Culture

Capecitabine is a chemotherapy drug used for breast and colorectal Cancer cancer. It can extend survival rate by nearly 10%. However, recent studies revealed that almost 50% of patients develop palmar-plantar erythrodysesthesia, a skin reaction also called hand-foot syndrome with mild to serious symptoms. Up to 17% of these patients can have a burning pain in their hands or feet that can prevent them from doing their usual activities. This adverse reaction is the main cause of dose reductions or therapy delays, with dangerous consequences for cancer patients.

There is, therefore, a pressing need to find predictive markers to identify those patients that are more likely to have this toxic reaction before the treatment starts. Patients might be classified according to their genetic risk and get personalised treatment accordingly.

Recently, a team of researchers led by Anna González-Neira, Head of the Human Genotyping-CEGEN Unit at the Spanish National Cancer Research Centre (CNIO), identified genetic markers associated with a higher risk to develop capecitabine-induced hand-foot syndrome. The study is being published in Clinical Pharmacology & Therapeutics.

The team carried out a genome-wide association study (GWAS) analysing more than 600,000 genetic variants across the genome in 166 patients treated with capecitabine in three major hospitals: Gregorio Marañón University Hospital, Virgen de la Victoria Hospital and San Carlos Clinical Hospital.

"Our study identified regulatory variants that affect the levels of CDH4 mRNA and the protein it encode (R-cadherin), which is key to maintaining the normal structure of the skin," explains Anna González Neira, corresponding author of the study. "The association of the genetic variants with the risk of developing the above-mentioned skin condition was replicated in a independent cohort of 85 new patients and validated in several functional studies," she adds.

The CDH4 gene encodes R-cadherin, a protein in the epidermis that plays a relevant role in maintaining the good condition of the skin. The CNIO researchers found that patients who developed hand-foot syndrome during chemotherapy with capecitabine carried these regulatory variants that resulted in the reduced expression of CDH4, as compared to other patients.

"In addition, in human cell cultures, CDH4 down-regulation resulted in the reduced expression of involucrin, another skin protein that is essential for the skin barrier function," González-Neira remarks.

In their observation of the normal skin of cancer patients before starting the treatment, the scientists at CNIO found that the patients with the alleles associated with a risk to develop the hand-foot syndrome had low levels of R-cadherin and involucrin before chemotherapy with capecitabine. The study results indicate that low levels of these two proteins could contribute to increase the cytotoxic effects of the drug. "This effect can be extremely severe in the palms of the hands and the soles of the feet for a number of reasons: epidermal cells divide at a high rate, there is a pressure and temperature effect on the palms and soles, and the numerous sweat glands on these parts of the body have a high drug concentration."

To conclude, the authors of the study detected genetic markers that, together with the levels of R-cadherin and involucrin, could be useful biomarkers to identify patients with a higher risk to develop hand-foot syndrome. "Oncologists could then decide to take preventive measures for these patients, like dose reduction or treatments with alternative drugs."

(Boston)-- Responding to the COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, requires models that can duplicate disease development in humans, identify potential targets and enable drug testing. Specifically, access to primary human lung in vitro model systems is a priority since a variety of respiratory epithelial cells are the proposed targets of viral entry.

Now, a team of infectious disease, pulmonary and regenerative medicine researchers at Boston University, studying human stem cell-derived lung cells called type 2 pneumocytes, infected with SARS-CoV-2, have shown that the virus initially suppresses the lung cells' ability to call in the help of the immune system with interferons to fight off the viral invaders and instead activates an inflammatory pathway called NFkB. "The infected lung cells pour out inflammatory proteins. In the body of an infected person, those proteins drive up levels of inflammation in the lungs," explains corresponding author Darrell Kotton, MD, the David C. Seldin Professor of Medicine at BUSM and Director of the BU/BMC Center for Regenerative Medicine (CReM).

According to the researchers, the inflammatory signals initiated by the infected pneumocytes attract an army of immune cells into lung tissue laden with infected and already dead and dying cells. "Our data confirms that SARS-CoV-2 blocks cells from activating one of the anti-viral branches of the immune system early on after infection has set in. The signal the cells would typically send out, a tiny protein called interferon that they exude under threat of disease, are instead delayed for several days, giving SARS-CoV-2 plenty of time to spread and kill cells, triggering a buildup of dead cell debris and other inflammation," added Kotton.

The data is based on experiments the research team performed in the laboratory of co-senior author Elke Mühlberger, PhD, associate professor of microbiology at BUSM and a researcher at BU's National Emerging Infectious Diseases Laboratories (NEIDL). Kotton and other members of the CReM have developed sophisticated models of human lung tissue--three-dimensional structures of lung cells, called "lung organoids," grown from human stem cells--which they've used at BU and with collaborators elsewhere to study a range of chronic and acute lung diseases.

The research team, led by co-first authors, Jessie Huang, PhD, Kristy Abo, BA, Rhiannon Werder, PhD and Adam Hume, PhD, adapted an experimental model previously used to study the effects of smoking cigarettes to study the coronavirus in lung tissue. Droplets of live coronavirus were then added on top of the lung cells, infecting them from the air the way the virus infects cells lining the inside of the lungs when air containing the virus is breathed into the body. "This adaptation of human stem cell-derived pneumocytes to air, known as an 'air-liquid interface' cell culture was a key advance that allowed us to simulate how SARS-CoV-2 enters cells deep in the lungs of the most severely affected patients," said co-senior author Andrew Wilson, MD, associate professor of medicine at BUSM. "Type 2 pneumocytes are also infected and injured in patients with COVID-19, making this a clinically meaningful system to understand how the disease injures patient lungs."

