Culture

CLEVELAND - COVID-19 is known primarily as a respiratory disease, with symptoms that include cough, shortness of breath, and, in severe cases, acute respiratory distress syndrome and pneumonia. Now, researchers from Cleveland Clinic's Department of Biomedical Engineering note in a recent review that infection with the coronavirus may also affect the central nervous system and cause corresponding neurological disorders, including ischemic stroke, encephalitis, encephalopathy and epileptic seizures.

According to the review--published in Cells and authored by Chaitali Ghosh, PhD, and Aneesha Achar--the symptoms of COVID-19-related neurological manifestations include dizziness, headache, a loss of consciousness and ataxia (loss of balance and muscle control).

he coronavirus gains access to the body by attaching to a specific receptor most abundantly found on cells that line many organs and tissues throughout the respiratory system, called the ACE2 (angiotensin-converting enzyme 2) receptor. ACE2 can be found less abundantly on cells in other areas of the body--including the heart, esophagus, kidneys and bladder--which increases the chances of viral infection, including through the central nervous system.

As reported in the review, the coronavirus may enter the central nervous system either through a porous bone in the nasal cavity (which causes the loss of smell and/or taste commonly experienced with COVID-19), or through the body's circulatory system, subsequently crossing the blood-brain barrier.

"Ordinarily, the blood-brain barrier allows nutrients to reach the brain while protecting it from circulating toxins or pathogens that could cause infections," Dr. Ghosh said. "However, the exact mechanisms underlying COVID-19-associated neurological disorders remain unknown. Such viral infectivity could alter blood-brain barrier function, which may influence disease progression."

Cytokine storms: An early warning system

Once in the central nervous system, the virus activates proteins called cytokines (central players in the body's immune response) and initiates a "cytokine storm." This can cause inflammation in the central nervous system and affect blood-brain barrier integrity.

What's more, while cytokine storms are usually associated with severe cases of COVID-19, Dr. Ghosh sounded a note of warning. "Central nervous system disorders can occur in patients who have only mild or moderate COVID disease," Dr. Ghosh said. "In fact, they can also come about even before the patient has any respiratory symptoms."

While there is currently limited evidence on long-term consequences of COVID-19-associated neurodegenerative and inflammation-mediated brain diseases, investigations into whether these comorbidities are risk factors for COVID-19 would be critical to follow.

"I am eager to define and learn more about which signaling pathways are linked to which neurological disorders, and think this will be an exciting new frontier in COVID-19 research," said Dr. Ghosh.

Hospital-based laboratories and doctors at the front line of the COVID-19 pandemic might soon add artificial intelligence to their testing toolkit. A recent study conducted with collaborators from the University of Vermont and Cedars-Sinai describes the performance of Biocogniv's new AI-COVID™ software. The team found high accuracy in predicting the probability of COVID-19 infection using routine blood tests, which can help hospitals reduce the number of patients referred for scarce PCR testing.

Their study in the Journal of Medical Internet Research is available online at https://www.jmir.org/2020/12/e24048 .

"Nine months into this pandemic, we now have a better understanding of how to care for patients with COVID-19," says lead author and University of Vermont Assistant Professor Timothy Plante, M.D., M.H.S., "but there's still a big bottleneck in COVID-19 diagnosis with PCR testing."

PCR testing is the current standard diagnostic for COVID-19, and requires specific sampling, like a nasal swab, and specialized laboratory equipment to run.

Biocogniv Chief Operating Officer Tanya Kanigan, Ph.D., says, "According to data from over 100 US hospitals, the national average turnaround time for COVID-19 tests ordered in emergency rooms is above 24 hours, far from the targeted one-hour turnaround."

Complete Blood Count and Complete Metabolic Panels are common laboratory tests ordered by emergency departments and have a rapid turnaround time. These tests provide insight into the immune system, electrolytes, kidney, and liver. The researchers were able to train a model that analyzes changes in these routine tests and assigns a probability of the patient being COVID-19 negative with high accuracy.

"AI-COVID takes seconds to generate its informative result once these blood tests return, which can then be incorporated by the laboratory into its own test interpretation," says Jennifer Joe, M.D., an emergency physician in Boston, Mass. and Biocogniv's Chief Medical Officer. "In an efficient emergency department that prioritizes these routine blood tests, the door-to-result time could be under an hour."

Cedars-Sinai pulmonary and internal medicine specialist Victor Tapson, M.D., says such assistive tools that help physicians rule out possible diagnoses are familiar in emergency medicine.

"For example, a low D-dimer blood test can help us rule out clots in certain patients, allowing providers to skip expensive, often time-consuming diagnostics such as chest CT scans," says Tapson.

The Biocogniv team believes a secondary benefit of laboratories incorporating AI-COVID might be reduced time for traditional PCR results.

"With the help of AI-COVID, laboratories might relieve some of the testing bottleneck by helping providers better allocate rapid PCR testing for patients who really need it," says Joe.

The AI-COVID model was validated on real world data from Cedars-Sinai as well as on data from geographically and demographically diverse patient encounters from 22 U.S. hospitals, achieving an area under the curve (or AUC) of 0.91 out of 1.00.

