Culture

Boston, MA (April 30, 2021) - A new set of guidelines, developed by AATS and ESTS (European Society for Thoracic Surgery) presented today at the AATS 101st Annual Meeting, recommends a 30-day course of Venous Thromboembolism (VTE) prophylaxis post-discharge for patients undergoing surgical resection for lung or esophagus cancer. The AATS and ESTS formed a multidisciplinary guideline panel that included broad membership to minimize potential bias when formulating recommendations. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic reviews and meta-analyses. The results are endorsed by the American Society of Hematology (ASH) and the International Society on Thrombosis and Haemostasis, Inc (ISTH).

VTE is a potentially preventable postoperative complication for thoracic surgery patients, occurring in up to 14% of cases where patients underwent surgical resection for cancer. The panel made conditional recommendations for use of parenteral anticoagulation for VTE prevention, in combination with mechanical methods, over no prophylaxis for cancer patients undergoing anatomic lung resection or esophagectomy. Other key recommendations included conditional recommendations for using parenteral anticoagulants over direct oral anticoagulants (DOACs), with use of DOACs suggested only in the context of clinical trials and using extended prophylaxis for 28-35 days over in-hospital prophylaxis for patients at high risk of thrombosis, including those undergoing pneumonectomy and esophagectomy. Future research priorities include the role of preoperative thromboprophylaxis and the role of risk stratification to guide use of extended prophylaxis.

"The two largest thoracic surgery groups combined forces using the highest levels of diligence to develop a potentially practice-changing guidelines that meet the unique profile of thoracic surgery patients," said Dr. Yaron Shargall, professor and thoracic surgery division head, McMaster University. "Until now, guidelines provided the same standard of care for both cardiac and thoracic patients. Now, we are able to provide revised guidance based on real-world evidence working specifically with thoracic patients."

The guideline panel undertook a survey of thoracic surgeons and found that 95 percent indicated a willingness to accept new evidence-based guidelines in their practices. According to Shargall and Dr. Virginia Litle, Chief of Thoracic Surgery at Boston Medical Center and
Professor of Surgery, Boston University School of Medicine, "This indicated to us that the Cardio Thoracic community was awaiting new guidelines. Clearly, there is value in applying a systematic, evidence-based approach to add weight to the guidelines."

Global sea level rise associated with the possible collapse of the West Antarctic Ice Sheet has been significantly underestimated in previous studies, meaning sea level in a warming world will be greater than anticipated, according to a new study from Harvard researchers.

The report, published in Science Advances, features new calculations for what researchers refer to as a water expulsion mechanism. This occurs when the solid bedrock the West Antarctic Ice Sheet sits on rebounds upward as the ice melts and the total weight of the ice sheet decreases. The bedrock sits below sea level so when it lifts, it pushes water from the surrounding area into the ocean, adding to global sea level rise.

The new predictions show that in the case of a total collapse of the ice sheet, global sea level rise estimates would be amplified by an additional meter within 1,000 years.

"The magnitude of the effect shocked us," said Linda Pan, a Ph.D. in earth and planetary science in GSAS who co-led the study with fellow graduate student Evelyn Powell. "Previous studies that had considered the mechanism dismissed it as inconsequential."

"If the West Antarctic Ice Sheet collapsed, the most widely cited estimate of the resulting global mean sea level rise that would result is 3.2 meters," said Powell. "What we've shown is that the water expulsion mechanism will add an additional meter, or 30 percent, to the total."

But this is not just a story about impact that will be felt in hundreds of years. One of the simulations Pan and Powell performed indicated that by the end of this century global sea level rise caused by melting of the West Antarctic Ice Sheet would increase 20 percent by the water expulsion mechanism.

"Every published projection of sea level rise due to melting of the West Antarctic ice sheet that has been based on climate modeling, whether the projection extends to the end of this century or longer into the future, is going to have to be revised upward because of their work," said Jerry X. Mitrovica, the Frank B. Baird Jr. Professor of Science in the Department of Earth and Planetary Sciences and a senior author on the paper. "Every single one."

Pan and Powell, both researchers in Mitrovica's lab, started this research while working on another sea level change project but switched to this one when they noticed more water expulsion from the West Antarctic ice sheet than they were expecting.

The researchers wanted to investigate how the expulsion mechanism affected sea level change when the low viscosity, or the easy flowing material of the Earth's mantle beneath West Antarctica, is considered. When they incorporated this low viscosity into their calculations they realized water expulsion occurred much faster than previous models had predicted.

"No matter what scenario we used for the collapse of the West Antarctic Ice Sheet, we always found that this extra one meter of global sea level rise took place," Pan said.

The researchers hope their calculations show that, in order to accurately estimate global sea level rise associated with melting ice sheets, scientists need to incorporate both the water expulsion effect and the mantle's low viscosity beneath Antarctica.

"Sea level rise doesn't stop when the ice stops melting," Pan said. "The damage we are doing to our coastlines will continue for centuries."

An international research group led by Prof. WANG Bo and Prof. SHI Gongle from the Nanjing Institute of Geology and Palaeontology of the Chinese Academy of Sciences (NIGPAS) collected approximately 25,000 fossil-containing amber samples and about 5,000 fossil plants in Zhangpu County, Fujian Province, southeast China from 2010 to 2019.

Their findings were published in Science Advances on April 30.

The Zhangpu biota, including amber biota and co-occurring megafossils, is the richest tropical seasonal rainforest biota discovered so far. It reveals that extraordinary species diversity existed within a 14.7 million-year-old tropical rainforest and sheds light on the evolution of the rainforest.

Diverse winged fruits of Dipterocarpaceae and legumes as well as leaves of 78 different broadleaf trees show that tropical seasonal rainforests extended further north than today, offering an insight into what changes might take place in a future warmer world if ecosystems are able to adapt.

The Zhangpu amber biota contains a diverse, exquisitely preserved fossil arthropod fauna and abundant botanical and other inclusions such as fungi, snails, and even feathers. Botanical inclusions include bryophytes (liverworts and mosses) and flowering plants.

