Culture

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Prediction model uses patient data at admission to determine potential disease trajectory for COVID-19 patients
Older age and obesity independent risk factors for severe disease and death
Data can be used to determine resource allocation and care decisions

Data collected from participants upon hospital admission at a single health care system were used to develop a decision tool called the COVID-19 Inpatient Risk Calculator (CIRC). This prediction model proved accurate at determining potential disease trajectory, or whether a patient's disease would worsen while being treated in the hospital and at what point in their care that might happen. Older age and obesity were found to be independent risk factors for progression of COVID-19 to severe disease or death. Findings from a cohort study are published in Annals of Internal Medicine.

Researchers from Johns Hopkins University School of Medicine and Johns Hopkins Bloomberg School of Public Health reviewed 827 consecutive COVID-19 admissions in five Maryland and Washington, D.C. area hospitals to determine the factors on hospital admission that are predictive of severe disease or death from COVID-19. Among the risk factors researchers considered as part of the model were a patient's age, body mass index (BMI), lung health and chronic disease, as well as vital signs and the severity of a patient's COVID-19 symptoms at the time of admission. The researchers found that 90 percent of deaths occurred in patients 60 years and older. Other risk factors included older age and living in a nursing home, especially in patients over 70. BMI, independent of age, was also associated with progression to severe disease or death. The researchers noted how quickly patients could progress to severe illnesses when patients had all or some of the risk factors.

MELBOURNE, Australia, September 22, 2020 - Is the world prepared a wave of neurological consequences that may be on its way as a result of COVID-19? This question is at the forefront of research underway at the Florey Institute of Neuroscience and Mental Health. A team of neuroscientists and clinicians are examining the potential link between COVID-19 and increased risk of Parkinson's disease, and measures to get ahead of the curve.

"Although scientists are still learning how the SARS-CoV-2 virus is able to invade the brain and central nervous system, the fact that it's getting in there is clear. Our best understanding is that the virus can cause insult to brain cells, with potential for neurodegeneration to follow on from there," said Professor Kevin Barnham from the Florey Institute of Neuroscience & Mental Health.

In a review paper published today, researchers put spotlight on the potential long-term neurological consequences of COVID-19, dubbing it the 'silent wave'. They are calling for urgent action to be taken to have available more accurate diagnostic tools to identify neurodegeneration early on and a long-term monitoring approach for people who have been infected with the SARS-CoV-2 virus.

The researchers report that neurological symptoms in people infected with the virus have ranged from severe, such as brain hypoxia (lack of oxygen), to more common symptoms such as loss of smell.

"We found that loss of smell or reduced smell was on average reported in three out of four people infected with the SARS-CoV-2 virus. While on the surface this symptom can appear as little cause for concern, it actually tells us a lot about what's happening on the inside and that is that there's acute inflammation in the olfactory system responsible for smell," explained Florey researcher Leah Beauchamp.

Inflammation is understood to play a major role in the pathogenesis of neurogenerative disease and has been particularly well studied in Parkinson's. Further research into these illnesses may prove critical for future impacts of SARS-CoV-2.

"We believe that loss of smell presents a new way forward in detecting someone's risk of developing Parkinson's disease early. Armed with the knowledge that loss of smell presents in around 90% of people in the early stages of Parkinson's disease and a decade ahead of motor symptoms, we feel we are on the right track," added Ms Beauchamp.

Clinical diagnosis of Parkinson's disease currently relies on presentation of motor dysfunction, but research shows that by this time 50-70% of dopamine cell loss in the brain has already occurred.

"By waiting until this stage of Parkinson's disease to diagnose and treat, you've already missed the window for neuroprotective therapies to have their intended effect. We are talking about an insidious disease affecting 80,000 people in Australia, which is set to double by 2040 before even considering the potential consequences of COVID, and we currently have no available disease-modifying therapies," said Professor Barnham.

The researchers hope to establish a simple, cost-effective screening protocol aiming to identify people in the community at risk of developing Parkinson's, or who are in early stages of the disease, at a time when therapies have the greatest potential to prevent onset of motor dysfunction. They plan to put the proposal forward for funding from the Australian Government's Medical Research Future Funding scheme.

Additionally, the team have developed two neuroprotective therapies currently under investigation and have identified a cohort of subjects who are ideally suited to study the treatments. Through their research they gained new evidence that people with REM sleep behaviour disorder have a higher predisposition to go on to develop Parkinson's disease.

Parkinson's disease is a significant economic burden costing the Australian economy in excess of $10 billion a year.

"We have to shift community thinking that Parkinson's not a disease of old age. As we've been hearing time and time again, the coronavirus does not discriminate - and neither does Parkinson's," said Professor Barnham.

"We can take insight from the neurological consequences that followed the Spanish Flu pandemic in 1918 where the risk of developing Parkinson's disease increased two to three-fold. Given that the world's population has been hit again by a viral pandemic, it is very worrying indeed to consider the potential global increase of neurological diseases that could unfold down track."

He added, "The world was caught off guard the first-time, but it doesn't need to be again. We now know what needs to be done. Alongside a strategized public health approach, tools for early diagnosis and better treatments are going to be key."

Before the pandemic, there wasn't any difference in the rates at which Democratic and Republican voters actually cast their ballots by mail or in-person. That may change now.

Based on nationally representative surveys conducted in the spring of 2020 and through the summer, researchers report a significantly greater preference for mail, or absentee, ballots among Democrats than among Republicans. The researchers document for the first time a partisan gap in stated preferences in April 2020. By June, that gap had doubled - from a 10% difference in April to a 20% one in June. The gap was even wider among those exposed to scientific projections about the COVID-19 pandemic, with Democrats then expressing even greater preferences for mail ballots while Republicans were unaffected.

