Culture

Climate change is leaving its mark on the bog complexes of the German Black Forest. Due to rising temperatures and longer dry periods, two plant species have already gone extinct over the last 40 years. The populations of many others have decreased by one third. In the next couple of decades ten more species could become extinct, researchers from Martin Luther University Halle-Wittenberg (MLU) and the German Centre for Integrative Biodiversity Research (iDiv) write in Diversity and Distributions.

There are only a few healthy ombrotrophic bogs, raised bogs and spring mires left in Germany. They used to cover large swathes of north-western Germany. Today they are still found in the foothills of the Alps and on low mountain ranges, for example in the Black Forest. They are very sensitive ecosystems that are highly dependent on certain climatic conditions. “These bogs and spring mires are seismographs of climate change. They react very sensitively to small changes in precipitation and temperature,” says professor Helge Bruelheide, a geobotanist at MLU and a member of iDiv. Bog complexes also have a very high proportion of endangered plant and animal species.

Bruelheide joined forces with Thomas Sperle, a biologist and wetlands expert, to investigate the trends in biodiversity in bogs and spring mires in the southern region of the Black Forest. The two scientists drew on data from the 1970s about the vegetation of 124 complete bogs. Sperle completely re-surveyed nearly all of the areas over a period of four years. "It is really tricky to prove the extinction of a species for an entire bog. I had to carefully scan the whole area to ensure that specific individuals were not overlooked," says Sperle. Bruelheide then used the data to analyse the 88 plant species. Two species have already become extinct. The population size of another 37 have decreased by about one third since the 1970s. This has disproportionately affected so-called specialist species that are adapted to specific climatic conditions and make up a large portion of the biodiversity in Germany. However, there were also 46 so-called generalist species that have coped better with the changes and whose numbers have increased over time.

The researchers also checked whether their observations could be explained by other factors, such as the size of the bogs, the distance from one bog to another and whether adjacent areas were used for agriculture. However, no factor could explain the data better than climate change. "Our analyses clearly show that species are declining and dying out in places where it is drier and warmer for longer periods of time in the summer. This is the first indication that climate change has already arrived in our latitudes," concludes Bruelheide. "It is getting noticeably drier and hotter in the Black Forest, which is why this change is evident there. Presumably, the same thing will happen in other low mountain ranges such as the Harz. Our study can serve as an example for other regions in Germany, but also for other habitats and groups of species."

In their study, the biologists predict that ten more specialist species will disappear by 2045 if conditions progress as expected. This is an alarming sign as there is no way to counteract this extinction in raised bogs and spring moors. "You cannot really replace missing rain in those bogs," says Bruelheide.

A team of biophysics from leading Russian research and educational institutions (MSU, RUDN University, and the Federal Research and Clinical Center of the Federal Medical-Biological Agency of Russia) developed a computer model that shows the effect of antiseptics on bacterial membranes. The common concepts regarding the mode of action of antiseptics turned out to be incorrect: instead of destroying bacterial membranes, they cause changes in their structure. These changes make the bacteria weaker and more susceptible to adverse external factors. The results of the study were published in The Journal of Physical Chemistry.

Antiseptics are chemical agents that affect the internal processes or external structures of harmful microorganisms causing them to die. For example, alcohols break down important building and regulation blocks of bacteria and viruses. Other antiseptics target the integrity of bacterial membranes. They are effectively used against a wide range of pathogens, but their mode of action remains elusive. Scientists are aware of some general patterns, such as the presence of electrically charged particles in the molecules of antiseptic agents. The team developed a computer model of a bacterial membrane and found out the mechanism of the antiseptic activity. The results of the study can help to combat bacterial resistance.

"Some pathogens, especially those associated with hospital infections, show resistance to antiseptics. It is important to understand the physics behind the interaction of antiseptics and microorganisms to use antiseptics more efficiently and to develop new agents," said professor Ilya Kovalenko, Ph.D., Doctor of Science in Physics and Mathematics, working under Project 5-100 at RUDN University.

The scientists developed a model of a bacterial membrane and put the molecules of four antiseptics (miramistin, chlorhexidine, picloxydine, and octenidine) on it. All these substances are cationic antiseptics, i.e. their molecules are positively charged. However, to the researchers' surprise, the antiseptics failed to damage the membrane and just slightly changed its structure. Even when the ratio of antiseptics to membrane lipids was increased from 1/24 to 1/4, the membrane was not destroyed.

The destruction of the membrane took place only when an external electric field (with the intensity of 150 mV/nm) was added to the model. The membrane started to restructure, and pores began to form around the molecules of the antiseptics. Then, water got into them and made them bigger; and eventually, the membrane was torn apart. This was because the membrane became thinner around positively charged molecules: the molecules of the membrane had no charge and therefore were pushed away. An uneven membrane became more susceptible to adverse external factors, which led to the death of the cell.

"We studied the reaction of the model membrane to several cationic antiseptics and found out that structural changes in the membrane in the presence of an electrical field play a key role in the formation of pores. We plan to use this model to predict the effect of existing and new antiseptics on different microorganisms," added professor Ilya Kovalenko, Ph.D., Doctor of Science in Physics and Mathematics, working under Project 5-100 at RUDN University.

Knee replacement surgery, also known as total knee arthroplasty (TKA), is increasing among patients 65 and younger. One study projects a potential 183% increase in the number of TKA and revision TKA surgeries by the year 2030 in that age group, raising concerns about poorer clinical outcomes, lower patient satisfaction and diminished joint survival compared to an older patient population.

Researchers from the University of Missouri School of Medicine and MU Health Care compared past TKA and revision TKA cases in older and younger patient populations. They found younger patients had early reoperation and component revision surgery nearly twice as often as older patients.

"Advances in the field of joint replacement along with newer implant designs have encouraged surgeons to expand TKA to a younger age group," said senior author James Keeney, MD, associate professor of orthopaedic surgery. "Most of our younger patients who have had knee replacement surgery are doing very well, but this patient group has a higher likelihood of needing an additional surgery during their lifetime. A small percentage of these patients may undergo a revision surgery during the first five years after their knee replacement. We wanted to know more about the potential causes of poor outcomes."

