Culture

Metabolic activators were found to reduce recovery time by as many as 3.5 days in patients with mild-to-moderate Covid-19, according to a Swedish-British study published today in Advanced Science.

The researchers also found that treatment with the metabolic activators improved liver health and decreased the levels of inflammation, as shown by inflammatory markers.

Conducted by researchers at Science for Life Laboratory at KTH Royal Institute of Technology in Stockholm, in collaboration with the Sahlgrenska Academy in Gothenburg and King's College, London, the human phase three clinical study showed that patients with mild-to-moderate Covid-19--who were also receiving standard care--experienced a 3.5 day reduction in recovery time when receiving the combination of metabolic activators, nicotinamide riboside (NR), L-serine, N-acetyl-L-cysteine (NAC), and L-carnitine tartrate. All four activators are aimed at improving mitochondrial function. The results of the study build on findings from phase two clinical data.

Through a randomized, placebo controlled, double blind phase three clinical trial, 309 outpatients at Umraniye Teaching and Research Hospital, University of Health Sciences, Istanbul, Turkey were randomly assigned on a 3:1 basis to receive the metabolic activators or placebo. Patients received the combined activators or placebo twice a day for 14 days and clinical status was evaluated through daily telephone check-ins.

"Our phase three data shows that metabolic activators significantly improve the recovery, liver health, and markers of inflammation of patients with COVID-19," says the study's lead author, Adil Mardinoglu, professor at KTH and Kings College and research fellow at Science for Life Laboratory.

"Dysfunctional mitochondria have been implicated in worsened progression for Covid-19, and we are pleased to find that the combination of these metabolic activators helps to remedy the stress put on the body of an infected patient."

Want to have a happy relationship? Make sure both partners feel they can decide on issues that are important to them. Objective power measured by income, for example, doesn't seem to play a big role, according to a new study in the "Journal of Social and Personal relationships" by the Martin Luther University Halle-Wittenberg (MLU) and the University of Bamberg. Instead, how lovers perceive power dynamics in their relationship is most important for relationship satisfaction.

Power is about being able to influence people and successfully resist the attempts of others to influence you. "It sounds like a dog-eat-dog world or the world of business. But power also plays a role in romantic relationships. The feeling of being able to make decisions in a marriage, for example, has a big influence on the quality of the relationship," says Robert Körner from the Institute of Psychology at MLU. Earlier studies show that there was rarely a balance of power within couples. Most of the time, men had more influence on decisions than women.

However, traditional gender roles have changed. "Romantic relationships have become more equal - especially in western societies," says Körner. Together with Professor Astrid Schütz, a personality researcher from the University of Bamberg, he investigated how power and the perception of power impact couples. They interviewed 181 heterosexual couples who had been living together for at least one month. The respondents were between 18 and 71 years old and had been in a relationship for an average of eight years. The team investigated how actual and perceived power influence different aspects of a relationship - such as satisfaction and commitment - and how they affect the quality of that relationship. The survey included questions about the admiration for one's partner, trust, sexual satisfaction, feelings of oppression and constraint, as well as a commitment and willingness to invest in the relationship. "We also calculated the balance of power to investigate the extent to which the traits of each partner were similar to each other," Körner explains.

The results of the study show that men still had more positional power - based on higher income and higher education. The need to make decisions in general was also stronger among the men on average. Interestingly, however, the two factors did not appear to influence the quality of the relationship that the couple experienced. The same applies to the balance of power: Even if men and women within the same couple were very similar with regard to the measured traits, no connection to relationship quality could be found. "The results surprised us, as earlier research has often suggested a direct link between the balance of power and relationship-based outcomes," says Körner.

The happiest couples were those in which both partners reported a high sense of personal power. "It appears that the subjective feeling of power and the feeling of being able to act freely significantly impact the quality of the relationship," Körner concludes. In most of these couples, both sexes stated that they were able to assert their preferences when making decisions that are important to them. According to psychologist Schütz, this is not necessarily a contradiction. "Maybe this feeling extends to different aspects of the relationship. Whereas the woman might want to decide on where to go on vacation, the husband chooses where to go for dinner. One thing to keep in mind is that our sample included rather happy couples, which favours effective negotiation. In other partnerships, there is definitely potential for conflict in this respect." However, it appears that both parties need to be able to make decisions about aspects that are important to them in order to be satisfied with the relationship.

The examined tissue does not need to be marked for this. The analysis only takes around half an hour. "This is a major step that shows that infrared imaging can be a promising methodology in future diagnostic testing and treatment prediction," says Professor Klaus Gerwert, director of PRODI. The study is published in the American Journal of Pathology on 1 July 2021.

Treatment decision by means of a genetic mutation analysis

Lung tumours are divided into various types, such as small cell lung cancer, adenocarcinoma and squamous cell carcinoma. Many rare tumour types and sub-types also exist. This diversity hampers reliable rapid diagnostic methods in everyday clinical practice. In addition to histological typing, the tumour samples also need to be comprehensively examined for certain changes at a DNA level. "Detecting one of these mutations is important key information that influences both the prognosis and further therapeutic decisions," says co-author Professor Reinhard Büttner, head of the Institute of General Pathology and Pathological Anatomy at University Hospital Cologne.

Patients with lung cancer clearly benefit when the driver mutations have previously been characterised: for instance, tumours with activating mutations in the EGFR (epidermal growth factor) gene often respond well to tyrosine kinase inhibitors, whereas non-EGFR-mutated tumours or tumours with other mutations, such as KRAS, do not respond at all to this medication. The differential diagnosis of lung cancer previously took place with immunohistochemical staining of tissue samples and a subsequent extensive genetic analysis to determine the mutation.

Fast and reliable measuring technique

The potential of infrared imaging, IR imaging for short, as a diagnostic tool to classify tissue, called label-free digital pathology, was already shown by the group led by Klaus Gerwert in previous studies. The procedure identifies cancerous tissue without prior staining or other markings and functions automatically with the aid of artificial intelligence (AI). In contrast to the methods used to determine tumour shape and mutations in tumour tissue in everyday clinical practice, which can sometimes take several days, the new procedure only takes around half an hour. In these 30 minutes, it is not only possible to ascertain whether the tissue sample contains tumour cells, but also what type of tumour it is and whether it contains a certain mutation.