These findings are detailed in a study published in the Proceedings of the National Academy of Sciences.

After finalizing their PNAS paper, the research team - members of the New Electorate Project from UC San Diego, UC Riverside and the University of Southern California - continued to survey America's eligible voters. The partisan gap, they say, has continued to grow: By late August, more than half of Democrats but less than a quarter of Republicans said they personally preferred to vote by mail.

"A serious partisan divide has opened up on preferences for voting by mail and has grown from a gap to a gulf over the past several months," said Thad Kousser, a UC San Diego professor of political science, who is senior author on the PNAS study and the New Electorate Project's principal investigator.

Study also finds widespread, bipartisan support for mail ballots

An encouraging finding: Personal preferences aside, there is bipartisan support for making mail ballots available to all voters who want them.

"Despite the polarization, we see support across the board for making voting more accessible," said Mackenzie Lockhart, corresponding author on the PNAS study and a political science doctoral candidate at UC San Diego.

"In all our surveys, a majority of Republicans and Democrats supported not only making vote-by-mail ballots available to anyone who wants them," Lockhart said, "but also sending ballots directly to every registered voter, regardless of how they intend to vote."

Kousser notes that policies allowing any voter who requests an absentee ballot to cast their vote this way are place in most states, including nearly every swing state in the presidential election.

Why the gap?

The researchers attribute the growth in the partisan divide to two things: signals from partisan elites in both parties and Republican partisans' distrust in science and experts.

"Republican and Democratic lawmakers have staked out very different positions on voting by mail and voters have begun to notice," Lockhart said. "But on top of that, our evidence suggests that voters' views on COVID-19 are probably also polarizing the issue. We found that scientific predictions about the COVID-19 pandemic had much smaller effects on Republicans than Democrats and contributed to a larger gap between partisans."

Will the gap matter in November?

Each of the surveys was conducted with more than 5,600 Americans of voting age. What remains an open question is whether there will now also be a partisan difference in actual voting behaviors, with Republicans turning out to vote in person at polling places at greater rates than Democrats. And will Democrats, in turn, vote at greater rates by mail ballot - which, depending on state laws, they'll then drop off at polling places or secure drop-boxes, or send through the mail?

Also an open question: Will this gap affect the outcomes of the 2020 U.S. presidential election?

"We don't know what will happen in November," Lockhart said, "and if things go smoothly with both voting methods, then the partisan differences we found might not matter. But, based on our results, if either mode of voting (in-person or by mail) ends up not running smoothly, that's when these differences in how partisans want to vote could matter."

If a spike in infection rates makes voting in-person more difficult or delays in the mail mean mail ballots arrive after the deadline, Lockhart said, how exactly partisans decide to vote could have a big effect on the election.

The study's other co-authors are Seth Hill of UC San Diego, Jennifer Merolla of UC Riverside and Mindy Romero of the University of Southern California

The New Electorate Project is funded by the UC Office of the President.

The recent deaths of George Floyd, Breonna Taylor and Ahmaud Arbery added new momentum to the Black Lives Matter social movement in the United States. But Stanford researchers have found that local news media have not treated Black and Hispanic lives as equal in value to white lives in stories.

Forrest Stuart, associate professor of sociology in Stanford's School of Humanities and Sciences, worked with University of Chicago researchers Kailey White and Shannon L. Morrissey to quantify how local news organizations cover homicide victims in minority neighborhoods.

The team focused on Chicago, Illinois, in 2016 - one of the deadliest years in the nation's third-largest city - when 762 people were killed. The study, published Sept. 17 in the journal Sociology of Race and Ethnicity, found that victims killed in predominantly Black neighborhoods - common to Chicago's West and South Sides - received less news coverage than those killed in mostly white neighborhoods - common to Chicago's North Side. The disparities extend to the city's Hispanic-majority neighborhoods, where victims received more coverage than killings in Black neighborhoods.

But both categories of victims were often not covered with "complex personhood," the researchers concluded, meaning any mention of the fullness of their lives as spouses, parents, children, siblings or community members. This is something the family of recent police shooting victim Jacob Blake, of Kenosha, Wisconsin, has talked about. "I am my brother's keeper," Blake's sister Letetra Widman said in news interviews. "And when you say the name Jacob Blake, make sure you say father, make sure you say cousin, make sure you say son, make sure you say uncle."

"We all have these universal things about us that make us human," Stuart said, "so the question very quickly becomes: Who has the privilege, who has the honor of being talked about in any of those ways?"

"We can assume that anyone who dies is a family member - they have people who are going to be mourning their death, a community that is going to be affected," Morrissey added. "So why is it that only some victims are written about in that way? What makes a reporter choose to put in the effort to track down a middle-school teacher or talk to a neighbor?"

Building an article database

The study was motivated by the 2014 police killings of Michael Brown in Ferguson, Missouri, and Laquan McDonald in Chicago. Stuart began subscribing to news alerts about homicides across Chicago and thought there was something different about the way shootings were covered on the mostly white North Side compared to other largely minority areas of the city.

"As a social scientist, I thought, 'Wouldn't it be even more powerful to quantify the value of different folks' lives from different racial identities and backgrounds in news coverage and hold those up next to each other?'" he said.

Stuart and his colleagues spent two years collecting and manually analyzing thousands of news articles. They combed through every article on every death to determine the victim's name, race and gender as well as time and location of death and then reconciled that information with police data.

The team examined 2,245 news articles about homicide victims from the Chicago Sun-Times' Homicide Watch, the Chicago Tribune's Homicide Tracker and the now-defunct DNAInfo database to determine how the individuals were covered. They looked at how much coverage each person received, considering factors like word count, and which articles recognized someone as more than a victim - as a complex, multi-dimensional human being with a family and community connections. The articles were cross-referenced with official Chicago Police Department public records.

