Culture

More than half of people with acute COVID-19 infection continue to have persistent fatigue 10 weeks after their initial illness, according to a new study published November 9 in the open-access journal PLOS ONE by Liam Townsend of Trinity College Dublin, Ireland and colleagues.

Fatigue is one of the most common initial presenting complaints of people infected with SARS-CoV-2, the virus that causes COVID-19. The long-term consequences of COVID-19 have not been well-studied and concern has been raised that the virus has the potential to trigger a post-viral fatigue syndrome.

In the new study, researchers tracked fatigue, as well as patient characteristics including COVID-19 severity, laboratory markers, levels of inflammatory markers and pre-existing conditions, in 128 study participants who had previously been infected with SARS-CoV-2. The participants, all recruited from a post-COVID-19 outpatient clinic at St. James Hospital in Dublin, Ireland, were 54% female and averaged 49.5 years old (standard deviation ±15 years). 55.5% of the participants had been admitted to the hospital for their COVID-19 treatment while the remainder were treated as outpatients. On average, they were assessed for the study 72 days after discharge from a hospital or, if managed as an outpatient, after a timepoint 14 days following diagnosis.

Based on their score on the Chalder Fatigue Scale (CFQ-11), 52.3% (67/128) of study participants met the criteria for fatigue at the assessment point at least 6 weeks following COVID-19 infection. Only 42.2% of the patients (54/128) reported feeling back to their full health. Importantly, there was no association between COVID-19 severity, need for hospital admission, or routine laboratory markers of inflammation with the likelihood of experiencing persistent fatigue after infection. Though the study is limited in that the population cohort was predominantly white and Irish, and patients were only assessed at a single timepoint with no follow-up, the authors also found that female gender and a history of anxiety or depression was more common in the severe fatigue group (X2=9.95, p=0.002 for female; X2=5.18, p=0.02 for depression history).

The authors add: "This study highlights the burden of post-COVID fatigue. It also demonstrates that post-COVID fatigue is unrelated to severity of initial infection, so predicting its development is not easy."

More investment and important changes are needed to boost UK testing services, to tackle the COVID-19 pandemic and build a diagnostics service that will head off future UK health challenges, says a meeting report* published by the Academy of Medical Sciences today [Wednesday 11 November 2020].

The report highlights that the UK did not have an established national testing system at the start of the COVID-19 pandemic, so new systems had to be put in place rapidly. The Academy of Medical Sciences brought together 23 leading experts, to share learnings from the past ten months and discuss what changes should be made to strengthen future diagnostic testing services, at a virtual meeting on Friday 2 October 2020.

The resulting meeting report and a statement** from the Academy's Council ask for swift action to be taken to strengthen UK disease testing, including:

Enhancing collaboration across the NHS, universities and industry to make best use of their combined strengths. Representatives from these three sectors must be involved in the development of future testing strategies, with greater transparency and timely communication of decisions to all involved. This will inform academia and industry about how they can most usefully contribute.

Making sure that local laboratories can play their part in COVID-19 testing and support national approaches.

Developing and adopting more innovative ways of testing for COVID-19, for example pooling multiple samples for testing, testing for several viruses at the same time and improving packaging to speed up the analysis of samples.

Adopting a more flexible approach to regulation - also known as laboratory accreditation - so that as many laboratories as possible can contribute to national testing without unnecessary delays.

Providing longer term testing contracts to reduce any risks for companies wanting to carry out COVID-19 testing, and to enable them to contribute to current efforts.

Ensuring a sustainable workforce with a strategy to bring staff into testing laboratories, providing much needed career opportunities, including for recent graduates, in a challenging jobs market.

Professor Sir John Tooke FMedSci, Chair of the virtual roundtable, said:

"COVID-19 has shown us how important accurate, speedy diagnosis at scale is for fighting this infection. The pandemic required the expansion of UK testing services beyond anything we have ever needed in the past. At the beginning of the UK COVID-19 epidemic, important decisions around testing were necessarily made at speed. Inevitably, there were things that, with the benefit of hindsight, could have been done better and which we must address to cope with subsequent waves or future pandemics.

"We must continue to build on the collaborations between industry, academia and the NHS to take full advantage of all the talent and capabilities we possess. Despite its importance and many notable strengths the UK diagnostic sector is fragmented and underdeveloped. Now is the time to invest in our UK diagnostic services and build a system that can cope with the pandemic and whatever future health challenges we may face."

As the pandemic continues to spread over the autumn and winter months, the UK's testing capacity needs to be expanded further.

Helen Dent, Chief Operations Officer at British In Vitro Diagnostics Association (BIVDA) and attendee of the virtual roundtable, said:

"To carry out the number of tests needed, we have to bring in skills and capacity from across the UK and coordinate different sectors in a better way. This didn't happen enough in the early stages of the pandemic, for example smaller companies found it hard to get involved as the financial and contractual risks they faced were too large.

