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Major trial shows increasing bone density fails to cut fracture risk in brittle bone disease

An international clinical trial involving Aston University researchers has challenged long held assumptions about how brittle bone disease is treated in adults, after finding that substantially increasing bone density did not reduce the risk of fractures. The study, published in the Journal of the American Medical Association (JAMA), examined whether a two stage treatment using the bone building drug teriparatide followed by the bone preserving drug zoledronic acid could reduce fractures in adults with osteogenesis imperfecta, often referred to as brittle bone disease, a rare genetic condition that causes bones to break easily throughout life. Researchers followed 349 adults treated at 27 specialist centres across the UK and Europe. While the treatment led to clear increases in bone density in the spine and hip, fracture rates were no lower than among patients receiving standard care, suggesting that bone quality may matter more than bone density alone in preventing fractures in people with the condition. The findings underline a key distinction between brittle bone disease and more common bone conditions such as osteoporosis, where increasing bone density is known to reduce fracture risk. In osteogenesis imperfecta, the study suggests that bones can become denser without becoming less likely to break, indicating that the underlying quality and structure of bone tissue may play a greater role in fracture risk than density alone. Dr Zaki Hassan Smith, an endocrinologist at Aston Medical School who contributed to the research, said: “This study shows that in osteogenesis imperfecta, simply increasing bone density doesn’t necessarily translate into fewer fractures. That’s important, because it tells us that the disease is more complex than what we see on a scan. The findings help shift the focus towards understanding bone quality and how bones behave in real life, which is essential if we are to develop more effective treatments that genuinely reduce harm for patients.” Osteogenesis imperfecta is a genetic condition that affects collagen, leaving bones fragile and prone to fracture throughout life. There is currently no licensed treatment specifically approved to prevent fractures in adults with the condition, and patients often experience repeated fractures, chronic pain and long term disability. The trial tested a sequential treatment strategy commonly used in osteoporosis, where a bone building drug is followed by a treatment designed to preserve gains in bone strength. Although this approach successfully increased bone density in people with osteogenesis imperfecta, it did not reduce fracture rates, suggesting that treatment strategies effective in osteoporosis may not directly translate to rare bone diseases. Researchers did observe improvements in some quality of life measures among participants receiving the treatment, including reduced pain interference and improved mobility. However, fracture prevention remained unchanged, reinforcing the need for new approaches that target the fundamental properties of bone in osteogenesis imperfecta rather than density alone. The study was led by the University of Edinburgh and funded by the Medical Research Council and the National Institute for Health and Care Research. Aston University contributed clinical and academic expertise through Aston Medical School as part of the large international collaboration, which involved specialist centres across the UK and Europe. The study was led by the University of Edinburgh, with Aston University contributing clinical and academic expertise as part of a wider international collaboration involving multiple specialist centres across the UK and Europe. The research was funded by the Medical Research Council and the National Institute for Health and Care Research. Researchers say the findings provide important guidance for future research, helping to steer efforts towards treatments that focus on bone quality, strength and resilience in everyday life. They also highlight the value of large scale clinical trials in rare diseases, where learning what does not reduce harm is an essential step towards better care. The paper, Teriparatide Plus Zoledronic Acid for Osteogenesis Imperfecta, is published in JAMA. https://doi.org/10.1001/jama.2026.6889

