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URBANA, Ill. - Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks. Various approaches, developed over decades, have been used to control coccidiosis, but the disease remains widespread.

Recent research from the University of Illinois supports the use of immunomodulatory and antioxidant feed additives to reduce the effects of coccidiosis.

"In the last two decades, partially to get around the parasite's resistance to pharmaceuticals, vaccination has become more prevalent. That's when I got interested, because nutrition is a key element in the effectiveness of vaccines. Diet and health go together in that way," says Ryan Dilger, associate professor in the Department of Animal Sciences at Illinois and principal investigator on the research. "So, what we're talking about here is not a vaccine. Instead, we used nutritional technologies to disrupt the normal reproductive cycle of the parasite."

When a chicken picks up the parasite, of which there are seven major Eimeria species affecting broilers, its body mounts an immune response, starting with a cascade of inflammatory proteins known as cytokines. These cause the bird to stop eating and rest, so the immune system can do its work. In normal disease progression, an anti-inflammatory mediator known as interleukin-10 (IL-10) is eventually produced to keep the inflammation from ramping up too high and causing tissue damage through oxidative stress.

However, Eimeria tricks chickens into over-producing IL-10 earlier than expected, before the immune system can produce enough cytokines to effectively attack the invader. "It's like the parasite is saying, 'Everything's fine. I'm not actually here!' It's really trying to evade the immune response," Dilger says.

To reverse that effect, doctoral student Muhammed Shameer Abdul Rasheed included a novel feed ingredient, a dried egg product with IL-10 antibody activity, in the diet of broiler chickens before inducing coccidiosis.

"We want the bird to have an acute pro-inflammatory response in order to clear the parasite, and that response is dampened when the parasite tricks the bird into overproducing IL-10 antibody. We're trying to take away the parasite's ability to manipulate the bird's own immune system against itself," Rasheed says.

The IL-10 dried egg product has been shown to be effective against mild Eimeria infection in other studies, but it hadn't been tested in severe cases and in the absence of vaccine administration.

"Our results suggested that dietary dried egg product could be beneficial in promoting gut health during severe infection for particular strains of the parasite, even though suppression of the IL-10 response may promote an exaggerated inflammatory reaction in the intestinal epithelium, which may cause subsequent tissue damage," Dilger says.

Uncontrolled inflammatory responses can lead to oxidative stress, where chemicals with unpaired electrons, known as free radicals, start to damage healthy tissue. When Rasheed saw the intestinal damage in this study, he decided to test the combined effects of the IL-10 antibody and an antioxidant known as methylsulfonylmethane or MSM. He had previously tested MSM in chickens and found it had no adverse effects on health or growth, but it had never been tried as a treatment for oxidative stress during coccidiosis.

"The IL-10 antibody works to combat the infection through an immune mechanism, which may inadvertently cause oxidative stress, so MSM was used in combination to specifically combat that tissue damage," Rasheed says. "So the hypothesis was that if these two interventions are working through different mechanisms, combining them together may actually give us a better response than either of them alone."

When the research team fed infected birds a combination of MSM and IL-10 antibody, the treatment showed promise. First, chickens that got the treatment showed greater body weight gain 7-14 days post-infection than birds that didn't consume the dietary products. Also, total antioxidant capacity, an overall indicator of how well an animal can counteract oxidative stress, remained higher in treated birds three and four weeks after infection, suggesting lasting dietary effects.

"In the end, the birds still got sick; they still had an infection that reduced their growth for a certain amount of time. Just like with some pharmaceutical agents designed to lessen the effects of the flu in humans, it's not actually going to prevent you from getting the disease in the first place. However, our goal is to shorten the length of time you're sick," Dilger says. "That's just as meaningful for broiler chickens."

Dilger thinks the dietary interventions may be even more effective in real-world production settings. In the clean, controlled environment of a laboratory study, these broiler chickens were raised on wire flooring to separate the birds from their excrement. However, broiler chickens raised on a commercial farm would be raised on the floor, in direct contact with litter, which is partly how the Eimeria infection cycle continues. In the end, the nutritional strategies studied here may act as a kind of insurance for producers to help birds bounce back sooner.

"Producers may not have coccidiosis when they mix this in the feed, but by the time the chickens consume it, the disease may have reared up again. So if the product is already there, you have some protection," Dilger says. "Again, it's not going to prevent the birds from getting coccidiosis, but hopefully it can reduce the untoward effects and allow them to get back to a healthy state faster and continue growing, such that they can remain productive during that time. It's another important tool in the arsenal for producers."

Studies have long suggested that oxytocin -- a hormone that can also act as a neurotransmitter -- regulates prosocial behavior such as empathy, trust and bonding, which led to its popular labeling as the "love hormone." Mysteriously, oxytocin has also been shown to play a role in antisocial behaviors and emotions, including reduced cooperation, envy and anxiety. How oxytocin could exert such opposite roles had largely remained a mystery, but a new UC Davis study sheds light on how this may work.

Working with California mice, UC Davis researches showed that the "love hormone" oxytocin can sometimes have antisocial effects depending on where in the brain it is made. (Mark Chappell/UC Riverside)

While most oxytocin is produced in an area of the brain known as the hypothalamus, some oxytocin is produced in another brain area known as the bed nucleus of the stria terminalis, or BNST. The BNST is known for its role in the stress response, and it may play a key role in psychiatric disorders such as depression, addiction and anxiety.

The findings of the study, published this week in Proceedings of the National Academy of Sciences USA, show that oxytocin produced in the BNST increases stress-induced social anxiety behaviors in mice. This may provide an explanation as to why oxytocin can sometimes have antisocial effects. The lead author is Natalia Duque-Wilckens, a former doctoral researcher at UC Davis who is now at Michigan State University. The senior author is Brian Trainor, professor of psychology and director of the Behavioral Neuroendocrinology Lab at UC Davis.

"Before this study, we knew that stress increased the activity of the oxytocin-producing neurons located in the BNST, but we didn't know if they could affect behavior. Our experiments show that production of oxytocin in the BNST is necessary for social anxiety behaviors in California mice," said Duque-Wilckens.

