Culture

MIAMI - Scientists from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science analyzed ground movements measured by Interferometric Synthetic Aperture Radar (InSAR) satellite data and GPS stations to precisely model where magma intruded and how magma influx changed over time, as well as where faults under the flanks moved without generating significant earthquakes. The GPS network is operated by the U.S. Geological Survey's Hawaii Volcano Observatory.

"An earthquake of magnitude-6 or greater would relieve the stress imparted by the influx of magma along a sub-horizontal fault under the western flank of the volcano," said Bhuvan Varugu, a Ph.D. candidate at the UM Rosenstiel School and lead author of the study. "This earthquake could trigger an eruption."

The researchers found that during 2014-2020 a total of 0.11 kilometers3 of new magma intruded into a dike-like magma body located under and south of the summit caldera, with the upper edge at 2.5 - 3 kilometers depth beneath the summit. They were able to determine that in 2015 the magma began expanding southward, where the topographic elevation is lower and the magma had less work to do against the topographic pressure. After the magma flux waned in 2017, the inflation center returned to its previous 2014-2015 horizontal position. Such changes of a magma body have never been observed before.

"At Mauna Loa, flank motion and eruptions are inherently related," said Varugu. "The influx of new magma started in 2014 after more than four years of seaward motion of the eastern flank - which opened up space in the rift zone for the magma to intrude."

The researchers also found that there was movement not associated with an earthquake along a near-horizontal fault under the eastern flank, however, no movement was detected under the western flank. This led the researchers to conclude that an earthquake under the western flank is due. Motions along near-horizontal faults under the flanks are essential features of long-term volcano growth.

Will the volcano erupt in the near future? "If magma influx continues it is likely, but not required," says Varugu. "The topographic load is pretty heavy, the magma could also propagate laterally through the rift zone".

"An earthquake could be a game changer," said Falk Amelung, a professor at the UM Rosenstiel School's Department of Marine Geosciences and senior author of the study. "It would release gases from the magma comparable to shaking a soda bottle, generating additional pressure and buoyancy, sufficient to break the rock above the magma."

According to the researchers there are many uncertainties. Though the stress that was exerted along the fault is known, the magnitude of the earthquake will also depend on the size of the fault patch that will actually rupture. Additionally, there are no satellite data available to determine movements prior to 2002.

"It is a fascinating problem," said Amelung, "We can explain how and why the magma body changed during the past six years. We will continue observing and this will eventually lead to better models to forecast the next eruption site."

Standing 9 kilometers tall from the base on the seafloor to the summit, Mauna Loa is the largest volcano on Earth. In the 1950 eruption, it took only three hours for the lava to reach the Kona coast. Such rapid flows would leave very little time to evacuate people in the path of its lava. Another large eruption of Mauna Loa occurred in 1984.

The combination of earthquakes and eruptions is nothing unusual. The 1950 eruption was preceded by a magnitude 6.3 earthquake three days prior, and was followed by a magnitude 6.9 earthquake more than a year later. The 1984 eruption was preceded by a magnitude 6.6 earthquake 5 months prior.

The satellite data were acquired by the Italian Cosmo-Skymed satellites in the framework of the Geohazard Supersites and Natural Laboratories (GSNL) initiative of the Group on Earth Observation (GEO), an international umbrella organization to enhance the use of Earth Observation for societal benefits. Several space agencies pool their satellite resources to enable new studies of hazardous volcanoes. Other volcano supersites include the Icelandic, Ecuadorian and New Zealand volcanoes as well as Italy's Mt. Etna.

A research group from Osaka University led by Professor Hisashi Arase and consisting of researchers from the Research Institute for Microbial Diseases, the Institute for Protein Research, the Immunology Frontier Research Center, the Center for Infectious Diseases, and the Graduate School of Medicine has discovered for the first time that both neutralizing antibodies that protect against infection as well as infection-enhancing antibodies that increase infectivity are produced after infection with SARS-CoV-2 by analyzing antibodies derived from COVID-19 patients.

Antibodies against the receptor binding site (RBD) of the SARS-CoV-2 spike protein play an important function as neutralizing antibodies that suppress SARS-CoV-2 infection by inhibiting its binding to the human receptor, ACE2. On the other hand, the function of antibodies against other sites of the spike protein was unknown.

"We found that when infection-enhancing antibodies bind to a specific site on the spike protein of SARS-CoV-2, the antibodies directly cause a conformational change in the spike protein, resulting in the increased infectivity of SARS-CoV-2. Neutralizing antibodies recognize the RBD, whereas infection-enhancing antibodies recognize specific sites of the N-terminal domain (NTD)," explains Professor Hisashi Arase. "Furthermore, the production of infection-enhancing antibodies attenuated the ability of neutralizing antibodies to prevent infection."

Higher production of infection-enhancing antibodies was found in patients with severe COVID-19. It was also found that non-infected individuals may have small amounts of infection-enhancing antibodies.

Although the production of infection-enhancing antibodies may be involved in the development of severe disease, further analysis is required to ascertain whether they are actually involved in the exacerbation of infection in the body.

By analyzing the antibody titer of infection-enhancing antibodies, it may be possible to check for people who are prone to severe disease. The results of this research are also important for the development of vaccines that do not induce the production of infection-enhancing antibodies.

"It is important to analyze not only neutralizing antibodies but also infection-enhancing antibodies. In the future, it may be necessary to develop vaccines that do not induce the production of infection-enhancing antibodies, because infection-enhancing antibodies may be more effective against mutant strains in which neutralizing antibodies are not sufficiently effective," says Professor Hisashi Arase.