"There are a growing number of smaller biotech companies who are willing to pitch in and support the UK testing system. Let's find a way to get as many labs as possible involved so we can get the country through this pandemic while also putting much needed funds into our own economy."

Professor Sir Robert Lechler PMedSci, President of the Academy of Medical Sciences, said:

"One of the most wicked and unusual features of COVID-19 is that you can have it, not know you have it and yet still infect others. The fact that COVID-19 symptoms have commonalities with many other diseases such as the common cold means that testing is one of the most important tools to fight COVID-19, alongside handwashing and physical distancing, so that people can isolate and reduce the spread of infection. So it is vital that we do all we can to improve and strengthen our testing services to head off the pandemic.

"When testing services were rapidly expanded at the start of the UK epidemic, there was not enough energy put into building up partnerships between university research laboratories, the NHS and industry. This held up progress earlier in the year, but there are a few fantastic examples where collaboration increased testing capacity that we can learn from. For example, in Norfolk a local collaboration between the Norwich Research Park Partners has seen The Earlham Institute and the University of East Anglia (UEA) support the Norfolk and Norwich University Hospital to scale up COVID-19 testing capacity, leading to a seven-fold increase in test processing.

"The pandemic has now catalysed a level of cross sector collaboration we have never seen before. The crucial thing is to prioritise retaining and strengthening these bonds. If we manage to do this, we can build a diagnostic system that will be able to cope with further waves of COVID-19 infections, possible future epidemics and help meet the demands for tests for other diseases such as cancer and heart disease."

Professor Sir John Tooke added:

"Doing the best job of testing demands the inclusion of expert voices from NHS, academia and industry in developing plans, and ensuring that local efforts complement national strategy.

"To meet increasing testing requirements, we need faster accreditation for diagnostic laboratories, by cutting red tape to get as many labs as possible involved in the national testing effort. We have seen how new treatments can be approved more quickly during the pandemic without losing important safety and efficacy checks - the same needs to happen for accrediting laboratories doing testing.

"In the early stages of the pandemic many volunteer technicians and students were brought into testing laboratories. Many of these skilled volunteers have returned to their day jobs, so we now need to reinvest and train more laboratory staff to replenish this pool of workers. This will provide much needed employment opportunities, including for graduates, in a challenging jobs market.

"Finally we need to find new and innovative ways of testing for COVID-19 - and to make sure that the incredible discoveries being made in UK and international research institutes make it through to testing facilities. Innovative testing systems combined with hand washing, physical distancing and isolation will help us get a hold on the spread of infection and get us back to what we remember as 'normal' life - visiting grandparents, going to the theatre and football matches and travelling abroad safely."

HANOVER, N.H. - Tuesday, November 10, 2020 - A "molecular volume knob" regulating electrical signals in the brain helps with learning and memory, according to a Dartmouth study.

The molecular system controls the width of electrical signals that flow across synapses between neurons.

The finding of the control mechanism, and the identification of the molecule that regulates it, could help researchers in their search for ways to manage neurological disorders, including Alzheimer's disease, Parkinson's disease and epilepsy.

The research, published in Proceedings of the National Academy of Sciences, describes the first study of how the shapes of electrical signals contribute to the functioning of synapses.

"The synapses in our brain are highly dynamic and speak in a range of whispers and shouts," said Michael Hoppa, an assistant professor of biological sciences at Dartmouth and the research lead. "This finding puts us on a straighter path toward being able to cure stubborn neurological disorders."

Synapses are tiny contact points that allow neurons in the brain to communicate at different frequencies. The brain converts electrical inputs from the neurons into chemical neurotransmitters that travel across these synaptic spaces.

The amount of neurotransmitter released changes the numbers and patterns of neurons activated within circuits of the brain. That reshaping of synaptic connection strength is how learning happens and how memories are formed.

Two functions support these processes of memory and learning. One, known as facilitation, is a series of increasingly rapid spikes that amplifies the signals that change a synapse's shape. The other, depression, reduces the signals. Together, these two forms of plasticity keep the brain in balance and prevent neurological disorders such as seizures.

"As we age, its critical to be able to maintain strengthened synapses. We need a good balance of plasticity in our brain, but also stabilization of synaptic connections," said Hoppa.

The research focused on the hippocampus, the center of the brain that is responsible for learning and memory.

In the study, the research team found that the electric spikes are delivered as analog signals whose shape impacts the magnitude of chemical neurotransmitter released across the synapses. This mechanism functions similar to a light dimmer with variable settings. Previous research considered the spikes to be delivered as a digital signal, more akin to a light switch that operates only in the "on" and "off" positions.

