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For an embryo to survive, it must attach to the lining of the uterus within days of conception. However, if this lining, called the endometrium, is too thin, the embryo can’t latch on. Now, researchers reporting in ACS Biomaterials Science & Engineering have developed a new system intended to treat infertility in women with thin endometria. Their tiny, micro-scale particles stimulated blood vessel growth, producing promising results in preliminary experiments in cells and mice.
Poor blood flow within the endometrium limits its thickness, and researchers have struggled to find an effective way to encourage the formation of new blood vessels. Some have begun exploring the use of microspheres to deliver treatment. However, current methods for making these tiny particles face challenges, including the need for complex, demanding production methods and too much variation in the sizes of the spheres. So, Xiangguo Wang, Lei Yang and their colleagues wanted to devise a simple, efficient technique for manufacturing uniform microspheres loaded with a compound known to be a potent stimulator of blood vessel growth.
To formulate their tiny particles, the researchers looked to hyaluronic acid, a substance known to contribute to the growth of the endometrium. Using a method called electrospray, they generated hyaluronic acid-containing droplets that were all very similar in size, about 400 µm in diameter. They then collected the droplets and stuck them together with an ultraviolet light treatment. By manipulating the composition of the spheres, the researchers found they could alter their ability to take up and release drugs. They then loaded the particles up with their second active ingredient: the blood vessel-promoting compound called vascular endothelial growth factor (VEGF). In experiments with female mice with thin endometria, they found that microspheres containing only the hyaluronic acid produced some thickening of the tissue compared to the control, but VEGF-carrying spheres generated the most thickening. While promising, this system needs further safety testing, note the researchers. They add that limits on the spheres’ drug releasing ability may make multiple treatments necessary for fertility patients.
The authors acknowledge funding the Natural Science Foundation of Jiangxi Province, National Key R&D Program of China, Beijing Dairy Cattle Industry Innovation Team project, and Outstanding Young Talent Project of Beijing Municipal Party Committee Organization Department.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.

Researchers at McMaster University have developed a sophisticated new tool that could help provide early warning of rare and unknown viruses in the environment and identify potentially deadly bacterial pathogens which cause sepsis, among other uses.
The new algorithm is an advanced tool that can help develop probes to capture trace quantities of pathogens, both known and unknown from a wide variety of situations, like the animal-to-human transmission of infections such as SARS-CoV-2 or monitor reservoirs in the environment for possible emerging pathogens.
To date most labs have bulk sequenced samples, a laborious and costly process that typically requires scientists to tease out and then reassemble minute fragments of specific DNA, which are difficult to detect and often contaminated by the billions of other organisms in the same sample or environment.
Pathogens in clinical or wildlife settings samples of blood or saliva, for example, are particularly challenging to isolate, since they can easily make up less than one one-millionth of a sample, especially in early stages of an infection, when concentrations are still low and detection is most critical for patients.
Researchers successfully tested the probes on the entire family of coronaviruses, including SARS-CoV-2. The probes provide a shortcut by targeting, isolating and identifying the DNA sequences — specifically and simultaneously — that are shared among related organisms, most often due to evolutionary history or ancestry.
“There are thousands of bacterial pathogens and being able to determine which one is present in a patient’s blood sample could lead to the correct treatment faster when time is very important,” explains Zachery Dickson, lead author of the study and a graduate student in the Department of Biology.
“The probe makes identification much faster, meaning we could potentially save people who might otherwise die,” he says.
Researchers also demonstrated the effectiveness of probes for capturing the incredibly wide array of pathogens associated with sepsis, a life-threatening and rapidly developing condition that occurs when the body overreacts to an infection which typically starts in the lungs, urinary tract, skin or gastrointestinal tract.
“We currently need faster, cheaper and more succinct ways to detect pathogens in human and environmental samples that democratize the hunt and this pipeline does exactly that,” says evolutionary geneticist Hendrik Poinar, a lead author on the study and director of McMaster’s Ancient DNA Centre.
The discovery also holds promise for much broader applications for human health and scientific discovery, including the identification of intestinal parasites in ancient DNA, which could reveal new information on the evolution of catastrophic disease.
The process used to design the probes, a pipeline called HUBdesign or Hierarchical Unique Baits, is described in the journal Cell Reports: Methods, published online today.
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Materials provided by McMaster University. Original written by Michelle Donovan. Note: Content may be edited for style and length.

