Conditions: Pulmonary Tuberculosis; Tuberculosis (TB); Tuberculosis Active
Sponsors: Huashan Hospital; The Hong Kong Polytechnic University
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Sponsors: Huashan Hospital; The Hong Kong Polytechnic University
Not yet recruiting
Centering People, Centering Stories: Folklore as an Unlikely Ally in the OCD Misdiagnosis Crisis
By: Rebecca Bernstein, MA Folklore
The International OCD Foundation’s (IOCDF) recent landmark white paper reveals more than 80% of OCD cases in America remain undiagnosed (International OCD Foundation, 2025). Considering the size of this clinical challenge, it might seem odd to suggest that a small, humanities-based field like folklore— yes, folklore — has any role to play in the solution. As someone who studies OCD personal narratives (stories people tell about their lived experiences), my research suggests otherwise. In a situation that invokes the feeling of all-hands-on-deck, the tools and perspectives of this field may offer more benefit than we might initially give it credit for.
Folklore is the study of informal, creative communication. Dr. Lynn McNeill describes it as anything people “say, do, make, or believe” (McNeill, 2013). Folklore includes everything you’d think of (quilts, traditional music, fairy tales) and a lot of things you wouldn’t (occupational culture, gossip, internet memes.) We find examples of folklore everywhere. It’s in our holidays and our hobbies, our food and our fads, our jokes and our grieving. Folklorists study the infinite ways people express themselves in daily life. This, in turn, helps us better understand the cultural realities in which they live. And because what we “say, do, make, or believe” describes most of human behavior, the folkloric lens can be an indispensable one with which to investigate the world.
The benefit of studying how people express themselves is obvious when we recognize that in mental health, conversation and narrative are the primary tools we use to give and receive care. OCD isn’t just a diagnosis. It’s also a fundamentally creative experience. (Creative things don’t necessarily have to be beautiful, pleasing, or even wanted. They just have to be new and meaningful.) (Dictionary.com, 2023). Although ego-dystonic, extraordinary beliefs and elaborate rituals are hallmark features of OCD. When sufferers discuss their experiences, they are naturally inclined to do so through their own personal and cultural lenses. Therefore, descriptions of OCD vary infinitely. If the issue is our failure to recognize OCD when it presents itself, an approach designed to make sense of something as messy as human expression may offer insights that quantitative research methods still struggle to obtain.
How Folklorists Research
Just like in biomedical research, the research methods folklorists use matter. Our goal is to better understand people and their communities. That means we strategically build relationships, listen deeply, and intentionally embrace the complexity of those we talk to.
When I started researching OCD narratives, I wanted to know: What were the internal realities like for people who lived with this illness? What made their stories distinct? And how might those stories be connected? One of the biggest challenges I faced in my fieldwork was the potential for my participants to self-censor. As someone who also lives with OCD, I knew all too well the role shame and fear could play in the choice to fully share one’s reality with others. Using both field-tested approaches and my own lived knowledge, I conducted interviews with people with OCD, approaching them in a way I hoped would ease interviewees into difficult conversations:
- I provided anonymity. I held all interviews on Zoom, where participants were free to keep their cameras off. I also assigned each one an alphanumeric signifier (A1, B2, etc.) in my writing.
- I emphasized the importance of story. Although I asked specific questions, I also allowed participants to go off topic and engage in two-way conversation. The story was the point.
- I used the “kitchen table” interview method. Based on the work of Carl Lindahl, this method tries to recreate the intimacy of two individuals talking around a kitchen table. It discourages framing the interviewer as an objective party, recognizes storytellers as experts in their own experiences, and suggests that interviewers only ask questions they themselves would be willing to answer (Lindahl, 2012).
- I disclosed. My choice to openly discuss my own OCD diagnosis with interviewees allowed conversations to proceed with a certain warmth and vulnerability.