Social stress stronger in females

The researchers were able to show this by using a tool called morpholino-oligos, which, when injected directly into the BNST, prevents oxytocin from being produced in this area. Interestingly, while oxytocin neurons in the BNST are present in both males and females, previous studies from this group showed that social stress has stronger long term effects on these neurons in females. This is interesting because social anxiety disorders are more common and more severe in women compared to men.

This study further showed that oxytocin-producing neurons in the BNST are connected to brain regions that control anxiety-related behavior. This was achieved by using a virus to express a fluorescent molecule only in oxytocin neurons.

Remarkably, "simply infusing oxytocin into the parts of the brain that BNST oxytocin neurons connect to caused ordinarily non-stressed mice to show social anxiety behaviors as if they had experienced social stress," said Trainor. Previous studies from this and other labs had shown that oxytocin acting in other areas of the brain, including areas involved in motivated behaviors, had prosocial effects. This suggests that whether the effects of oxytocin are pro- or antisocial will largely depend on which areas of the brain oxytocin is acting in, he said.

"The results are exciting because they provide a potential explanation for why oxytocin sometimes increases anxiety in humans. The vast majority of previous work has focused on the neural mechanisms that underlie the anxiety-reducing effects of oxytocin," Trainor said. "If combined with further studies of how anxiety is connected with brain circuits in humans, these results could give us a better understanding of what conditions oxytocin could be beneficial or harmful for treating anxiety."

It's also possible that in some situations, using a drug that blocks the actions of oxytocin could reduce anxiety, he said. In future studies, researchers will try to understand how these neurons activate in response to stress and why this effect is long-lasting in females, with the final aim of finding therapeutic strategies that could help patients suffering from social anxiety disorder.

Same-gender couples have higher-quality interactions with one another than heterosexual couples in Southern California, a new UC Riverside study finds.

The study also holds that couples with two men have the smallest social networks.

Researcher Megan Robbins says the recently published study is the first to compare same- and different-sex couples' social networks and daily interactions with one another.

Past research shows that same-gender couples enjoy strengths including appreciation of individual differences, positive emotions, and effective communication. But research hasn't compared the quality of their daily interactions - inside and outside the couple dynamic - to those of heterosexual couples. 

"The comparison is important because there is so much research linking the quality of romantic relationships and other social ties to health and well-being, yet it is unclear if this applies similarly or differently to people in same-gender romantic relationships because they have been historically excluded from past research.," said Robbins, who is an associate professor of psychology at UCR. Reasons for potential differences include the stigma sexual minorities face, and also their resilience.

For the study, Robbins and her team recruited same-gender and different-gender couples throughout Southern California. The couples had to be in a married or "married-like" committed relationship; living together for at least a year; and have no physical or mental health conditions that impeded their daily functioning.

Among those who applied to be in the study, 78 couples were found to be eligible, 77 of which provided enough data to be used. Twenty-four of the couples were woman-woman; 20 were man-man, and 33 were man-woman.

Participants met with the researchers on two separate Fridays, a month apart, completing surveys. They received text or email prompts several times in the days following the in-person meetings. In the text/email prompts, participants were asked whether they had an interaction with their partner, a family member, or a friend in the past 10 minutes, then asked to rate the quality of the social interaction using a five-point scale - one being unpleasant; three, neutral; five, pleasant.

In terms of social networks, the study found couples in man-man relationships had smaller social networks than woman-woman and man-woman couples. On the other end of the results spectrum, women in relationships with men were most likely to have the largest social networks.

Robbins said the finding is consistent with previous research showing men with men experience the least acceptance among family members.

"We hypothesized that one model for how the social life of people in same-gender couples might differ from those in different-gender couples was a honing model, where people in same-gender couples reduce their social networks down to only those people who are supportive. We found some support for this by learning that the men with men had the smallest social networks in our sample.," Robbins said.

The quality of interactions with families was reported to be greatest by same-gender couples. There was no difference for interaction quality with friends.

In terms of the quality of interactions with their partners, the study found same-gendered relationships had better-quality interactions than found in different-gendered relationships.

Robbins said that may be due to greater similarity between partners when they share a gender identity, and greater equality within the couple, compared to people in different-sex couples.

"When male and female partners interact, they may do so from a culturally imposed frame wherein men and women are considered 'opposites,' which creates more potential for tension in interactions," Robbins wrote in the paper, titled Social Compensation and Honing Frameworks, and published in the Journal of Social and Personal Relationships.

Fast facts:

In a recent study, NYU Abu Dhabi faculty Alberto Gandolfi proposes alternate weeks of in-classroom and remote teaching as a way to allow students to learn in the classroom while protecting them from COVID-19.

The optimal strategy results in the school opening 90 days out of 200, with the number of COVID-19 cases among the individuals related to the school increasing by nearly 66 percent, instead of the almost 250 percent increase, which is predicted should schools fully reopen.

In the broader context, the model gives the first classification of areas or countries in which schools can reopen full time, or can reopen for a fraction of the days, with distancing and frequent testing, or cannot reopen for the time being.

Abu Dhabi, UAE - October 7, 2020: In a recent study, NYU Abu Dhabi Professor of Practice in Mathematics Alberto Gandolfi has developed a mathematical model to identify the number of days students could attend school to allow them a better learning experience while mitigating infections of COVID-19.

Published in Physicsa D journal, the study shows that blended models, with almost periodic alternations of in-class and remote teaching days or weeks, would be ideal. In a prototypical example, the optimal strategy results in the school opening 90 days out of 200, with the number of COVID-19 cases among the individuals related to the school increasing by about 66 percent, instead of the almost 250 percent increase, which is predicted should schools fully reopen.

The study features five different groups; these include students susceptible to infection, students exposed to infection, students displaying symptoms, asymptomatic students, and recovered students. In addition, Gandolfi's study models other factors, including a seven hour school day as the window for transmission, and the risk of students getting infected outside of school.

