Culture

Novel treatment for mesothelioma shows promise for patients

FAIRFAX, Va. (June 15, 2020) -- A novel treatment for advanced mesothelioma is safe and effective and may improve the quality of life for patients who have few treatment options, according to a research abstract presented during a virtual session of the Society of Interventional Radiology's 2020 Annual Scientific Meeting on June 14. Transarterial chemoperfusion treatment for malignant pleural mesothelioma (MPM) comes with minimal side effects and shows promise for extending the lives of patients who have limited or no remaining treatment options.

"MPM is a devastating cancer of the pleura, the membranes surrounding the lungs, that is very difficult to treat," said Bela Kis, MD, PhD, the principal investigator on the study and an interventional radiologist at the Moffitt Cancer Center in Tampa. "The typical survival rate of patients with stage 3 and 4 MPM is around 12 months from diagnosis; but with this new treatment, we are hoping we might be able to extend patients' lives beyond that--giving them more time with friends and family."

Twenty-seven patients with MPM were enrolled in the Phase II clinical trial and underwent chemoperfusion treatment. All patients had received prior chemotherapy, many of whom received multiple lines of chemotherapy. Four of the patients had prior radiation therapy and three patients had pleurectomy. All continued to have disease progression before enrollment.

Transarterial chemoperfusion delivers a relatively high concentration of drugs to diseased tissue in the lining of the lungs to maximize the treatment effect with limited side effects. Unlike other chemotherapy that is delivered intravenously and circulates through the entire body, interventional radiologists inject one-third of the chemotherapy cocktail of cisplatin, methotrexate, and gemcitabine directly into the internal mammary artery that supplies the pleura. The other two-thirds of the drugs are injected into the descending aorta, which reaches the intercostal vessels that also supply the pleura. The treatment is an outpatient procedure and typically lasts an hour, followed by a one-hour recovery.

The interim results of the study show 70.3 percent disease control rate and median overall survival rate of 8.5 months from the start of the chemoperfusion treatment. The treatment was well-tolerated by patients with a major complication rate of 1.4 percent. Most side effects were relatively minor, including mild nausea and chest pain.

"We were pleasantly surprised to find that this treatment doesn't come with the same side effects of traditional intravenous chemotherapy," said Kis. "To see these promising results with so few side effects means we are able to make a positive impact on quality of life for these patients."

Currently, surgery is the only truly effective treatment for MPM, but the disease must be diagnosed early. Unfortunately, only 10 to 20 percent of patients are candidates for surgery and often experience surgical complications.

The researchers are looking to expand their study to other cancer centers with larger MPM patient populations, since the cancer is so rare. They also hope to add flexibility to the study to allow for increasing the dosage and changing the combination of medications for individual patients to determine whether either approach could further improve outcomes.

Additional information about the clinical trial is available at ClinicalTrials.gov, using the identifier NCT02611037.

Abstract 1: Transarterial chemoperfusion treatment of unresectable pleural mesothelioma - interim results of a phase 2 prospective study. B. Kis; M. Pereira; J. Logeman; Z. Makovich; G. El-Haddad; J. Choi; J. Fontaine; B. Creelan; T. Tanvetyanon; Moffitt Cancer Center, Morsani College of Medicine, University of South Florida, Tampa, FL.

The research was originally scheduled to be presented in person at SIR's Annual Scientific Meeting, March 28-April 2, in Seattle before the meeting was canceled due to COVID-19 concerns. Visit sirmeeting.org for the latest information.

Credit: 
Society of Interventional Radiology

One minute simultaneous analysis of pungency components in kimchi

image: High-sensitivity, simultaneous analysis technique of pungency components in kimchi.

Image: 
The World Institute of Kimchi(Wikim)

The World Institute of Kimchi (WiKim) announced its development of a rapid analysis method for quantifying capsaicin (CAP) and dihydrocapsaicin (DHC), which are major pungency components in kimchi, within 1 min.

The new analysis method, which was jointly developed by the research teams of Prof. Seong Ho Kang at Kyung Hee University and Dr. Ji-Hyoung Ha at WiKim, refers to high-sensitivity capillary electrophoresis that is performed in submillimeter diameter capillaries filled with surfactants in conjunction with an applied electric field and a laser. This analytical technique intends to quickly and accurately detect only CAP and DHC among various components in the samples.

Conventional tests, such as high-performance liquid chromatography (HPLC), have been employed to identify the pungency components using specialized analysis equipment. However, the HPLC method takes about an hour to analyze the CAP and DHC content in kimchi.

Moreover, the new analytical method developed by the joint research team is designed to utilize voltage program (VP)-based micellar electrokinetic chromatography (MEKC), which uses a combination of the two types of surfactants with different charge characteristics for enhanced detection sensitivity that is applied to samples, in particular.

A micelle is a cluster of colloidal particles, which are formed spontaneously through the self-assembly of molecules or ions.

Micellar electrokinetic chromatography (MEKC) is a modification of capillary electrophoresis, where analytes are separated based on analyte-micelle interaction mechanism in the capillaries that is mainly determined by hydrophobicity.

As a result of the experiment, CAP and DHC were simultaneously separated and detected in only 53 s, which shows the improved detection sensitivity of the major pungency components by 4,230 times and 2,382 times, respectively, compared with the conventional HPLC method.

"Our new analysis will allow detailed information on the spicy tastes of kimchi to be provided for the consumers, allowing them to choose different kimchi products that suit their preferences. We will also continue pursuing standardization research regarding the tastes and smells of kimchi in the future," Acting Director Dr. Hak-Jong Choi remarked.

The findings of this research will be published in the September issue of Food Chemistry, an international journal in the field of food science and technology.

