Degeneration of retinal ganglion cells can cause irreversible vision loss. Pluripotent stem cells (PSCs) could, in theory, be used to replace lost ganglion cells. However, past attempts at injection of these cells have failed because the cells are not able to reach the retina.
Now, researchers have successfully demonstrated that disrupting an eye structure long suspected of blocking the growth and survival of transplanted nerve cells—the internal limiting basement membrane (ILM)—may help restore vision in people with optic nerve damage.
The work suggests that altering or removing the thin layer of tissue, which separates the light-sensing retinal tissue at the back of the eye from the gel-like vitreous fluid that fills the eye, was needed for the survival and migration of donor human PSC-derived retinal ganglion cells into the retina of mice, rats, and nonhuman primates. This technique could help transplanted retinal ganglion cells survive and grow in people with blinding optic nerve damage.
Damage, or optic neuropathy, occurs when retinal ganglion cells die of disease, inflammation, or injury and stop carrying electrical signals to the brain. Common causes of damage include glaucoma, optic nerve inflammation (optic neuritis), and ischemic optic neuropathy (sudden loss of blood flow to the optic nerve).
Healthy, functional human retinal ganglion cells can be grown in a lab, but most die when transplanted, said Thomas Vincent Johnson III, MD, PhD, a professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute. “Even when the retinal ganglion cells survive, they remain on the retina’s surface and do not migrate into the tissue or form the connections with other nerve cells necessary to detect light,” he noted.
Researchers have speculated that the internal limiting membrane, present in many vertebrates, including humans, may be causing transplant failures.
Starting with immunosuppressed rodents, the researchers injected lab-grown human retinal ganglion cells (hRGCs) into the vitreous humors of mice with an inborn gene mutation that caused an incomplete, patchy internal limiting membrane to form. They then injected the human retinal ganglion cells into a second group of mice treated with an enzyme solution known to partially digest the membrane without damaging the eye. Lastly, they injected a third, control group of mice treated with an inactive sterile solution. After two weeks, the team observed transplantation survival in 95% of eyes (45/50) with the inborn structural defect, 80% of enzymatically disrupted eyes (32/40), and 75% of control group eyes (12/16).
The researchers then traced where the surviving human retinal ganglion cells settled and grew in the mice, noting that a much greater percentage reached the retinal ganglion cell layer in mice born with a patchy internal limiting membrane and in those treated with the enzyme.
Capturing 3D images of the migrated cells, the researchers say they observed that 2% (plus or minus 0.6%) and 7.1% (plus or minus 1.6%) surviving cells in enzyme-treated and mutant eyes, respectively, matured to form dendrites. In contrast, migration and maturation only occurred in 0.01% plus or minus 0.01% of surviving control human retinal ganglion cells.
Conducting similar experiments in larger eyes and donated eye tissue replicated the group’s findings, establishing evidence that the inner limiting membrane is indeed a structural obstacle to neuron replacement, the researchers noted. They also established a surgical procedure for retinal ganglion cell transplantation that could be used in clinical trials, thus advancing potential methods for restoring vision in humans with optic neuropathy.
While the study’s results are promising, Johnson cautions that further work is still needed before their experimental findings can be applied to people. “We know our methods are effective, but we don’t know if completely removing the internal limiting membrane helps or harms the retinal ganglion cells in the long run,” he said. “It will likely take several years before our findings could become available as an experimental therapy, but the methods we developed will guide the field moving forward.”
After months of anticipation, Supreme Court justices heard arguments about a long-standing tactic used by generic companies to carve out a distinct market for a medicine, and did not appear inclined to alter legal standards for the maneuver.
At issue is skinny labeling, which refers to moves by generic companies that seek regulatory approval to market a drug for a specific use, but not other patented uses for which a brand-name medicine is prescribed. For instance, a generic drug could be marketed to treat one type of heart problem but not another. In doing so, the generic company seeks to avoid lawsuits claiming patent infringement.
This tactic has been a key tool for generic companies ever since the Hatch-Waxman Act was signed into law more than four decades ago. The law established the mechanisms by which generic drugs can more readily enter the marketplace. And skinny labeling is one way that Congress attempted to foster more competition and benefit consumers.
