Culture

Analyzing tumor microenvironment at single cell level sheds light on metastatic melanoma outcomes

TAMPA, Fla. -- There are several new treatment options available for patients with advanced melanoma. While these therapies have greatly improved the prognosis for patients, each person can respond to the treatments differently. Treatment of melanomas that have spread to the central nervous system is especially challenging. In a new article published in Clinical Cancer Research, Moffitt Cancer Center researchers reveal how different therapies impact the surrounding immune environment of metastatic melanoma tumors according to location and identify a rare population of immune cells that is associated with improved overall survival.

Different types of cancer tend to spread to specific sites throughout the body. Common sites of melanoma metastases are the brain, lungs, liver and bones. Approximately 40% to 60% of melanoma patients develop metastatic disease within the central nervous system, while 5% of patients develop metastatic disease within the area of the leptomeninges, the two innermost layers of tissue that cover the brain and spinal cord, and the cerebrospinal fluid. Patients with leptomeningeal melanoma metastases have a very poor prognosis, with a mean survival of only eight to 10 weeks. Despite this poor prognosis, a handful of patients with leptomeningeal melanoma metastases show increased survival, but the reasons for this are unclear.

"Overall, we know very little about the tumors at this site or why they prove to be so deadly. We hope these insights will lead to the development of novel therapies, with the ultimate goal of improving clinical outcomes of patients with leptomeningeal melanoma metastases," said Inna Smalley, Ph.D., first author on this study and assistant member of the Cancer Physiology Department.

Moffitt researchers want to improve their understanding of why some metastatic melanoma patients respond better than others and determine which cellular factors contribute to these improved responses across different metastatic sites. They analyzed the RNA expression patterns of individual melanoma and immune cells from 26 patients with metastatic melanoma of the skin, brain and leptomeninges/cerebrospinal fluid, and used this information to determine the specific immune cell types that were present within each sample. They discovered that the types of cells within the tumor microenvironment varied according to the site of metastasis. Leptomeningeal melanoma metastases were characterized by an immune-suppressed environment, with a high percentage of dysfunctional CD4 and CD8 T cells that are incapable of mounting an immune response, and low levels of B cells. Alternatively, samples from brain and skin metastases were much more alike in their immune environment, with an enrichment for activated CD4 T cells.

The researchers analyzed how the immune environment of metastatic sites is modulated by different regimens and what types of immune cells are associated with better responses. They compared data from a patient with leptomeningeal melanoma metastases who had a good response to treatment and survived for more than 38 months, to data from five patients who had poor responses to treatment. They found that the long-term survivor had an immune environment that was more like patients without leptomeningeal disease, whereas poor responding patients had immune environments characterized by immunosuppressive myeloid cells and exhausted lymphocytes, a recipe for diminished antitumor responses. Samples derived after treatment revealed that the long-term survivor had cells characteristic of an active immune response, and patients who responded poorly to therapy did not have these cells present.

A further analysis of dendritic cells that play an important role in therapy response showed that a subpopulation, called DC3s, were associated with improved overall survival and the presence of an active T cell immune response, regardless of the site of metastasis or treatment history. The researchers confirmed the importance of DC3s to patient outcomes through preclinical studies in mouse models.

"Our study provides the first insights into the immune microenvironment of patients with leptomeningeal melanoma metastases and helps to clarify why these individuals do so poorly," said Keiran Smalley, Ph.D., director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence at Moffitt. "The tissue microenvironments of brain and leptomeningeal metastatic sites are very distinct and show differential responses to systemic therapy."

Credit: 
H. Lee Moffitt Cancer Center & Research Institute

URI scientists discover function of microbes living in oysters

KINGSTON, R.I. - June 3, 2021 - Scientists from the University of Rhode Island have taken the first steps toward understanding the function of microbes that live on and in Eastern oysters, which may have implications for oyster health and the management of oyster reefs and aquaculture facilities.

"Marine invertebrates like oysters, corals and sponges have a very active microbiome that could potentially play a role in the function of the organism itself," said Ying Zhang, URI associate professor of cell and molecular biology. "We know very little about whether there are resident microbes in oysters, and if there are, what their function may be or how they may help or bring harm to the oyster."

Zhang and doctoral student Zachary Pimentel extracted the DNA of microbes living in or on the gut, gill, inner shell, mantle and other tissues of oysters to identify the microbes that live there. They then applied a metagenomics technology to reconstruct the genome of the most abundant microbes to better understand the nature of the oyster microbiome and the function of some of the microbes.

"This was the first overview of what microbes live in certain parts of Eastern oysters," said Pimentel, the lead author on a paper about the study published in May by the American Society for Microbiology. "In humans, we know that the microbes that live in the gut versus the skin are quite different. But we didn't know about the compartmentalization of certain microbes in certain oyster tissues."

The researchers identified one microbe, a bacterium in the class Mollicutes, that gains energy from the consumption of chitin, a substance found throughout the marine environment. It was most abundant in the gut of the oysters and appears to be an indicator of a healthy oyster, but when found in other tissues, it may be correlated with infections.

"When they're abundant in the gut of healthy oysters, that may indicate that the oysters are happy to have them," Zhang said. "But when the microbe gains abundance in other tissues, that may be a sign that the oyster is not doing well, maybe because the immune system is freaked out."

The same microbe was also discovered to consume arginine, an amino acid found in all organisms that is used to create proteins.

"We're really interested in that one because it has potential implications for the immune system of oysters," Pimentel said. "Oysters rely on arginine for its immune response. A pathogen has been found to steal the arginine to hide from the oyster's immune system, so it's really interesting that there's another microbe that uses arginine and has potential implications for oyster immunity."

Once the researchers have identified the function of key beneficial microbes, the next step is to learn when and where the microbes are acquired.

"One microbe was found to be abundant in adult oysters but very rare in larval samples," Zhang said. "So they could be acquired at some point in their growth, but when and how they are acquired is a big question. If we know they are important and we can identify the source of where they came from, then perhaps we can help preserve the population of this specific microbe."

