Culture

WASHINGTON (Oct. 26, 2020) - Non-generic queries in the online tool Google Trends may yield better insight into health information-seeking behavior, according to a new study by researchers from the George Washington University (GW).

Google Trends analyzes the popularity of top Google queries geographically and longitudinally. More recently it has been used as a surveillance and retrospective epidemiological tool to study the impact of COVID-19 around the world. However, studies focusing on the pandemic's impact in the United States have been lacking, according to the researchers.

"What's interesting about Google Trends is that it is a free platform that allows researchers like me to assess information-seeking behavior from a big data perspective," said King John Pascual, a third-year MD student at the GW School of Medicine and Health Sciences (SMHS) and first author on the study. "Just like with any big-data platform, if you have the right research questions, it can be a powerful epidemiological tool."

The study, conducted by Pascual and his mentor Ali Pourmand, MD, MPH, professor of emergency medicine at SMHS, utilized Google Trends to assess the extent of the public's perceived exposure to COVID-19 as it relates to disease prevalence during the early phase of the pandemic in the U.S. The team collected four weeks of search volume index (SVI) data from March 2020.

Out of the five queries analyzed, two that signal perceived exposure to the virus, "How do I get tested for coronavirus?" or "Do I have coronavirus?" had statistically significant differences in mean SVI between states with the highest and lowest numbers of COVID-19 cases. Generic queries such as "What is coronavirus?" or "How is coronavirus spread?" that do not necessarily reflected perceived exposure to the virus were not associated with the number of COVID-19 cases. The study findings imply how analyzing specific phrases, in lieu of those borne out by general interest, may yield more meaningful data about perceived exposure to a communicable disease on a population level.

"Early access to population health data is crucial and potentially lifesaving," said Pascual. "Digital tools such as Google Trends may help bridge the gap in knowledge and transparency."

THIS year due to the pandemic the 8th International Skin Integrity and Infection Prevention Conference had to be redesigned. In its place arose an online international Wounds Week and it was so successful it is certainly going to happen again.

Wounds Week, hosted by the University of Huddersfield's Institute of Skin Integrity and Infection Prevention in conjunction with the Journal of Wound Care, happened over five days, between 6pm and 7.30pm (UK time) and included a roster of multidisciplinary expert international speakers. They explored and investigated issues surrounding wound infection, identification, prevention and management of pressure.

With 10 engaging topics, Wounds Week was an opportunity for the wound care community to come together during an extremely difficult time due to the ongoing global pandemic and allowed them to engage in key education free of charge.

Anonymous feedback

"Well done to Huddersfield Uni and all the brilliant staff. It is not always convenient to attend full study days so the online training is enough to keep you interested. I was very surprised to see people watching from TEXAS, HAWAII and USA - this must be very rewarding for you all."

Keynote session by Dr Sarah Jarvis

The opening session entitled 'COVID-19: State of the Nation' was by the new patron of the University's Institute of Skin Integrity and Infection Prevention Dr Sarah Jarvis, MBE, a renowned Medical Broadcaster and Clinical Director at Patient.info.

Dr Jarvis cleared up numerous myths surrounding COVID and spoke about how well she feels the public and UK Government have handled the pandemic, how close we really are to finding a vaccine and whether or not she thinks the nation will see a second wave of infection as winter approaches.

Each session had live Q&A where participants asked questions of the experts which allowed the audience to feel connected to others taking part no matter their COVID-19 situation. All the webinars can now be viewed for free online via https://www.woundsweek.com/webinars-on-demand/.

Antimicrobial Stewardship

The Director of the ISIaIP Professor Karen Ousey delivered a session on 'Antimicrobial Stewardship - Is this important in a pandemic?' where she discussed how COVID-19 has challenged all aspect of healthcare, including both recognition and management of serious acute bacterial infection and effective delivery of antimicrobial stewardship.

Professor Ousey was recently announced as being the new European Director of the International Skin Tear Advisory Panel (ISTAP) in recognition of her excellent research in the field of wound care.

The International Skin Tear Advisory Panel (ISTAP) was formed to raise international awareness of the prediction, assessment, prevention & management of skin tears. The panel includes healthcare professionals representing Africa, Asia, Australia, Europe, Middle East, North America and South America.

Wound Hygiene

Dr Leanne Atkin, a senior lecturer and Vascular Nurse Consultant at the University of Huddersfield/Mid Yorks NHS Trust delivered a session on the Treatment of hard to heal wounds: Investigating international consensus documents (TIMERS and Wound Hygiene) - what does this mean to clinical practice?.

In a second session, Dr Atkin spoke alongside Phil Bowler, Vice-president of Science & Technology at Convatec who outlined the role of biofilm, how it develops and acts as a primary barrier to healing, followed by Dr Atkin who demonstrated the benefits of implementing wound hygiene into daily practice.

Additional sessions looked at Negative Pressure Wound Therapy, recent developments in Pressure Ulcer Prevention, Evidence-based prevention of surgical site infection, point-of-care biomarker testing and fluorescence imaging and diabetic foot ulcers.

Researchers at Yale University and the Broad Institute of MIT and Harvard screened hundreds of millions of cells exposed to the COVID-19 and MERS viruses and identified dozens of genes that both enable the viruses to replicate in cells and also those that seem to slam the door on the virus.