"The finding that these electric spikes are analog unlocks our understanding of how the brain works to form memory and learning," said In Ha Cho, a postdoctoral fellow at Dartmouth and first author of the study. "The use of analog signals provides an easier pathway to modulate the strength of brain circuits."

Nobel laureate Eric Kandel conducted work on the connection between learning and the change in shapes of electrical signals in marine sea slugs in 1970. The process was not thought to occur in the more complex synapses found in the mammalian brain at the time.

Beyond discovering that the electrical signals which flow across synapses in the brain's hippocampus are analog, the Dartmouth research also identified the molecule that regulates the electrical signals.

The molecule--known as Kvβ1--was previously shown to regulate potassium currents, but was not known to have any role in the synapse controlling the shape of electrical signals. These findings help explain why loss of Kvβ1 molecules had previously been shown to negatively impact learning, memory and sleep in mice and fruit flies.

The research also reveals the processes that allow the brain to have such high computational power at such low energy. A single, analog electrical impulse can carry multi-bit information, allowing greater control with low frequency signals.

"This helps our understanding of how our brain is able to work at supercomputer levels with much lower rates of electrical impulses and the energy equivalent of a refrigerator light bulb. The more we learn about these levels of control, it helps us learn how our brains are so efficient," said Hoppa.

For decades, researchers have searched for molecular regulators of synaptic plasticity by focusing on the molecular machinery of chemical release. Until now, measurements of the electrical pulses had been difficult to observe due to the small size of the nerve terminals.

The new research finding was enabled by technology developed at Dartmouth to measure voltage and neurotransmitter release with techniques using light to measure electrical signals in synaptic connections between neurons in the brain.

In future work, the team will seek to determine how the discovery relates to changes in brain metabolism that occur during aging and cause common neurological disorders.

According to the research team, the molecular system exists in an area of the brain that is easily targeted by pharmaceuticals and could lend itself to the development of drug therapies.

Hearing loss is the second most common disability in the United States and comes with it a higher risk for being diagnosed with significant health conditions, such as hypertension, diabetes, dementia and depression, as well as higher health care cost and use. The Early Auditory Referral-Primary Care (EAR-PC) study was designed to address the lack of data about hearing loss screening. Implemented in real-world, community-based clinics, it evaluated the effect of a tailored electronic clinical alert appearing at all visits of patients 55 and older, to encourage clinicians to ask, "Do you have difficulty with your hearing?" The study's lead author is Philip Zazove, M.D., who is hearing impaired. He and his team of researchers evaluated a screening paradigm for identifying patients 55 years and older at risk of hearing loss from 10 family medicine clinics in two health systems for formal hearing evaluation and treatment. An electronic prompt alerted clinicians to screen for hearing loss during visits. About 25 percent of the patients had signs of hearing loss with the primary care screener (Hearing Handicap Inventory for the Elderly). Referral rates to audiology specialists increased from baseline rates of 3.2 percent to 14.4 percent at one health system and 0.7 percent to 4.7 percent at the other. Considering the high prevalence of hearing loss and the impact on quality of life, increasing referral rates for audiology testing may improve health outcomes.

Effective Hearing Loss Screening in Primary Care: The Early Auditory Referral-Primary Care Study
Philip Zazove, MD, MM, et al
University of Michigan, School of Medicine, Ann Arbor, Michigan
https://www.annfammed.org/content/18/6/520

Primary Care Teams Test New Tool to Prescribe Referrals for Community Health and Social Services

Family physicians provide the majority of health care for underserved rural and urban populations in the U.S. and treat a more diverse population of patients than any other medical specialty. They have an important role to play in helping to mitigate health inequities by connecting patients to community-based wellness and self-care resources such as food and nutrition supports, weight management and smoking cessation to support them in preventing and managing cardiovascular disease.

CommunityRx-H3 is a practice-level, customizable community resource referral system that uses evidence-based algorithms to auto-generate a list of community resources to address such needs. This study evaluated the implementation of CommunityRx-H3 through the perspective of primary care practice facilitators.

This study found that practice facilitators can play a key role in implementing quality improvement initiatives like CommunityRx-H3. However, it also underscores the importance of support from an engaged practice leadership to address such barriers as: limited time, lack of staff, staff apathy, material resources (e.g., printers and paper) and lack of integration between a community resource referral system and the practice's EMR system.

Implementation of Community-Based Resource Referrals for Cardiovascular Disease Self-Management
Emily Abramsohn, MPH, et al
The University of Chicago, Chicago, Illinois
https://www.annfammed.org/content/18/6/511

Under-Insured Transgender Americans Turn to Riskier, Non-Licensed Sources for Gender-Affirming Hormones

Transgender people who lack access to insurance coverage for gender-affirming hormone therapy are more likely to use hormones from sources other than a licensed prescriber, compared to those with insurance coverage. Analysis of the most recent United States Transgender Survey shows that about 9 percent of transgender adults - which comes to about 170,000 transgender adults in the U.S. today - access hormones from non-licensed sources like friends or online. The study found an association between the use of non-prescribed hormones and lack of health insurance or denial of insurance coverage for gender-affirming medical care. Survey respondents also identified insurance coverage as a prevailing barrier; it was ranked as a top issue affecting transgender people in the United States, ranked second only to direct violence.

