Culture

Scientific studies rarely focus on long non-coding RNA molecules (lncRNAs), even though they potentially regulate several diseases. The role of several lncRNAs in anti-viral inflammatory response regulation has recently been reported. Considering their significant regulatory function in immune response, researchers from the Azrieli Faculty of Medicine of Bar-Ilan University sought to identify lncRNAs co-expressed with human genes involved in immune-related processes during severe SARS-CoV-2 infection in the lungs.

Recent studies demonstrated that patients afflicted with severe SARS-CoV-2 infections present increased levels of pro-inflammatory plasma cytokines, as opposed to milder cases, highlighting the release of inflammatory cytokines as being central to COVID-19 severity. However, the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive.

In a paper recently published in the journal Viruses, the researchers demonstrated that lncRNAs are indeed potential regulators of anti-viral response during severe SARS-CoV-2 infection. Using the available transcriptome data from the lung cells of severely affected COVID-19 patients and SARS-CoV-2 infected lung-cell-lines, they constructed a gene co-expression network that can measure the relationship of gene expression patterns across a group of samples. This analysis enables them to identify four differentially expressed lncRNAs that are found to be strongly correlated to the protein-coding genes in a novel network enriched for different immune-related processes associated with dysregulated cytokine production. These four lncRNAs were also identified as "hubs" - important nodes in this co-expression network, signifying their association with cytokine over-production due to fierce immune response.

The finding suggests that the aberrant expression of lncRNAs can be associated with cytokine storms and anti-viral responses during severe SARS-CoV-2 infection. Thus, the present study uncovers the potential associations of lncRNAs in cytokine and interferon signaling during the response to severe SARS-CoV-2 infection in the lungs. This could provide valuable insight into pro-inflammatory cytokine production and how to mitigate it. It could also potentially be utilized as a future drug target to combat the hyper-inflammation caused by SARS-CoV-2 infection.

"It is remarkable that a major part of the human genome is filled in by non-coding regulatory elements, formerly known as "junk DNA". Among these are the long non-coding RNAs (lncRNAs). These lncRNAs are receiving more and more recognition as the potential regulators of several diseases," says Dr. Milana Frenkel-Morgenstern, of Bar-Ilan University's Azrieli Faculty of Medicine, who led the study with Prof. David Karasik.

This study sheds light on the mechanisms behind COVID-19 severity and dysfunctional immune responses. Understanding the molecular interactions behind the immune dysfunction during severe COVID-19 infection in the lungs should help inform the design and development of novel approaches for treating severe COVID-19 patients.

The researchers plan to validate their findings on human samples in collaboration with several of Israel's health care centers. Further, they will aim to determine which drugs from their COVID-19 drug database may inhibit the cytokine storm generation in COVID-19, and will design experiments to test the efficacy of those drugs.

This study was supported by a grant from the COVID-19 Data Science Institute (DSI) at Bar-Ilan University and a PBC fellowship for outstanding postdoctoral researchers from China and India (to Dr. Sumit Mukherjee, who participated in the research) from the Israel Council for Higher Education.

COLUMBUS, Ohio - A new treatment is among the first known to reduce the severity of acute respiratory distress syndrome caused by the flu in animals, according to a new study.

Tests in mice infected with high doses of influenza showed that the treatment could improve lung function in very sick mice and prevent progression of disease in mice that were pre-emptively treated after being exposed to the flu.

The hope is that it may also help humans infected with the flu, and potentially other causes of acute respiratory distress syndrome (ARDS) such as SARS-CoV-2 infection.

Specific cells in mice are less able to make key molecules after influenza invades the lungs, reducing their ability to produce a substance called surfactant that enables lungs to expand and contract. The shortage of surfactant is linked to ARDS, an illness so serious that it typically requires mechanical ventilation in an ICU.

Researchers bypassed the blocked process in mice by re-introducing the missing molecules alone or in combination as an injected or oral treatment. The results: normalized blood oxygen levels and reduced inflammation in mouse lungs - effects that could make a person well enough for hospital discharge.

"The most important and impressive thing in this study is the fact that we have benefits even when we treat late in the disease process. If we could develop a drug based on these findings, you could take somebody who's going to have to go on a ventilator and stop that completely," said Ian Davis, professor of veterinary biosciences at The Ohio State University and senior author of the study. "There's nothing out there now that can do this for ARDS that will bring them back to that degree, and certainly not for flu."

ARDS can also result from infections, cancer, trauma and many other ailments. Though this therapy has been tested in the context of the flu, Davis said its reliance on fixing a broken cell function in the host rather than killing the virus suggests it has potential to treat virtually any lung injury.

The study was published online recently in the American Journal of Respiratory Cell and Molecular Biology.

The experimental treatment consists of molecules known as liponucleotides, which are essential for making surfactant in the lungs. Davis analyzed lung cells from flu-infected mice and determined that the pathway to surfactant production was disrupted, with one of the two necessary liponucleotides completely undetectable.

"The thinking before was that the reason there was less surfactant in mice with flu-related ARDS was because cells are dying. This defect is in some ways better - if cells are dying, there's not much you can do, but if there's a problem with the cell's metabolism, maybe you can fix it," Davis said.

And fix it - in mice - he did, developing therapies containing the missing liponucleotide molecule alone or combined with one or two others.

Davis and colleagues inoculated mice with high doses of H1N1 influenza and then treated some mice with liponucleotides once daily for five days and others just a single time five days after exposure. The mice receiving daily treatment were protected from getting seriously ill, and the very sick mice treated on the fifth day, whose severe blood-oxygen loss and lung inflammation had cause ARDS, showed significant improvement.