According to Zhang and Pimentel, oysters play an important role in building reefs, filtering water, and providing other ecological functions, in addition to their role in supporting the aquaculture industry. Further research about the microbiome of oysters could be beneficial to understanding more about oyster health and the health of their ecosystem.

"We know for other organisms that the microbiome is a really important factor when considering health and disease, so we're laying the groundwork for future research that might implicate certain microbes in important processes related to health and disease," Pimentel said.

"The more we know about oysters and their interactions with microbes, the more we'll understand about how to conserve them," added Zhang.

Credit: 
University of Rhode Island

Athletic competition after COVID

MEMPHIS, Tenn. - Cardiovascular imaging demonstrated no evidence of myocardial injury or myocarditis in athletes after COVID-19 infection, according to a research letter published in Circulation by Le Bonheur Children's Hospital and the University of Tennessee Health Science Center cardiologists. The screening and evaluation was conducted by the Le Bonheur Children's Heart Institute Sports Cardiology team, Benjamin S. Hendrickson, MD, Ranjit R. Philip, MD, and Ryan E. Stephens, NP-C, MBA, and Le Bonheur Director of Cardiac MRI Jason N. Johnson, MD, MHS. Researchers say this study confirms existing recommendations that cardiovascular screening can be deferred in COVID-19 positive athletes who are asymptomatic or have milder symptoms.

"Concern for cardiovascular disease as a result of COVID-19 brought about recommendations for evaluating athletes after infection," said Johnson. "Our results show that none of the athletes who underwent cardiac MRI had abnormal findings."

137 collegiate athletes from three universities competing across the National Collegiate Athletic Association (NCAA) Divisions 1, 2 and 3 were evaluated in sports cardiology clinic no sooner than 10 days after testing positive. The athletes were young adults from a broad range of sports and various racial ethnic backgrounds - 48% black, 47% white and 7% Hispanic.

Le Bonheur Children's and UTHSC cardiologists used an algorithm-guided screening to evaluate the athletes. Regardless of symptoms or illness severity, cardiologists obtained a 12-lead electrocardiogram (ECG), transthoracic echocardiogram and conventional cardiac troponin I (cTn) level from each COVID-19 positive athlete. If any of these tests were abnormal or the athlete had a clinical evaluation of concern, they were referred for cardiac MRI (CMR). Athletes with normal evaluations and negative tests or negative CMR had exercise slowly reintroduced and eventually returned to full participation.

Study findings include:

Most athletes (82%) were symptomatic and experienced mild (67%) or moderate (33%) symptoms. None of the athletes had severe COVID-19 illness.

Only five (3.6%) athletes had abnormal testing that required CMR. Of these five, none had abnormal CMR results consistent with myocardial injury or myocarditis.

None of the athletes had new symptoms or other health problem after resuming exercise and normal competition.

"On the basis of the outcomes and follow-up in our cohort, it is reasonable to defer cardiovascular screening in asymptomatic athletes or those with milder COVID-19," said Philip. "Cardiac screening, testing and imaging can be guided by the severity of symptoms and illness in an athlete."

Credit: 
Le Bonheur Children's Hospital

Mockingbird song decoded

image: The mockingbird uses musical techniques like those of humans.

Image: 
MPI for Empirical Aesthetics

The North American mockingbird is famous for its ability to imitate the song of other birds. But it doesn't just mimic its kindred species, it actually composes its own songs based on other birds' melodies. An interdisciplinary research team has now worked out how exactly the mockingbird constructs its imitations. The scientists determined that the birds follow similar musical rules as those found in human music, from Beethoven to Kendrick Lamar.

The song of the mockingbird is so complex that to investigate it required a joint effort of experts from very different fields. Neuroscientist Tina Roeske of the Max Planck Institute for Empirical Aesthetics, field biologist Dave Gammon of Elon University, and the music philosopher David Rothenberg of the New Jersey Institute of Technology combined their different approaches and areas of expertise to conduct this highly unusual study, the findings of which have just been published in the open-access journal Frontiers in Psychology.

Lead author Tina Roeske designed the algorithms used in testing the team's hypotheses.

"When you listen for a while to a mockingbird," she explains, "you can hear that the bird isn't just randomly stringing together the melodies it imitates. Rather, it seems to sequence similar snippets of melody according to consistent rules. In order to examine this hunch scientifically, however, we had to use quantitative analyses to test whether the data actually supported our hypotheses."

The results were unambiguous. The authors identified four compositional strategies that mockingbirds use in transitioning from one sound to the next: changing timbre, changing pitch, stretching the transition (lengthening it in time), and squeezing it (shortening it in time). The complex melodies they create are music to the ears not only of other birds but of humans as well. So, it should come as no surprise that (human) composers of varied musical styles use similar techniques in their work.

As co-author David Rothenberg explains in a YouTube video, the Tuvan throat singing group Huun-Huur-Tu presents examples of timbre change, and pitch change can be heard in the famous opening of Beethoven's Fifth Symphony; the song "Show Yourself" from the Disney film Frozen 2 itself shows the stretching of sound transitions; and if you listen very closely to Kendrick Lamar's song "Duckworth" from the album Damn, you'll hear transitions being squeezed, or shortened.

Credit: 
Max-Planck-Gesellschaft

The dream team: Scientists find drug duo that may cure COVID-19 together

image: Researchers screened a panel of drugs that are already approved for clinical use and identified two drugs that provided effective SARS-CoV-2 suppression: cepharanthine and nelfinavir

Image: 
Louis Reed on Unsplash

COVID-19 continues to claim lives across the world and is infecting millions more. Although several vaccines have recently become available, making significant strides towards preventing COVID-19, what about the treatment of those who already have the infection? Vaccines aren't 100% effective, highlighting the need--now more than ever--for effective antiviral therapeutics. Moreover, some people can't receive vaccines due to health issues, and new variants of SARS-CoV-2, the virus that causes COVID-19, that can penetrate vaccine-conferred immunity, are being reported, indicating that we need to think beyond prevention.

Given this need, a team of researchers based in Japan, the US, and the UK launched a project to develop effective therapeutics. This team included several researchers based at Tokyo University of Science: Visiting Professor Koichi Watashi, Dr. Hirofumi Ohashi, Professor Shin Aoki, Professor Kouji Kuramochi, and Assistant Professor Tomohiro Tanaka. Their goal was clear and simple: finding a cure for COVID-19.

