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Treatment for glioma has long relied on MRI imaging to track tumor markers and treatment response. But findings from a team at the University of Michigan Rogel Cancer Center, led by Carl Koschmann, M.D., pediatric neuro-oncologist at University of Michigan Health C.S. Mott Children’s Hospital and researcher with the Chad Carr Pediatric Brain Tumor Center, suggest a new method could provide additional data about tumor markers before changes appear on an MRI, indicating possible strategies to help clinicians address this aggressive form of cancer. The recent study appeared in Neuro-Oncology.
As part of a phase 1, multi-site clinical trial, Koschmann’s team collected cerebrospinal fluid and plasma from patients with Diffuse Midline Glioma, or DMG, through blood draws and lumbar punctures over many months, collecting hundreds of samples. They wanted to track changes in cell-free tumor DNA as patients received treatment concurrent with the clinical trial.
“We examined DNA floating in the plasma and CSF at various points in treatment and used a very sensitive machine called digital droplet polymerase chain reaction (ddPCR) to assess the fraction, called a variant allele fraction (VAF), of mutated DNA versus non-mutated,” Koschmann said.
A higher VAF indicates more mutant DNA. Koschmann’s team found that patients whose allele fraction went down after receiving the drug in the clinical trial took longer for the tumor to grow larger or relapse, data consistent with the team’s expectations.
But the findings from the CSF also revealed a marker that hadn’t been shown in this kind of study before, one that couldn’t be found relying on MRI imaging alone.
“When the treatment wasn’t working and tumors were growing, as captured on an MRI, that didn’t always correlate with the VAF rising and the tumor DNA getting worse,” said Evan Cantor M.D., first author of the study who performed work at U-M and is now a pediatric neuro-oncology fellow at Washington University. “More often, we saw a spike in the allele fraction in the tumor DNA before the tumor grew, on average about three to four months before.”
Koschmann explains that this is the first study of its kind to collect serial CSF in a clinical trial for any type of glioma. “It is very clear that DNA in the CSF can provide a lot of new information about the state of the tumor,” he said.

Mechanical engineers at Duke University are using two electronic “voices” singing a harmonic duet to control suspended particles and cells in new and valuable ways. Their prototype device can form and rotate a single-layer crystal from a group of particles, create arbitrary shapes with a given number of particles, and move pairs of biological cells together and apart again hundreds of times.
These abilities could serve a wide variety of fields, such as materials science, soft condensed-matter physics, biophysics, life science and medicine.
For example, the researchers have shown that the device can selectively pair two individual cells and measure their adhesion forces — a feat that doctors could use to determine treatment for individual cancer patients. Because of the dexterity and gentleness of the acoustic device, the researchers have named it the HANDS platform. (Harmonic Acoustics for Non-contact, Dynamic, Selective particle manipulation.)
The results appear online on March 24 in the journal Nature Materials.
“The separation of paired particles or cells has been a major target in the field of acoustic manipulation for many years,” said Tony Jun Huang, the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke. “Our HANDS platform is the first method of separating paired objects, which provides a way into cell-cell interaction studies that are needed extensively in biophysics studies and drug discovery.”
Acoustic tweezers are a rapidly developing field that uses various physical phenomena of sound waves to gently manipulate particles or cells suspended in liquids without touching them. Some examples pinch particles between two sound waves and adjust the waves’ phase or origination point to move them. Others create patterns by combining two static standing sound waves together to separate particles into different formations, such as a grid.

Muscular dystrophy is a debilitating disease that causes the weakness and breakdown of skeletal muscles that progressively worsens over time. According to a team of University of Maine researchers, certain activities may help strengthen muscles affected by muscular dystrophy — and they figured it out by stimulating zebrafish and watching them work out.
Zebrafish are an effective test model of muscular dystrophy because of the molecular similarities between zebrafish and human muscles. Zebrafish can also be bred with a mutation that closely models Duchenne muscular dystrophy, a severe type of muscular dystrophy that affects young boys.
Zebrafish can’t lift weights, though, so UMaine researchers used a process called neuromuscular electrical stimulation (NMES), which stimulates specific nerves to elicit muscle contraction. The researchers designed four NMES regimens and named them after four common weight lifting routines: power, strength, hypertrophy and endurance. The zebrafish were then put into an underwater 3D printed “gym” made up of tunnels and electrodes, and the researchers analyzed their skeletal muscles to see how they had changed.