"Obviously that's what you need in someone with severe influenza - we want to take someone who is already in the ICU and help them get out faster, or head going to the ICU off at the pass," Davis said.

Liponucleotides don't kill the flu virus - which is the point.

"I've always been interested in finding new therapies to treat lung injury," he said. "The problem with anti-viral drugs is you probably need a different drug for every virus. Also, many viruses can quickly mutate to become resistant to these drugs.

"Our approach is to fix the patient. Once the virus has caused the injury - the inflammation - it doesn't really matter if it stays or goes away."

There's still a lot to learn. The agents have a strong anti-inflammatory effect, but don't fully restore the surfactant-production process - and Davis isn't sure why that is. Studies so far have been based on findings in a single type of lung cell, but the scientists haven't confirmed that those cells are the ones responding to the therapy - any number of other cells in the immune system, blood vessels or heart could also play a role.

Despite the unknowns, Davis said that because the missing liponucleotides naturally exist in mammals, including humans, they are considered safe and unlikely to cause side effects, even if they go unused in the body.

The Ohio State Innovation Foundation has filed patents covering the scope of Davis' discoveries, which may also extend to patients suffering from other forms of lung damage that cause inflammation and a drop in blood oxygen levels.

A research group led by Professor Xiang David LI from the Research Division for Chemistry and the Department of Chemistry, The University of Hong Kong, has developed a novel chemical tool for elucidating protein interaction networks in cells. This tool not only facilitates the identification of a protein's interacting partners in the complex cellular context, but also simultaneously allows the 'visualisation' of these protein-protein interactions. The findings were recently published in the prestigious scientific journal Molecular Cell.

In the human body, proteins interact with each other to cooperatively regulate essentially every biological process ranging from gene expression and signal transduction, to immune response. As a result, dysregulated protein interactions often lead to human diseases, such as cancer and Alzheimer's disease. In modern biology, it is important to comprehensively understand protein interaction networks, which has implications in disease diagnosis and can facilitate the development of treatments.

To dissect complex protein networks, two questions need to be answered: the 'who' and 'how' of protein binding. The 'who' refers to the identification of a protein's interacting partners, whereas the 'how' refers to the specific 'binding regions' that mediate these interactions. Answering these questions is challenging, as protein interactions are often too unstable and too transient to detect. To tackle this issue, Professor Li's group has previously developed a series of tools to 'trap' the protein-to-protein interactions with a chemical bond. This is possible because these tools are equipped with a special light-activated 'camera' - diazirine group that capture every binding partner of a protein when exposed to UV light. The interactions can then be examined and interpreted. Unfortunately, the 'resolution' of this 'camera' was relatively low, meaning key information about how proteins interact with each other was lost. To this end, Professor Li's group has now devised a new tool (called ADdis-Cys) that has an upgraded 'camera' to improve the 'resolution'. An alkyne handle installed next to the diazirine makes it possible to 'zoom in' to clearly see the binding regions of the proteins. Coupled with state-of-the-art mass spectrometry , ADdis-Cys is the first tool that can simultaneously identify a protein's interacting partners and pinpoint their binding regions.

In the published paper, Professor Li's lab was able to comprehensively identify many protein interactions -- some known and some newly discovered -- that are important for the regulation of essential cellular processes such as DNA replication, gene transcription and DNA damage repair. Most importantly, Professor Li's lab was able to use ADdis-Cys to reveal the binding regions mediating these protein interactions. This tool could lead to the development of chemical modulators that regulate protein interactions for treating human diseases. As a research tool, ADdis-Cys will find far-reaching applications in many areas of study, particularly in disease diagnosis and therapy.

The researchers in this study reached this conclusion by drawing on network modelling research and mapped the job landscapes in cities across the United States during economic crises.

Knowing and understanding which factors contribute to the health of job markets is interesting as it can help promote faster recovery after a crisis, such as a major economic recession or the current COVID pandemic. Traditional studies perceive the worker as someone linked to a specific job in a sector. However, in the real-world professionals often end up working in other sectors that require similar skills. In this sense, researchers consider job markets as being something similar to ecosystems, where organisms are linked in a complex network of interactions.

In this context, an effective job market depends on many aspects, such as diversity and the number of job offers or training opportunities that workers have in order to acquire new skills, for example. In this scientific study, researchers have found that cities where all of these factors are very similar respond differently in regard to recovering from an economic crisis. Why? "We have discovered that the difference comes, in part, from the jobs 'map', a network that tells us how jobs within a city are related, according to the similarity of the skills required to perform those jobs," explains Esteban Moro, an associate professor at the UC3M's Department of Mathematics and co-author of the study, who is currently a visiting professor at the MIT Media Lab.

"When that map is extremely limited, in other words, when there is very little chance of finding another similar job (what we call "job connectivity"), cities are less prepared for a job crisis. In contrast, when that map offers lots of possibilities of moving from one job to another similar one, the city is better prepared. It also has an effect on workers' wages: workers in cities that have a more diverse network earn more than those in the same occupation in cities where this network is more limited," adds Esteban Moro.

Ecology, complex networks and job connectivity

In ecology and other domains where complex networks are present, resilience has been closely linked to the "connectivity" of the networks. In nature, for example, ecosystems with lots of connections have proven to be more resistant to certain shocks (such as changes in acidity or temperature) than those with fewer connections. Inspired by this idea and drawing on previous network modelling research, the authors of the study modelled the relationships between jobs in several cities across the United States. Just as connectivity in nature fosters resilience, they predicted that cities with jobs connected by overlapping skills and geography would fare better in the face of economic shock than those without such networks.