- I emphasized participants’ humanity. I treated each participant as a full individual rather than just a source of information. This meant I worked on a model of enthusiastic consent. It also meant I asked them for feedback on my writing to ensure I portrayed their experiences accurately.
- I compensated participants well. Each received a $100 gift card.
The Results
The universal theme I discovered during these interviews was a profound concern with social isolation. Every single participant mentioned this issue. Interviewees shared how OCD made it difficult for them to maintain relationships and how challenging it was to hide their illness from others. They also recalled their joy and gratitude when discussing moments in which they felt understood.
Their narratives also contained four other common themes:
1.) Logic and patterns of personal concern. Participants often discussed their particular obsessions and compulsions, and the influence those specific thoughts and behaviors had on their daily lives.
2.) Issues of negotiation. People talked about navigating certain types of conflicts as a result of their illness. These conflicts generally fell into two categories: self-negotiation and existential negotiation. In the first, people struggled with the desire to take their thoughts and urges seriously despite knowing they didn’t make sense. In the second, they wrestled with their relationships to the divine.
3.) Positive approaches to the illness. Many interviewees made a point to mention the silver linings they saw in being sick. They noted how OCD made them safer, more empathetic, or provided them with particular skills. Others discussed productive choices they’d made despite living with such a debilitating condition.
4.) Interactions with medical systems. Participants talked about their experiences as patients. For some, dealing with doctors, therapists, and other health professionals helped them understand their experience or relieved their suffering. For others, these encounters were confusing, unhelpful, or even traumatizing.
It’s important to note these themes represent a truly broad range of content. Not every story included every theme, and within those themes, the specific details I heard varied as much as the individuals themselves.
Implications
Say you were to hear four stories: one about someone’s preferred cleaning routine, one about someone’s waning belief in God, one about a good decision made in a difficult circumstance, and one about a doctor’s visit. It’s unlikely you’d consider these stories connected. And yet the data shows they are. The fact that stories with dramatically different content can reflect the same illness highlights the way OCD can remain elusive and camouflaged.
The problem with recognizing these stories as OCD stories isn’t just the variation in content. It’s also in how others hear them. In folklore, we don’t just study cultural expressions. We also study how they move from person to person. “Tellable narratives” travel easily. Both speakers and listeners understand what a certain type of story should sound like and the meaning it’s supposed to convey. If I tell you a tale about a persecuted young woman who escapes a bad home life and marries a prince, you can probably guess you’ve heard Cinderella. If we’re both excited that she went from rags to riches, we share an understanding that her journey is a positive one. In contrast, an “untellable narrative” hits some kind of barrier. If you’ve never heard Cinderella before or think the stepmother is actually the hero, my meaning in telling you the story gets lost. Untellable narratives can be misinterpreted.
This misalignment between the stories people tell and the ones listeners expect to hear happens all the time. We’ve all said things misunderstood by others. Sometimes this process is harmless; other times it results in difficult consequences. Dr. Kristiana Willsey writes about veterans who censor themselves in front of civilian audiences. Because civilians usually only expect to hear tales of “war heroes” or “PTSD survivors,” veterans often choose not to tell the full and complicated stories of their service experiences (Willsey, 2015). Dr. Amy Shuman and Carol Bohmer discuss the case of rejected asylum seekers. If asylum applicants don’t tell their stories of oppression and escape in a way that fits immigration officials’ expectations of what a traumatic asylum story should look like, their applications get denied (Shuman & Bohmer, 2016). If we consider just how different any two OCD stories can be and add the public assumption that OCD is an illness of specific doings (hand washing, checking locks) rather than tellings, it highlights just how difficult it is for most of these narratives to get heard, and heard correctly.
