Culture

In humans, adenoviruses can infect the cells of the respiratory tract, while herpes viruses can infect those of the skin and nervous system. In most cases, this does not lead to the production of new virus particles, as the viruses are suppressed by the immune system. However, adenoviruses and herpes viruses can cause persistent infections that the immune system is unable to completely suppress and that produce viral particles for years. These same viruses can also cause sudden, violent infections where affected cells release large amounts of viruses, such that the infection spreads rapidly. This can lead to serious acute diseases of the lungs or nervous system.

Automatic detection of virus-infected cells

The research group of Urs Greber, Professor at the Department of Molecular Life Sciences at the University of Zurich (UZH), has now shown for the first time that a machine-learning algorithm can recognize the cells infected with herpes or adenoviruses based solely on the fluorescence of the cell nucleus. "Our method not only reliably identifies virus-infected cells, but also accurately detects virulent infections in advance," Greber says. The study authors believe that their development has many applications - including predicting how human cells react to other viruses or microorganisms. "The method opens up new ways to better understand infections and to discover new active agents against pathogens such as viruses or bacteria," Greber adds.

The analysis method is based on combining fluorescence microscopy in living cells with deep-learning processes. The herpes and adenoviruses formed inside an infected cell change the organization of the nucleus, and these changes can be observed under a microscope. The group developed a deep-learning algorithm - an artificial neural network - to automatically detect these changes. The network is trained with a large set of microscopy images through which it learns to identify patterns that are characteristic of infected or uninfected cells. "After training and validation are complete, the neural network automatically detects virus-infected cells," explains Greber.

Reliably predicting severe acute infections

The research team has also demonstrated that the algorithm is capable of identifying acute and severe infections with 95 percent accuracy and up to 24 hours in advance. Images of living cells from lytic infections, in which the virus particles multiply rapidly and the cells dissolve, as well as images of persistent infections, in which viruses are produced continuously but only in small quantities, served as training material. Despite the great precision of the method, it is not yet clear which features of infected cell nuclei are recognized by the artificial neural network to distinguish the two phases of infection. However, even without this knowledge, the researchers are now able to study the biology of infected cells in greater detail.

The group has already discovered some differences: The internal pressure of the nucleus is greater during virulent infections than during persistent phases. Furthermore, in a cell with lytic infection, viral proteins accumulate more rapidly in the nucleus. "We suspect that distinct cellular processes determine whether or not a cell disintegrates after it is infected. We can now investigate these and other questions," says Greber.

Hypoxia, or the inadequate oxygenation of a tissue, is a condition occurring frequently in all solid tumours such as melanoma skin cancer. Melanoma cells are not only able to survive oxygen deprivation, but also to use it to their own advantage by hijacking the anti-tumour immune response and developing resistance mechanisms to conventional anti-cancer therapies. A key gene responsible for cancer cell adaptation to hypoxia is HIF-1α (Hypoxia Inducible Factor-1 alpha). Led by Dr Bassam Janji, head of the Tumor Immunotherapy and Microenvironment (TIME) research group at the Luxembourg Institute of Health (LIH) and in collaboration with Gustave Roussy Cancer Center in France and the Thumbay Research Institute of Precision Medicine at Gulf Medical University in the United Arab Emirates, the team used gene editing technologies to show how targeting HIF-1α could not only inhibit tumour growth, but also drive cytotoxic (toxic to cells) immune cells to the cancer tissue. This discovery provided a valuable new target to make resistant melanomas more vulnerable to available anti-cancer treatments. Their findings were recently published in the reputable Oncogene Journal.

Melanoma is a type of skin cancer that develops from melanocytes, cells that are responsible for the production of pigments. Melanomas become harder to treat if not detected early, with emerging treatment resistance being an important barrier to their effective management. Due to their rapid growth rate and low blood supply, solid tumours including melanoma often exhibit areas of hypoxia. Hypoxia, or the decrease of oxygen in the tumour microenvironment, would normally cause tumour cell death. "However, certain solid tumours have evolved to survive this hostile microenvironment by activating HIF-1α, a gene reported to be a major factor mediating the adaptive response to changes in tissue oxygen level," explains Dr Janji. William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza were awarded the Nobel Prize in Physiology or Medicine in 2019 for their discovery of HIF-1? and how cells use it to sense hypoxia. Hypoxia has also been reported to be responsible for the failure of tumour response to conventional anti-cancer therapies and can prevent the infiltration of immune cells into the tumour. It is therefore crucial to understand the mechanisms by which cancer cells overcome this hypoxic environment to improve the effectiveness of available anti-cancer therapies.

In this context, the team led by Dr Janji sought to inactivate the functionality of the HIF-1α gene using CRISPR gene editing technology and investigate the impact of such inactivation on tumour growth, immune cell infiltration and response to immunotherapy in a preclinical melanoma mouse model.

"Our study revealed that blocking the activity of HIF-1α significantly inhibited melanoma growth and amplified the infiltration of immune cells into the tumour microenvironment by increasing the release of CCL5, a well-defined mediator involved in driving cytotoxic immune cells to the tumour battlefield", summarises Dr Audrey Lequeux, first author of the publication. Importantly, the study also showed that combining a drug devised to stop hypoxia significantly improves melanoma immunotherapy. When the results were validated retrospectively in a cohort of 473 melanoma patients, the hypoxic signature of tumours was correlated to worsened outcomes and the lack of immune cell infiltration into tumours, which is considered as a major characteristic of tumour resistance to immunotherapies.

"Together, our data strongly argue that therapeutic strategies disrupting HIF-1α would be able to modulate the tumour microenvironment to permit the infiltration of immune cells. Such strategies could be used to improve vaccine-based and immune checkpoint blockade-based cancer immunotherapies in non-responder melanoma patients," conclude Dr Chouaib and Dr Janji from Gulf Medical University and Luxembourg Institute of Health, respectively.

