Category: 8. Health

A new study from Gladstone Institutes and UC San Francisco (UCSF) reveals that many genetic risk factors for neurological diseases like Alzheimer’s and stroke exert their effects within these very guardian cells.

“When studying diseases affecting the brain, most research has focused on its resident neurons,” says Gladstone Investigator Andrew C. Yang, PhD, senior author of the new study. “I hope our findings lead to more interest in the cells forming the brain’s borders, which might actually take center stage in diseases like Alzheimer’s.”

The findings, published in Neuron, address a long-standing question about where genetic risk begins and suggest that vulnerabilities in the brain’s defense system may be a key trigger for disease.

Mapping the Brain’s Guardians

For years, large-scale genetic studies have linked dozens of DNA variants to a higher risk of neurological diseases like Alzheimer’s, Parkinson’s, or multiple sclerosis.

Yet, a major mystery has persisted: over 90% of these variants lie not in the genes themselves, but in the surrounding DNA that does not contain the code for making proteins, once dismissed as “junk DNA.” These regions act as complex dimmer switches, turning genes on or off.

Until now, scientists haven’t had a full map of which switches control which genes or in which specific brain cells they operate, hindering the path from genetic discovery to new treatments.

A New Technology Finds Answers

The blood-brain barrier is the brain’s frontline defense — a cellular border made up of blood vessel cells, immune cells, and other supporting cells that meticulously controls access to the brain.

Yet, these important cells have been difficult to study, even using the field’s most powerful genetic techniques. To overcome this, the Gladstone team developed MultiVINE-seq, a technology that gently isolates the vascular and immune cells from postmortem human brain tissue.

This technology allowed the team, for the first time, to simultaneously map two layers of information: the gene activity and the “dimmer switch” settings — known as chromatin accessibility — within each cell. The scientists studied 30 brain samples from individuals with and without neurological disease, giving them a detailed look at how genetic risk variants function across all major brain cell types.

Working closely with Gladstone Investigators Ryan Corces, PhD, and Katie Pollard, PhD, lead authors Madigan Reid, PhD, and Shreya Menon integrated their single-cell atlas with large-scale genetic data from studies of Alzheimer’s, stroke, and other brain diseases. This revealed where disease-associated variants are active — and many were found to be active in vascular and immune cells rather than neurons.

“Before this, we knew these genetic variants increased disease risk, but we didn’t know where or how they acted in the context of brain barrier cell types,” Reid says. “Our study shows that many of the variants are actually functioning in blood vessels and immune cells in the brain.”

Different Diseases, Different Disruptions

One of the study’s most striking findings is that genetic risk variants affect the brain’s barrier system in fundamentally different ways, depending on the disease.

“We were surprised to see that the genetic drivers for stroke and Alzheimer’s had such distinct effects, even though they both involve the brain’s blood vessels,” Reid says. “That tells us they involve really distinct mechanisms: structural weakening in stroke, and dysfunctional immune signaling in Alzheimer’s.”

In stroke, genetic variants primarily affected genes responsible for the structural integrity of blood vessels, potentially weakening the vessels’ physical structure. Whereas in Alzheimer’s, the variants amplified genes that regulate immune activity, suggesting that overactive inflammation — not structural weakness — is the key issue.

Among the Alzheimer’s-associated variants, one stood out. A common variant near the PTK2B gene, which is found in more than a third of the population, was most active in T cells, a type of immune cell. The variant enhances expression of the gene, which may promote T cell activation and entry into the brain, putting immune cells into overdrive. The team found these super-charged immune cells near amyloid plaques, the sticky protein buildups that mark Alzheimer’s.

“Scientists are debating the role of T cells and related components of the immune system in Alzheimer’s,” Yang says. “Here, we provide genetic evidence in humans that a common Alzheimer’s risk factor may work through T cells.”

Excitingly, PTK2B is a known “druggable” target, and therapies that inhibit its function are already in clinical trials for cancer. The new study opens a fresh avenue to investigate whether such drugs could be repurposed for Alzheimer’s disease.

Location, Location, Location

The study’s findings on the brain’s “guardian” cells point to two new opportunities for protecting the brain.

Located at the critical interface between the brain and the body, the cells are continually influenced by lifestyle and environmental exposures, which could synergize with genetic predispositions to drive disease. Their location also makes them a promising target for future therapies, potentially allowing for drugs that can bolster the brain’s defenses from the “outside” without needing to cross the formidable blood-brain barrier.

“This work brings the brain’s vascular and immune cells into the spotlight,” Yang says. “Given their unique location and role in establishing the brain’s relationship with the body and outside world, our work could inform new, more accessible drug targets and lifestyle interventions to protect the brain from the outside in.”

About the Study

The study, “Human brain vascular multi-omics elucidates disease risk associations,” was published in the journal Neuron on July 28, 2025.

