Culture

An international team of interdisciplinary researchers has identified mathematical metrics to characterize the fragility of financial markets. Their paper "Network geometry and market instability" sheds light on the higher-order architecture of financial systems and allows analysts to identify systemic risks like market bubbles or crashes.

With the recent rush of small investors into so-called meme stocks and reemerging interest in cryptocurrencies talk of market instability, rising volatility, and bursting bubbles is surging. However, "traditional economic theories cannot foresee events like the US subprime mortgage collapse of 2007" according to study author Areejit Samal. He and his colleagues from more than ten mathematics, physics, economics, and complex systems focused institutions around the globe have made a great stride in characterizing stock market instability.

Their paper abstracts the complexity of the financial market into a network of stocks and employs geometry-inspired network measures to gauge market fragility and financial dynamics. They analyzed and contrasted the stock market networks for the USA S&P500 and the Japanese Nikkei-225 indices for a 32-year period (1985-2016) and for the first time were able to show that several discrete Ricci curvatures are excellent indicators of market instabilities. The work was recently published in the Royal Society Open Science journal and allows analysts to distinguish between 'business-as-usual' periods and times of fragility like bubbles or market crashes.

The network created by connecting stocks with highly correlated prices and trading volumes forms the structural basis of their work. The researchers then employ four discrete curvatures, developed by the director of Max Planck Institute for Mathematics in the Sciences Jürgen Jost and his coworkers, to study the changes in the structure of stock market networks over time. Their comparisons to other market stability metrics have shown that their four notions of curvature serve as generic indicators of market instability.

One curvature candidate, the Forman-Ricci curvature (FRE), has a particularly high correlation with traditional financial indicators and can accurately capture market fear (volatility) and fragility (risk). Their study confirms that in normal trading periods the market is very fragmented, whereas in times of bubbles and impending market crashes correlations between stocks become more uniform and highly interconnected. The FRE is sensitive to both sector-driven and global market fluctuations and whereas common indicators like the returns remain inconspicuous, network curvatures expose these dynamics and reach extreme values during a bubble. Thus, the FRE can capture the interdependencies within and between sectors that facilitate the spreading of perturbations and increase the danger of market crashes.

Max Planck Institute for Mathematics in the Sciences director Jürgen Jost summarizes the struggle of analyzing market fragility: "there are no easy definitions of a market crash or bubble and merely monitoring established market indices or log-returns does not suffice, but our methodology offers a powerful tool for continuously scanning market risk and thus the health of the financial system". The insights gained by this study can help decision-makers to better understand systemic risk and identify tipping points, which can potentially forecast coming financial crises or possibly even avoid them altogether.

Igor Stagljar made his career building molecular tools to combat cancer. But when the pandemic hit last March, he aimed his expertise at a new adversary, SARS-CoV-2.

Stagljar is a professor of biochemistry and molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research at U of T's Temerty Faculty of Medicine. Last spring, with support from U of T's Toronto COVID-19 Action Fund, his team began developing a new method for measuring immunity to coronavirus in those who recovered from COVID-19.

They are now ready to reveal their creation -- a pinprick test that accurately measures in under one hour concentration of coronavirus antibodies in blood. And it's cheap, costing a toonie or about tenth of the cost of the market gold standard.

Their method has been published in a study out today in the journal Nature Communications.

"Our assay is as sensitive, if not better than any other currently available assay in detecting low levels of IgG antibodies, and its specificity, also known as false-positive rate, is as good as the best antibody test on the market," said Stagljar who collaborated with public health agencies and blood banks from across Canada to have the test validated on blood samples taken from former COVID-19 patients.

Serological tests detect antibodies, protein molecules in blood that recognize and neutralize Sars-CoV-2 to prevent infection. Such tests are seen as a key tool for public health experts wanting to measure population immunity to be better able to manage the ongoing pandemic.

According to a January report by the national COVID Immunity Task Force, the majority of Canadians remain vulnerable to coronavirus infection with less than two percent testing positive for antibodies.

Population level studies can also help reveal duration of coronavirus immunity across patients who had different experiences of disease, from asymptomatic to severe. They also have the potential to reveal threshold antibody level required for protection after natural infection and vaccination.

"That level is still to be determined, but we do know that people who have been infected with SARS-CoV-2 have very diverse levels of antibodies, and it would not be surprising to find that below some baseline level they might not be protective," said Zhong Yao, senior research associate in Stagljar's lab and coinventor of the testing method.

Several serological tests have received regulatory approval with ELISA-based methods as the gold standard when it comes to measuring antibody concentration as a strength of individual immune response. But it comprises several laboratory steps that take six hours to complete, making it unsuitable for rapid diagnostics. Simpler methods using test strips, similar to pregnancy tests, provide fast results but are not quantitative and are less reliable.

The new method is called SATiN, for Serological Assay based on split Tripart Nanoluciferase. It is the first COVID-19 serology test that uses highly sensitive protein complementation chemistry in which a light-emitting luciferase protein is reconstituted from separate fragments as test readout.

Luciferase is initially supplied in fragments that cannot not glow on their own. One piece is attached on the viral spike protein, which antibodies bind to neutralise the virus, while another is hooked to a bacterial protein that antibodies also interact with. By binding simultaneously to the coronavirus spike protein and the bacterial protein, the antibody helps lock luciferase pieces together into a whole molecule. A flash of light ensues whose intensity is detected and converted into antibody concentration by a plate reader instrument. All reagents can be prepared from scratch and in bulk and this keeps the cost down.