Background: Due to the high burden on health care, home-based rehabilitation (HBR) has gained increasing interest. A new HBR program for stroke survivors, containing a gaming app with upper-limb exercises, monitoring system, and virtual coach was being developed. Objective: This study aimed to assess the user requirements of an HBR tool including a gaming app, monitoring system, and virtual coach, and to examine potential differences between end users and countries. Methods: Thirteen stroke survivors, 12 caregivers, and 15 health care professionals from centers in the Netherlands, Italy, and Spain, participated in focus groups or interviews. Each center used the same interview guide with open questions about each component. An inductive thematic analysis was conducted separately at each center, and results were combined during a physical meeting. Results: User requirements were categorized into three main themes: (1) customization: aligning with individual preferences and capabilities; (2) motivational elements: these included reminders, a variety of levels and games, and ease of use; and (3) feedback elements: maintaining interactions with therapists. These themes apply to both home-based exercises as well as daily-life activities during HBR. There were minor differences between end users or centers. Conclusions: All end users across the participating countries emphasized the importance of integrating gamified exercises, monitoring, and virtual coaching into an HBR system. The user requirements for such a system can be categorized into three key areas: customization, motivational elements, and feedback elements.
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Background: Nearly all youth use the internet daily, with many maintaining several social media accounts. As increasing numbers of young people engage online and the ways we communicate fundamentally change, it is increasingly important to ask: how do these shifts influence youth mental health? To better understand how social media may affect mental health, researchers require validated tools that capture young people’s heterogeneous experiences with social media. However, few available measures evaluate the full range of positive and negative behaviors associated with its use, limiting our ability to meaningfully advance interventions promoting online hygiene. Objective: This study aims to develop and validate the Comprehensive Assessment of Social Media Use (CASM). The CASM is a self-report survey measure that moves beyond simple duration or frequency of use and captures how young people engage with social media. Importantly, the CASM assesses both the positive and negative dimensions of social media engagement. Methods: Two studies are outlined in this paper. Study 1 outlines the process of item generation and exploratory factor analysis. Study 2 outlines confirmatory factor analysis and validity testing. Both studies were conducted online and enrolled a convenience sample of college-aged young adults. Study 1 enrolled 260 participants (mean age 19.73, SD 2.91; n=172, 66.2% female; n=164, 63.1% White; n=38, 14.6% lesbian, gay, bisexual, transgender/transsexual, and queer [LGBTQ]). Study 2 enrolled 508 participants (mean age 18.99, SD 1.17; n=323, 63.6% female; n=272, 53.5% White; n=58, 11.4% LGBTQ). Results: Exploratory and confirmatory factor analysis resulted in a 29-item CASM scale that assesses 7 distinct aspects of young adult social media use: self-branding, compulsive use, disruptive use, impulsive sharing, social engagement, induce negative emotions, and induce positive emotions. This model accounted for 61% of the variance in responses. The chi-squared test of model fit was significant (²=941, <.001; root mean square error of approximation=0.064; comparative fit index=0.855; Tucker-Lewis index=0.848; standardized root mean squared residual=0.060). Factor internal consistency reliability ranged from 0.699 to 0.817. Validity testing suggested moderate discriminant, convergent, and criterion validity. Conclusions: The CASM measures a broad range of social media behaviors, enabling researchers to more effectively examine associations between online engagement and mental health outcomes. We hope the CASM will help researchers better understand how young people interact with social media, and that this knowledge will inform the development of more targeted interventions promoting healthy online habits.