Wilson and Kotton, are also pulmonary and critical care physicians taking care of patients with COVID-19 pneumonia at Boston Medical Center, while also leading their laboratories to produce the human lung cells that were then transported into the NEIDL. There Hume, a senior research scientist in the Mühlberger's lab, worked in a BSL-4 suit to perform the infections of the cells that the three collaborating teams then analyzed together through weekly zoom calls.

"These cells are an amazing platform to study SARS-CoV-2 infection," adds Mühlberger. "They likely reflect what is going on in the lung cells of COVID-19 patients. If you look at the damage SARS-CoV-2 inflicts on these cells, you definitely don't want to get the disease."

An international team of astrophysicists has found distinctive signatures of black hole event horizon, unmistakably separating them from neutron stars -- objects, comparable to black holes in mass and size but confined within a hard surface. This is by far the strongest steady signature of stellar-mass black holes to date. The team consisting of Mr. Srimanta Banerjee and Professor Sudip Bhattacharyya from the Tata Institute of Fundamental Research, India, and Professor Marat Gilfanov and Professor Rashid Sunyaev from Max Planck Institute for Astrophysics, Germany and Space Research Institute of Russian Academy of Sciences, Russia is publishing this research in a paper that has been accepted for publication in Monthly Notices of the Royal Astronomical Society.

A black hole is an exotic cosmic object without a hard surface predicted by Einstein's theory of General Relativity. Although it does not have a surface, it is confined within an invisible boundary, called an event horizon, from within which nothing, not even light, can escape. Definitive proof of the existence of such objects is a holy grail of modern physics and astronomy.

Only one supermassive black hole -- with the mass more than 6 billion times the mass of the Sun -- has so far been imaged using the surrounding radiation in radio wavelengths. But stellar-mass black holes -- with masses of about ten times the mass of the Sun -- should bend the spacetime around them at least ten thousand trillion times more than such a supermassive black hole does. Such smaller black holes are therefore indispensable to probe some extreme aspects of nature. When these smaller black holes merge with each other, they could be inferred from gravitational waves. Such waves are transient events, lasting for a fraction of a second and it is of immense interest to have a definitive proof of the existence of a stable stellar-mass black hole, which shine mainly in X-rays by devouring material from a companion star.

A neutron star, the densest known object in the universe with a hard surface, can also shine in X-rays by accreting matter from a companion star in a similar way, characterized by extremely high efficiency of conversion of the rest-mass energy mc2 to radiation, of the order of 20%. In order to prove the existence of stellar-mass black holes, one needs to distinguish them from such neutron stars. The authors of this research have done exactly that. Using the archival X-ray data from the now decommissioned astronomy satellite Rossi X-Ray Timing Explorer, they have identified the effect of the lack of hard surface on the observed X-ray emission, and thus have found an extremely strong signature of accreting stellar-mass black holes.

Scientists from the University of Bristol and the Royal Veterinary College (RVC) used three-dimensional computer modelling to investigate the hindlimb of Euparkeria capensis-a small reptile that lived in the Triassic Period 245 million years ago-and inferred that it had a "mosaic" of functions in locomotion.

The study, which was published today in Scientific Reports, was led by researcher Oliver Demuth, joined by Professors Emily Rayfield (Bristol) and John Hutchinson (RVC). Their new micro-computed tomography scans of multiple specimens revealed unprecedented information about the previously hidden shape of the hip bones and structure of the foot and ankle joint.

Euparkeria has been known from numerous fossil specimens since the early 1900s and was found to be a close relative of the last common ancestor of both crocodiles and birds. While birds and crocodiles show different locomotion strategies, two-legged birds with an upright (erect) posture, shared with two and four-legged dinosaurs, and crocodiles having a four-legged (quadrupedal) sprawling posture, their ancestor once shared a common mode of locomotion and Euparkeria can provide vital insight into how these differences came to be.

The authors' new reconstruction of the hip structure showed that Euparkeria had a distinctive bony rim on the pelvis, called a supra-acetabular rim, covering the top of the hip joint. This feature was previously known only from later archosaurs on the line to crocodiles and often was used to infer a more erect posture for these animals; reversed in crocodiles as they became more amphibious. The hooded rim allowed the pelvis to cover the top of the thigh bone and support the body with the limbs in a columnar arrangement; hence this type of joint is called 'pillar-erect'. Euparkeria is so far the earliest reptile with this structure preserved. Could it therefore have assumed a more erect, rather than more sprawling, posture as well?

To test how the hindlimb could or could not have moved in life, the team estimated how far the thigh bone could have rotated until it collided with the hip bones, and their models addressed how the ankle joint could have been posed, too. The computer simulations suggested that while the thigh bone could have been held in an erect posture, the foot could not have been placed steadily on the ground due to the way the foot rotates around the ankle joint, implying a more sprawling posture. However, the bony rim covering the hip joint restricted the movement of the thigh bone in a way that is unknown in any living animal capable of a more sprawling gait, hinting at a more upright posture.