In order to validate this, the researchers examined data from the Bureau of Labor Statistics for all metropolitan areas in the US from the beginning to the end of the Great Recession (2008-2014). Based on this data, they created maps of the job landscape in each area, including the number of specific jobs, their geographical distribution, and the extent to which the skills they required overlapped with other jobs in the area. The size of a given city, as well as its employment diversity, played a role in resilience, with bigger, more diverse cities obtaining better results than smaller and less-diverse ones. However, by controlling size and diversity and taking job connectivity into account, predictions of peak unemployment rates during the recession improved significantly. In other words, cities where job connectivity was higher before the crash were significantly more resilient and recovered faster than those with less-connected markets.

Even in the absence of temporary crises like the Great Recession or the COVID pandemic, phenomena, such as automation, might radically change the job landscape in many areas in the coming years. How can cities prepare for this disruption? The researchers in this study extended their model to predict how job markets would behave when facing job loss due to automation. They found that while cities of similar sizes would be affected similarly in the early stages of automation shocks, those with well-connected job networks would provide better opportunities for displaced workers to find other jobs. This prevents widespread unemployment and, in some cases, even leads to more jobs being created as a result of the initial automation shock.

The findings of this study suggest that policymakers should consider job connectivity when planning for the future of employment in their regions, especially where automation is expected to replace a large number of jobs. Furthermore, increased connectivity does not just result in lower unemployment, it also contributes to a rise in overall wages. These results provide a new perspective on discussions about the future of employment and may help guide and complement current decisions about where to invest in job creation and training programmes, say researchers.

During the Bronze Age, Mesopotamia was witness to several climate crises. In the long run, these crises prompted the development of stable forms of State and therefore elicited cooperation between political elites and non-elites. This is the main finding of a study published in the journal PNAS and authored by two scholars from the University of Bologna (Italy) and Eberhard Karls Universität Tübingen (Germany).

This study investigated the impact of climate shocks in Mesopotamia between 3100 and 1750 bC. The two scholars looked at these issues through the lenses of economics and adopted a game-theory approach. They applied this approach to the first detailed database on climate and institutional evolution of the 44 most important states of Mesopotamia.

"Severe and prolonged droughts pushed elites of landowners to grant political and property rights to the non-elites, who had the skills and tools to stem the damages brought by climate change. Elites did so to persuade non-elites that a sufficient part of the crops would be shared through the production of public goods", explains Carmine Guerriero, a professor at the Department of Economics at the University of Bologna and one of the authors of this study. "On their end, non-elites promoted institutional changes, embracing a culture of cooperation to persuade elites of their commitment to future cooperations".

Three severe droughts seem to confirm these intuitions. In the last stages of the Urban Revolution (3800-3300 b.C.), religious groups stepped in and eventually coordinated the effort of building the first human-made canals. Then, during the Protodynastic Period (3100-2550 b.C.), the Palatine military promoted the cooperation between farmers, granting them protection and the resources of the military enlistment. During the Imperial Period (2350-1750 b.C.), a valuable and climate shock-independent alternative to agricultural activities was put forward by corporations of merchants that had increasingly taken hold. Conversely, periods of milder climate promoted the cooperation between non-elites and elites while elites were not forced to give up their power and non-elites were not obliged to adopt a culture of intense cooperation.

"Because of their primarily agricultural economic systems, some developing countries are experiencing climate change in a way that resembles that of Mesopotamian States, and they will also experience politically relevant consequences", adds Guerriero. "On the one hand, unfavourable climate shocks can promote cooperation between normally contrasting parties by granting more rights to non-elites. On the other hand, favourable climate conditions allow for the cooperation between elites and non-elites through less inclusive social orders and with some degree of cultural accumulation. Therefore, two major objectives in this sense are spreading a strong culture of cooperation and avoiding the random transfer of more inclusive social orders in developing countries".

All in all, analyzing events concerning lost civilizations can offer useful insights to understand and solve issues of present times. "The past offers a more encouraging perspective against which we can measure the gravity of today's crises including the pandemic", suggests Guerriero. "Moreover, the past shows the importance of an interdisciplinary approach involving social and natural sciences to obtain a more precise evaluation of short-, medium- and long-term effects of climate change".

This paper appeared in the journal PNAS with the title "Climate Change and State Evolution". It reports about a research project funded by the Alma Idea Programme of the University of Bologna and the Programme for Young Researchers "Rita Levi Montalcini". The authors are Giacomo Benati, Eberhard Karls Universität Tübingen, and Carmine Guerriero, University of Bologna. Federico Zaina (Research Fellow at the Department of Architecture, Construction and Constructed Environment Engineering of the Polytechnic University of Milan) and Laura Righi (Research Fellow at John XXIII Foundation of Religious Sciences) also took part in the study.

CHAMPAIGN, Ill. -- People up to age 40 living in economically depressed municipalities in the Greater Santiago, Chile, metropolitan area were three times more likely to die as a result of the infection than their counterparts in wealthier areas, researchers report in the journal Science. People ages 41-80 in low socioeconomic-status municipalities also suffered more from the pandemic than their peers in more affluent areas, the team found.