The authors note that hormones accessed from an unlicensed source may pose health and safety risks, as medications may be unmonitored for content, quality, formulation and dosing. Additionally, use of non-prescription hormones likely entails decreased monitoring of hormone levels and less opportunity for mitigating risks or other forms of harm reduction and preventive care.

Insurance Coverage and Use of Hormones Among Transgender Respondents to a National Survey
Daphna Stroumsa, MD, MPH, et al
University of Michigan, Ann Arbor, Michigan
https://www.annfammed.org/content/18/6/528

New Analysis Finds Lung Cancer Screening Reduces Rates of Lung Cancer-Specific Death

Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening. Researchers at the University of Georgia analyzed the health outcomes of 90,275 patients, comparing those who were screened versus those who received usual medical care or chest x-rays. Their analysis found a clinically and statistically significant 0.4 percent reduction in lung cancer-caused death long term, which translates into one preventable death per 250 at-risk adults screened. The authors recognize the important potential harm of overdiagnosis in cancer screening programs, and there was some evidence of overdiagnosis due to increased incidence in the screened group. However, based on the reduction in all-cause mortality being in the same direction and magnitude as lung cancer mortality, the authors interpret that the associated harms "do not appear to increase other causes of mortality," and the results of the study align with the U.S. Preventive Services Task Force recommendations for CT-based lung cancer screenings for adults age 55 to 80 who have a history of regular smoking.

Cancer-Specific Mortality, All-Cause Mortality, and Overdiagnosis in Lung Cancer Screening Trials: A Meta-Analysis
Mark H. Ebell MD, MS, et al
University of Georgia, College of Public Health, Athens, Georgia
https://www.annfammed.org/content/18/6/545

Representation of Female Authors in Family Medicine Academic Journals is Trending Upward

After decades of underrepresentation in medicine, women are now entering many specialties in the United States, including family medicine, at higher rates than men. Despite the rising proportion of female physicians in family medicine, they continue to be underrepresented in the highest levels of professional attainment, particularly in academic settings. This study from the Robert Graham Center examines female authorship of research published in three leading U.S. family medicine journals over time. They found a statistically significant increase in female authorship of published research over time, with a 13-point jump in original research with female senior authors, from 29 percent in 2008 to 42 percent by 2017. In that same time period, the gender composition of the journals' editorial boards remained roughly the same. Published research was more likely to be male led if it did not have grant funding or if there were no other co-authors. This study's authors discuss the importance of increasing female representation in peer-reviewed publications, closing the gender gaps in the highest levels of academic medicine, and ensuring appropriate representation of thoughts and ideas in the field of family medicine.

Has Female Authorship Distribution in Family Medicine Research Evolved Over Time?
Yalda Jabbarpour, MD, et al
Robert Graham Center, Washington, D.C.
https://www.annfammed.org/content/18/6/496

Most women are receiving fewer than half the services recommended during their comprehensive postpartum medical checkup, according to a study by University of Massachusetts Amherst researchers.

"These findings underscore the importance of efforts to reconceptualize postpartum care to ensure women have access to a range of supports to manage their health during this sensitive period," concludes the study, published Nov. 10 in JAMA Network Open. "There is substantial room to improve the delivery of postpartum care."

Authors Kimberley Geissler and Laura Attanasio, both assistant professors of health policy and management in the School of Public Health and Health Sciences, were joined in the study by graduate student Brittany Ranchoff and undergraduate Michael Cooper. The study received funding from the National Heart, Lung and Blood Institute and the Agency for Healthcare Research and Quality.

"This research is very important because we were able to look at care that was actually provided and really understand what happened during health care visits, not just that the visits are happening. This information is critical for improving the quality of care," says Geissler.

The medical visits averaged about 17 minutes, the researchers found, which may help explain the incomplete postpartum care. "Is that enough time to provide these services? I don't know," Geissler says. "The pressure to see more patients in an increasingly short time is a known issue in the U.S. health care system, so it's not surprising we see that here, too."

In one of the most startling findings, despite an increased awareness of perinatal depression, only one in 11 patients received a screening for depression, part of the assessment of physical, social and psychological well-being recommended by the American College of Obstetricians and Gynecologists (ACOG).

"We need to look at why depression screening is not happening," Attanasio says. "This is an important factor in women's health for the rest of their lives. Even if you're missing some of the recommended services, this one should be universal among this population."