Speaking on the development of this model, Gandolfi commented: "The research comes as over one billion students around the world are using remote learning models in the face of the global pandemic, and educators are in need of plans for the upcoming 2020 - 2021 academic year. Given that children come in very close contact within the classrooms, and that the incubation period lasts several days, the study shows that full re-opening of the classrooms is not a viable possibility in most areas. On the other hand, with the development of a vaccine still in its formative stages, studies have placed the potential impact of COVID-19 on children as losing 30 percent of usual progress in reading and 50 percent or more in math."

He added: "The approach aims to provide a viable solution for schools that are planning activities ahead of the 2020 - 2021 academic year. Each school, or group thereof, can adapt the study to its current situation in terms of local COVID-19 diffusion and relative importance assigned to COVID-19 containment versus in-class teaching; it can then compute an optimal opening strategy. As these are mixed solutions in most cases, other aspects of socio-economic life in the area could then be built around the schools' calendar. This way, children can benefit as much as possible from a direct, in class experience, while ensuring that the spread of infection is kept under control."

Using the prevalence of active COVID-19 cases in a region as a proxy for the chance of getting infected, the study gives a first indication, for each country, of the possibilities for school reopening: schools can fully reopen in a few countries, while in most others blended solutions can be attempted, with strict physical distancing, and frequent, generalized, even if not necessarily extremely reliable, testing.

Washington, DC - October 7, 2020 - Researchers have outlined an approach to characterize and develop an effective environmental monitoring methodology for SARS CoV-2 virus, that can be used to better understand viral persistence in built environments. The investigators from 7 institutions published their research this week in mSystems, an open-access journal of the American Society for Microbiology. Built environment refers to the human-made environment that provides the setting for human activity, ranging in scale from buildings to cities and beyond.

"As we all know, SARS CoV-2 is of worldwide concern," said principal investigator of the study Dr. Kasthuri Venkateswaran, senior research scientist at NASA's Jet Propulsion Laboratory (JPL) in Southern California.

For the studies, the researchers used inactivated noninfectious virus that is viable and can be used as a surrogate. "Our group adapted the CDC-approved reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) methodology and then tested the efficacy of RT-qPCR in detecting SARS CoV-2 from various environmental surface samples," said Dr. Ceth W. Parker, one of the 3 lead study authors, a post-doctoral fellow at JPL. The researchers tested a variety of surface materials common in built environments, including bare stainless steal, painted stainless steel, plastics and reinforced fiberglass.

"We tested these surfaces by seeding inactivated noninfectious SARS CoV-2 particles and then determining how well we could actually recover them from the surfaces," said Dr. Parker. "It takes a minimum of 1,000 viral particles per 25 cm2 to effectively and reproducibly detect SARS-CoV-2 virus on the surface. We found that viral RNA can persist on surfaces for at least 8 days. We also found that inhibitory substances and debris have to be taken into account on the surfaces they are being tested on."

A Dartmouth-Gallup study finds that women are more concerned about COVID-19 than men, a difference that transcends party lines. This female perspective towards the pandemic may be overlooked due to the underrepresentation of women in the workplace that is compounded by an underrepresentation in politics, creating what the researchers refer to as a representational "double whammy" effect. The study's findings are published in Politics & Gender.

"Men are less likely to favor precautions for COVID-19 than women, basically across the board," said co-author Deborah Jordan Brooks, an associate professor of government at Dartmouth. "We find that substantial differences exist among male and female Republicans, Independents, and Democrats, and among workplace leaders and rank-and-file workers."

Brooks adds, "The positioning of many high-profile Republicans, including President Trump, regarding a minimal need for precautions regarding COVID-19 does not match up with the substantially more cautious COVID-related preferences of women. In light of President Trump's recent COVID-19 diagnosis and its spread throughout White House staff, our findings imply that the heightened focus on the coronavirus in the final weeks of the campaign has the potential to put the Republican Party at a further disadvantage with female voters."

The study was based on a nationally, representative online survey conducted by Gallup from May 18 to June 14, 2020 on questions relating to COVID-19 concerns, individual preferences and workplace structure. (Confirmatory results from more recent surveys on many of these measures have just been posted by the co-authors on the Gallup website today, Oct. 7). The researchers sought out to examine how views towards COVID-19 may vary by gender, as well as by partisanship and an individual's role in the workplace (worker vs. workplace leader).

Women vs. Men on COVID-19 Overall

The results illustrate that women have a substantially greater concern for COVID-19 than men. One of the survey questions asked whether it was better advice for people without symptoms who are otherwise healthy to stay home as much as possible to avoid contracting or spreading the coronavirus, or lead normal lives as much as possible to avoid interruptions to work and business. The findings show that 28 percent of women thought it was better to lead normal lives versus staying at home, as compared to 40 percent of men.

When asked how soon respondents would return to normal day-to-day activities if there were no government restrictions, 37 percent of men at the time of the study answered "right now," as compared to just 24 percent of women.

These findings that men perceive COVID-19 as less of a risk seem particularly notable in light of the fact that medical research indicates that men are significantly more likely to die from the coronavirus than women.

Gender Differences by Party

While Democrats tend to view COVID-19 as a greater public health risk than Republicans, and women are more likely to be Democrats than men, this study shows that the gender findings go well beyond that. The findings show that women are more concerned and cautious about COVID-19 than their male co-partisans regardless of the party in question.

For example, if there were no government restrictions on being out in public, 69 percent of Republican men would resume regular activities immediately, versus 55 percent of Republican women (the same is true for 36 percent of independent men and 28 percent of independent women, and 7 percent of Democratic men versus 4 percent of Democratic women). Similarly, 37 percent of Republican men reported being "not worried at all" about contracting the coronavirus, versus just 25 percent of Republican women, with significant differences observed for independents and Democrats, as well. (See Table at the end of this release).