Keeney's team completed its own detailed medical record review of 147 patients age 55 and younger and compared them to 276 patients between 60 and 75 years old at the time of surgery. They documented reoperation rates, the timing of reoperation, complications, patient demographics and chronic conditions. They found younger patients were twice as likely to undergo revision surgery within two years of their primary procedure and had higher incidence of infection, mechanism complications and five-year failure of the joint.

"A combination of factors may contribute to the risk of failure, but the general observation of higher tobacco use among the younger patients suggests a possible primary culprit," Keeney said. "Smokers have been noted in previous studies to experience increased joint infection risk after primary hip and knee replacement surgery and higher rates of wound complications."

While younger age is thought to be associated with better physical health, previous studies also have suggested that younger TKA patients potentially have poorer health characteristics, including increased obesity, higher body mass index and lower activity levels. However, Keeney's team found no significant differences in comorbidities between the younger and older patient groups, with the exception of a history of tobacco use.

"Based on our findings, smoking cessation efforts should be part of the treatment plan following initial surgery, and may be even more important for patients undergoing revision surgery," Keeney said. "Efforts should also be made to decrease the risk of infection, mechanism failure, stiffness and instability, which are the common reasons for reoperation."

Researchers worldwide have been surprised to see that individuals can be infected with the SARS-CoV-2 virus - the virus that produces COVID-19 - without showing symptoms. Since these individuals expose others to infection without knowing it, it is important to find an explanation and hopefully a solution to this.

On the inside of our lungs are specialised immune cells, called alveolar macrophages, which help maintain a healthy environment in the lungs. The lungs contain a large number of alveolar macrophages, so they are probably also the first cell type an invading virus encounters.

When the body recognises a viral infection, our immune system initiate the production of interferons. Interferons are a group of cytokines that help shape the immune response and are therefore essential in the fight against a viral infection. Alveolar macrophages have previously been shown to produce large amounts of interferons upon infection with respiratory viruses, such as influenza.

SARS-CoV-2 is a respiratory virus that typically infects the outermost cell layer of the lungs, the epithelial layer. New research has shown that interferon production in the infected epithelial cells can be inhibited by the SARS-CoV-2 virus. This results in low interferon production and therefore also a limited activation of the immune system to fight against the virus. Although the epithelial layer is the target of the virus, it must be assumed that the first cell type the virus encounters is the alveolar macrophages, and therefore these cells are important for how quickly an immune response to a SARS-CoV-2 infection can be initiated.

Therefore, a team of researchers from Aarhus University and Aarhus University Hospital in Denmark set out to investigate how these important cells react to the SARS-CoV-2 virus. To answer this, they isolated the alveolar macrophages from lung lavage and examined the activation of the immune system in these cells when they encounter the SARS-CoV-2 virus.

The SARS-CoV-2 virus can hide its genome from being recognised

The results of their research show that alveolar macrophages effectively produce interferons when infected with known viruses, such as influenza. They have thereby confirmed that they have the potential to produce large amounts of interferons during a viral infection. Contrary to their expectations, the researchers saw no interferon production in the cells when the alveolar macrophages were exposed to the SARS-CoV-2 virus.

These results therefore suggest that the SARS-CoV-2 virus may hide its genomic material from being recognised in the alveolar macrophages, thereby not inducing the production of interferons. This is why there will be no activation of the immune system in the early stages of a SARS-CoV-2 infection, allowing the virus to spread further in the community before symptoms occur. However, more research is needed to understand how SARS-CoV-2 can avoid being recognised by the immune system.

Hurricanes and other tropical cyclones can severely impact human health in communities across the country, but data for these events is limited, especially in a format that is easy to link with human health outcomes.

Scientists have looked at death certificates to see if the cause could be linked up clearly to a storm, but it is easy to miss something in this type of data review. A person could have a heart attack brought on by stress from clearing tree limbs in a yard, following a storm.

An interdisciplinary team - including epidemiologists, engineers, an atmospheric scientist and software developer - led by Colorado State University (CSU) has created an open source data set that can be used for epidemiological research on tropical cyclones. The new tool also provides insights that can guide the design and analysis of this type of research.

The paper describing the new data set, "Assessing United States County-Level Exposure for Research on Tropical Cyclones and Human Health," is published Oct. 28 in Environmental Health Perspectives.

Interdisciplinary team tackles lack of data

Brooke Anderson, lead author of the paper and an associate professor in the Department of Environmental and Radiological Health Sciences at CSU, teamed up on this project with scientists including Andrea Schumacher, research associate with the Cooperative Institute for Research in the Atmosphere (CIRA) at CSU.

"For heatwaves, there has already been a lot of research on what the risks are for human health," said Anderson. Scientists can estimate community-wide deaths and illnesses associated with several types of climate-related disasters, including heat waves, floods and wildfires, she added.

Anderson said that with this new data set, scientists can now analyze multiple storms in different places and time periods, and drill down to see what happens in different health outcomes for people. Prior to the release of this new tool, most research has focused on data related to a single storm.

Schumacher said she's always been interested in looking at how counties across the country are affected by hurricane winds on a broad scale. And she found the perfect research partner in Anderson.

"Brooke and I found that we had a similar interest in characterizing hurricane winds," said Schumacher, who helps develop satellite-based products for hurricane forecasters.

Data set designed for others to build upon
The team used what's known as the R programming language to create the data set, which will allow scientists from around the world to add new facets and enrich what the team has started.

Anderson said the concept is similar to when a child gets a toy train set, and it just comes with an oval. "Next, the grandparents come along, and you get a bridge or you get new roads that head off in different directions," she said.

The new tool - maintained by an international group of volunteers on the Comprehensive R Archive Network, CRAN - also provides very precise data. A scientist can look at rainfall during Hurricane Floyd from several days before (or after) the storm came, Anderson said.