UNIVERSITY PARK, Pa. -- A new map of dark matter in the local universe reveals several previously undiscovered filamentary structures connecting galaxies. The map, developed using machine learning by an international team including a Penn State astrophysicist, could enable studies about the nature of dark matter as well as about the history and future of our local universe.

Dark matter is an elusive substance that makes up 80% of the universe. It also provides the skeleton for what cosmologists call the cosmic web, the large-scale structure of the universe that, due to its gravitational influence, dictates the motion of galaxies and other cosmic material. However, the distribution of local dark matter is currently unknown because it cannot be measured directly. Researchers must instead infer its distribution based on its gravitational influence on other objects in the universe, like galaxies.

"Ironically, it's easier to study the distribution of dark matter much further away because it reflects the very distant past, which is much less complex," said Donghui Jeong, associate professor of astronomy and astrophysics at Penn State and a corresponding author of the study. "Over time, as the large-scale structure of the universe has grown, the complexity of the universe has increased, so it is inherently harder to make measurements about dark matter locally."

Previous attempts to map the cosmic web started with a model of the early universe and then simulated the evolution of the model over billions of years. However, this method is computationally intensive and so far has not been able to produce results detailed enough to see the local universe. In the new study, the researchers took a completely different approach, using machine learning to build a model that uses information about the distribution and motion of galaxies to predict the distribution of dark matter.

The researchers built and trained their model using a large set of galaxy simulations, called Illustris-TNG, which includes galaxies, gasses, other visible matter, as well as dark matter. The team specifically selected simulated galaxies comparable to those in the Milky Way and ultimately identified which properties of galaxies are needed to predict the dark matter distribution.

"When given certain information, the model can essentially fill in the gaps based on what it has looked at before," said Jeong. "The map from our models doesn't perfectly fit the simulation data, but we can still reconstruct very detailed structures. We found that including the motion of galaxies--their radial peculiar velocities--in addition to their distribution drastically enhanced the quality of the map and allowed us to see these details."

The research team then applied their model to real data from the local universe from the Cosmicflow-3 galaxy catalog. The catalog contains comprehensive data about the distribution and movement of more than 17 thousand galaxies in the vicinity of the Milky Way--within 200 megaparsecs. The resulting map of the local cosmic web is published in a paper appearing online May 26 in the Astrophysical Journal.

The map successively reproduced known prominent structures in the local universe, including the "local sheet"--a region of space containing the Milky Way, nearby galaxies in the "local group," and galaxies in the Virgo cluster--and the "local void"--a relatively empty region of space next to the local group. Additionally, it identified several new structures that require further investigation, including smaller filamentary structures that connect galaxies.

"Having a local map of the cosmic web opens up a new chapter of cosmological study," said Jeong. "We can study how the distribution of dark matter relates to other emission data, which will help us understand the nature of dark matter. And we can study these filamentary structures directly, these hidden bridges between galaxies."

For example, it has been suggested that the Milky Way and Andromeda galaxies may be slowly moving toward each other, but whether they may collide in many billions of years remains unclear. Studying the dark matter filaments connecting the two galaxies could provide important insights into their future.

"Because dark matter dominates the dynamics of the universe, it basically determines our fate," said Jeong. "So we can ask a computer to evolve the map for billions of years to see what will happen in the local universe. And we can evolve the model back in time to understand the history of our cosmic neighborhood."

The researchers believe they can improve the accuracy of their map by adding more galaxies. Planned astronomical surveys, for example using the James Web Space Telescope, could allow them to add faint or small galaxies that have yet to be observed and galaxies that are further away.

SILVER SPRING, Md.--People who are successful at weight-loss maintenance spend less time sitting during the week and weekends compared to weight-stable individuals with obesity, according to a paper published online in Obesity, The Obesity Society's flagship journal. This is the first study to examine time spent in various sitting activities among weight-loss maintainers.

Prior findings from 2006 in the National Weight Control Registry indicated that weight-loss maintainers watched significantly less television than controls, but other sitting activities were not examined. In the current study, weight-loss maintainers did not significantly differ from controls in reported weekly sitting time spent watching television, but did differ in time spent in non-work-related time using a computer or video game.

Differences between the current study and National Weight Control Registry findings could reflect changes over the past 15 years in available electronic devices, including the rise in availability of computers and video games. Weight-loss maintainers and controls also did not appreciably differ in time spent sitting while reading or studying, traveling; or talking, texting and socializing. These could be considered more mentally active forms of sedentary behavior.

"The findings hopefully will prompt future weight maintenance intervention research testing the effects of and optimal approaches for reducing sedentary behavior, including non-work-related computer and video game usage. Future research should include objective measures of sedentary behavior and activity," said Suzanne Phelan, Department of Kinesiology and Public Health and The Center for Health Research, California Polytechnic State University, in San Luis Obispo. Phelan is the corresponding author of the study.

Participants in the study included 4,305 weight-loss maintainers from WW (formerly Weight Watchers) who had maintained >9.1 kg of weight loss (24.7 kg on average) for 3.3 years and had an average current BMI of 27.6 kg/m2. The group of weight-stable individuals with obesity had an average BMI of 38.9 kg/m2. To gather data, the Multicontext Sitting Time and Paffenbarger physical activity questionnaires were administered.