Credit: 
National Research Council of Science & Technology

Treatment plan helps keep young cancer patients home

Research at a Glance:

A new Australian-developed treatment decision model has allowed more young cancer patients to recover from mild infections at home

The rule has been fast-tracked in the UK to help to ease pressure on a hospital system still battling COVID-19

The decision model, dubbed AUS-rule, could help patients globally avoid onerous hospital stays

An Australian program that avoids hospital admission for some young cancer patients with a fever is helping to ease pressure on the UK health system during the COVID-19 crisis. The AUS-rule system, now published in E Clinical Med, guides doctors when deciding whether patients can be treated and supported at home.

Led by experts at Murdoch Children's Research Institute (MCRI) and the Peter MacCallum Cancer Centre, AUS-rule has already been successfully deployed in several Australian hospitals including the Royal Children's Hospital. It has also been fast-tracked in some UK hospitals.

Children undergoing cancer treatment face an increased risk of febrile neutropenia (FN), a fever with low numbers of a white blood cell important in fighting infections. Febrile neutropenia may require hospital admission for antibiotics, but an international collaboration is working to manage suitable cases at home.

Paediatric cancer researcher Dr Gabrielle Haeusler, from MCRI and the Peter MacCallum Cancer Centre, recalibrated a febrile neutropenia decision rule, with input by UK researchers.

AUS-rule was formulated by the Australian and UK Predicting Infectious Complications In Children With Cancer Projects (PICNICCs) and the Swiss Paediatric Oncology Group (SPOG). The University of York PICNICC project was led by Dr Bob Phillips. The AUS-rule (Australia-UK-Switzerland) name reflects this international collaboration.

The AUS-rule helps doctors decide which children with febrile neutropenia are suitable for home management using antibiotics and temperature monitoring. It considers platelet and white cell counts and chemotherapy intensity.

Dr Haeusler said, "Over half of these patients do not have a severe infection and can be treated at home with antibiotics and the appropriate supports. This reduces their time spent in hospital by 3-4 days and allows kids to recover in the comfort of their own home. We are currently in the process of scaling up the program across Australia so more children with cancer can benefit from this research."

Dr Phillips is leading the UK push to roll out the Low-risk Febrile Neutropenia Program using the AUS-rule, endorsed by the Children's Cancer and Leukaemia Group (CCLG). Those using it can access vital AUS-rule guidelines, patient information, checklists and tip sheets online.

Dr Phillips said it was early days, but the simple and robust system was already popular with families who had trialled it in Leeds, London, and Liverpool.

Of the 32 children who have presented with febrile neutropenia at Leeds Teaching Hospital so far, nine have gone home with support and an antibiotic treatment plan within a day, compared to a usual minimum hospital stay of three days. Families have embraced the development.

"They absolutely want to get out of hospital quicker," Dr Phillips said. "It means that we don't do unnecessary tests on kids and just annoy them, and they actually do better at home.

"It's been wonderful to have the direct support of Dr Haeusler and the Australian teams in implementing this program in the UK. Without her input we'd be struggling to make this work. The more we show it works across different hospitals in different countries, the more robust it is because it's experiencing variation and being effective."

Credit: 
Murdoch Childrens Research Institute

Otago researchers discover the origins of the beloved guinea pig

image: Professor Lisa Matisoo-Smith from University of Otago

Image: 
University of Otago

New University of Otago research sheds light on guinea pig domestication and how and why the small, furry animals became distributed around the world.

Just published in the international science journal, Scientific Reports, the researchers use ancient DNA from archaeological guinea pig remains which reveals the transition from the animals being used as a wild food source 10,000 years ago to their domestication and later role as beloved pets and medical animal models.

It builds on previous research over many years by Professor of Biological Anthropology, Lisa Matisoo-Smith, tracing the DNA from plants and animals that Pacific settlers carried in their canoes and using that as a proxy for identifying human population origins and tracking their movement around the Pacific.

As part of her Otago Master's thesis research in Professor Matisoo-Smith's lab, Edana Lord, now at Stockholm University, Sweden and Dr Catherine Collins from Otago's Department of Anatomy and other international researchers, set about finding out where the guinea pigs that were introduced to the islands of the Caribbean came from.

Professor Matisoo-Smith explains it is generally accepted that modern guinea pigs were domesticated in the Andes region of what is now Peru. As an important food item that was also included in religious ceremonies, they were transported and traded around South America.

Sometime around AD500, guinea pigs were taken out to the islands of the Caribbean, through at least one of several established trade networks. The researchers expected that the guinea pigs found in the Caribbean would came from Colombia, one of the closer locations in South America to the Caribbean.

Using ancient DNA of guinea pigs remains excavated from several sites in the Caribbean, Peru, Colombia, Bolivia, Europe and North America, they found the guinea pigs on the islands did not originate in Colombia, but most likely originated in Peru.

What was a bigger surprise to the team was that the guinea pig remains found in the Colombian Highlands appeared to be from a totally different species. This suggests that guinea pig domestication likely took place independently in both Peru and Colombia.

The genetic information, along with archaeological contexts, also shows how the guinea pigs had different roles through time.

"They were and still are important food item in many parts of South America and cultures that derived from South America - people took them live to introduce to new islands where they were not native or they traded them for other goods," Professor Matisoo-Smith explains.

"The guinea pig was brought to Europe in the late 1500s or early 1600s by the Spanish and to North America in the early 1800s as part of the exotic pet trade. In the 18th century guinea pigs began to be used by medical researchers as laboratory animals because they have many biological similarities to humans, thus the origin of the phrase 'being a guinea pig' in research.

"All guinea pigs today - pets, those that are sold for meat in South America and Puerto Rico, and those used in medical research - are derived from the Peruvian domesticated guinea pigs."

Why the guinea pig was viewed as a pet in some cultures and a food source in others can likely be attributed to long-established cultural notions of what is acceptable as food.

Professor Matisoo-Smith says the research demonstrates that the history of guinea pigs is more complex than previously known and has implications for other studies regarding mammal domestication, translocation and distribution.

