Culture

Oncotarget published "Occurence of RAS reversion in metastatic colorectal cancer patients treated with bevacizumab" which reported that a disappearance of RAS mutations in the plasma of about 50% of mCRCs treated with bevacizumab-based chemotherapy has been reported.

Using next-generation sequencing and real-time PCR approaches, these authors characterized the primary tumor and paired liver metastases in 28 RAS mutant mCRCs.

RAS mutant alleles are at the same percentage in PT and liver metastases in the control group, while a significant reduction of the level of RAS mutations was detected in 57.1% of cases in group 1 and in 8.3% of cases in group 2. Differences among groups are statistically significant.

Most mCRC patients treated with bevacizumab-containing regimens experience a strong reduction of RAS mutant cells, suggesting bevacizumab as particularly active against RAS mutant cells.

This Oncotarget finding might have potential therapeutic implications, as anti-EGFR could be reconsidered in primarily RAS mutant patients reverted to a wild-type status after bevacizumab exposure.

Dr. Samantha Epistolio from The EOC said, "The overall survival (OS) for patients with metastatic colorectal cancer (mCRC) has markedly improved within the last 2 decades, reaching approximately 30 months."

Thus, it is crucial to perform an extended RAS and BRAF mutation analysis before considering EGFR inhibitors in mCRC patients.

In first-line, data support the use of anti-EGFR MoAbs in patients with left-sided, RAS and BRAF wild-type tumors, whilst bevacizumab is preferred in combination with chemo-doublets or -triplet in RAS/BRAF mutated tumors or RAS/BRAF wild-type right-sided primaries.

More recently, two intriguing studies showed that cetuximab sensitivity might be restored either in RAS/BRAF wild-type mCRC patients who acquired resistance to cetuximab-based therapy in first-line therapy or in those with primarily RAS mutated tumors treated with bevacizumab-containing regimens in second-line.

These studies may lead to the hypothesis that anti-angiogenic agents through action on RAS mutated cells could revert tumors from RAS mutant to RAS wild-type status, which theoretically could lead to the possibility to treat these patients with anti-EGFR MoAbs, otherwise precluded.

To substantiate these findings at tissue level, here they analyzed molecular changes in RAS mutated mCRC patients treated with chemotherapy alone or in combination with bevacizumab, by examining tumor tissue samples before and after the systemic therapy using two independent methodologies, next-generation sequencing and real-time PCR.

The Epistolio Research Team concluded in their Oncotarget Research Output, "this retrospective observational study, strongly suggests the existence of a link between bevacizumab exposure and RAS status changes in mCRC patients. In addition to other reports using liquid biopsies, our findings on tissue samples corroborate the hypothesis that bevacizumab could revert RAS mutant mCRC to a wild-type pattern, conceptually opening to the possibility to treat with anti-EGFR MoAbs mCRC patients otherwise excluded based on initial RAS mutated status."

COLUMBUS, Ohio - Although some people may yearn for sports to be free of political or racial divisiveness, a new study shows how impossible that dream may be.

Researchers found that Americans' views on two hot-button issues in sports were sharply divided by racial, ethnic and political identities. In addition, their opinions on topics unrelated to sports, like the Black Lives Matter (BLM) movement, also were linked to their beliefs about the two sports issues.

The study analyzed opinions on whether college athletes should be paid and whether it is acceptable for pro athletes to protest racial injustice by not standing during the national anthem.

The gap between Americans on those two topics was sometimes stark - there was an 82-percentage-point difference in whether people supported athletes protesting during the national anthem (a low of 13% to a high of 95%) depending on combinations of race, political orientation, voting intentions and beliefs about issues like BLM.

"Sports are and have increasingly become a central part of the culture wars," said Chris Knoester, co-author of the study and associate professor of sociology at The Ohio State University.

"Sports are not a neutral ground."

The study, published online recently in the journal Du Bois Review: Social Science Research on Race, was co-authored by Rachel Allison, associate professor of sociology at Mississippi State University, and David Ridpath, associate professor of sports administration at Ohio University.

While many people believe the political divide concerning sports found in this study is a modern phenomenon, it really is not, Allison said.

"We like to think that sport is all about fun and entertainment, what we like to do or watch outside of our 'real' lives at work or in our families, and so in a sphere somehow outside of politics," she said.

"But the history of sport shows that it has never been outside of the political. Our study shows that continues to be the case."

Data for the study came from the online Taking America's Pulse 2016 Class Survey, designed and run by researchers at Cornell University and the GfK Group. The survey included 1,461 Americans.

Overall, the study found white adults were particularly likely to be opposed to paying college athletes (69%) and protests during the national anthem (73%). Black adults were especially likely to be supportive, with only 29% and 32%, respectively, opposed to these rights for athletes.

Latino adults and other adults of color were generally more supportive of these rights for athletes than white adults, but not as supportive as Black adults.