Results revealed that weight-loss maintainers versus weight-stable individuals with obesity spent three hours less per day sitting during the week (10.9 versus 13.9) and weekends (9.7 versus 12.6). Weight-loss maintainers compared with controls also spent one hour less per day in non-work-related sitting using a computer or playing a video game during the week (1.4 versus 2.3) and weekends (1.5 versus 2.5). There were no meaningful differences between weight-loss maintainers and weight-stable individuals with obesity in the number of television sets and sedentary-promoting devices in the home (15.8 versus 14.8). Weight-loss maintainers expended significantly more calories per week in physical activity (1,835 versus 785).

"These findings are important for understanding behaviors that may enhance weight loss maintenance, and one of those may be to reduce sitting time and other modes of sedentary behavior. However, this study also showed that physical activity was associated with improved weight-loss maintenance. Thus, this study does not imply that simply standing more rather than sitting will contribute to weight-loss maintenance, but may suggest that less sitting that results in more movement is what is key to weight loss maintenance. Hence, sit less and move more," said John M. Jakicic, PhD, FACSM, FTOS, Distinguished Professor, and Director of the Healthy Lifestyle Institute and the Physical Activity and Weight Management Research Center at the University of Pittsburgh in Pennsylvania. Jakicic was not associated with the research.

Other authors of the study include James Roake, Noemi Alarcon and Sarah Keadle of the Department of Kinesiology and Public Health and The Center for Health Research, California Polytechnic State University, in San Luis Obispo. Chad Rethorst of Texas A&M Agrilife in Dallas, Texas and Gary Foster of WW International, Inc. of New York and the Center for Weight and Eating Disorders, Perelman School of Medicine, University of Pennsylvania, in Philadelphia also co-authored the study.

While many might consider a walk in the woods to be a quiet, peaceful escape from their noisy urban life, we often don't consider just how incredibly noisy some natural environments can be. Although we use soothing natural sounds in our daily lives - to relax or for meditation - the thunder of a mountain river or the crash of pounding surf have likely been changing how animals communicate and where they live for eons. A new experimental study published in the journal Nature Communications finds that birds and bats often avoid habitat swamped with loud whitewater river noise.

Dr. Dylan Gomes, a recent PhD graduate of Boise State University and first author on the paper, summarizes the aims of the work this way, "naturally-loud environments have been largely neglected in ecological research. We aimed to test the hypothesis that intense natural noise can shape animal distributions and behavior by experimentally broadcasting whitewater river noise at a massive scale." In fact, the scientists had to transport literal tons of gear across roadless terrain to place solar-powered speaker arrays in half of their 60 locations in the Pioneer Mountains of Idaho where they monitored bird and bat populations for two summers.

The speaker arrays were arranged along riparian areas, filling each bubbling brook with the auditory experience of a rushing whitewater river. The team took advantage of their experimental approach to broadcast both realistic reproductions of river noise, as well as river noise that had been shifted upwards in frequency to understand how the noise caused changes in animal numbers. "The prevailing hypothesis for why many animals avoid noise is called masking. Masking occurs when noise overlaps in frequency (what we perceive as pitch) with a biological signal or cue. By broadcasting noise of different frequencies, we hoped to assess the role that masking of important sounds, such as birdsong, plays in the avoidance of noisy places", said the senior author of the study, Dr. Jesse Barber of Boise State University. The scientists found that overlap between background noise and song frequency predicted bird declines until acoustic environments became about as loud as a highway, at which point other forces, such as an inability to hear predators and prey, likely become more important.

Understanding how noise drives animals out of otherwise good habitat is clearly important, but what about the animals that stay behind? To study foraging in birds that remained in naturally-loud places the authors set out hundreds of caterpillar decoys made of clay across their study sites. By carefully examining the types of marks predators left in the clay, the scientists found that more noise meant less foraging by birds. This means that, even after controlling for the fact that fewer birds were found in loud places, birds were less efficient at visually hunting for these silent, decoy caterpillars in the presence of noise. This is not unlike the difficulty people can experience when trying to listen to a friend talk while a muted television is on, dividing our attention.

To understand how bats that remained in noise-exposed areas fared, the team deployed two foraging puzzles to solve. The first was a "robo-moth" that lured in bats with its insect-like wing beats. The second was a speaker playing a "mix tape" of cricket and katydid calls and insect walking sounds. After almost 150 nights of data collection the scientists found that, as the world gets louder, some bats switch from listening for prey sounds to using echolocation. Dr. Gomes explains, "this behavioral switch is likely driven by prey calls and footsteps being masked by river noise and this type of problem-solving likely explains why some bats can remain near the ruckus of a raging whitewater river".

When putting all these pieces together, the authors argue that by studying how animals respond to noise sources that they have faced throughout their evolutionary history, we can get a better handle on how animals will deal with human-caused noise. Dr. Clinton Francis from California Polytechnic State University and Co-Principal Investigator of the study says, "our work showing that natural noise can structure where animals live and how they behave only increases the call to manage human-caused noise. The spatial and temporal footprint of anthropogenic noise is far greater than loud natural environments."

Despite a daunting more than 130 million cases of SARS-CoV-2 infections to date worldwide, another global pathogen - the Aedes mosquito-borne dengue virus - saw a record number of over 400 million cases in 2019. But vaccine development has been challenging due to the need to protect equally against all four dengue strains. The discovery of new possible biomarkers to predict clinical and immune responses to dengue virus infection, published today in Nature Communication, could be critical to informing future vaccines.

As with SARS-CoV-2 infection, the effects of dengue virus infection can range from asymptomatic to severe disease that can be fatal. Climate change has expanded the viruses' geographic distribution far beyond tropical areas like Southeast Asia and Latin America to the southern U.S. and Europe. Only one vaccine, Dengvaxia, has been approved for a subset of at-risk individuals in endemic areas.

