Tech

Teamwork is becoming increasingly common in modern science. In this context, the effect of different characteristics of a team on its research performance has been studied extensively. Various factors such as team size, number of countries involved, universities, disciplines, and workload distribution have been found to have a significant contribution on the paper's role in advancing science.

The question of how the freshness of the team influences its research performance, however, has not been studied systematically. A research team may consist of some researchers who haven't worked with each other before, resulting in a freshness of the team. On the contrary, authors of a paper who have already collaborated can be regarded as an old team. To date little is known regarding the effect of the freshness of the team on advancing science.

In a paper recently published in Nature Human Behaviour, network scientists Prof. An Zeng, of Beijing Normal University and Prof. Shlomo Havlin, of the Department of Physics at Bar-Ilan University, and their colleagues address the effect of team freshness on the originality and multidisciplinary impact of the produced work, by systematically investigating prior collaboration relations between team members. They develop the concept of team freshness of a paper and define it as the fraction of team members that have not collaborated earlier with other team members. Their study reveals that papers of fresher teams are significantly more effective than papers of older teams in creating studies of higher originality and greater multidisciplinary impact. The effect is found to be even more prominent in larger teams. The results also suggest that having new team members is more significant than new collaboration relations in increasing the originality and impact diversity of the resultant papers. Finally, they studied the effect of career freshness of team members before joining the team, finding that the younger the team, the higher the originality and impact diversity of the produced studies. In summary, research of a fresh team is related to better creativity.

The findings in this paper may have some practical applications in stimulating more original and multidisciplinary research works. Funders and decision makers could encourage scientists forming fresh teams in research. Scientists themselves should also seize opportunities to interact with new colleagues for future collaboration as a new team.

Aqueducts are very impressive examples of the art of construction in the Roman Empire. Even today, they still provide us with new insights into aesthetic, practical, and technical aspects of construction and use. Scientists at Johannes Gutenberg University Mainz (JGU) investigated the longest aqueduct of the time, the 426-kilometer-long Aqueduct of Valens supplying Constantinople, and revealed new insights into how this structure was maintained back in time. It appears that the channels had been cleaned of carbonate deposits just a few decades before the site was abandoned.

The late Roman aqueduct provided water for the population of Constantinople

The Roman Empire was ahead of its time in many ways, with a strong commitment to build infrastructure for its citizens which we still find fascinating today. This includes architecturally inspiring temples, theaters, and amphitheaters, but also a dense road network and impressive harbors and mines. "However, the most ground-breaking technical achievement of the Roman Empire lies in its water management, particularly its long-distance aqueducts that delivered water to cities, baths, and mines," said Dr. Gül Sürmelihindi from the Geoarchaeology group at Mainz University. Aqueducts were not a Roman invention, but in Roman hands these long-distance aqueducts developed further and extensively diffused throughout one of the largest empires in history.

Almost every city in the Roman Empire had an ample supply of fresh running water, in some cases actually with a larger volume than is the case today. "These aqueducts are mostly known for their impressive bridges, such as the Pont du Gard in southern France, which are still standing today after two millennia. But they are most impressive because of the way problems in their construction were solved, which would be daunting even for modern engineers," said JGU Professor Cees Passchier. More than 2,000 long-distance Roman aqueducts are known to date, and many more are awaiting discovery. The study undertaken by Dr. Gül Sürmelihindi and her research team focuses on the most spectacular late-Roman aqueduct, the water supply lines of Constantinople, now Istanbul in present-day Turkey.

Carbonate deposits provide insights into Byzantine water management

In AD 324, the Roman Emperor Constantine the Great made Constantinople the new capital of the Roman Empire. Although the city lies at the geopolitically important crossroads of land routes and seaways, fresh water supply was a problem. A new aqueduct was therefore built to supply Constantinople from springs 60 kilometers to the west. As the city grew, this system was expanded in the 5th century to springs that lie even 120 kilometers from the city in a straight line. This gave the aqueduct a total length of at least 426 kilometers, making it the longest of the ancient world. The aqueduct consisted of vaulted masonry channels large enough to walk through, built of stone and concrete, 90 large bridges, and many tunnels up to 5 kilometers long.

Sürmelihindi and her team studied carbonate deposits from this aqueduct, i.e., the limescale that formed in the running water, which can be used to obtain important information about water management and the palaeoenvironment at that time. The researchers found that the entire aqueduct system only contained thin carbonate deposits, representing about 27 years of use. From the annals of the city, however, it is known that the aqueduct system worked for more than 700 years, until at least the 12th century. "This means the entire aqueduct must have been maintained and cleaned of deposits during the Byzantine Empire, even shortly before it ceased working," explained Sürmelihindi. Carbonate deposits can block the entire water supply and have to be removed from time to time.

Double construction over 50 kilometers was likely built for maintenance

Although the aqueduct is late Roman in origin, the carbonate found in the channel is from the Byzantine Middle Ages. This made the researchers think about possible cleaning and maintenance strategies - because cleaning and repairing a channel of 426 kilometers implies that it cannot be used for weeks or months, while the city population depends on its water supply. They then found that 50 kilometers of the central part of the water system is constructed double, with one aqueduct channel above the other, crossing on two-story bridges. "It is very likely that this system was set up to allow for cleaning and maintenance operations," said Passchier. "It would have been a costly but practical solution."

Unfortunately for the research team, it is no longer possible to study the exact operation of the system. One of the most imposing bridges, that of Ballıgerme, was blown up with dynamite in 2020 by treasure hunters who erroneously believed they could find gold in the ruins.

Researchers at Chalmers University of Technology, Sweden, have developed a new material that prevents infections in wounds - a specially designed hydrogel, that works against all types of bacteria, including antibiotic-resistant ones. The new material offers great hope for combating a growing global problem.

The World Health Organization describes antibiotic-resistant bacteria as one of the greatest threats to global health. To deal with the problem, there needs to be a shift in the way we use antibiotics, and new, sustainable medical technologies must be developed.

"After testing our new hydrogel on different types of bacteria, we observed a high level of effectiveness, including against those which have become resistant to antibiotics," says Martin Andersson, research leader for the study and Professor at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology.