The study used new methods to analyze COVID-19 death counts, reported cases, testing rates and delays in testing results across location, time and age group. The results reveal striking disparities between high and low socioeconomic-status municipalities, and also help explain the factors that contribute to differences in COVID-19-related infections and mortality in these regions, said Pamela Martinez, a professor of microbiology and of statistics at the University of Illinois Urbana-Champaign who led the research with Gonzalo Mena, a postdoctoral fellow at the University of Oxford.

Greater Santiago is composed of 34 municipalities and is home to nearly 7 million people. The researchers used anonymized mobile phone data available through the Facebook Data for Good initiative to assess residents' mobility during the pandemic.

"People living in municipalities with low socioeconomic status did not reduce their mobility during lockdowns as much as those in more affluent municipalities," the researchers wrote. "This supports the hypothesis that people in poorer regions cannot afford to stay at home during lockdowns."

Access to COVID-19 testing and health care services in lower-income communities also appear to have contributed to the observed differences in health outcomes, the researchers report.

In the early weeks of the pandemic, COVID-19 testing was more available to people in the affluent parts of the metropolitan area than in the poorer locations, the researchers found. People in less affluent regions also appear to have waited longer for their test results.

"Because public health authorities plan their response based on the number of reported infections in a given area, this led to a poorer health care response in lower income areas than was needed," Martinez said. "This likely contributed to higher death counts in those areas."

This dynamic changed somewhat a few months into the pandemic - with testing ramping up in the poorer areas by late August, but the disparities in testing availability continued from mid-March to the end of September, the time period assessed.

"The Greater Santiago metropolitan area experienced more than 70% more deaths between May and July 2020 than in previous years, and places at the lower end of the socioeconomic spectrum were affected the most," Martinez said.

Access to health care also was less abundant in the economically depressed areas, another contributor to worse health outcomes there, the researchers report.

"We found that the south and west zones of the Greater Santiago metropolitan area had four times fewer beds per 10,000 residents and four times fewer people enrolled in the private health system than the east zone, which includes all of the most affluent municipalities," Martinez said. "We also discovered that more than 90% of the deaths attributed to COVID-19 in the south and west zones occurred in places other than health care facilities."

In the more affluent east zone, 55% of COVID-19-attributed deaths occurred outside health care facilities, she said.

Perhaps most strikingly, the team found that people under the age of 40 in less affluent parts of the region experienced significantly higher COVID-19-related mortality than their peers in wealthier areas.

"The infection-fatality rate for people 0-40 years old was 3.1 times higher in municipalities with the lowest socioeconomic status," Mena said. "Our results show that the socioeconomic inequalities we documented disproportionately affected younger people."

Understanding how demographic and socioeconomic factors contribute to health outcomes is essential to designing health care responses, the authors wrote.

"Our results align with the recent literature on uneven health risks globally, which has highlighted how socially and economically deprived populations are more vulnerable to the burden of epidemics," they wrote.

Cryopreservation, or the long-term storage of biomaterials at ultralow temperatures, has been used across cell types and species. However, until now, the practical cryopreservation of the fruit fly (Drosophila melanogaster) — which is crucial to genetics research and critical to scientific breakthroughs benefiting human health — has not been available.
“To keep alive the ever-increasing number of fruit flies with unique genotypes that aid in these breakthroughs, some 160,000 different flies, laboratories and stock centers engage in the costly and frequent transfer of adults to fresh food, risking contamination and genetic drift,” said Li Zhan, a postdoctoral associate with the University of Minnesota College of Science and Engineering and the Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio).In new research published in Nature Communications, a University of Minnesota team has developed a first-of-its-kind method that cryopreserves fruit fly embryos so they can be successfully recovered and developed into adult insects. This method optimizes embryo permeabilization and age, cryoprotectant agent composition, different phases of nitrogen (liquid vs. slush), and post-cryopreservation embryo culture methods.
Researchers were able to:

show that the method is broadly applicable and easily adopted by non-specialists, with it being successfully implemented in 25 distinct strains for fruit flies from different sources (e.g., laboratories);

demonstrate that for most strains, more than 50% of embryos hatch and more than 25% of the resulting larvae develop into adults after cryopreservation; and

show that flies retain normal sex ratio, fertility and original mutation after successive crypropreservation through generations and long-time storage in liquid nitrogen.

“Our multi-disciplinary team is pleased to contribute an accessible protocol to cryopreserve numerous strains of Drosophila, an important biomedical model, while also hopefully informing other insect and related species embryo preservation,” said study co-author John Bischof, director of the Institute for Engineering in Medicine and a professor in the College of Science and Engineering and Medical School.
As humans share more than half of their genes with the fruit fly, Drosophila research and its implications for human health are significant.
“By studying mutants in the Drosophila model system, it can reveal how those genes function in human development and disease,” said Tom Hays, head of the Department of Genetics, Cell Biology and Development in the Medical School and College of Biological Sciences. "Fly studies have provided crucial insights on human diseases from Alzheimer’s to Zika and revealed genetic pathways and mechanisms underlying embryonic development, olfaction and innate immunity.”
Beyond training individuals in this method, the University of Minnesota team is looking to adapt it to other applications.
"It will be important to understand the genetics that influence cryopreservation in Drosophila and other insects," said study co-author Mingang Li, a research associate in the Department of Genetics, Cell Biology and Development. "This method could support research aimed at pest control for Drosophila suzukii, a fruit fly that infests ripening fruits and has become a pest in the Americas and Europe, as well as for malaria research in Anopheles mosquitoes."
Funding for the research was provided by the U.S. National Institutes of Health, the National Science Foundation, ATP-Bio from the Institute for Engineering in Medicine, and the University’s Doctoral Dissertation Fellowship.