Stagljar is now working with U of T's intellectual property office and Toronto Innovation Acceleration Partners to find industry partners that would help make the method widely available. He is also collaborating with Dr. Prabhat Jha, Director of the Centre for Global Health Research at St. Michael's Hospital and a professor at U of T's Dalla Lana School of public Health, who is leading a long-term study to establish duration of immunity across 10,000 Canadians. In another project, Stagljar is working with Dr. Allison McGeer, Senior Clinician Scientist at Sinai Health System and also a professor at Dalla Lana, to assess antibody levels in people after vaccination.

"It's really useful to have that quantitative ability to know what someone's antibody status is, whether it's from a past infection or a vaccination. This will be of crucial importance for the next stage of the pandemic, especially now when governments of all countries started with mass vaccinations with recently approved anti-COVID-19 vaccines", Stagljar said.

"You have to win the battle against depression", "what counts is not surrendering" and "this is not a short road" are examples of conceptual metaphors typically used to describe experiences and issues associated with disorders like depression. Such expressions allude to abstract concepts but do so using familiar terms that enable better understanding of the experience. This kind of metaphor is often used unconsciously, going unnoticed by both speaker and listener. However, the study of metaphors can help access and understand the thinking, beliefs and feelings of individuals with mental disorders.

The conceptual metaphors of depression found in 23 blogs written by people with major depressive disorders were analysed by a multidisciplinary UOC team composed of Marta Coll-Florit and Salvador Climent Roca - professors from the Faculty of Arts and Humanities, both members of the GRIAL-UOC group - and Eulàlia Hernández, a professor from the Faculty of Psychology and Education Sciences and researcher in the PSiNET group. Recently published open-access in Metaphor and Symbol, the article is the first of its kind to analyse Catalan texts and is also one of the few studies that focuses on content written spontaneously online. In relation to the experience of depression, the results signal the importance of social factors, the surroundings and especially medical practice; they also point to the usefulness of blogs as an outlet for expressing and understanding the experiences of people with depression.

The research is part of the MOMENT project on mental disorder metaphors, in which linguists, psychologists, medical anthropologists, social educators and engineers are working together to study conceptual metaphors from the mental health field. As explained by the researchers: "The mental disorder experience is difficult to communicate given the associated abstractness, but studying cognitive metaphors can enhance understanding of mental health, contribute to more accurate and respectful public discourses and facilitate communication between professionals and patients."

Metaphors do not depend on specific languages

The research involved an exhaustive and quantified analysis of the main types of metaphors used by people affected by depression. Findings were then compared with previous studies with a view to identifying differences in expression in a new textual genre and a different language. The research not only analysed the metaphors of depression, but also metaphors related to the experience of living with a severe mental disorder, specifically in terms of symptoms, medication, communication and emotions.

The results confirm those of studies carried out in other languages - mainly English - showing, according to the researchers, "that, significantly, the metaphors are conceptual and intercultural, that is, they do not depend on a specific language." Among the more common expressions used to speak of depression and the associated emotions, the authors highlight the notions of fall, containment and darkness, of life with depression as a fight against obstacles and of the disorder itself as a malignant agent.

"In general, the metaphors reveal that affected individuals have positive perceptions of situations that allow them agency, that is, control over their lives and emotions, and negative perceptions of situations that deny them that agency. The metaphors of struggle are thus not always negative," continued the researchers, "as they are positive if they reinforce agency. Also positive are metaphors that perceive life with a disorder as a journey to a better situation; however, the journey metaphor can be negative if the affected person feels they have no control over the journey."

Medical practice as the enemy

The researchers have identified metaphors not featuring in previous studies, mostly corresponding to social, communicational and medical factors. They say that expressions referring to being "locked" in a diagnosis, describing prejudice as a "stone slab" and the appointment with the psychiatrist as an "interrogation" point to key factors that worsen the experience of living with depression. They further underlined how "these metaphors reflect a rejection of various social and environmental conditions, such as those associated with stigma, non-communication and medical professionals, often considered more an enemy than an ally."

Most metaphors regarding medical aspects are highly critical of psychiatry and the medical system in terms of limiting the patient's capacity for agency. "The results are not exactly flattering for the professional," according to the authors, who suggest that "the therapy relationship between the patient and the professional is clearly something that needs working on."

According to the researchers, a plausible explanation for this negative perception is that the bloggers analysed have gone through a healthcare system that is more focused on the problem than on the person. Patients consequently "seek more empathy and understanding of their suffering from medical staff". Professionals working in any communication field related to mental health disorders need to be aware of and understand the expressive power of conceptual metaphors and the importance of social and contextual factors in the lives of patients.

A textual genre that allows for free expression

The researchers have linked the discovery of the new types of metaphors to blogging, because expressing oneself online is more spontaneous than in clinical settings. "Blogs, being a kind of first-person non-mediated text," they underlined, "allow people to explain what is more intimate and more critical for them and what most deeply affects them."

This openness can also be a tool to raise awareness of mental disorders, according to the authors, as it can help "society better understand what it means for people with diagnoses of mental disorder to live with depression, what their experience of the disorder is beyond 'feeling sad' and so contribute to the fight against stigma."

Reflecting on how we talk about mental disorders

As well as depression, the MOMENT project has been exploring other major disorders such as schizophrenia, obsessive compulsive disorder and bipolar disorder, as well as other media, such as Twitter. To help improve understanding of mental disorders, the researchers have been analysing the discourse not only of patients but also of mental health professionals. They summed it up saying "The idea is to detect and systematize the predominant ideas and assumptions about severe mental disorders, to encourage reflections on how disorders are talked about and how they should be talked about and, ultimately, to promote change in relation to metaphors that can create stigma."

