Publisher Health

Exposure to several combinations of toxic atmospheric pollutants may be triggering asthma symptoms among children, a recent analysis suggests.
The study, published in the journal Science of the Total Environment, showed that 25 different combinations of air pollutants were associated with asthma symptoms among 269 elementary school children diagnosed with asthma in Spokane, Washington. In line with previous research, the Washington State University-led study revealed a socioeconomic disparity — with one group of children from a lower-income neighborhood exposed to more toxic combinations, a total of 13 of the 25 identified in this research.
“It’s not just one pollutant that can be linked to asthma outcomes. This study examined the variety and combinations of air toxics that may be associated with asthma symptoms,” said lead author Solmaz Amiri, a WSU researcher in the Elson S. Floyd College of Medicine.
While other studies have focused on a limited number of pollutants, Amiri and her colleagues used the data-crunching power of machine learning techniques to analyze the potential exposure effects of 109 air pollutants and their combinations on asthma outcomes.
The researchers drew on data collected and modeled by the Environmental Protection Agency on air toxics present in individual neighborhoods surrounding 10 Spokane elementary schools. They also accessed anonymized data from the elementary schools for reports of students diagnosed with asthma who experienced symptoms such as coughing, wheezing, difficulty breathing and the need to use an inhaler.
The study looked at asthma symptoms occurring in 2019 and 2020 in the six months before the pandemic lockdowns started in March 2020. The researchers then associated these data with air pollutant exposures that occurred within those six months and with two longer-term exposure periods of three years and five years prior to the asthma symptoms.
The researchers found that three specific pollutants were significantly associated with asthma symptoms across all three exposure periods.

The toxicants involved may have unfamiliar names — 1,1,1 trichloroethane, 2-nitropropane and 2, 4, 6 trichlorophenol — but they derive from commonly used materials. The first is a widely used solvent in industry but was formerly used in household cleaners and glues. The second is an additive to paints and other finishes, and the third is an anti-septic and anti-mildew agent that was banned in the 1980s but may still be found in some pesticides and preservatives made before then.
“Some of these air toxics were discontinued in the U.S., but they can still be found in materials that may be in storage or people have in their backyard or garage. Other air toxics still exist at least in the environment,” said Amiri.
This study did not intend to pinpoint the source of any one air pollutant or the exact reason why one group of children from a lower-income neighborhood was highly exposed to air pollutants. However, proximity of known air pollution sources may play a role, Amiri said, such as living close to a highway with a lot of traffic or facilities that use solvents, such as paint producers or factories.
The finding of a likely socioeconomic disparity in air toxic exposures is consistent with previous research showing that children from lower-income areas, often indicated by schools with a higher percentage of students who qualify for free or reduced meals, are exposed to a wide variety of air pollutants in the neighborhoods where they live.
While the current study is limited to the mid-sized city of Spokane, Amiri noted that the findings align with another study in New York City which found similar air pollutants significantly associated with asthma outcomes.
“Both in Spokane and New York City, regardless of the setting — how large or small the cities are — these air toxics appear to be influencing asthma among children,” she said.
This study received support from the National Institutes of Health and the Ramboll Foundation.

Hitting targets embedded within the cell membrane has long been difficult for drug developers due to the membrane’s challenging biochemical properties. Now, Scripps Research chemists have demonstrated new custom-designed proteins that can efficiently reach these “intramembrane” targets.
In their study, published March 13, 2024, in Nature Chemical Biology, the researchers used a unique computer-based approach to design novel proteins targeting the membrane-spanning region of the erythropoietin (EPO) receptor, which controls red blood cell production and can go awry in cancers. In addition to these new EPO-targeting molecules, the study yielded a general computational process, or “workflow,” for streamlining the flexible custom design of proteins aimed at intramembrane targets.
The researchers are now using their approach to develop potential new intramembrane-targeting treatments across a wide range of diseases.
“This work opens up many new possibilities for the modulation of targets within the cell membrane, including for therapeutic applications and understanding signaling mechanisms across cell biology,” says study co-corresponding author Marco Mravic, PhD, an assistant professor in the Department of Integrative Structural and Computational Biology at Scripps Research.
The study’s other co-corresponding authors were Daniel DiMaio, MD, PhD, of the Yale School of Medicine; and William DeGrado, PhD, of the University of California, San Francisco School of Pharmacy, where Mravic was previously a PhD student.
“A major goal of synthetic biology is to design proteins with biological activity — here, we report the design and testing of a small protein that specifically perturbs the activity of a much larger protein receptor involved in blood cell growth and differentiation,” says DiMaio, who is a professor of Genetics and of Molecular Biophysics and Biochemistry, and deputy director of Yale Cancer Center. “We accomplished this by targeting the segment of the receptor that crosses the cell membrane. Because many cell proteins contain structurally conserved membrane-spanning segments, this general approach may be applicable to many other protein targets and provides a new tool to modulate the behavior of cells.”
Hitting intramembrane targets has long been an important goal in biomedicine since many proteins in cells — especially receptor proteins — have functionally important domains inside the membrane. Such proteins have prominent roles in almost every area of health and disease.