Patient/practitioner interactions can be particularly vulnerable to this type of miscommunication. The problem with considering OCD as just a medical issue is that most people don’t think of their lives as medical events. Practitioners enter the room ready to make sense of problems in clinical terms. Patients enter with stories. They share their concerns in a way that cannot be easily separated from their personal frames of reference or cultural understandings of life. Practitioners are often taught to mistrust the details that emerge from these narratives, to kindly but efficiently work around them in order to do their jobs. But for patients, these details are how they make meaning. If misdiagnoses also occur during these interactions, it’s worth taking a closer look at what’s being lost in translation.
Folklore ultimately offers the promise of new solutions to old problems. It allows us to reconsider how we listen to patients, collect data, and address communication issues— all clear benefits in the fight for better diagnostic care. It is also equipped to help us make sense out of the lived reality of OCD— perhaps uniquely so. I see folklore as an exciting potential ally to traditional research and clinical spaces. My hope is that this partnership can help us work more effectively toward our common goals: a better understanding of OCD, and quicker ease for its sufferers.
Works Cited
Dictionary.com. (2023). Creativity. In Random House Unabridged Dictionary. Random House, Inc. https://www.dictionary.com/browse/creativity.
International OCD Foundation. (2025). America’s OCD care crisis: National findings on the failure of effective OCD treatment to research patients. International OCD Foundation. https://iocdf.org/wp-content/uploads/2025/12/Full-Report-Americas-OCD-Care-Crisis-12-9-2025.pdf.
Lindahl, C. (2012). Legends of Hurricane Katrina: The right to be wrong, survivor-to- survivor storytelling, and healing. The Journal of American Folklore, 125 (496), 139–176. https://doi.org/10.5406/jamerfolk.125.496.0139.
McNeill, L. (2013). Folklore rules: A fun, quick, and useful introduction to the field of academic folklore studies. Utah State University Press. https://muse.jhu.edu/book/27822.
Shuman, A. & Bohmer, C. (2016). The stigmatized vernacular: Political asylum and the politics of visibility/recognition. In D. Goldstein & A. Shuman (Eds.), The stigmatized vernacular: Where reflexivity meets untellability. Indiana University Press.
Willsey, K. (2015). Falling out of performance: Pragmatic breakdown in veterans’ storytelling. In T.J. Blank & A. Kitta (Eds.), Diagnosing folklore: Perspectives on disability, health and trauma. University Press of Mississippi.
The post Centering People, Centering Stories: Folklore as an Unlikely Ally in the OCD Misdiagnosis Crisis appeared first on International OCD Foundation.
[Comment] The changing context of intergenerational health inequalities
Social inequalities in mortality and health have been recognised as serious public health issues since the 1980s, yet researchers continue to find social gradients in health nearly everywhere they look.1,2 Despite decades of research, our understanding of how and when socioeconomic factors and health interact to produce health inequalities remains work in progress. Some research on health inequalities has extended focus from adulthood social position to parental social background and early life conditions, and the accumulation of advantage and disadvantage across the life course.
[Articles] The effects of the Rx Kids unconditional cash prescription programme during pregnancy and infancy on birth outcomes in the USA: a population-based, quasi-experimental study
With significant reductions in adverse birth outcomes, the treatment of perinatal poverty with a place-based intervention as replicable and scalable as Rx Kids has important implications for infants and society. These findings suggest that the economic hardship of the perinatal period, starting in utero, contributes to adverse outcomes and is addressable.