CEOs 5 times more likely to survive fraud than a personal scandal

If the CEO of Astronomer had overseen tax fraud instead of being caught on a kiss cam cuddling his HR chief in an extramarital affair, he might still have a job. That’s because, according to a new study, CEOs are five times more likely to be fired for personal misconduct than for overseeing financial fraud. “For financial fraud, the CEO can easily say, ‘Hey, it wasn’t me,’” said Aaron Hill, Ph.D., an associate professor in the University of Florida Warrington College of Business who led the study. “With personal misconduct, there’s no excuse.” The research, forthcoming in Strategic Organization, examined 59 cases of personal misconduct and compared them with more than 300 financial scandals at publicly traded companies between 1997 and 2020. The personal cases included inappropriate relationships, drug or alcohol incidents, domestic violence, falsifying credentials and derogatory speech. Hill and his colleagues found that boards move decisively when a CEO’s private behavior becomes public. By contrast, financial misconduct — such as accounting restatements that can wipe out billions in shareholder value — often leaves room for a chief executive to deflect blame onto others in the organization. Recent company performance influenced how boards responded, to a point. A CEO whose company was thriving could often survive a financial scandal because directors had both plausible deniability and a strong incentive not to disrupt success. But good numbers offered little protection when the problem was personal behavior. For example, McDonald’s ousted Steve Easterbrook in 2019 over a consensual relationship with a subordinate, even though the company’s stock price had doubled under his leadership. Hewlett-Packard similarly dismissed CEO Mark Hurd after harassment allegations despite his reputation for turning the firm around. “Even strong performance can’t erase certain kinds of misconduct,” Hill said. “There are some things you just can’t excuse.” The study also uncovered how scandals influenced succession decisions. When personal misconduct led to a firing, boards were more likely to promote an insider, signaling that the problem lay with one person rather than the culture of the company. Financial scandals, on the other hand, often prompted boards to recruit outsiders as a way of reassuring markets that the firm was serious about change. “It’s a signaling move,” Hill said. “Bring in an outsider after fraud, and the market reacts positively. Stick with an insider after a personal scandal, and it says the organization itself is sound.” The researchers argue that these choices reveal how boards balance their fiduciary duty with the reputational risks of scandal. While dismissing a CEO can serve as a public relations reset, Hill emphasized that it is almost always a financially motivated calculation. “Boards are supposed to look out for the company and its shareholders,” he said. “But when they decide to keep a CEO after misconduct, I think it sends the wrong message — to employees, to investors and to the public.”

National Academy of Inventors welcomes five VCU College of Engineering researchers