Previous studies have shown that women with Medicaid insurance receive fewer preventive services than women with private insurance, leading the UMass Amherst team to examine insurance type in their review. "We hypothesized recommended services would be less frequently provided during postpartum visits for women with Medicaid insurance compared to women with other coverage types," the researchers write.

However, Attanasio says, "we found that there were not significant differences in the services received between women with Medicaid coverage and private insurance. That could reflect the fact that a lot of these services were not provided to most of the women."

The researchers analyzed data from the National Ambulatory Medical Care Survey, which represented more than 20 million postpartum office visits to an ob-gyn or family medicine doctor from 2009 to 2016.

Recommended services include blood pressure screening; depression screening; pelvic exam; pap test; breast exam; blood glucose exam; contraceptive counseling or provision; counseling for weight reduction, exercise, stress management, diet/nutrition, and/or tobacco use; medication review; and referral to another physician, if needed.

The study calculated the percentage of visits during which the recommended postpartum care services were provided, including the following:

Blood pressure, 91.1%

Depression screening, 8.7%

Pelvic exam, 47.3%

Pap test, 15.9%

Breast exam, 21.9%

Contraceptive counseling or provision, 43.8%

The first mining experiments conducted in space could pave the way for new technologies to help humans explore and establish settlements on distant worlds, a study suggests.

Tests performed by astronauts on the International Space Station suggest that bacteria can extract useful materials from rocks on Mars and the Moon.

The findings could aid efforts to develop ways of sourcing metals and minerals - such as iron and magnesium - essential for survival in space.

Bacteria could one day be used to break rocks down into soil for growing crops, or to provide minerals for life support systems that produce air and water, researchers say.

Matchbox-sized mining devices - called biomining reactors - were developed by scientists at the UK Centre for Astrobiology at the University of Edinburgh over a 10-year period.

Eighteen of the devices were transported to the space station - which orbits the Earth at an altitude of around 250 miles - aboard a SpaceX rocket launched from Cape Canaveral in Florida, US, in July 2019.

Small pieces of basalt - a common rock on the Moon and Mars - were loaded into each device and submerged in bacterial solution. The three-week experiment was conducted under space gravity conditions to simulate environments on Mars and the Moon.

The team's findings suggest bacteria could enhance the removal of rare earth elements from basalt in lunar and Martian landscapes by up to around 400 per cent. Rare earth elements are widely used in technologies including mobile phones, computers and magnets.

Microbes are also routinely used on Earth in the process of so-called biomining to extract economically useful elements such as copper and gold from rocks. The new experiments have also provided new data on how gravity influences the growth of communities of microbes here on Earth, researchers say.

The study, published in the journal Nature Communications, received funding from the UK Space Agency and the European Space Agency. The research was supported by the Science and Technology Facilities Council, part of UK Research and Innovation. The miniature mining reactors used in the experiment were built by engineering company Kayser Italia.

Professor Charles Cockell, of the University of Edinburgh's School of Physics and Astronomy, who led the project, said: "Our experiments lend support to the scientific and technical feasibility of biologically enhanced elemental mining across the Solar System. While it is not economically viable to mine these elements in space and bring them to Earth, space biomining could potentially support a self-sustaining human presence in space.

"For example, our results suggest that the construction of robotic and human-tended mines in the Oceanus Procellarum region of the Moon, which has rocks with enriched concentrations of rare earth elements, could be one fruitful direction of human scientific and economic development beyond Earth."

Dr Rosa Santomartino, a postdoctoral scientist in the University's School of Physics and Astronomy, who worked on the project, said: "Microorganisms are very versatile and as we move into space, they can be used to accomplish a diversity of processes. Elemental mining is potentially one of them."

Libby Jackson, Human Exploration Programme Manager at the UK Space Agency, said: "It is wonderful to see the scientific findings of BioRock published. Experiments like this is show how the UK, through the UK Space Agency, is playing a pivotal role in the European Space Agency's exploration programme.

"Findings from experiments like BioRock will not only help develop technology that will allow humans to explore our Solar System further, but also helps scientists from a wide range of disciplines gain knowledge that can benefit all of us on Earth."

There was a time when the idea of growing organs in the lab was the stuff of science fiction. Today, stem cell biology and tissue engineering are turning fiction into reality with the advent of organoids: tiny lab-grown tissues and organs that are anatomically correct and physiologically functional.

The appeal of organoids is obvious. Essentially, they can provide us with an on-demand production of tissues and mini-organs for pharmaceutical and medical research, without constantly having to rely on donors. And although that goal might still be a long way off, we're slowly getting closer.

EPFL has been involved in the development of organoids for a while now, with the lab of Matthias Lütolf at the School of Life Sciences leading the charge. This year alone, Lütolf's group has published papers on standardizing organoid growth, 3D-printing organoids, and actually producing a functional organoid-based mini-intestine - a groundbreaking Nature paper that is leading the way in this field.