A research group led by Professor Sachie Hiratsuka, Institute for Biomedical Research, Shinshu University, has found that a specific sequence of messenger RNA (mRNA), which exists outside cells, binds to receptors on the surface of natural killer (NK) cells and is taken up into the nucleus. The group found that NK cells with mRNA uptake are able to enhance their migration activity and interferon gamma production. Furthermore, NK cells incorporating the mRNA showed an inhibitory effect on cancer metastasis in animal experiments.

In recent years, the results of cancer treatment have been improving with the increase of medical technology. However, it is still difficult to effectively prevent cancer metastasis, so there is a need to develop new treatment methods. Cancer metastasis occurs when cancer cells in the body metastasize to other organs and grow again in those organs. The process is extremely complex, with various reactions occurring simultaneously, and it is difficult to say that we have enough basic knowledge at present.

In cancer metastasis, the cancer cells themselves undergo changes that increase their malignant potential, such as invasion of the surrounding tissues. At the same time, the target organ is in a condition to accept metastasizing cancer cells. Therefore, in order to prevent cancer metastasis, basic research is being conducted for a method that not only works directly on cancer cells but also works on the target organs.

Professor Hiratsuka's research team has been conducting basic research on the role of immune cells and pulmonary vascular endothelial cells in lung metastasis using a mouse model of cancer metastasis. It was found that in the mice with a primary tumor transplanted subcutaneously, some NK cells stimulated by cancer tissue migrate from the liver to the lung. Furthermore, these cells were found to have the function of suppressing cancer metastasis in the lungs, and these cells were named "anti-metastatic cells," but their molecular mechanism was not unknown. Therefore, the team decided to conduct research to elucidate the activation mechanism of anti-metastatic cells.

Messenger RNA exists inside the cell and is the blueprint for protein synthesis. Until now, it has been unclear whether mRNA also exists outside the cell, or if it does, whether it has any function other than making proteins. In this study, the group first showed the presence of mRNA in tissue-cultured medium. At the same time, they demonstrated anti-metastatic cells isolated from mice incorporated mRNA into their cells. The uptake of mRNA was attributed to the action of the ZC3H12D protein, which binds strongly to a specific part of the RNA called the AU-rich region. It was also found that the incorporated RNA was transported to the cell nucleus. Mouse anti-metastatic cells showed increased expression of genes resistant to death, activation of cell migration ability, and production of interferon gamma after incorporation of RNA. Furthermore, when the RNA-incorporated anti-metastatic cells were injected into mice, they inhibited cancer metastasis. These results indicate that some mRNAs are taken up by cells and transported to the nucleus, which may inhibit cancer metastasis. (Figure)

Special diets, exercise programs, supplements and vitamins, there is everywhere something supposed to help us live longer. Whether it actually works has not always been shown, but the average life expectancy of people has increased over the last 150 years. A study by an international team of researchers, including Claudia Fichtel and Peter Kappeler, scientists in the Behavioral Ecology and Sociobiology Unit at the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen, indicates that we probably cannot slow down aging. The comparative studies with humans and non-human primates, indicates that it is not the rate at which humans age that slows down, but that the survival rate of younger individuals has changed over time (Nature Communications).

The team of scientists led by biologist Susan Alberts from Duke University, North Carolina, USA, compared data from nine human populations and 30 populations of non-human primates. Claudia Fichtel and Peter Kappeler participated in this study with data collected over 25 years from ten sifaka groups, a lemur species from Madagascar. The researchers have been conducting behavioral studies on lemurs for over 25 years at the DPZ Kirindy Forest field station on the west coast of the island.

The research team, comprising scientists from 14 different countries, analyzed patterns of births and deaths, looking at the relationship between life expectancy and lifespan equality.

Lifespan equality tell us how much the age of death varies in a population. If everyone tends to die at around the same age - for instance, if almost everyone can expect to live a long life and die in their 70s or 80s - lifespan equality is very high. If death could happen at any age - because of disease, for example - lifespan equality is very low.

In humans, lifespan equality is closely related to life expectancy: people from populations that live longer also tend to die at a similarly old age, while populations with shorter life-expectancies tend to have deaths distributed across a wider range of ages.

To understand if this pattern is uniquely human, the researchers turned to our closest relatives: non-human primates. What they found is that the tight relationship between life expectancy and lifespan equality is widespread among primates as well as humans. But why?

In most mammals, risk of death is high at very young ages, relatively low at adulthood, then it increases again after the onset of aging. Could higher life-expectancy be due to individuals ageing slower and living longer?

The primate populations tell us that the answer is probably no. Instead, the main sources of variation in the average age of death in different primate populations were infant, juvenile and young adult deaths. In other words, life expectancy and lifespan equality are not driven by the rate at which individuals senesce and become old, but by how many children and young adults die of reasons that have nothing to do with old age.

"In our research area in Madagascar, female sifakas have an average life expectancy of about 5 years, although some females can live up to 23 years," says Claudia Fichtel. "Because infant mortality is very high - about 65 percent of infants die within the first year of life - only few females manage to live to such an advanced age. Most juveniles are probably preyed upon by the fossa, the largest predator living in Madagascar."

Susan Alberts, professor of biology and evolutionary anthropology at Duke University and senior author of the study, adds: "Populations get older and older mostly because more and more individuals get through those early stages of life. Early life used to be so risky for humans, whereas now we prevent most early deaths."

TEL AVIV, Israel and RALEIGH, NC, June 21, 2021, RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced presentation of the positive Phase 2 safety and efficacy data for oral opaganib (Yeliva®, ABC294640) in hospitalized patients with COVID-19 pneumonia at the World Microbe Forum (WMF) 2021 (poster #: 5574).