The results argue for a comprehensive approach to disease prevention. The scientists have now published their findings in the journal Nature Medicine.

Many elderly people suffer simultaneously from several, frequently very different diseases, a condition also known as multimorbidity. Their quality of life is severely restricted, and they receive medication from different doctors, a process which is difficult and often insufficiently coordinated. Observations indicate that certain diseases commonly occur together, but the causes of this are largely unknown.

Data from over 11,000 participants

In a recent study, a team led by Dr. Claudia Langenberg, BIH Professor of Computational Medicine, and scientists from Munich and the United Kingdom have now identified a number of metabolic processes that are associated not only with one, but simultaneously with up to 14 diseases. The scientists analyzed data from more than 11,000 participants in the EPIC-Norfolk prospective cohort study. This records hundreds of measurements from blood samples, as well as clinical data on diseases over more than 20 years of follow-up.

"We wanted to know whether there are certain markers in the blood that indicate a risk, not only for one but for several diseases at the same time," Langenberg explains. To do this, the scientists first examined the concentration of hundreds of different molecules in the blood samples of a total of 11,000 study participants. They then examined how the concentration of individual metabolites was related to the onset of a total of 27 serious diseases in the participants. The metabolites included not only known metabolic products such as sugars, fats and vitamins, but also substances whose concentration depends on genetic or environmental factors. For example, the scientists were able to detect the degradation products of medications, coffee consumption or the presence of gut bacteria using a process known as "molecular profiling."

Over 20 years of electronic medical data

The blood samples had already been taken from the participants more than 20 years ago and been stored at minus 196 degrees Celsius since then. At that time, the people were mostly healthy. The diseases they developed afterwards were systematically recorded in detail for more than 20 years through electronic hospital data. "This allowed us to explore how the concentration of hundreds of molecules in the blood is linked to the development of one or multiple diseases," Langenberg explains.

For example, the team found that the concentration of many metabolites in the blood that were associated with disease onset were explained by impaired liver and kidney function, obesity or chronic inflammation. But they also discovered that certain lifestyle factors or a reduced diversity of intestinal bacteria, also known as the gut microbiome, influence blood levels and can thus provide clues to the development of diseases over time. It turned out that half of all detected molecules were associated with an increased or decreased risk of at least one disease - the majority with multiple, sometimes very different, diseases, pointing to metabolic pathways that increase the risk of multimorbidity.

Two-thirds of all metabolites associated with more than one disease

"We found, for example, that an increased concentration of the sugar-like molecule N-acetylneuraminate increased the risk of no less than 14 diseases," explains Maik Pietzner, a scientist working with Claudia Langenberg and lead author of the paper. "Gamma-glutamylglycine, on the other hand, is exclusively associated with the occurrence of diabetes. Other members of the same molecular groups simultaneously increase the risk of liver and heart disease." Langenberg adds: "Overall, we observed that two-thirds of the molecules are associated with the occurrence of more than one disease. This is in line with the fact that patients often develop a range of diseases in the course of their lives. If we succeed in influencing these key factors, this could make it possible to counter multiple diseases simultaneously."

All results are publicly available

The scientists' extensive analysis enables insights into the various factors influencing human metabolism that were previously not possible in this level of detail. To make this reference available to scientists around the world, the authors have developed a web application called "omicscience.org." It makes all the results publicly available in graphical form so that they can be used in new studies. Langenberg adds: "The website enables scientists to determine key influencing factors for any molecule they are interested in or to uncover completely new connections between diseases. All of this was only possible due to our systematic, data-driven approach."

March 22, 2021 (BRONX, NY)-- Most people with cancer who are infected by the novel coronavirus produce antibodies at a rate comparable to the rest of the population--but their ability to do so depends on their type of cancer and the treatments they've received, according to a new study by researchers at Montefiore Health System and Albert Einstein College of Medicine. The findings, published online today in Nature Cancer, may lead to better care for cancer patients, who face a heightened risk of dying from COVID-19, and suggests that cancer patients should respond well to COVID-19 vaccines.

"We conducted the study out of our concern that cancer patients who develop COVID-19 may not benefit from the same degree of antibody protection as people without cancer, given that many are immuno-compromised," said Astha Thakkar, M.B.B.S., a Montefiore hematologic oncology fellow and first author of the paper. "Our findings provide assurance that most people with cancer are able to mount an antibody response to the coronavirus that is similar to the general population. People with a history of cancer are likely as protected from reinfection as those without a history of disease and are likely to respond well to vaccines, according to our study."

The retrospective study involved 261 cancer patients, 77% of whom were diagnosed with solid malignancies and 23% with hematologic (blood) malignancies. Their overall rate of seroconversion (production of antibodies in response to infection) was 92%. However, when patients with solid and blood malignancies were compared, patients with blood cancers had a seroconversion rate of only 81.7%--significantly lower than the 94.5% seroconversion rate for patients with solid tumors.

"The treatments commonly given to patients with blood cancers--anti-CD20 antibody therapy, stem-cell transplants, and steroids--are known to suppress the immune system, which may explain the lower rate of antibodies developed in these patients and their increased risk for severe COVID-19 disease," said senior author Balazs Halmos, M.D., M.S., director of the Multidisciplinary Thoracic Oncology Program at Montefiore, professor of medicine at Einstein, and a member of the Albert Einstein Cancer Center (AECC).