Arthropod inclusions cover an impressive array of more than 250 families including various spiders, mites, millipedes, and at least 200 families of insects in 20 orders. The extremely high variety of arthropods renders the Zhangpu amber biota one of the world's four richest, along with the widely known Cretaceous Burmese amber biota (> 568 families), Eocene Baltic amber biota (> 550 families), and Miocene Dominican amber biota (205 families).

The insect fauna in Zhangpu amber include many ants, bees, lacewings, stick insects, termites, and grasshoppers that are today restricted to tropical Southeast Asia and/or New Guinea.

"The most unexpected finding is that the high diversity of ants and springtails all belong to living genera. In addition, the vast majority of previously identified insects in Zhangpu amber, such as bark lice, grasshoppers, beetles, and bees, also belong to living genera," said Prof. WANG.

These results suggest that Asian rainforest insect communities have remained stable since the middle Miocene (at least 15 million years ago). It also highlights that tropical rainforests act as museums of biological diversity at the generic level. The relative ecological stability of such "megathermal" environments facilitates the continued accumulation of species diversity and makes them even more precious than previously realized.

The Zhangpu amber biota is unique because the samples are not commercially extracted and consequently the species census is minimally skewed by human selective bias. Moreover, its precise age is well-constrained by radioisotopic dating and the associated plant compression/impression fossils allow quantitative reconstruction of the ancient climate.

Compared to the modern climate of Zhangpu, the most notable difference is that the middle Miocene climate had a warmer winter, leading to a relatively stable temperature throughout the year.

In scenarios of global warming, winter warming is commonly more pronounced than summer warming, and has larger and more widespread effects on terrestrial and marine ecosystems. It reduces "winterkills" and is beneficial for reproduction and growth of tropical animals and plants.

"Winter warming is likely to have been a major driver of the northern expansion of the megathermal biota in South China during the Mid-Miocene Climatic Optimum," said Prof. SHI.

WILMINGTON, Del. (April 30, 2021) - Social, economic, and demographic factors that can influence health did not affect families' acceptance of telehealth for their children's cardiac care during the COVID-19 pandemic, according to a study presented at the Pediatric Academic Society 2021 Virtual Meeting. The study, by research team members at the Nemours Children's Health System, suggests that telehealth is a feasible tool for families regardless of household income, language, or insurance type.

"When we saw that the use of telehealth would be necessary for maintaining children's cardiac care during COVID, we worried that some of our families would face barriers in using it," said lead author Carissa M. Baker-Smith, MD, MPH, director of Preventive Cardiology at Nemours. "We saw that these factors were not a barrier in families' choice to use telehealth and in fact may have been a welcome option."

A total of 849 pediatric patients were scheduled for cardiac visits at Nemours Cardiac Center, Wilmington, Del., between March 30 and May 8, 2020. When all non-urgent care was paused, families were given the option of using telehealth for their visit, or rescheduling the visit until a future date. The study team found that 52 percent agreed to telehealth visits, while 48 percent chose to reschedule. Patients with a primary diagnosis of abnormal heart rhythm, acquired heart disease, chest pain, dysautonomia/dizziness, and dyslipidemia, as well as families of children of Hispanic ethnicity were more likely to accept telehealth appointments. Families of older children, children scheduled for follow-up rather than new visits, and families who lived in Delaware, the same state as the care facility, were less likely to accept telehealth care.

Based on the high acceptance levels, the Cardiac Center has continued to offer telehealth appointments for certain appointment types even as in-person care has largely resumed.

Key takeaways

The basis of the ACS Quality Verification Program rests on 12 standards; all of which are being reviewed in the medical literature to demonstrate evidence for the program.
Five principles key in on the role of data surveillance, standardized process, and systems; all are interrelated.
The most robust evidence has been identified around the standards for data and use of data.

CHICAGO (April 30, 2021): Evidence from the medical literature that contributes to adopting a new practice into clinical care is integral for surgical quality improvement. Part II of a comprehensive review of five key principles of the American College of Surgeons (ACS) Quality Verification Program demonstrates the role of data surveillance and standardized processes and systems to identify problems and improve the quality and safety of surgical patient care. The peer-reviewed article is published on the Journal of the American College of Surgeons (JACS) website in advance of print.

"Data is critical to quality improvement because it's impossible to know your problems without objective measures of what they may be. However, the existence of data alone is not enough to further quality improvement. That's where processes come into play; processes of focused review help to find problems and provide appropriate avenues to address them," said Chelsea Fischer, MD, MS, ACS Clinical Scholar in Residence and co-first author of the literature review.

"Systems, in turn, are needed to accompany data review in order to make it useful to clinicians and anyone involved in surgical quality improvement. A system may be a process of how often data is reviewed--and in what format--along with the outputs of that review, meaning who looks at it and how it's dealt with," she explained.

The ACS Quality Verification Program helps surgeons and hospitals identify the resources needed for robust surgical quality improvement. The program is based on a set of principles or standards at the foundation of surgical quality. These principles were gleaned from the knowledge and experience of surgical experts as well as the ACS experience with 3,000 hospitals that participate in ACS Quality Programs. The principles were published in the Optimal Resources for Surgical Quality and Safety, also known as the "ACS Red Book."

The basis of the Quality Verification Program rests on 12 standards: leadership commitment and engagement, surgical quality officer, surgical quality and safety committee, safety culture, data collection and surveillance, continuous quality improvement using data, case review, surgeon review, surgical credentialing and privileging, standardized and team-based processes of care, disease-based management, and compliance with regulatory performance metrics.

"The Red Book, which serves as the framework for the ACS Quality Verification Program, provides a detailed overview of the essential elements that any hospital or surgical practice should have in place to deliver safe, reliable, quality care. Through its 12 standards, it provides the resources and support that surgeons and their institutions need as they traverse the road to surgical quality improvement," said article coauthor, David B. Hoyt, MD, FACS, ACS Executive Director.

This new literature review in JACS is the second of three investigations to examine the evidence that supports these standards. The study group gathered and analyzed evidence associated with five principles that address processes for identification and resolution of quality improvement issues: case review, peer review, credentialing and privileging, data for surveillance, and continuous quality improvement using data.

