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Research and treatment of psychiatric disorders are stymied by a lack of biomarkers — objective biological or physiological markers that can help diagnose, track, predict, and treat diseases. In a new study, researchers use a very large dataset to identify predictive brain imaging-based biomarkers of mental illness in adolescents. The work appears in Biological Psychiatry, published by Elsevier.
Traditionally, psychiatric disorders such as depression have been diagnosed based on symptoms according to subjective assessments. The identification of biomarkers to aid in diagnosis and treatment selection would greatly advance treatments.
In the current study, the investigators used brain imaging data from the Adolescent Brain Cognitive Development (ABCD) Study of nearly 12,000 children aged 9 to 10 at the beginning of the study. Modern neuroimaging techniques, including resting-state functional connectivity (rsFC) analysis, allow researchers to investigate the organization of brain circuits through their interaction with one another over time.
Yihong Yang, PhD, senior author of the study, at the Neuroimaging Research Branch, National Institute on Drug Abuse, said, “Using a functional MRI dataset, we identified a brain connectivity variate that is positively correlated with cognitive functions and negatively correlated with psychopathological measures.”
Cognition has long been studied in the context of mental disorders, and recent research has pointed to shared neurobiology between the two, as supported in this new study.
This brain-based variate predicted how many psychiatric disorders were identified in participants at the time of the scan and over the following two years. It also predicted the transition of diagnosis across disorders over the two-year follow-up period.”
Dr. Yang added, “These findings provide evidence for a transdiagnostic brain-based measure that underlies individual differences in developing psychiatric disorders in early adolescence.”
John Krystal, MD, Editor of Biological Psychiatry, said of the work, “Mental illness in adolescence has emerged as a cardinal public health challenge in the post-COVID era. More than ever before, we would benefit from better ways to identify adolescents at risk. This study uses data from the landmark ABCD Study to illustrate how neuroimaging data could illuminate risk for mental illness across the spectrum of diagnoses.”
Dr. Yang added, “Finding biomarkers of mental illnesses, rather than relying on symptoms, may provide a more precise means of diagnosis, and thereby aligning psychiatric diagnosis with other medical diagnoses.”

The 11 young firefighters went through a rigorous training exercise, carrying up to 40 pounds of gear over hilly terrain during a 45-minute training exercise in the California sun. Gloves, helmets, flashlights, goggles, and more weighted them down as they sprinted through the countryside wearing fire-resistant clothing to show they were ready to serve as wildland firefighters.
When the training was over, they immediately went to the medical tent — not to rest and recover but to give samples of their blood, saliva, and urine for analysis by a team of scientists equipped with needles, test tubes, cold packs, and the gear of their own trade.
Then, the scientists from the Department of Energy’s Pacific Northwest National Laboratory (PNNL) analyzed more than 4,700 molecules — proteins, lipids, and metabolites — from each of the firefighters, looking to understand what happens when the body undergoes intense physical exercise. Measuring and interpreting the data from thousands of such measurements is a specialty of PNNL scientists who explore issues related to climate science and human health by analyzing millions of sensitive measurements using mass spectrometry each year.
For this study, the intent was to increase safety for first responders and others.
“Heat stress can be life threatening,” said Kristin Burnum-Johnson, a corresponding author of the study. “We wanted to take an in-depth look at what’s happening in the body and see if we’re able to detect danger from exhaustion in its earliest stages. Perhaps we can reduce the risk of strenuous exercise for first responders, athletes, and members of the military.”
As expected, the team detected hundreds of molecular changes in the firefighters. The differences before and after exercise underscored the body’s efforts at tissue damage and repair, maintenance of fluid balance, efforts to keep up with increased energy and oxygen demand, and the body’s attempts to repair and regenerate its proteins and other important substances.
But in the saliva, the team found some unexpected results. There was a change in the microbial mix of the mouth — the oral microbiome — showing that the body was increasingly on the lookout for bacterial invaders. Scientists also saw a decrease in signaling molecules important for inflammation and for fighting off viral infections.