Self-Monitoring Risk Factors for Diabetic Foot Ulceration With the Feetchecker App: Mixed Methods Study
Background: A prevalent and serious complication of diabetes mellitus is the development of diabetic foot ulcer (DFU). There is a need for effective solutions that help prevent DFU to support our increasingly stressed health care systems. The use of mobile health (mHealth) tools has been shown to improve awareness and effective self-care management skills in people at risk of developing diabetic foot ulceration. Objective: In this study, we aimed to investigate the perceived usefulness, engagement, and overall user experience of the Feetchecker app, a self-monitoring mHealth app for people at risk of DFU. Methods: A total of 24 patients (mean age 71, SD 8.6 years) with type 2 diabetes mellitus at risk of developing diabetic foot ulceration completed a 3-month evaluation period (70 recruited, 36 included, 12 dropped out) of a self-monitoring mobile app called Feetchecker app. A mixed methods approach was used to combine insights from app data with qualitative data from a pre- and postsurvey as well as interviews with patients and involved podiatrists. Data were analyzed using descriptive statistics and thematic analysis. We evaluated overall use of the app, patient engagement, and user experiences. Results: Patients who fully completed the study conducted 393 feetchecks. In total, 7 patients sent in 9 pictures; all 7 were called for follow-up by a podiatrist. Overall, patients had a positive experience with the app and perceived the Feetchecker app as a valuable tool to monitor their feet for potential risk factors of DFU. Ease of use in performing a feetcheck and sending the podiatrist a picture was described as an important feature. Three main types of engagement with the Feetchecker app emerged: continuous, frequent, and no to little engagement. These patterns highlight enablers for self-monitoring such as ease-of-use, easy access to a podiatrist, and social support, as well as barriers such as digital skills and sustained engagement. Podiatrists highlighted the benefits of having patients report potential issues quicker and the ability to monitor their patients remotely. Challenges remain in integrating the promotion of the Feetchecker app into their consultations. Conclusions: The Feetchecker app supported patients in self-monitoring risk factors associated with DFU through routine checks and quick contact with a health care professional in case of a potential issue. Overall, patients described a positive user experience and considered the app helpful. While mHealth tools are not for everyone, user engagement for many patients was high and shows that such apps can offer support for people able to use them. Future research should focus on improving usability and engagement with the app as well as extend the way patients can communicate with health care professionals beyond a picture.
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Sea Cucumber Tissues Demonstrate Natural Immortality in Seawater
From the revived corpse of Frankenstein’s monster to the disembodied hand, “Thing,” in the Addams Family, reanimated tissue is one of the most enduring images in science fiction. The discovery of a sea floor-dwelling sea cucumber that scientists are calling a “real-life zombie” suggests that there may be some basis for that image in nature.
Scientists headed by a team at Memorial University of Newfoundland showed the continued viability of amputated tissue from the sea cucumber Psolus fabricii for more than three years in natural seawater. It’s the first known report of the long-term survival—and continued growth—of discarded tissue outside of a highly controlled, sterilized environment.
The discovery that these living P. fabricii explants (LiPfe) can survive for years in natural seawater without any supplementation challenges assumptions of what’s possible for tissue immortality and could have implications in areas including regenerative biology and tissue engineering. The findings could also lead to the development of experimental models for biological research that are more widely accessible, without the ethical and logistical challenges associated with many existing cell lines.
“We haven’t grown a new, complete sea cucumber yet, but we are seeing pretty stunning growth and diversification of cells literally years after this tissue was removed,” said research lead Rachel Sipler, PhD, a Bigelow Laboratory for Ocean Sciences senior research scientist. “It’s like a lizard that loses its tail. We know some lizards can grow new tails; we’re talking about whether the tail can grow a new lizard.”
Reporting on their findings in Science Advances (“Natural tissue immortality: Indefinite survival of sea cucumber explants,”) Sipler and colleagues stated, “Our findings challenge conventional perceptions of tissue immortality and present a new class of experimental model, free from ethical concerns, with substantial implications for regenerative biology, biomedical research, and tissue engineering.”
Over the last 200 years, scientists have tried to achieve cellular and tissular survival outside living hosts, “… but efforts have been met with limited success due to the highly degradable nature of tissue itself,” the authors wrote. Since the mid-20th century, scientists have made significant breakthroughs with immortal cell lines, such as HeLa cells, that can be grown in a lab and proliferate indefinitely for long-term research. In earlier studies, tissue cultures have only been maintained under axenic conditions that are tightly controlled, rigorously maintained, and lack any bacteria or other organisms. Even then, they have not demonstrated signs of actual healing and growth, nor retained the ability to move independently. “While immortal cell lines demonstrate indefinite proliferation in vitro, they lack structural integrity and complex tissue interactions,” the team continued. “Achieving this with complex, structured tissue represents the next step.”
