Cleveland Clinic researchers found higher amounts of the sugar alcohol xylitol are associated with increased risk of cardiovascular events like heart attack and stroke.
The team, led by Stanley Hazen, M.D., Ph.D., confirmed the association in a large-scale patient analysis, preclinical research models and a clinical intervention study. Findings were published today in the European Heart Journal.
Xylitol is a common sugar substitute used in sugar-free candy, gums, baked goods and oral products like toothpaste. Over the past decade, the use of sugar substitutes, including sugar alcohols and artificial sweeteners, has increased significantly in processed foods that are promoted as healthy alternatives.
The same research team found a similar link between erythritol and cardiovascular risk last year. Xylitol is not as prevalent as erythritol in keto or sugar-free food products in the U.S. but is common in other countries.
“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combatting conditions like obesity or diabetes,” said Dr. Hazen, Chair of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute and Co-Section Head of Preventive Cardiology in the Heart, Vascular & Thoracic Institute. “It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot related events.”
In this new study, researchers identified that high levels of circulating xylitol were associated with an elevated three-year risk of cardiovascular events in an analysis of more than 3,000 patients in the U.S. and Europe. A third of patients with the highest amount of xylitol in their plasma were more likely to experience a cardiovascular event. To confirm the findings, the research team conducted pre-clinical testing and found that xylitol caused platelets to clot and heightened the risk of thrombosis. Researchers also tracked platelet activity from people who ingested a xylitol-sweetened drink versus a glucose-sweetened drink and found that every measure of clotting ability significantly increased immediately following ingestion of xylitol but not glucose.
The authors note that further studies assessing the long-term cardiovascular safety of xylitol are warranted. The research had several limitations, including that clinical observation studies demonstrate association and not causation. They recommend talking to your doctor or a certified dietitian to learn more about healthy food choices and for personalized recommendations.

The research is part of Dr. Hazen’s ongoing investigation into factors that contribute to residual cardiovascular risk. His team follows patients over time and finds chemical signatures in blood that can predict the future development of heart and metabolic disease. He has made pioneering discoveries in atherosclerosis and inflammatory disease research, including the seminal discovery linking gut microbial pathways to cardiovascular disease and metabolic diseases.
Dr. Hazen also directs Cleveland Clinic’s Center for Microbiome and Human Health and holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis.
The study was supported in part by National Institutes of Health and the Office of Dietary Supplements.
Disclosures: Dr. Hazen is named as co-inventor on pending and issued patents held by Cleveland Clinic in relation to cardiovascular diagnostics and therapeutics.

People with high blood pressure have a higher risk of cognitive impairment, including dementia, but a new study from researchers at Wake Forest University School of Medicine suggests that engaging in vigorous physical activity more than once a week can lower that risk.
The findings appear online today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“We know that physical exercise offers many benefits, including lowering blood pressure, improving heart health and potentially delaying cognitive decline,” said Richard Kazibwe, M.D., assistant professor of internal medicine at Wake Forest University School of Medicine and lead author of the study. “However, the amount and the intensity of exercise needed to preserve cognition is unknown.”
In 2015, published findings from the landmark Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure management reduced cardiovascular disease and lowered the risk of death.
SPRINT began in the fall of 2009 and included more than 9,300 participants with hypertension ages 50 and older, recruited from about 100 medical centers and clinical practices throughout the United States. Participants were randomly assigned to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment) or less than 140 mm Hg (standard treatment). The National Institutes of Health (NIH) stopped the blood pressure intervention earlier than originally planned to quickly disseminate the significant preliminary results, resulting in a new set of guidelines for controlling blood pressure.
In 2019, results of the ancillary SPRINT MIND trial, led by Wake Forest University School of Medicine, showed that intensive control of blood pressure in older people significantly reduced the risk of developing mild cognitive impairment, a precursor of early dementia.
In a secondary analysis of the SPRINT MIND study, Kazibwe and team examined the effect of self-reported sessions of vigorous physical activity (at least once a week) on the risk of mild cognitive impairment and dementia.

People who engaged in one or more sessions of vigorous physical activity per week had lower rates of mild cognitive impairment and dementia.
Kazibwe said that nearly 60% of study participants reported vigorous physical activity at least once a week, even among those aged 75 and up.
“It is welcome news that a higher number of older adults are engaging in physical exercise. This also suggests that older adults who recognize the importance of exercise may be more inclined to exercise at higher intensity,” Kazibwe said.
However, the research team found the protective impact of vigorous exercise was more pronounced for those under 75.
“While this study provides evidence that vigorous exercise may preserve cognitive function in high-risk patients with hypertension, more research is needed to include device-based physical activity measurements and more diverse participant populations,” Kazibwe said.

