Tech

Drinking plenty of both green tea and coffee is linked to a lower risk of dying from any cause among people with type 2 diabetes, suggests research published in the online journal BMJ Open Diabetes Research & Care.

Drinking 4 or more daily cups of green tea plus 2 or more of coffee was associated with a 63% lower risk of death over a period of around 5 years, the findings show.

People with type 2 diabetes are more prone to circulatory diseases, dementia, cancer, and bone fractures. And despite an increasing number of effective drugs, lifestyle modifications, such as exercise and diet, remain a cornerstone of treatment.

Previously published research suggests that regularly drinking green tea and coffee may be beneficial for health because of the various bioactive compounds these beverages contain.

But few of these studies have been carried out in people with diabetes. The researchers therefore decided to explore the potential impact of green tea and coffee, separately and combined, on the risk of death among people with the condition.

They tracked the health of 4923 Japanese people (2790 men, 2133 women) with type 2 diabetes (average age 66) for an average of just over 5 years.

All of them had been enrolled in The Fukuoka Diabetes Registry, a multicentre prospective study looking at the effect of drug treatments and lifestyle on the lifespan of patients with type 2 diabetes.

They each filled in a 58-item food and drink questionnaire, which included questions on how much green tea and coffee they drank every day. And they provided background information on lifestyle factors, such as regular exercise, smoking, alcohol consumption and nightly hours of sleep.

Measurements of height, weight and blood pressure were also taken, as were blood and urine samples to check for potential underlying risk factors.

Some 607 of the participants didn't drink green tea; 1143 drank up to a cup a day; 1384 drank 2-3 cups; and 1784 drank 4 or more. Nearly 1000 (994) of the participants didn't drink coffee; 1306 drank up to 1 cup daily; 963 drank a cup every day; while 1660 drank 2 or more cups.

During the monitoring period, 309 people (218 men, 91 women) died. The main causes of death were cancer (114) and cardiovascular disease (76).

Compared with those who drank neither beverage, those who drank one or both had lower odds of dying from any cause, with the lowest odds associated with drinking higher quantities of both green tea and coffee.

Drinking up to 1 cup of green tea every day was associated with 15% lower odds of death; while drinking 2-3 cups was associated with 27% lower odds. Getting through 4 or more daily cups was associated with 40% lower odds.

Among coffee drinkers, up to 1 daily cup was associated with 12% lower odds; while 1 cup a day was associated with 19% lower odds. And 2 or more cups was associated with 41% lower odds.

The risk of death was even lower for those who drank both green tea and coffee every day: 51% lower for 2-3 cups of green tea plus 2 or more of coffee; 58% lower for 4 or more cups of green tea plus 1 cup of coffee every day; and 63% lower for a combination of 4 or more cups of green tea and 2 or more cups of coffee every day.

This is an observational study, and as such, can't establish cause. And the researchers point to several caveats, including the reliance on subjective assessments of the quantities of green tea and coffee drunk.

Nor was any information gathered on other potentially influential factors, such as household income and educational attainment. And the green tea available in Japan may not be the same as that found elsewhere, they add.

The biology behind these observations isn't fully understood, explain the researchers. Green tea contains several antioxidant and anti-inflammatory compounds, including phenols and theanine, as well as caffeine.

Coffee also contains numerous bioactive components, including phenols. As well as its potentially harmful effects on the circulatory system, caffeine is thought to alter insulin production and sensitivity.

"This prospective cohort study demonstrated that greater consumption of green tea and coffee was significantly associated with reduced all-cause mortality: the effects may be additive," the researchers conclude.

With a little tweak of the color palette, University of Virginia School of Medicine researchers have made it easier for scientists to understand biological processes, track happenings inside individual cells, unravel the mysteries of disease and develop new treatments.

UVA's Hui-wang Ai, PhD, and Shen Zhang, PhD, have developed a simple and effective improvement to fluorescent "biosensors" widely used in scientific and medical research. The biosensors detect specific targets inside cells and sets them aglow, so that scientists can monitor and quantify biological events they otherwise could not.

Most fluorescent protein biosensors give a green or yellow glow, but Ai and Zhang have discovered a way to shift the green to red. This comes with big benefits, including making it easier for scientists to monitor multiple targets at a time and to peer more deeply into tissues.

"This innovative method can convert not only existing biosensors, but also any green biosensors developed in the future," Ai said. "Multicolor and/or multiplexed imaging with fluorescent biosensors cells will thus become widely accessible."