"This article furthers our understanding of the evidence that forms the foundation for the ACS Quality Verification Program. Using 12 standards, the program can be implemented by any hospital regardless of location or size. Real and demonstrable achievements have been demonstrated by participating hospitals including increasing value and reliability and improving the resource and infrastructure that leads to even better care and results for their surgical patients. Interestingly, benefits have been appreciated by the operating surgeons, the surgical team members, and surgeon and hospital leadership," said article coauthor, Clifford Y. Ko, MD, MSHS, FACS, FASCRS, Director of the ACS Division of Research and Optimal Patient Care.

For this analysis, the U.S. National Library of Medicine's Medline database was searched for articles published between its inception in 1964 and January 2019. Articles evaluated the relationship between one of the Red Book principles and patient or organizational quality outcomes. Two reviewers synthesized and summarized information in a hierarchical fashion from these studies.

After identifying 9,098 studies involving the five principles, a total of 184 were selected for systematic review for this portion of the research. Several primary studies also were included for assessment. The authors primarily looked at observational, retrospective studies; not all were directly related to surgery, some came from other procedural specialties. A summary of the evidence follows.

Case review
A review of individual surgeon cases

Evidence from these investigations showed that outcomes can be improved through the implementation of case reviews in two areas: quantitative outcomes and in identifying systems issues for quality improvement. Authors note that "characteristics of effective [case] review include standardized data-driven case identification, multidisciplinary input, and follow-up status of issues."

A total of 79 unique studies were included in this review; 14 included a prospective analysis from one single institution, 12 were retrospective single-institution studies, and one was a mixed-methods analysis.

Peer review
A review of surgeon and performance

The evidence reviewed supports peer review as a means to improve patient outcomes and contribute to quality improvement projects. Potential challenges identified included process variability, reviewer agreement of performance, and a long implementation time for the process. Authors note that, "Despite challenges, a well-implemented program is found to be useful by providers."

Ten studies were reviewed for this category encompassing a collective of 24 studies. All looked at peer review from a quality improvement perspective.

Credentialing and privileging
The process of ensuring proper credentialing, privileging, and onboarding

The evidence supports standardized credential and privileging processes for surgeons to potentially improve patient outcomes, but the authors note that "current processes have considerable variation and opportunities for improvement."

This analysis included 73 articles: a collective of 70 unique studies, two multi-institutional surveys, a single-institution retrospective review, and one multi-institutional retrospective review.

Data for surveillance and quality improvement
Effective use of data to surveil for potential quality and safety issues

In all articles analyzed, the evidence supports the use of registries to identify clinical problems. Furthermore, one-half of the articles supported using registries for implementation and surveillance of quality improvement initiatives.

This analysis used 20 articles: one systematic review, 10 multi-institutional retrospective reviews, four single-institutional retrospective reviews, and four descriptive case studies.

Continuous quality improvement using data
Driving continuous quality improvement

The authors also focused on three of the data surveillance studies (noted above) to look at how surveillance contributes to continuous quality improvement over time, which they write "can be just as important to quality and safety as the initial identification of problems." Registries were cited as the tool of implementation for this practice when used to provide a clinical practice audit paired with feedback to clinicians.

In terms of the role of administrative claims data, the authors noted that "combining administrative claims data with prospectively collected clinical data through EHR linkages can allow providers real-time data for continuous monitoring of quality issues." However, while data is an important tool, they note that it's "likely insufficient" by itself, and "development of quality improvement initiatives is essential to drive patient care improvement."

"While there's some face validity to these quality improvement concepts, our analysis of the medical literature does supply the evidence supporting the framework for these concepts as well. This is particularly true around the standards of data and use of data. We found robust literature supporting these data concepts for the program standards, and certainly evidence in the areas of case review, peer review, and credentialing and privileging too," Dr. Fischer concluded.

In addition to Dr. Ko and Dr. Hoyt, Dr. Fischer's other study authors include Q. Lina Hu, MD, MS, ACS Clinical Scholar in Residence and co-first author, Annie B. Wescott, MLIS, and Melinda Maggard-Gibbons, MD, MSHS.

"FACS" designates that a surgeon is a Fellow of the American College of Surgeons.

Authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Citation: Evidence Review for the American College of Surgeons Quality Verification. Part II: Processes for Reliable Quality Improvement. DOI: /10.1016/j.jamcollsurg.2021.03.028.

For many of us, adding salt to a meal is a perfectly normal thing to do. We don't really think about it. But actually, we should. As well as raising our blood pressure, too much salt can severely disrupt the energy balance in immune cells and stop them from working properly.

Back in 2015, the research group led by Professor Dominik Müller of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and the Experimental and Clinical Research Center (ECRC) found that elevated sodium concentrations in the blood affect both the activation and the function of patrolling monocytes, which are the precursors to macrophages. "But we didn't know exactly what was happening in the cells," says Dr. Sabrina Geisberger of the Berlin Institute for Medical Systems Biology (BIMSB) at the MDC. She is lead author of the study of an international research team led by MDC scientists together with colleagues from University of Regensburg and from Flanders Institute for Biotechnology (VIB) /Hasselt University in Belgium. It was funded by the German Center for Cardiovascular Research (DZHK) and has now been published in the journal Circulation.

Salt disrupts the respiratory chain in cells

Working with biochemist and metabolomics expert Dr. Stefan Kempa of BIMSB, the researchers began in the lab by looking at the metabolism of immune cells that had been exposed to high salt concentrations. Changes appeared after just three hours. "It disrupts the respiratory chain, causing the cells to produce less ATP and consume less oxygen," explains Geisberger. ATP (adenosine triphosphate) is the universal fuel that powers all cells. It provides energy for the "chemical work" - synthesizing proteins and other molecules - required for muscle power and metabolic regulation. ATP is produced in the mitochondria, the cell's "power plant," using a complex series of biochemical reactions known as the respiratory chain. "Salt very specifically inhibits complex II in the respiratory chain."