CSU scientists are already using the new data set to look at Medicare hospitalizations following storms over a decade in the Eastern United States. Anderson said the team found that the number of people being hospitalized for respiratory conditions tended to increase when the storm hit, and a week after.

Another team she's part of used the dataset to look at how tropical cyclones affect different birth outcomes, including pre-term birth and pregnancy outcomes.

Schumacher said she sees lots of possibilities for where this research tool can go.

"From my end, there's still plenty of work to do," she said. "What we've created is a really good start. I can see all kinds of ways that we can improve on it, especially as we get better and better observations."

Since the famous discovery of dinosaur eggs in the Gobi Desert in the early 1920s, the fossilized remains have captured the imaginations of paleontologists and the public, alike. Although dinosaur eggs have now been found on every continent, it's not always clear to scientists which species laid them. Now, researchers reporting in ACS Omega have narrowed down the list for an unknown eggshell from Mexico by comparing its microstructure and composition with four known samples.

Because many dinosaur eggs are similar in size and shape, it can be difficult to determine what type of dinosaur laid them. Clues can come from fossilized embryos (which are rare), hatchlings in the same nest or nearby adult remains. Scientists also have identified microscopic features of eggshells that differ among groups of dinosaurs. In addition, researchers have studied the elemental composition of fossil eggshells to learn more about the paleoenvironment and conditions that led to the eggs' fossilization. Abel Moreno and colleagues wanted to compare the microstructure and composition of five dinosaur eggshells from nests in the El Gallo Formation of Baja California, Mexico. Based on the eggs' shapes and sizes and the fossil record of the area, the researchers had concluded that three of the eggs were laid by ornithopods (bipedal herbivores) of the hadrosaur family (duck-billed dinosaurs) and one by a theropod (bipedal carnivores) of the troodontidae family (small, bird-like dinosaurs). The remaining sample was too damaged to classify by the naked eye.

Using scanning electron microscopy, the team examined the external and internal surfaces and a cross-section of each eggshell. In contrast to the smooth outer surface of the theropod shell, the shells from the ornithopods and the unknown sample had nodes at different distances across the shell. Images of shell cross-sections from the ornithopods revealed that mammillary cones -- calcite crystals on the inner surface of the shell -- formed thin, elongated columns arranged in parallel, with irregular pores. In contrast, the eggshell from the theropod showed thicker, shorter cones arranged in a bilayer, with wider pores. The unknown sample more closely resembled the ornithopod eggshells, leading the researchers to hypothesize that it was probably also from the hadrosaur family. In addition, the researchers conducted an elemental composition analysis, which they say is the first such analysis on dinosaur eggshells collected in Mexico. They say the findings might help reveal how the fossilization process varied among species and locales.

If you've ever had a cold, you know that too much mucus can be an annoyance, but mucus plays a very important role in the body. The respiratory system creates mucus as part of the immune system, meant to trap inhaled bacteria, viruses, and dirt so they can be removed before causing infection. However, for people with the genetic disorder cystic fibrosis (CF), the mucus that their bodies produce is thicker and stickier, leading to an increased risk from infection and decreased ability to breathe over time.

New research led by the University of Pittsburgh's Swanson School of Engineering examines the properties of the mucus of CF patients and the role it plays in a pathogens' ability to survive. The new information could have important implications for CF treatment.

The researchers examined nonmucoid (PANT) and mucoid (PASL) strains of P. aeruginosa, a common pathogen that infects the lungs. P. aeruginosa adapts to the host environment mutating from a non-mucoid phenotype (PANT) to a mucoid phenotype (PASL). This mutation in P. aeruginosa creates a protective film of mucus around the bacteria thereby forming a more hydrated and slimy biofilm in the mucus.

"Think of the cells like grains of rice. PANT cells are like basmati rice, while PASL cells are like sushi rice: coated in such a way that they stick together when they're compressed," explained Tagbo Niepa, assistant professor of chemical and petroleum engineering, whose lab led the study. Niepa also has appointments in the Departments of Bioengineering, Civil and Environmental Engineering, and Mechanical Engineering and Materials Science. "We can measure how investigational drugs can alter the sticky nature of the coating that pathogens such as P. aeruginosa create upon mutation."

This mutation gives the mucus unique properties that contribute to increased antibiotic resistance. It also shields them against phagocytic cells, which help the immune system clear out dead or harmful cells by ingesting them.

In order to study these properties, the researchers used pendant drop elastometry to compress and expand the biofilm that the cells formed. They also assessed the transcriptional profile of the cells to correlate the film's mechanics to cell physiology.

"This is the first time that the pendant drop elastometry technique has been used to study the mechanics of these cells. We demonstrate that these techniques can be used to investigate the efficacy of mucolytic drugs--drugs that are used to break down the film of mucus that the cells are making," noted Niepa. "This technique could be powerful for investigating those agents, to see if they have the anticipated effect."

According to the American Heart Association, heart disease is the leading cause of death worldwide in recent years. During a heart attack, or myocardial infarction (MI), a blocked artery and the resulting oxygen deprivation cause massive cardiac cell death, blood vessel impairment and inflammation. Now, researchers reporting in ACS Biomaterials Science & Engineering have developed a cardiac patch with tiny engineered blood vessels that improved recovery from MI in rats and pigs.

To effectively treat MI, lost heart muscle tissue must regenerate and new blood vessels must form to restore oxygen and nutrients to cells. Scientists have tried to develop patches containing various therapeutic cells to treat MI, but so far most have been too cumbersome to make, or they don't restore both cardiac muscle and blood supply to the injured site. Ke Cheng and colleagues previously developed a relatively easy-to-make pre-vascularized cardiac patch, which contained engineered microvessels in a fibrin gel spiked with cardiac stromal cells. When implanted into rats after an MI, the cells in the patch secreted growth factors that made cardiac muscle and blood vessels regrow. Now, the researchers wanted to test the patch further in rats, as well as in pigs, which have cardiovascular systems more similar to humans than those of rodents.