A team of scientists has found that women's football was common across Japan between the Meiji restoration and the start of the Second World War. In the process, they also uncovered the oldest known photograph of women playing football in Japan, from 1916.

The history of men's football in Japan is well documented. In particular, the introduction of association football into Japan in the late 19th and 20th centuries has been extensively investigated. The same degree of attention had not been paid to women's football.

A team of researchers from six institutions, including Associate Professor Yoshihiro Sakita of Hokkaido University's Graduate School of Education, has reported the first study into the history of women's football in Japan. Their findings, published in the journal Japan Journal of Physical Education, Health and Sports Science, focus on the extent and popularity of women's football in pre-war Japan -- the Meiji, Taisho and early Showa eras.

The researchers examined 422 books carrying historical records of 286 public high schools for girls from Hokkaido (northern Japan) to Kyushu (southern Japan). The researchers first focused their attention on whether young women at higher educational institutions, which trained them to become teachers, had instructors, guidance books or extracurricular activities involving football. They then examined how the sport proliferated at the 286 schools to which the female teachers were dispatched, investigating how girls engaged with football--either via the regular curriculum, club activities, free time or athletic meetings--as well as their instructors, uniforms, equipment and rules.

The researchers found 53 of the books (19%) had descriptions or photos of football played by girls from 1902 to 1940. The descriptions, however, included casual play, involving throwing the ball with their hands and competitions to kick the ball highest or furthest--elements which are not features of present-day association football, or soccer. Football was one of the sports enthusiastically adopted at public high schools for girls, especially in the Taisho era (1912-26), just like boys and men eagerly took up the sport in the pre-war period.

The researchers also discovered the oldest photo of women's football in Hundred Years' History, a book published in 1986 detailing the history of the Oita Prefectural Public High School for Girls (now, the Oita Prefectural Oita Uenogaoka High School). The photo was of a match held in 1916. In the archives of the Oita Prefectural Library, they also discovered another photo of girls playing football in 1918. The previously known oldest photos were from picture postcards showing girls playing football at Kagawa Prefectural Marugame Public High School for Girls around 1919-1920. These photos had been reprinted in the Shikoku Shimbun newspaper on December 2, 2011, attracting much public attention at the time.

The researchers plan to expand the scope of their research to higher educational institutions for women and private high schools for women and investigate not only books of historical records but also newsletters for alumni to find more details about women's soccer in prewar Japan.

The Middle East and North Africa Region (MENA) is a climate change hot spot where summers warm much faster than in the rest of the world. Some parts of the region are already among the hottest locations globally. A new international study predicts that ignoring the signals of climate change and continuing business-as-usual will lead to extreme and life-threatening heatwaves in the region. Such extraordinary heat events will have a severe impact on the people of the area.

The study, which aims at assessing emerging heatwave characteristics, was led by scientists from the Climate and Atmosphere Research Center (CARE-C) of The Cyprus Institute and the Max Planck Institute for Chemistry, with the contribution of researchers from the CMCC Foundation - Euro-Mediterranean Center on Climate Change and other research institutes, mainly from the MENA region.

"Our results for a business-as-usual pathway indicate that especially in the second half of this century unprecedented super- and ultra-extreme heatwaves will emerge", explains George Zittis of The Cyprus Institute, first author of the study. These events will involve excessively high temperatures of up to 56 degrees Celsius and higher in urban settings and could last for multiple weeks, being potentially life-threatening for humans and animals, even high-temperature tolerant animals such as camels. In the second half of the century, about half of the MENA population, or approximately 600 million people, could be exposed to such annually recurring extreme weather conditions, which will affect health, agriculture, biodiversity.

The research team used a first-of-its-kind multi-model ensemble of climate projections designed exclusively for the geographic area. The researchers then projected future hot spells and characterised them with the Heat Wave Magnitude Index, which allows quantifying the intensity of single events, considering both their duration and the temperature anomaly.

Such detailed downscaling studies had been lacking for this region. "The scientific community dealing with regional climate modelling is mainly concentrated in Europe and North America, and there is still little interest and funding for studying the impacts of climate change in the Mediterranean and North African region" explains Paola Mercogliano, director of the Regional Models and geo-Hydrological Impacts division at the CMCC Foundation. "Having such an important and detailed study on this area, which is still poor in terms of data and scientific knowledge on climate change, is a great success for us. At CMCC, we believe in the importance of advancing scientific research in the Mediterranean region, which is highly vulnerable to the impacts of climate change, and we are investing strengths and resources to provide these countries with data that can allow them to know more about the characteristics of their future climate and to act accordingly".

To avoid such extreme heat events in the region, the scientists recommend immediate and effective climate change mitigation measures. It is expected that in the next 50 years, almost 90 percent of the exposed population in the MENA will live in urban centers, which will need to cope with these societally disruptive weather conditions.

"Heat waves are among the main climate change impacts affecting the Mediterranean area, including Italy" concludes Edoardo Bucchignani, CMCC research scientist, among the authors of the study. "It is great to have such a valid study focused on this region, with scientific data that can support and guide decision-makers in managing impacts in time, to protect the health of citizens, especially the most vulnerable ones. At CMCC, our investment in this direction now continues to provide even more detailed data and to make it available to the entire scientific community, to encourage the production of knowledge about the expected climate in this area for the next century".

