Culture

(Philadelphia, PA) - While the COVID-19 pandemic brought most of the country to a standstill in March 2020, Philadelphia trauma surgeons noticed an alarming trend in the incidence of firearm violence. Instead of decreasing with containment measures, firearm-injured patients were presenting at even higher rates to Temple University Hospital and other trauma centers around the city.

A team led by Jessica H. Beard, MD, MPH, FACS, Assistant Professor of Surgery and Director of Trauma Research at the Lewis Katz School of Medicine at Temple University (LKSOM), sought to determine the magnitude of Philadelphia's increase in firearm violence during the COVID-19 pandemic. They also aimed to understand potential causes of the increase by trying to pinpoint when the increase occurred. They hypothesized that two major events of 2020 could explain the increase in firearm violence in Philadelphia: the enactment of public health policies designed to contain COVID-19 and a national reckoning with systemic racism, including widespread protests sparked by the police killing of George Floyd.

In a new research letter published in JAMA, Dr. Beard and her team used the Philadelphia Police registry data of shooting victims from January 1, 2016 through November 26, 2020 to determine when the spike in firearm violence began. They examined changes in the number of individuals shot per week in the city following the enactment of Philadelphia's first COVID-19 containment policy (closure of non-essential businesses) on March 16, 2020, and following the killing of George Floyd on May 25, 2020.

The team found that there were 7,159 individuals shot in the city overall during the 256 weeks included in the study. Prior to Philadelphia's first COVID-19 containment policy, there was an average of 25 individuals shot per week. In the weeks after that policy was put in place on March 16, 2020, the average number of individuals shot per week climbed to 46. A time-series analysis found that the increase in firearm violence was strongly associated with the enactment of COVID-19 containment policies. The killing of George Floyd was not associated with any significant increase in the rate of gun violence in the study model.

These findings indicate a significant and sustained increase in firearm violence in Philadelphia following enactment of COVID-19 containment policies.

"In the city of Philadelphia, shootings are often geographically concentrated in lower-income communities," Dr. Beard said. "These communities have not only been disproportionately affected by the coronavirus disease itself, but the pandemic and its associated policies have also exacerbated issues that were already present, including unemployment, poverty, structural racism and place-based economic disinvestment, which are empirically tied to firearm violence in Philadelphia. Our research shows that the measures put in place to contain the pandemic for health and safety reasons had a significant and sustained association with increased firearm violence in the city. In addition to mitigating the impact of COVID-19 in Philadelphia, we must also come together to address what is now an epidemic of gun violence in the city."

One of the many mysteries still surrounding COVID-19 is why some people experience only mild, flu-like symptoms, whereas others suffer life-threatening respiratory problems, vascular dysfunction and tissue damage. Now, researchers reporting in ACS' Analytical Chemistry have used a combination of metabolomics and machine learning to identify possible biomarkers that could both help diagnose COVID-19 and assess the risk of developing severe illness.

Although some pre-existing conditions, such as diabetes or obesity, can increase the risk of hospitalization and death from COVID-19, some otherwise healthy people have also experienced severe symptoms. As most of the world's population awaits vaccination, the ability to simultaneously diagnose a patient and estimate their risk level could allow better medical decision-making, such as how closely to monitor a particular patient or where to allocate resources. Therefore, Anderson Rocha, Rodrigo Ramos Catharino and colleagues wanted to use mass spectrometry combined with an artificial intelligence technique called machine learning to identify a panel of metabolites that could do just that.

The cross-sectional study included 442 patients who had different severities of COVID-19 symptoms and tested positive by a reverse transcriptase-polymerase chain reaction (RT-PCR) test, 350 controls who tested negative for COVID-19 and 23 people who were suspected of having the virus despite a negative RT-PCR test. The researchers analyzed blood plasma samples from the participants with mass spectrometry and machine learning algorithms, identifying 19 potential biomarkers for COVID-19 diagnosis and 26 biomarkers that differed between mild and severe illnesses. Of the COVID-19-suspected patients, 78.3% tested positive with the new approach, possibly indicating these were RT-PCR false negatives. Although the identified biomarkers, which included metabolites involved in viral recognition, inflammation, lipid remodeling and cholesterol homeostasis, need to be further verified, they could reveal new clues to how SARS-CoV-2 affects the body and causes severe illness, the researchers say.

A team of scientists from Immanuel Kant Baltic Federal University with their colleagues from the Institute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences (Perm) studied the effect of trophoblastic β1-glycoprotein in the blood of pregnant women on pro-inflammatory immune cells. Thanks to trophoblastic β1-glycoprotein, a woman's body does not adversely react to the fetus and supports its normal development until birth. It turned out that trophoblastic β1-glycoproteins also suppressed the development of pro-inflammatory lymphocytes and reduced their activity. The results of the work could be used to develop medicinal drugs for pregnancy maintenance and treatment of various autoimmune diseases.

For a pregnant woman's body, a fetus is a source of antigens. However, there is a natural protection mechanism that prevents a mother's immune system from fighting the fetus and helps it adapt to it. This happens thanks to a fine balance between the pro-inflammatory and anti-inflammatory components, namely the Th17 and Treg populations of lymphocytes, respectively. Th17 lymphocytes belong to the group of helpers that support other immune cells and are identified by the presence of the CD4 receptor. On the contrary, Treg lymphocytes suppress the activity of the immune system. Treg cells prevail in the normal course of pregnancy and in case of any issues, the count of Th17 begins to grow.