Many echinoderms, including sea cucumbers, are known to display impressive regeneration capacity and negligible cell aging. “In the ongoing effort to understand tissue culture, regeneration, and immortality, researchers have naturally been drawn to echinoderms, a phylum with genetic and evolutionary links to vertebrates and examples of both extreme regenerative capacity and negligible cellular senescence,” the investigators noted. Lost tissue, though, was always assumed to eventually decay or die.
Yet, in what Sipler calls a product of “keen observation,” the researchers noticed that some discarded tissue from a tube foot of a sea cucumber hadn’t decayed after a number of weeks. In fact, it seemed to be growing. The researchers then ran a number of experiments in flowing seawater with tissue removed from the feet, main body, and tentacles of three individuals of P. fabricii, a cold-water species of sea cucumber.
They found evidence of diversifying cells, immune activity, and tissue reorganization in the explanted tissue. “In experimental trials, these explants, termed LiPfe (living immortal P. fabricii explants), displayed immune activity, cell cycling, tissue reorganization, and absorption of dissolved amino acids, underscoring their active living state,” they noted. And in the absence of a mouth, the cells appeared to be getting nutrients by absorbing amino acids dissolved in the seawater.
Even after three years, when the researchers stopped the experiments in order to publish, the tissue was still active. This ability to survive in a complex, stressful environment, Sipler said, makes this cell line unique compared to other tissue cultures. “Compared to other cells or tissues grown under laboratory setups that required strict parameters, including axenic conditions, LiPfe required nothing apart from natural running seawater,” they wrote. “Comparative experiments conducted on explanted tissues from related species demonstrated no equivalent tissue survival, highlighting the unique properties of P. fabricii, which do not have parallels in the current literature.”
“Natural seawater is just about the most microbially diverse, least clean approach we could take experimentally,” Sipler added. “Yet, that rich environment full of bacteria and all this organic matter was actually feeding them and allowing this tissue to heal and grow.”
The implications for biomedical sciences and engineering, the authors said, are profound, with potential applications in everything from tissue regrowth to anti-microbial healing. In their paper, the authors stated, “The discovery of LiPfe challenges the boundary between organismal life and cellular autonomy, compelling a redefinition of what it means for tissue to be alive.”
The discovery opens up new opportunities for biological research and education more broadly. The tissue they’ve preserved not only shows an unprecedented ability to maintain its structural integrity and complexity in culture. It can also be grown more easily in the lab and, as an invertebrate, isn’t subject to as many research restrictions, making it useful in contexts where there are legal obstacles or limited biosafety infrastructure for using human-based or other vertebrate cell lines.
As an oceanographer, Sipler noted that the exciting discovery drives home the incredible untapped potential of ocean life. “The best advances in science are made when you find a natural analog for what you’re studying,” she said. “Here is this species that has this groundbreaking ability, and we had no idea. It’s a reminder of how much is yet to be discovered in the marine environment, and how important it is to protect these resources that may hold really valuable knowledge for us.”
The post Sea Cucumber Tissues Demonstrate Natural Immortality in Seawater appeared first on GEN – Genetic Engineering and Biotechnology News.