Infrared spectroscopy makes genetic mutations visible

The Bochum researchers were able to verify the procedure on samples from over 200 lung cancer patients in their work. When identifying mutations, they concentrated on by far the most common lung tumour, adenocarcinoma, which accounts for over 50 per cent of tumours. Its most common genetic mutations can be determined with a sensitivity and specificity of 95 per cent compared to laborious genetic analysis. "For the first time, we were able to identify spectral markers that allow for a spatially resolved distinction between various molecular conditions in lung tumours," explains Nina Goertzen from PRODI. A single infrared spectroscopic measurement offers information about the sample which would otherwise require several time-consuming procedures.

A further step towards personalised medicine

The results once again confirm the potential of label-free digital pathology for clinical use. "To further increase reliability and promote a translation of the method as a new diagnostic tool, studies with larger patient numbers adapted to clinical needs and external testing in everyday clinical practice are required," says Dr. Frederik Großerüschkamp, IR imaging project manager. "In order to translate IR imaging into everyday clinical practice, it is crucial to shorten the measuring time, ensure simple and reliable operation of the measuring instruments, and provide answers to questions that are important and helpful both clinically and for the patients."

There are spiders that eat snakes. Observations of snake-eating spiders have been reported around the world. Two researchers from Basel and the US consolidated and analyzed over 300 reports of this unusual predation strategy.

Spiders are primarily insectivores, but they occasionally expand their menu by catching and eating small snakes. Dr. Martin Nyffeler, arachnologist at the University of Basel, and American herpetologist Professor Whitfield Gibbons of the University of Georgia, USA, got to the bottom of this phenomenon in a meta-analysis. Their findings from a study of 319 occurrences of this unusual feeding behavior recently appeared in the American Journal of Arachnology.

It turns out that spiders eat snakes on every continent except Antarctica. Eighty percent of the incidents studied were observed in the US and Australia. In Europe, on the other hand, this spider feeding behavior has been observed extremely rarely (less than 1 percent of all reported incidents) and is limited to the consumption of tiny, non-venomous snakes of the blind snake family (Typhlopidae) by small web-building spiders.

Black widows are particularly successful

Incidents of snake predation by spiders have never been reported from Switzerland. A possible explanation is that Switzerland's native colubrids and vipers are too big and heavy even when freshly hatched for Swiss spiders to subdue them.

The data analysis also showed that spiders from 11 different families are able to catch and eat snakes. "That so many different groups of spiders sometimes eat snakes is a completely novel finding," Nyffeler emphasizes.

Black widows of the family Theridiidae were the successful snake hunters in about half of all observed incidents. Their potent venom contains a toxin that specifically targets vertebrate nervous systems. These spiders build webs composed of extremely tough silk, allowing them to capture larger prey animals like lizards, frogs, mice, birds and snakes.

Big catch

Another new finding from the meta-analysis: spiders can subdue snakes from seven different families. They can outfight snakes 10 to 30 times their size.

The largest snakes caught by spiders are up to one meter in length, the smallest only about six centimeters. According to the statistical analysis done by the two researchers, the average length of captured snakes was 26 centimeters. Most of the snakes caught were very young, freshly hatched animals. That some spiders are able to subdue oversized prey is attributable to their highly potent neurotoxins and strong, tough webs.

Possible insights into the effect of spider venom

Many spider species that occasionally kill and eat snakes have venom that can also be lethal to humans. That means the venom of various spider species has a similar effect on the nervous systems of snakes and humans. For this reason, observations of vertebrate-eating spiders can also be important for neurobiology, as they allow conclusions to be drawn about the mechanisms by which spider neurotoxins affect vertebrate nervous systems.

"While the effect of black widow venom on snake nervous systems is already well researched, this kind of knowledge is largely lacking for other groups of spiders. A great deal more research is therefore needed to find out what components of venoms that specifically target vertebrate nervous systems are responsible for allowing spiders to paralyze and kill much larger snakes with a venomous bite," says Martin Nyffeler.

The captured snakes are anything but helpless themselves: about 30 percent are venomous. In the US and South America, spiders sometimes kill highly venomous rattlesnakes and coral snakes. In Australia, brown snakes (which belong to the same family as cobras) often fall prey to redback spiders (Australian black widows). Martin Nyffeler says, "These brown snakes are among the most venomous snakes in the world and it's really fascinating to see that they lose fights with spiders."

Additional information

Storage of energy reserves

When a spider catches a snake, it will often spend hours or days feasting on such a large prey. Spiders have an irregular feeding pattern. When a lot of food is available, they eat in excess, only to go hungry for long periods again afterward. They store excess food as energy reserves in their body and use it to tide them over longer periods of starvation.

Still, a spider often eats only a small part of a dead snake. Scavengers (ants, wasps, flies, molds) consume what remains.

Hotels that opened their doors to homeless people in their community during lockdown generated greater positive word-of-mouth marketing than those that offered free accommodation to frontline healthcare workers, finds new University research.

However, despite the positive impact on tourists' intentions to share the good news story, the immediate impact on intention to book a visit was the reverse, with people less inclined to book a stay at a hotel that had housed homeless people.

Researchers at the Universities of Bath and Southampton were struck by news reports of the 'heart-warming initiatives' to offer free accommodation and wanted to investigate how they compared in terms of business benefit to the tourism sector.

"Our study found that hotels that provided community support in the form of free accommodation to medical professionals had little impact on how tourists felt about them, we think because showing gratitude to healthcare workers had quickly become a social norm, said Dr Haiming Hang from Bath's School of Management.

"In contrast, the hotels that offered accommodation to homeless people really seemed to move tourists and generate a feeling of warmth and a perception of the hotel as kind and generous. Going beyond the social norm was seen as a marker of genuine concern for social welfare. The hotels were rewarded with a marked intention by tourists to spread positive word of mouth."