The National Academy of Inventors (NAI) recently inducted five Virginia Commonwealth University (VCU) College of Engineering researchers as senior members. Chosen for their innovative engineering contributions, the honorees are recognized as visionary inventors whose groundbreaking research and patented technologies are driving meaningful societal and economic advancements across the national innovation landscape. “Invention represents the practical application of knowledge and stands as one of the many ways engineers can make a positive impact on their communities and the world,” said Azim Eskandarian, D.Sc, the Alice T. and William H. Goodwin Jr. Dean of the VCU College of Engineering. “This year’s honorees exemplify the interdisciplinary nature of our field, leveraging advanced concepts from mechanical, biomedical, chemical and pharmaceutical engineering to address today’s most pressing challenges. We are immensely proud that our dedicated researchers have earned recognition as members of the esteemed National Academy of Inventors.” The VCU College of Engineering NAI inductees are: Jayasimha Atulasimha, Ph.D. Engineering Foundation Professor Department of Mechanical & Nuclear Engineering An internationally recognized pioneer of straintronics, an approach to electrically control magnetism for ultra-low-energy computing, Atulasimha has made significant research contributions to next-generation memory, neuromorphic hardware and emerging quantum computing technologies. He holds four U.S. patents spanning energy-efficient magnetic memory, nanoscale computing architectures and medical tools. Atulasimha’s commercially viable inventions are funded by organizations like the Virginia Innovation Partnership Corporation and he leads multi-institutional collaborations that drive innovation in computing hardware, AI and quantum technologies with more than $10 million in funded research. Casey Grey, Ph.D. Postdoctoral Research Associate Department of Mechanical & Nuclear Engineering Bridging engineering and medicine, Grey’s work spans life‑saving stroke technologies, breakthrough respiratory and neurological care, and sustainable packaging. As a lead R&D scientist at WestRock, he helped create and commercialize the CanCollar® portfolio, a recyclable paperboard replacement for plastic beverage rings now used on five continents, eliminating thousands of tons of single‑use plastic annually. In medical device innovation, Grey’s patent and development work on a novel cyclic aspiration thrombectomy platform, currently in clinical trials, is advancing stroke treatment by enhancing clot removal efficiency and reducing long‑term disability. At the VCU College of engineering, Grey built a research and commercialization pipeline around neurological and respiratory technologies, securing eight provisional patents and leading multidisciplinary teams in neurology, neurosurgery, surgery, pharmacology and toxicology, internal medicine, and respiratory medicine. His work includes developing dry powder inhaler strategies for delivering life‑saving drugs to patients with acute respiratory distress syndrome (ARDS), a pediatric bubble CPAP system designed to protect brain development in premature infants, and non‑invasive, non‑pharmacological 40 Hz neuromodulation therapies to treat neurodegeneration and conditions with significant central nervous system complications, like sickle cell disease. In collaborations with the VCU Children’s Hospital and VCU Critical Care Hospital, Grey is leading two clinical studies that are translating these innovations to improve patient care. Ravi Hadimani, Ph.D. Associate Professor and Director of Biomagnetics Laboratory Department of Mechanical & Nuclear Engineering Hadimani founded RAM Phantoms LLC, a VCU startup company, commercializing anatomically accurate, MRI-derived brain phantoms for neuromodulation and neuroimaging applications. These brain phantoms help test and tune transcranial magnetic and deep brain stimulation technologies, improving clinical safety and enabling personalized therapy for patients. RAM Phantoms is also developing a highly-skilled workforce for employment in Virginia’s growing biomedical device industry. Beyond commercialization, Hadimani maintains a productive research program with more than $4.5 million in funding resulting in 125 original peer-reviewed publications, 17 current and pending patents, a book, and several book chapters. His biomagnetics lab serves as a training ground for undergraduate, graduate and Ph.D. students to hone their skills in innovation management, intellectual property strategy and startup development. Several students from Hadimani’s lab have engaged in translational research, patent co-authorship and start-up formation, cultivating a new generation of engineer-entrepreneurs equipped to drive future technological advances. Before joining VCU, Hadimani led the development of hybrid piezoelectric–photovoltaic materials that established FiberLec Inc., which commercialized multifunctional energy-harvesting fibers capable of converting solar, wind and vibrational energy into usable electricity. Worth Longest, Ph.D. Alice T. and William H. Goodwin, Jr. Distinguished Chair Department of Mechanical & Nuclear Engineering Uniting aerosol science, biomedical engineering and computational modeling, Longest is revolutionizing inhaled drug delivery. Working with collaborators, his lab has developed novel devices, formulations and delivery platforms that precisely target medications to the lungs, addressing conditions like cystic fibrosis, pneumonia, acute respiratory distress syndrome and neonatal respiratory distress syndrome. These innovations have resulted in multiple patents. Some of them have been licensed through commercial partnerships like Quench Medical, an organization advancing inhaled therapies for applications like lung cancer. Collaborating with the Gates Foundation and the lab of Michael Hindle, Ph.D., from the VCU Department of Pharmaceutics, Longest’s team developed a low-cost, high-efficacy aerosol surfactant therapy for pre-term infants based entirely on technology developed at VCU. The invention eliminates intubation, reduces dosage by a factor of 10, and cuts treatment costs. Over 9 million infant lives are projected to be saved by this technology between 2030 and 2050. Through a long-term collaboration with the U.S. Food and Drug Administration, Longest’s in vitro and computational methods provide federal regulatory guidance for generic inhaled medications. The VCU mouth-throat airway models developed under his leadership are used globally across the pharmaceutical industry and in government laboratories. Hong Zhao, Ph.D. Associate Professor Department of Mechanical & Nuclear Engineering Zhao holds 40 patents with innovations spanning additive manufacturing, stretchable electronics, inkjet printing technologies and superoleophobic materials that repel oils, greases, and low-surface-tension liquids. Her research has applications across health care, sustainable energy and advanced manufacturing. Prior to joining the College of Engineering, Zhao served as a senior research scientist and project leader at the Xerox Research Center, where she developed high-performance materials and printing technologies for commercial deployment. Her industry experience makes Zhao’s lab a hub for innovation and mentorship, with students engaging in innovative research and co-authoring publications. Zhao is an invited reviewer for more than 50 premier journals and grant agencies. “Working with distinguished researchers and innovators like those inducted into the National Academy of Inventors is a great honor for me,” said Arvind Agarwal, Ph.D., chair of the Department of Mechanical & Nuclear Engineering and NAI fellow. “They are an inspiration and showcase the kind of impact engineers can make. Having all five of these innovators as part of our department amplifies the scientific richness of our college and its societal impact. They advance the college’s mission of Engineering for Humanity, with research that brings a positive change to our world.” The 2026 NAI class of senior members, composed of 231 emerging inventors from NAI’s member institutions, is the largest to date. Hailing from 82 NAI member institutions across the globe, they hold over 2,000 U.S. patents.