To achieve this goal, the researchers first established an experimental system for screening drugs that may help to control infections. This system used a type of cells called VeroE6/TMPRSS2 cells, which were manipulated to efficiently be infected with and produce SARS-CoV-2. "To determine whether a drug of interest could help combat infection by SARS-CoV-2, we simply had to expose VeroE6/TMPRSS2 cells to both the drug and SARS-CoV-2 and then observe whether the drug's presence served to hinder the virus's efforts to infect cells," explains Professor Watashi.

The researchers used this experimental system to screen a panel of drugs that are already approved for clinical use, including drugs like remdesivir and chloroquine that have already being approved or are being trialed as treatments for COVID-19. In an exciting outcome, the researchers found two drugs that provided effective SARS-CoV-2 suppression: cepharanthine, which is used to treat inflammation, and nelfinavir, which is approved for the treatment of HIV infection.

Cepharanthine inhibited the entry of the virus into cells by preventing the virus from binding to a protein on the cell membrane, which it uses as a gateway. In contrast, nelfinavir worked to prevent the virus from replicating inside the cell by inhibiting a protein that the virus relies on for replication. Given that these drugs have distinct antiviral mechanisms, using both of them together could be especially effective for patients, with computational models predicting that combined cepharanthine/nelfinavir therapy can hasten the clearance of SARS-CoV-2 from a patient's lungs by as few as 4.9 days.

So, does this mean we will be seeing these new drugs in COVID-19 treatment centers? Of course, the drug duo isn't ready to be rolled out into healthcare systems just yet. These findings justify further research into the clinical potential of cepharanthine/nelfinavir therapy, and only following this can we say for sure that it is useful and helpful.

Nevertheless, given the ongoing nature of the COVID-19 pandemic and the ever-increasing death toll, the development of cepharanthine/nelfinavir therapy may provide clinicians and patients with a much-needed new treatment option.

Credit: 
Tokyo University of Science

People who use methamphetamine likely to report multiple chronic conditions

People who use methamphetamine are more likely to have health conditions, mental illness, and substance use disorders than people who do not use the drug, according to a new study by researchers at the Center for Drug Use and HIV/HCV Research (CDUHR) at NYU School of Global Public Health. The findings are published in the Journal of General Internal Medicine.

The use of methamphetamine--a highly addictive and illegal stimulant drug--has increased in recent years, as have overdose deaths. Methamphetamine can be toxic for multiple organs including the heart, lungs, liver, and neurological system, and injecting the drug can increase one's risk for infectious diseases.

"Methamphetamine can complicate the management of existing chronic illnesses, but we know little about the chronic disease profile of people who use it," said study author Benjamin Han, MD, a clinician-researcher in the Division of Geriatrics, Gerontology, and Palliative Care in the Department of Medicine at the University of California San Diego.

Using data from the 2015-2019 National Survey on Drug Use and Health, a nationally representative survey of U.S. adults, the researchers estimated the prevalence of medical conditions, mental illnesses, and other substance use among those who reported using methamphetamine within the past year.

Compared to adults who do not use the drug, people who use methamphetamine were nearly twice as likely to have medical multimorbidity (two or more chronic medical conditions), more than three times as likely to have mental illness, and more than four times as likely to have a substance use disorder. Many have a combination of medical, mental, and substance use issues, including all three concurrently.

Of the chronic illnesses studied, people using methamphetamine had a higher prevalence of liver disease (hepatitis or cirrhosis), lung disease (COPD or asthma), and HIV/AIDS. The researchers also found that those using methamphetamine had a considerably higher likelihood of substance use disorders for all drugs studied, including heroin, prescription stimulants, prescription opioids, cocaine, and sedatives.

"Our results certainly do not suggest that meth use causes most of these conditions, but they should inform clinicians that this population is at risk. Future studies are needed to determine how dose and frequency of use relate to these conditions--for instance, occasional use on a night out versus chronic use that can lead to a host of adverse effects on the body," said study author Joseph Palamar, PhD, an associate professor of population health at NYU Grossman School of Medicine and a CDUHR researcher. "We also confirmed the well-known link between meth use and HIV, which can result from injection drug use or sexual transmission, but more research is needed to determine the extent to which meth use increases risk for STDs due to the drug's libido-enhancing effects."

The researchers note the importance of a harm reduction and patient-centered approach to care for people who use methamphetamines, and one that can coordinate management of mental illness, medical disease, and substance use disorders.

"Methamphetamine use adds complexity to the already-challenging care of adults who have multiple chronic conditions," added Han, who is also a CDUHR researcher. "Integrated interventions that can address the multiple conditions people are living with, along with associated social risks, are needed for this population."

Credit: 
New York University

UN urges intense restoration of nature to address climate and biodiversity crises

image: Launching the UN Decade on Ecosystem Restoration, a new UNEP/FAO report says the world must deliver on existing commitments to restore at least 1 billion degraded hectares of land - an area comparable to China - in the next decade and add similar commitments for oceans.
The report documents the urgent need for restoration, the financial investment required, and the potential returns for people and nature.

Image: 
UNEP/FAO

Facing the triple threat of climate change, loss of nature and pollution, the world must deliver on its commitment to restore at least one billion degraded hectares of land in the next decade - an area about the size of China. Countries also need to add similar commitments for oceans, according to a new report by the UN Environment Programme (UNEP) and the Food and Agriculture Organization of the UN (FAO), launched as the UN Decade on Ecosystem Restoration 2021-2030 gets underway.

The report, #GenerationRestoration: Ecosystem restoration for People, Nature and Climate, highlights that humanity is using about 1.6 times the amount of services that nature can provide sustainably.

That means conservation efforts alone are insufficient to prevent large-scale ecosystem collapse and biodiversity loss. Global terrestrial restoration costs - not including costs of restoring marine ecosystems - are estimated to be at least USD 200 billion per year by 2030. The report outlines that every 1 USD invested in restoration creates up to USD 30 in economic benefits.