The team's simulations thus revealed seemingly contradictory patterns in the hip and ankle joint. While Euparkeria is so far the earliest reptile with this peculiar hip structure, an ankle joint allowing a more erect posture appeared later on in Triassic archosaurs. Dr John Hutchinson, Professor of Evolutionary Biomechanics at the RVC, commented:

"The mosaic of structures present in Euparkeria, then, can be seen as a central stepping-stone in the evolution of locomotion in archosaurs."

First author Oliver Demuth, research technician at the RVC and former Masters student at the University of Bristol, commented:

"The hip structure of Euparkeria was extremely surprising, especially as it functionally contradicts the ankle joint. Previously it was thought that both were linked and evolved synchronously. However, we were able to demonstrate that these traits were in fact decoupled and evolved in a step-wise fashion."

Dr Emily Rayfield, Professor of Palaeobiology at the University of Bristol commented:

"This approach is exciting because Using CT scan datasets and computer models of how the bones and joints fitted together has allowed us to test long-standing ideas of how these ancient animals moved and how the limbs of the earliest ancestors of birds, crocodiles and dinosaurs may have evolved"

Doctors like to remind patients not to monkey around with their health, suggesting that a good diet and regular exercise improve longevity.

A new study on health in chimpanzees, which are the closest species to humans genetically, showed the benefits in what they eat and how they can travel and climb.

When chimpanzees have a plant-based diet and substantial opportunities to exercise, they fall into "healthy" human ranges. Lab chimpanzees, whose diet and exercise were limited, showed conditions indicative of cardiovascular disease risk, more like sedentary people.

Chimpanzees are critical for understanding the evolution of human health and longevity. Cardiovascular disease--a major source of mortality during aging in humans--is a key issue for comparative medicine.

Prior data indicated that compared to humans, chimpanzees have high levels of blood lipids that can promote cardiovascular disease in humans. However, most work on chimpanzee heart health comes from the animals living in laboratories where lifestyles diverge from a wild context.

Researchers from the University of Michigan and University of New Mexico partnered with wildlife veterinarians in Uganda and Congo to examine cardiovascular profiles in chimpanzees living in African sanctuaries. These chimpanzees occupy large rainforest enclosures, consume a diet of fruits and vegetables, and generally experience conditions more similar to a wild chimpanzee lifestyle.

They measured blood lipids, body weight and body fat in 75 sanctuary chimpanzees during annual veterinary health check-ups, and then compared them to published data from laboratory-living chimpanzees.

Free-ranging chimpanzees in sanctuaries exhibited lower body weight and lower levels of lipids, both risk factors for human cardiovascular disease. Some of these disparities increased with age, indicating that the free-ranging chimpanzees stayed healthy as they got older.

"Our findings support the hypothesis that lifestyle shapes health in chimpanzees, similar to effects in humans, and contribute to an emerging understanding of cardiovascular health in evolutionary context," said Alexandra Rosati, U-M assistant professor of psychology and anthropology.

This is the first evidence that chimpanzees show differences in blood lipids related to their lifestyle, such as diet and ranging opportunities, and indicates that these health effects in humans are rooted in our evolutionary past, said Megan Cole, a researcher at the University of New Mexico and the study's lead author.

Prior work suggested that chimpanzees have very high levels of blood lipids that are cardiovascular risk factors--higher than humans in post-industrial societies in some cases. The work also showed that chimpanzees living a naturalistic life have much lower levels even as they age, providing a new reference for understanding human health. In biomedical research labs, chimpanzees have more limited space and often consume a processed diet (food such as primate chow), unlike wild chimpanzees.

"These results show how the high-quality, natural conditions that chimpanzees experience in African sanctuaries fosters their long-term health," Rosati said.

PITTSBURGH, Sept. 21. 2020 - Researchers at the University of Pittsburgh School of Medicine and Carnegie Mellon University College of Engineering have created a machine-learning algorithm that can detect subtle signs of osteoarthritis--too abstract to register in the eye of a trained radiologist--on an MRI scan taken years before symptoms even begin. These results will publish this week in PNAS.

With this predictive approach, patients could one day be treated with preventative drugs rather than undergoing joint replacement surgery.

"The gold standard for diagnosing arthritis is x-ray. As the cartilage deteriorates, the space between the bones decreases," said study co-author Kenneth Urish, M.D., Ph.D., associate professor of orthopaedic surgery at Pitt and associate medical director of the bone and joint center at UPMC Magee-Womens Hospital. "The problem is, when you see arthritis on x-rays, the damage has already been done. It's much easier to prevent cartilage from falling apart than trying to get it to grow again."

Right now, the primary treatment for osteoarthritis is joint replacement. And the condition is so prevalent that knee replacement is the most common surgery in the U.S. for people over age 45.

For this study, the researchers looked at knee MRIs from the Osteoarthritis Initiative, which followed thousands of people for seven years to see how osteoarthritis of the knee develops. They focused on a subset of patients who had little evidence of cartilage damage at the beginning of the study.

In retrospect, we now know which of these participants went on to develop arthritis and which didn't, and the computer can use that information to learn subtle patterns on the MRI scans of presymptomatic people that are predictive of their future osteoarthritis risk.

"When doctors look at these images of the cartilage, there isn't a pattern that jumps out to the naked eye, but that doesn't mean there's not a pattern there. It just means you can't see it using conventional tools," said lead author Shinjini Kundu, M.D., Ph.D., who completed this project as part of her graduate training in the Pitt Medical Scientist Training Program and Carnegie Mellon Department of Biomedical Engineering.

