Mayo Clinic researchers have developed a genetic test that can help predict how people will respond to weight loss medications such as GLP-1s.

The test estimates an individual's calories to satiation (CTS) — how much food it takes for a person to feel full — and links this biological trait to treatment success. The findings, published in Cell Metabolism, represent a promising step toward more personalized and effective treatments for people living with obesity.

"Patients deserve treatments that reflect their biology, not just their body size," says Andres Acosta, M.D., Ph.D., a gastroenterologist at Mayo Clinic and senior author of the study. "This test helps us deliver the right medication to the right person from the start."

Beyond body size

Obesity is a chronic, complex disease that affects more than 650 million adults worldwide. It stems from a mix of genetic, environmental and behavioral factors that vary from person to person. This complexity helps explain why people respond differently to weight-loss interventions. Yet treatment decisions often rely on simple measures such as body mass index (BMI) rather than the biological processes that drive weight gain and weight loss.

To uncover these processes, Dr. Acosta has focused on satiation, the physiological signal that tells the body it has eaten enough. In 2021, he and his colleagues defined a series of obesity phenotypes to describe eating patterns. For example, some people with obesity tend to eat very large meals ("hungry brain"), while others may eat average portions but snack frequently throughout the day ("hungry gut").

In this study, the researchers studied satiation in nearly 800 adults with obesity by inviting them to partake in an all-you-can-eat meal of lasagna, pudding and milk until they felt "Thanksgiving full." The results revealed striking variation: Some participants stopped after 140 calories whereas others consumed more than 2,000. On average, men consumed more calories than women.

The team investigated possible explanations for this variability. Several factors, including body weight, height, percentage of body fat, waist-to-hip ratio and age — as well as appetite-related hormones such as ghrelin and leptin — played a small role. But none accounted for the huge range in calorie intake. So the researchers turned to genetics.

Using machine learning, the researchers combined variants in 10 genes known to influence food intake into a single metric called the CTS-GRS (Calories to Satiation Genetic Risk Score). The score, calculated from a blood or saliva sample, provides a personalized estimate of a person's expected satiation threshold.

Matching genes to medications

Mayo Clinic researchers then calculated this CTS-GRS metric in clinical trials of two FDA-approved medications: a first-generation weight loss drug, phentermine-topiramate (brand name Qsymia), and a newer GLP-1 drug, liraglutide (Saxenda). They found that:

• People with a high satiation threshold lost more weight on phentermine-topiramate. This drug may help control portion size and reduce large-meal overeating (hungry brain).
• People with a low satiation threshold responded better to liraglutide. This drug may reduce overall hunger and frequency of eating (hungry gut).

"With one genetic test, we can predict who is most likely to succeed on two different medications," says Dr. Acosta. "That means more cost-effective care and better outcomes for patients."

The team has conducted additional studies to predict response to semaglutide, another GLP-1 medication (sold under the brand names Ozempic and Wegovy), and results are expected soon. They are working to expand the test by incorporating data from the microbiome and metabolome, as well as developing models to predict common side effects such as nausea and vomiting.

Conflict of interest or disclosure: The CTS-GRS technology was licensed to Phenomix Sciences, a Mayo Clinic innovation commercialization partner.  The technology is already being used in 300 clinics in the U.S. 

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Mayo Clinic researchers have developed a new way to predict whether existing drugs could be repurposed to treat heart failure, one of the world’s most pressing health challenges. By combining advanced computer modeling with real-world patient data, the team has created "virtual clinical trials" that may facilitate the discovery of effective therapies while reducing the time, cost, and risk of failed studies.

"We've shown that with our framework, we can predict the clinical effect of a drug without a randomized controlled trial. We can say with high confidence if a drug is likely to succeed or not," says Nansu Zong, Ph.D., a biomedical informatician at Mayo Clinic and lead author of the study, which was published in npj Digital Medicine.

An urgent need

Heart failure affects more than 6 million Americans and is a leading cause of hospitalization and death. Despite decades of research, treatment options remain limited and many clinical trials fail. Traditional drug development is costly and slow, often taking more than a decade and $1 billion to bring a single therapy to market.

Drug repurposing — finding new uses for medicines already approved for other conditions — could offer a faster, less costly pathway. Because the safety of these drugs is already established, researchers can move directly to studying their potential benefits for new diseases. Yet determining which drugs are worth pursuing remains a major challenge.