"In large part, we think these racial and ethnic differences occur because paying college athletes and allowing protests during the national anthem are frequently seen as antiracist actions particularly supporting Black athletes," Knoester said.

Other results in the study support this, particularly those related to Americans' beliefs about two race-related issues outside of sports.

One issue was racial discrimination in education: Participants were asked whether white students, or Black and Latino students, are advantaged in U.S. educational institutions.

The second issue was BLM. Survey participants were asked whether BLM advocates for Black lives mattering more than other lives.

Participants' beliefs on these two issues were strongly linked to their views on paying colleges athletes and athlete protests, the study found. As expected, the impact of these beliefs was compounded by the race and ethnicity of those surveyed.

White adults who were upset about BLM and who believed Black and Latino students were advantaged in education had a 75% predicted probability of being opposed to athletes being paid and an 85% probability of being opposed to athletes protesting.

Meanwhile, Black adults who believed white students were advantaged and who supported BLM had a 28% predicted probability of opposing athlete payments and a 21% probability of opposing athlete protests.

Self-identified conservativism and intentions to vote for Donald Trump for president (the survey was done in the month before the 2016 election) were also strongly linked to opposing pay for college athletes and pro athlete protests. Liberals and those intending to vote for Hillary Clinton were much more supportive of athletes' rights on both issues.

"We found that race, ethnicity and political beliefs all were linked to views about these two sports issues," Ridpath said.

"While political views were important, they did not completely erase the effects of people's race and ethnicity."

For example, it wasn't just conservative white adults who opposed paying college athletes. White adults who identified as middle-of-the-road politically were also generally opposed to paying college athletes (a 66% predicted probability).

Meanwhile, Black adults with moderate political views had only a 35% probability of being opposed. Other people of color with moderate political views were about 50/50 on opposing payment to college athletes.

Combining various identities solidified opposition or support on these two issues, the study found.

For example, a Black adult who was extremely liberal, intended to vote for Clinton, who thought white students were advantaged in education and who didn't think BLM inappropriately valued Black lives had a 13% predicted probability of being opposed to athletes' protests during the national anthem.

Meanwhile, a white adult who was extremely conservative, intended to vote for Trump, thought white students were not advantaged and believed BLM inappropriately valued Black lives had a 95% predicted probability of being opposed to athlete protests.

Since the data in this study was collected, public opinions have appeared to shift somewhat toward the rights of college athletes to get paid and pro athletes to protest, Knoester said. And those shifts have translated into policy changes.

NCAA college athletes have recently been given the opportunity to financially benefit from their name, image and likeness.

And the International Olympic Committee recently gave athletes more scope to protest at the Tokyo games, although significant restrictions remain.

But the controversies are likely to persist, and politics and race will remain a presence in sports, Knoester said.

"Racial and political issues are a part of society, so they will be a part of sports," he said.

DALLAS, July 15, 2021 -- Statement Highlights:

The new scientific statement, "Primary Care of Adult Patients After Stroke," acknowledges the importance of primary care in the system of care for patients with stroke, summarizing the available literature and providing a roadmap for holistic, goal-directed and patient-centered care.

The statement is published today in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

Primary care professionals provide essential comprehensive and consistent care to patients after a stroke. Most people will seek guidance from their primary care team to reduce their high risk for recurrent stroke, prevent complications and optimize overall well-being. It outlines the need for comprehensive post-stroke management that includes engaging caregivers and family members to support the patient.

Stroke is a complex disease with many causes, consequences and treatments. According to the statement, approximately 800,000 U.S. adults will have a new stroke each year, and 10% will die within 30 days. At the time of their stroke, approximately 5% of patients younger than 55 years of age and 40% over 85 years have moderate disability. By 90 days after a stroke, new stroke-related disability of at least moderate severity develops in 10% of younger adults to 30% of adults over age 65 years. There are about 7 million adults in the U.S. living with stroke.

The first primary care appointment after a stroke should occur soon after discharge from the acute care or rehabilitation hospital, generally within 1-3 weeks. The current average interval to first medical visit for patients discharged home after stroke is 27 days. An earlier post-stroke visit may reduce hospital readmission and address inadvertent gaps in care that may exacerbate the high risk for stroke recurrence that marks the first three months after hospital discharge.

Screening at the first and all subsequent appointments should include assessing new or chronic risks for recurrent stroke such as high blood pressure, high cholesterol, diabetes, atrial fibrillation and blockage in the carotid or other arteries.

Additional screening is also important for complications including anxiety or depression, cognitive impairment, bone fracture and fall risk, osteoporosis, pressure ulcers and post-stroke seizures.

Specialist referrals should be recommended for any of these complications as appropriate.