To validate this approach, Kundu, who now is a resident physician and medical researcher at the Johns Hopkins Department of Radiology, trained the model on a subset of the knee MRI data and then tested it on patients it had never seen before. Kundu did this dozens of times, with different participants withheld each time, to test the algorithm on all the data.

Overall, the algorithm predicted osteoarthritis with 78% accuracy from MRIs performed three years before symptom onset.

Currently, there are no drugs that prevent presymptomatic osteoarthritis from developing into full-blown joint deterioration, though there are a few highly effective drugs that can prevent patients from developing a related condition--rheumatoid arthritis.

The goal is to develop the same types of drugs for osteoarthritis. Several candidates already are in the preclinical pipeline.

"Instead of recruiting 10,000 people and following them for 10 years, we can just enroll 50 people who we know are going to be getting osteoarthritis in two or five years," Urish said. "Then we can give them the experimental drug and see whether it stops the disease from developing."

September 21, 2020 - The amount Medicare reimburses for orthopaedic trauma surgery has fallen by nearly one-third over the past two decades, reports a study in the Journal of Orthopaedic Trauma. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"When adjusted for inflation, [Medicare] reimbursement for common procedures in orthopaedic trauma surgery has steadily decreased from 2000 and 2020," according to the new research by Kenneth A. Egol and colleagues in the Department of Orthopedic Surgery at NYU Langone Health, New York City. They add: "Given increasing volumes and costs associated with medical practice in the United States, continued change may be necessary to ensure the financial health and success of physicians and hospitals caring for victims of orthopedic trauma."

'Steady Annual Decline' in Orthopaedic Trauma Surgery Reimbursements

Using publicly available data from the Centers for Medicare & Medicaid Reimbursement (CMS), the researchers examined reimbursement trends for the 20 most commonly billed surgical procedure codes in orthopaedic trauma from 2000 to 2020 - the majority of which are traumatic bone fractures requiring surgical repair with some type of hardware (internal fixation). Costs were adjusted for inflation to 2020 dollars, based on the Consumer Price Index (CPI).

During the study period, the CPI - a widely used measure of inflation - increased by 52.8 percent. Meanwhile, average Medicare reimbursement for the 20 orthopaedic trauma surgery procedures rose by only 4.9 percent, demonstrating the Government failing to keep up with increases in the cost of living.

After correction to 2020 dollars, average reimbursement for health care procedures for orthopaedic trauma decreased by 30 percent. Annual data showed a steady decline of 1.5 percent per year.

The trends varied by procedure type, with foot and ankle procedures demonstrating the sharpest drop in reimbursement: 42.6 percent. Decreases were 31.9 percent for hip fracture surgery (often a lifesaving procedure), 30.9 percent for lower extremity long bone procedures, and 23.7 percent for shoulder and upper extremity procedures.

Medicare reimbursements are calculated using "Relative Value Units" (RVUs) for individual procedures, an arbitrary multiplier that is supposed to reflect the value of the physician's work, practice expenses, and malpractice coverage. Average total RVUs for the 20 procedures increased 4.4 percent from 2000 to 2020. The majority of the increase was in malpractice RVUs, with a small decrease in practice expense RVUs - despite evidence showing that practice costs have increased in recent years.

The US healthcare system has seen major changes in policies and payment structures throughout the last several decades, including Medicare. With the aging of the population, there will be increased demand on the Medicare system to fund orthopaedic trauma surgery and fracture care in older Americans.

Orthopaedic surgery has been a major focus of Medicare payment reforms, with experiments including "bundled" payment programs for joint replacement surgery. "[T]he decisions made by the Centers for Medicare and Medicaid Services (CMS) have had a large-scale impact on reimbursement, influencing both the public and private healthcare sectors," according to the authors.

They review some of the policy actions that have led to declining Medicare reimbursements, as well as the possible impact of new initiatives designed to incentivize quality and value of care rather than quantity of care. "Despite this uncertainty regarding the future, the evidence demonstrates a clear trend of decreasing Medicare reimbursement in orthopedic trauma surgery," Dr. Egol and colleagues write.

They conclude: "Increased awareness and consideration of these trends will be important for policy-makers, hospitals, and surgeons in order to assure continued access to high quality surgical orthopedic trauma care in the United States." The authors hope their findings will serve as a "springboard" for efforts to develop sustainable policies to provide fair reimbursement for essential trauma surgery for the growing population of older adults covered by Medicare.

A discovery of more than a thousand dinosaur teeth, by a team of researchers from the University of Portsmouth, proves beyond reasonable doubt that Spinosaurus, the giant predator made famous by the movie Jurassic Park III as well as the BBC documentary Planet Dinosaur was an enormous river-monster.

Research published today in the journal Cretaceous Research proves that Spinosaurus aegyptiacus, a 15 metre long, six-tonne beast was in fact the most commonly found creature in the Kem Kem river system, which flowed through the Sahara Desert 100 million years ago.

Until recently it was believed that dinosaurs lived exclusively on land. However, research published earlier this year showed that Spinosaurus was well adapted to an aquatic lifestyle, due to its newly discovered tail. This latest research of 1,200 teeth found in the same region further supports this theory.