Now, Lütolf's lab has successfully produced a mouse heart organoid in its early embryonic stages. The project was led by Giuliana Rossi, a post-doctoral researcher from Lütolf's laboratory, and published in the journal Cell Stem Cell.

The researchers grew their organoids from mouse embryonic stem cells, which, under the right conditions, can self-organize into structures that "mimic aspects of the architecture, cellular composition, and function of tissues found in real organs", as the researchers put it in the paper. Placed in cell-culture under specific conditions, the embryonic stem cells form a three-dimensional aggregate called a "gastruloid", which can follow the developmental stages of the mouse embryo.

The idea behind this study was that the mouse gastruloid can be used to mimic the early stages of heart development in the embryo. This is a rather unexplored use of organoids, which are generally grown to mimic adult tissues and organs. But there are three features of mouse gastruloids that make them a suitable template for mimicking embryonic development: they establish a body plan like real embryos, and they show similar gene expression patterns. And when it comes to the heart, which is the first organ to form and function in the embryo, the mouse gastruloid also preserves important tissue-tissue interactions that are necessary to grow one.

Armed with this, the researchers exposed mouse embryonic stem cells to a "cocktail" of three factors known to promote heart growth. After 168 hours, the resulting gastruloids showed signs of early heart development: they expressed several genes that regulate cardiovascular development in the embryo, and they even generated what resembled a vascular network.

But more importantly, the researchers found that the gastruloids developed what they call an "anterior cardiac crescent-like domain". This structure produced a beating heart tissue, similar to the embryonic heart. And much like the muscle cells of the embryonic heart, the beating compartment was also sensitive to calcium ions.

Opening up an entirely new dimension to organoids, the breakthrough work shows they can also be used to mimic embryonic stages of development. "One of the advantages of embryonic organoids is that, through the co-development of multiple tissues, they preserve crucial interactions that are necessary for embryonic organogenesis," says Giuliana Rossi. "The emerging cardiac cells are thus exposed to a context similar to the one that they encounter in the embryo."

The research suggests that teaching materials science, mechanical engineering, computer science, biology and chemistry as a combined discipline could help students develop the skills they need to create lifelike artificially intelligent (AI) robots as researchers.

Known as Physical AI, these robots would be designed to look and behave like humans or other animals while possessing intellectual capabilities normally associated with biological organisms. These robots could in future help humans at work and in daily living, performing tasks that are dangerous for humans, and assisting in medicine, caregiving, security, building and industry.

Although machines and biological beings exist separately, the intelligence capabilities of the two have not yet been combined. There have so far been no autonomous robots that interact with the surrounding environment and with humans in a similar way to how current computer and smartphone-based AI does.

Co-lead author Professor Mirko Kovac of Imperial's Department of Aeronautics and the Swiss Federal Laboratories for Materials Science and Technology (Empa)'s Materials and Technology Centre of Robotics said: "The development of robot 'bodies' has significantly lagged behind the development of robot 'brains'. Unlike digital AI, which has been intensively explored in the last few decades, breathing physical intelligence into them has remained comparatively unexplored."

The researchers say that the reason for this gap might be that no systematic educational approach has yet been developed for teaching students and researchers to create robot bodies and brains combined as whole units.

This new research, which is published today in Nature Machine Intelligence defines the term Physical AI. It also suggests an approach for overcoming the gap in skills by integrating scientific disciplines to help future researchers create lifelike robots with capabilities associated with intelligent organisms, such as developing bodily control, autonomy and sensing at the same time.

The authors identified five main disciplines that are essential for creating Physical AI: materials science, mechanical engineering, computer science, biology and chemistry.

Professor Kovac said: "The notion of AI is often confined to computers, smartphones and data intensive computation. We are proposing to think of AI in a broader sense and co-develop physical morphologies, learning systems, embedded sensors, fluid logic and integrated actuation. This Physical AI is the new frontier in robotics research and will have major impact in the decades to come, and co-evolving students' skills in an integrative and multidisciplinary way could unlock some key ideas for students and researchers alike."

The researchers say that achieving nature-like functionality in robots requires combining conventional robotics and AI with other disciplines to create Physical AI as its own discipline.

Professor Kovac said: "We envision Physical AI robots being evolved and grown in the lab by using a variety of unconventional materials and research methods. Researchers will need a much broader stock of skills for building lifelike robots. Cross-disciplinary collaborations and partnerships will be very important."

One example of such a partnership is the Imperial-Empa joint Materials and Technology Centre of Robotics that links up Empa's material science expertise with Imperial's Aerial Robotics Laboratory.

The authors also propose intensifying research activities in Physical AI by supporting teachers on both the institutional and community level. They suggest hiring and supporting faculty members whose priority will be multidisciplinary Physical AI research.