The researchers implanted the cardiac patch in rats that recently had a heart attack. Four weeks later, rats that received the patch had less scar tissue, increased cardiac muscle and improved cardiac pump function compared with untreated rats. The team observed similar effects in pigs that had undergone MI and were treated with the patches. The patch increased recruitment of the pigs' progenitor cells to the damaged area and enhanced the growth of new blood vessels, as well as decreased cardiac cell death and suppressed inflammation. Although prior studies have used blood vessel-forming cells or natural blood vessels to vascularize cardiac patches, this study is the first to demonstrate the success of pre-vascularized cardiac stromal cell patches using microengineered synthetic blood vessels for treating MI in a large animal model. More studies on the mechanisms, safety and efficacy of patch repair are needed before the technology can be applied to humans, the researchers say.

Dementia and other cognitive disorders now appear to be risk factors for developing severe COVID-19, according to research from the University of Georgia. The findings highlight the need for special care for populations with these preexisting conditions during the pandemic.

In a blind study, the researchers analyzed data from nearly 1,000 diseases and two specific genes to compare the health profiles of COVID-19 patients with those testing negative, looking for commonalities in the COVID-19 patients.

The study, published online in the journal Brain, Behavior and Immunity, relied on data from UK Biobank, a long-term study of more than 500,000 participants investigating the respective contributions of genetic predisposition and environmental exposure to the development of disease.

Beginning in March, the UK Biobank started to report the COVID-19 status of its participants. The team in the Franklin College of Arts and Sciences department of genetics, led by assistant professor Kaixiong Ye and his postdoc, Jingqi Zhou, promptly connected the COVID-19 status to the electronic health data.

"We took a hypothesis-free approach and the most statistically significant ones are the cognitive disorders and Type 2 diabetes," said Ye, the senior author on the study. "Right now, we don't know the mechanisms behind these associations, we only know these are more common in COVID-19 patients."

Analyzing the genetic factors that make some individuals at higher risk for severe COVID-19, the team focused on two genes: ACE2 and TPMPRSS2, known to be critical for the virus to enter into human cells.

"In the TMPRSS2 gene we found that a specific genetic variation is more common in the COVID-19 patient," he said, adding that while the discovery was novel at the time, the team knows more data now exists about host genetic factors than even three months ago.

The research team also found that variations in genes related to SARS-CoV-2 infection may be associated with severe COVID-19 that requires hospitalization.

"And we are starting to understand how those genetic variations are making a difference," he said, noting the extraordinary pace of research worldwide during the pandemic as scientists work on SARS CoV 2. Since they began in spring 2020, Ye's group has been able to follow up on its own earlier work and communicate with peers around the world to contribute to the overall body of knowledge about the disease.

"Working on one disease, the whole field is converging together, around the world, at the same time. It really showcases the power of science," Ye said. "What my group is doing is really just data analysis, large-scale data mining, but from vaccine development to studies in patients, scientists are attacking the disease from different aspects, and that's moving us forward very quickly in combating COVID-19."

DALLAS - Oct. 28, 2020 - Two new studies suggest Medicare's system of penalizing hospitals if too many patients are readmitted within 30 days should also look at whether the patients were well enough to remain in their home during that time.

The studies propose adding a new metric to examine how many of the initial 30 days following hospitalization are actually spent at home - a "risk-adjusted 30-day home time" test to balance the current "30-day risk-standardized readmission rate" measure.

"The current readmission penalty has been a matter of debate," says Ambarish Pandey, M.D., first author of the study published today in JAMA Cardiology, as well as of an earlier study published in Circulation in July.

"Some hospitals that have had lower readmission rates were actually having high mortality rates," says Pandey, assistant professor of internal medicine at UT Southwestern. "If you die, you're not going to be readmitted."

In addition, the current focus on hospital readmissions does not take into account patients who wind up in a skilled nursing facility or intermediate/long-term care facility after hospital discharge, Pandey points out.

A "30-day home time" metric, he says, would paint a more comprehensive picture and be more patient-centered.

The federal Centers for Medicare & Medicaid Services (CMS) tracks readmissions as part of its effort to improve the quality of care in the nation's hospitals. In 2019, CMS penalized almost 2,600 U.S. hospitals by withholding an estimated $563 million in Medicare payments after determining they exceeded the expected number of patient readmissions, according to the Circulation study.

CMS focuses its readmissions standard on cases involving heart failure, myocardial infarction (heart attack), and pneumonia.

The studies examined how applying a 30-day home-time metric would have affected the quality rankings of hospitals treating heart failure (the JAMA Cardiology study) and acute myocardial infarction (Circulation), based on Medicare claims data. In both studies, the researchers found that using the 30-day home-time metric changed the quality ranking a hospital had received under the readmission standard about 30 percent of the time.

The JAMA Cardiology study found that heart failure patients spent a risk-adjusted median of 21.77 days at home in the 30 days after discharge. However, 6.61 days were spent in an intermediate/long-term or skilled nursing facility, and another 1.37 days were lost to death. Readmission accounted for only 1.25 of the days lost.

Similarly, in the Circulation study, patients stayed home a risk-adjusted median of 24.0 days, with 4.7 days subtracted for nursing facilities, 2.5 days for death, and 1.0 days for readmission.

Hospitals with higher 30-day home time were larger and more likely to be academic medical centers, according to the studies.

The findings suggest that the 30-day home-time metric complements the existing readmission rate metric "by not only accounting for post-discharge mortality but also the variability in the post-acute care utilization of intermediate/long-term care facility and [skilled nursing facilities]," according to today's JAMA Cardiology study.

In addition, "a home time metric may be more easily understood by patients and clinicians," the study says.

Fourteen out of every 1,000 COVID-19 patients admitted to hospital experience a stroke, a rate that is even higher in older patients and those with severe infection and pre-existing vascular conditions, according to a report published this week.

COVID-19 has become a global pandemic, affecting millions of people worldwide. In many cases, the symptoms include fever, persistent dry cough and breathing difficulties, and can lead to low blood oxygen. However, the infection can cause disease in other organs, including the brain, and in more severe cases can lead to stroke and brain haemorrhage.