"In this statement, we affirm in a new way the role of the primary care professional in caring for people with stroke. The core functions of primary care as a specialty include: 1) diagnosis and management of acute symptoms, 2) chronic disease management and 3) disease prevention," said Walter N. Kernan, M.D., chair of the statement writing group and a professor of medicine at Yale University School of Medicine, in New Haven, Conn. "Primary care professionals can ensure consistent and comprehensive care for the full needs of patients, including coordinating any additional care or services patients may need from community services providers or from subspecialty health care providers."

Patients who experience long COVID have reported more than 200 symptoms across 10 organ systems*, in the largest international study of 'long-haulers' to date, led by UCL scientists together with a patient-led research collaborative.

For the study, published in the Lancet's EClinicalMedicine, patient researchers who connected through the Body Politic online COVID-19 support group created a web-based survey designed to characterise the symptom profile and time course in patients with confirmed or suspected long COVID, along with the impact on daily life, work, and return to health.

With responses from 3,762 eligible participants from 56 countries, the researchers identified a total of 203 symptoms in 10 organ systems; of these, 66 symptoms were tracked for seven months. The most common symptoms were fatigue, post-exertional malaise (the worsening of symptoms after physical or mental exertion), and cognitive dysfunction, often called brain fog.

Of the diverse range of symptoms, others included: visual hallucinations, tremors, itchy skin, changes to the menstrual cycle, sexual dysfunction, heart palpitations, bladder control issues, shingles, memory loss, blurred vision, diarrhea, and tinnitus.

The research team, who have all had or continue to have long COVID, are now calling for clinical guidelines on assessing long COVID to be significantly widened beyond currently advised cardiovascular and respiratory function tests to include neuropsychiatric, neurological, and activity intolerance symptoms.

Furthermore, with large numbers of long haulers 'suffering in silence', the authors advocate that a national screening programme, accessible to anyone who thinks they have long COVID, should be undertaken. Given the heterogeneous (diverse) make-up of symptoms that affect multiple organ systems, it is only by detecting the root cause that patients will receive the correct treatment.

Explaining the study, senior author Dr Athena Akrami (neuroscientist at the Sainsbury Wellcome Centre at UCL) said: "While there has been a lot of public discussion around long COVID, there are few systematic studies investigating this population; hence relatively little is known about its range of symptoms, and their progression over time, the severity, and expected clinical course (longevity), its impact on daily functioning, and expected return to baseline health. In this unique approach, we have gone directly to 'long haulers' around the world in order to establish a foundation of evidence for medical investigation, improvement of care, and advocacy for the long COVID population. This is the most comprehensive characterisation of long COVID symptoms, so far."

The survey was open to those aged 18 or over who had experienced symptoms consistent with COVID-19, including those with and without positive SARS-CoV-2 test. It consisted of 257 questions.

In order to characterise long COVID symptoms over an extended duration, analysis of survey data was limited to respondents with illnesses lasting longer than 28 days and whose onset of symptoms occurred between December 2019 and May 2020, allowing analysis of symptoms from week one to month seven.

While the study did not estimate how common long COVID is overall, other studies have estimated that one in seven people have some symptoms 12 weeks after a positive test result (from the Office for National Statistics), or almost 30% of people 12 weeks after symptomatic disease (from Imperial College London's REACT study).

Survey summary

In this long COVID cohort, the probability of symptoms lasting beyond 35 weeks (eight months) was 91.8%. Of the 3,762 respondents, 3,608 (96%) reported symptoms beyond 90 days, 2,454 (65%) experienced symptoms for at least 180 days (six months) and only 233 had recovered.

In those who recovered in less than 90 days, the average number of symptoms (11.4 out of 66 symptoms that were measured over time) peaked at week two, and for those who did not recover in 90 days, the average number of symptoms (17.2) peaked at month two. Respondents with symptoms over six months experienced an average of 13.8 symptoms in month seven. During their illness, participants experienced an average of 55.9 symptoms (out of the longer list of 203 measured in the study), across an average of 9.1 organ systems.

89.1% of participants experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 45.2% reported requiring a reduced work schedule compared to pre-illness and 22.3% were not working at all at the time of the survey.

Dr Akrami said: "For the first time this study shines a light on the vast spectrum of symptoms, particularly neurological, prevalent and persistent in patients with long COVID.

"Memory and cognitive dysfunction, experienced by over 85% of respondents, were the most pervasive and persisting neurologic symptoms, equally common across all ages, and with substantial impact on work.

"Headaches, insomnia, vertigo, neuralgia, neuropsychiatric changes, tremors, sensitivity to noise and light, hallucinations (olfactory and other), tinnitus, and other sensorimotor symptoms were also all common, and may point to larger neurological issues involving both the central and peripheral nervous system.

"Along with the well-documented respiratory and cardiovascular symptoms, there is now a clear need to widen medical guidelines to assess a far wider range of symptoms when diagnosing long COVID. Furthermore, there are likely to be tens of thousands of long COVID patients suffering in silence, unsure that their symptoms are connected to COVID-19. Building on the network of long COVID clinics, which take GP referrals, we now believe a national programme could be rolled out into communities able to screen, diagnose and treat all those suspected of have long COVID symptoms."