Background: The ongoing adoption and use of digital interventions offer promising opportunities to meet the growing demand for mental health support. The effectiveness, implementation, and usage of these interventions depend on how well they are designed and evaluated. However, given the emerging nature of design research in this area, there is still no clear consensus on the specific principles and guidelines for developing digital mental health interventions (DMHIs). There seems to be a lack of clarity regarding the best practices for designing and evaluating these tools. Objective: We aimed to investigate and report on the design principles and evaluation approaches used in digital interventions specific to mental health care. Additionally, we sought to outline how these principles and approaches are applied in research. Methods: This scoping review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews. The literature search was performed in 2 electronic databases, SCOPUS and Web of Science, across 3 iterations from January 2024 to January 2025. A total of 2 independent reviewers screened and selected papers based on predefined inclusion and exclusion criteria, followed by data extraction from the selected studies. The data were then synthesized by categorizing the papers according to the primary research aim of each study. The inclusion criteria covered studies involving populations with mental health challenges or users of DMHIs, any digital tools for mental health care, and principles or strategies related to the design, evaluation, or implementation of DMHIs. Results: Our search identified 401 papers, of which 17 met the inclusion criteria for this review. Among these, 11 focused on evaluation studies, while 6 covered both design and evaluation studies (mixed). An iterative user-centered development process, expert inclusion, usability testing, specification of design elements, and user tracking and feedback were identified as common design principles used in studies focused on DMHIs. Evaluation approaches were shaped by the evaluation goal, which influenced the chosen methodologies. We also summarize the recommendations for implementation highlighted in some studies. Based on our findings, we propose 8 guidelines emphasizing stakeholder involvement in the development process and the need for clear justifications for design decisions, among other considerations. Conclusions: Design principles used in DMHI development include user-centered development, expert inclusion, and usability testing, while evaluation approaches often rely on randomized controlled trials to assess efficacy. Qualitative and mixed-method approaches are commonly adopted by studies to capture user experience and bridge both process and outcome measures. We recommend that future research explicitly report its design justification and adopt a multiperspective approach in the research and design of DMHIs.
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Background: Patients’ digital access to their personal health data is becoming increasingly common worldwide. However, medical documentation often contains technical language and sensitive information, which can lead to potential misunderstandings and distress among patients. These issues may be particularly impactful in mental health contexts. Large language models (LLMs) offer a promising approach by transforming clinician-generated health notes into language that is more patient-centered, nonmedicalized, and empathetic. However, risks related to accuracy and clinical safety have not been adequately investigated in psychiatry. Objective: This study aimed to qualitatively analyze the errors introduced by LLMs when transforming notes written by psychiatrists into patient-facing formats. It also highlights the implications for clinical communication and patient safety. Methods: Clinical notes (n=63) written by 19 psychiatrists in an outpatient treatment setting were collected, anonymized, and translated from German to English by humans. OpenAI GPT-3.5 Turbo was used to develop a preprompt that transformed these notes into a patient-centered, lay-readable form through an iterative process. Three psychiatrists qualitatively analyzed the LLM-revised documentation using Kuckartz content analysis. They compared the preconversion and postconversion notes to systematically identify and categorize LLM-induced errors. Results: Five categories of clinically relevant errors were identified: (1) clinical misinterpretations, particularly in critical assessments such as suicidality, where nuanced terminology was oversimplified or inaccurately represented; (2) attribution errors, where behaviors or roles within family dynamics or interactions were incorrectly attributed to different individuals; (3) content distortion errors, which were characterized by speculative additions, emotional exaggerations, and inappropriate contextual assumptions; (4) abbreviation and terminology errors, which resulted from inaccurate expansions of medical abbreviations and terms; and (5) structural and syntax errors, which resulted in ambiguity, particularly when the original notes were brief or bulleted. Despite significant improvements in the readability and overall linguistic fluency of the converted notes, these errors occurred. Conclusions: LLMs have the potential to transform psychiatric notes into patient-friendly formats. However, critical errors remain prevalent and can impair clinical judgment, understanding of patient circumstances, clarity of medication regimens, and interpretation of clinical observations. To safely integrate artificial intelligence–generated documentation into psychiatric care, clinician oversight and targeted model refinement are essential. Future research should explore strategies to mitigate these errors, assess their comprehensive clinical impact, and incorporate patient and provider perspectives to ensure robust implementation.
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SAN DIEGO, CA – At the 2026 American Association for Cancer Research (AACR) Annual Meeting, Verismo Therapeutics unveiled early data that could reshape CAR T-cell design. Built on a novel “KIR-CAR” platform, the experimental therapy SynKIR-310 uses a multi-chain, split-signaling architecture that mimics natural immune receptors, enabling T cells to stay active through repeated tumor attacks while potentially reducing exhaustion and safety risks that have long limited conventional approaches.
In preclinical studies, SynKIR-310 delivered potent anti-tumor responses in B-cell cancer models, including 100% survival in treated mice. The therapy targets CD19 using a canine-derived binding domain and is now being tested in patients with relapsed or refractory B-cell non-Hodgkin lymphoma in the Phase I CELESTIAL-301 trial.
Early clinical findings included a 70-year-old patient with follicular lymphoma who achieved a complete response just 28 days after receiving the lowest dose, an outcome still holding at six months. While preliminary, the results suggest that reengineering CAR T-cell biology itself may unlock more durable responses with fewer toxic side effects, tackling two of the field’s toughest challenges.