Results and post hoc analyses of data from the 40-patient U.S. Phase 2 study were presented in a poster entitled, "Opaganib, an Oral Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: A Randomized, Double-blind, Placebo-controlled Phase 2A Study, in Adult Subjects Hospitalized with SARS-CoV-2 Positive Pneumonia (NCT: 04414618)" . Patients in the study were randomized to receive either opaganib or placebo in addition to standard of care (SoC), predominantly including dexamethasone and/or remdesivir. Findings include:

50% of patients treated with opaganib (n=22) reached room air by Day 14 compared to 22% in the placebo group (n=18). The benefit of reaching room air by Day 14 for patients on opaganib was maintained regardless of whether the patients were receiving dexamethasone and/or remdesivir

86.4% of patients treated with opaganib were discharged from hospital by Day 14 compared to 55.6% of patients treated with placebo

Median time to discharge was 6 days for the opaganib group compared to 7.5 days for the placebo group

81.8% of opaganib patients achieved a 2-point improvement in the WHO Ordinal Scale compared to 55.6% of patients in the placebo group - achieved in a median time of 6 days versus 7.5 days, respectively

No significant differences in safety-related measures between the two groups (with diarrhea being the main treatment-emergent difference in tolerability)

"The need for an effective oral therapy to treat COVID-19 is clear. Such a therapy would greatly improve our ability to manage this pandemic," said Kevin Winthrop, MD, MPH, Professor of Infectious Diseases at Oregon Health & Science University, who presented the findings at WMF. "These data, from this proof-of-concept clinical study of opaganib in patients with severe COVID-19, suggest a potential role of SK2 inhibition in combating the effects of this virus. With much more data on opaganib expected in the coming weeks, we could make some real progress toward having access to a much-needed oral therapy for patients who currently have a paucity of options available to them."

"Presentation of these positive data from our exploratory Phase 2 study support our growing confidence that opaganib could be the first novel, oral therapy to demonstrate efficacy in the treatment of COVID-19 in a large late-stage study. With the recent completion of enrollment of our 475-patient global Phase 2/3 study, we will have a clearer picture of that in the very near future," said Mark L. Levitt, MD, Ph.D., Medical Director at RedHill. "Opaganib acts on both the cause and effect of COVID-19 via a unique dual antiviral and anti-inflammatory mode of action. Being host-targeted, opaganib is also expected to maintain effect against the emerging SARS-CoV-2 variants, which continue to threaten the progress being made against the pandemic and underscore the urgent need for effective COVID-19 therapeutics."

The global 475-patient Phase 2/3 study of opaganib in severe COVID-19 has been approved in 10 countries and completed enrollment, through 57 participating sites, on June 6th. The primary endpoint of the study is the proportion of patients breathing room air without oxygen support by Day 14. Additional important outcome measures, such as time to discharge from hospital, improvement according to the World Health Organization Ordinal Scale for Clinical Improvement and incidence of intubation and mortality, will also be captured in the follow-up period of up to 6 weeks. The study received four independent DSMB recommendations to continue following unblinded safety reviews and a futility review. Additionally, an evaluation of the blinded blended intubation and mortality rates to date was encouraging as compared to reported rates of mortality from large platform studies such as RECOVERY, and other studies in similar patient populations .

Extreme heat waves in urban areas are much more likely than previously thought, according to a new modeling approach designed by researchers including University of Illinois Urbana-Champaign Civil and Environmental Engineering (CEE) assistant professor Lei Zhao and alumnus Zhonghua Zheng (MS 16, PhD 20). Their paper with co-author Keith W. Oleson of the National Center for Atmospheric Research, "Large model structural uncertainty in global projections of urban heat waves," is published in the journal Nature Communications.

Urban heat waves (UHWs) can be devastating; a 1995 heat wave in Chicago caused more than 1,000 deaths. Last year's heat wave on the west coast caused wildfires. Global warming is expected to increase the incidence and severity of UHWs, but if cities fully understand their risk, they can prepare better with forecasts and warnings, safety guidance and improving access to health facilities like cooling centers and hospitals. Longer-term strategies include adaptation practices, which help cities adapt to the warmer temperatures induced by climate change - such as highly reflective roofs and pavements and green infrastructure - and mitigation practices, which help reduce the carbon emission - like renewable energy.

In recent years, though, an increase in record-breaking UHWs has caused concerns that the computer models used to predict them are flawed, leading to a systematic underestimation of their frequency and severity. Without accurate models, cities may dramatically misjudge their risk and fail to prepare accordingly, putting their citizens at greater risk as the world heats up.

Zhao's team has developed a model that closes two major gaps in urban climate modeling. First, most traditional climate models effectively ignore cities entirely. Urban areas make up only 2-3 percent of the earth's land, so their effect on global models is negligible, but more than half of the world's population lives in urban areas, so their impact is significant. The team's new modeling approach addresses that by providing urban-specific climate signals.

Second, because of this lack of urban representation in state-of-the-art climate models, there were no global-scale, multi-model projections for urban climates. The multi-model projections are critical to characterize the robustness and uncertainty of the projections, which is very important for estimating the climate-driven risks, for example, the likelihood of climate extremes. The new model provides global multi-model projections of local urban climates.

The paper also highlights four high-stakes regions - the Great Lakes region, southern Europe, central India and north China - and finds that cities in those areas had dramatically lower probabilities of risk with a single-model approach than with the researchers' multi-model approach. For example, the researchers found that using only traditional models, the Great Lakes region was expected to experience an extreme heat event only once in 10,000 years; with the researchers' new modeling technique, such events could be expected once every four years.