The research team's future work will focus on emerging topics in long COVID: mental health outcomes, diagnostic and antibody testing, symptom clustering, and socioeconomic impact from the illness.

Study limitations

There are several limitations to this study. First, the retrospective nature of the study exposes the possibility of recall bias. Second, as the survey was distributed in online support groups, there exists a sampling bias toward long COVID patients who joined support groups and were active participants of the groups at the time the survey was published. Additionally, despite eight translations and inclusive outreach efforts, the demographics were strongly skewed towards English speaking (91.9%), white (85.3%) respondents.

Symptom prevalence - summary

Top three symptoms: Fatigue 98.3%, post-exertional malaise (PEM) 89.0%, and brain fog and cognitive dysfunction in 85.1% (3,203) of respondents.

The top three most debilitating symptoms listed by patients were: fatigue (2,652 patients), breathing issues (2,242), and cognitive dysfunction (1,274).

Symptoms remaining at six months

A total of 2,454 (65.2%) respondents were experiencing symptoms for at least six months. Over 50% experienced the following symptoms: fatigue (80%) post-exertional malaise (73.3%), cognitive dysfunction (58.4%), sensorimotor symptoms (55.7%), headaches (53.6%), and memory issues (51%). In addition, between 30%-50% of respondents were experiencing the following symptoms after six months of symptoms: insomnia, heart palpitations, muscle aches, shortness of breath, dizziness and balance issues, sleep and language issues, joint pain, tachycardia, and other sleep issues.

A small regulatory RNA found in many problematic bacteria, including Escherichia coli, appears to be responsible for managing the response of these bacteria to environmental stresses. Professor Charles Dozois from Institut national de la recherche scientifique (INRS) and doctoral student Hicham Bessaiah see a promising avenue for more effective treatment of antibiotic-resistant bacteria. Their results have been published in the journal PLOS Pathogens.

In conducting their work, the researchers and their team observed that the elimination of this regulatory RNA sequence had an effect on urinary tract infections related to E. coli. These infections are among the world's most common, especially in women, but they are sometimes hard to treat due to antibiotic resistance.

E. coli is normally found in the intestinal flora, but when it migrates to the bladder, the conditions there are completely different. The bacteria have to withstand the environmental stressors in order to cause a bladder infection. "Without the regulatory RNA, the bacteria is more sensitive to changes in the environment and loses its infectious capacity," explained the doctoral student.

Inhibiting the RNA sequence

The idea is to block the RNA and make the bacteria less infectious, especially in the case of chronic infection, which can lead to increased resistance to treatment. If the bacteria are less resistant to stress, it will be more vulnerable to the host's immune response. Regulation of the systems that make it virulent will also be disrupted.

"People with recurrent urinary tract infections take antibiotics regularly. This leads to resistance and limits treatment options, which is why it's important to find alternatives," explained Professor Dozois.

The relationship between virulence and stress isn't unique to urinary tract infections. The regulatory RNA sequence studied by the researchers is also found in a number of other major pathogenic bacteria. Given that the RNA seems to impact multiple functions, the research group is working to better understand the mechanisms of regulation before pursuing additional research on antibiotic-resistant strains of bacteria.

Combined perceptions of the risk and availability of cannabis influence the risk of cannabis use more than perceived risk and perceived availability alone, according to a new study at Columbia University Mailman School of Public Health. Researchers observed that those who perceived cannabis as low-risk and available were more likely to report using the drug in the past year and almost daily compared to those individuals who perceived cannabis as high-risk and unavailable. This is the first study to consider the joint effects of perceived risk and perceived availability. The results are published in the journal Drug and Alcohol Dependence.

"Our study described the evolution of joint perceptions of cannabis risk and availability from 2002-2018 and estimated the relationship between combined perceptions and past-year cannabis use, frequent use, and cannabis use disorder," said Natalie Levy, MPH, doctoral student in the Department of Epidemiology at Columbia Mailman School, and first author. "Studying perceived risk and availability in conjunction revealed more nuanced patterns than considering each perception in isolation.."

Using data on 949,285 participants from the National Surveys on Drug Use and Health from 2002-2018, researchers observed that the prevalence of perceiving cannabis use as low-risk doubled over this period while the prevalence of perceiving cannabis as available increased only marginally. When looking at joint categories of perceived risk and perceived availability, they found that prevalence of perceiving cannabis as both low-risk and available increased, from 17 percent in 2002 to 36 percent in 2018 while the proportion of the population perceiving cannabis as high-risk and available or high-risk and unavailable declined. By 2018, a larger proportion of the population perceived marijuana as low-risk and available (36 percent) than both high-risk and available and high-risk and unavailable, at 26 percent and 27 percent, respectively.