The pro-viral and anti-viral role of these genes will help guide scientists in development of new therapies to combat COVID-19, the researchers say.

The findings were reported Oct. 26 in the journal Cell.

Scientists have previously identified how the SARS-CoV-2 coronovirus, which causes COVID-19, attaches to and invades cells, but less is known about why some cells are more susceptible to infection. Understanding the genetics behind the host cells' susceptibility to infection may help explain why some people exposed to the virus experience few or no symptoms and others become extremely ill or die.

For the study, researchers performed a genome-wide screen of a line of green monkey cells, which are more likely to die after exposure to SARS-CoV-2 than commonly used human cell lines. The screens for the first time allowed researchers to simultaneously track interactions of virus and cells. The screens confirmed earlier findings that the ACE-2 gene, which encodes a receptor on the cell surface, promotes infection by SARS-CoV-2.

However, the screens also identified two new pro-viral protein complexes and a third, which seems to assist in preventing infection. They found that SWI/SNF complex, which turns genes on and off, and HMGB1, which has a myriad of functions including regulation of inflammation, were linked to increased cell death after infection.

The researchers then introduced small molecule drugs that inhibit function of two of the identified gene products and found they could increase survival of cells after infection in a dish.

By contrast, the histone H3 complex, which helps regulate expression of genes within the cell nucleus, seemed to provide a protective effect, inhibiting ability of SARS-CoV-2 to infect and kill cells.

"It is very important to understand wide variation of responses to COVID-19, for instance why advanced age makes it much more likely that people will die," said Yale's Craig Wilen, assistant professor in laboratory medicine and immunobiology and corresponding author of the paper. "We have identified both proviral and antiviral genes that may help us predict who is likely to get severely ill and what kind of drugs would be helpful or detrimental in treating patients."

Wilen noted the information may not only be helpful in current pandemic, but also help prepare for outbreaks of future emerging coronaviruses.

Roughly half of U.S. dentists experienced verbal or reputational aggression by patients in the past year, and nearly one in four endured physical aggression, according to a new study led by researchers at NYU College of Dentistry.

The study, published in the October issue of the Journal of the American Dental Association, is the first to document aggression toward dentists in the United States.

Workplace aggression toward health care professionals is common, with health care settings second only to law enforcement in the rate of violent incidents. However, there are no studies of aggression toward dentists in the U.S.--a workforce of 200,000--and only four studies have been conducted in other countries.

"Workplace violence toward health care professionals is both widespread and widely overlooked," said Kimberly Rhoades, a research scientist in the Family Translational Research Group at NYU College of Dentistry and the study's lead author. "The purpose of this study was to provide an initial estimate of rates of patient aggression in dental practices in the United States."

Rhoades and her colleagues surveyed 98 dentists practicing in the New York City metropolitan area; the dentists had been working an average of 17 years. Participants completed a confidential online survey assessing whether they had experienced any of 21 specific types of aggressive behaviors from their patients, including types of physical (e.g. being pushed or kicked), verbal (e.g. being insulted or sworn at), and reputational (e.g. threats of lawsuits or posting nasty comments on social media) aggression.

A substantial proportion of dentists reported experiencing aggression from patients in the past year, including physical (22.2%), verbal (55%), and reputational (44.4%) aggression. An even larger proportion of dentists surveyed were subjected to physical (45.5%), verbal (74%), and reputational (68.7%) aggression at some point during their career. These rates of patient aggression toward dentists are high and comparable with those reported in other health care settings.

Rates of aggression did not differ by dentists' sex, race, ethnicity, specialty, age, years practicing, or average number of patients treated per day.

The rates of physical and reputational aggression toward dentists were similar to those from a parallel study by NYU researchers of aggression toward dental students published earlier this year in the Journal of Dental Education. However, practicing dentists experienced less verbal aggression from patients than dental students (55% versus 86%), suggesting that additional experience may reduce the risk of verbal aggression.

"Dentistry is rife with situations that can elicit strong negative emotions, such as fear, pain, distrust, and anger. Many patients also experience high levels of anxiety and vulnerability, which may increase negative responses or aggression," said Rhoades. "Establishing that aggression toward dentists is a problem and how often it occurs can help us develop interventions to prevent aggression in dental practices."

The researchers note that, while a larger, national study is needed to determine the true prevalence of aggression in U.S. dental settings, dental practices should consider implementing training that incorporates strategies for handling workplace violence. Training could address how to prevent patient aggression, and manage or de-escalate aggression when it does occur.

Stubbornly, frustratingly, pancreatic cancer has remained resistant to immunotherapies that are revolutionizing the treatment of many types of cancer.

A new study led by the University of Michigan Rogel Cancer Center combined single-cell RNA sequencing with two other investigative techniques to create what is believed to be the most robust and detailed portrait to date of the network of interactions that suppress the body's immune response in and around pancreatic tumors.

The team's findings, which appear in the journal Nature Cancer, put a new spotlight on the large degree to which immune response varies from patient to patient and tumor to tumor -- which will need to be taken into account as new immunotherapy combinations are developed against the deadly disease.

"Pancreas cancers just have not been sensitive to immune therapy, and those of us in the field are trying to sort out is why that is, what makes this cancer so different," says study senior author Marina Pasca di Magliano, Ph.D., a professor of surgery and of cell and developmental biology at Michigan Medicine. "What has been lacking is even a basic understanding of the variety and individual differences in immune response between patients."