"This work highlights the critical importance of having multi-model projections to accurately estimate the likelihood of extreme events that will occur in the future under climate change," Zhao said.

An increasing number of studies on artificial intelligence (AI) are published in the dental and oral sciences but aspects of these studies suffer from a range of limitations. Standards towards reporting, like the recently published CONSORT-AI extension, can help to improve studies in this emerging field. Watch authors Falk Schwendicke and Joachim Krois of the Charité - Universitätsmedizin Berlin, Germany, discuss the Journal of Dental Research (JDR) article "Better Reporting of Studies on Artificial Intelligence: CONSORT-AI and Beyond," moderated by JDR Editor-in-Chief Nicholas Jakubovics, Newcastle University, England.

Watch: https://bit.ly/3zBpRUW
View article: https://bit.ly/2SHWf81

For AI studies in healthcare, only a limited number of randomized controlled trials are available, many studies are low quality and reporting is often insufficient to fully comprehend and possibly replicate these studies. Reporting standards such as the CONSORT (Consolidated Standards of Reporting Trials) statement, which provides evidence-based recommendations for reporting of randomized controlled trials, have been widely adopted by journals and have been shown to increase reporting quality. The new CONSORT-AI extension specifically addresses issues relating to the use of AI in clinical trials.

Randomized controlled trials are often used to inform decision-makers in health policy, regulatory, and clinical care, comprehensive and systematic reporting, allowing to gauge a trial's methodology, validity and bias as well as facilitating replication, is crucial. With the rapid expansion of AI as a tool to enhance clinical trials and other research studies, it is critical that steps are made to standardize reporting in this area.

"Given the emergence of studies on AI in dentistry, action is needed," said Jakubovics. "Standards like the recently published CONSORT-AI extension will improve reporting of AI studies in dentistry. The Journal of Dental Research encourages authors, reviewers and readers to adhere to these standards. A range of further aspects along the AI lifecycle should be considered when conceiving, conducting, reporting or evaluating studies on AI in dentistry."

Forces of nature have been outsmarting the materials we use to build our infrastructure since we started producing them. Ice and snow turn major roads into rubble every year; foundations of houses crack and crumble, in spite of sturdy construction. In addition to the tons of waste produced by broken bits of concrete, each lane-mile of road costs the U.S. approximately $24,000 per year to keep it in good repair.

Engineers tackling this issue with smart materials typically enhance the function of materials by increasing the amount of carbon, but doing so makes materials lose some mechanical performance. By introducing nanoparticles into ordinary cement, Northwestern University researchers have formed a smarter, more durable and highly functional cement.

The research was published today (June 21) in the journal Philosophical Transactions of the Royal Society A.

With cement being the most widely consumed material globally and the cement industry accounting for 8% of human-caused greenhouse gas emissions, civil and environmental engineering professor Ange-Therese Akono turned to nanoreinforced cement to look for a solution. Akono, the lead author on the study and an assistant professor in the McCormick School of Engineering, said nanomaterials reduce the carbon footprint of cement composites, but until now, little was known about its impact on fracture behavior.

"The role of nanoparticles in this application has not been understood before now, so this is a major breakthrough," Akono said. "As a fracture mechanics expert by training, I wanted to understand how to change cement production to enhance the fracture response."

Traditional fracture testing, in which a series of light beams is cast onto a large block of material, involves lots of time and materials and seldom leads to the discovery of new materials.

By using an innovative method called scratch testing, Akono's lab efficiently formed predictions on the material's properties in a fraction of the time. The method tests fracture response by applying a conical probe with increasing vertical force against the surface of microscopic bits of cement. Akono, who developed the novel method during her Ph.D. work, said it requires less material and accelerates the discovery of new ones.

"I was able to look at many different materials at the same time," Akono said. "My method is applied directly at the micrometer and nanometer scales, which saves a considerable amount of time. And then based on this, we can understand how materials behave, how they crack and ultimately predict their resistance to fracture."

Predictions formed through scratch tests also allow engineers to make changes to materials that enhance their performance at the larger scale. In the paper, graphene nanoplatelets, a material rapidly gaining popularity in forming smart materials, were used to improve the resistance to fracture of ordinary cement. Incorporating a small amount of the nanomaterial also was shown to improve water transport properties including pore structure and water penetration resistance, with reported relative decreases of 76% and 78%, respectively.

Implications of the study span many fields, including building construction, road maintenance, sensor and generator optimization and structural health monitoring.

By 2050, the United Nations predicts two-thirds of the world population will be concentrated in cities. Given the trend toward urbanization, cement production is expected to skyrocket.

Introducing green concrete that employs lighter, higher-performing cement will reduce its overall carbon footprint by extending maintenance schedules and reducing waste.

Alternately, smart materials allow cities to meet the needs of growing populations in terms of connectivity, energy and multifunctionality. Carbon-based nanomaterials including graphene nanoplatelets are already being considered in the design of smart cement-based sensors for structural health monitoring.

Akono said she's excited for both follow-ups to the paper in her own lab and the ways her research will influence others. She's already working on proposals that look into using construction waste to form new concrete and is considering "taking the paper further" by increasing the fraction of nanomaterial that cement contains.

"I want to look at other properties like understanding the long-term performance," Akono said. "For instance, if you have a building made of carbon-based nanomaterials, how can you predict the resistance in 10, 20 even 40 years?"

The study, "Fracture toughness of one- and two-dimensional nanoreinforced cement via scratch testing," was supported by the National Science Foundation Division of Civil, Mechanical and Manufacturing Innovation (award number 18929101).

Akono will give a talk on the paper at The Royal Society's October meeting, "A Cracking Approach to Inventing Tough New Materials: Fracture Stranger Than Friction," which will highlight major advances in fracture mechanics from the past century.

