Culture

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly across the globe at an alarming pace, causing considerable anxiety and fear among the general public. In response to the growing number of new cases, many countries have imposed lockdown measures to slow the spread of coronavirus. However, nearly every individual, community, business, and economy has been adversely affected by lockdown measures - an impact to society that cannot be ignored.

The health and well-being of the population will be affected if the community is kept open, but the lockdown strategy also incurs economic and financial impacts. Each strategy on its own will increase the total 'cost' to society. Can both losing strategies be combined in a manner that leads to a winning outcome? That is the question that researchers from the Singapore University of Technology and Design (SUTD) set out to answer in a recent paper published in Advanced Science.

The team, led by Assistant Professor Kang Hao Cheong from SUTD, seeks to answer this question by modeling the population using Parrondo's paradox with a view to relieve the cost of the epidemic by means of a switching strategy. The model takes into account the health and well-being of the population, as well as economic impacts and describes the interaction and flow between the different population compartments during the COVID-19 epidemic.

The researchers were inspired by a phenomenon called Parrondo's paradox. The paradox states that it is possible to alternate between a pair of losing strategies and still end up winning. Their results represent one of the first studies to focus on the lockdown exit strategy. It is also one of the first to link Parrondo's paradox to epidemiology.

From this study, the researchers show that keeping the community open results in a large number of infected individuals and a sharp increase in the number of deaths over time, so naturally the 'cost' increases. At the same time, a lockdown strategy reduces the possibility of infection, but has an adverse effect on the socio-economic cost.

"This means that each strategy cannot individually result in a decline to the 'cost' in the long-term during an epidemic. Such rising 'cost' allows us to classify them as losing strategies," explained Tao Wen, a research student from SUTD and a co-author of the study.

"When one switches between the losing strategies in accordance with any of the proposed alternating strategies, the 'cost' per day will decline. This, in itself, is a winning strategy to control the loss caused by COVID-19," he added.

This is a manifestation of the game theory Parrondo's paradox: two losing strategies can be combined into an outcome that wins.

The researchers have introduced three different switching rules. They are the time-based switching, result-based switching, and random switching schemes. Each switching rule comes with its own strengths and is applicable across a wide range of real-world scenarios.

"Such novel strategies can be implemented to curb the spread of COVID-19 or future epidemics, and have the potential to alleviate suffering, preserve and promote health and well-being among the population," observed Assistant Professor Kang Hao Cheong, the principal investigator for this study from SUTD.

"COVID-19 is a complex of medical conditions and not a cause. The ultimate causative agent is not a virus in isolation, but a virus in complexity with particular social factors -- the Four Horsemen: a) overpopulation, b)globalization, c) hyperconnectivity, and d) extreme centralization and increasing fragility of supply chains," cautioned Assistant Professor Cheong.

Most diseases are caused by aberrant cell signaling processes and basic research in cell signaling is needed to identify targets for future therapeutic approaches, especially in cases where no cures or effective treatments are currently available.

Cellular optogenetics uses light to precisely control cell signaling in space and over time, making it an invaluable technique for disease research. However, this potentially revolutionary method has been difficult for many researchers to use as, over long periods of time, the used light can itself have adverse effects on biological systems and the optogenetic tools can inactivate unexpectedly rapidly.

Now, researchers from the University of Turku in Finland, in collaboration with Frankfurt University Hospital in Germany, have developed a novel way to harness the quantum mechanical phenomenon of resonance energy transfer to design optogenetic tools that are more sensitive to light. The new method also informs the user exactly when an optogenetic tool is going to inactivate in cells. If continued activity is required, just the right amount of additional light can then be re-applied to re-activate the tool.

Combining these advances with existing tools and knowledge, the researchers were able to design and build more efficient optogenetic tools to investigate signaling pathways. With the improved tools, they studied two common chemotherapy drugs known to cause side effects on neurons and cause neuropathic pain. The new tools revealed how both activatory and inhibitory pathways contribute to the actions of these drugs on the investigated disease-associated pathway.

"Now we can develop more powerful tools to understand precisely how harmful conditions disrupt signaling in living cells. This information is likely to help us in identifying targets and designing better therapeutic compounds for conditions such as chemotherapy-induced neuropathic pain," says Lili Li, the lead author of the study and Postdoctoral Researcher at the Turku Bioscience Centre.

"There is still considerable potential to further exploit these quantum mechanical phenomena to devise even better quantitative and informative methods in biology and medicine, which could support the future discovery of new therapeutic approaches," adds senior author of the study Michael Courtney.

Millions of years ago, several species of crocodiles of different genera and characteristics inhabited Europe and sometimes even coexisted. But among all these species, it was thought unlikely that crocodiles of the genus Crocodylus, of African origin, had ever lived in the Mediterranean basin. The remains found in the Italian regions of Gargano, Tuscany and Scontrone over the last few decades confirm that they did.

Now, a study published in the Journal of Paleontology corroborates this with the fossils of two crocodiles measuring about three metres in length that were discovered in the Valencian Venta del Moro site -excavated by researchers from the University of Valencia between 1995 and 2006-, and which were ascribed at the time to the Crocodylus checchiai species . This new work describes the remains more than 14 years after they were found for the first time.

"Our comparisons indicate that this material clearly does not belong to the Diplocynodon genera -an extinct genus of alligatoroid, similar to today's caimans- or Tomistoma -similar to gavials-, the only other two crocodilians described so far for the late European Miocene," as Ángel Hernández Luján, a palaeontologist at the Miquel Crusafont Catalan Institute of Palaeontology (ICP) and co-author of the work, has explained to Sinc.