Research and development of the material has been ongoing for many years at Martin Andersson's group at Chalmers, growing in scope along the way, with a particular focus on the possibilities for wound care. Now, the important results are published as a scientific article in the journal ACS Biomaterials Science & Engineering.

The main purpose of the studies so far has been to explore new medical technology solutions to help reduce the use of systemic antibiotics. Resistant bacteria cause what is referred to as hospital-acquired infection - a life-threatening condition and is increasing in incidence worldwide.

Mimicking the natural immune system

The active substance in the new bactericidal material consists of antimicrobial peptides, small proteins which are found naturally in our immune system.

"With these types of peptides, there is a very low risk for bacteria to develop resistance against them, since they only affect the outermost membrane of the bacteria. That is perhaps the foremost reason why they are so interesting to work with," says Martin Andersson.

Researchers have long tried to find ways to use these peptides in medical devices, but so far without much success. The problem is that they break down quickly when they come into contact with bodily fluids such as blood. The current study describes how the researchers managed to overcome the problem through the development of a nanostructured hydrogel, into which the peptides are permanently bound, creating a protective environment.

"The material is very promising. It is harmless to the body's own cells and gentle on the skin. In our measurements, the protective effect of the hydrogel on the antimicrobial peptides is clear - the peptides degrade much slower when they are bound to it," says Edvin Blomstrand, doctoral student at the Department of Chemistry and Chemical Engineering at Chalmers, and one of the main authors of the article.

"We expected good results, but we were really positively surprised at quite how effective the material has proven," adds Martin Andersson.

According to the researchers, this new material is the first medical device to make successful use of antimicrobial peptides in a clinically and commercially viable manner. There are many varied and promising opportunities for clinical application.

Startup company Amferia takes the research from lab to market

In recent years, foundational research into the antimicrobial peptide hydrogel has run in parallel with commercial development of the innovation through the spin-off company Amferia AB.

The company was founded in 2018 by Martin Andersson together with Saba Atefyekta and Anand Kumar Rajasekharan, who both defended their dissertations at Chalmers' Department of Chemistry and Chemical Engineering.

The material and the idea, which is currently developed as an antibacterial wound patch, has generated interest around the world, attracting significant investment and receiving several awards. The company is working intensively to get the material to market so that it can benefit wider society.

Before the new material can benefit hospitals and patients, clinical studies are needed, which are ongoing. A CE marking of the material is expected to be completed in 2022. Furthermore, the wound patch version of the new material is undergoing trials in veterinary care, for treating pets. The company Amferia AB is already collaborating with a number of veterinary clinics around Europe where the hydrogel is now being tested.

"Amferia has recently entered into a strategic partnership with Sweden's largest distributor of premium medical & diagnostic devices to jointly launch these wound care products for the Swedish veterinary market during 2021" says Martin Andersson.

More about antimicrobial peptides and the new material

The beneficial properties of antimicrobial peptides have been known for some decades, and thousands of different varieties occurring in the natural immune systems of humans, animals and plants have been discovered. Researchers have long tried to mimic and use their natural function to prevent and treat infections without having to use traditional antibiotics. However, because the peptides are broken down as soon as they come in contact with blood or other body fluids, successful clinical usage has proved elusive. The researchers knew that smart new solutions were needed to protect the peptide from degradation. The new material in the study has been shown to work very well, allowing the peptides to be applied directly to wounds and injuries on the body, with the effect of both preventing and treating infection. The material is also non-toxic, so it can be used directly on the skin. The potential of this new material can also be seen in the flexibility that it offers for different types of products.

"So far, we have mainly envisioned the material as a wound care dressing, but we are working on a new study investigating the potential for a wound care spray," says Edvin Blomstrand.

Most of us have imagined how free it would feel to float around, like an astronaut, in conditions of reduced gravity. But have you ever considered what the effects of reduced gravity might have on muscles? Gravity is a constant force on Earth which all living creatures have evolved to rely on and adapt to. Space exploration has brought about many scientific and technological advances, yet manned spaceflights come at a cost to astronauts, including reduced skeletal muscle mass and strength.

Conventional studies investigating the effects of reduced gravity on muscle mass and function have used a ground control group that is not directly comparable to the space experimental group. Researchers from the University of Tsukuba set out to explore the effects of gravity in mice subjected to the same housing conditions, including those experienced during launch and landing. "In humans, spaceflight causes muscle atrophy and can lead to serious medical problems after return to Earth" says senior author Professor Satoru Takahashi. "This study was designed based on the critical need to understand the molecular mechanisms through which muscle atrophy occurs in conditions of microgravity and artificial gravity."

Two groups of mice (six per group) were housed onboard the International Space Station for 35 days. One group was subjected to artificial gravity (1 g) and the other to microgravity. All mice were alive upon return to Earth and the team compared the effects of the different onboard environments on skeletal muscles. "To understand what was happening inside the muscles and cells, at the molecular level, we examined the muscle fibers. Our results show that artificial gravity prevents the changes observed in mice subjected to microgravity, including muscle atrophy and changes in gene expression," explained Prof. Takahashi. Transcriptional analysis of gene expression revealed that artificial gravity prevented altered expression of atrophy related genes and identified novel candidate genes associated with atrophy. Specifically, a gene called Cacng1 was identified as possibly having a functional role in myotube atrophy.

This work supports the use of spaceflight datasets using 1 g artificial gravity for examining the effects of spaceflight in muscles. These studies will likely aid our understanding of the mechanisms of muscle atrophy and may ultimately influence the treatment of related diseases.

Numerous disease development processes are linked to epigenetic modulation. One protein involved in the process of modulation and identified as an important cancer marker is BRD4. A recent study by the research group of Giulio Superti-Furga, Principal Investigator and Scientific Director at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, now shows that the supply of purines as well as the purine synthesis of a cell can influence BRD4 activity and thus play a role in the carcinogenesis process. The findings were published in Nature Metabolism.