Dr. Zong led efforts with a multidisciplinary team of experts in biochemistry, molecular pharmacology, cardiovascular medicine and quantitative health sciences to combine two powerful tools: computer models that predict how drugs interact with biological systems, and electronic health records (EHRs) from nearly 60,000 patients with heart failure.

Using these tools, the researchers designed virtual clinical trials — also called trial emulations — that mimic the structure of a randomized clinical trial. Instead of recruiting participants, they used existing patient data to create comparison groups and measure outcomes such as changes in biomarkers that track heart failure progression.

To strengthen the accuracy of these predictions, the team added drug-target modeling, a method that uses AI to analyze chemical structures alongside biological data, such as protein sequences or genes. This addition helped bridge the gap between real-world patient data and traditional randomized trials.

The team tested this approach with 17 drugs that had already been studied in 226 Phase 3 heart failure clinical trials. Seven had shown benefit, while 10 had not. The virtual clinical trials accurately predicted the "direction" of those real-world results.

"This model has the potential to guide drug development pipelines at scale," says Dr. Zong. "Right now, it can tell us the direction of efficacy — whether a drug will be beneficial — but not yet the level of that effect. That's our next step."

Faster, smarter clinical research

By identifying which repurposed drugs are most promising, researchers can prioritize them for further clinical testing and focus resources where success is most likely. That could mean faster access to therapies for patients and lower costs for healthcare systems.

Originally developed as an AI-enabled framework for virtual clinical trials, this technology has now led to a broader initiative within Mayo Clinic under the guidance of Cui Tao, Ph.D., the Nancy Peretsman and Robert Scully Chair of Department of Artificial Intelligence and Informatics and vice president of Mayo Clinic Platform Informatics. The new effort is exploring three complementary approaches:

• Trial emulation — replicating the design and analysis of a completed or hypothetical trial using real-world data to validate findings or generate evidence
• Trial simulation — creating a mock trial with real-world data to estimate how an existing treatment would perform in a different population or for a new indication
• Synthetic trials — constructing a trial that replaces or augments one or more arms with real-world or modeled patient data

"Clinical trials will always remain essential," says Dr. Tao. "But this innovation demonstrates how AI can make research more efficient, affordable and broadly accessible. Integrating trial emulation, simulation, synthetic trials and biomedical knowledge modeling opens the door to a new paradigm in translational science."

Looking ahead, these innovations could become an integral part of Mayo Clinic's enterprise strategy. They could support Mayo's strategic efforts such as Precure by advancing proactive risk prediction and prevention and Genesis by informing intelligent transplant care delivery and personalized interventions.

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At the first U.S. 'Undiagnosed Hackathon,' scientists from around the world will team up at Mayo Clinic to solve unsolved medical mysteries. 

Young Julian Limon clutches his blanket wherever he goes, a source of comfort during hospital stays, procedures and tests. At 17 months, he has not yet reached walking or talking milestones. His brittle hair and unexplained neurological symptoms compound his challenges. He has endured pneumonia and other respiratory illnesses, and his weak immune system leaves him vulnerable. Despite extensive evaluations and genetic testing, Julian's condition remains a mystery.

This September, Julian's family will travel to Mayo Clinic in Minnesota to take part in the Undiagnosed Hackathon, a global effort to solve rare diseases that have long gone unexplained. 

The Hackathon was inspired by Helene and Mikk Cederroth, founders of the Wilhelm Foundation, who lost two young sons and a daughter to an undiagnosed condition. Their grief became a call to action. Over the past two decades, they've built a global network of scientists, clinicians and advocates committed to finding answers. 

An unprecedented collaboration

Over three days at Mayo Clinic, more than 125 scientists, clinicians and AI experts will gather for the first U.S.-based Undiagnosed Hackathon. They will come from 30 countries across six continents. Their goal: to uncover answers for Julian and 28 others whose conditions have eluded diagnosis. 

Having families in person at the Hackathon allows researchers to observe traits and ask questions that data alone can't capture. 

"If you put a molecular biologist next to a bioinformatician next to a clinician who have come from different parts of the world, each will bring a unique lens to the same investigation shaped by their training and lived experience," Dr. Klee says. "That's how breakthroughs happen." 