This study, led by University of Vermont (UVM) Associate Professor of Microbiology and Molecular Genetics (MMG) Sean Diehl, Ph.D., set out to determine biomarker candidates and predictors for clinical and immunological responses resulting from dengue infection. Previous research published by Diehl and MMG Chair Beth Kirkpatrick, M.D., director of the UVM Vaccine Testing Center, has shown how a dengue vaccine being developed together with Johns Hopkins and the National Institutes of Health activates an immune response that protects against challenge with this dengue virus.

Live, weakened viruses are the basis for the most-effective and longest-lasting vaccines against many viral diseases. This "live attenuated" approach is used in the next-generation dengue vaccine that is being co-developed at UVM. To better understand how live attenuated dengue viruses turn on the immune system, Diehl and colleague John Hanley, Ph.D., a UVM research specialist, in collaboration with Kirkpatrick and the Vaccine Testing Center, investigated which genes are activated or repressed in the immune cells from subjects exposed to a well-characterized and safe live attenuated dengue virus. Hanley developed a new statistical approach to integrate the genomics data with the extensive clinical data collected during the careful monitoring of dengue virus-exposed study participants.

The team found strong correlations between the activation of specific immune genes and the ability of participants' immune systems to turn on early cellular defense mechanisms and make protective antibodies against dengue virus.

"These data offer new potential biomarkers for characterizing dengue virus infection and novel pathways that could be leveraged to combat viral replication," says Diehl. "Our results also gave us some clues about how we might be able to boost protective immune responses, which is the goal of developing effective vaccines."

Diehl adds that for some of the genes identified in this study, little is known about their role in the response against dengue virus.

"This is very exciting, because it could lead to new ways to fight dengue, so we are now investigating these in the lab" says Diehl.

He and Kirkpatrick are also working to determine how long protective immunity lasts after receiving a dengue vaccine and are in the process of identifying volunteers who received the NIH-developed dengue vaccine up to 11 years ago to obtain a current blood sample for further testing.

"A durable protective immune response is the goal of a good vaccine," says Kirkpatrick.

Within the European Union alone, about three million people are affected by an autism spectrum disorder (ASD). Some are only mildly affected and can live independent lives. Others have severe disabilities. What the different forms have in common is difficulty with social interaction and communication, as well as repetitive-stereotypic behaviors. Mutations in a few hundred genes are associated with ASD. One of them is called Cullin 3, and it is a high-risk gene: A mutation of this gene almost certainly leads to a disorder. But how exactly does this gene affect the brain? To learn more about it, Jasmin Morandell and Lena Schwarz, PhD students at Professor Gaia Novarino's research group, turned to mice whose Cullin 3 gene has been partially deactivated and compared them to their healthy siblings. Their results have just been published in the journal Nature Communications.

In a series of behavioral and motoric tests, the team wanted to see if the modified mice mimicked some of the characteristics of patients with this form of autism and could therefore be used as model organisms. In one of these tests, the so-called three-chamber sociability test, a mouse could freely explore three adjacent chambers of a box connected by little doors. Now, the scientists put two other mice in the outer boxes: One was already familiar to the studied mouse, the other mouse it had never met. "Healthy mice usually prefer the new over the already familiar mouse," Jasmin Morandell, co-first author of the study, explains. The mouse with the altered Cullin 3 gene, however, showed no sign of recognition. Furthermore, the mice had motor coordination deficits as well as other ASD-relevant cognitive impairments. With the help of this mouse model, the team was then able to get to the bottom of the mechanisms that bring about these changes.

A Dangerous Accumulation of Proteins

While studying the mouse brain, the researchers noticed a very subtle but consistent change in the position of some brain cells. These so-called neurons or nerve cells originate from a special region in the brain. From there, they migrate toward the uppermost layers until they find their designated place in the cortex. It is a very sensitive process, where even small changes in the speed at which they travel can change the structure of the cortex. By marking the migrating neurons, the scientists could trace their movements. "We could observe migration deficits - the neurons are stranded in the lower cortex layers," Lena Schwarz, the other co-first author of the study, describes. But why are the cells not moving as they should?

The answer lies in the important role Cullin 3 plays at the end of life of proteins. When their time has come, the gene Cullin 3 tags them for degradation - a process that has to be tightly regulated to prevent proteins from accumulating. To find out, which proteins are misregulated when Cullin 3 is defective, Morandell and Schwarz systematically analyzed the protein composition of the mouse brain. "We were looking at proteins that accumulate in the mutant brain and found a protein called Plastin 3. Then Gaia came across a poster describing the work of IST Austria's Schur group in the hallway, and we got very excited," says Jasmin Morandell. "They independently had been working on Plastin 3 as a regulator of cell motility and had complementary results to ours. That's when we started working together," Professor Gaia Novarino remembers.

It turned out that the protein Plastin 3, which was previously unknown in the context of neuronal cell migration, actually plays an important role in this process. "If the Cullin 3 gene is deactivated, the Plastin 3 protein accumulates, causing cells to migrate slower and over shorter distances. This is exactly what we saw happening in the cortex of the Cullin 3 mutant mice," says PhD student Lena Schwarz.

A Risky Pathway?

All this is taking place during a very early stage of brain development around halfway through pregnancy - long before anyone would notice any difference in the fetus. "Determining these critical windows during brain development could be extremely important to fine-tune the treatment of patients with specific forms of ASD," explains Novarino, who is committed to improving diagnosis and treatment options for people with ASD. "Following up with the research on Plastin 3 could pave the way for some therapeutics. Inhibiting the accumulation of this protein could eventually alleviate some of the symptoms patients have," Schwarz says.

