the CAST mice didn’t recover, some strains did but displayed lingering symptoms resembling long-COVID.

“The CAST mice gave us insight into the acute symptoms of COVID-19, but now we are going to look at the long-term effects,” said Baker.

In follow-up work, Rosenthal and Baker plan to investigate long-term impacts using this same panel of eight mice.

Overcoming the early challenges of COVID-19 research

When the pandemic began, traditional mouse models were unsuitable for SARS-CoV-2 research, as their cells lack the receptors needed for the virus to bind. In 2023, Rosenthal and her team at JAX and NIH’s Rocky Mountain Laboratories addressed this by using mice engineered with human versions of these receptors, but the resulting infections were overly severe and failed to mimic the spectrum of human responses.

By crossing genetically engineered mice with diverse strains, Rosenthal’s team replicated a range of human-like responses. But these engineered human receptors don’t always give a clinically relevant disease phenotype. The CAST mouse is invaluable, as its genetic background avoids artificial receptor modifications, making it a more natural model for studying severe COVID-19.

“CAST mice stand poised to transform COVID-19 research and prepare us for future challenges,” said Rosenthal. “Equally important, the work reinforces the critical role of genetic diversity in science.”

The MARCO study — MAgnetic Resonance Imaging in COliac disease — which is published in Clinical Gastroenterology and Hepatology (CGH), was led by experts from the School of Medicine at the University of Nottingham, alongside colleagues at the Quadram Institute.

Coeliac disease is a chronic condition affecting around one person in every 100 in the general population. When people with coeliac disease eat gluten, which is found in pasta and bread, their immune system produces an abnormal reaction that inflames and damages the gut tissue and causes symptoms such as abdominal pain and bloating.

The only treatment is a life- long commitment to a gluten free diet, which helps recovery of the gut tissue but still leaves many patients with gastrointestinal symptoms.

Luca Marciani, Professor of Gastrointestinal Imaging at the University, led the study. He said: “Despite being a common chronic condition, we still don’t precisely know how coeliac disease affects the basic physiological functioning of the gut and how the gluten free diet treatment may further change this.

“We launched the MARCO study to try and address this issue, by using MRI along with gut microbiome analysis to give us new insights into how a gluten-free diet affects people with coeliac disease.”

The team recruited 36 people who had just been diagnosed with coeliac disease and 36 healthy volunteers to participate in the study. Images were taken of their guts with MRI, along with blood and stool samples. The patients then followed a gluten free diet for one year and came back to repeat the study. The healthy participants came back one year later too and repeated the study, but they did not follow any diet treatment.

The study found that the newly diagnosed patients with coeliac disease had more gut symptoms, more fluid in the small bowel and that the transit of food in the bowel was slower than in the healthy controls.

The microbiota (the ‘bugs’ living in the colon) of the patients showed higher levels of ‘bad bugs’ such as E.coli. After one year of a gluten free diet, gut symptoms, bowel water and gut transit improved in the patients, but without returning to normal values. By contrast, the gluten free diet reduced some of the ‘good bugs’ in the microbiota, such as Bifidobacteria associated with reduced intake of starch and wheat nutrients, due to the different diet.

The patient study was conducted by Radiographer Dr Carolyn Costigan, from Nottingham University Hospitals, as part of her PhD studies at the University of Nottingham.

Professor Marciani said: “It was particularly interesting to see how the imaging results on gut function correlated with changes in the ‘bugs’ in the colon microbiota. The findings increase our understanding of gut function and physiology in coeliac disease and open the possibility of developing prebiotic treatments to reverse the negative impact of the gluten free diet on the microbiome.”

Dr Frederick Warren from the Quadram Institute said: “This study is the result of an exciting and innovative research collaboration bringing together medical imaging technology and gut microbiome analysis. We provide important insights which pave the way for future studies which may identify novel approaches to alleviate long-term symptoms in coeliac patients.”

Because of the low air pressure and low partial pressure of oxygen at high altitude, the brain does not have an adequate oxygen supply (hypoxia). This not only happens when skiing or mountain climbing if you get to 2500 m too fast, but people who live in regions above 3000 m in South America or Asia, for example, can also be affected despite their acclimation (chronic altitude sickness). The mild form of acute altitude sickness begins about four to six hours after climbing, with a headache. If the climb is not interrupted, additional problems may develop, such as dizziness, nausea, and a racing heart. At this point, descent to lower altitude or treatment in a (portable) pressure chamber and administration of oxygen are critical to prevent hypoxia and life-threatening high-altitude hypoxic brain injury (HHBI).

Most current methods for the early detection of HHBI leave a lot to be desired with regard to speed and precision. A team led by Lin Zhou and Bin Su at Zhejiang University (China) has proposed an approach for a novel strategy based on changes in the oxygen content of regions of the brain over time.

By using fine biocompatible electrodes, the team examined the relationship between the oxygen content in different areas of mouse brains and the degree of HHBI under simulated exposure to high altitude (3000 to 7500 m) in a low-pressure chamber. Hypoxia in the brain immediately triggered the transport of oxygen from other organs to the brain. Within about two hours, the brain additionally redistributed the oxygen: brain regions with higher tolerance for hypoxia received less oxygen to support supply to more important areas.

The electrochemical measurements showed that at a simulated altitude of 3000 m, the oxygen content of the primary somatosensory cortex (responsible for the sense of touch) sank more rapidly than that of the hippocampus (responsible for memory). In both areas, it sank more rapidly than the reduction of blood oxygen saturation. These measurements correlate with memory and sensory tests. Under normal pressure, the animals recovered completely. In contrast, after three days at simulated 7500 m, the oxygen content of both areas sank to roughly similarly low values. The mice suffered from severe HHBI, including cell death. At intermediate heights, individual animals reacted differently. Based on the currents measured within the first one or two hours of low-pressure simulation, it was possible to predict whether and in which area a mouse would suffer HHBI three days later.

Based on the characteristics of the changes in brain oxygen level, it was possible to predict the risk of HHBI several days in advance. The team hopes to use these insights as the basis for possible early detection of impending HHBI.

A multinational team led by Josef Penninger (MedUni Vienna, IMBA — Institute of Molecular Biotechnology, Vienna, University of British Columbia, Canada, Helmholtz Centre for Infection Research, Germany) observed that the intestinal villi reorganise during pregnancy and breastfeeding and significantly enlarge, doubling their surface area. The studies were carried out in genetically modified mice and intestinal organoids from mice and humans — self-organised three-dimensional tissues derived from stem cells in the intestine. Mechanistically, the researchers identified the RANK receptor/RANK ligand (RANK/RANKL) system as the key to the villous enlargement of the small intestine during reproduction, which is regulated by sex and lactation hormones. When mice were engineered to lack the RANK/RANKL system in the intestine, the villous expansion during pregnancy and breastfeeding was significantly impaired.

Fundamental importance for evolution

For decades, researchers have studied the RANK/RANKL system as a key facilitator of essential, evolutionarily conserved processes. The Penninger group has already identified key functions of the RANK/RANKL system in bone turnover, in the biology of the mammary gland, in breast cancer, and in immune tolerance in pregnancy, contributing to the development of drugs against bone loss used by millions of people and clinical trials for breast cancer prevention and cancer immunotherapies are underway. The researchers now discovered that these intestinal changes, which appear to be completely reversible when nursing is stopped, are important for proper feeding and nourishment of the babies. “Our study shows that the impairment of this intestinal expansion by the lack of the RANK/RANKL system during pregnancy changes the milk of the nursing mothers. This results in lower weights of the babies and transgenerational long-term metabolic consequences,” states the lead author Masahiro Onji. “Mothers need to eat for themselves and their babies. These new studies provide for the first time a molecular and structural explanation of how and why the intestine changes to adapt to enhanced nutrient demand of mothers, which is probably the case in all pregnant and nursing mammals,” adds study leader Josef Penninger.

How mothers adapt to the demands of pregnancy and breastfeeding remains a central question of evolution and human health. During this phase, female hormones influence multiple organs to control and change their structure and functions, which is crucial for the health of the mother and the development of the offspring. It was known that pregnant women have enhanced nutrient demands. However, this fundamental aspect has not been well studied until now: “By identifying the RANK/RANKL system as the driving force behind intestinal adaptation during pregnancy and lactation, our study contributes to a deeper understanding of biological processes that are of fundamental importance for evolution and human health,” says Josef Penninger, summarising the impact of the findings.

This massive expansion is controlled by sex and pregnancy hormones, which change the stem cells in the gut via the RANK/RANKL system and then give the intestinal cell a survival signal to grow much larger. This growth then leads to a near doubling of the intestinal surface area, which also increases the molecular machinery for the uptake of sugar, protein, and fat, and even leads to a profound architectural change in the intestinal villi, which probably slows down the flow of food, again maximising the uptake of nutrients. Josef Penninger: “Our team has discovered an amazing new way how mother’s bodies change to keep babies healthy. Hardly anybody knew about this, apart from a few old studies that have largely been forgotten. We have also found that this system, via stem cells, can directly affect tumours in the intestine; maybe we can learn from pregnant and nursing mothers to reversibly rewire this system to develop new treatments and a better understanding of intestinal cancer or gut regeneration.”

The study was a close collaboration between the Medical University of Vienna, the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna, the Life Sciences Institute in Vancouver, the Helmholtz Centre for Infection Research, Braunschweig, the Hubrecht Institute, Utrecht, and the Kiel University. Researchers from the University of Tokyo and the University of Cambridge also participated.

Age is considered the most important risk factor for cancer. That’s because genetic mutations build up in cells over years and decades, and ultimately drive the development of cancer.

Now a study from researchers at Memorial Sloan Kettering Cancer Center (MSK) and their collaborators provides new evidence about how advanced age can also be protective against cancer. The study, conducted in a mouse model of lung cancer, was published in Nature on December 4.

“We know that as people get older, they’re more likely to get cancer,” says study first author Xueqian Zhuang, PhD, a postdoctoral fellow in the lab of senior study author Tuomas Tammela, PhD, at MSK’s Sloan Kettering Institute. “But there’s still a lot that’s unknown about how aging actually changes the biology of cancer.”

As with many types of cancer, lung cancer is diagnosed in most people around age 70, Dr. Zhuang says. But once you get to 80 or 85, the incidence rate starts to come down again.

“Our research helps show why,” she adds. “Aging cells lose their capacity for renewal and therefore for the runaway growth that happens in cancer.”

Overall, the findings have two key implications, the researchers say:

• First, they point to the underappreciated role that iron plays in aging cells’ ability to regenerate — suggesting that therapies that target iron metabolism may work better in younger people than older ones.
• Second, they underline the potential value of early intervention and prevention efforts, targeting the window when most cancers initiate.

Cells’ Ability to Regenerate Linked to Iron Metabolism

To investigate why cancer incidence peaks in the early senior years and then starts to decline again, the MSK research team studied a genetically modified mouse model of lung adenocarcinoma, a common type of lung cancer that accounts for about 7% of all cancer deaths worldwide.

One of the things that makes it challenging to study aging in laboratory models is that mice take two years to develop to an age that’s equivalent to 65-70 years in people, making experiments a lengthy and resource-intensive proposition.

But for the MSK researchers, the effort was worth it.

The scientists found that as the mice get older, they make more of a protein called NUPR1. More NUPR1 makes the cells in the lungs function as if they are iron deficient.

“The aging cells actually have more iron, but for reasons we don’t yet fully understand, they function like they don’t have enough,” Dr. Zhuang says.

Since the cells in the older mice functioned as though they didn’t have enough iron, they lost some of their ability to regenerate. And because that regenerative capacity is directly linked to the rise of cancer, the older mice developed far fewer tumors than their younger counterparts.

Intriguingly, this effect could be reversed by giving the older mice additional iron or by reducing the amount of NUPR1 in their cells.

“We think this discovery may have some immediate potential to help people,” Dr. Tammela says. “Right now, millions of people, especially following the COVID-19 pandemic, live with insufficient lung function because their lungs didn’t fully heal from an infection, or for some other reason. Our experiments in mice showed that giving iron can help the lungs regenerate, and we have really good ways of delivering drugs directly to the lungs — like asthma inhalers.”

But this is also where the double-edged nature of the discovery comes into play. By restoring the ability of the cells in the lungs to regenerate, one is also increasing the tissue’s ability to develop cancer, the study showed.

“So this type of approach might not be appropriate for people who are at a high risk of developing cancer,” he adds.

Older and Younger Patients May Respond Differently to Treatments That Target Iron Metabolism

The team’s findings also have important implications for therapies based on a type of cell death called ferroptosis, which is triggered by iron. Ferroptosis was discovered in 2012, and there are a number of ferroptosis-inducing small molecule compounds, as well as drugs previously approved by the FDA, that are being investigated for their potential to kill cancer cells.

Older cells are far more resistant to ferroptosis than younger cells because they function as if they don’t have enough iron, the researchers found. This means treatments that target ferroptosis may not be as effective in older patients as they are in younger ones.

“One of the things that we showed exploring all of this iron biology is that ferroptosis is tumor suppressive, as everybody suspected — but much more profoundly in younger animals,” Dr. Tammela says.

Dr. Zhuang adds: “To us, this says that because the biology of cells changes with aging, the sensitivity to drugs also changes. So doctors might need to really be careful in clinical trials, for example, to look at the effects in both older and younger patients.”

And for Dr. Tammela, the research ultimately has an even bigger takeaway.

“What our data suggests in terms of cancer prevention is that the events that occur when we’re young are probably much more dangerous than the events that occur later,” he says. “So, preventing young people from smoking, or from tanning, or from other obvious carcinogenic exposures are probably even more important than we thought.”

The biopesticide is a powder made from the dead cells of a common soil-dwelling bacterial species. The researchers showed that the biopesticide efficiently kills both ordinary and chemical-pesticide-resistant mosquitoes when included in standard baits. Even at sub-lethal doses, the biopesticide inhibits malaria transmission and makes mosquitoes more vulnerable to standard chemical pesticides. The encouraging findings from initial trials in western Africa suggest larger field tests could, if successful, one day lead to broad use of the new biopesticide in malaria-endemic parts of the world.

The study was published online December 4in Science Advances.

“This biopesticide has a unique set of features that suggest it could be a powerful new weapon against malaria,” says study senior author George Dimopoulos, PhD, deputy director of the Johns Hopkins Malaria Research Institute in the Bloomberg School’s Department of Molecular Microbiology and Immunology.

Malaria, a parasitic disease spread by Anopheles mosquitoes, has long been one of the world’s top killers. According to World Health Organization estimates, there are about 250 million cases and 600,000 deaths annually, mostly children under five in sub-Saharan Africa. Malaria vaccines have been developed, but are not broadly available or very efficient in preventing disease. While mosquito-killing chemical pesticides have been the most effective weapons against malaria to date, the insects have developed significant resistance to these compounds. New antimalarial tools are urgently needed.

The new biopesticide emerged from a project conducted by Dimopoulos and his team in Panama more than a decade ago. The team caught wild mosquitoes and catalogued bacterial species in their gastrointestinal tracts to see if any could affect the mosquito’s ability to harbor and transmit pathogens. Ultimately, they found one, a species of Chromobacterium, that at low doses inhibits the insects’ ability to transmit pathogens such as the malaria parasite and dengue virus — and at higher doses kills both adult and larval mosquitoes. This discovery suggested the bacterium could be the first biopesticide for use against disease-transmitting mosquitoes.

To avoid the complications of working with a live organism, the researchers developed a powder preparation made from dead, dried cells of the bacterium. They found that the powder retains the bacterium’s mosquitocidal properties, and also has a years-long shelf life and very high heat stability. Early tests also found that the biopesticide has no evident toxic effects on mammalian cells, is readily ingested by mosquitoes when dissolved in standard mosquito baits, and — unlike chemical insecticides — does not lead to the development of genetic resistance in mosquitoes even after ten generations of mild exposure.

In the new study, the researchers tested the new biopesticide in laboratory conditions, and in “MosquitoSphere” facilities — large, net-enclosed spaces simulating village and agricultural settings — in Burkina Faso. The biopesticide killed both laboratory and wild-caught strains of Anopheles, including those with resistance to different kinds of chemical pesticides. Even when the biopesticide didn’t kill the insects, it largely reversed their chemical insecticide resistance.

At the highest dose of 200 mg/ml, the biopesticide wiped out the vast majority of the mosquitoes in the MosquitoSphere facilities, and the researchers’ mathematical modeling suggested that it would dramatically reduce local mosquito populations in real-world conditions.

Mosquitoes exposed to the biopesticide even at low doses were also severely impaired in their ability to seek out a host for blood meals. In the relatively few insects that succeeded in ingesting malaria parasite-infected blood in experiments, the ability of the parasites to infect the mosquito was sharply reduced as well. These results suggest that the biopesticide overall could have a very potent effect at reducing malaria transmission.

The researchers’ results so far suggest that the biopesticide works by modifying the activity of a key detoxification enzyme in mosquitoes, essentially turning the insects’ detox systems against them — which would explain why the biopesticide has such a strong synergy with chemical pesticides.

The researchers now plan to seek U.S. Environmental Protection Agency approval for the new biopesticide, and to set up larger-scale field tests to further assess its ability to reduce malaria incidence.

They also plan more experiments to identify the component or components of the Chromobacterium that account for its potent anti-mosquito effects.

“It was never my intention to focus on biopesticides,” says Dimopoulos, whose primary focus has been malaria mosquito immunity. “But that’s how these discoveries have worked out, and it’s exciting that we’ve identified something novel with malaria control potential.”

“Chromobacterium biopesticide overcomes insecticide resistance in malaria vector mosquitoes” was co-authored by Chinmay Tikhe, Sare Issiaka, Yuemei Dong, Mary Kefi, Mihra Tavadia, Etienne Bilgo, Rodrigo Corder, John Marshall, Abdoulaye Diabate, and George Dimopoulos.

Funding was provided by the U.S. Agency for International Development (USAID), the Innovative Vector Control Consortium, and the Johns Hopkins Malaria Research Institute.

The use of natural and minimally processed ingredients in many modern diets has decreased, more often being replaced with ingredients that have been industrially processed, artificially flavored, colored or chemically altered.