"This enables the model to achieve a high sensitivity of 95% while maintaining moderate specificity of 49%, which is very similar to the performance of other commonly used rule-out tests," says Biocogniv Chief Scientific Officer George Hauser, MD, a pathologist.

Biocogniv CEO Artur Adib, Ph.D., says, "I'm honored to have such an impressive team of medical scientists from the University of Vermont and Cedars-Sinai as collaborators in validating this timely model. AI has progressed considerably; the time is now to leverage this powerful tool for new healthcare breakthroughs, and we're glad to direct it to help hospital laboratories and providers combat the current COVID-19 crisis."

New Rochelle, NY, December 10, 2020--The phenomenon of AAV capsid-promoter interaction recently seen in the rat central nervous system has now been shown to occur in the non-human primate brain. This interaction can directly determine cell-specific transgene expression, as described in Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website through January 10, 2021.

An adeno-associated virus (AAV) contains a single-stranded DNA genome encapsulated in a capsid comprised of three structural proteins.

"We document a unique attribute of AAV vectors in both rodent and primate models that until recently remained undescribed: namely capsid/promoter interactions, that dictated cell type transduction profiles regardless of virus permissivity," state R. Jude Samulski, University of North Carolina School of Medicine, and coauthors.

"Up until now, we have thought of the AAV capsid as a 'delivery truck,' and once it dropped off its payload at the right cellular address, the vector promoter would do the rest. This work refutes that concept, showing that the capsid continues to have an effect on gene expression within specific cells of the brain and spinal cord. This has profound implications for vector design in the future," according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School.

Research reported in this publication was supported by the National Institutes of Health under Award Numbers NEI R21, EY030278, EY013692, NS082289. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Scientists at Tokyo Institute of Technology decipher how to quantitatively assess the effects of specific epigenetic changes on the rate of transcription by developing a mathematical model. For this, they successfully generated reconstituted chromatin bearing histone modifications in vitro. Their study published in Nucleic Acids Research provides an accurate quantitative approach for understanding how site-specific changes to histone proteins impact the accessibility of chromatin and gene expression levels.

The creation of a single protein is a long and complicated process. Even just the generation of its blueprint itself, known as a coding transcript, from a DNA template involves numerous steps and players. To start with, the DNA is usually found neatly wrapped around proteins called histones to form a nucleosome, the fundamental subunit of a tightly condensed structure called chromatin. The extent of its condensation determines how much of the DNA is "available" for the transcription process. Changes to these histones, such as acetylation, also influence the accessibility of chromatin for gene expression. These "epigenetic" modifications play a crucial role in regulating gene expression. To date, much remains to be explored regarding how these epigenetic effects can be accurately quantified and how site-specific histone modifications can affect gene expression.

To answer these questions, a group of researchers led by Prof. Masahiro Takinoue from Tokyo Institute of Technology, Prof. Kohki Okabe from The University of Tokyo, and Prof. Takashi Umehara from RIKEN Center for Biosystems Dynamics Research, Japan have developed a kinetic model to quantify the contribution of epigenetic changes on transcription rates based on highly quantitative experimental results. Talking about their recent work published in Nucleic Acids Research, Takinoue explains, "The contribution of each modification state of each histone to the sequential steps of chromatin transcription was yet to be quantified because of the difficulty in precise reconstitution of a chromatin template with the epigenetic modification(s) of interest and quantification of RNA transcription from it. Using genetic code expansion and cell free protein synthesis, we synthesized histone H4 containing designed site-specific acetylation(s) and reconstituted a tetra-acetylated nucleosome."

Histone modifications target various stages (as described in Figure 1) in the process of transcription at the chromatin level, which could in turn affect the rate of transcription. The first stage, 'chromatin accessibility', involves the opening up of the tightly condensed structure and making it accessible to the transcription machinery. The second stage is the 'formation of transcriptionally competent chromatin', which prepares the chromatin for the binding of transcript synthesizing complexes. The third stage is 'priming before transcription', which aids the assembly of accessory proteins required to begin transcription. The final stage of transcription involves the sequential addition of nucleotides to form the transcript.

To study how site-specific histone modifications, including acetylation, affect the stages of transcription, the researchers created a reconstituted nucleosome carrying two copies of an RNA coding sequence from Xenopus, a frog species, with acetylation on specific sites of the histone proteins. This system simulates the dynamic changes in chromatin within the living cell, which affect transcription. They developed an accurate and highly sensitive fluorescence-based detection system that can measure the minute concentrations of transcripts in real time. On applying their kinetic model (see Figure 2), they found that acetylation at four specific histone sites increases the accessibility of chromatin threefold when compared with chromatin lacking acetylation.

The model's versatility also allows for it to be used for quantifying other epigenetic modifications. Highlighting the potential applications of their study, Takinoue states, "Our mathematically described kinetic model allowed us to determine the rates of chromatin transcription from non-acetylated and tetra-acetylated chromatin templates. Our methodology will be applicable to a wide variety of chromatin-mediated reactions for quantitative understanding of the importance of epigenetic modifications."

WASHINGTON--Drinks with sucrose compared to glucose may cause young adults to produce lower levels of appetite-regulating hormones, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Too much sugar consumption is a contributing factor for obesity. Sucrose, or "table sugar," is composed of equal parts glucose and fructose and is often added to processed foods like soda, candy, cereal and canned foods. Glucose can be found in foods like honey and dried fruits.