"We now know that defective Cullin 3 leads to increased levels of Plastin 3. This tight correlation shows that Plastin 3 protein levels may be an important factor for the control of cell-intrinsic movements," says Jasmin Morandell. She recently graduated and may use her expertise in brain development to study Huntington's disease. Lena Schwarz will next turn to additional high-risk ASD genes to see how other proteins in the degradation pathway may be linked to ASD. For the present study, the Novarino group joined forces with the Danzl and Schur groups and a colleague from the University of Rome. "Finishing this extensive study in around two and a half years despite the pandemic was only possible with the support from our neighbors at IST Austria," Novarino praises the multidisciplinarity at the Institute.

A study of 1,095 patients hospitalized with COVID-19 discovered that two easily measurable signs of health - respiration rate and blood-oxygen saturation - are distinctly predictive of higher mortality. Notably, the authors said, anyone who receives a positive COVID-19 screening test can easily monitor for these two signs at home.

This context is lacking in current guidance from the Centers for Disease Control and Prevention, which tells people with COVID-19 to seek medical attention when they experience overt symptoms such as "trouble breathing" and "persistent pain or pressure in the chest" - indications that may be absent even when respiration and blood oxygen have reached dangerous levels, the authors say.

"These findings apply to the lived experience of the majority of patients with COVID-19: being at home, feeling anxious, wondering how to know whether their illness will progress and wondering when it makes sense to go to the hospital," said Dr. Neal Chatterjee of the University of Washington School of Medicine.

Chatterjee and fellow cardiologist Dr. Nona Sotoodehnia were co-lead authors of the paper, which was to be published May 24 in the journal Influenza and Other Respiratory Viruses.

They said the findings suggest that, for some people with COVID-19, by the time they feel bad enough to come to the hospital, a window for early medical intervention might have passed.

"Initially, most patients with COVID don't have difficulty breathing. They can have quite low oxygen saturation and still be asymptomatic," said Sotoodehnia. "If patients follow the current guidance, because they may not get short of breath until their blood oxygen is quite low, then we are missing a chance to intervene early with life-saving treatment."

The researchers examined the cases of 1,095 patients age 18 and older who were admitted with COVID-19 to UW Medicine hospitals in Seattle or to Rush University Medical Center in Chicago. The study span was March 1 to June 8, 2020. The lone exclusions were people who chose "comfort measures only" at time of their admission.

While patients frequently had hypoxemia (low blood-oxygen saturation; 91% or below for this study) or tachypnea (fast, shallow breathing; 23 breaths per minute for this study), few reported feeling short of breath or coughing regardless of blood oxygen.

The study's primary measure was all-cause in-hospital mortality. Overall, 197 patients died in the hospital. Compared to those admitted with normal blood oxygen, hypoxemic patients had a mortality risk 1.8 to 4.0 times greater, depending on the patient's blood oxygen levels. Similarly, compared to patients admitted with normal respiratory rates, those with tachypnea had a mortality risk 1.9 to 3.2 times greater. By contrast, other clinical signs at admission, including temperature, heart rate and blood pressure, were not associated with mortality.

Nearly all patients with hypoxemia and tachypnea required supplemental oxygen, which, when paired with inflammation-reducing glucocorticoids, can effectively treat acute cases of COVID-19.

"We give supplemental oxygen to patients to maintain blood oxygen saturation of 92% to 96%. It's important to note that only patients on supplemental oxygen benefit from the life-saving effects of glucocorticoids," Sotoodehnia said. "On average our hypoxemic patients had an oxygen saturation of 91% when they came into the hospital, so a huge number of them were already well below where we would've administered life-saving measures. For them, that care was delayed."

The findings have relevance for family-medicine practitioners and virtual-care providers, who typically are first-line clinical contacts for people who have received a positive COVID-19 test result and want to monitor meaningful symptoms.

"We recommend that the CDC and [World Health Organization] consider recasting their guidelines to account for this population of asymptomatic people who actually merit hospital admission and care," Chatterjee said. "But people don't walk around knowing WHO and CDC guidelines; we get this guidance from our physicians and news stories."

Sotoodehnia recommended that people with positive COVID-19 test results, particularly those at higher risk of adverse outcomes due to advanced age or obesity, buy or borrow a pulse oximeter and monitor for blood-oxygen below 92%. The clip-like devices fit over a fingertip and can be purchased for under $20.

"An even simpler measure is respiratory rate - how many breaths you take in a minute. Ask a friend or family member to monitor you for a minute while you're not paying attention to your breathing, and if you hit 23 breaths per minute, you should contact your physician," she said.

Oncotarget published "Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens" which reported that the current study examines urine samples from 66 subjects, comprising of 31 Urology clinic controls and 35 bladder cancer patients, using a Luminex based screening platform.

ELISA validation was carried out for the top 4 prospective urine biomarkers using an independent cohort of 20 Urology clinic controls and 60 bladder cancer subjects.

Eight of these urine proteins were able to differentiate BC from control urine with ROC AUC values exceeding 0.70 at p

These Oncotarget findings suggest that urine IL-1α, IL-1ra and IL-8 are useful indicators of bladder cancer.

These Oncotarget findings suggest that urine IL-1α, IL-1ra and IL-8 are useful indicators of bladder cancer.

Urine IL-8 not only distinguishes bladder cancer from controls, it also discriminates high grade from low grade disease, and the successive clinical stages of bladder cancer.