"Identifying the origins of the guinea pig remains from the Caribbean helps us to understand how the human trade networks in the region moved in the past 1000 years or so.

"Through this analysis of ancient guinea pig DNA, we better understand the history of human social interactions over thousands of years and across three continents. It also provides a critical historical perspective of the genetic diversity in guinea pigs and the relationship humans have had with this important domestic animals."

Credit: 
University of Otago

A new family of nanocars ready for the next nano Grand Prix

image: Chemical structure of the nanocar qualified.

Image: 
G. Rapenne, NAIST and UPS

Gwénaël Rapenne, Professor at NAIST (Nara, Japan) and University Paul Sabatier (Toulouse, France) - June 12th, 2020

According to the British Royal Automobile and the French Automobile clubs, the first car was created in 1770 by the Frenchman Joseph Cugnot. This "Fardier" (French name for a trolley used to transport heavy loads) was a car propelled by a steam engine and powered by a boiler. This 7 m long self-propelled machine reached a speed of 4 km/h, for an average autonomy of 15 min. 250 years later, researchers at the Nara Institute of Science and Technology (NAIST), Japan, in partnership with colleagues in the University Paul Sabatier (Toulouse, France), report in Chemistry - A European Journal a new family of nanocars integrating a dipole to speed up their motion in the nanoworld.

After the first nanocar race organized in spring 2017, in Toulouse (France) we designed a new family of molecules to behave as cars in the nanoworld. When I established my laboratory in NAIST in April 2018, Toshio Nishino (Assistant Professor) and Hiroki Takeuchi (Master student) started the synthesis. Two years later, we are reporting the results in a publication presenting the synthesis of 9 dipolar nanocars. The result is amazing. In every flask, about 100 mg of green or blue powders (i.e. 60 x 1018 nanocars) stick to the walls. These are the Franco-Japanese racing cars that sleep wisely in the garage waiting for the next Grand Prix in 2021.

"To hope to win the race, nanocars have to be fast but they need also to be controllable," emphasizes Gwénaël Rapenne. The design of the molecules has long been thought to need a compromise between opposite requirements. Consistently, the nanocar Rapenne and his colleagues designed is made up of 150 atoms (chemical formula C85H59N5Zn). A planar chassis made from porphyrin, a fragment already used in nature for many processes like oxygen transportation (hemoglobin) or photosynthesis (chlorophyl). Ultimately, the presence of a zinc atom could allow transportation of small molecules on the car body. "The nanocar is 2 nm long and surrounded by four wheels designed to minimize contact with the ground and has two legs which are able to donate or accept electrons making the nanocar dipolar" specifies the researcher.

What kind of application could be envisioned with such small vehicles?

"Honestly, today, we do not know yet what this technology will be used for. But just like the liquid crystals discovered in 1910 and not used until half a century later in calculator screens and now in all our LCD supports, the manipulation of molecules could well be revolutionary, " dreams Gwénaël Rapenne. One of the directions of the research could be to carry a load to transport reactants or drugs from one place to another.

Credit: 
Nara Institute of Science and Technology

The Lancet Global Health: Estimates suggest one in five people worldwide have an underlying health condition that could increase their risk of severe COVID-19 if infected

image: How many people could be at increased risk of severe COVID-19 due to underlying health conditions?

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The Lancet Global Health

The share of the population at increased risk (with at least one underlying health condition relevant to COVID-19) is highest in countries with ageing populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence.

The share of the population with an underlying health condition varies by age, from less than 5% of those under 20, to over 66% of those aged 70 and above.

As lockdown restrictions are eased, governments could use the new estimates to understand how many people should be prioritised for enhanced physical distancing measures [1] and vaccination (if available)

The authors estimate that fewer individuals worldwide would actually require hospitalisation if infected - around 4% of the world population - suggesting that for many with underlying conditions, the increase in risk may be modest.

An estimated 1.7 billion people, 22% of the world population, have at least one underlying health condition that could increase their risk of severe COVID-19 if infected, according to a modelling study that uses data from 188 countries, published in The Lancet Global Health journal.

"As countries move out of lockdown, governments are looking for ways to protect the most vulnerable from a virus that is still circulating. We hope our estimates will provide useful starting points for designing measures to protect those at increased risk of severe disease. This might involve advising people with underlying conditions to adopt social distancing measures appropriate to their level of risk, or prioritising them for vaccination in the future," says Associate Professor Andrew Clark from the London School of Hygiene & Tropical Medicine (LSHTM), UK. [2]

Although the estimates provide an idea of the number of people governments should prioritise for protective measures, not all individuals with these conditions would go on to develop severe symptoms if infected. The authors estimate that 4% of the world's population (349 million of 7.8 billion people) would require hospitalisation if infected, suggesting that the increased risk of severe COVID-19 could be quite modest for many with underlying conditions.

Guidelines published by the WHO and by public health agencies in the UK and USA identify risk factors for severe COVID-19, including cardiovascular disease, chronic kidney disease, diabetes and chronic respiratory disease. The new study provides global, regional and national estimates for the number of people with underlying health conditions. The authors caution that they focused on underlying chronic conditions and didn't include other possible risk factors for COVID-19 that are not yet included in all guidelines, such as ethnicity and socioeconomic deprivation. Their estimates are therefore unlikely to be exhaustive, but serve as a starting point for policy-makers.

The authors based their estimates on disease prevalence data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2017, UN population estimates for 2020 and the list of underlying health conditions relevant to COVID-19, as defined by current guidelines. The authors point out that the GBD prevalence estimates are likely to be higher than those from national databases, because they're designed to capture cases that might be undiagnosed or not severe enough to be included in electronic health records. They analysed the number of people with an underlying condition by age group, sex and country for 188 countries.