"We need to pay special attention to patients with blood cancers and think through proactive strategies to ensure this patient population is appropriately cared for," said Sanjay Goel, M.B.B.S., a medical oncologist at Montefiore, professor of medicine at Einstein, a member of AECC, and a coauthor on the paper. "This study also raises the need for additional research on COVID-19 vaccines and current treatments for people with blood cancer."

In a paper published last year in Cancer Discovery, Dr. Halmos and colleagues found that COVID-19 patients with blood cancers had significantly higher mortality rates compared with patients who had solid tumors. Mortality was more closely related to age and co-morbidities than active cancer therapy.

The study participants were cared for at Montefiore between March 1, 2020 and September 15, 2020 and tested positive for COVID-19 through PCR tests to detect coronavirus or prior COVID-19 exposure through antibody testing, or both. The patients had an average age of 64 and were almost evenly split between men and women. Fifty-six percent of patients (147/261) had symptomatic coronavirus infection, while 44% (114/261) had an asymptomatic infection.

More than 40% of patients were African American; 30% were Hispanic, nearly 15% were Caucasian, 3% were Asian, and 6% belong to other ethnic groups.

PHILADELPHIA--Hormone drugs that reduce androgen levels may help disarm the coronavirus spike protein used to infect cells and stop the progression of severe COVID-19 disease, suggests a new preclinical study from researchers in the Abramson Cancer Center at the University of Pennsylvania and published online in Cell Press's iScience.

Researchers show how two receptors--known as ACE2 and TMPRSS2--are regulated by the androgen hormone and used by SARS-CoV-2 to gain entry into host cells. Blocking the receptors with the clinically proven inhibitor Camostat and other anti-androgen therapies prevented viral entry and replication, they also showed in lab studies.

The findings provide more insight into the molecular mechanisms of the virus but also support the use of anti-androgen therapies to treat COVID-19 infections, which are currently being investigated in clinical trials and have produced promising results. They also support data showing increased mortality and severity of disease among men compared to women, who have much lower levels of androgen.

"We provide the first evidence that not only TMPRSS2, which is known to be regulated by androgen, but ACE2 can also be directly regulated by this hormone," said senior author Irfan A. Asangani, PhD, an assistant professor of Cancer Biology in the Perelman School of Medicine at the University of Pennsylvania. "We also show that the SARS-CoV-2 spike relies on these two receptors to impale and enter cells, and that they can be blocked with existing drugs. That's important because if you stop viral entry, you reduce the viral load and disease progression."

Camostat is a drug approved for use in Japan to treat pancreatitis that inhibits TMPRSS2. Other anti-androgen therapies, including androgen deprivation therapy used to treat prostate cancer, serve similar functions.

Driven by the disparity in COVID-19 rates between men and women, the cancer researchers sought to better understand the role androgen and its receptors played in infections, which has long been known to be a driver of prostate cancer.

The researchers performed experiments with a pseudotype SARS-CoV-2, which carries the spike proteins of the virus but not its genome.

In mice with significantly reduced androgen levels and cells treated with anti-androgen treatments, the researchers found little to no expression of TMPRSS2 and ACE2, suggesting both are regulated by the hormone. They also observed how inhibiting TMPRSS2 with Camostat blocked priming of the spike for entry into cells. That drug, as well as enzalutamide, an anti-androgen therapy used to treat prostate cancer, also blocked the virus' entry into lung and prostate cells. Combining these therapies, they found, significantly reduced virus entry into cells.

"Together, our data provide a strong rationale for clinical evaluations of TMPRSS2 inhibitors, androgen-deprivation therapy / androgen receptor antagonists alone or in combination with antiviral drugs as early as clinically possible to prevent COVID-19 progression," the authors wrote.

In March, researchers from Brazil reported preliminary results of 600 hospitalized patients in a clinical trial investigating proxalutamide, a new anti-androgen therapy, for the treatment of COVID-19. The drug reduced mortality risk by 92 percent and shortened the median hospital stay by nine days versus the standard of care, the researchers reported.

Next, Asangani and his colleagues will partner with Susan R. Weiss, PhD, a professor of Microbiology and co-director of the Penn Center for Research on Coronaviruses and Other Emerging Pathogens, to investigate the findings further using live SARS-CoV-2, as well as anti-androgen therapies' ability to block different variants of the virus, which continue to emerge and are often differentiated by their spike proteins.

A Korean research team has recently developed an innovative vesico-vaginal fistula treatment method using the mussel adhesive protein (MAP) that can effectively seal fistulas in organs even when exposed to urine.

Professor Hyung Joon Cha, Dr. Hyo Jeong Kim (currently at Korea Research Institute of Chemical Technology), and Dr. Tae Yoon Park of POSTECH's Department of Chemical Engineering with Professor Seok Ho Kang of the Department of Urology at Korea University School of Medicine and Professor Jong Hyun Pyun of the Department of Urology at Kangbuk Samsung Hospital have together improved the underwater adhesive using mussel protein and applied it to a pig model that simulated a vesico-vaginal fistula. As a result, it was confirmed that the fistula was sealed much quicker and more effectively than the conventional treatment method that uses sutures, and its treatment efficacy was proven to be superior.

