tbuckley/cabot-search huggingface dataset:
Abstract P3152: Cost-Effectiveness of Dietary Salt Reduction and Universal Screening Programs to Control Hypertension in US Young Adults
Authors: Ciaran Kohli-Lynch, Brandon Bellows, Andrew Moran, Norrina Allen
Journal: Circulation (2025)

Introduction: Almost half of US young adults (aged 18-39 years) have hypertension. This is due to a high prevalence of risk factors, including the fact that most young adults exceed recommended daily sodium intake, alongside underdiagnosis and undertreatment. Cumulative exposure to elevated blood pressure (BP) in young adulthood increases later life risk of cardiovascular disease (CVD), so interventions that reduce BP levels in this age-group could improve population health. Objective: We aimed to estimate the cost and health-related quality of life benefits of two interventions at different points in the pathway of hypertension control in young adults: reducing dietary salt intake (to reduce HTN incidence) and increasing BP screening rates (to increase diagnosis and treatment). Methods: The CVD Policy Model, an established computer simulation model, estimated lifetime costs and quality-adjusted life years (QALYs) associated with BP-reducing interventions in a cohort of 100,000 US young adults. Risk of CVD events in the model was determined by a range of CVD risk factors, including cumulative exposure to systolic BP throughout the lifecourse. We modelled two hypothetical interventions: a population-level policy that reduces average sodium consumption by 1 g/day and an annual hypertension screening program for all young adults. We estimated the maximum price at which each intervention would be cost-effective (incremental cost-effectiveness ratio [ICER] less than $100,000/QALY) compared to usual care. Results: In a cohort of 100,000 US young adults, reducing dietary salt consumption by 1 g/day would produce around 19,300 QALYs and prevent around 1,400 CVD events over a lifetime horizon. For policymakers, it would be cost-effective to invest up to $55 million ($550 per young adult) to achieve this reduction in salt intake. Universal screening would also improve health outcomes (575 QALYs gained, 190 CVD events prevented), but the maximum cost-effective price for this policy was much lower ($17 per young adult). Conclusion: Reducing incidence and improving treatment of hypertension in young adulthood could improve population health substantially.
Abstract P3035: Assessing the Influence of ApoE Gene Polymorphisms on the Risk of Developing Cardiovascular Disease in Type 2 Diabetes Mellitus patients: A Systematic Review
Authors: Gareema Naik, Kashish Parmar, Vibhu Amrutiya, Yamunesh Patel, Dhaval Patel
Journal: Circulation (2025)

Background: Apolipoprotein E is an essential component of lipoprotein metabolism and it is modulated by the ApoE gene. This gene has three known polymorphic variants: ε2, ε3 and ε4. Several studies showed that the presence of these polymorphisms may increase the risk of cardiovascular diseases (CVD) like coronary artery disease (CAD), peripheral artery disease (PAD), heart failure (HF), atherosclerosis and stroke, especially in type 2 diabetes mellitus (T2DM) patients. Objective: This systematic review aims to evaluate the impact of ApoE gene polymorphisms on the risk of developing cardiovascular disease (CVD) in T2DM patients. Methods: We performed a comprehensive search in the following databases: PubMed, ScienceDirect, and Google Scholar. All observational studies available in English, that provided full text and published before July 2024 were included. Studies were chosen based on the documentation of ApoE gene polymorphisms and their correlation with cardiovascular diseases in individuals with Type 2 diabetes mellitus (T2DM). A qualitative synthesis of the findings was conducted to summarize the associations observed across the studies. Due to heterogeneity of the population characteristics and outcome measures in the included studies, we were not able to conduct statistical testing. Results: A total of 17 studies involving 9,497 participants were included in this review. Results from 11 studies (6 focusing on CAD, 2 on PAD, 1 on CAD+cerebral infarction, 1 on HF and 1 on diabetic atherosclerosis) concluded that there was an increased frequency of the ε3/4 genotype among T2DM patients with CVD and that the presence of the ε4 allele significantly increased the risk of CVD. Ten studies showed that individuals with ε4-bearing genotypes, particularly ε3/4, had lower levels of plasma high-density lipoprotein cholesterol (HDL-C) and higher levels of plasma low-density lipoprotein cholesterol (LDL-C) and total cholesterol. There were two studies on stroke in T2DM patients which reported that the ε2/ε3 genotype was associated with an increased risk of ischemic stroke. Two studies also showed that the presence of ε2 allele may provide certain protection against CVD. Conclusion: ApoE gene polymorphisms, particularly the ε4 allele, are associated with an increased risk of CVD and altered plasma lipid profiles in T2DM patients. These findings suggest that ApoE gene polymorphisms can be a potential screening tool to assess CVD risk in diabetic patients.
Abstract 019: Association Of Sleep Irregularity And Variability With Leptin And Adiponectin Levels In Adolescents
Authors: Pura Ballester-Navarro, Natasha Morales-Ghinaglia, Kristina Lenker, Susan Calhoun, Jiangang Liao, Alexandros Vgontzas, Duanping Liao, Edward Bixler, Julio Fernandez-Mendoza
Journal: Circulation (2025)