In addition to Yang, Reid, Corces, and Pollard, the study’s other authors are Shreya Menon, Hao Liu, Haoyue Zhou, Zhirui Hu, Bella Ding, Zimo Zhang, Sophia Nelson, and Amanda Apolonio of Gladstone; Simon Frerich of UC San Francisco; Shahram Oveisgharan and David A. Bennett of Rush University Medical Center; and Martin Dichgans of LMU Munich.

The work was supported by the National Institute of Neurological Disorders and Stroke (1R01NS128909-01), Alzheimer’s Association (ADSF-24-1345199-C, AARF-22-923641), BrightFocus Foundation (A2022027F), Cure Alzheimer’s Fund, the Ludwig Family Foundation, the Dolby Family Fund, the Bakar Aging Research Institute, National Institute of Mental Health (R01- 503 MH123178), National Institute of Aging (P01-AG073082, U01-AG072573), The Leducq Foundation (22CVD01, BRENDA), the Joachim Herz Foundation, and the National Human Genome Research Institute (UM1-HG012076).

At the time when patients with lupus, or systemic lupus erythematosus (SLE), are diagnosed, approximately 15% to 30% will already have the inflammation-caused kidney disease lupus nephritis, which compromises kidney function and can lead to kidney failure. Between 30% and 50% of SLE patients will ultimately go on to develop lupus nephritis, and half of them will eventually develop end-stage renal disease.

A Medical University of South Carolina research team led by Jim Oates, M.D., director of the Division of Rheumatology and Immunology and vice chair for Research in the Department of Medicine, is developing a new approach to preventing lupus nephritis – improving the health and function of the cells that line the kidney blood vessels, or renal endothelial cells, to prevent immune cells from leaking into kidney tissue and damaging it.

The team reports in Lupus Science & Medicine that the exposure of renal endothelial cells to serum from patients with lupus nephritis who are experiencing a flare caused the cells to malfunction, leading to inflammation. In contrast, when those same cells were exposed simultaneously to flare lupus nephritis serum and the investigational drug L-sepiapterin, inflammation was reduced, and genes associated with the production of nitric oxide, known to be protective against inflammation, were enhanced. Serum was obtained from a biobank with specimens from patients with lupus, and the South Carolina Clinical & Translational Research Institute assisted with the processing and banking of samples.

In patients with SLE, an autoimmune disease, the body musters its immune defenses not against an invading germ but against the body itself, causing inflammation, tissue damage and sometimes organ failure. In lupus nephritis, it is the kidney that is targeted by the immune system.

“I liken this targeting by the immune system to what happens after a transplant,” said Oates. “So patients who have had a transplanted kidney require drugs that suppress the immune system to prevent rejection. In the case of those with lupus nephritis, they’re rejecting their own kidney.”

Immune suppression has also been the go-to therapy for patients with lupus nephritis, but it carries a cost – patients become much more vulnerable to infection.

The treatment approach being developed by the Oates Lab does not suppress natural body functions, such as immunity, but uses pharmaceuticals to dial back inflammation and establish a more protective environment for endothelial cells, enabling proper functioning.

“When the endothelial cells that line your blood vessels are impaired, it puts people at risk for things like heart attacks and strokes but also inflammatory or scarring events in the kidney. It puts people at risk for organ damage,” said Oates. “That’s a major focus of my laboratory – to restore the protective effects of properly functioning endothelial cells.”

Oates Laboratory manager Dayvia Russell, first author of the recent publication, sums up the new approach.

“The vasculature is the gateway to your organs,” she said. “The concept of our research is to try to protect the kidneys in patients with lupus nephritis by preventing vascular damage.”

The key to maintenance of healthy endothelial cells is the production of the molecule nitric oxide, which can protect against inflammation and oxidative stress as well as help to maintain healthy blood flow and prevent leakage of immune cells into the tissue. However, oxidative stress, such as that produced by risk factors for chronic disease, such as obesity, smoking and diabetes, can cause endothelial cells to malfunction, making inflammation more likely.

Specifically, oxidative stress interrupts nitric oxide production by disabling the enzyme endothelial nitric oxide synthase (eNOS), causing superoxide, a powerful free radical, to be produced instead. Superoxide has an unpaired electron, making it highly reactive with and damaging to other molecules.

“eNOS is a yin and yang molecule,” said Oates. “When it’s functioning properly, it can produce nitric oxide, which is protective against inflammation, but when it’s not, it can have the opposite effect, making superoxide that causes oxidative stress.”