Chromatin is a central component of the cell nucleus. It refers to the complex of the approximately two-meter-long human DNA with proteins that organize it so that - depending on the cell type - certain genes are activated or deactivated. In order to be able to adapt to diverse situations and influences, cells read the information relevant to them from the DNA. If this process is disturbed, diseases such as cancer develop. Scientists have been researching for many years what influences this process. The protein BRD4, which makes a decisive contribution to the unpacking and packaging of DNA in chromatin, was identified as a marker for cancer. Since then, scientists have been investigating how BRD4 can be modulated. A recent study by scientist Kai-Chun Li and the research group of CeMM Scientific Director Giulio Superti-Furga makes an important contribution to answering this question. She investigated how certain externally supplied nutrients, so-called purines, influence BRD4 and thus the development process of various cancer diseases. Purines are basic building blocks of the cell. Disturbances of the purine metabolism in the cell have already been associated with some disease patterns in the past. The study showed, on the one hand, that inhibiting purine supply as well as disturbing purine synthesis can trigger a functional disturbance of BRD4 and thus impact chromatin accessibility. On the other hand, BRD4 functionality could be restored by adding adenine.

Analysis of the transport pathways

Giulio Superti-Furga's research group focuses particularly on those transport proteins in the genome that transport numerous important substances such as nutrients and metabolites into and out of the cell - so-called solute carriers (SLC). First author Kai-Chun Li explains: "Our aim was to investigate the involvement of SLC-mediated purine uptake and cellular metabolism in the modulation of cellular epigenetic states, because purine metabolism plays an essential role in cell metabolism." With the help of SLCs, the scientists were able to modulate the purine supply for their study and observe the direct effects. They used both a genetic screening based on a CRISPR/Cas9 library focused on transporters, and a drug screening using a compound library mainly consisting of cellular metabolites and drugs, both to track down the modulation of BRD4-dependent chromatin states in myeloid leukemia cells. The scientists compared "normal" cancer cells with those cancer cells in which the SLCs that transport purines were inhibited. In addition, purines were added to or omitted from the growth medium of the cells in various experiments, thus modulating purine biosynthesis in the cells.

Adenine brings BRD4 back into balance

The study shows that an imbalance of intracellular purine pools leads to a dysfunction of BRD4-dependent transcriptional modulation of chromatin, which means that the correct reading of DNA information is disturbed. "These results demonstrate a pharmacologically effective axis between purine metabolism and BRD4-dependent chromatin states," explains study leader Giulio Superti-Furga. Drugs that influence BRD4 have already been developed in the past. At the same time, some cancer types also became resistant to such BET inhibitors. "With our study, we show another way to modulate BRD4 - by influencing the purine metabolism." The scientists also found an answer to the question of how BRD4 functionality could be restored: they were able to show that adenine, a purine-derived compound, plays a strong role in BRD4 interaction. "Our results suggest that adenylates (adenine, ATP, etc.) are important for healthy cells. This could be a significant starting point for developing new therapies against BRD4-induced cancer types," says Superti-Furga.

Despite the rapid and significant changes in consumption patterns witnessed during the initial months of the COVID-19 pandemic, Japanese households maintained their normal levels of greenhouse gases emissions. The "anthropause" -- reduction of human activity due to the pandemic -- made headlines last summer, but factory shutdowns and broken global supply chains did not translate into the adoption of eco-friendly lifestyles for the average household.

"During the early COVID-19 period, we could witness lifestyle changes happening around us fast, so we decided to explore the environmental impacts of these lifestyle changes. Some other research at that period was showing that the production-side greenhouse gases emissions decreased, but when assessing the emissions from the consumer side we noticed that they did not change so much compared to 2015 through 2019 levels," said Project Assistant Professor Yin Long from the University of Tokyo Institute for Future Initiatives. Long is first author of the research recently published in One Earth.

Experts say that around the world, half of a nation's carbon footprint is due to the consumption of goods and services by individual households. A carbon footprint is a measure of both the direct and indirect greenhouse gases emissions associated with growing, manufacturing and transporting the food, goods, utilities and services we use.

Researchers considered in this study approximately 500 consumption items and then tracked the carbon emissions embedded in all the associated goods and services. Eating out, groceries, clothing, electronics, entertainment, gasoline for vehicles, as well as home utilities were all included.

"The real beauty of it is the consistency of the long-term data collection in these government statistics, even during the COVID-19 period, which allows us to compare it with historical patterns" said Associate Professor Alexandros Gasparatos, an expert on ecological economics who led the study. Gasparatos holds a dual appointment with the University of Tokyo and the United Nations University in Tokyo.

The monthly carbon footprints of household consumption for the period January to May of 2020 were compared to the carbon footprints of the same months from the previous five years. In Japan, COVID-19 diagnoses began increasing in February and the first nationwide COVID-19 state of emergency was declared from mid-April to mid-May 2020.

The research team's analyses revealed that the 2020 carbon footprint of all households, both aggregate and across different age groups, largely remained within the range of 2015 through 2019.

The carbon footprint of the emissions associated with eating out decreased during the state of emergency, but emissions from groceries increased, especially due to the purchase of more meat, eggs and dairy. Emissions associated with clothing and entertainment decreased sharply during the state of emergency, but rebounded rapidly when the emergency measure ended.

"This kind of natural experiment is telling us that the very quick and consistent change in lifestyle during the early stages of the COVID-19 pandemic did not materialize into significant and sustained changes in the carbon footprints of households," said Gasparatos.

The nonbinding state of emergency declarations by the national and local governments in Japan requested that people limit social gatherings, dining out in groups and nonessential travel between prefectures. Compared to the legally enforced lockdowns in other countries, researchers say Japan's minimal impositions are likely a better model of the lifestyle changes that eco-conscious households might make voluntarily.

"If we see lifestyle change as a strategy to achieve decarbonization, our results suggest that it might not automatically translate into environmental benefits. It will require a lot of effort and public education focused on the most emission-intensive household demands, such as private car use, and space and water heating," said Gasparatos.

"We saw that factories shut down when COVID-19 happened, but consumer demand stayed the same, so factories reopened to satisfy those demands. As written in the United Nations Sustainable Development Goals, consumers and producers should share responsibility for achieving sustainable lifestyles," said Long.