New research, led by experts at the University of Nottingham, has found that teachers may be attributing signs of age-related immaturity in children, to conditions such as Attention-Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder (ASD).
The results of the study, which are published in the journal European Child and Adolescent Psychiatry, showed that the youngest students in a class, with birth dates just before the school entry cut-off date, were overrepresented among children receiving an ADHD diagnosis or medication for the condition.
Experts looked at how being one of the youngest children in a class can influence the likelihood of being diagnosed with ADHD or ASD. ADHD is a condition where individuals have significant challenges with attention and can be overly active. ASD is a complex developmental condition that relates to how a person communicates and interacts.
Professor Kapil Sayal from the School of Medicine at the University, and senior author of the paper, said: “This review shows that adults involved in identifying or raising concerns over a child’s behaviour — such as parents and teachers — may be inadvertently misattributing relative immaturity as symptoms of ADHD. The child’s age in relation to their classmates (their ‘relative’ age) needs to considered when making this kind of diagnosis.”
Detailed searches were used to identify all studies written on this topic worldwide. Researchers reviewed the 32 studies identified. Most of these studies focused on ADHD and two focused on ASD.
The findings confirmed that younger students in the school year are more likely to be diagnosed with ADHD and receive medication for this, compared to their older classmates. The scale of this ‘relative age’ effect varied between the studies.
For ASD, the youngest children in a class were also more likely to be diagnosed but more research is needed due to there only being a small number of studies available.

Interestingly, there was a more notable difference in how teachers rated these younger children compared to how parents do.
Dr Eleni Frisira, from the School of Medicine and lead author of the study, said: “Teachers play an important role in identifying ADHD symptoms in children. Our findings suggest that they can be more likely to rate younger students in a class as having ADHD symptoms than their older classmates. It is important teachers are supported in considering the relative age of a child in a classroom when ADHD is being queried.”
Dr Josephine Holland, one of the authors of the paper added: “This phenomenon has been shown in research for over a decade, but knowing about it does not seem to be changing practice.”
The research emphasises how important it is to consider a child’s age in relation to their classmates when assessing for and diagnosing conditions like ADHD and ASD. This is an important take-home message for healthcare professionals who assess young children, but also for teachers and parents, when observing and reporting symptoms.

America’s poison centers are fielding increasingly severe cases that are dramatically more likely to lead to severe harm or death in both adults and children, a new study from the University of Virginia School of Medicine reveals.
The number of calls about intentional exposures that resulted in death among adults increased a whopping 233.9% between the beginning of 2007 and the end of 2021, the study reveals. “Intentional exposures” include cases such as suicide attempts, use of illegal drugs and incorrect use of medications for reasons other than their intended purpose, such as to get high.
The severity of unintentional exposures increased as well, with the number resulting in severe harm (such as disfigurement or disability) increasing by 37.4% and the number resulting in death increasing by 65.3%. This spike in serious outcomes occurred even as the total number of calls for unintentional exposures decreased slightly, by .8%. These cases include unintentional medication misuse, such as taking an incorrect dose; workplace and environmental exposures to harmful substances; bites and stings; and food poisoning.
The severity of cases among children was up, too: The number of pediatric intentional exposures resulting in severe harm or death was up by 76.6%, even as the total number of cases declined by 33%. The number of unintentional exposures resulting in severe harm or death was up by 190.1% and 122.7%, respectively.
“As a society, we should be concerned at these trends pertaining to children,” said researcher Christopher Holstege, MD, director of UVA Health’s Blue Ridge Poison Center and chief of the Division of Medical Toxicology at UVA’s School of Medicine. “We need to collaboratively strategize on better delineating the root causes for such severe cases of pediatric poisonings, especially in the realms of mental health and substance use and misuse.”
Troubling Poison Trends
With drug overdose deaths rising around the nation, Holstege and his collaborators — UVA epidemiologist Rita Farah, PharmD, PhD, and Ryan J. Cole, MD — wanted to get a better sense of the outcomes for calls poison centers have received in recent years. So, they reviewed more than 33.7 million poison exposures reported to the 55 poison centers in the United States between Jan. 1, 2007, and Dec. 31, 2021. These calls included almost 8 million unintentional exposures among adults 19 and older, 3.9 million intentional adult exposures, 18.7 million unintentional pediatric exposures and more than 1.6 million intentional pediatric exposures.