Unlocking hidden clues with advanced tools 

Among the international team are Mayo Clinic's Dr. Cherisse Marcou, assistant professor and co-director of the Clinical Genomics laboratory, and Dr. Eric Klee, the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation. After participating in last year’s Undiagnosed Hackathon in the Netherlands, they return with momentum to co-lead this year’s event. 

Working with global colleagues, they’ll explore DNA, RNA and other signals using tools that reveal what standard tests can miss. This includes examining long DNA stretches, studying RNA to see which genes are active and identifying chemical changes that turn genes on or off — a process called methylation.

This complex approach, known as omics, combines layers of biological information to better understand how the body works and why disease occurs. Bringing multiple omics together is more like a moving picture than a still photo, where hidden patterns emerge. Artificial intelligence will help scientists integrate these layers and interpret the results.

Breaking silos to spark breakthroughs 

"I come from a place where many families are not afforded the access to the latest and greatest diagnostic testing options in their diagnostic journey," Dr. Marcou says. "To be part of something that brings hope worldwide is deeply personal."

The idea behind the Hackathon is bringing people together who might not otherwise work side by side. 

"If you put a molecular biologist next to a bioinformatician next to a clinician who have come from different parts of the world, each will bring a unique lens to the same investigation shaped by their training and lived experience," Dr. Klee says. "That's how breakthroughs happen." 

Fueled by passion, and personal connection 

Now in its third year, the Hackathon has become a global engine for rare disease discovery. The Cederroths have co-led every one. 

"They've poured their lives into this mission," Dr. Marcou says. "Their energy is transformative. You leave the Hackathon changed." 

For Dr. Marcou, the work is personal. She grew up in the Bahamas, where access to advanced diagnostics is limited. 

"I come from a place where many families are not afforded the access to the latest and greatest diagnostic testing options in their diagnostic journey," she says. "To be part of something that brings hope worldwide is deeply personal." 

Dr. Marcou clinically interprets and decodes genomic data to deliver real-time insights for patients every day and has been involved in the development of AI tools at Mayo Clinic to advance this work. Dr. Klee, a leader in rare disease research, is building the Research Data Atlas to accelerate discoveries by unifying Mayo Clinic's extensive research data. 

Hope for families, and ripple effects worldwide

The Hackathon's goal is ambitious: solve as many cases as possible. Last year, 10 of 26 participants received diagnoses, with promising leads for nine more. One person's diagnosis can also unlock recognition, testing and potential treatment options for others with the same condition. 

"Our ultimate goal is to find answers for all our participants. That said, if we can find an answer for even one person, that would be amazing. If we find answers for 10 or 12 participants, that would be incredible," Dr. Klee says. "And for the participants where a clear answer eludes us, we hope to find strong leads that guide future research and testing for others." 

The Hackathon doesn't end when the event does. The findings must be clinically confirmed before they become diagnoses. For those who receive answers, the next goal is treatment, if one exists. For cases that remain unsolved, the work continues. 

It's also a powerful exchange of knowledge. Collaborators from places with fewer resources gain exposure to advanced techniques, while all experts have the opportunity to learn new approaches from those working alongside them. 

"It's peer-to-peer learning at its best," Dr. Marcou says. "We're all better for it." 

Julian's diagnostic journey

Even after long days of doctor visits and tests, Julian still breaks into bright smiles. He is working with physical therapists to build strength as his family continues to hope for a diagnosis. 

"I feel incredibly grateful that we'll have so many experts looking closely at Julian," says his mother, Jasmine Limon. "I just want to know what we're facing so we can give him the best possible care." 

At its heart, the Hackathon is where some of the world's brightest minds gather around families like Julian's, determined to give all they can and to open new doors in medicine. 

The post When diagnosis hits a wall, this global hackathon opens new doors  appeared first on Mayo Clinic News Network.

World Heart Day is September 29

ROCHESTER, Minn. — You may have heard of the mind-body connection: the broad concept that  thoughts and feelings, especially those related to stress, can influence physical health. Mohamad Alkhouli, M.D., an interventional cardiologist at Mayo Clinic in Rochester, Minnesota, is researching the relationship between the brain and the heart. Each can have a powerful impact on the other, Dr. Alkhouli explains.