"An increased share of Th17 is associated with preeclampsia, a condition of pregnant women that causes high blood pressure, edema, and protein in the urine and in severe cases may lead to multi-organ failure. Also, high Th17 can be the reason for preterm delivery, miscarriage, or repeated pregnancy loss of unknown etiology. Even when the course of pregnancy is relatively normal, increased Th17 levels can interfere with the development of a baby's nervous system and lead to higher risks of neuropsychic disorders," explained Larisa Litvinova, the Head of the Center for Immunology and Cellular Biotechnology, BFU.

Th17 immune regulation disorders are the cause of autoimmune diseases such as asthma, psoriasis, rheumatoid arthritis, Crohn's disease (chronic intestine inflammation), multiple sclerosis, and many others. However, these diseases can go into the remission stage in pregnant women. The team concluded that the bodies of pregnant women must produce some active substances to fight the inflammation caused not only by the presence of a fetus but also by an actual disease.

These substances are known as β1-glycoproteins, special protein-carbohydrate molecules that regulate congenital and adaptive (or acquired) immunity. The authors of the work tested the effect of these compounds on CD4+ lymphocytes with the specific receptor. To do so, the team took samples of venous blood from healthy 21-39 years old pregnant women. After that, immune cells were separated from the blood and cultivated together with trophoblastic β1-glycoproteins. The method of its preparation was patented at the Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences.

It turned out that trophoblastic β1-glycoproteins suppressed the division of CD4+ lymphocytes and the production of cytokines by them. Cytokines are small peptide molecules that act as signal agents in cases of inflammation. Based on these results, the authors suggested using medicinal drugs with trophoblastic β1-glycoproteins against pregnancy complications to save the lives and health of both mothers and children.

Exposure to some odorless, colorless and tasteless gases, such as nerve agents, can be toxic or even lethal. And having the ability to detect other types of vapors could save people from eating spoiled or rotten food. Easy-to-use portable devices could, therefore, go a long way toward protecting the public. Now researchers reporting in ACS Materials Letters have created a pen-like sensor that changes color when exposed to harmful gases.

Humans can't detect many toxic vapors, such as poisonous nerve agents or volatile amines released from spoiled foods, so a sensor that can notice these gases' very minute concentrations would be useful. Fluorescence-based sensors are a potential solution because they are inexpensive and can reveal trace amounts of compounds. However, some fluorescing compounds clump together once they react with gases, reducing their intensity, and they can require complex fabrication processes. Yet other fluorophores produce more intense light when they are clumped together -- aggregation-induced emission fluorogens (AIEgens). Most of the current detection methods using AIEgens are liquid-based, requiring gases to be dissolved in solution before analysis, and are not easily portable. So, Zhe Jiao, Pengfei Zhang, Haitao Feng, Ben Zhong Tang and colleagues wanted to adapt AIEgens to be integrated into a needle-thin fiber, creating a handheld device whose tip "turns on" in the presence of a particular gas.

The researchers developed two AIEgen-based "handy pens," one for identifying the nerve agent diethyl chlorophosphite (DCP) and the other for amines produced by rotting food. First, they coated silicon dioxide polymer fibers with a thin sol-gel layer to immobilize AIEgens. Next, they added an AIEgen that changes color when it reacts with DCP on one set of fibers, and an AIEgen that reacts with amines on another set. The coated fibers were then placed at the end of a pen-like device with a UV light source inside. The DCP sensor's tip changed from a yellow fluorescence to blue within 30 minutes of exposure to DCP. The amine sensor's tip was initially a mild blue-gray color, but it generated a vibrant yellow-colored light within five minutes when it was exposed to volatile amine vapors. Both sensors reverted to the original hue when exposed to neutralizing vapors, demonstrating that they were reversible. Finally, the team used the amine-responsive handy pen to distinguish between a salmon sample that had been refrigerated and one that had been left at room temperature for 48 hours. The researchers say that other handy pens could be easily developed by using different vapor-sensitive AIEgens, which could be applied to food safety, environmental monitoring or public safety applications.

A potent ozone-depleting chemical whose emissions unexpectedly spiked in recent years has quickly dropped back to much lower levels, putting the recovery of the stratospheric ozone layer back on track, according to a new study by scientists at MIT, the University of Bristol, and other institutions in South Korea, the U.S., Japan, Australia, and Switzerland.

The chemical in question is CFC-11, a chlorofluorocarbon that was once commonly used for refrigeration, insulation, and other purposes. When emitted to the atmosphere, CFC-11 can loft into the stratosphere, where the sun's ultraviolet radiation breaks the chemical down to release chlorine -- a noxious chemical that then eats away at ozone, stripping away the Earth's natural shield against UV rays.

CFC-11 and other chlorofluorocarbons are now banned under the Montreal Protocol, an international treaty under which every country agreed to phase out the chemicals' production and use by 2010. But in 2018, a team of scientists reported a concerning spike in global emissions of the chemical beginning in 2013. In 2019, a second team reported that a significant portion of the emissions could be traced to eastern China, predominately the Shandong and Hebie provinces.

Now, in two papers published today in Nature, the same teams report that global annual emissions of CFC-11 into the atmosphere have declined sharply, by about 20,000 U.S. tons, from 2018 to 2019. The researchers traced a substantial fraction of the global emission reductions to the very same regions of eastern China where they had previously reported the original spike. The results are consistent with evidence that the country has taken successful actions to stamp out illegal production of this ozone-depleting chemical.