Previous research has identified negative public perception of homeless people in terms of cleanliness and the authors of this new study believes that this stereotype could be a factor in immediate impact on intention to book.

"If hotel management can successfully communicate how they maintain high standards of cleanliness then their community initiatives should not pose a long term risk to bookings," said Dr Zhifeng Chen at the Southampton Business School. "In the long run, positive word of mouth is very important because it can attract both prospective employees and new customers."

Reported in Tourism Management, the study is unusual in examining the impact of a hotel's community support, or corporate social responsibility, during a crisis, and focusing on initiatives aimed at the local community rather than employees or shareholders.

Local communities have been noted as crucial to the success of a hotel, partly because tourists' memorable experiences are significantly influenced by the nature of the local people they meet.

Over 450 American tourists, who intended to travel after the pandemic, took part in the research and were allocated to one of three experimental scenarios that focused on a hotel's commitment to cleanliness and its cancellation policy as its responses to COVID-19; community support through donating rooms to medical professionals; or to homeless people.

The coronavirus pandemic has had a significant impact on tourism, with the United Nations World Tourism Organization (UNWTO) estimating a contraction of the tourism sector by 20 to 30 per cent in 2020.

Corporate social responsibility in times of need: Community support during the COVID-19 pandemics is published in the journal Tourism Management: https://www.sciencedirect.com/science/article/pii/S0261517721000832

Up to 7 million people each year receive care in an emergency department (ED) for chest pain, a symptom of a potential heart condition. Over 80 percent of chest pain patients, however, ultimately have no evidence of cardiovascular disease or acute coronary syndrome. To disincentivize patients from over-utilizing costly care, insurers and employers are increasingly opting for high-deductible health plans (HDHPs) that require significant out-of-pocket spending before coverage begins. Researchers from Brigham and Women's Hospital and Harvard Pilgrim Health Care Institute investigated whether switching to an HDHP influenced the frequency of ED visits and hospitalizations for chest pain. Their findings, published in Circulation, report a 4.3 percent decrease in ED visits for chest pain and an 11.3 percent decrease in visits that led to inpatient hospitalization based on the initial ED evaluation. Low-income patients were particularly less likely to visit the ED for chest pain and subsequently more likely to be hospitalized with a serious heart condition.

"Our research, along with past studies, has shown that lower-income patients disproportionately suffer from delays in care and worse clinical outcomes," said corresponding author Shih-Chuan Chou, MD, MPH, SM, of the Department of Emergency Medicine at the Brigham. "Low-income patients need the most attention if employers or insurers are to expand the use of high-deductible plans."

In their study, the researchers used a national medical insurer database to identify more than a half a million patients aged 19-63 whose employers offered only low-deductible health plans (requiring less than $500/year of out-of-pocket spending) before mandating enrollment in an HDHP (greater than $1,000/year) the next year. A control group of nearly 6 million employees included those enrolled in a low-deductible health plan for two straight years.

The researchers did not observe significant differences in cardiac testing after ED admission between low- and high-deductible groups. However, HDHP patients living in neighborhoods with higher poverty rates had a 29.4 percent higher rate of heart attack hospitalization 30 days after their initial ED diagnosis of chest pain, compared to those with addresses in other neighborhoods.

"At the clinician level, our research certainly demonstrates that it is quite important for clinicians to be aware of patients' out-of-pocket costs, as high burdens may indicate that a patient has likely deferred care and may suffer worse outcomes," Chou said.

With 57 percent of U.S. employees enrolled in HDHPs for single coverage in 2020, the researchers emphasize that when evaluating ED patients with chest pain, particularly low-income patients with HDHPs, clinicians should account for possible delays in care preceding the patients' presentation. Going forward, the researchers hope to examine whether HDHPs are associated with patient outcomes for significant medical emergencies, such as heart attack, while also exploring on a deeper level how out-of-pocket spending influences patient-clinician interactions and discussions about testing or treatment.

"Potential solutions may be to ameliorate financial burden by funding health savings accounts, or to keep out-of-pocket costs proportional to patients' incomes," said Chou.

The exoplanet satellite hunter CHEOPS of the European Space Agency (ESA), in which the Instituto de Astrofísica de Canarias (IAC) is participating along with other European institutions, has unexpectedly detected a third planet passing in front of its star while it was exploring two previously known planets around the same star. This transit, according to researchers, will reveal exciting details about a strange planet "without a known equivalent".

The discovery is one of the first results of CHEOPS (CHaracterising ExOPlanet Satellite) and the first time that an exoplanet has been seen with a period longer than 100 days transiting a star which is sufficiently bright to be seen with the naked eye. The discovery was published today in the journal Nature Astronomy.

This bright star similar to the sun, called Nu2 Lupi, is a little more than 50 light years from Earth, in the constellation of Lupus. In 2019, HARPS (High Accuracy Radial velocity Planet Searcher) of the European Southern Observatory (ESO) in Chile discovered three exoplanets in this system (called b, c, and d) with masses between those of the Earth and Neptune, and with orbital periods of 11.6, 27.6 and 107.6 days respectively. Afterwards NASA's TESS satellite, designed to detect transiting planets, found that the two interior planets, b and c, transit Nu2 Lupi, making it one of the only three naked eye stars which have more than one transiting planet.

"Transiting systems such as Nu2 Lupi are of great importance in our understanding of how planets form and evolve, because we can compare several planets around the same bright star in detail", explains Laetitia Delrez, a researcher at the University of Liege (Belgium) and first author of the article.

"Our idea was to follow up previous studies of Nu2 Lupi and to observe planets b and c passing in front of Nu2 Lupi with CHEOPS, but during a transit of planet c we were amazed to see an unexpected transit of planet d, which is further out within the system", she adds.

Transits of planets give a valuable opportunity to study their atmospheres, their orbits, their sizes and their compositions. A transiting planet block out a tiny but detectable proportion of the light of its star when it passes in front of it, and it was this tiny drop in the light which led the researchers to their discovery. Because exoplanets with long periods orbit far away from their stars, the possibility of detecting a planet during transit is very small indeed, which makes the finding with CHEOPS a real surprise.