Their analysis determined that about 35 percent of murder victims in majority-white neighborhoods are likely to be covered as a complex person - about double that of victims in majority-Black neighborhoods (17 percent) and majority-Hispanic neighborhoods (18 percent). Furthermore, homicide victims in majority-white neighborhoods received about 450 words more of text on average than those killed in majority-Black neighborhoods. The researchers found that Black victims' names were sometimes misspelled or had transposed letters in the news reports.

"Even just reading the news articles, there was a palpable difference in the way that victims and neighborhoods were talked about," said Morrissey, a doctoral student in the Department of Sociology at the University of Chicago. "This paper does well to remind us that the disparities are on a neighborhood and community level."

Disparities in news coverage

Victims across races were covered in an average of 2.8 newspaper articles, with an average of 3.8 articles for white victims, 2.8 for Black victims and 2.6 for Hispanic victims. "Not all of these articles - even for the same person - are made the same," Stuart explained. "Just because someone's name is showing up in an article doesn't mean the article has the same kind of essence."

The researchers differentiated between articles that simply listed a victim in a weekend review of homicides and more nuanced articles that tried to capture an individual's life.

"There were other articles especially about victims from majority-white neighborhoods where the reporters were doing interviews with family members, with friends, with teachers, coaches, with all sorts of people in the victim's life, and they were providing quotes," said White, a fourth-year doctoral student in the Department of Sociology at the University of Chicago. "They talked about the victim in a very different way - like this complex person who has value and who is being missed by the community, family members and friends."

The researchers acknowledged an important caveat in the study: Chicago remains deeply segregated. Only 4 percent of Chicago's 2016 murders happened to white victims and few of them were killed in majority-Black neighborhoods. Similarly, only a few Black victims were killed in mostly white neighborhoods. They also acknowledged that their study focused on one city and the results could look different in various parts of the country, as well as in suburban versus urban centers.

But in Chicago, a city that is almost a third white, a third Black and a third Hispanic, racial disparities in news coverage persist, even when controlling for each neighborhood's unique homicide rate, according to the researchers. They emphasized that their study demonstrates the importance of understanding the racialization of places at the neighborhood level and the cycle of devaluing minority lives.

"Race isn't just your phenotypical coloring," Stuart said. "Race is a series of historic, economic, symbolic and, importantly, geographical set of power relations where some people are stigmatized and rendered powerless or less powerful. These are systems of domination."

DURHAM, N.C. -- A study appearing next week in the journal Nature Communications offers some good news in the search for antiviral drugs for hard-to-treat diseases. Researchers have identified a potential new drug candidate against enterovirus 71, a common cause of hand, foot and mouth disease in infants and young children.

The compound of interest is a small molecule that binds to RNA, the virus's genetic material, and changes its 3-D shape in a way that stops the virus from multiplying without harming its human host.

There are currently no FDA-approved drugs or vaccines for enterovirus 71, which affects hundreds of thousands of children each year, particularly in Southeast Asia. While most people get better within 7 to 10 days after suffering little more than a fever and rash, severe cases can cause brain inflammation, paralysis and even death.

The work could pave the way for new treatments for other viral infections as well, says a team of scientists at Duke University, Case Western Reserve University and Rutgers University.

Traditionally, most drugs are designed to bind to proteins to block or disrupt their role in causing disease. But much of the genome in humans and their microbial pathogens doesn't code for proteins, which means that only a fraction of their genetic material is targeted by existing drugs.

"For diseases that don't have good treatments, maybe the problem is we've been targeting the wrong thing," said co-author Amanda Hargrove, associate professor of chemistry at Duke.

Instead of targeting proteins, Hargrove and others are looking for small molecules that target RNA, which most drug discovery programs have overlooked.

When a virus like enterovirus 71 (or SARS-CoV-2, the virus that causes COVID-19) infects a human cell, it injects its RNA into the cell, hijacking the internal machinery to make copies of itself that eventually burst out to infect neighboring cells.

Previous work on enterovirus 71 singled out one part of its RNA structure that helps the virus co-opt the host machinery it needs to replicate. This RNA region folds over on itself to form a hairpin, with a bulge in the middle where unpaired nucleotides balloon out to one side.

If a drug can be developed to inhibit this region, the researchers say, we might be able to block the virus before it has a chance to spread.

For the current study, Hargrove and colleagues screened a library of some 30 small molecules, looking for ones that bind tightly to the bulge and not other sites in the virus's RNA.

RNA is a wiggly molecule; when it binds to other molecules such as host proteins or small molecule drugs it takes on different 3-D shapes.

The researchers identified one molecule, dubbed DMA-135, that enters infected human cells and attaches itself to the surface of the bulge, creating a kink in this region.

This shape change, in turn, opens access to another molecule -- a human repressor protein that blocks the "reading out" of the virus's genetic instructions, stopping viral growth in its tracks.

In an experiment, the researchers were able to use the molecule to stop the virus from building up inside human cell cultures in the lab, with bigger effects at higher doses.

Hargrove says it would take at least five years to move any new drug for hand, foot and mouth disease from the lab to medicine cabinets. Before their small molecule could reach patients, the next step is to make sure it's safe and effective in mice.

In the meantime, the researchers are building on their success with enterovirus 71 and looking at whether RNA-targeting small molecules could be used to tackle other RNA viruses too, including SARS-CoV-2.

Researchers around the world are a step closer to a better understanding of the intricacies of COVID-19 thanks to two new web resources developed by investigators at Baylor College of Medicine and the University of California San Diego.
The resources are freely available through the Signaling Pathways Project (Baylor) and the Network Data Exchange (UCSD). They put at researchers' fingertips information about cellular genes whose expression is affected by coronavirus infection and place these data points in the context of the complex network of host molecular signaling pathways. Using this resource has the potential to accelerate the development of novel therapeutic strategies. The study appears in the journal Scientific Data.