Foods such as breakfast cereals, margarines/spreads, packaged snacks, hot dogs, soft drinks and energy drinks, candies and desserts, frozen pizzas, ready-to-eat meals, mass-produced packaged breads and buns, and more, include synthesized ingredients and are highly processed.

These ultra-processed foods usually have longer shelf lives and are highly appealing, as they are convenient and contain a combination of sugar, fat, salt and carbohydrates which affect the brain’s reward system, making it hard to stop eating.

For the study, researchers set out to assess the association of ultra-processed food intake and their relationship to intramuscular fat in the thigh.

“The novelty of this study is that it investigates the impact of diet quality, specifically the role of ultra-processed foods in relation to intramuscular fat in the thigh muscles assessed by MRI,” said author Zehra Akkaya, M.D., researcher and former Fulbright Scholar in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco. “This is the first imaging study looking into the relationship between MRI-based skeletal muscle quality and quality of diet.”

For the study, researchers analyzed data from 666 individuals who participated in the Osteoarthritis Initiative who were not yet affected by osteoarthritis, based on imaging. The Osteoarthritis Initiative is a nationwide research study, sponsored by the National Institutes of Health, that helps researchers better understand how to prevent and treat knee osteoarthritis.

“Research from our group and others has previously shown that quantitative and functional decline in thigh muscles is potentially associated with onset and progression of knee osteoarthritis,” Dr. Akkaya said. “On MRI images, this decline can be seen as fatty degeneration of the muscle, where streaks of fat replace muscle fibers.”

Of the 666 individuals, (455 men, 211 women) the average age was 60 years. On average, participants were overweight with a body mass index (BMI) of 27. Approximately 40% of the foods that they ate in the past year were ultra-processed.

The researchers found that the more ultra-processed foods people consumed, the more intramuscular fat they had in their thigh muscles, regardless of energy (caloric) intake.

“In an adult population at risk for but without knee or hip osteoarthritis, consuming ultra-processed foods is linked to increased fat within the thigh muscles,” Dr. Akkaya said. “These findings held true regardless of dietary energy content, BMI, sociodemographic factors or physical activity levels.”

Targeting modifiable lifestyle factors — mainly prevention of obesity via a healthy, balanced diet and adequate exercise — has been the mainstay of initial management for knee osteoarthritis, Dr. Akkaya noted.

“Osteoarthritis is an increasingly prevalent and costly global health issue. It is the largest contributor to non-cancer related health care costs in the U.S. and around the world,” Dr. Akkaya said. “Since this condition is highly linked to obesity and unhealthy lifestyle choices, there are potential avenues for lifestyle modification and disease management.”

By exploring how ultra-processed food consumption impacts muscle composition, this study provides valuable insights into dietary influences on muscle health.

“Understanding this relationship could have important clinical implications, as it offers a new perspective on how diet quality affects musculoskeletal health,” Dr. Akkaya said.

Co-authors are Gabby B. Joseph, Ph.D., Katharina Ziegeler, M.D., Wynton M. Sims, John A. Lynch, Ph.D., and Thomas M. Link, M.D., Ph.D.

Guided by previous research of spider brains, the scientists uncovered evidence of a “waste canal system” in the human brain that internalizes waste from healthy neurons. They discovered that this system can undergo catastrophic swelling, which leads to the degeneration of brain tissue, a hallmark of Alzheimer’s disease.

With over 50 million affected people worldwide, Alzheimer’s disease is among the leading causes of death in the U.S.

The findings, which have been published by The Journal of Comparative Neurology, offer a compelling new explanation for commonly described brain pathologies observed in Alzheimer’s disease, including amyloid-beta plaques, tau tangles, and spongiform abnormalities.

Supported by the Vermont Biomedical Research Network (VBRN), the research was carried out in collaboration among Dr. Ruth Fabian-Fine (Saint Michael’s College, UVM Robert Larner, M.D. College of Medicine), Dr. John DeWitt (UVM Robert Larner, M.D. College of Medicine, UVM Medical Center), Dr. Adam Weaver (Saint Michael’s College), and Saint Michael’s undergraduate research students Abigail Roman and Melanie Winters, both members of the Class of 2025.

“The Vermont Biomedical Network has been thrilled to support Dr. Fabian-Fine’s research from its initial focus on animal neuroscience to the more recent and potentially groundbreaking emphasis on the cellular basis of human neurodegeneration,” said UVM’s Dr. Christopher Francklyn, the Director of VBRN. “Her exciting work, and the outstanding training she has provided to her undergraduate co-investigators, epitomizes what NIH hopes to accomplish with its national IDEA program.”

Neuroscientist Dr. Fabian-Fine and her team initially investigated the underlying causes for neurodegeneration in Central American wandering spiders that suffer from conditions similar to degenerative diseases in humans. Because the spider neurons were a larger size, the scientists were better able to observe their brain functions. They quickly discovered a waste-internalizing glial canal system that undergoes structural abnormalities in degenerating spider brains, which leads to uncontrolled depletion and death of brain cells.

This discovery prompted Fabian-Fine, a Vermont Center for Cardiovascular and Brain Health Pipeline Investigator, to explore whether a similar system could be found in both rodent and human brain tissue, so she teamed up with neuropathologist Dr. DeWitt at UVM’s Larner College of Medicine. The collaborative undertaking led the scientists to gather overwhelming evidence that neurodegeneration in human and rodent brains may have similar underlying causes compared to those observed in spider brains. The scientists’ report outlines possible underlying causes for neurodegeneration that may offer a promising new avenue for drug development that can address the structural abnormalities that lead to neurodegeneration.

Dozens of student researchers at Saint Michael’s College contributed to the multi-year research that provided the foundation for this breakthrough. Experiments occurred at Saint Michael’s College, the University of Vermont Medical Center, and at the UVM’s Center for Biomedical Shared Resources.

“The marriage of innovation, social media and telehealth consultations has changed how patients perceive and seek beauty and how they engage with dermatologists,” says

corresponding author Neelam Vashi, MD, associate professor of dermatology at Boston University Chobanian & Avedisian School of Medicine. “Technology should serve as a means of empowerment, that celebrates individuality and authenticity, not distortion.”

Her editorial in the Journal of Clinical Medicine, explores how dermatologists must learn to harness the power of technology while upholding the core values of safety, ethics and patient satisfaction.

Vashi, who also directs the Boston University Cosmetic and Laser Center at Boston Medical Center, describes how technologies such as artificial intelligence (AI), augmented reality and high-resolution imaging are powerful tools that are pushing the boundaries of what physicians can offer their patients in cosmetic dermatology. While these tools empower patients by offering a tangible, visual sense of what they could potentially expect, she stresses that they are not without challenges. “While AI can generate recommendations based on an enormous amount of data in seconds, it cannot fully account for the complexity and unpredictability of human skin and response to treatment.”

Vashi also addresses the “social media effect” which she describes as a double-edged sword. Even though social media makes information and personal experiences related to cosmetic dermatology treatments easily accessible to social media users, Vashi points out that influencers without background expertise promote skincare products or cosmetic procedures, dispensing unqualified skin advice that can potentially be harmful.

While access to care has expanded through telemedicine, Vashi warns that dermatologists must be wary of the limitations of virtual consultations. She believes some conditions, consultations, and procedures require in-person appointments to ensure safety and accuracy. “Relying solely on virtual tools misses valuable information that can only be obtained by seeing the patient in person. It is the responsibility of dermatologists to balance the convenience of telehealth with the necessity of in-person exams to ensure the patient’s safety and cosmetic goals are best met,” Vashi says.

As both cosmetic dermatology information and procedures become more accessible in the digital age, the need for greater awareness, patient education and regulation become more necessary. According to Vashi, cosmetic dermatologists have an important role to play in educating patients about the risks associated with self-administered treatments and unregulated services sold online. “Dermatologists should emphasize and recommend receiving procedures from licensed professionals who adhere to safety standards and ethical guidelines. On an institutional level, dermatologists should advocate for strong regulatory oversight of digital platforms to minimize misinformation and ensure patient safety.”

Vashi concludes her editorial by addressing the relationship between digital beauty standards and mental health and self-esteem. “Supporting our patients and understanding the effects of social media on their psyche is vital. The digital age and all its powerful tools must be the center of further research so that we may not only better utilize it, but also uphold ethical standards and foster a healthy relationship with beauty in the digital age.”

Inequities in educational resources, especially those in science, engineering, technology and math (STEM), where experiments are expensive, have kept some students underrepresented in these fields. By engaging a group of these students early in real, high-quality research, a team from the University of Illinois at Chicago led by Brian Murphy is providing young learners a chance to see themselves as scientists and explore careers in science with hands-on experience. The team partnered with a Boys and Girls Club in Chicago to bring interested middle schoolers into a 14-week applied science program.

Murphy’s lab is focused on discovering antibiotics from natural sources, and the cohort of young scientists participated by supplying environmental samples from their local communities. And the students’ contributions to the research group didn’t end there. They stayed actively involved throughout the scientific discovery process by programming a specialized robot to scoop up bacterial colonies from growth plates and test them for antibiotic activity.

One of the 14 samples collected — goose poop from the Garfield Park Lagoon — contained a strain of bacteria called Pseudomonas idahoensis. The students interpreted the bacterium’s bioassay data and concluded it had antibiotic activity and produced a never-before-seen compound. Then, the university researchers determined the compound’s molecular structure using nuclear magnetic resonance and mass spectrometry, named it orfamide N after the family of molecules it belongs to, and investigated its biological activity. Although orfamide N was not responsible for the antibiotic activity that the team initially observed from P. idahoensis, the compound inhibited the growth of human melanoma and ovarian cancer cells in culture tests. Further studies could reveal other advantageous properties of this newly characterized molecule.

The researchers say that this work proves that it’s possible to combine educational outreach with natural product discovery research, and it emphasizes the importance of a strong relationship between universities and their local communities.

The authors acknowledge funding from the University of Illinois at Chicago Graduate College, Illinois-Indiana Sea Grant, an Illinois-Indiana Sea Grant Faculty Scholar Award, the Illinois-Indiana Sea Grant Graduate Student Scholar Award, and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. They extend special thanks to the volunteer outreach mentors at the Boys and Girls Clubs of Chicago.

The incidence of kidney cancer in the United States rose by an average of 1.2 percent each year between 2011 and 2019 to become the seventh most common cancer. In the meantime, smoking — a well-established risk factor for kidney cancer — has continued to decline.

This led researchers to consider other possible contributing factors, including arsenic, a known cause of various cancers that is naturally occurring in groundwater in Texas and other areas. Unlike previous studies, the Texas A&M study focused on low levels of arsenic exposure (below the regulatory threshold of 10 parts per billion) in both public water systems, which are regulated by various government agencies, and private well systems, which are not regulated.

“Some public water systems are poorly managed and could expose customers to arsenic, but the 40 million people in the United States who rely on private wells are particularly vulnerable,” said Taehyun Roh, with the Department of Epidemiology and Biostatistics.

Others involved with the study were Daikwon Han, Xiaohui Xu, and then-doctoral student Nishat Tasnim Hasan, with the Department of Epidemiology and Biostatistics, and Garett Sansom, with the Department of Environmental and Occupational Health. The project was supported by grants from the Houston Methodist Research Institute, Robert and Janice McNair Foundation and National Institute of Environmental Health Sciences.

Their findings, published in Environmental Pollution, examined the relationship between kidney cancer rates and arsenic levels in drinking water across 240 Texas counties. The team analyzed cancer data from the Surveillance, Epidemiology, and End Results on 28,896 cases of cancer among adults in Texas aged 20 and older, alongside water testing data from the Texas Department of State Health Services and the Texas Water Development Board.

They used a statistical model that accounts for geographic location and adjusted the model for demographic and socioeconomic factors and cancer risk factors such as obesity, smoking and diabetes. They also adjusted for covariates that included pesticide density, social vulnerability, income level, rurality, cardiovascular disease hospitalization rates and the prevalence of chronic kidney disease.

The analysis found that exposure to between 1 and 5 parts per billion raised kidney cancer risk by 6 percent, and exposure above 5 parts per billion raised the risk by 22 percent. In addition, the risk of cancer increased by 4 percent with each doubling of water arsenic levels.

“This suggests that even low-level arsenic exposure in drinking water may be associated with an increased risk of kidney cancer, which aligns with previous research indicating an association between this exposure and lung, bladder and skin cancers,” Roh said.

Hasan noted that their study design can indicate associations between factors but not causality and recommended that future studies focus on individual-level and biometric data — rather than the county-level data used here — to better assess the effects of factors such as lifestyle, family history of kidney cancer and other possible sources of arsenic exposure.

“Still, our findings indicate that reducing arsenic exposure could reduce the incidence of kidney cancer, and this could be achieved through efforts such as enhanced regulatory oversight and targeted public health interventions,” Hasan said.

The findings, published today in The Lancet Respiratory Medicine, could be “game-changing” for millions of people with asthma and COPD around the world, scientists say.

Asthma attacks and COPD flare-ups (also called exacerbations) can be deadly. Every day in the UK four people with asthma and 85 people with COPD will tragically die. Both conditions are also very common, in the UK someone has an asthma attack every 10 seconds. Asthma and COPD costs the NHS £5.9B a year.

The type of symptom flare-up the injection treats are called ‘eosinophilic exacerbations’ and involve symptoms such as wheezing, coughing and chest tightness due to inflammation resulting from high amounts of eosinophils (a type of white blood cell). Eosinophilic exacerbations make up to 30% of COPD flare-ups and almost 50% of asthma attacks. They can become more frequent as the disease progresses, leading to irreversible lung damage in some cases.

Treatment at the point of an exacerbation for this type of asthma has barely changed for over fifty years, with steroid drugs being the mainstay of medication. Steroids such as prednisolone can reduce inflammation in the lungs but have severe side-effects such as diabetes and osteoporosis. Furthermore, many patients ‘fail’ treatment and need repeated courses of steroids, re-hospitalisation or die within 90 days.

Results from the phase two clinical trial ABRA study, led by scientists from King’s College London and sponsored by the University of Oxford, show a drug already available can be re-purposed in emergency settings to reduce the need for further treatment and hospitalisations. The multi-centre trial was conducted at Oxford University Hospitals NHS Foundation Trust and Guy’s and St Thomas’ NHS Foundation Trust.

Benralizamab is a monoclonal antibody which targets specific white blood cells, called eosinophils, to reduce lung inflammation. It is currently used for the treatment of severe asthma. The ABRA trial has found a single dose can be more effective when injected at the point of exacerbation compared to steroid tablets.

The study investigators randomised people at high risk of an asthma or COPD attack into three groups, one receiving benralizumab injection and dummy tablets, one receiving standard of care (prednisolone 30mg daily for five days) and dummy injection and the third group receiving both benralizumab injection and standard of care. As a double-blind, double-dummy, active-comparator placebo-controlled trial, neither the people in the study, or the study investigators knew which study arm or treatment they were given.

After 28 days, respiratory symptoms of cough, wheeze, breathlessness and sputum were found to be better with benralizumab. After ninety days, there were four times fewer people in the benralizumab group that failed treatment compared to standard of care with prednisolone.

Treatment with the benralizumab injection took longer to fail, meaning fewer episodes to see a doctor or go to hospital. There was also an improvement in the quality of life for people with asthma and COPD.

Lead investigator of the trial Professor Mona Bafadhel from King’s College London said: “This could be a game-changer for people with asthma and COPD. Treatment for asthma and COPD exacerbations have not changed in fifty years despite causing 3.8 million deaths worldwide a year combined.

“Benralizumab is a safe and effective drug already used to manage severe asthma. We’ve used the drug in a different way — at the point of an exacerbation — to show that it’s more effective than steroid tablets which is the only treatment currently available. The big advance in the ABRA study is the finding that targeted therapy works in asthma and COPD attacks. Instead of giving everyone the same treatment, we found targeting the highest risk patients with very targeted treatment, with the right level of inflammation was much better than guessing what treatment they needed.”

The benralizumab injection was administered by healthcare professionals in the study but can be potentially administered safely at home, in the GP practice, or in the Emergency Department. Benralizumab was safe in the study and similar in safety to many past studies.

Professor Mona Bafadhel said, “We hope these pivotal studies will change how asthma and COPD exacerbations are treated for the future, ultimately improving the health for over a billion people living with asthma and COPD across the world.”

Dr Sanjay Ramakrishnan, Clinical Senior Lecturer at the University of Western Australia, who is the first author of the ABRA trial and started the work while at the University of Oxford, said: “Our study shows massive promise for asthma and COPD treatment. COPD is the third leading cause of death worldwide but treatment for the condition is stuck in the 20th century. We need to provide these patients with life-saving options before their time runs out.

“The ABRA trial was only possible with collaboration between the NHS and universities and shows how this close relationship can innovate healthcare and improve people’s lives.”

Geoffrey Pointing, 77 from Banbury, who took part in the study, said: “Honestly, when you’re having a flare up, it’s very difficult to tell anybody how you feel — you can hardly breathe. Anything that takes that away and gives you back a normal life is what you want. But on the injections, it’s fantastic. I didn’t get any side effects like I used to with the steroid tablets. I used to never sleep well the first night of taking steroids, but the first day on the study, I could sleep that first night, and I was able to carry on with my life without problems. I want to add that I’m just grateful I took part and that the everyone involved in the ABRA study are trying to give me a better life.”

Dr Samantha Walker, Director of Research and Innovation, at Asthma + Lung UK, said: “It’s great news for people with lung conditions that a potential alternative to giving steroid tablets has been found to treat asthma attacks and chronic obstructive pulmonary disease (COPD) exacerbations. But it’s appalling that this is the first new treatment for those suffering from asthma and COPD attacks in 50 years, indicating how desperately underfunded lung health research is.

“Every four minutes in the UK, someone dies from a lung condition. Thousands more live with the terror of struggling to breathe every day. With your help, we’re fighting for more life-changing, life-saving research to transform the future for everyone living with breathing problems. Together, we’ll make sure that families everywhere never face a lung condition without the best treatment and care.