"Our study found that when young adults consumed drinks containing sucrose, they produced lower levels of appetite-regulating hormones than when they consumed drinks containing glucose (the main type of sugar that circulates in the bloodstream)," said study author Kathleen Page, M.D., of the USC Keck School of Medicine in Los Angeles, Calif. "This study is the first to show how individual characteristics, including body weight, sex and insulin sensitivity, affect hormone responses to two different types of sugar, sucrose and glucose. These findings highlight the need to consider how individual characteristics affect the body's responses to different types of sugar and other nutrients in our food supply."

The researchers studied 69 young adults between the ages of 18-35 years old who participated in two study visits where they consumed drinks containing either sucrose or glucose. They found that when the young adults consumed drinks containing sucrose, they produced lower amounts of hormones that suppress hunger compared to when they consumed drinks containing an equal dose of glucose. They also found that individual characteristics, including body weight and sex, affected the hormone responses to the different sugars.

An article published in the Journal of Counseling & Development examines how pre-existing racial and ethnic disparities, exacerbated by COVID-19, have negatively affected communities of color that tend to be overrepresented in lower socioeconomic groups, have limited access to health care and education, have an undocumented status, and work in jobs considered "essential."

The authors provide specific cultural considerations, aspects of crisis management, and creative interventions that counselors can use with clients of color at an appropriate social distance. Because the impact of COVID-19 is likely to be felt for years, it is crucial that counselors be prepared to address the needs of those most affected.

"I believe this article will cultivate a deeper understanding of how intersecting cultural factors may influence treatment and empower professional counselors to connect with diverse client populations in meaningful ways," said co-author Stacey Diane Arañez Litam, PhD, of Cleveland State University.

Washington, December 10, 2020--By not adjusting for school and classroom factors outside the control of educators, classroom observation scores for Black teachers in Chicago Public Schools unfairly penalize them for being more likely to teach in schools in low-income neighborhoods with students who are academically disadvantaged, according to a study published today in Educational Evaluation and Policy Analysis, a peer-reviewed journal of the American Educational Research Association.

VIDEO: Watch the authors discuss study findings and implications

The study found that the typical Black teacher in Chicago ranked at the 37th percentile in classroom observation scores, compared to the 55th percentile for the typical White teacher. Once the researchers controlled for differences in school and classroom factors, including student poverty, misconduct rates, and incoming academic achievement, the gap statistically disappeared. This race gap in scores is important because the evaluation of teacher performance through classroom observations is a common practice in schools across the country, often paired with other measures of teaching effectiveness, such as those based on student test scores. Teachers' classroom observation scores are used by school districts nationwide to determine teacher tenure and promotion decisions.

The study, conducted by Matthew P. Steinberg of George Mason University and Lauren Sartain of the University of North Carolina at Chapel Hill, analyzed student data from Chicago Public Schools for academic years 2013-14 and 2014-15, the first two years of a newly implemented teacher evaluation system. More than 5,500 K-5 teachers from 411 CPS elementary schools were examined.

The study found that 89 percent of the explained Black-White gap in classroom observation scores was driven by differences between the characteristics of schools where Black and White educators typically worked, such as the proportion of students receiving free or reduced-price lunch or average student achievement on end-of-year standardized exams. The other 11 percent of the explained gap was related to classroom-level differences within individual schools, including student poverty, misconduct, and academic achievement. None of the race gap was explained by differences in teachers' measured effectiveness in improving student achievement, by school culture, or by the race of the teachers' evaluators.

"Our findings indicate that these classroom observation scores do not equitably compare the performance of teachers who taught in very different classroom and school settings," said Steinberg, an associate professor of education policy at George Mason University. "The race gap in teacher scores does not reflect real differences in teacher performance."

"Left unadjusted, these scores may lead to disproportionate and incorrect identification of Black teachers for remediation and dismissal, and may have serious implications for the diversity of the teacher workforce," Steinberg said. "Our study, which focused on Chicago, raises questions about how classroom observation scores are being analyzed and used by school leaders across the United States. School leaders everywhere need to account for the potential impact of school and classroom factors on teacher scores."

The authors noted that policymakers and school leaders should encourage the type of teacher sorting that increases opportunities for minority students to be exposed to minority teachers, but that minority teachers might not seek out teaching assignments in some of the country's most economically and racially segregated schools if they believe their evaluation ratings will suffer.

"Across school districts in the United States, and in particular, urban school districts, there is a widening demographic and racial gap between teachers and their students," said Steinberg. "At the same time, prior evidence shows that minority students experience both short- and long-term educational benefits when taught by minority teachers. The potential labor market consequences which we observe in the context of Chicago's teacher evaluation system should be of concern to students, families, and school and policy leaders nationwide."

"Our findings underscore the importance of policymakers refining personnel evaluation systems in ways that ensure greater equity and improve the educational circumstances of teachers and students in the most disadvantaged schools," Steinberg said.

The authors noted that during the COVID-19 pandemic, how teachers are evaluated, particularly in remote environments, is top of mind for school districts and unions.