To help determine the degree of increased risk, the researchers also provided separate estimates of the proportion of all people (with and without underlying conditions) who would require hospitalisation if infected. The authors calculated those at high risk using infection hospitalisation ratios for COVID-19 [3] and made adjustments for differences between countries.

Countries and regions with younger populations have fewer people with at least one underlying health condition, while those with older populations have more people with at least one condition. For example, the proportion of the population with one or more health condition ranges from 16% in Africa (283 million people out of 1.3 billion) to 31% in Europe (231 million out of 747 million).

However, Associate Professor Clark cautions that the evidence needs to be carefully communicated to avoid complacency about risk in Africa: "The share of the population at increased risk of severe COVID-19 is generally lower in Africa than elsewhere due to much younger country populations, but a much higher proportion of severe cases could be fatal in Africa than elsewhere." [2]

Small island nations with high diabetes prevalence, such as Fiji and Mauritius, have among the highest proportion of people with an underlying condition. In Africa, countries with the highest HIV/AIDS prevalence, such as eSwatini and Lesotho, have a greater proportion of people with an underlying condition than countries with lower prevalence, such as Niger.

Globally, less than 5% of people aged under 20 years, but more than 66% of those aged 70 and above, have at least one underlying condition that could increase their risk of severe COVID-19. Among the working age population (15 to 64 years), 23% are estimated to have at least one underlying condition. The prevalence of one or more condition listed on current guidelines is similar between the sexes, but the authors assumed males were twice as likely as females to require hospitalisation if infected.

The authors estimate that 349 million people worldwide are at high risk of severe COVID-19, meaning they would require hospital treatment if infected. This risk varies from less than 1% of people under 20 to nearly 20% of those aged 70 or older, rising to more than 25% in males over 70. In all age groups under 65, around twice the number of men as women would require hospitalisation. Above 65 years, the ratio becomes less marked because women are over-represented in older age groups due to longer life expectancy.

"Our estimates suggest that age-based thresholds for shielding could play a role in reducing deaths and reducing the number of people who require hospital treatment, but the choice of threshold needs to be balanced against the proportion of people of working age affected, as well as the health and economic consequences that might be associated with long periods of isolation," says Dr Rosalind Eggo from LSHTM. [21]

Writing in a linked Comment, lead author Professor Nina Schwalbe, MPH, (who was not involved in the study) from Columbia University Mailman School of Public Health, USA, says: "An increased understanding of risk factors, including the effects of social determinants and their interplay, provides an opportunity to target mitigation strategies and helps to allay the popular misconception that everyone is at equal risk of severe illness. As the authors note, it is time to evolve from a one-size-fits-all approach to one that centres on those most at risk. This will need to happen at both the individual and community level. Considering the relevance of social determinants, such an approach requires urgently improving communication about COVID-19; increasing access to health services, including palliative care, for those already socially vulnerable; and providing economic support to cope with the mitigation."

Credit: 
The Lancet

Super-potent human antibodies protect against COVID-19 in animal tests

LA JOLLA, CA--A team led by Scripps Research has discovered antibodies in the blood of recovered COVID-19 patients that provide powerful protection against SARS-CoV-2, the coronavirus that causes the disease, when tested in animals and human cell cultures.

The research, published today in Science, offers a paradigm of swift reaction to an emergent and deadly viral pandemic, and sets the stage for clinical trials and additional tests of the antibodies, which are now being produced as potential treatments and preventives for COVID-19.

"The discovery of these very potent antibodies represents an extremely rapid response to a totally new pathogen," says study co-senior author Dennis Burton, PhD, the James and Jessie Minor Chair in Immunology in the Department of Immunology & Microbiology at Scripps Research.

In principle, injections of such antibodies could be given to patients in the early stage of COVID-19 to reduce the level of virus and protect against severe disease. The antibodies also may be used to provide temporary, vaccine-like protection against SARS-CoV-2 infection for healthcare workers, elderly people and others who respond poorly to traditional vaccines or are suspected of a recent exposure to the coronavirus.

The project was led by groups at Scripps Research; IAVI, a nonprofit scientific research organization dedicated to addressing urgent, unmet global health challenges; and University of California San Diego School of Medicine.

"It has been a tremendous collaborative effort, and we're now focused on making large quantities of these promising antibodies for clinical trials," says co-lead author Thomas Rogers, MD, PhD, an adjunct assistant professor in the Department of Immunology & Microbiology at Scripps Research, and assistant professor of Medicine at UC San Diego.

An approach that's worked for other deadly viruses

Developing a treatment or vaccine for severe COVID-19 is currently the world's top public health priority. Globally, almost 8 million people have tested positive for SARS-CoV-2 infection, and more than 400,000 have died of severe COVID-19. The daily toll of new infections is still rising.

One approach to new viral threats is to identify, in the blood of recovering patients, antibodies that neutralize the virus's ability to infect cells.

These antibodies can then be mass-produced, using biotech methods, as a treatment that blocks severe disease and as a vaccine-like preventive that circulates in the blood for several weeks to protect against infection. This approach already has been demonstrated successfully against Ebola virus and the pneumonia-causing respiratory syncytial virus, commonly known as RSV.

Potent patient antibodies block the virus

For the new project, Rogers and his UC San Diego colleagues took blood samples from patients who had recovered from mild-to-severe COVID-19. In parallel, scientists at Scripps Research and IAVI developed test cells that express ACE2, the receptor that SARS-CoV-2 uses to get into human cells. In a set of initial experiments, the team tested whether antibody-containing blood from the patients could bind to the virus and strongly block it from infecting the test cells.

The scientists were able to isolate more than 1,000 distinct antibody-producing immune cells, called B cells, each of which produced a distinct anti-SARS-CoV-2 antibody. The team obtained the antibody gene sequences from these B cells so that they could produce the antibodies in the laboratory. By screening these antibodies individually, the team identified several that, even in tiny quantities, could block the virus in test cells, and one that could also protect hamsters against heavy viral exposure.