"This is tremendously encouraging," says Ronald Prinn, the director of the Center for Global Change Science at MIT and a co-author on both papers. "If emissions of CFC-11 had continued to rise or even just leveled off, there would have been a much bigger problem building up. The global monitoring networks really caught this spike in time, and subsequent actions have lowered emissions before they became a real threat to recovery of the ozone layer."

A brief history of the spike

Both the original spike and subsequent drop in CFC-11 emissions were detected by the researchers using two independent networks.

One is a global monitoring network operated by the National Oceanographic and Atmospheric Administration (NOAA), comprising about 30 stations. Researchers at each site collect air samples and send them to a central laboratory, where the air is analyzed for CFC-11 and many other trace gases. The weekly measurements, from sites around the world, give an accurate average picture of the chemical species circulating in the global atmosphere.

The other network is the Advanced Global Atmospheric Gases Experiment, or AGAGE, an MIT-led effort funded in part by NASA, with more than a dozen monitoring stations situated on coastal and mountain sites around the world. The AGAGE stations take automated on-site measurements of passing air parcels about every hour, monitoring for more than 50 trace gases, including CFC-11, to provide detailed records of the regional and global atmosphere.

In a 2018 Nature report, the researchers analyzed measurements from NOAA and observed that, from 2014 to 2016, global emissions of CFC-11 grew by more than 14,000 U.S. tons a year -- a 25 percent increase from emissions between 2002 and 2012. In a subsequent 2019 Nature report, regional measurements taken by AGAGE stations in Hateruma, Japan, and Gosan, South Korea, along with three-dimensional modeling, showed that about half or more of these emissions came from eastern China, primarily from the factory-heavy Shandong and Hebei provinces.

Following these 2018 and 2019 reports, the scientists continued to track the chemical through the atmosphere, at both global and regional levels.

In the first of the two new Nature papers, they analyze both NOAA and AGAGE global data and report a dramatic turnaround: From 2018 to 2019, CFC-11 annual emissions dropped throughout the global atmosphere by about U.S. 20,000 tons, returning to levels prior to 2012, following the chemical's 2010 global phaseout.

In the second paper, based on AGAGE measurements, the scientists observed that CFC-11 emissions specifically from eastern China hit a peak around 2017. At some point soon afterward, levels began to drop, although the researchers cannot say exactly when the regional turnaround occurred, as the South Korean station sustained typhoon-related damage that resulted in some data gaps. Despite these gaps, the group observed a decline in CFC-11 annual emissions, by about 11,000 U.S. tons from eastern China, through 2019.

As the researchers write in the paper, "it seems that any substantial delay in ozone-layer recovery has been avoided, perhaps owing to timely reporting, and subsequent action by industry and government in China."

"Continuous vigilance"

However, there is still work to be done. While it appears that CFC-11 emissions from eastern China have declined, indicating that significant illegal production of the chemical there has ceased, these emissions only account for roughly half of the global emissions. Where the remainder could have come from is still unknown.

In general, CFC-11 is currently emitted in large amounts through leakages during new production and during subsequent use in refrigeration and manufacture of foams. The chemicals can also leak out from "banks" of old, discarded refrigerators and foams, though at a much slower and more diffuse rate than the rapid regional increase observed in 2013.

"The challenge now is to ask, where's the rest of it coming from?" says Prinn, the TEPCO Professor of Atmospheric Science in MIT's Department of Earth, Atmospheric and Planetary Sciences. "We will need to expand measurements and modeling to identify new sources, and continue to keep watch. Hopefully, emission levels will continue to drop."

Going forward, the scientists hope to add more stations to the AGAGE network, so that they might identify and quantify other regional sources of CFC-11, particularly in rapidly industrializing parts of the world.

"Clearly this story shows that, in order to ensure that countries are adhering to international agreements like the Montreal Protocol, continuous vigilance is required," Prinn says. "You can't stop measuring these chemical species and assume the problem is solved."

In the face of a changing climate and crop diseases, manufacturers of products containing natural flavors and fragrances are pivoting to a new way to source ingredients. Companies have been partnering with biotechnology firms to manufacture scents and flavors using fermented microbes, which experts say are more sustainable. A new story in Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society, details how the industry is brewing up new fragrances.

Although the availability of natural fragrances and flavors like citrus and vanilla is dwindling, the demand for them has increased, writes Senior Business Editor Melody Bomgardner. In recent years, flavor and fragrance companies have been working with the biotech industry to shore up supply chains and avoid issues like seasonality and poor harvests, without having to use synthetic compounds. Fermentation-derived ingredients can be listed as natural in the U.S. and Europe, which appeals greatly to consumers. Biotech firms and major chemical companies are stepping up their production of fermented products while also making the process more efficient and less expensive.

To be commercially viable, engineered microbes need to make a flavor or scent molecule at a much higher concentration than what's found in plants. Once microbial engineers figure out which plant genes they need to get microbes to produce a new flavor or scent molecule, it's relatively easy to make variants of that structure, they say. For example, γ-decalactone, which smells like peaches, is just one of 20 fruity and buttery molecules that can be made from a lactone process. These new fragrance molecules can be used in products such as hard seltzers, laundry detergents and fine perfumes. Another advantage of fermented molecules is consistency of flavor and smell, which is hard to achieve with naturally derived ingredients. With sustainability being a must-have for consumers and manufacturers alike, experts are hopeful that this is a versatile, cost-effective solution.