Modest weight loss can lead to meaningful risk reduction in adults with obesity. Although both behavioral economic incentives and environmental change strategies have shown promise for initial weight loss, to date their efficacy alone or in combination have not been compared.
In a two-year randomized clinical trial, researchers investigated whether financial incentives and environmental change strategies, together or separately, help employed adults with obesity lose weight and keep it off. Of note, the strategies tested in this study did not include any individual counseling sessions or classes. While participants across all study groups lost a modest amount of weight, study participants felt they would have benefitted more from intensive guidance such as on-going counseling and coaching. The findings have been published in the Journal of the American Medical Association (JAMA).
“In our Healthy Weight trial, incentives and environmental strategies led to modest but nonsignificant improvements in weight loss,” explains Karen Glanz, PhD, MPH, the George A. Weiss University Professor and Professor of Nursing at the University of Pennsylvania School of Nursing (Penn Nursing). Glanz is the lead author of the article. “From a translational standpoint, benefits designs could consider incorporating ongoing financial incentives for weight loss among employees with obesity, while linking online support to more intensive personalized approaches.”
The article, “Effect of Financial Incentives and Environmental Strategies on Weight Loss in the Healthy Weight Study,” is available online. Coauthors of the article include Pamela Shaw, PhD, Pui Kwong, MPH, Ji Rebekah Choi, MPH, Jingsan Zhu, MS, MBA, Qian Erin Huang, MPH, Karen Hoffer, BS, and Kevin G. Volpp, MD, PhD, all of the Perelman School of Medicine at the University of Pennsylvania; and Annie Chung, BA, of Children’s Hospital of Philadelphia. This research reported was supported by Cooperative Agreement 1U48DP005053 from the U.S. Centers for Disease Control and Prevention.
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Materials provided by University of Pennsylvania School of Nursing. Note: Content may be edited for style and length.

Throughout history, pandemics have been a key driver of human population change, thanks to mortality and declining fertility rates. And, according to a new study co-authored by Seth Sanders, the Ronald Ehrenberg Professor of Economics in the ILR School, COVID-19 is no exception.
Births declined 7.1% in the United States, according to the study, “Early Assessment of the Relationship Between the COVID-19 Pandemic and Births in High-Income Countries,” published Sept. 7 in the Proceedings of the National Academy of Sciences.
In their research, Sanders and his co-authors reported on the relationship between the COVID-19 pandemic and births for 22 high-income countries. They found particularly strong declines in southern Europe: Italy (-9.1%), Spain (-8.4%) and Portugal (-6.6%), while Denmark, Finland, Germany, and The Netherlands saw no decline at all.
Of the results, the authors wrote, “When compared to the large fall in southern Europe, the relative stability of [crude birth rates] in northern Europe points to the role of policies in support of families and employment in reducing any impact on births.”
Said Sanders: “The bottom line is that there was a lot of variation across countries in the decline. We don’t address why, but we think a lot of it has to do with the degree of economic disruption, coupled with the degree of social support in the absence of employment.”
To conduct their study, the researchers used monthly live birth data from January 2016 to March 2021, which corresponds to conceptions (carried to term) from April 2015 to June 2020. They then matched information on monthly live births with mid-year population estimates from the United Nations (UN) Population Division’s World Population Prospects to establish their formula.
The authors only included countries that belong to the high-income group, according to the World Bank, and that had both population and birth data available up to at least November 2020.
The paper was co-authored by Arnstein Aassve, Nicolò Cavalli, Letizia Mencarini and Samuel Plach, all from the Università Commerciale Luigi Bocconi in Italy.
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Materials provided by Cornell University. Original written by Julie Greco, courtesy of the Cornell Chronicle. Note: Content may be edited for style and length.

This time of year, you hear a lot about heat-related illnesses in athletes. Thousands of student-athletes are sidelined by heat illnesses each year, and some don’t recover.
But while guidelines exist to help coaches and trainers keep their students safe, there’s another group on the field that’s still at risk: students in marching bands.
“You read all these stories in newspapers about marching band members experiencing heat-related illnesses, but no one’s pulled together a comprehensive study of how often those illnesses occur, what the affected students were doing,” said Andrew Grundstein, a professor in the University of Georgia’s Franklin College of Arts and Sciences. “There are no national standards for keeping marching band members safe like there are for other active populations.”
Working with Rashawn Merchant, an undergraduate in the College of Agricultural and Environmental Sciences and lead author of the study, Grundstein and his team set out to fill that gap.
Heat illnesses
Published in the International Journal of Biometeorology, this study analyzed news reports of band members suffering heat-related illnesses from 1990 to 2020 and found almost 400 band students who overexerted themselves and became ill due to heat exposure. About half of these students were treated on site and didn’t require hospitalization, but 44% wound up in the hospital for treatment before being released the same day. The others suffered from heat stroke, requiring more than just one day in the hospital.