All of this work--including the development of the cell and animal infection models, and studies to discover where the antibodies of interest bind the virus--was completed in less than seven weeks.

"We leveraged our institution's decades of expertise in antibody isolation and quickly pivoted our focus to SARS-CoV-2 to identify these highly potent antibodies," says study co-author Elise Landais, PhD, an IAVI principal scientist.

If further safety tests in animals and clinical trials in people go well, then conceivably the antibodies could be used in clinical settings as early as next January, the researchers say.

"We intend to make them available to those who need them most, including people in low- and middle-income countries," Landais says.

In the course of their attempts to isolate anti-SARS-CoV-2 antibodies from the COVID-19 patients, the researchers found one that can also neutralize SARS-CoV, the related coronavirus that caused the 2002-2004 outbreak of severe acute respiratory syndrome (SARS) in Asia.

"That discovery gives us hope that we will eventually find broadly neutralizing antibodies that provide at least partial protection against all or most SARS coronaviruses, which should be useful if another one jumps to humans," Burton says.

Credit: 
Scripps Research Institute

Three new studies identify neutralizing antibodies against SARS-CoV-2

A trio of papers describes several newly discovered human antibodies that target the SARS-CoV-2 virus, isolated from survivors of SARS-CoV-2 and SARS-CoV infection. Several of these antibodies showed protective, neutralizing capabilities, offering promising therapeutic leads, and eight antibodies from one analysis were discovered to cross-react with a related bat-specific coronavirus - with implications for the identification of broadly neutralizing antibodies to protect against potential new coronavirus outbreaks in the future. Philip Brouwer and colleagues isolated 403 monoclonal antibodies from 3 convalescent COVID-19 patients, showing that the patients had strong immune responses against the viral spike, a protein complex that binds to the ACE2 receptor to facilitate entry into human host cells. A subset of these antibodies neutralized the virus by targeting diverse epitopes on the spike, with the two most potent ones targeting the domain that binds the host receptor. In another study, Thomas Rogers and colleagues used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors, selecting for antibodies that bind to the viral spike. Several of the isolated antibodies bound to the receptor binding domain (RBD) and demonstrated neutralizing capabilities, with the most potent ones binding at a site that overlaps the ACE2 binding site. Two of these neutralizing antibodies gave protection against SARS-CoV-2 infection when tested in Syrian hamsters. In a third study to identify broadly protective, cross-reactive antibodies, Anna Wec and colleagues isolated and characterized hundreds of antibodies against the viral spike of SARS-CoV-2 from the memory B cells of a SARS-CoV survivor. Both of these closely related viruses rely on the spike to gain host cell entry by binding the ACE2 receptor. Of nine antibodies that showed strong cross-neutralization of both viruses, eight target the domain that binds the ACE2 receptor - and also neutralized a closely related species of bat coronavirus. Taken together, the trio of studies offers several new human antibodies to help inform the design of therapeutic antibody drugs and vaccines against SARS-CoV-2, as well as the design of broadly protective vaccines against a range of related coronaviruses.

Credit: 
American Association for the Advancement of Science (AAAS)

New study reveals racial disparities in fear of police brutality

image: Melissa Sloan is an associate professor of sociology at the University of South Florida.

Image: 
University of South Florida

SARASOTA, Fla. (June 15, 2020) - A recently published nationwide study by two University of South Florida professors indicates that blacks are five times more likely and Latinos four times more likely to fear police brutality than whites.

Criminology instructor Murat Haner and Melissa Sloan, associate professor of sociology, report In "Race and Worrying about Police Brutality: The Hidden Injuries of Minority Status in America" that while only 6.6 percent of whites "worry a lot" about police violence, some minorities experience much greater fear, with 32.4 percent of blacks and 26.5 percent of Latinos reporting they "worry a lot" about becoming victims of police violence.

Conversely, three-fourths of whites "do not worry at all" about officer violence, while only one-third of minority respondents "do not worry at all" about police brutality.

Haner and Sloan, researchers at USF's Sarasota-Manatee campus, conducted the study with four other professors over three months in 2018. Their article was published online on May 26 in the journal, Victims & Offenders: An International Journal of Evidence-based Research, Policy and Practice.

"Blacks and Hispanics live with these worries that whites really have no concept of," Sloan said, summing up. "Given the long history of racial discrimination in the United States, this divide likely has been occurring for a long time, across generations."

The study is based on a national survey of 1,000 respondents to measure fear by how much the study's participants "worry" about experiencing police violence.

Participants were asked how much they worry about six potential areas of concern:

Experiencing police brutality

Becoming the victim of a racial/hate crime

Becoming the victim of a violent crime

Someone breaking into your house when you are home

A mass shooting at some event or at work/school

Becoming the victim of a terrorist attack

The goal of asking about these other worries was to determine if racial/ethnic differences were unique to the worry of police brutality or found within other examples of victimization, and if so, to what extent.

Also collaborating in the study in addition to Haner and Sloan were researchers from Georgia Southern University, the University of Cincinnati, Xaiver University and the University of Nebraska at Omaha.

Previous studies have examined fear of police generally, but this is the first study to specifically examine the fear of police brutality. Further, the study includes a representative proportion of Latino respondents - a subgroup of the U.S. population often omitted from the area of research.

In addition to considering racial differences as related to police violence, the study suggests that for blacks, as well as Hispanics to an extent, worrying about police brutality exacts an emotional toll that is pervasive and largely hidden from view. This emotional burden is hazardous because research shows excessive worry leads to psychological and physical health consequences as well as behavioral changes.