"Our motivation for developing this resource is to contribute to making research about COVID-19 more accessible to the scientific community. When researchers have open access to each other's work, discoveries move forward more efficiently," said leading author Dr. Neil McKenna, associate professor of molecular and cellular biology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

The Signaling Pathway Project

For years, the scientific community has been generating and archiving molecular datasets documenting how genes are expressed as cells conduct their normal functions, or in association with disease. However, usually this information is not easily accessible.

In 2019, McKenna and his colleagues developed the Signaling Pathways Project, a web-based platform that integrates molecular datasets published in the scientific literature into consensus regulatory signatures, or what they are calling consensomes, that rank genes according to their rates of differential expression.

In the current study, the researchers generated consensomes for genes affected by infection with three major coronaviruses, Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome coronaviruses 1 (SARS1) and 2 (SARS2, which causes COVID-19).

McKenna and his colleagues provide a resource that assists researchers in making the most out of coronavirus' datasets. The resource identifies the genes whose expression is most consistently affected by the infection and integrates those responses with data about the cells' molecular signaling pathways, in a sense getting a better picture of what happens inside a cell infected by coronavirus and how the cell responds.

"The collaboration with UCSD makes our analyses available as intuitive Cytoscape-style networks," says McKenna. "Because using these resources does not require training in meta-analysis, they greatly lower the barriers to usability by bench researchers."

Providing new insights into COVID-19

The consensus strategy, the researchers explain, can bring to light previously unrecognized links or provide further support for suspected connections between coronavirus infection and human signaling pathways, ultimately simplifying the generation of hypotheses to be tested in the laboratory.

For example, the connection between pregnancy and susceptibility to COVID-19 has been difficult to evaluate due to lack of clinical data, but McKenna and colleagues' approach has provided new insights into this puzzle.

"We found evidence that progesterone receptor signaling antagonizes SARS2-induced inflammatory signaling mediated by interferon in the airway epithelium. This finding suggests the hypothesis that the suppression of the interferon response to SARS2 infection by elevated circulating progesterone during pregnancy may contribute to the asymptomatic clinical course," McKenna said.

Consistent with their hypothesis, while this paper was being reviewed, a clinical trial was launched to evaluate progesterone as a treatment for COVID-19 in men.

COLUMBUS, Ohio - The disruptive inventions that make people go "Wow!" tend to come from research in the heart of cities and not in the suburbs, a new study suggests.

Researchers found that, within metro areas, the majority of patents come from innovations created in suburbs - often in the office parks of big tech companies like Microsoft and IBM.

But the unconventional, disruptive innovations - the ones that combine research from different technological fields - are more likely to be produced in cities, said Enrico Berkes, co-author of the study and postdoctoral researcher in economics at The Ohio State University.

These unconventional patents are ones that, for example, may blend research on acoustics with research on information storage - the basis for digital music players like the iPod. Or patents that cite previous work on "vacuum cleaning" and "computing" to produce the Roomba.

"Densely populated cities do not generate more patents than the suburbs, but they tend to generate more unconventional patents," said Berkes, who did the work as a doctoral student at Northwestern University.

"Our findings suggest that cities provide more opportunities for creative people in different fields to interact informally and exchange ideas, which can lead to more disruptive innovation."

Berkes conducted the study with Ruben Gaetani, assistant professor of strategic management at the University of Toronto. Their research was published online recently in The Economic Journal.

Previous research had shown that large metropolitan areas are where patenting activity tends to concentrate, Berkes said, suggesting that population density is an important factor for innovation.

But once Berkes and Gaetani started looking more closely at metro areas, they found that a sizable share of these patents was developed in the suburbs - the least densely populated part.
Nearly three-quarters of patents came from places that had density below 3,650 people per square mile in 2000, about the density of Palo Alto, California.

"If new technology is spurred by population density, we wanted to know why so much is happening in the least dense parts of the metro areas," Berkes said.

So Berkes and Gaetani analyzed more than 1 million U.S. patents granted between January 2002 and August 2014. They used finely geolocated data from the U.S. Patent and Trademark Office that allowed them to see exactly where in metro areas - including city centers and specific suburbs - that patented discoveries were made.

But they were also interested in determining the type of innovations produced - whether they would be considered conventional or unconventional. They did this by analyzing the previous work on which each patent was based.

The researchers tagged new patents as unconventional if the inventors cited previous work in widely different areas.

For example, a patent from 2000 developed in Pittsburgh is one of the first recorded inventions in wearable technologies and one of the precursors to products such as Fitbit. It was recognized as unconventional because it cites previous patents in both apparel and electrical equipment - two very distant fields.

After analyzing the data, the researchers found that both urban and suburban areas played a prominent role in the innovation process, but in different ways, Berkes said.

Large innovative companies, such as IBM or Microsoft, tend to perform their research in large office parks located outside the main city centers.

"These companies are very successful in taking advantage of formal channels of knowledge diffusion, such as meetings or conferences, where they can capitalize on the expertise of their scientists and have them work together on specialized projects for the company," Berkes said.

"But it is more difficult for them to tap ideas from other scientific fields because this demands interactions with inventors they're not communicating with every day or running into in the cafeteria or in the hallway."

That's where the urban cores excelled. In cities like San Francisco and Boston, researchers may meet people in entirely different fields at bars, restaurants, museums and cultural events. Any chance encounter could lead to productive partnerships, he said.

"If you want to create something truly new and disruptive, it helps if you have opportunities to casually bump into people from other scientific fields and exchange ideas and experiences and knowledge. That's what happens in cities," he said.