Cerebral aneurysms are malformations caused by abnormalities on the walls of blood vessels in the brain. When these blood vessels rupture, about 30% of the sufferers die on the spot, giving these the rightful label of 'ticking bombs in the head'. Recently, a research team at POSTECH has come up with a new treatment that can disassemble these time bombs by filling the aneurysm in blood with a new method.

In order to overcome the shortcomings of coil embolization, POSTECH's joint research team (Professor Joonwon Kim and Dr. Jongkyeong Lim of the Department of Mechanical Engineering with Professor Hyung Joon Cha and Ph.D. candidate Geunho Choi of the Department of Chemical Engineering) has developed a new structurally stable, biocompatible embolization material that does not decompose in the human body. In addition, a new concept of cerebral aneurysm therapy (treatment device) capable of stably forming and controlling the material in the form of microfibers in the intravascular environment was presented. These research findings were published as the outside back cover paper of Advanced Materials on April 8, 2021.

Early detection of cerebral aneurysms is increasing due to periodic health examinations. The current treatment method uses coil embolization, which lowers the direction and pressure of internal blood flow by filling the aneurysm with a platinum coil before it ruptures. However, coil embolization surgery is a financial burden since it requires many platinum coils (KRW 600,000 (USD 550) per coil) commensurate to the aneurysm size. Moreover, due to the coil's fine spring structure, the aneurysm may burst during surgery or the inside of the aneurysm may not be completely filled. There are also other problems in which the coil may be detached from the affected area due to recompression caused by the low filling rate after operation.

Hydrogels, which respond to various stimuli such as temperature, pH, and light, and exhibit soft mechanical strength, have attracted great attention as an embolic material that can fill an aneurysm at a high rate. Among them, photocrosslinkable hydrogels are considered to be most suitable for embolization thanks to their easy spatiotemporal control. But their practical usage is limited. In addition, materials being developed for aneurysm embolization currently use high concentrations of biologically inactive synthetic hydrogels that are toxic and not biocompatible. These can also cause severe swelling in the body - often leading to ruptures - and have thwarted their commercialization. In addition, conventional surgical methods could not be applied to clinical applications because it was impossible to produce and control hydrogels using light in an intravascular environment, which has a tortuous geometric structure and high absorbance.

The research team led by Professor Hyung Joon Cha of the Department of Chemical Engineering proposed an alginate-based hydrogel derived from algae that can be double-crosslinked as a new material for aneurysm embolization. This new embolic material exhibits excellent biocompatibility and uses the synergistic effect of rapid covalent crosslinking by irradiation with the harmless visible light and ionic crosslinking using calcium ions present in the blood. In addition, since no degrading enzymes exist in the human body, it does not degrade and exhibits outstanding structural stability without swelling. This can safely and effectively fill the aneurysm and successfully prevent rupture. Since it is possible to mount a contrast medium, it exhibits radiopacity so that the embolic material applied through CT or MRI can be monitored continuously for a long time.

The research team led by Professor Joonwon Kim of the Department of Mechanical Engineering developed a microfluidic device with an integrated optical fiber. This device is a new concept surgical device that can stably produce and control photocrosslinkable hydrogels in the form of microfibers in an extreme intravascular environment, which has a tortuous geometric structure and high absorbance.

Double-crosslinked alginate-based hydrogel microfibers produced and controlled in these microfluidic devices can safely and evenly fill the aneurysms. During this stage, the microfibers intertwine with each other to form a lump to block the flow of fluid from entering the aneurysm and maintain the structural shape and constant mechanical strength without dissociation even in the pulsating environment after surgery. This minimizes a resurge of the pressure inside the aneurysm or its rupture.

"This research is the first in the world to develop a new material for embolization that may be biocompatible without side effects and be stably maintained in the human body for a long time," remarked Professor Hyung Joon Cha. "We plan to deliberate on commercialization through a technology transfer."

Professor Joonwon Kim explained, "This research is the first in the world to develop a method that can be used to treat aneurysms by microfibrillating a photocrosslinkable hydrogel microfiber in blood vessels." He added, "It is anticipated these materials will be effectively applicable to many vascular diseases requiring embolization."

"The new concept of embolization method developed in this study was verified using the Advanced Dynamic Angio Model (ADAM) simulator implemented by the new deep coating technology and 3D vascular replica production technology using liquid embolic materials previously developed by the research team. The ADAM simulator is a system that provides a virtual environment that is very similar to the surgical environment of a real patient, and can be used for simulation of various vascular diseases," explained Professor Kim.

The skin, which covers the surface of the human body, is its largest organ. It is the first organ to show changes stemming from organ or physiological activity. It is especially common for diabetic patients to suffer from skin diseases or infections. Recently, a POSTECH research team has succeeded in creating a 3D artificial skin that enables observation of skin diseases of diabetic patients.

A research team led by Professor Dong-Woo Cho and Minjun Ahn of POSTECH's Department of Mechanical Engineering and Professor Byoung Soo Kim of School of Biomedical Convergence Engineering at Pusan National University has successfully produced an in vitro diseased skin model that displays the pathophysiological hallmarks of type 2 diabetes based on 3D cell printing system. These research findings were recently published in Biomaterials, a world-renowned international journal in biomaterials.

Despite continuous research to produce artificial skin with 3D cell printing technology, artificial skin displaying the pathological process present in the native skin has not been reported yet.

Inspired by the interaction between the epidermis and skin cells found in real skin, the research team hypothesized that when normal keratinocytes interact with the dermal layer made of diabetic fibroblasts, they will differentiate into diabetic epidermis. To prove this, diabetic artificial skin with skin wounds based on 3D printing technique was fabricated using each cell.

In this diabetic artificial skin, slow re-epithelialization, a typical feature of diabetic skin, was observed. In addition, when the diabetic fat tissue layer containing blood vessels was added, insulin resistance, adipocyte hypertrophy, pro-inflammatory response, and vascular dysfunction, which are commonly observed in diabetes, were confirmed.

"Through 3D cell printing, we can now observe skin diseases in vitro, without actually experiencing it," remarked the researchers. "We anticipate it to be a way to replace animal models that have been conventionally used to observe skin diseases. It is significant that its applicability as a disease model for new drug development has been proven."