In their study, the MUSC researchers showed for the first time the impact of lupus nephritis on the genetic profile of renal endothelial cells and the ways in which L-sepiapterin, which enhances eNOS function, alters those genetic profiles. The team showed that the exposure of renal endothelial cells to serum from patients with a flare-up of lupus nephritis led to higher expression of genes associated with inflammation. In contrast, simultaneous exposure of renal endothelial cells to both flare lupus nephritis serum and L-sepiapterin resulted in decreased expression of genes associated with oxidative stress and increased expression of genes associated with nitric oxide production, suggesting a protective effect.

This line of research is novel in that it seeks to control the inflammatory environment that can cause tissue and organ damage, not by suppressing the immune system, which can leave people susceptible to infection, but by using pharmaceuticals to adjust the natural cell processes to restore endothelial cell function and thereby protect against inflammation.

If these findings are borne out in animal studies of lupus-prone mice, the team would next like to perform a small-scale proof-of-concept study in humans once it obtains the necessary funding.

The findings could also have implications for L-sepiapterin use in diseases other than lupus nephritis, said Russell. One of the genes increased with L-sepiapterin is known to be reduced in the kidney in Type 2 diabetes.

“This suggests that L-sepiapterin has potential not only in the treatment of lupus nephritis but also other vascular diseases and maybe even Type 2 diabetes,” she said.

Unlike most cells in the human body, neurons-the functional cells of our nervous system-cannot typically replace themselves with healthy copies after being damaged. 

Rather, after an injury from something like a stroke, concussion or neurodegenerative disease, neurons and their axons, fiber-like projections that relay electrical signals, are far more likely to degrade than regenerate. 

But new research from the University of Michigan opens new ways to think about neurodegeneration that could help protect patients against that degradation and neurological decline in the future. The study, published in the journal Molecular Metabolism, could even bring us a step closer to understanding the rare cases when brains do heal and open new pathways to developing treatments, the researchers said. 

Their findings, made using a well-established fruit fly model, suggest that how resilient neurons are to degradation is connected to the fundamental process of how these cells process sugar. The work was supported by the National Institutes of Health, the U.S. National Science Foundation, the Rita Allen Foundation and the Klingenstein Fellowship in the Neurosciences.

“Metabolism is often changed in brain injury and diseases like Alzheimer’s, but we do not know whether this is a cause or consequence of the disease,” said senior author Monica Dus, U-M associate professor of molecular, cellular, and developmental biology.

“Here we found that dialing down sugar metabolism breaks down neural integrity, but if the neurons are already injured, the same manipulation can preemptively activate a protective program. Instead of breaking down, axons hold on longer.” 

Postdoctoral research fellow TJ Waller, the lead scientist in the study, found that two particular proteins appear to be involved in extending the health of axons. One is called dual leucine zipper kinase, or DLK, which senses neuronal damage, and is activated by a disrupted metabolism. The other protein is known as SARM1-short for Sterile Alpha and TIR Motif-containing 1-which has been implicated in axon degeneration and is coupled with the DLK response.

“What surprised us is that the neuroprotective response changes depending on the cell’s internal conditions,” Dus said. “Metabolic signals shape whether neurons hold the line or begin to break down.”

Generally, in cases where neurons and axons don’t degrade, DLK becomes more active and the movement of SARM1 is suppressed. But there are wrinkles. In fact, prolonged DLK activation over time leads to progressive neurodegeneration, the study showed, effectively reversing earlier neuroprotective effects. 

DLK, in particular, has emerged as a target for treating and studying neurodegenerative disease. But researchers will need to confront technical challenges to control DLK’s dual harmful and beneficial functionality, Waller said.

“If we want to delay the progression of a disease, we want to inhibit its negative aspect,” Waller said. “We want to make sure that we’re not at all inhibiting the more positive aspect that might actually be helping to slow the disease down naturally.” 

Mediating a molecule like DLK’s double functionality presents a compelling puzzle researchers have yet to solve. Uncovering the mechanisms underlying how modulators like DLK switch between these protective and harmful states could hold massive implications for the treatment of neurodegenerative disease and brain injury, directly impacting clinical populations. 

Dus and Waller said that understanding this mechanism “provides a new perspective on injury and disease, one that goes beyond simply blocking damage to focusing on what the system is already doing to reinforce it.” 

Ōtākou Whakaihu Waka-led research has found stress-controlling brain cells switch on and off in a steady rhythm about once every hour – even when nothing stressful is happening.

Senior author Associate Professor Karl Iremonger, of Otago’s Department of Physiology and Centre for Neuroendocrinology, says these rhythms shape activity patterns and alertness.

“These bursts of brain cell activity seem to act like a natural ‘wake-up’ signal, and often lead to a rise in stress hormones, or cortisol.

“This world first research opens the door to exploring how these patterns affect health, mood, and sleep,” he says.

For the study, published in high-profile journal PNAS, the researchers used an optical technique called photometry to track brain cell activity of mice and rats.