Addenbrooke’s Hospital in Cambridge along with 20 other hospitals from across the world and healthcare technology leader, NVIDIA, have used artificial intelligence (AI) to predict Covid patients’ oxygen needs on a global scale.
The research was sparked by the pandemic and set out to build an AI tool to predict how much extra oxygen a Covid-19 patient may need in the first days of hospital care, using data from across four continents.
The technique, known as federated learning, used an algorithm to analyse chest x-rays and electronic health data from hospital patients with Covid symptoms.
To maintain strict patient confidentiality, the patient data was fully anonymised and an algorithm was sent to each hospital so no data was shared or left its location.
Once the algorithm had ‘learned’ from the data, the analysis was brought together to build an AI tool which could predict the oxygen needs of hospital Covid patients anywhere in the world.
Published today in Nature Medicine, the study dubbed EXAM (for EMR CXR AI Model), is one of the largest, most diverse clinical federated learning studies to date.

A team of scientists from Nanyang Technological University, Singapore (NTU Singapore) has developed a predictive computer model that, when tested on real pandemic data, proposed strategies that would have reduced the rate of both COVID-19 infections and deaths by an average of 72 per cent, based on a sample from four countries.
The model, called NSGA-II, could be used to alert local governments in advance on possible surges in COVID-19 infections and mortalities, allowing them time to put forward relevant counter measures more rapidly.
Through the testing of NSGA-II in four Asian countries using data available from 1 January 2020 to 31 December 2020, the team demonstrated that it could have helped reduce the number of COVID-19 infections and deaths by up to 76 per cent in Japan, 65 per cent in South Korea, 59 per cent in Pakistan, and 89 per cent in Nepal.
The computer model achieved the result by recommending timely and country-specific advice on the optimal application and duration of COVID-19 interventions, such as home quarantines, social distancing measures, and personal protective measures that would help to thwart the negative impact of the pandemic.
The team also showed NSGA-II could make predictions on the daily increases of COVID-19 confirmed cases and deaths that were highly accurate, at a confidence level of 95 per cent, compared to the actual cases that took place in the four countries over the past year.
Harnessing the power of machine learning, the research team developed NSGA-II by inputting large amounts of data on COVID-19 mortalities and infections worldwide that is available for the whole of 2020, helping it learn the dynamics of the pandemic. The research was reported in the peer-reviewed scientific journal Sustainable Cities and Society in August.

The chemical steps in an important cellular modification process that adds a chemical tag to some RNAs have been revealed in a new study. Interfering with this process in humans can lead to neuronal diseases, diabetes, and cancers. A research team, led by chemists at Penn State, has imaged a protein that facilitates this RNA modification in bacteria, allowing the researchers to reconstruct the process. A paper describing the modification process appears Sept. 15 in the journal Nature.
Transfer RNAs (tRNA) are the RNAs that “read” the genetic code and translate it into a sequence of amino acids to make a protein. The addition of a chemical tag — a methyl sulfur group — to a particular location on some tRNAs improves their ability to translate messenger RNA into proteins. When this modification process — called methylthiolation — doesn’t occur properly, mistakes can be incorporated into the resulting proteins, which in humans can lead to neuronal disease, cancer, and increased risk of developing Type 2 diabetes.
“Methylthiolation is ubiquitous across bacteria, plants, and animals,” said Squire Booker, a biochemist at Penn State and investigator with the Howard Hughes Medical Institute who led the research team. “In this study, we determined the structure of a protein called MiaB to better understand its role in facilitating this important modification process in bacteria.”
The MiaB protein from the bacteria Bacteroides uniforms is a member of the radical SAM (S-adenosylmethionine) family of enzymes. Radical SAM enzymes typically use one of their own iron-sulfur clusters to convert a SAM molecule into a “free radical” that helps move the reaction forward. Unlike most other radical SAM enzymes, MiaB contains two iron-sulfur clusters: a radical SAM cluster and an auxiliary cluster, where most of the intricate chemistry takes place.
Imaging MiaB in action with SAM molecules and tRNA at several points during methylthiolation allowed the researchers to infer the chemical steps during the modification process. First, a molecule of SAM donates its methyl group to the auxiliary iron-sulfur cluster on MiaB.
“The source of the sulfur atom attached to the tRNA has been controversial, but our structures reveal that a methyl group from SAM attaches to a sulfur atom on MiaB’s auxiliary iron-sulfur cluster,” said Olga Esakova, assistant research professor in chemistry at Penn State and first author of the paper. “This methyl group and the sulfur it attaches to on MiaB are ultimately what transfers to the tRNA, but some additional steps occur before the tRNA can accept the methylthio group.”
The addition of an electron fragments a second molecule of SAM into a free radical. The radical ultimately takes a hydrogen atom from the tRNA, which is replaced with the methylthio group on MiaB.
“Initially, the hydrogen on the tRNA is not positioned in a way that allows both access to the radical that removes it and access to the methylthio group that needs to be transferred, because the hydrogen and the atoms attached nearby are all aligned in the same plane,” said Booker. “Our structures show that the methylthio group on MiaB’s auxiliary cluster induces a change in geometry at that spot in the tRNA undergoing methylthiolation, which changes into more of a tetrahedral shape, with the hydrogen in an optimal position to be plucked off by the radical and the methylthio group in an optimal position for subsequent transfer.”
The result of these steps is tRNA with the added methylthio group and a successful modification.
Next, the researchers hope to identify how the auxiliary cluster is rebuilt after each turnover so that the process can proceed for multiple rounds. They are also investigating analogous proteins that play a similar role in the modification process in humans.
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Materials provided by Penn State. Original written by Gail McCormick. Note: Content may be edited for style and length.