Yet intramembrane targets are not ordinary targets. Cell membranes generally are made of two layers of tightly spaced, fat-related “lipid” molecules, which are water-repellent and have other unique and complex properties. This makes the intramembrane space a much harder target for drug designers, compared to the watery zones of cell surfaces or interiors.
“There have been very few successful examples of drugs that target this space inside the membrane,” Mravic says.
Those few successes, which include treatments for low-blood-platelet disorders and cystic fibrosis, have come from blind screenings of large compound libraries or from close mimicry of proteins known to interact with partner proteins within the cell membrane. By contrast, Mravic and colleagues set out to design completely novel proteins — small ones called peptides — to hit intramembrane protein targets in new and diverse ways. To do that, they had to extend the frontier of computational methods, combining “data mining” of known protein-to-protein interactions in membranes with traditional physics-based predictions of protein interactions.
Ultimately, Mravic and his colleagues designed the first proteins that bind the EPO receptor’s membrane-spanning portion in a new way — not seen in nature. The team showed that these proteins very specifically and potently block the receptor’s function, in contrast to prior approaches.
The results may be of most immediate interest to researchers seeking new ways to inhibit the EPO receptor, which is often abnormally activated by tumor cells to maintain their growth and survival. But for Mravic and his colleagues, the study above all represents a proof of principle of a new and more flexible approach to intramembrane targeting.
“We intend to use this approach to target membrane proteins across multiple biological processes and disease areas, including cancers, immune disorders, and pain,” Mravic says.
He also expects the computational workflow he designed for the project to be a general accelerator of membrane-targeting drug design.
“Before, the process basically involved two people in a dark room looking at a computer screen and saying, ‘Yeah, I think this looks better than that,'” Mravic says. “Now, we’ve automated a lot of that molecule design process and decision making in the computer. Being more modular, flexible and streamlined allows the method to be more accessible for a broader range of scientists.”

Participation in recreational activities — including golfing, gardening or yard work, woodworking and hunting — may be associated with an increase in a person’s risk for developing amyotrophic lateral sclerosis, or ALS, a Michigan Medicine study finds.
While many activities were associated with increased ALS risk, several were sex specific. The results are published in the Journal of the Neurological Sciences.
“We know that occupational risk factors, like working in manufacturing and trade industries, are linked to an increased risk for ALS, and this adds to a growing literature that recreational activities may also represent important and possibly modifiable risk factors for this disease,” said first author Stephen Goutman, M.D., M.S., director of the Pranger ALS Clinic and associate director of the ALS Center of Excellence at University of Michigan.
“Future studies should include these activities to pinpoint how they can be understood in the context of ALS prevention, diagnosis and treatment.”
Investigators surveyed 400 people living with ALS and nearly 300 without the condition to assess their hobbies and non-work related activities.
They found that golf was associated with three times greater risk for developing ALS among men. Participation in gardening or yard work, as well as woodworking and hunting, was also linked with a heightened risk for men.
When broken down by sex, no recreational activities had significant associations with ALS for females. None of the hobbies were linked to earlier onset of, or death from, ALS for either sex.

“It is surprising that the risk factors we identified appear to be specific to males,” Goutman said.
“While these activities may also increase ALS risk in females, the number of females in our study was too small for us to come to that conclusion.”
The findings join the growing body of evidence suggesting that environmental exposures affect a person’s risk for getting and dying from amyotrophic lateral sclerosis. Researchers call this lifetime accumulation of exposures the ALS exposome.
Hobbies such as golfing and gardening or yardwork, Goutman says, may confer risk due to the use of pesticides. A past study connected occupations in golf and garden maintenance to increased ALS risk.
Extensive studies of woodworking lead researchers to believe that formaldehyde exposure during the hobby could be attributed to higher risk.
“Our goal is to understand what occupations and hobbies increase ALS risk because identifying these activities provides the first step towards ALS prevention,” said senior author Eva Feldman, M.D., Ph.D., director of the ALS Center of Excellence at U-M and James W. Albers Distinguished University Professor at U-M.
“For a disease like Alzheimer’s, we know that a list of factors — including smoking, obesity and high lipids — can increase risk by 40%. Our goal is to establish a similar list for ALS to create a roadmap to decrease risk. With apologies to Robert Frost, it is currently the ‘road not taken’, and we want to change that.”
Prospective studies are underway to examine individuals who work in production, manufacturing and jobs that involve use of metals, and for persons with a family history of ALS.
Both Goutman and Feldman say it is too early for clinicians to advise that patients stop doing any of these activities.