"Research on the fear of crime shows that worries like these can lead to avoidance behaviors where people restrict normal activities and social interaction out of fear, which can lead to feelings of isolation and lower quality of life," Sloan said. "More concerning is that this worry is justified as demonstrated by the killing of George Floyd as well as the numerous other black Americans who have been brutalized and killed by police in the past."

The extent of this worry among blacks suggests that these consequences may affect entire communities, not only individuals in contact with police and the criminal justice system.

"Taken as a whole, what remains is an insidious picture in which communities worry about those they are supposed to trust during their greatest time of need," Haner said. "There is a substantial subpopulation in America that worries about being victimized, not by some perpetrator, but by the state - the very people who are sworn to protect and serve them."

To provide further context, the researchers analyzed responses about worries across the five other victimization scenarios, which are listed above.

Worries about becoming the victim of a violent crime or a mass shooting appeared homogeneous, with black and Latino respondents worrying no more or less than white respondents. However, it appeared that younger Americans worry more than older Americans about both of these events.

Uniquely, Latino respondents worried more than white respondents about someone breaking into their house when they were present. Black respondents, on the other hand, did not worry about this crime any differently than white respondents. Finally, black and Latino respondents worried significantly more than white respondents about being victims of a racial or hate crime or being victims of a terrorist attack.

Credit: 
University of South Florida

Genetic rescue of SHANK3 is potential therapy in rare forms of autism spectrum disorder

image: Craig Powell

Image: 
UAB

BIRMINGHAM, Ala. - A mouse study by Craig Powell, M.D., Ph.D., and colleagues suggests that early genetic rescue may be a potential therapy in autism spectrum disorder, or ASD. Powell looked at one gene called SHANK3, whose alteration is seen in about 0.5 percent of ASD patients.

The study is published in eNeuro and was highlighted on the ASD news site Spectrum. Powell is professor and chair of the Department of Neurobiology at the University of Alabama at Birmingham and also heads the UAB Civitan International Research Center. The UAB researcher has a longstanding focus on autism, intellectual disability and cognitive dysfunction.

The SHANK3 gene product acts in the brain as a postsynaptic scaffolding protein. A synapse is a gap between two nerve cells where a signal is passed from one nerve to the other. A human brain may have more than 100 trillion synapses in its neuronal circuitry.

Powell and colleagues previously showed that mice deficient in SHANK3 protein have behavioral abnormalities, including repetitive grooming and deficits in social interaction, locomotor activity and rearing. Rearing is standing on hind legs to investigate the surroundings. Some of these behaviors are reminiscent of ASD in humans, which is characterized by deficits in social interaction and communication, restricted interests, and repetitive behaviors.

Powell's lab and other labs, including that of Guoping Feng, Ph.D., Massachusetts Institute of Technology, have sought mouse models where a SHANK3 deficit could be reversed early or later in life, to see if that reversal removed some of the behavioral deficits. Powell says his and Feng's labs used different experimental approaches, and their two studies are complementary.

Powell's lab used genetic tools to construct mice that had a stop signal inserted into one or both genes for SHANK3, creating heterozygous or homozygous mice for the mutation they call ShankE13. The activation of another inserted gene called Cre-recombinase can excise that stop signal, restoring full function of the mutated SHANK3 gene.

In Feng's mouse model, the SHANK3 gene was activated when the mice were given tamoxifen, which leads to some toxicity, including weight loss. In the Powell mouse model, the Cre-recombinase was negatively controlled by the antibiotic doxycycline; as long as mice were fed doxycycline, the Cre-recombinase was supposed to be shut off. When the doxycycline is stopped, the SHANK3 gene should be restored. Another genetic tool in the mouse model was supposed to limit reactivation of the SHANK3 gene to the striatum and cerebellum of the brain.

The plan was to activate the Cre-recombinase at different ages and test those mice for changes in ASD-like behaviors.

This elegant approach had two problems, the researchers learned. First, there was more widespread rescue of the SHANK3 gene in the brain than expected, including in the cortex. Second, the doxycycline control was "leaky," allowing expression of the Cre-recombinase even as the mice were fed the antibiotic. Thus, Powell and colleagues were only able to look at the effect of early developmental genetic reversal of ShankE13, occurring about embryonic day 18.

Still, as Powell told Spectrum, "It is important to publish experiments that do not work out exactly as planned."

In a wide variety of behavioral tests, the researchers found that early genetic restoration of SHANK3 rescued a variety of behaviors that included repetitive grooming and social, locomotor and rearing deficits.

The social tests included the amount of social interaction with another mouse; social recognition memory, where a test mouse was introduced to another mouse, and then reintroduced three days later; and social novelty exploration, which compares the amount of time spent with a novel caged mouse versus an inanimate object.

The locomotor tests included placing mice in a novel cage with minimal bedding and measuring how much they freely explored over two hours. In a different series of tests, the mice -- as expected -- showed no changes in anxiety-related behaviors. That lack of change in anxiety in mutant and rescued mice had also been shown in previous work.

"Overall," Powell said, "our studies suggest early genetic rescue as a potential genetic therapy for ASD-like behaviors in ASD associated with SHANK3 deletion or mutation. Taken together with previously published studies, genetic intervention in SHANK3-related ASD may be most effective earlier in development."

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University of Alabama at Birmingham

Calling for nursing support amid COVID-19 pandemic

image: In an editorial published in the International Journal of Nursing Studies, researchers, including two from the University of Pennsylvania School of Nursing (Penn Nursing), call for rapid policy reform and investment in nurses and nursing in order to leverage the skills of this global workforce.

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Penn Nursing

PHILADELPHIA (June 15, 2020) - There are close to 28 million nurses around the world who comprise a global workforce that delivers about 90 percent of primary healthcare, including frontline response to the COVID-19 pandemic. Ensuring their optimal contribution and continued well-being amid the myriad consequences of COVID-19 will increase the potential for measurable and improved health outcomes.