Using the high precision techniques of CHEOPS planet d was found to have some 2.5 times the radius of the Earth, and its orbital period around its star of a little over 107 days, was confirmed. In addition, using archive observations from terrestrial telescopes its mass could be estimated at 8.8 times that of the Earth.

"The amount of radiation from the star which falls onto planet d is quite small compared to many other known exoplanets. If it were in our own solar system Nu2 Lupi d would orbit between Mercury and Venus", says Mahmoudreza Oshagh, a senior postdoctoral researcher at the IAC, and a co-author of the paper. "Combined with its bright parent star, its long orbital period and its ideal situation for follow-up, this means that planet d is very exciting: it is an exceptional object, with no known equivalent, and it will certainly be a fundamental object for future studies".

The majority of long period transiting exoplanets discovered until now are orbiting stars which are too faint to allow detailed follow-up observations, which means that we know little about their properties. Nu2 Lupi is, however, sufficiently bright to be an attractive object for other powerful space telescopes such as the NASA/ESA Hubble Space Telescope, the future James Webb Space Telescope, as well as major observatories on the ground. "Given its general properties and its orbit, planet d will be an exceptionally favourable objective to study an exoplanet with a moderate atmospheric temperature around a star similar to the Sun", adds Laetitia Delrez.

Combining the new data from CHEOPS with archive data from other observatories, the researchers found that planet b is mainly rocky, while planets c and d appear to have large quantities of water surrounded by hydrogen and helium gas. In fact, planets c and d contain much more water than the Earth, a quarter of the mass of each of them is water, in comparison with less than 0.1% on Earth. But this water is not liquid, it is high pressure ice, or high temperature water vapour.

"Although none of these planets would be habitable, their diversity makes the system very exciting and a great future perspective to show how these bodies formed and how they have changed with time", explains Enric Pallé, an IAC researcher and a co-author of the article. "We can also look for rings or moons within the Nu2 Lupi system, because the extreme accuracy and stability of CHEOPS could allow us to detect bodies close to the size of Mars".

CHEOPS is designed to gather high precision data of individual stars known to harbour planets, rather than to make a more general survey of possible exoplanets around many stars. This approach and accuracy are proving exceptionally useful to understand the planetary systems around the stars around us.

"These exciting results show, yet again, the major potential of this satellite", says Enric Pallé. CHEOPS will not only give us a better understanding of known exoplanets, but as shown by this result and others in the initial phase of the mission, it will enable us to discover new ones, and to reveal their secrets".

HOUSTON - (June 28, 2021) - Rice University computer scientists are sending RAMBO to rescue genomic researchers who sometimes wait days or weeks for search results from enormous DNA databases.

DNA sequencing is so popular, genomic datasets are doubling in size every two years, and the tools to search the data haven't kept pace. Researchers who compare DNA across genomes or study the evolution of organisms like the virus that causes COVID-19 often wait weeks for software to index large, "metagenomic" databases, which get bigger every month and are now measured in petabytes.

RAMBO, which is short for "repeated and merged bloom filter," is a new method that can cut indexing times for such databases from weeks to hours and search times from hours to seconds. Rice University computer scientists presented RAMBO last week at the Association for Computing Machinery data science conference SIGMOD 2021.

"Querying millions of DNA sequences against a large database with traditional approaches can take several hours on a large compute cluster and can take several weeks on a single server," said RAMBO co-creator Todd Treangen, a Rice computer scientist whose lab specializes in metagenomics. "Reducing database indexing times, in addition to query times, is crucially important as the size of genomic databases are continuing to grow at an incredible pace."

To solve the problem, Treangen teamed with Rice computer scientist Anshumali Shrivastava, who specializes in creating algorithms that make big data and machine learning faster and more scalable, and graduate students Gaurav Gupta and Minghao Yan, co-lead authors of the peer-reviewed conference paper on RAMBO.

RAMBO uses a data structure that has a significantly faster query time than state-of-the-art genome indexing methods as well as other advantages like ease of parallelization, a zero false-negative rate and a low false-positive rate.

"The search time of RAMBO is up to 35 times faster than existing methods," said Gupta, a doctoral student in electrical and computer engineering. In experiments using a 170-terabyte dataset of microbial genomes, Gupta said RAMBO reduced indexing times from "six weeks on a sophisticated, dedicated cluster to nine hours on a shared commodity cluster."

Yan, a master's student in computer science, said, "On this huge archive, RAMBO can search for a gene sequence in a couple of milliseconds, even sub-milliseconds using a standard server of 100 machines."

RAMBO improves on the performance of Bloom filters, a half-century-old search technique that has been applied to genomic sequence search in a number of previous studies. RAMBO improves on earlier Bloom filter methods for genomic search by employing a probabilistic data structure known as a count-min sketch that "leads to a better query time and memory trade-off" than earlier methods, and "beats the current baselines by achieving a very robust, low-memory and ultrafast indexing data structure," the authors wrote in the study.

Gupta and Yan said RAMBO has the potential to democratize genomic search by making it possible for almost any lab to quickly and inexpensively search huge genomic archives with off-the-shelf computers.

"RAMBO could decrease the wait time for tons of investigations in bioinformatics, such as searching for the presence of SARS-CoV-2 in wastewater metagenomes across the globe," Yan said. "RAMBO could become instrumental in the study of cancer genomics and bacterial genome evolution, for example."

A connective tissue protein known to support the framework of organs also encourages immune responses that fight bacterial infections, while restraining responses that can be deadly in the condition called sepsis, a new study finds.

Led by researchers from NYU Grossman School of Medicine, the work revolves around the extracellular matrix (ECM) of connective tissues, once thought of as an inert framework that shapes bodily compartments, but increasingly recognized as a signaling partner with nearby cells in normal function, and a contributor to disease when signals go awry. Among the key players in the ECM are fibroblasts, the cells that make tough structural matrix proteins like collagen.