"The mind-heart connection is part of the broader mind-body relationship, but it’s uniquely powerful. Emotional states like anxiety, grief, or even joy can directly influence heart rhythms, blood pressure, and even the risk of heart attacks," Dr. Alkhouli says. "At the same time, the heart sends signals back to the brain through nerves, hormones, and pressure receptors — affecting our mood, attention, and stress levels. So, it’s not just the brain talking to the heart; the heart talks back."

Conditions with a brain-heart connection include spontaneous coronary artery dissection (SCAD) and stress-induced cardiopathy (SICM), also known as broken heart syndrome. Both conditions can result from stress. Dr. Alkhouli has been part of Mayo Clinic research teams exploring aspects of each.

Broken heart syndrome often is sparked by stressful situations and extreme emotions; it briefly interrupts the way the heart pumps blood. People experiencing it may have sudden chest pain and think they're having a heart attack.

The tools typically used to screen for heart attacks cannot identify when broken heart syndrome is actually the cause of a patient's chest pain. In most cases, invasive coronary angiography is required to differentiate SICM from myocardial infarction due to coronary obstruction. Mayo research found that a novel technology called magnetocardiography, which measures magnetic fields generated by the heart, can help identify broken heart syndrome. 

Another Mayo study suggests that SCAD, a type of heart attack that often results from physical or emotional stress, can be a secondary event instigated by broken heart syndrome.

In broken heart syndrome, the heart's temporary weakening doesn't happen evenly: Some parts of the heart fail to contract well, while others work harder to compensate, Dr. Alkhouli says. This uneven motion creates twisting forces on the heart muscle. 

"Because the coronary arteries, the main blood vessels that supply blood to the heart, sit on top of the heart, they can be stretched or stressed at the junctions between these overactive and underactive areas during broken heart syndrome," he explains. "In some cases, this stress may cause a tear in the artery wall, what we call SCAD."

A question still to be answered is why some people develop broken heart syndrome after emotional trauma while others do not, Dr. Alkhouli notes.

Emotional stress also can increase the risk of other heart conditions, such as:

• High blood pressure, also known as hypertension.
• Heart disease.
• Atrial tachycardia.
• Bradycardia.

"What fascinates me most is how deeply intertwined our emotional and cardiovascular systems are, and how much we still don't understand," Dr. Alkhouli says. "Could we one day 'rewire' this connection for healing, using therapy, neuromodulation (alteration of nerve activity at targeted sites in the body by electrical or chemical means), or even digital tools? At Mayo Clinic, we're exploring these questions, and we're beginning to see the heart and brain not as separate organs, but as a single, dynamic network."

That network works in both directions. Dr. Alkhouli is part of Mayo's Heart Brain Clinic, where cardiologists and neurologists work together to evaluate patients who may have neurological symptoms that can be attributed to a cardiac event.

In these patients, the heart and brain are closely linked, such as strokes caused by clots that form in the heart, known as cardioembolic strokes. The causes of a transient ischemic attack, a short period of stroke-like symptoms, may include a blood clot that moves from another part of the body, such as the heart, to an artery that supplies the brain. The heart condition atherosclerosis, the buildup of fats, cholesterol and other substances in and on the artery walls, can also lead to a transient ischemic attack.  

More research is needed to better understand how to harness the mind-heart connection for disease prevention and healing. There are steps you can take now for your mental health that will benefit your heart, and things you can do for your heart health that will benefit your brain, Dr. Alkhouli says.

"The good news is that what's good for your mind is often good for your heart, and vice versa," he explains. That includes:

• Managing stress.
• Getting quality sleep.
• Staying socially connected.
• Practicing mindfulness or prayer.

"All have measurable benefits for heart health," Dr. Alkhouli says. "Likewise, regular physical activity, a heart-healthy diet and controlling blood pressure and cholesterol can boost mood and cognitive function. It's a powerful feedback loop: Caring for one supports the other."

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu

The post The brain-heart connection: Mayo Clinic expert explains powerful tie that works both ways appeared first on Mayo Clinic News Network.

Mayo Clinic researchers have pinpointed how excessive alcohol consumption contributes to fatty liver disease, a condition that affects more than one in three people in the U.S. Also known as Metabolic Dysfunction Associated Steatotic Liver Disease, it is a long-lasting disease that can lead to type 2 diabetes and even liver cancer. Excessive alcohol can contribute to this fatty disease as well — and Mayo Clinic researchers recently discovered a reason why.