A team of scientists from DTU and other European universities have uncovered an overlooked mechanism in the gut immune system of patients suffering from severe cases of Crohn’s disease. The discovery may help define how to treat patients with severe Crohn’s disease.
Tricks played by certain disease-driving gut bacteria might help explain differences in how patients experience Crohn’s disease (CD) — a severe and painful chronic inflammatory bowel disease. A new study by researchers from DTU and 3 European universities shows that antibodies in the gut immune system, which line the stomach and intestinal walls and keep harmful bacteria at bay, may be crucial in understanding why some CD patients suffer more than others.
These antibodies — immunoglobulins — are integral to our immune system. They bind to pathogens such as bacteria, viruses, and fungi that enter the gut and cover parts of their cell surface. The term for this is “coating,” which helps in several ways. For one, the coating effectively inhibits the bacteria from spreading and makes them lump together under certain circumstances. Also, it alerts the rest of the immune system and marks the pathogens for destruction.
The main issue regarding Crohn’s disease, specifically, is that there isn’t enough evidence to explain precisely why some people end up with severe inflammation in their gut. We also do not know the influence bacterial coating with different antibody types may have on this. Hence, there is currently no cure for Crohn’s disease.
“We know that some bacteria can hide from the immune system, and in this study, we find that especially two — Campylobacter and Mannheimia — seem to be prevalent in severe cases. They appear to hold properties that allow them to escape from antibody coating while simultaneously being able to activate and cause an uncontrolled inflammation,” says Susanne Brix Pedersen, a professor at DTU Bioengineering, Technical University of Denmark.
She is the corresponding author of the study — “Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn’s disease” — recently published in the journal Gut. The study shows that the immune system of patients with severe Crohn’s disease holds a remarkably high coating of certain gut bacteria with a specific antibody type indicative of inflammation. At the same time, Campylobacter and Mannheimia can circumvent this coating.
An overlooked antibody is active in severe cases
Several types of antibodies fight off pathogens, and the primary antibody responsible for coating bacteria in the gut is Immunoglobulin A (IgA). Limited effort has been put into mapping out the roles of other antibodies, such as IgM and IgG, at mucosal surfaces.

However, the new paper shows that IgG plays a significant role in the gut immune system, especially concerning severe cases of Crohn’s disease. This is somewhat surprising since IgG is found mainly in the blood and other body fluids and is generally considered a second line of defence against pathogens, whereas IgA is regarded as the primary antibody to prevent incoming pathogens from entering the body and bloodstream via the gut and other mucosal surfaces.
IgG exists as four subtypes: IgG 1, 2, 3, and 4. They serve different purposes in our immune system. While the paper shows that bacterial coating with IgG1 and IgG4 was indistinguishable between patients with Crohn’s disease and healthy controls, the fraction of patients with severe Crohn’s disease exhibited higher bacterial coating with IgG2.
The immune system of patients with severe CD is thus acting differently from healthy individuals and patients with less severe CD. This is important information since it may, with time, turn out that clinicians can use this altered state to have a so-called ‘biomarker’ — a measurable, biological indicator of more serious cases of CD.
“Although it is a bit weird to try and differentiate between people with Crohn’s disease because everyone is suffering, we do show that the level of IgG2 bacterial coating in Crohn’s patients can be used to differentiate between those who have severe disease and those who may have a slightly milder disease course. It would be a bit far-fetched to call it a biomarker. Still, we do show a strong association between IgG2 bacterial coating and disease severity, and therefore have a good indicator that IgG2 plays a substantial role in the body’s defence against bacterial infections associated with severe Crohn’s disease,” says Carsten Eriksen, first author of the paper and a postdoc at DTU Bioengineering and the Center of Excellence PREDICT.
He explains that these heightened levels of IgG2 coating of bacteria are rarely found in patients with milder symptoms or in people who don’t have Crohn’s disease.
Several possible outcomes
Further studies are needed to evaluate exactly how these results may be used to lessen the symptoms of severe cases of CD, but Susanne Brix Pedersen explains that the fact that we now know these bacteria can circumvent our immune system in this way provides an angle to explore further which other invasive bacteria might be able to do the same. And also to explore how to produce constructs that mimic the effects of antibodies, thereby hindering the targeted pathogens from causing inflammation. This approach may achieve a targeted coating of invasive bacteria responsible for worsening CD symptoms.

“Suppose we could provide the coating the immune system cannot handle alone. Then you might not have to take all sorts of other medications because you remove the thing causing the inflammation,” she says.
Carsten Eriksen highlights another possible outcome of their research:
“Today, we have no way of knowing who will end up with severe Crohn’s and who will have a less serious disease course. Crudely put, we only know for sure just before they are on the operating table. However, if we could track the appearance of bacterial IgG2 coating in the gut, we may be able to use it as an actual biomarker and differentiate between patients. In any case, I imagine clinicians looking at this research would be able to see that it is associated with several clinical outcomes, and they may find other ways to translate our results into the clinic to benefit patients.”