Lighting the Way

While there are existing red biosensors, they are typically outperformed by their green counterparts. So scientists have been eager to find ways to shift the green color into red, retaining the benefits of the green sensors while adding new ones, such as reducing the visual confusion that can be caused by the natural fluorescence of tissues and cells.

Ai and Zhang found a solution partly by a stroke of luck - or "serendipity," as they describe it in a new scientific paper. In the course of their regular lab work, they found that adding a particular amino acid, 3-aminotyrosine, to the green biosensor made it turn red. This is simple to do and quite effective, they report. The red version preserved the brightness, dynamic range and responsiveness of the green sensor, while offering the additional benefits of a red one.

"We modified a panel of green biosensors for metal ions, neurotransmitters and cell metabolites," Zhang said. "Spontaneous and efficient green-to-red conversion was observed for all tested biosensors, and little optimization on individual sensors was needed."

The researchers tested their improved biosensor on cells that make insulin in the pancreas. They were able to monitor the effect of high levels of glucose on the cells, gaining new insights and giving the researchers new directions to explore.

They hope their quick-and-easy sensor upgrade will offer similar benefits to many other scientists and lines of scientific research.

"It will have lots of applications," Ai said, "such as acceleration of our understanding of how pancreas controls insulin secretion or how neuronal activity patterns in the brain correlate with complex behavior."

(Vienna, 20 October 2020) Patients with thyroid dysfunction are routinely treated with drugs to regulate the hormone imbalance. The effect of these drugs is clinically evaluated by means of blood tests. A team led by Michael Krebs from MedUni Vienna's Division of Endocrinology and Metabolism has now conducted a study to test the use of magnetic resonance spectroscopy (NMRS) to measure the effect in body tissue as well. They were able to identify certain phosphorus-containing compounds that are visible in NMRS as markers for thyroid hormone action in tissue. The study has been published in the prestigious "Journal of Clinical Endocrinology and Metabolism".

Thyroid dysfunction affects up to 10% of the Western population, an underactive thyroid (hypothyroidism) being the most prevalent form. Patients are routinely treated with thyroxine and the success of the treatment is monitored by means of blood tests. However, it has been found that approximately 10 to 15% of all those treated continue to experience problems such as lethargy and tiredness.

It has been known from the animal model that, although animals that have been treated with hormones to combat thyroid insufficiency display normal blood concentrations, a hypofunction is nonetheless detected in their tissue. An increasing number of studies have subsequently shown that the effect of many hormones is not only dependent upon the blood concentration but also upon complex regulation mechanisms in the cells, which are controlled in the short term.

Working in close collaboration with the Center of Excellence for High-Field MR, a team of researchers led by Michael Krebs from the Division of Endocrinology and Metabolism of the Department of Medicine III at MedUni Vienna has now developed a non-invasive method for measuring thyroid hormone action not only in blood but also in tissue. They were able to identify certain phosphorus-containing compounds that are visible in NMRS as markers for thyroid hormone action in tissue. This allows hormone action to be determined in different areas of the body, such as in muscles or in the liver, like in a "virtual tissue section".

Says Krebs: "The regulation of hormone action not only via the blood concentration but also via local control in the tissues has long been underestimated. If we are able to develop methods for visualising this phenomenon in practice, we are opening up completely new worlds." As a next step, studies are planned to try out the new method in clinical practice, with the aim of providing better care for patients.

What The Study Did: Researchers in this randomized clinical trial compared the effect of early administration of tocilizumab with standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia.

Authors: Carlo Salvarani, M.D., of Unita Operativa di Reumatologia in Reggio Emilia, Italy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamainternmed.2020.6615)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

CAR-T biotherapeutics company Carina Biotech and researchers at the University of South Australia have developed a novel approach based on microfluidic technology to "purify" the immune cells of patients in the fight against cancer.

UniSA's Future Industries Institute PhD student Mona Elsemary has developed a microfluidic approach to purify chimeric antigen receptor (CAR-T) cells, the bioengineered immune cells that are the basis of groundbreaking cellular immunotherapy - a transformative cancer therapy that harnesses the power of a patient's immune system to fight their cancer.

Ms Elsemary's work is part of Carina Biotech's CAR-T development platform, which aims to produce effective treatments for solid cancers. Ms Elsemary will present her work tomorrow at the American Association for Cancer Research Conference on Tumor Immunology and Immunotherapy.