Discovery pinpoints potential Achilles’ Heel in HIV, opening new frontier in drug development

Scientists have long known that detecting HIV early is crucial in slowing and treating the virus. During the acute stage of infection, a single human cell can produce as many as 10,000 new HIV particles. A discovery led by the University of Delaware's Juan Perilla offers hope: A new drug target early in the virus's life cycle that could save millions of lives. In the surprising discovery, published Feb. 18 in Nature, Perilla and collaborators in the U.S. and the United Kingdom, have revealed a previously unknown role for the viral protein integrase. Scientists already knew that integrase helps HIV insert itself into human DNA. But this new study provides the first direct evidence that integrase plays a critical structural role earlier on in HIV’s life cycle — when the virus matures into an infectious force. Using high-resolution cryo-electron microscopy (cryo-EM), the research team – which also included UD doctoral student Juan S. Rey – found that integrase proteins form gluey filaments that line the inside of the capsid. Each segment of the filament slots neatly into the capsid’s hexagon-shaped tiles, while gripping tightly to HIV’s RNA genome. This zipper-like arrangement organizes and packs the virus, preparing it to hijack a cell and start making copies of itself. “Integrase plays a structural role inside the HIV capsid — nobody expected that,” Perilla said. “This protein forms filaments that anchor the RNA to the capsid. Without these filaments, the virus is non-infective.” Seeing inside HIV is no small feat. The capsid is only about 120 nanometers wide —roughly 1/800th the thickness of a human hair. It is incredibly small, fragile, densely packed and constantly changing, Perilla said. To reveal its hidden architecture, the researchers relied on deep collaboration and a combination of sophisticated microscopy, molecular modeling and experimentation. Read more about the science behind the study here. “The thing with HIV is that people are chronically living with it,” Perilla said. “Treatments are effective, but patients always need new therapeutics. We want to help develop the next generation of inhibitors and hope to have a significant contribution.” To reach Perilla directly and arrange an interview, visit his profile page. Interested reporters can also email MediaRelations@udel.edu.