The researchers found that exposure to excessive alcohol alters an important enzyme that recycles damaged proteins.

How the liver works

The liver is the primary filter for everything you ingest. Liver cells, or hepatocytes, support this organ's giant job by releasing dozens of various proteins while collecting, sorting, degrading and recycling nearly everything that passes through this massive, sieve-like organ. Fat coming from the gut, for example, is absorbed then stored in hepatocytes as lipid droplets, which are globular structures that store fat. The body can use these lipid droplets as an energy source, especially during periods of fasting. However, too many lipid droplets can lead to fatty liver disease.

The researchers found the key lies with an important enzyme called the valosin-containing protein (VCP). VCP plays a role in many important processes including recycling unwanted proteins and is found in cells throughout the body.

"We were surprised to see VCP removing a specific protein from the surface of the lipid droplet. When that particular protein called HSD17β13 accumulates, the fat content in liver cells balloons and contributes to fatty liver disease," says Mark McNiven, Ph.D., senior author on the study, which was published and highlighted in the Journal of Cell Biology.

In people without fatty liver disease, the enzyme, VCP, appears to keep the protein, HSD17β13, in check to prevent lipid droplets from over-accumulating in the liver cells.

However, the researchers found that exposure to excessive alcohol removes VCP almost completely from the lipid droplet surface, allowing HSD17β13 to significantly accumulate.

Watch: The Mayo Clinic Minute

The researchers also saw and captured the elaborate recycling mechanism of VCP. They witnessed VCP working with a chaperone protein to deliver damaged proteins to an organelle called a lysosome, which then broke apart the unwanted proteins.

"It was astounding to see this. We tried several experiments to confirm what we were seeing, and every result indicated VCP directs the HSD17β13 protein from the lipid droplet to the lysosome," says Sandhya Sen, Ph.D., a Mayo Clinic research fellow and lead author of the study.

Their findings mean HSD17β13 is a target for potential new therapies to prevent or treat fatty liver disease, says Dr. McNiven.

"This study increases our understanding of the biology of lipid droplets, the central culprit of fatty liver, and how the hepatocyte works in an effort to reduce its fat content," Dr. McNiven says. "It also could help predict which patients are prone to the detrimental effect of excessive alcohol consumption on their liver if this cellular system is compromised."

The research is part of a larger effort at Mayo Clinic called the Precure initiative focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding. 

The post New research reveals a link between excessive alcohol and fatty liver disease appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Clinicians typically classify meningiomas — the most common type of brain tumor — into three grades, ranging from slow-growing to aggressive.

But a new multi-institutional study suggests that appearances may be deceiving. If a tumor shows activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low-grade under the microscope.

"High TERT expression is strongly linked to faster disease progression," says Gelareh Zadeh, M.D., Ph.D., a neurosurgeon at Mayo Clinic and senior author of the study. "This makes it a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease."

An early warning sign

Meningiomas — tumors of the meninges, the protective tissue that surrounds the brain and spinal cord — are generally considered benign. But a small subset of these tumors has a mutation in the TERT gene, which is linked to faster growth and a shorter time before the tumor returns after treatment.

TERT is the active part of telomerase, an enzyme that maintains telomeres, the protective ends of chromosomes. In most healthy adult cells, TERT is switched off. But if it becomes switched back on, it can fuel cancer development by driving unchecked cell growth.

In this study, the researchers wanted to see whether high TERT expression, even in the absence of the TERT genetic mutation, also predicted worse outcomes. They looked at more than 1,200 meningiomas from patients across Canada, Germany and the U.S., and they found that nearly one-third of them had high TERT expression despite not having the mutation.

These patients had earlier tumor regrowth compared to those without TERT expression, though their outcomes were better than patients with full-blown TERT mutations.

"TERT-positive tumors behaved like they were one grade worse than their official diagnosis," says Dr. Zadeh. "For example, a grade 1 tumor with TERT expression acted more like a grade 2."

Guiding treatment decisions

The findings suggest that testing for TERT activity could help doctors predict which patients are at higher risk for recurrence and may need closer monitoring or more intensive treatment.

"Because meningiomas are the most common primary brain tumor, this biomarker could influence how thousands of patients are diagnosed and managed worldwide," says Dr. Zadeh.