Scientists from the University of Portsmouth collected the fossilised remains from the site of an ancient river bed in Morocco. After analysing all of them it was discovered there was an abundance of Spinosaurus teeth, which are distinct and easily identifiable.

David Martill, Professor of Palaeobiology at the University of Portsmouth, said:

"The huge number of teeth we collected in the prehistoric river bed reveals that Spinosaurus was there in huge numbers, accounting for 45 per cent of the total dental remains. We know of no other location where such a mass of dinosaur teeth have been found in bone-bearing rock.

"The enhanced abundance of Spinosaurus teeth, relative to other dinosaurs, is a reflection of their aquatic lifestyle. An animal living much of its life in water is much more likely to contribute teeth to the river deposit than those dinosaurs that perhaps only visited the river for drinking and feeding along its banks.

"From this research we are able to confirm this location as the place where this gigantic dinosaur not only lived but also died. The results are fully consistent with the idea of a truly water-dwelling, "river monster"."

Professor Martill worked alongside two students studying for their Masters Degree in Paleontology at the University of Portsmouth.

Thomas Beevor said: "The Kem Kem river beds are an amazing source of Spinosaurus remains. They also preserve the remains of many other Cretaceous creatures including sawfish, coelacanths, crocodiles, flying reptiles and other land-living dinosaurs. With such an abundance of Spinosaurus teeth, it is highly likely that this animal was living mostly within the river rather than along its banks."

Aaron Quigley, explained the process of sorting through the teeth: "After preparing all the fossils, we then assessed each one in turn. The teeth of Spinosaurus have a distinct surface. They have a smooth round cross section which glints when held up to the light. We sorted all 1200 teeth into species and then literally counted them all up. Forty-five per cent of our total find were Spinosaurus teeth."

Tokyo, September 21, 2020- The ongoing coronavirus disease 2019 (COVID-19) pandemic has substantially affected patients with dementia and their caregivers. Owing to the restrictive measures taken worldwide to block the spread of COVID-19 outbreaks (including the declaration of a state of emergency in Japan), patients with dementia and their caregivers have not been able to receive the usual support and care. Therefore, this is expected to lead to adverse effects on the patients and their caregivers, and many investigators have warned about the risks (1-3). In fact, many scheduled appointments for routine outpatients' examinations and care services have been canceled and postponed owing to the COVID-19 outbreak. When dementia outpatients came to our clinic for their postponed outpatient appointments after the state of emergency declaration was lifted, we found that some patients were afraid of COVID-19 infection whereas some were not. We noticed that patients with severe dementia tended to be less susceptible to COVID-19 than patients with mild dementia in the daily clinical setting. Based on the hypothesis that patients with severe dementia tend to be unaware of the COVID-19 outbreak and hence may be less depressed, we compared the rate of recognition of the COVID-19 outbreak and resultant depressive tendencies between patients with mild dementia and those with severe dementia.

In this study, patients with Alzheimer disease (AD) (4) are included in this study because the depressive tendency depends on the cause of dementia. A total of 126 consecutive outpatients with AD from the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo Medical University, were enrolled in this study from May 25, on the day when the declaration of emergency was lifted, to June 30, 2020. In addition to the Mini Mental State Examination (MMSE) (5) and Geriatric Depression Scale - Short Version (GDS-S) (6) performed as routine psychological tests, the participants were asked the following 2 questions: "Do you know COVID-19?" and "Why are you wearing a face mask?". The patients were divided into the mild AD group (MMSE score ? 21, n = 51) and the moderate to severe AD group (MMSE score

An international research team has developed "electronic skin" sensors capable of mimicking the dynamic process of human motion. This work could help severely injured people, such as soldiers, regain the ability to control their movements, as well as contribute to the development of smart robotics, according to Huanyu "Larry" Cheng, Dorothy Quiggle Early Career Professor in the Penn State Department of Engineering Science and Mechanics.

Cheng and collaborating researchers based in China published their work in a recent issue of Nano Energy.

"The skin of the human hand is amazing -- that's what we tried to imitate," Cheng said. "How do we capture texture and force? What about the years of evolution that produced the impressive sensitivity of the fingertip? We're attempting to reproduce this biological and dynamic process to enable objects to behave similarly to the human hand."

The dual-mode sensor measures both the magnitude and load of movement, such as the effort of swinging a tennis racquet, as well as rate, duration and direction. The trick was to decouple this measurement and understand how the separate parameters influence each other.

For example, bouncing a tennis ball gently on a racquet requires different input than serving a ball to an opponent. Those same variables come into play when a person with a prosthetic arm needs to differentiate between handling an egg or carrying a watermelon.

"We can apply these sensors to help people capture the magnitude for pressing, bending and more," Cheng said. "We can also use these sensors on soft robotics to manipulate delicate objects, like catching a fish, or even in a disaster when they may need to crawl into irregular spaces and move debris."

The data is informed by synergy created between the piezoelectric and piezoresistive signals, according to Cheng. Piezoelectric signals measure outside force -- such as pressure -- to create electrical charge, while piezoresistive signals mitigate the current.?The dual mode sensors are sandwiched together, with two internal layers of pyramid-shaped microstructures facing one another. The microstructures measure magnitude and duration measurements from the piezoresistive layer and the dynamic loading rate and direction from the piezoelectric layer. This synergistic effect allows for a high sensitivity over a broad pressure and frequency range, meaning that researchers can precisely measure the force and flexibility needed to imitate specific movements.