Individuals who perceived cannabis as low-risk were six times more likely to have used cannabis in the past-year than individuals who perceived the drug as high-risk. Similarly, individuals who perceived cannabis as available were five times more likely to have used cannabis in the past year than individuals who perceived it as unavailable. However, individuals who perceived marijuana as both low-risk and available were 22 times more likely to have used the drug in the past year than those who perceived cannabis as high-risk and unavailable.

In 2018, most individuals who reported no past-year cannabis use perceived cannabis as high-risk, whether or not they distinguished between its availability or non-availability. In contrast, the majority of individuals who used cannabis in the past year perceived the drug as low-risk and available and this perception rose to even higher levels among those reporting frequent use.

Cannabis perceptions also differed by gender. Overall, a larger proportion of males viewed cannabis as lower risk and more available compared with females, but patterns differed by age. "We found minimal differences in perceptions by gender in the 12-17-year age group while among all those 18 years of age and older, the prevalence of perceiving cannabis as low-risk and available was higher for males than females; perceiving cannabis as high-risk and unavailable was more common among females in every year," noted Levy.

"Our results provide an important starting point for exploring specific hypotheses regarding the effects of perceptions on individual cannabis outcomes and highlight the importance of exploring perceived risk and availability together," said Silvia Martins, MD, PhD, Columbia Mailman School associate professor of Epidemiology, director of the Substance Use Epidemiology Unit of the Department of Epidemiology, and senior author. "For example, our findings suggest that prevention efforts that focus only on the risks of cannabis use may be less effective among individuals who perceive cannabis as easily available.

"Trends in perceptions - especially among younger age groups -- may also identify priority groups for intervention," observed Levy. "Further understanding of these relationships is particularly important in light of rapidly changing cannabis policies, a contextual factor that may influence perceptions of both risk and availability of cannabis and subsequent use."

What The Study Did: In this observational study using data from the Veterans Health Administration for 2,344 U.S. veterans hospitalized with COVID-19, remdesivir treatment was associated with prolonged hospitalization but wasn't associated with improved survival.

Authors: Michael E. Ohl, M.D., M.S.P.H., of the Carver College of Medicine at the University of Iowa in Iowa City, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.14741)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2021.14741?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=071521

About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

What The Study Did: Among the few New York state public school districts providing full-time in-person elementary school instruction during the COVID-19 pandemic, most districts served predominately white students, rural/suburban students and children who were not disadvantaged (children who were not from a low-income family, were not English language learners, did not have homelessness, and did not have a disability).

Authors: Ashley M. Fox, Ph.D., M.A., of the University at Albany, State University of New York (SUNY), is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.17267)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2021.17267?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=071521

About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

By combining oil drops with water containing a detergent-like substance, the scientists found they could produce artificial swimmers that are able to swim independently and even harvest energy to recharge.

The oil droplets use fluctuating temperature changes in their surrounding environment to store energy and to swim. When cooled, the droplets release thin 'tail-like' threads into the environment. The friction generated between the tails and surrounding fluid, pushes the droplet causing them to move. On heating, the droplets then retract their tails returning to their original state, and harness the heat from their environment to recharge.

The researchers show that the droplets recharge multiple times and are able to swim for periods of up to 12 minutes at a time.

Dr Stoyan Smoukov, Reader in Chemical Engineering at Queen Mary University of London and author of the study, said: "In biology, research shows that to create even the simplest artificial cells we need over 470 genes. However, through this international collaboration, we show that just by using a few simple and inexpensive components we can create a new type of active matter that can change shape and move just like a living thing."

"We hope that this study will open up the opportunity for people to engage in cutting-edge science. As the only equipment needed is a simple optical microscope, people could create these microswimmers with the most basic laboratory set-ups, or even at home. With thousands of swimmers per drop of water, it's a world in a drop situation. And when it costs 7p per teaspoon, there's plenty for everyone."

Other types of artificial swimmers exist however their movements are either driven by chemical reactions, which create bubbles that propel the swimmers through fluids, or by physical forces such as magnetic or electric fields. Instead, this new class of swimmers, which are around the size of a red blood cell, are able to spontaneously assemble and move without using external forces.

As the swimmers are not harmful to other living things, the scientists hope they could be used to study the basic interactions between living organisms such as bacteria and algae.

"In nature we often see large numbers of organisms such as bacteria, grouping together but our understanding of how these organisms interact with each other is incomplete. By mixing our simple artificial swimmers with groups of living organisms we could develop a clearer picture of how biological microswimmers communicate with each other. For example, do they only communicate due to the physical act of 'bumping' into each other, or are there other chemicals or signals released into the environment essential for their interaction."

Adenovirus vaccine vectors, such as the ChAdOx1 nCov-19 construct which has risen to prominence as a major vaccine for COVID-19, may generate robust long-term immune system responses, according to scientists from the Universities of Oxford and the Cantonal Hospital St.Gallen, Switzerland.

Writing in the journal Nature Immunology, they detail an investigation into one of the key features of adenovirus vaccines - their ability to generate strong and sustained populations of the 'killer' T-cell element of the immune system.