TAMPA, Fla (June 21, 2021) -- A blood gene profile associated with a high risk of dying from a severe lung disease can also predict poor outcomes in patients with COVID-19, a multicenter retrospective study led by the University of South Florida Health (USF Health) demonstrated. The risk profile based on 50 genes could help customize how COVID-19 is treated, improve allocation of limited health care resources such as intensive care beds and ventilators, and potentially save lives.

Idiopathic pulmonary fibrosis (IPF), a disease of unknown cause, affects the lung interstitium or the space between the lung sacs and the bloodstream, leading to severe lung scarring. Severe COVID-19 can also damage the lung interstitium leading to severe lung scarring.

"Our study identified at the molecular level, a gene risk profile that predicts worse COVID-19 outcomes before the patient becomes severely ill," said principal investigator Jose Herazo-Maya, MD, an associate professor and associate chief of pulmonary, critical care and sleep medicine at the USF Health Morsani College of Medicine. "That means every patient with COVID-19 could potentially get a blood test that could tell us if they are at high or low risk of dying... And if we know in advance who will likely end up in the ICU and who will likely do well recovering at home with appropriate monitoring, we can tailor our interventions to individual patients based on their level of risk."

The USF Health study appeared online June 20 in EBioMedicine, a publication of THE LANCET. It builds upon previous genomic research by Dr. Herazo-Maya and colleagues at Yale School of Medicine. In 2017, they led an international team that studied and validated a gene expression signature in the blood that reliably forecasts the likelihood of IPF mortality. (Certain patients with lung scarring can live well for years, while others develop worsening disease and die quickly from IPF.)

As the COVID-19 pandemic unfolded, "the basic question we had was 'Can we repurpose the gene signature known to predict mortality in a fibrotic lung disease to predict mortality in those infected with a new coronavirus that can cause lung fibrosis as well?" said the EBioMedicine paper lead author Brenda Juan-Guardela, MD, assistant professor of medicine at the USF Health Morsani College of Medicine and medical director of Respiratory Care Services at Tampa General Hospital (TGH). "To the best of our knowledge, this study is the first to compare overlapping immune gene profiles in COVID-19 and IPF, which were remarkably similar."

The USF Health-led team analyzed gene expression patterns of 50 genes known to predict IPF mortality in three COVID-19 cohorts and two IPF cohorts. The researchers used a molecular scoring system to distinguish between high versus low-risk gene profiles in all five cohorts.

Among their findings:

In the COVID-19 validation cohorts, a 50-gene high risk profile was linked to greater risk of ICU admission, mechanical ventilation, and in-hospital death.

The researchers also performed single-cell, gene expression analyses and identified specific immune cells -- monocytes, neutrophils, and dendritic cells - as the primary source of gene expression changes in the high-risk, COVID-19 gene profile. This finding suggests COVID-19 and IPF may share common innate and adaptive immune responses that trigger lung scarring.

The 50-gene risk profile in COVID-19 can also predicts mortality in IPF at the exact same threshold.

At TGH, Dr. Herazo-Maya treats previously hospitalized COVID-19 patients who come to the Center for Advanced Lung Disease with severe lung fibrosis; some are being evaluated for lung transplantation. "Even though coronavirus cases are dropping, that doesn't mean all the patients will recover without complications," he said. "We're starting to see the damaging, long-term effects in the lungs of some COVID-19 survivors."

While more studies are needed, researchers and clinicians may soon be able to apply the gene risk profiles to help advance the care of both COVID-19 and IPF patients, Dr. Herazo-Maya said. His laboratory is currently developing a blood test, based on these genes, that can be easily applied in clinical practice to predict poor disease outcomes.

Besides outcome prediction, the identification of 50-gene risk profiles may also have significant therapeutic potentials. For example, a 10-day regimen of the steroid dexamethasone, a drug that suppresses the immune system, has been shown to increase survival of patients hospitalized with COVID-19.

Immunosuppressant drugs have been essentially discontinued for IPF treatment because they increase mortality when given at high doses and in combination over long periods, Dr. Herazo-Maya said. "But perhaps we could investigate the use of dexamethasone or a similar steroid treatment for a short period of time in a subgroup of IPF patients with a 50-gene high risk profile, using the principle of precision or personalized medicine."

The 50-gene high risk profile may also support the rationale to investigate the use of targeted IPF antifibrotic medications, which slow the rate of lung scarring, to prevent short and long-term sequelae of COVID-19, he added.

DURHAM, N.C. - In the fight against viruses, antibodies have the potential to either block infection or enable infection and make the disease worse, leading to concern about their use as a therapy for COVID-19.

In a study published in the journal Cell, Duke investigators demonstrated in mice and monkeys that human antibodies lacked the ability to make SARS-CoV-2 infection worse and, instead, exerted their defensive powers against the infection. The findings help reinforce evidence that antibodies are safe when given as treatments or induced by COVID-19 vaccines.

The two types of antibodies -- those that neutralize the virus or those that enhance virus replication -- have been the subjects of much research, raising concerns that antibodies could potentially trigger severe infections in some recipients.

But the current research, led by scientists at the Duke Human Vaccine Institute, is the first to use animal models to examine what occurs when SARS-CoV-2 antibodies are tested with the virus.

"Our study, using mice and monkeys, demonstrates that antibodies that are potentially harmful in the test tube do not appear to be harmful in the setting of SARS-CoV-2 infection in mice or monkeys," said co-senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute (DHVI).

"We tested a number of disease-enhancing antibodies in mouse and monkey experiments -- multiple trials with different antibodies -- and determined that disease enhancement does not occur in the animals, and that's good news for the development of effective treatments and vaccines." Haynes said.