Rates of overweight and obesity in children are rising around the world, with serious long-term consequences for health and health care costs. In prior research, video and mobile games have helped children eat healthier and exercise more. A new study examined how Indian 10- and 11-year-olds' food choices were affected by playing a pediatric dietary mobile game that uses implicit learning--educating players without making them aware of the lessons through innovations in neurocognitive training and immersive technology. The study found that the game significantly improved children's food choices immediately after play.

The study was conducted by researchers at Carnegie Mellon University (CMU), Hofstra University, Johns Hopkins University Center for Communication Programs (CCP), FriendsLearn, The Mithra Trust, Mind in Motion, the Center for Communication and Change - India (CCC-I), and Seethapathy Clinic and Hospital. The randomized controlled trial was designed and conducted by researchers from CCC-I and CCP and the data modeling and analytics were led by CMU. The study appears in JMIR mHealth and uHealth.

"While many factors contribute to overweight and obesity, dietary decisions are a leading cause," explains Rema Padman, trustees professor of management science and healthcare informatics at CMU's Heinz College, who led the study. "Video games that are perceived by children as a fun activity rather than a learning tool present a great opportunity to change children's health behaviors by delivering relevant knowledge implicitly. We are studying such gamified interventions as 'digital vaccine' candidates that have the potential to influence lifestyle behavior changes and lead to better health outcomes." (Digital vaccines are a subcategory of digital therapeutics, which are evidence-based, prevention approaches that use digital technologies, such as gamified applications delivered via mobile devices, to encourage positive behavior.)

Most video games for children use explicit education strategies, such as providing answers, feedback, instructions, or suggestions to players. This study examined how an action video game called fooya!, which uses implicit learning to promote healthy eating and physical activity in children, affected actual food choices. In the game, an avatar fights robots that represent unhealthy foods, and the avatar's speed and body shape vary in response to the type of food it eats.

Evidence of the effects of games that use implicit education strategies on pediatric healthy eating is limited. Using data about the clicks made by players as they played fooya!, researchers analyzed the relationship between patterns of game play and behavioral outcomes related to dietary health.

The study involved 104 children ages 10 and 11 years from three schools in Chennai, India. The children were randomly assigned to a treatment group that played fooya! or a control group that played a board game that did not feature dietary education. Children played the games for 20 minutes each in two sessions. After playing, they were shown three pairs of healthy and unhealthy food items from three categories--drinks (water and a carbonated soft drink), savory snacks (cashews and potato chips), and sweet snacks (raisins and a chocolate bar)--and asked to choose two items to eat.

Children who played fooya! were more likely to choose healthy foods immediately after playing the game, the study found. Children's food choices were not influenced by how many levels of the game they played, as previous research on this topic has found, but by food facts children read while playing the game: Reading more facts about healthy foods was associated with healthier food choices, while reading more facts about unhealthy foods was associated with more unhealthy food choices, a finding the authors called counterintuitive. Nonetheless, children searched for more food facts about healthy food than about unhealthy food, which drove the overall positive effect of playing the game.

"This finding will also influence how we communicate to children about healthy food choices for behavior change," says Uttara Bharath Kumar, technical advisor for social and behavior change at CCP. "It is consistent with what we know from behavioral science that fear and negative communication do not work as well as positive messaging and promoting self-efficacy--the notion that 'you can do it!'"

"Nutrition and lifestyle are at the root of lifelong risk of noncommunicable and infectious diseases," explains Bhargav Sri Prakash, founder & CEO of FriendsLearn, the life science and health technology company that serves as the research translation and innovation partner of the Digital Vaccine Project at CMU. "These findings indicate the potential for societal impact by developing rigorous evidence-based science for 'digital vaccines' based on neurocognitive computing and analytics. As we build a platform of scalable, rich, game-like, engaging experiences, we aim to protect the health of children and families through science."

Among the limitations of the study, the authors note, are its small size, homogeneous groups of children, and short-term food choices, limiting the generalizability of the findings. Longitudinal studies on this subject can help determine longer-term effects, the authors suggest.

"By examining the complex interactions between game-playing patterns and health behaviors, our findings can inform the design and use of more effective mobile games for improving children's dietary health," notes Yi-Chin Kato-Lin, assistant professor of information systems and business analytics at Hofstra University, who collaborated on the study. "For example, video game designers may want to limit the display of unhealthy foods in their games."

Because of their small size, some microorganisms can come through the pores of bacterial filters. Such filtrable microorganisms are difficult to grow in lab conditions and therefore remain understudied. Scientists believe that filtrable microorganisms are widely spread in the biosphere and participate in many biogeochemical processes, such as the restoration of sulfur in deep-see regions. They also play an important role in the production and use of dissolved organic matter. This term refers to a group of compounds (such as amino acids, organic acids and monomeric sugars) that are easily utilizable sources of nutrients in freshwater systems.

These compounds occur in pristine lotic systems at very low concentrations mainly from primary producers (photosynthetic bacteria or algae) or from land runoffs, wastewater discharges, and are consumed by heterotrophic microorganisms (i.e. the microorganisms that are unable to synthesize organic matter from inorganic carbon). Therefore, it is important to understand the major microbial groups and environmental factors important for the transformation of organic compounds at natural, very low (nanomolar) concentrations.