"We combined the best of the best models and sensors to create something new," Cheng said.

PHILADELPHIA -- New research has uncovered the previously unknown presence of CD19 -- a B cell molecule targeted by chimeric antigen receptor (CAR) T cell immunotherapy to treat leukemia, lymphoma, and multiple myeloma -- in brain cells that protect the blood brain barrier (BBB).

This discovery may potentially be the cause for neurotoxicity in patients undergoing CD19 directed CAR T cell immunotherapy, according to the research team led by Avery Posey, PhD, an assistant professor of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania and Research Health Science Specialist at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, PA.

"Our work has revealed that there is CD19 expression in a subset of cells that are, one, not B cells, and two, potentially related to the neurotoxicity we observe in patients treated with CAR T cell therapy targeting CD19," Posey said. "The next question is, can we identify a better target for eliminating B cell related malignancies other than CD19, or can we engineer around this brain cell expression of CD19 and build a CAR T cell that makes decisions based on the type of cell it encounters--for instance, CAR T cells that kill the B cells they encounter, but spare the CD19 positive brain cells?"

As so often happens in scientific endeavors, the path to this discovery was made somewhat by chance. Kevin Parker, a PhD student at Stanford and co-author on the paper, was at home analyzing previously published single cell sequencing data sets in his spare time. He found CD19 expression in a data set of fetal brain samples that looked odd, because the accepted wisdom was that CD19 only existed in B cells. So his lab reached out to the pioneers of CAR T cell immunotherapy, Penn Medicine.

"I suggested we test this as a preclinical model. When we treated the mouse model with CAR T cells targeting the mouse version of CD19, we found what looks like the start of neurotoxicities," Posey said.

The team observed an increase in BBB permeability when mouse CD19 was targeted by CAR T cells, even in mice that lack B cells, but not when human CD19 was targeted as a control treatment (mice do not express human CD19).

"Even more interesting, this BBB permeability was more severe when the CAR T cells were fueled by a costimulatory protein called CD28 than when the CAR T cells used 4-1BB," Posey said "This difference in the severity of BBB permeability correlates with what we know about the clinical observations of CAR T cell-related neurotoxicities -- the frequency of patients experiencing high-grade neurotoxicity is lower for those that received the 4-1BB-based CAR T cells."

His team sought to investigate the higher incidence of neurotoxicity in CD19-directed immunotherapies, compared to treatments targeting other B cell proteins, such as CD20. Notably, CD19 CAR T cells are sensitive to even low levels of CD19 antigen density, emphasizing the importance of identifying any potential reservoir of CD19 other than B cells.

The researchers' discovery of CD19 molecules in the brain provides evidence that this increase in neurotoxicity is due to CD19-directed CAR T cell immunotherapies. Posey said, though, that generally this neurotoxicity is temporary and patients recover.

This research also highlights the potential utility of developing a comprehensive human single-cell atlas for clinical medicine. Sequencing is an unbiased, genome-wide measurement of gene expression that can capture even rare populations of cells. These rare cell types might otherwise be missed in measurements of bulk tissue due to their low frequency, but as this study demonstrates could be critically important in understanding the clinical effects of targeted therapy. While current CAR T cells recognize only a single antigen, future generations of CAR T cells may be able to discriminate between unique combinations of target antigens to improve their cell-type specificity. The researchers envision that a comprehensive database of gene expression across all human cell types will enable the precise identification of cell type-specific target antigens which can be used to design safe and effective cellular immunotherapies.

"That's what we think one of the biggest take-home messages is," Posey said. "The incredible usefulness of single cell atlas or single cell sequencing technology to determine whether a potential immunotherapy or drug target is going to be present somewhere in the body that we would not normally expect it based on conventional thought and whether this expression may lead to toxicity."

CD19 is thought to be a lineage-restricted molecule -- behaving in a functionally and structurally limited way. But this study shows that some small percentage of brain cells also express CD19.

"We would not have identified that through bulk sequencing, where we're looking at a population of cells versus a single cell type," Posey said. "It's only through single cell sequencing that we're able to identify that there's this very small percentage of cells in the brain that also contain this molecule, contrary to popular thought."

On 8 May 2020, the Institute of Agrifood Research and Technology (IRTA) reported the case of the first cat infected with SARS-CoV-2 in Spain. It was a 4-year-old cat called Negrito, who lived with a family affected by COVID-19, with one case of death. Coinciding with these facts, the animal presented severe respiratory difficulties and was taken to a veterinary hospital in Badalona (Barcelona), where it was diagnosed with hypertrophic cardiomyopathy. Due to a terminal condition the hospital decided to do a humanitarian euthanasia. The necropsy, performed at the High Biosafety Level Laboratories of the Animal Health Research Center (CReSA) at IRTA, confirmed that Negrito suffered from feline hypertrophic cardiomyopathy and had no other lesions or symptoms compatible with a coronavirus infection. The RT-PCR test confirmed that the animal had become infected with SARS-CoV-2, but with a very low and residual viral load.