This has consequences: The lack of energy causes the monocytes to mature differently. "The phagocytes, whose task is to identify and eliminate pathogens in the body, were able to fight off infections more effectively. But this could also promote inflammation, which might increase cardiovascular risk," explains Müller.

Effects of salt are reversible

Professor Markus Kleinewietfeld of Hasselt University and VIB, and Professor Jonathan Jantsch of Universität Regensburg, were heavily involved in the work investigating human monocytes and macrophages. They were able to show that salt affects the functioning of human phagocytes in the same way.

Researchers at the ECRC, which is run jointly by the MDC and Charité - Universitätsmedizin Berlin, then conducted a study in which healthy male participants supplemented their usual diets with six grams of salt in tablet form every day for 14 days. In another clinical study, the researchers investigated a familiar scenario: eating a pizza delivered by an Italian restaurant. They then analyzed the monocytes in the participants' blood. The findings showed that the dampening effect on mitochondria doesn't just occur after an extended period of increased salt intake - it also happens after a single pizza. Data from the pizza experiment showed how long the effect lasted: Blood was taken from the participants after three and eight hours, and the effect was barely measurable in the second sample.

"That's a good thing. If it had been a prolonged disturbance, we'd be worried about the cells not getting enough energy for a long time," says Müller. The mitochondrial activity is therefore not permanently inhibited. That said, the continuous risk of sodium on mitochondrial function if a person eats very salty food several times a day cannot be ruled out, but needs to be tested in the future. The pizza, incidentally, contained ten grams of salt. Nutrition experts recommend that adults limit their daily intake to five or six grams at most. The calculation includes the salt that is hidden in processed foods.

Small ion, big effect

"The fundamental finding of our study is that a molecule as small as the sodium ion can be extremely efficient at inhibiting an enzyme that plays a crucial role in the respiratory chain," says Kempa. "When these ions flood into the mitochondria - and they do this under a variety of physiological conditions - they regulate the central part of the electron transport chain." It therefore appears to be a very fundamental regulatory mechanism in cells.

Now the task is to investigate whether salt can also influence this mechanism in other types of cells. Kleinewietfeld believes that this is extremely likely because mitochondria aren't just present in immune cells; with the exception of red blood cells, they exist in every cell of the body. They can be found in particularly high numbers wherever a lot of energy is consumed - in muscle cells, neurons, receptors, and egg cells.

It is still not fully elucidated how different cell types regulate the influx of sodium into the mitochondria. Nevertheless, the study confirms that consuming too much salt can be bad for our health. "Of course the first thing you think of is the cardiovascular risk. But multiple studies have shown that salt can affect immune cells in a variety of ways. If such an important cellular mechanism is disrupted for a long period, it could have a negative impact - and could potentially drive inflammatory diseases of the blood vessels or joints, or autoimmune diseases," says Kleinewietfeld.

A research team at the University of Cologne has discovered previously undescribed bacteria in amoebae that are related to Legionella and may even cause disease. The researchers from Professor Dr Michael Bonkowski's working group at the Institute of Zoology have named one of the newly discovered bacteria 'Pokemonas' because they live in spherical amoebae, comparable to Pokémon in the video game, which are caught in balls. The results of their research have been published in the journal Frontiers in Cellular and Infection Microbiology.

Bacteria of the order Legionellales have long been of scientific interest because some of these bacteria are known to cause lung disease in humans and animals - such as 'Legionnaires' disease', which is caused by the species Legionella pneumophila and can sometimes be fatal. Legionellales bacteria live and multiply as intracellular parasites in the cells of organisms as hosts. In particular, the hosts of Legionellales are amoebae. The term 'amoeba' is used to describe a variety of microorganisms that are not closely related, but share a variable shape and crawling locomotion by means of pseudopods. 'We wanted to screen amoebae for Legionellales and chose a group of amoebae for our research that had no close relationship to the hosts that were previously studied. The choice fell on the amoeba group Thecofilosea, which is often overlooked by researchers,' explains Marcel Dominik Solbach.

And indeed, the spherical Thecofilosea serve as host organisms for Legionellales. In Thecofilosea amoebae from environmental samples, the scientists were able to detect various Legionellales species, including two previously undescribed genera and one undescribed species from the genus Legionella. 'The results show that the range of known host organisms of these bacteria is considerably wider than previously thought. In addition, these findings suggest that many more amoebae may serve as hosts for Legionellales - and thus potentially as vectors of disease. To investigate this further, we are now sequencing the complete genome of these bacteria,' said Dr Kenneth Dumack, who led the project.

In the future, these new findings should help to better understand how Legionellales bacteria are related amongst each other, and clarify their interactions with their hosts as well as the routes of infection in order to prevent outbreaks of the diseases in humans.

The researchers named one of the genera of bacteria they discovered 'Pokemonas.' The genus name 'Pokemonas' is a play on words based on the video game franchise 'Pokémon,' which celebrates its 25th anniversary this year and which most schoolchildren, students, and their parents should be familiar with. The name alludes to the intracellular lifestyle of the bacteria in the ball-shaped Thecofilosea amoebae, because in the 'Pokémon' series games, little monsters are caught in balls, much like 'Pokemonas' in the Thecofilosea.

Humans have significantly altered biodiversity in all climate zones of the Earth. This has been shown by a study now published in Science. Led by Prof. Dr. Manuel Steinbauer at the University of Bayreuth, and Dr. Sandra Nogué at the University of Southampton, an international team has investigated how the flora on 27 islands in different regions has developed over the last 5,000 years. Almost everywhere, the arrival of humans has triggered a markedly accelerated change in species composition in previously pristine ecosystems. This dynamic was particularly pronounced on islands colonised in the last 1,500 years.

The 27 islands selected for this study were never connected to the mainland and had been colonised by humans during the study period. Within these islands, pollen of wind-pollinated plants lies since millenia deposited in the sediments of lakes and bogs. The pollen was extracted from the sediment layers, dated, and identified to a respective plant species.