Two decades of rethinking CAR T
Laura A. Johnson, PhD, Chief Scientific Officer and Chief Operating Officer at Verismo Therapeutics
Verismo’s presentation of the data at AACR itself was understated, unfolding among rows of posters and quiet conversations. In the eyes of Laura A. Johnson, PhD, it was the culmination of a nearly two-decade-long scientific journey. It all began as a postdoc in the lab of immunotherapy trailblazer Steve Rosenberg, MD, PhD, who is currently chief of surgery at the National Cancer Institute, among several other appointments.
Johnson, who is chief scientific officer and chief operating officer at Verismo, told Inside Precision Medicine, “My postdoc project was literally taking, finding, and choosing an antigen; finding a shared antigen T cell receptor; subcloning it; and making it into a T cell. Not a CAR drug, but a TCR engineered drug that worked so well in the first year that they used to have money on tap there, turned it into a clinical trial, and then put me as an academic in charge of overseeing the clinical trial, the making of the drug, and getting to go and visit and shake the patient’s hands. In the four years since then, we saw literally pounds of tumor fall off these patients when we visited them in the clinic.”
That dramatic and deeply personal experience showed Johnson the promise and limitations of immune-based cancer therapies. Even as she saw tumors regress in ways that seemed almost implausible, she saw that those responses were not universal or durable and that toxicity could complicate even the most striking successes.
She continued to gain experience and try out different things, eventually leading her to the University of Pennsylvania (UPenn) with CAR T-cell therapy pioneer Carl June, MD. Working with June at UPenn, Johnson expanded CAR T-cell research rapidly, supported by industry investment and a mandate to investigate engineered immune cells’ effects on a variety of cancers. It was during those “great five years” that Johnson began to tackle solid tumors with CARs. Even as the field struggled with relapse, toxicity, and solid tumor efficacy, she led the way in clinically implementing experimental therapies.
Johnson’s subsequent move into industry, including a leadership role at GlaxoSmithKline (GSK), broadened her perspective further. “At the time, I did not see myself as an industry kind of person,” said Johnson. “I didn’t know what that was, but I did go to GSK for five years. It was amazing. I learned so much there. You know how to run clinical trials across the globe for registration. These huge teams of support. It was great.”
Johnson added, “I also had a sponsored research agreement with GSK, which was then exploring cell therapy, and after a year of that, they decided to open up a whole cell therapy unit and invited me to come and lead the group.”
By the time she returned to academic collaborations, she had seen the field from multiple angles—scientific, clinical, and operational—and had developed a growing sense that the limitations of CAR T therapy might be rooted in something more fundamental than incremental improvements could fix.
The origins of KIR-CAR
That realization sharpened when she reconnected with colleagues at UPenn, including Carl June and Michael Milone, PhD, MD, the co-inventors of Kymriah, the first-ever approved CAR T, who had already begun questioning the underlying design of conventional CAR T systems. “Back then, Mike and Carl already saw that it worked, but they felt something was not right about it. You know that patients can have recurrences of cancer, and it doesn’t work in solid tumors, no matter what they do. So they were already in the background trying to tinker and figure it out.”
The success of Kymriah had proven that engineered immune cells could be transformative, but it had also exposed persistent problems that could not be ignored. “At the time, Mike had a great idea that the artificiality of the single-chain CAR T was causing these problems because it was not evolutionarily selected for. It’s not natural. Maybe this has something to do with it.”
That insight led Milone to revisit the basic biology of immune receptors, examining how natural systems separate recognition from activation rather than fusing them into a single, continuously active structure. “They all have the same receptor format to bind to the target on the cell’s outside. The receptor is anchored in place by a neck in the cell membrane, while a completely separate internal signaling mechanism is also anchored by a neck in the membrane and is activated from the inside. And these two actually don’t interact. They have nothing to do with each other unless and until that target is found unbound, which brings the two together.”
From this observation emerged the concept of KIR-CAR, a multi-chain system inspired by natural killer (NK) cell biology that attempts to restore a more controlled and conditional activation process. “T cells, their main job, is actually not to kill you but rather to kill bad things, so they try and shut everything down,” Johnson explained. “So, we said, ‘Let’s use NK cells.’ They’re the other main lymphocyte that attacks tumors, and they’re innate. Maybe they won’t have the same problems with shutting down. Let’s throw it at the wall and see what sticks.’”