“Our vision is a world where everyone has healthy lungs. We can only get there with your help.”

This research was conducted with support from AstraZeneca UK Limited.

These daily oral antiretrovirals, more commonly referred to as PrEP (pre-exposure prophylaxis), such as Truvada®, are extremely effective at HIV prevention, but only if they are taken daily as directed. Truvada’s efficacy is greatly compromised when taken inconsistently.

However, results from a recent Gilead-funded clinical trial (Purpose-2) led by physicians at Emory University and Grady Health System indicate that a twice-yearly injection of Lenacapavir offers a 96% reduced risk of infection overall, making the injection significantly more effective than the daily oral PrEP. The findings were recently published in the New England Journal of Medicine.

“Seeing these high levels of efficacy — at almost 100% — in an injectable that people only have to take every six months is incredible,” says Colleen Kelley, MD, lead author of the study and professor in the School of Medicine at Emory University. “This is a considerable and profound advancement in medicine, especially for people whose circumstances don’t allow them to take a daily oral medication, and for those among populations disproportionately impacted by HIV.”

In the randomized, double-blind, Phase III clinical trial comparing the efficacy of the two medications, 99% of the participants in the Lenacapavir group did not acquire an HIV infection. During the trial, only two participants in the Lenacapavir group, comprised of 2,179 people, acquired HIV. This compares to nine new HIV infections in the Truvadagroup, which had 1,086 people. The trial showed that adherence to the injectable was higher than of the daily oral pill.

Kelley, also the co-director of the Emory Center for AIDS Research, and Associate Dean for Research for Emory at Grady adds that while PrEP is incredibly effective at preventing infection, part of what made the injection more effective in the clinical trial was the challenges associated with adherence to a daily oral pill.

“What we see over time is that about half of people who start taking daily oral PrEP stop within a year due to various factors,” says Kelley, referencing healthcare disparities in general. “Having an effective injectable that is only needed twice annually is very significant for people who have trouble accessing healthcare or staying adherent to daily, oral pills.”

The inclusion of racially, ethnically, and gender-diverse participants in the clinical trial was notable because it was representative of populations disproportionately impacted by HIV in real time. For example, the trial groups were comprised of cisgender men and gender-diverse people at 88 sites in Peru, Brazil, Argentina, Mexico, South Africa, Thailand, and the U.S.

According to the study, the same populations that are disproportionately impacted by HIV are the same populations that have limited access to PrEP — or may have difficulty consistently taking the oral antiretroviral medication — ultimately highlighting the need for more options. The study also indicates that more than half of the new HIV infections nationwide in 2022 were among cisgender gay men, and 70% of those were among Black or Hispanic individuals.

Valeria Cantos, MD, associate professor in the School of Medicine at Emory University, physician at Grady Memorial Hospital, and the principal investigator for the clinical trial at the Grady research site, emphasized the importance of having trials that include populations truly representative of the patients that Grady serves.

“At Grady, our focus is on increased representation of underserved and vulnerable populations, acknowledging and addressing the distrust towards research held by some community members due to prior abuses or neglect of these populations by research institutions in the past,” Cantos says. “Grady is an established, trusted research site because of its commitment to equity.”

At the Grady clinical trial site, medical materials were available in Spanish, and bilingual staff members recruited and enrolled trial participants who only spoke Spanish. Cantos also indicated that the site enrolled participants who are representative of the populations that would benefit the most from Lenacapavir. In addition to Grady, the Hope Clinic and Emory Midtown Hospital were among the 88 sites supporting the clinical trial.

“We are not reaching everyone we need to reach with our current HIV prevention interventions, such as those who are disproportionately impacted by HIV and health care disparities,” says Kelley. “For people that are unable to take the daily oral pills, the injectable agents can really give incredible efficacy and be a game changer in helping them stay HIV negative.”

Since the Phase III clinical trial has been completed and submitted by the FDA for consideration, Kelley is hopeful that Lenacapavir may be approved by 2025 for commercial use.

“”The results of this study add to the armamentarium of novel tools for HIV prevention. Long acting antiretrovirals offer new hope for those who are not able to take oral medications,” says Carlos del Rio, MD, chair of the Department of Medicine at Emory University School of Medicine. “The challenge is now to roll out and make these tools available and accessible in an equitable way — only then we will see new HIV infections dramatically decreased locally and globally,” adds del Rio, also co-director of the Emory Center for AIDS Research.

According to a study led by Sylvana Côté, preschool education services significantly help bridge the gap between children whose mother tongue is French and those for whom French is a second or even a third language.

Professor Côté, from the School of Public Health at the Université de Montréal (ESPUM), is the director of the Observatory for Children’s Education and Health and a researcher at the CHU Sainte-Justine Research Center. The study, with Ophélie A. Collet as the lead author, was recently published in the journal JAMA Pediatrics.

“Being exposed to other children and a team of educators better prepares children for school than growing up in a home where neither French nor English is spoken. The period from one to five years old is absolutely crucial for language acquisition. It takes a village to raise a child, and in this case, the village is preschool,” summarizes Professor Côté.

Learning to Communicate

The findings are clear. Allophone children who attended daycare (or pre-kindergarten at age four, though to a lesser extent) show better cognitive development, improved social and emotional skills, and greater communication abilities. These benefits are partly attributed to a sufficient level of general knowledge.

At the time of the survey, 6.1% of kindergarten children in Quebec came from allophone families, amounting to 4,360 children. Of these, nearly 14% stayed home before starting school, compared to only 6% of children whose mother tongue was French.

The survey relied on the Early Development Instrument, a Canadian tool used internationally to measure children’s readiness for kindergarten. Teachers, who closely interact with the children, completed the questionnaires and provided information about whether the children had attended preschool services.

“It is crucial to ensure that children whose mother tongue is not French are not disadvantaged by the scarcity of spaces in preschool centers,” emphasizes Professor Côté. She adds that while bilingualism is an excellent mental exercise, the challenges of learning multiple languages are real. Children need support during this critical stage of development.

Academic Persistence

The best predictor of academic persistence is mastering social, emotional, cognitive, and physical skills by kindergarten. Children who lack these skills are less likely to graduate from high school.

Among the 80,000 children surveyed, 11.2% were excluded due to insufficient information, leaving 71,589 participants. Of these, 48.8% were girls, and 25.6% were learning more than one language. This includes 13,981 bilingual children (English and French) and 4,360 allophone children, representing 6.1% of the total. Within this group, 26% spoke Arabic, 18% Spanish, and 7.3% African languages. Others spoke various languages, including Creole, Chinese, Portuguese, Russian, or Persian.

Addressing Social Inequalities

Previous studies have shown that quality daycare services benefit all children, especially those from economically disadvantaged backgrounds. Introduced in 1997 in the province of Quebec (Canada), Quebec’s subsidized Early Childhood Centers (CPEs) were designed to reduce social inequalities and facilitate work-life balance. While the latter goal has been achieved, much work remains to reduce inequalities. Only 30% of children have access to CPEs, and there are 2.5 times fewer centers in disadvantaged areas.

The researchers adjusted their findings to account for families’ financial situations. “The study demonstrates the impact of preschool education services beyond economic status,” explains Professor Côté, noting that the best services are often in affluent neighborhoods.

“This study is a strong call to enhance quality daycare services. It’s a preventive measure to ensure better integration for children,” concludes Côté. This is the first study to specifically examine the impact of preschool services on the readiness of allophone children entering kindergarten.

Professor Côté also directs the Research Group on Child Psychosocial Maladjustment. She plans to revisit the children when they reach fifth grade to determine whether the benefits of daycare persist.

About this study

In addition to Ophélie Collet, the study’s investigators are Thuy Mai Luu, pediatrician at CHU Saint e-Justine; Pascale M. Domond and Tianna Loose, CHU Sainte-Justine Research Centre; Cédric Galéra, Université de Bordeaux; Alejandro Vasquez-Echeverria, University of the Republic of Uruguay; and Massimiliano Orri, Douglas Research Centre, McGill University.

“School Readiness and Early Childhood Education and Care Services Among Dual Language Learners,” by Ophélie Collet et al., was published in JAMA Pediatrics on November 11, 2024.

“We saw that transgender men treated with testosterone increased their muscle volume by an average of 21 percent over six years, but also that the amount of abdominal fat increased by 70 percent,” says Tommy Lundberg, docent at the Department of Laboratory Medicine, Karolinska Institutet. “In addition, they had more liver fat and higher levels of ‘bad’ LDL cholesterol, which may increase the risk of cardiovascular disease.”

The researchers followed 17 adult transgender men and 16 transgender women who were prescribed treatment with testosterone and oestrogen, respectively. They used magnetic resonance imaging (MRI) to map body composition and measured metabolic risk factors via blood tests, blood pressure and vascular stiffness. The scans were conducted before the start of hormone therapy, after one year and after five to six years.

The results show that long-term hormone therapy leads to several major changes in both body composition and metabolic risk factors, particularly in transgender men. The changes in fat volumes continued over time, while the greatest changes in muscle mass and strength occurred after just one year of treatment.

“Previous studies in this area have been relatively short-term, up to two years,” explains Tommy Lundberg. “Our results show that it is important to continue monitoring the long-term health effects of hormone therapy in transgender individuals to prevent cardiovascular disease and other health issues.”

In transgender women receiving oestrogen treatment, the changes were not as pronounced. Their muscle volume decreased by an average of seven percent after five years of treatment, whereas muscle strength remained unchanged. The transgender women increased their total fat volume but gained less abdominal fat.

Tissue samples from muscle, fat and skin were also taken as part of the study. The next step is to analyse these tissue samples to understand the interaction between genetic sex and sex hormones. The researchers are investigating, among other things, how hormone treatment affects skeletal muscle gene expression and the mechanisms behind changes in adipose tissue.

“In addition to the health aspects, our research contributes to increased knowledge about reasonable expectations of the masculinising and feminising effects of sex hormone treatment,” says Tommy Lundberg. “However, some of the changes were relatively modest and should raise caution regarding expectations of long-term and large changes in this patient group.”

The research was funded by Region Stockholm, the Thuring Foundation, the 1.6 Million Club, the Centre for Innovative Medicine at Karolinska Institutet, the Swedish Research Council, the Swedish Medical Association, the Novo Nordisk Foundation and the European Foundation for Studies of Diabetes.

Two of the co-authors are employed by AMRA Medical AB. Tommy Lundberg has been compensated for expert opinions on aspects related to skeletal muscle changes in transgender individuals and reimbursed for travelling to give lectures on the same topic.

To build proteins, the cell makes a copy of DNA, called mRNA. Then, another molecule called a ribosome reads the mRNA, translating it into protein. But this step has been a visual mystery: scientists previously did not know how the ribosome attaches to and reads mRNA.

Now, a team of international scientists, including University of Michigan researchers, have used advanced microscopy to image how ribosomes recruit to mRNA while it’s being transcribed by an enzyme called RNA polymerase, or RNAP. Their results, which examine the process in bacteria, are published in the journal Science.

“Understanding how the ribosome captures or ‘recruits’ the mRNA is a prerequisite for everything that comes after, such as understanding how it can even begin to interpret the information encoded in the mRNA,” said Albert Weixlbaumer, a researcher from Institut de génétique et de biologie moléculaire et cellulaire in France who co-led the study. “It’s like a book. Your task is to read and interpret a book, but you don’t know where to get the book from. How is the book delivered to the reader?”

The researchers discovered that the RNAP transcribing the mRNA deploys two different anchors to rope in the ribosome and ensure a solid footing and start of protein synthesis. This is similar to a foreperson at a construction site overseeing workers installing a complex section of the superstructure, confirming in two redundant ways that all the pieces are fastened securely at critical junctures for maximum stability and functionality.

Understanding these fundamental processes holds great potential for developing new antibiotics that target these specific pathways in bacterial protein synthesis, according to the researchers. Traditionally, antibiotics have targeted the ribosome or RNAP, but bacteria often find a way to evolve and mutate to create some resistance to those antibiotics. Armed with their new knowledge, the team hopes to outwit bacteria by cutting off multiple pathways.

“We know there is an interaction between the RNAP, the ribosome, transcription factors, proteins and mRNA,” said U-M senior scientist Adrien Chauvier, one of four co-leaders of the study. “We could target this interface, specifically between the RNAP, ribosome, and mRNA, with a compound that interferes with the recruitment or the stability of the complex.”

The team developed a mechanistic framework to show how the various components of the complex work together to bring freshly transcribed mRNAs to the ribosome and act as bridges between transcription and translation.

“We wanted to find out how the coupling of RNAP and the ribosome is established in the first place,” Weixlbaumer said. “Using purified components, we reassembled the complex — 10-billionth of a meter in diameter. We saw them in action using cryo-electron microscopy (cryo-EM) and interpreted what they were doing. We then needed to see if the behavior of our purified components could be recapitulated in different experimental systems.”

In more complex human cells, DNA resides in the walled-off nucleus, where RNAP serves as the “interpreter,” breaking down genetic instructions into smaller bites. This dynamo of an enzyme transcribes, or writes, the DNA into mRNA, representing a specifically selected copy of a small fraction of the genetic code that is moved to the ribosome in the much “roomier” cytoplasm, where it is translated into proteins, the basic building blocks of life.

In prokaryotes, which lack a distinct nucleus and internal membrane “wall,” transcription and translation happen simultaneously and in close proximity to each other, allowing the RNAP and the ribosome to directly coordinate their functions and cooperate with each other.

Bacteria are the best-understood prokaryotes, and because of their simple genetic structure, provided the team with the ideal host to analyze the mechanisms and machinery involved in the ribosome-RNAP coupling during gene expression.

The researchers employed various technologies and methodologies per each lab’s specialty — cryo-EM in Weixlbaumer’s group, and the Berlin group’s in-cell crosslinking mass spectrometry carried out by Andrea Graziadei — to examine the processes involved.

With expertise in biophysics, Chauvier and Nils Walter, U-M professor of chemistry, biophysics, utilized their advanced single molecule fluorescence microscopes to analyze the kinetics of the structure.

“In order to track the speed of this machinery at work, we tagged each of the two components with a different color,” Chauvier said. “We used one fluorescent color for the nascent RNA, and another one for the ribosome. This allowed us to view their kinetics separately under the high-powered microscope.”

They observed that the mRNA emerging from RNAP was bound to the small ribosomal subunit (30S) particularly efficiently when ribosomal protein bS1 was present, which helps the mRNA unfold in preparation for translation inside the ribosome.

The cryo-EM structures of Webster and Weixlbaumer pinpointed an alternative pathway of mRNA delivery to the ribosome, via the tethering of RNA polymerase by the coupling transcription factor NusG, or its paralog, or version, RfaH, which thread the mRNA into the mRNA entry channel of the ribosome from the other side of bS1.

Having successfully visualized the very first stage in establishing the coupling between RNAP and the ribosome, the team looks forward to further collaboration to find out how the complex needs to rearrange to become fully functional.

“This work demonstrates the power of interdisciplinary research carried out across continents and oceans,” said Walter.

Huma Rahil, a doctoral student in the Weixlbaumer lab, and Michael Webster, then a postdoctoral fellow in the lab and now of The John Innes Centre in the United Kingdom, co-led the paper as well.

Escherichia coli is a common bacterium which is often harmless but can cause serious infections. The researchers exposed E. coli to streptomycin and kasugamycin, two drugs which treat bacterial infections. Streptomycin has been a staple in treating tuberculosis and other infections since the 1940s, while kasugamycin is less known but crucial in agricultural settings to prevent bacterial diseases in crops.

Both antibiotics tamper with bacteria’s ability to make new proteins by specifically targeting their ribosomes. These molecular structures create proteins and are themselves made of proteins and ribosomal RNA. Ribosomal RNA is often modified with chemical tags that can alter the shape and function of the ribosome. Cells use these tags to fine tune protein production.

The study found that, in response to the antibiotics, E. coli begins to assemble new ribosomes that are slightly different from the ones produced under normal conditions. Depending on which antibiotic used, the new ribosomes lacked certain tags. The tags were specifically lost in the regions where antibiotics latch on to and halt protein production. The study found this made the bacteria more resistant to the drugs.

“We think the bacteria’s ribosomes might be altering its structure just enough to prevent an antibiotic from binding effectively,” says Anna Delgado-Tejedor, first author of the study and PhD student at the Centre for Genomic Regulation (CRG) in Barcelona.

Bacteria are known to develop antibiotic resistance in different ways, including mutations in their DNA. Another common mechanism is their ability to actively pump and transport antibiotics out of the cell, reducing the concentration of the drug inside the cell to levels that are no longer harmful.

The study is evidence of an entirely new survival strategy. “E. coli is altering its molecular structures with remarkable precision and in real time. It’s a stealthy and subtle way of dodging drugs,” says Dr. Eva Novoa, corresponding author of the study and researcher at the CRG.

The researchers made the findings using advanced nanopore sequencing technology, which read RNA molecules directly. Previous techniques would process RNA molecules in such a way that it would remove the chemical modifications. “Our approach has allowed us to see the modifications as they are, in their natural context,” says Dr. Novoa.

The study does not explore why or how the chemical modifications are lost in the first place. Further research could explore the underlying biology of the adaptive mechanism and uncover new ways to combat one of the biggest looming crises in global health. Global antimicrobial resistance has claimed at least one million lives each year since 1990 and is forecast to claim 39 million more lives between now and 2050.

“If we can delve deeper and understand why they are shedding these modifications, we can create new strategies that prevent bacteria from shedding them in the first place or make new drugs that more effectively bind to the altered ribosomes,” says Dr. Novoa.

CTE is a neurodegenerative disease associated with repeated head injuries, often seen in athletes and military personnel, that can lead to mood changes and dementia.

“This appears to be a case where together these risk factors add up to a greater risk for aggression than they each do on their own, where people with CTE and a family history of mental illness are much more likely to have aggressive behavior than those with just CTE or just the family history,” said study author Jesse Mez, MD, MS, of Boston University Chobanian & Avedisian School of Medicine and a member of the American Academy of Neurology.

The study involved 845 men who were exposed to repetitive head impacts through contact sports or military service. A total of 329 of them played professional football. All donated their brains to research after their death, which was at an average age of 60. Of the total group, 589, or 70%, had CTE and 383, or 45%, had a family history of mental illness.