In an editorial published in the International Journal of Nursing Studies, researchers, including two from the University of Pennsylvania School of Nursing (Penn Nursing), call for rapid policy reform and investment in nurses and nursing in order to leverage the skills of this global workforce. The editorial outlines multisectoral investments to redesign and innovate existing health services, expand nursing scopes of practice, forge supportive regulations and legislation for nurses, and optimize nursing contributions to best meet global public health needs and increase the potential to contain and manage the pandemic and future public health and humanitarian crises.

"The far-reaching consequences of COVID-19 have shown that we need widespread, rapid, and intelligent investment in nursing through informed action that fully leverages the healthcare workforce. Our communities and the health of populations worldwide depend on these urgently needed policy reforms and increased investment in nursing now more than ever," write the two Penn Nursing authors, William E. Rosa, PhD, MBE, NP-BC, FAANP, FAAN, a Robert Wood Johnson Foundation Future of Nursing Scholar; and Linda H. Aiken, PhD, RN, FAAN, FRCN, the Claire M. Fagin Leadership Professor; Director of the Center for Health Outcomes and Policy Research; and Senior Fellow at the Leonard Davis Institute of Health Economics.

The recommendations in the editorial are based on a 2018 World Innovation Summit for Health report and include implications for nurses and advanced practice nurses, policy makers, governmental and nongovernmental health partners, and those working in research, clinical practice, and education settings. The editorial, "Rapid Investment in Nursing to Strengthen the Global COVID-19 Response" is available online.

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University of Pennsylvania School of Nursing

Your brain shows if you are lonely or not

image: Loneliness was associated with lower self-other similarity in the medial prefrontal cortex (MPFC). Less self-other similarity in MPFC with greater loneliness was observed when participants thought about either their friends, acquaintances, or celebrities.

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Figure provided by Andrea L. Courtney and Meghan L. Meyer

Social connection with others is critical to a person's mental and physical well-being. How the brain maps relationships with other people in relation to one's self has long been a mystery. A Dartmouth study finds that the closer you feel to people emotionally, the more similarly you represent them in your brain. In contrast, people who feel social disconnection appear to have a lonelier, neural self-representation. The findings are published in the Journal of Neuroscience.

"If we had a stamp of neural activity that reflected your self-representation and one that reflected that of people whom you are close to, for most of us, our stamps of neural activity would look pretty similar. Yet, for lonelier people, the neural activity was really differentiated from that of other people," explained senior author Meghan L. Meyer, an assistant professor of psychological and brain sciences, and director of the Dartmouth Social Neuroscience Lab.

The study was comprised of 50 college students and community members ranging from age 18 to 47. Before going in an fMRI scanner, participants were asked to name and rank five people whom they are closest to and five acquaintances. During the scan, participants were asked to make trait judgements about themselves, the people they are closest to and the acquaintances that they had just named, and five celebrities. Participants were asked to rate how much a trait described a person (such as if the person is friendly) on a scale from 1 to 4 (from not at all to very much).

The results showed how the brain seemed to cluster representations of people into three different cliques: 1) oneself, 2) one's own social network, and 3) well-known people, like celebrities. The closer participants felt to someone, the more similarly their brain represented them throughout the social brain, including in the medial prefrontal cortex (MPFC), the region associated with the concept of self. Lonelier people showed less neural similarity between themselves and others in the MPFC, and the demarcations between the three cliques was blurrier in their neural activity. In other words, the lonelier people are, the less similar their brain looks when they think about themselves and others.

Meyer added, "It's almost as if you have a specific constellation of neural activity that is activated when you think about yourself. And when you think about your friends, much of the same constellation is recruited. If you are lonely though, you activate a fairly, different constellation when you think about others than when you think about yourself. It's as though your brain's representation of yourself is more disconnected from other people, which is consistent with how lonely people say they feel."

The findings illustrate how loneliness seems to be associated with distortions in the neural mapping of social connections with others.

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Dartmouth College

Most people accessing USC COVID-19 patient self-assessment tool report mild symptoms

Of the more than 275,000 people worldwide who accessed a USC web-based COVID-19 patient self-assessment tool, only 20 percent of those reporting COVID-19 symptoms had ones severe enough to require immediate medical attention, according to new research published in the Journal of General Internal Medicine.

The study was done by a group of researchers led by William Mehring, a first-year medical student at Keck School of Medicine of USC.

"Among users of our tool with symptoms of COVID-19, 80 percent reported mild symptoms that can likely be managed with simple home self-care," Mehring said.

The tool, which is freely available in English and Spanish, was developed in partnership with AltaMed Health Services, the nation's largest independent federally qualified community health center. AltaMed, which specializes in safety-net multi-ethnic populations, operates nine COVID-19 testing sites throughout Los Angeles County. AltaMed has been using the tool to help triage patients seeking care for symptoms that may be due to the infection.

Removing barriers to health care

"During normal times, there are many barriers to our communities seeking health care services," said Dr. Ilan Shapiro, Medical Director of Health Education and Wellness at AltaMed. "Digital tools like the patient self-assessment tool, coupled with access to in-person consultations like our testing and evaluation sites, are critical for ensuring patients can receive the care they need now and after the pandemic."

The self-assessment tool was initially developed in March by a team of researchers from the USC Gehr Center for Health Systems Science and Innovation, within the Keck School, and Akido Labs, a Los Angeles-based health data technology company. The team used information from the Centers for Disease Control as a guide. The tool asks users to provide answers to six simple questions about their current situation, including the nature of the user's symptoms; risk factors for COVID-19 such as advanced age or presence of high-risk chronic medical conditions; and whether they work in a high-risk environment that requires close physical interaction with others. Based on these answers, the tool provides an assessment along with customized recommendations regarding evaluation and treatment, self-care and infection-prevention practices.