The resulting design combined elements of NK cell receptors with T-cell machinery, creating what Johnson describes as a more natural on-off switch. The combination of the killer immunoglobulin receptor (KIR), which acts as the outside binder, with existing intracellular signaling machinery used for CARs resulted in the name KIR-CAR. “A chimera has the head of a lion, the body of a goat, and the tail of a snake,” said Johnson, using the hybrid from Greek mythology in describing a traditional CAR. “We’ve un-Frankensteined them and put them back. What we end up with is just a more natural on/off switch. Why would we think we can do better than a million years of evolution at figuring out a way to trigger and turn off these cells to get rid of bad things?”
Early signals of efficacy and safety
In early preclinical experiments, KIR-CAR cells were compared to single-chain CAR T cells, showing subtle differences in vitro but greater differences in complex systems. By the time Johnson presented SynKIR-310 at AACR, those differences had become a consistent pattern across preclinical studies and early clinical observations, suggesting that the KIR-CAR approach may improve tumor control without the toxicity of conventional CAR T therapies.
Johnson said, “It’s been surprising, but great news. Our preclinical team has reversed the process, gone back to mice, and successfully reproduced the same findings. Not only is the KIR-CAR superior at eliminating tumors, but it also has a shorter duration of interferon gamma. In contrast, the single-chain CAR T cells that everyone else on the planet is using appear to be frighteningly toxic because they go off script.”
Johnson vividly described that uncontrolled activation. “If you do any assay with them, presumably including in vivo, lasting more than a day, they start killing everything around them,” she said. “They start spitting out interferon gamma. They infect every cell they come into contact with; they proliferate; they produce cytokines; they cause lysis; and they have many other harmful off-target effects.”
That behavior aligns with her broader description of how conventional CAR T cells can become overactivated and exhausted. Johnson elaborated, “The CAR T cell is hyperactivated, and it’s going down. It knows it’s exhausted, but it also detects an activated state, so it sets off fireworks and hopes the grenade response will take out whatever is bad too.”
In contrast, biomarker data from SynKIR-310 suggest a more controlled and physiologic immune response. “When we look at the biomarkers, they’re not making a ton of interferon or TNF alpha,” said Johnson. “Even from the first dose we used, we showed clearly biological activity where the T cells go in; as of day seven, you start to see interferon pickup. It peaks out at about ten days.”
Johnson continued, “Then it’s textbook as for how a T cell activates when it sees its target; this process is crucial for the immune response. It showed that it’s very clearly encountering a target, activating and doing what it’s supposed to do. However, the blood levels we observed were significantly lower than expected due to hematologic malignancies, which involve widespread tumors throughout the body, including the bone marrow and blood.”
Clinical observations, though limited, reinforce that pattern. “The results were announced today for the first nine patients. It’s a basket study for both ovarian cancer and cholangiocarcinoma. So, there are three very high unmet and urgent needs for patients. Most of these have one line of approved therapy, or maybe two, and once they become advanced refractory or metastatic, there’s nothing for these patients. Overall survival is measured in weeks, not months.”
Within that context, even modest responses carry significance. “Four of the nine showed measurable tumor reductions and the last patient treated, the last one in cohort three, had a response that continued past our data cutoff and keeps going. So, it’s very good news.”
Perhaps most striking, however, is the KIR-CAR’s apparent safety profile. “The biggest thing they were worried about is toxicity. Everybody knows that CAR causes cytokine release syndrome (CRS), and interferon gamma causes neuropathic disease, leading to brain damage and other severe symptoms. It’s got a bad rap. I think they got a headache one night that was called ‘CRS.’ That was gone the next morning. That’s it.”
A broader vision for cancer treatment
For Johnson, the significance of these findings lies less in any single result than in their consistency across different models and targets, reinforcing her belief that the KIR-CAR platform reflects a fundamentally different—and potentially more effective—approach to engineering immune cells. “You can want something to work as much as you want, but if it doesn’t, it doesn’t, and you accept it,” said Johnson. “So it’s okay that the data was the same for both our platform assets, the CD19 and mesothelioma KIR-CARs; this result is real.”
That reproducibility has given her confidence to draw comparisons with existing therapies. “When we see the same things again, there are fewer CRS cytokines, less duration of toxicity, and way better treatment. It is better than both Kymriah and Yescarta. We did the in vivo models, but it’s a little better than Kymriah and a lot better than Yescarta.”