"While it is perhaps more important than ever that teachers receive feedback on their practice in order to best serve students in these less-than-ideal classroom contexts, teachers raise valid concerns about how observations and student test scores will be used to judge their effectiveness," said Sartain, an assistant professor of education at UNC-Chapel Hill. "The issues raised in our study may be of even greater concern now, in light of COVID-19, when some of the inequities in students' home environments are even more relevant."

Washington, December 10, 2020--By not adjusting for school and classroom factors outside the control of educators, classroom observation scores for Black teachers in Chicago Public Schools unfairly penalize them for being more likely to teach in schools in low-income neighborhoods with students who are academically disadvantaged, according to a study published today in Educational Evaluation and Policy Analysis, a peer-reviewed journal of the American Educational Research Association.

VIDEO: Watch the authors discuss study findings and implications (https://youtu.be/NHugd5koeOo)

The study found that the typical Black teacher in Chicago ranked at the 37th percentile in classroom observation scores, compared to the 55th percentile for the typical White teacher. Once the researchers controlled for differences in school and classroom factors, including student poverty, misconduct rates, and incoming academic achievement, the gap statistically disappeared. This race gap in scores is important because the evaluation of teacher performance through classroom observations is a common practice in schools across the country, often paired with other measures of teaching effectiveness, such as those based on student test scores. Teachers' classroom observation scores are used by school districts nationwide to determine teacher tenure and promotion decisions.

The study, conducted by Matthew P. Steinberg of George Mason University and Lauren Sartain of the University of North Carolina at Chapel Hill, analyzed student data from Chicago Public Schools for academic years 2013-14 and 2014-15, the first two years of a newly implemented teacher evaluation system. More than 5,500 K-5 teachers from 411 CPS elementary schools were examined.

The study found that 89 percent of the explained Black-White gap in classroom observation scores was driven by differences between the characteristics of schools where Black and White educators typically worked, such as the proportion of students receiving free or reduced-price lunch or average student achievement on end-of-year standardized exams. The other 11 percent of the explained gap was related to classroom-level differences within individual schools, including student poverty, misconduct, and academic achievement. None of the race gap was explained by differences in teachers' measured effectiveness in improving student achievement, by school culture, or by the race of the teachers' evaluators.

"Our findings indicate that these classroom observation scores do not equitably compare the performance of teachers who taught in very different classroom and school settings," said Steinberg, an associate professor of education policy at George Mason University. "The race gap in teacher scores does not reflect real differences in teacher performance."

"Left unadjusted, these scores may lead to disproportionate and incorrect identification of Black teachers for remediation and dismissal, and may have serious implications for the diversity of the teacher workforce," Steinberg said. "Our study, which focused on Chicago, raises questions about how classroom observation scores are being analyzed and used by school leaders across the United States. School leaders everywhere need to account for the potential impact of school and classroom factors on teacher scores."

The authors noted that policymakers and school leaders should encourage the type of teacher sorting that increases opportunities for minority students to be exposed to minority teachers, but that minority teachers might not seek out teaching assignments in some of the country's most economically and racially segregated schools if they believe their evaluation ratings will suffer.

"Across school districts in the United States, and in particular, urban school districts, there is a widening demographic and racial gap between teachers and their students," said Steinberg. "At the same time, prior evidence shows that minority students experience both short- and long-term educational benefits when taught by minority teachers. The potential labor market consequences which we observe in the context of Chicago's teacher evaluation system should be of concern to students, families, and school and policy leaders nationwide."

"Our findings underscore the importance of policymakers refining personnel evaluation systems in ways that ensure greater equity and improve the educational circumstances of teachers and students in the most disadvantaged schools," Steinberg said.

The authors noted that during the COVID-19 pandemic, how teachers are evaluated, particularly in remote environments, is top of mind for school districts and unions.

"While it is perhaps more important than ever that teachers receive feedback on their practice in order to best serve students in these less-than-ideal classroom contexts, teachers raise valid concerns about how observations and student test scores will be used to judge their effectiveness," said Sartain, an assistant professor of education at UNC-Chapel Hill. "The issues raised in our study may be of even greater concern now, in light of COVID-19, when some of the inequities in students' home environments are even more relevant."

Researchers at the University of Virginia have shed light on how our genes affect our risk for coronary artery disease, the most common form of heart disease. In addition to identifying gene variants that influence risk, they found that one gene in particular appears to have a protective effect.

Doctors may be able to use the findings to identify people at high risk and to develop better treatments and preventative interventions.

"Current drugs for coronary artery disease treat the risk factors, such as cholesterol or hypertension," said researcher Mete Civelek, PhD, of UVA's Department of Biomedical Engineering and UVA's Center for Public Health Genomics. "Our studies used a genetic approach to identify the mechanisms in the wall of the blood vessels where the disease actually develops."

About Coronary Artery Disease

Heart disease is the most common cause of death in the United States, killing one person every 36 seconds. About 18.2 million Americans have the form known as coronary artery disease, or CAD. The federal Centers for Disease Control and Prevention estimates that more than 350,000 Americans died from CAD in 2017.

Scientists have known that our risk for coronary artery disease is affected by diet, smoking, exercise and other factors, including family history, but the role of our genes remains poorly understood. To better understand that, Civelek and his colleagues began by examining cells from 151 ethnically diverse heart donors. These cells, called vascular smooth muscle cells, can prove either beneficial or harmful in the buildup of fatty plaques inside our blood vessels. That buildup, known as atherosclerosis, causes coronary artery disease.