Ecosystems requiring urgent restoration include farmlands, forests, grasslands and savannahs, mountains, peatlands, urban areas, freshwaters, and oceans.

Communities living across almost two billion of degraded hectares of land include some of the world's poorest and marginalized.

"This report presents the case for why we must all throw our weight behind a global restoration effort. Drawing on the latest scientific evidence, it sets out the crucial role played by ecosystems, from forests and farmland to rivers and oceans, and it charts the losses that result from a poor stewardship of the planet," UNEP Executive Director, Inger Andersen, and FAO Director-General, QU Dongyu, wrote in the report's foreword.

"Degradation is already affecting the well-being of an estimated 3.2 billion people - that is 40 percent of the world's population. Every single year we lose ecosystem services worth more than 10 percent of our global economic output," they added, stressing that "massive gains await us" by reversing these trends.

Ecosystem restoration is the process of halting and overturning degradation, resulting in cleaner air and water, extreme weather mitigation, better human health, and recovered biodiversity, including improved pollination of plants. Restoration encompasses a wide continuum of practices, from reforestation to re-wetting peatlands and coral rehabilitation.

It contributes to the realization of multiple Sustainable Development Goals (SDGs), including health, clean water, and peace and security, and to the objectives of the three 'Rio Conventions' on Climate, Biodiversity, and Desertification.

Actions that prevent, halt and reverse degradation are necessary to meet the Paris Agreement target of keeping global temperature rise well below 2 degrees Celsius.

Restoration, if combined with stopping further conversion of natural ecosystems, may help avoid 60 percent of expected biodiversity extinctions. It can be highly efficient in producing multiple economic, social and ecological benefits concurrently - for example, agroforestry alone has the potential to increase food security for 1.3 billion people, while investments in agriculture, mangrove protection and water management will help adapt to climate change, with benefits around four times the original investment.

Reliable monitoring of restoration efforts is essential, both to track progress and to attract private and public investments. In support of this effort, FAO and UNEP also launch today the Digital Hub for the UN Decade, which includes the Framework for Ecosystem Restoration Monitoring.

The Framework enables countries and communities to measure the progress of restoration projects across key ecosystems, helping to build ownership and trust in restoration efforts. It also incorporates the Drylands Restoration Initiatives Platform, which collects and analyses data, shares lessons and assists in the design of drylands restoration projects, and an interactive geospatial mapping tool to assess the best locations for forest restoration.

Restoration must involve all stakeholders including individuals, businesses, associations, and governments. Crucially, it must respect the needs and rights of Indigenous Peoples and local communities, and incorporate their knowledge, experience and capacities to ensure restoration plans are implemented and sustained.

Credit: 
Terry Collins Assoc

Secondary infections inflame the brain, worsening cognition in Alzheimer's disease

New research into Alzheimer's disease (AD) suggests that secondary infections and new inflammatory events amplify the brain's immune response and affect memory in mice and in humans - even when these secondary events occur outside the brain.

Scientists believe that key brain cells (astrocytes and microglia) are already in an active state due to inflammation caused by AD and this new research shows that secondary infections can then trigger an over-the-top response in those cells, which has knock-on effects on brain rhythms and on cognition.

In the study, just published in Alzheimer's & Dementia, the journal of the Alzheimer's Association, mice engineered to show features of AD were exposed to acute inflammatory events to observe the downstream effects on brain inflammation, neuronal network function and memory.

These mice showed new shifts in the output of astrocytes and microglia and displayed new cognitive impairment and disturbed 'brain rhythms' that did not occur in healthy, age-matched, mice. These new onset cognitive changes are similar to acute and distressing psychiatric disturbances like delirium, that frequently occur in elderly patients.

Although it is difficult to replicate these findings in patients, the study additionally showed that AD patients who died with acute systemic infection showed heighted brain levels of IL-1β - a pro-inflammatory molecule that was important in causing the heightened immune response and the new onset disruptions seen in the AD mice.

Colm Cunningham, Associate Professor in Trinity's School of Biochemistry and Immunology, and the Trinity Biomedical Sciences Institute, led the research. He said:

"Alzheimer's disease is the most common form of dementia, affecting more than 5% of those over 60 and this distressing, debilitating condition causes difficulties for a huge number of people across the globe. The more we know about the disease and its progression the better chance we have of treating those living with it. We believe our work adds to this knowledge base in a few ways. Primarily, we show that the Alzheimer's-affected brain has a greater vulnerability to acute inflammatory events, even if they occur outside the brain.

Placing this within the context of the slowly evolving progression of AD, we propose that these hypersensitive responses, now seen in multiple cell populations, may contribute to the negative outcomes that follow acute illness in older patients, including episodes of delirium and the accelerated cognitive trajectory that has been observed in patients who experience delirium before or during their dementia."

Credit: 
Trinity College Dublin

Engineers create a programmable fiber

image: MIT researchers have created the first fabric-fiber to have digital capabilities, ready to collect, store and analyze data using a neural network.

Image: 
Image: Anna Gittelson. Photo by Roni Cnaani.

MIT researchers have created the first fiber with digital capabilities, able to sense, store, analyze, and infer activity after being sewn into a shirt.

Yoel Fink, who is a professor of material sciences and electrical engineering, a Research Laboratory of Electronics principal investigator, and the senior author on the study, says digital fibers expand the possibilities for fabrics to uncover the context of hidden patterns in the human body that could be used for physical performance monitoring, medical inference, and early disease detection.

Or, you might someday store your wedding music in the gown you wore on the big day -- more on that later.

Fink and his colleagues describe the features of the digital fiber in Nature Communications. Until now, electronic fibers have been analog -- carrying a continuous electrical signal -- rather than digital, where discrete bits of information can be encoded and processed in 0s and 1s.

"This work presents the first realization of a fabric with the ability to store and process data digitally, adding a new information content dimension to textiles and allowing fabrics to be programmed literally," Fink says.