Gender Differences Among Workers & Workplace Leaders

The results also show that female workers are more worried about contracting COVID-19 at work and are significantly more worried about returning to work safely due to the pandemic than male workers. Female workers also think that the COVID-19 disruption will last longer than a year and indicated that they would prefer to work remotely, if employers were to leave the decision up to them. As the co-authors state, "male workers are far more bullish about returning to work life as usual than are their female colleagues, and similarly-gender patterns exist among workplace leaders."

The workplace in the U.S. may not reflect or even consider these distinct, female preferences towards COVID-19, since women are severely underrepresented at the highest leadership positions in healthcare, education and other fields. For example, the researchers point out how "only 3 percent of healthcare CEOs and medical divisions chiefs are women" while women account for 80 percent of healthcare workers.

Implications for Party Leadership

Brooks points out that the study's findings on workplace decision-making and political preferences regarding the coronavirus might be more related than they initially appear. "Many female leaders in the Democratic Party, including Speaker of the U.S. House of Representatives Nancy Pelosi (D-CA), have been positioned front-and-center in Democratic policymaking around COVID-19. In contrast, like most high-prestige organizations today, the Republican Party has shockingly few women in its leadership pipeline. The intense focus on COVID-19 during this election - an issue with so many substantial gender differences - may be contributing to the staggeringly-wide gender gap in candidate preference that has been evident in recent poll results," explained Brooks.

PHILADELPHIA--A pay-for performance program that offers enhanced reimbursement to oncology practices for prescribing high-quality, evidence-based cancer drugs increased use of these drugs without significantly changing total spending on care, Penn Medicine researchers report in a new study published online in the Journal of Clinical Oncology. This is the first study to demonstrate how a national insurer's voluntary pay-for-performance program can successfully change prescribing patterns among oncologists to deliver higher-quality cancer care.

"We know that prescribing evidence-based cancer drugs is high-quality care and increases both the length and quality of life for patients with cancer," said co-lead author Justin E. Bekelman, MD, director of the Penn Center for Cancer Care Innovation at the Abramson Cancer Center, a professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania, and senior fellow at the Leonard Davis Institute for Health Economics. "And yet, changing prescribing patterns has been and remains a big challenge. Based on what we found here, paying oncology practices to prescribe evidence-based drugs can serve as a valuable tactic to improve the quality of cancer care."

To study the program's impact on prescriptions and spending, the researchers analyzed insurance claims data of cancer patients between 2014 and 2017. They found that a payment of $350 a month per patient to oncology practices when oncologists prescribed evidence-based cancer drugs increased prescriptions of those drugs by 5.1 percentage points. The study included nearly 1,900 oncologists and more than 25,000 patients with breast, lung, or colorectal cancers across 14 states--62.2 percent of patients under the program received evidence-based drugs compared to 57.1 percent of those patients without the program.

Evidence-based cancer regimens have been shown to lead to better outcomes, including longer life and less toxicity; however, despite this, not all patients receive them.

Historically, pay-for-performance programs in health care have shown mixed results. Insurers, including private and government entities, have implemented these programs and others as a way to improve the quality of care and also decrease cost growth in health care.

In cancer care, where spending is driven in large part by the costs of cancer drugs and is expected to reach more than $170 billion in 2020, few programs to improve care or reduce spending have had success. A three-year evaluation of Medicare's Oncology Care Model program, an episode-based payment program with no specific incentive for prescribing evidence-based drugs, showed no significant impact on spending nor utilization of emergency department, hospitalizations or cancer drugs.

While not a silver bullet, the voluntary pay-for-performance program from Anthem, Inc., a national health benefits company, known as the Cancer Care Quality Program, is the first and largest to show a significant increase on evidence-based prescriptions in the cancer care setting.

In addition to finding an increase in prescriptions, the researchers found that overall spending did not significantly change under the pay-for-performance program. The amount spent on cancer drugs over a six-month period, however, increased in the pay-for-performance group, going from $48,030 to $51,369, and patient out-of-pocket expenses increased by a small but statistically significant amount, going from $2,217 to $2,470. The researchers also found substantial variability in cancer drug prescribing among oncology practices. Over the course of the study, physicians prescribed 402 unique drug regimens, even though only 60 of those regimens were evidence-based drug regimens in the program.

Both findings highlight the need for further interventions.

"The cost of cancer care is too high, just like other areas in health care," said senior author Amol S. Navathe, MD, PhD, an assistant professor of Medical Ethics and Health Policy and the Healthcare Transformation Institute, and a senior fellow at the Leonard Davis Institute for Health Economics at Penn. "This program is a much needed example of an effective program--one that improved quality of care for patients. As we look forward, we need to build on the success of this program to design programs that also decrease costs."

Researchers from HealthCore, a health outcomes subsidiary of Anthem, and AIM Specialty Health, a wholly owned subsidiary of Anthem, also served as co-authors on the paper.

"We are pleased that this analysis demonstrates that our program indeed can improve the rate of high-value, evidence-based prescribing in oncology," said David Debono, MD, Anthem national medical director for oncology. "Anthem and AIM have placed a considerable focus on the Cancer Care Quality Program since 2014 and will continue to analyze new therapies as they are approved."

Injuries to peripheral nerves -- tissues that transmit bioelectrical signals from the brain to the rest of the body -- often result in chronic pain, neurologic disorders, paralysis or disability. Now, researchers have developed a stretchable conductive hydrogel that could someday be used to repair these types of nerves when there's damage. They report their results in ACS Nano.

Injuries in which a peripheral nerve has been completely severed, such as a deep cut from an accident, are difficult to treat. A common strategy, called autologous nerve transplantation, involves removing a section of peripheral nerve from elsewhere in the body and sewing it onto the ends of the severed one. However, the surgery does not always restore function, and multiple follow-up surgeries are sometimes needed. Artificial nerve grafts, in combination with supporting cells, have also been used, but it often takes a long time for nerves to fully recover. Qun-Dong Shen, Chang-Chun Wang, Ze-Zhang Zhu and colleagues wanted to develop an effective, fast-acting treatment that could replace autologous nerve transplantation. For this purpose, they decided to explore conducting hydrogels -- water-swollen, biocompatible polymers that can transmit bioelectrical signals.