A team of researchers at the Stroke Research Group, University of Cambridge, carried out a systematic review and meta-analysis of published research into the link between COVID-19 and stroke. This approach allows researchers to bring together existing - and often contradictory or under-powered - studies to provide more robust conclusions.

In total, the researchers analysed 61 studies, covering more than 100,000 patients admitted to hospital with COVID-19. The results of their study are published in the International Journal of Stroke.

The researchers found that stroke occurred in 14 out of every 1,000 cases. The most common manifestation was acute ischemic stroke, which occurred in just over 12 out of every 1,000 cases. Brain haemorrhage was less common, occurring in 1.6 out of every 1,000 cases. Most patients had been admitted with COVID-19 symptoms, with stroke occurring a few days later.

Age was a risk factor, with COVID-19 patients who developed stroke being on average (median) 4.8 years older than those who did not. COVID-19 patients who experienced a stroke were on average (median) six years younger than non-COVID-19 stroke patients. There was no sex difference and no significant difference in rates of smokers versus non-smokers.

Pre-existing conditions also increased the risk of stroke. Patients with high blood pressure were more likely to experience stroke than patients with normal blood pressure, while both diabetes and coronary artery disease also increased risk. Patients who had a more severe infection with SARS­CoV­2 - the coronavirus that causes COVID-19 - were also more likely to have a stroke.

The researchers found that COVID-19-associated strokes often followed a characteristic pattern, with stroke caused by blockage of a large cerebral artery, and brain imaging showing strokes in more than one cerebral arterial territory. They argue that this pattern suggests cerebral thrombosis and/or thromboembolism are important factors in causing stroke in COVID-19. COVID-19-associated strokes were also more severe and had a high mortality.

An important question is whether COVID-19 increases the risk of stroke or whether the association is merely a result of COVID-19 infection being widespread in the community.

"The picture is complicated," explained Dr Stefania Nannoni from the Department of Clinical Neurosciences at the University of Cambridge, the study's first author. "For example, a number COVID-19 patients are already likely to be at increased risk of stroke, and other factors, such as the mental stress of COVID-19, may contribute to stroke risk.

"On the other hand, we see evidence that COVID-19 may trigger - or at least be a risk factor for - stroke, in some cases. Firstly, SARS­CoV­2 more so than other coronaviruses - and significantly more so than seasonal flu - appears to be associated with stroke. Secondly, we see a particular pattern of stroke in individuals with COVID-19, which suggests a causal relationship in at least a proportion of patients."

The researchers say there may be several possible mechanisms behind the link between COVID-19 and stroke. One mechanism might be that the virus triggers an inflammatory response that causes thickening of the blood, increasing the risk of thrombosis and stroke. Another relates to ACE2 - a protein 'receptor' on the surface of cells that SARS-CoV-2 uses to break into the cell. This receptor is commonly found on cells in the lungs, heart, kidneys, and in the lining of blood vessels - if the virus invades the lining of blood vessels, it could cause inflammation, constricting the blood vessels and restricting blood flow.

A third possible mechanism is the immune system over-reacting to infection, with subsequent excessive release of proteins known as cytokine. This so-called 'cytokine storm' could then cause brain damage.

The team say their results may have important clinical implications.

"Even though the incidence of stroke among COVID-19 patients is relatively low, the scale of the pandemic means that many thousands of people could potentially be affected worldwide," said Professor Hugh Markus, who leads the Stroke Research Group at Cambridge.

"Clinicians will need to look out for signs and symptoms of stroke, particularly among those groups who are at particular risk, while bearing in mind that the profile of an at-risk patient is younger than might be expected."

While the majority of strokes occurred after a few days of COVID-19 symptoms onset, neurological symptoms represented the reason for hospital admission in more than one third of people with COVID-19 and stroke.

Dr Nannoni added: "Given that patients admitted to hospital with symptoms of stroke might have mild COVID-19-related respiratory symptoms, or be completely asymptomatic, we recommend that all patients admitted with stroke be treated as potential COVID-19 cases until the results of screening in the hospital are negative."

We're told from a young age not to eat too much sugar, but in reality, our bodies are full of the stuff. The surface of every living cell, and even viruses, is covered in a mess of glycans: long, branching chains of simple sugars linked together by covalent bonds. These cell-surface sugars are crucial for regulating cell-cell contact, including the attachment of bacteria to healthy host cells. Glycans are also found on all other biological polymers, including proteins and RNA, and their presence impacts the polymers' stability and function.

Despite their ubiquity and importance, glycans remain poorly understood because of their complexity. Rather than just the four nucleotide "letters" that make up DNA and RNA molecules, glycans have an "alphabet" of hundreds of different monosaccharides that can be strung together into sequences with a seemingly infinite array of lengths and branches. In addition, an individual glycan sequence can be changed due to the interplay of multiple enzymes and conditions both within and outside a cell, without the need for genetic mutations.

Now, a team of scientists from the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Massachusetts Institute of Technology (MIT) has cracked the glycan code by developing new machine learning and bioinformatics methods that enable researchers to systematically study glycans and identify sequences that play a role in the interactions of microbes and their host cells, as well as other still-unknown functions. The tools are presented in a new paper published today in Cell Host & Microbe, and are available online as a free Wyss WebApp that researchers can use to perform their own analyses of thousands of glycans.

"The language-based models that we have created can be used to predict whether and how a given glycan will be detected by the human immune system, thus helping us determine whether a strain of bacteria that harbors that glycan on its surface is likely to be pathogenic," said first author Daniel Bojar, Ph.D., a Postdoctoral Fellow at the Wyss Institute and MIT. "These resources also enable the study of glycan sequences involved in molecular mimicry and immune evasion, expanding our understanding of host-microbe interactions."