Fistula refers to an abnormal opening between the organs consisting of two spaces, such as blood vessels or intestines. Among them, the bladder is in contact with various organs such as the intestine, uterus, and vagina in the abdominal cavity and a fistula here causes urine leakage that can induce serious complications such as fecal incontinence or bladder inflammation. This not only impairs the patients' quality of life, but female fistulas are stigmatized in many developing countries, affecting the human rights and dignity of women.

Currently, a physical suture method is typically used for treating vesico-vaginal fistulas. However, this technique has multiple limitations since the surgeries are difficult and the repetitive contraction and expansion of the bladder damages the tissue, which results in delayed healing of the wound.

To this, the POSTECH-Korea University joint research team developed a formulation in 2016 that uses the phase separation property of mussel adhesive proteins to develop a water-immiscible bioadhesive that does not dissolve in body fluids like blood or urine and exhibits excellent underwater adhesion. Moving further, the researchers conducted experiments on a pig model with vesico-vaginal fistula with improved water-immiscible bioadhesive for practical applications in clinical practice.

The joint research team used a liquid-liquid phase separation formulation with thixotropy to develop the adhesive so that the high-viscosity liquid adhesive can be accurately delivered to the fistula area via a thin syringe. In addition, after the fistula is sealed, it is designed so that it does not flow out or fall out of the fistula.

The researchers confirmed that by maximizing the concentration of catechol - which acts as an important functionality in underwater adhesion - the stability of the adhesion is increased even more in the presence of body fluids. It was also confirmed that the fistula's closing force continued to be maintained in the bladder, an organ that repeatedly contracts and expands, thanks to the flexible property of a protein-based adhesive, and the protein adhesive biodegrades and the fistula naturally regenerates.

With no immune response or inflammation observed around the sealed fistula, low surgical difficulty, and easy access to large quantities of materials, the adhesive is anticipated to be used widely in developing countries with poor medical facilities. The water-immiscible mussel protein-based bioadhesive (imWIMBA) has undergone a technology transfer to Nature Gluetech Co., Ltd. and is currently being commercialized.

"We have confirmed the mussel adhesive protein - a technology that originated in Korea - as an effective vesico-vaginal fistula treatment method by applying it to an actual vesico-vaginal fistula of a large animal model," explained Professor Hyung Joon Cha of POSTECH. "It is anticipated to be successfully applicable to fistulas and perforations in other similar environments."

"Vesico-vaginal fistula is a disorder difficult to treat and it significantly impacts the patient's quality of life," remarked Professor Seokho Kang of Korea University. "We expect the newly developed treatment method to be applicable to minimally-invasive surgical methods such as robotic surgery and endoscopic surgery as well as open surgeries in the future based on its excellent water-immiscibility and underwater adhesion."

Hearing loss and other auditory problems are strongly associated with Covid-19 according to a systematic review of research evidence led by University of Manchester and NIHR Manchester Biomedical Research Centre (BRC) scientists.

Professor Kevin Munro and PhD researcher Ibrahim Almufarrij found 56 studies that identified an association between COVID-19 and auditory and vestibular problems.

They pooled data from 24 of the studies to estimate that the prevalence of hearing loss was 7.6%, tinnitus was 14.8% and vertigo was 7.2%.

They publish their findings in the International Journal of Audiology.

However, the team - who followed up their review carried out a year ago - described the quality of the studies as fair.

Their data primarily used self-reported questionnaires or medical records to obtain COVID- 7 19-related symptoms, rather than the more scientifically reliable hearing tests.

The study was funded by is NIHR Manchester Biomedical Research Centre (BRC)

Kevin Munro, Professor of Audiology at The University of Manchester and Manchester BRC Hearing Health Lead said: "There is an urgent need for a carefully conducted clinical and diagnostic study to understand the long-term effects of COVID-19 on the auditory system.

"It is also well-known that viruses such as measles, mumps and meningitis can cause hearing loss; little is understood about the auditory effects of the SARS-CoV-2 virus."

"Though this review provides further evidence for an association, the studies we looked at were of varying quality so more work needs to be done."

Professor Munro, is currently leading a year-long UK study to investigate the possible long-term impact of COVID-19 on hearing among people who have been previously treated in hospital for the virus.

His team hope to accurately estimate the number and severity of COVID-19 related hearing disorders in the UK, and discover what parts of the auditory system might be affected

They will also explore the association between these and other factors such as lifestyle, the presence of one or more additional conditions and critical care interventions.

A recent study led by Professor Munro, suggested that more than 13 per cent of patients who were discharged from a hospital reported a change in their hearing.

Ibrahim Almufarrij said: "Though the evidence is of varying quality, more and more studies are being carried out so the evidence base is growing. What we really need are studies that compare COVID-19 cases with controls, such as patients admitted to hospital with other health conditions.

"Though caution needs to be taken, we hope this study will add to the weight of scientific evidence that there is a strong association between Covid-19 and hearing problems."

Professor Munro added: "Over the last few months I have received numerous emails from people who reported a change in their hearing, or tinnitus after having COVID-19.

"While this is alarming, caution is required as it is unclear if changes to hearing are directly attributed to COVID-19 or to other factors, such as treatments to deliver urgent care."

Scientists from the University of Leeds's Nutritional Epidemiology Group used data from 500,000 people, discovering that consuming a 25g serving of processed meat a day, the equivalent to one rasher of bacon, is associated with a 44% increased risk of developing the disease.

But their findings also show eating some unprocessed red meat, such as beef, pork or veal, could be protective, as people who consumed 50g a day were 19% less likely to develop dementia.