MIT PhD student Gabriel Loke and MIT postdoc Tural Khudiyev are the lead authors on the paper. Other co-authors MIT postdoc Wei Yan; MIT undergraduates Brian Wang, Stephanie Fu, Ioannis Chatziveroglou, Syamantak Payra, Yorai Shaoul, Johnny Fung, and Itamar Chinn; John Joannopoulos, the Francis Wright Davis Chair Professor of Physics and director of the Institute for Soldier Nanotechnologies at MIT; Harrisburg University of Science and Technology master's student Pin-Wen Chou; Rhode Island School of Design Associate Professor Anna Gitelson-Kahn, and Professor Anais Missakian, who holds the Pevaroff-Cohn Family Endowed Chair in Textiles at RISD.

Memory and more

The new fiber was created by placing hundreds of square silicon microscale digital chips into a preform that was then used to create a polymer fiber. By precisely controlling the polymer flow, the researchers were able to create a fiber with continuous electrical connection between the chips over a length of tens of meters.

The fiber itself is thin and flexible and can be passed through a needle, sewn into fabrics, and washed at least 10 times without breaking down. According to Loke, "When you put it into a shirt, you can't feel it at all. You wouldn't know it was there."

Making a digital fiber "opens up different areas of opportunities and actually solves some of the problems of functional fibers," he says.

For instance, it offers a way to control individual elements within a fiber, from one point at the fiber's end. "You can think of our fiber as a corridor, and the elements are like rooms, and they each have their own unique digital room numbers," Loke explains. The research team devised a digital addressing method that allows them to "switch on" the functionality of one element without turning on all the elements.

A digital fiber can also store a lot of information in memory. The researchers were able to write, store, and read information on the fiber, including a 767-kilobit full-color short movie file and a 0.48 megabyte music file. The files can be stored for two months without power.

When they were dreaming up "crazy ideas" for the fiber, Loke says, they thought about applications like a wedding gown that would store digital wedding music within the weave of its fabric, or even writing the story of the fiber's creation into its components.

Fink notes that the research at MIT was in close collaboration with the textile department at RISD led by Anais Missakian. Associate Professor Anna Gitelson-Kahn incorporated the digital fibers into a knitted garment sleeve, thus paving the way to creating the first digital garment.

On-body artificial intelligence

The fiber also takes a few steps forward into artificial intelligence by including, within the fiber memory, a neural network of 1,650 connections. After sewing it around the armpit of a shirt, the researchers used the fiber to collect 270 minutes of surface body temperature data from a person wearing the shirt, and analyze how these data corresponded to different physical activities. Trained on these data, the fiber was able to determine with 96 percent accuracy what activity the person wearing it was engaged in.

Adding an AI component to the fiber further increases its possibilities, the researchers say. Fabrics with digital components can collect a lot of information across the body over time, and these "lush data" are perfect for machine learning algorithms, Loke says.

"This type of fabric could give quantity and quality open-source data for extracting out new body patterns that we did not know about before," he says.

With this analytic power, the fibers someday could sense and alert people in real-time to health changes like a respiratory decline or an irregular heartbeat, or deliver muscle activation or heart rate data to athletes during training.

The fiber is controlled by a small external device, so the next step will be to design a new chip as a microcontroller that can be connected within the fiber itself.

"When we can do that, we can call it a fiber computer," Loke says.

Credit: 
Massachusetts Institute of Technology

Most Americans support Medicare negotiation despite claims it would hurt innovation

image: Few Americans Believe Negotiating Drug Prices Will Hurt Pharmaceutical Innovation and Competition; Most Want Government to Play Major Role in Controlling Costs

Image: 
West Health-Gallup

WASHINGTON, DC - JUNE 3, 2021 -- A new West Health/Gallup survey finds nearly all Democrats (97%) and the majority of Republicans (61%) support empowering the federal government to negotiate lower prices of brand-name prescription drugs covered by Medicare. Overall, 8 in 10 Americans prefer major government action to control prices over concerns about it hurting innovation and competition from the pharmaceutical industry. The results come from a nationally representative poll of more than 3,700 American adults.

While President Joe Biden, Democrats in Congress and former President Donald Trump have called for such negotiation, Republicans on Capitol Hill and the pharmaceutical industry itself have been fiercely opposed to the measure, claiming lower prices would hurt competition and reduce innovation. However, this belief is not widely shared among the American people. According to the survey, less than 20% of all Americans believe Medicare negotiation would hurt innovation or market competition, including a minority of Republicans (39%).

"Americans aren't buying the claim that attempts to reign in drug prices will stifle innovation and devastate the pharmaceutical industry," said Tim Lash, Chief Strategy Officer for West Health, a family of nonprofit and nonpartisan organizations dedicated to lowering healthcare costs to enable successful aging. "These misleading arguments are meant to preserve profits rather than protect patients. The time has come to finally enable Medicare negotiation. Americans are becoming increasing restless for it to happen even if the pharmaceutical companies are not."

If enacted, Medicare negotiation as described in H.R. 3, the Elijah E. Cummings Lower Drug Costs Now Act, is projected to save the federal government, businesses, and workers hundreds of billions of dollars by 2030. According to a new analysis from West Health and its Council for Informed Drug Spending Analysis (CIDSA), private employers could also save $195 billion and workers would see another $98 billion in savings. These savings are in addition to the estimated savings of $456 billion in federal direct spending forecast by the Congressional Budget Office (CBO).

When choosing between the need for major reform in drug pricing and maintaining the status quo, 90% of Americans chose to support reforms, including 96% of Democrats, 88% of Independents and 83% of Republicans. Sweeping support also exists for specific actions including setting limits on out-of-pocket costs for prescription drugs (87% strongly or somewhat supporting) and general healthcare (84%) in Medicare and limiting hospital charges for those with private insurance (83%), and allowing Medicare to negotiate drug prices for all Americans, not just Medicare beneficiaries, is supported by 70% of respondents.

"There is little question that substantial public support exists for more government action when it comes to addressing drug costs," said Dan Witters, Gallup senior researcher. "And while there are differences across the political spectrum, even among Republicans, sentiment for public action is substantial."

Credit: 
West Health Institute

Mason scientists explore herbal treatment for COVID-19

image: School of Systems Biology Associate Professor Ramin Hakami (left) and School of Systems Biology Professor Yuntao Wu (right).