The researchers examined the smooth muscle cells for 12 different characteristics that influence the stability of the plaque patches. Stability is important - plaques that break loose can cause strokes or heart attacks.

The researchers then compared their findings with vast amounts of genetic data to determine how genes were affecting the smooth muscle cells. They found that naturally occurring gene variations have "significant influence" on the functions of these cells that lead to atherosclerosis and CAD.

These variants, they found, affect how smooth muscle cells behave - how they proliferate, migrate and calcify. These factors determine the stability of the protective caps atop the plaque lesions.

"We found that nearly half of the gene variants that increase the risk for coronary artery disease also affect how the smooth muscle cells behave," said Rédouane Aherrahrou, a postdoctoral fellow in Civelek's team. "This implies that we should study these cells in more detail when it comes to understanding the inherited risk for coronary artery disease."

Protective Effect

Civelek's team also identified a gene, MIA3, that appears very important in ensuring thick, stable protective caps - the desirable kind.

The gene produces a protein that seems to have beneficial effects for cap formation, possibly by promoting smooth muscle cell proliferation. In lab models, reducing the activity of the gene suggested thinner, less stable caps, the researchers found.

"If we can increase the abundance of MIA3 protein in smooth muscle cells," Civelek said, "we may be able to stabilize the plaque lesions and prevent heart attacks."

Researchers at Tokyo Medical and Dental University (TMDU) in Japan show that melatonin and its metabolites promote the formation of long-term memories in mice and protect against cognitive decline.

Chiba, Japan -- Walk down the supplement aisle in your local drugstore and you'll find fish oil, ginkgo, vitamin E, and ginseng, all touted as memory boosters that can help you avoid cognitive decline. You'll also find melatonin, which is sold primarily in the United States as a sleep supplement. It now looks like melatonin marketers might have to do a rethink. In a new study, researchers led by Atsuhiko Hattori at Tokyo Medical and Dental University (TMDU) in Japan have shown that melatonin and two of its metabolites help memories stick around in the brain and can shield mice, and potentially people, from cognitive decline.

One of the easiest ways to test memory in mice is to rely on their natural tendency to examine unfamiliar objects. Given a choice, they'll spend more time checking out unfamiliar objects than familiar ones. The trick is that for something to be familiar, it has to be remembered. Like in people, cognitive decline in mice manifests as poor memory, and when tested on this novel object recognition task, they behave as if both objects are new.

The group of researchers at TMDU were curious about melatonin's metabolites, the molecules that melatonin is broken down into after entering the body. "We know that melatonin is converted into N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK) in the brain," explains Hattori, "and we suspected that they might promote cognition." To test their hypothesis, the researchers familiarized mice to objects and gave them doses of melatonin and the two metabolites 1 hour later. Then, they tested their memory the next day. They found that memory improved after treatment, and that AMK was the most effective. All three accumulated in the hippocampal region of the brain, a region important for turning experiences into memories.

For young mice, exposure to an object three times in a day is enough for it to be remembered the next day on the novel object recognition task. In contrast, older mice behave as if both objects are new and unfamiliar, a sign of cognitive decline. However, one dose of AMK 15 min after a single exposure to an object, and older mice were able to remember the objects up to 4 days later.

Lastly, the researchers found that long-term memory formation could not be enhanced after blocking melatonin from being converted into AMK in the brain. "We have shown that melatonin's metabolite AMK can facilitate memory formation in all ages of mice," says Hattori. "Its effect on older mice is particularly encouraging and we are hopeful that future studies will show similar effects in older people. If this happens, AMK therapy could eventually be used to reduce the severity of Mild Cognitive Impairment and its potential conversion to Alzheimer's disease."

Young adults who increased their use of social media were significantly more likely to develop depression within six months, according to a new national study authored by Dr. Brian Primack, dean of the College of Education and Health Professions and professor of public health at the University of Arkansas.

Compared with participants who used less than 120 minutes per day of social media, for example, young adults who used more than 300 minutes per day were 2.8 times as likely to become depressed within six months.

The study, which will be published online Dec. 10 and is scheduled for the February 2021 issue of the American Journal of Preventive Medicine, is the first large, national study to show a link between social media use and depression over time.

"Most prior work in this area has left us with the chicken-and-egg question," said Primack. "We know from other large studies that depression and social media use tend to go together, but it's been hard to figure out which came first. This new study sheds light on these questions, because high initial social media use led to increased rates of depression. However, initial depression did not lead to any change in social media use."

In 2018, Primack and his colleagues at the University of Pittsburgh sampled more than 1,000 U.S. adults between 18 to 30. They measured depression using the validated nine-item Patient Health Questionnaire and asked participants about the amount of time they used social media on platforms like Facebook, Twitter, Reddit, Instagram, and SnapChat. Their analyses controlled for demographic factors like age, sex, race, education, income and employment, and they included survey weights so the results would reflect the greater U.S. population.

"One reason for these findings may be that social media takes up a lot of time," said Dr. Cesar Escobar-Viera, assistant professor of psychiatry at the University of Pittsburgh and co-author on the study. "Excess time on social media may displace forming more important in-person relationships, achieving personal or professional goals, or even simply having moments of valuable reflection."