Accuracy in the Estimation of Self-Reported Knee Brace Wear Time in Young Adults With a Symptomatic Knee Following ACL Reconstruction: Secondary Analysis of a Pilot Randomized Controlled Trial
Background: Knee braces may improve symptoms and physical function following anterior cruciate ligament reconstruction (ACLR). However, their effectiveness depends on adherence, which typically relies on self-reported wear time, prone to recall and response bias. Objective measures (eg, temperature sensors), validated in footwear and orthotics research, offer a potentially more accurate alternative to self-reporting. Despite this, there is no research comparing self-reported and sensor-measured wear times in a knee brace. Objective: This study aimed to determine how well self-reported wear times reflect sensor-measured data in a slim-fit knee brace. Methods: Young adults (aged 18-45 years), 1-8 years post-ACLR, with a symptomatic knee (the 4 Knee injury and Osteoarthritis Outcome Score subscales [KOOS] score <80/100) wore a slim-fit brace during a 6-week feasibility trial. This study reports a secondary analysis of participants allocated to the brace group. Self-reported wear times were recorded in daily logs. An undisclosed, embedded temperature sensor recorded temperature every 10 minutes. A wear detection algorithm identified brace donning and doffing. These data were used to calculate aggregated measures (ie, summary measures across the entire 6-week intervention period, including cumulative wear time, average daily wear time, and total number of days worn) and repeated measures (daily wear duration, 3- and 7-day rolling averages, where wear time is averaged over consecutive days). Agreement between self-reported and sensor-based measures was assessed using concordance correlation coefficients (CCCs) and limits of agreement (LoA). Results: Of the 14 randomized participants, 10 (30% male [n=3]; mean age: 33, SD 6 years; time post-ACLR: 4, SD 1 years) had both temperature sensor and self-reported wear data. Six participants (60%) underreported average daily wear time (mean 29, SD 24 minutes across all 10 participants), while nine (90%) overreported the number of days worn (mean 9, SD 6 days across all 10 participants). Daily wear time showed moderate agreement between the sensor and self-reporting (CCC 0.70, 95% CI 0.58-0.79), but wide LoA (−223 to 217 minutes). Using 3- or 7-day rolling averages narrowed LoA (−47 to 36 minutes per day and −14 to 10 minutes per day, respectively) and slightly improved CCCs (0.74, 95% CI 0.58-0.85, and 0.73, 95% CI 0.51-0.86, respectively). Greater agreement was observed with more aggregated outcomes; for total 6-week wear time, the CCC was 0.84 (95%CI 0.50-0.95). When expressed as daily average wear time, the CCC was excellent (0.92, 95% CI 0.73-0.98), although daily LoA remained wide (−68 to 32 minutes), indicating substantial individual variability between self-reported and sensor-based measures. For the total number of days worn, the CCC was moderate (0.64, 95% CI 0.15-0.88) and LoA was wide (−10 to 22 days). Conclusions: Self-reported daily brace wear time is inaccurate compared to wear time measured by the temperature sensor. Aggregated data and rolling averages showed better agreement. Future intervention studies should consider objective adherence measures. Failing this, averaging self-reported wear time across the intervention period could improve accuracy. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12623001027606; https://tinyurl.com/2spr7bnu
Largest Rare Variant–Lipid Association Study Finds Heart Disease Targets
A landmark week for cardiovascular genetics opened with huge news from the gene-editing field: Eli Lilly’s experimental therapy VERVE-102, a single-dose PCSK9 base editor designed for patients with heterozygous familial hypercholesterolemia (FH) and premature coronary artery disease (CAD), demonstrated durable cholesterol-lowering effects in early studies. While the result marks one of the strongest signs yet that in vivo gene editing could become a practical treatment for inherited cardiovascular disease, it’s just scratching the surface of the enormous number of uncharacterized genetic variants that influence cholesterol levels and heart disease risk across global populations.
The largest rare variant association with blood lipids study ever reported may provide the roadmap to heart disease mechanistic and clinical insights. In a Nature Genetics study analyzing data from more than one million individuals, researchers identified thousands of rare coding variants linked to cholesterol and triglyceride (TG) levels, including several genes strongly associated with coronary artery disease. The findings could accelerate the development of precision medicines for dyslipidemia and improve the diagnosis of inherited lipid disorders such as familial hypercholesterolemia.