The researchers prepared a tough but stretchable conductive hydrogel containing polyaniline and polyacrylamide. The crosslinked polymer had a 3D microporous network that, once implanted, allowed nerve cells to enter and adhere, helping restore lost tissue. The team showed that the material could conduct bioelectrical signals through a damaged sciatic nerve removed from a toad. Then, they implanted the hydrogel into rats with sciatic nerve injuries. Two weeks later, the rats' nerves recovered their bioelectrical properties, and their walking improved compared with untreated rats. Because the electricity-conducting properties of the material improve with irradiation by near-infrared light, which can penetrate tissues, it could be possible to further enhance nerve conduction and recovery in this way, the researchers say.

The authors acknowledge funding from the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Program for Changjiang Scholars and Innovative Research Team in University, and Program B for Outstanding Ph.D. Candidate of Nanjing University.

The paper's abstract will be available on October 7 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acsnano.0c05197

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS' mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and its people. The Society is a global leader in providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a specialist in scientific information solutions (including SciFinder® and STN®), its CAS division powers global research, discovery and innovation. ACS' main offices are in Washington, D.C., and Columbus, Ohio.

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A public health advisory issued by the US Food and Drug Administration (FDA) in 2003, followed by drug label warnings, indicated that children and adolescents taking antidepressants were at increased risk of developing suicidal thoughts and behaviors. Research has shown that these warnings reduced the diagnosis and treatment of depression among young people. Now, a new study suggests that the warnings may also have contributed to an increase in suicide deaths among youth.

The authors of the study, which is published in Psychiatric Research and Clinical Practice, estimate that there may have been 5,958 excess suicides nationally by 2010 among 43 million adolescents and 21 million young adults.

"Our findings suggest the boxed warnings may have contributed to the very thing the FDA was trying to prevent. More than two-thirds of depressed teens do not receive any depression care whatsoever, an issue now further exacerbated by COVID-19. We strongly recommend the FDA reexamine the use of these warnings," said principal investigator Stephen Soumerai, ScD, of Harvard Medical School and the Harvard Pilgrim Health Care Institute.

DNA and RNA have been compared to "instruction manuals" containing the information needed for living "machines" to operate. But while electronic machines like computers and robots are designed from the ground up to serve a specific purpose, biological organisms are governed by a much messier, more complex set of functions that lack the predictability of binary code. Inventing new solutions to biological problems requires teasing apart seemingly intractable variables - a task that is daunting to even the most intrepid human brains.

Two teams of scientists from the Wyss Institute at Harvard University and the Massachusetts Institute of Technology have devised pathways around this roadblock by going beyond human brains; they developed a set of machine learning algorithms that can analyze reams of RNA-based "toehold" sequences and predict which ones will be most effective at sensing and responding to a desired target sequence. As reported in two papers published concurrently today in Nature Communications, the algorithms could be generalizable to other problems in synthetic biology as well, and could accelerate the development of biotechnology tools to improve science and medicine and help save lives.

"These achievements are exciting because they mark the starting point of our ability to ask better questions about the fundamental principles of RNA folding, which we need to know in order to achieve meaningful discoveries and build useful biological technologies," said Luis Soenksen, Ph.D., a Postdoctoral Fellow at the Wyss Institute and Venture Builder at MIT's Jameel Clinic who is a co-first author of the first of the two papers.

Getting ahold of toehold switches

The collaboration between data scientists from the Wyss Institute's Predictive BioAnalytics Initiative and synthetic biologists in Wyss Core Faculty member Jim Collins' lab at MIT was created to apply the computational power of machine learning, neural networks, and other algorithmic architectures to complex problems in biology that have so far defied resolution. As a proving ground for their approach, the two teams focused on a specific class of engineered RNA molecules: toehold switches, which are folded into a hairpin-like shape in their "off" state. When a complementary RNA strand binds to a "trigger" sequence trailing from one end of the hairpin, the toehold switch unfolds into its "on" state and exposes sequences that were previously hidden within the hairpin, allowing ribosomes to bind to and translate a downstream gene into protein molecules. This precise control over the expression of genes in response to the presence of a given molecule makes toehold switches very powerful components for sensing substances in the environment, detecting disease, and other purposes.

However, many toehold switches do not work very well when tested experimentally, even though they have been engineered to produce a desired output in response to a given input based on known RNA folding rules. Recognizing this problem, the teams decided to use machine learning to analyze a large volume of toehold switch sequences and use insights from that analysis to more accurately predict which toeholds reliably perform their intended tasks, which would allow researchers to quickly identify high-quality toeholds for various experiments.

The first hurdle they faced was that there was no dataset of toehold switch sequences large enough for deep learning techniques to analyze effectively. The authors took it upon themselves to generate a dataset that would be useful to train such models. "We designed and synthesized a massive library of toehold switches, nearly 100,000 in total, by systematically sampling short trigger regions along the entire genomes of 23 viruses and 906 human transcription factors," 
said Alex Garruss, a Harvard graduate student working at the Wyss Institute who is a co-first author of the first paper. "The unprecedented scale of this dataset enables the use of advanced machine learning techniques for identifying and understanding useful switches for immediate downstream applications and future design."

Armed with enough data, the teams first employed tools traditionally used for analyzing synthetic RNA molecules to see if they could accurately predict the behavior of toehold switches now that there were manifold more examples available. However, none of the methods they tried - including mechanistic modeling based on thermodynamics and physical features - were able to predict with sufficient accuracy which toeholds functioned better.

A picture is worth a thousand base pairs

The researchers then explored various machine learning techniques to see if they could create models with better predictive abilities. The authors of the first paper decided to analyze toehold switches not as sequences of bases, but rather as two-dimensional "images" of base-pair possibilities. "We know the baseline rules for how an RNA molecule's base pairs bond with each other, but molecules are wiggly - they never have a single perfect shape, but rather a probability of different shapes they could be in," said Nicolaas Angenent-Mari, a MIT graduate student working at the Wyss Institute and co-first author of the first paper. "Computer vision algorithms have become very good at analyzing images, so we created a picture-like representation of all the possible folding states of each toehold switch, and trained a machine learning algorithm on those pictures so it could recognize the subtle patterns indicating whether a given picture would be a good or a bad toehold."