Published online June 28 in the Proceedings of the National Academy of Sciences, the new analysis found that lumican, a protein-sugar combination (proteoglycan) secreted by fibroblasts, and known to partner with collagen in connective tissues, also promotes immune system responses in immune cells called macrophages that fight bacterial infections. At the same time, the study found that lumican protects tissues by restraining a different type of immune response that reacts to DNA, whether from an invading virus, or from human cells that spill their DNA as they die (a signal that tissues are under stress).

Such inflammatory responses represent as a transition into healing, but grow too big in sepsis, damaging the body's own tissues to the point of organ failure. Sepsis affects 48.9 million people worldwide, the authors say, but the role of the ECM in the condition is largely unknown.

"Lumican may have a dual protective role in ECM tissues, promoting defense against bacteria on the one hand, and on the other, limiting immune overreactions to DNA that cause self-attack, or autoimmunity," says corresponding study author Shukti Chakravarti, PhD, professor in the departments of Ophthalmology and Pathology at NYU Langone Health.

The findings suggest that connective tissue, and extracellular matrix proteins like lumican, operate outside of cells normally, but as disease or damage break down ECM, get sucked into and regulate immune cells homing in on the damage.

Maintaining the Balance

Lumican happens to interact with two proteins on surfaces of immune cells that control the activity of proteins called toll-like receptors known to recognize structural patterns common to molecules made by invading microbes, say the study authors. Because they are less specific than other parts of the immune system, toll-like receptors can also cause attacks by immune cells on the body's own tissues if over-activated.

The current study authors found that lumican promotes the ability of toll-like receptor (TLR)-4 on the surfaces of immune cells to recognize bacterial cell-wall toxins called lipopolysaccharides (LPS). Specifically, the study found that lumican, by attaching to two proteins, CD14 and Caveolin1, likely using regions normally covered by collagen, stabilizes their interactions with TLR4 to increase its ability to react to LPS. This in turn leads to production of TNF alpha, a signaling protein that amplifies immune responses.

Along with describing the effect of lumican on the surfaces of immune cells, the new study finds that lumican is taken up from outside cells into membrane-bound pouches called endosomes, and pulled into cells. Such compartments deliver ingested bacteria to other endosomes that destroy them, or heighten inflammation or protective interferon responses. Once pulled inside, the researchers found, lumican bolstered TLR4 activity by slowing down its passage into lysosomes, pockets where such proteins are broken down and recycled.

While it encouraged TLR4 activity on cell surfaces, lumican, once inside immune cells, had the opposite effect on toll-like receptor 9 (TLR9), which is known react to DNA instead of bacterial LPS. Experiments showed that lumican's binding of DNA in endosomes keeps it away from, and prevents it from activating, TLR9.

Experiments confirmed that mice engineered to lack the gene for lumican have trouble both fighting off bacterial infections (less cytokine response, slower clearance, greater weight loss), and trouble restraining the immune overreaction to bacteria (sepsis). The study authors also found elevated lumican levels in human sepsis patients' blood plasma, and that human immune cells (blood monocytes) treated with lumican had elevated TLR4 activity, but suppressed TLR9 responses.

"As an influencer of both processes, lumican-based peptides could be used as a lever, to tweak inflammation related to TNF-alpha, or endosomal interferon responses, to better resolve inflammation and infections," says George Maiti, PhD, a post-doctoral fellow in Chakravarti's lab. "Our results argue for a new role for ECM proteins at sites of injury. Taken up by incoming immune cells it shapes immune responses beyond the cell surface by regulating the movement and interaction of endosomal receptors and signaling partners," says

India and Pakistan have fought four wars in the past few decades, but when India faced an oxygen shortage in its hospitals during its recent COVID-19 surge, Pakistan offered to help.

On Twitter, hashtags like #IndiaNeedsOxygen and #PakistanStandsWithIndia trended. Finding these positive tweets, however, was not as easy as simply browsing the supportive hashtags or looking at the most popular posts. Negative tweets often hijack the supportive hashtags for trolling or fighting with other users. And Twitter's algorithm isn't tuned to surface the most positive tweets during a crisis.

Ashique KhudaBukhsh of Carnegie Mellon University's Language Technologies Institute led a team of researchers who used machine learning to identify supportive tweets from Pakistan during India's COVID crisis. In the throes of a public health crisis, words of hope can be welcome medicine.

"When a country is experiencing a national health crisis, the more supportive messages you see, the better," KhudaBukhsh said. "If you're just randomly searching, you'll find positive tweets about 44% of the time. Our method gives a person positive tweets 83% of the time. That person will have to do a lot less work to find the supportive tweets."

By combining existing language classifiers -- algorithms trained by machine learning that determine, for example, whether speech is positive or negative, hopeful or distressing -- the team developed a system that identified supportive or positive Pakistani tweets about India 83% of the time, far better than existing methods. The team used their method to conclude that more than 85% of the tweets posted about the COVID crisis in India from Pakistan were supportive.

"We have boundaries but not in our hearts," one tweet detected by the team began.

The team included KhudaBukhsh, Clay H. Yoo and Rupak Sarkar from the LTI and Shriphani Palakodety, an engineer the blockchain and AI company Onai who earned his master's from the LTI. They published their results in a paper titled, "Empathy and Hope: Resource Transfer To Model Inter-country Social Media Dynamics," which was accepted into the ACL Association for Computational Linguists Workshop on Natural Language Processing for Positive Impact. The work was performed in real-time with the crisis and as members of the team worried about the health of loved ones in India.

The research is significant on several fronts. First, the team showed that existing language classifiers could be useful in broad contexts. This is important because to deploy a classifier that will be useful in the middle of the crisis, it must be built quickly. It cannot be built from scratch, and the team wanted to see if existing research into language classifiers could help.

To detect supportive tweets during India's COVID crisis, the team used a hope-speech classifier that KhudaBukhsh and Palakodety built with the late Jaime Carbonell, a distinguished professor in the School of Computer Science who founded the LTI, to identify positive YouTube comments on videos posted about the 2019 escalation of conflict between India and Pakistan over Kashmir. The team then combined the hope-speech classifier with a known empathy-distress classifier.