Surprising finding could pave way for universal cancer vaccine

An experimental mRNA vaccine boosted the tumor-fighting effects of immunotherapy in a mouse-model study, bringing researchers one step closer to their goal of developing a universal vaccine to “wake up” the immune system against cancer. Published today in Nature Biomedical Engineering, the University of Florida study showed that like a one-two punch, pairing the test vaccine with common anticancer drugs called immune checkpoint inhibitors triggered a strong antitumor response in laboratory mice. A surprising element, researchers said, was that they achieved the promising results not by attacking a specific target protein expressed in the tumor, but by simply revving up the immune system — spurring it to respond as if fighting a virus. They did this by stimulating the expression of a protein called PD-L1 inside of tumors, making them more receptive to treatment. The research was supported by multiple federal agencies and foundations, including the National Institutes of Health. Senior author Elias Sayour, M.D., Ph.D., a UF Health pediatric oncologist and the Stop Children's Cancer/Bonnie R. Freeman Professor for Pediatric Oncology Research, said the results reveal a potential future treatment path — an alternative to surgery, radiation and chemotherapy — with broad implications for battling many types of treatment-resistant tumors. “This paper describes a very unexpected and exciting observation: that even a vaccine not specific to any particular tumor or virus — so long as it is an mRNA vaccine — could lead to tumor-specific effects,” said Sayour, principal investigator at the RNA Engineering Laboratory within UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy. “This finding is a proof of concept that these vaccines potentially could be commercialized as universal cancer vaccines to sensitize the immune system against a patient’s individual tumor,” said Sayour, a McKnight Brain Institute investigator and co-leader of a program in immuno-oncology and microbiome research. Until now, there have been two main ideas in cancer-vaccine development: To find a specific target expressed in many people with cancer, or to tailor a vaccine that is specific to targets expressed within a patient's own cancer. “This study suggests a third emerging paradigm,” said Duane Mitchell, M.D., Ph.D., a co-author of the paper. “What we found is by using a vaccine designed not to target cancer specifically but rather to stimulate a strong immunologic response, we could elicit a very strong anticancer reaction. And so this has significant potential to be broadly used across cancer patients — even possibly leading us to an off-the-shelf cancer vaccine.” For more than eight years, Sayour has pioneered high-tech anticancer vaccines by combining lipid nanoparticles and mRNA. Short for messenger RNA, mRNA is found inside every cell — including tumor cells — and serves as a blueprint for protein production. This new study builds upon a breakthrough last year by Sayour’s lab: In a first-ever human clinical trial, an mRNA vaccine quickly reprogrammed the immune system to attack glioblastoma, an aggressive brain tumor with a dismal prognosis. Among the most impressive findings in the four-patient trial was how quickly the new method — which used a “specific” or personalized vaccine made using a patient’s own tumor cells — spurred a vigorous immune-system response to reject the tumor. In the latest study, Sayour’s research team adapted their technology to test a “generalized” mRNA vaccine — meaning it was not aimed at a specific virus or mutated cells of cancer but engineered simply to prompt a strong immune system response. The mRNA formulation was made similarly to the COVID-19 vaccines, rooted in similar technology, but wasn’t aimed directly at the well-known spike protein of COVID. In mouse models of melanoma, the team saw promising results in normally treatment-resistant tumors when combining the mRNA formulation with a common immunotherapy drug called a PD-1 inhibitor, a type of monoclonal antibody that attempts to “educate” the immune system that a tumor is foreign, said Sayour, a professor in UF’s Lillian S. Wells Department of Neurosurgery and the Department of Pediatrics in the UF College of Medicine. Taking the research a step further, in mouse models of skin, bone and brain cancers, the investigators found beneficial effects when testing a different mRNA formulation as a solo treatment. In some models, the tumors were eliminated entirely. Sayour and colleagues observed that using an mRNA vaccine to activate immune responses seemingly unrelated to cancer could prompt T cells that weren’t working before to actually multiply and kill the cancer if the response spurred by the vaccine is strong enough. Taken together, the study’s implications are striking, said Mitchell, who directs the UF Clinical and Translational Science Institute and co-directs UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy. “It could potentially be a universal way of waking up a patient’s own immune response to cancer,” Mitchell said. “And that would be profound if generalizable to human studies.” The results, he said, show potential for a universal cancer vaccine that could activate the immune system and prime it to work in tandem with checkpoint inhibitor drugs to seize upon cancer — or in some cases, even work on its own to kill cancer. Now, the research team is working to improve current formulations and move to human clinical trials as rapidly as possible. While the experimental mRNA vaccine at this point is in early preclinical testing — in mice not humans — information about available nonrelated human clinical trials at UF Health can be viewed here.

Experts in the Media: What You Need to Know About Medication Safety and Everyday Health

From medication safety to seasonal illness prevention, pharmacists are often the most accessible, and overlooked,  healthcare professionals in our communities. In a recent segment on NBC, Dr. Shannon Yarosz breaks down common misconceptions about prescriptions, explains how drug interactions really work, and shares practical advice patients can use immediately to better manage their health. Dr. Shannon Yarosz is an Assistant Professor of Pharmacy Practice. Prior to joining the faculty at Cedarville University, served in multiple pharmacy roles. Her career reflects a deep commitment to patient care with experience in pediatrics, community pharmacy practice, and clinical healthcare services. As healthcare systems face growing pressure and patients navigate increasingly complex medication regimens, pharmacists are playing a larger role than ever before. This discussion highlights why their expertise matters, from helping patients avoid costly mistakes to providing front-line guidance on everyday health concerns. When should I stop taking antibiotics? Is it ok to stop when I begin feeling better? This question and several others were addressed in this week's Ask the Pharmacist segment on WDTN TV in Dayton, Ohio. Looking to know more or connect with Dr. Shannon Yarosz? Simply contact: Mark D. Weinstein Executive Director of Public Relations Cedarville University mweinstein@cedarville.edu

Study: What makes a smell bad?