ADELPHI, Md. -- Army researchers developed a technique that allows robots to remain resilient when faced with intermittent communication losses on the battlefield.

The technique, called α-shape, provides an efficient method for resolving goal conflicts between multiple robots that may want to visit the same area during missions including unmanned search and rescue, robotic reconnaissance, perimeter surveillance and robotic detection of physical phenomena, such as radiation and underwater concentration of lifeforms.

Researchers from the U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory and the University of Nebraska, Omaha Computer Science Department collaborated, which led to a paper featured in ScienceDirect's journal Robotics and Autonomous Systems.

"Robots working in teams need a method to ensure that they do not duplicate effort," said Army researcher Dr. Bradley Woosley. "When all robots can communicate, there are many techniques that can be used; however, in environments where the robots cannot communicate widely due to needing to stay covert, clutter leading to radios not working for long distance communications, or to preserve battery or bandwidth for more important messages, the robots will need a method to coordinate with as few communications as possible."

This coordination is accomplished through sharing their next task with the team, and select team members will remember this information, allowing other robots to ask if any other robot will perform that task without needing to communicate directly with the robot that selected the task, Woosley said.

The robot that remembers a task is based on the topology of their wireless communications network and the geometric layout of the robots, he said. Each robot is assigned a bounding shape representing the area of the environment that they are caching goal locations for, which enables a quick search in the communications network to find the robot that would know if there were any goals requested in that area.

"This research enables coordination between robots when each robot is empowered to make decisions about its next tasks without requiring it to check in with the rest of the team first," Woosley said. "Allowing the robots to make progress towards what the robots feel is the most important next step while handling any conflicts between two robots as they are discovered when robots move in and out of communications range with each other."

The technique uses a geometric approximation called α-shape to group together regions of the environment that a robot can communicate with other robots using multi-hop communications over a communications network. This technique is integrated with an intelligent search algorithm over the robots' communication tree to find conflicts and store them even if the robot that selects the goal disconnects from the communication tree before reaching the goal.

The team reported experimental results on simulated robots within multiple environments and physical Clearpath Jackal Robots.

"To our knowledge, this work is one of the first attempts to integrate geometry-based prediction of potential conflict regions to improve multi-robot information collection under communication constraints, while gracefully handling intermittent connectivity loss between robots," Woosley said.

According to Woosley, other available approaches can only get input from the robots that are inside the same communications network, which is less efficient when robots can move in and out of communications range with the team.

In contrast, he said, this research provides a mechanism for the robot to quickly find potential conflicts between its goal and the goal another robot selected, but is not in the communications network anymore.

What specifically makes this research unique includes:

-Providing an efficient method (fast and with few messages) for resolving goal conflicts between multiple robots that is robust to intermittent communications loss and robots joining or leaving local sets of robots that are in communications with each other

-Performing as good as querying every robot in the communications range while saving radio bandwidth for more important communications

-Performing better than each robot operating fully on its own without communications

Woosley said that he is optimistic this research will pave the way for other communications limited cooperation methods that will be helpful when robots are deployed in a mission that requires covert communications.

He and the research team, including DEVCOM ARL researchers Dr. John Rogers and Jeffrey Twigg and Naval Research Laboratory research scientist Dr. Prithviraj Dasgupta, will continue to work on collaboration between robotic team members through limited communications, especially in directions of predicting the other robot's actions in order to avoid conflicting tasks to begin with.

As researchers continue to study the neurological impacts of COVID-19, a Houston Methodist international collaboration has documented an unexpectedly frequent occurrence of acute transverse myelitis (ATM) - inflammation of the spinal cord - in 43 COVID-19 patients. Led by Houston Methodist neurologist Dr. Gustavo Roman, the study of existing scientific literature found that patients from 21 countries developed spinal cord lesions after contracting the virus. Symptoms included paralysis and sphincter/bowel dysfunction. The patients ages ranged from 21 to 73 and included about half-and-half women and men. ATM, a rare neurological condition, affects between 1.34 and 4.6 cases per million per year, and researchers believe the unusually high rate in post-COVID-19 patients merits additional investigation. Moreover, 3 ATM cases were reported during the trials of the Oxford AstraZeneca vaccine. The study is published in Frontiers in Immunology. Dr. Roman collaborated with researchers from Hospital Paitilla, Interamerican University of Panama and Hospital Santo Tomas (Drs. Fernando Gracia, Antonio Torres, Alexis Palacios, Karla Gracia and Diogenes Harris).

3D printing has opened up a completely new range of possibilities. One example is the production of novel turbine buckets. However, the 3D printing process often induces internal stress in the components which can in the worst case lead to cracks. Now a research team has succeeded in using neutrons from the Technical University of Munich (TUM) research neutron source for non-destructive detection of this internal stress - a key achievement for the improvement of the production processes.

Gas turbine buckets have to withstand extreme conditions: under high pressure and at high temperatures they are exposed to tremendous centrifugal forces . In order to further maximize energy yields, the buckets have to hold up to temperatures which are actually higher than the melting point of the material. This is made possible using hollow turbine buckets which are air-cooled from the inside.

These turbine buckets can be made using Laser Powder Bed Fusion, an additive manufacturing technology: Here the starter material in powder form is built up layer by layer by selective melting with a laser. Following the example of avian bones, intricate lattice structures inside the hollow turbine buckets provide the part with the necessary stability.

Manufacturing process creates internal stress in the material

"Complex components with such intricate structures would be impossible to make using conventional manufacturing methods like casting or milling," says Dr. Tobias Fritsch of the German Federal Institute for Materials Research and Testing (BAM).