A team of researchers from Immanuel Kant Baltic Federal University, the Kurchatov Institute, and the Winogradsky Institute of Microbiology together with their colleagues from the UK, and Spain, participated in the study led by Bangor University (UK) on the taxonomic composition and functional characteristics of filtrable freshwater organisms, as well as their contribution to the carbon cycle. To do so, they compared the samples of unfiltered and filtered water from the River Conwy (UK). In their experiment, the team used radioisotope tracers (radiolabelled organic substrates) and targeted metabolomics (mass-spectrometry) to measure substrates' uptake and respiration alongside the molecular analysis of microbial DNA to identify major microbial groups.

"Based on the results of the study, we concluded that filtrable fraction of microorganisms has a lower efficiency than the microbial community as a whole, and play a minor role in the processing of dissolved organic carbon. Moreover, their role in the system is further reduced because they have only a limited time to uptake dissolved organic matter in rivers and streams," explained Evgenii Lunev, a co-author of the work.

Orange, Calif. - The mutually beneficial relationship between legumes and rhizobia, the nitrogen-fixing soil bacteria that make their home in legume root nodules and create nutrient-rich fertilizer for them, is one of the most well-known and agronomically important examples of symbiosis. New research from Dr. Kenjiro Quides, a Postdoctoral Teaching and Research Fellow in the Grand Challenges Initiative at Chapman University, tested the boundaries of this relationship -- and found that it's not always as perfectly harmonious as previously thought.

The results are reported in a new paper in the journal Evolution.

Legumes provide carbohydrates for rhizobial bacteria that live in root nodules, while the rhizobia fix atmospheric nitrogen into a form that's usable for the legume (nitrogen is often a limiting nutrient for plants). In theory, if legumes have greater root nodule growth, they should be able to host more rhizobia, which should produce more nitrogen and enable larger plant growth in general.

The research, carried out by Quides and colleagues at UC Riverside during his doctorate, tested the relationship between root nodule growth and rhizobia using a smaller relative of Soybeans, named Lotus japonicus. By using multiple genetic variants that formed a low, medium, and high number of nodules, the study showed that legumes grew to maximum size when a low and medium number of nodules formed, but legumes that formed a high number of nodules had drastically reduced growth.

The investigation then turned to the rhizobia. The size of the rhizobial population, a standard measure of bacterial growth, was found to continue to increase as the number of nodules formed increased. This suggests a hidden conflict in the symbiotic relationship. It seems that the legume and rhizobia interests are only aligned until the host optimum is reached, a point at which their interests diverge. This provides support for the conclusion that in the symbiotic relationship, rhizobia have an evolutionary advantage.

The results demonstrate that to avoid conflict in symbiotic relationships, hosts must tightly regulate their investment into symbiotic organs (like legumes' root nodules) to maximize their own benefit-to-cost ratio of associating with their symbiotic partner.

"Legumes seem to play a balancing act to maximize their growth, but rhizobia continue to grow and that is a really exciting result," Dr. Quides said.

He noted that this study opens the door to more research. "Although we found diminishing returns for the host from nodulation, the fact that rhizobia population size continued to increase is promising. We found the costs outweigh the benefits at high nodule numbers. However, if we can increase the number of nodules and therefore the rhizobia population size while minimizing the cost to the plant, we have the potential to increase the productivity of legume crops in the future."

Firefighters and emergency medical services workers are at high risk of exposure to COVID-19 while on the job and pose an additional risk of transmitting the virus to others. Although vaccines are a promising public health tool for reducing COVID-19 transmission, little has been known about the perceptions of the COVID-19 vaccine among first responders.

To provide insight, a University of Miami Miller School of Medicine-led study queried a national sample of U.S. firefighters and emergency medical services workers through an anonymous online survey. The study results, published online Feb. 1 in the Journal of Occupational and Environmental Medicine, revealed that more than half of the first responders who replied were uncertain about or reported low acceptance of the vaccine.

"Through the national sample of firefighters and emergency medical services workers, we gained insight into the workforce's hesitancy about the COVID-19 vaccine," said study lead and senior author Alberto J. Caban-Martinez, D.O., Ph.D., M.P.H., associate professor of public health sciences in the Division of Environment & Public Health at the Miller School. "We can leverage this study's information to design workplace interventions that educate and encourage our first responders to receive the COVID-19 vaccine."

Demographics determine perceptions

Of the 3,169 respondents to the survey, 48.2% expressed high acceptability of the COVID-19 vaccine, 24.2% were unsure, and 27.6% reported low acceptability. The results also revealed key demographic characteristics -- such as age, race, ethnicity, education, marital status, and job ranking -- for each group of respondents.

Additionally, across all ten geographic regions of the Federal Emergency Management Agency, the southeast (43.1%), the southwest (32.7%) and the west (34.1%) had the highest proportion of first responders who showed low COVID-19 vaccine acceptability.

"An important predictor we discovered from our study was that first responders who had not reported receipt of the influenza vaccine in the prior season had higher odds of being unsure about or not wanting to receive the COVID-19 vaccine," Dr. Caban-Martinez said.

In the study, the co-authors note the importance of tailoring public health campaigns for educating those sub-groups of firefighters and emergency medical service workers who identified as unsure or expressed low COVID-19 acceptability.

Researchers at the University of Maryland School of Medicine (UMSOM) and their colleagues published a new analysis today in the journal Nature from genetic sequencing data of more than 53,000 individuals, primarily from minority populations. The early analysis, part of a large-scale program funded by the National Heart, Lung, and Blood Institute, examines one of the largest and most diverse data sets of high-quality whole genome sequencing, which makes up a person's DNA. It provides new genetic insights into heart, lung, blood and sleep disorders and how these conditions impact people with diverse racial and ethnic backgrounds, who are often underrepresented in genetic studies.