The researchers were exploring a potential link between consumption of meat and the development of dementia, a health condition that affects 5%-8% of over 60s worldwide.

Their results, titled Meat consumption and risk of incident dementia: cohort study of 493888 UK Biobank participants, are published today in the American Journal of Clinical Nutrition.

Lead researcher Huifeng Zhang, a PhD student from the University of Leeds' School of Food Science and Nutrition, said: "Worldwide, the prevalence of dementia is increasing and diet as a modifiable factor could play a role. Our research adds to the growing body of evidence linking processed meat consumption, to increased risk of a range of non-transmissible diseases."

The research was supervised by Professor Janet Cade and Professor Laura Hardie, both at Leeds.

The team studied data provided by UK Biobank, a database containing in-depth genetic and health information from half a million UK participants aged 40 to 69, to investigate associations between consuming different types of meat and risk of developing dementia.

The data included how often participants consumed different kinds of meat, with six options from never to once or more daily, collected in 2006-2010 by the UK Biobank. The study did not specifically assess the impact of a vegetarian or vegan diet on dementia risk, but it included data from people who said they did not eat red meat.

Among the participants, 2,896 cases of dementia emerged over an average of eight years of follow up. These people were generally older, more economically deprived, less educated, more likely to smoke, less physically active, more likely to have stroke history and family dementia history, and more likely to be carriers of a gene which is highly associated with dementia. More men than women were diagnosed with dementia in the study population.

Some people were three to six times more likely to develop dementia due to well established genetic factors, but the findings suggest the risks from eating processed meat were the same whether or not a person was genetically predisposed to developing the disease.

Those who consumed higher amounts of processed meat were more likely to be male, less educated, smokers, overweight or obese, had lower intakes of vegetables and fruits, and had higher intakes of energy, protein, and fat (including saturated fat).

Meat consumption has previously been associated with dementia risk, but this is believed to be the first large-scale study of participants over time to examine a link between specific meat types and amounts, and the risk of developing the disease.

There are around 50 million dementia cases globally, with around 10 million new cases diagnosed every year. Alzheimer's Disease makes up 50% to 70% of cases, and vascular dementia around 25%. Its development and progression are associated with both genetic and environmental factors, including diet and lifestyle.

Ms Zhang said: "Further confirmation is needed, but the direction of effect is linked to current healthy eating guidelines suggesting lower intakes of unprocessed red meat could be beneficial for health."

Professor Cade said: 'Anything we can do to explore potential risk factors for dementia may help us to reduce rates of this debilitating condition. This analysis is a first step towards understanding whether what we eat could influence that risk."

A combination of an array of atomic-level techniques has allowed researchers to show how changes in an environment-sensing protein enable bacteria to survive in different habitats, from the human gut to deep-sea hydrothermal vents.

"The study gives us unprecedented atomic-level insight into how bacteria adapt to changing conditions," says Stefan Arold, professor of bioscience at KAUST. "To obtain these insights, we pushed the limits of three different methods of investigation and combined their results into a unified picture."

The histone-like nucleoid-structuring (H-NS) protein allows bacteria to sense changes in their environment, such as changes in temperature and salinity. Previously, the team had shown how the intestinal pathogen Salmonella typhimurium uses H-NS to control its gene expression profile, enabling it to live optimally inside its warm-blooded host or outside in the soil.

The H-NS protein is also found in bacteria that do not experience massive temperature fluctuations, such as plant pathogens, insect symbionts and free-living microbes that inhabit deep-sea hydrothermal vents. Still puzzling, however, is how different bacteria have adapted the same sensing mechanism to suit a variety of lifestyles.

No single analysis technique has been able to unravel the inner workings of this mechanism and so, to gain a more integrated view, Arold assembled a diverse team from KAUST and international collaborators. Arold and Lukasz Jaremko, a molecular biochemist at KAUST, collaborated with Jianing Li from the University of Vermont to combine several methods: protonless nuclear magnetic resonance spectroscopy, all-atom molecular dynamics simulations and biophysics techniques. This synergistic approach allowed the researchers to analyze the reaction of different H-NS proteins to temperature and salinity on an atomistic level.

All H-NS proteins displayed the same ancestral sensing mechanism, whereby temperature and salinity promoted melting of one of the two dimerization domains of H-NS, releasing its grip on DNA.

However, site-specific amino acid substitutions, mostly in residues involved in salt bridges, produced a range of static and dynamic features. These effects dampen or amplify the protein's response to suit the bacteria's lifestyle.

"Although the sequences of these proteins are largely conserved, small targeted changes lead to big differences in how they behave," says KAUST research scientist Umar Farook Shahul Hameed.

Thus, the H-NS protein of the apple pathogen Erwinia amylovora lost its sensitivity to heat, which is consistent with the pathogen's lifestyle in stable temperate climates. And only a few amino-acid changes made H-NS from Buchnera aphidicola almost environment insensitive, in line with its role as an obligate endosymbiont of aphids.

"If you tickle the right positions, the behavior changes very easily," says Arold. "Approaches interfering with this sensing mechanism might find applications in areas ranging from climate change mitigation to tackling antibiotic resistance".

The excavation of shell middens off two sites in the Gulf of Mexico and Northern Europe dating back to when the seabed was dry land thousands of years ago, reveal how they can offer new ground-breaking insights into the hidden history of submerged landscapes.