A new study published in The Lancet Infectious Diseases journal has found that the risk of delayed acute complications after non-hospitalised SARS-CoV-2 infection is low, but persistent symptoms in this group could lead to increased visits to general practitioners or outpatient clinics in the six months following infection. The study assessed only those complications that led to contact with hospitals.

Researchers assessed the risk of initiating medication and receiving a hospital diagnosis for a new condition by comparing individuals who tested positive via a PCR test for SARS-CoV-2 with individuals who had a negative test during the first wave of the pandemic in Denmark. Results found SARS-CoV-2 positive individuals were at a slightly increased risk of initiating medications to help improve breathing and alleviate migraines, and had a slightly increased risk of receiving a first diagnosis for breathing problems and blood clots in the veins.

Senior author, Professor Anton Pottegård from the University of Southern Denmark says: "Until now, most research investigating long-term complications from COVID-19 has been focused on hospitalised patients. But the reality is that the majority of people with COVID-19 are not admitted to the hospital. Our study finds a very low risk of severe delayed effects from COVID-19 in people who didn't require hospitalisation for the infection. However, our research provided evidence for some long-term effects that did not require hospitalisation or the use of new medicines, which we found reflected in higher use of primary health-care services after infection. This highlights the need to ensure clinicians have the resources and support to manage any potential long-term conditions." [1]

The researchers used data from the Danish health registries on all individuals who were tested for SARS-CoV-2 between Feb 27, 2020, and May 31, 2020. The study followed up 8,983 non-hospitalised SARS-CoV-2 positive people and 80,894 SARS-CoV-2-negative people during the period from two weeks to six months after the test. By comparing data from the two groups, researchers assessed the relative risk of starting new medications and of receiving a diagnosis of a new health condition during this time.

The analysis took into account variables that could be associated with having a positive versus negative test and with the risk of a more severe course of COVID-19, such as obesity, cancer, and kidney disease.

The cohorts had a median age of 43 years and 64% were female. Among SARS-CoV-2 positive individuals, 31% had initiated new medication treatments during the follow up period. A more detailed analysis found that compared with those with a negative SARS-CoV-2 test those with a positive test were at an increased risk of initiating medications to widen the airways (1.8% compared with 1.5%), and medications to treat migraines (0.4% compared with 0.3%). As such, observed differences were generally small.

The risks of receiving a hospital diagnosis for a new health condition during follow up were similar in the two groups (around 26%). Compared with individuals who tested negative, those with a positive SARS-CoV-2 test were at an increased risk of receiving a first diagnosis of breathing difficulties (1.2% compared with 0.7%) and blood clots in the veins (0.2 % compared with 0.1%). No increased risk of serious complications identified by previous research conducted among individuals hospitalised for COVID-19, such as stroke, encephalitis, and psychosis, was identified among individuals who did not require hospitalisation.

The research also analysed the use of health services in the follow-up period and found that those with a positive SARS-CoV-2 test visited their general practitioners around 20% (1.2 times) more often than those that tested negative, and visited outpatient clinics 10% (1.1 times) more often. However, there was no difference in the visits to emergency department or being hospitalised.

The follow-up of the study was limited to six months after the positive test, which means the data may not have captured the longer-term complications and symptoms of COVID-19 that could occur after this time. In addition, due to the limited resources during the pandemic, some individuals with complications may have been referred to hospitals but not actually attended clinics before the end of the follow-up. This may have affected the numbers of hospital diagnoses recorded.

Commenting on the limitations of the study, co-author Stine Hasling Mogensen, PhD, from the Danish Medicines Agency adds: "Our analysis only captures specific symptoms leading to contact with hospitals, so it is likely that the study underestimates symptoms which do not require this level of care, like fatigue and breathing difficulties which are not severe enough for hospitalisation or require initiation of new medical treatment. Previous research has found a high level of these symptoms reported by patients, so the differences between patient reports and healthcare encounters could be important to investigate in regards to potential unmet healthcare needs and the need for new medications for treatment." [1]

The researchers call for large population-based studies of patient-reported symptoms and healthcare visits to fully evaluate the duration and range of any persisting symptoms after SARS-CoV-2 infection.

Due to the chaotic nature of the atmosphere, weather forecasts, even with ever improving numerical weather prediction models, eventually lose all skill. Meteorologists have a strong desire to better understand this process as they try to trace forecast error back to observational gaps and to provide a means for improvement.

Root mean square error (rms, or its square, the variance distance) is often used to measure differences between simulated and observed fields. In this case, scientists measured the distance between a model forecast field within its grid and the verifying analysis field that represents all real-world observations. However, one must consider that atmospheric features, like fronts and pressure systems are three dimensional weather features in space that computer models displace and also structurally distort as the numerical forecast moves away from initiation. Variance or rms error metrics do not quantify the displacement and distortion of weather systems.

In a recently published paper in Advances in Atmospheric Sciences, a team of scientists with the National Oceanic and Atmospheric Administration (NOAA), the Massachusetts Institute of Technology (MIT), and the University of Connecticut set out to find a general approach to assess the positional and structural components of the total difference between two fields. Essentially, meteorologists want to assess the accuracy of many different weather features within a model forecast compared to a verifying analysis based on real-world observations.

Sai Ravela from MIT, a co-author of this study, previously developed a Field Alignment method. In this case, his approach aligns the model forecast field with the observationally based analysis in a smooth fashion so their difference is minimized (Step 1 in schematic diagram, see also example map). Next, small scale errors from uncertain origins are removed from all three fields (the original and aligned forecast as well as the verifying analysis, or proxy for observations) through a process called spatial filtering or smoothing (Step 2). The total variance distance, or difference, is then partitioned into three unique components (Step 3). Positional error, which is the variance distance between the smoothed original model forecast and smoothed aligned forecast fields, and structural error that is the variance distance between the smoothed aligned forecast and the smoothed verifying analysis fields, are two sides of the right angle triangle in Fig. 1, and fine scale noise, which are the uncertain small-scale errors removed from the original model forecast and verifying analysis, or observation fields (see smoothing arrows orthogonal to the triangle in Fig. 1).