Co-lead author Dr Aslan Miriyev of Empa and the Department of Aeronautics at Imperial said: "Such backing is especially needed as working in the multidisciplinary playground requires daring to leave the comfort zones of narrow disciplinary knowledge for the sake of a high-risk research and career uncertainty.

"Creating lifelike robots has thus far been an impossible task, but it could be made possible by including Physical AI in the higher education system. Developing skills and research in Physical AI could bring us closer than ever to redefining human-robot and robot-environment interaction."

The researchers hope that their work will encourage active discussion of the topic and will lead to integration of Physical AI disciplines in the educational mainstream.

The researchers intend to implement the Physical AI methodology in their research and education activities to pave the way to human-robot ecosystems.

Before an effective treatment can be devised, we have to be able to understand the specific effect of an anti-cancer substance on the cell type, or even the cell, that produces metastases in the enormous cellular heterogeneity of tumours. A team from the University of Geneva (UNIGE) used a pioneering technique, spiked-scRNAseq, that links the transcriptomic to single cell metastatic phenotypes of colon cancer tumour cells. The importance of the VSIG1 gene involved in intercellular interactions has been identified: it prevents metastases. In addition to this discovery--which offers hope for developing future treatments--the article published in Cell Reports validates the use of this technology for testing drugs that are active against metastases, including for personalised approaches.

Most drug treatments for cancer do not work optimally against metastases. In fact, they have been developed to have a global action and the greatest possible effect on the average patient. To be effective, however, "Drugs should be targeted only to cells that generate metastases," explains Professor Ariel Ruiz i Altaba at UNIGE's Faculty of Medicine. Tumours are made up of cells that are very heterogeneous, some of which will produce metastases while others will not. The question is how to target the right type of tumour cells as a means to beat cancer.

The team led by Professor Ruiz i Altaba set up a methodology for defining the cellular phenotypes for tumours, as well as cloning and tracing them, using a cell-scale analysis of both the genome and the resulting mRNA expression. As a reminder, the genes of a cell, or its genotype, are first copied into messenger RNA which is then often used for protein synthesis. These proteins are the visible expression of genes, and their action underlies measurable characteristics of the cell, i.e. its phenotype. "Our approach means it's possible to identify the missing pieces of the tumour puzzle by linking the expressed genotype to the cellular phenotype. In essence, we want to know how cells become metastatic and where they come from."

Model Validation

By developing and using the spiked-scRNAseq technique, which combines omic approaches and phenotype determination of single cells that are then "spiked" into the original, heterogeneous cell population, the researchers succeeded in precisely defining the composition of the tumour populations while determining their phenotype at the cellular level. To do this, they first genetically labelled several types of tumour cells so they could observe their metastatic behaviour. Once the phenotype was known, cells of the same clone were "spiked" into the heterogeneous colon cancer primary cell population and subjected to single cell sequencing. The molecular profile of cells with metastatic potential was thus identified by the homing of spiked metastatic cells to a specific cell group or cluster.

Based on this approach, drugs and their anti-metastatic effects could be precisely tested. "In other words, we can use this approach to analyse compounds for their action on the cells that generate metastasis in individual patients," explains Dr. Marianna Silvano, a postdoctoral fellow at UNIGE and co-first author of the study.

Identifying a Metastasis Suppressor Gene

The researchers then applied this approach to understanding tumour behaviour. "We set about defining the pre-metastatic status of a tumour and assessing its metastatic potential," continues Dr Silvano. The Geneva research team discovered that by mixing cells that have a metastatic phenotype with non-metastatic cells, the former stopped the migration of the latter. "This indicates that restrictive cellular interactions are important in the process of metastasis formation," explains Professor Ruiz i Altaba.

On the back of these results--and with genomic and transcriptomic analyses in hand--the research team focused on the genes involved in the signalling pathways that are important for cellular interactions. Dr Carolina Bernal, a postdoctoral fellow and co-first author of the study, identified the VSIG1 gene and she and Dr Silvano nailed it as critical of the restrictive interaction between non-metastatic and metastatic tumour cells. "By expressing it in a tumour cell, metastases are reduced in vivo and in vitro. If it's removed, we find an increase in metastases," concludes Dr Silvano. Metastatic cells in primary tumours can be pinpointed with spiked-scRNAseq, and essential genes and active drugs identified to develop new and effective treatments for colon and other cancers.

Loneliness is a prevalent and serious public health problem impacting health, well-being and longevity. Seeking to develop effective interventions, researchers at University of California San Diego School of Medicine examined the psychological and environmental factors that lead to patterns of loneliness in different age groups.

Researchers used a web-based survey of 2,843 participants, ages 20 to 69 years, from across the United States.

The study, published in the November 10, 2020 online edition of the Journal of Clinical Psychiatry, found that levels of loneliness were highest in the 20s and lowest in the 60s, with another peak in the mid-40s.