At the same time, she remains grounded in the understanding that these are early results, requiring validation in larger trials and over longer follow-up periods, even as they point toward a broader shift in how the field might approach the design of next-generation immunotherapies. Rather than continuing to build increasingly complex artificial systems, the KIR-CAR approach suggests that aligning more closely with the immune system’s natural architecture—its built-in checks, balances, and conditional activation mechanisms—may offer a path to therapies that are both more effective and less toxic.
That idea, rooted in the biology she has spent her career studying, connects her earliest experiences watching tumors disappear in clinical trials to the work she now presents. It formed a narrative for Johnson that is less about a single product than about a way of thinking: that progress in cancer immunotherapy may ultimately depend not on pushing the immune system harder but on understanding it more deeply and working within the logic it has evolved over millions of years to follow.
Researchers at McGill University have developed a rapid way to engineer blood clots that stop severe bleeding and support tissue healing more effectively. Their technique, called “click clotting,” links red blood cell surface proteins through a chemical reaction, resulting in a biocompatible clot that is 13 times more resistant to fracturing and four times more adhesive than natural blood clots. The team said the method could be used to develop life-saving biomaterials to help control severe bleeding, as well as benefit people with clotting disorders.
“Natural blood clots can be slow to form and mechanically fragile, which limits their ability to stop severe bleeding and can compromise healing,” said Jianyu Li, PhD, senior author and professor of mechanical engineering and Canada research chair in tissue repair and regeneration. “Our work shows that, when engineered appropriately, red blood cells can play a central structural role, enabling the design of stronger and more functional biomaterials.”
Senior and corresponding author Li, together with first author Shuaibing Jiang, PhD, reported on the development in Nature, in a paper titled “Engineering tough blood clots for rapid hemostasis and enhanced regeneration.” In their paper the team concluded, “Our strategy enables instantaneous clotting and markedly enhanced fracture resistance despite low structural polymer content, while preserving the intrinsic bioactivity of blood clots to enhance hemostasis and regeneration.”
Jiang, now a postdoctoral associate at Harvard Medical School, led the research during his PhD studies at McGill. Researchers at the University of British Columbia, the Medical College of Wisconsin, the University of Colorado Boulder, the University of Toronto and the research institute Versiti also contributed.
“Blood clots are pivotal for hemostasis and regeneration, but they are mechanically weak and form slowly, posing risks for life-threatening hemorrhage and limiting broader applications,” the authors wrote. “These limitations are attributed to complex coagulation cascades, abundant mechanically ineffective cells, and little structural polymers.”
Previous efforts to crosslink red blood cells (RBCs) have used chitosan, a polymer derived from crustacean shells, but these led to brittle clots, ruptured cells, and inconsistent clotting. In “click clotting,” the clot structure is fundamentally strengthened through a fast, bio-safe chemical reaction that connects proteins on the red blood cell surface, forming a solid gel in just five seconds. Because the “click” reaction doesn’t interfere with normal blood chemistry, it can work alongside the body’s natural clotting process. As a result, the artificial cell‑based gel, called a “cytogel,” can be added to whole blood, where it becomes embedded within the body’s own fibrin clot.
Shuaibing Jiang (left) and Jianyu Li [Jianyu Li]
“Here we report a strategy that rapidly crosslinks red blood cells into tough cytogels and integrates them within blood clots,” the team further explained. “The resulting engineered blood clots (EBCs) form within seconds and exhibit a 13-fold increase in fracture toughness, and a 4-fold improvement in adhesion energy compared with native clots … Our strategy is advantageous over previously reported methods using chitosan to crosslink RBCs, which lead to brittle clots, hemolysis or inconsistent clotting.”
Li added, “The technology enables both autologous clots (using the patient’s own blood) and allogeneic clots (using type-matched donor blood). Autologous clots can be prepared in approximately 20 minutes, while allogeneic clots can be prepared within about 10 minutes. Given typical clinical time constraints, this approach has strong potential for in-patient emergency care, wound management and related settings.”