Diversity and scale
FH is caused by rare mutations that raise LDL-C, increasing the risk of early-onset CAD, a leading cause of premature death worldwide. Although statins and other lipid-lowering therapies can significantly lower cardiovascular risk, FH is underdiagnosed and undertreated. Many FH-associated variants have variable penetrance, so some carriers have severe disease and others have milder symptoms, adding to the complexity.
Accurate variant-specific risk assessment is becoming increasingly important as genetic screening expands. Most genetic databases are biased toward Europeans, making it difficult to classify disease-causing variants in non-Europeans.
To fill this gap, Satoshi Koyama, MD, PhD, led a research team across academic and medical institutions in the Boston area that analyzed exome sequencing and blood lipid data (total cholesterol, LDL-C, HDL-C, and TG) from Million Veteran Program, UK Biobank, and All of Us participants. More than 230,000 participants came from historically underrepresented populations, making this one of the most diverse large-scale lipid genetics studies conducted to date.
Mechanistic and clinical implications
Their analysis uncovered nearly three million rare coding variants, including more than 214,000 predicted loss-of-function mutations, 2.7 million missense variants, and over 23,000 cryptic splice variants that may disrupt gene processing. In total, the team evaluated over 10 million variant-phenotype associations. The results revealed 800 exome-wide significant additive associations across 184 genetic loci, along with 109 recessive associations involving 53 genes. Many of the strongest signals appeared in genes already known to regulate lipid metabolism and cardiovascular disease, including PCSK9, LDLR, APOB, NPC1L1, and APOC3.
The study also identified five lipid-associated genes significantly linked to CAD risk, highlighting potential therapeutic targets. One particularly intriguing gene was RORC, which encodes the transcription factor RORγ. Previous laboratory and animal studies suggested that suppressing RORγ improves metabolic health and reduces atherosclerosis. Consistent with those findings, the study showed that loss-of-function variants in RORC appeared protective against CAD in humans.
Another key finding involved cryptic splice variants, a class of mutations often overlooked in clinical genetics. The researchers used machine-learning-based splice prediction tools to show that these variants had biological effects similar to canonical loss-of-function mutations, suggesting that many clinically important variants may be underestimated.
The study also found that 13% of missense mutations produced hypermorphic alleles that increased gene activity, unlike most loss-of-function variants. Existing computational prediction tools frequently fail to identify these variants, potentially limiting the sensitivity of current genetic testing approaches.
Koyama and colleagues also detected strong recessive genetic effects that standard additive models may miss entirely. Because homozygous rare variants are uncommon, their contribution to disease has historically been difficult to measure. The findings suggest that recessive inheritance may explain part of the “missing heritability” in complex cardiovascular disease.
The researchers found that most rare variants exerted similar effects across populations, even when variant frequencies differed substantially between ancestries. The study identified 130 alleles observed primarily or exclusively in non-European populations, emphasizing the importance of expanding genetic research beyond European cohorts to improve equitable diagnosis and drug discovery.
From screening to saving hearts
Beyond biological discovery, the study carries important clinical implications. By comparing their findings with curated pathogenic variant databases, the investigators confirmed many established classifications while identifying variants that may warrant reclassification. Two newly highlighted variants enriched in non-European populations may represent previously underrecognized causes of familial hypercholesterolemia.
Although the research focused mainly on rare coding variants rather than noncoding DNA, the authors argue that population-scale sequencing studies can now provide clinically actionable insights into disease mechanisms, pathogenicity, penetrance, and prognosis. Together, the findings offer a powerful new resource for cardiovascular genetics at a time when therapies such as PCSK9 gene editing are beginning to move from concept to clinic.
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STAT+: Heart patch engineered from stem cells revved up weakened hearts
Hearts can’t heal themselves.
After a heart attack or other cardiovascular insult, hearts can’t regenerate weakened muscles, leaving them less able to pump blood throughout the body. While medications to manage symptoms of heart failure — including newer obesity drugs — have been improving outcomes, many people ultimately face only two solutions: a heart transplant or heart device implant.