However, as the remains are too fragmented, an analysis of the cranial bones, isolated teeth and osteoderms (bone plaque on the skin) suggests that they could belong to the C. checchiai species, as assigned at the time of their discovery, but their taxonomy is still not completely clear and hinders a more precise specific identification. In any case, "the morphology of the Venta del Moro crocodile remains is congruent with the Crocodylus genus," the researcher states.

Swimming from Africa to Europe

The fossil remains of this Valencian site, which are the first Crocodylus in the Iberian Peninsula, "unequivocally" support the non-occasional dispersion of this genus from Africa to Europe during the late Miocene, according to palaeontologists. The discovery of two partial individuals, instead of just one, could indicate that a whole population was present in this area.

During their "colonisation", these reptiles spread more significantly in the southern areas of Mediterranean Europe, as suggested by the Italian and Spanish areas where the fossils have been found. "All European localities with late Miocene crocodilians, including Venta del Moro, were at that time close to the northern Mediterranean coast and therefore easily accessible thanks to specimens that became scattered in the seawater," the authors stress in the study.

"What is most certain is that it would have also inhabited the coasts of Murcia and Andalusia, although we cannot rule out that it would also have become dispersed along the coast of Catalonia and the Balearic Islands," Hernández Luján has pointed out to SINC. But how could they have got there from the African coasts?

The researchers' hypothesis is that these crocodiles swam from one continent to another in the sea before a land connection was established between Africa and Europe. This idea would be supported by the behaviour of modern crocodiles, which are good swimmers and can even reach 32 km/h in the water.

An example of this is the current saltwater crocodile (Crocodylus porosus), which can make significant forays into the open sea to colonise other islands or other continents between Oceania and South-East Asia. "You only have to look at how easily it moves in the open sea to be seen in the waters of the Solomon Islands or even in French Polynesia," says the palaeontologist.

But there are more examples that reinforce this hypothesis. Because of its anatomical similarity to American crocodiles, the extinct species Crocodylus checchiai, which originated in Libya and Kenya, could well be its ancestor. This suggests that crocodiles were able to cross the Atlantic Ocean during the Miocene, which would explain the appearance of the genus in America.

Therefore, in the case of the specimens found in Venta del Moro, swimming from the African to the European continent "must not have meant a great effort for them before they reached the Peninsula," the researcher concludes.

CHAMPAIGN, Ill. -- A multidisciplinary group that studies the physical and chemical properties of insect wings has demonstrated the ability to reproduce the nanostructures that help cicada wings repel water and prevent bacteria from establishing on the surface. The new technique - which uses commercial nail polish - is economical and straightforward, and the researchers said it will help fabricate future high-tech waterproof materials.

The team used a simplified version of a fabrication process - called nanoimprinting lithography - to make a template of the complex pillar-shaped nanostructures on the wings of Neotibicen pruinosus, an annual cicada found in the central region of the United States. The templates are fully dissolvable and produce replicas that average 94.4% of the pillar height and 106% of the original wing, or master structure's pillar diameter, the researchers said.

The results of the study are published in the journal Nano Letters.

"We chose to work with wings of this species of cicada because our past work demonstrates how the complex nanostructures on their wings provide an outstanding ability to repel water. That is a highly desirable property that will be useful in many materials engineering applications, from aircraft wings to medical equipment," said Marianne Alleyne, an entomology professor at the University of Illinois at Urbana-Champaign, who co-led the study with Donald Cropek, of the U.S. Army Corps of Engineers' Construction Engineering Research Laboratory, and Nenad Miljkovic, a professor of mechanical science and engineering at Illinois.

Nanoimprinting lithography is not new but can be labor-intensive and expensive, the researchers said. Some approaches use toxic materials that can damage the original copied object, like a delicate cicada wing. Others require high temperatures that are not compatible with biological samples such as plants or insects.

"Our process allows us to do this in an open lab at room temperature and atmospheric pressure," Cropek said. "We use nail polish and rubbing alcohol, which does not inflict any damage to the delicate wing nanostructures."

In the lab, the team applies a quick-drying nail polish directly to a cicada wing, which is then left to cure at room temperature.

"It was not easy to find the right formula of nail polish because we want to avoid one that will warp or stretch the template during removal," Alleyne said. Once completed, the template can be coated with a polymer or metal then dissolved away, leaving only the replica metal or polymer.

To show the versatility of the new method, the team experimented with two very different replica materials: copper metal and a flexible silicon-based organic polymer called PDMS.

"We showed that the technique is compatible with physical vapor deposition and electrochemical deposition of metals, oxides or ceramics, as well as chemical vapor deposition and spin coating of softer materials like polymers," Miljkovic said.

"Copper is particularly interesting to us because of its inherent antimicrobial properties, and our past work indicates that some cicada species display antimicrobial properties on their wings," Alleyne said. "We don't know if it is the chemicals on the wing's surface or the physical nanostructures, or a combination of both chemistry and topography, that produce the bactericidal activity, but being able to produce materials with different chemistries and structures will help us answer that fundamental question. This new, relatively simple fabrication method will ultimately help us design multifunctional engineered materials."

Based on digital endocranial cast models the canine brain does not increase proportionally with body size. Researchers at ELTE Eötvös Loránd and Kaposvár University in Hungary reconstructed the surface morphology of 28 canine brains, including various dog breeds, wolves, coyotes, and jackals. The shortening of the facial skeleton greatly influences the ratio of certain brain regions, primarily the olfactory bulb and the frontal lobe. These changes might have profound implications for olfactory and problem-solving abilities.