The team confirmed their results through in vitro testing, as well as through tests in rodents. “In vivo studies demonstrate that EBCs can rapidly halt hemorrhage, promote tissue regeneration, mitigate inflammation and foreign body reactions, and prevent postoperative adhesion,” the authors stated. Of particular note was effective healing and regeneration observed in the injured liver, with performance exceeding that of a clinically used product tested also tested as part of the study. “Compared with previously reported biomaterials for liver regeneration, EBC demonstrated milder inflammation and more efficient tissue regeneration,” the authors noted. Analyses showed minimal evidence of immune reactivity and no toxicity in major organs.
The researchers say that while further study is required before the cytogel can be used in clinical settings, the research establishes a foundation for its design and application. “Overall, EBC, as a native scaffolding material, can promote tissue regeneration with minimal inflammation and foreign body responses, and prevent postoperative adhesions, outperforming the clinically used products,” the scientists concluded. “This work may motivate the development and translation of highly cellularized materials for bleeding control, wound management, tissue repair and regenerative medicine.”
“Engineered blood clots have strong potential for broad clinical use and could improve outcomes across many medical situations,” Li said.
Researchers at the Mass General Brigham Heart and Vascular Institute and collaborators have developed and validated a new integrated polygenic risk score (PRS) that estimates inherited risk across eight cardiovascular conditions using a single genetic test. The tool is a combination of a handful of genetic risk models collected into a comprehensive risk tool and is designed to improve identification of individuals at elevated risk for coronary artery disease (CAD), atrial fibrillation, type 2 diabetes, venous thromboembolism, thoracic aortic aneurysm, extreme hypertension, severe hypercholesterolemia, and elevated lipoprotein(a).
The validation study, published in the Journal of the American College of Cardiology, showed that individuals with high genetic risk scores had significantly higher odds of developing disease compared with those at average risk, including a 3.7-fold higher odds for CAD and a 4.1-fold higher odds for severe hypercholesterolemia.
“Interpreting DNA risk is new for the public as well as clinicians,” said co-senior author Pradeep Natarajan, MD, director of preventive cardiology at Mass General Brigham Heart and Vascular Institute. “It was very important to us to provide a clear genetic risk report that would be accessible and patient-friendly.”
The researchers developed the integrated PRS tool using PRSmix, an elastic-net approach that combines previously published polygenic risk scores from the Polygenic Score Catalog. The model was trained using genotype and clinical data from 245,394 participants in the NIH All of Us Research Program and validated using data from 53,306 people from the Mass General Brigham Biobank. In the validation cohort, the integrated scores demonstrated strong discrimination across all eight conditions, with individuals in the top 10% of genetic risk showing increased odds of disease, including CAD (odds ratio 3.7), type 2 diabetes (3.1), atrial fibrillation (3.0), venous thromboembolism (1.9), hypertension (2.1), and lipoprotein(a) (41.0).
Current cardiovascular risk assessments typically rely on age, sex, blood pressure, cholesterol, and other clinical factors. The Mass General team noted that these methods may miss individuals with substantial inherited risk who do not yet show clinical symptoms. By comparison, the new PRS tool gives a single genetic assessment that can be applied early in life and across multiple disease pathways simultaneously.
“Although PRS have typically been evaluated one condition at a time, a single genotyping assay enables calculation of PRS for any heritable trait without significant additional cost, creating an opportunity to assess inherited risk across multiple cardiovascular conditions simultaneously,” the researchers wrote noting the value of this new method.
In this study, the integrated PRS improved risk classification when incorporated into clinical prediction models, including better stratification of individuals near clinical decision thresholds for cardiovascular disease. The system also generated standardized risk categories—high, average, or low—for each condition and presented results in clinician-facing and patient-facing formats that can be integrated into electronic health records.
Clinically, the new PRS is could be use to identify people whose inherited risk could provide the opportunity for preventive interventions such as increased monitoring, lifestyle modification, or preventive therapies, even when conventional risk factors appear normal. For CAD specifically, the findings suggest that individuals with high polygenic risk may have risk levels comparable to other established high-risk groups, despite modest or normal cholesterol levels.
The researchers also evaluated how the tool could work across diverse populations and clinical settings. They found that while the PRS performed consistently across ancestry groups, predictive strength was reduced in individuals with greater genetic variation from people of European ancestry, exposing the inherent limitations in current genomic reference datasets. Despite this, the integrated framework was designed to allow updating as new data become available.
The PRS is currently available through Mass General Brigham Laboratory for Molecular Medicine and Broad Clinical Labs. The researchers said that next steps to further refine the tool include broader prospective validation across diverse populations, evaluation its cost-effectiveness, and research to determine how genetic risk information should influence clinical decision-making.