"For each of the 27 islands, our study shows how vegetation composition has changed over the last 5,000 years. Humans' colonisation of the previously undisturbed islands falls within this period. We can therefore trace how natural systems change as a result of human arrival. This transformation from a natural to a human-dominated system can only be observed on islands. On continents, humans have been extensively changing ecological systems for a very long time. What a natural ecosystem would look like here, we can often no longer tell," says Steinbauer.

The researchers compared the data obtained through pollen analyses with archaeological findings that provide information about when the islands were first settled by humans. The result provide a clear message. On 24 of the 27 islands studied, the arrival of humans marked a turning point in vegetation turnover. From this point on, vegetation changed at a significantly higher rate, its rate of change was accelerated by a factor of eleven.

The species composition changed particularly on islands that were colonised in the past 1,500 years, such as the Galapagos Islands and Robinson Crusoe Island off Chile. If, on the other hand, the first settlement took place longer ago, the increase in the rate of species turnover was less pronounced. The authors attribute this difference to an increasing technical know-how of agriculture and the associated effects on biodiversity. In addition, as a result of their increasing mobility, people may have introduced plant species from the mainland, compeating with native species on the islands.

"The results of the study highlight the extensive changes we humans are causing in ecological systems. The change in pollen composition in our study mainly reflects human land use over millennia. With the beginning of the industrial age, human induced transformation of ecological systems has accelerated even further. Adding to this, ecological systems are now additionally affected by human induced climate change" explains Prof. Dr. Manuel Steinbauer, corresponding author of the study. He is a member of the Bayreuth Centre for Ecology and Environmental Research (BayCEER), a research centre of the University of Bayreuth, and has been working here for several years on human influences on ecological systems. In this context, he is also leading a DFG (German Research Foundation) project that is investigating how climate change of geological time periods has influenced the risk of extinction of species.

"Feel-good films" are usually dismissed by film critics as being sentimental and without intellectual merit. But their popularity with audiences, who seek them out precisely because of their "feel-good" qualities, tells a more favorable story. Now, for the first time, this popular movie genre has been examined scientifically. A new study from the Max Planck Institute for Empirical Aesthetics investigates which feel-good films are considered by viewers to be prototypical and which factors constitute their feel-good effect.

Around 450 participants from Germany, Austria, and the German-speaking regions of Belgium and Switzerland took part in the study. Their responses point to romantic comedies as having a particularly high potential for emotional uplift. The feel-good films they identified as typical include Love Actually, Pretty Woman, Amélie, and The Intouchables. The study's findings provide clues as to which content-related and formal characteristics films must have in order for audiences to feel particularly good while watching them.

"In addition to an element of humor and the classic happy ending, feel-good films can be identified by certain recurring plot patterns and characters," explains study leader and first author Keyvan Sarkhosh. "Often these involve outsiders in search of true love, who have to prove themselves and fight against adverse circumstances, and who eventually find their role in the community."

But feel-good films are characterized not just by romance and humor, but also by moments of drama, which usually have a strong emotional effect on viewers. At the same time, these features are often embedded in a fairy-tale setting, which is another typical aspect of the genre and contributes considerably to its perceived lightness. Not least, the mixture of all these elements can be considered constitutive of the feel-good film.

The results of this study have just been published in the journal Projections. The article emphasizes the fact that many people watch feel-good films specifically to relax and lift their spirits. Many of the study participants agreed that while feel-good films may be sentimental, they were not kitschy, and that above all they were technically well made. In this respect, the positive use of the genre label by viewers differs considerably from the predominantly negative perspective brought to it by professional film critics.

Original Publication:

Original Publication:
Sarkhosh, K., und Menninghaus, W. (2021). The feel-good film: Genre features and emotional rewards. Projections, 15 (1), 55-92.
DOI:10.3167/proj.2021.150104

Journal

Projections

DOI

10.3167/proj.2021.150104

Muscle stem cells enable our muscle to build up and regenerate over a lifetime through exercise. But if certain muscle genes are mutated, the opposite occurs. In patients suffering from muscular dystrophy, the skeletal muscle already starts to weaken in childhood. Suddenly, these children are no longer able to run, play the piano or climb the stairs, and often they are dependent on a wheelchair by the age of 15. Currently, no therapy for this condition exists.

"Now, we are able to access these patients' gene mutations using CRISPR-Cas9 technology," explains Professor Simone Spuler, head of the Myology Lab at the Experimental and Clinical Research Center (ECRC), a joint institution of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin. "We care for more than 2,000 patients at the Charité outpatient clinic for muscle disorders, and quickly recognized the potential of the new technology." The researchers immediately started working with some of the affected families, and have now presented their results in the journal JCI Insight. In the families studied, the parents were healthy and had no idea they possessed a mutated gene. The children all inherited a copy of the disease mutation from both parents.

Edited human muscle stem cells developed into muscle fibers in mice

The term "muscular dystrophy" is used to refer to some 50 different diseases. "They all take the same course, but differ due to the mutation of different genes," explains Spuler. "And even within the genes, different sites can be mutated." Following a genomic analysis of all patients, the researchers chose one family because of their particular form of the disease: Limb-girdle muscular dystrophy 2D/R3 is relatively common, progresses rapidly, and has a suitable docking site for the "genetic scissors" close to the mutation on the DNA.

For the study, the researchers took a sample of muscle tissue from a ten-year-old patient, isolated the stem cells, multiplied these in vitro, and used base editing to replace a base pair at the mutated site. They then injected the edited muscle stem cells into mouse muscles, which can tolerate foreign human cells. These multiplied in the rodent and most developed into muscle fibers. "With this, we were able to show for the first time that it is possible to replace diseased muscle cells with healthy ones," says Spuler. Following further tests, the repaired stem cells will be reintroduced to the patient.

Base editing - a sophisticated technique

Base editing is a newer and highly sophisticated variant of the CRISPR-Cas9 gene-editing tool. Whereas in the "classic" method, both strands of DNA are cut by these molecular scissors, the Cas enzymes used for base editing merely snip off the residual glucose from a particular base and attach a different one, thus creating a different base at the targeted site. "This tool works more like tweezers than scissors, and is perfect for carrying out targeted point mutations in a gene," says Dr. Helena Escobar, a molecular biologist in Spuler's team. "It is also a much safer method, because unwanted changes are extremely rare. In the genetically repaired muscle stem cells, we have not witnessed any misediting at unintended regions of the genome." Escobar is the study's lead author and the one who developed the technique for the muscle cells.