[Link to study: https://www.nature.com/articles/s41586-021-03205-y]

The program, called Trans-Omics for Precision Medicine (TOPMed), seeks to understand the genetic variations that occur among individuals both in nuclear families and in populations from diverse ethnicities residing on different continents. The project's ultimate goal is to improve the diagnosis, treatment and prevention of the most common conditions that lead to disability or death.

"We have already identified some surprising new insights," said study corresponding author Timothy O'Connor, PhD, Associate Professor of Medicine & Endocrinology at the Institute for Genome Sciences (IGS) at UMSOM. For example, the team identified more than 400 million genetic variations, but 97 percent of them are extremely rare, occurring in less than 1 percent of the population. Gene variations or variants can occur by random chance when genes get recombined or mutate.

"Most of the time, these variants mean nothing," said Dr. O'Connor, "but they can provide a new understanding of mutational processes and recent human evolutionary history."

The TOPMed team includes more than 180 researchers from leading institutions in genomics worldwide who have been compiling huge datasets in systematic and defined ways to increase knowledge about diversity in genetic studies. Since its launch in 2014, the TOPMed investigators have begun adding whole genome sequencing and "omics" analysis (which includes a study of genetic and molecular profiles like proteins) to research studies in order to better understand how variations affect different organ systems giving rise to disease in, for example, the heart and lungs.

In the new Nature paper, the researchers pointed out that the program "aims to identify causal genetic variants and how they interact with the environment, to characterize disease and its molecular subtypes, to understand differences in disease across diverse ancestries, and to establish a foundation for personalized disease prediction, prevention, diagnosis, and treatment." Braxton Mitchell, PhD, Professor of Medicine at UMSOM, and Jeffrey O'Connell, PhD, Associate Professor of Medicine at UMSOM, were co-authors on this paper.

TOPMed is the largest sequencing project to date and has identified over 400 million gene variants with an overarching mission of understanding global genetic diversity. Since joining the TOPMed program in 2016, UMSOM researchers have published valuable new insights on genetic diversity including sequencing data from the initial flagship paper on the first 53,831 TOPMed samples.

The increasing diversity of the population samples will help investigators learn more about how specific diseases impact different ethnic populations around the world. In addition, the group has established uniform standards for sequencing performed on a massive scale. The standards maximizes the integrity of the data as the large group of international researchers use uniform methods as they continue to add other "omics" methods for analysis such as the study of metabolic differences.

In addition to enabling detailed analysis of the combined genomic and health data for sequenced samples, TOPMed has enhanced the analyses of genotyped samples through a new reference panel that now includes over 97,000 individuals. The TOPMed imputation reference panel is publicly available for review and input of new genetic data by researchers.

The first stage of the data release in the Nature study demonstrated a greater inclusion of a diversity of sampling, which will be invaluable to the international group to learn more about the diseases impacting these populations. Because of the vast sample sizes and the longitudinal scope of many of the population samples, the investigators were able to demonstrate that the rare variants represent recent and potentially deleterious changes that can impact protein function, gene expression or other biologically important elements.

"This is a major effort to rectify the underrepresentation of minority participants in genomic studies and tracks with a broader mission within the School of Medicine to increase diversity in clinical trials," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "This will hopefully move the genomics field closer to extending personalized medicine for all patients."

Cashell Jaquish, Ph.D., an NHLBI program officer for TOPMed and a corresponding author on the Nature paper, agrees. "The NHLBI's TOPMed program is a huge resource for the scientific community. We didn't really know what genomic variation looked like in diverse groups until now. This new study represents truly historic findings and we look forward to continued research studies in this area as we move toward personalized medicine."

A team, including an astronomer from the University of Hawai?i Institute for Astronomy (IfA), have confirmed a planetoid that is almost four times farther from the Sun than Pluto, making it the most distant object ever observed in our solar system. The planetoid, nicknamed "Farfarout," was first detected in 2018, and the team has now collected enough observations to pin down the orbit. The Minor Planet Center has now given it the official designation of 2018 AG37.

Farfarout's name distinguished it from the previous record holder "Farout," found by the same team of astronomers in 2018. The team includes UH Mānoa's David Tholen, Scott S. Sheppard of the Carnegie Institution for Science, and Chad Trujillo of Northern Arizona University, who have an ongoing survey to map the outer solar system beyond Pluto.

Journey around the Sun

Farfarout's current distance from the Sun is 132 astronomical units (au); 1 au is the distance between the Earth and Sun. For comparison, Pluto is only 34 au from the Sun. The newly discovered object has a very elongated orbit that takes it out to 175 au at its most distant, and inside the orbit of Neptune, to around 27 au, when it is closest to the Sun.

Farfarout's journey around the Sun takes about a thousand years, crossing the giant planet Neptune's orbit every time. This means Farfarout has probably experienced strong
gravitational interactions with Neptune over the age of the solar system, and is the reason why it has such a large and elongated orbit.

"A single orbit of Farfarout around the Sun takes a millennium," said Tholen. "Because of this long orbital period, it moves very slowly across the sky, requiring several years of observations to precisely determine its trajectory."

Discovered on Maunakea

Farfarout will be given an official name after its orbit is better determined over the next few years. It was discovered at the Subaru 8-meter telescope located atop Maunakea in
Hawai?i, and recovered using the Gemini North and Magellan telescopes in
the past few years to determine its orbit based on its slow motion across the sky.