Reconstructing the brain based on the internal surface patterns of a skull is a well-known method among archeologists studying the brains of extinct species, e.g. dinosaurs, mammoths and even cavemen. One way to achieve a model of the brain is to fill the endocranial space with specific gradually hardening fluids, and after the solidifying of the material the bones can be removed to reveal the cast, which reflects the surface of the brain with high fidelity. These are called endocranial casts, or endocasts.

Skull and endocast of a beagle. Video created by dr. Kálmán Czeibert: https://youtu.be/R7k-b-soVN4

Nowadays, rather than utilising endocasts, invasive process diagnostic imaging techniques are highly preferred. Computer tomography (CT) is the best and easiest way to visualize the bones, with all of their external and internal structures and composition. Using CT is also advantageous in endocranial analysis, as researchers can create virtual endocasts based on the digitized skulls. This allows for a higher freedom during examinations, because these virtual models can be rotated, colorized, cut, and completed. They can be shown not only on mobile phones, tablets or computers, but with the help of 3D-printing technology one can replicate them in the requested number and scale as well.

This digital endocasting technique was used by researchers from ELTE who scanned skulls from the collection of dr. Tibor Csörg? (ELTE, Department of Anatomy, Cell and Developmental Biology), which comprises almost 400 dog skulls from 152 canine breeds. "Due to the high resolution scanning, detailed 3D models could be created. This means that not only the main convolutions, that is, the cerebral gyri, can be recognized on the final model, but the location of the major blood vessels can also be seen on the surface." - explains dr. Kálmán Czeibert, veterinarian and postdoctoral researcher at the Senior Family Dog Project, first author of the publication. "We compared the shape, volume and surface features of the endocasts from 28 specimens in our recent study in Frontiers in Veterinary Science. These models clearly show how the shortening of the facial part of the skull affected the morphology of the brain, distorting the olfactory bulb, which is pushed back and underneath the frontal lobe in certain breeds (like the French bulldog or pug), changing the ratio between the cerebral areas."

In order to clarify how this change affects dogs' olfactory and cognitive performance, further imaging and behavioral investigations are needed. The new collection is part of the Canine Brain and Tissue Bank at ELTE, funded by a European Research Council (ERC) grant. The bank will help researchers to link the brain with behaviour. "In some areas, where volume has diminished, neuronal density and the relationship with other brain regions may act to counteract these changes. To further examine these speculations, behavioural testing, diagnostic imaging (like CT, MR or EEG), and histological and molecular assessment will be needed." - said dr. Eniko Kubinyi, senior researcher at ELTE, principal investigator of the research group.

"One of our primary aims was the widespread dissemination of scientific knowledge.' - adds dr. Czeibert. "How dog skulls and brains vary is striking. For example, despite the 30-fold difference in body weight between a Neapolitan mastiff and a chihuahua, their endocasts' volumes have only a 2-fold difference." The researchers from ELTE plan to increase the number of skulls by digitizing more specimens for microevolutionary studies in the framework of an international cooperation.

OCTOBER 22, 2020 - Nutley, NJ - A more efficient and much faster method to assess high levels of neutralizing antibodies to COVID-19 could point the way to better understanding and treatment of the disease, according to new published findings by scientists from the Hackensack Meridian Center for Discovery and Innovation (CDI) and the University of Michigan (U-M).

A new portable "lab on a chip," developed by the U-M scientists and demonstrated with help of the CDI, can identify the presence of COVID-19 antibodies in blood donors with greater speed and efficiency than the current standard "enzyme-linked immunosorbent assay" or ELISA technology.

Together, the CDI and U-M researchers have shown the device can identify COVID-19 antibodies in human blood in 15 minutes - much shorter than the few days the process normally takes. The test can also be done with smaller amounts of blood.

The work could have particular value for the validation of convalescent plasma as a treatment for COVID-19. A paper on the findings is published in Biosensors and Bioelectronics.

"Convalescent plasma is a treatment that can be very effective - but for it to have the best chance to work, it needs to have rigorous standards, which include assessing the presence of high-titer neutralizing antibodies," said David Perlin, Ph.D., chief scientific officer and senior vice president of the Hackensack Meridian Center for Discovery and Innovation, and one of the new study's authors. "This paper shows how the antibody thresholds can mean a better potential COVID-19 treatment - and also better outcomes."

"This research shows what an important role microfluidics can play in both saving lives and costs during the COVID-19 pandemic," said Xudong (Sherman) Fan, U-M biomedical engineering professor and co-founder of Optofluidic Bioassay.

The U-M device detects the presence and amount of neutralizing immunoglobulin--antibodies created by the immune system within seven to 10 days of a COVID-19 infection. Only donors with high levels are likely to provide samples that could be effective in treatment, such as convalescent plasma therapy.

The treatment involves taking plasma - the liquid portion of the blood that contains antibodies - from survivors and infusing it into sick patients to boost their immune response.

Thousands of patients nationally have been administered convalescent plasma through a program overseen by the Mayo Clinic. Hackensack University Medical Center also has its own clinical trial underway involving high-titer (levels) of antibodies.

The lab-on-a-chip approach developed by U-M analyzes on-site and requires just a finger prick's worth of blood--8 microliters. The traditional ELISA methods require 100 microliters to do its work. The U-M system is contained in a device the size of a portable 3D printer.