Autologous cell therapy - which involves removing a patient's own stem cells, editing them outside the body and then injecting them back into the muscle - will not enable sufferers who are already wheelchair-bound to walk again. "We cannot repair muscle that has already atrophied and been replaced by connective tissue," Spuler stresses. And the number of cells that can be edited in vitro is also limited. However, the study provides the first proof that a form of therapy may even be possible for a group of previously incurable diseases, and it could be used to repair small muscle defects, such as those in the finger flexor.

One step closer to a cure

But this is just the first step. "The next milestone will be to find a way to inject the base editor directly into the patient. Once inside the body, it would 'swim' around for a short while, edit all the muscle stem cells, and then quickly break down again." The team wants to start the first trials in a mouse model soon. If this also works, newborns could be tested for corresponding gene mutations in the future and the curative therapy could be initiated at a time when comparatively few cells would need to be edited.

So, what might an in vivo therapy for muscular dystrophy look like in concrete terms? This is something that scientists have been testing on animal models for some time using viral vectors. However, Helena Escobar explains that because these vectors remain in the body for too long, the risk of misediting and toxic effects is too high. "An alternative would be for mRNA molecules that contain the information for the editor to synthesize the tools in vivo," says the molecular biologist. "mRNA breaks down very quickly in the body, so the therapeutic enzymes can only remain in an active state for a short time." The therapy could probably also be repeated, if necessary. "We do not yet know whether this would need to be a therapy cycle involving several applications."

This therapeutic avenue would mean that, unlike with autologous cell therapy, not every patient would need to be treated individually. For each form of muscle therapy, one "tool" would be sufficient to cure muscle atrophy before major damage even occurred. But, for now, that is still a long way off.

DALLAS (SMU) - NASA has a long tradition of unexpected discoveries, and the space program's TESS mission is no different. SMU astrophysicist and her team have discovered a particularly bright gamma-ray burst using a NASA telescope designed to find exoplanets - those occurring outside our solar system - particularly those that might be able to support life.

It's the first time a gamma-ray burst has been found this way.

Gamma-ray bursts are the brightest explosions in the universe, typically associated with the collapse of a massive star and the birth of a black hole. They can produce as much radioactive energy as the sun will release during its entire 10-billion-year existence.

Krista Lynne Smith, an assistant professor of physics at Southern Methodist University, and her team confirmed the blast - called GRB 191016A - happened on Oct. 16 and also determined its location and duration. A study on the discovery has been published in The Astrophysical Journal.

"Our findings prove this TESS telescope is useful not just for finding new planets, but also for high-energy astrophysics," said Smith, who specializes in using satellites like TESS (Transiting Exoplanet Survey Satellite) to study supermassive black holes and gas that surrounds them. Such studies shed light on the behavior of matter in the deeply warped spacetime around black holes and the processes by which black holes emit powerful jets into their host galaxies.

Smith calculated that GRB 191016A had a peak magnitude of 15.1, which means it was 10,000 times fainter than the faintest stars we can see with the naked eyes.

That may sound quite dim, but the faintness has to do with how far away the burst occurred. It is estimated that light from GRB 191016A's galaxy had been travelling 11.7 billion years before becoming visible in the TESS telescope.

Most gamma ray bursts are dimmer - closer to 160,000 times fainter than the faintest stars.

The burst reached its peak brightness sometime between 1,000 and 2,600 seconds, then faded gradually until it fell below the ability of TESS to detect it some 7000 seconds after it first went off.

This gamma-ray burst was first detected by a NASA's satellite called Swift-BAT, which was built to find these bursts. But because GRB 191016A occurred too close to the moon, the Swift-BAT couldn't do the necessary follow-up it normally would have to learn more about it until hours later.

NASA's TESS happened to be looking at that same part of the sky. That was sheer luck, as TESS turns its attention to a new strip of the sky every month.

While exoplanet researchers at a ground-base for TESS could tell right away that a gamma-ray burst had happened, it would be months before they got any data from the TESS satellite on it. But since their focus was on new planets, these researchers asked if any other scientists at a TESS conference in Sydney, Australia were interested in doing more digging on the blast.

Smith was one of the few high-energy astrophysics specialists there at that time and quickly volunteered.

"The TESS satellite has a lot of potential for high-energy applications, and this was too good an example to pass up," she said. High-energy astrophysics studies the behavior of matter and energy in extreme environments, including the regions around black holes, powerful relativistic jets, and explosions like gamma-ray bursts.

TESS is an optical telescope that collects light curves on everything in its field of view, every half hour. Light curves are a graph of light intensity of a celestial object or region as a function of time. Smith analyzed three of these light curves to be able to determine how bright the burst was.

She also used data from ground-based observatories and the Swift gamma-ray satellite to determine the burst's distance and other qualities about it.

"Because the burst reached its peak brightness later and had a peak brightness that was higher than most bursts, it allowed the TESS telescope to make multiple observations before the burst faded below the telescope's detection limit," Smith said. "We've provided the only space-based optical follow-up on this exceptional burst."

Researchers from the Carl R. Woese Institute for Genomic Biology in collaboration with scientists at Oxford University have published a paper in Cell reporting the function of LanCL proteins. These proteins are found in eukaryotic cells but their function was previously unknown. The study is the first step towards understanding the importance of these ubiquitous proteins.

Bacteria contain enzymes called LanC that are capable of producing small proteins called lanthipeptides, which are characterized by the addition of a thiol group to a modified serine or threonine amino acid. Similar proteins--called LanC-like or LanCL--have been found in different eukaryotic cells for decades, but their function was unknown.