"Density plays an important role in the type, rather than the amount, of innovation."

These findings show the potential value of tech parks that gather technology startup companies in a variety of fields in one place, Berkes said. But they have to be set up properly.

"Our research suggests that informal interactions are important. Tech parks should be structured in a way that people from different startups can easily interact with each other on a regular basis and share ideas," he said.

Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept. 18 in the journal Science Translational Medicine.

A widespread and dangerous immune response to the virus has been linked to acute respiratory distress syndrome, the need for ventilation, and increased mortality in adults with COVID-19. These outcomes are less common in children, which has led to speculation that immune system response to the virus is somehow suppressed. But the new study, which examined serum and cell samples obtained from pediatric and adult patients diagnosed with COVID-19, found that children actually express higher levels of two specific immune system molecules. The researchers believe this may contribute to the better outcomes.

"To our surprise, we found these particular serum cytokines were at higher levels in children than adults," said Kevan Herold, the C.N.H. Long Professor of Immunology and Internal Medicine at Yale and co-senior author of the paper.

Intriguingly, the analysis also showed that certain types of antibody responses thought to be protective were actually higher in adults, including those with severe cases, than in children, the research found.

Since the earliest days of the COVID-19 outbreak, scientists have observed that children infected with the virus tend to fare much better than adults. To determine why that is, Herold, along with his spouse, Betsy Herold, the co-senior author and a professor of pediatrics and microbiology-immunology at Albert Einstein College of Medicine, decided to study blood and cell samples collected from patients of different ages who were admitted with COVID-19 symptoms to the Montefiore Medical Center in New York City.

Specifically, they looked for variations in the types of immune system responses in patients who experienced different health outcomes from the novel coronavirus. The subjects also included children and adolescents diagnosed with multi-system inflammatory syndrome or MIS-C, a rare complication of COVID-19 infection in young people that is associated with a variety of severe health complications.

They found that levels of two immune system molecules -- interleukin 17A (IL-17A), which helps mobilize immune system response during early infection, and interferon gamma (INF-?), which combats viral replication -- were strongly linked to the age of the patients. The younger the patient, the higher the levels of IL-17A and INF-?, the analysis showed.

These two molecules are part of the innate immune system, a more primitive, non-specific type of response activated early after infection, Kevan Herold noted. Conversely, the adults showed a more vigorous adaptive immune system response including higher neutralizing antibody levels, which record signatures of pathogens and target them for elimination.

They also found that children with rare cases of MIS-C also have high levels of IL-17A and INF-?, but seldom exhibit severe damage to lung tissue that characterizes severe adult cases. These children, however, share other immune response signatures linked to more severe adult cases. The source of the IL-17A and INF-? molecules remain unknown, but its identification may shed light on cells that can be targeted to prevent severe effects from COVID-19.

Boosting certain types of immune responses may be beneficial to patients, the authors theorize.

"The suggestion is that kids have a more robust, earlier innate immune response to the virus, which may protect them from progressing to severe pulmonary disease," Betsy Herold said.

An international research team led by scientists from Estonian University of Life Sciences has for the first time sequenced and assembled the genome of the wels catfish (Silurus glanis). The maximum reported size of the wels catfish is 5 m and up to 300 kg, which makes it one of the largest freshwater fish species in the whole world. By deciphering the genetic code of the barbelled giant, scientists expect to better understand the secrets of the wels catfish's exceptionally rapid growth, enormous appetite and longevity.

The wels catfish lives in large European rivers and lakes. Catfish is hunting mainly at night and is not a picky eater, with invertebrates, fish, frogs, rodents and birds in its regular diet. When the water is warm and food is plentiful, the catfish grows extremely rapidly: ten-year-old fish can reach one and a half metres length. Given that a catfish can live up to 80 years, it is no wonder it has rightly become the prized trophy fish and a central character in many legends among anglers.

Due to its rapid growth and tender, boneless flesh, the catfish is increasingly gaining popularity for recreational fishing and aquaculture. The greatest number of wels catfish are being caught from the inland waters of Russia, Kazakhstan and Turkey, and its aquaculture production is currently approximately 2000 tonnes per year. At the same time, the lack of genetic information in wels catfish has inhibited application of modern selective breeding methods that utilize genomic information instead of phenotypic traits to estimate the breeding values of fish. "Assembled wels catfish genome allows researchers to find genomic regions and gene variants that impact growth rate, age at sexual maturity, disease resistance and other relevant traits for aquaculture," explained Riho Gross, Chair professor of Aquaculture at Estonian University of Life Sciences, who led the research.

According to Anti Vasemägi, senior researcher of Estonian University of Life Sciences and professor of Swedish University of Agricultural Sciences, who participated in the work, the size of wels catfish genome can be compared to that of other bony fishes (800 million base pairs), and contains a little more than 21 000 genes. He added that the genome assembly will serve as a springboard for future research aimed at addressing the bottlenecks in catfish aquaculture and challenges linked to conservation of wild populations.

The toughest organisms on Earth, called extremophiles, can survive extreme conditions like extreme dryness (desiccation), extreme cold, space vacuum, acid, or even high-level radiation. So far, the toughest of all seems to be the bacterium Deinococcus radiodurans - able to survive doses of radiation a thousand times greater than those fatal to humans. But to this date, scientists remained puzzled by how radio-resistance could have evolved in several organisms on our planet, naturally protected from solar radiation by its magnetic field. While some scientists suggest that radio-resistance in extremophile organisms could have evolved along with other kinds of resistance, such as resistance to desiccation, a question remained: which genes are specifically involved in radio-resistance?