A new discovery about how the body transports dexamethasone, a drug that can increase the survival chances of patients with severe COVID-19, suggests diabetes and other factors may reduce its potentially lifesaving effectiveness. Based on their findings, the researchers say doctors may need to rethink how they dose the drug for certain groups of patients.

The team of scientists, based at the University of Virginia School of Medicine, the University of South Carolina, and in Poland, has determined how a protein in our blood called serum albumin picks up dexamethasone and takes it where it is needed. Low serum albumin levels are already considered a major risk factor for severe COVID-19, as is diabetes.

The new research suggests diabetes or low albumin levels may make it difficult for patients to get the benefits of dexamethasone, a corticosteroid that calms the hyperactive immune response that can lead to death in severe COVID-19.

Diabetes is associated with high blood sugar levels, which results in a modification of albumin that may alter the binding site for dexamethasone. Other drugs may also compete with dexamethasone for the limited space in serum albumin's cargo holds. Albumin's cargo capacity is also naturally decreased when there is a low albumin level in the blood.

"At this point, we do not have a readily available treatment better than dexamethasone for severe COVID-19 cases, but, like COVID-19 itself, its effectiveness is somewhat unpredictable," said lead researcher Wladek Minor, PhD, of UVA's Department of Molecular Physiology and Biological Physics. "In order to provide a comprehensive picture, this research was conducted in collaboration among structural biologists, computer scientists and clinicians. So, every author of this paper had to step out of the box to combine medical data with structural biology results in order to suggest possible modifications of the treatment that could potentially save more human lives."

Researcher Ivan Shabalin, PhD, the first author of a new paper outlining the findings, added: "Working on this interdisciplinary team and seeing how our research in fundamental science may save lives in the current pandemic felt extremely rewarding."

Dexamethasone and COVID-19

For the first time, Minor and his colleagues have demonstrated exactly how serum albumin binds with dexamethasone so that the drug can be distributed through our bodies.

Serum albumin binds with dexamethasone the same way it binds with the hormone testosterone, suggesting that the two could compete with each other, the researchers report. More men die of COVID-19 than women, and low testosterone levels have already been associated with worse outcomes. The authors of the study hypothesized that high dexamethasone levels might affect testosterone transport by competing for the same drug site on albumin.

Serum albumin also uses the same binding dock to pick up several common nonsteroidal anti-inflammatory drugs, so doctors may need to consider the potential for competition in deciding COVID-19 treatment plans, the research suggests.

That said, it's not as simple as increasing the dexamethasone dose for patients with diabetes or low serum albumin. Too much dexamethasone can be harmful or have unwanted side effects. More research is needed to determine the best dosing in various patient populations, particularly for people with diabetes or low albumin levels, the researchers say.

To better understand serum albumin's role in COVID-19, the researchers analyzed data from 373 patients at a hospital in Wuhan, China, that treated many severe cases of the disease. The scientists found that patients who died had lower albumin levels than those who survived. Those who died also had higher levels of blood sugar. That aligned with the researchers' conclusion that high blood sugar could affect serum albumin's ability to carry its cargo.

"In order to provide rapid response to emerging biomedical challenges and threats like COVID-19, we need to analyze medical data in the context of other in-vitro and in-vivo results," Minor said. "Five years ago, I wrote in Expert Opinion in Drug Discovery that, 'The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.' This assessment is still valid, and, clearly, not enough progress has been made, because it is mistakenly not recognized as a grand challenge for biomedical sciences."

"Until a vaccine or new drugs are widely available, we have to make the best use of the drugs we know can help fight COVID-19," added team member Dariusz Brzezinski, PhD.

Being highly connected to a strong social network has its benefits. Now a new University of Alberta study is showing the same goes for trees, thanks to their underground neighbours.

The study, published in the Journal of Ecology, is the first to show that the growth of adult trees is linked to their participation in fungal networks living in the forest soil.

Though past research has focused on seedlings, these findings give new insight into the value of fungal networks to older trees--which are more environmentally beneficial for functions like capturing carbon and stabilizing soil erosion.

"Large trees make up the bulk of the forest, so they drive what the forest is doing," said researcher Joseph Birch, who led the study for his PhD thesis in the Faculty of Agricultural, Life & Environmental Sciences.

When they colonize the roots of a tree, fungal networks act as a sort of highway, allowing water, nutrients and even the compounds that send defence signals against insect attacks to flow back and forth among the trees.

The network also helps nutrients flow to resource-limited trees "like family units that support one another in times of stress," Birch noted.

Cores taken from 350 Douglas firs in British Columbia showed that annual tree ring growth was related to the extent of fungal connections a tree had with other trees. "They had much higher growth than trees that had only a few connections."

The research also showed that trees with more connections to many unique fungi had much greater growth than those with only one or two connections.

"We found that the more connected an adult tree is, the more it has significant growth advantages, which means the network could really influence large-scale important interactions in the forest, like carbon storage. If you have this network that is helping trees grow faster, that helps sequester more carbon year after year."

It's also possible that if the trees grow faster, they'd have some ability to better survive drought that is expected to intensify with climate change, he added.

"These networks may help them grow more steadily even as conditions become more stressful, and could even help buffer trees against death."

Birch hopes his findings lead to further studies in different kinds of forests in other geographical areas, because it's likely that the connections among trees change from year to year, he said.

"It's a very dynamic system that is probably being broken apart and re-formed quite a bit, like family relationships, so we don't know how they will change under future climates either. Maybe a dry year or a beetle outbreak impacts the network.