"CAR-T therapy has produced some remarkable results against blood cancers and there is a huge international research effort underway to transform this success into producing CAR-T treatments for solid cancers," Ms Elsemary says.

"However, the CAR-T manufacturing process continues to be hindered by significant barriers and high costs - preventing the full potential of this life-saving therapy being reached."

Such problems include the presence of non-viable cells and debris in the formulation and the presence of cryoprotectants (e.g., dimethyl sulfoxide or DMSO), typically used for the freezing and storage of CAR-T cell products.

The presence of dead cells can cause potentially severe side effects in recipients, and the US Federal and Drug Administration (FDA) has set strict viability specifications for CAR-T products, with approximately 10% of patients not receiving their treatment due to failure in meeting them.

The presence of cryoprotectants in final CAR-T products can also cause severe allergic reactions and toxic side effects in some patients.

"Current commercial CAR-T cell products still contain significant amounts of DMSO," Ms Elsemere says. "Therefore, there is a significant need for a method that effectively purifies CAR T cells prior to infusion to patients. "

The approach was developed by the University of South Australia team led by Prof Benjamin Thierry in collaboration with Assoc Prof Majid Warkiani at the University Technology Sydney, and could achieve, within 30 minutes, depletion of over 70% of dead cells in the CAR T products, leading to an average of 20% increase in cell viability.

In addition, over 90% of the cryoprotectant DSMO is removed - all with no detrimental effect on the quality and functionality of the cells.

This microfluidic technology used in the method could easily be integrated within an automated closed-cell processing system and used in non-clean room facilities, researchers say.

Ms Elsemary's research could greatly benefit patients by reducing both manufacturing cost and side-effects commonly associated to CAR T cell therapy.

A highly effective drug therapy is urgently required to combat coronavirus disease 2019 (COVID-19). The authors of this article have developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies, the other is for identifying lead compounds against potential drug targets via docking. This server has several unique features:

1. Potential target proteins and their different conformations involved in the whole process from virus infection to replication and release are included.
2. All potential ligand-binding sites with a volume larger than 200 Å3 on a protein structure were identified for docking.
3. Correlation information among some conformations or binding sites are annotated.
4. The server is easily updatable, and publicly available.

Currently, the webserver contains 46 proteins [22 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 24 human proteins involved in virus infection, replication and release] with 86 different conformations/structures and 797 potential ligand-binding pockets in total. In this article the authors demonstrate that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against SARS-CoV-2 to combat COVID-19.

Discovering and synthesizing symmetry-protected topological (SPT) band degeneracies, including nodal points and nodal lines (NLs), is a rapidly growing frontier in the field of topological materials. Interestingly, since the crystallographic space groups impose fewer constraints on the energy bands than the continuous Poincaré group, more exotic multifold band crossings were found in lattice systems, which have no counterparts in high-energy physics. In PhCs, the topology of band structures is usually thought to be adequately described by spinless space groups, provided that special internal symmetries, such as electromagnetic (EM) duality, are not imposed on the EM materials. However, in dielectric PhCs, there are always two gapless bands emerging from the origin of light cone (ω=|k|=0), irrespective of the space group representations at that point. It was recently demonstrated that this intrinsic singularity of EM fields permits higher minimal connectivity for the lowest photonic bands than for their electronic counterparts without spin-orbit coupling and may further enforce unique photonic band crossings even in symmorphic lattices.

In a new paper published in Light Science & Application, a team of scientists, led by Professor C. T. Chan from the Hong Kong University of Science and Technology and Associate Professor Yuntian Chen from Huazhong University of Science and Technology, and co-workers have discovered a new kind of hidden symmetry in PhCs, due to the special characters of Maxwell equations. Based on this hidden symmetry, they found that in an AB-layer-stacked photonic crystal composed of anisotropic dielectrics, the unique photonic band connectivity leads to a new kind of symmetry-enforced triply degenerate points at the nexuses of two nodal rings and a Kramers-like nodal line. More interestingly, the nexus points of three NLs behaver as a new kind of magnetic monopole terminating Berry flux strings in the momentum space, and show novel spin-1 canonical diffraction.