The new research lays a foundation for future translational studies and clinical trials, with the ultimate goal of one day being able to use personalized molecular profiles to determine which immunotherapies would be of greatest benefit to each patient, she adds.

Years in the making, the study represents the effort of nearly 40 U-M clinicians and bench scientists working closely together to develop a trove of data that research groups in the field can draw upon for years to come, the team says.

Along with single-cell analysis, the group employed high-definition multiplex immunofluorescence and mass cytometry -- which combines mass spectrometry and flow cytometry -- to evaluate the complex biology of tumor samples in multiple ways.

"I think the key lesson for me as a clinician is that getting immunotherapy to work in this disease will continuing to be challenging because there are complexities that we're only just starting to appreciate," says study co-senior author Filip Bednar, M.D., an assistant professor of surgery. "This work opens the door to understanding those complexities and to figuring out how we might overcome them."

One key finding of the study was a new potential biomarker that showed up in the bloodstream of a subset of patients with pancreatic cancer -- an immune receptor called TIGIT (for T cell immunoreceptor with Ig and ITIM domains.)

"When people talk about immunotherapy, they're primarily talking about targeting a couple of specific molecules -- PD-1 and CTLA4," says co-senior author Howard Crawford, Ph.D., a professor of molecular and integrative physiology and of internal medicine. "What these research efforts have shown is that there's a lot more than just those two bad actors that are inhibiting the immune system and contributing to the ineffectiveness of immune therapy. TIGIT has been barely a blip on the radar."

Importantly, the researchers found that expression of TIGIT in patients' blood corresponded closely with its activity in tumors.

"So that suggests there could be a non-invasive way to assay individual patients to see whether they might be candidates for a future therapy targeting that particular checkpoint receptor -- which would be a significant advancement to the current standard of care," says Nina Steele, Ph.D., a postdoctoral research fellow in Pasca di Magliano's lab and one of four first authors of the study.

Another unique aspect of the study was the breadth and depth of the samples that were collected, the researchers note.

Unusually, the analysis included a significant number of samples from patients with advanced pancreatic cancer. Only about 1 in 4 pancreatic cancer patients are candidates for surgery, so those with earlier stage disease are greatly over-represented in many studies because they rely on samples collected during surgery, explains co-first author Eileen Carpenter, M.D., Ph.D., a gastroenterology fellow.

Early in their cancer journey, however, most patients have a tissue sample collected via needle biopsy so that doctors can obtain a definitive diagnosis -- so Carpenter coordinated the collection of research samples at the same time.

Blood samples were also collected from patients, allowing researchers to examine changes to immune cells circulating in the blood and correlate them with what was happening in a patient's tumor microenvironment, adds co-first author Samantha Kemp, a graduate student studying molecular and cellular pathology.

"I think there is often a surprising disconnect between research labs and clinics, even in something as straightforward as bio-specimen collection," Carpenter notes. "I think the bridges we were able to build and the contributions made by so many different labs really speak to the collaborative environment at the University of Michigan. There's a reason we were able to accomplish this work here."

Along with the clinical and laboratory efforts, data analysis was critical to the study, Pasca di Magliano stresses. Those efforts were led by Steel, Kemp and Veerin Sirihorachai, a graduate student in cancer biology.

"With single-cell sequencing especially, the actual acquisition of the data is relatively straightforward, but then analyzing the data is incredibly complex," Pasca di Magliano says.

In single-cell analysis, spatial information about the cells is lost. So the group, led by co-senior author Timothy Frankel, M.D., an assistant professor of surgery, also used a technique called multiplex immunohistochemistry, which allows for the identification of multiple cell types within a tissue slide while preserving the position of tumor cells relative to components of the microenvironment.

DALLAS (October 26, 2020) - After the COVID-19 pandemic crippled the global economy, scientists at the Center for BrainHealth®, part of The University of Texas at Dallas, worked with researchers across the world to develop a science-based plan that could help the economy recover and prevent similar collapses in the future. The Brain Capital Grand Strategy is an economic reimagination wherein organizations invest in employees' brain health as a critical, measurable asset. Improving brain health - emotional, behavioral and cognitive functioning - helps people tap into their brain's limitless potential, catalyze innovative thinking and improve their productivity, in turn strengthening the transforming economy.

The paper was recently published in Molecular Psychiatry. The Brain Capital Grand Strategy was a massive collaborative effort by numerous researchers, including Sandra Bond Chapman, PhD, founder and chief director of the Center for BrainHealth, and Ian Robertson, PhD, both co-directors of The BrainHealth Project. The author group also included experts from the Organisation for Economic Co-operation and Development (OECD) and the Asia-Pacific Economic Cooperation (APEC).

Science has shown that many people think about intellect as fixed. This is inaccurate and limits the potential of the human mind. The BrainHealth Project - the largest scientific study to redefine brain health and provide strategies for improving and maintaining the brain's performance - is central to the Brain Capital Grand Strategy. The BrainHealth Project defines brain health as a holistic health measure that includes components like a person's psychological well-being, social adeptness, and capacity for innovation.

This measure, known as the BrainHealth Index™, could serve as a predictor of when a community, corporation or country have the wherewithal to be resilient.