Glycan grammar rules

Because glycans are the outermost layer of all living cell types, they are necessarily involved in the process of infection, both in the interaction of a prokaryotic bacterium binding to a eukaryotic host cell, and the interactions between the cells of the immune system. This has created an evolutionary arms race, in which bacterial glycans evolve to mimic those found on their hosts' cells to evade immune detection, and hosts' glycans are modified so that pathogens can no longer use them to gain access. To trace this history of glycan sequence development and identify meaningful trends and patterns, the research team turned to machine learning algorithms -- specifically, natural language processing (NLP), which has previously demonstrated success in analyzing other biopolymers, like RNA and proteins.

"Languages are actually quite similar to molecular sequences: the order of the elements matters, elements that are not next to each other can still influence each other, and their structures evolve over time," said co-author Rani Powers, Ph.D., a Senior Staff Scientist at the Wyss Institute.

First, the team needed to assemble a large database of glycan sequences on which an NLP-based algorithm could be trained. They combed through existing datasets both online and in the academic literature to create a database of 19,299 unique glycan sequences, which they dubbed SugarBase. Within SugarBase they identified 1,027 unique glycan molecules or bonds they termed "glycoletters" making up the glycan alphabet, which could theoretically be combined into "glycowords" that the team defined as three glycoletters and two bonds.

To develop an NLP-based model that could analyze sequences of glycoletters and pick out distinct glycowords, the team chose to use a bidirectional recurrent neural network (RNN). RNNs, which also underlie the "autocomplete" feature of text messaging and email software, predict the next word in a sequence given the preceding words, enabling them to learn complex, order-dependent interactions. They trained their glycoletter-based language model, dubbed SweetTalk, on sequences from SugarBase, and used it to predict the next most probable glycoletter in a glycan sequence based on the preceding glycoletters, in the context of glycowords.

SweetTalk revealed that from the close to 1.2 trillion theoretically possible glycowords, only 19,866 distinct glycowords (~0.0000016%) were present in the database of existing glycans. The observed glycowords also tended to be clustered together in groups with highly similar sequences, partly indicating the taxonomic groups in which the glycowords are found, rather than distributed evenly among all possible sequence combinations. These outcomes likely reflect the high "cost" to an organism of evolving dedicated enzymes to construct specific glycan substructures - in that scenario, it is more evolutionarily efficient to tweak existing glycowords rather than generate completely new ones.

Given the important role glycans play in human immunity, the researchers fine-tuned SweetTalk using a smaller, curated list of glycans that are known from the literature to cause an immune response. When predicting the immunogenicity of glycan sequences from SugarBase, the SweetTalk model achieved an accuracy of ~92%, compared to an accuracy of ~51% for a model trained on scrambled glycan sequences. For example, glycans that are rich in a simple sugar called rhamnose, which is found in bacteria but not in mammals, were unambiguously labeled as immunogenic by SweetTalk. The model's excellent performance indicated that language-based models could be used to study characteristics of glycans on a large scale and with many potential applications, such as the exploration of glycan-immune system interactions.

Pour some sugar on me

Based on the success of their first glycan-focused deep learning model, the team had a hunch that deep learning could also illuminate the "family tree" of glycan sequences. To achieve this, they constructed a language model-based classifier called SweetOrigins. They first pre-trained SweetOrigins with a SweetTalk model, then used the language-like properties of glycans to fine-tune the new model on a different task: predicting the taxonomic group of glycans by learning species-specific features of glycans that indicate their evolutionary history. They replicated this structure for each level of classification, from individual species all the way up to domains (e.g., Bacteria, Eukarya), creating eight SweetOrigins models that were able to classify the taxonomic group of a glycan with high accuracy. For example, the model accurately predicted glycans from the kingdoms Animalia (91.1%) and Bacteria (97.2%), allowing a glycan of unknown origin to be quickly classified as either animal-associated, microbe-associated, or found on both cell types.

The researchers then used SweetOrigins to investigate host-pathogen interactions, reasoning that differences in the glycans associated with various strains of E. coli bacteria could be used to predict how infectious the strains are. They trained a deep learning-based classifier with the same language model architecture as SweetOrigins on E. coli-specific glycan sequences, and were able to predict E. coli strain pathogenicity with an accuracy of ~89%. It also placed the majority of glycans that are associated with E. coli strains of unknown pathogenicity at various places along the spectrum of infectiousness, helping to identify strains that are likely to be pathogenic to humans.

"Interestingly, the glycans that our model predicts are most associated with infection bear a striking resemblance to glycans found on the cells that form the mucosal barriers in animals' bodies, which keep pathogens out," said Diogo Camacho, Ph.D., a co-corresponding author of the paper and Senior Bioinformatics Scientist at the Wyss Institute. "This suggests that the glycans on pathogenic bacteria have evolved to mimic those found on the hosts' cells, facilitating their entry and evasion of the immune system."

To more deeply probe how glycans function in host-microbe interactions, the team developed a glycan sequence alignment method, which compares individual glycan sequences to determine regions that are conserved between glycans and, therefore, likely serve a similar function. They chose a specific polysaccharide sequence from the pathogen Staphylococcus aureus that is known to increase bacterial virulence and hypothesized that this glycan helped the bacterium escape immune detection. When they compared that polysaccharide to similar glycan sequences in the dataset, they found the best alignment result with the enterobacterial common antigen (ECA), a glycan found on the Enterobacteriaceae family of symbiotic and pathogenic bacteria.

The team also found ECA-like sequences associated with bacteria in the Staphylococcus, Acinetobacter, and Haemophilus genera, which are not part of the Enterobacteriaceae family that typically carries the ECA. This insight suggests that, in addition to mimicking the glycans found on their hosts, bacterial glycans can also evolve to mimic those found on other bacteria such as those in our microbiome, and that pathogenicity can arise via glycans on microbes that are not traditionally thought to be dangerous.

"The resources we developed here -- SugarBase, SweetTalk, and SweetOrigins -- enable the rapid discovery, understanding, and utilization of glycan sequences, and can predict the pathogenic potential of bacterial strains based on their glycans," said co-corresponding author Jim Collins, Ph.D., a Wyss Core Faculty member who is also the Termeer Professor of Medical Engineering & Science at MIT. "As glycobiology progresses, these tools can be readily expanded and updated, eventually allowing for the precise classification of glycans and facilitating the glycan-based study of host-microbe interactions at unprecedented resolution, potentially leading to new antimicrobial therapeutics."