An international team of archaeologists from Moesgaard Museum (Denmark), the University Of Georgia (USA), the University of York (UK) Flinders University and James Cook University partnered to excavate two sites containing shell middens in the Gulf of Mexico and Eastern Jutland in Denmark in 2018, showing that middens can be clearly differentiated from natural shells on the seabed to reveal a coastline’s inhabitation past.

The research, published in two companion papers in Quaternary Science Reviews, shows they are culturally significant underwater sites which challenge the current understanding of coastal life in the Gulf of Mexico and Northern Europe, by pushing back the inhabitation timeframe by hundreds of years.

The shell middens also represent deep connections with the underwater environments and seascapes to many First Nations people, and the new evidence will support policy changes towards the adequate management and cultural heritage of their ancestral land.

“Shell middens are a classic, world-wide marker for the intensive use of marine resources, but archaeologist have always assumed that these sites would have been destroyed by sea-level rise”, says Professor Geoff Bailey of the University of York and Visiting Professor at Flinders University.

In Denmark, the discovery of these shell middens, which are rare in the south, hints that this type of site was more common than previously thought, shifting understandings of how intensive coastal use was 5000-7300 years ago.

“Importantly, both studies show that as more of these sites are found, our histories of past coastal use may have to be rewritten. The underwater archaeological aspect to shell midden studies is extremely important moving forward,” says Dr Peter Moe Astrup, Lead Author and Curator of the Maritime Archaeology division at the Moesgaard Museum in Denmark.

“The team of archaeologists used cutting-edge techniques, including microscopy, geological and geophysical techniques, 3D reconstructions, and biological and ecological studies to tease out evidence that offers new insights into midden sites, particularly on how to locate other sites in watery depths around the globe.”

“For a large portion of humanity’s existence, sea levels have been significantly lower, up to 130 metres than what they are today, exposing millions of square kilometres of land. And the archaeological record clearly demonstrates that people in the past lived on these coastal plains before they were drowned by past sea-level rise” says Associate Professor Jonathan Benjamin who is the Director of the Deep History of Sea Country Project and Maritime Archaeology Program Coordinator at Flinders University's College of Humanities, Arts and Social Sciences.

"Within archaeological shell middens, we can find old food remains, discarded tools and ornaments, old living surfaces, and in some cultures, human burials,” says Dr Katherine Woo at the Australian Research Council Centre of Excellence for Australian Biodiversity and Heritage, James Cook University in Australia.

“These in turn provide us with fundamental information about past food choices, tool technology, and trade practices. More importantly, these different types of information allow us to understand how people adapted their cultures over time, and how they interacted with their surrounding environments including during times of sea level rise and climate change.”

The excavation of these sites emphasises the need for stronger recognition and rights to protect and manage the cultural heritage of underwater ancestral lands around the globe, which hold significant insights into human history and deep connections to marine environments.

“The discovery of these underwater sites, and the promise of more to be found, means that industry, developers, archaeologists, and government bodies must reassess how we classify and handle Indigenous heritage on the continental shelf,” says Dr Jessica Cook Hale from the University of Georgia. “This is especially critical because offshore development is accelerating; here in North America the big push for offshore windfarms is underway, but Indigenous voices must remain foremost. These new findings support ongoing work to ensure that Indigenous and First Nations have a critical seat at the table, so to speak, in managing the offshore cultural heritage of their ancestral lands by documenting these relationships into the deep past.”

“They are real, they are important, and we must all engage with them in a rigorous and serious fashion.

WASHINGTON--Nearly one in five U.S. children and teenagers has obesity, and statistics show a higher prevalence of obesity in certain ethnicities, such as Hispanics and Blacks. Now results of a study being presented at ENDO 2021, the Endocrine Society's annual meeting, suggest that Spanish as a family's primary language is a predictor of childhood obesity, regardless of ethnicity.

The prevalence of obesity among children and teens from Spanish-speaking households in the nation was 24.4 percent, approximately 50 percent higher than those from English-speaking households, according to results of a new analysis of the U.S. National Health and Nutrition Examination Survey. This survey examines a nationally representative sample of the U.S. population each year, and the study researchers used statistics from the 1999 to 2018 surveys regarding 2- to 19-year-olds. The survey found overall obesity among this age group climbed to 19.2 percent in 2018, up from 14.7 percent in 1999.

"Childhood obesity is associated with multiple diseases in adulthood," said the Hang-Long ("Ron") Li, a medical student at the University of Hong Kong (HKU) LKS Faculty of Medicine in Hong Kong, China, who carried out the analysis under the supervision of Prof. Bernard M.Y. Cheung, Ph.D., the Sun Chieh Yeh Heart Foundation Professor in Cardiovascular Therapeutics at HKU. "Public health measures specifically catering to children from Spanish-speaking families should be put in place to raise awareness of childhood obesity and implement health interventions."

Li said they are the first group to identify an association between childhood obesity and language. He speculated that language barriers could prevent Spanish-speaking families from understanding health education materials or accessing Spanish-language health promotion resources. Additionally, he noted that food labels, which play an important role in obesity prevention efforts, may be in English only. Alternatively, these families may be aware of available health materials but are not taking action to make essential lifestyle changes.

Existing programs to combat childhood obesity should be promoted to Spanish-speaking households and should be sensitive to different cultural traditions, Li said.

"Health talks and activities could also be carried out in Spanish to improve the dissemination of important public health knowledge, such as healthy eating and physical activity," he said.

The researchers also found that obesity is more prevalent in children from households with a low socioeconomic status. The obesity rate was 23.8 percent in children from low-income households versus 11 percent for children in high-income households, they reported. Likewise, the prevalence of obesity was 26.2 percent in children from households with a low educational level compared with 9.4 percent from highly educated families.