"LanCLs are found in nearly all higher organisms, including humans. Although scientists have worked on these proteins for over 20 years, we didn't know their function. We had several hypotheses, which we kept ruling out based on our experiments," said Wilfred van der Donk (MMG), a professor of chemistry and investigator of the Howard Hughes Medical Institute.

The first breakthrough came in 2015, when the Nair lab in the Department of Biochemistry solved the crystal structure of a LanC-containing protein in bacteria. The protein was bound to another enzyme called a kinase, which modifies proteins by adding a phosphate group. Inspired by this discovery, the researchers tested whether LanCL proteins were also binding to kinases in eukaryotic cells. "We saw that they were able to bind to many kinases, including AKT and mTOR, and all of a sudden the pieces of the puzzle started forming a picture," van der Donk said.

The next piece fell into place in collaboration with Benjamin Davis, a professor of chemistry at the University of Oxford. The Davis group showed that eliminating a particular phosphate group in kinases causes them to become activated. Scientists had assumed that such processed proteins would be inactive. Together, the Illinois and Oxford groups were able to show that LanCL adds glutathione to kinases with eliminated phosphate groups, after which the kinases became deactivated. "We realized that when the LanCL proteins are absent, the cell has a big problem because there are active proteins floating around that need to be turned off," van der Donk said.

The importance of these proteins became evident in mice that lacked them. "A third of the mice that lack these enzymes die when they are between four to six months old. They die suddenly without getting sick and we still don't understand why," said Jie Chen (GNDP), a professor of cell and developmental biology.

The researchers are interested in understanding the role of these proteins and making a complete list of all the possible targets of LanCLs. "When you have abnormal kinases, it can cause all kinds of problems, including cancer. LanCL proteins eliminate these damaged kinases and it is possible that they also affect other proteins that we are not aware of. We need to connect their cellular functions to the results we saw in the mice," Chen said.

"This study is just the tip of the iceberg. Since these proteins are found everywhere, you can also imagine their effects in feedstock and the future of farming," said Satish Nair (MME/MMG), Head of the Department of Biochemistry.

"This study was possible because of the persistence of our graduate students. Most of us would have given up long ago because the studies were initially going nowhere," Nair said. "It also shows the importance of exploratory research, where you're essentially just looking around. Although it is risky, it is great to see that there are rewards for students who stick it out," van der Donk said.

Scientists from several hospitals and research centers have shown what happens in individual cells of patients who died of COVID-19. In a study published in Nature, the researchers describe how infected cells from multiple organs exhibited a range of molecular and genomic changes. They also saw signs of multiple, unsuccessful attempts by the lungs to repair themselves in response to respiratory failure, which is the leading cause of death in COVID-19 patients.

"You really feel the tragedy of the disease when you see that result," said Aviv Regev, co-senior author of the study and a core institute member at the Broad Institute of MIT and Harvard when the study began. "The lung tries everything at its disposal, and it still can't fix itself. This was a very emotional study. We are grateful to the patients and families who agreed to donate tissue for COVID-19 research to help advance understanding of this devastating disease."

The researchers studied tissue obtained at autopsies of 17 individuals who succumbed to COVID-19 and were cared for at Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, and Massachusetts General Hospital.

The team investigated how the SARS-CoV-2 virus interferes with the function of cells and their genetic programs. They used single-cell RNA sequencing data from tissue samples taken from 11 organ systems--including the lungs, heart, liver, and kidneys--to build a comprehensive "cell atlas" of hundreds of thousands of individual cells showing how COVID-19 can lead to organ failure and death.

"We knew people were passing away from COVID-related pneumonia and extrapulmonary complications," said Alexandra-Chloé Villani, an associate member of the Broad, a principal investigator at Mass General, an assistant professor of medicine at Harvard Medical School, and co-senior author on the study. "Before this study, we had limited knowledge of the cellular and molecular mechanisms that were involved in driving a patient's demise."

The study details the results of a collaboration of researchers from the Broad Institute, Mass General, the Ragon Institute of MGH, MIT and Harvard, MIT, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Columbia University Irving Medical Center, and other institutions. A team led by the Columbia collaborators co-authored a companion study that is also published in Nature.

The team's cell atlas is freely and openly available for other scientists to explore. They also created a 420-specimen biobank from the autopsy samples that can be used for other COVID-19 studies. "We created a foundational resource for other researchers to use in the future to ask specific questions," said Orit Rozenblatt-Rosen, co-senior author and an institute scientist and the scientific director of the Klarman Cell Observatory at the Broad when the study began. "Hopefully our findings will allow people to find better therapeutics for COVID-19."

Novel techniques for a novel virus

To learn about cellular mechanisms underlying organ failure caused by COVID-19, the researchers knew they needed to study the organs themselves. For that, they would need samples from autopsies.

Working with autopsy samples is challenging under normal circumstances. To deal with samples that might carry a novel, highly contagious pathogen, the researchers developed new tissue collection and processing protocols compatible with requirements for a Biosafety Level 3 lab.

"We wanted to ensure we could learn and share as much as humanly possible to help prevent future deaths, while prioritizing the safety and well-being of all involved. This was no small feat, given COVID-related restrictions and all the surrounding uncertainties. It was amazing to see dozens of scientists and medical professionals from several institutes come together as a collaborative partnership to carefully design and coordinate our experimental and computational efforts," said institute member and co-senior author Alex K. Shalek, who is also a member of the Ragon Institute, and an associate professor of chemistry, a core member of the Institute for Medical Engineering and Science, and an extramural member of the Koch Institute for Integrative Cancer Research at MIT.

The team then profiled RNA from the individual cells and developed new methods to analyze and annotate the large amounts of sequence data. They compared gene expression signatures from different cells: COVID-19-damaged cells and uninfected cells from the COVID-19 patients, as well as cells from patients with other diseases and from healthy individuals.

Havoc in the lungs

The most extensive suite of findings were from the lungs. The scientists were astounded by the extent of the changes in genetic programs they found there. "The virus wreaks havoc in the lungs and we see it in the cells," Regev said.