The researchers found that calls were increasingly likely to result in severe harm or death as time went on, and this held true across all age groups. Calls about cases that had minor effects, meanwhile, declined.
That aligned with what Holstege expected. “We were not surprised by the study findings. In fact, what prompted us to look at the data on a national level is the increased severity of cases we are seeing at UVA Health’s Blue Ridge Poison Center,” he said. “The cause for this trend is multifactorial: We have experienced a growing mental health crisis in the nation’s youth, and we are finding an increasing number of dangerous novel psychoactive substances such as synthetic opioids and designer benzodiazepines entering society.”
Despite the increasing severity of calls to poison centers, the researchers did not find a consistent, corresponding increase to critical care units. This may have resulted, in part, from the COVID-19 pandemic limiting available healthcare resources, the researchers say.
With poisons centers being called upon to handle increasingly severe cases, they may need to rethink how they allocate resources, the researchers note. For example, they may need to have more toxicologists available to field complex cases that go beyond the expertise of the poison specialists who answer calls.
“Poison centers are an integral part of the medical management team as we see an increase in the severity of cases of poisoning,” Holstege said. “Poison centers are staffed with clinical toxicologists who provide free expert recommendations on a vast array of toxicologic emergencies to the public and to professionals who call. Involving toxicologists early can save lives and reduce the length of hospital stay.”

Scientists from Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago have discovered a way to regenerate damaged heart muscle cells in mice, a development which may provide a new avenue for treating congenital heart defects in children and heart attack damage in adults, according to a study published in the Journal of Clinical Investigation.
Hypoplastic left heart syndrome, or HLHS, is a rare congenital heart defect that occurs when the left side of a baby’s heart doesn’t develop properly during pregnancy. The condition affects one in 5,000 newborns and is responsible for 23 percent of cardiac deaths in the first week of life.
Cardiomyocytes, the cells responsible for contracting the heart muscle, can regenerate in newborn mammals, but lose this ability with age, said senior author Paul Schumacker, PhD, Patrick M. Magoon Distinguished Professor in Neonatal Research at Lurie Children’s and Professor of Pediatrics, Cell and Molecular Biology, and Medicine at Northwestern University Feinberg School of Medicine.
“At the time of birth, the cardiac muscle cells still can undergo mitotic cell division,” Dr. Schumacker said. “For example, if the heart of a newborn mouse is damaged when it’s a day or two old, and then you wait until the mouse is an adult, if you look at the area of the heart that was damaged previously, you’d never know that there was damage there.”
In the current study, Dr. Schumacker and his collaborators sought to understand if adult mammalian cardiomyocytes could revert to that regenerative fetal state.
Because fetal cardiomyocytes survive on glucose, instead of generating cellular energy through their mitochondria, Dr. Schumacker and his collaborators deleted the mitochondria-associated gene UQCRFS1 in the hearts of adult mice, forcing them to return to a fetal-like state.
In adult mice with damaged heart tissue, investigators observed that the heart cells began regenerating once UQCRFS1 was inhibited. The cells also began to take in more glucose, similar to how fetal heart cells function, according to the study.

The findings suggest that causing increased glucose utilization can also restore cell division and growth in adult heart cells and may provide a new direction for treating damaged heart cells, Dr. Schumacker said.
“This is a first step to being able to address one of the most important questions in cardiology: How do we get heart cells to remember how to divide again so that we can repair hearts?” said Dr. Schumacker.
Building off this discovery, Dr. Schumacker and his collaborators will focus on identifying drugs that can trigger this response in heart cells without genetic manipulation.
“If we could find a drug that would turn on this response in the same way the gene manipulation did, we could then withdraw the drug once the heart cells have grown,” Dr. Schumacker said. “In the case of children with HLHS, this may allow us to restore the normal thickness to the left ventricular wall. That would be lifesaving.”
The approach could also be used for adults who have suffered damage due to a heart attack, Dr. Schumacker said.
The study was supported by National Institutes of Health grants HL35440, HL122062, HL118491 and HL109478.
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute, which is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is a nonprofit organization committed to providing access to exceptional care for every child. It is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. Lurie Children’s is the pediatric training ground for Northwestern University Feinberg School of Medicine.