The authors suggest that social comparison may also underlie these findings.

"Social media is often curated to emphasize positive portrayals," said Jaime Sidani, assistant professor of medicine at the University of Pittsburgh and co-author of the study. "This can be especially difficult for young adults who are at critical junctures in life related to identity development and feel that they can't measure up to the impossible ideals they are exposed to."

The findings are of particular importance given that depression was recently declared to be the leading global cause of disability by the World Health Organization and accounts for more disability-adjusted life years than all other mental disorders.

"These findings are also particularly important to consider in the age of COVID-19," Primack said. "Now that it's harder to connect socially in person, we're all using more technology like social media. While I think those technologies certainly can be valuable, I'd also encourage people to reflect on which tech experiences are truly useful for them and which ones leave them feeling empty."

Charles Darwin's landmark opus, On the Origin of the Species, ends with a beautiful summary of his theory of evolution, "There is a grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved." In fact, scientists now know that most species that have ever existed are extinct. This extinction of species has on the whole been roughly balanced by the origination of new ones over Earth's history, with a few major temporary imbalances scientists call mass extinction events. Scientists have long believed that mass extinctions create productive periods of species evolution, or "radiations," a model called "creative destruction." A new study led by scientists affiliated with the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology used machine learning to examine the co-occurrence of fossil species and found that radiations and extinctions are rarely connected, and thus mass extinctions likely rarely cause radiations of a comparable scale.

Creative destruction is central to classic concepts of evolution. It seems clear that there are periods in which suddenly many species suddenly disappear, and many new species suddenly appear. However, radiations of a comparable scale to the mass extinctions, which this study, therefore, calls the mass radiations, have received far less analysis than extinction events. This study compared the impacts of both extinction and radiation across the period for which fossils are available, the so-called Phanerozoic Eon. The Phanerozoic (from the Greek meaning "apparent life"), represents the most recent ~ 550-million-year period of Earth's total ~4.5 billion-year history, and is significant to palaeontologists: before this period most of the organisms that existed were microbes that didn't easily form fossils, so the prior evolutionary record is hard to observe. The new study suggests creative destruction isn't a good description of how species originated or went extinct during the Phanerozoic, and suggests that many of the most remarkable times of evolutionary radiation occurred when life entered new evolutionary and ecological arenas, such as during the Cambrian explosion of animal diversity and the Carboniferous expansion of forest biomes. Whether this is true for the previous ~ 3 billion years dominated by microbes is not known, as the scarcity of recorded information on such ancient diversity did not allow a similar analysis.

Palaeontologists have identified a handful of the most severe, mass extinction events in the Phanerozoic fossil record. These principally include the big five mass extinctions, such as the end-Permian mass extinction in which more than 70% of species are estimated to have gone extinct. Biologists have now suggested that we may now be entering a "Sixth Mass Extinction," which they think is mainly caused by human activity including hunting and land-use changes caused by the expansion of agriculture. A commonly noted example of the previous "Big Five" mass extinctions is the Cretaceous-Tertiary one (usually abbreviated as "K-T," using the German spelling of Cretaceous) which appears to have been caused when a meteor hit Earth ~65 million years ago, wiping out the non-avian dinosaurs. Observing the fossil record, scientists came to believe that mass extinction events create especially productive radiations. For example, in the K-T dinosaur-exterminating event, it has conventionally been supposed that a wasteland was created, which allowed organisms like mammals to recolonise and "radiate," allowing for the evolution of all manner of new mammal species, ultimately laying the foundation for the emergence of humans. In other words, if the K-T event of "creative destruction" had not occurred, perhaps we would not be here to discuss this question.

The new study started with a casual discussion in ELSI's "Agora," a large common room where ELSI scientists and visitors often eat lunch and strike up new conversations. Two of the paper's authors, evolutionary biologist Jennifer Hoyal Cuthill (now a research fellow at Essex University in the UK) and physicist/machine learning expert Nicholas Guttenberg (now a research scientist at Cross Labs working in collaboration with GoodAI in the Czech Republic), who were both post-doctoral scholars at ELSI when the work began, were kicking around the question of whether machine learning could be used to visualise and understand the fossil record. During a visit to ELSI, just before the COVID-19 pandemic began to restrict international travel, they worked feverishly to extend their analysis to examine the correlation between extinction and radiation events. These discussions allowed them to relate their new data to the breadth of existing ideas on mass extinctions and radiations. They quickly found that the evolutionary patterns identified with the help of machine learning differed in key ways from traditional interpretations.

The team used a novel application of machine learning to examine the temporal co-occurrence of species in the Phanerozoic fossil record, examining over a million entries in a massive curated, public database including almost two hundred thousand species.

Lead author Dr Hoyal Cuthill said, "Some of the most challenging aspects of understanding the history of life are the enormous timescales and numbers of species involved. New applications of machine learning can help by allowing us to visualise this information in a human-readable form. This means we can, so to speak, hold half a billion years of evolution in the palms of our hands, and gain new insights from what we see."

Using their objective methods, they found that the "big five" mass extinction events previously identified by palaeontologists were picked up by the machine learning methods as being among the top 5% of significant disruptions in which extinction outpaced radiation or vice versa, as were seven additional mass extinctions, two combined mass extinction-radiation events and fifteen mass radiations. Surprisingly, in contrast to previous narratives emphasising the importance of post-extinction radiations, this work found that the most comparable mass radiations and extinctions were only rarely coupled in time, refuting the idea of a causal relationship between them.