Introduction: Hormone fluctuations and circadian rhythms, including the sleep-wake cycle, are reciprocally associated. Lipid and glucose metabolism pace depend on leptin and adiponectin levels. Alignment of the sleep-wake cycle is associated with optimal sleep duration and metabolic regulation. Therefore, deviations in sleep timing and duration resulting from circadian misalignment, which is highly prevalent in adolescents, are potentially impacting this association. Hypothesis: Objective metrics of sleep timing and duration are associated with adiponectin and leptin levels in adolescents. Methods: We assessed 344 adolescents from the Penn State Child Cohort [16.2 (2.2) years; 44.4% female; 21.5% racial/ethnic minority], of whom 215 were evaluated while in school and 129 while on break. All subjects had a minimum of 3-nights of at-home actigraphy and 9-hour in-lab polysomnography. Sleep midpoint (SM) was calculated as the central point of the sleep period, while sleep irregularity (SI) and sleep variability (SV) as the intra-individual standard deviation of the SM and total sleep time, respectively. Adiponectin and leptin levels were assayed via ELISA from blood samples. Linear regression models adjusted for sex, race/ethnicity, age, apnea/hypopnea index, BMI percentile, and SES. Results: Greater SI and SV while attending school were associated with lower log-adiponectin levels (B=-0.155, SD=0.057, p=0.007 and B=-0.127, SD=0.054, p=0.021, respectively). SM was not significantly associated with either log-leptin or log-adiponectin levels. Conclusions: Increased irregularity and variability in the timing and duration of sleep during the academic year affect glucose and fatty acid control mechanisms in adolescents. Our findings further support targeting sleep from a multidimensional standpoint to better prevent its impact on cardiometabolic health. Support: National Institutes of Health (R01HL136587, UL1TR000127)
Antioxidant and Anti‐Senescence Polyvinyl Alcohol‐Gallic Acid Supramolecular Hydrogels for Stem Cell Culture
Authors: Yiduo Zhou, Matías L. Picchio, Yan Nie, Lei Wang, Oihane Sanz, Yue Liu, Xun Xu, Lukas Prantl, Oliver Felthaus, Weiwei Wang, Marcelo Calderón, Nan Ma
Journal: Advanced Healthcare Materials (2025)

Abstract Replicative senescence presents a significant challenge in mesenchymal stem cell (MSC) expansion due to high reactive oxygen species (ROS) levels generated during culture. Elevated ROS levels lead to oxidative stress, cellular damage, and senescence, limiting the biomedical applications of MSCs. In this study, a supramolecular thermo‐reversible hydrogel composed of the natural polyphenolic compound gallic acid (GA) and polyvinyl alcohol (PVA) was designed to scavenge ROS and mitigate MSC senescence. The PVA‐GA hydrogel, stabilized by strong hydrogen bonding forces, exhibited an elastic modulus comparable to that of human soft tissue and facilitated the sustained release of GA over 14 days. It enhanced MSC survival, protected against oxidative stress, reduced intracellular ROS levels, diminished mitochondrial damage, and decreased cellular senescence. The hydrogel maintained the multilineage differentiation potential and typical phenotype of MSCs. Additionally, it preserved vascular endothelial growth factor (VEGF) secretion from MSCs under oxidative stress and enhanced their pro‐angiogenic effect. The conditioned medium derived from MSCs in the hydrogel group promoted migration and tube formation of human umbilical vein endothelial cells (HUVECs). These findings suggest that the PVA‐GA hydrogel holds significant promise for the biomedical applications of MSCs, potentially addressing the challenges posed by oxidative stress and cellular senescence.
Pneumococcal Hemolytic Uremic Syndrome in Children in Sweden
Authors: Helena Hildenwall, Valya Georgieva, Joachim Luthander, Susanne Westphal Ladfors, Lisa Sartz, Milan Chromek
Journal: JAMA Network Open (2025)

This cohort study of children in Sweden reviewed pneumococcal hemolytic uremic syndrome cases between 2009 and 2024 for incidence rates and serotype data.
T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments
Authors: Maxim Buckley, David T Yeung, Deborah L White, Laura N Eadie
Journal: Leukemia (2025)

Abstract T-cell Acute Lymphoblastic Leukaemia (T-ALL) is a high-risk hematological disease constituting ~20% of acute leukemias. To date, the only subtype recognized by the World Health Organization’s International Consensus Classification is early T-cell precursor ALL. To improve clinical outcomes, several studies have investigated and defined T-ALL genomic subtypes within cohorts of varied ages and geographical locations. These studies have also utilized differing analysis methods including whole transcriptome, exome, or genome sequencing as well as immunophenotyping and cytogenetic testing. As a result, there are significant differences in reported subtypes as well as the frequency at which each occurs. The reported clinical outcomes for specific genomic alterations also depend on patient demographics and treatment protocols. This review synthesizes the data from four T-ALL genomic landscape studies establishing consensus and highlighting differences, details clinical outcomes for the most common genomic alterations observed in T-ALL patients, and proposes novel avenues for future investigation and treatment.
Deficiency of the Fanconi anemia core complex protein FAAP100 results in severe Fanconi anemia
Authors: Benjamin A Harrison, Emma Mizrahi-Powell, John Pappas, Kristen Thomas, Subrahmanya Vasishta, Shripad Hebbar, Anju Shukla, Shalini S Nayak, Tina K Truong, Amy Woroch, Yara Kharbutli, Bruce D Gelb, Cassie S Mintz, Gilad D Evrony, Agata Smogorzewska
Journal: Journal of Clinical Investigation (2025)