This method outputs the three orthogonal error components as scalar fields, as well as a vector field (Fig. 2) indicating the large-scale displacement of the forecast compared to the observational analysis field. Interestingly, throughout all regions and lead times that the team studied, more than half of the total error variance is associated with the misplacement of weather features. Therefore, displacement is more pronounced than distortion in forecast fields: only about 25% error variance is associated with structural inaccuracies of the partially predictable features, such as fronts and low pressure systems. The rest of the error variance remains unexplained or unpredictable variability, or noise.

"How noise grows in error variance as a function of forecast lead time, and whether a positional-structural-noise decomposition of the spread among an ensemble of perturbed forecasts captures forecast error components is the subject of ongoing studies," said Dr. Jankov from NOAA, the lead author of the study.

A pioneering study by UCL scientists has discovered the presence of a harmful inflammatory protein in patients with symptomatic tuberculosis (TB).

Researchers say, by targeting the IL-17 cytokine, a component produced naturally by the immune system in response to infection, excessive and damaging lung inflammation caused by TB may be significantly reduced to help speed up patient recovery.

TB is an infection caused by the bacterium Mycobacterium tuberculosis and is the leading cause of death from infections worldwide. The World Health Organisation estimates that 1.4 million people died of TB disease worldwide in 2019.

Explaining the experimental study, lead author Dr Gabriele Pollara (UCL Division of Infection & Immunity), said: "For most people the body's immune response to TB is a vital defence strategy to contain the infection, but when disease develops it can worsen symptoms, cause lung damage, and promote transmission of the infection to others.

"For some time, we have thought that the body's own immune response to TB could in fact be causing more tissue damage and promoting the spread of infection - but we did not know how this happens.

"In this study, we found that in patients with active TB, the immune system may be responding pathologically (causing harm), and that this immune response was not present in those with latent TB, who have controlled the infection."

As part of the study, published in Science Translational Medicine, medical centres in the UK, South Africa and Peru recruited patients to take a tuberculin skin test (TST), which involves injecting a small amount of fluid (called tuberculin) into the skin on the lower part of the arm. Raised skin or swelling, detected 48 hours later, denotes a positive test.

Subsequent tests confirmed 48 of the people recruited had symptomatic TB and 191 people had asymptomatic/latent TB. Genome-wide transcriptional profiling of biopsies of the TSTs was then carried out to make detailed measurements of the immune response.

Researchers discovered that samples from patients with symptomatic TB disease showed increased activity of IL-17 cytokine, which is an immune response known to cause tissue damage in other inflammatory conditions.

Dr Pollara, an NIHR Clinical Lecturer, added: "This new research has identified for the first time the nature of these potentially harmful immune pathways. We show that a specific immune pathway, the IL-17 cytokine, is present exclusively in the immune response of patients with TB disease, but not those who never develop symptoms.

"This is a fascinating finding because IL-17 cytokine responses cause disease and tissue damage in other inflammatory conditions, such as psoriasis and ankylosing spondylitis. In both conditions, drugs that block the IL-17 pathway are highly effective at improving patient symptoms, and so our findings indicate these same drugs could also be beneficial in treating patients with TB disease."

For over 50 years, the mainstay of treatment for tuberculosis has been antibiotics that kill bacteria. Although effective, this strategy carries a lot of challenges; treatment involves taking four antibiotics and lasts for at least six months, and its efficacy is being increasingly challenged by rising rates of antibiotic resistance. Therefore, developing new approaches to treating TB disease is an urgent global research priority.

Senior author, Professor Mahdad Noursadeghi (UCL Division of Infection & Immunity) said: "Our work has the potential to make a step change in care of TB patients, providing a rationale for targeting specific immune components, alongside the conventional use of antibiotics.

"We anticipate this would accelerate clinical recovery, interrupt transmission between individuals and reduce the time antibiotic treatment is required. More broadly, these findings open the door to an exciting new frontier in treating infectious diseases.

"By understanding immune responses to infections that are detrimental, it justifies the use of focused 'host-directed' drugs that complement the action of antibiotics. In turn this strategy has the potential to limit disease severity, shorten antibiotic courses, and therefore mitigate against the rise in antibiotic resistance worldwide."

Next steps

Researchers aim to devise a clinical trial to test whether drugs targeting IL-17 cytokine in patients with symptomatic TB reduce symptoms and improve patient outcomes.

In a time of a global crisis such as the ongoing COVID-19 pandemic, it is easy to note how people move through different phases to buckle up for such unprecedented and arduous times.

In the very beginning of the pandemic last year, we observed "an epidemic of fear", where it was all about the calamitous nature of a totally unknown virus and its worrying contagiousness and mortality rate. A few months later, with lockdown and restrictions already in place across the world, the fear was replaced by "an epidemic of explanations", where people even in their naivety, started to seek a sense of comfort by placing the blame on someone or something out of their control.

This is why a research team at the SWPS University of Social Sciences and Humanities and the Polish Academy of Sciences sought to figure out whether the government was indeed the main culprit for the spread of the COVID-19 pandemic in the eyes of the public. After all, it fitted best the role of an actor of higher authority, allegedly powerful enough to protect the community and resolve the issue at hand and provide the necessary comfort. In the meantime, it comes as an easy target to point a finger at for 'not doing enough'. On the other hand, the public could as well be explaining the situation with the virulence of the Coronavirus or with the irresponsible behaviour of others in the society. Regardless of the answer, the team was interested in understanding what's behind one's reasoning: was it their political views, well-being or emotions?

To test their hypotheses, the researchers chose to conduct their study in Poland: a country currently politically divided between Liberalism and Communitarianism, with the latter being the ruling party at the time of the survey, which took place between May and June 2020. A total of 850 Polish adults fully diversified in terms of gender, age, and education participated. The findings are now published in the open-access, peer-reviewed scientific journal Social Psychological Bulletin.