Despite these two language classifiers being built for different reasons and trained on different data, they effectively detected positive tweets during India's COVID surge.

"We showed that there is some sort of universality in how we express emotions," KhudaBukhsh said. "And we showed that we can use existing solutions, combine them and attack future crises quickly.

The research was also potentially significant to the crisis in India. KhudaBukhsh and Carbonell envisioned the hope-speech classifier as an alternative way to combat hate speech. Instead of detecting and deleting, downplaying or blocking hate speech -- which exists in droves on the internet -- the pair sought to use their hope-speech classifier to identify and amplify supportive messages. People are influenced by what they see and read, and if hopeful messages are put in front of them rather than hateful ones, it could affect how they think and act.

The team identified tweets that offered prayers to India, spoke to the common humanity of two countries, and sent love.

"Heartbreaking to see this situation in our neighbourhood. Send love and prayers from Pakistan. May Almighty Allah help humanity through this pandemic. Stay strong. Stay safe," a tweet found by the team read.

Emphasizing the support between India and Pakistan could make a difference, KhudaBukhsh said. And since so many fights now happen over the internet, maybe that's the place to start.

"These two countries have such an acrimonious past," KhudaBukhsh said. "Any positive behavior from either side can help promote world peace."

Public opinion surveys could be used more widely to understand regional variation in vaccine hesitancy, experts have recommended.

The research shows vaccine uptake rates for childhood vaccines are significantly lower in regions where hesitancy observed in mass public opinion surveys is more pronounced.

This data is often not widely available, which makes it challenging for experts to analyse the links between attitudes and real-world behaviour. The study says this data should be used by public health officials to understand where vaccines are more likely to be rejected, and who should be the target of information campaigns.

The research published in the journal Vaccine, was carried out by Dr Florian Stoeckel and Professor Jason Reifler from the University of Exeter, Professor Ben Lyons from the University of Utah and Charlie Carter from the London School of Economics.

They analysed regional level data for the EU from 2019 for the uptake of various childhood vaccines in 177 regions of 20 European countries - DTP3 (diphtheria, tetanus toxoids, and pertussis), MCV1 (the first dose of the measles-containing vaccine), and MCV2 (second dose of the measles vaccine) for 2019. Data on vaccine hesitancy was taken from the Eurobarometer survey of Spring 2019, which included about 1,000 respondents from each EU country except for Luxembourg, Cyprus, and Malta, where about 500 individuals were interviewed.

Dr Stoeckel said: "Our analysis shows public opinion surveys can play a valuable role in public health as a tool to understand immunization behaviour. It is currently high time for more opinion surveys on citizens' attitudes towards vaccines. Assessing the link between survey responses and actual uptake is important, because public opinion survey data on vaccine hesitancy is only useful if it is in fact related to behaviour."

"We found statistically significantly lower regional vaccine immunization rates in regions where vaccine hesitancy is more pronounced. Surveys can be used to observe where vaccine uptake is likely to be low (when vaccine uptake data is incomplete) and to learn from regions with high uptake (despite high vaccine hesitancy) so that best practices could be applied elsewhere."

Vaccine uptake for the childhood vaccines that we examined differs both between countries and within countries. Most national uptake rates of the childhood vaccines examined are above 90 percent. For instance, average national level uptake of the MCV1 vaccine varies between 85.94 percent in Cyprus and 99.87 percent in Hungary. However, there is a considerable amount of variation within countries. Uptake of MCV1 in Croatia ranges from 73.24 percent to 98.38 percent.

The analysis shows average country level vaccine hesitancy is lowest in Denmark and highest in Latvia. The least vaccine hesitant sub-national region in Latvia is more vaccinate hesitant than the most vaccine-hesitant region in Denmark.

An incredibly rare hybrid warbler with mismatched color patterns has allowed researchers to disentangle the genetic drivers of two traits that usually come as a package deal--the black face mask and the black throat patch in blue-winged and golden-winged warblers. A new study describing the peculiar bird and pinpointing the location in the genome that controls the face mask and throat patch appears online in the journal Ecology.

"Golden-winged warblers have both a black face mask and a black throat patch, while blue-winged warblers have neither," said Marcella Baiz, postdoctoral researcher at Penn State and first author of the study. "When individuals of each species mate with each other, almost all of their hybrid offspring have matched traits, so both black plumage traits are present or both are absent. But we captured this very weird bird that looks almost entirely like a golden-winged warbler but is missing the black throat patch."

The researchers believe this unique combination occurs in less than 0.5% of the hybrid warblers. To their knowledge, this type of hybrid had been previously documented only once in a bird that was collected in 1934 and described in 1951 from a museum collection.

"We originally found this bird thanks to a tip from a local birder who works at Shaver's Creek Environmental Center," said David Toews, professor of biology at Penn State and an author of the study. "He suggested that a nearby area seemed like good warbler habitat and also uploaded observations of warblers onto the app eBird, which scientists can use in their research. We went to scout the location when we spotted this unique and exciting bird. We carefully captured the bird so we could document its plumage, took a blood sample so we could sequence its genome, and then released it."

In a previous study, the researchers sequenced the genomes of blue- and golden-winged warblers and their hybrids and identified a small region that drives the black coloration in these birds upstream of the Agouti-signaling protein (ASIP) gene. But because the two traits are almost always inherited together, it was unclear if ASIP regulated the traits together or separately.

"Because we already had genome sequencing data from the parent species and hybrids with the matched face and throat color, sequencing the genome of the mismatched bird allowed us to separate out the genetic regions underlying the face mask versus the throat patch," said Baiz.

The team confirmed that the previously identified region is connected to the black throat patch, and also identified a new location--nearby, but further upstream in the genome--that they believe is connected to the black face mask. For black pigment to occur in these birds, the two copies (one on each chromosome) must have originally come from the golden-winged warbler, suggesting that these are "recessive" traits. Having one or both copies from the blue-winged warbler in these spots results in no face mask or throat patch.