“This involved shining light into the animals’ brains, allowing us to monitor brain cell activity over the day and night as the animals moved around freely. We could then look at how the activity of brain pathways is coordinated with sleep/wake patterns and stress hormone levels.”

A group of brain cells called corticotropin-releasing hormone (CRH) neurons were found to be particularly important for the daily rhythms of stress hormone release.

“These neurons turn on and off in a regular pattern about once every hour. Interestingly, we found that these changes were coordinated with patterns of sleep and waking which suggests that the pattern of release is coordinated with wakefulness or alertness.

“We also found when the CRH neurons were artificially activated, this changed the animals’ behaviour – animals that were previously quietly resting became hyper-active.”

Associate Professor Iremonger says the research findings may lead to a better understanding of how disrupted stress rhythms can result in changes in mood and disrupted sleep.

Drugs that decrease CRH stress neuron activity may also be beneficial at treating conditions associated with hyper-active stress responses.

“Our new research is helping us to understand how the brain controls these normal rhythms of stress hormone release. Knowing how these brain signals work will help us understand the links between stress hormone levels, alertness and mental health.”

More than a decade ago, researchers found that an acute complication of type 1 diabetes, diabetic ketoacidosis (DKA), can be resolved with the hormone leptin, even in the absence of insulin. 

An analysis published today in The Journal of Clinical Investigation explains how leptin affects the brain and how it might be used in future therapeutics. 

DKA happens when the body is unable to make insulin and begins to break down fat for fuel. This can lead to a life-threatening buildup of sugar (glucose) and ketoacids in the blood. Doctors have typically administered insulin to address the complication, authors noted. 

But evidence now shows that, when insulin is insufficient, the brain plays a key role in driving DKA, according to the new analysis, based in literature and research that includes studies conducted at UW Medicine since 2011. 

When the pancreas can’t make insulin, “the brain gets the message that the body is out of fuel, even if it’s not. This information is being communicated in part by a low blood level of the hormone leptin,” said senior author Dr. Michael Schwartz, professor of medicine, Division of Metabolism, Endocrinology and Nutrition at the University of Washington School of Medicine. 

Leptin helps the brain regulate appetite and body weight. Leptin is produced by your body’s fat cells. The hormone is carried by the bloodstream into your brain, particularly an area called the hypothalamus. This is the part of your brain that controls when and how much you eat. Insufficient leptin leads the brain to activate circuits that mobilize energy sources, including glucose and ketones. 

Schwartz and his team discovered this connection in 2011 when they first administered leptin into the brain of rats and mice with type 1 diabetes. At first, nothing happened. But four days later, they were astonished when the animals’ blood glucose and ketone levels became completely normal, despite ongoing severe insulin deficiency.

“I think the most amazing thing is that the blood sugars just didn’t come down, but that the levels stayed down,” he said. “If you tried to get them to rise, they came back down. If you tried to lower them, they came back up.” 

These responses suggested that the brain can maintain normal blood sugar levels even in the absence of insulin, Schwartz said. 

At the time, the diabetes research community didn’t know what to make of the discovery. 

“We now have a much better understanding of a finding that was largely ignored by the scientific community when it was first reported in 2011,” Schwartz said. 

Schwartz said he will seek FDA approval to begin human trials to test whether leptin is capable of normalizing blood sugar levels in people with type 1 diabetes. 

Positive results would open the door to pharmaceutical therapies for type 1 diabetes that target the brain.

“This is one of the most exciting discoveries of my career,” said co-author Dr. Irl Hirsch, a UW Medicine’s diabetes treatment and teaching chair and a professor of metabolism, endocrinology and nutrition at the University of Washington School of Medicine. 

Hirsch said controlling blood glucose with leptin could unlock new avenues of treatment for patients.

“Don’t get me wrong, discovering insulin 104 years ago is one of the greatest discoveries of the last century,” said Hirsch, who has had type 1 diabetes since childhood. “But this, this is the next step. This might be a better way.” 

Schwartz noted that insulin management is a substantial burden for patients and their families. 

“I think if you could treat type 1 diabetes without daily insulin injections and blood sugar monitoring, patients would say that is the greatest thing ever,” he added.

If the brain can be convinced that fuel stores are not depleted, or if specific brain neurons that trigger the production of glucose and ketones are turned off, the body stops the reaction that leads to severe hyperglycemia and DKA. 

“This new framework challenges that conventional wisdom about insulin deficiency as the sole cause of diabetic ketoacidosis that has been widely accepted for decades,” said Schwartz. “It shows that the brain plays a powerful role in the genesis of uncontrolled diabetes – and may hold the key to new treatments.” 

Funding for this research was supported by National Institutes of Health (grants DK083042, DK101997, DP2DK128802, DK089056, DK124238 and S10OD036208); the NIH-NIDDK funded Nutrition Obesity Research Center (NORC P30DK035816), Diabetes Research Center (DRC P30DK017047) and the Diabetes, Obesity and Metabolism Training Grant (T32 DK007247) at the University of Washington; and the Department of Defense Peer-Reviewed Medical Research Program (W81XWH-20-1-0250). 