As a result, the study concluded that not only was it the government and the system that most of the participants attributed responsibility to for the COVID-19 incidence rates, but that the political views and party preferences of the participants played an incomparably more significant role in their responses than factors such as anxiety, stress and depression levels or overall self-reported well-being. In fact, amongst the mental health symptoms, the study found that only increased anxiety was statistically significantly related to the tendency to blame the government and its decisions. This could be explained by the fact that people experiencing higher anxiety levels are more likely to exaggerate external responsibility, note the scientists. Curiously, the more educated participants were found to be more likely to emphasise governmental responsibility.

Furthermore, the people with lebaral views who did not support the ruling communitarian party blamed the government to a higher degree than their counterparts, who would often place the responsibility for the spread of COVID-19 on non-governmental factors.

In their study, the research team uses several theories to explain this finding, including the Terror Management Theory, which notes that reminding people of their mortality induces an existential threat that also leads to an increased need for protection provided by worldview-based beliefs. On the other hand, the theories of attribution and social roles suggest that people see the 'adequate protection against epidemic' as part of the government's duties.

In conclusion, the authors remind that their observations during the survey are consistent with previous reports as a result of natural disasters.

"Citizens observe governmental activities during the epidemic period and evaluate government responsibility. In the light of the results of previous studies on the social perception of natural disasters, we think that this is a rather general phenomenon. Looking for an explanation of the epidemic effects, people tend to blame salient external causes," say the researchers.

In cancer, a lot of biology goes awry: Genes mutate, molecular processes change dramatically, and cells proliferate uncontrollably to form entirely new tissues that we call tumors. Multiple things go wrong at different levels, and this complexity is partly what makes cancer so difficult to research and treat.

So it stands to reason that cancer researchers focus their attention where all cancers begin: the genome. If we can understand what happens at the level of DNA, then we can perhaps one day not just treat but even prevent cancers altogether.

This drive has led a team of researchers from EPFL and the University of Lausanne (UNIL) to make a breakthrough discovery concerning a critical genetic aberration that occurs in cancer. Working together, the groups of Elisa Oricchio (EPFL) and Giovanni Ciriello (UNIL) have used a novel algorithm-based method to study how cancer cells re-organize the 3D structure of their DNA in order to ramp up the activity of cancer-promoting genes called "oncogenes." The work is published in two journals, Nature Genetics and Nature Communications.

The research focuses on chromosomes, where our DNA is packaged, and how the chromosomes are organized in the tight space of the cell nucleus. Given that every single one of the billions of cells in our body contains about two meters of DNA, it's understandable that we evolved mechanisms to store it properly. That mechanism involves winding DNA around specialized proteins called histones, like a string spooling around a yoyo.

The resulting super-packed and well-protected DNA-protein complex is called chromatin. Multiple units of chromatin make up the structures we know as chromosomes. Normally, each cell carries 23 chromosomes and two copies for each chromosome, but in cancer cells, their structure and organization change. For example, a piece of a copy of chromosome 8 can be attached to a copy of chromosome 14. Moreover, a chromosome can take on a more relaxed or compact structure, which depends on chemical modifications called "epigenetic marks".

The researchers investigated how changes in specific epigenetic marks modify chromosome structures and the expression of genes that promote tumor growth, known as oncogenes.

Giovanni Ciriello's team at UNIL developed a novel algorithmic approach called Calder (after the American sculptor Alexander Calder) to track how genomic regions are positioned with respect to each other in the nucleus. "We used Calder to compare the spatial organization of the genome in more than a hundred samples," says Ciriello. "But this organization is not static and, just like Alexander Calder's mobile sculptures, it can rearrange its pieces." The researchers used Calder to track regions of chromatin that "moved" from one area of the nucleus to another as a result of changing epigenetic marks.

Meanwhile, Oricchio's team at EPFL used Calder to track changes of the chromatin 3D structure in normal and B-cell lymphoma cells. They discovered that in the lymphoma cells, specific epigenetic changes cause chromatin regions to be repositioned in different areas of the nucleus, which lead to novel local interactions that over-activate the expression of oncogenes.

The also found that, when two fragments from different chromosomes are broken off and swapped, they assume a 3D structure that is distinguishable from the normal copies. Importantly, these changes of 3D structure correspond to different epigenetic marks, and induce high expression of genes that support tumor cell expansion.

"Most of the time we think of our DNA as a long, linear molecule, and it's only recently that we started to understand how its 3D organization is altered in cancer cells," says Oricchio. "Considering the spatial organization of DNA in the nucleus provides a new lens to understand how tumor cells originate, and how therapeutic modulation of epigenetic marks can block tumor progression."

COLUMBUS, Ohio - The symptoms of grief people feel for a loved one facing a life-limiting illness fluctuate over time, a new study found - suggesting that individuals can adjust to their emotional pain, but also revealing factors that can make pre-loss grief more severe.

Researchers examined changes in the severity of pre-loss grief symptoms in people whose family members had either advanced cancer or dementia.

The study is the first to document pre-loss grief at two points in time, and found that about 70% of participants' symptoms decreased over a month. However, compared to initial symptoms reported by participants, women and those with a heavy caregiving burden were more likely to be experiencing more intense symptoms a month later.

The results also showed that family members of patients with dementia, for which there is no long-term treatment or cure, were significantly more likely than family members of cancer patients to have severe pre-loss grief - but that some people anticipating losing a loved one to cancer also had unexpectedly high levels of pre-loss grief.

Participants reported similar symptoms no matter how long they had been living with the knowledge that their loved one had a life-limiting illness - another surprising finding for Jonathan Singer, lead author of the study and a clinical psychology intern in psychiatry and behavioral health at The Ohio State University.

"People in this study had pre-loss grief at a very high rate after many years. That was shocking, because one might think over time it would get easier. But with Alzheimer's disease, it can get harder, and with cancer there could be a similar trajectory, starting with hope at the beginning but feeling worse over time," Singer said.

"What's happening with these family members still struggling - is it the caregiver burden, is it that they've lost their identity, is it that they're not engaging in pleasurable activities anymore? That's what we want to hit on next."

The study was published recently in the Journal of Health Psychology.

Though pre-loss grief is not a clinical diagnosis, prolonged grief disorder in people mourning the death of a loved one has been added to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) released this year. Clinical criteria for a diagnosis include preoccupation with thoughts or memories of the lost family member combined with a number of symptoms such as intense emotional pain, a sense of disbelief and difficulty moving on with life.