In an animal model, they observed that adenoviruses are able to get into long-lived tissue cells, known as fibroblastic reticular cells, which in turned formed small, well organised clusters, acting as 'training grounds' for these T-cells, appearing to explain how these vaccines sustain robust immune system responses.

Paul Klenerman, Sidney Truelove Professor of Gastroenterology at the University of Oxford's Nuffield Department of Medicine, and one of the lead authors of the paper, said:

'Millions of people will have received adenovirus vaccines around the world, not only the Oxford-AstraZeneca vaccine, but the J&J vaccine, and also the Chinese and Russian versions. The ultimate goal with these vaccines is the induction of long-term immune system protection using both antibodies and T-cells. This research helps us to understand more on the process of vaccination, and why the effects on killer T-cells are so prolonged.'

The researchers show that adenovirus vectors can target specific cells - known as stromal cells in tissues such as the lung - generating antigen 'depots' in these long-lived cells. These stromal cells were originally thought just to provide an inert scaffold for the tissues, but it appears that they are very dynamic cells with a major role in immune control. The long lived nature of the cells means that the antigen can be 'shown' to the immune system many times, effectively boosting the response, a critical element of generation of protective T-cells.

They were also able to investigate other mechanisms which may explain the particular efficacy of adenovirus vectors, including the key chemical messenger involved in signalling to T cells. This is a factor called IL-33 - a so-called "alarmin" released when the stromal cells receive signals of distress. IL-33 acts to strongly boost to the metabolism of the T cells, resulting in effectively more energetic cells and a highly protective immune response.

Burkhard Ludewig, Professor at the University of Zurich, and Head of the Medical Research Center, Cantonal Hospital St. Gallen, Switzerland, also a lead author of the paper, said:

'Adenoviruses have co-evolved with humans over a very long time, and learned a lot about the human immune system in the process. Viruses are always the best teachers, and here they have taught us an important lesson about how best to boost killer T cell responses. The T cells that come from these cellular training camps appear to have a very high level of "fitness". Hopefully we can put this to good use in designing new vaccines - vaccines that we still desperately need for diseases such as TB, HIV, hepatitis C and cancers.'

The researchers will now continue to investigate these particular pathways for immunization against emerging pathogens, both in pre-clinical models, and clinical studies, with the goal of helping to accelerate further development of crucial vaccines.

During mating in wildlife species, males transfer millions of sperm into the female genital tract. On the way to the egg cell the sperm have to pass through the genital tract. Very few of the sperm cells actually succeed in passing through and reaching the vicinity of the egg cell. Those that do will then be conditioned for fertilisation. Mechanisms underlying sperm selection and, therefore, reproductive success are largely unknown, as their experimental study in the living organism is very difficult for both ethical and practical reasons. A deeper understanding of the factors which favour successful sperm migration and selection in the context of species-specific reproductive systems would be of great fundamental as well as of applied interest, since for threatened wildlife species this will help recognise reproductive problems and optimise assisted reproduction techniques such as artificial insemination.

The scientist team developed a spatio-temporal computer simulation model of the mammalian female genital tract, in which individual sperm cells were treated as independent agents equipped with a set of biophysical characteristics specifying concrete properties and subjected to specific rules for motion and interaction with the female genital tract. The first implementation used data on bovine genital tract geometry and the biophysical properties and principles of sperm motion of bovine sperm as observed in test tubes. Thus, sperm preferentially swam against a fluid stream (positive rheotaxis) and moved along wall structures (thigmotaxis).

In order to ensure that the model was reasonably realistic in depicting salient features of the interaction between sperm and the female genital tract, the simulation results were compared with published data derived from cattle. The simulation results demonstrated a close match with the observed timing and number of sperm actually reaching the entry of the oviducts.

"As expected, we found that physical sperm characteristics such as velocity and directional stability are essential for successful sperm. In addition, the ability to swim against the mucus flow of cervical secretions as well as the ability of sperm to align to epithelial walls of the genital tract turned out to have a tremendous impact on the chances of a successful transit of sperm to the oviduct," explains Jorin Diemer, doctoral student at the Humboldt-Universität zu Berlin. Karin Müller, leader of the andrology lab at Leibniz-IZW, concludes, "that these identified characteristics of sperm should be considered in future attempts to condition sperm in artificial selection procedures since natural selection processes are normally bypassed in reproductive test tube technologies." This is of particular importance because a species-specific optimal time window for sperm accumulation in the oviduct exists in relation to the timing of ovulation when the oocyte is liberated for fertilisation. "The big advantage of our model is its flexibility, it can be extended and generalised to other systems," highlights Edda Klipp, leader of the Theoretical Biophysics department at Humboldt-Universität zu Berlin. Predictions from this computer simulation system have the potential to improve assisted reproduction in endangered species, livestock and perhaps humans without using animal experiments.