"Knowing whether fungal networks are operating the same way in other tree species could factor into how we reforest areas after harvesting them, and it could inform how we want to plant trees to preserve these networks."

DURHAM, N.C. -- A team of Duke University researchers has developed a lab-grown living lung model that mimics the tiny air sacs of the lungs where coronavirus infection and serious lung damage take place. This advance has enabled them to watch the battle between the SARS-CoV-2 coronavirus and lung cells at the finest molecular scale.

The virus damages the delicate, balloon-like air sacs, known as alveoli, leading to pneumonia and acute respiratory distress, the leading cause of death in Covid-19 patients. But scientists have been hampered in Covid-19 studies by the lack of experimental models that mimic human lung tissues.

Now, a team led by Duke cell biologist Purushothama Rao Tata has developed a model using "lung organoids," also dubbed mini-lungs in a dish. The organoids are grown from alveolar epithelial type-2 cells (AT2s) which are the stem cells that repair the deepest portions of the lungs where SARS-CoV-2 attacks.

Earlier research at Duke had shown that just one AT2 cell, isolated into tiny dishes, could multiply to produce millions of cells that assemble themselves into balloon-like organoids that look just like alveoli. However, the "soup" in which the cells were grown contained complex ingredients such as serum from cows that is not completely defined.

Tata's group took on the big challenge of predicting and testing many combinations of chemically pure factors that would do the job just as well, a problem that required close co-operation with Duke's shared computing cluster.

The result is a purely human organoid without any helper cells. Mini-lungs grown in tiny wells will enable high throughput science, in which hundreds of experiments can be run simultaneously to screen for new drug candidates or to identify self-defense chemicals produced by lung cells in response to infection.

"This is a versatile model system that allows us to study not only SARS-CoV-2, but any respiratory virus that targets these cells, including influenza," Tata said. A paper describing the development of the mini-lungs and some early experiments with coronavirus infection appeared early online Oct. 21 in the journal Cell Stem Cell.

In using mini-lungs to study SARS-CoV-2 infection, Tata's team collaborated with virology colleagues at Duke and the University of North Carolina in Chapel Hill. To safely handle these deadly viruses, the researchers utilized state-of-the art biosafety level 3 facilities at Duke and UNC-CH to infect lung organoids. The researchers watched the gene activity and chemical signals that are produced by the lung cells after infection.

"This is a major breakthrough for the field because we were using cells that didn't have purified cultures," said Ralph Baric, a co-author on the paper who is a distinguished professor of epidemiology, microbiology and immunology at UNC and world authority on coronaviruses. The Duke mini-lungs are 100 percent human with no supporting cells that could confuse findings. "This is incredibly elegant work to figure out how to purify and grow AT2 cells in culture in pure form," Baric said.

Baric's lab is capable of changing any nucleotide of the Covid-19 virus's genetic code at will, so it produced a glowing version that would reveal where it went in the mini-lungs, confirming that it did indeed home in on the crucial ACE2 cell surface receptor, leading to infection.

When infected with the virus, the organoids were shown to launch an inflammatory response mediated by interferons. The researchers have also witnessed the cytokine storm of immune molecules the lungs launch in response to the virus.

"It was thought cytokine storm happened due to the large influx of immune cells, but we can see it also happens in the lung stem cells themselves," Tata said.

Tata's lab found the cells produced interferons and experienced self-destructive cell death, just as samples from Covid-19 patients have shown. The signal for cell suicide was sometimes triggered in uninfected neighboring lung cells as well, as the cells struggled to get ahead of the virus. The researchers also compared the gene activity patterns between the mini-lungs and samples from six severe Covid-19 patients and found they agreed with "striking similarity."

"We've only been able to see this from autopsies until now," Tata said. "Now we have a way to figure out how to energize the cells to fight against this deadly virus."

In another series of experiments, mini-lungs treated with low doses of interferons before infection were able to slow viral copying. But suppressing interferon activity before infection led to increased viral replication.

Tata, who is a part of Duke's regenerative medicine initiative, Regeneration Next, said his lab was working on growing the mini lungs in mid-2019 and had achieved a working model just as the coronavirus pandemic emerged. He said his group will be working with both academic and industry partners to use these cells for cell-based therapies and eventually to try to grow a complete lung for transplantation.

Baric said his lab will probably be using the mini-lungs to better understand a new strain of SARS-CoV-2 called D614G that has become the dominant version of the virus. This strain, which emerged in Italy, has a spike protein that is apparently more efficient at recognizing the ACE2 receptor on lung cells, making it even more infectious.

UNIVERSITY PARK, Pa. -- A new tool created by researchers at Penn State and Houston Methodist Hospital could diagnose a stroke based on abnormalities in a patient's speech ability and facial muscular movements, and with the accuracy of an emergency room physician -- all within minutes from an interaction with a smartphone.

"When a patient experiences symptoms of a stroke, every minute counts," said James Wang, professor of information sciences and technology at Penn State. "But when it comes to diagnosing a stroke, emergency room physicians have limited options: send the patient for often expensive and time-consuming radioactivity-based scans or call a neurologist -- a specialist who may not be immediately available -- to perform clinical diagnostic tests."

Wang and his colleagues have developed a machine learning model to aid in, and potentially speed up, the diagnostic process by physicians in a clinical setting.

"Currently, physicians have to use their past training and experience to determine at what stage a patient should be sent for a CT scan," said Wang. "We are trying to simulate or emulate this process by using our machine learning approach."