"TERT expression can help us more accurately identify patients with aggressive meningiomas," Chloe Gui, M.D., a neurosurgery resident at the University of Toronto, Mayo Clinic research collaborator and the study's lead author, explains on a podcast hosted by The Lancet Oncology. "This information allows us to offer treatment tailored to the tumor's behavior." "This information allows us to offer treatment tailored to the tumor's behavior."

The team is currently investigating ways to incorporate TERT expression into the clinical workflow. The research is part of a larger effort at Mayo Clinic called the Precure initiative, focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and to providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post New genetic biomarker flags aggressive brain tumors appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A Mayo Clinic study finds that a shortened, less intense course of radiation and chemotherapy after minimally invasive surgery for HPV-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) results in less toxicity, substantially lowering the rates of treatment-related side effects while maintaining high cure rates. The findings were published in The Lancet Oncology.

"This is a game-changer for patients," says Daniel Ma, M.D., senior author of the study and head and neck radiation oncologist at Mayo Clinic Comprehensive Cancer Center. "We've significantly reduced the burden of long-term side effects without compromising the effectiveness of the treatment. This shorter, less intensive regimen allows patients to return to their lives more quickly and with a better quality of life."

Standard treatments for HPV-related oropharyngeal cancer typically involve seven weeks of daily radiation and chemotherapy, or surgery followed by six weeks of radiation and chemotherapy. While highly effective, these treatments often lead to significant long-term side effects due to high toxicity, such as jawbone failure, dry mouth, changes in taste and challenges with swallowing. "These greatly affect the quality of life for patients, many of whom are young, in their 40s and 50s," says Dr. Ma.

In the randomized phase 3 study, Mayo Clinic researchers compared the standard treatment to a new approach involving minimally invasive transoral surgery followed by a two-week course of gentler radiation therapy called de-escalated regimen of adjuvant radiotherapy (DART). DART uses about half as much radiation and a reduced dose of chemotherapy, one-fifth of the standard dose.

The results demonstrated that the less intensive treatment approach significantly reduced both severe (grade 3 or higher) and moderate (grade 2) toxicities, indicating fewer adverse events and improved symptom burden for patients following treatment. Importantly, disease control rates were comparable to the standard treatment for intermediate-risk patients.

For specific high-risk patients, namely those with five or more lymph nodes and disease extending outside of the lymph nodes, the standard treatment showed slightly better disease control, potentially due to chemotherapy-related factors rather than radiation. The researchers add that these patients should still receive the standard six-week treatment.

The study involved 228 patients treated at Mayo Clinic in Minnesota and Arizona. The researchers say that this study represents the largest cohort of postsurgical de-escalation patients in the published literature.

Further, ongoing research will continue to explore using biomarkers such as circulating DNA to find the best patient populations for this treatment strategy.

Review the paper for a complete list of authors, disclosures and funding. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

About Mayo Clinic Comprehensive Cancer Center 
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives.

Media contact:

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post Shorter, less intense radiation-chemo regimen effective for HPV-linked oropharyngeal cancer, Mayo study shows appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — Mayo Clinic's pioneering exploration of stem cell-based therapies for bone loss is headed to space. Abba Zubair, M.D., Ph.D., is medical director of Transfusion Medicine and Stem Cell Therapy at Mayo Clinic in Florida.

He is leading research exploring how bone-forming stem cells behave in microgravity in hopes of developing novel treatments for diseases that cause bone loss, including osteoporosis. 

Dr. Zubair's research is one of several science experiments selected by NASA as part of the 33rd SpaceX Commercial Resupply Mission to the International Space Station.

The SpaceX Dragon spacecraft on a Falcon 9 rocket is targeted for 2:45 a.m. EDT, Sunday, Aug. 24, from Cape Canaveral Space Force Station in Florida.

In addition to the science experiments, the Dragon spacecraft will deliver 5,000 pounds of supplies, including food and equipment to the crew at the orbital laboratory.

"For this project, our goal is to really understand how gravity affects bone formation and bone loss, particularly in relation to mesenchymal stem cells and other bone-forming cells," says Dr. Zubair.

"This is going to be significant because it will help us better understand the mechanisms of bone loss during vital times such as in menopausal women or people who are bedridden for extended amounts of time." 