You wouldn’t microwave fish around your worst enemy — the smell lingers both in kitchen and memory. It is one few of us like, let alone have positive associations with. But what makes our brains decide a smell is stinky? A new study from UF Health researchers reveals the mechanisms behind how your brain decides you dislike — even loathe — a smell. Or as first author and graduate research fellow Sarah Sniffen puts it: How do odors come to acquire some sort of emotional charge? In many ways, our world capitalizes upon the importance of smells to influence emotions, running the gamut from perfumes to cooking and even grocery store design. “Odors are powerful at driving emotions, and it’s long been thought that the sense of smell is just as powerful, if not more powerful, at driving an emotional response as a picture, a song or any other sensory stimulus,” said senior author Dan Wesson, Ph.D., a professor of pharmacology and therapeutics in the UF College of Medicine and interim director of the Florida Chemical Senses Institute. But until now, researchers have puzzled over what circuitry connects the parts of the brain vital to generating an emotional response with those responsible for smell perception. The team started off with the amygdala, a brain region that curates your emotional responses to sensory stimuli. Although all our senses (sound, sight, taste, touch and smell) interact with this small part of your brain, the olfactory system takes a more direct route to it. “This is, in part, what we mean when we say your sense of smell is your most emotional sense,” Sniffen said. “Yes, smells evoke strong, emotional memories, but the brain’s smell centers are more closely connected with emotional centers like the amygdala.” In the study, researchers looked at mice, who share neurochemical similarities with people. They can learn about odors and categorize them as good or bad. After observing their behavior and analyzing brain activity, the team found two genetically unique brain cell types that allow odors to be assigned into a bucket of good feelings or bad feelings. Initially, the team expected that one cell type would generate a positive emotion to an odor, and another would generate a negative emotion. Instead, the brain’s cellular organization gives the cells the capability of doing either. “It can make an odor positive or negative to you,” Wesson said. “And it all depends upon where that cell type projects in your brain and how it engages with structures in your brain.” But why is knowing more about how we categorize smells important? Well, for starters, smells — and our reactions to them — are a part of life. Sometimes, however, our reactions to them can be outsized, or take on a negative association so strong it disrupts how we live. “We’re constantly breathing in and out and that means that we’re constantly receiving olfactory input,” Sniffen said. “For some people that’s fine, and it doesn’t impact their day-to-day life. They might even think, ‘Oh, odors don’t matter that much.’ But for people who have a heightened response to sensory stimuli, like those with PTSD or anxiety or autism, it’s a really important factor for their day-to-day life.” In the future, the research could help clinicians adjust for heightened sensory response that some people struggle with in their everyday lives, Wesson added. One example? A patient associating a clinic’s smell with transfusions that made them queasy. Based upon the receptor systems in these specific brain pathways, the team members believe they might be able to change those associations. Potentially, medications could suppress some of these pathways’ activity to allow you to overcome stressful and aversive emotional responses. Conversely, these pathways could be activated to restore enjoyment to things that people might have grown indifferent to — like those who lose their appetite from illness. “Emotions in part dictate our quality of life, and we’re learning more about how they arise in our brain,” Wesson said. “Understanding more about how our surroundings can impact our feelings can help us become happier, healthier humans.” This research was supported by funding from the National Institute on Deafness and Other Communication Disorders and the National Institute on Drug Abuse. Sarah Sniffen was supported by a fellowship from the National Institute on Deafness and Other Communication Disorders.