The team's novel approach is the first to analyze the presence of stroke among actual emergency room patients with suspicion of stroke by using computational facial motion analysis and natural language processing to identify abnormalities in a patient's face or voice, such as a drooping cheek or slurred speech.

The results could help emergency room physicians to more quickly determine critical next steps for the patient. Ultimately, the application could be utilized by caregivers or patients to make self-assessments before reaching the hospital.

"This is one of the first works that is enabling AI to help with stroke diagnosis in emergency settings," added Sharon Huang, associate professor of information sciences and technology at Penn State.

To train the computer model, the researchers built a dataset from more than 80 patients experiencing stroke symptoms at Houston Methodist Hospital in Texas. Each patient was asked to perform a speech test to analyze their speech and cognitive communication while being recorded on an Apple iPhone.

"The acquisition of facial data in natural settings makes our work robust and useful for real-world clinical use, and ultimately empowers our method for remote diagnosis of stroke and self-assessment," said Huang.

Testing the model on the Houston Methodist dataset, the researchers found that its performance achieved 79% accuracy -- comparable to clinical diagnostics by emergency room doctors, who use additional tests such as CT scans. However, the model could help save valuable time in diagnosing a stroke, with the ability to assess a patient in as little as four minutes.

"There are millions of neurons dying every minute during a stroke," said John Volpi, a vascular neurologist and co-director of the Eddy Scurlock Stroke Center at Houston Methodist Hospital. "In severe strokes it is obvious to our providers from the moment the patient enters the emergency department, but studies suggest that in the majority of strokes, which have mild to moderate symptoms, that a diagnosis can be delayed by hours and by then a patient may not be eligible for the best possible treatments."

"The earlier you can identify a stroke, the better options (we have) for the patients," added Stephen T.C. Wong, John S. Dunn, Sr. Presidential Distinguished Chair in Biomedical Engineering at the Ting Tsung and Wei Fong Chao Center for BRAIN and Houston Methodist Cancer Center. "That's what makes an early diagnosis essential."

Volpi said that physicians currently use a binary approach toward diagnosing strokes: They either suspect a stroke, sending the patient for a series of scans that could involve radiation; or they do not suspect a stroke, potentially overlooking patients who may need further assessment.

"What we think in that triage moment is being either biased toward overutilization (of scans, which have risks and benefits) or underdiagnosis," said Volpi, a co-author on the paper. "If we can improve diagnostics at the front end, then we can better expose the right patients to the right risks and not miss patients who would potentially benefit."

He added, "We have great therapeutics, medicines and procedures for strokes, but we have very primitive and, frankly, inaccurate diagnostics."

Other collaborators on the project include Tongan Cai and Mingli Yu, graduate students working with Wang and Huang at Penn State; and Kelvin Wong, associate research professor of electronic engineering in oncology at Houston Methodist Hospital.

WASHINGTON, Oct. 22, 2020 -- Over the last century, the compound ammonium nitrate has been involved in at least 30 disasters and terrorist attacks. Under normal circumstances, it's totally harmless and used in things like fertilizer, so what makes ammonium nitrate turn deadly?: https://youtu.be/-SeT3N3A19c.

Conducted by an international consortium, led by the London School of Hygiene & Tropical Medicine and the University of Maryland School of Medicine, the research is the first meta-analysis of preventive malaria treatments among school-age children.

The team pooled data from 11 different clinical studies that tested malaria preventative medications in 15,000 children aged 5 to 15 living in seven different countries across sub-Saharan Africa. Half were given preventive malaria treatment, whereas the other half were either given a placebo or not treated as a control.

Doses of preventive drugs were given as often as once a month, or as infrequently as once a year, depending on the study. The children were monitored for an average of 43 weeks. Six of the clinical trials evaluated cognitive function between children who received the malaria preventatives and those who did not.

Overall, the team found that preventive antimalarial treatment across all malaria transmission settings cuts the prevalence of malaria among schoolchildren by 46% and subsequent cases of clinical malaria by 50%.

Preventive treatment provided consistent protection for schoolchildren regardless of transmission setting - from areas where the underlying prevalence of malaria was greater than 50% and where it was less than 10%. Preventive treatment also reduced cases of anaemia among schoolchildren by 15% and, among children over 10 years of age, was associated with improved learning.

An estimated 3.4 billion people worldwide are at risk of contracting malaria, and 400,000 die from the disease every year, according to the World Health Organization (WHO). While the WHO recommends providing intermittent preventive treatment to pregnant women, infants and young children in some malaria-endemic areas, they have not issued recommendations for school-age children. This is despite growing evidence that use of these preventive mediations works to prevent infections.

Dr Matthew Chico, Assistant Professor of Public Health at the London School of Hygiene & Tropical Medicine and senior author, said: "School-aged children in malaria-endemic areas of sub-Saharan Africa are at substantial risk of infection, and often need treatment. Furthermore, this age group is a major reservoir for human-human transmission.

"Our study shows that preventive treatment of malaria among school-aged children reduces the burden of malaria in this age group. Combined with a malaria vaccine and insecticide treated bednets, a three-pronged approach might just produce the silver bullet we need for malaria elimination."

Malaria is transmitted by mosquitos infected with a parasite and remains prevalent in Africa, Central and South America, and Southeast Asia.

Malaria can cause fevers, headache and chills, as well as anaemia due to the parasite's destruction of red blood cells. Anaemia can cause severe fatigue, headaches, delayed development and poor performance in school. Malaria can also lead to organ failure and can be fatal if left untreated.