Senior author Kevin Saunders, Ph.D., director of research at DHVI, isolated more than 1,700 antibodies from people who had COVID and screened them for their effects on the virus.

"We quickly found a set that were capable of blocking infection, including a set of antibodies that are candidates for clinical trials to prevent people from getting COVID," Saunders said. "We also found a set of antibodies that, instead of preventing infection in tissue culture, they enhanced infection in the test tube."

But in tests administering the antibodies to mice and monkeys, there were no such effects in the body that could be attributed to antibody administration. The presence of the infection-enhancing antibodies also did not counter how well the protective antibodies functioned in the body.

"These results in animal models suggest that SARS-CoV-2 antibody treatments or the induction of SARS-CoV-2 antibodies by vaccination have a low likelihood of exacerbating COVID-19 disease in humans," Saunders said. "Our findings are immediately applicable to COVID-19 vaccine candidates under development in use, and to antibodies and plasma being used to treat COVID-19."

A team of scientists from NUST MISIS and MIPT have developed and tested a new platform for realization of the ultra-strong photon-to-magnon coupling. The proposed system is on-chip and is based on thin-film hetero-structures with superconducting, ferromagnetic and insulating layers. This discovery solves a problem that has been on the agenda of research teams from different countries for the last 10 years, and opens new opportunities in implementing quantum technologies. The study was published in the highly ranked journal Science Advances.

The last decade has seen significant progress in the development of artificial quantum systems. Scientists are exploring different platforms, each with its own advantages and disadvantages. The next critical step for advancing quantum industry requires an efficient method of information exchange between platform hybrid systems that could benefit from distinct platforms. For example, hybrid systems based on collective spin excitations, or magnons, are being developed. In such systems, magnons must interact with photons, standing electromagnetic waves trapped in a resonator. The main limiting factor for developing such systems is the fundamentally weak interaction between photons and magnons. They are of different sizes, and follow different dispersion laws. This size difference of a hundred times or more considerably complicates the interaction.

Scientists from MIPT together with their colleagues managed to create a system with what is called the ultra-strong photon-to-magnon coupling.

Vasily Stolyarov, deputy head of the MIPT Laboratory of Topological Quantum Phenomena in Superconducting Systems, commented: "We created two subsystems. In one, being a sandwich from superconductor/insulator/superconductor thin films, photons are slowed down, their phase velocity is reduced. In another one, which is also a sandwich from superconductor/ferromagnetic/superconductor thin ?lms, superconducting proximity at both interfaces enhances the collective spin eigen-frequencies. The ultra strong photon-to-magnon coupling is achieved thanks to the suppressed photon phase velocity in the electromagnetic subsystem."

Igor Golovchanskiy, leading researcher, senior researcher at the MIPT Laboratory of Topological Quantum Phenomena in Superconducting Systems, head of the NUST MISIS Laboratory of Cryogenic Electronic Systems, explained: "Photons interact very weakly with magnons. We managed to create a system in which these two types of excitations interact very strongly. With the help of superconductors, we have significantly reduced the electromagnetic resonator. This resulted in a hundred times reduction of the phase velocity of photons, and their interaction with magnons increased by several times."

This discovery will accelerate the implementation of hybrid quantum systems, as well as open up new possibilities in superconducting spintronics and magnonics.

WASHINGTON -- Although quantum technology has proven valuable for highly precise timekeeping, making these technologies practical for use in a variety of environments is still a key challenge. In an important step toward portable quantum devices, researchers have developed a new high-flux and compact cold-atom source with low power consumption that can be a key component of many quantum technologies.

"The use of quantum technologies based on laser-cooled atoms has already led to the development of atomic clocks that are used for timekeeping on a national level," said research team leader Christopher Foot from Oxford University in the U.K. "Precise clocks have many applications in the synchronization of electronic communications and navigation systems such as GPS. Compact atomic clocks that can be deployed more widely, including in space, provide resilience in communications networks because local clocks can maintain accurate timekeeping even if there is a network disruption."

In The Optical Society (OSA) journal Optics Express, S. Ravenhall, B. Yuen and Foot describe work carried out in Oxford, U.K. to demonstrate a completely new design for a cold atom source. The new device is suitable for a wide range of cold-atom technologies.

"In this project we took a design we made for research purposes and developed it into a compact device," said Foot. "In addition to timekeeping applications, compact cold-atom devices can also be used for instruments for gravity mapping, inertial navigation and communications and to study physical phenomena in research applications such as dark matter and gravitational waves."

Cooling atoms with light

Although it may seem counterintuitive, laser light can be used to cool atoms to extremely low temperatures by exerting a force that slows the atoms down. This process can be used to create a cold-atom source that generates a beam of laser-cooled atoms directed toward a region where precision measurements for timekeeping or detecting gravitational waves, for example, are carried out.

Laser cooling usually requires a complicated arrangement of mirrors to shine light onto atoms in a vacuum from all directions. In the new work, the researchers created a completely different design that uses just four mirrors. These mirrors are arranged like a pyramid and placed in a way that allows them to slide past each other like the petals of a flower to create a hole at the top of the pyramid through which the cold atoms are pushed out. The size of this hole can be adjusted to optimize the flow of cold atoms for various applications. The pyramid arrangement reflects the light from a single incoming laser beam that enters the vacuum chamber through a single viewport, thus greatly simplifying the optics.

The mirrors, which are located inside the vacuum region of the cold-atom source, were created by polishing metal and applying a dielectric coating. "The adjustability of this design is an entirely new feature," said Foot. "Creating a pyramid from four identical polished metal blocks simplifies the assembly, and it can be used without the adjustment mechanism."

Better measurements with more atoms

To test their new cold-atom source design, the researchers constructed laboratory equipment to fully characterize the flux of atoms emitted through a hole at the apex of the pyramid.