To address this question, the team of Dr. Cox, at the University of Wisconsin-Madison, decided to "let the cells tell them". The researchers started with the naturally non-resistant bacteria, E. coli, and exposed it to iterative cycles of high-level irradiation. After many rounds of radiation exposure and outgrowth, a few radio-resistant populations emerged. Using whole-genome sequencing, the researchers studied the genetic alterations present in each radio-resistant population and determined which mutation provided radio-resistance to the bacteria.

In their first study, the team of Dr. Cox started by exposing E. coli to 50 rounds of ionization (Bruckbauer et al 2019b). After about 10 rounds, some radio-resistant populations emerged, and after 50, the study of their genetic profile highlighted three mutations responsible for radio-resistance - all in genes linked to DNA repair mechanisms. Here, in their new study, the team exposed the bacteria to 50 more rounds of radiation exposure and selection.

The results published in Frontiers in Microbiology show that the populations of radioresistant E. coli, continued to evolve and sub-populations emerged. Surprisingly, while radio-resistance induced by the first series of ionization could mainly be associated with three mutations, the second induced hundreds of mutations including large deletions and duplications of several genes. "The four populations we are evolving in this new trial have now achieved levels of radio-resistance that are approaching the levels seen with Deinococcus radiodurans. As the current trial has progressed, the genomic alterations have proven to be much more complex than anticipated." Dr. Cox says.

Although it is harder to pinpoint all the mutations contributing to the increase of radio-resistance this time around, the researchers show that more cellular metabolisms are affected (ATP synthesis, iron-sulfur cluster biogenesis, cadaverine synthesis, and reactive oxygen species response). Furthermore, this study proves that radio-resistance can develop to the level of Deinococcus radiodurans, independently to desiccation-resistance. As the exposition to radiation and experimental evolution continues, more data are gathered on how to induce radio-resistance in bacteria. This could one day constitute a precious toolbox of mutations to engineer radioresistant probiotics helping for example patients treated with radiotherapy, or astronauts exposed to space radiation.

BATON ROUGE, Louisiana – More than 18 percent of U.S. adults do not know whether they will have enough to eat from day to day, and the numbers are worse for Hispanics, Blacks, people with obesity, and women, a new report shows.

“The percentage of adults with food insecurity ­– the lack of access to adequate food – more than doubled between 1999 and 2016,”  said Candice Myers, PhD, assistant professor at Pennington Biomedical Research Center and lead author of the article published in JAMA.  “The COVID-19 pandemic has undoubtedly worsened the situation.  The country may face long-term economic and health consequences unless we solve this public health crisis.”

The study looked at national trends in food insecurity among U.S. adults from 1999 to 2016 using data from the National Health and Nutrition Examination Survey. The study found that food insecurity rates jumped to:

35 percent among Hispanic adults, from 19.5 percent
1 percent among Blacks, from 12.4 percent.
6 percent among people with obesity, from 10.4 percent.
2 percent among women, from 8.7 percent.

Dr. Myers said the study further solidifies the link between food insecurity and unhealthy body weight.

Food insecurity has a range of health consequences, all of them negative, she said.  Obesity is key among them. 

“Food insecurity and obesity are not mutually exclusive,” Dr. Myers said.  “Rather, these health issues are linked in such a way that a solution will require public policy that addresses both at the same time.”

Pennington Biomedical Executive Director John Kirwan, PhD, said the intersection of food insecurity and chronic disease highlights the impact of the research center’s work.

“Our research has set the stage to not only continue our current efforts to explore these issues, but also develop new and innovative projects that delve into understanding their impact on the health of the citizens of our community, state and the entire country,” Dr. Kirwan said.

To find out more about how to help, go to:

Greater Baton Rouge Food Bank
Feeding Louisiana
Feeding America

Dr. Myers’ study is at https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2769137.

This work was supported by award GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center, and by grant P30DK072476 from Nutrition Obesity Research Centers (titled “Nutrition and Metabolic Health Through the Lifespan”) sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Instagram users who post self-harm content online are choosing ambiguous hashtags in an attempt to circumvent the social media platform's ban on harmful content, a researcher at the University of Otago, Wellington, has found.

PhD student Jacobo Picardo reviewed research published during the past 10 years about suicide and self-harm content posted on Instagram. Only 10 studies had been published up to the beginning of 2020. Seven of the studies described samples of publicly available Instagram content, while three surveyed or interviewed Instagram users.

Instagram, which has more than a billion active monthly users, is one of the most popular social media platforms among young people.

The studies showed the photo and video-sharing site was a popular platform for posting self-harm content, with depictions of cuts, usually on the arms or legs, the most common.

Users often choose ambiguous hashtags designed to avoid censorship by Instagram, which banned graphic self-harm images from its platform in February 2019, and extended the ban to fictional depictions of self-harm or suicide last October.

Mr Picardo says online communities have emerged around these hashtags, allowing users with self-harm or suicide interests to come together online.

"Instagram's ability to flag such content is limited because hashtags are evolving faster than they can be tracked and assessed by the platform's content moderators.

"Surveillance methods drawing on hashtag and captions to identify self-harming content do not appear to be very effective. Moreover, Instagram's tool for users to report negative content has not been widely adopted, with few Instagram users aware of it.

"Instagram is looking into new technologies, such as using AI automatic image recognition algorithms, which help identify such content. However, there is a lack of consensus about how to best tackle this content."

Mr Picardo says the actual prevalence of self-harm or suicide content on Instagram is unknown, but researchers have found the nature of the content to be diverse, with posts ranging from pictures of wounds and selfies to memes and references to movies or lines from songs.

"In general, self-harm content on Instagram receives a high volume of audience engagement and attention, and visual and gorier posts are likely to receive a greater number of 'likes'."

Users' comments are most likely to show empathic support and care for the content posters, but studies show concerns there may be negative impacts on viewers engaging with such content.