Researchers interviewed family members or spouses of the participants about their aggressive behavior. They were also asked whether the participants’ parents, siblings or children were ever diagnosed with major depression, bipolar disorder, anxiety, post-traumatic stress disorder, obsessive-compulsive disorder or other mood or psychiatric disorders. If any family member had a diagnosis, the participant was considered to have a family history of mental illness.

Researchers then divided participants into four groups: 256 people, or 30%, with CTE and a family history of mental illness; 333 people, or 40%, with CTE and without a family history of mental illness; 127 people, or 15%, without CTE and with a family history of mental illness; and 129 people, or 15%, without CTE and without a family history of mental illness.

Researchers asked family members about the participants’ aggressive behavior, such as whether they had severe arguments with others or got in physical fights, where scores ranged from zero to 44. They found that during adulthood people with CTE and a family history of mental illness had an average score of 19 compared to people with CTE without a family history of mental illness who had an average score of 17.

“This relationship was most striking for participants who died between 40 and 59 years old,” Mez added.

After adjusting for other factors, such as total years playing contact sports and military history, researchers found that those who died between 40 and 59 years old who had CTE and a family history of mental illness scored an average of 0.64 standard deviations higher on a scale measuring aggression when compared to those with CTE, but without a family history of mental illness. For people who did not have CTE, having a family history of mental illness did not increase their risk for aggressive behavior.

“The link between a family history of mental illness and aggression may be through a shared genetic background and also through shared environment and common behaviors, such as childhood experiences with family members,” said Mez. “Identifying people who are more likely to show symptoms of aggression based on family history of mental illness would give us a way to predict the consequences of CTE and identify who may benefit most from treatment options.”

A limitation of the study was that the study relied on past information from family members and spouses who may not have remembered information accurately.

The study was funded by the National Institutes of Health, Department of Veterans Affairs and the Nick and Lynn Buoniconti Foundation.

Led by Xing Wang, a professor of bioengineering and of chemistry at the U. of I., the researchers describe their advance in the journal Science Robotics.

Inspired by the gripping power of the human hand and bird claws, the researchers designed the NanoGripper with four bendable fingers and a palm, all in one nanostructure folded from a single piece of DNA. Each finger has three joints, like a human finger, and the angle and degree of bending are determined by the design on the DNA scaffold.

“We wanted to make a soft material, nanoscale robot with grabbing functions that never have been seen before, to interact with cells, viruses and other molecules for biomedical applications,” Wang said. “We are using DNA for its structural properties. It is strong, flexible and programmable. Yet even in the DNA origami field, this is novel in terms of the design principle. We fold one long strand of DNA back and forth to make all of the elements, both the static and moving pieces, in one step.”

The fingers contain regions called DNA aptamers that are specially programmed to bind to molecular targets — the spike protein of the virus that causes COVID-19, for this first application — and trigger the fingers to bend to wrap around the target. On the opposite side, where the wrist would be, the NanoGripper can attach to a surface or other larger complex for biomedical applications such as sensing or drug delivery.

To create a sensor to detect the COVID-19 virus, Wang’s team partnered with a group led by Illinois electrical and computer engineering professor Brian Cunningham, who specializes in biosensing. They coupled the NanoGripper with a photonic crystal sensor platform to create a rapid, 30-minute COVID-19 test matching the sensitivity of the gold-standard qPCR molecular tests used by hospitals, which are more accurate than at-home tests but take much longer.

“Our test is very fast and simple since we detect the intact virus directly,” Cunningham said. “When the virus is held in the NanoGripper’s hand, a fluorescent molecule is triggered to release light when illuminated by an LED or laser. When a large number of fluorescent molecules are concentrated upon a single virus, it becomes bright enough in our detection system to count each virus individually.”

In addition to diagnostics, the NanoGripper could have applications in preventive medicine by blocking viruses from entering and infecting cells, Wang said. The researchers found that when NanoGrippers were added to cell cultures that were then exposed to COVID-19, multiple grippers would wrap around the outside of the viruses. This blocked the viral spike proteins from interacting with receptors on the cells’ surface, preventing infection.

“It would be very difficult to apply it after a person is infected, but there’s a way we could use it as a preventive therapeutic,” Wang said. “We could make an anti-viral nasal spray compound. The nose is the hot spot for respiratory viruses, like COVID or influenza. A nasal spray with the NanoGripper could prevent inhaled viruses from interacting with the cells in the nose.”

The NanoGripper could easily be engineered to target other viruses, such as influenza, HIV or hepatitis B, Wang said. In addition, Wang envisions using the NaoGripper for targeted drug delivery. For example, the fingers could be programmed to identify specific cancer markers, and grippers could carry cancer-fighting treatments directly to the target cells.

“This approach has bigger potential than the few examples we demonstrated in this work,” Wang said. “There are some adjustments we would have to make with the 3D structure, the stability and the targeting aptamers or nanobodies, but we’ve developed several techniques to do this in the lab. Of course it would require a lot of testing, but the potential applications for cancer treatment and the sensitivity achieved for diagnostic applications showcase the power of soft nanorobotics.”

The National Institutes of Health and the National Science Foundation supported this work. Wang and Cunningham are affiliated with the Carl R. Woese Institute for Genomic Biology and the Holonyak Micro and Nanotechnology Lab at the U. of I.

Editor’s note: To reach Xing Wang, email @illinois.edu” title=”mailto:[email protected]”>[email protected].

The paper “Bioinspired designer DNA NanoGripper for virus sensing and potential inhibition” is available from @aaas.org” title=”mailto:[email protected]”>[email protected]. DOI: 10.1126/scirobotic

This work was supported in part by NIH grants R21EB031310, R44DE030852 and R21AI166898.

Existing research shows that natural sounds, like birdsong, can lower blood pressure, heart, and respiratory rates, as well as self-reported stress and anxiety. Conversely, anthropogenic soundscapes, like traffic or aircraft noise, are hypothesized to have negative effects on human health and wellbeing in a variety of ways.

In the new study, 68 student volunteers listened to three 3-minute soundscapes: a nature soundscape recorded at sunrise in West Sussex, U.K., the same soundscape combined with 20 mile per hour road traffic sounds, and the same soundscape with 40 mile per hour traffic sounds. General mood and anxiety were assessed before and after the soundscapes using self-reported scales.

The study found that listening to a natural soundscape reduced self-reported stress and anxiety levels, and also enhanced mood recovery after a stressor. However, the benefits of improved mood associated with the natural soundscape was limited when traffic sounds were included. The natural soundscape alone was associated with the lowest levels of stress and anxiety, with the highest levels reported after the soundscape that included 40 mile per hour traffic.

The authors conclude that reducing traffic speed in urban areas might influence human health and wellbeing not only through its safety impacts, but also through its effect on natural soundscapes.

The authors add: “Our study shows that listening to natural soundscapes can reduce stress and anxiety, and that anthropogenic sounds such as traffic noise can mask potential positive impacts. Reducing traffic speeds in cities is therefore an important step towards more people experiencing the positive effects of nature on their health and wellbeing.”

“Our goal is to find the best model with the most similar activity to what we see in the brains of patients with Alzheimer’s disease,” said co-senior author Doo Yeon Kim, PhD, of the Department of Neurology at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. “We developed this 3D cell culture model for Alzheimer’s 10 years ago. Now we have the data that show that this model can accelerate drug discovery.”

The new study was made possible through a collaboration between researchers with expertise in neurology and data-driven systems, with a shared goal of finding better treatments for Alzheimer’s disease (AD). For decades, the field of AD research has faced challenges due to some of the limitations of mouse models of the disease, which do not develop amyloid plaques or other hallmarks of AD seen in humans. Different models have been developed by Kim and colleagues but, until now, it had not been possible to determine the extent to which these models accurately reflect the molecular and functional changes seen in the brain.

“We faced a fundamental challenge: understanding which models truly reflect the complexity of Alzheimer’s in the human brain,” said co-senior author Winston Hide, PhD, of the Department of Pathology at BIDMC. “By shifting focus from individual genes to the broader biological pathways they shape, we’ve created a system that transforms how we discover and test drugs.”

To address this need, the research team, led by Pourya Naderi Yeganeah, PhD, and Sang Su Kwak, PhD, co-lead authors, developed a novel integrative pathway activity analysis (IPAA) platform. The platform can determine which models most closely recapitulate the functional changes seen in AD and identify the most relevant pathways for drug discovery. In their paper, the researchers identified 83 dysregulated pathways shared across brain samples from deceased patients with Alzheimer’s disease and 3D cellular models. The researchers looked at one pathway — p38 mitogen-activated protein kinase (MAPK) — as a proof of concept, testing drugs that target this pathway. Interestingly, they discovered that a clinical p38 MAPK inhibitor, which has not yet been tested in AD patients, is highly effective at reducing AD pathology in a dish, highlighting its potential for future clinical trials. Even more compelling, their findings extend beyond a single pathway — the platform’s capacity to identify promising drug targets, combined with the speed and scalability of the Alzheimer’s in a dish model, enables simultaneous testing of multiple drugs to identify potential therapies. Already, the researchers have tested hundreds of approved drugs and natural products using the Alzheimer’s in a dish model, setting the stage for clinical trials.

“Now we have a system that not only allows us to test new drugs quickly, but also an algorithmic platform that can predict which drugs will work best.” said co-senior author Rudolph Tanzi, PhD, Director of the McCance Center for Brain Health and Genetics and Aging Research Unit at MGH. “Together, these advancements bring us closer to finding better drugs and getting them to patients.”

This is because iron and H₂O₂ react in what’s known as the Fenton reaction, producing hydroxyl radicals, destructive molecules that attack DNA and RNA indiscriminately. But there’s a catch. In the presence of carbon dioxide — that pesky gas disrupting global climate systems — our cells gain a secret weapon in the form of bicarbonate which helps keep pH levels balanced.

A team of University of Utah chemists has discovered that bicarbonate doesn’t just act as a pH buffer but also alters the Fenton reaction itself in cells. Instead of producing chaotic hydroxyl radicals, the reaction instead makes carbonate radicals, which affect DNA in a far less harmful way, according to Cynthia Burrows, a distinguished professor of chemistry and senior author of a study published this week in PNAS.

“So many diseases, so many conditions have oxidative stress as a component of disease. That would include many cancers, effectively all age-related diseases, a lot of neurological diseases,” Burrows said. “We’re trying to understand cells’ fundamental chemistry under oxidative stress. We have learned something about the protective effect of CO₂ that I think is really profound.”

Co-authors include Aaron Fleming, a research associate professor, and doctoral candidate Justin Dingman, both members of the Burrows Laboratory.

Without bicarbonate or CO₂ present in experimental DNA oxidation reactions, the chemistry is also different. The free radical species generated, hydroxyl radical, is extremely reactive and hits DNA like a shotgun blast, causing damage everywhere, Burrows said.

In contrast, her team’s findings show that the presence of bicarbonate from dissolved CO₂ changes the reaction to make a milder radical striking only guanine, the G in our four-letter genetic code.

“Like throwing a dart at the bullseye where G is the center of the target,” Burrows said. “It turns out that bicarbonate is a major buffer inside your cells. Bicarbonate binds to iron, and it completely changes the Fenton reaction. You don’t make these super highly reactive radicals that everyone’s been studying for decades.”

What do these findings mean for science? Potentially a lot.

For starters, the team’s discovery shows cells are a lot smarter than previously imagined, which could reshape how we understand oxidative stress and its role in diseases like cancer or aging.

But it also raises the possibility that many scientists studying cell damage have been conducting laboratory experiments in ways that don’t reflect the real world, rendering their results suspect, Burrows said. Chemists and biologists everywhere grow cells in a tissue culture in an incubator set to 37 degrees Centigrade, or body temperature. In these cultures, carbon dioxide levels are raised to 5%, or about 100 times more concentrated than what’s found in the atmosphere.

The elevated CO₂ recreates the environment the cells normally inhabit as they metabolize nutrients, however, it is lost when researchers start their experiments outside the incubator.

“Just like opening up a can of beer. You release the CO₂ when you take your cells out of the incubator. It’s like doing experiments with a day-old glass of beer. It’s pretty flat. It has lost the CO₂, its bicarbonate buffer,” Burrows said. “You no longer have the protection of CO₂ to modulate the iron-hydrogen peroxide reaction.”

She believes bicarbonate needs to be added to ensure reliable results from such experiments.

“Most people leave out bicarbonate/CO₂ when studying DNA oxidation because it is difficult to deal with the constant outgassing of CO₂,” Burrows said. “These studies suggest that to get an accurate picture of DNA damage that occurs from normal cellular processes like metabolism, researchers need to be careful to mimic the proper conditions of the cell and add bicarbonate, i.e. baking powder!”

Burrows anticipates her study could result in unintended outcomes that may someday benefit research in other areas. Her lab is seeking new funding from NASA, for example, to study the effect of CO₂ on people confined to enclosed spaces, such as inside of space capsules and submarines.

“You’ve got astronauts in a capsule living and breathing, and they are exhaling CO₂. The problem is how much CO₂ can they safely handle in their atmosphere? One of the things we found is that, at least in terms of tissue culture, CO₂ does have a protective effect from some of the radiation damage these astronauts might experience. So what you might want to do is push up that CO₂ level. You certainly don’t want to go very high, but having it slightly higher might actually have a protective effect against radiation, which generates hydroxyl radicals.”

The research, which analyzed the global, regional, and national burden of HIV/AIDS among 204 countries and territories from 1990 to 2021 and forecasted trends to 2050, highlighted a mixed landscape of achievements and challenges in the battle against this global epidemic.

Between 2010 and 2021, new HIV infections decreased from 2.1 million to 1.7 million, and HIV-related deaths decreased from 1.2 million to 718,000. Despite this progress, researchers found regional variation in the HIV response and forecast the world is not on track to meet UNAIDS 2030 targets to cut new HIV infections and AIDS-related deaths by 90%.

Sub-Saharan Africa leads the world in cutting new HIV infections and deaths from the disease

The global decline in HIV incidence is largely driven by sub-Saharan Africa, where the likelihood of getting HIV over a lifetime has fallen by 60% since its peak in 1995. This region also achieved the largest decrease in population without a suppressed level of HIV (PUV), from 19.7 million people in 2003 to 11.3 million people in 2021.

In contrast, the lifetime probability of HIV acquisition increased from 0.4% to 2.8% between 1995 and 2021, while PUV rose from 310,000 people to 680,000 people between 2003 and 2021 in Central Europe, Eastern Europe, and Central Asia.

“The world has made remarkable global progress to significantly reduce the number of new HIV infections and lives lost to the disease, yet there are remaining challenges to overcome,” said Dr. Hmwe Kyu, IHME Associate Professor and study author. “More than a million people acquire a new HIV infection each year and, of the 40 million people living with HIV, a quarter are not receiving treatment,” she added.

Despite progress, UNAIDS’s HIV infection reduction and AIDS-related deaths 2030 targets won’t be met

Although substantial progress has been made against HIV incidence and AIDS-related mortality, the world is not on target to meet the UN’s 2030 targets to reduce new HIV infections and AIDS-related deaths by 90%.

The number of people living with HIV is expected to peak at 44.4 million by 2039, followed by a gradual decrease to 43.4 million people by 2050.

“The global community must make sustained and substantive efforts to sharpen the focus on prevention, optimize access to antiretroviral therapy, and make HIV testing widely available to achieve prompt diagnosis and linkage to care,” said Dr. Kyu.

New cases of HIV, and deaths associated with the disease, are expected to continue to decrease globally. However, long-term increases have been forecast in North Africa and the Middle East, where only 67% of people living with HIV are aware of their status, 50% access ART, and 45% are virally suppressed.

“Although new HIV infections and HIV-related mortality have fallen globally, they are increasing in several nations and regions. Our analysis is designed to inform countries’ sustained response to HIV that includes expanded access to lifesaving antiretroviral therapy (ART), effective prevention options, and innovative care models,” said Austin Carter, IHME Research Scientist.

The study authors set a series of recommendations to sustain and invigorate the global HIV response, including the strengthening of the US President’s Emergency Plan for AIDS Relief (PEPFAR) and other similar public health programs dedicated to HIV control, as well as the expansion of prevention services, with a multitude of existing and emerging technologies. Additionally, interventions and care delivery models that work must be studied and implemented effectively and equitably, with special emphasis on measuring progress and addressing remaining gaps in our collective goal of ending the HIV epidemic.

The findings and recommendations from the new study by the GBD 2021 HIV collaborators serve as a call to action for governments, health care providers, and the global community to renew their commitment to ending the HIV epidemic. Only through sustained, comprehensive, and equitable efforts will the world be able to achieve the UNAIDS 2030 targets and ultimately eradicate HIV/AIDS as a public health threat.

This revolutionary field still faces many challenges, including the nontrivial task of convincing stem cells to differentiate into desired cell types for treatment. And even if the correct cells or tissues are created and can function successfully in the body, immune rejection presents a formidable barrier to their use. To overcome this obstacle, regenerative medicine treatments in use today require systemic immunosuppression, leaving patients vulnerable to environmental hazards like viruses, bacteria and cancer cells.

In a novel approach to tackle these obstacles, researchers at the Medical University of South Carolina and the University of Florida recently collaborated on a novel, highly specific strategy to treat type 1 diabetes (T1D) using a tagged beta cell transplant in tandem with localized immune protection provided by specialized immune cells also tagged with a complementary but inert targeting molecule.

According to Leonardo Ferreira, Ph.D., a researcher at MUSC Hollings Cancer Center and one of the principal investigators on the study, marrying stem cell engineering and regulatory T cell (Treg) engineering allowed the first step toward a readily available, off-the-shelf solution to treating T1D.

In their recent study published in the journal Cell Reports, the researchers described a unique collaboration that leveraged the beta cell engineering expertise of the lab of Holger Russ, an associate professor of pharmacology and therapeutics at the University of Florida, combined with the delicate surgical expertise and chimeric antigen receptor (CAR) T cell expertise available at Hollings.