In general, the stationary Maxwell's equations can be written as a generalized eigenvalue problem . Since all space group transformations leave the curl matrix N ?(r) invariant, a PhC respects a space group symmetry A ? only if its constitutive tensor obeys A ??M ?(r)A ?^(-1)=M ?(r). However, a generic symmetry A ? of Maxwell's equations (1) operates on the Hamiltonian H ?(r)=M ?(r)^(-1) N ?(r) of EM fields, namely, requiring ?A H ?(r) A ?^(-1)=H ?(r), and not on N ?(r) and M ?(r) separately. This fact implies that the conventional space groups alone are insufficient to determine the symmetry properties as well as the band connectivities of photonic systems.

In this work, they proposed a simple layer-stacked photonic structure consisting of anisotropic dielectrics to exemplify such hidden symmetries of Maxwell's equations beyond space groups. They show that a hidden symmetry, more specifically, a generalized fractional screw rotation symmetry, together with time reversal symmetry guarantees the emergence of Kramers-like straight NLs passing through the Brillouin zone centre and results in unusual photonic band connectivities. Furthermore, they demonstrated the lowest Kramers-like NL can almost always intersect with two other SPT nodal rings at two triply degenerate nexus points (NPs), which can be seen as a new kind of magnetic monopole connecting Berry flux strings in momentum space. By breaking the hidden symmetry, the two NPs are lifted and type-II and type-III nodal rings are achieved in the PhC for the first time.

In addition, the peculiar anisotropic band structure near the NPs, especially the spin-1 conical dispersion of the iso-frequency surfaces, lead to novel transport phenomena.

Unlike the usual conical diffraction of light scattered at an ordinary linearly crossing point on the nodal lines characterized by spin-1/2 dynamics, , the diffraction at the triple NPs appears strikingly different spin-1 wave behavior described by a Schrödinger equation with the 2D spin-1 Hamiltonian. The authors showed that such unconventional spin-1 conical diffraction can be used to generate optical vortices with a maximum topological charge of 2.

In humans, vitamin D is formed in the skin following its exposure to sunlight. In comparison to the body's own formation of vitamin D, dietary consumption generally makes up only a relatively small proportion of the vitamin D supply to the body. While an overdose resulting from the body's own production is not possible, it certainly can result from the consumption of highdoses of vitamin D - such as via certain food supplements.

An overdose of this kind leads to elevat ed calcium values in blood serum (hyperc alcaemia). The clinical symptoms associated with hypercalcaemia in humans range from fatigue and muscular weakness to vomiting and constipation, and can even lead to cardiac arrhythmias and the calcification of blood vessels. If persistent, hypercalcaemia can lead to kidney stones, kidney calcification and, ultimately, to a loss of renal function.

Even without exposure to sunlight, a daily consumption of 20 μg of vitamin D is adequate to meet the body's needs for this vitamin for the vast majority (97.5%) of the population.

The European Food Safety Authority (EFSA) has set a UL value (tolerable upper intake level) of 100 μg for vitamin D. According to the latest scientific research, if adults and children aged eleven and older consume a daily quantity of no more than 100 μg, any impairments to health are unlikely. This UL value includes the intake of vitamin D from all sources, and thusincludes intake from supplements, normal dietary intake and intake from food that has been fortified with vitamin D. If high-dose vitamin D preparations are also consumed, this figure may be exceeded in combination with other sources of the vitamin.

From the perspective of nutritional science, the daily consumption of vitamin D preparations containing a 50 μg or 100 μg dose is not necessary. On the other hand, the BfR considers it unlikely that impairments to health will result from the occasional consumption of such high-dose preparations. If such high-dose vitamin D products are consumed on a daily basis over a longer period of time, however, the latest research does point to an elevated risk to health.

The BfR notes that, given an adequate length of time spent outdoors with corresponding exposure of the skin to sunlight, plus a balanced diet, an adequate supply of Vitamin D can be achieved by individuals without having to take vitamin D preparations. Individuals in risk groups for which a serious lack of vitamin D or a vitamin deficiency requiring medical intervention may be more likely to occur, should first clarify any need to take such preparations with their attending physician or general practitioner.

This opinion does not constitute a decision as to whether or not a product should be classified as a foodstuff, nor should it be interpreted as such.

The discovery and formulation of new drugs, antivirals, antibiotics and in general chemicals with tailored properties is a long and painstaking process. Interdisciplinary research at the crossroads of biochemistry, physics and computer science can change this. The development of machine learning (ML) methods, combined with first principles of quantum and statistical mechanics and trained on increasingly available molecular big datasets, has the potential to revolutionise the process of chemical discovery.