"More than a hundred years ago, a biologist named John Treadwell Nichols hypothesized that the black throat coloration was a recessive trait," said Toews. "Later, when Kenneth Parkes described the rare hybrid in 1951, he suggested that if throat and mask color were controlled separately, they would need to be linked in some way or located very close together on the genome. Parkes described his theory as a 'genetic problem for future study,' and we were able to confirm both theories using modern genetic tools."

The researchers suggest that the locations they identified might be located within two separate promoter regions for the ASIP gene, which turn the gene on or off in different contexts. Because they are located so close to each other on the chromosome, the promoters would usually be inherited together--even if genetic material is shuffled between chromosomes during reproduction--which would explain why most hybrids carry both or neither of these black plumage traits. The mismatched bird, however, was likely a result of an extremely rare instance where this was not the case, followed by several generations of backcrossing with golden-winged warblers.

"If coloration genes in warblers have a similar genetic architecture, with multiple promoters controlling where pigment is deposited, it's easy to see how just a few mutations could produce a variety of different color patterns among these songbird species," said Baiz. "This may help explain why there are so many different species of warblers with such a diversity of colors."

Because a warbler's coloration is an important cue for behaviors like mating, it is possible there are implications of the mismatched hybrid bearing only one of the traits. For example, it may be attractive to females of both species because it has qualities of both, or to neither. The researchers hope to observe this bird in the future and determine if it has a mate, and future research linking plumage traits to reproductive success would clarify these implications.

"We have now observed this bird two years in a row, so it has survived at least two migration events," said Toews. "This study and the story of how we found this bird is an excellent example of how birders and citizen scientists can make a real difference in research."

WASHINGTON, D.C.--A new study in Annals of Emergency Medicine highlights the importance of protecting physician residents--early-career doctors still in training--and emergency care teams from incidents of physical or verbal abuse.

The survey of 123 physicians, residents, and staff in one emergency department found that 78 percent of all health care workers experienced a violent assault in the prior 12 months, including more than one in five (22 percent) emergency physician residents. Eighty-nine percent of residents experienced verbal assault by a patient in the prior 12 months, compared to 80 percent of other health care workers.

"Violent or threatening incidents in the emergency department pose risks to everyone's safety but can also impact health workers' mental health and may increase the likelihood of burnout," said Lauren Querin, MD, MS, lead author and emergency physician with the University of North Carolina (UNC) Chapel Hill Department of Emergency Medicine. "These encounters happen frequently and often go unreported."

Of the total respondents who experienced physical assault or violence, 19 percent did not discuss the incident with anyone. About half (53 percent) only discussed the incident with colleagues while only 20 percent filed a formal incident report with the hospital or police. Among residents, 96 percent discussed incidents with only a colleague or no one at all. None of the residents filed formal reports.

Residents' experience with assault became more common with time in the program, the analysis shows. Sixty-two percent of first year residents and 100 percent of second- and third-year residents experienced verbal assault. While no first-year residents reported a physical assault, 25 percent of second-year residents and 36 percent of third-year residents indicated that they have been physically assaulted.

"More can be done to make sure that every member of the emergency care team can prioritize patient care rather than worrying about their own safety at work," said RJ Sontag, MD, president of the Emergency Medicine Residents' Association (EMRA). "This study looks at one emergency department but stories like these are common nationwide. We must empower residents and others to report these incidents and take the necessary steps to protect health care workers and patients."

Only 24 percent of the residents believe that workplace violence protocols in place at their facility are adequate while 30 percent do not think the protections are sufficient and 38 percent were unsure. Eight percent were not certain what the protocols were.

Anonymous firsthand accounts of violence, sexual assault, or personal threats are detailed in the analysis:

One resident reported that a patient being discharged threatened to "come find me and shoot me in the kneecaps."

Another resident commented, "I was not only scared for myself and other staff...but also scared regarding the injuries the patient would sustain and I would need to treat."

This qualitative analysis echoes findings from a 2018 poll of more than 3,500 emergency physicians across the nation from the American College of Emergency Physicians (ACEP). ACEP is leading efforts with physicians, hospitals, care teams, regulators, and policymakers to address violence in the emergency department, including extensive work to support the introduction of the "Workplace Violence Prevention for Health Care and Social Service Workers Act of 2021," by Rep. Joe Courtney (D-CT) and a bipartisan coalition in the House of Representatives.

For its members, ACEP offers education, training, and advocacy opportunities aimed at curbing violence in the emergency department. The association also launched "No Silence on ED Violence," a campaign with the Emergency Nurses Association (ENA) that gives those impacted a chance to share stories and increase awareness of workplace violence while providing resources and a peer network that supports emergency nurses and physicians.

Philadelphia, June 28, 2021--Researchers at Children's Hospital of Philadelphia (CHOP) have discovered that a specific type of lung cell exhibits unconventional immune properties and may contribute to the outcome of respiratory viral infections. The researchers focused on type II alveolar (AT2) cells, which are non-immune cells of the lung that are critical for basic lung health and tissue repair after lung injury. They found that AT2 cells express high levels of major histocompatibility complex II (MHC-II), an important immune system trigger, and that AT2 MHC-II expression appears to confer an appreciable advantage in the outcome of respiratory viral infection. The findings were published today in Nature Communications.

"This study shows that MHC-II expression is regulated in a unique way in AT2 cells, which has important implications for the health of lungs when faced with infection," said senior author Laurence Eisenlohr, VMD, PhD, investigator and Professor of Pathology and Laboratory Medicine at CHOP. "Future research should explore whether alterations in AT2 MHC-II expression or function contribute to the wide variation in outcome of lung diseases in humans, particularly SARS-CoV-2 infection, as AT2s are a major cell type infected with this virus in the human lung."