"The BrainHealth Index will be a central component of the Brain Capital strategy," said Harris Eyre, MD PhD, the senior author on the paper. "This measurement of brain health will allow for us to track, benchmark and implement the Brain Capital Grand Strategy in policy. This Index can also be used by executives, human resource managers and board members," he said.

In today's economy, many jobs require strong cognitive, emotional and social skills. Holistic education and policies promoting brain health through investment in brain capital could help people build cognitive resilience. Cognitive resilience is crucial in an economy where brain skills are central to productivity, especially in the midst of massive change. By redefining brain health and improving employees' resilience, The BrainHealth Project provides an avenue for lasting economic reform.

"Brain Capital is the economic benefit that accrues from keeping our brains powered at the highest level," said Dr. Chapman. "This is exactly what The BrainHealth Project is all about: helping people everywhere realize that they have this limitless power to become a more resilient version of themselves at all ages."

Introduced to the United States over 60 years ago, soybean cyst nematode (SCN) has spread broadly throughout the Midwest and eastern parts of the country. After penetrating the root tissue, SCN take nutrients away from the soybean plant and reduce plant growth and yield. These nematodes are the leading cause of soybean losses in the United States--in 2014, SCN resulted in the loss of 3.5 million tons of soybean.

While there are management strategies in place, many of them have become less effective in curtailing SCN populations. University of Illinois and USDA plant pathologists M.L. Pawlowski and G.L. Hartman, respectively, have been involved in an on-going effort to increase soybean productivity by reducing soybean diseases and pests. Their latest research found that arbuscular mycorrhizal fungi in a potential tool in SCN management.

Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with the roots of most plants, including soybean. Previous research has shown that these fungi can reduce the severity of plant disease caused by pathogens and pests including SCN. Pawlowski and Hartman set out to understand how AMF suppress SCN populations.

In one experiment they found that several different AMF species from different families reduced the number of cysts on soybean roots by 59 to 80 percent. They also found that one AMF species reduced counts of SCN by 60 percent and was able to suppress egg hatching by as much as 30 percent.

"We were surprised to find that AMF was so good at repressing SCN," said Hartman. "This opens up new avenues of research, which is needed to determine the efficacy of using AMF in field conditions, with a goal of providing another management tool to reduce the impact of SCN on soybean production."

Hartman also suggests that industries interested in biological control using arbuscular mycorrhizal fungi might consider commercializing the strain (F. mosseae) that was effective in reducing SCN. For more information, read "Impact of Arbuscular Mycorrhizal Species on Heterodera glycines" in the September issue of Plant Disease.

Boulder, Colo., USA: Floating gardens sound so idyllic. Now, a study proves that they are more than just a pretty place. The study, by researchers at Illinois State University, demonstrates that such constructed gardens can have a measurable, positive impact on water quality.

Floating gardens are essentially rafts built on a frame of plastic caging, wrapped in coconut husks, and filled in with native plantings. As plants grow, they extend their roots into the water, growing hydroponically. On Chicago's North Branch of the Chicago River, non-profit Urban Rivers and partners are developing a mile-long, floating eco-park. Dubbed the Wild Mile, the re-development of this former industrial canal is Urban Rivers' flagship project. As part of the park, floating gardens, attached to shore, are being installed.

The primary intent of the floating gardens is beautification. But the Illinois State team, from the University's Department of Geology, Geography, and the Environment, saw an ideal setup for a controlled experiment. "We got involved because it's the perfect opportunity to see if there's an impact on water quality," explains lead author Abigail Heath.

Heath will present the results of the study in an online talk on Tuesday from 10:45 to 11:00 a.m. EDT, during the Geological Society of America's annual meeting.

The study is novel: previous studies have explored floating gardens' impact on water quality over time, primarily in wastewater treatment ponds, but not over space, in moving water. The project also meshes well with Urban Rivers' broader goals. "The city is interested in water quality," says Phil Nicodemus, Urban Rivers Director of Research. "Happily, Illinois State got involved."

Starting in spring 2018, Heath and co-authors have sampled water immediately upstream and downstream of a narrow 3 meter by 50 meter floating garden installed along the shoreline. Samples are collected weekly, at the surface and from 0.3 meters deep, the depth where roots reach from the garden's base into the water. Although the garden is set at the edge of Chicago's urban core, water quality is also impacted by upstream agriculture. Analyses are focused on nutrients including nitrate as nitrogen, chloride, sulfate, and phosphate.

Could this small slice of human-made paradise improve water quality? An average of data collected over the course of the study show modest but definitive improvement. For example, nitrate as nitrogen dropped from 4.69 milligrams per liter in surface water just upstream of the garden to 4.43 milligrams per liter just downstream, a drop of about 1 percent. Phosphate was also lower downstream of the garden.

"Despite how small this garden was there was measurable improvement in water quality from upstream to downstream, especially for nitrates," notes Heath. She and colleagues see this as a scalable model for how larger floating gardens might help remediate water in similar settings. "Even this tiny garden makes a difference," she says.

A new study on genetic pathways in the common liverwort could have future implications for crop manipulation.

The findings of the US-led study, co-authored by genetic biologist Professor John Bowman from the Monash University School of Biological Sciences, are published today in Nature Plants.