"Chemical discovery and machine learning are bound to evolve together, but achieving true synergy between them requires solving many outstanding challenges," says Alexandre Tkatchenko, Professor of Theoretical Chemical Physics at the University.

Machine learning to help identify drug candidates

The University initiated a collaboration with Belgian company Janssen Pharmaceuticals in spring 2020 to develop novel ML methods for identifying compounds that have a strong therapeutic potential (also called drug candidates). So far, ML approaches have been developed for small molecules. This research project aims to extend the architecture and transferability of quantum mechanics-based machine learning approaches to large molecules of pharmaceutical importance.

"The generation of novel chemicals with activity on relevant biological targets is the core business of pharmaceutical companies. Machine learning approaches have the potential to speed up the process and reduce failure rates in drug discovery. Having been approached by a leading pharmaceutical company to work together in identifying drug candidates is a gratifying sign of the industrial recognition of our expertise," comments Dr. Leonardo Medrano-Sandonas, a postdoctoral researcher in Prof. Tkatchenko's group.

Partner in an Innovative Training Network funded by the European Commission

Together with three large European pharma companies (Bayer, AstraZeneca, Janssen), the chemical company Enamine and ten academic partners with expertise in computational drug design, Prof. Tkatchenko has been granted the Marie Sk?odowska-Curie Actions - Innovative Training Network grant for the project Advanced machine learning for Innovative Drug Discovery (AIDD) for the period 2021 - 2023. This project aims to develop innovative ML methods to contribute to an integrated "One Chemistry" model that can predict outcomes ranging from molecule generation to synthesis and understand how to intertwine chemistry and biology to develop new drugs.

Here scientific expertise joins forces with medicinal and synthetic chemistry expertise of the industrial partners, and benefits from large valuable datasets. For the first time, all methodological developments will be available open source. The training network will prepare a generation of scientists who have skills both in machine learning and chemistry to advance medicinal chemistry.

"Making accurate predictions using machine learning critically depends on access to large collections of high-quality data and domain expertise to analyse them," explains Prof. Tkatchenko. "Putting our forces together is a first step towards chemical discovery revolution driven by machine learning".

The field of machine learning for chemical discovery is emerging and substantial advances are expected to happen in the near future. Prof. Tkatchenko has recently published an article in the journal Nature Communications in which he discusses recent breakthroughs in this field and highlights the challenges for the years to come. The article is available online.

As early as December 2018, EFSA published a re-evaluation of health risks arising from the presence of certain PFAS in food and derived significantly lower guidance values for two compounds, perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) than before.

In its recent opinion, EFSA has now derived a tolerable weekly intake (TW I) for the sum of four PFAS, namely PFOA, PFOS, perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) of 4.4 nanograms (ng) per kilogram (kg) of body weight per week. This value indicates the amount of a substance that can be ingested weekly over a lifetime with no appreciable health risk.

The TWI derivation is based on observations from epidemiological studies that indicate that these PFAS affect the immune system. In these studies, it was observed that children who had higher concentrations of certain PFAS in their blood serum produced fewer antibodies after having common vaccinations.

Consumers can barely influence their intake of PFAS. The primary sources for human exposure are food and drinking water.

The BfR will examine EFSA's opinion.

The BfR has updated its FAQs on PFAS based on the new EFSA opinion:
https://www.bfr.bund.de/en/frequently_asked_questions_about_per__and_polyfluoroal-kyl_substances__pfas_-244188.html

Those with food allergies must avoid allergens in food. Health problems can be triggered by even the smallest traces for those affected. This is why manufacturers of ready-made foods must list the ingredients on the packaging. A special declaration obligation applies to major allergens, such as peanuts, celery or egg, even if these are only found in small quantities in the recipe. However, the declaration of allergens that inadvertently enter a food, in other words which are not part of the regular ingredients, is not regulated. These kinds of inadvertent allergenic entries can happen due to transport and production conditions, for example, and pose a health risk to those with allergies.

According to estimates from the Food and Agriculture Organization of the United Nations (FAO), more than 1900 insect species are consumed worldwide. They are subject to rules related to novel foods in the EU.

It is also probable that insects will be increasingly used as components in food in the future. The role of insects as a potential new food allergen is currently being discussed. Although only a few cases of allergies caused by insect components have been described to date, there is considerable potential for cross-reaction notably with arthropods (including crustaceans and dust mites) due to the similarity (homology) of numerous proteins such as e.g. tropomyosin and arginine kinase.