For T1D patients, the trouble begins with an immune system self-attack on pancreatic beta cells, the cells that produce the hormone insulin to regulate blood sugar levels. Without a reliable way to self-regulate blood glucose levels, patients are forced to live with a high-maintenance regimen of glucose monitoring and insulin management to maintain health and avoid dangerous complications like neuropathy, amputation and blindness.

For now, some patients with poorly controlled T1D may consider islet cell transplantation using beta cells from a donor. Beta cells are isolated from a donor pancreas, purified and delivered to the patient’s liver, where they can take up residence and begin secreting insulin. However, this option requires patients to undergo immunosuppression for the rest of their lives to keep the body from rejecting the foreign beta cells. It also requires the availability of donor cells, which might require long waits or may not happen at all.

To focus on an alternative solution, the researchers used an engineering strategy with tagged beta cells generated from stem cells. And to induce localized immune protection, the researchers chose to use Tregs, a type of immune cell that monitors and controls the immune response.

“Most of the cells of the immune system are focused on killing invasive elements,” Ferreira said. “But Tregs are the generals of the immune system. They make sure that nothing goes overboard, and they train the immune system on how to respond in the future.”

The researchers used a mouse model to test their strategy. By transplanting beta cells that were engineered from stem cells and included a nonreactive tag — an inactivated version of epidermal growth factor receptor — into the kidney capsules of immunodeficient mice, they showed that the cells were incorporated and began to manufacture functional insulin. In the next phase of testing, the mice were exposed to an aggressive type of immune cell to check on the viability of the transplanted beta cells in the face of a simulated immune response. As expected, all of the beta cells were killed by the immune response, the same thing that happens in people with T1D.

To avoid the killing response in the next phase, the researchers added specialized Tregs along with the immune challenge. These cells were tagged with CAR technology using a receptor that specifically recognized the inert EGFR tag present on the transplanted beta cells. With this added step, the researchers observed the immune protection they hoped for, as they observed the transplanted beta cells remaining safe, sound and functional in their new home.

Ferreira was delighted with the results and energized to take the next steps. “With this approach,” he said, “we made both the lock and the key for creating immune tolerance.”

Now that Ferreira and colleagues have shown the feasibility of their approach to T1D treatment, they plan to continue their research efforts, including building a whole library of locks and keys — differentiated stem cells and tagged protective Tregs — for multiple purposes, such as targeting certain cancers, lupus and other autoimmune diseases.

A few questions remain, such as the specific ligand that should be used for human transplantation and the longevity of Treg-mediated immune protection. The ligand or tag must be inert and have no negative impact on the function of the cells or create any reaction that could cause side effects. And it is still unknown if one Treg treatment will be effective or might need to be repeated at intervals that have yet to be established. Because Tregs can educate immune cells to maintain immune tolerance, it is possible that one treatment will be adequate, but further research is needed to understand the long-term effects.

Answering these questions and confirming the validity of the approach in humans may soon transform T1D from a chronic, high-maintenance disease with many complications to one that can be managed much more easily.

Political distancing affects us more deeply than was previously known and governs our choices even when it is completely irrelevant. The studies show that even chocolate can be political.

“From a social perspective, it can unfortunately be rational to distance ourselves from these neutral things, but this contributes to a more polarised society,” says Arvid Erlandsson, senior associate professor at the Department of Behavioural Sciences and Learning at Linköping University.

In four studies, researchers investigated people’s attitudes to completely non-political products before and after these were linked to people or groups with different political views. As far as is known, this is the first time such an investigation has been conducted. The results have been presented in the journal Personality and Social Psychology Bulletin.

The first study concerned clothing. The more than 600 participants were first shown a number of pictures of people wearing formal clothes. The heads of the people were hidden. Participants were asked to give their opinion on the design, fit and colour of the clothes and how much they would want to buy them. They were also asked their views on political parties. They then had to re-evaluate the clothes, but this time the faces of the people wearing them were visible. It turned out that the faces belonged to well-known Swedish politicians.

This clearly affected the results in the second round. Clothes worn by a politician from the participants’ least liked party were now more often perceived as less stylish than in the first assessment.

In the next study, more than 800 participants first gave scores to eight well-known chocolate brands and stated their political stance. They were then divided into groups for a second round. One group was told that a previous pilot study showed that their political opponents liked a particular chocolate the best. A second group was instead told which kind their own side preferred. They then made a new assessment.

It turned out that chocolate that was liked by political opponents had now become significantly less appealing. However, varieties that were liked by their own side did not become more popular.

“It’s less about you associating with what your own side likes and more about avoiding what’s liked by the opposing side,” summarises Arvid Erlandsson.

A third study similarly examined willingness to donate money to various charities. More than 1,200 people participated and the results were the same as in the previous studies. Participants were less likely to give money to organisations they were told were preferred by political opponents.

The researchers think that we unconsciously behave this way to maintain a consistent self-image. What the participants did not know was that the pilot study showed that everyone — regardless of their political affiliation — had actually liked the same chocolate varieties and the same charities.

In the last study, 1,295 people participated. They also had to choose between products, but with a difference. One group made their choices while being observed by animated faces they were told belonged to their own political grouping. It turned out that the tendency to distance oneself from products liked by political opponents was further reinforced. The researchers’ conclusion is that we attach great importance to how we appear to others.

“Knowing about it might make you think twice, instead of just going on a gut feeling,” says Arvid Erlandsson.

Melanoma arising from pigment-producing cells known as melanocytes is the deadliest form of skin cancer. A major cause of melanoma is excessive exposure to ultraviolet light, from sunlight or other sources, which can trigger mutations that promote tumor formation. A team led by LMU pharmacologist Professor Christian Grimm (Walther Straub Institute of Pharmacology and Toxicology) and Dr. Karin Bartel (Faculty of Chemistry and Pharmacy) has now investigated the molecular mechanisms of tumorigenesis. As the researchers demonstrate, the interplay of two proteins — the ion channel TPC2 and the enzyme Rab7a — plays a decisive role, as they promote the growth and metastasis of melanoma.

Studies have shown that certain activity-boosting mutations in the ion channel TPC2 are associated with fair skin, blond hair, and albinism. These traits make people particularly susceptible to melanoma, as their skin offers less protection against harmful ultraviolet radiation. Conversely, loss of TPC2 is associated with decreased melanoma risk. The ion channel controls the breakdown of important proteins in endolysosomes — cell organelles that are involved in transport and degradation processes — and thus influences signaling pathways that regulate tumor growth.

Molecular pathways influencing tumor progression

Like TPC2, the protein Rab7a is an important regulator for the endolysosomal system. Earlier proteome analyses had shown, moreover, that Rab7a is a potential interaction partner of TPC2. Using modern methods such as endolysosomal patch-clamp electrophysiology and the measurement of lysosomal calcium release via fluorescence microscopy, the researchers established that there was indeed an interaction between Rab7a and TPC2 at the functional level, which promoted the growth and invasiveness of melanoma cells. Conversely, the pharmacological inhibition of Rab7a decreased TPC2 activity and thus melanoma growth.

“Our results show that Rab7a, by amplifying TPC2 activity, plays a key role in the regulation of tumor growth,” says Grimm. “Specifically, the activation of TPC2 by Rab7a reduces the levels of a certain protein. This protein boosts the stability of a transcription factor that is a key regulator in melanocytes and melanomas and promotes their proliferation and survival.”

A particularly notable finding, according to the researchers, was that effects of the interaction of Rab7a and TPC2 could be demonstrated in vivo. In mouse models with melanoma cells without Rab7a or TPC2, they found that tumor size and metastasis were much reduced. “The interaction between Rab7a and TPC2 could pave the way for new therapeutic strategies which target the specific signaling pathways that promote melanoma growth and metastasis” concludes Grimm.

The research, published in Science, reveals how NREM sleep — the lighter sleep one experiences when taking a nap, for example — fosters brain synchronization and enhances information encoding, shedding new light on this sleep stage. The researchers replicated these effects through invasive stimulation, suggesting promising possibilities for future neuromodulation therapies in humans. The implications of this discovery potentially pave the way for innovative treatments for sleep disorders and even methods to enhance cognitive and behavioral performance.

The investigation involved an examination of the neural activity in multiple brain areas in macaques while the animals performed a visual discrimination task before and after a 30-minute period of NREM sleep. Using multielectrode arrays, the researchers recorded the activity of thousands of neurons across three brain areas: the primary and midlevel visual cortices and the dorsolateral prefrontal cortex, which are associated with visual processing and executive functions. To confirm that the macaques were in NREM sleep, researchers used polysomnography to monitor their brain and muscle activity alongside video analysis to ensure their eyes were closed and their bodies relaxed.

The findings demonstrated that sleep improved the animals’ performance in the visual task with enhanced accuracy in distinguishing rotated images. Importantly, this improvement was unique to those who actually fell asleep — the macaques that experienced quiet wakefulness without falling asleep did not show the same performance boost.

“During sleep, we observed an increase in low-frequency delta wave activity and synchronized firing among neurons across different cortical regions,” said first author Dr. Natasha Kharas, a former researcher in Dragoi’s lab and current resident in neurological surgery at Weill Cornell. “After sleep, however, neuronal activity became more desynchronized compared to before sleep, allowing neurons to fire more independently. This shift led to improved accuracy in information processing and performance in the visual tasks.”

The researchers also simulated the neural effects of sleep through low-frequency electrical stimulation of the visual cortex. They applied a 4-Hz stimulation to mimic the delta frequency observed during NREM sleep while the animals were awake. This artificial stimulation reproduced the desynchronization effect seen after sleep and similarly enhanced the animals’ task performance, suggesting that specific patterns of electrical stimulation could potentially be used to emulate the cognitive benefits of sleep.

“This finding is significant because it suggests that some of the restorative and performance-enhancing effects of sleep might be achieved without the need for actual sleep,” said Dragoi, study co-author, professor of electrical and computer engineering at Rice, the Rosemary and Daniel J. Harrison III Presidential Distinguished Chair in Neuroprosthetics at Houston Methodist and professor of neuroscience at Weill Cornell. “The ability to reproduce sleeplike neural desynchronization in an awake state opens new possibilities for enhancing cognitive and perceptual performance in situations where sleep is not feasible — such as for individuals with sleep disorders or in extenuating circumstances such as space exploration.”

The researchers further investigated their findings by building a large neural network model. They found that during sleep, both excitatory and inhibitory connections in the brain become weaker, but they do so asymmetrically, making inhibitory connections weaker than excitatory connections, which causes an increase in excitation.

“We have uncovered a surprising solution that the brain employs after sleep whereby neural populations participating in the task reduce their level of synchrony after sleep despite receiving synchronizing inputs during sleep itself,” Dragoi said.

The idea that NREM sleep effectively “boosts” the brain in this way, and that this resetting can be mimicked artificially, offers potential for developing therapeutic brain stimulation techniques to improve cognitive function and memory.

“Our study not only deepens our mechanistic understanding of sleep’s role in cognitive function but also breaks new ground by showing that specific patterns of brain stimulation could substitute for some benefits of sleep, pointing toward a future where we might boost brain function independently of sleep itself,” Dragoi said.

This research was supported by National Eye Institute grants 5R01EY026156 (V.D.) and 5F31EY029993 (N.K.).

It’s a core function, but little studied in the setting of cancer immunology, especially when compared to other organelles like the mitochondria or endoplasmic reticulum.

“So we were interested in looking a little bit more at the Golgi apparatus. It’s obviously an important organelle. How is it being changed or what is its role in T-cells in terms of fighting cancer?” said Nathaniel Oberholtzer, an M.D./Ph.D. student who worked in the lab of Shikhar Mehrotra, Ph.D., co-leader of the Cancer Biology & Immunology Research Program at MUSC Hollings Cancer Center and scientific director of the Center for Cellular Therapy in the MUSC College of Medicine.

As it turns out, the healthy function of the Golgi apparatus has a lot to do with how well T-cells function in killing cancer cells. Understanding how a signaling axis mitigates Golgi stress, enabling it to perform properly, points to a possible new therapeutic target for researchers to pursue to strengthen T-cells. Not only that, but Oberholtzer’s research shows how the Golgi could be used as a biomarker to select the strongest T-cells for immunotherapy.

Oberholtzer, as first author, and Mehrotra, as senior author, along with a team of Hollings scientists published the research this month in Science Advances.

T-cells, part of the immune system, can kill cancer cells. CAR-T cells are T-cells that have been modified in the lab to home in on proteins on the surface of an individual’s cancer cells. CAR-T cells are custom-made for each patient.

Both T-cells and CAR-T cells can become “exhausted” in the hostile tumor microenvironment. Mehrotra’s lab looks at ways to boost these cells so that they can fight cancer for a longer time.

“The whole tumor microenvironment is conducive for the tumor itself, but not for the other cells which are trying to get in there,” Mehrotra said.

Just like people, cells are constantly subjected to stress — stress from biochemical reactions that have become unbalanced and mechanical stress from moving. Transient stress can be good. Stressing your muscles through exercise strengthens them, and transient stress on cells can prompt them to a response that ultimately strengthens them.

“But if this stress stays there, which it does in the tumor microenvironment, the cells are just in continuous stress, and that will then lead to a very different phenotype and death,” Mehrotra said.

However, the researchers found that treating the Golgi apparatus with hydrogen sulfide created T-cells that could take more stress.

“Hydrogen sulfide is a gaseous signaling molecule present in pretty much all mammalian cell types. Typically, it’s a byproduct of different cellular processes, but it’s actually been shown to have really important signaling roles as well,” Oberholtzer said.

“It can modify proteins through a process called sulfhydration, where it modifies cysteine residues and can change their activity.”

In this project, Oberholtzer found that this sulfhydration process, in modifying a protein called Prdx4 within the Golgi apparatus, confers protection in an oxidative setting.

“When you have the stressors that the tumor microenvironment puts on T-cells, you get a disruption, or fragmentation, of the Golgi apparatus where it essentially isn’t able to do its job. Hydrogen sulfide protects against that disruption,” Oberholtzer said.

Looking into this protective effect then led the researchers to look more closely at the Golgi apparatus by itself.

“Essentially, if you just use the Golgi apparatus as a simple marker, if T-cells have a lot of Golgi versus less, the ones that have more Golgi are much more robust at killing tumor cells and controlling tumors,” Oberholtzer explained.

Using cell sorting technology at the Flow Cytometry & Cell Sorting Shared Resource at Hollings, the researchers sorted T-cells according to the amount of Golgi they contained. The top 30% were labeled Golgi-hi and the bottom 30% were labeled Golgi-lo.

“Basically, all the cells which are expressing high Golgi have a very different phenotype. They are less exhausted, and they are much more potent in controlling tumors,” Mehrotra said.

This pre-clinical work suggests that sorting T-cells into Golgi-hi and Golgi-lo and reinfusing only the Golgi-hi cells into a patient would create a better chance of controlling the tumor.

“Right now, we’re working on doing some validation studies in the Center for Cellular Therapy to potentially be able to start a clinical trial to see if that has a translational ability as well,” Oberholtzer said.

More work is also needed to understand the role of Golgi stress when all of the organelles in a cell are under stress because of the tumor microenvironment.

The study highlights significant racial and socioeconomic disparities, finding that non-Hispanic Black mothers faced more than double the rate of severe complications compared to non-Hispanic white mothers, and that living in high-poverty neighborhoods elevated maternal health risks across all racial groups.

“Despite significant recent statewide quality-improvement efforts, these birth outcomes are worsening for all ages, reflecting the worsening pre-pregnancy health of the reproductive-age population in Illinois,” said corresponding author Dr. Mugdha Mokashi, aresident physician in obstetrics and gynecology at the McGaw Medical Center at Northwestern.

The findings reflect national trends demonstrating the increasing prevalence of conditions such as obesity, hypertensive disorders of pregnancy and gestational diabetes among pregnant people of all ages, she added. The study provides the most updated data on maternal morbidity and delivery complications within the state of Illinois.

The findings were published Nov. 21 in the journal Obstetrics & Gynecology Open.

“Our findings underscore the role of social determinants of health — such as race and income — in driving disparities in maternal health, suggesting that efforts to reduce maternal morbidity need to address both racial inequalities and economic hardship,” said study co-author Dr. Lynn Yee, associate professor of obstetrics and pulmonology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine maternal fetal medicine physician.

Breaking down of the findings:

In the study cohort of 988,480 births at 127 Illinois hospitals between January 2016 to June 2023, the overall rate of severe maternal morbidity rose from 1.4% in 2016 to 2% in 2023. Vaginal birth complications increased 22.4%, and cesarean birth complications increased 48.9%.

Hypertensive disorders of pregnancy and anemia — both of which increased over the study period — were significant risk factors for severe maternal morbidity and birth complications. The largest increase by far was in annual rates of obesity from 2016 to the first six months of 2023 (7.8% to 22.3%). Additionally, there were increases in gestational diabetes (4.2% to 5.5%), depression (2.5% to 6.6%), anxiety (3.1% to 10.4%) and other chronic comorbidities (4.7% to 7.4%). Non-Hispanic Black patients had more than double the severe maternal morbidity rate (2.6%) compared to non-Hispanic white patients (1.1%).

Health counseling before pregnancy is important

Maternal health affects almost everyone, and those thinking about pregnancy should be sure to check in with their health care provider to screen for any chronic conditions they may have before getting pregnant, the study authors said.

“Pre-conception counseling is such an important way to make sure that all of your health conditions are optimized prior to pregnancy,” Mokashi said. “There are many important policy and public health initiatives in Illinois that people may be interested in learning more about.”

‘It’s not just because the people getting pregnant are older’

While not the original aim of the study, the scientists did additional analysis that found the increased prevalence of maternal health issues and birth complications is not simply because the people getting pregnant are older. The findings reflected an increase in hospital coding for hypertensive disorders of pregnancy, gestational diabetes, anemia, depression, serious mental illness and other chronic conditions, especially obesity, even among those giving birth who are younger than 30.

“In brief, even young pregnant patients have more medical conditions and complications in pregnancy,” Mokashi said.

What can be done?