Now a small new study reports progress with a novel method. After people received patches of heart muscle engineered from induced pluripotent stem cells, their re-muscularized heart walls thickened, revving up pumping ability and modestly improving quality of life. The biological ventricular assist tissue in a patch, called BioVAT for short, was conceived as a bridge to either transplant, where wait times are long, or to implantation of a left ventricular assist device, or LVAD, in end-stage heart failure. A larger trial will help determine who might be the best candidate for this approach and how durable it might be.
Women’s Memory Decline Linked to ECM Changes from Brain Estrogen Loss
New research from investigators at Northwestern Medicine, published in Aging Cell, shows that loss of estrogen production in the brain after menopause is associated with changes in the brain’s extracellular matrix (ECM), a structure between brain cells that supports communication and memory. The findings suggest that estrogen decline may alter hippocampal brain environment in ways that contribute to memory impairment and may help explain why nearly two-thirds of all people with Alzheimer’s disease (AD) are women.
“This study tells us that females—but not males—may be uniquely sensitive to loss of brain estrogen at old age, potentially contributing to an increased risk of Alzheimer’s disease,” said senior author Hong Zhao, MD, PhD, a research professor of obstetrics and gynecology in the division of reproductive science in medicine at Northwestern University Feinberg School of Medicine.
The researchers found that estrogen loss, aging, and female sex are closely linked to changes in the ECM in the hippocampus, a brain region central to learning and memory. The ECM is a network of molecules that fills the spaces between neurons and glial cells to support cell communication and function. It makes up nearly 20% of brain volume and is important for memory and brain development.
To date, most research into AD has focused on neurons and glial cells, with less attention paid to the ECM. In the Northwestern study, ECM changes were examined as a central feature of brain biology affected by estrogen loss, the first study of its kind, the researchers noted.
For their research, the investigators use genetically engineered mouse models in which estrogen production was disrupted by removing aromatase, an enzyme required for estrogen synthesis. The enzyme was eliminated either throughout the body or restricted to the brain. The investigators examined young and old male and female mice, allowing comparison of sex-specific and age-related effects. The team assessed, behavior and social function, and also collected data on genome-wide gene expression changes in the hippocampus.
The research also built upon the current understanding of estrogen’s role in brain function. In the brain, estrogen has been associated with memory and mood-related functions.
“We have provided some of the most compelling evidence that estrogen is so important for memory function and other mood functions in the female brain,” said author Serdar Bulun, MD, chair of the department of obstetrics and gynecology at Feinberg and a Northwestern Medicine physician. “This should motivate clinicians to be more aware of the essential role of estrogen for women’s brains, because once memory is gone, it’s gone.”
The findings indicate that loss of brain estrogen may disrupt ECM organization in the hippocampus, which may impair communication between brain cells. Because the ECM provides a structural and signaling environment for neurons, any alterations of the ECM potentially affect processes required for memory formation and maintenance.
Prior research has shown that women with AD may have lower brain estrogen levels than women without AD. Hormone replacement therapy (HRT), created restore estrogen levels, has produced mixed results in clinical studies however.
The investigators noted that understanding how estrogen affects brain structures such as the ECM may help explain variability in HRT outcomes and could serve as a new avenue for developing future treatments. Rather than focusing only on restoring hormone levels, future therapies could address downstream changes in brain architecture.
ECM restoration could represent one such therapeutic approach. If estrogen loss leads to ECM disruption in the hippocampus, then interventions aimed at normalizing ECM structure before memory decline may support brain function in postmenopausal women.
The Northwestern team are continuing their investigation of how estrogen regulates ECM composition and signaling in specific brain regions, and whether these changes directly drive memory impairment. The noted that more research is also needed to determine how ECM-related mechanisms interact with other known AD pathways.
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