To date there have been few cases of feline SARS-CoV-2 infection worldwide, which is why researchers have deepened the case study and published it recently in the journal Proceedings of the National Academy of Sciences (PNAS). They performed serological tests on the cat Negrito and another cat that also lived in the same home, Whisky, which did not show any signs of disease. The tests, carried out by the AIDS Research Institute (IrsiCaixa), show that the two cats had developed antibodies against SARS-CoV-2. "In both cases we have detected neutralizing antibodies, in other words, they have the ability to bind to the virus and block it," explains Julià Blanco, IGTP researcher at IrsiCaixa. He goes on to say "this is important because it shows us that the immune system of cats can deal with SARS-CoV-2 and, in these specific cases, protect them from developing symptoms".

Experimental studies currently being conducted show that cats, in addition to becoming infected with SARS-CoV-2, can transmit it to other nearby cats, but without any clinical signs. However, the first suspicions of researchers were that both Negrito and Whisky had been infected by their owners because they had not had contact with other cats. To check this, the team analyzed the genetic sequence of the virus that Negrito had and found that "it has a 99.9% similarity to the virus of the owner who died, this suggests that the cat became directly infected from family members", explains Marc Noguera-Julián, researcher at IrsiCaixa.

Given the number of people infected worldwide and the few reported cases of animals, experts continue to note that "pets play a negligible role in the epidemiology of SARS-CoV-2 and, in particular, cats become very residually infected and there is no evidence of transmission of the virus to humans. This is a case of reverse zoonosis, in which cats are the side victims without the virus causing them health problems", states Júlia Vergara-Alert, researcher at IRTA-CReSA. So far, there has only been one reported episode in the Netherlands in which a farmer became infected through minks, which would be the first known potential case of COVID-19 zoonosis.

IRTA and the Council of Veterinary Associations of Catalonia, with the collaboration of the Veterinary Clinical Hospital of the Universitat Autònoma de Barcelona are studying whether pets can become infected with SARS-CoV-2

Following the Negrito case, in May the IRTA-CReSA coronavirus research team, in coordination with the Council of Colleges of Veterinarians of Catalonia and the Veterinary Clinical Hospital of the Universitat Autònoma de Barcelona, started a study to assess how often cats, dogs and ferrets have become infected with SARS-CoV-2 from people in a family setting. The study is being carried out with the voluntary participation of veterinary clinics and hospitals in Catalonia and consists of taking samples of oropharyngeal and rectal swabs, as well as animal serum.

"We want to check if the case of Negrito and Whisky has been punctual or is repeated in more cases; in this way we will have more scientific information on how the most common pets can become infected with SARS-CoV-2 and to what degree", explains Joaquim Segalés, IRTA-CReSA researcher and professor at the Faculty of Veterinary Medicine of the Universitat Autònoma de Barcelona (UAB). The professor also remarks that "so far, it is known that around the world there have been some cases of cats and dogs that have become infected through their owners, but these animals have not suffered a serious illness and there is no evidence that they have transmitted the virus to their owners".

Monday, September 21, 2020, CLEVELAND: A new Cleveland Clinic study has found that receiving the influenza vaccine does not increase a person's risk for contracting COVID-19 or worsen associated morbidity or mortality. Published in the Journal of Clinical and Translational Science, the study shows the flu vaccine is the single most important intervention to help stay healthy this fall and winter.

Seasonal flu activity is unpredictable, and otherwise healthy people are hospitalized due to serious respiratory infection each year. This year, it's even more important to receive the flu vaccination to help prevent a twindemic of flu and COVID-19.

In this new study, a team of researchers led by Joe Zein, M.D. - a pulmonologist at Cleveland Clinic - analyzed more than 13,000 patients tested for COVID-19 at Cleveland Clinic between early March and mid-April of this year.

Comparing those who had received unadjuvanted influenza vaccines in the fall or winter of 2019 (4,138 patients) against those who did not received the vaccine (9,082 patients) revealed that influenza vaccination was not associated with increased COVID-19 incidence or disease severity, including risk for hospitalization, admission to the intensive care unit or mortality.

"Our findings suggest that we should proceed as usual with our vaccination strategy for global influenza this flu season," said Dr. Zein. "Getting the annual flu vaccine remains the best safeguard against the influenza virus--both for yourself and the people around you."

Since much is still unknown about the possible outcomes of concurrent SARS-CoV-2 (the virus that causes COVID-19) and influenza infection--including disease pathology and burden to the healthcare system--researchers and clinicians believe that the population's adherence to widespread and early flu vaccination while researchers continue to collect data will help to mitigate the risk of simultaneous viral infections and epidemics/pandemics.

"We have already seen the stress that COVID-19 can put on our hospitals and resources," said Dr. Zein. "While we're not yet sure how flu season will affect COVID-19 susceptibility and infections, we strongly advise people to get their influenza vaccines, both for their individual health and the collective health of our care systems."

This study is the latest to utilize data from patients enrolled in Cleveland Clinic's COVID-19 Registry, which includes all individuals tested at Cleveland Clinic for the disease, not just those that test positive. Cleveland Clinic was one of the first organizations to develop a data registry and biobank for the emergent disease. Data from the registry has already been used in several landmark COVID-19 studies, including those that have led to the development of models that can predict a patient's likelihood of testing positive for COVID-19 and being hospitalized due to the disease.

By studying 488 public airports in the United States, University of Colorado Denver School of Public Affairs researcher Serena Kim, PhD, found that 20% of them have adopted solar photovoltaic (PV), commonly known as solar panels, over the last decade. Solar photovoltaic (PV) is the conversion of light into electricity using semiconducting materials that exhibit the photovoltaic effect. 