Nearly half of New York City mothers who had been trying to become pregnant again before the coronavirus pandemic began stopped in the first few months of the outbreak, a new study shows.
Led by researchers at NYU Grossman School of Medicine, the survey of 1,179 mothers in New York City also found that one-third of women who had been thinking about becoming pregnant before the pandemic but had not yet begun trying, said they were no longer considering it.
“Our findings show that the initial COVID-19 outbreak appears to have made women think twice about expanding their families and, in some cases, reduce the number of children they ultimately intend to have,” says study lead author and epidemiologist Linda Kahn, PhD, MPH. “This is yet another example of the potential long-lasting consequences of the pandemic beyond the more obvious health and economic effects.”
Pregnancy becomes riskier and more difficult to achieve as women age, so the delays prompted by the pandemic may lead to increased health risks for both mother and child, as well as the need for costly fertility treatments, she adds.
Kahn, an assistant professor in the Departments of Pediatrics and Population Health at NYU Langone Health, notes that all of the women in the study already had at least one child age 3 or younger. As a result, it is possible that the challenges of caring for a young child during the peak of New York City’s outbreak and subsequent lockdown may have played a role in their hesitancy to have another baby.
Early evidence has already identified a birthrate decline in the United States during the coronavirus pandemic. Recent data showed that the country saw roughly 300,000 fewer births in 2020 than experts had expected based on annual fertility trends, with a particular drop in the last two months of the year, which corresponds with fewer conceptions at the beginning of the outbreak in March. However, until now, few investigations have explored the root causes behind individual parents’ decisions to delay pregnancy.

Physicians prescribed opioids more often to their white patients who complained of new-onset low back pain than to their Black, Asian and Hispanic patients during the early days of the national opioid crisis, when prescriptions for these powerful painkillers were surging but their dangers were not fully apparent, according to a UCLA study.
The findings suggest that doctors may have commonly dispensed pain treatments unequally based on race and ethnicity. The study shows that physicians were more likely to prescribe non-steroidal anti-inflammatory drugs, or NSAIDs — a less-powerful alternative — to their patients of color who came to them for back pain care.
“This appears to be a case of differential treatment of pain or bias by physicians, in which the pain of certain patients deserves opioids and the pain of others does not,” said Dr. Dan Ly, the study’s author and an assistant professor of medicine at the David Geffen School of Medicine at UCLA. “The fact that, in hindsight, more white patients developed dangerous long-term opioid use doesn’t absolve physicians of this differential treatment.”
The paper is published today in the peer-reviewed JAMA Health Forum.
Ly examined nationwide medical claims data from 2006 through 2015 for about 275,000 Medicare beneficiaries who were 66 or older and were experiencing new-onset low back pain. Approximately 81% of these patients were white, 6% were Black, 6% were Asian/Pacific Islander and 8% were Hispanic.
Focusing on how individual doctors prescribed opioids differently based on their patients’ race and ethnicity, Ly found that, on average, these drugs were dispensed to 11.5% of white patients, versus about 10% of Black patients, 9% of Asian/Pacific Islander patients and 10.5% of Hispanic patients.
Among patients who seemed to have severe or longer-lasting pain — measured as five or more visits to the doctor for back pain in a year — the differences were starker: 36% of white patients were prescribed opioids, versus about 30% of Black patients, 21% of Asian/Pacific Islanders and 24% of Hispanics. Physicians, Ly said, also tended to prescribe opioids sooner to their white patients.
Conversely, doctors prescribed NSAIDs to 25% of their Black patients, 25% of Asian/Pacific Islanders and 28% of Hispanics but only to 24% of whites — again, with greater differences for patients with more visits for their back pain.
The study also found that white patients with new low back pain were subsequently more likely to develop long-term reliance on opioids than patients of Black, Asian/Pacific Islander or Hispanic origin.
One possible reason for these prescribing discrepancies, Ly said, is that physicians may have had less confidence that patients of color would not misuse opioids, even though studies have shown no difference in rates of opioid misuse between patients of color and white patients. It’s also possible, he said, that patients of color may have asked for opioids less frequently than white patients, although there is no evidence for this.
Ly noted that because this was an observational study, there may have been other, non-observable factors that contributed to prescribing discrepancies. The findings do not include results from physical exams, which may have influenced prescribing decisions, and over-the-counter medications were not included in the data.
The National Institute on Aging funded this study.