Another benefit of their visually-based approach is that the team was able to "see" which parts of a toehold switch sequence the algorithm "paid attention" to the most when determining whether a given sequence was "good" or "bad." They named this interpretation approach Visualizing Secondary Structure Saliency Maps, or VIS4Map, and applied it to their entire toehold switch dataset. VIS4Map successfully identified physical elements of the toehold switches that influenced their performance, and allowed the researchers to conclude that toeholds with more potentially competing internal structures were "leakier" and thus of lower quality than those with fewer such structures, providing insight into RNA folding mechanisms that had not been discovered using traditional analysis techniques.

"Being able to understand and explain why certain tools work or don't work has been a secondary goal within the artificial intelligence community for some time, but interpretability needs to be at the forefront of our concerns when studying biology because the underlying reasons for those systems' behaviors often cannot be intuited," said Jim Collins, Ph.D., the senior author of the first paper. "Meaningful discoveries and disruptions are the result of deep understanding of how nature works, and this project demonstrates that machine learning, when properly designed and applied, can greatly enhance our ability to gain important insights about biological systems." Collins is also the Termeer Professor of Medical Engineering and Science at MIT.

Now you're speaking my language

While the first team analyzed toehold switch sequences as 2D images to predict their quality, the second team created two different deep learning architectures that approached the challenge using orthogonal techniques. They then went beyond predicting toehold quality and used their models to optimize and redesign poorly performing toehold switches for different purposes, which they report in the second paper.

The first model, based on a convolutional neural network (CNN) and multi-layer perceptron (MLP), treats toehold sequences as 1D images, or lines of nucleotide bases, and identifies patterns of bases and potential interactions between those bases to predict good and bad toeholds. The team used this model to create an optimization method called STORM (Sequence-based Toehold Optimization and Redesign Model), which allows for complete redesign of a toehold sequence from the ground up. This "blank slate" tool is optimal for generating novel toehold switches to perform a specific function as part of a synthetic genetic circuit, enabling the creation of complex biological tools.

"The really cool part about STORM and the model underlying it is that after seeding it with input data from the first paper, we were able to fine-tune the model with only 168 samples and use the improved model to optimize toehold switches. That calls into question the prevailing assumption that you need to generate massive datasets every time you want to apply a machine learning algorithm to a new problem, and suggests that deep learning is potentially more applicable for synthetic biologists than we thought," said co-first author Jackie Valeri, a graduate student at MIT and the Wyss Institute.

The second model is based on natural language processing (NLP), and treats each toehold sequence as a "phrase" consisting of patterns of "words," eventually learning how certain words are put together to make a coherent phrase. "I like to think of each toehold switch as a haiku poem: like a haiku, it's a very specific arrangement of phrases within its parent language - in this case, RNA. We are essentially training this model to learn how to write a good haiku by feeding it lots and lots of examples," said co-first author Pradeep Ramesh, Ph.D., a Visiting Postdoctoral Fellow at the Wyss Institute and Machine Learning Scientist at Sherlock Biosciences.

Ramesh and his co-authors integrated this NLP-based model with the CNN-based model to create NuSpeak (Nucleic Acid Speech), an optimization approach that allowed them to redesign the last 9 nucleotides of a given toehold switch while keeping the remaining 21 nucleotides intact. This technique allows for the creation of toeholds that are designed to detect the presence of specific pathogenic RNA sequences, and could be used to develop new diagnostic tests.

The team experimentally validated both of these platforms by optimizing toehold switches designed to sense fragments from the SARS-CoV-2 viral genome. NuSpeak improved the sensors' performances by an average of 160%, while STORM created better versions of four "bad" SARS-CoV-2 viral RNA sensors whose performances improved by up to 28 times.

"A real benefit of the STORM and NuSpeak platforms is that they enable you to rapidly design and optimize synthetic biology components, as we showed with the development of toehold sensors for a COVID-19 diagnostic," said co-first author Katie Collins, an undergraduate MIT student at the Wyss Institute who worked with MIT Associate Professor Timothy Lu, M.D., Ph.D., a corresponding author of the second paper.

"The data-driven approaches enabled by machine learning open the door to really valuable synergies between computer science and synthetic biology, and we're just beginning to scratch the surface," said Diogo Camacho, Ph.D., a corresponding author of the second paper who is a Senior Bioinformatics Scientist and co-lead of the Predictive BioAnalytics Initiative at the Wyss Institute. "Perhaps the most important aspect of the tools we developed in these papers is that they are generalizable to other types of RNA-based sequences such as inducible promoters and naturally occurring riboswitches, and therefore can be applied to a wide range of problems and opportunities in biotechnology and medicine."

Additional authors of the papers include Wyss Core Faculty member and Professor of Genetics at HMS George Church, Ph.D.; and Wyss and MIT Graduate Students Miguel Alcantar and Bianca Lepe.

"Artificial intelligence is wave that is just beginning to impact science and industry, and has incredible potential for helping to solve intractable problems. The breakthroughs described in these studies demonstrate the power of melding computation with synthetic biology at the bench to develop new and more powerful bioinspired technologies, in addition to leading to new insights into fundamental mechanisms of biological control," said Don Ingber, M.D., Ph.D., the Wyss Institute's Founding Director. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences.

Engineers have invented a way to spray extremely thin wires made of a plant-based material that could be used in N95 mask filters, devices that harvest energy for electricity, and potentially the creation of human organs.

The method involves spraying methylcellulose, a renewable plastic material derived from plant cellulose, on 3D-printed and other objects ranging from electronics to plants, according to a Rutgers-led study in the journal Materials Horizons.