While studying institutional arrangements as a factor that contributes to airport solar PV deployment, Kim found that airports operated by general-purpose governments (cities, states, or counties) have deployed solar panels more than special-purpose governments (port or airport authorities) as of 2020. Kim discovered that airports involved in professional organizations are more likely to deploy solar panels, but this relationship is contingent on airport governance. Airport solar deployment increases by airports’ professional organization membership, but with a higher rate for special-purpose airports than general-purpose airports. 

According to Kim, airports provide an ideal venue for studying how institutional arrangements shape renewable energy deployment due to the notable differences between the general-purpose and special-purpose airports. The biggest difference between these two types of airports is how each selects its board members. More than 80% of general-purpose board members are elected, while only 7% of special-purpose airport board members are elected. 

“Airport board members, directors, and managers’ leadership, and their interactions with other airport professionals can promote renewable energy transitions at airports,” said Kim. 

Colorado Connection  

One of the airports studied was Denver International Airport (DIA, as state residents know it, although the official abbreviation is DEN). Since 2008, DIA has become one of the largest solar projects in the U.S., installing 42,614 solar panels on a total of 56 acres.   

According to airport officials interviewed for the study, DIA has been successful in rolling out solar energy because of support from the city government, airport leadership, and its electricity provider, Xcel Energy. Being at the forefront of on-site solar energy at airports, DIA has built an economically and environmentally sustainable energy management system. While reducing the airport’s carbon footprint by operating 10 megawatts (MW) solar facilities, DIA pays less than the average electricity cost for the energy generated from the solar arrays built after 2012. Excess electricity is sold back to the utility under the Xcel Solar Rewards program. All contracts go through the city council approval process, and the aviation department works closely with the city government’s sustainability department.  

“DIA’s solar energy project is an example of successful collaborative partnerships,” said Kim. “All solar arrays at DIA are developed by public-private partnerships. Private solar companies own and operate the solar systems, and DIA executes power purchase agreements with the private solar companies. Xcel Energy plays a key role in the partnership as they offer rebates to offset the construction costs, purchase excess energy, and retain renewable energy certificates.” 

Other airports involved in this study include Minneapolis-St. Paul International Airport, Tallahassee International Airport, and Orlando International Airport.  

Next Steps for Policymakers

According to Kim’s research findings, on-site solar deployment potentials are shaped by utilities’ engagement and interest in renewable energy development. Airport solar energy is more likely to appear in the service area of investor-owned utilities, which have greater resources and expertise to invest in renewable energy.  

“Accessing clean, reliable, and affordable energy is integral to resilient, sustainable, and equitable futures,” said Kim. “Policymakers who wish to facilitate on-site solar use should consider strategies for addressing resource and information gaps across investor-owned utilities, municipal utilities, and rural electric cooperatives.” 

Journal

Energy Policy

DOI

10.1016/j.enpol.2020.111536

In a paper published today in Nature Astronomy, researchers report the first ever clear images of nanojets -- bright thin lights that travel perpendicular to the magnetic structures in the solar atmosphere, called the corona -- in a process that reveals the existence of one of the potential coronal heating candidates: nanoflares.

In pursuit of understanding why the Sun's atmosphere is so much hotter than the surface, and to help differentiate between a host of theories about what causes this heating, researchers turn to NASA's Interface Region Imaging Spectrograph (IRIS) mission. IRIS was finely tuned with a high-resolution imager to zoom in on specific hard-to-see events on the Sun.

Nanoflares are small explosions on the Sun - but they are difficult to spot. They are very fast and tiny, meaning they are hard to pick out against the bright surface of the Sun. On April 3, 2014, during what's known as a coronal rain event when streams of cooled plasma fall from the corona to the Sun's surface looking almost like an enormous waterfall, researchers noticed bright jets appearing near the end of the event. These telltale flashes are nanojets -- heated plasma traveling so fast that they appear on images as bright thin lines seen within the magnetic loops on the Sun. Nanojets are considered a "smoking gun," key evidence of the presence of nanoflares. Each nanojet is believed to be initiated by a process known as magnetic reconnection where twisted magnetic fields explosively realign. One reconnection can set off another reconnection, creating an avalanche of nanojets in the corona of the Sun, a process that could create the energy that is heating the corona. In the visualization above, the Solar Dynamic Observatory gives us a full view of the Sun before zooming into IRIS's up close view of the nanojets, which briefly light up in the magnetic loops.

IRIS gathers its high resolution images by focusing in on a small portion of the Sun at a time. So observing specific events is a combination of educated guesswork and looking at the right place at the right time. Once the nanojets were identified against the backdrop of the coronal rain, researchers coordinated with NASA's Solar Dynamics Observatory (SDO) and the Hinode observatory, a partnership among the Japan Aerospace Exploration Agency, ESA (European Space Agency), and NASA to get a complete view of the Sun, and confirm whether they were detecting nanojets, and assess their effects on the corona.

The researchers combined the many observations with advanced simulations to recreate the events they saw on the Sun. The models showed that the nanojets were a telltale signature of magnetic reconnection and nanoflares, contributing to coronal heating in the simulations. More studies will need to be done to establish the frequency of nanojets and nanoflares all over the Sun, and how much energy they contribute to heating the solar corona. Going forward, missions like Solar Orbiter and Parker Solar Probe can give more detail into the processes that heat the solar corona.