New experimental evidence suggests that substances known as narrow-spectrum Wnt signaling inhibitors — which could have fewer side effects than other related substances — are capable of suppressing the growth of breast cancer tumors in mice. Aina He of Shanghai Jiaotong University Affiliated Sixth People’s Hospital, China, and colleagues present these findings November 9 in the open access journal PLOS Biology.
While certain subtypes of breast cancer can be targeted with special medications, others can only be treated with standard chemotherapy. For some patients, chemotherapy may lead to the growth of stem cell-like cancer cells that are drug resistant. Previous studies suggest that medications that inhibit a specific biological process called Wnt signaling could potentially combat these cells, but so far, the potential benefits of Wnt signaling inhibitors have been hampered by their damaging side effects, particularly on bone density.
These side effects arise from the fact that humans have ten different versions of the Wnt signaling receptor, Frizzled, with distinct functions. Researchers have therefore recently developed new Wnt signaling inhibitors that could reduce side effects by targeting just three of these receptors. However, it has been unclear how effective these narrow-spectrum Wnt signaling inhibitors might be at treating cancer.
To shed new light, He and colleagues conducted a series of experiments with a specific narrow-spectrum Wnt signaling inhibitor known as TcdBFBD, which was derived from a toxin found naturally in the bacterial species Clostridium difficile. They tested TcdBFBD in several different mouse models that mimic different types of breast cancer — basal-like and luminal-like — found in humans.
The researchers found evidence suggesting that TcdBFBD suppressed tumor growth and reduced the activity of stem cell-like cancer cells in the mice, without side effects on bone density. They also found evidence that TcdBFBD can synergize with the standard chemotherapy drug cisplatin to inhibit both basal-like and luminal-like breast cancer tumors in mice.
These findings provide preliminary evidence for the potential therapeutic promise of narrow-spectrum Wnt signaling inhibitors like TcdBFBD. However, more research will be needed to investigate their effectiveness in humans, examine how they might synergize with other cancer treatments beyond cisplatin, and explore their effects in additional types of cancer — such as serous ovarian cancer and oral squamous cell carcinoma.
The authors add, “A bacterial toxin fragment targets and suppresses breast cancer tumor-initiating and chemo-resistant cells.”

UCLA researchers have described a previously unknown step in the complex process by which dietary cholesterol is processed in the intestines before being released into the bloodstream — potentially revealing a new pathway to target in cholesterol treatment.
Although an existing drug and statins impact part of the process, an experimental drug being studied in UCLA research labs appears to specifically target the newfound pathway, possibly adding a new approach to the cholesterol management toolbox.
“Our results show that certain proteins in the Aster family play a critical role in moving cholesterol through the absorption and uptake process,” said Dr. Peter Tontonoz, a UCLA professor and researcher in Pathology and Laboratory Medicine and Biological Chemistry, senior author of an article in Science. “The Aster pathway appears to be a potentially attractive target for limiting intestinal cholesterol absorption and reducing levels of plasma cholesterol.”
Cholesterol from food is absorbed by cells that line the inner surface of the intestines — enterocytes — where it is processed into droplets that eventually reach the bloodstream. But this journey involves a multistep process.
Free cholesterol is drawn into the cell’s plasma membrane — the external boundary of the cell — by a protein called NPC1L1. It then must move to another membranous network in the cell called the endoplasmic reticulum. This is where an enzyme called ACAT2 prepares the cholesterol for packaging and transport, in a process called esterification.
Scientists have not known how cholesterol finds its way into the endoplasmic reticulum to be acted upon by ACAT2. In this study, the researchers investigated the Aster protein family, which is known to bind cholesterol and help it move from one membrane to another.
“How cholesterol that enters the cell through NPC1L1 reaches the endoplasmic reticulum for esterification and regulation of cholesterol synthesis has been a longstanding mystery,” Tontonoz said. “We solve that mystery by showing that two members of the Aster protein family — Aster-B and -C — provide the link between NPC1L1 and ACAT2. By attaching to the plasma membrane, these proteins facilitate cholesterol transport to the endoplasmic reticulum.”