As the proportion of the global population living in cities rises to 70% by 2050, mental health challenges more common in urbanites – such as anxiety and mood disorders – become even more broadly relevant. A new study from the Stanford University-based Natural Capital Project (NatCap) shows that spending even a little time in nature provides significant benefits for a broad range of mental health conditions. The results, published today in Nature Cities, offer guidance to urban planners, policymakers, and others for how to use greenspace as a mental health solution, one that comes with additional benefits like lowering temperatures and sequestering carbon. The research team is now incorporating its findings into a modeling tool for urban planners. 

“We are working to translate the effect size we found through this analysis to more intuitive indicators that would be useful for decision-makers by way of a new mental health-focused InVEST model,” said Yingjie Li, postdoctoral scholar at NatCap and lead author of the study. “For example, we could run scenarios like: if a city currently has 20% green space or tree cover, how many preventable cases of mental health disorders could be avoided if that were increased to 30%? We will also be working to include estimates of the potential avoided healthcare costs associated with such improvements in urban nature.”

NatCap’s flagship mapping and modeling tools, known as InVEST, are used around the world to quantify ecosystem services, or nature’s benefits to people. For years the team has been building a collection of tools focused specifically on nature in cities. Yet while research in multiple countries has shown this includes both mental and physical health, that evidence had not yet been pulled into InVEST.

“Previous studies have documented strong links between contact with nature and mental health,” said Anne Guerry, chief strategy officer and lead scientist at NatCap and senior author on the paper. “But with most studies, you either can’t infer a causal link, they can’t be easily generalized, or they aren’t designed to distinguish the effects of different types of nature. This analysis helps fill that gap.”

The team’s analysis collates data from close to 5,900 participants across 78 field-based experimental studies, all either randomized controlled trials or pre-post intervention studies. While all types of urban nature provided benefits, the researchers found urban forests were even better for certain measures like reducing depression and anxiety. Young adults experience even greater benefits than the general population – an important data point because most mental health disorders emerge before the age of 25. Perhaps surprisingly, spending non-active, stationary time in greenspaces was more effective at reducing negative mental health outcomes like depression than active time in nature, though both are equally beneficial for positive outcomes like vitality (measured by asking how alive, alert, and energized people feel). They also found effects to be greater in Asian countries, where physiological effects may be enhanced by cultural associations with nature that “prime” people to their benefits. 

Based on the findings of this analysis, while larger city parks and forests are critical, the researchers suggest it is also important to create smaller “pocket parks” and additional street trees to increase access throughout cities. Even additional windows with views facing green spaces could be beneficial, as well as quiet, nature-filled spaces and community programming that provides passive nature exposure such as guided park meditation – relatively low-cost methods for improving public health in cities. 

At the personal level, Li has found that doing this work has improved his own lifestyle. He walks to the office more frequently and finds he is more curious about birds and plants he encounters along the way. “I also talk to my friends about thinking this way and encourage them to notice how even small moments with nature can make a difference. This work has helped me see that urban nature isn’t just good for cities – it’s good for us.” said Li. 

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Li is also a postdoctoral scholar in the Department of Biology in Stanford’s School of Humanities and Sciences (H&S). Additional Stanford NatCap co-authors on the paper are Lisa Mandle (NatCap/Woods Institute), Anders Rydström (NatCap/Biology, H&S), Tong Wu (NatCap/Woods Institute), Yougeng Lu (NatCap/Biology, H&S), and Gretchen Daily (NatCap/Biology, H&S and Woods Institute). The other co-authors are Yuanyuan Mao and Roy P. Remme from the Institute of Environmental Sciences at Leiden University; Xin Lan from the Department of Geography, Environment, and Spatial Sciences at Michigan State University; Chao Song from the College of Ecology at Lanzhou University; Kari C. Nadeau from the Department of Environmental Health at the Harvard T.H. Chan School of Public Health; and Andreas Meyer-Lindenberg from the Department of Psychiatry and Psychotherapy, Central Institute of Mental Health and Medical Faculty Mannheim/University of Heidelberg.

This research is supported by grants from the Stanford Woods Institute for the Environment’s Realizing Environmental Innovation Program, the Cyrus Tang Foundation, the Marcus and Marianne Wallenberg Foundation, the Heinz Foundation, the Winslow Foundation, and individual contributors John Miller and Kristy Hsiao.

The Natural Capital Project is based out of the Woods Institute for the Environment in the Stanford Doerr School of Sustainability and the Department of Biology in the Stanford School of Humanities and Sciences.