But the laser's highly localized heat input and the rapid cooling of the melt pool lead to residual stress in the material. Manufacturers usually eliminate such stress in a downstream heat-treatment step, which however takes time and thus costs money.

Unfortunately, these stresses can also damage the components as early as during the production process and up until post-processing takes place. "The stress can result in deformations and in the worst cases lead to cracks," says Tobias Fritsch.

Therefore, he investigated a gas turbine component for internal stress using neutrons from the Research Neutron Source Heinz Maier-Leibnitz (FRM II). The component was made using additive production processes by gas turbine manufacturer Siemens Energy.

Post-processing intentionally omitted

For the neutron experiment at the FRM II, Siemens Energy printed a lattice structure only a few millimeters in size using a nickel-chrome alloy typical of those used for gas turbine components. The usual heat-treatment after production was intentionally omitted.

"We wanted to see whether or not we could use neutrons to detect internal stresses in this complex component," explains Tobias Fritsch. He had already gained experience with neutron measurements at the Berlin research reactor BER II, which however was shut down in late 2019.

"We're very glad to be able to make measurements in the Heinz Maier-Leibnitz Zentrum in Garching; with the equipment provided by STRESS-SPEC we were even able to resolve internal stress in lattice structures as intricate and complex as these," the physicist says.

Even distribution of heat during printing

Now that the team has succeeded in detecting the internal stress within the component, the next step is to reduce this destructive stress. "We know that we have to modify the production process parameters and thus the way in which the component is built up during printing," says Fritsch. Here the crucial factor is the heat input over time when building up the individual layers. "The more localized the heat application is during the melting process, the more internal stress results."

For as long as the printer's laser is aimed at a given point, the heat of the point rises relative to adjacent areas. This results in temperature gradients that lead to irregularities in the atomic lattice.

"So we have to distribute the heat as evenly as possible during the printing process," says Fritsch. In the future the group will research the situation with new components and modified printing parameters. The team is already working together with Siemens to plan new measurements with the TUM neutron source in Garching.

Fixing traumatic injuries to the skin and bones of the face and skull is difficult because of the many layers of different types of tissues involved, but now, researchers have repaired such defects in a rat model using bioprinting during surgery, and their work may lead to faster and better methods of healing skin and bones.

"This work is clinically significant," said Ibrahim T. Ozbolat, Hartz Family Career Development Associate Professor of Engineering Science and Mechanics, Biomedical Engineering and Neurosurgery, Penn State. "Dealing with composite defects, fixing hard and soft tissues at once, is difficult. And for the craniofacial area, the results have to be esthetically pleasing."

Currently, fixing a hole in the skull involving both bone and soft tissue requires using bone from another part of the patient's body or a cadaver. The bone must be covered by soft tissue with blood flow, also harvested from somewhere else, or the bone will die. Then surgeons need to repair the soft tissue and skin.

Ozbolat and his team used extrusion bioprinting and droplet bioprinting of mixtures of cells and carrier materials to print both bone and soft tissue. They report their results in Advanced Functional Materials.

"There is no surgical method for repairing soft and hard tissue at once," said Ozbolat. "This is why we aimed to demonstrate a technology where we can reconstruct the whole defect -- bone to epidermis -- at once."

The researchers attacked the problem of bone replacement first, beginning in the laboratory and moving to an animal model. They needed something that was printable and nontoxic and could repair a 5-millimeter hole in the skull. The "hard tissue ink" consisted of collagen, chitosan, nano-hydroxyapatite and other compounds and mesenchymal stem cells -- multipotent cells found in bone marrow that create bone, cartilage and bone marrow fat.

The hard tissue ink extrudes at room temperature but heats up to body temperature when applied. This creates physical cross-linkage of the collagen and other portions of the ink without any chemical changes or the necessity of a crosslinker additive.

The researchers used droplet printing to create the soft tissue with thinner layers than the bone. They used collagen and fibrinogen in alternating layers with crosslinking and growth enhancing compounds. Each layer of skin including the epidermis and dermis differs, so the bioprinted soft tissue layers differed in composition.

Experiments repairing 6 mm holes in full thickness skin proved successful. Once the team understood skin and bone separately, they moved on to repairing both during the same surgical procedure.

"This approach was an extremely challenging process and we actually spent a lot of time finding the right material for bone, skin and the right bioprinting techniques," said Ozbolat.

After careful imaging to determine the geometry of the defect, the researchers laid down the bone layer. They then deposited a barrier layer mimicking the periosteum, a heavily vascularized tissue layer that surrounds the bone on the skull.

"We needed the barrier to ensure that cells from the skin layers didn't migrate into the bone area and begin to grow there," said Ozbolat.

After laying down the barrier, the researchers printed the layers of dermis and then the epidermis.

"It took less than 5 minutes for the bioprinter to lay down the bone layer and soft tissue," said Ozbolat.

The researchers performed more than 50 defect closures and achieved 100% closure of soft tissue in four weeks. The closure rate for bone was 80% in six weeks, but Ozbolat noted that even with harvested bone replacement, bone closure usually does not reach 100% in six weeks.

According to Ozbolat, blood flow to the bone is especially important and inclusion of vascularizing compounds is a next step.

The researchers also want to translate this research to human applications and are continuing to work with neurosurgeons, craniomaxillofacial surgeons and plastic surgeons at Penn State Hershey Medical Center. They operate a larger bioprinting device on larger animals.