Earlier this year researchers confirmed a new role for the well-known plant molecule known as 1-aminocyclopropane-1-carboxylic acid (ACC), providing the first clear example of it acting on its own as a likely plant hormone.

ACC is the precursor of the plant hormone ethylene which has many roles in growth and development.

"Ethylene was the first gaseous hormone identified over 100 years ago in flowering plants," explains Professor Bowman.

"It is the 'ripening hormone', that is, the one bad apple spoils the lot," he said.

"The ethylene signalling pathway has been characterised in flowering plants, and its disruption results in a number of defects, including fruit ripening.

However, land plants evolved from an aquatic alga, and genes encoding the ethylene signalling pathway can be found in extant algae, and were likely acquired from the cyanobacterial endosymbiont that evolved into the chloroplast, suggesting the pathway long predated the evolution of fruit ripening.

"Being able to understand and control ethylene production has major implications for agriculture and horticulture."

Professor Bowman and collaborators investigated the ethylene signalling pathway in the liverwort Marchantia, and showed that while ethylene acted as a signalling molecule similar to the situation in flowering plants, the enzymatic precursor to ethylene in flowering plants, ACC, was a biologically active molecule as well.

"As liverworts do not make ethylene via ACC, it suggests that ACC was a biologically active molecule in the ancestral land plant, and that the ethylene pathway as we know it in flowering plants evolved via co-option of pre-existing pathways," Professor Bowman said.

"These pathways likely still exist in flowering plants and may be able to be manipulated to affect ethylene signalling, and its incumbent biological processes in crop plants," he said.

Chainsaw-wielding maniacs and brain-munching zombies are common tropes in horror films and haunted houses, which, in normal years, are popular Halloween-season destinations for thrill seekers. But what makes such fearsome experiences so compelling, and why do we actively seek them out in frightful recreational settings?

New research accepted for publication in the journal Psychological Science reveals that horror entertains us most effectively when it triggers a distinct physical response--measured by changes in heart rate--but is not so scary that we become overwhelmed. That fine line between fun and an unpleasant experience can vary from person to person.

"By investigating how humans derive pleasure from fear, we find that there seems to be a 'sweet spot' where enjoyment is maximized," said Marc Malmdorf Andersen, a researcher at the Interacting Minds Center at Aarhus University and lead author of the paper. "Our study provides some of the first empirical evidence on the relationship between fear, enjoyment, and physical arousal in recreational forms of fear."

For years, researchers have suspected that physiological arousal, such as a quickening pulse and a release of hormones in the brain, may play a key role in explaining why so many people find horror movies and haunted houses so attractive.

Until now, however, a direct relationship between arousal and enjoyment from these types of activities has not been established. "No prior studies have analyzed this relationship on subjective, behavioral, as well as physiological levels," said Andersen.

To explore this connection, Andersen and his colleagues studied how a group of 110 participants responded to a commercial haunted house attraction in Vejle, Denmark. The researchers fitted each participant with a heart rate monitor, which recorded real-time data as they walked through the attraction. The nearly 50-room haunted house produced an immersive and intimate live-action horror experience. The attraction used a variety of scare tactics to frighten guests, including frequent jump scares, in which zombies or other monstrous abominations suddenly appeared or charged toward the guest.

The researchers also studied the participants in real time through closed-circuit monitors inside the attraction. This enabled the team to make first-hand observations of participants' reactions to the most frightening elements, and, subsequently, to have independent coders analyze participants' behavior and responses. After the experience, participants evaluated their level of fright and enjoyment for each encounter. By comparing these self-reported experiences with the data from the heart rate monitors and surveillance cameras, the researchers were able to compare the fear-related and enjoyment-related elements of the attraction on subjective, behavioral, and physiological levels.

What Is Recreational Fear?

Recreational fear refers to the mixed emotional experience of feeling fear and enjoyment at the same time. Fear is generally considered to be an unpleasant emotion that evolved to protect people from harm. Paradoxically, humans sometimes seek out frightening experiences for purely recreational purposes. "Past studies on recreational fear, however, have not been able to establish a direct relationship between enjoyment and fear," said Andersen.

Studies on fearful responses to media, for example, have mostly been conducted in laboratory settings with relatively weak stimuli, such as short video clips from frightening films. Such experimental setups can sometimes make it difficult to measure physiological arousal because responses may be modest in a laboratory context.

"Conducting our study at a haunted attraction, where participants are screaming with both fear and delight, made this task easier," said Andersen. "It also presented unique challenges, such as the immensely complex logistics associated with conducting empirical studies in a 'messy' real-world context like a haunted house."

Discovering the "Goldilocks Zone"

Plotting the relationship between self-reported fear and enjoyment, the researchers discovered an inverted U-shape trend, revealing an apparent sweet spot for fear where enjoyment is maximized.

"If people are not very scared, they do not enjoy the attraction as much, and the same happens if they are too scared," said Andersen. "Instead, it seems to be the case that a 'just-right' amount of fear is central for maximizing enjoyment."

The data also showed a similar inverted U-shape for the participants' heart rate signatures, suggesting that enjoyment is related to just-right deviations from a person's normal physiological state. However, when fearful encounters trigger large and long-lasting deviations from this normal state, as measured by pulse rates going up and down frequently over a longer period of time, unpleasant sensations often follow.