Policies for poverty alleviation — such as the proposed refundable child tax credit in Illinois, House Bill 4917, if passed — have demonstrated improvement in maternal health, the study authors said.

Perinatal quality initiatives in California have reduced postpartum hemorrhage-related morbidity. Similarly, the Illinois Perinatal Quality Collaborative is working to reduce cesarean births and address racial disparities through Promoting Vaginal Birth and Birth Equity initiatives.

Increasing access to doula support and patient navigator programs could also be useful supports, Mokashi said. In 2024, the Illinois Department of Healthcare and Family Services adjusted reimbursement for doula services. At Northwestern, research on patient-navigator programs have shown promise in reducing care disparities for low-income minoritized patients postpartum. And at the federal level, passage of the 13 bills comprising the Black Maternal Health Momnibus Act re-introduced in 2023 would provide critical funding support to increase data collection and quality initiatives for prevention of maternal morbidity.

In a new Northwestern Medicine study, scientists sought to better understand how humans evolved to become so skilled at thinking about what’s happening in other peoples’ minds. The findings could have implications for one day treating psychiatric conditions such as anxiety and depression.

“We spend a lot of time wondering, ‘What is that person feeling, thinking? Did I say something to upset them?'” said senior author Rodrigo Braga. “The parts of the brain that allow us to do this are in regions of the human brain that have expanded recently in our evolution, and that implies that it’s a recently developed process. In essence, you’re putting yourself in someone else’s mind and making inferences about what that person is thinking when you cannot really know.”

The study found the more recently evolved and advanced parts of the human brain that support social interactions — called the social cognitive network — are connected to and in constant communication with an ancient part of the brain called the amygdala.

Often referred to as our “lizard brain,” the amygdala typically is associated with detecting threats and processing fear. A classic example of the amygdala in action is someone’s physiological and emotional response to seeing a snake: startled body, racing heart, sweaty palms. But the amygdala also does other things, Braga said.

“For instance, the amygdala is responsible for social behaviors like parenting, mating, aggression and the navigation of social-dominance hierarchies,” said Braga, an assistant professor of neurology at Northwestern University Feinberg School of Medicine. “Previous studies have found co-activation of the amygdala and social cognitive network, but our study is novel because it shows the communication is always happening.”

The study was published Nov. 22 in the journal Science Advances.

High-resolution brain scans were key

Within the amygdala, there’s a specific part called the medial nucleus that is very important for social behaviors. This study was the first to show the amygdala’s medial nucleus is connected to newly evolved social cognitive network regions, which are involved in thinking about other people. This link to the amygdala helps shape the function of the social cognitive network by giving it access to the amygdala’s role in processing emotionally important content.

This was only possible because of functional magnetic resonance imaging (fMRI), a noninvasive brain-imaging technique that measures brain activity by detecting changes in blood oxygen levels. A collaborator at the University of Minnesota and co-author on the study, Kendrick Kay, provided Braga and co-corresponding author Donnisa Edmonds with fMRI data from six study participants’ brains, as part of the Natural Scenes Dataset (NSD). These high-resolution scans enabled the scientists to see details of the social cognitive network that had never been detected on lower-resolution brain scans. What’s more, they were able to replicate the findings up to two times in each individual.

“One of the most exciting things is we were able to identify network regions we weren’t able to see before,” said Edmonds, a neuroscience Ph.D. candidate in Braga’s lab at Northwestern. “That’s something that had been underappreciated before our study, and we were able to get at that because we had such high-resolution data.”

Potential treatment of anxiety, depression

Both anxiety and depression involve amygdala hyperactivity, which can contribute to excessive emotional responses and impaired emotional regulation, Edmonds said. Currently, someone with either condition could receive deep brain stimulation for treatment, but since the amygdala is located deep within the brain, directly behind the eyes, it means having an invasive, surgical procedure. Now, with this study’s findings, a much less-invasive procedure, transcranial magnetic stimulation (TMS), might be able to use knowledge about this brain connection to improve treatment, the authors said.

“Through this knowledge that the amygdala is connected to other brain regions — potentially some that are closer to the skull, which is an easier region to target — that means people who do TMS could target the amygdala instead by targeting these other regions,” Edmonds said.

The study is titled, “The human social cognitive network contains multiple regions within the amygdala.” Other Northwestern co-authors include Christina Zelano, Joseph J. Salvo, Nathan Anderson, Maya Lakshman and Qiaohan Yang.

An Innovative Approach to Pain Management

Current medications used to treat chronic abdominal pain often rely on opioids. However, opioids can cause severe side effects such as addiction, nausea, and constipation. Additionally, they affect the central nervous system, often leading to fatigue and drowsiness, which impairs the quality of life of those affected. The addiction risk is particularly problematic and has contributed to the ongoing global opioid crisis. Therefore, there is an urgent need for alternatives that minimise these risks.

This new therapeutic approach targets oxytocin receptors in the gut. Oxytocin is commonly known as the ‘love hormone’ because of its role in social bonding. Less well-known is that oxytocin can also affect pain perception. When the peptide hormone oxytocin binds to these receptors, it triggers a signal that reduces pain signals in the gut. The advantage of this approach is that the effect is gut-specific, thus having a lower risk of side effects due to its non-systemic, gut-restricted action.

Oxytocin itself cannot be taken orally because it is rapidly broken down in the gastrointestinal tract. However, Prof. Muttenthaler’s team has successfully created oxytocin compounds that are fully gut-stable yet can still potently and selectively activate the oxytocin receptor. This means these newly developed oxytocin-like peptides can be taken orally, allowing for convenient treatment for patients. This approach is especially innovative since most peptide drugs (such as insulin, GLP1 analogues) need to be injected as they are also quickly degraded in the gut.

“Our research highlights the therapeutic potential of gut-specific peptides and offers a new, safe alternative to existing pain medications, particularly for those suffering from chronic gut disorders and abdominal pain,” explains Muttenthaler.

Next Steps and Future Outlook

With support from the European Research Council, the scientists are now working to translate their research findings into practice. The goal is to bring these new peptides to market as an effective and safe treatment for chronic abdominal pain. Moreover, the general approach of oral, stable, and gut-specific peptide therapeutics could revolutionise the treatment of gastrointestinal diseases, as the therapeutic potential of peptides in this area has not yet been fully explored.

The team has already secured a patent for the developed drug leads and is now actively seeking investors and industrial partners to advance the drug leads towards the clinic.

Now, researchers at the Broad Institute of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear in Nature, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.

“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the Broad, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.

“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.

Xavier is the director of Broad’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.

“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”

Mapping the intestine

Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.

In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.

To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.

The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.

“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”

Immune control

Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.

Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.

The findings, published in the journal Scientific Reports, shed new light on what may underlie sleep differences in men and women and could have broad implications for biomedical research, which for decades has focused primarily on males.

“In humans, men and women exhibit distinct sleep patterns, often attributed to lifestyle factors and caregiving roles,” said senior author Rachel Rowe, assistant professor of integrative physiology. “Our results suggest that biological factors may play a more substantial role in driving these sleep differences than previously recognized.”

Sleep research has exploded in recent years, with thousands of animal studies exploring how insufficient sleep impacts risk of diseases like diabetes, obesity, Alzheimer’s and immune disorders — and how such diseases impact sleep. Meanwhile, mice have often been the first to be tested to see whether new drugs, including medications for sleep, work and what the side effects are.

But many of those results may have been skewed due to a lack of female representation, the study suggests.

“Essentially, we found that the most commonly used mouse strain in biomedical research has sex-specific sleep behavior and that a failure to properly account for these sex differences can easily lead to flawed interpretations of data,” said first author Grant Mannino, who graduated with degrees in psychology and neuroscience and was named outstanding undergraduate of the College of Arts and Sciences in May.

How mice sleep

For the non-invasive study, the authors used specialized cages lined with ultrasensitive movement sensors to assess the sleep patterns of 267 “C57BL/6J” mice.

Males slept about 670 minutes total per 24-hour period, about an hour more than female mice. That extra sleep was non-Rapid Eye Movement (NREM) sleep — the restorative sleep when the body works to repair itself.

Mice are nocturnal and are “polyphasic sleepers” — napping for a few minutes before arousing briefly to survey their environment and then resuming their slumber. Females, the study found, have even shorter bouts of sleep — essentially, their sleep is more fragmented.

Similar sex differences have been seen in other animals, including fruit flies, rats, zebrafish and birds. Evolutionarily, it makes sense.

“From a biological standpoint, it could be that females are designed to be more sensitive to their environment and be aroused when they need to be because they are typically the one who is caring for the young,” Rowe said. “If we slept as hard as males sleep, we would not move forward as a species, right?”

Stress hormones like cortisol (which promotes wakefulness) and sex hormones likely play a role. For instance, women tend to report worse sleep during the time in their menstrual cycle when estrogen and progesterone are at their lowest.

Some have hypothesized that females inherently require less sleep.

“For me, the question is: Are we creating too much stress for ourselves because we don’t sleep as much as our husband or partner and think our sleep is poor when actually that is a normal sleep profile for ourselves?” said Rowe.

The authors hope their findings inspire more research into underlying biological differences. More importantly, they hope the study prompts scientists to re-evaluate how they do research.

Progress made but more work to be done

In 2016, the National Institutes of Health began requiring scientists applying for funding for animal studies to consider “sex as a biological variable.” Progress has been made, but research has shown that sex bias still exists. And it can have real consequences, the authors found.

When they simulated a sleep treatment that worked best in females, they found that it was accurately reflected only if the sample size was made up evenly of males and females.

Bottom line: If females are underrepresented, drugs that work best for them may seem ineffective, or side effects that hit hardest may go unnoticed.

“The pipeline from bench to bedside is decades-long and often things that work in animals fail when they get to clinical trials. Is it taking so long because sex isn’t being considered enough?” said Rowe.

The authors encourage researchers to include both sexes equally when possible, analyze data for males and females separately, and re-evaluate past studies that underrepresented females.

“The most surprising finding here isn’t that male and female mice sleep differently. It’s that no one has thoroughly shown this until now,” said Rowe. “We should have known this long before 2024.”

Mortality attributable to air pollution and extreme temperatures is a major concern, and it is expected to heighten in the future. In a new study led by the Max Planck Institute for Chemistry, an international research team found that, under the most probable projection, annual mortality rates linked to air pollution and extreme temperatures could reach 30 million by the end of the century. The research, based on advanced numerical simulations, suggests a concerning trend: pollution-related deaths are expected to increase five-fold, while temperature-related mortality could rise seven-fold, posing a more critical health risk than air pollution for at least 20% of the world’s population.

The researchers base their calculations on projections from 2000 to 2090, analyzed in ten-year intervals. “In 2000, around 1.6 million people died each year due to extreme temperatures, both cold and heat. By the end of the century, in the most probable scenario, this figure climbs to 10.8 million, roughly a seven-fold increase. For air pollution, annual deaths in 2000 were about 4.1 million. By the century’s close, this number rises to 19.5 million, a five-fold increase,” explains Dr. Andrea Pozzer, group leader at the Max Planck Institute for Chemistry in Mainz and adjunct associate professor at The Cyprus Institute in Nicosia, Cyprus.

The study shows significant regional differences in future mortality rates. South and East Asia are expected to face the strongest increases, driven by aging of the population, with air pollution still playing a major role. In contrast, in high-income regions — such as Western Europe, North America, Australasia, and Asia Pacific — deaths related to extreme temperatures are expected to surpass those caused by air pollution. In some countries within these regions, such as the United States, England, France, Japan and New Zealand, this shift is already occurring. The disparity is likely to grow, with extreme temperatures becoming a more significant health risk than air pollution also in countries of Central and Eastern Europe (e.g., Poland and Romania) and parts of South America (e.g., Argentina and Chile).

By the end of the century, temperature-related health risks are expected to outweigh those linked to air pollution for a fifth of the world’s population, underscoring the urgent need for comprehensive actions to mitigate this growing public health risk.

“Climate change is not just an environmental issue; it is a direct threat to public health,” says Andrea Pozzer. “These findings highlight the critical importance of implementing decisive mitigation measures now to prevent future loss of life,” adds Jean Sciare, director of the Climate and Atmosphere Research Center (CARE-C) of The Cyprus Institute, key contributor to the study.

Cardiovascular disease and dementia are major public health challenges that cause a significant burden on both healthcare and society. A new study from Karolinska Institutet in Sweden shows that long-term use of common cardiovascular drugs is associated with lower risk of dementia later in life.

“We can see a clear link between long-term use — five years or more — of these drugs and reduced risk of dementia in older age,” says Mozhu Ding, assistant professor at the Institute of Environmental Medicine, Karolinska Institutet, and one of the lead authors of the paper.

The researchers used Swedish national registers. Around 88,000 people over the age of 70 who were diagnosed with dementia between 2011 and 2016 were included in the study, as well as 880,000 controls. Information on cardiovascular medicines was obtained from the Swedish Prescribed Drug Register.

The results show that long-term use of antihypertensive drugs, cholesterol-lowering drugs, diuretics and blood-thinning drugs is associated with between 4 and 25 percent lower risk of dementia. Combinations of the drugs had stronger protective effects than if they were used alone.

“Previous studies have focused on individual drugs and specific patient groups but in this study, we take a broader approach,” says Alexandra Wennberg, affiliated researcher at the Institute of Environmental Medicine and the other lead author of the paper.

The researchers also found that, on the contrary, the use of antiplatelet drugs may be linked to a higher risk of dementia. Antiplatelet drugs are medicines used to prevent strokes and stop platelets from clumping together. One possible explanation is that these drugs increase the risk of microbleeds in the brain, which are associated with cognitive decline.

The study is an important piece of the puzzle for finding new treatments for dementia, according to the researchers.

“We currently have no cure for dementia, so it’s important to find preventive measures,” says Alexandra Wennberg.

The researchers stress the importance of further studies, especially randomised controlled clinical trials, to better understand the mechanisms behind the findings. Among other things, they will continue to study how diet and lifestyle, in addition to drug treatment for cardiovascular disease, affect the risk of developing dementia.

The research was carried out by Karolinska Institutet and Lund University with research funding from Karolinska Institutet. Alexandra Wennberg has received funding from Janssen Phamaceutica NV for an unrelated project. No other potential conflicts of interest are disclosed.

Parkinson’s disease, a neurological disorder best known for causing tremors, stiffness, slow movement and poor balance, also causes cognitive symptoms that can progress to Parkinson’s dementia. While there are medications that control the disease’s motor symptoms, there are no effective treatments for its cognitive symptoms.

“When patients are diagnosed with Parkinson’s disease, 25% to 30% already have mild cognitive impairment. As the disorder progresses into its later stages, 50% to 70% of patients complain of cognitive problems,” said Lalitha Madhavan, MD, PhD, an associate professor of neurology at the University of Arizona College of Medicine — Tucson. “The sad part is we don’t have a clear way to treat cognitive decline or dementia in Parkinson’s disease.”

A research team led by Madhavan, in collaboration with Torsten Falk, PhD, a research professor of neurology, is investigating PNA5, which was developed by Meredith Hay, PhD, a professor of physiology. They recently published a paper in Experimental Neurology showing that, in an animal model, PNA5 appears to have a protective effect on brain cells.

“With PNA5, we’re targeting cognitive symptoms but, in particular, we’re trying to prevent further degeneration from occurring,” said Kelsey Bernard, PhD, a postdoctoral researcher in the Madhavan Lab and the study’s first author. “By going down the protective route, we can hopefully prevent cognitive decline from continuing.”

Dialing back inflammation

The causes of neurodegenerative diseases are largely mysterious, but the current thinking is that they involve inflammation, a normal function of the immune system that is usually short-lived in response to infections or wounds. If inflammation becomes chronic, however, it can do lasting damage.

Bernard said inflammation plays a significant role in Parkinson’s disease when microglia, specific immune cells in the brain, enter a supercharged state.

“Normally, microglia are looking for things like viruses or injury and secreting substances that block off the damage,” she said. “In Parkinson’s disease, when they’re constantly activated, microglia can propagate further damage to the surrounding tissue. That’s what we see in Parkinson’s brains, particularly in regions associated with cognitive decline.”

The team found that these supercharged microglia flooded their environments with an inflammatory chemical, supporting previous research linking that chemical with cognitive status.

“This inflammatory chemical can directly interact with neurons in a region of the brain important for learning and memory,” Bernard said.

After treatment with PNA5, researchers watched blood levels of the inflammatory chemical decrease, correlating with a reduced loss in brain cells. They said they believe PNA5 dials back the microglia’s overly active immune response and brings it closer to a normal state.

The researchers hope that by suppressing production of this inflammatory chemical, PNA5 can protect the brain.

Expanding treatment options

When developing PNA5, Hay, in collaboration with Robin Polt, PhD, a professor of chemistry and biochemistry at the U of A’s College of Science, made small tweaks to the structure of a chemical the body naturally makes, enhancing its ability to enter the brain and stay there longer. Hay is studying PNA5’s potential in treating other types of dementia, such as vascular dementia and Alzheimer’s disease.

“It has already been tried and tested in other models, and that makes me more optimistic,” said Madhavan, who, along with Polt and Hay, is a member of the BIO5 Institute.

She said she hopes the team’s investigations into PNA5 will eventually lead to a drug that people with Parkinson’s disease can take to alleviate cognitive symptoms, though they may still need to take other drugs to control motor symptoms.

“I think about it as a cog in the wheel — there are going to be other drugs that support other aspects of Parkinson’s. Taking multiple drugs is never fun, but it’s a complex condition and there can only be complex solutions,” she said. “The beauty of the brain is the interconnectedness, but it also adds to the complexity.”

The researchers said their next steps are to conduct further studies to identify biomarkers, refine dosages, investigate sex differences and figure out how PNA5 might work.

“PNA5 seems to have a possibility of stopping or delaying Parkinson’s progression to some extent and could improve the health of brain cells or prevent cells from dying,” Madhavan said.

The publication was the product of Bernard’s doctoral research, which she performed under the mentorship of co-senior authors Madhavan and Falk.

“The brain is the most interesting part of the body,” Bernard said. “These cells are fascinating — what causes them to work correctly and what causes them to go awry.”