It was previously understood that NPC1L1 was a key player, but this study breaks the process into distinct steps. When NPC1L1 pulls cholesterol from the intestine into the enterocyte, it triggers the recruitment of the Aster proteins.

Published33 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Fergus WalshMedical editorAstraZeneca is facing legal action over its Covid vaccine, by a man who suffered severe brain injury after having the jab in April 2021.Father-of-two Jamie Scott suffered a blood clot that left him with brain damage and unable to keep working.The action, taken under the Consumer Protection Act, alleges the vaccine was “defective” as it was less safe than individuals were entitled to expect.Studies suggest Covid vaccines have saved millions of lives. In June 2022, the World Health Organization said the AstraZeneca vaccine was “safe and effective for individuals aged 18 and above”.’Stringent standards’The legal action is at least a year away from a full court hearing.A further claim from about 80 people who say they were injured by the AstraZeneca vaccine is also due to be launched later this year but Mr Scott’s case is expected to be heard first. AstraZeneca said: “Patient safety is our highest priority and regulatory authorities have clear and stringent standards to ensure the safe use of all medicines, including vaccines. “Our sympathy goes out to anyone who has lost loved ones or reported health problems.”From the body of evidence in clinical trials and real-world data, Vaxzevria [the vaccine against Covid] has continuously been shown to have an acceptable safety profile and regulators around the world consistently state that the benefits of vaccination outweigh the risks of extremely rare potential side effects.” ‘Wholly insufficient’Many of the claimants have received one-off fixed tax-free payments of £120,000 under the government’s Vaccine Damage Payment Scheme (VDPS), which provides compensation for those injured or to bereaved next of kin. Official figures obtained under a Freedom of Information request showed at least 144 out of 148 VDPS payments had gone to recipients of the AstraZeneca vaccine, the Daily Telegraph reported. And an attempt to have the VDPS overhauled is at the heart of these legal actions.Claimants have to show the vaccine caused serious disability of at least 60%. And the families say the level of compensation is wholly insufficient and has not been adjusted for inflation since 2007. On 7 April 2021, the Joint Committee on Vaccination and Immunisation advised adults aged under 30 be offered an alternative to the AstraZeneca vaccine, “following reports of extremely rare blood clots in a very small number of people”.On 7 May 2021, the guidance was amended to apply to adults aged under 40.Mr Scott was aged 44 when he received the AstraZeneca vaccine, on 23 April 2021.Kate Scott, Jamie’s wife, told the BBC: “Jamie has had over 250 rehabilitation sessions from specialists, he had to learn to walk again, to swallow, to talk. [He has had] memory problems. “Although he has done very well with them we are at the point now where this new version of Jamie… is the version that will go forward. He has cognition problems…he has aphasia..severe headaches, blindness.”She added: “We need the government to reform the vaccine damage payment scheme. It is inefficient and unfair…and then fair compensation.”Not-for-profit basisOn 4 January 2021, Brian Pinker, 82, became the first person to receive the AstraZeneca Covid vaccine outside of a clinical trial. He was given the jab in Oxford, just a few hundred metres away from the Jenner Institute, where the vaccine had been developed. The government called it a pivotal moment in the fight against the virus. The immunisation came just weeks after the rollout of the Pfizer-BioNTech jab. By September 2022, some 53 million people in the UK had received at least one dose of Covid vaccine.AstraZeneca manufactured the Oxford vaccine on a not-for-profit basis. And the vaccine had saved more than six million lives in its first year of use, more than any other Covid jab, an independent study by disease-forecasting company Airfinity, published last year, estimated.But within a few months of the AstraZeneca vaccine rollout, cases began emerging of a potential side effect from blood clots. And a condition known as vaccine-induced immune thrombosis and thrombocytopenia (VITT) was eventually identified.The cases were so rare they had not been identified in the global trials of the vaccine. More on this storyUnder 40s to be offered alternative to AZ vaccinePublished7 May 2021Under-30s offered alternative to Oxford-AZ jabPublished7 April 2021Related Internet LinksCOVID-19 vaccination – NHS.websiteThe BBC is not responsible for the content of external sites.