Americans already living in housing supported by federal housing assistance programs have significantly lower blood lead levels than counterparts who would later join these programs, according to new research led by environmental health scientists at Columbia University Mailman School of Public Health and Tufts Medical Center. The findings appear in the peer-reviewed journal Environmental Health Perspectives.
“Living in federally-supported housing — especially public housing — limited opportunities for residents’ exposure to lead,” says first author MyDzung Chu, Ph.D., assistant professor in the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center. “This likely relates to stricter compliance and enforcement of federal residential lead paint laws in HUD housing compared to non-assisted housing in the private market.”
“Federal housing assistance is an important social-structural safety net for very low-income households to access both affordable and safe, healthy housing,” adds senior author Ami Zota, PhD, associate professor of environmental health sciences at Columbia University Mailman School of Public Health. “Lead is a major health risk at any level of exposure.”
The new study is the first to examine blood lead levels (BLLs) by federal housing assistance status in a nationally representative sample of HUD-eligible adolescents and adults. Researchers used the 1999-2018 National Health and Nutrition Examination Survey (NHANES) linked with housing records from the U.S. Department of Housing and Urban Development (HUD) to compare BLLs of NHANES participants on housing assistance (a total of 3,071) at the time of the survey and those who would receive assistance within two years after the survey (i.e., pseudo-waitlist recipients, a total of 1,235).
Participants living with HUD housing assistance had 11.4 percent lower BLLs than those in the pseudo-waitlist group. They also had 40 percent lower odds of having a BLL greater than or equal to 3.5 µg/dL — a level used to identify children with BLLs higher than those of most U.S. children, determine appropriate follow-up actions, and prevent further exposure. These numbers were adjusted to account for demographic and socioeconomic confounders.
Additional findings: Comparing three main HUD housing assistance programs, public housing was the most protective against lead exposure followed by multifamily income-restricted housing. No protective effect was seen for tenant-based housing choice vouchers (HCVs). HUD enforces more stringent lead control strategies in public housing units, which provide more long-term/permanent solutions to reduce lead exposure, such as requiring lead-based paint inspections and lead abatement for affected units. In contrast, tenant-based rental assistance programs like HCVs only require that HCV-eligible units undergo a visual assessment and lead paint stabilization if lead is found, which are considered short-term/interim controls and thus less effective. The link between HUD housing assistance and BLLs was weaker for non-Hispanic Black and Mexican American participants than for non-Hispanic Whites. This discrepancy could be due to Black and Mexican American individuals’ exposure to other lead sources, such as lead-contaminated drinking water and proximity to industrial pollution, though authors could not directly assess these sources in the NHANES or HUD data. Moreover, Black households face barriers to high quality housing due to legacies of racist housing policies and urban planning practices. Black families receiving vouchers tend to live in more disadvantaged, racially segregated, and overcrowded neighborhoods compared to White families receiving vouchers. The researchers say more attention is needed to ensure quality housing and racial equity across HUD’s housing assistance programs.Key Background
BLLs in adults are linked with elevated blood pressure and risk of cardiovascular disease, renal insufficiency, and cognitive impairments. Elevated BLLs among children have been associated with neurocognitive and intellectual impairments, poor school performance, behavioral problems, and criminality later in life, even at low levels of exposure.

HUD provides affordable housing assistance to nearly 5 million families, including about 3 million children through three major programs administered by local public housing agencies: public housing (0.84 million households), tenant-based housing choice vouchers (HCVs) (2.3 million households), and multifamily income-restricted housing (1.4 million households).
Additional study co-authors include Andrew Fenelon, University of Minnesota; and Gary Adamkiewicz, Harvard T.H. Chan School of Public Health.
The study was funded by a grant from the U.S. Department of Housing and Urban Development.