Some say the next step in human evolution will be the integration of technology with flesh. Now, researchers have used virtual reality to test whether humans can feel embodiment — the sense that something is part of one’s body — toward prosthetic “hands” that resemble a pair of tweezers. They report June 6 in the journal iScience that participants felt an equal degree of embodiment for the tweezer-hands and were also faster and more accurate in completing motor tasks in virtual reality than when they were equipped with a virtual human hand.
“For our biology to merge seamlessly with tools, we need to feel that the tools are part of our body,” says first author and cognitive neuroscientist Ottavia Maddaluno, who conducted the work at the Sapienza University of Rome and the Santa Lucia Foundation IRCCS with Viviana Betti. “Our findings demonstrate that humans can experience a grafted tool as an integral part of their own body.”
Previous studies have shown that tool use induces plastic changes in the human brain, as does the use of anthropomorphic prosthetic limbs. However, an open scientific question is whether humans can embody bionic tools or prostheses that don’t resemble human anatomy.
To investigate this possibility, the researchers used virtual reality to conduct a series of experiments on healthy participants. In the virtual reality environment, participants had either a human-like hand or “bionic tool” resembling a large pair of tweezers grafted onto the end of their wrist. To test their motor ability and dexterity, participants were asked to pop bubbles of a specific color (by pinching them with their tweezers or between their index finger and thumb). For this simple task, the researchers found that participants were faster and more accurate at popping virtual bubbles when they had tweezer-hands.
Next, the team used a test called the “cross-modal congruency task” to compare implicit or unconscious embodiment for the virtual hand and bionic tool. During this test, the researchers applied small vibrations to the participants’ fingertips and asked them to identify which fingers were stimulated. At the same time, a flickering light was displayed on the virtual reality screen, either on the same finger as the tactile stimulus or on a different finger. By comparing the participants’ accuracy and reaction times during trials with matched and mismatched stimuli, the researchers were able to assess how distracted they were by the visual stimulus.
“This is an index of how much of a mismatch there is in your brain between what you feel and what you see,” says Maddaluno. “But this mismatch could only happen if your brain thinks that what you see is part of your own body; if I don’t feel that the bionic tool that I’m seeing through virtual reality is part of my own body, the visual stimulus should not give any interference.”
In both cases, participants were faster and more accurate at identifying which of their real fingers were stimulated during trials with matched tactile and visual stimuli, indicating that participants felt a sense of embodiment toward both the virtual human hand and the tweezer-hands.

However, there was a bigger difference between matched and mismatched trials when participants had tweezer- rather than human hands, indicating that the non-anthropomorphic prosthesis resulted in an even greater sense of embodiment. The researchers speculate that this is due to the tweezer-hands’ relative simplicity compared to a human-like hand, which might make it easy for the brain to compute and accept.
“In terms of the pinching task, the tweezers are functionally similar to a human hand, but simpler, and simple is also better computationally for the brain.” says Maddaluno.
They note that it could also relate to the “uncanny valley” hypothesis, since the virtual human hands might have been too eerily similar yet distinct for perfect embodiment.
In addition to the tweezer-hands, the researchers also tested a wrench-shaped bionic tool and a virtual human hand holding a pair of tweezers. They found evidence of embodiment in all cases, but the participants had higher embodiment and were more dexterous when the tweezers were grafted directly onto their virtual wrists than when they held them in their virtual hand.
Participants also displayed a higher sense of embodiment for the bionic tools when they had the opportunity to explore the virtual reality environment before undertaking the cross-modal congruency test. “During the cross-modal congruency task participants had to stay still, whereas during the motor task, they actively interacted with the virtual environment, and these interactions in the virtual environment induce a sense of agency,” says Maddaluno.
Ultimately, the researchers say that this study could inform robotics and prosthetic limb design. “The next step is to study if these bionic tools could be embodied in patients that have lost limbs,” says Maddaluno. “And we also want to investigate the plastic changes that this kind of bionic tool can induce in the brains of both healthy participants and amputees.”