Dr. Chandra Mohan from The University of Houston said, "Bladder cancer (BC) is the sixth most common cancer diagnosis in the United States and is over four times more common in men than women."

Urine biomarkers could potentially provide preliminary confirmation of low-grade BC before invasive procedures are performed and facilitate surveillance of BC, as reviewed.

The present study implements a Luminex based screening platform with a cytokine/chemokine panel that simultaneously interrogates 16 urine biomarkers, followed by ELISA validation of 4 prospective urine biomarkers.

Of the 16 proteins screened by Luminex, 12 were within the detectable range and among these, 10 urine biomarkers showed significant elevation in BC compared to the controls.

ELISA validation for these 4 urine biomarkers was carried out using an independent cohort of 20 urology clinic controls and 60 BC subjects.

Of these 4 proteins, IL-8 displayed the highest significance in discriminating between controls and BC patients and discriminating highly advanced stages/grades of BC from less advanced stages/grades of BC.

The Mohan Research Team concluded in their Oncotarget Research Output that these studies indicate that urine IL-1α, IL-1ra, and IL-8 are potential biomarkers of BC, two of which re-affirm previous reports.

These studies shed additional light on the potential utility of these markers, since some of them also exhibit the ability to discriminate T1 and/or T2-T4 from Ta BC, as well as high grade from low grade BC.

Looking forward, systematic studies in larger patient cohorts are warranted to establish the specific clinical contexts in which these markers may be used, including the following: for initial diagnosis of BC, for surveillance of tumor recurrence, and/or for assessing treatment response following BCG therapy or other therapeutic modalities.

Finally, these newer urine biomarkers need to be compared against the performance of current yardsticks such as the Bladderchek and UroVysion FISH assay.

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DOI - https://doi.org/10.18632/oncotarget.27941

Full text - https://www.oncotarget.com/article/27941/text/

Correspondence to - Chandra Mohan - cmohan@central.uh.edu

Keywords -
urothelial,
proteomics,
targeted screens,
interleukins,
inflammation

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Journal

Oncotarget

DOI

10.18632/oncotarget.27941

Oncotarget published "Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas" which reported that herein the authors evaluate expression of TAZ and YAP, the p53-MDM2 axis, and RABL6A, a novel oncoprotein with potential ties to both pathways, in sarcomas of different histological types.

Immunohistochemical staining of a tissue microarray including 163 sarcomas and correlation with clinical data showed that elevated YAP and TAZ independently predict worse overall and progression-free survival, respectively.

In the absence of p53 expression, combined TAZ and YAP expression adversely affect overall, progression free, and metastasis free survival more than TAZ or YAP activation alone.

RABL6A independently predicted shorter time to metastasis and was positively correlated with p53, MDM2 and YAP expression, supporting a possible functional relationship between the biomarkers.

Network analysis further showed that TAZ is positively correlated with MDM2 expression.

Dr. Munir R. Tanas from The University of Iowa said, "Sarcomas are difficult to treat malignant mesenchymal neoplasms arising in bone or soft tissue."

In epithelioid hemangioendothelioma, a vascular sarcoma, a WWTR1-CAMTA1 gene fusion encodes a constitutively activated form of TAZ that activates a TAZ-like transcriptional program.

Alterations of the p53 pathway are among the most frequent aberrations observed in human cancers, including sarcomas.

Among the most common type of tumors noted in individuals with LFS are sarcomas, specifically soft tissue sarcomas and osteosarcomas.

As such, the amplification of the MDM2 gene region in several sarcomas including well-differentiated liposarcoma/dedifferentiated liposarcoma, parosteal and low-grade central osteosarcoma, and intimal sarcomas represents an effective mechanism of p53 inactivation.

RABL6A is a newly recognized oncoprotein that has been implicated in various human cancers, including pancreatic neuroendocrine tumors, breast cancer, colon cancer, non-small cell lung cancer, pancreatic ductal adenocarcinomas and osteosarcoma.

The Tanas Research Team concluded in their Oncotarget Research Output, "We expect that combination therapies targeting this network will be most effective in the treatment of sarcomas. Furthermore, there is a need to further validate these RABL6A/YAP/p53 and TAZ/MDM2 expression signatures in larger numbers of different histological types of sarcoma to determine if it differentially predicts prognosis or response to therapy within individual subsets of these sarcomas. We anticipate these above efforts will lead to a more effective, tailored approach for these cancers for which few effective medical therapies are currently available."

For the first time, researchers have observed plasma jets interacting with magnetic fields in a massive galaxy cluster 600 million light years away, thanks to the help of radio telescopes and supercomputer simulations. The findings, published in the journal Nature, can help clarify how such galaxy clusters evolve.

Galaxy clusters can contain up to thousands of galaxies bound together by gravity. Abell 3376 is a huge cluster forming as a result of a violent collision between two sub-clusters of galaxies. Very little is known about the magnetic fields that exist within this and similar galaxy clusters.

"It is generally difficult to directly examine the structure of intracluster magnetic fields," says Nagoya University astrophysicist Tsutomu Takeuchi, who was involved in the research. "Our results clearly demonstrate how long-wavelength radio observations can help explore this interaction."

An international team of scientists have been using the MeerKAT radio telescope in the Northern Cape of South Africa to learn more about Abell 3376's huge magnetic fields. One of the telescope's very high-resolution images revealed something unexpected: plasma jets emitted by a supermassive black hole in the cluster bend to form a unique T-shape as they extend outwards for distances as far as 326,156 light years away. The black hole is in galaxy MRC 0600-399, which is near the centre of Abell 3376.