Repairing complex electrical appliances is time consuming and rarely cost-effective. The working group led by Prof. Dr. Karl Mandel, Professorship of Inorganic Chemistry at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), has now developed a smart microparticle that enables defective components in these appliances to be identified more quickly and easily by using light signals. In the long-term, this could make repairs easier and extend the operating life of devices. The results have been published in the journal Advanced Functional Materials.

To identify defective components in a device, particles known as supraparticles are applied to the individual parts. These particles measure between one and ten micrometres and under black light they provide information about the component's identity and temperature history (the temperatures the specific component was recently subjected to) by emitting blue, green and red light. This allows the device to be checked for defects while it is still assembled. The signal ratio between building blocks emitting green and red light determines the identity of the component. The maximum temperature can be read from the signal ratio of blue and green particles. If a specific temperature limit is exceeded, the blue signal irreversibly loses intensity. An overheated and therefore usually damaged micro-component can be detected by the weaker blue light signal it emits. The developed particles make it easier and faster to repair complex electrical devices and extend their operating life.

The supraparticles themselves consist of organic and anorganic nanoparticle building blocks that communicate information only when they are combined. The structure and quantity ratios of the nanoparticles determine the identity signals and temperature sensitivity. By changing the composition of the smart microparticles, the temperature sensitivity and the identity signal can be adapted to a specific product.

Fukuoka, Japan--At this very moment, the billions of neurons in your brain are using their trillions of connections to enable you to read and comprehend this sentence.

Now, by studying the neurons involved in the sense of smell, researchers from Kyushu University's Faculty of Medical Sciences report a new mechanism behind the biomolecular bonsai that selectively strengthens these connections.

How neuronal circuits remodel themselves over time, especially during early development, is an open question in neurobiology. At the start of neuronal development, neurons form excessive amounts of connections that are gradually eliminated as others are strengthened.

Studying a type of olfactory neuron known as a mitral cell in mice, the research team found that the protein BMPR-2 is one of the key regulators of selective stabilization of neuron branching and that the strengthening only happens when the branch receives signals from other neurons.

"A main reason we use olfactory neurons is because they are easy to access and study, and mitral cells develop only a single branch," explains Shuhei Aihara, first author of the study published in Cell Reports.

"When an olfactory neuron detects a specific molecule that we smell, it sends the signal to a specific 'way station' in the brain's olfactory bulb called a glomerulus. That signal is then relayed to the brain through mitral cells. One mitral cell receives signals for one specific smell."

At a very early stage in development, these mitral cells send branches into many glomeruli. As time progresses, these branches--known as dendrites--are pruned away to leave only a single, strong connection. The research team set out to uncover what kind of molecular cues caused one branch to be favored over others.

After analyzing candidate factors known to control dendritic growth and remodeling from extrinsic signals, the team focused on the protein BMPR-2.

"When we disrupted BMPR-2, mitral cells would fail in the selective stabilization and form multiple connections to multiple glomeruli," explains Aihara. "In our next step, we found that BMPR-2 is bound to a protein called LIMK, and only when BMPR-2 is activated by the cell-signaling protein called BMP does it release LIMK into the cell."

LIMK is known to activate the process to assemble actin, the cell's 'skeleton.' Once activated, actin begins to build long fibers that stabilize dendrites.

However, this still did not explain how this mechanism strengthens specific dendrites. The team's next step was to find the elements that activate LIMK. Their investigation led them to identify a well-known neurotransmitter, glutamic acid, as one of the factors that kicks off the process.

"Glutamic acid is required for signals to be transmitted between neurons. Taken together, this means that both BMP and neural signals are necessary to form actin, thereby inducing the construction of a stable dendrite," states Aihara.

"It's like the brake and accelerator in your car. You need to release the brake, in this case BMPR-2 releasing LIMK, and then press on the accelerator--the neurotransmitter signal--for your machinery to move forward. The necessity of simultaneous control, or inputs, is the basis of selective branch stabilization."

Takeshi Imai, who led the team, concludes, "Hopefully these new insights into neural development can lead to further understanding of the fundamental mechanisms behind critical brain functions and possible treatments into pathologies underlined by synaptic dysfunction."

"Our next step is to find the factors that promote dendrite pruning, and we also want to see if this mechanism in the olfactory bulb is fundamental throughout the neocortex."

New research will help doctors identify, treat and prevent potentially dangerous irregular heartbeats in patients with hypertrophic cardiomyopathy (HCM), a common heart condition in which the heart thickens and strains to pump blood.

These chaotic heart rhythms are known as atrial fibrillation. Atrial fibrillation can be asymptomatic, but it can lead to blood clots, stroke or even heart failure. The new research, from an international team of doctors and scientists, identifies risk factors for major atrial fibrillation outcomes, such as the need for procedures or hospitalization for more than 24 hours, in patients with hypertrophic cardiomyopathy.