"We demonstrated an exceptionally high flux of rubidium atoms," said Foot. "Most cold-atom devices take measurements that improve with the number of atoms used. Sources with a higher flux can thus be used to improve measurement accuracy, boost the signal-to-noise ratio or help achieve larger measurement bandwidths."

The researchers say that the new source is suitable for commercial application. Because it features a small number of components and few assembly steps, scaling up production to produce multiple copies would be straightforward.

The human intestine is made up of more than 40 square meters of tissue, with a multitude of folds on its internal surface that resemble valleys and mountain peaks in order to increase the absorption of nutrients. The intestine also has the unique characteristic of being in a continuous state of self-renewal. This means that approximately every 5 days all the cells of its inner walls are renewed to guarantee correct intestinal function. Until now, scientists knew that this renewal could take place thanks to stem cells, which are protected in the so-called intestinal crypts, and which give rise to new differentiated cells. However, the process that leads to the concave shape of the crypts and the migration of new cells towards the intestinal peaks was unknown.

Now, an international team led by Xavier Trepat, ICREA Research Professor and Group Leader at the Institute for Bioengineering of Catalonia (IBEC), in collaboration with the IRB, researchers from the UB and UPC universities in Barcelona, and the Curie Institute of Paris, has deciphered the mechanisms leading the crypts to adopt and maintain their concave shape, and how the migration movement of the cells towards the peaks occurs, without the intestine losing its characteristic folded shape. The study, published in the prestigious journal Nature Cell Biology, has combined computer modelling, led by Marino Arroyo, professor at the UPC, researcher associated with IBEC and member of CIMNE, with experiments with intestinal organoids from mouse cells, and shows that this process is possible thanks to the mechanical forces exerted by the cells. An important part of this study has been supported by the "la Caixa" Foundation within the framework of the CaixaResearch programme. The entity has also awarded a scholarship to the first co-author, Gerardo Ceada, to carry out his PhD at IBEC.

The forces determine and control the shape of the intestine and the movement of the cells

Using mouse stem cells and bioengineering and mechanobiology techniques, researchers have developed mini-intestines, organoids that resemble the three-dimensional structure of peaks and valleys, recapitulating tissue functions in vivo. Using microscopy technologies developed by the same group, researchers carried out high-resolution experiments for the first time that have allowed them to obtain 3D maps showing the forces exerted by each cell.

In addition, with this in vitro model, scientists have shown that the movement of new cells to the peak is also controlled by mechanical forces exerted by the cells themselves, specifically by the cytoskeleton, a network of filaments that determines and maintains cell shape.

"Contrary to what was believed up until now, we have been able to determine that it is not the cells of the intestinal crypt that push the new ones up, but that it is the cells at the peak pulling the new ones up, akin to a mountaineer who helps another climber by pulling them up", explains Gerardo Ceada from IBEC

"With this system, we have discovered that the crypt is concave because the cells have more tension on their upper surface than on the bottom, which causes them to adopt a conical shape. When this occurs in several cells next to each other, the result is that the tissue folds, giving rise to a pattern of peaks and valleys", adds Carlos Perez-Gonzalez, (IBEC and Curie Institute).

The new mini-intestine model will allow further studies of diseases such as cancer, celiac disease or colitis to be conducted in reproducible and real conditions, in which there is an uncontrolled proliferation of stem cells or a destructuring of the folds. In addition, intestinal organoids can be manufactured with human cells and used for the development of new drugs or for the study of the intestinal microbiota.

LAWRENCE -- Tulsa may not be the first town one thinks of when talking about jazz, and flood management may not be the first vocation one compares to the musical genre. But the success Tulsa displayed in going from one of the nation's most flood-prone cities to a nationally recognized model of long-term risk reduction in just two decades is analogous to the evolution of one of the most American styles of music, a University of Kansas professor points out in a new study.

Tulsa, the second-largest city in Oklahoma, suffered several devastating floods in the 1970s and 1980s, then became a national model for flood mitigation by the 1990s. What hasn't been studied closely is how a group of engineers, planners, government officials, journalists, attorneys and citizens came together as a network of champions that adapted and evolved over a period of decades.

Ward LylesWard Lyles, associate professor of public affairs & administration at KU, co-wrote a study with Penn Pennell, KU urban planning graduate, and Rachel Riley of the University of Oklahoma detailing the group central to Tulsa's success. It was published in the journal Natural Hazards Review. The authors conducted interviews with local champions from multiple professions who began work on a flood mitigation plan in the 1970s, two of whom remained active in the work well into the 2000s, Ron Flanagan and journalist Ann Patton.

After a rapid succession of floods in the early 1970s, residents and some of the local professionals, functioning similarly to a loosely organized improvisational jazz band, seized the "window of opportunity" to press for change. Myriad approaches were pursued, including buying and demolishing homes in the floodplain and building more flood control structures. However, the band's style fell out of favor, so to speak, when a more conservative city government came to power in the late '70s and instituted more developer-friendly policies focused more on growth than floodplain safety. In their own words, some of the local champions were "exiled" from work in Tulsa and had to find jobs in other states. Meanwhile, flood control efforts cooled.

Tulsa U.S. 66 highway signTulsa suffered another devastating event, the "Memorial Day Flood" of 1984, just weeks after the election of new city leadership dedicated to renewing the commitment to flood mitigation. In subsequent years, members of the original band came back together and became more of a swing-style big band with organized sections compared to its more loosely arranged organization it the 1970s. Engineers, planners, attorneys, local residents and elected officials worked in concert to amplify and extend the efforts of the 1970s. Large swaths of flood-prone homes were purchased and the land was converted to open space suited to recreation and, when needed, flood storage. Land use regulations, engineered structure and education programs helped Tulsa become one of the dozen or so leading flood reduction communities in the early 1990s, when the Federal Emergency Management Agency initiated a program that rewarded proactive communities with lower insurances rates for residents.