Image: 
George Mason University

Could an over-the-counter health "shot" help fight COVID-19? George Mason University researchers think it just might.

Cell and Bioscience recently highlighted research led by Yuntao Wu and Ramin Hakami in which they examined the potential anti-coronavirus activities of an over-the-counter drink called Respiratory Detox Shot (RDS).

RDS is a remedy containing nine herbal ingredients traditionally used in Eastern medicine to manage lung diseases. The researchers reported that RDS inhibited the infection of target cells by SARS-CoV and SARS-CoV-2 pseudoviruses and by infectious wild-type SARS-CoV-2. Their results suggest that RDS might broadly inhibit respiratory viruses, such as influenza.

SARS-CoV is the viral pathogen causing Severe Acute Respiratory Syndrome (SARS), and its sister virus, SARS-CoV-2, is the pathogen that causes COVID-19. The COVID-19 global pandemic is a major focus of researchers around the world. While effective vaccines have been developed, there is still a need for developing effective treatments. In particular, new variants of the virus are continuously emerging, and some of these variants may make the vaccines less effective.

Ramin Hakami, an Associate Professor in Mason's School of Systems Biology and one of the authors of the study, said that the fact that RDS is a drinkable food supplement is helpful.

"If it proves effective in vivo, it should be a treatment for COVID-19 that is easy to administer," said Hakami, who also works at Mason's National Center for Biodefense and Infectious Diseases. "That's a big plus."

For their study, Hakami, Wu, and Mason researchers Brian Hetrick, Adeyemi A. Olanrewaju, Linda D. Chillin, Sijia He, and Deemah Debbagh worked with Dongyang Yu of Virongy LLC, Yuan-Chun Ma of Dr. Ma's Laboratories Inc., and Lewis A. Hoffman of the World Health Science Organization.

The team screened extracts from approximately 40 medicinal herbs using a SARS-CoV-2 pseudovirus and human lung cells. They also screened for possible anti-SARS-CoV-2 activity of RDS.

For the study, they pretreated cells with diluted RDS and then infected the cells in the presence of RDS for four to six hours. After infection, they cultured cells in the absence of RDS and then quantified the cells to determine if viral infection was inhibited at 48 and 72 hours.

Subsequently, the researchers used the Biomedical Research Lab on Mason's Science and Technology Campus to confirm the in vitro efficacy of RDS against infectious SARS-CoV-2 virus.

[The] study revealed that RDS contains very potent ingredients that can destroy the infectivity of SARS-CoV, SARS-CoV-2, and influenza A virus, even at very low dosages, said Wu, a professor in Mason's National Center for Biodefense and Infectious Diseases and a study co-author. In addition, the investigators have demonstrated that RDS is effective against the SARS-CoV-2 variants in vitro.

Hetrick, a PhD student in biosciences working on the study, said that the discovery was a happy surprise for him. It would be great if there are safe and effective herbal drugs available for the management of COVID-19 in the future.

Hakami is currently conducting in vivo animal studies to build on the in vitro discovery that RDS may be used as a SARS-CoV-2 treatment. He is testing RDS using K18-hACE2 transgenic mice that will be infected with SARS-CoV-2. Depending on the results, Dejia Harmony, the sponsor of the above pre-clinical trial, may seek FDA approval to begin human clinical trials.

"This study points to the possibility of using a readily available, over-the-counter herbal beverage to provide protection against SARS-CoV-2 and influenza A infections," said Ali Andalibi, senior associate dean in Mason's College of Science. "It will also be quite interesting to see if RDS shows activity against other respiratory viruses."

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George Mason University

Salt marshes trap microplastics in their sediments, creating record of human plastic use

image: Claire McGuire obtaining a sediment core sample from Waquoit Bay, Falmouth, Mass. McGuire was a student in the Marine Biological Laboratory's Semester in Environmental Science program, where this paper originated.

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Semester in Environmental Science (SES)/MBL

WOODS HOLE, Mass. -- Plastics are everywhere. From cell phones to pens and cars to medical devices, the modern world is full of plastic-- and plastic waste. New research from scientists at the Marine Biological Laboratory (MBL) Ecosystems Center found that some of that plastic waste has been accumulating in salt marshes for decades. The study was published in Environmental Advances.

Salt marshes are the link between the land and open ocean ecosystems, and -- in a way --between urban environments and the wild ocean. Microplastics (plastic particles smaller than 5 millimeters) tend to float on the water surface, but salt marshes fill and empty with the tides, so particles that would normally float get trapped within branches and roots and settle into the marsh soil.

Sediments accumulate in the salt marsh layer after layer, like tree rings, keeping an historical record of sedimentation within the ecosystem. "By accumulating sediments, they are keeping a record in time," says Javier Lloret, MBL research scientist and co-first author on the paper.

Globally, scientists estimate that about 8 million tons of plastic enter the ocean each year. But until now, there's been no estimation of the amount of that plastic that gets trapped in salt marsh ecosystems.

By taking core samples of the marsh sediment at six different estuaries in the Waquoit Bay system on Cape Cod, as well as New Bedford, Mass., harbor, the researchers were able to trace the abundance of microplastics dating back decades in areas with very contrasted degrees of land use.

"As you go into the past, the amount of microplastics you find decreases clearly," says Lloret. "The amount of microplastics you find in sediments is related to the population numbers... but also the amount of plastic that people use."

"Waquoit Bay is the perfect salt marsh system to study plastic pollution because we can contrast one area that is almost pristine... with another area that is highly impacted by human activity," says Rut Pedrosa-Pàmies, also an MBL research scientist and co-first author on the paper. "We found a broad range of plastic pollution."

The researchers focused on two types of microplastic pollution: fragments (from the breakdown of larger plastic pieces) and fibers (thread-like plastics which tend to shed from clothing and fishing gear). They found that fragment pollution increased both through time and with urbanization. The more populated the area surrounding the collection site, the more plastic fragments the researchers observed.

One surprise in the data was that microplastic concentration in the sediments wasn't linear as urbanization grew. Up to 50% development, the concentration of microplastic fragments was relatively unchanged, but once the land was occupied at 50%, the number of microplastics grew exponentially.