Age was the dominant predictor, the researchers found. But they also identified a list of other predictors, including obesity as measured by body mass index (BMI). Obesity was particularly important in younger patients, the researchers conclude.

"The latter finding points out the importance of weight loss and exercise in HCM patients," said researcher Christopher Kramer, MD, the chief of the Division of Cardiovascular Medicine at UVA Health, Virginia's only designated Center of Excellence by the Hypertrophic Cardiomyopathy Association. "Until only recently, exercise was thought to be contraindicated in HCM. This is no longer the case based on recent studies."

Atrial Fibrillation in Hypertrophic Cardiomyopathy

Like atrial fibrillation, hypertrophic cardiomyopathy often goes undiagnosed. It is, however, the most common inheritable heart disease, and it is the most common cause of sudden cardiac death in young athletes.

Atrial fibrillation is a common complication among patients with hypertrophic cardiomyopathy. Previous studies have focused on detecting atrial fibrillation, as patients may require blood thinners to prevent stroke. But Kramer and his colleagues wanted to look at atrial fibrillation outcomes to better identify those who need early or tailored interventions.

The researchers examined data from 2,631 patients, identifying 127 major end- points, such as needing hospitalization or catheter ablation, in 96 of the patients. Key risk factors for reaching an endpoint included age; BMI; size and function of the heart's left atrium; moderate or severe failure of the heart's mitral valve to close completely; and history of arrhythmia (irregular heartbeat).

Obesity was a stronger risk factor in younger patients than older ones. The remaining risk factors were greater risk factors for middle-aged and older patients.

The researchers say their findings can be used to create a risk-assessment tool for patients, to identify those at risk and help keep them out of the hospital.

"These findings will help physicians who treat HCM patients, as they can target the risk factors that lead to atrial fibrillation," Kramer said.

Scientists have developed a rapid, highly accurate test to detect antibodies against the spike protein of SARS-CoV-2 in human serum, opening a new avenue for understanding the full extent of the pandemic and evaluating the effectiveness of vaccines.

In the 18 months since the emergence of Covid-19 pandemic, great strides have been made in discovering and inventing various approaches to track and control the spread of the SARS-CoV-2 virus. Rapid and accurate diagnosis has always been vital in this regard. The gold standard since the beginning of the pandemic has been the RT-PCR method; however, it is time-consuming, labor-intensive, and requires sophisticated equipment, and can only detect the presence of viral RNA in the samples.

A team of scientists from Japan, including Professor Manabu Tokeshi of Hokkaido University's Faculty of Engineering, have developed a 20-minute test to detect and quantify antibodies against SARS-CoV-2 in human serum. Their findings were published in the journal Biosensors and Bioelectronics.

It is estimated that between 40% to 45% of individuals infected with SARS-CoV-2 are asymptomatic -- despite being infected, they do not develop any symptoms of the disease. Identifying individuals who may have had asymptomatic Covid-19 is important to understanding the full extent of the pandemic. RT-PCR can only detect the presence of the viral RNA in samples; individuals who have recovered from the pandemic will only have antibodies to the virus, which RT-PCR cannot detect.

There are commercially available tests to detect the presence of antibodies against SARS-CoV-2; however, the majority of these tests are inaccurate. Lateral flow immunoassay is one of the most common tests for diagnosis of Covid-19 based on antibody detection. While rapid, it is a qualitative method, and cannot be used for the quantification of antibodies. Further, the method does not scale well, resulting in a low cost efficiency.

The scientists developed a method of detecting antibodies against SARS-CoV-2 in human serum using a method called non-competitive fluorescence polarization immunoassay (FPIA). This method is not just rapid, but can also be used to quantify the antibodies. FPIA has been used in the food and medical industry; the team has previously made many innovations to the method and associated equipment, including the development of a portable fluorescence polarization analyzer.

FPIA requires fluorescently-labelled recombinant SARS-CoV-2 spike proteins (F-RBD) and human serum to be mixed together for the test. Individuals who have been infected with or vaccinated against SARS-CoV-2 will have anti-spike protein antibodies in their serum. When these antibodies bind to F-RBD, polarised light is emitted, while F-RBD alone emits depolarized light. By measuring the degree of polarisation using a fluorescence polarization analyser, the concentration of antibodies can be determined. The scientists optimised the test and evaluated it using samples of human serum from individuals diagnosed with Covid-19 and from those who had not been infected by SARS-CoV-2.

The test was demonstrated to be highly accurate, quick and easy to perform, with high throughput. This test requires about 20 minutes to complete, compared to about 2 hours for other tests; furthermore, the equipment required for the test is highly portable, weighing only 4.3 kg. Taken all together, these features make the test an excellent option for detecting and quantifying antibodies against SARS-CoV-2. The test can now be used for two purposes: screening large populations to determine the exact extent of the pandemic, and from evaluating the effectiveness of SARS-CoV-2 vaccines based on the antibody response.