"This is strikingly similar to what scientists have found to characterize human play," said Andersen. "We know, for instance, that curiosity is often aroused when individuals have their expectations violated to a just-right degree, and several accounts of play stress the importance of just-right doses of uncertainty and surprise for explaining why play feels enjoyable."

In other words, when horror fans are watching Freddy Krueger on TV, reading a Stephen King novel, or screaming their way through a haunted attraction, they are essentially playing with fear.

Phytoplasma are a type of bacteria that live within the cells and cause devastating diseases with damaging effects. For example, in many cases plants infected with phytoplasma are no longer able to develop flowers. These plants have actually been described as "zombies," since they allow the reproduction of phytoplasma but are unable to reproduce themselves anymore. A group of biologists based at Friedrich Schiller University and the Fritz Lipmann Institute in Germany are working to help better understand exactly how phytoplasma cells bring about the so-called zombification of plants.

"Our group has been studying the proteins that are targeted by the phytoplasma effector proteins for almost 30 years," said Günter Theißen, one of the scientists involved in the study. "In our latest research, based on just few data and some simple assumptions, we predicted the structure of the respective effector protein (termed SAP54) about 5 years ago. With the new work, we tested our hypothesis experimentally, and found that our prediction was quite accurate."

Phytoplasma cells bring about devastating changes in plants by secreting effector proteins that interact with some molecules of the plant host, which leads to developmental abnormalities. This interaction is very specific as only very special host molecules are recognized by the phytoplasma effector molecules.

"This specificity is achieved by the effector proteins adopting a special structure that somewhat mimics part of the structure of the host molecules bound," explained Theißen. "This way, structural analyses at the molecular level help explain an important group of plant diseases."

Almost simultaneously, two other groups of scientists determined the crystal structure of very similar and highly related proteins, providing strong confirmation of the findings of Theißen and his colleagues. The team at Friedrich Schiller University also found that the effector protein SAP54 binds better to multimeric complexes of the target proteins than to protein dimers (pairs of proteins), suggesting an exciting avenue for future research.

"We are doing basic research," said Theißen. "However, there is no effective cure for phytoplasma infections that can be used in agronomy yet so, for example, when an orchard is affected, the only solution is to cut down all the infected trees, with dramatic economic ramifications. We hope that the more we know about how phytoplasma cells affect their hosts, the more we can help avoid the damage."

Over-activity in a single brain region underlies multiple symptoms of stress-related disorders

Targeting this region with ketamine only treats some of the symptoms

The region disrupts different brain networks: one involved in threat responses and one involved in responses to rewards

Distinct brain networks may explain the differential sensitivity of symptoms to treatments

Over-activity in a single brain region called the subgenual anterior cingulate cortex (sgACC) underlies several key symptoms of mood and anxiety disorders, but an antidepressant only successfully treats some of the symptoms. A new study, published today in the journal Nature Communications, suggests that sgACC is a crucial region in depression and anxiety, and targeted treatment based on a patient's symptoms could lead to better outcomes.

Depression is a debilitating disorder affecting hundreds of millions of people worldwide, but people experience it differently. Some mainly have symptoms of elevated negative emotion like guilt and anxiety; some have a loss of ability to experience pleasure (called anhedonia); and others a mix of the two.

Research at the University of Cambridge has found that increased activity in sgACC - a key part of the emotional brain- could underlie increased negative emotion, reduced pleasure and a higher risk of heart disease in depressed and anxious people. More revealing still is the discovery that these symptoms differ in their sensitivity to treatment with an antidepressant, despite being caused by the same change in brain activity.

Using marmosets, a type of non-human primate, the team of researchers infused tiny concentrations of an excitatory drug into sgACC to over-activate it. Marmosets are used because their brains share important similarities with those of humans and it is possible to manipulate brain regions to understand causal effects.

The researchers found that sgACC over-activity increases heart rate, elevates cortisol levels and exaggerates animals' responsiveness to threat, mirroring the stress-related symptoms of depression and anxiety.

"We found that over-activity in sgACC promotes the body's 'fight-or-flight' rather than 'rest-and-digest' response, by activating the cardiovascular system and elevating threat responses," said Dr Laith Alexander, one of the study's first authors from the University of Cambridge's Department of Physiology, Development and Neuroscience.

"This builds on our earlier work showing that over-activity also reduces anticipation and motivation for rewards, mirroring the loss of ability to experience pleasure seen in depression."

To explore threat and anxiety processing, the researchers trained marmosets to associate a tone with the presence of a rubber snake, an imminent threat which marmosets find innately stressful. Once marmosets learnt this, the researchers 'extinguished' the association by presenting the tone without the snake. They wanted to measure how quickly the marmosets could dampen down and 'regulate' their fear response.

"By over-activating sgACC, marmosets stayed fearful for longer as measured by both their behaviour and blood pressure, showing that in stressful situations their emotion regulation was disrupted," said Alexander.

Similarly, when the marmosets were confronted with a more uncertain threat in the form of an unfamiliar human, they appeared more anxious following over-activation of sgACC.

"The marmosets were much more wary of an unfamiliar person following over-activation of this key brain region - keeping their distance and displaying vigilance behaviours," said Dr Christian Wood, one of the lead authors of the study and senior postdoctoral scientist in Cambridge's Department of Physiology, Development and Neuroscience.