"Although the new study does not validate the appropriateness of the guidance provided by the tool, it highlights the eagerness of the public to engage with digital health tools and self-assessment in this time of public health crisis," said Andrew Poksay, from Akido Labs.

De-stressing overburdened health care systems

Mehring sees the COVID-19 assessment tool as a potential way to ease the burden on overwhelmed health care systems while gathering data on the pandemic's spread.

"This could be a way to de-stress the system, which in some areas became quickly overburdened and still is," said Mehring. "In the future it could be used as a way to collect data on outbreaks and determine where they are occurring."

Close to 450,000 people have accessed the tool since it was launched. The USC Gehr Center, Akido and AltaMed teams plan to continue developing the self-assessment tool as part of a holistic digital approach that other communities around the nation can use as the COVID-19 pandemic continues to unfold.

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Keck School of Medicine of USC

Mindfulness combined with hypnotherapy aids highly stressed people, study finds

A new treatment for stress which combines mindfulness with hypnotherapy has shown positive results in a Baylor University pilot study.

The intervention is called "mindful hypnotherapy."

"Mindfulness is a type of meditation that involves focusing attention on present moment awareness. It can help people cope with stress, but can require months of practice and training," said researcher Gary Elkins, Ph.D., director of the Mind-Body Medicine Research Laboratory at Baylor University. "Hypnosis also involves focusing attention, but it includes mental imagery, relaxation and suggestions for symptom reduction."

Hypnosis interventions are typically brief and have been used in pain and symptom management in clinical practice.

The study's basic premise is that using hypnosis to deliver mindfulness goals could have many advantages, Elkins said.

"Combining mindfulness and hypnotherapy in a single session is a novel intervention that may be equal to or better than existing treatments, with the advantage of being more time-effective, less daunting and easier to use," he said. "This could be a valuable option for treating anxiety and stress reduction."

As a brief intervention, mindful therapy could be widely disseminated and is an innovative new mind-body therapy, he said.

The study is published in the International Journal of Clinical and Experimental Hypnosis.

Elkins noted that while mindfulness by itself can be an effective treatment for stress and anxiety for some people, it typically is provided in eight weekly sessions that last two hours or more each week and include an all-day retreat of eight or more hours. That amount of time -- more than 24 therapy hours -- may be a burden in cost and time for some people. Also, research has not shown that mindfulness-based treatments are consistently superior to standard cognitive behavioral therapy, he said.

For the study of mindful hypnotherapy, the Baylor research team recruited 42 individuals with self-reported high stress. Half took part in an intervention of one-hour weekly individual sessions that included hypnosis inductions and suggestions for greater mindfulness. Participants also were given self-hypnosis audio recordings lasting about 20 minutes, each with suggestions for a hypnotic induction, relaxation and greater mindfulness.

The second group did not take part in the intervention.

Intervention material focused on present-moment awareness, nonjudgmental awareness of the five senses, nonjudgmental awareness of thoughts and feelings, self-hypnosis, compassion for self and others, awareness of personal values and meaning in life and transition to long-term practice of mindful hypnotherapy, Elkins said.

At study's end, the intervention group reported a large decrease in stress and a significant increase in mindfulness. Most were highly satisfied with the number of sessions, the ease of home practice and the clarity of content, Elkins said. The average participant practiced almost every day, and overall satisfaction with the intervention was 8.9 on a scale of 10.

In comparison, those who did not participate in the intervention reported no significant difference between pre- and post-study stress level.

A limitation of the study was its small sample size, Elkins said. Future studies of a larger number of people could be of value, as well as testing mindful hypnotherapy for such concerns as anxiety, depression or chronic pain, he said.

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Baylor University

Circular reasoning: Spiraling circuits for more efficient AI

image: Researchers from The University of Tokyo create a new integrated 3D-circuit architecture for AI applications with spiraling stacks of memory modules, which may help lead to specialized machine-learning hardware that uses much less electricity

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Institute of Industrial Science, The University of Tokyo

Tokyo, Japan - Researchers from the Institute of Industrial Science at The University of Tokyo designed and built specialized computer hardware consisting of stacks of memory modules arranged in a 3D-spiral for artificial intelligence (AI) applications. This research may open the way for the next generation of energy efficient AI devices.

Machine learning is a type of AI that allows computers to be trained by example data to make predictions for new instances. For example, a smart speaker algorithm like Alexa can learn to understand your voice commands, so it can understand you even when you ask for something for the first time. However, AI tends to require a great deal of electrical energy to train, which raises concerns about adding to climate change.

Now, scientists from the Institute of Industrial Science at The University of Tokyo have developed a novel design for stacking resistive random-access memory modules with oxide semiconductor (IGZO) access transistor in a three-dimensional spiral. Having on-chip nonvolatile memory placed close to the processors makes the machine learning training process much faster and more energy efficient. This is because electrical signals have a much shorter distance to travel compared with conventional computer hardware. Stacking multiple layers of circuits is a natural step, since training the algorithm often requires many operations to be run in parallel at the same time.

"For these applications, each layer's output is typically connected to the next layer's input. Our architecture greatly reduces the need for interconnecting wiring," says first author Jixuan Wu.

The team was able to make the device even more energy efficient by implementing a system of binarized neural networks. Instead of allowing the parameters to be any number, they are restricted to be either +1 or -1. This both greatly simplifies the hardware used, as well as compressing the amount of data that must be stored. They tested the device using a common task in AI, interpreting a database of handwritten digits. The scientists showed that increasing the size of each circuit layer could enhance the accuracy of the algorithm, up to a maximum of around 90%.

"In order to keep energy consumption low as AI becomes increasingly integrated into daily life, we need more specialized hardware to handle these tasks efficiently," explains Senior author Masaharu Kobayashi.

This work is an important step towards the "internet of things," in which many small AI-enabled appliances communicate as part of an integrated "smart-home."

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Institute of Industrial Science, The University of Tokyo