The team combined their MeerKAT radio telescope data with X-ray data from the European Space Agency's space telescope XXM-Newton to find that the plasma jet bend occurs at the boundary of the subcluster in which MRC 0600-399 exists.

"This told us that the plasma jets from MRC 0600-399 were interacting with something in the heated gas, called the intracluster medium, that exists between the galaxies within Abell 3376," explains Takeuchi.

To figure out what was happening, the team conducted 3D 'magnetohydrodynamic' simulations using the world's most powerful supercomputer in the field of astronomical calculations, ATERUI II, located at the National Astronomical Observatory of Japan.

The simulations showed that the jet streams emitted by MRC 0600-399's black hole eventually reach and interact with magnetic fields at the border of the galaxy subcluster. The jet stream compresses the magnetic field lines and moves along them, forming the characteristic T-shape.

"This is the first discovery of an interaction between cluster galaxy plasma jets and intracluster magnetic fields," says Takeuchi.

An international team has just begun construction of what is planned to be the world's largest radio telescope, called the Square Kilometre Array (SKA).

"New facilities like the SKA are expected to reveal the roles and origins of cosmic magnetism and even to help us understand how the universe evolved," says Takeuchi. "Our study is a good example of the power of radio observation, one of the last frontiers in astronomy."

Bethesda, MD (May 23, 2021) -- Patients' irritable bowel syndrome (IBS) symptoms unexpectedly improved when they were under COVID-19 stay-at-home orders, reaffirming the gut-brain connection in functional gastrointestinal disorders, according to research that was selected for presentation at Digestive Disease Week® (DDW) 2021.

"One of our main hypotheses was that these patients were going to be worse because of pressure and stress due to COVID-19," said Juan Pablo Stefanolo, MD, a lead author on the study and a physician with the Neurogastroenterology and Motility section, Hospital de Clínicas José de San Martín, Buenos Aires University, Argentina. "We think the results have something to do with people staying at home. They were not exposed to outside stress, and at home they were able to avoid food triggers."

Pandemic lockdown orders in Argentina created a unique opportunity for researchers to study the impact of pandemic stressors and reduced social interaction on 129 IBS patients whose pre-pandemic data had already been collected through an earlier research project. The patients were re-assessed during the lockdown with the same online survey that included multiple validated measures of IBS severity, anxiety and depression, along with questions about co-occurring illnesses, including heartburn, regurgitation, indigestion, chronic fatigue, fibromyalgia and nonmigraine headaches.

During the lockdown in Argentina -- one of the longest lockdowns in the world -- the number of patients experiencing severe IBS fell sharply from 65 to 39. The mean Irritable Bowel Syndrome Severity Scale score for the group also fell 66 points, from 278 to 212 on a 500-point scale. IBS symptoms of pain, distention, stool consistency, anxiety, somatization, fibromyalgia and chronic fatigue symptoms all improved during the lockdown.

Patients with functional gastrointestinal disorders experience symptoms even though no structural or biochemical abnormalities are present. The gut-brain connection refers to the role of stress and psychological difficulties in triggering debilitating gut-related symptoms. Headache, heartburn and regurgitation -- all outside the category of functional disorders -- became worse during the study, likely due to the increase in weight that nearly 60 percent of patients reported.

"Our results reinforce the concept that IBS, or functional gastrointestinal disorders, have a connection to psychosocial factors, as well as food and other factors," Dr. Stefanolo said. "The gut-brain axis has a lot of facets."

"If you build it, they will come," so says the idiom but it's the storytellers, knowledge-makers and an "agentic" or open-minded population who help create great entrepreneurial cities.

A new research study, conducted by QUT, RMIT and the University of Indiana, analysed data from 362 American cities with a focus on human agency, entrepreneurial spirit, and economic growth.

The study, based on geographic psychological profiles of millions of people based in the US, found people and an empowered city life matter in shaping urban vitality.

The research points to San Francisco and Austin as the zip codes that drive the highest-impact entrepreneurship conducive to economic growth. Other cities scoring high included New York, Los Angeles, Dallas, Miami, San Jose, Riverside, Sacramento and Tampa.

Professor Martin Obschonka, Director of QUT's Australian Centre for Entrepreneurship Research and a joint author of the research, said the findings needed to be tested in other areas like Australia.

"Our study describes an ideal and what cities should strive for," Professor Obschonka said. "Future research could provide a more nuanced picture on how local populations with their unique psychological makeup interact with a structural city environment."

The researchers acknowledge a "people-focused view" on great entrepreneurial cities builds on the work by influential author, theorist, journalist, and activist Jane Jacobs who wrote the book The Death and Life of Great American Cities.

The 1961 publication spearheaded a movement against a four-lane road through New York's Greenwich Village dismissing the scientific rationalism of urban planning and coining metaphoric concepts such as the "ballet of sidewalk" and "eyes on street".

The new study, published in Research Policy, tests and extends Jane Jacob's theory by revealing best performing cities in terms of growth-oriented entrepreneurship are those that empower open and agentic people.

"They are empowered by a physical and industrial city landscape that enables them to act in more innovative and entrepreneurial ways," Professor Obschonka said.

Professor Martin Obschonka said most empirical research addressing the economic performance of cities focus on the physical and industrial structures of cities, underestimating the role of people.

"The core message and spirit of Jane Jacobs has been overlooked," he said.

"The most compelling finding of our study suggests that a strong open orientation of people in cities, designed to be dense and diverse, results in high impact entrepreneurship with start-ups that have the potential to grow significantly," he said.

Professor Obschonka said by building a psychological profile of a city, a model was developed to identify geographic personality traits.