Dr. Zubair believes the research also will provide hope for hundreds of millions of people worldwide affected by osteoporosis, the disease that weakens bones and increases the risk of fractures.

Dr. Zubair's research also is aimed at improving the health of astronauts. Astronauts lose measurable bone density while living in space.

Dr. Zubair's team has identified a protein in the body called IL-6 that can send signals to stem cells to promote bone formation or bone loss. Dr. Zubair's research will investigate whether a new compound can block IL-6 signals and reduce bone loss while in space. 

"If this compound we are testing is able to block the impact of microgravity to slow or stop bone loss, then we can find a treatment for the bone loss in space, and that might also give us a clue into how we may treat people on Earth," says Dr. Zubair.

For more than 20 years, Dr. Zubair has led the Stem Cell Laboratory on Mayo Clinic's Florida campus, developing safe, clinical-grade cell therapy products. His broader research focus aims to harness stem cells to treat degenerative diseases and engineer immune cells to enhance therapeutic outcomes and meet regulatory standards. 

Dr. Zubair's research could potentially advance treatments for brain injury, lung disease, stroke and neurological recovery, cancer, blood stem cell therapies, and epilepsy.

His newest research on bone loss will be his fourth space project selected by NASA at the space station. In recognition of his work, Dr. Zubair received an Exceptional Scientific Achievement Medal from NASA.

From an early age in Nigeria, Dr. Zubair was captivated by space, spending countless hours gazing at the night sky and dreaming of becoming an astronaut. His work as a physician-scientist conducting research in space to improve humanity allows him the best of both worlds.

"I love it. It will be my fourth time attending a launch at the space center. I always get a thrill and wish I was on that rocket heading out," says Dr. Zubair. "It is an unbelievable experience."

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contacts:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu
• Marty Velasco Hames, Mayo Clinic Communications, newsbureau@mayo.edu

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The post Mayo Clinic research set to launch aboard NASA mission to International Space Station to explore new therapies for bone loss appeared first on Mayo Clinic News Network.

For years, cancer researchers have been trying to halt a type of molecule that's involved in several cancers. The molecules — enzymes known as trypsins — split proteins that help tumors grow and spread.

Mayo Clinic cancer biologist Evette Radisky, Ph.D., previously found that one trypsin, called mesotrypsin, plays a role in breast, prostate, pancreatic and lung cancer. Like other enzymes, the molecule has an active site that kicks off reactions with other molecules. Researchers have tried to block the active site but haven’t found a molecule with a specific enough lock-and-key fit to jam the active region.

Recently, however, Dr. Radisky's lab at Mayo Clinic in Florida discovered a new way to block mesotrypsin. They found a "hidden pocket" in the molecule.

"The hidden pocket is separate from the active site, but we found that blocking it has a similar effect of locking the enzyme in an inactive state," says Dr. Radisky, principal investigator of the study that appeared in Science Advances. The team now is taking steps to discover drugs that fit the hidden pocket.

A mystery in the data

"It was a serendipitous finding," says the study’s lead author, Mathew Coban, of the pocket's discovery. As a research technologist in the Radisky lab and a master's degree student at Mayo Clinic Graduate School of Biomedical Sciences, Coban had aimed to understand the structure of mesotrypsin through X-ray crystallography.

The complex technique, which records scattered X-rays as shadows, can describe the overall folds of amino acids in the enzyme and suggest complementary molecules that fit like a puzzle. While reviewing the X-ray crystallography results, Coban noticed a segment of the enzyme that looked out of place. The research team thought it might be an error in the data and set the results aside.

But Coban continued to wonder about the strange area. He had the idea to begin looking for alternate nooks in the mesotrypsin enzyme that could potentially contribute to a stable, non-active enzyme.

What Coban found was a site that was hidden. The team dubbed it a "cryptic pocket." The pocket, adjacent to the active site, opened at moments when mesotrypsin stabilized itself. The next step was clear. "If the pocket is there some of the time, maybe a drug would be able to bind at that site and trap the enzyme in its inactive state," he says.

Finding a drug that binds

The team worked with a colleague, Thomas Caulfield, Ph.D., a former Mayo researcher and drug discovery expert, to conduct a computational screen of potential drug compounds that might fit in the cryptic pocket. They found a single molecule that could bind in the cryptic pocket and inhibit the activity of mesotrypsin.