A drug currently in clinical trials as a cancer therapy can also stimulate pancreatic beta cells to secrete insulin, revealing a previously unknown mechanism for insulin regulation in type 2 diabetes, according to a new study by Weill Cornell Medicine investigators. The preclinical discovery, reported Nov. 9 in Nature Chemical Biology, provides a new chemical tool for probing the biology of diabetes, and could point the way toward better treatments for the disease.
“We have known about insulin for a century, but when it comes to the major mechanisms controlling insulin secretion, there are still a lot of things which are unknown,” said senior author Dr. Shuibing Chen, director of the Center for Genomic Health and the Kilts Family Professor of Surgery at Weill Cornell Medicine.
To search for new insulin-regulating mechanisms, Dr. Chen and her colleagues, including first author Dr. Angie Chi Nok Chong, a postdoctoral associate in Dr. Chen’s lab, began by testing a library of drugs on cultures of mouse pancreatic beta cells, looking for compounds that stimulated insulin secretion in response to glucose.
“Instead of running a large-scale drug screening, we decided to do a focused library,” said Dr. Chen who is also a member of the Hartman Institute for Therapeutic Organ Regeneration at Weill Cornell Medicine. “So, we had candidates that we knew might be involved in certain important biological processes.”
The screen identified three compounds that promoted insulin secretion, two of which targeted known insulin-regulating mechanisms in pancreatic beta cells. A third, however, targeted a protein called CHEK2, which is often mutated in cancer but hadn’t previously been associated with glucose metabolism.
With collaborators at two other institutions, the researchers confirmed that the compound increases glucose-mediated insulin secretion in multiple tests on human and non-human pancreatic cells grown in the laboratory, and various mouse models of type 2 diabetes. “That makes the data very exciting, because it’s really consistent from mouse to human islets in vitro, as well as both mouse and nonhuman primate in vivo,” said Dr. Chen.
Probing the mechanism more closely, the team uncovered a previously unknown insulin secretion-regulating molecular pathway that operates in multiple mammalian species. Dr. Chen says the compound they identified in their initial screen, called AZD7762, promises to be a useful tool for exploring other aspects of insulin regulation.

A treatment to move blood from the umbilical cord into an infant’s body may provide a safe option for preterm infants born after 28 weeks who need rapid support, suggests a study supported by the National Institutes of Health. The procedure, called umbilical cord milking, involves gently squeezing the cord between the thumb and forefinger and pushing the blood into the newborn’s abdomen. The new findings suggest that concerns raised by a 2019 study of infants born before 28 weeks — which concluded that umbilical cord milking might increase the risk of bleeding inside the brain — do not apply to preterm infants born after 28 weeks. The current study appears in Pediatrics.
The standard procedure, delaying cord clamping while blood naturally flows into the infant’s body, takes 30 to 180 seconds. However, cord milking, takes about 20 seconds, reducing delay for infants who need immediate assistance, such as respiratory support. Both procedures allow for umbilical cord blood to reach the infant’s body before clamping, reducing the risk of anemia and other complications seen among infants receiving immediate cord clamping and cutting.
The study was conducted by Anup Katheria, M.D., of the Sharp Mary Birch Hospital for Women & Newborns in San Diego, and colleagues in the United States, Canada and Europe. It was supported by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.
More than 1,000 infants were randomly assigned either to umbilical cord milking or delayed cord clamping. Rates of severe intraventricular hemorrhage (bleeding inside the brain) and/or death did not differ significantly between the two groups (just over 1%). Moreover, the rates of overall intraventricular hemorrhage were also similar between the groups (approximately 12%). The researchers will follow all the infants in the study for two years to observe longer term outcomes.