MHC-II triggers an immune cascade that activates helper T cells, which in turn drive B cells, cytotoxic T cells and other important immune cells required to fight an infection. The sequence begins when a peptide from the infectious pathogen connects with MHC-II protein, and that complex is presented on the surface of the cell, a process known as "antigen presentation." Historically, only certain types of specialized immune cells, termed "professional antigen presenting cells," have been shown to express MHC-II at steady state, including B cells, dendritic cells, and macrophages; other cells outside of the immune system are thought to express MHC-II only when inflammation is present, such as during an infection. However, recent research has shown that some of these other "non-immune" cell types, including AT2s, can also express MHC-II under normal conditions as well, and this is thought to be driven by small amounts of inflammation that are still present even at homeostasis.

AT2 cells are epithelial cells in the lung parenchyma that produce surfactant and promote cell renewal. Previous studies of AT2 MHC-II expression and function have varied widely, and as a result, researchers have not fully understood how well AT2 cells express MHC-II, what triggers AT2 MHC-II expression, and how AT2 MHC-II functions in lung immunity both at baseline and during lung infection.

To better understand the role of AT2 MHC-II, the researchers analyzed mouse and human AT2 cells and found that despite being non-immune cells, AT2s express MHC-II uniformly and to high levels under normal conditions, at levels similar to the "professional antigen presenting cells." They also found that in AT2 cells, MHC-II expression is activated independently of the inflammation cascade that is thought to set the complex into action in essentially all other non-immune cells, suggesting it is triggered in AT2s by unique mechanisms.

Given the role of MHC-II in initiating an immune response, the researchers examined the role of AT2 MHC-II in protecting the lungs from respiratory disease. To test this, the researchers generated mice with an AT2-specific deletion of MHC-II. Under normal conditions, the health of the mice did not seem to be affected by the deletion of MHC-II; they did not develop spontaneous respiratory disease and the lung tissue was comparably healthy to mice with functional AT2 MHC-II, leading researchers to conclude that MHC-II does not seem to be required for effective surfactant production or lung regeneration, or lung immunity at homeostasis. However, when the mice were exposed to influenza A virus and Sendai virus, the mice with MHC-II deletions had higher morbidity and mortality than those with intact MHC-II, implying that it does contribute to improved outcomes during lung infection.

Although loss of AT2 MHC-II worsened respiratory virus disease, the effect was smaller than the researchers had anticipated based on the abundance of AT2 cells in the lung and the magnitude of AT2 MHC-II expression. Surmising this might be a result of a limitation in the actual function of MHC-II on AT2 cells, the researchers examined the ability of AT2 cells to present infectious and non-infectious antigens via MHC-II to stimulate other immune cells. They found that AT2 cells are capable of presenting antigen via MHC-II and that this is enhanced in the setting of inflammation, but compared to the specialized "professional antigen presenting cells," AT2 cells exhibit very limited antigen presentation capacity.

"Although future studies will need to explore the reasons why this combination of high MHC-II expression but limited antigen presentation occurs in AT2 cells, we propose that this is actually part of a carefully balanced system in the lung, where excessive T cell activation would be especially damaging," Eisenlohr said. "We propose that high MHC-II expression by AT2s allows them to participate in immune responses, but restrained MHC-II antigen presentation establishes a higher threshold that must be overcome in order to for them to activate the immune system, allowing for AT2s to contribute in a more tempered manner. This way, MHC-II presentation by AT2s would only trigger T cell activation in the setting of high antigen burden, such as a severe lung infection, but would prevent AT2-induced amplification of T cells in response to low levels of inhaled innocuous environmental antigens."

The use of transparent masks during communication increases comprehension of speech by about 10% for people with hearing loss and people with normal hearing, according to a study published in the journal Ear and Hearing.

The study was conducted at the University of Texas in Dallas (USA), with the participation of Regina Tangerino, a professor at the University of São Paulo's Bauru Dental School (FOB-USP) in Brazil, and with support from São Paulo Research Foundation - FAPESP.

"Our findings show that wearing a transparent mask can facilitate communication for everyone, minimizing stress and improving interaction. Protection obviously has to be the primary concern, and no clear models with proven effectiveness are sold in Brazil right now," Tangerino told.

In the US, she explained, two models of mask with a see-through portion in the mouth area have been approved by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC). "One of our aims is calling attention to the importance of the topic," she said.

The study began early in the pandemic, in 2020, when the group posted on the internet a set of videos lasting 40 minutes, with Tangerino voicing several utterances against background noise without a mask, wearing a mask with a clear mouth panel, and wearing an opaque fabric mask.

The study used 154 volunteers recruited via social media or by email. They were divided into three groups based on whether they had normal hearing, or confirmed or suspected hearing loss (with or without cochlear implants or hearing aids). They were invited to watch the videos in a quiet place and to type what they understood after each sentence. They also had to rate their level of confidence in responding and how intensely they had to concentrate to understand what was said. Each volunteer's score was computed at the end.

On average, the volunteers in all three groups correctly understood 83.8% of the sentences spoken without a mask, 68.9% of utterances with a see-through mask, and 58.9% with an opaque mask.

"The difference of 10 percentage points [between the latter two averages] is statistically significant. This benefit applies to more than just comprehension: the participants also felt more self-confident and were able to follow what was said with less effort when the see-through mask was used," Tangerino said. "In another study, conducted in the UK with 460 participants, the researchers noted that opaque masks influenced fatigue, anxiety and emotions in both listeners and speakers."

Visual cues

To find out if the difference in comprehension between transparent and opaque masks was due to visual cues such as lip reading, acoustic differences between the recordings, or the tendency for some masks to muffle sound, a follow-up study using audio only was conducted with 29 volunteers, who were not told which sentences were recorded with or without a mask.

"In this case, the average performance was actually worse for sentences spoken with a clear mask than with an opaque mask, confirming the significance of visual cues in the first study. They helped listeners surmount the problem of muffled sound when a mask is worn," Tangerino said.

Production of transparent masks certified by ANVISA, the national health surveillance agency, should be stimulated in Brazil, she added. Currently, the only see-through type available is a vinyl mask, considered insufficiently effective to block transmission of the novel coronavirus.