Importantly, the researchers note, the molecule blocks mesotrypsin selectively, without affecting other trypsins. This could mean less toxicity or fewer side effects for a patient. The finding also means that other cryptic pockets may exist in other trypsin molecules related to cancer, presenting new potential drug targets.  

The team is continuing to look for drug molecules that fit mesotrypsin even better. "Based on the structural information of mesotrypsin that we have now, we've been able to do more computational prediction to identify additional, more potent compounds that we’re now testing in the laboratory," says Dr. Radisky.

"This has been an important step in the understanding of this key enzyme. Our next steps will be to start testing how well our candidate drug molecules fit the cryptic pocket and block cancer invasion and metastasis in models of disease," she says.

The study was funded by grants from the National Institutes of Health, Mayo Clinic Medical Scientist Training Program and Department of Energy Office of Science User Facility.  The authors declare that they have no competing interests.

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While doctors are often focused on monitoring the health and vital signs of others, a new study had some tuning in to their own health and vital statistics as well. The results suggest that doing so may offer doctors real benefits to their own well-being, in a scalable way. 

Physicians who wore a smartwatch and had access to their personal health data — including information on their heart rate, sleep, breathing patterns and physical activity — reported greater resilience and 54% saw a reduction in the overall odds of burnout compared to those who did not receive a study smartwatch, according to new research published in JAMA Network Open. Mayo Clinic investigators conducted the study in collaboration with the University of Colorado School of Medicine.

"Advancing care starts with caring for those who deliver it. We're shaping a future where the well-being of our workforce is integral to the care we deliver."   - Colin West, M.D., Ph.D., Medical Director of Employee Well-Being at Mayo Clinic

Physician well-being is essential not only to personal health, but also to the quality of care patients receive. It's tied to job performance, patient safety, access to care and workforce sustainability.  

That’s why Mayo Clinic and others are prioritizing strategies to strengthen and sustain the well-being of healthcare professionals. 

How the smartwatch trial was designed and conducted 

The 12-month trial was conducted at Mayo Clinic and the University of Colorado School of Medicine. It included 184 physicians across specialties such as primary care, surgery, neurology and oncology. Researchers randomly assigned about half of the participants to wear a smartwatch for the full 12 months, while they gave the other half the watch during the study’s second half.

All participants received brief newsletters with general tips on smartwatch use and reminders to sync their devices. These resources aimed to support awareness of the tools and encourage engagement with personal health data.

Physicians in both study groups wore the device more than 70% of the time during the trial. Participants also completed validated well-being surveys at the beginning and end of the study. 

Participants could view their health data through a mobile app but were not prompted to take specific actions in response to it. Researchers say even this passive approach may help support well-being.  

Designing smarter tools for a healthy workforce

The study was co-designed and led by Arjun Athreya, Ph.D., an electrical and computer engineer in Mayo Clinic's Department of Molecular Pharmacology and Experimental Therapeutics; Colin West, M.D., Ph.D., medical director of Employee Well-Being at Mayo Clinic; and study Principal Investigator Liselotte Dyrbye, M.D., M.H.P.E., senior associate dean for faculty and chief well-being officer at the University of Colorado School of Medicine.  

"We're entering an era where wearable technology, when paired with thoughtful design and artificial intelligence methods that use the data, could help personalize well-being strategies in clinical settings," Dr. Athreya says. "This study shows we can support healthcare professionals with passive monitoring digital technologies with innovative engagement strategies to provide potentially helpful data without adding burden to their day."  

The researchers say this approach can offer timely support as part of a broader physician well-being strategy. 

"While this is an individually focused intervention, it offers an evidence-based way to support physicians in the short term, complementing longer-term efforts aimed at addressing systemic contributors to physician stress," says Dr. Dyrbye. 

Caring for caregivers: A vision for the future

Next steps for the researchers include evaluating long-term outcomes of the smartwatch project. They also plan to explore whether this approach can support other healthcare professionals.

"Advancing care starts with caring for those who deliver it," says Dr. West. "We’re shaping a future where the well-being of our workforce is integral to the care we deliver."   

The Physicians Foundation, Mayo Clinic's Center for Individualized Medicine, and the University of Colorado School of Medicine partly funded the study. Review the study for a complete list of authors, disclosures and funding details. 

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