Measures to halt this trend could include promotion of healthy school meals and improved accessibility and affordability of nutritious fresh foods in poor communities, Li said.

The researchers looked at U.S. trends in childhood obesity over the last two decades and found a large increase in overall obesity among 2- to 19-year-olds. Severe obesity at those ages increased from 3.9 to 6.1 percent in the same period, a more than 55 percent upsurge, Li reported.

In children, severe obesity is weight at or above the 120th percentile for age and sex, and the definition of obesity is weight at or greater than the 95th percentile.

"Improved public health interventions are urgently needed to halt the rising trend of childhood obesity," Li said.

WASHINGTON--Children with adrenal insufficiency--a condition in which the adrenal gland does not function properly--are at more than 10 times higher risk for COVID-19 complications and death compared with children with normal adrenal glands, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

Adrenal insufficiency is a disorder that occurs when the adrenal glands, located just above the kidneys, don't make enough of the hormone cortisol. The primary form of adrenal insufficiency is also called Addison's disease. Known as the "stress hormone," cortisol helps break down fats, proteins and carbohydrates. It also controls blood pressure and affects the immune system. Children with adrenal insufficiency are treated with daily cortisol replacement therapy. They need increased doses when they are sick.

"Adrenal insufficiency may put a person at higher risk of infections due to a lack of normal stress response by the body," said lead researcher Manish Rasingani, M.D., of the University of Arkansas for Medical Sciences and Arkansas Children's in Little Rock, Ark. "Until now, there has been limited data on children with adrenal insufficiency and COVID-19."

In the new study, the researchers analyzed data from an international database on children up to age 18 who had COVID-19. The study included 846 children with adrenal insufficiency and more than 250,000 without adrenal disease. The mortality rate was much higher among children who had adrenal insufficiency, compared to children who did not have the condition.

"This study shows it is important to take extra precautions to prevent and treat COVID-19 infection in children with adrenal insufficiency," Raisingani said.

WASHINGTON--The chemicals present in white button mushrooms may slow the progression of prostate cancer, according to a mouse study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"Androgens, a type of male sex hormone, promote the growth of prostate cancer cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells," said lead researcher Xiaoqiang Wang, M.D., Ph.D., M.B. (A.S.C.P.), of the Beckman Research Institute of City of Hope, a comprehensive cancer center in Duarte, Calif. "White button mushrooms appear to suppress the activity of the androgen receptor."

City of Hope's Shiuan Chen, Ph.D., the principal investigator of this project, previously conducted a phase one clinical trial of white button mushroom powder in patients with recurrent prostate cancer, which indicated that the mushrooms reduced levels of prostate-specific antigen (PSA) in the blood, with minimal side effects. Heightened blood levels of PSA in men may indicate the existence of prostate tumors.

The new study aimed to understand the mechanism behind this finding. The researchers studied the mushroom extract's effect on prostate cancer cells that were sensitive to androgen. They also studied the extract's effect on mice implanted with human prostate tumors, which creates an animal model whose results would be more reliable as the research is translated to human clinical trials.

The researchers found that in prostate cancer cells, white button mushroom extract suppressed androgen receptor activity. They also found that in mice treated with white button mushroom extract for six days, prostate tumor growth was significantly suppressed, and levels of PSA decreased.

"We found that white button mushrooms contain chemicals that can block the activity of the androgen receptor in mouse models, indicating this fungus can reduce PSA levels," Wang said. "While more research is needed, it's possible that white button mushrooms could one day contribute to the prevention and treatment of prostate cancer."

WASHINGTON--Patients with low vitamin D levels who are hospitalized for COVID-19 may have a lower risk of dying or requiring mechanical ventilation if they receive vitamin D supplementation of at least 1,000 units weekly, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"Given how common vitamin D deficiency is in the world and the United States, we believe that this research is highly relevant right now," said co-author Sweta Chekuri, M.D., of Montefiore Health System and Albert Einstein College of Medicine in the Bronx, New York.

Research has shown that vitamin D supplementation can prevent inflammation in other respiratory diseases, but there have been limited studies examining the role of vitamin D supplementation in COVID-19. The purpose of the study was to determine whether being supplemented with vitamin D before being admitted to the hospital with COVID-19 resulted in less severe COVID-19 disease in patients with a low vitamin D level.

The researchers studied 124 adult patients with low vitamin D that was measured up to 90 days before their admission for COVID-19. They compared the patients who were supplemented with at least 1,000 units of vitamin D weekly to those who had not received vitamin D supplements in terms of whether they were mechanically ventilated or died during admission.

They found that patients who were supplemented were less likely to be mechanically ventilated or to die following admission, though the finding wasn't statistically significant (37.5 percent of patients who were not supplemented vs. 33.3 percent of those who were) They also found that more than half of those who should have been supplemented were not.

"Though we weren't able to show a definitive link to severe COVID-19, it is clear that patients with low vitamin D should receive supplementation not only for bone health, but also for stronger protection against severe COVID-19," said co-author Corinne Levitus, D.O., of Montefiore Health System and Albert Einstein College of Medicine. "We hope this research will encourage clinicians to discuss adding this supplement with their patients who have low vitamin D, as this may reduce the odds of people developing severe COVID-19."

A study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism last fall found over 80 percent of 200 COVID-19 patients in a hospital in Spain had vitamin D deficiency.