He said regions that demonstrated agentic tendencies, whereby people are more open-minded, learning-oriented, and creative acted in more innovative and entrepreneurial ways.

"One secret of great entrepreneurial cities seems to be that open-minded people are empowered by a city environment, bringing many similarly open-minded people together in dense and diverse places to interact, share new ideas and knowledge and inspire creativity," he said.

"Empowering people liberates their imaginations and not only is the human spirit lifted through interactions among people in a city, but the flow of new ideas inspires vital new innovations."

Professor Obschonka said the study also has major implications for entrepreneurial ecosystems and cities, including those in Australia.

"It's not only about promoting diversity of people but diversity of economic activities within sectors with cities to help create a fertile environment for sharing knowledge," Professor Obschonka said.

"Cities and regions can promote a local open psychological orientation to stimulate growth in innovation processes."

Feeling anxious can direct our attention and memory toward supernatural beings such as gods, a University of Otago study has found.

Lead author Dr Thomas Swan, of the Department of Psychology, says the research may help explain how religious beliefs are formed.

For the study, published in the International Journal for the Psychology of Religion, 972 participants completed an online recall test to determine if a bias to recall supernatural agents was stronger in anxious people, rather than non-anxious people.

Those who felt anxious were more likely to remember beings with supernatural abilities than beings without.

"Anxiety is an emotion that evolved to make us pay greater attention to potential threats, so when we feel anxious, a god that can read our thoughts and punish us for them, or flood the Earth, is going to be memorable," he says.

Previous research has shown anxiety can lead to greater levels of religious belief, with the explanation being that belief provides comfort. However, this so-called 'comfort theory' has problems: why are there punishing gods and hellish afterlives when these are far from comforting?

Dr Swan believes the theory also fails to address what comes between feeling anxious and becoming a believer. This research suggests the first step involves the cognitive effects of anxiety, which cause people to attend to and recall threats.

"In our previous research, we found that supernatural beings are perceived as potentially threatening because they have abilities that defy our expectations about the world. The present research confirms that the cognitive effects of anxiety also extend to the threat that is afforded by supernatural beings.

"Ironically then, our research suggests comfort theory has it somewhat backwards: anxious people are attracted, at least initially, to the scary traits of gods, which may explain why so many gods have scary features. Comfort, we suspect, comes later when some people transform their view of the god into something more palatable that they are happier believing," he says.

The research also suggests other supernatural concepts - such as ghosts, psychics, and astrology - will be digested in the same way because of how they alarmingly defy our expectations about what is possible.

Dr Swan hopes the research prompts people to develop a greater understanding of how their emotional states affect the information they look at and remember, particularly religious information.

"We should all be mindful of how we came to believe the things we do, especially those with anxiety disorders who feel anxious much of the time - they should be mindful of what they are attracted to and why. If they find themselves reading fantasy novels, that may be harmless. If they find themselves joining a cult, then it's time for some reflection. The same goes for people without disorders who are just in anxious situations, such as sitting in a hospital bed or suffering financial troubles."

On the flipside, he hopes religious groups pay more attention to people's mental states.

"They should be providing care but also giving people time to overcome their troubles before integrating them into a highly religious system of beliefs and practices. If they are still willing to join the religion when the turmoil is over, that might be a more ethical moment."

Free access to essential medicines increases patient adherence to taking medication by 35 per cent and reduces total health spending by an average of over $1,000 per patient per year, according to a two-year study that tested the effects of providing patients with free and convenient access to a carefully selected set of medications.

The findings, published May 21 in PLOS Medicine, come as advocates urge Canada to carve a path toward single-payer, public pharmacare. Canada is the only country with universal healthcare that does not have a universal pharmacare program.

A group of researchers led by St. Michael's Hospital of Unity Health Toronto recruited a total of 786 patients across nine primary care sites in Ontario who reported cost-related non-adherence to medications. Most of the study participants were recruited from St. Michael's Department of Family and Community Medicine and others were recruited from three rural sites. Participants were randomized into two groups - half received free medications via mail, the other half had their usual access to medications.

Two years into the study, adherence to all appropriate prescribed medicines was 35 per cent higher in the free distribution group compared with the group that had usual access to medications. Free distribution of medication also showed to reduce healthcare costs, including hospitalization, by an average of $1,222 per patient per year.

"The cost savings are substantial, but they are less important than people simply being able to afford taking lifesaving medications," said Dr. Nav Persaud, a scientist at the Li Ka Shing Knowledge Institute of St. Michael's and lead author of the study.

"This is the first study of providing people with free access to a comprehensive set of medicines, and hopefully it will be the last one needed before policy changes," said Dr. Persaud, who is also a family physician at St. Michael's Hospital.

In June 2019, the Advisory Council on the Implementation of National Pharmacare recommended a universal, single-payer, public pharmacare, estimating such a program would save Canada an estimated $5 billion per year. The report cited a list of medicines like the one used in the CLEAN Meds study as "a starting point" for determining which drugs all Canadians should have free access to.

The CLEAN Meds Trial focused on 128 essential medicines, adapted from the WHO Model List of Essential Medicines and removed treatments not needed in Canada. The medicines in the study included treatments for acute conditions, such as antibiotics and pain relievers, as well as chronic conditions, such as antipsychotics and HIV-AIDS medications.

The paper is the final result of the CLEAN Meds Trial. Preliminary results of the trial after one year of free medication indicated improved adherence, improvements in some health outcomes, and that free distribution of essential medicines led to a 160 per cent increase in the likelihood of participants being able to make ends meet.