Co-author Dr Nicholas Guttenberg said, "the ecosystem is dynamic, you don't necessarily have to chip an existing piece off to allow something new to appear."

The team further found that radiations may in fact cause major changes to existing ecosystems, an idea the authors call "destructive creation." They found that, during the Phanerozoic Eon, on average, the species that made up an ecosystem at any one time are almost all gone by 19 million years later. But when mass extinctions or radiations occur, this rate of turnover is much higher.

This gives a new perspective on how the modern "Sixth Extinction" is occurring. The Quaternary period, which began 2.5 million years ago, had witnessed repeated climate upheavals, including dramatic alternations of glaciation, times when high latitude locations on Earth, were ice-covered. This means that the present "Sixth Extinction" is eroding biodiversity that was already disrupted, and the authors suggest it will take at least 8 million years for it to revert to the long term average of 19 million years. Dr Hoyal Cuthill comments that "each extinction that happens on our watch erases a species, which may have existed for millions of years up to now, making it harder for the normal process of 'new species origination' to replace what is being lost."

Researchers in South Korea have developed a technology that enables immediate detection of specific airborne viruses in the field. The Korea Institute of Science and Technology (KIST)
announced that the collaborative research team led by Dr. Joonseok Lee from Molecular Recognition Research Center, Professor Min-Gon Kim from the Department of Chemistry, Gwangju Institute of Science and Technology (GIST), and Professor Chan-Seon Song from the Department of Veterinary Medicine, Konkuk University, developed a detection platform that can simultaneously sample and monitor airborne viruses in the field.

Testing the biological hazards such as various bacteria, fungi, and viruses present in the air generally requires collecting the sample air from the field and conducting a separate analysis on the sample in the laboratory. This analysis process may take a few hours to even several days. Although the existing techniques that support on-site analysis without having to transfer the sample back to the laboratory enabled monitoring the concentration of bacteria or fungi, they displayed limitations in distinguishing the specific microorganism existence or being used without further cleaning.

The KIST-GIST collaborative research team developed an integrated sampling/monitoring platform that uses a disposable kit to easily collect and detect airborne viruses on-site. The disposable virus sampling/monitoring kit developed by the team is similar to the pregnancy test kit, and enables completion of both sampling and diagnosing on airborne viruses within 50 minutes on-site (10 to 30 minutes of sampling and 20 minutes of diagnosis) without requiring a separate cleaning or separation process.

The developed monitoring platform collects and concentrates the airborne virus on a porous glass fiber pad, and then the virus is flowed to the detection zone by a capillary force. The flowed virus is combined with the near-infrared (NIR) emission of synthesized nanoprobes conjugated with antibodies that react only to specific viruses in order to selectively detect the desired viruses even in an environment having simultaneous existence of several types of viruses. In addition, the platform supports injection of more than four kits at once to enable monitoring of multiple virus types at once.

The airborne viruses are affected by external factors such as the indoor space area size, the use of air conditioning system, and temperature and humidity. Thus, the collaborative research team established an artificial aerosolization chamber system that can regulate external factors to verify the developed platform and conducted experiments under certain conditions. The team was able to sample influenza viruses spread out in a large space, concentrate the virus to about more than one million times concentration in a porous pad, and recover the viruses attached to the pad surface with an efficiency of about 82% through surface pretreatment and test solution optimization to finally detect the virus in the detection zone.

"This platform supports an immediate analysis on the field collected sample, and it can be implemented as an indoor air pollution monitoring system for diagnosing airborne biological hazards such as the COVID-19 virus," Dr. Joonseok Lee at KIST said.

Researchers from Temple University, Tsinghua University, and Fudan University published a new paper in the Journal of Marketing that explores the business impact of PPI on buyers' purchase behaviors and sellers' sales activities.

The study, forthcoming in the Journal of Marketing, is titled "The Impact of Platform Protection Insurance on Buyers and Sellers in the Sharing Economy: A Natural Experiment" and is authored by Xueming Luo, Siliang Tong, Zhijie Lin, and Cheng Zhang. The research: (1) quantifies the impact of PPI in the sharing economy; (2) reveals buyer-side and seller-side responses to PPI; and (3) describes the role of the prior experiences of buyers and sellers.

The rise of the sharing economy has dramatically reshaped marketing thought and practice. The projected revenue from sharing accommodations and transportation alone will surpass $335 billion in 2025. The recent initial public offerings of Uber and Lyft exemplify this remarkable growth.

However, consumers continue to face high transaction uncertainty and purchase risks on sharing platforms, which host unbranded individual sellers offering products of mixed quality. Although most sharing platforms have review-based reputation systems, these systems are insufficient to fully eliminate consumer risks due to review bias, inflation, and manipulation on the platform. Therefore, major sharing economy players have adopted platform-level buyer protection insurance (PPI), which refers to a blanket safeguard program that provides buyers with insurance protection against product-quality failures caused by sellers on the platform.