"Self-harm or suicide content online often does not follow media guidelines to prevent negative effects, and some studies show concerns that such content could trigger others to self-harm, as well as perpetuating such behaviour by normalising and validating it and through the sharing of self-harm methods and tips for concealment. However, causal copycat effects have not been proven, and further studies are needed to look into this."

Recent research suggests such content reflects users' expressions of distress, and that there could be some benefits from others engaging with it online, such as by providing a supportive online community and offering alternative coping strategies and tips on reducing self-harming.

Mr Picardo says more accurate and reliable information about those who engage with self-harm content on Instagram is needed.

"We need researchers to speak directly to online users in order to obtain reliable information about them and their views of what constitutes self-harm content online, why they engage with it, how it affects them and how it relates to their lives offline," he says.

As part of his PhD research, he has begun interviewing young adults in Wellington to gain a better understanding of their views of the issue.

New research from UBC Okanagan shows that salvage logging on land damaged by wildfires has negative impacts on a variety of animals.

While post-fire salvage logging is used to mitigate economic losses following wildfire, Karen Hodges, a biology professor in the Irving K. Barber Faculty of Science, says the compounded effects of wildfire and post-fire salvage logging are more severe than what wildlife experience from fire alone.

Wildfires have been increasing in prevalence and severity in recent decades, Hodges says, and salvaging trees after a fire is a common practice. However, the scale and intensity of post-fire logging removes important regenerating habitat for a variety of forest species.

"When trees are removed from a newly burned landscape, birds and mammals lose the last remnants of habitat," she adds. "Salvage logging decreases forest biodiversity and changes ecological processes of post-fire forest regeneration. Mosaics of regenerating forest are changed through the removal of standing and downed trees, which would naturally remain on the landscape following fire."

Hodges notes while BC's logging industry is heavily regulated, harvesting differs between normal harvests and post-fire logging. More frequent wildfires mean an increase in post-fire salvage logging.

"Salvage logging is often done urgently as harvesters attempt to get burned timber to market before the wood deteriorates," she says. "Salvage logging is also done at larger scales and intensities than a standard harvest. This post-fire harvest means wildlife species that can manage after a wildfire do not rebound as quickly from this second disturbance."

The research led by master's student Angelina Kelly studied populations of snowshoe hares and red squirrels in post-fire and salvage-logged areas of the Chilcotin--an area severely impacted by wildfires in 2010 and 2017. Hares and squirrels are important species because predators such as coyote, bobcats, marten, lynx, goshawks and great horned owls rely on them to survive.

"The main concern of a snowshoe hare is to avoid predators. Hares select stands with protective vegetation cover and avoid open areas like clearcuts--even if those areas provide food," says Kelly. "Because of their need for vegetative cover, snowshoe hare populations decrease immediately following fires, clearcut logging or salvage logging."

Their study area, about 32,000 hectares on the eastern edge of the Chilcotin Plateau, was ravaged by wildfire in 2017. While looking for evidence of hares and squirrels, the researchers also conducted vegetation surveys to quantify important habitat attributes in mature forests, burned forest and areas where salvage logging had taken place.

"Post-fire salvage logging greatly changed the habitat structure of post-fire stands, removing vegetative cover and rendering those sites unsuitable for hares and red squirrels," says Kelly. "The post-fire salvage-logged areas supported no hares or red squirrels for at least eight to nine years after the initial wildfire. Burn areas where no post-fire harvesting took place supported low densities of hares and red squirrels by that time."

This loss of prey species contributes to declines in forest predators such as lynx, marten and owls, as Hodges and her team have documented in this region and other studies.

Hodges and Kelly stress that any trees or vegetation left after a wildfire are critical for wildlife immediately after a fire, and promote a healthy mosaic of post-fire habitat. Residual trees facilitate regeneration of burned areas, while also supporting wildlife.

MADISON, Wis. -- As Americans begin pulling up their sleeves for an annual flu vaccine, researchers at the University of Wisconsin-Madison have provided new insights into an alternative vaccine approach that provides broader protection against seasonal influenza.

In a study published in Cell Reports Medicine today (Sept. 22), scientists describe a T-cell-based vaccine strategy that is effective against multiple strains of influenza virus. The experimental vaccine, administered through the nose, delivered long-lasting, multi-pronged protection in the lungs of mice by rallying T-cells, specialist white blood cells that quickly eliminate viral invaders through an immune response.

The research suggests a potential strategy for developing a universal flu vaccine, "so you don't have to make a new vaccine every year," explains Marulasiddappa Suresh, a professor of immunology in the School of Veterinary Medicine who led the research. The findings also aid understanding of how to induce and maintain T-cell immunity in the respiratory tract, a knowledge gap that has constrained the development of immunization strategies. The researchers believe the same approach could apply to several other respiratory pathogens, including the novel coronavirus that causes COVID-19.

"We don't currently have any vaccine for humans on the market that can be given into the mucosa and stimulate T-cell immunity like this," says Suresh, a veterinarian with specialty training in studying T-cell responses to viral infections.

The strategy addresses the Achilles' heel of flu vaccines, which is to achieve specific antibody responses to different circulating influenza strains annually, by harnessing T-cell immunity against multiple strains. In particular, the new approach calls into action tissue-resident memory T-cells, or TRM cells, which reside in the airways and lining of lung epithelial cells and combat invading pathogens. Like elite soldiers, TRM cells serve as front line defense against infection.

"We didn't previously know how to elicit these tissue-resident memory cells with a safe protein vaccine, but we now have a strategy to stimulate them in the lungs that will protect against influenza," explains Suresh. "As soon as a cell gets infected, these memory cells will kill the infected cells and the infection will be stopped in its tracks before it goes further."