The study found that while each of the NMES weight lifting “routines” affected the zebrafish neuromuscular junction morphology, swimming and survival differently, only one — the endurance neuromuscular stimulation (eNMES) — improved all three, as long as it was accompanied by a certain antioxidant, heme oxygenase, and a receptor called integrin alpha7.
“eNMES is defined by high-frequency, low-voltage pulses, which is similar to a high-repetition, low-weight workout that we would do in the gym. The longstanding consensus in the muscular dystrophy field is that minimizing resistance training preserves muscle strength and mass because it lowers the risk for muscle damage. However, our data suggest that a certain level of NMES-induced activity is actually beneficial for overall muscle health,” says Elisabeth Kilroy, first author of the study who conducted the research for her Ph.D. at UMaine. Kilroy is now the director of the neuroMuscular ObserVational Research (MOVR) at the Muscular Dystrophy Association.
The study was published March 24, 2022, in the journal ELife.
The research suggests that the right type of resistance training might be beneficial to human patients with muscular dystrophy. There is also potential for NMES to improve mobility and strength in patients with muscular dystrophy, though not much is known about applying the technology this way.
“I think the most exciting aspect is that we established a model for neuromuscular plasticity in healthy versus diseased muscle, and this model will allow us to elucidate mechanisms that could be the basis for potential therapeutics in the future,” says Clarissa Henry, professor of biological sciences, director of Graduate School of Biomedical Science and Engineering, and principal director of the Henry Lab.
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Scientists have long puzzled about a critical way that cells communicate with one another, but Rutgers researchers have used a simple roundworm to solve the mystery.
The study, which appears in the journal Current Biology, could help to develop treatments for Alzheimer’s and other neurodegenerative diseases.
Cells share good news and bad news with each other, and one way in which they do that is through tiny bubbles called extracellular vesicles (EVs). Once considered to be cellular debris, EVs carry beneficial or toxic cargo that promotes good health or disease. In the human brain, for example, EVs carry disease-causing proteins that may influence the progression of Alzheimer’s disease.
“Although EVs are of profound medical importance, the field lacks a basic understanding of how EVs form, what cargo is packaged in different types of EVs originating from same or different cell types and how different cargos influence the range of EV targeting and bioactivities,” said lead author Inna Nikonorova, a postdoctoral researcher.
EVs, which are found in human fluids including urine and blood, may be used in liquid biopsies as biomarkers for disease because healthy and sick cells package different EV cargo.
The Rutgers’ research team decided to use a simple experimental animal — C. elegans, or roundworms — and cutting edge genetic, molecular, biochemical and computational tools to study the unknown function that EVs have within our bodies.
Maureen Barr, a professor in the Department of Genetics, and Nikonorova developed a large-scale identification project that identified 2,888 EV cargo candidates.
Given the importance of EVs in the human nervous system, Nikonorova focused on EVs produced by cilia, the cellular antennae that transmit and receive signals for intercellular communication. Specifically, the researchers focused on EV cargo produced by nerve cells and discovered that EVs carry RNA-binding proteins as well as RNA, whose role in effective therapies is seen in the COVID-19 mRNA vaccine.
Nikonorova and Barr hypothesized that neurons package RNA-binding proteins and RNA into EVs to drive communication between cells and between animals. A fundamental understanding of EV-RNA biology is important for developing tailor-made EVs for RNA-based therapies.
“We developed an innovative method to label, track and profile EVs using genetically encoded, fluorescent-tagged EV cargo and conducted a large-scale isolation and protein profiling,” Nikonorova said. “Using this strategy, we discovered four novel cilia EV cargo. Combined, these data indicate that C. elegans produces a complex and heterogeneous mixture of EVs from multiple tissues in living animals and suggests that these environmental EVs play diverse roles in animal physiology.”
Future efforts in the Barr laboratory will be directed toward understanding EV-mediated RNA communication. Research in the Barr laboratory is funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Diabetes and Digestive and Kidney Diseases.
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Materials provided by Rutgers University. Original written by John Cramer. Note: Content may be edited for style and length.