Residential heating by coal has for decades been the major contributor to the high levels of air pollution in Kraków, Poland. New research finds a nearly 40 percent decline in the annual average concentration of respirable particulate matter (PM2.5) in Kraków, Poland, between 2010 and 2019 following the implementation of policies targeting emissions from the burning of coal and other solid fuels. Researchers show the improvement in air quality translated to substantial benefits for children’s outcomes, including fewer cases of asthma and better birth outcomes.
The findings by researchers at Columbia University Mailman School of Public Health and Jagiellonian University Medical College in Krakow appear in the journal Environmental Research Letters.
The researchers modeled health gains that would have occurred in 2010 if PM2.5 had been at the lower level achieved in 2019 through policy changes The benefits included 505 fewer new cases of asthma in the 1-14 age group (a 35.7% decline), 81 fewer preterm births (16.8% decrease), and 52 fewer cases of low birth weight (12.3% decrease).
They also modeled gains based on a second hypothetical, which assumed that city had adhered to the WHO’s 2005 guidelines on PM2.5. They found this scenario of a 74% reduction in PM2.5 would have avoided 780 new asthma cases in the 1-14 age group (54.5% decrease), 138 preterm births (28.3% decrease), and 90 cases of low birth weight (21.2% decrease).
In 2021, Krakow was ranked 28th out of 858 European studies in air pollution related-mortality in the ISGlobal-Ranking of Cities survey. These high levels of pollution have been attributed largely to the use of coal-burning ovens in residential spaces, and to a lesser extent transportation and power plant emissions. Government interventions, including a co-financing program to replace coal-burning stoves in the 1990s, markedly improved the city’s air quality, positively impacting children’s health outcomes. However, according to researchers, levels of human-derived air pollution, such as emissions from motor vehicles, is still a concern.
“Fetuses, infants, and children are uniquely vulnerable to air pollution,” explains study senior author Frederica Perera, PhD, DrPH, professor of environmental health sciences and director of translational research at the Columbia Center for Children’s Environmental Health at Columbia Mailman, “Our results show very large benefits can be achieved for children’s health by curbing fossil fuel emissions.”
“This is one of the first studies describing the impact of pollution on the Polish pediatric population,” noted study first author Agnieszka Pac, MSc., PhD, chair of Epidemiology and Preventive Medicine at Jagiellonian University Medical College, Krakow, Poland. “New policies must take into account children’s health, especially given that children often engage in vigorous outdoor activities, making them vulnerable to higher doses of pollutants.”
In earlier studies, the researchers reported a significant improvement in air quality based on personal air monitoring in our Kraków cohort study of pregnant women and their children based on personal air monitoring. They also identified links between air pollution exposure and birth outcomes, growth trajectories, lung function, developmental delays, behavioral problems, and cancer risk.
Additional authors of the new study include Renata Majewska, Natalia Nidecka, and Elzbieta Sochacka-Tatara from Jagiellonian University Medical College. This study was supported by a grant from an anonymous foundation.

Nagoya University researchers and their colleagues in Japan have found that middle-age obesity is caused by age-related changes in the shape of neurons in the hypothalamus, a region of the brain that controls metabolism and appetite.
A protein called melanocortin-4 receptor (MC4R) detects overnutrition and regulates metabolism and appetite to prevent obesity. According to their study in rats, MC4Rs were concentrated in primary cilia (antenna-like structures) that extend from a couple of groups of hypothalamic neurons. The study also showed that the primary cilia became shorter with age, which decreased MC4Rs accordingly, resulting in weight gain.
“We believe that a similar mechanism exists in humans as well,” said Professor Kazuhiro Nakamura of the Nagoya University Graduate School of Medicine, the lead author of the study. “We hope our finding will lead to a fundamental treatment for obesity.” The researchers published the results of the study in the journal Cell Metabolism.
As we get older, we become more prone to being overweight and obesity. Obese people are more susceptible to diabetes, hyperlipidemia, and other chronic diseases. Previous studies have suggested that middle-age weight gain is caused by a decline in overall metabolism due to aging, but the mechanism was unclear.
A research team of the Nagoya University Graduate School of Medicine, in collaboration with researchers from Osaka University, the University of Tokyo, and the Nagoya University Research Institute of Environmental Medicine, conducted a study focusing on MC4Rs.
MC4Rs stimulate metabolism and suppress food intake in response to an overeating signal from melanocortin. Initially, the research team examined the distribution of MC4Rs in the rat brain by utilizing an antibody they had developed specifically to make MC4Rs visible. They found that MC4Rs are present exclusively in primary cilia of specific groups of hypothalamic neurons.
The team next investigated the length of the primary cilia that had MC4Rs (MC4R+ cilia) in the brains of 9-week-old (young) rats and 6-month-old (middle-age) rats. The team found that MC4R+ cilia in middle-aged rats were significantly shorter than those in young rats. Accordingly, the metabolism and the fat-burning capacity of middle-aged rats were much lower than those of young rats.

The team next analyzed MC4R+ cilia in rats under different dietary conditions. The results showed that MC4R+ cilia in rats on a normal diet gradually shortened with age. On the other hand, MC4R+ cilia in rats on a high-fat diet shortened at a faster pace, while those in rats on a restricted diet shortened at a slower pace.
Interestingly, the team also found that MC4R+ cilia that once disappeared with age were regenerated in rats raised under two months of dietary restriction.
In the study, the team also used genetic technologies to make MC4R+ cilia shorter in young rats. These rats showed increased food intake and decreased metabolism, leading to weight gain.
The team also administered a hormone called leptin to the brains of rats with artificially shortened MC4R+ cilia. Leptin is thought to help reduce food intake. Surprisingly, however, their appetite was not reduced, indicating that leptin could not exert anti-obesity effects.
“This phenomenon, called leptin resistance, is often observed in obese human patients as well. This is an obstacle to the treatment of obesity, but the cause has long been unknown,” explained Dr. Manami Oya, the first author of the study.
“In obese patients, adipose tissue secretes excessive leptin, which triggers the chronic action of melanocortin. Our study suggests that this may promote the age-related shortening of MC4R+ cilia and put animals into a downward spiral where melanocortin becomes ineffective, increasing the risk of obesity.”
The study concluded that the age-related shortening of MC4R+ cilia causes middle-age obesity and leptin resistance in rats. The researchers demonstrated that dietary restriction is one method to prevent and treat overweight and obesity. Prof. Nakamura said, “Moderate eating habits could maintain MC4R+ cilia long enough to keep the brain’s anti-obesity system in good shape even as we age.”