Adding prolonged grief disorder to the DSM-5 represents progress, Singer said - but the relatively new area of research on pre-loss grief demonstrates a need to consider therapies that can ease symptoms of people who are grieving for an ill loved one who is still alive.

"There's a lot of research on anticipatory grief, which involves worry about the future. But pre-loss grief in that moment is pretty ignored," said Singer, who treats patients at Ohio State Wexner Medical Center.

"With medical advances, people are going to be living longer with life-limiting illnesses, so there will be a bigger and bigger issue with grief before the person passes away. Symptoms of pre-loss grief can predict long-term negative outcomes after a loved one's death, so this is a good intervention target that we should figure out now."

Though it's too soon to tell what types of therapies might work best, Singer noted two approaches that hold promise: behavioral activation that encourages people to engage in pleasurable activities, and meaning-centered psychotherapy designed to enhance spiritual well-being and quality of life.

For this study, the researchers recruited family members of patients with advanced cancer (100) and dementia (38) who completed questionnaires assessing their symptoms of grief, depression, post-traumatic stress and caregiving burden. Of those, 33 family members of cancer patients and 28 family members of dementia patients completed a follow-up assessment one month later.

The initial assessment showed that participants were experiencing substantial pre-loss grief. Women and participants with a higher caregiver burden were the most likely to be experiencing more intense grief one month later.

Overall, 69% of participants reported decreases in symptoms a month after the first assessment - a phenomenon that Singer plans to explore in follow-up studies.

There were no differences in pre-loss grief at baseline or one month later based on the nature of the life-limiting illness. But in a secondary analysis of the severity of reported symptoms, the researchers found that 10.5% of family members of dementia patients and 2% of family members of cancer patients met the criteria for a diagnosis of prolonged-grief disorder.

"We expected to see this severity in family members of patients with dementia," Singer said. "But there is a lot of hope in the cancer community, so it was a big surprise to see so much pre-loss grief in family members of cancer patients."

Singer led a recent study designed to help pave the way to a better understanding of how preparing for the death of a family member may prevent mental health problems for their survivors. He is currently involved in a study of a longer-term trajectory of pre-loss grief and is interested in investigating its biological effects.

NEW YORK, NY (May 10, 2021)--Scientists have discovered that many esophageal cancers turn on ancient viral DNA that was embedded in our genome hundreds of millions of years ago.

"It was surprising," says Adam Bass, MD, the Herbert and Florence Irving Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, who led the study published May 10 in Nature Genetics. 

"We weren't specifically searching for the viral elements, but the finding opens up a huge new array of potential cancer targets that I think will be extremely exciting as ways to enhance immunotherapy."

Fossil Viruses and Cancer

The idea that bits of ancient retroviruses within the human genome--known as endogenous retroviral elements, or ERVs--play a role in cancer is not new. Though ERV sequences have degraded over time and cannot produce viral particles, the viral fossils are sometimes inserted into other genes, which disrupts their normal activities, or act as switches that turn on cancer-causing genes.

More recently, however, research suggests ERVs may also fight cancer if they are transcribed into strands of RNA.

"When cells activate lots of ERVs, a lot of double-stranded RNA is made and gets into the cell cytoplasm," Bass says. "That creates a state that's like a viral infection and can cause an inflammatory response. In that way, ERVs may make the cancer more susceptible to immunotherapy, and many researchers are working on ways to trick cancer cells into activating ERVs."

Esophageal Cancers Turn on ERVs

In the new study, Bass and his colleagues created esophageal organoids from mouse tissue to follow the development of cancer from normal cells to malignancy.

Using these organoids, Bass found that a specific cancer-promoting gene in esophageal cancers called SOX2 leads to induction of expression of many ERVs.  

As the expression of ERVs and the accumulation of double-stranded RNAs that can result from ERV expression can be toxic to cells, the researchers found that there is a specific enzyme called ADAR1 that quickly degrades these double-stranded RNAs. 

ADAR1 has been implicated in esophageal cancer by other researchers, although its role had been unclear. Levels of ADAR1 are known to correlate with poor survival. "The cancers are dependent on ADAR1 to prevent an immune reaction that can be very toxic to the cells," Bass says.

Some patients with esophageal cancer are currently treated with immunotherapy, which has been shown to increase survival by several months. "We have a lot of enthusiasm that blocking ADAR1 may both have direct efficacy for esophageal cancers and that ADAR1 inhibition may have even great effects by enhancing the efficacy of cancer immunotherapy in patients with esophageal cancer," Bass says. 

Organoids Reveal Other Potential Targets in SOX2 Cancers

Beyond the results regarding ADAR1 and ERVs, the process of modeling the development of esophageal cancer via genomic engineering of organoids also revealed many other processes in esophageal cancer that could lead to new treatments.

"The way we used organoids to build cancers up from the normal cell is a powerful system for uncovering cancer-causing activities and testing therapeutic targets," Bass says. "By making individual genome alterations in these models one at a time, we can see which combinations of genetic alterations lead to cancer and then determine specific mechanisms of tumor formation."

The organoids in the current study started with overexpression of the SOX2 gene, a commonly amplified factor that promotes the development of squamous cancers. 

In the study, the Bass team built a panel of organoids modeling the spectrum from normal esophagus to fully transformed cancer. 

By being able to evaluate the differential features of normal and cancerous organoids, the team could dissect how the activity of SOX2 differs in normal and cancerous tissues. "It's important to understand the difference, since potential treatments need to target the cancer functions but have lesser impact upon normal tissue," he says. "It's relatively easy to kill cancer cells. The problem is, how do you kill cancer cells but spare other cells?"

The organoids revealed that when SOX2 is overactive--and two tumor suppressors are inactivated--SOX2 works with other factors to turn on an assortment of cancer-causing genes in addition to their effects upon induction of ERVs.  

"These findings reveal new vulnerabilities in SOX2 esophageal cancers," Bass says, "that will now allow us to begin developing therapies that can precisely target the cancer cell and improve the treatment of patients."