Mount Sinai researchers have developed a novel method to identify aggressive early-stage lung cancers and target drugs known as aurora kinase inhibitors to tumors that are especially likely to respond to them. The findings, published in Nature Communications on March 24, could lead to great advances in treatment for lung adenocarcinoma, the most common type of lung cancer.
The Mount Sinai team used a genomics network model to measure tumor invasiveness — distinguishing aggressive tumors from so-called “indolent” ones, which often cannot be told apart via chest CT scan — and identify those that will respond to aurora kinase inhibitors, molecules that can inhibit gene signature regulators.
“The approaches to diagnosing and treating early-stage lung adenocarcinoma are evolving and are based upon advances in understanding the biology and clinical activities of these tumors,” said senior author Charles Powell, MD, MBA, Janice and Coleman Rabin Professor of Medicine and Chief of Pulmonary, Critical Care and Sleep Medicine at the Icahn School of Medicine at Mount Sinai. “Our work using novel network approaches, in collaboration with Sema4, to identify signatures of invasiveness and to identify drugs that can intercept progression of these cancers should contribute to advancing the understanding and outcomes for this cancer.”
The research team used a genetically engineered mouse model to define the role of aurora kinases in early progression of the disease. They performed molecular profiling of early-stage lung cancer samples with RNA sequencing and identified signature genes associated with invasiveness of tumors. Researchers from Sema4 used novel genomic networking approaches to identify key network regulators and therapeutic drugs to demonstrate that targeting the signaling pathway reduces lung cancer spread and improves survival. They identified and tested aurora kinase inhibitors, including AMG900, as an effective treatment to intercept lung cancer progression in the models.
The researchers encourage further validation and clinical testing in human tumors. Future studies should examine opportunities to similarly intervene in signaling by immune cells or other cells in the surrounding tumor stroma, researchers said, since cancer progression relies on the interaction between tumor cells and surrounding cells.
Researchers from Weill Cornell Medicine-NewYork-Presbyterian Hospital and Sema4, a patient-centered health intelligence company, contributed to this study. This work was supported by grants from the National Institutes of Health (R01CA163772, R01HL130826, and R01CA240342), the New York State Stem Cell Science Program (C34052GG), the American Thoracic Society Foundation-Unrestricted Grant (ATS-2017-24), the American Lung Association of the Northeast Lung Cancer Discovery Award (LCD-504985), and the Department of Defense (W81XWH-19-1-0613).
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Over one in four women (or 27 per cent) experience intimate partner violence before the age of 50, according to a worldwide analysis led by researchers from McGill University and the World Health Organization. The largest of its kind, the analysis covers 366 studies involving more than 2 million women in 161 countries.
“Intimate partner violence against women — which includes physical and sexual violence by husbands, boyfriends, and other partners — is highly prevalent globally,” says McGill University Professor Mathieu Maheu-Giroux, a Canada Research Chair in Population Health Modeling.
According to the finding published in The Lancet, one in seven women (or 13 per cent) experienced intimate partner violence within the last year of the study period between 2000 and 2018. The analysis also found high levels of violence against young women, estimating that 24 per cent of those between the ages of 15 to 19 experienced domestic violence in their lifetime.
While the numbers are alarming the true scale of violence is likely even higher, the researchers say, noting that the studies were based on self-reported experiences. Given the stigmatized nature of the issue, women can be hesitant to report their experiences, they explain.
High-income countries reported lower rates of domestic violence
The researchers found regional variations, with high-income countries having lower prevalence of both lifetime and past year violence. The lifetime prevalence among women aged 15 to 49 was highest in Africa, South Asia, and parts of South America. The regions with the lowest estimated lifetime domestic violence against women were Central Asia and Central Europe.

Artificial sweeteners reduce added sugar content and corresponding calories while maintaining sweetness. A study publishing March 24 in PLOS Medicine by Charlotte Debras and Mathilde Touvier at the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, France and colleagues suggests that some artificial sweeteners are associated with increased cancer risk.