One main cause of lung damage in COVID-19 is the destruction of AT1 cells, which enable breathing and gas transfer. The scientists found that as AT1 cells died, related lung cells called AT2 attempted to convert themselves into AT1 cells through a process called transdifferentiation. But this attempt halted mid-way through, leaving the cells in an intermediary state that is often seen in patients with other lung diseases such as pulmonary fibrosis.

In a last-ditch attempt at self-repair, the lungs tried to turn cells from higher up in the airways, known as intrapulmonary basal-like progenitor cells, into AT1 cells. This attempt at transdifferentiation had only previously been seen in mouse models.

The findings suggest that the lung failure in patients was caused by the inability of lung cells to outpace the damage caused by the virus as the cells tried to regenerate.

Changing programs

The paper also describes how the virus impacts other tissues outside of the lungs. One surprising finding was that while the heart sustained significant damage and showed evidence of altered genetic programs in many different cell types, there was very little viral RNA in the heart tissue itself. "Whether that means the virus had already been cleared, or that the heart was collateral damage is an area for further research," said Regev.

The researchers also looked at 27 different genes that previous genome-wide association studies have linked to severe COVID-19. They zeroed in on a handful that were highly expressed in key cell types in the new study, particularly those in infected lungs. This finding helps narrow down the list of potential genetic factors for severe disease and highlights the cell types that may be most relevant in severe COVID-19.

The team now plans to finish analyzing the other autopsied tissues, such as brain, spleen and trachea, to paint a more complete picture of COVID-19 pathology and provide a resource for future studies.

Jeremy Edwards, director of the Computational Genomics and Technology (CGaT) Laboratory at The University of New Mexico, and his colleagues at Centrillion Technologies in Palo Alto, Calif. and West Virginia University, have developed a chip that provides a simpler and more rapid method of genome sequencing for viruses like COVID-19.

Their research, titled, "Highly Accurate Chip-Based Resequencing of SARS-CoV-2 Clinical Samples" was published recently in the American Chemical Society's Langmuir. As part of the research, scientists created a tiled genome array they developed for rapid and inexpensive full viral genome resequencing and applied their SARS-CoV-2-specific genome tiling array to rapidly and accurately resequenced the viral genome from eight clinical samples acquired from patients in Wyoming that tested positive for SARS-CoV-2. Ultimately, they were able to sequence 95 percent of the genome of each sample with greater than 99.9 percent accuracy.

"This new technology allows for faster and more accurate tracing of COVID and other respiratory viruses, including the appearance of new variants," said Edwards, who is a professor in the UNM Department of Chemistry and Chemical Biology. "With this simple and rapid testing procedure, scientists will be able to more accurately track the progression and better prevent the onset of the next pandemic."

With more than 142 million people worldwide having contracted the virus, vigilant testing and contact tracing are the most effective ways to slow the spread of COVID-19. Traditional methods of clinical testing often produce false positives or negatives, and traditional methods of sequencing are time-consuming and expensive. This new technology will virtually eliminate all of these barriers.

"Since the submission of the paper, the technology has further evolved with improved accuracy and sensitivity," said Edwards. "The chip technology is the best available technology for large-scale viral genome surveillance and monitoring viral variants. This technology could not only help control this pandemic and also prevent future pandemics."

The mission of the Computational Genomics and Technology (CGaT) Laboratory is to provide training in bioinformatics research for undergraduate, master's and Ph.D. students, as well as postdoctoral fellows; provide collaborative research interactions to utilize bioinformatics computing tools for researchers at UNM, and to conduct state-of-the-art and innovative bioinformatics and genomics research within the center.

Researchers at Karolinska Institutet in Sweden have discovered a mechanism through which meningitis-causing bacteria can evade our immune system. In laboratory tests, they found that Streptococcus pneumoniae and Haemophilus influenzae respond to increasing temperatures by producing safeguards that keep them from getting killed. This may prime their defenses against our immune system and increase their chances of survival, the researchers say. The findings are published in the journal PLoS Pathogens.

"This discovery helps to increase our understanding of the mechanisms these bacteria use to evade our normal immune defenses," says co-corresponding author Edmund Loh, researcher in the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. "It could be an important piece of the puzzle in examining what turns this usually harmless bacterium into a lethal killer."

Meningitis is an inflammation of the membranes surrounding the brain and the spinal cord. It can be caused by viruses, bacteria, fungi and parasites.

Bacterial meningitis is one of the most severe types and a major cause of death and disability in children worldwide. Several kinds of bacteria can cause the infection, including the respiratory pathogens Streptococcus pneumoniae and Haemophilus influenzae, which can be attributed to some 200,000 meningitis-caused deaths annually.

These two bacteria often reside in the nose and throat of healthy people without making them ill. In some cases they spread into the bloodstream and cause invasive diseases, but the reasons for this remain largely unknown.

In this study, the researchers set out to investigate the connection between temperature changes and survival of these bacteria in a laboratory setting. The experiments were prompted by another recent finding that linked the temperature sensing abilities of the bacterium N. meningitidis to invasive meningococcal disease.

One of the signs of an infection is elevated temperatures and fever, which typically boost our immune system's ability to fight illness. In this study, however, the researchers found that both S. pneumoniae and H. influenzae activated stronger immune protections when challenged with higher temperatures.

They did so through mechanisms involving four specific so-called RNA thermosensors (RNATs), which are temperature-sensitive non-coding RNA molecules. These RNATs helped boost the production of bigger protective capsules and immune modulatory Factor H binding proteins, both of which help shield these bacteria from immune system attacks.

"Our results indicate that these temperature sensing RNATs create an additional layer of protection that helps the bacteria colonize their normal habitat in the nose and throat," says the paper's first author Hannes Eichner, PhD student at the same department. "Interestingly, we saw that these RNATs do not possess any sequence similarity, but all retain the same thermosensing ability, which indicates that these RNATs have evolved independently to sense the same temperature cue in the nasopharynx to avoid immune killing."

More research is needed to understand exactly what triggers these pathogens to breach from the mucous membrane into the bloodstream and further into the brain. Future studies encompassing in vivo infection model are warranted to characterize the role of these RNATs during colonization and invasion, the researchers say.