Farfarout is very faint, and based on its brightness and distance from the Sun, the team estimates its size to be about 400 km across, putting it on the low end of being a dwarf planet, assuming it is an ice-rich object.

"The discovery of Farfarout shows our increasing ability to map the outer solar system and observe farther and farther towards the fringes of our solar system," said Sheppard. "Only with the advancements in the last few years of large digital cameras on very large telescopes has it been possible to efficiently discover very distant objects like Farfarout. Even though some of these distant objects are quite large, being dwarf planet in size, they are very faint because of their extreme distances from the Sun. Farfarout is just the tip of the iceberg of solar system objects in the very distant solar system."

Interacting with Neptune

Because Neptune strongly interacts with Farfarout, its orbit and movement cannot be used to determine if there is another unknown massive planet in the very distant solar system, since these interactions dominate Farfarout's orbital dynamics. Only those objects whose orbits stay in the very distant solar system, well beyond Neptune's gravitational influence, can be used to probe for signs of an unknown massive planet. These include Sedna and 2012 VP113, which, although they are currently closer to the Sun than Farfarout (at around 80 au), they never approach Neptune and thus would be most influenced by the possible Planet X instead.

"Farfarout's orbital dynamics can help us understand how Neptune formed and evolved, as Farfarout was likely thrown into the outer solar system by getting too close to Neptune in the distant past," said Trujillo. "Farfarout will likely interact with Neptune again since their orbits continue to intersect."

The United States spends more than $200 billion every year in efforts to treat and manage mental health. The onset of the coronavirus pandemic has only deepened the chasm for those experiencing symptoms of depression or anxiety. This breach has also widened, affecting more people.

New research from Carnegie Mellon University, University of Pittsburgh and University of California, San Diego found that 61% of surveyed university students were at risk of clinical depression, a value twice the rate prior to the pandemic. This rise in depression came alongside dramatic shifts in lifestyle habits.

The study documents dramatic changes in physical activity, sleep and time use at the onset of the COVID-19 pandemic. Disruptions to physical activity emerged as a leading risk factor for depression during the pandemic. Importantly, those who maintained their exercise habits were at significantly lower risk than those who experienced the large declines in physical activity brought on by the pandemic. While physical activity resumed in early summer, mental well-being did not automatically rebound. The results of the study are available online in the February 10 issue of the Proceedings of the National Academy of Sciences.

"There is an alarming rise in the rate of anxiety and depression among young adults, especially among college students," said Silvia Saccardo, assistant professor in the Department of Social and Decision Sciences at CMU and senior author on the paper. "The pandemic has exacerbated the mental health crisis in this vulnerable population."

Saccardo and her colleagues, Osea Giuntella, Kelly Hyde and Sally Sadoff, examined data gathered from 682 college students who used a smartphone app and a Fitbit wearable tracker for spring 2019, fall 2019 and spring 2020. Their results show large disruptions in physical activity, sleep and computer/phone screen time and social interaction, alongside large declines in well-being. This data set spans the onset of social isolation during the early months of the pandemic, offering an insight into the factors that exacerbated mental health disorders in this age group.

"We used this unique dataset to study what factors are predictive of changes in depression," said Saccardo. "[In the dataset,] we can see that mental health gets worse as the semester progresses, but it is dramatically worse in 2020 compared to the previous cohort."

The team found that participants who maintained healthy habits prior to the pandemic -- scheduled physical active and an active social life -- were at a higher risk for depression as the pandemic continued. The researchers point to a decline in physical activity as the leading risk factor for diminished mental health. However, restoration of physical activity was not met with a rebound in mental well-being.

"We randomized a group of individuals to receive incentive to exercise. While our short intervention increased physical activity among this group, it did not have an impact on mental health. These results open up a lot of opportunities for future research," said Saccardo. "It is an interesting puzzle for future studies to understand why we do not see a symmetric relationship between the resumption of physical activity and mental health."

This research documents how COVID-19 has generated large disruptions in mental well-being among college students, a vulnerable population.

"The results are generalizable to the young adult population, a highly exposed group which has exhibited rising depression rates over the last decades and was dramatically exposed to the disruptions caused by the current epidemic," said Giuntella, assistant professor of economics at Pitt. "We need more work to understand whether similar trends were observed in other age groups."

EAST LANSING, Mich. - The 1918 influenza pandemic provides a cautionary tale for what the future may hold for COVID-19, says a Michigan State University researcher.

After a decade studying a flu virus that killed approximately 15,000 Michigan residents, Siddharth Chandra, a professor in MSU's James Madison College, saw his research come to life as he watched the spread of the COVID-19 pandemic.

"It was so surreal," said Chandra, who has a courtesy appointment in epidemiology and biostatistics. "All of a sudden, I was living my research."

Chandra's research is published in the American Journal of Public Health with co-authors Julia Christensen, a graduate of James Madison College; Madhur Chandra, Senior Community Epidemiologist with the Ingham County Health Department and graduate of the Department of Epidemiology and Biostatistics at MSU; and Nigel Paneth, professor of epidemiology and biostatistics and pediatrics at MSU.

Using influenza infection and mortality data on Michigan from 1918-1920, Chandra identified four distinct waves. The first large peak was in March 1918. "After a second spike in cases in October 1918, the governor instituted a statewide ban on public gatherings," Chandra said. "Much like the restrictions that were put in place during the COVID-19 pandemic."