The researchers used brain imaging to explore other brain regions affected by sgACC over-activity during threat. Over-activation of sgACC increased activity within the amygdala and hypothalamus, two key parts of the brain's stress network. By contrast, it reduced activity in parts of the lateral prefrontal cortex - a region important in regulating emotional responses and shown to be underactive in depression.

"The brain regions we identified as being affected during threat processing differed from those we've previously shown are affected during reward processing," said Professor Angela Roberts in the University of Cambridge's Department of Physiology, Development and Neuroscience, who led the study.

"This is key, because the distinct brain networks might explain the differential sensitivity of threat-related and reward-related symptoms to treatment."

The researchers have previously shown that ketamine - which has rapidly acting antidepressant properties - can ameliorate anhedonia-like symptoms. But they found that it could not improve the elevated anxiety-like responses the marmosets displayed towards the human intruder following sgACC over-activation.

"We have definitive evidence for the differential sensitivity of different symptom clusters to treatment - on the one hand, anhedonia-like behaviour was reversed by ketamine; on the other, anxiety-like behaviours were not," Professor Roberts explained.

"Our research shows that the sgACC may sit at the head and the heart of the matter when it comes to symptoms and treatment of depression and anxiety."

For the more than 6.2 million Americans living with heart failure, the disease is a cruel thief. It robs patients of vitality, making even the simplest tasks seem exhausting and stealing years off of their lives.

But a glimmer of hope is rising. In a new multicenter study, researchers report that an emerging heart failure treatment could potentially reverse structural damage to the heart, allowing it to heal itself over time. They say the treatment could eliminate the need for heart transplants and long-term use of artificial heart pumps in certain cases.

The research team, co-led by University of Utah Health physicians, concluded that this approach, which combines the use of medications with temporary use of an artificial heart pump, known as a left ventricular assist device (LVAD), could help a select group of patients live longer, healthier, and more productive lives.

"For decades, heart transplantation and LVADs have been the therapeutic cornerstones of advanced heart failure," says Stavros Drakos, M.D., PhD, co-corresponding author of the study, cardiologist and director of Cardiovascular Research for the U of U Health Division of Cardiology. "But this alternative approach is different. It appears to be a bridge to heart recovery without requiring transplantation or long-term use of an artificial heart pump."

The study, which was conducted at six specialized medical centers nationwide, appears in Circulation, an American Heart Association journal.

What hadn't been appreciated until relatively recently is that LVADs significantly reduce the strain on failing hearts. In some cases, using LVADs for limited periods of time has allowed hearts to "rest" and remodel their damaged structures. As a result of these repairs, described as "reverse remodeling," heart function improves to the point that the LVAD can be removed.

In initial trials, researchers developed a treatment that combines LVAD uses with standard heart failure drugs known to enhance repair of heart tissue. The treatment appeared to be successful, with several patients surviving more than three years after their LVADs were removed.

The new study sought to broaden the reach of the research with a multicenter trial involving physicians and scientists at U of U Health, the University of Louisville, University of Pennsylvania, the Albert Einstein College of Medicine/Montefiore Medical Center, the Cleveland Clinic, and the University of Nebraska Medical Center.

The researchers recruited 40 advanced heart failure patients between the ages of 18 to 59 who were so severely ill that they required surgical implantation of a LVAD pump to remain alive. Overall, 19 patients (40%) who were treated with this protocol that combined LVAD support with standard heart failure medications had sufficient improvement in their cardiovascular health that the LVAD could be removed. These improvements included successfully completing a six-minute treadmill test and having sustained blood flow and blood pressure with the LVAD at low pump settings.

Following up, the researchers found that 90% of these patients were still alive one year after the removal of the LVAD, while 77% survived and were doing very well at two and three years of follow up. This rate of recovery is significantly higher than expected for this stage of the heart failure disease.

The research team concluded that this strategy of LVAD support combined with standardized medication and regular cardiovascular checkups led to high rates of LVAD removal, demonstrating it as a feasible substitute for transplantation or lifelong LVAD use. LVADs are physically burdensome and can be a source of complications, while heart transplants are difficult to come by.

"People that look at heart disease are usually trying to figure out why a heart is becoming worse," says Craig Selzman, M.D., a study co-author and chief of U of U Health's Division of Cardiothoracic Surgery. "This research is important because it's an alternative approach that is trying to figure out why these failing hearts are actually getting better."

The study had limitations, including a small number of patients, a lack of a control group, and a focus on patients younger than 60 years old. However, the researchers note that this does not necessarily mean that older patients and those who have varying degrees of heart failure would not benefit from this treatment.

Moving forward, the U of U Health researchers in conjunction with others plan to continue exploring how and why this treatment works. In particular, they have been focused on the metabolic pathways in the heart. Based on recent findings the team also published in Circulation, Drakos says these pathways appear to play a key role in the restructuring and remodeling that occurs.

"This multi-center study builds on and validates more than a decade of research conducted by Utah physician-scientists in this exciting field of heart recovery," Drakos says. "We are invested in figuring how to help a failing heart recover its function with just a little help from us."

Oncotarget Volume 11, Issue 33 features Figure 8, "Haplotype estimates in follicular lymphoma patients," by Assis-Mendonça, et al. which reported that the authors tested associations between SNPs, clinicopathological features and TME composition, and proposed survival models in R-CHOP/R-CVP-treated patients.