Many food products and beverages containing artificial sweeteners are consumed by millions of people daily. However, the safety of these additives has been a subject of debate. To evaluate the potential carcinogenicity of artificial sweeteners, researchers analyzed data from 102,865 French adults participating in the NutriNet-Santé study. The NutriNet-Santé study is an ongoing web-based cohort initiated in 2009 by the Nutritional Epidemiology Research Team (EREN). Participants enroll voluntarily and self-report medical history, sociodemographic, diet, lifestyle, and health data. Researchers gathered data concerning artificial sweetener intake from 24-hour dietary records. After collecting cancer diagnosis information during follow-up, the researchers conducted statistical analyses to investigate the associations between artificial sweetener intakes and cancer risk. They also adjusted for a range of variables including age, sex, education, physical activity, smoking, body mass index, height, weight-gain during follow-up, diabetes, family history of cancer, as well as baseline intakes of energy, alcohol, sodium, saturated fatty acids, fiber, sugar, whole-grain foods, and dairy products.
The researchers found that enrollees consuming larger quantities of artificial sweeteners, particularly aspartame and acesulfame-K, had higher risk of overall cancer compared to non-consumers (hazard ratio 1.13, 95% confidence interval 1.03 to 1.25). Higher risks were observed for breast cancer and obesity-related cancers.
The study had several important limitations; dietary intakes are self-reported. Selection bias may also have been a factor, as participants were more likely to be women, to have higher educational levels, and to exhibit health-conscious behaviors. The observational nature of the study also means that residual confounding is possible and reverse causality cannot be ruled out. Additional research will be required to confirm the findings and clarify the underlying mechanisms.
According to the authors, “Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effects. While these results need to be replicated in other large-scale cohorts and underlying mechanisms clarified by experimental studies, they provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally.”
Debras adds, “Results from the NutriNet-Santé cohort (n=102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo / in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies.”
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In mice, the immune response mounted against tuberculosis prevents them from developing COVID-19, according to a new study by Richard Robinson at The Ohio State University, U.S. and colleagues publishing March 24th in the open-access journal PLOS Pathogens.
Currently, the bacterium that causes tuberculosis, Mycobacterium tuberculosis, and the virus that causes COVID-19, SARS-CoV-2, are the leading causes of death from infectious disease worldwide. Tuberculosis is widespread, and scientists have questioned whether the immune response triggered by this serious respiratory infection might protect people from developing COVID-19. To find out more, researchers worked with two different strains of mice and infected them with M. tuberculosis. Then they exposed the mice to the COVID-19 virus and monitored them for signs of infection. They discovered that mice with tuberculosis showed no signs of COVID-19, likely because the pre-existing immune response to tuberculosis prevented the virus from proliferating in the lungs.
Altogether, the findings demonstrate that tuberculosis infection makes the lungs inhospitable to the COVID-19 virus in mice. If the same is true for humans, then this discovery may be one reason why there have been few reports of individuals with both tuberculosis and COVID-19 in the absence of other complications. The findings may also explain why countries tend to have high rates of infection of COVID-19 or tuberculosis, but not both. The researchers propose that future research should focus on the interaction between COVID-19 and tuberculosis infections in humans.
“TB and COVID are pandemics that affect every part of the world,” Robinson adds. “Our study reflects the work of a diverse and talented group of OSU scientists to better understand how these two diseases influence one another, a surprising observation being that mice with TB are resistant to COVID in a lab setting.”
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When we initiate an action in our everyday lives—chasing after a runaway napkin or getting out of the car—the brain releases a chemical messenger called dopamine that helps regulate the brain area that controls this action.
Dopamine signaling is a highly complex process, and one that scientists are eager to understand—especially given its role in movement disorders such as Parkinson’s disease.
Now, a team at Harvard Medical School has identified a new mechanism that underlies dopamine release in the brain. The research, conducted in mice and published March 24 in Science, shows that another chemical messenger called acetylcholine can trigger the firing of dopamine neurons by binding to a part of these neurons not previously known to initiate firing.
The findings reveal more about how the acetylcholine and dopamine systems in the brain interact, and challenge the existing dogma that signals are initiated at one end of neurons and flow to the other end, where they prompt the release of chemical messengers. More specifically, the research suggests that the axon of a neuron, which has traditionally been considered an output structure, can also initiate signaling.
If confirmed in further animal studies and then in humans, the discovery could inform new strategies for treating diseases such as Parkinson’s, in which dopamine signaling is disrupted.
“Defining the interactions of dopamine and acetylcholine is fundamental to understanding how the actions we perform in our daily lives are generated and modulated,” said senior author Pascal Kaeser, professor of neurobiology in the Blavatnik Institute at Harvard Medical School.