"This could be the first step towards 3D manufacturing of organs with the same kinds of amazing properties as those seen in nature," said senior author Jonathan P. Singer, an assistant professor in the Department of Mechanical and Aerospace Engineering in the School of Engineering at Rutgers University-New Brunswick. "In the nearer term, N95 masks are in demand as personal protective equipment during the COVID-19 pandemic, and our spray method could add another level of capture to make filters more effective. Electronics like LEDs and energy harvesters also could similarly benefit."

Thin wires (nanowires) made of soft matter have many applications, including the cilia that keep our lungs clean and the setae (bristly structures) that allow geckos to grip walls. Such wires have also been used in small triboelectric energy harvesters, with future examples possibly including strips laminated on shoes to charge a cell phone and a door handle sensor that turns on an alarm.

While people have known how to create nanowires since the advent of cotton candy melt spinners, controlling the process has always been limited. The barrier has been the inability to spray instead of spin such wires.

Singer's Hybrid Micro/Nanomanufacturing Laboratory, in collaboration with engineers at Binghamton University, revealed the fundamental physics to create such sprays. With methylcellulose, they have created "forests" and foams of nanowires that can be coated on 3D objects. They also demonstrated that gold nanoparticles could be embedded in wires for optical sensing and coloration.

Projections of potentially dramatic sea-level rise from ice-sheet melting in Antarctica have been wide-ranging, but a Rutgers-led team has created a model that enables improved projections and could help better address climate change threats.

A major source of sea-level rise could come from melting of large swaths of the vast Antarctic ice sheet. Fossil coral reefs jutting above the ocean's surface show evidence that sea levels were more than 20 feet higher about 125,000 years ago during the warm Last Interglacial (Eemian) period.

"Evidence of sea-level rise in warm climates long ago can tell us a lot about how sea levels could rise in the future," said lead author Daniel M. Gilford, a post-doctoral associate in the lab of co-author Robert E. Kopp, a professor in the Department of Earth and Planetary Sciences within the School of Arts and Sciences at Rutgers University-New Brunswick. "This evidence suggests that as climate change drives warming in the atmosphere and oceans, future global sea-level rise could reach considerable heights."

The study, published in the journal JGR: Earth Surface, delves into how paleoclimate evidence from about 125,000 years ago can be used to improve computer model projections of Antarctic ice-sheet collapse and sea-level rise. Such evidence is increasingly effective for improving projections, providing valuable insights into ice sheet vulnerability through at least 2150.

The study takes advantage of the similarities between past and potential future sea levels to train a statistical ice-sheet model, using artificial intelligence. The fast, simple, less expensive "emulator" - a form of machine learning software - is taught to mimic the behavior of a complex model that focuses on ice-sheet physics, enabling many more simulations than could be explored with the complex model alone. This avoids the costly run times of the complex ice-sheet model, which considers such phenomena as ice-sheet fractures due to surface melting and the collapse of tall seaside ice cliffs.

What may happen to the Antarctic ice sheet as the climate warms is the biggest uncertainty when it comes to global sea-level rise this century, the study notes. When combined with evidence of past sea levels, the new model can boost confidence in sea-level rise projections through at least 2150.

"If big swaths of the Antarctic ice sheet melted and collapsed about 125,000 years ago, when the polar regions were warmer than today, parts of the ice sheet may be similarly prone to collapse in the future as the climate warms, affecting our expectations of sea-level rise and coastline flooding over the next 130 years," Gilford said.

New estimates of sea levels about 125,000 years ago could be used to indicate whether, 75 years from now, Hurricane Sandy-like flooding (about 9 feet above ground level in New York City) is likely to occur once a century or annually along parts of the Northeast U.S. coastline. Improved projections could also be included in reports such as the Intergovernmental Panel on Climate Change's upcoming Sixth Assessment Report, likely helping officials and others decide how to address climate change threats.

Co-authors include Erica L. Ashe, a post-doctoral scientist in Kopp's lab, along with scientists at the University of Massachusetts Amherst, Pennsylvania State University and the University of Bremen.

Two-thirds of older adults rely on at least two prescription drugs, and more than half take two or more non-prescription drugs or supplements. And two in ten take five or more prescription drugs. Some of those pills, capsules and tablets may interact with one another in ways that could put them at risk.

But a new poll shows that most people over 50 haven't connected with a pharmacist to check for potential clashes among their prescription drugs, non-prescription drugs, and supplements, or the potential to save money by switching to lower-cost options.

Medicare Part D plans offer free in-depth medication reviews for enrollees who meet their eligibility criteria. However, participation has historically been low. The new poll shows 85% of Medicare Part D enrollees who had not had a medication review didn't know they could be eligible for one. Some non-Medicare plans also cover reviews, but 86% of all older adults without a medication review said they weren't aware that it could be covered.

The new findings come from the National Poll on Healthy Aging, based at the University of Michigan's Institute for Healthcare Policy and Innovation with support from AARP and Michigan Medicine, U-M's academic medical center. The new report draws on responses from a national sample of more than 2,000 adults aged 50 to 80.

The poll team worked with two faculty in the U-M College of Pharmacy who have studied the issue of multiple medication use, and the policies and practices aimed at improving use and reducing the risky side effects they can cause.

"These results show the importance of continuing efforts by physicians, pharmacists, other health care providers, insurers and policymakers to help older adults understand the importance of medication reviews," says Antoinette B. Coe, Pharm.D., Ph.D., an assistant professor of clinical pharmacy.

"Since older adults with multiple chronic illnesses and medications, high medication costs and Part D Medicare coverage may qualify for a covered medication review, and their health plans are graded publicly on how many qualified participants receive a review, our finding that so many are unaware of the option is surprising," says Karen B. Farris, Ph.D., M.P.A., a professor of clinical pharmacy.

Coe and Farris do note that the older adults at the highest risk of drug interactions - those taking five or more prescription medications - were more likely to have had a comprehensive medication review than those taking fewer medications, though there is still room for improvement.