Presence of the IL12A rs568408 “A” allele associated with the follicular pattern of FOXP3 cells.

The IL12A AA haplotype included rs583911 and rs568408 and was an independent predictor of worse survival, together with the follicular patterns of T-cells and high IL-17F tumor levels.

The patterns of CD3, CD4, and CD8 cells displayed as a principal component, also associated with survival.

The survival of FL patients who were treated in the rituximab era shows a strong dependence on TME signals, especially the T-cell infiltration patterns and IL-17F tumor levels.

Dr. Guilherme Rossi Assis-Mendonça from The University of Campinas said, "Follicular lymphoma (FL) is the most common low-grade non-Hodgkin lymphoma (NHL) subtype and is characterized by an indolent clinical course and frequent relapses."

For instance, SNPs in key inflammatory genes, such as IL10 and IL2, are more consistently studied in large NHL cohorts and have been implicated in disease risk or in prognosis in the pre-rituximab era, including certain FL cohorts.

Nevertheless, the respective SNPs have been examined in a few studies and in a non-integrated fashion with other components of the TME.

No study has yet evaluated the function of SNPs within immune genes in the TME composition of FL.

This study aimed to verify whether SNPs in immune response genes modify the TME composition and clinical features of FL.

"This study aimed to verify whether SNPs in immune response genes modify the TME composition and clinical features of FL"

Another goal was to test the prognostic impact of these SNPs and the TME components in a cohort of patients who have been treated with rituximab-containing regimens.

The Assis-Mendonça Research Team concluded in their Oncotarget Research Paper that, we demonstrated the adverse prognostic role of several TME elements in FL, considering both protein and genetic data.

Importantly, the follicular pattern of the T-CD8 cells, the high expression of IL-17F, and the AA haplotype of IL2A were all independently associated with a worse prognosis.

The latter variable was also associated with the pattern of FOXP3 cell infiltration, which was validated in this study as a prognostic factor in the rituximab era.

The Oncotarget authors believe that the simultaneous study of the tumor biopsies and immune response-related SNPs in patients' peripheral blood allowed for a novel and more integrative approach that will provide new insights on follicular lymphoma biology.

The COVID-19 pandemic started earlier than previously thought in New York City and Long Island by dozens of people infected mostly with strains from Europe. A new analysis also shows that most of the spread was within the community, as opposed to coming from people who had traveled.

Previous testing had detected the first case of the virus on March 3 before infections exploded throughout the metropolitan area, leading to 260,600 positive cases by mid-May.

Led by NYU Grossman School of Medicine researchers, the new study used gene testing to trace the origins of SARS-CoV-2, the pandemic virus, throughout the New York City region in the spring. It showed that the virus first took root in late February, seeded by at least 109 different sources that burst into chains of infection, rather than from a single "patient zero."

Notably, the study authors say, more than 40 percent of people who tested positive had no known contact with another infected person before they contracted the virus.

"Our findings show that New York's early screening test methods missed the onset and roots of the outbreak by several days at the minimum," says study co-lead author Matthew Maurano, PhD, an assistant professor in the Department of Pathology at NYU Langone Health. "The work strongly suggests that to nip future outbreaks in the bud, we need a system of rapid, plentiful real-time genetic surveillance as well as traditional epidemiologic indicators."

The investigators also found that more than 95 percent of New Yorkers with COVID-19 had a strain of the virus with a mutation that may make it easier to transmit to others. This finding, Maurano says, helps explain why the virus spread so aggressively in New York, even when accounting for the city's high population density.

In gene sequencing, researchers compare small snips of genetic code to identify mutations that are only found in a particular strain of the virus. These "flags," Maurano says, can then be used to track how the strain has spread over time, similarly to tests used to trace ancestry in people. Experts have previously used this technique to follow outbreaks of influenza, methicillin-resistant Staphylococcus aureus (MRSA), and Ebola, among other infections.

The new study, published online Oct. 22 in the journal Genome Research, is the largest effort to date to trace the COVID-19 pandemic using gene sequencing, according to Maurano.

For the study, the researchers collected viral genetic information on 864 nasal swabs taken from New Yorkers who had tested positive for COVID-19 between March 12 and May 10. Most of the people were from Manhattan, Brooklyn, and Nassau County on Long Island. Then, the investigators compared the gene sequences of the virus from these samples to those seen in the original strain isolated last winter from patients in Wuhan, China, where the pandemic is believed to have begun.

The study revealed that the genetic codes of the virus in New York more closely matched those of strains from Europe or other U.S. states rather than those from China, where the virus originated. In addition, some of the early chains of infection from person to person ran at least 50 people long.

"Our gene sequencing techniques allowed us to evaluate the precision of our screening tests," says senior study author Adriana Heguy, PhD, a professor in the Department of Pathology at NYU Langone. "Based on these results, it is clear that we need a system of plentiful testing that provides rapid results."

She notes that the sequences analyzed in the study accounted for just 10 percent of COVID-19 patients within a single hospital system in New York. The true scale of the community infection was therefore likely much higher, and the original introduction of the virus to New York City was possibly earlier.

Heguy says the team next plans to investigate whether the mutations uncovered by genetic testing could affect the coronavirus in other ways, such as causing new or more severe symptoms of COVID-19.