Public health campaigns to provide antimalarial medications to school-aged children may be a way to improve the health and wellness of children, but also to curb the disease spread in communities where malaria is endemic.

Dr Lauren Cohee, faculty member in the Malaria Research Program in the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine and study first author, said: "Utilizing schools as a platform to deliver preventive treatment improves the feasibility of this intervention and builds upon the ever increasing rates of primary school enrolment across the malaria endemic world.

"Preventive treatment of malaria could be added to existing school-based health programs, including nutrition and deworming, to further promote the overall health of the learner."

The authors acknowledge limitations of their study, including the variability between studies. However, because the team combined individual participant data from 11 studies, it was possible to account for differences in study design and setting, treatment type, as well as participant characteristics in ways that would not otherwise be possible.

Doctors and biostatisticians at the University of Michigan Rogel Cancer Center have led the development and validation of a staging system to better predict outcomes and inform treatment decisions for men diagnosed with non-metastatic prostate cancer.

Although it is one of the most common cancers worldwide, prostate cancer remains one of the few major cancers for which the familiar, numerical staging system -- ranging from stage 1 to stage 4 -- has not been adopted into national guidelines for treatment or for the testing of new medicines in clinical trials.

The new proposed system -- dubbed STAR-CAP -- which appears in JAMA Oncology, draws on patient, tumor and outcomes data from nearly 20,000 patients from 55 centers in the U.S., Canada and Europe to create a robust model with strong prognostic power.

"Localized prostate cancer is sometimes less aggressive, sometimes more -- and whether we're patients, physicians or researchers, we all want to know as best we can how aggressive a particular cancer is likely to be," says study co-first author Robert Dess, M.D., an assistant professor of radiation oncology at Michigan Medicine. "That information helps with our conversations with patients, it helps with clinical trial design and it is particularly valuable when you can make those estimates based off of standard information that you would collect when you first see a patient to discuss their treatment options."

The system assigns patients to a particular stage through a point system based on several key variables. These include the patient's age, tumor category, Gleason grade of cell abnormality and prostate-specific antigen levels, also known as PSA levels. And STAR-CAP uses more granularity in these categories than many of the previous models, the authors note.

The model divides patients into nine stages of non-metastatic prostate cancer based on their point score -- from stage 1 to stage 3, with each stage split into substages of A, B and C.

STAR-CAP's predictions outperformed or equaled previous, non-validated models, including the current American Joint Committee on Cancer staging system, the study notes. And for a significant number of patients, the new model would reclassify them as having less advanced disease -- 22% of patients, for example, who would be classified as stage 3A under the AJCC's 8th edition criteria would be classified as stage 1C using the STAR-CAP system, a downgrade of four classification steps.

"This is the kind of information that can give patients and doctors more confidence when discussing treatment options and expected outcomes," Dess says.

Several years ago, the AJCC established criteria to evaluate prediction models for the staging of prostate cancer -- however, since no models met the criteria, the most recent staging designations were based on the consensus of experts in the field, says study co-senior author Daniel Spratt, M.D., the Laurie Snow Endowed Research Professor of Radiation Oncology at Michigan Medicine.

"None of the previous models evaluated met the criteria, so none of them could be used," Spratt says. "So we said, 'Well, let's make one.' We wanted it to be transparent, robust and validated, so that we can start moving closer to communicate using a common staging system, similar to other cancers. Right now we primarily categorize people as low risk, intermediate risk or high risk -- which is a fairly blunt and imprecise system."

Moreover, the new scoring system is designed to be able to be used worldwide with information that is commonly gathered about a patient and their cancer.

"We're leveraging a backbone of more than three decades of research," Dess says. "And we wanted to do it in a formal way and provide the best validated prognostic system we could come up with that was simple, easy to use, and that relied on readily available information."

The team has made the scoring system available to doctors and researcher worldwide via a web-based app at STAR-CAP.org.

"We know that some of the newest tools that we have that are just coming online like genomics or molecular imaging may improve upon this system, but we wanted to create the best, most widely accessible model based on the data we currently have -- understanding that new tools may help us develop even better models in the future," Dess says.

Both Dess and Spratt stressed that the effort would not have been possible without co-first author Krithika Suresh, Ph.D., a former biostatistics graduate student, and co-senior author Matthew Schipper, Ph.D., a research professor of biostatistics at the School of Public Health and research associate professor of radiation oncology at Michigan Medicine, who led the work's complex statistical analyses. Elizabeth Chase, a doctoral candidate in biostatistics was also instrumental, helping to design and develop the online web application, they said.

Nor would the work have been possible without the participation of numerous national and international collaborators.

"This work doesn't get done unless you have the collaborative spirit of investigators across the country and around world," Dess adds.

White Americans support strict immigration policies while at the same time favor the DREAM Act that would grant legal status to some immigrants who were brought to the United States as children, a contradiction linked to racial resentment and the belief that equality already exists, according to a Rutgers-led study.

"White Americans' support for punitive immigration policies hurt the very same group for which they support a pathway to legalization," said author Yalidy Matos, an assistant professor of political science at Rutgers' School of Arts and Sciences. "Racial resentment and the belief that equal opportunity is already available to all, known as anti-egalitarianism, are predispositions that underscore American values such as work ethic, meritocracy and individualism. The same values that lead people to support restrictive immigration policies also lead them to support the DREAM Act."