Sensitivity to common food allergens such as dairy and peanuts could be an important and previously unappreciated cause of heart disease, new research suggests — and the increased risk for cardiovascular death includes people without obvious food allergies.
That increased risk could be comparable to — or exceed — the risks posed by smoking, as well as diabetes and rheumatoid arthritis, the researchers report.
UVA Health scientists and their collaborators looked at thousands of adults over time and found that people who produced antibodies in response to dairy and other foods were at elevated risk of cardiovascular-related death. This was true even when traditional risk factors for heart disease, such as smoking, high blood pressure and diabetes, were taken into account. The strongest link was for cow’s milk, but other allergens such as peanut and shrimp were also significant.
The troubling finding represents the first time that “IgE” antibodies to common foods have been linked to increased risk of cardiovascular mortality, the researchers report. The findings do not conclusively prove that food antibodies are causing the increased risk, but the work builds on prior studies connecting allergic inflammation and heart disease.
Approximately 15% of adults produce IgE antibodies in response to cow’s milk, peanuts and other foods. While these antibodies cause some people to have severe food allergies, many adults who make these antibodies have no obvious food allergy. The new research found that the strongest link with cardiovascular death was in people who had the antibodies but continued to consume the food regularly — suggesting they didn’t have a severe food allergy.
“What we looked at here was the presence of IgE antibodies to food that were detected in blood samples,” said researcher Jeffrey Wilson, M.D., Ph.D., an allergy and immunology expert at the University of Virginia School of Medicine. “We don’t think most of these subjects actually had overt food allergy, thus our story is more about an otherwise silent immune response to food. While these responses may not be strong enough to cause acute allergic reactions to food, they might nonetheless cause inflammation and over time lead to problems like heart disease.”
Unexpected Food Allergy Findings
The researchers were inspired to investigate the possibility that common food allergies could be harming the heart after members of the UVA team previously linked an unusual form of food allergy spread by ticks to heart disease. That allergy, first identified by UVA’s Thomas Platts-Mills, M.D., Ph.D., is transmitted by the bite of the lone star tick, found throughout much of the country.

Leveraging artificial intelligence and the largest pediatric brain MRI dataset to date, researchers have now developed a growth chart for tracking muscle mass in growing children. The new study led by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, found that their artificial intelligence-based tool is the first to offer a standardized, accurate, and reliable way to assess and track indicators of muscle mass on routine MRI. Their results were published today in Nature Communications.
“Pediatric cancer patients often struggle with low muscle mass, but there is no standard way to measure this. We were motivated to use artificial intelligence to measure temporalis muscle thickness and create a standardized reference,” said senior author Ben Kann, MD, a radiation oncologist in the Brigham’s Department of Radiation Oncology and Mass General Brigham’s Artificial Intelligence in Medicine Program. “Our methodology produced a growth chart that we can use to track muscle thickness within developing children quickly and in real-time. Through this, we can determine whether they are growing within an ideal range.”
Lean muscle mass in humans has been linked to quality of life, daily functional status, and is an indicator of overall health and longevity. Individuals with conditions such as sarcopenia or low lean muscle mass are at risk of dying earlier, or otherwise being prone to various diseases that can affect their quality of life. Historically, there has not been a widespread or practical way to track lean muscle mass, with body mass index (BMI) serving as a default form of measurement. The weakness in using BMI is that while it considers weight, it does not indicate how much of that weight is muscle. For decades, scientists have known that the thickness of the temporalis muscle outside the skull is associated with lean muscle mass in the body. However, the thickness of this muscle has been difficult to measure in real-time in the clinic and there was no way to diagnose normal from abnormal thickness. Traditional methods have typically involved manual measurements, but these practices are time consuming and are not standardized.