Cases of bowel and ovarian cancer are rising, but only among people under 50, according to research published in the British Medical Journal Oncology today, April 28, 2026. While other types of cancer are also rising in older adults, this particular trend among younger adults is striking.
A key factor, the researchers’ work suggests, is excess weight. But that does not fully explain the trends they saw.
In particular, there was a significant rise in 11 cancers among the younger adults with known behavioral risk factors. These cancers were: thyroid, multiple myeloma, liver, kidney, gallbladder, bowel, pancreatic, womb lining (endometrial), mouth, breast, and ovarian cancers.
Rates of all these cancers also rose significantly among the older adults, with the notable exceptions of bowel and ovarian cancers.
Besides mouth cancer, all 11 cancers associated with known behavioral risks were linked to obesity. And six (liver, bowel, mouth, pancreas, kidney, and ovary) were also linked to smoking; four (liver, bowel, mouth, and breast) were associated with alcohol intake; three (bowel, breast, and endometrial) were linked to physical inactivity; and one (bowel) was associated with dietary factors.
“Of the 11 cancers we identified which were increasing and linked to known lifestyle factors—the most common by far in younger adults was breast cancer,” the study’s lead author, professor Montserrat Garcia-Closas, MD, DrPH, told Inside Precision Medicine. Garcia-Closas is in Integrative Cancer Epidemiology, Division of Genetics and Epidemiology, and The Cancer Epidemiology and Prevention Research Unit, The Institute of Cancer Research, London.
The rising incidence of certain cancers among people under 50 isn’t unique to England, and one major question is whether changes in behavioral risk factors might be to blame.
This research group analyzed cancer incidence trends in England from the National Disease Registry Service for the period 2001 to 2019, comparing patterns by sex in two age groups: 20–49 year olds and those aged 50+ for more than 20 different cancer types.
This database, “Captures virtually every cancer diagnosis in England going back decades—one of the most complete registries in the world. That scale is what allows us to track trends reliably across the whole population, not just a sample,” said Garcia-Closas.
The team used national health surveys to look at trends in established risk factors: smoking, alcohol intake; diet (high red/processed meat, low fiber intake), excess weight (BMI), and physical inactivity to quantify any changes by age and sex and estimate the proportion of cancers attributable to specific risk factors.
Their analysis showed that new cases of 16 out of 22 cancers in younger women, and 11 out of 21 cancers in younger men, increased significantly in England between 2001 and 2019.
And five cancers—endometrial, kidney, pancreatic, multiple myeloma, and thyroid cancer— increased significantly faster in younger than in older women, while multiple myeloma increased faster in younger than in older men.
But with the exception of excess weight, trends in these risk factors over the past one to two decades have been stable or improving for younger adults, with the largest reductions of around 7% in red meat consumption.
The average daily amount of red meat eaten, they report, fell from 38 grams in 2008 to 17 grams in 2018 among younger men, and from 22 grams to 10 grams in younger women. And average processed meat intake in younger women was half that of younger men: 10 grams versus around 20 grams. And while more than 90% of younger adults weren’t eating enough fiber in 2018, their intake remained stable or slightly improved in both sexes between 2009 and 2019. And these trends were similar in older adults.
Established behavioral risk factors accounted for a substantial share of cancer cases. In 2019 these contributed 68%–65% of mouth cancers for younger and older men, respectively; 42%–48% of liver cancers; 49%–53% of bowel cancers, 29%–33% of kidney cancers, and 36%–34% of pancreatic cancers.
Among women they accounted for 52%–45% of mouth cancers; 35%–42% of endometrial cancers; 44%–46% of liver cancers; 38%–42% of bowel cancers; 33%–37% of kidney cancers; 31%–28% of pancreatic cancers; and 19% to 24% of gallbladder cancers.
Excess weight was the risk factor associated with most cancers in 2019, ranging from 5% for ovarian cancer to 37% for endometrial cancers.
“These patterns suggest that while similar risk factors across ages are likely, some cancers may have age-specific exposures, susceptibilities, or differences in screening and detection practices,” write the researchers.
“Prevention takes a long time and we must act now with what we know, with better and more effective public health policy and programs to address the overweight and obesity epidemic,” said Garcia-Closas.
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