Johns Hopkins Medicine scientists say they have developed an artificial lymph node with the potential to treat cancer, according to a new study in mice and human cells. The newly developed lymph node — a sac filled with immune system components — is implanted under the skin, and is designed to act like a learning hub and stimulator to teach immune system T-cells to recognize and kill cancer cells.
Details of the experiments are published recently online and in the June 6 issue of Advanced Materials.
Lymph nodes — tiny glands throughout the body, mainly in the neck, armpits and groin — are part of the immune systems of mammals, including mice and people. They number in the hundreds so that immune cells in one area of the body don’t have to travel far to alert the immune system to impending danger.
“They are a landing spot where T-cells, the immune system’s fighting cells, lay dormant, waiting to be activated to fight infections or other abnormal cells,” says Natalie Livingston, Ph.D., first author of the research and currently a postdoctoral researcher at Massachusetts General Hospital. “Because cancers can trick T-cells into staying dormant, the artificial lymph node was designed to inform and activate T-cells that are injected alongside the lymph node.”
To create the artificial lymph node, the scientists used hyaluronic acid, a moisturizing substance commonly used in cosmetics and lotions and found naturally in the body’s skin and joints.
Because of its properties, hyaluronic acid is often used in biodegradable materials such as wound healing patches meant to be implanted or applied to the body. Among those properties, hyaluronic acid can connect with T-cells via a cell surface receptor.
Johns Hopkins scientists led by Jonathan Schneck, M.D., Ph.D., published research in 2019 showing that hyaluronic acid boosts T-cell activation.

For the current study, the Johns Hopkins team used hyaluronic acid as the scaffolding, or base, for their new lymph node, and added MHC (major histocompatibility complex) or HLA (human histocompatibility antigen) molecules, which rev up T-cells and other immune system components. Then, they also added molecules and antigens common to cancer cells to “teach” T-cells what to look for.
“By adding different antibodies to the artificial lymph node, we have the ability to control what the T-cells are being activated to search for,” says Livingston.
The resulting artificial lymph node is about 150 microns in size, about twice the width of a human hair. It’s small enough to remain under the skin and large enough to avoid being swept away in the blood stream.
“An advantage to this approach over other cell-based therapies such as CAR-T is fewer manufacturing steps,” says Schneck, who is a professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine, director of the Johns Hopkins Center for Translational Immunoengineering, and a member of the Institute for Cell Engineering, Kimmel Cancer Center and Institute for Nanobiotechnology.
Current cell-based therapies require extracting T-cells from a patient, manipulating them outside of the body to recognize a particular type of cancer, and injecting them back into the patient. “In our approach, we inject T-cells along with an artificial lymph node, and the T-cells get primed and educated by the artificial lymph node inside of the body. Then, the T-cells can travel anywhere to destroy cancer cells,” says Schneck, who led the research team, along with Hai-Quan Mao, Ph.D., director of Johns Hopkins’ Nanobiotechnology Institute.
Livingston, Schneck and the research team tested the artificial lymph node in mice that were implanted with either melanoma or colon cancers. Six days after the tumors were implanted, the mice received injections of the artificial lymph node and T-cells.

The Johns Hopkins team compared these mice with ones receiving the artificial lymph node alone, those receiving T-cells alone (which have not been activated by the artificial lymph node) and those receiving T-cells in combination with a class of immunotherapy drug called anti-PD-1.
Nine days later, mice with melanomas and colon cancers that received a combination of the artificial lymph node, T-cells and the anti-PD-1 drug had the best survival rates (three of the seven mice were still alive at 33 days), compared with other groups that only lived to about 26 days. This group of mice also had the slowest cancer growth rate. It took between five and 10 days longer for their cancers to double in size than the other groups.
The scientists also found that the artificial lymph node attracted an influx of other immune cells and acts as an “immunologically active niche” to help to further stimulate the immune system. When T-cells were injected into the mice alongside the artificial lymph node, T-cell numbers grew as much as nine times more plentiful.
Livingston says the artificial lymph node approach is different from a cancer vaccine, which typically activates a dendritic cell, an immune system component that teaches T-cells what to search for. People with cancer often develop malfunctioning dendritic cells, and the artificial lymph node skips the dendritic cell to directly activate T-cells.
The research team plans to conduct additional laboratory studies to add more immune signaling molecules to the lymph node and recruit more of the host’s immune cells to the artificial lymph node environment.
“We blended the disciplines of materials science and immunology to create a potential therapy that forms its own immunology community — a kind of living drug,” says Schneck.
The researchers have filed for a patent involving the technology described in their research.
Funding for the research was provided by the National Institutes of Health (R01EB029341, R21CA185819, P41EB028239, T32AI007417), the National Science Foundation, the Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31CA275271), the NIH Cancer Nanotechnology Training Center at the Johns Hopkins Institute for NanoBioTechnology, the National Science Foundation Graduate Research Fellowship, the ARCS Foundation, the Siebel Foundation, and the Natural Sciences and Engineering Research Council of Canada’s Postgraduate Scholarships — Doctoral Award.
Other Johns Hopkins researchers who contributed to the study are John Hickey, Hajin Sim, Sebastian Salathe, Joseph Choy, Jiayuan Kong, Aliyah Silver, Jessica Stelzel, Mary Omotoso, Shuyi Li, Worarat Chaisawangwong, Sayantika Roy, Emily Ariail, Mara Lanis, Pratibha Pradeep, Joan Glick Bieler, Savannah Est Witte, Elissa Leonard, Joshua Doloff and Jamie Spangler.