This research was supported in part by the Michael J. Fox Foundation under award no. MJFF 024922, the National Institutes of Health under award no. T32 AG1081797, and the ARCS Foundation Scholarship.

Pain sensations and other information are mainly conducted through our nervous system as electrical signals. Yet at decisive moments, this information is converted to biochemical signals, in the form of specific molecules. To develop future drugs against pain, researchers must understand the details of what happens at the molecular level when pain signals are converted from one form to another.

When the electrical signal reaches the end of one nerve cell it is converted into a biochemical signal, in the form of calcium. In turn, an increase in calcium triggers the release of signalling molecules called neurotransmitters. This biochemical signal is received by the next nerve cell, that converts the signal back into electricity. Along this chain of information transfer in the nervous system, one class of proteins is of particular interest: the voltage-sensitive calcium channels. These channels are like molecular machines that sense electrical signals and then open to allow calcium to flow into the nerve cell.

In the current study, researchers at Linköping University have focused on a specific type of calcium channel called CaV2.2, that is involved in the transmission of pain signals. In fact, these channels are more active during chronic pain. They are specifically located in the ends of sensory nerve cells.

Drugs that dampen their activity reduce the communication of pain signals from the sensory nerve cells to the brain. Such drugs exist, but there is a catch: a drug that blocks CaV2.2 completely has such severe side-effects that it needs to be given directly into the spinal fluid. Drugs that decrease the number of CaV2.2, like gabapentin, do not reduce chronic pain very efficiently. Another class of drugs that exploit a natural mechanism to decrease the ability of CaV2.2 to respond to pain signalling are the opioid drugs, like morphine and heroin. While very effective at blocking pain, they are also addictive and can cause devastating dependency.

“Calcium channels are very attractive drugs targets for pain treatment, but today’s solutions are inadequate,” says Antonios Pantazis, associate professor at the Department of Biomedical and Clinical Sciences at Linköping University, who has led the study published in the journal Science Advances.

The researchers studied the mechanism by which opioids decrease CaV2.2 activity. It has been known for a long time that opioids release molecules called G proteins, which directly bind to calcium channels and make them “reluctant” to open. But how does this happen?

“It is as if G-protein signalling causes the channel to need more ‘persuasion’ — in terms of stronger electrical signals — to open. In our study, we describe at the molecular level how this is done,” says Antonios Pantazis.

In the calcium channel there are four so-called voltage sensors that detect electrical nerve impulses. When the voltage is high enough, the voltage sensors move and make the channel open, so that calcium can flow through. The researchers used tiny light-emitting molecules to detect how these voltage sensors move in response to electrical signals. They discovered that G-proteins impact the function of specific voltage sensors, but not others, making them more “reluctant” to sense electrical signals.

“Our finding points to a very specific part of the large calcium channel that next-generation drugs can target to provide pain relief in a similar way to opioids. Instead of blocking the calcium channel completely, which is a less refined method, future drugs can be designed to fine-tune calcium channel activity in pain signalling,” says Antonios Pantazis.

It is hoped that future drugs designed to impact the CaV2.2 calcium channel can have a better pain-relieving effect and less side effects.

The research was funded with support from the Knut and Alice Wallenberg Foundation through the Wallenberg Centre for Molecular Medicine at Linköping University, the Swedish Brain Foundation, the Swedish Research Council, the National Institute of General Medical Sciences and Lions Forskningsfond.

Food choices made during periods of stress can influence the effect of stress on cardiovascular health. For example, recent research from the University of Birmingham found that high-fat foods can negatively affect vascular function and oxygen delivery to the brain, meanwhile flavanol compounds found in abundance in cocoa and green tea can protect vascular function during periods of everyday stress.

Now, in a new study, the same research team has found that drinking cocoa high in flavanols in combination with a fatty meal can counteract some of the impact of fatty food and protect the vascular system from stress.

The research has been published today (18^th November) in the journal Food and Function.

Dr Catarina Rendeiro, Assistant Professor in Nutritional Sciences at the University of Birmingham, and leading author said: “We know that when people are stressed, they tend to gravitate towards high-fat foods. We have previously shown that fatty food can impair the body’s vascular recovery from stress. In this study, we wanted to see if adding a high-flavanol food to the fatty meal would alleviate the negative impact of stress in the body.”

Rosalind Baynham, first author on the paper, explained: “Flavanols are a type of compound that occur in different fruits, vegetables, tea and nuts including berries and unprocessed cocoa. Flavanols are known to have health benefits, particularly for regulating blood pressure and protecting cardiovascular health.

“We took a group of young healthy adults and gave them two butter croissants with 10 g salted butter, 1.5 slices of cheddar cheese and 250 ml whole milk as breakfast, and either a high-flavanol cocoa or a low-flavanol cocoa drink. Following a rest period, we asked the participants to complete a mental maths test which increased in speed for eight minutes, alerting them when they got an answer wrong. During the 8 minute rest period and 8 minute mental maths test, we measured forearm blood flow, cardiovascular activity and prefrontal cortex (PFC) tissue oxygenation. We also measured vascular function using Brachial Flow-mediated dilatation (FMD), which is a prognostic measure for future risk of cardiovascular disease. This stress task induced significant increases in heart rate and blood pressure, similar to the stress you may encounter in daily life.”

The cocoa beverages were prepared by dissolving 12 g cocoa powder into 250 ml of whole milk. The low-flavanol powder was an alkalized cocoa powder which was processed to reduce total flavanols to 5.6 mg per serving; and the high-flavanol cocoa powder was a non-alkalized powder, delivering 695.0 mg total flavanols per serving. Alkalization is a process typically used in chocolate making to enhance flavour, but unfortunately it reduces the amount of flavanols.

The team confirmed that consuming fatty foods with the low-flavanol drink when mentally stressed reduced vascular function (by 1.29% FMD) and lasted up to 90 minutes after the stressful event was over. The findings also showed that the cocoa drink high in flavanols was effective at preventing the decline in vascular function following stress and fat consumption. Brachial flow-mediated dilatation was significantly higher following high-flavanol cocoa compared to low-flavanol cocoa 30 and 90 minutes after the stressful period. The team had also found in their previous work, that eating high-fat foods attenuated cerebral oxygenation in the pre-frontal cortex, during stress. However, cocoa flavanols did not improve cerebral oxygenation or impact mood.

Dr Catarina Rendeiro, Assistant Professor in Nutritional Sciences at the University of Birmingham, added: “This research shows that drinking or eating a food high in flavanols can be used as a strategy to mitigate some of the impact of poorer food choices on the vascular system. This can help us make more informed decisions about what we eat and drink during stressful periods.”

In the supermarket look for a minimally processed cocoa powder, and if cocoa isn’t quite your beverage of choice, there are other ways you can get a higher dose of flavanols, such as green tea, black tea and berries. Recent published guidelines for flavanol intake recommend between 400 to 600 mg/day, which can be achieved for example, by consuming two cups of black or green tea, or a combination of berries, apples and high-quality cocoa.

Jet Veldhuijzen van Zanten, Professor of Biological Psychology at the University of Birmingham, and author of this paper added: “Modern life is stressful and the impact of stress on our health and the economy has been well documented, so any changes we can make to protect ourselves from some of the symptoms of stress is positive. For those who tend to reach for a treat when stressed or depend on convenient food because they work high-pressure jobs or are time-poor, incorporating some of these small changes could make a real difference.”

“This is a deadly disease with very poor outcomes for patients. The median survival is eight months with treatment, probably less without treatment, and the five-year survival is tiny,” says Joe Cullen, MD, University of Iowa professor of surgery, and radiation oncology, and senior author of the study. “When we started the trial, we thought it would be a success if we got to 12 months survival, but we doubled overall survival to 16 months. The results were so strong in showing the benefit of this therapy for patient survival that we were able to stop the trial early.”

The findings, published in the November issue of Redox Biology, mark another success for high-dose, intravenous vitamin C, which has overcome many hurdles in the almost 20 years UI researchers have persevered to demonstrate its benefit for cancer patients.

“We’ve had ups and downs, of course, but this is a culmination of a lot of people’s hard work,” says Cullen, who also is a member of UI Health Care Holden Comprehensive Cancer Center. “It’s really a positive thing for patients and for the University of Iowa.”

Increased survival, improved quality of life

In the study, 34 patients with stage 4 metastatic pancreatic cancer were randomized to receive either standard chemotherapy (gemcitabine and nab-paclitaxel), or the chemotherapy plus infusions of high-dose vitamin C. The results showed that average overall survival was 16 months for the patients receiving the chemotherapy plus vitamin C, compared to eight months for the patients getting just chemotherapy. In addition, progression-free survival was extended from four months to six months.

“Not only does it increase overall survival, but the patients seem to feel better with the treatment,” Cullen says. “They have less side effects, and appear to be able to tolerate more treatment, and we’ve seen that in other trials, too.”

The new study is not the only evidence of the benefit of including IV vitamin C as part of cancer treatment. Earlier this year, the results of another UI phase 2 clinical trial in patients with glioblastoma, a deadly form of brain cancer, were published. That study also showed a significant increase in survival when high-dose, IV vitamin C was added to standard of care chemotherapy and radiation. Cullen was also part of that trial along with his colleague Bryan Allen, MD, PhD, UI professor and head of radiation oncology.

A third phase 2 trial in non-small cell lung cancer is still underway, with results expected within the year. All three trials were funded by a grant from the National Cancer Institute (NCI).

“This NCI funding was incredibly important for us to conduct these phase 2 trials and obtain these really encouraging results. Our aim is to show that adding high-dose, IV vitamin C, which is very inexpensive and very well tolerated, can improve treatment for these cancers that are among the deadliest affecting the U.S. population,” Cullen adds.

A long journey to clinical trials

Cullen, Allen, and their colleagues at UI Health Care have been researching the anti-cancer effect of high-dose, IV vitamin C for decades. Their work revealed a critical difference between vitamin C given intravenously and vitamin C taken orally. Giving vitamin C through an IV produces very high levels in the blood, which cannot be achieved with oral delivery. These high concentrations result in unique chemical reactions within cancer cells that render the cells more vulnerable to chemo- and radiation therapies.

Cullen notes that despite skepticism towards vitamin C as a cancer therapy, the results he and his colleagues have obtained, from basic science findings to understand the biological mechanisms at work, through the various clinical trials, have been highly encouraging and robust.

“Through every step of the process, it continued to improve. We did it in cells, it worked great. We did it in mice, it worked great. Then our phase one trials looked very promising. So, the progression has just been phenomenal, really,” Cullen says. “For example, in one of our phase 1 trials for pancreatic cancer, where we combine high-dose IV vitamin C with radiation, we still have three long-term survivors. They’re out nine years at this point, which is far beyond the typical survival range.”

In addition to Cullen and Allen, the UI team also included cancer physicians and researchers from the Departments of Surgery, Radiation Oncology, Internal Medicine in the UI Carver College of Medicine, the UI College of Public Health, and the Medical College of Wisconsin in Milwaukee.

In an effort to counteract this public health crisis, scientists are looking for new solutions inside the intricate mechanics of bacterial infection. A study led by researchers at the University of California San Diego has discovered a vulnerability within strains of bacteria that are antibiotic resistant.

Working with labs at Arizona State University and the Universitat Pompeu Fabra (Spain), Professor Gürol Süel and colleagues in UC San Diego’s School of Biological Sciences investigated the antibiotic resistance of the bacterium Bacillus subtilis. Their research was motivated by the question of why mutant variants of bacteria do not proliferate and take over the population once they have developed an antibiotic-resistant advantage. With an upper hand over other bacteria lacking similar antibiotic resistance, such bacteria should become dominant. Yet they are not. Why?

The answer, reported in the journal Science Advances, is that antibiotic resistance comes at a cost. While antibiotic resistance provides some advantages for the bacteria to survive, the team discovered that it’s also linked with a physiological limitation that hinders potential dominance. This fact, the researchers note, potentially could be exploited to stop the spread of antibiotic resistance.

“We discovered an Achilles heel of antibiotic resistant bacteria,” said Süel, a member of the Department of Molecular Biology at UC San Diego. “We can take advantage of this cost to suppress the establishment of antibiotic resistance without drugs or harmful chemicals.”

Spontaneous mutations of DNA arise in all living cells, including those within bacteria. Some of these mutations lead to antibiotic resistance. Süel and his colleagues focused on physiological mechanisms related to ribosomes, the micro machines within cells that play a key role in synthesizing proteins and translating genetic codes.

All cells rely on charged ions such as magnesium ions to survive. Ribosomes are dependent upon magnesium ions since this metal cation helps stabilize their structure and function. However, atomic-scale modeling during the new research found that mutant ribosome variants that bestow antibiotic resistance excessively compete for magnesium ions with adenosine triphosphate (ATP) molecules, which provide energy to drive living cells. Mathematical models further showed that this results in a ribosome versus ATP tug-of-war over a limited supply of magnesium in the cell.

Studying a ribosome variant within Bacillus subtilis called “L22,” the researchers found that competition for magnesium hinders the growth of L22 more than a normal “wild type” ribosome that is not resistant to antibiotics. Hence the competition levies a physiological toll linked to mutant bacteria with resistance.

“While we often think of antibiotic resistance as a major benefit for bacteria to survive, we found that the ability to cope with magnesium limitation in their environment is more important for bacterial proliferation,” said Süel.

This newly discovered weakness can now be used as a target to counteract antibiotic resistance without the use of drugs or toxic chemicals. For example, it may be possible to chelate magnesium ions from bacterial environments, which should selectively inhibit resistant strains without impacting the wild type bacteria that may be beneficial to our health. “We show that through a better understanding of the molecular and physiological properties of antibiotic-resistant bacteria, we can find novel ways to control them without the use of drugs,” said Süel.

In October Süel and colleagues at the University of Chicago announced a separate approach to combating the antibacterial-resistant bacteria health crisis. Their development of a bioelectronic device that taps into the natural electrical activity of certain bacteria found on our skin paves the way for another drug-free approach to managing infections. The advancement was proven to reduce the harmful effects of Staphylococcus epidermidis, a common bacterium known for causing hospital-acquired infections and contributing to antibiotic resistance. In both studies the researchers used charged ions to control bacteria.

“We are running out of effective antibiotics and their rampant use over the decades has resulted in antibiotics being spread across the globe, from the arctic to the oceans and our groundwater,” said Süel. “Drug-free alternatives to treating bacterial infections are needed and our two most recent studies show how we can indeed achieve drug-free control over antibiotic resistant bacteria.”

The authors of the new study were: Eun Chae Moon, Tushar Modi, Dong-yeon Lee, Danis Yangaliev, Jordi Garcia-Ojalvo, S. Banu Ozkan and Gürol Süel.

The study, published Wednesday in the journal Clinical Ophthalmology, is among the first to look into how climate change may affect the eyes.

“The World Health Organization has declared climate change to be “the single biggest health threat facing humanity,” said the study’s lead author Jennifer Patnaik, PhD, MHS, assistant professor of epidemiology and ophthalmology at the University of Colorado School of Medicine. “Yet there are limited studies on the impact of climate change-related air pollution on ocular health.”

The researchers, including Associate Professor Katherine James, PhD, who directs the Climate & Human Health program at the Colorado School of Public Health, examined the associations between ocular surface irritation and allergy-related daily outpatient office visits with daily ambient particular matter (PM) levels in the Denver Metropolitan area.

They obtained data of PM concentrations that were 10 micrometers or less and 2.5 micrometers or less in diameter. The researchers found 144,313 ocular surface irritation and allergy visits to ophthalmic clinics during the study period. The daily visit counts were 2.2 times higher than average when PM₁₀ concentrations were 110. The clinic visit rate ratio increased as daily concentrations increased.

The study reported that conjunctivitis was the second most common eye disease among the clinic visits in the study, representing exactly one-third of all the visits. The prevalence of ocular allergic conjunctivitis has increased worldwide and varies across regions. Socioeconomic and environmental factors such as temperature, humidity and air pollution have been proposed as reasons for the increase.

Patnaik said the health risks of air pollution and climate change span a wide range of outcomes including infectious disease, weather-related morbidity and a variety of lung, kidney and cardiovascular maladies.

“Less studied chronic diseases such as dementia have also been shown to be associated with temperature and air pollutants,” she said. “Research on the topic of ocular conditions and climate is still in its early stages; therefore, more studies are needed to better understand how climate and air pollutants impact eye health.”

James agreed.

“This study highlights the systemic health impacts of climate stressors including air quality, wildfires, temperature, and drought conditions and the continued need to for transdisciplinary research,” she said.

The researchers hope to build and expand on these initial discoveries, said the study’s senior author Malik Kahook, MD, professor of ophthalmology at the CU School of Medicine.

“These findings open the door to a deeper understanding of how environmental factors affect eye health. From a clinical standpoint, we’re now seeing more evidence suggesting that particulate matter in the air isn’t just affecting respiratory or cardiovascular health but also directly impacting ocular surface health,” Kahook said. “Our next steps are to investigate how other air pollutants might influence eye health and to expand our focus to areas outside of Colorado. By doing so, we aim to identify preventive strategies and consider new treatment protocols tailored to address these environmental influences, ultimately protecting the most vulnerable patients in areas heavily affected by pollution.”

Amy Dye-Robinson, from the Department of Biostatistics & Informatics at CU Anschutz, is a study co-author.

“We already know that abusive leadership takes a serious toll on workers — but now we’re seeing that leaders who swing back and forth between abusive and ethical leadership do even more damage to employees,” says Dr. Haoying Xu, the study’s lead author and an assistant professor of management in the Stevens School of Business. “It turns out that reverting to an ethical leadership style doesn’t magically erase the impact of prior bad behavior — and in some circumstances, it can actually make things worse.”

The research, published in the Journal of Applied Psychology, used surveys and field experiments to examine the impact of “Jekyll-and-Hyde” leadership on more than 650 full-time employees based in the United States and Europe. Dr. Xu’s team confirmed that the workers struggled when their supervisors were abusive — but found an even stronger negative impact when supervisors alternated unpredictably between abusive and ethical leadership styles.