Flu vaccines work by arming the immune system with an enhanced ability to recognize and fight off the flu virus. Vaccines introduce proteins found on the surface of flu viruses, prompting the immune system to produce antibodies that are primed to react should the virus attack.

However, because strains must be predicted ahead of flu season in order to produce vaccines, the vaccine in any given year may not completely match the viral strains in circulation that season. Flu viruses frequently mutate and can differ across time and from region to region. In addition, protection is neither long-lasting nor universal.

"Even though current vaccines that people get annually stimulate antibody responses, these antibodies don't cross-protect," notes Suresh. "If there is a new flu strain not found in that year's vaccine, the antibodies that we generated last year won't be able to protect. That's when pandemics happen because there is a completely new strain for which we have no antibodies. That is a really big problem in the field."

The vaccine developed by Suresh and his team is directed against an internal protein of influenza -- specifically, nucleoprotein. This protein is conserved between flu strains, meaning its genetic sequences are similar across different strains of flu.

The vaccine also utilizes a special combination of ingredients, or adjuvants, that enhance an immune response, which the researchers developed to stimulate protective T-cells in the lungs. These adjuvants spur T-cells to form into different subtypes -- in the case of the experimental flu vaccine, memory helper T-cells and killer T-cells. By doing so, the vaccine leverages multiple modes of immunity.

Killer T-cells hunt down and kill influenza virus-infected cells. Helper T-cells assist killer T-cells and produce molecules to promote influenza control. In laboratory studies, the team found that both T-cell types were needed to protect against flu.

Researchers demonstrated in a mouse model of influenza that the vaccine provides long-lasting immunity -- at least 400 days after vaccination -- against multiple flu strains. They will next test the vaccine in ferrets and nonhuman primates, two animal models of influenza research more biologically similar to human infection and transmission.

The vaccine's combination of adjuvants makes it adaptable to other pathogens and "expands the toolbox" for vaccine research, notes Suresh. He and his team have devised ways to program immunity to target multiple respiratory viruses. They are currently testing the same vaccine strategy against tuberculosis, which infects more than 10 million people globally each year, and human respiratory syncytial virus, or RSV, a major cause of lower respiratory tract infections during infancy and childhood.

The researchers believe the same vaccine technology can applied against SARS-CoV-2, the coronavirus that causes COVID-19. "Based on the COVID-19 immunology, we know this vaccine strategy would most likely work," says Suresh.

The team is now developing an experimental vaccine against COVID-19 and conducting laboratory tests to measure its effectiveness in mice and hamsters, animal models for COVID-19. Initial unpublished studies in mice show that the vaccine stimulates strong T-cell immunity against COVID-19 in the lungs.

Along with its adaptability, this vaccine approach may harbor important safety benefits. Typically, long-lasting T-cell immune responses are stimulated by live vaccines. For instance, the measles, mumps and chickenpox vaccines administered worldwide are live, replicating vaccines -- essentially benign versions of the pathogenic organism. These live vaccines stimulate strong, almost lifelong immunity. However, they can't typically be given to pregnant or immunocompromised individuals due to health risks.

In the case of the UW-Madison team's vaccine, because it is a protein vaccine and not a live vaccine, it should be safe for delivery to those who are pregnant or immunocompromised -- an advantage in delivering protection to a wider patient population. Suresh says that in recent years, vaccine development efforts have shifted away from live vaccines toward protein vaccines because an increasing number of people are living with compromised immune systems due to chemotherapy, radiation treatments or conditions such as HIV/AIDS.

"Previously, we didn't know how to induce T-cell immunity in the lung without live viruses," says Suresh. "If we cleverly use a combination adjuvant, which we have developed, you can induce T-cell immunity that should stay in the lungs and protect longer."

A group of social scientists who conduct cross-cultural research are casting a critical lens on their own practices.

While this is by no means the first time that such self-reflection has been undertaken, the analysis, published in the Sept. 23 issue of Proceedings of the Royal Society B, is particularly timely given the growing appetite for including diverse populations in work on demography, health, economic development, cooperation, cognition, infant and child development, and belief systems. The push to expand research beyond western, educated, industrialized, rich, and democratic societies has meant that scientists are striving to capture evermore cultural diversity -- but how does this actually work when embarking on a research endeavor and selecting a community to study?

The international group of authors, led by Tanya Broesch (Simon Fraser University, British Columbia), Alyssa Crittenden (University of Nevada, Las Vegas, USA), and Monique Borgerhoff Mulder (UC Davis, USA; Max Planck Institute for Evolutionary Anthropology, Germany), draw upon years of cross-cultural work in anthropology and psychology to provide actionable suggestions to address the logistical and ethical quandaries of study site selection, engagement with communities in research, and the significance of culturally-appropriate research methods and reporting practices - both in publications and in media representations.

The authors argue that if researchers, like themselves, fail to seriously consider "the historical, political, sociological and cultural forces" acting on both the communities where they work, and the individuals within those societies, inaccurate and possibly harmful inferences might be drawn. This is particularly the case where investigators have limited time and budget, something that might be glossed as "helicopter anthropology", Borgerhoff Mulder commented.

They suggest that it is the general approach of the researchers -- from project development through to publication and data management -- that matters, where establishing and maintaining communication with participants is always prioritized.

"There is no one-size-fits-all approach, yet a productive baseline may be for researchers to consider community inclusion as part of their project design from the start," the authors write. "Ideally, the community is not only central to the planned research, but is leading it."

The research team, which spans all stages of academic careers from doctoral students to senior scholars, argues that despite the long history of exploitation and colonialism inherent in much ethnographic discourse, comparative research in the 21st century can be successfully and ethically conducted in a wide range of communities (including small-scale societies) across a variety of academic disciplines - as long as a community-centered approach is taken.

Access the full article here: http://dx.doi.org/10.1098/rspb.2020.1245.