After three weeks, the number of cases decreased and the ban was lifted, which led to another peak in December 1918. "The ban didn't stop the spread of the flu. It just delayed the spike in cases," he said.

Chandra mapped the data showing the peaks and spikes in cases from October 1918 and December 1918 and tracked flu virus case growth by county over time. In October, counties in the southern part of the state and near the Mackinac Straits had the highest numbers but by December, the highest numbers of cases were in the heart of the state.

The most surprising piece of data came 18 months later in February 1920, when a statewide explosion of cases created a massive spike even larger than the one in October 1918. For Chandra, it is an educated guess as to the reasons for this delayed increase.

"Assuming it's the same influenza virus, World War I ended in 1918 and the men were coming home to their families," he said. "We had a mobile agent that brought the virus home to infect family members, which would explain the increase in cases among children and the elderly."

Unfortunately, there is not a way to confirm this, Chandra noted. "We would need samples from patients in 1920 from across the state. Then, we would need to compare those with samples from patients in 1918 from across the state, and that's not likely to happen."

The weather may have also been a factor since cool temperatures with low humidity likely provided optimal conditions for the virus to live and spread. Another factor that played a role was the absence of a vaccine.

"In 1918, there was no hope for a vaccine. In 2021, we have a vaccine available," he said.

One of the key insights from the 1918 pandemic that can inform the public health response to the 2020 COVID-19 pandemic is the number of people who are susceptible to the virus. Which means that it is possible that a spike like the February 1920 one will occur in late 2021 or early 2022.

"So many people will remain susceptible until they get vaccinated," Chandra said. "Bad things can still happen a year or two from now even if we see a decrease in the number of cases now. We still have over 200 million people walking around who are susceptible to the virus, including myself."

MUSC Hollings Cancer Center researchers found that a single strain of bacteria may be able to reduce the severity of graft-versus-host disease (GVHD), as reported online in February 2021 in JCI Insight.

Bone marrow transplant can be a lifesaving procedure for patients with blood cancers. However, GVHD is a potentially fatal side effect of transplantation, and it has limited treatment options. This proof-of-concept study demonstrates that better treatment options may be on the horizon for patients with GVHD.

Xue-Zhong Yu, M.D., associate director of Basic Science at Hollings Cancer Center, and lead author Hanief Sofi, Ph.D., realized that protecting the health of the gastrointestinal tract is a good target for reducing severe GVHD.

"If we can figure out how to keep a patient's intestinal tissue healthy before and after bone marrow transplant, then the patient's outcome will be much better. We know that restoring the microbiota diversity in the gut is an effective solution, but that comes with many challenges," said Yu.

Patients with blood cancers, such as leukemia, must undergo radiation and chemotherapy before they can get their new cancer-free immune system through bone marrow transplantation. The balance between the immune system and intestinal microbiota, communities of microorganisms that live in the gut, is especially important for proper intestinal health. Unfortunately, the radiation and chemotherapy radically throw off this balance, and the diversity of the microbiota is reduced 100- or even 1,000-fold. This leads to a condition called "leaky gut."

Clinical studies have shown that patients who recover microbiota diversity faster have better outcomes and less severe GVHD. Reduced microbiota diversity is associated with more severe GVHD.

Other studies have shown that fecal microbial transplantation (FMT) can be effective at reducing GVHD, but the challenge is how to get the right donor. Patients are heavily immune-deficient after bone marrow transplantation, and there is a great risk of bad infection if FMT is used in humans.

The Yu laboratory used two different strains of mice to establish a GVHD model that closely resembles the biology that occurs in humans after bone marrow transplantation. The mice developed acute GVHD. FMT significantly reduced acute GVHD in this model and reduced donor T cell proliferation in the organs, which is what triggers GVHD.

The researchers then used genetic sequencing to see which bacteria strains were most different between the fecal material of GVHD mice that received FMT and those that did not receive FMT.

Mice that had the best outcome, the lowest GVHD, had the highest levels of a bacteria called B. fragilis. Mice given this single bacterial strain had significantly reduced acute and chronic (long-term) GVHD compared to mice that did not get B. fragilis. In fact, B. fragilis alone was as good or even better than FMT.

Administration of B. fragilis increased overall gut microbial diversity, including increasing the amount of other beneficial bacteria strains. Surprisingly, GVHD was reduced in this model not only by live bacteria but also by bacteria that had been killed by short exposure to high heat.

The observation that B. fragilis was the main effective bacteria in the FMT process was not entirely new: B. fragilis also reduces autoimmunity in type 1 diabetes and colitis.

The current study by Yu and colleagues has two important findings. First, a molecule called polysaccharide A on the surface of B. fragilis appears to be critical for the GVHD-reducing functions of this bacteria. When the bacteria were modified to lack polysaccharide A, GVHD was not reduced compared to mice that did not receive any B. fragilis.

Secondly, the administration of B. fragilis did not reduce the graft-versus-leukemia or cancer-killing effect of the bone marrow transplantation, even though it did reduce donor T cell expansion in the gut. This is critical, since GVHD treatment options that reduce the graft-versus-leukemia effect would not be clinically significant.

"If this can be translated into the clinic, it would be a safer, easier and more effective treatment option," said Yu.

Further study in humans is needed to get this potential treatment into the clinic. Hematopoietic stem cells, given via bone marrow transplant, are classic immunotherapies for liquid tumors, but strategies to make the transplantation safer and more beneficial are sorely needed. Hollings Cancer Center researchers continue to search for the most effective therapies to improve patient outcomes and quality of life, he said.