"Just a few people in the surrounding area is not going to change much, but when urban uses occupy more than 50% of the land, the number of microplastics goes crazy," says Lloret.

The microplastic fibers didn't have the same relationship with urbanization. "Even in the more pristine areas that don't have urbanization, we find fiber plastic pollution" says Pedrosa-Pàmies.

The researchers believe the fragments have a local origin (people using and disposing of plastics where they live) whereas fibers can be transported long distances by air or by water from large-scale urban areas.

"When we started, we didn't know if microplastics were an issue here on Cape Cod, or not. No one had analyzed the marsh sediments on Cape Cod for microplastics before," says Lloret.

Now that the scientists have shown there is microplastic pollution in New England salt marshes, the next step is to gain further insight. How are those particles arriving in the ecosystem? What are the sources? How are they impacting the ecosystem and the food web of the organisms that live there?

"There are still a lot of unanswered questions," says Pedrosa-Pàmies. "This is the first step for management, too."

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Marine Biological Laboratory

UW researchers investigate mining-related deforestation in the Amazon

image: Most gold mines in the Peruvian Amazon are unregulated, small-scale operations, leaving governments without ways to protect the surrounding environment or track how much forest is lost to mining.

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Photo courtesy of Lisa Naughton

MADISON, Wis. -- If you're wearing gold jewelry right now, there's a good chance it came from an illegal mining operation in the tropics and surfaced only after some rainforest was sacrificed, according to a team of University of Wisconsin-Madison researchers and alumni who studied regulatory efforts to curb some of these environmentally damaging activities in the Amazon.

The researchers, including UW-Madison geography Professor Lisa Naughton, investigated mining-related deforestation in a biodiverse and ecologically sensitive area of the Peruvian Amazon to see whether formalizing and legalizing these mining operations might curb some of their negative effects.

Their study, published June 2 in the journal Environmental Research Letters, was co-authored by a group including UW-Madison alumnae Nora Álvarez-Berríos, now studying land-use and climate impacts at the International Institute of Tropical Forestry, and Jessica L'Roe, now a geography professor at Middlebury College.

The team focused on an area around the Tambopata National Reserve in Peru from 2001 to 2014. During this time period, Naughton says, demand for gold rose, roads penetrated the region and mining surged. In turn, mining-related deforestation rose by almost 100,000 acres over their study period.

"Because the gold is in the sediment scattered under the forest floor, to extract the gold, you have to remove the forest and dig," Álvarez-Berríos says. "You have to cut a lot of the forest and excavate sensitive waterways."

While these mining operations are often called "artisanal" or "small-scale," in aggregate they are very destructive. In many countries they operate outside the law, and millions of people are involved across the tropics. Álvarez-Berríos says the typical first step to reducing the environmental impact of artisanal mining is bringing it under governmental oversight, formalizing the activity. That way, local agencies can manage the impacts and protect both ecologically sensitive areas and the economic well-being of poor mine workers.

"Peruvian authorities, like authorities in other gold-rush sites, have given up on trying to stop gold mining. They're trying to confine it and contain it," L'Roe says. "Most of the studies about formalization are mainly about trying to help the poor, or make it more fair for the poor. Seldom, almost never, as far as we can tell, have these formalization projects been assessed for their environmental impact. So that's what we were looking at."

During their study period, local agencies issued provisional titles to miners to conduct their operations safely. After receiving a provisional title, miners would, in theory, undergo a series of environmental impact and compliance assessments before they started work.

But, as L'Roe says they found, the regulation process took a long time. Many miners simply took their provisional title as a green light to start mining, and never went through with the environmental impact assessments. Over their study period, no mining operations made it through the full compliance process, and as such they found little evidence for improved environmental outcomes in formalized mining areas.

To assess environmental outcomes, the team used satellite imagery analysis to see how much of the forest had been cut down, as compared to areas without formalized mining regulations.

Naughton says while formalizing mining has the potential to decrease environmental damage, it needs enforcement and regulations that match the local context. Formalization without environmental impact assessment or enforcement could just encourage more damaging and dangerous mining, or the expansion of these operations under the pretense that what they're doing is legal.

But gold rushes are exactly what they sound like, Naughton says: rushed. They're fast, and slow formalization processes with many steps and provisions and impact assessments often cannot keep up with the pace of extraction.

"To sort out in a fair way who owns what land, with what rights, that is a slow process," Naughton says. "This gold rush is explosive. By the time you have well-regulated and transparent public land and property rights, the forest will be gone."

The team plans to go back to Tambopata to present its results to local stakeholders. Many members of the community are already aware of the problems with mining formalization but have not had a chance to systematically study the environmental consequences. The three co-authors hope their study will set a precedent for monitoring formalization interventions in Tambopata and other tropical sites losing forest to mining. They are already sharing results and methods with colleagues concerned about gold mining impacts in Colombia, Brazil and Bolivia.

"We'll go back to our study site and share the results -- but in a humble way because folks there know that it hasn't worked well, and they know the problems," says Álvarez-Berríos. "So, yes, it's important to share it with that group of stakeholders and experts, but maybe even more important is to share the results and our methods and design for studying this problem with folks working in the many, many other areas where there's uncontrolled small-scale gold mining and where formalization efforts are being launched with best intentions."

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University of Wisconsin-Madison

Study of UK dental professionals shows extent of occupational risk of SARS-CoV-2 infection

A University of Birmingham-led study of over a thousand dental professionals has shown their increased occupational risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK.

The observational cohort study, published today (3 June 2021), in the Journal of Dental Research, involved 1,507 Midland dental care practitioners. Blood samples were taken from the cohort at the start of the study in June 2020 to measure their levels of antibodies against SARS-CoV-2, the virus that causes COVID-19.

The team found 16.3% of study participants - which included dentists, dental nurses and dental hygienists - had SARS-CoV-2 antibodies, compared to just 6% of the general population at the time. Meanwhile, the percentage of dental practice receptionists, who have no direct patient contact, with SARS-CoV-2 antibodies was comparable to the general population, supporting the hypothesis that occupational risk arose from close exposure to patients.