"This achievement is yet another example of the power of applying computational approaches to biological problems that have so far defied resolution because of their complexity. I am also very impressed with this team for making their tools openly available to researchers around the world, which promises to accelerate the pace of our collective understanding of glycans and their impact on human health," said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences.

Ann Arbor, October 28, 2020 - A new study in the American Journal of Preventive Medicine, published by Elsevier, presents new data that address important questions pertaining to the containment of the coronavirus pandemic: When should COVID-19 quarantine really end and which continuing symptoms may be more indicative of a positive test in recovered patients?

The study was conducted by the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy, where a multidisciplinary healthcare service was established for all patients who have recovered from COVID-19 to study what happens to them after recovery and to assess the impact of the virus on their bodies.

Investigators report that close to 17 percent of patients considered fully recovered from COVID-19 tested positive for the virus in follow-up screening. Patients who continued to have respiratory symptoms, especially sore throat and rhinitis, were more likely to have a new positive test result. This suggests the persistence of these two symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19.

"Clinicians and researchers have focused on the acute phase of COVID-19, but continued monitoring after discharge for long-lasting effects is needed," explained lead investigator Francesco Landi, MD, PhD, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, and Catholic University of the Sacred Heart, Rome, Italy.

The study included 131 patients who met the World Health Organization (WHO) criteria for discontinuation of quarantine at least two weeks prior to the follow-up visit. The WHO criteria specify that the patient should be fever-free without fever-reducing medications for three days, show improvement in any symptoms related to COVID-19, be more than seven days past symptom onset, and test negative for the SARS-CoV-2 virus twice, at least 24 hours apart, with reverse transcription PCR (RT-PCR) testing.

A new RT-PCR test was administered at the time of post-acute care admission. Demographic, medical, and clinical information was collected, with an emphasis on the persistence of symptoms and signs related to COVID-19 such as cough, fatigue, diarrhea, headache, smelling disorders, loss of appetite, sore throat, and rhinitis.

Twenty-two (16.7 percent) of the patients tested positive again. There was no significant difference between patients with positive and negative test results in terms of age or sex. None of the patients had fever and all reported improvement in their overall clinical condition. Time since onset of disease, number of days hospitalized, and treatments received while hospitalized were not significant. However, some symptoms such as fatigue (51 percent), labored breathing (44 percent) and coughing (17 percent) were still present in a significant percentage of the patients studied, although there were no significant differences between individuals with a positive or negative test. The only two symptoms that were higher and significantly prevalent in patients with a positive test were sore throat (18 percent vs. 4 percent) and signs of rhinitis (27 percent vs. 2 percent).

Our findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus," Dr. Landi observed. "The main question for the containment of SARS-CoV-2 pandemic infection that still needs to be answered is whether persistent presence of virus fragments means the patients is still contagious. The RT-PCR test looks for small fragments of viral RNA. A positive swab test can reveal if patients are still shedding viral fragments, but it is not able to discern whether they are or aren't infectious."

Importantly, the investigators recommend that for patients who continue to have symptoms potentially related to COVID-19, it is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab.

Stromboli, the 'lighthouse of the Mediterranean', is known for its low-energy but persistent explosive eruptions, behaviour that is known scientifically as Strombolian activity. This feature has long been an attraction for tourists and volcanologists from all over the world.

Occasionally, however, more intense and sudden explosions occur, most recently in July and August last year (2019). These are known as 'Strombolian paroxysms'. During such events several of Stromboli's craters are active simultaneously and much greater volumes of pyroclastic materials are erupted than is usual for the volcano.

In a new study, Major explosions and paroxysms at Stromboli (Italy): a new historical catalog and temporal models of occurrence with uncertainty quantification, published in the journal Nature Scientific Reports, researchers from Italy's National Institute of Geophysics and Volcanology (INGV) and the University of Bristol use historical records to estimate the frequency of these bigger Strombolian paroxysms and investigate if the volcano has its own eruption 'memory' as evidenced, in statistical terms, by a temporal recurrence relationship between one paroxysmal eruption and the next.

The catalogue describes 180 violent explosive events of varying scale that occurred at Stromboli from 1879 to 2020. The researchers critically evaluated events described in past scientific works and information recorded in historical texts, and then determined, on an objective and homogeneous evidential basis, the type and intensity of the explosive events. This involved appraising any narrative hyperbole in the old descriptions.

Massimo Pompilio, senior researcher at INGV and co-author of the study, said: "The new catalogue makes it possible to review the classification of numerous events through the critical analysis of historical sources. From the analysis it emerges that the average annual rate of paroxysms over the last 140 years was, roughly, one event every four years or so". This rate is close to that observed for the last ten years, but is much lower than in the 1940s, when these paroxysmal events were much more frequent.

"The volcano therefore alternates between periods of intense activity and periods of relative quiet. The short span of 56 days observed between the two paroxysms of summer 2019 is not a rare situation. Five times in the past 140 years there have been even shorter inter-event times (intervals between events). Conversely, there have been four periods without paroxysms lasting from between nine to 15 years, and one interval without paroxysms that lasted for 44 years, from 1959 to 2003."

This information is useful in a forecasting context as it can help estimate the probabilities of future occurrence of these volcanic phenomena.

Andrea Bevilacqua, INGV researcher and first author of the study explains: "When a phenomenon such as a volcanic explosion occurs at irregular intervals in time, what is studied is the distribution of the 'inter-event' times, i.e. the times elapsed in passed between one explosion and the next. In particular, the development of inter-event models allows us to calculate the probability of an explosion occurring as a function of the time elapsed since the last event of that type".

"An important finding that emerged from our research concerns the tendency of paroxysms to occur in clusters. On the basis of data from the last 140 years, we have estimated that there is a 50 per cent probability that another Stromboli paroxysm might follow a previous explosion within 12 months, and a 20 per cent probability that it could follow in less than two months; on the other hand, there is a 10 per cent probability that more than ten years could pass without any other paroxysm occurring."