In a new study aimed at identifying the best approach to promote colorectal cancer screening in adults ages 45 to 49, UCLA researchers found that simply mailing a stool-based test directly to people’s homes was the most effective strategy for increasing screening rates.

The study, published in JAMA, compared four strategies to increase colorectal cancer screening in this population, which only recently became eligible for screening. Of the four options tested, the researchers found that automatically mailing a stool-based screening test without an option to opt in or out resulted in the highest screening rates. 

Only about 15% to 17% of people completed screening when they had to actively opt into screening or pick a screening test. But when an at-home test was automatically mailed to them, more than 26% got screened. 

“When national guidance recommended screening adults age 45 to 49 for colorectal cancer for the first time, it wasn’t clear how to best reach and screen this newly eligible population,” said Dr. Folasade May, a gastroenterologist and cancer prevention researcher at the UCLA Health Jonsson Comprehensive Cancer Center and senior author of the study. “Removing the need for patients to actively opt into screening can lead to better outcomes, particularly when trying to engage younger, generally healthy adults who may not yet perceive themselves at risk for cancer.”

The study, which included more than 20,000 patients, is among the first large-scale efforts to examine how to effectively engage this newly eligible age group in potentially life-saving colorectal cancer screening.

This is vital as colorectal cancer rates have been rising among younger adults. It is now the leading cause of cancer-related deaths in men aged 20 to 49 years and the second leading cause in women in the same age group. In 2021, the U.S. Preventive Services Task Force lowered the recommended screening age from 50 to 45. Yet participation among this newly eligible group has remained dismally low, with fewer than 2% getting screened within 20 months of the guideline change. 

“There has been an urgent need for evidence on how to reach adults in their 40s with effective, scalable screening strategies,” said May, an associate professor of medicine at the David Geffen School of Medicine at UCLA. 

The team tested four different outreach strategies by sending information through UCLA Health’s electronic patient portal to 20,509 patients who were considered at average risk for colorectal cancer. The researchers wanted to see which approach led to the most people actually getting screened, which type of test they chose and whether certain groups were more or less likely to participate. 

The four strategies were:

1. Asking patients if they would like to opt into screening by receiving a mailed stool test (known as a FIT kit).
2. Asking patients if they would like to opt into screening with a colonoscopy.
3. Asking patients if they would like to opt into screening and to make a choice between FIT and colonoscopy.
4. Simply mailing the FIT kit to patients without asking them to opt in.

The researchers found that participants who were asked to actively opt into screening (strategies 1-3) had lower overall screening rates. Among those offered the option to opt into the at-home stool test (FIT), 16.4% completed screening. In the group offered to opt into colonoscopy, the rate was 14.5%. When patients were given the option to opt into FIT or colonoscopy, 17.4% completed screening. 

The most effective strategy involved default mailing patients a FIT kit without requiring them to opt into screening or to make a choice between screening tests, resulting in a screening rate of 26.2%.

The team also found that 73% of those with abnormal FIT results followed up with a colonoscopy within six months, a key next step in cancer screening and encouraging given typically low follow-up rates. 

Although mailing the FIT kit directly performed best, overall screening rates were still low, researchers note. Still, this approach represents a meaningful step forward, highlighting a simple, low-cost intervention that can help close critical screening gaps and save lives. Further research is needed to optimize and tailor mailed FIT outreach strategies to boost participation even more.

“Our study showed that automated outreach can get results quickly and efficiently,” said May. “More than 3,800 people were screened in just six months with minimal work required from our busy doctors. That’s thousands of opportunities to catch cancer early or prevent it altogether.”

The first authors of the study are Dr. Artin Galoosian, a former fellow in the Vatche and Tamar Manoukian Division of Digestive Diseases at the David Geffen School of Medicine at UCLA, and Dr. Hengchen Dai, Associate Professor of Management and Organizations, Anderson School of Management at UCLA. Additional authors include Dr. Folasade May (senior author), Dr. Daniel Croymans, Dr. Maria Han, Dr. Sitaram Vangala, Dr. Sadie De Silva, and Dr. Gregory Goshgarian from the department of medicine at UCLA, Dr. Craig Fox from the Anderson School of Management at UCLA, and Dr. Silvia Saccardo from Carnegie Mellon University and the Anderson School of Management at UCLA. 

Using a custom-built tool to analyze electrical activity from neurons, researchers at Brown University have identified a brain-based biomarker that could be used to predict whether mild cognitive impairment will develop into Alzheimer’s disease.

“We’ve detected a pattern in electrical signals of brain activity that predicts which patients are most likely to develop the disease within two and a half years,” said Stephanie Jones, a professor of neuroscience affiliated with Brown’s Carney Institute for Brain Science who co-led the research. “Being able to noninvasively observe a new early marker of Alzheimer’s disease progression in the brain for the first time is a very exciting step.” 