Researchers at the University of Michigan and Brown University have developed a new computational method to analyze complex tissue data that could transform our current understanding of diseases and how we treat them.
Integrative and Reference-Informed tissue Segmentation, or IRIS, is a novel machine learning and artificial intelligence method that gives biomedical researchers the ability to view more precise information about tissue development, disease pathology and tumor organization.
The findings are published in the journal Nature Methods.
IRIS draws from data generated by spatially resolved transcriptomics and uniquely leverages single-cell RNA sequencing data as the reference to examine multiple layers of tissue simultaneously and distinguish various regions with unprecedented accuracy and computational speed.
Unlike traditional techniques that yield averaged data from tissue samples, SRT provides a much more granular view, pinpointing thousands of locations within a single tissue section. However, the challenge has always been to interpret this vast and detailed dataset, says Xiang Zhou, professor of biostatistics at the University of Michigan School of Public Health and senior author of the study.
Interpreting large and complex datasets is where IRIS becomes a helpful tool — its algorithms sort through the data to identify and segment various functional domains, such as tumor regions, and provide insights into cell interactions and disease progression mechanisms.
“Different from existing methods, IRIS directly characterizes the cellular landscape of the tissue and identifies biologically interpretable spatial domains, thus facilitating the understanding of the cellular mechanism underlying tissue function,” said U-M doctoral alum Ying Ma, assistant professor of biostatistics at Brown University, who helped develop IRIS.
“We anticipate that IRIS will serve as a powerful tool for large-scale multisample spatial transcriptomics data analysis across a wide range of biological systems.”
Zhou and Ma applied IRIS to six SRT datasets and compared its performance to other commonly used spatial domain methods. Ultimately, as SRT technology continues to grow in popularity and use, the researchers hope to see methods like IRIS help to potentially develop targets for clinical interventions or drug targets, improving personalized treatment plans and patient health outcomes.
“The computational approach of IRIS pioneers a novel avenue for biologists to delve into the intricate architecture of complex tissues, offering unparalleled opportunities to explore the dynamic processes shaping tissue structure during development and disease progression,” Zhou said. “Through characterizing refined tissue structures and elucidating their alterations during disease states, IRIS holds the potential to unveil mechanistic insights crucial for understanding and combating various diseases.”

An injectable emulsion containing two omega-3 fatty acids found in fish oil markedly reduced brain damage in newborn rodents after a disruption in the flow of oxygen to the brain near birth, a study by researchers at Columbia University Vagelos College of Physicians and Surgeons has found.
Brain injury due to insufficient oxygen is a severe complication of labor and delivery that occurs in one to three out of every 1,000 live births in the United States. Among babies who survive, the condition can lead to cerebral palsy, cognitive disability, epilepsy, pulmonary hypertension, and neurodevelopmental conditions.
“Hypoxic brain injury can have devastating, lifelong consequences, and we suggest our novel therapeutic approach using intravenous omega-3 emulsions could markedly reduce these adverse outcomes,” says Richard Deckelbaum, a professor of nutrition and pediatrics and a coordinating author of the study.
The study also found that the novel omega-3 preparation is far more effective in rodents when compared to therapeutic hypothermia, the current standard therapy for this condition and the only one approved by the FDA. This treatment, which involves using cooling blankets for three days, only benefits about 15% of patients and can cause heart and respiratory complications.
“We need to find another treatment for hypoxic brain injury that will be much more effective and feasible than therapeutic cooling and can be used in the immediate hours after the injury when therapy is likely to be most effective,” says Hylde Zirpoli, an associate research scientist in Deckelbaum’s group and senior author of the study.
New injectable fish oil formulation
Previous studies by Deckelbaum’s team and others have shown that omega-3 emulsions — tiny droplets of omega-3 fatty acids dispersed in liquid — may have neuroprotective effects and that omega-3 fatty acids found in fish oil reduce inflammation and cell death caused by oxygen deprivation. But the bioactive compounds contained in commercially available oral omega-3 supplements take weeks or months to have an effect, so they aren’t ideal for protecting organs immediately after injury.