One aim of the Allergen-Pro joint research project is to provide food monitoring authorities and, ultimately, food producers with methods for identifying insect components in food in due course. A total of seven partners from Switzerland and Germany are involved in developing suitable and reproducible methods for the detection of insect components even in highly processed food products. These methods are based either on detecting the genetic material that is unique to each species, or on directly detecting any allergenic proteins.

Furthermore, the clinical relevance of insects as a health-relevant potential food allergen is still unclear. It is still difficult to predict the clinical relevance of food sensitisation using so-called in-vitro methods. Innovative, high-through-put in vitro methods for identifying allergenic IgE/G epitopes in insect proteomes will also be developed to improve safety for those suffering from allergies and food manufacturers. The project is also working on developing an in-vitro test system for the first time that should make it possible to determine, with minimal stress for the test subjects, whether they are allergic or only demonstrate sensitisation without clinical reactions.

Researchers from 68 sites across the country, led by David E. Leaf, MD, MMSc and Shruti Gupta, MD, MPH from the Division of Renal Medicine at Brigham and Women's Hospital, have investigated the effects of the anti-inflammatory drug tocilizumab on critically ill patients with laboratory-confirmed COVID-19. Unlike steroids, which suppress the immune system more broadly, tocilizumab specifically inhibits the receptor for the pro-inflammatory cytokine, IL-6. The investigators found that when tocilizumab was administered within the first two days of intensive care unit (ICU) admission, there was a 30 percent relative decrease (and a 10 percent absolute decrease) in mortality compared to patients whose treatment did not include early use of tocilizumab. Results are published in JAMA Internal Medicine.

"Tocilizumab has been used for several years to treat a condition known as cytokine release syndrome, which can be observed in cancer patients receiving certain types of immunotherapy," said Leaf, the senior author of the study. "In the setting of COVID-19, it has been observed that much of the morbidity and mortality that occurs may be due to our own body's inflammatory response to the virus as opposed to the virus itself."

The monoclonal antibody tocilizumab is currently approved to treat rheumatoid arthritis and giant cell arteritis, an inflammatory condition affecting large blood vessels. It is also administered to cancer patients who have received chimeric-antigen receptor therapy (CAR-T), a treatment that can stoke the body's immune system to attack cancer cells but can also cause toxic side effects due to cytokine release syndrome (CRS), an overwhelming inflammatory response that can cause multiorgan failure. Tocilizumab is used to treat CRS in cancer patients and is currently under investigation for use in COVID-19 patients. Since the start of the pandemic, several tocilizumab studies have been conducted in Europe and China, but none this large or thorough.

The multicenter study utilized data accumulated from over 4,000 critically ill patients with COVID-19 admitted to ICUs at 68 sites across the US as part of the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID). STOP-COVID was initiated by Leaf and Gupta in March 2020 as an unfunded, grassroots network, and now includes over 400 collaborators across the U.S. These collaborators ascertained detailed data from critically ill adults with COVID-19 by manually reviewing electronic medical records and entering over 800 unique data elements per patient into a centralized electronic database. For the current study, Leaf and his team used a 'target trial emulation' approach to examine whether tocilizumab reduces mortality in COVID-19. Target trial emulation, a novel method of analyzing observational data, is the idea of simulating a randomized control trial to reduce bias.

"Discussions about the biases of observational studies tend to focus on lack of randomization, but many common biases of observational analyses have nothing to do with lack of randomization," said co-author Miguel Hernán, pioneer of this technique and professor of biostatistics and epidemiology at the Harvard T.H. Chan School of Public Health. "Emulating a target trial using observational data allows us to eliminate those common biases and appropriately focus the discussion on potential confounding due to lack of randomization."

Of the 3,924 patients included in the analysis, 433 received tocilizumab in the first two days of ICU admission. The risk of death at 30-days was 27.5 and 37.1 percent among tocilizumab-treated and non-tocilizumab-treated patients, respectively (absolute risk difference, 9.6 percent). The beneficial effect of tocilizumab on survival was consistent across categories of age, sex, and illness severity, and was also observed in patients who either did or did not receive corticosteroids. Notably, patients with a more rapid disease trajectory, defined as three days or fewer from symptom onset to ICU admission, benefited from tocilizumab to a greater extent than patients with a slower disease trajectory.