"What we found was a range of predictors of loneliness across the lifespan," said corresponding senior author Dilip V. Jeste, MD, senior associate dean for Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine.

The researchers noted that lower levels of empathy and compassion, smaller social networks, not having a spouse or a partner and greater sleep disturbances were consistent predictors of loneliness across all decades. Lower social self-efficacy -- or the ability to reflect confidence in exerting control over one's own motivation, behavior and social environment -- and higher anxiety were associated with worse loneliness in all age decades, except the 60s.

Loneliness was also associated with a lower level of decisiveness in the 50s.

The study confirmed previous reports of a strong inverse association between loneliness and wisdom, especially the pro-social behaviors component (empathy and compassion).

"Compassion seems to reduce the level of loneliness at all ages, probably by enabling individuals to accurately perceive and interpret others' emotions along with helpful behavior toward others, and thereby increasing their own social self-efficacy and social networks," said Jeste.

The survey suggested that people in their 20s were dealing with high stress and pressure while trying to establish a career and find a life partner.

"A lot of people in this decade are also constantly comparing themselves on social media and are concerned about how many likes and followers they have," said Tanya Nguyen, PhD, first author of the study and assistant clinical professor in the Department of Psychiatry at UC San Diego School of Medicine. "The lower level of self-efficacy may lead to greater loneliness."

People in their 40s start to experience physical challenges and health issues, such as high blood pressure and diabetes.

"Individuals may start to lose loved ones close to them and their children are growing up and are becoming more independent. This greatly impacts self-purpose and may cause a shift in self-identify, resulting in increased loneliness," said Nguyen.

Jeste said the findings are especially relevant during the COVID-19 global pandemic.

"We want to understand what strategies may be effective in reducing loneliness during this challenging time," said Jeste. "Loneliness is worsened by the physical distancing that is necessary to stop the spread of the pandemic."

Nguyen said intervention and prevention efforts should consider stage-of-life issues. "There is a need for a personalized and nuanced prioritizing of prevention targets in different groups of people," said Jeste.

Researchers have developed a neuron-growing ink that uses the body's own electrical signals to precisely guide the growth of nerve cells.

The bioconductive ink can be printed in lines to direct where neurons grow, cracking a major challenge in the emerging field of nerve engineering.

The team of researchers from Australia, India and Bangladesh have tested the ink on a biocompatible scaffold, with their promising lab results published in the journal RSC Advances.

Lead author, RMIT University's Dr Shadi Houshyar, said concentrating the growth of nerve cells in precisely ordered lines was essential to be able to reconnect nerves and heal traumatic nerve injuries.

"Nerve cells need to be meticulously guided to regrow between the broken ends of a nerve - if they just build up anywhere they will cause more pain or sensory problems," Houshyar said.

"With our bioconductive ink, we can concentrate the neuron growth where we need it.

"Our research is in early stages but with further development, we hope one day to enable damaged nerves to be fully reconnected, to improve the lives of millions of people worldwide."

Currently, there are limited options for rebuilding function when an injury results in large peripheral nerve gaps.

Nerve grafts, where surgeons harvest nerves from elsewhere in the body to bridge across a gap, can lead to complications including painful neuromas, misalignment of neural cell growth and injury at the harvest site.

Although emerging alternative techniques such as artificial nerve guides exist, they often fail to achieve full functional or sensory recovery because they don't properly replicate nerve tissue.

Powering nerve cell regeneration

The new nerve-regenerating ink combines the neurotransmitter dopamine - known to help nerve cell survival - with a conductive carbon nanofibre and polymer.

The nanofibre and polymer enables the controlled release of dopamine from the ink, supporting the survival of developing neurons for longer.

Because it is conductive, the nanofibre can also harness the power of bioelectricity - the electrical signals generated by the nervous system that play a key role in maintaining biological function and can accelerate wound healing.

"Using conductive materials allows free movement of electrons, stimulates cell growth and helps connect injured neural tissue," Houshyar, a Vice-Chancellor's Research Fellow in the RMIT School of Engineering, said.

As part of the research, the team also developed a biocompatible scaffold, so the ink could be printed in lines and tested with human cells.

The study found the printed lines supported neural cell attachment and migration - both important for nerve regeneration.

Cell differentiation was also boosted, with the neural cells becoming more specialised as they grew along the lines.

"This supports proper communication with other neurons, which is promising for the establishment of neural circuits for sensory and motor processing - offering hope the technology could lead to a real recovery of nerve function," Houshyar said.

The next stage for the research is testing the ink and scaffold in pre-clinical animal trials, as well as exploring other applications.

"Our end goal is a nerve engineering solution that can direct the growth of the right nerve cells in the right places," she said.

"We're also keen to investigate how we can expand the potential uses of this technology, for speeding up wound healing and improving patient recovery."