Allergic transfusion reactions (ATRs), a potentially life-threatening side effect of blood transfusions with unclear mechanisms, may be linked to food allergies in pediatric patients as per a recent study by scientists from Japan. They found that ATRs may be triggered by the presence of allergens in the donor’s blood, influenced by their pre-donation diet. These findings could pave the way for safer blood transfusions through the development of preventive measures and countermeasures for ATRs.
Blood transfusions are often life-saving procedures in various medical settings. They are required not only after severe blood loss due to surgery or trauma but also as standard treatment for certain blood disorders like anemia and sickle cell disease. However, blood transfusions can have serious side effects, with allergic transfusion reactions (ATRs) being particularly prevalent among children. Although scientists believe ATRs are caused by immunoglobulin E (IgE)-mediated type 1 allergy (or “immediate hypersensitivity”), the responsible allergens are not always known.
Against this backdrop, a research team composed of Dr. Ryu Yanagisawa of Shinshu University Hospital, Japan, alongside Dr. Minoru Tozuka and Dr. Yasunori Ito from Nagano Children’s Hospital, Japan, set out to find more answers. In their latest study, published online in the journal Allergy on January 11, 2024, the researchers focused their attention on what might have appeared to be an unlikely suspect. Dr. Yanagisawa, who led the study at the University’s Division of Blood Transfusion, explains: “In our previous study, we found that pediatric patients with food allergies were characteristically more prone to ATRs. Considering that food allergies are also more prevalent in children, we decided to investigate whether the food the donor ate before giving blood could be associated with the development of ATRs in children with food allergies.”
Between May 2022 and December 2023, the researchers collected blood samples from over 100 pediatric patients with diagnosed food allergies toward either eggs, wheat, or milk. They also collected blood from two healthy donors before and after substantial ingestion of these food products and extracted the serum. Shortly after collecting blood from each allergic patient, the researchers conducted basophil activation tests (BATs) by exposing the sample to the corresponding sera. As the name implies, these tests assess the activation of basophils, a particular type of white blood cell that is strongly involved in allergic reactions.
Interestingly, in patients with egg allergy, BAT levels were significantly higher when the blood was exposed to the serum of donors who had ingested eggs. Moreover, serum obtained from blood donor samples collected four hours after egg ingestion resulted in markedly higher BAT levels than those collected two hours after egg ingestion. In contrast, the results for milk and wheat were more varied, with BAT levels only being elevated after exposure to the serum of one of the two donors.
To gain deeper insights and lend more weight to the results, the researchers decided to run BAT tests with sera from sixteen additional donors. “Although some differences were observed among donors, blood samples obtained after egg ingestion generally activated basophils in cases of egg allergy with high egg white-specific IgE levels,” comments Dr. Yanagisawa. “Similarly, elevated BAT levels in patients with milk and wheat allergies were also associated with allergen-specific IgE levels.”
Overall, the evidence obtained through this study strongly suggests that ATRs could be triggered by the food consumed by donors prior to a blood donation. Although further analyses and experiments will be needed to confirm this with more certainty, these efforts constitute a necessary first step towards elucidating the mechanisms underlying ATRs. “In future, it could be possible to predict in advance who is likely to suffer from an ATR. Given enough time, preventive measures and countermeasures to ATRs could be developed, leading to safer blood transfusions,” concludes Dr. Yanagisawa.
It is hoped that this study puts scientists on the right path toward cracking the mysteries of ATRs to improve the outcome of blood transfusions.

A four-year study by Dartmouth researchers captures the most in-depth data yet on how college students’ self-esteem and mental health fluctuates during their four years in academia, identifying key populations and stressors that the researchers say administrators could target to improve student well-being.
The study also provides among the first real-time accounts of how the coronavirus pandemic affected students’ behavior and mental health. The stress and uncertainty of COVID-19 resulted in long-lasting behavioral changes that persisted as a “new normal” even as the pandemic diminished, including feeling more stressed, less socially engaged, and sleeping more.
The researchers tracked more than 200 Dartmouth undergraduates in the classes of 2021 and 2022 for all four years of college. Students volunteered to let a specially developed app called StudentLife tap into the sensors that are built into smartphones. The app cataloged their daily physical and social activity, how long they slept, their location and travel, the time they spent on their phone, and how often they listened to music or videos. Students also filled out weekly behavioral surveys, and selected students gave post-study interviews.
The study — which is the longest mobile-sensing study ever conducted — is published in the Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies. The researchers will present it at the Association of Computing Machinery’s UbiComp/ISWC 2024 conference in Melbourne, Australia, in October. The team made their anonymized data set publicly available — including self-reports, surveys, and phone-sensing and brain-imaging data — to help advance research into the mental health of students during their college years.
Andrew Campbell, the paper’s senior author and Dartmouth’s Albert Bradley 1915 Third Century Professor of Computer Science, said that the study’s extensive data reinforces the importance of college and university administrators across the country being more attuned to how and when students’ mental well-being changes during the school year.
“For the first time, we’ve produced granular data about the ebb and flow of student mental health. It’s incredibly dynamic — there’s nothing that’s steady state through the term, let alone through the year,” he said. “These sorts of tools will have a tremendous impact on projecting forward and developing much more data-driven ways to intervene and respond exactly when students need it most.”
First-year and female students are especially at risk for high anxiety and low self-esteem, the study finds. Among first-year students, self-esteem dropped to its lowest point in the first weeks of their transition from high school to college but rose steadily every semester until it was about 10% higher by graduation.