Luo says, "We find that PPI significantly increases buyer spending and seller revenues, affirming the benefits of this service in the sharing economy. We also uncover multifaceted buyer-side and seller-side responses that enable such benefits." PPI boosts buyer spending by increasing product orders and variety-seeking behavior among buyers. PPI boosts seller revenues by increasing customer retention and acquisition. Additional preliminary findings show that PPI does not increase adverse selection among buyers (i.e., buyers did not purchase more items from lower-quality sellers) or opportunistic behaviors among sellers (i.e., sellers did not raise their prices or receive more consumer complaints) in the short run. Further, the insurance benefits are amplified for buyers with worse prior experiences and sellers with shorter tenure on the platform, suggesting that PPI acts as a reputable quality signal to reduce transaction uncertainty and purchase risks on the sharing platform.

Tong adds that "Our research also offers useful and actionable implications for platform managers. Managers can use PPI to affect buyer and seller behaviors and subsequent business performance. Our findings suggest that PPI may nurture trust among consumers and boost sales transactions for sellers, which will improve the business performance of sharing platforms. Results on whether and how PPI affects the efficacy of sharing platforms also enable platform managers to better communicate and build a trusted relationship with external stakeholders to gain more institutional legitimacy from public-policymakers, raise funding from venture capital and stock markets, and boost platform reputation in news channel and social media."

Furthermore, platform managers may craft more targeted communication strategies across different user segments to earn higher returns on PPI. For example, PPI has a stronger beneficial impact for buyers with worse prior experiences and for sellers with less experience on the platform. Thus, for more vulnerable customers with dire needs of protection in the marketplace, a targeted marketing message that emphasizes the risk-reduction benefit of PPI might offer a more effective signal to boost their purchase confidence on the sharing platform.

To justify sharing platforms' investment on PPI, platform managers are often challenged to scientifically quantify the causal impact because randomized field experiments that protect some buyers through insurance but exclude others are unethical in the real world. Lin explains that "Our DID modelling with two-way fixed effects based on a natural experiment provides managers with a viable solution or toolbox to scientifically gauge the causal impact of insurance and other platform governance policies in the sharing economy."

A single protein that appears necessary for the COVID-19 virus to reproduce and spread to other cells is a potential weakness that could be targeted by future therapies.

The molecule, known as transmembrane protein 41 B (TMEM41B), is believed to help shape the fatty outer membrane that protects the virus' genetic material while it replicates inside an infected cell and before it infects another.

The latest finding comes from a pair of studies led by researchers at NYU Grossman School of Medicine and NYU Langone Health's Perlmutter Cancer Center, and colleagues at Rockefeller University and elsewhere.

Published in the journal Cell online Dec. 8, the studies revealed that TMEM41B was essential for SARS-CoV-2 to replicate. In a series of experiments, researchers compared how the COVID-19 virus reproduces in infected cells to the same processes in two dozen deadly flaviviruses, including those responsible for yellow fever, West Nile, and Zika disease. They also compared how it reproduces in infected cells to three other seasonal coronaviruses known to cause the common cold.

"Together, our studies represent the first evidence of transmembrane protein 41 B as a critical factor for infection by flaviviruses and, remarkably, for coronaviruses, such as SARS-CoV-2, as well," says the studies' co-senior investigator John T. Poirier, PhD.

"An important first step in confronting a new contagion like COVID-19 is to map the molecular landscape to see what possible targets you have to fight it," says Poirier, an assistant professor of medicine at NYU Langone Health. "Comparing a newly discovered virus to other known viruses can reveal shared liabilities, which we hope serve as a catalogue of potential vulnerabilities for future outbreaks."

"While inhibiting transmembrane protein 41 B is currently a top contender for future therapies to stop coronavirus infection, our results identified over a hundred other proteins that could also be investigated as potential drug targets," says Poirier, who also serves as director of the Preclinical Therapeutics Program at NYU Langone and Perlmutter Cancer Center.

For the studies, researchers used the gene-editing tool CRISPR to inactivate each of more than 19,000 genes in human cells infected with each virus, including SARS-CoV-2. They then compared the molecular effects of each shutdown on the virus' ability to replicate.

In addition to TMEM41B, some 127 other molecular features were found to be shared among SARS-CoV-2 and other coronaviruses. These included common biological reactions, or pathways, involved in cell growth, cell-to-cell communication, and means by which cells bind to other cells. However, researchers say, TMEM41B was the only molecular feature that stood out among both families of viruses studied.

Interestingly, Poirier notes, mutations, or alterations, in TMEM41B are known to be common in one in five East Asians, but not in Europeans or Africans. He cautions, however, that it is too early to tell if this explains the relatively disproportionate severity of COVID-19 illness among some populations in the United States and elsewhere. Another study finding was that cells with these mutations were more than 50 percent less susceptible to flavivirus infection than those with no gene mutation.

Poirier says more research is needed to determine if TMEM41B mutations directly confer protection against COVID-19 and if East Asians with the mutation are less vulnerable to the disease.

The research team next plans to map out TMEM41B's precise role in SARS-CoV-2 replication so they can start testing treatment candidates that may block it. The team also has plans to study the other common pathways for similar potential drug targets.

Poirier adds that the research team's success in using CRISPR to map the molecular weaknesses in SARS-CoV-2 serves as a model for scientists worldwide for confronting future viral outbreaks.