The findings were published in Imaging Neuroscience.

Working with collaborators at the Complutense University of Madrid in Spain, the research team analyzed recordings of brain activity from 85 patients diagnosed with mild cognitive impairment and monitored disease progress over the next several years. The recordings were made using magnetoencephalography, or MEG – a noninvasive technique to record electrical activity in the brain – while patients were in a resting state with their eyes closed.

Most methods for studying MEG recordings compress and average the detected activity, making it difficult to interpret at the neuronal level. Jones and other researchers at Brown pioneered a computational tool, called the Spectral Events Toolbox, that reveals neuronal activity as discrete events, showing exactly when and how often activity occurs, how long it lasts and how strong or weak it is. The tool has become widely used and has been cited in more than 300 academic studies.

Using the Spectral Events Toolbox, the team looked at brain activity events in patients with mild cognitive impairment, occurring in the beta frequency band –– a frequency that has been implicated in memory processing, making it important to study in Alzheimer’s disease, according to Jones. They discovered distinct differences in the beta events of the participants who developed Alzheimer’s disease within two and a half years, in comparison with those who did not.

Two and a half years prior to their Alzheimer’s disease diagnosis, patients were producing beta events at a lower rate, shorter in duration and at a weaker power. To our knowledge, this is the first time scientists have looked at beta events in relation to Alzheimer’s disease.”

Danylyna Shpakivska, the Madrid-based first author of the study

Spinal fluid and blood biomarkers can identify the presence of toxic beta amyloid plaques and tau tangles –– proteins that build up in the brain and are thought to contribute to Alzheimer’s disease symptoms. A biomarker from brain activity itself represents a more direct method of assessing how neurons respond to this toxicity, said David Zhou, a postdoctoral researcher in Jones’ lab at Brown who will lead the next phase of the project.

Jones envisions that the Spectral Events Toolbox could be used by clinicians to diagnose Alzheimer’s disease before it progresses. 

“The signal we’ve discovered can aid early detection,” Jones said. “Once our finding is replicated, clinicians could use our toolkit for early diagnosis and also to check whether their interventions are working.”

Meanwhile, Jones and her team will move into a new phase of research, funded by a Zimmerman Innovation Award in Brain Science from the Carney Institute. 

“Now that we’ve uncovered beta event features that predict Alzheimer’s disease progression, our next step is to study the mechanisms of generation using computational neural modeling tools,” Jones said. “If we can recreate what’s going wrong in the brain to generate that signal, then we can work with our collaborators to test therapeutics that might be able to correct the problem.”

The research was supported by the National Institutes of Health, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, in addition to funding from agencies in Spain. 

The World Health Organization (WHO) announces the reclassification of hepatitis D as cancerous, emphasizing the urgent need for the elimination of viral hepatitis, according to an official news release. The agency calls on governments to act amid a growing public health crisis.

Viral hepatitis is highly prevalent across the globe, affecting nearly 300 million people and claiming the lives of over 1.3 million each year. Hepatitis is a viral infection that can be acute or chronic, depending on the specific type. For chronic infections, symptom management is the standard of care. However, vaccines can help prevent infection with viral hepatitis.^1,2

“Every 30 seconds, someone dies from a hepatitis-related severe liver disease or liver cancer. Yet we have the tools to stop hepatitis,” Tedros Adhanom Ghebreyesus, MD, WHO Director-General, said in an official news release.¹

There are 5 types of hepatitis viruses. They include³:

• Hepatitis A: Caused by the hepatitis a virus (HAV); contracted from consuming contaminated food or water
• Hepatitis B: Caused by hepatitis B virus (HBV); most common liver infection in the world; often acute but can be chronic
• Hepatitis C: Spreads through shared needles or syringes; more likely to be chronic
• Hepatitis D: Caused by the hepatitis D virus (HDV); most common in those with hepatitis B
• Hepatitis E: Caused by the hepatitis E virus (HEV); typically resolves without treatment; treatment required for pregnant individuals

All types of hepatitis are associated with acute liver infection; however, only hepatitis B, C, and D can lead to chronic infections with a higher risk of liver cirrhosis, failure, or cancer. According to the authors of the study’s findings, hepatitis D is associated with a 2- to 6-fold higher risk of liver cancer compared with hepatitis B.¹

The WHO’s announcement stems from the International Agency for Research on Cancer’s (IARC) reclassification of hepatitis D as carcinogenic, supported by data from a study published in The Lancet Oncology. The study assessed the carcinogenic potential of HDV, human cytomegalovirus (HCMV), and Merkel cell polyomavirus (MCPyV).^4,5

HDV is a single-stranded RNA virus that depends on the presence of the hepatitis B virus for replication and infection. HCMV, a member of the beta-herpesvirus family, is commonly transmitted via bodily fluids and can be passed from mother to fetus during pregnancy. MCPyV is a widely circulating virus typically acquired during early childhood through direct contact and is known to persist on the skin as part of the normal virome.⁵

The WHO’s classification of hepatitis D as carcinogenic marks a pivotal moment in the global fight against viral hepatitis. With mounting evidence linking HDV to significantly elevated cancer risk, health leaders are urging swift policy action, expanded access to hepatitis B vaccination, and stronger surveillance systems. As the burden of viral hepatitis continues to grow—despite the availability of effective prevention tools—experts stress that eliminating hepatitis is not only possible but also essential to reducing liver cancer worldwide.