Gene Editing Breakthrough Offers New Hope for Head and Neck Cancer Patients

Researchers at the ChristianaCare Gene Editing Institute have made an important advance in treating head and neck cancers. By using CRISPR gene editing, the team found a way to restore how well chemotherapy works in tumors that have stopped responding to treatment. Their results, now published in Molecular Therapy Oncology, could change how doctors treat these aggressive cancers and give new hope to many patients who face limited options. Head and neck cancer is the seventh most common cancer worldwide, and cases are expected to rise by 30 percent every year by 2030. Even with progress in surgery, chemotherapy and immunotherapy, many patients still reach a point where treatment no longer works. The ChristianaCare team aimed to solve this challenge at its source. Targeting the Heart of Drug Resistance The researchers focused on a gene called NRF2. This gene acts like a master switch that helps cancer cells survive stress and resist chemotherapy. Because NRF2 plays such a central role in tumor growth, the team chose to develop a genetic therapy that disables the gene itself rather than targeting a single protein, which is common in traditional drug development. Since NRF2 is a transcription factor, shutting it down in a lasting way is more likely to succeed through CRISPR gene editing. Their major advance was showing that CRISPR can successfully disrupt NRF2 in head and neck cancer cells and in esophageal cancer cells. This work builds on earlier studies in lung cancer, where blocking NRF2 made tumors more sensitive to chemotherapy and improved survival in animal models. “Our goal was to break through the wall of drug resistance that so many patients face,” said Natalia Rivera Torres, Ph.D., the study’s lead author. “By precisely editing the NRF2 gene, we can make cancer cells vulnerable again to standard treatments. This could improve outcomes and quality of life.” Precision Matters: The Power of Target Choice The study also showed that the location of the CRISPR cut within the NRF2 gene makes a big difference. The strongest results came from targeting exon 4, a part of the gene that controls a key section of the NRF2 protein. Editing this region reduced NRF2 levels by 90 percent and made cancer cells much more sensitive to chemotherapy. In comparison, editing exon 2 was less effective even though it still caused high levels of gene disruption. The team also found that a process called exon skipping, where sections of genetic code are rearranged, can affect the outcome of gene editing. This discovery highlights how important careful design and testing are when building gene editing therapies. A Platform for Broader Impact ChristianaCare researchers saw the same results in both head and neck cancer cells and esophageal cancer cells. This suggests the strategy could help treat many solid tumors that have high levels of NRF2 and are known for strong drug resistance. “This is more than just a single experiment,” said Eric Kmiec, Ph.D., director of the Gene Editing Institute and senior author of the study. “We are building a platform that can be adapted to different cancers. Our earlier work in lung cancer showed the promise of this approach, and now we see it working in other hard to treat tumors. It is an exciting step toward making gene editing a meaningful part of cancer treatment.” Looking Ahead: Toward Clinical Application With these strong results, the team is now focused on finding the safest and most effective way to deliver the gene editing tools directly to tumors. Their goal is to reduce how much standard treatment a patient needs in order to get the best result with fewer side effects. “Drug resistance is one of the biggest challenges in cancer care,” Rivera Torres said. “If we can overcome it with gene editing, we could give patients more time, better quality of life and a renewed sense of hope.” Kmiec added, “We are committed to moving this technology forward quickly while always keeping the patient in mind. The future of cancer treatment is personal, precise and, we believe, within reach.”