One in five pharmacies refuse to dispense a key medication to treat addiction, according to new research.

The study, published in the journal Drug and Alcohol Dependence, was conducted by researchers at Oregon Health & Science University and the Oregon State University College of Pharmacy. Researchers called hundreds of pharmacies around the country to ask whether they would dispense Suboxone, also known as buprenorphine.

"Buprenorphine is a vital, lifesaving medication for people with opioid use disorder, but improving access has been a problem for a variety of reasons," said senior author Daniel Hartung, Pharm.D., M.P.H., professor in the College of Pharmacy. "Although anecdotes and smaller studies have suggested problems, our study is the first to systematically characterize this barrier."

It turns out it's quite common for pharmacies to block access.

"This study is the largest and most comprehensive pharmacy-focused assessment of buprenorphine availability to date and confirms that pharmacies can be a significant barrier to buprenorphine access nationwide," the authors write.

Four researchers called a total of 921 pharmacies around the country in May and June of 2020, focusing on 473 U.S. counties with high rates of death from opioid-related overdoses. Of all the pharmacies contacted, they found that 183 - 20% of the total - indicated they would not dispense buprenorphine. They found that independent pharmacies and those in southern U.S. states were significantly more likely to restrict buprenorphine.

Any disruption in access to buprenorphine can put a patient's recovery at serious risk.

"If I see a patient and they want to get started on buprenorphine, they've already gone through a lot of processing to make that behavior change," said co-author Ximena A. Levander, M.D., M.C.R., clinical instructor (general internal medicine and geriatrics) in the OHSU School of Medicine. "Any barrier can be very disruptive, especially when initiating treatment because they're at high risk to return to use."

Buprenorphine, approved by the Food and Drug Administration in 2002, relieves withdrawal symptoms and pain, and normalizes brain function by acting on the same targets in the brain as prescription opioids or heroin. It is one of three medicines approved by the FDA to treat opioid dependence, along with methadone and naltrexone.

Lead author Neda Kazerouni, a fourth-year student in the OHSU/OSU College of Pharmacy, said she hopes the research raises awareness of the stigma against people with opioid use disorder. As the nation's opioid epidemic continues to claim more than 70,000 lives annually in overdose deaths, Kazerouni said she hopes the new findings will encourage pharmacists to do their part to roll back the epidemic.

"Pharmacists can have a role in reducing opioid use disorder by reducing stigma," Kazerouni said. "Furthermore, community pharmacists should be encouraged to work collaboratively with a patient's provider to ensure there is continuity of care in all stages of treatment."

Nearly 80 percent of higher education faculty report dealing with student mental health issues—issues that more than 90 percent of faculty believe have worsened or significantly worsened during the pandemic, according to a new nationwide survey led by a Boston University mental health researcher.

"The vast majority of faculty members, myself included, are not trained mental health professionals, but we have a role to play in supporting student well-being," says survey principal investigator Sarah Ketchen Lipson, a BU School of Public Health assistant professor of health law, policy, and management. "These data underscore a real opportunity to better equip faculty with knowledge and basic skills to support and refer students."

These findings, detailed in a first-of-its-kind report, underscore faculty's growing involvement in the health and well-being of students and their willingness to serve as mental health "gatekeepers"—a role that has become increasingly important as students continue to navigate online learning, social isolation, and other COVID-19-related stressors.

But the survey revealed that less than 30 percent of faculty have received training from their academic institutions to handle these issues, even though almost 70 percent say they would welcome this guidance and are eager to strengthen their support for students experiencing mental or emotional health challenges.

Another key survey finding: more than one in five faculty members said that students' mental health has taken a toll on their own mental health. Almost half of respondents said that their institution should invest more in supporting faculty mental health and well-being.

"I am hopeful that our new research in this area will raise awareness of the reality that many faculty members are struggling with their own mental and emotional health," Lipson says.

She says she leveraged BU's mental health resources to help her find a therapist. "I know that I am a better teacher, advisor, and colleague because I am able to prioritize my own mental health in a way that meets my needs," she says.

The pilot survey, which was funded by the Hazelden Betty Ford Foundation and conducted in partnership with the Mary Christie Foundation and the Healthy Minds Network, was administered during the spring 2021 semester to almost 1,700 faculty members at 12 colleges and universities across the United States. The results indicate that more work needs to be done on campuses to enable faculty to identify and refer students in mental distress.

"These data make it clear that college and university faculty members are attuned to the mental health needs of their students," Lipson says.

Importantly, she says, while 75 percent of faculty reported that they would reach out to a student in mental or emotional distress, only 51 percent were confident that they could recognize signs of student mental distress. More than 60 percent of faculty believe that it should be mandatory for institutions to provide basic training on handling student mental health, and faculty want additional resources, such as a checklist of warning signs, guides for how to initiate conversations, and a list of available mental health resources.

The survey also found that while 55 percent of faculty believe their institutions are welcoming or somewhat welcoming towards students of color, 58 percent of Hispanic or Latinx faculty and 39 percent of Black or African American faculty believe their institution is hostile or somewhat hostile towards students of color. These results indicate that institutions should not only make campuses more inclusive for students, but also build the level of trust needed among faculty of color to refer students to campus resources, the report said.

"Data are powerful in creating change in higher education, and for so long, there has been a lack of national data on the mental health of college and university faculty," says Lipson. "I hope that investments in new resources to support faculty well-being will yield benefits not only to individual faculty members, but also to students and institutions writ large."