“If you’re constantly guessing which boss will turn up — the good cop or the bad cop — then you wind up emotionally exhausted, demoralized, and unable to work to your full potential,” Dr. Xu explains.

The new research also shows for the first time that “Jekyll-and-Hyde” leadership can take a serious toll even when employees aren’t directly impacted by a leader’s on-again, off-again misbehavior. When a supervisor’s own boss alternated between abusive and ethical leadership, the study found, it created additional uncertainty and eroded employees’ confidence in the supervisor’s capabilities.

“In today’s workplaces, employees are very attuned to their supervisors’ relationships with more senior leaders,” Dr. Xu says. “If that relationship becomes unpredictable, or is marked by repeated bouts of good and bad behavior, it can cause real problems for the whole team.”

For organizations, the research offers some important new insights — most notably the fact that leaders who seek to atone for intermittent bad behavior are often doing real harm to their employees. “Organizations tend to intervene when bosses are consistently abusive, but are more tolerant of leaders whose abusive behavior only shows through from time to time,” Dr. Xu says. “With this study, however, we’ve shown that intermittent bad behavior can actually be more toxic for organizations.”

To counter Jekyll-and-Hyde leadership, Dr. Xu says, organizations should pay attention to employees who voice concerns, and hold leaders accountable for sporadic abusive behavior. It’s also worth considering anger management coaching for leaders who show signs of volatility. “This kind of intermittent abusive leadership tends to be impulsive,” Dr. Xu says. “That means there’s scope to reduce or eliminate it by helping leaders to manage their tempers and improve their impulse control.”

In future research, Dr. Xu hopes to explore how employees respond to and learn from Jekyll-and-Hyde leadership, and how a leader’s periodic abusive behavior impacts individual behavior and team dynamics. “There are some indications that this kind of leadership could be contagious, with a leader’s volatility fostering volatility in others,” he says.

There is also some intriguing early evidence that employees might learn from and emulate a leader’s bad behavior more than they replicate their good behavior. “If that’s the case, then it would be another big reason for organizations to take Jekyll-and-Hyde leadership seriously,” Dr. Xu warns.

T cells are a type of immune cell that seeks out and destroys cells infected by viruses, bacteria as well as tumour cells. Originally designed to detect SARS-CoV-2-specific T cells, this technology has now been adapted for use in cancer immunotherapy applications. The test, which uses less than a quarter teaspoon of blood, works by stimulating the target T cells in the blood to release chemical signals, called cytokines, through which the quantity and quality of the target T cells can be measured.

In this proof-of-concept study, which was published in Immunotherapy Advances,the research team introduced fragments, called peptides, that stimulate the T cells engineered to fight Hepatitis B virus-related liver cancer present in the treated patients. Using their test, they assessed whether the engineered T cells remained in the blood and continued to function properly after infusion into the patient.

Assistant Professor Anthony Tan, from Duke-NUS’ Emerging Infectious Diseases Programme and first author of the study, commented:

“Our innovative test enables us to swiftly detect and analyse engineered T cells in patient blood samples. Its simplicity and speed could have a significant impact on the clinical field helping to make advanced treatments more accessible.”

With engineered T-cell therapies becoming more widely used to treat malignancies, including Hepatitis B virus-induced liver cancer and a range of blood cancers, being able to accurately and easily track how these engineered cells behave in the body over time will be crucial in monitoring the effectiveness of these therapies in individual patients.

At the same time, this plug-and-play concept can help accelerate the translation of new T-cell-based therapies from the laboratory to patient bedside. The research team has already demonstrated that the test can be adapted for use in numerous viral infections, but this is their first foray into cancer therapies, where the test can be harnessed for T-cell receptor (TCR) engineered T cells, as well as chimeric antigen receptor (CAR) T-cell therapies.

Professor Antonio Bertoletti, from Duke-NUS Emerging Infectious Diseases Programme and senior author of the study, added:

“Tracking the functionality of adoptively transferred engineered T-cell products could provide important information on treatment efficacy over time, an assessment which at the moment remains largely unexplored. We hope that with this proof-of-concept, we can help accelerate research into other CAR and TCR T-cell therapies as well as support clinicians on the frontline caring for patients receiving these novel therapies.”

In collaboration with Lion TCR Pte Ltd, the test has been deployed in a Hepatitis B virus-TCR T-cell therapy clinical trial, called the SAFE-T-HBV trial, evaluating the effectiveness of a novel therapy in two patients and demonstrating the test’s impact on improving the precision of immunotherapy outcomes.

The team is now looking to advance this proof-of-concept through larger clinical studies.

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, said that he sees potential in the new test. He added:

“This innovation isn’t just a step forward in cancer therapy, it’s a significant advancement in patient care that could extend across multiple diseases. By offering clinicians real-time data on the functionality of these engineered T cells, we are paving the way for highly personalised treatment strategies that could significantly enhance patient outcomes.”

As a leader in biomedical research, Duke-NUS combines basic scientific research with translational applications to innovate treatments approaches and diagnostic tools to advance health globally.

This research is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd under the NMRC Singapore Translational Research Investigator Award (MOH-000019). The SAFE-T-HBV clinical trial was sponsored by Lion TCR Pte Ltd.

The digestive system is home to trillions of bacteria, many of which produce short-chain fatty acids (SCFAs) that help fight harmful pathogens. But Salmonella manages to grow and spread in the gut, even though these protective compounds are present. The study asks: How does Salmonella get around this defense?

“We knew that Salmonella invades the small intestine, although it is not its primary site of replication. The colon is,” said the lead author of the study Andreas Bäumler. Bäumler is a UC Davis distinguished professor and vice chair of research in the Department of Medical Microbiology and Immunology.

Bäumler and his team discovered that the answer lies in how the pathogen changes the gut’s nutrient balance. When Salmonella enters the small intestine, it causes inflammation in the gut lining and disrupts the normal absorption of amino acids from food. This creates an imbalance in nutrients in the gut.

The imbalance gives Salmonella the resources it needs to survive and multiply in the large intestine (colon), where beneficial bacteria usually curb its growth. The study showed that salmonella causes inflammation in the small intestine in order to derive nutrients that fuel its replication in the colon.

Salmonella alters gut nutrient environment to survive

Using a mouse model, the team looked closely at how Salmonella changed the chemical makeup of the gut. They traced amino acid absorption in the small and large intestines.

They found that in mice that were infected with Salmonella, there was less absorption of amino acids into the blood. In fact, two amino acids, lysine and ornithine, became more abundant in the gut after infection. These amino acids helped Salmonella survive by preventing the growth-inhibiting effects of SCFAs. They did this by restoring Salmonella’s acidity (pH) balance, allowing the pathogen to bypass the microbiota’s defenses.

“Our findings show that Salmonella has a clever way of changing the gut’s nutrient environment to its advantage. By making it harder for the body to absorb amino acids in the ileum, Salmonella creates a more favorable environment for itself in the large intestine,” Bäumler said.

In the study, the team showed that Salmonella uses its own virulence factors (disease causing molecules) to activate enzymes that break down key amino acids like lysine. This helps the pathogen avoid the SCFAs’ protective effects and grow more easily in the gut.

New insights could lead to better gut infection treatments

The new insights potentially explain how the gut environment changes during inflammatory bowel disorders , such as Crohn’s disease and ulcerative colitis, and could lead to better treatments for gut infections. By understanding how Salmonella changes the gut environment, researchers hope to develop new ways to protect the gut microbiota and prevent these infections.

“This research uses a more holistic approach to studying gut health. It not only gives us a better understanding of how Salmonella works, but also highlights the importance of maintaining a healthy gut microbiota,” said Lauren Radlinski, the study’s first author and postdoctoral fellow in the Bäumler Lab. “Our findings could lead to new treatments that help support the microbiota during infection.”

The study’s results could inspire future treatments, including probiotics or dietary plans designed to strengthen the body’s natural defenses against harmful pathogens.

“By learning how a pathogen manipulates the host’s system, we can uncover ways to boost the host’s natural defenses,” Radlinski said.

Coauthors of the study are Andrew Rogers, Lalita Bechtold, Hugo Masson, Henry Nguyen, Anaïs B. Larabi,Connor Tiffany, Thaynara Parente de Carvalho and Renée Tsolis of UC Davis.

Published in the journal Science, StitchR — short for “stitch RNA” — restored expression of large therapeutic muscle proteins to normal levels in two different animal models of muscular dystrophy. StitchR enabled expression of the protein Dysferlin, which is lacking in individuals with limb girdle muscular dystrophy type 2B/R2, as well as the protein Dystrophin, which is absent in patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy is the most common early onset form of muscular dystrophy; many boys become wheelchair bound in their teens and die in their twenties. People with limb girdle muscular dystrophy experience weakness and wasting in the shoulder, hip, and thigh muscles, and often have difficulty standing, moving, and doing everyday tasks.

“Gene therapy is a powerful tool for delivering a healthy gene copy back to a patient’s cells to correct genetic diseases, but the vectors used to deliver this information are small, which has so far precluded their use for treating a whole host of diseases caused by mutations in large genes,” said Douglas M. Anderson, PhD, lead study author and assistant professor of Medicine in the Aab Cardiovascular Research Institute at the University of Rochester School of Medicine and Dentistry (SMD). “Instead of delivering the full gene in a single vector, which isn’t possible, we’ve developed an efficient dual vector system where two halves of a gene are delivered separately but come together to reconstitute the large mRNA in the affected tissues.”

The technology first arose from a serendipitous observation made in the lab several years ago, that when two separate mRNAs were cut by small RNA sequences called ribozymes, they became seamlessly ligated (joined) and translated into full-length protein. The team found that when ribozymes cleave or cut RNA, they leave ends that are recognized by a natural repair pathway.

“Similar to when CRISPR enzymes are used to cut DNA, the CRISPR enzymes are just the scissors, and it’s a cell’s natural repair enzymes that glue the DNA back together,” noted Anderson, who is also a member of the University of Rochester Center for RNA Biology. “We think something similar is happening here, but for RNA. The ribozymes are acting as the scissors and the cell’s natural repair pathways are able to join the two RNAs back together. It’s remarkable that two separate mRNAs are able to find themselves and that the process can be so efficient.”

The lab optimized efficiency of the process (over 900-fold from their initial experiments) and adapted the technology into a powerful gene delivery mechanism. When two halves of a large therapeutic gene are encoded into adeno-associated virus (AAV) vectors, which are the most commonly used vectors for gene therapy because they are safe and don’t cause disease in humans, the ribozymes cut the ends of the mRNAs and they subsequently join, forming a single, seamless mRNA capable of producing protein in a desired tissue.

The research team, including co-first author Sean Lindley, who recently received his PhD from the Anderson lab, found that the stitched mRNAs appear to behave essentially the same way as their natural full-length counterparts, effectively translating genetic information into functional proteins.

Self-cleaving ribozymes, which are essential for StitchR activity, are found naturally throughout the animal kingdom and are comprised of different families, which exhibit different cleavage activities. After testing numerous ribozyme families and sequences, they ultimately identified a formula that led to a high level of protein production and approached the levels achieved by genes expressed from just a single vector.

“Doug is extremely creative and detail oriented, and the fact that he’s worked out how two different pieces of mRNA can find one another in a cell and be joined seamlessly to create a functional mRNA is really exciting,” said Lynne E. Maquat, PhD, director of the UR Center for RNA Biology. “The concept sounds simple, but this required considerable bench work to optimize the molecules involved, ensure they are stable in cells, and make the process as efficient as possible.”

According to Anderson, StitchR can be coupled with many different types of vectors that are used to deliver or express a gene in cells and that it appears to work efficiently with any mRNA sequence, opening the door for its use in a wide range of diseases and applications. “StitchR is really plug and play at this point. The sequence requirements for StitchR are minimal, and we’ve now tested this with many different genes and sequences,” he said.

Another feature of this technology is that only the full-length protein is produced.

“Other dual vector approaches have been in development for decades but have been plagued by lack of efficiency and the production of less than full-length products. Because StitchR occurs at the level of RNA, we can control and ensure that only the full-length protein product gets made. This differentiates StitchR from other dual vector technologies, for example inteins, a protein-ligation technology, which can be efficient but requires the expression of smaller protein fragments that may have unknown effects in a cell,” added Anderson.

“It’s been a long but fulfilling process to go from an initial research observation to a therapeutic application, but that’s always been a major goal of our lab, and I think the promise of basic research. With StitchR and other tools we are working towards treatments for some of the most debilitating genetic diseases on the planet, many of which have no current treatments or cures,” said Anderson.

The lab is now in the process of forming collaborations with other research labs and generating StitchR vectors to treat numerous diseases caused by large genes, of which there are thousands.

In addition to Anderson and Lindley, SMD staff scientists Kadiam C. Venkata Subbaiah (co-first author), Pornthida Poosala, FNU Priyanka and technicians William Richardson and Tamlyn Thomas contributed to the work, as well as CANbridge Pharmaceuticals scientists Yijie Ma, Leila Jalinous, and Jason A. West. The work was funded by the University of Rochester, Jain Foundation, CANbridge Phamaceuticals, and Scriptr Global, Inc. Anderson is a co-founder of Scriptr Global, Inc. and holds several US and foreign patent applications for his research related to StitchR and other RNA-based technologies. Scriptr licensed the StitchR technology from the University of Rochester.

Learning and decision-making change considerably from adolescence into adulthood. Adolescents undergo developmental changes in specific choice behaviors, such as goal-directed behaviors and motivational influences over choice. They also consistently show high levels of decision noise, i.e., choosing suboptimal options. However, it remains unknown whether these observations — the development of specific and more sophisticated choice processes and higher decision noise — are independent or related. It is possible that the development of specific choice processes might be impacted by age-dependent changes in decision noise.

To test this idea, Scholz, Deserno, and colleagues analyzed data from 93 participants between 12 and 42 years of age. The participants completed three reinforcement learning tasks: a task assessing motivational influences over choices, a learning task capturing adaptive decision-making in response to environmental changes, and a task measuring goal-directed behavior.

The results revealed that noise levels were strongly correlated across reinforcement learning tasks. Critically, noise levels mediated age-dependent increases in more sophisticated choice behaviors and performance gains. The findings suggest that unspecific noise mediates the development of highly specific functions or strategies.

One reason for these mediation effects could be a limited availability of cognitive resources in adolescents due to the ongoing development of brain areas related to cognitive control. Having fewer cognitive resources might make adolescents more prone to rely on computationally cheaper decision strategies, rendering them more susceptible to emotional, motivational and social influences.

Overall, the study provides novel insights into the computational processes underlying developmental changes in decision-making. According to the authors, future work may unravel the neural basis as well as the developmental and clinical real-life relevance of decision noise for neurodevelopmental disorders.

The authors add, “Teenagers make less optimal, so-called ‘noisy’ decisions. While these noisy decisions decrease when growing older, this decrease is also linked to the development of improved complex decision-making skills, such as planning and flexibility.”

Our intestines are home to a microbiotic universe in which bacteria train our immune systems to be resilient, produce vitamins and transform the foods that we consume into beneficial compounds. Imbalances in this gut microbiome can be linked to various illnesses, including obesity, diabetes and diarrhea.

In developing countries, acute and chronic diarrhea is a widespread problem among children and leads to the deaths of half a million children under the age of five every year. Acute diarrhea often resolves on its own and can typically be treated with antibiotics. But once it progresses to a chronic form, it can leave children severely ill and underdeveloped, making treatment much harder. Until now, the cause of chronic diarrhea has remained unclear.

“Persistent diarrhea in adults can be extremely unpleasant but is rarely life-threatening. However, for a child, it can have lifelong consequences. While acute diarrhea has become much more treatable over the past fifty years, little progress has been made in treating the chronic type, which is what sparked our interest,” explains Dennis Sandris Nielsen, a professor at the University of Copenhagen’s Department of Food Science.

In a new study published in Nature Communications, Nielsen and his Ethiopian colleague Getnet Tesfaw mapped the gut microbiome of over 1,300 children under five years of age in Ethiopia. The study’s main conclusion is clear: children with chronic or persistent diarrhea have significantly lower and different bacterial diversity compared to healthy children.

“Our results show a clear link between gut bacteria composition and the duration of diarrhea. Children with chronic diarrhea not only have more harmful bacteria, but notably fewer beneficial ones,” explains Tesfaw, who will defend his PhD thesis on the topic later in November.

A vicious cycle of diarrhea

Researchers used DNA sequencing to identify various beneficial and harmful bacteria in stool samples. Results indicate that children with chronic diarrhea have an overrepresentation of harmful bacteria, such as Escherichia and Campylobacter, while the presence of beneficial bacteria, such as Faecalibacterium, is significantly reduced.

The study also revealed that children with chronic diarrhea lack bacteria that produce short-chain fatty acids, which are typically produced by beneficial bacteria and play an essential role in gut health.

Acute diarrhea is defined as lasting from one to six days, while chronic diarrhea persists for a week or more. According to Nielsen, the results indicate that chronic diarrhea develops if beneficial, short-chain fatty acids producing microbes are lost to an extent that the children’s gut microbiomes for unkonwon reasons fail to recover from after for instance antibiotic treatment for acute cases.

“The progression into persistent diarrhea seems to be driven by a loss of beneficial bacteria. We do not yet know the exact cause, but we speculate that while antibiotics may be necessary to treat acute diarrhea, they also kill off good gut bacteria. As a result, children may enter a vicious cycle where chronic diarrhea takes over because they don’t consume the right foods to restore these beneficial bacteria,” the researcher explains.

Local “superfood” to the rescue

The new mapping of gut bacteria in children with chronic diarrhea offers a deeper understanding of the problem’s causes and makes it easier to develop new, targeted treatments that could restore a healthy gut microbiome.

According to Tesfaw, the primary focus of treatment should be on designing an optimal diet to help restore the microbiome in affected children. Ideally, this diet would be familiar to the local population, accessible and sustainable. The researchers already have a potential main ingredient in mind.

“In Ethiopia, they have a superfood grain called teff, which is rich in nutrients and fiber. It clearly has the potential to serve as a dietary supplement that could help stop chronic diarrhea,” says Nielsen.

However, further studies are needed, and the researchers hope to secure funding for a new research project in the near future.