The evolution was so successful that Tulsa received a major infusion of federal grant support in the late 1990s, cementing the transition of Tulsa's mitigation jazz band from a popular local group to a nationally emulated act, the authors wrote. A novel local nonprofit spun out of this effort and became a jazz institute of sorts, engaging more deeply with the Tulsa community on other hazards like tornadoes, and extending its work more broadly across the state of Oklahoma. The successful evolution illustrates many key points of successful city planning and management; namely, the importance of weaving together a network of many local champions committed to thinking long term, as opposed to the common approach of dealing with disasters solely in the moment and mainly by depending on narrow groups of experts to set policy.

"Our approach nationally has long been to try to engineer your way out of disasters, frantically respond to them when they happen, or not deal with them at all," Lyles said. "We often fail to think carefully about how land use and infrastructure decisions expose the entire community to risk until it is too late. Floods are a perfect example of this problem because flooding happens along rivers and streams, and we know very precisely where they are. The same tends to be true of areas at risk from hurricanes and wildfires, in contrast to tornados, which touch down randomly within a community."

Through the study, the interviewees revealed the critical importance of having a diverse group of local champions with a wide-ranging set of skills, not only in professional expertise like engineering, planning or law, but perhaps most importantly in communication and collaboration. Varied skills and leadership styles among these champions provided adaptability and resilience to the network but also posed challenges, the authors wrote. A key finding of the study is the role Patton played in facilitating and managing relationships, sometimes between people with very different communication styles, political attitudes and even core beliefs. Patton's professional journey - as a journalist working the "Black beat" in Tulsa in the 1970s, as a political operative and government official in the 1970s through the 1990s and a nonprofit entrepreneur in the 2000s -- is all the more remarkable because she completed her college degree just shy of turning 80 years old in the 2010s.

Emergency response groups regularly feature experts who leverage skills in fire, law enforcement and logistics to prepare for and respond to events. The same is true for city planners, engineers and other public service professionals whose responsibilities relate more to long-term risk reduction. But, across each of these professions, historically dominated by older, white males, the so-called "soft skills" of emotional intelligence, social intelligence and cultural humility -- just the kinds of skills Patton exhibited on top of her more traditional expertise -- are often minimized or ignored in favor of technical skills or specialized forms of knowledge.

"The thing we don't talk enough about in managing disasters - including public health emergencies like COVID -- is critical importance of the 'special sauce' of relationship skills essential for fostering, sustaining and harnessing a diverse and dynamic network of people," said Lyles, who has written previously on the value of caring as part of public planning. "You need someone who can help deploy the hard skills with the soft skills."

That aspect is true in a city like Tulsa with a dark history of race relations, just as it is in any location that has people of different backgrounds, cultures and experiences living together, he added. The experiences of Tulsa and others who have successfully, or even unsuccessfully, handled emergency response and planning have a great deal of parallels to the current COVID-19 pandemic response, as political differences, poor collaboration, egos and poor communication hampering responses on national, state and local levels. Understanding differences, or cultural competence, paired with cultural humility, or acknowledging that one does not completely understand the experience of others, could go a long way in improving responses to current disasters and preparation for those that will come in the future.

"It shouldn't be revolutionary that relationships matter," Lyles said. "But it takes skill to weave relationships together. It's not enough to be professionally passionate. We need social and emotional intelligence as well, and especially cultural humility."

All coronaviruses produce four primary structural proteins and multiple nonstructural proteins. However, the majority of antibody-based SARS-CoV-2 research has focused on the spike and nucleocapsid proteins. A study published in PLOS Biology by Anna Heffron, Irene Ong and colleagues at the University of Wisconsin-Madison, USA, suggests that immune responses may develop against other proteins produced by the SARS-CoV-2 virus.

The efficacy of spike protein-based vaccines is variable and not everyone infected with SARS-CoV-2 produces detectable antibodies against the spike or nucleocapsid proteins. Therefore, expanded antibody-based options have the potential to play an important role in improving vaccines, diagnostics, and therapeutics, particularly given the emergence of new variants. To investigate whether SARS-CoV-2 infection induces robust antibody responses against all SARS-CoV-2 proteins, researchers mapped 79 "epitopes" - specific regions of the viral proteome that antibodies recognize and bind to. They also tested whether antibodies that develop in response to SARS-CoV-2 or existing antibodies from previous exposures to coronaviruses might bind to any of the proteins in the six other known human coronaviruses to identify potential cross-reactive epitopes.

In addition to spike and nucleocapsid proteins, the authors located previously unknown, highly reactive B cell epitopes throughout the full array of proteins in SARS-CoV-2 and other coronaviruses, expanding the potential for future vaccine and therapeutic development. Future research is needed, however, to determine how long these antibodies remain and whether responses of vaccinated individuals differ from those who contracted COVID-19 prior to vaccination. Dr. Ong and colleagues will continue to investigate these aspects in adults and children.

Although the authors did not directly profile variants of concern that have emerged since the beginning of the COVID-19 pandemic, a comparison of the original SARS-CoV-2 genome with a few of the variants of concern identified numerous variations in regions that are at or within 3 amino acids of identified antibody binding epitopes.

According to the authors, "Our extensive profiling of epitope-level resolution antibody reactivity in COVID-19 convalescent subjects, confirmed by independent assays, provides new epitopes that could serve as important targets in the development of improved diagnostics, vaccines, and therapeutics against SARS-CoV-2, variants of concern, and dangerous human coronaviruses that may emerge in the future".