The Columbia team developed an injectable omega-3 therapy that can be used in just such situations. The therapy is a diglyceride formulation — two omega-3 fatty acids, DHA and EPA, bound to a glyceride molecule — which enhances their ability to emulsify into tiny, concentrated particles. These fatty acids are also found in fish oil, though fish oil and dietary sources of fatty acids are mainly triglycerides, which have three fatty acids per molecule.
The new diglyceride is predicted to cause a higher concentration of omega-3 molecules to rapidly penetrate the blood-brain barrier.
Study results
The researchers gave the therapy to week-old mice and rats with hypoxic brain injury. The experimental emulsion reduced brain damage far more than a commercially available omega-3 injectable emulsion (only approved as a nutritional supplement for infants with intravenous nutrition-related liver disease). Doses for both omega-3 preparations were similar.
The experimental emulsion may have worked better than the commercial emulsion because it was absorbed into the animals’ bloodstream two times faster.
The researchers also found that animals treated with the new therapy had normal motor coordination and reflexes — indicators of neurologic function — similar to the animals with no brain injury.
“The omega-3 diglyceride emulsion not only prevented brain cell death, but it also preserved neurologic function, which is important in reducing the cost of disabilities, both to the patient’s well-being and to the health care system,” Deckelbaum says.
Next steps
The researchers hope to begin clinical trials in newborns within two years and plan to expand studies on the therapy’s effectiveness in preventing damage to the central nervous system in animals with traumatic brain injury and spinal cord injury. Additional studies will explore applications in other acute injuries and conditions in which oxygen deprivation causes organ damage, including heart attack and stroke.

In a groundbreaking advance that could revolutionize bladder cancer treatment, a novel combination of cretostimogene grenadenorepvec and pembrolizumab has shown remarkable efficacy in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer. Results from the phase 2 CORE-001 trial, published in Nature Medicine, reveal a significant improvement in complete response rates and long-term disease control, offering new hope for patients with this challenging condition who face limited treatment options.
The trial included patients with BCG-unresponsive carcinoma in situ of the bladder, a condition that is notoriously difficult to treat and often leads to radical cystectomy. The combination therapy of intravesical cretostimogene grenadenorepvec (an intravesically delivered oncolytic immunotherapy) with systemic pembrolizumab (an immune checkpoint inhibitor) demonstrated a complete response rate of 57.1% at 12 months, surpassing previous benchmarks set by other therapies. The trial also demonstrated durable responses; findings show a complete response rate of 82.9% at three months, with a median duration of response not yet reached after a median follow-up of 26.5 months.
“This study marks an important step forward in the treatment of BCG-unresponsive NMIBC,” said Roger Li, M.D., principal investigator of the trial and urologic oncologist at Moffitt Cancer Center. “Our findings indicate that the combination of cretostimogene grenadenorepvec and pembrolizumab offers a unique, efficacious and durable bladder-preserving alternative strategy to radical cystectomy.”
The oncolytic immunotherapy directly enters the bladder cancer cells, destroys them, and then stimulates an anti-tumor response from the body’s immune system. Pembrolizumab, a well-known PD-1 inhibitor, further enhances the immune system’s ability to attack cancer cells. The observed clinical benefits stem from the synergistic effect of these two therapies.
“These encouraging results highlight the potential for oncolytic immunotherapy to synergize with immune checkpoint inhibitors, offering a new avenue for patients who have exhausted other treatment options,” Li said. “We are optimistic that additional clinical trials will confirm these benefits and support the integration of both monotherapy and combination therapies into the standard-of-care for BCG-unresponsive non-muscle invasive bladder cancer.”
The study noted that adverse events were manageable and consistent with those observed in previous monotherapy trials. The most common side effects related to cretostimogene were bladder-related symptoms, while pembrolizumab-related adverse events were typical of systemic immunotherapy.