The novelty and uniqueness of this new research will be of great interest to volcanologists and scientists worldwide. Augusto Neri, Director of the Volcanoes Department of the INGV and co-author of the study, said: "The analysis of Stromboli's data suggests the existence of a physical process that influences the recurrence of this volcano's explosions, meaning they not completely random, out-of-the-blue events". Statisticians describe such repeating sequences as 'memory' processes. "Understanding the reasons and physical mechanisms that determine this memory represents a further scientific challenge. But the estimation of the memory in episodes of intense explosive activity of Stromboli will make a significant contribution to the quantification of the likelihood of these dangerous phenomena and, consequently, to the reduction of associated risks".

Willy Aspinall, Emeritus Professor in the School of Earth Sciences at Bristol, added: "Volcano tourism has grown substantially in recent years, and an unexpected eruption at a popular setting can be fatal, as happened last year at White Island/Whakaari volcano, New Zealand. Knowing that a particular volcano exhibits this eruption memory effect means any temporary increase in explosion probability can be appraised and, for example, inform decisions about volcanological fieldwork at the craters. However, it is premature at this stage to discuss possible implications of this research for wider aspects of civil protection on Stromboli."

The University of Cincinnati is decoding the genetics of agricultural pests in projects that could help boost crop and livestock production to feed millions more people around the world.

Joshua Benoit, an associate professor in UC's College of Arts and Sciences, contributed to genetic studies of New World screwworms that feed on livestock and thrips, tiny insects that can transmit viruses to tomatoes and other plants.

It's the latest international collaboration for Benoit, who previously sequenced the DNA for genomes of  dreaded creatures such as bedbugs.

Just in time for Halloween, Benoit's new study subject is no less creepy. The New World screwworm's Latin name means "man-eater." These shiny blue flies with pumpkin-orange eyes lay up to 400 eggs in open cuts or sores of cattle, goats, deer and other mammals. Emerging larvae begin gnawing away on their hosts, feeding on living and dead tissue and creating ghastly wounds.

"Sometimes you'll see a deer missing a chunk of its head. The flies can cause small wounds to become massive injuries," he said.

Benoit and his co-authors sequenced the genome of screwworms and identified ways of slashing populations by targeting particular genes that determine sex and control growth and development or even particular behaviors that help the flies find a suitable animal host.

The study led by entomologist Maxwell Scott at North Carolina State University was published in the journal Communications Biology.

"Our main goal was to use the genomic information to build strains that produce only males for an enhanced sterile-insect program," Scott said.

The New World screwworm is an agricultural menace that causes billions of dollars in livestock losses each year in South America, where it is common. The fly was a scourge in North America as well but was eradicated from the United States in 1982 with intense and ongoing population controls.

Today, a lab operated by Panama and the U.S. Department of Agriculture has established a biological barrier outside Panama City, a geographic choke point between the two continents.

"They rear flies in a lab, sterilize them with chemicals or  radiation and dump  these sterile male flies into the environment from a plane so they mate with the females and produce no offspring," Benoit said.

Year by year, agriculture experts gradually pushed the screwworm out of Texas, Mexico and most of Central America.

"They just used straight brute force and good science ," Benoit said. "They just drove them down all the way to Panama."

Today, Panama and the United States continue to air-drop sterile screwworms by the millions each week over the choke point to prevent the species from moving north.

A 2016 outbreak in the Florida Keys threatened to wipe out endangered Key deer before the USDA intervened, treating infected animals with a parasite medicine and releasing millions of sterile screwworms on the island chain until they disappeared.

"The U.S. still helps pay for control programs in Panama mainly because we don't want screwworms coming back here. It's the cheapest way to prevent potentially billions of dollars in damage," Benoit said.

One possible way to cut costs would be to raise only male screwworms that are intended for release so the lab wouldn't incur the huge costs of feeding female screwworms. UC's genetic study could help scientists cull females before they hatch.

"So you're left with surviving males. Then you sterilize the males and that would save a lot of money because you'd only have to raise the males for release," he said.

Next, Scott said he wants to understand how the livestock-devouring screwworm Cochliomyia hominivorax evolved as a parasitic meat eater while similar species prefer carrion.

Benoit also contributed to a genomic study in the journal BMC Biology for an insect not much bigger than the dot over the letter i. Thrips, a tiny winged insect, are legion around the world and feed on a wide variety of crops, including soybeans, tomatoes -- even cannabis. They can destroy crops both by eating them and transmitting harmful viruses.

In a study led by entomologist Dorith Rotenberg at North Carolina State University, researchers mapped 16,859 genes that helped understand the thrips' sensory and immune systems and the salivary glands that transmit the viruses.

"The genome provides the essential tools and knowledge for developing genetic pest management strategies for suppressing thrips pest populations," Rotenberg said.
 

One thrips virus is a particular agricultural concern: the spotted wilt virus, which studies have found can reduce a crop's yield by as much as 96%.

"We're talking hundreds of millions of dollars in losses," Benoit said. 

The study found that thrips can be finicky eaters and have unique genetic adaptations that likely allows them to feed on many insects. They pierce the plant and suck the juices.

And thrips have surprisingly sophisticated immune systems, the study found. Researchers identified 96 immune genes, more than many other insects studied to date. 

"We mapped the genome, but we also characterized immune aspects and how they feed," Benoit said. "It was the first study of its kind to explain what underlies their reproductive mechanisms. It was far more detailed than previous genomic studies we've done."

The study was funded in part by the National Science Foundation and a UC faculty development research grant.

Benoit said the solution to a thrips infestation predictably has been pesticides. But the UC study could help find better environmental solutions, he said.

"Pesticides do not discriminate at all. The same pesticide that kills a termite can kill a bee. When you spray, it can kill other beneficial insects," Benoit said. "So we don't want to eradicate species as much as find better ways to control them so we don't have to use as much pesticide."