Maduro is gone; expert details potential impact on the Caribbean

Globally, the ousting of Nicolás Maduro in Venezuela has been met with a mix of reactions and cautious optimism. The University of Delaware’s Kalim Shah can discuss how regime change will play across the Caribbean and the spillover effect that will ripple throughout the region – and the world – in the years and decades to come. Shah, professor of energy and environmental policy and an expert on the island nations of the Caribbean, says that although public statements have been muted and restrained, there is a shared understanding. “For small island states that have absorbed the effects of Venezuelan collapse for more than two decades, this moment represents the possible end of a long and destabilizing chapter,” Shah said. Caribbean governments are not celebrating regime change, Shah said. Rather, they are responding to the prospect of reduced systemic risk. “A Venezuela that no longer exports large-scale displacement, opaque energy leverage and permissive criminal governance is objectively preferable for the region.” Shah can discuss several aspects of Venezuela’s political history, how the nation has arrived where it is, where it might be headed and the impact this will have on the Caribbean as a whole. Those include: • Venezuela’s political and economic deterioration during the Chávez–Maduro era and how that has translated directly into pressures felt across the Caribbean in the form of migration, fiscal exposure, security risks and regional uncertainty. • How the nation’s institutional collapse coincided with deepening organized crime activity across the Caribbean basin. Data from the United Nations Office on Drugs and Crime consistently places the region within major cocaine trafficking corridors linking South America with North American and European markets. For Caribbean governments, this meant higher interdiction costs, increased exposure to transnational criminal networks and growing pressure on already limited security institutions. • This moment invites a reassessment of China’s expanding footprint in the Caribbean, Shah says. He can discuss the ways in which Beijing has deepened its presence throughout the region. Shah says that as this transition unfolds, five policy developments will determine whether the cautious optimism proves warranted: • The impact on Venezuelan outward migration to the Caribbean. • Whether Caribbean public systems receive durable support rather than short-term humanitarian fixes. • Organized crime and drug trafficking pressures in the Caribbean basin. • External security engagement in the Caribbean. • Whether the region avoids a return to dependency-driven energy and infrastructure politics. “For the Caribbean, hope today is not naïve. It is conditional. The Chávez–Maduro years imposed real costs on the region. Their end creates an opening…but only if policy follows through,” Shah said. To contact Shah directly for interviews, visit his expert page and click on the "contact" button. Interested reporters can also send an email to mediarelations@udel.edu.

AI-driven software is 96% accurate at diagnosing Parkinson's

Existing research indicates that the accuracy of a Parkinson’s disease diagnosis hovers between 55% and 78% in the first five years of assessment. That’s partly because Parkinson’s sibling movement disorders share similarities, sometimes making a definitive diagnosis initially difficult. Although Parkinson’s disease is a well-recognized illness, the term can refer to a variety of conditions, ranging from idiopathic Parkinson’s, the most common type, to other movement disorders like multiple system atrophy Parkinsonian variant and progressive supranuclear palsy. Each shares motor and nonmotor features, like changes in gait — but possess a distinct pathology and prognosis. Roughly one in four patients, or even one in two patients, is misdiagnosed. Now, researchers at the University of Florida and the UF Health Norman Fixel Institute for Neurological Diseases have developed a new kind of software that will help clinicians differentially diagnose Parkinson’s disease and related conditions, reducing diagnostic time and increasing precision beyond 96%. The study was published recently in JAMA Neurology and was funded by the National Institutes of Health. “In many cases, MRI manufacturers don’t communicate with each other due to marketplace competition,” said David Vaillancourt, Ph.D., chair and a professor in the UF Department of Applied Physiology and Kinesiology. “They all have their own software and their own sequences. Here, we’ve developed novel software that works across all of them.” Although there is no substitute for the human element of diagnosis, even the most experienced physicians who specialize in movement disorder diagnoses can benefit from a tool to increase diagnostic efficacy between different disorders, Vaillancourt said. The software, Automated Imaging Differentiation for Parkinsonism, or AIDP, is an automated MRI processing and machine learning software that features a noninvasive biomarker technique. Using diffusion-weighted MRI, which measures how water molecules diffuse in the brain, the team can identify where neurodegeneration is occurring. Then, the machine learning algorithm, rigorously tested against in-person clinic diagnoses, analyzes the brain scan and provides the clinician with the results, indicating one of the different types of Parkinson’s. The study was conducted across 21 sites, 19 of them in the United States and two in Canada. “This is an instance where the innovation between technology and artificial intelligence has been proven to enhance diagnostic precision, allowing us the opportunity to further improve treatment for patients with Parkinson’s disease,” said Michael Okun, M.D., medical adviser to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at UF Health. “We look forward to seeing how this innovation can further impact the Parkinson’s community and advance our shared goal of better outcomes for all.” The team’s next step is obtaining approval from the U.S. Food and Drug Administration. “This effort truly highlights the importance of interdisciplinary collaboration,” said Angelos Barmpoutis, Ph.D., a professor at the Digital Worlds Institute at UF. “Thanks to the combined medical expertise, scientific expertise and technological expertise, we were able to accomplish a goal that will change the lives of countless individuals.” Vaillancourt and Barmpoutis are partial owners of a company called Neuropacs whose goal is to bring this software forward, improving both patient care and clinical trials where it might be used.