REFERENCES

1. WHO urges action on hepatitis, announcing hepatitis D as carcinogenic. WHO. July 28, 2025. Accessed August 4, 2025. https://www.who.int/news/item/28-07-2025-who-urges-action-on-hepatitis-announcing-hepatitis-d-as-carcinogenic

2. Global viral hepatitis. CDC. July 25, 2025. Accessed August 4, 2025. https://www.cdc.gov/hepatitis/global/index.html

3. What is viral hepatitis? Cleveland Clinic. March 27, 2025. Accessed August 4, 2025. https://my.clevelandclinic.org/health/diseases/4245-hepatitis-viral-hepatitis-a-b–c#overview

4. Karagas M, Kaldor J, Michaelis M, et al. Carcinogenicity of hepatitis D virus, human cytomegalovirus, and Merkel cell polyomavirus. The Lancet Oncology. June 27, 2025. doi: 10.1016/S1470-2045(25)00403-6

5. IARC Monographs evaluation of the carcinogenicity of hepatitis D virus, human cytomegalovirus, and Merkel cell polyomavirus. International Agency for Research on Cancer. June 27, 2025. Accessed August 4, 2025. https://www.iarc.who.int/news-events/iarc-monographs-evaluation-of-the-carcinogenicity-of-hepatitis-d-virus-human-cytomegalovirus-and-merkel-cell-polyomavirus/

For decades, medical professionals debated whether a common antiviral medication used to treat flu in children caused neuropsychiatric events or if the infection itself was the culprit.

Now researchers at Monroe Carell Jr. Children’s Hospital at Vanderbilt have debunked a long-standing theory about oseltamivir, known as Tamiflu.

According to the study, published in JAMA Neurology, oseltamivir treatment during flu episodes was associated with a reduced risk of serious neuropsychiatric events, such as seizures, altered mental status and hallucination.

“Our findings demonstrated what many pediatricians have long suspected, that the flu, not the flu treatment, is associated with neuropsychiatric events,” said principal investigator James Antoon, MD, PhD, MPH, assistant professor of Pediatrics in the Division of Pediatric Hospital Medicine at Monroe Carell. “In fact, oseltamivir treatment seems to prevent neuropsychiatric events rather than cause them.”

Key points:

• Influenza itself was associated with an increase in neuropsychiatric events compared to children with no influenza, regardless of oseltamivir use.
• Among children with influenza, those treated with oseltamivir had about 50% reduction in neuropsychiatric events.
• Among children without influenza, those who were treated with oseltamivir prophylactically had the same rate of events as the baseline group with no influenza.

“Taken together, these three findings do not support the theory that oseltamivir increases the risk of neuropsychiatric events,” said Antoon. “It’s the influenza.”

The team reviewed the de-identified data from a cohort of children and adolescents ages 5-17 who were enrolled in Tennessee Medicaid between July 1, 2016, and June 30, 2020.

During the four-year period, 692,295 children, with a median age of 11 years, were included in the study cohort. During follow-up, study children experienced 1,230 serious neuropsychiatric events (898 neurologic and 332 psychiatric).

The clinical outcomes definition included both neurologic (seizures, encephalitis, altered mental status, ataxia/movement disorders, vision changes, dizziness, headache, sleeping disorders) and psychiatric (suicidal or self-harm behaviors, mood disorders, psychosis/hallucination) events.

“The 2024-2025 influenza season highlighted the severity of influenza-associated neurologic complications, with many centers reporting increased frequency and severity of neurologic events during the most recent season,” said Antoon. “It is important for patients and families to know the true risk-benefit profile of flu treatments, such as oseltamivir, that are recommended by the American Academy of Pediatrics.”

“These flu treatments are safe and effective, especially when used early in the course of clinical disease,” added senior author Carlos Grijalva, MD, MPH, professor of Health Policy and Biomedical Informatics at Vanderbilt University Medical Center.

Investigators hope the findings will provide reassurance to both caregivers and medical professionals about the safety of oseltamivir and its role in preventing flu-associated complications.

The study was funded by the National Institutes of Health (grants K23AI168496, K24AI148459 and P50HD106446).

Source:

Vanderbilt University Medical Center