The study, published in the journal Perspective on Politics, found that in 2012, more than 48 percent of white Americans who supported the DREAM Act also supported police enforcement of immigration. Of these 48 percent, approximately 19 percent were Democrats, 40 percent were Independents and 41 percent were Republicans.

White Democrats' support for the DREAM Act and local immigration enforcement by the police is influenced by racial resentment and the belief that opportunity and equality already exists. White Republicans are only influenced by racial resentment.

Matos says white Americans' political behavior demonstrates that predispositions to these opposing beliefs can override partisanship for Democrats, leaving some to defect from party-aligned immigration policy preferences.

According to the data, Democrats (0.58), Independents (0.69) and Republicans (0.75) who support the DREAM Act and oppose sanctuary cities, a term applied to jurisdictions with policies designed to limit involvement in federal immigration enforcement actions, have higher levels of racial resentment than Democrats (0.24), Independents (0.34) and Republicans (0.59) who support the DREAM Act and support sanctuary cities.

Matos recommends Americans think broadly about supporting restrictive immigration policies, especially local level immigration enforcement programs that can nullify their own support towards the DREAM Act.

"Support for the DREAM Act is a great start but ultimately not enough to diminish the indirect effects of other immigration policies," Matos said. "Immigration reform at-large will continue to struggle in Congress if white Americans continue to be driven by the values of meritocracy and work ethic and define equality as equality of opportunity without regard to structural barriers. This is especially the case for Democrats and Independents."

SPOKANE, Wash. - Increasing the amount of time spent asleep immediately after a traumatic experience may ease any negative consequences, suggests a new study conducted by researchers at Washington State University's Elson S. Floyd College of Medicine.

Published today in Scientific Reports, the study helps build a case for the use of sleep therapeutics following trauma exposure, said William Vanderheyden, an assistant research professor and the lead author on the study. "Basically, our study has found that if you can improve sleep, you can improve function."

The finding holds particular promise for populations that are routinely exposed to trauma, such as military personnel and first responders, and may also benefit victims of accidents, natural disaster, violence, and abuse.

Vanderheyden made the discovery following a series of experiments in rats in which he and coauthor Christopher Davis examined the links between poor sleep and post-traumatic stress disorder (PTSD)--a psychiatric condition that affects an estimated 8 million Americans each year.

"People with PTSD oftentimes experience nightmares and other types of sleep disturbances, such as frequent awakenings and insomnia," said Vanderheyden. "One thought was that those sleep disturbances may cause further cognitive impairment and worsen the effects of PTSD or the initial trauma. So we wanted to see whether repairing the sleep disturbances associated with trauma exposure could help alleviate the symptoms of PTSD."

Their study used methods reviewed and approved by Washington State University's Institutional Animal Care and Use Committee, which oversees all university animal research procedures to ensure animals' humane treatment throughout their lifecycle. This included a commonly used PTSD rodent model in combination with optogenetics, a technique that uses light-sensitive proteins to control the activity of brain cells.

After going through the PTSD protocol, rats were assigned to two groups. In one group, the researchers used optogenetic stimulation to activate melanin-concentrating hormone (MCH)--a sleep-promoting brain cell type--over a period of seven days. Animals in the second group served as controls.

Comparing the two groups, the researchers found that optogenetic stimulation increased the duration of rapid eye movement (REM) sleep--the sleep phase thought to be important for learning and memory--across the rats' rest and active phases.

The researchers then assessed the rats' behavior on a three-day classical conditioning experiment involving a memory task. On day one, rats learned to associate an audible tone with the mildly unpleasant experience of receiving a small foot shock immediately after hearing the tone. After several occurrences, rats would freeze after hearing the tone, anticipating the foot shock. On day two, they heard the tone 30 times without receiving the shock, allowing them to gradually extinguish that memory. On the third day, the researchers played the tone 10 times to test to what extent the previous day's memory extinction had stuck. They found that rats that had received optogenetic stimulation to increase their sleep time had more successfully extinguished the memory, freezing less than control rats.

"This highlights that there is a time-sensitive window when--if you intervene to improve sleep--you could potentially stave off the negative effects of trauma," Vanderheyden said. "Conversely, it seems likely that if you are kept awake after a trauma, this could potentially be harmful to your cognitive function, though we haven't directly tested this as part of our study."

As an example, he mentioned victims of traffic accidents, who may not get much opportunity to sleep as they are poked, prodded, examined, and treated after being hospitalized for injuries. Though prioritizing sleep may not be feasible in victims with potentially life-threatening injuries, increasing sleep in other trauma-exposed populations could practically be done. Military personnel coming back from patrol could be encouraged to sleep and potentially be given sleep-promoting drugs to help them stave off any trauma experienced during their patrol, Vanderheyden said.

Vanderheyden cautioned that although their experiments suggest that manipulating sleep immediately after a trauma may be beneficial, such an intervention may or may not be effective for traumatic experiences that occurred in the more distant past.

As a next step, Vanderheyden and Davis want to delve deeper into molecular mechanisms that improve function in response to increased sleep. Their goal is to pinpoint those molecules that are important for regulating sleep or learning and memory, which will help them identify targets for the development of better drugs to help trauma-exposed populations.

Based on their findings, Vanderheyden also suggested that the use of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) in people with PTSD may need to be reexamined, as SSRIs are known to suppress REM sleep.

"We may be doing our trauma victims a disservice by prescribing a class of drugs that actually eliminates a potential therapeutic avenue for them by removing their REM sleep when our findings suggest that we should be increasing REM sleep," Vanderheyden said.