“We can see that students came out of high school with a certain level of self-esteem that dropped off to the lowest point of the four years. Some said they started to experience ‘imposter syndrome’ from being around other high-performing students,” Campbell said. “As the years progress, though, we can draw a straight line from low to high as their self-esteem improves. I think we would see a similar trend class over class. To me, that’s a very positive thing.”
Female students — who made up 60% of study participants — experienced on average 5% greater stress levels and 10% lower self-esteem than male students. More significantly, the data show that female students tended to be less active, with male students walking 37% more often.
Sophomores were 40% more socially active compared to their first year, the researchers report. But these students also reported feeling 13% more stressed than during their first year as their workload increased, they felt pressure to socialize, or as first-year social groups dispersed.
One student in a sorority recalled that having pre-arranged activities “kind of adds stress as I feel like I should be having fun because everyone tells me that it is fun.” Another student noted that after the first year,” students have more access to the whole campus and that is when you start feeling excluded from things.”
In a novel finding, the researchers identify an “anticipatory stress spike” of 17% experienced in the last two weeks of summer break. While still lower than mid-academic year stress, the spike was consistent across different summers.
In post-study interviews, some students pointed to returning to campus early for team sports. Others specified reconnecting with family and high school friends during their first summer home, saying they felt “a sense of leaving behind the comfort and familiarity of these long-standing friendships” as the break ended, the researchers report.

“This is a foundational study,” said Subigya Nepal, first author of the study and a PhD candidate in Campbell’s research group. “It has more real-time granular data than anything we or anyone else has provided before. We don’t know yet how it will translate to campuses nationwide, but it can be a template for getting the conversation going.”
The depth and accuracy of the study data suggest that mobile-sensing software could eventually give universities the ability to create proactive mental-health policies specific to certain student populations and times of year, Campbell said.
For example, a paper Campbell’s research group published in 2022 based on StudentLife data showed that first-generation students experienced lower self-esteem and higher levels of depression than other students throughout their four years of college.
“We will be able to look at campus in much more nuanced ways than waiting for the results of an annual mental health study and then developing policy,” Campbell said. “We know that Dartmouth is a small and very tight-knit campus community. But if we applied these same methods to a college with similar attributes, I believe we would find very similar trends.”
Weathering the pandemic
When students returned home at the start of the coronavirus pandemic, the researchers found that self-esteem actually increased during the pandemic by 5% overall and by another 6% afterward when life returned closer to what it was before. One student suggested in their interview that getting older came with more confidence. Others indicated that being home led to them spending more time with friends talking on the phone, on social media, or streaming movies together.
The data show that phone usage — measured by the duration a phone was unlocked — indeed increased by nearly 33 minutes, or 19%, during the pandemic, while time spent in physical activity dropped by 52 minutes, or 27%. By 2022, phone usage fell from its pandemic peak to just above pre-pandemic levels, while engagement in physical activity had recovered to exceed the pre-pandemic period by three minutes.
Despite reporting higher self-esteem, students’ feelings of stress increased by more than 10% during the pandemic. Since the pandemic, stress fell by less than 2% of its pandemic peak, indicating that the experience had a lasting impact on student well-being, the researchers report.
In early 2021, as students returned to campus, the reunion with friends and community was tempered by an overwhelming concern of the still-rampant coronavirus. “There was the first outbreak in winter 2021 and that was terrifying,” one student recalls. Another student adds: “You could be put into isolation for a long time even if you did not have COVID. Everyone was afraid to contact-trace anyone else in case they got mad at each other.”
Female students were especially concerned about the coronavirus, on average 13% more than male students. “Even though the girls might have been hanging out with each other more, they are more aware of the impact,” one female student reported. “I actually had COVID and exposed some friends of mine. All the girls that I told tested as they were worried. They were continually checking up to make sure that they did not have it and take it home to their family.”
Students still learning remotely had social levels 16% higher than students on campus, who engaged in activity an average of 10% less often than when they were learning from home. However, on-campus students used their phones 47% more often. When interviewed after the study, these students reported spending extended periods of time video-calling or streaming movies with friends and family.
Social activity and engagement had not yet returned to pre-pandemic levels by the end of the study in June 2022, recovering by a little less than 3% after a nearly 10% drop during the pandemic. Similarly, the pandemic seems to have made students stick closer to home, with their distance traveled cut by nearly half during the pandemic and holding at that level in the time since.
Campbell and several of his fellow researchers are now developing a smartphone app known as MoodCapture that uses artificial intelligence paired with facial-image processing software to reliably detect the onset of depression before the user even knows something is wrong.