The study also found ethnicity was also a significant risk factor for infection, with 35% of Black participants and 18.8% of Asian participants having SARS-CoV-2 antibodies, compared to 14.3% of white participants.

Blood samples were taken from participants three months later, in September 2020, when dental practices in England had re-opened with enhanced PPE and infection control measures in place, and once again in January 2021, six months after the start of the study, during the second wave of the pandemic when healthcare workers were being vaccinated.

The results showed that of those who had previous COVID-19 infection, over 70% continued to have SARS-CoV-2 antibodies both at three months and six months later, and they were at a 75% reduced risk of re-infection with the virus.

The study also demonstrated the immunological impact of COVID-19 vaccination, with 97.7% of those without previous infection developing an antibody response at least 12 days after their first Pfizer vaccine. In those with evidence of previous infection, the antibody response was more rapid and higher in magnitude after a single dose of the Pfizer vaccine.

Furthermore, none of the cohort with a level of SARS-CoV-2 antibodies greater than 147.6 IU/ml in their blood tested positive for COVID-19 throughout the six-month period from the first to the final blood tests.

First author Dr Adrian Shields, of the University of Birmingham's Institute of Immunology and Immunotherapy, said: "Understanding what an antibody test result means to an individual with respect to their risk of infection is essential to controlling the pandemic.

"Our study has taken the first steps in defining the level of antibody in a persons' blood necessary to protect them from infection for six months. Furthermore, by comparing the antibody levels we have found in dentists to those contained in widely available reference material produced by the World Health Organization, we hope the protective level we found can be easily confirmed and compared by other laboratories."

Corresponding author Professor Thomas Dietrich, of the University of Birmingham's School of Dentistry, adds: "Critically, only 5.3% of the cohort developed an antibody response that exceeded this threshold of 147.6 IU/ml following the first wave of the UK pandemic. This suggests that natural infection alone is unlikely to generate meaningful, durable herd immunity."

Co-corresponding author Iain Chapple, Professor of Periodontology at the University of Birmingham and Consultant in Restorative Dentistry at Birmingham Community Healthcare Trust, adds: "Dental professionals are thought to be at high risk of exposure to SARS-CoV-2 because they routinely operate within patients' aerodigestive tract and regularly carry out aerosol-generating procedures that result in the production of airborne particles.

"Through our research, we have clearly shown that dental professionals were at increased occupational risk of exposure to SARS-CoV-2 prior to the new PHE guidance on PPE. The occupational health measures that have been put in place in general dental practice as a consequence of COVID-19 appear to remove that increased risk, however, this will need to be thoroughly investigated to see if they have successfully interrupted transmission of SARS-CoV-2 and other respiratory viruses."

Co-corresponding author Professor Alex Richter, also of the University of Birmingham, said: "This is the first time the occupational risk of exposure to a potentially fatal respiratory virus has been studied in a large dental cohort.

"It is important that we now progress our research to ensure we have an understanding of how people are protected from re-infection with COVID-19 following natural infection and vaccination.

"The nature and duration of immunity in these cohorts will be critical to understand as the COVID-19 pandemic progresses, particularly with respect to the efficacy of vaccination strategies -single-dose, multiple-doses, vaccine combinations - and in relation to novel viral variants of concern."

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University of Birmingham

Neuroscience doesn't undermine free will after all

For decades, researchers have debated whether the buildup of certain electrical activities in the brain indicates that human beings are unable to act out of free will.

Experiments spanning the 1960s and 1980s measured brain signals noninvasively and led many neuroscientists to believe that our brains make decisions before we do--that human actions were initiated by electrical waves that did not reflect free, conscious thought.

However, a new article in Trends in Cognitive Science argues that recent research undermines this case against free will.

"This new perspective on the data turns on its head the way well-known findings have been interpreted," said Adina Roskies, the Helman Family Distinguished Professor and professor of philosophy at Dartmouth College, who co-wrote the article. "The new interpretation accounts for the data while undermining all the reasons to think it challenges free will."

The debate over free will centers mostly around research from the 1980s that used electroencephalograms to study brain activity. The EEG-based research measured when electrical signals begin to build in the brain relative to when a person is aware of their desire to make a movement. The averaged data described a ramp before movement that became known as the "readiness potential," or "RP."

The 1980s research, conducted by neurophysiologist Benjamin Libet, contended that if the readiness potential was evident prior to a person having a conscious thought about moving, free will could not be responsible for either the buildup of electrical signals or the subsequent movement.

According to the research team, this part of Libet's logic was based on a premise that is likely false.

"Because the averaged readiness potential reliably precedes voluntary movement, people assumed that it reflected a process specifically directed at producing that movement. As it turns out, and as our model has shown, that is not necessarily the case," said Aaron Schurger, an assistant professor of psychology at Chapman University who co-wrote of the article.

The article highlights new research using computational modeling that indicates that the standard interpretation of the readiness potential should be reassessed, particularly for its relevance to the question of free will.

The study points to findings that suggest that the readiness potential--the pre-movement buildup of activity--reflects the neural activity that underlies the formation of a decision to move, rather than the outcome of a decision to move.

"These new computational models account for the consistent finding of the readiness potential without positing anything like an RP in individual trials. The readiness potential itself is a kind of artifact or illusion, one which would be expected to appear just as it does given the experimental design, but doesn't reflect a real brain signal that begins with the RP onset or is read out by other areas," said Roskies.

The article also highlights several challenges to the idea that the readiness potential causes humans to act: difficulty distinguishing the readiness potential from other electrical signals in the brain; the presence of a readiness potential when tasks do not involve motor activity; and "noise" in analyses which makes it difficult to confirm whether the readiness potential always predicts movement.

False positives, in which readiness potential is observed but fails to initiate movement, and inconsistencies in the amount of time between the buildup of the brain waves and movement also complicate the understanding of the connection between the electrical activity in the brain and free will.

Finally, the article emphasizes the philosophical aspects of attempting to address the problem of free will with brain data.

Pengbo Hu at Pomona College and Joanna Pak from Chapman University, also contributed to this paper.

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Dartmouth College