"I think the single most important thing we can do with the large and granular database that we assembled in STOP-COVID is to evaluate which interventions are helpful in reducing death," said Leaf. "Obviously, randomized clinical trials are the gold standard for determining treatment efficacy, but when data from large, well-designed trials aren't available, observational studies like STOP-COVID can be used to help guide clinical practice as well as the design of future trials."

Despite the observational design, this study provides crucial and robust data on tocilizumab efficacy and safety in a large population of critically ill patients with COVID-19. On average, there was a 30 percent relative reduction in mortality for patients treated with tocilizumab in their first two days of ICU admission, there were no signs of increased risk for secondary infection, and there was only a small increase in risk of liver function test abnormalities.

"Though there are conflicting data from clinical trials regarding the efficacy of tocilizumab in COVID-19, our study differs from these trials in several important ways: we specifically focused on critically ill patients; we focused on early use of tocilizumab (defined as the first 2 days of ICU admission); and we included a much larger number of patients (approximately 4,000 compared to approximately 400)," said Gupta, the lead author. "We hope that our findings stimulate further investigation of tocilizumab in COVID-19, particularly as we are seeing cases rise across the country."

In their analyses, the investigative team controlled for a comprehensive list of covariates, such as age, sex, race, ethnicity, comorbidities, acute severity of illness, and concurrent treatments received. They excluded patients who would not have been eligible to participate in a hypothetical randomized clinical trial of tocilizumab, such as patients with elevated liver function tests. They also used methods to eliminate the potential for immortal time bias, which can occur when there is a delay between time zero (e.g., admission to the ICU) and initiation of treatment (e.g., receipt of tocilizumab on ICU day 2). The main limitation of the study is potential confounding due to the observational design.

"I hope that these findings will help inform the design of future, well-powered clinical trials assessing early use of tocilizumab in critically ill patients with COVID-19," said Leaf. "However, given the cost and complexity of performing large-scale clinical trials in COVID-19, the current study may be the best available evidence we have for tocilizumab in this setting for quite some time."

An international team of scientists from NUST MISIS (Russia), Linköping University (Sweden) and University of Bayreuth (Germany) found that, contrary to the usual physical and chemical laws, the structure of some materials does not condense at ultrahigh pressures. Actually, it forms a porous framework filled with gas molecules. This happened with samples of Os, Hf, and W put together with N in a diamond anvil at a pressure of one million atmospheres. The discovery is described in Angewandte Chemie.

"You can transform a pencil lead into diamond if you squeeze it very hard" -- this fact heard by many of us in childhood sounded like a complete nonsense. However, science laws make it clear that there is no miracle: both pencil lead and diamond are formed by the same chemical element, i.e. carbon, which actually forms a different crystal structure under very high pressure. It makes sense: ar pressure the empty space between atoms decreases and the material becomes denser. Until recently, this statement could be applied to any material.

It turned out that a number of materials can become porous at ultrahigh pressure. Such a conclusion was made by a group of scientists from NUST MISIS (Russia), Linköping University (Sweden) and University of Bayreuth (Germany). The team examined three metals (hafnium Hf, tungsten W, and osmium Os) with an addition of N when placed in a diamond anvil at a pressure of 1 million atmospheres, which corresponds to a pressure at a depth of 2.5 thousand kilometers underground. Scientists believe that it was the combination of pressure and nitrogen N that influenced the formation of a porous framework in the crystal lattice.

"Nitrogen itself is quite inert and without ultrahigh pressure it would not react with these metals in any way. Materials without nitrogen would simply condense in a diamond anvil. However, a combination gave an amazing result: some of the nitrogen atoms formed a kind of reinforcing framework in the materials, allowing the formation of pores in the crystal lattice. Consequently, additional nitrogen molecules entered the space", said Professor Igor Abrikosov, head of the theoretical research group and NUST MISIS Laboratory for the Modeling and Development of New Materials.

The experiment was initially conducted physically by Sweden and German part of the group, and then its results were confirmed by theoretical modeling on NUST MISIS supercomputer. Scientists emphasize that the research is fundamental, i.e. materials with such properties are not yet created for specific tasks. At the moment, the very fact that previously unthinkable modifications of materials can be obtained is important.

A whole new step will be to preserve such materials at normal atmospheric pressure. In one of the previous works, scientists managed to preserve a special modification of rhenium nitride. Currently, rapid cooling to critical low temperatures is considered as one of the ways to stabilize new materials.