To address this, the research team applied their deep learning pipeline to MRI scans of patients with pediatric brain tumors treated at Boston Children’s Hospital/Dana-Farber Cancer Institute in collaboration with Boston Children’s Radiology Department. The team analyzed 23,852 normal healthy brain MRIs from individuals aged 4 through 35 to calculate temporalis muscle thickness (iTMT) and develop normal-reference growth charts for the muscle. MRI results were aggregated to create sex-specific iTMT normal growth charts with percentiles and ranges. They found that iTMT is accurate for a wide range of patients and is comparable to the analysis of trained human experts.
“The idea is that these growth charts can be used to determine if a patient’s muscle mass is within a normal range, in a similar way that height and weight growth charts are typically used in the doctor’s office,” said Kann.
In essence, the new method could be used to assess patients who are already receiving routine brain MRIs that track medical conditions such as pediatric cancers and neurodegenerative diseases. The team hopes that the ability to monitor the temporalis muscle instantly and quantitatively will enable clinicians to quickly intervene for patients who demonstrate signs of muscle loss, and thus prevent the negative effects of sarcopenia and low muscle mass.
One of the limitations lies in the algorithms reliance on scan quality, and how a suboptimal resolution can affect measurements and the interpretation of results. Another drawback is the limited amount of MRI datasets available outside of the United States and Europe that can give an accurate global picture.
“In the future, we may want to explore if the utility of iTMT will be high enough to justify getting MRIs on a regular basis for more patients,” said Kann. “We plan to improve model performance by training it on more challenging and variable cases. Future applications of iTMT could allow us to track and predict morbidity, as well as reveal critical physiologic states in patients that require intervention.”

In 2021, a Northwestern University-led research team received a Defense Advanced Research Projects Agency (DARPA) contract worth up to $33 million to develop an implantable “living pharmacy” to control the human body’s sleep/wake cycles. Now, the researchers have completed a major step toward achieving this goal.
In new work, researchers have developed a novel device that produces oxygen at the site in order to keep cells alive inside the self-contained implant. Oxygen is a major ingredient for keeping cells alive — and thriving — for longer periods of time inside of the implantable pharmacy. Because the longer cells can stay alive and healthy, the longer they can autonomously produce therapeutics for the body.
By using electricity to split water that the cells are already bathed in, the researchers were able to produce oxygen while avoiding the production of harmful byproducts such as chlorine or hydrogen peroxide. And by controlling the amount of electricity used, the researchers could change how much oxygen it produces.
In new experiments, the novel device (called the “electrocatalytic on-site oxygenator” or “ecO2”) kept cells (70-80%) alive for close to a month in low oxygen conditions in vitro or for weeks in vivo. Without ecO2, only about 20% of cells were alive after 10 days, but the researchers hypothesize that the cells would lose their ability to secrete drugs long before that. With advances in wireless power and communication, the researchers are confident that chronic operation over multiple months or more is within reach.
The research will be published on Thursday (Nov. 9) in the journal Nature Communications.
“Our device can be used to improve the outcomes of cell-based therapies, which use biological cells to treat diseases or injuries in the body,” said Northwestern’s Jonathan Rivnay, who co-led the study. “Cell-based therapies could be used for replacing damaged tissues, for drug delivery or augmenting the body’s own healing mechanisms, thus opening opportunities in wound healing and treatments for obesity, diabetes and cancer, for example. Generating oxygen on site is critical for many of these ‘biohybrid’ cell therapies. We need many cells to have sufficient production of therapeutics from those cells, thus there is a high metabolic demand. Our approach would integrate the ecO2 device to generate oxygen from the water itself.”
Rivnay is a professor of biomedical engineering and materials science and engineering at Northwestern’s McCormick School of Engineering and principal investigator of the DARPA-funded NTRAIN (Normalizing Timing of Rhythms Across Internal Networks of Circadian Clocks) project. He co-led the new study with Tzahi Cohen-Karni, a professor of biomedical engineering and materials science and engineering at Carnegie Mellon University (CMU). The study’s co-first authors are Northwestern’s Abhijith Surendran and CMU’s Inkyu Lee.