Targeting a non-encoding stretch of RNA may help shrink tumors caused by an aggressive type of brain cancer in children, according to new research in mice reported March 8 in Cell Reports by Johns Hopkins Kimmel Cancer Center investigators.
Medulloblastoma are the most common type of malignant brain cancer in children. The most aggressive and difficult-to-treat form of the disease is group 3 medulloblastoma, which is often fatal. By targeting long, noncoding genetic material called lnc-RNAs that drive the expression of cancer-causing genes, the study’s senior author, Ranjan Perera, Ph.D., director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida, and his colleagues have demonstrated an innovative new approach that shrinks group 3 medulloblastoma tumors in mice.
“Group 3 medulloblastoma is very aggressive, and there are currently no targeted therapies,” says Perera, who has a primary affiliation in the Department of Neurosurgery, is a member of the Johns Hopkins Kimmel Cancer Center and is an associate professor of oncology at the Johns Hopkins University School of Medicine. He is also a senior scientist at the Johns Hopkins All Children’s Hospital Cancer and Blood Disorders Institute, and has a secondary affiliation with the hospital’s Institute for Fundamental Biomedical Research. “Our novel therapeutic approach based on noncoding RNA could fill an urgent need for new therapies for this devastating disease in children.”
RNA acts as a template for building proteins based on instructions encoded in the DNA. Until recently, scientists thought 97% of RNA was “junk” because only 3% is used to build proteins. However, scientists have realized that RNA’s nonprotein encoding stretches control gene expression. A previous study by Perera and colleagues showed that a long noncoding stretch of RNA called lnc-HLX-2-7 contributes to the growth of group 3 medulloblastoma tumors by attaching to a DNA promoter that increases expression of cancer-causing genes. Promoters are nongene coding stretches of DNA adjacent to genes that act like switches turning them on.
The new study provides additional details showing that lnc-HLX-2-7 specifically binds to the HLX promoter region of DNA, increasing HLX gene expression and causing the tumor to grow. HLX triggers tumor growth by binding to promoter regions for several other cancer-causing genes, increasing their expression. One gene that HLX increases expression of is MYC, which also increases the expression of several other cancer-causing genes, causing a cascade of activity that accelerates the growth of group 3 medulloblastoma tumors.
Perera and his team developed an intravenous treatment to block lnc-HLX-2-7 from binding to the HLX promoter to stop this cascade of cancer-gene expression. They assembled a sequence of nucleotides (called antisense oligo nucleotides), the building blocks of RNA, that can bind to the corresponding nucleotides that make up lnc-HLX-2-7, preventing it from binding to the HLX promoter in the DNA and leading to its destruction. They coated the sequence with microscopic particles called cerium oxide nanoparticles to protect the lnc-HLX-2-7 until it reaches its target.
When the team treated a mouse model of group 3 medulloblastoma with the experimental intravenous therapy, it reduced tumor growth by 40%-50%. Adding cisplatin, a chemotherapy drug currently used to treat medulloblastomas, alongside the new therapy caused the tumors to shrink even more and prolonged the animals’ survival. The combination therapy extended the animals’ lives by about 84 days compared with a 44-day increase in survival on lnc-HLX-2-7 alone.

“When you combine the two treatments, you see dramatic effects,” Perera says.
Perera and his colleagues will collaborate with Johns Hopkins neurosurgeons to plan studies of the therapy in humans to further test its safety and efficacy.
“Understanding why MYC is elevated in these tumors is extremely important, and this new link to HLX provides insights that open new therapeutic possibilities,” says study co-author and Kimmel Cancer Center researcher Charles Eberhart, M.D., Ph.D., director of neuropathology and ophthalmic pathology and a professor of oncology and pathology at the Johns Hopkins University School of Medicine.
The work was supported by the Schamroth Project, funded by Ian’s Friends Foundation, the Hough Family Foundation, the National Institutes of Health (grant P30 CA006973), the National Cancer Institute (grants 5P30CA030199, R01NS124668-01A1, and R35NS122339), and a CPRIT Scholar award from the MD Anderson Cancer Center.
Study co-authors were Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Stacie Stapleton and George Jallo from Johns Hopkins. Other authors were from the University of Delaware; the University of Central Florida, Orlando; Institute Curie at PSL University in Paris; Texas Children’s Cancer Center, Houston; Baylor College of Medicine, Houston; and Columbia University Medical Center, New York.