Next on the list of concerns, though notably less frequently mentioned, are unhealthy or wrong diet as well as climate and environmental pollution - these were the most frequently mentioned concerns in February's survey. "The coronavirus pandemic dominates public perception", says BfR President Professor Dr. Dr. Andreas Hensel.

Go to the Consumer Monitor information booklet 08/2020:
https://www.bfr.bund.de/cm/364/bfr-consumer-monitor-08-2020.pdf

Go to the interactive website (only in German):
https://www.bfr.bund.de/epaper/vm-dashboard/

Since the study series began in 2014, no other topic has been so often spontaneously named as the greatest health risk as the novel coronavirus. In spite of this, however, only a third of respondents had heard of coronaviruses on food at the time the data was collected in August 2020. Correspondingly, few people (12 percent) are concerned about this. From a scientific perspective, it is unlikely that the coronavirus is transmitted via food. Nevertheless, the general rules of hygiene for preparing food should always be observed. Current information on the perception of the novel coronavirus among the German population is available in the special series "BfR-Corona-Monitor", which is published every 14 days.

When asked about selected topics, antimicrobial resistance and microplastics in food are still the issues that most people worry about. In each case, nearly 60 percent say they are concerned about these topics. Genetically modified foods rank third - the concern here has increased by six percentage points compared to the previous survey.

The results of the current BfR Consumer Monitor as well as the previous issue (February 2020) can now also be viewed interactively. On the new website set up for this, the results can be broken down by different groups of people (e. g., gender and age) and the data can be downloaded at the touch of a button. Feedback on the new presentation format is welcome - just click on the button "Wie gefällt Ihnen diese Seite?".

Popular wisdom holds that tall, fast-growing trees are best for biomass, but new research by two U.S. Department of Energy National Laboratories reveals the size of trees is only part of the equation.

Of equal economic importance, according to scientists from the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) and Oak Ridge National Laboratory (ORNL), is the amount of sugars that can be produced from the ligno-cellulosic biomass that can be converted into fuels.

In the production of biofuels from woody biomass, feedstocks represent a significant expense with costs incurred for planting, harvesting, and transporting the trees. Growers typically look at how many trees they can plant per acre with little consideration given to how much fuel those trees will produce or the quality of that fuel.

The researchers analyzed 900 samples of black cottonwood trees grown in Oregon to determine how variations in their size and composition affect feedstock quality and biorefinery economics.

"Those differences do make an economic difference," said Brian Davison, a biochemical engineer with ORNL and a lead on the project.

The findings are detailed in a new paper, "Economic Impact of Yield and Composition Variation in Bioenergy Crops: Populus trichocarpa," published in the journal Biofuels, Bioproducts & Biorefining. In addition to Davison, the other co-authors are Renee Happs, Andrew Bartling, Crissa Doeppke, Anne Harman-Ware, Mary Biddy, and Mark Davis from NREL; and Erin Webb, Robin Clark, Jin-Gui Chen, Gerald Tuskan, and Wellington Muchero from ORNL.

The amount of fuel produced per acre each year and the minimum fuel selling price (MFSP) are most strongly connected to the size of a tree. But when considering the largest 25% of trees, the size and sugar content were of nearly identical importance to the MFSP, the researchers found.

"Over the long run, in the case of a biorefinery, that adds up to millions of dollars by taking the genotypes that give you the most sugar," said Happs, an analytical chemist at NREL and lead author of the paper.

The scientists chose the black cottonwood tree to study because of its fast growth and its prevalence across North America. The tree can be ready to harvest after about seven years from planting. In addition to the sugar content, the researchers also analyzed the amount of lignin, which forms rigid cell walls and bark that is difficult to break down. The analyses informed a techno-economic analysis of using the black cottonwood as a biofuel feedstock.

The trees with the best attributes can be cloned for rapid propagation. "We can also breed for the key genes to increase both sugar content and growth," Davison said.

"We observed that there was no correlation between composition and size--hinting that we could selectively breed for maximizing both of these attributes simultaneously without trading one for the other," said Bartling, who conducted the techno-economic analysis of the poplar samples.

Genetic engineering may allow for further improvement of sugar content. The researchers used computer modeling to evaluate a hypothetical scenario involving two clones in which the sugar was increased by 5% among a smaller set of the trees. The additional sugar content reduced the MFSP, highlighting how composition can begin to compensate for economic losses in smaller trees--perhaps in a region where poor conditions may not allow them to grow as large.