The poll shows an opportunity for progress. When the poll team asked older adults who take multiple prescription medications if they'd be interested in going over them with a pharmacist, more than a third said yes.

The older a poll respondent was, the more likely she or he was to take multiple prescription and over-the-counter medications. In all, 30% of those over 65 took five or more prescription medications, compared with 19% of those aged 50 to 64. And 15% of those over 65 said they take five or more over-the-counter medications, vitamins and supplements, compared with 9% of those in their 50s and early 60s.

Preeti Malani, M.D., the poll director and a Michigan Medicine physician specializing in geriatrics and infectious diseases, notes that every older adult should keep a list of everything they take, whether they get it via a prescription or buy it directly. A providers or pharmacist can look at the list to try to spot any potential for interactions or opportunities to switch to lower-cost options that could provide the same benefits.

"It's also important to make sure you tell your doctors and other health care providers about everything you take, even over-the-counter vitamins or herbal remedies," she says. "Not only may they spot potential risks, but the computer systems that they use to track your care might identify potential interactions." She also notes that medication reviews can take place in person, by phone or via a video appointment.

"Managing multiple medications may be especially important for older adults," says Alison Bryant, Ph.D., senior vice president of research for AARP. "We know that people enrolled in Medicare Part D take an average of 4.5 medications each month. We encourage everyone taking medications or supplements to regularly discuss them with a health care provider."

The National Poll on Healthy Aging results are based on responses from a nationally representative sample of 2,048 adults aged 50 to 80 who answered a wide range of questions online. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have them.

A full report of the findings and methodology is available at http://www.healthyagingpoll.org, along with past National Poll on Healthy Aging reports.

COLUMBUS, Ohio - It's good to have friends and family to back you up when you need it - but it's even better if your supporters are close with each other too, a new set of studies suggests.

Researchers found that people perceived they had more support from a group of friends or family who all knew and liked each other than from an identical number of close relationships who were not linked.

The results suggest that having a network of people to lean on is only part of what makes social support so beneficial to us, said David Lee, who led the study as a postdoctoral fellow in psychology at The Ohio State University.

"The more cohesive, the more dense this network you have, the more you feel you can rely on them for support," said Lee, who is now an assistant professor of communication at the University at Buffalo.

"It matters if your friends can depend on each other, just like you depend on them."

Lee conducted the study with Joseph Bayer, assistant professor of communication, and Jonathan Stahl, graduate student in psychology, both at Ohio State. Their research was published online recently in the journal Social Psychology Quarterly.

The researchers conducted two online studies.

In one study, 339 people were asked to list eight people in their lives that they could go to for support in the last six months. Participants rated on a scale of 1 to 7 how much support they received from each person. (Most were listed as friends or family members, but some people also named co-workers, romantic partners, classmates or roommates).

Crucially for this study, participants were also asked to rate on a scale of 1 to 7 how close each possible pair of their eight supporters were to each other (from "they don't know each other" to "extremely close.")

Based on those answers, the researchers calculated the density of each participant's network - the closer and more interconnected their friends and family were to each other, the denser the network.

Results showed that the denser the networks, the more support that participants said they would be able to receive from them.

"We found that our support networks are more than the sum of their parts," said Bayer, who is a core faculty of Ohio State's Translational Data Analytics Institute.

"People who feel they have more social support in their lives may be focusing more on the collective support they feel from being part of a strong, cohesive group. It's having a real crew, as opposed to just having a set of friends."

A second study, involving 240 people, examined whether the density of a social network mattered in a specific situation where people needed help.

In this case, participants were asked to list two different groups of four people they could go to if they needed support. One group comprised four people who were not close to one another and the other group consisted of four people who were close with each other.

Participants were then asked to imagine a scenario in which their house had been broken into and they went to their network for support.

Half the people were told to think about going to the four people who were not close to one another, while the other half imagined reaching out to their four connected supporters.

Results showed that those who imagined going to their tight-knit group of friends or family perceived that they would receive more support than did participants who thought about going to their unconnected friends.

The results also offered preliminary evidence of two psychological mechanisms that could help explain why people feel better supported by a tight-knit group of friends.

In answers to survey questions, participants suggested that they thought of their group of close friends or family as one entity. They also were more likely to see a closer-knit group as part of their own identities. Both of these factors were related to perceiving more support, results showed.

The researchers said the results of both studies show it isn't just the number of friends and family you have in your network that is important.

"You can have two friends who are both very supportive of you, but if they are both friends with each other, that makes you feel even more supported," Stahl said.

On a practical level, that means it is important which friends we think about when we most need help or when we are feeling lonely in the midst of daily life.

"Focus on those friends who are connected to each other," Bayer said. "That's where we really perceive the most support."

A new study published in Arthritis Care & Research has examined patterns of 24-hour physical activity and sleep among patients with rheumatoid arthritis, lupus, and knee osteoarthritis.

In the 172-participant study, four profiles were apparent with differences characterized by variations in time spent sleeping (High and Low sleepers), non-ambulatory activities (High Sitters), and ambulatory activities (Balanced Activity).

Younger age, not having a job that involved a lot of sitting, and having outside walking as a habit were each associated with Balanced Activity relative to High Sitters.

Considering these profiles may be useful in efforts to help individuals with arthritis modify their activity or sleep behaviors.

"We all live our daily lives over 24 hours, and our study found that people with arthritis are likely to have one of four distinctly different patterns for how they allocate time in sleep and a variety of activities throughout their day," said lead author Lynne Feehan, PT, PhD, Department of Physical Therapy, University of British Columbia. "This suggests that a one-size-fits-all approach to supporting people with arthritis to modify their daily sleep or physical activity choices may not be appropriate."

Alison Hoens a patient partner on this study, noted, "As a patient living with rheumatoid arthritis and as a physical therapist, the findings of this study resonate strongly with me. The recognition that patients, even with similar diagnoses, are 'not all the same' speaks to the potential of tailoring support from healthcare providers to encourage healthy sleep, rest, and activity that align with a patient's habits and needs."