Fanconi anemia (FA) is a rare genetic disease characterized by loss-of-function variants in any of the 22 previously identified genes (FANCA-FANCW) that encode proteins participating in the repair of DNA interstrand crosslinks (ICLs). Patient phenotypes are variable, but may include developmental abnormalities, early onset pancytopenia, and predisposition to hematologic and solid tumors. Here, we describe two unrelated families with multiple pregnancy losses and offspring presenting with severe developmental and hematologic abnormalities leading to death in utero or in early life. Homozygous loss-of-function variants in FAAP100 were identified in affected children of both families. The FAAP100 protein associates with FANCB and FANCL, the E3 ubiquitin ligase responsible for the monoubiquitination of FANCD2 and FANCI, which is necessary for FA pathway function. Patient-derived cells exhibited phenotypes consistent with FA. Expression of the wild-type FAAP100 cDNA, but not the patient-derived variants, rescued the observed cellular phenotypes. This establishes FAAP100 deficiency as a cause of Fanconi anemia, with FAAP100 gaining an alias as FANCX. The extensive developmental malformations of individuals with FAAP100 loss-of-function variants are among the most severe across previously described FA phenotypes, indicating that the FA pathway is essential for human development.
B cells shape naïve CD8 T cell programming
Authors: Cameron Manes, Miguel Guerrero Moreno, Jennifer Cimons, Marc A D'Antonio, Tonya M Brunetti, Michael G Harbell, Sean Selva, Christopher Mizenko, Tyler L Borko, Erika L Lasda, Jay R Hesselberth, Elena Wy Hsieh, Michael R Verneris, Amanda L Piquet, Laurent Gapin, Ross M Kedl, Jared Klarquist
Journal: Journal of Clinical Investigation (2025)

The presence of B cells is essential for the formation of CD8 T cell memory after infection and vaccination. In this study, we investigated whether B cells influence the programming of naïve CD8 T cells prior to their involvement in an immune response. RNA sequencing indicated that B cells are necessary for sustaining the FOXO1-controlled transcriptional program, which is critical for their homeostasis. Without an appropriate B cell repertoire, mouse naïve CD8 T cells exhibit a terminal, effector-skewed phenotype, which significantly impacts their response to vaccination. A similar effector-skewed phenotype with reduced FOXO1 expression was observed in naïve CD8 T cells from human patients undergoing B cell-depleting therapies. Furthermore, we show that patients without B cells have a defect in generating long-lived CD8 T cell memory following COVID vaccination. In summary, we demonstrate that B cells promote the quiescence of naïve CD8 T cells, poising them to become memory cells upon vaccination.
IL-7-mediated expansion of autologous lymphocytes increases CD8+ VLA-4 expression and accumulation in glioblastoma models
Authors: Kirit Singh, Kelly M Hotchkiss, Sarah L Cook, Pamy Noldner, Ying Zhou, Eliese M Moelker, Chelsea O Railton, Emily E Blandford, Bhairavy J Puviindran, Shannon E Wallace, Pamela K Norberg, Gary E Archer, Beth H Shaz, Katayoun Ayasoufi, John H Sampson, Mustafa Khasraw, Peter E Fecci
Journal: Journal of Clinical Investigation (2025)

The efficacy of T cell-activating therapies against glioma is limited by an immunosuppressive tumor microenvironment and tumor-induced T cell sequestration. We investigated whether peripherally infused non-antigen specific autologous lymphocytes (ALT) could accumulate in intracranial tumors. We observed that non-specific autologous CD8+ ALT cells can indeed accumulate in this context, despite endogenous T cell sequestration in bone marrow. Rates of intratumoral accumulation were markedly increased when expanding lymphocytes with IL-7 compared to IL-2. Pre-treatment with IL-7 ALT also enhanced the efficacy of multiple tumor-specific and non-tumor-specific T cell-dependent immunotherapies against orthotopic murine and human xenograft gliomas. Mechanistically, we detected increased VLA-4 on mouse and human CD8+ T cells following IL-7 expansion, with increased transcription of genes associated with migratory integrin expression (CD9). We also observed that IL-7 increases S1PR1 transcription in human CD8+ T cells, which we have shown to be protective against tumor-induced T cell sequestration. These observations demonstrate that expansion with IL-7 enhances the capacity of ALT to accumulate within intracranial tumors, and that pre-treatment with IL-7 ALT can boost the efficacy of subsequent T cell-activating therapies against glioma. Our findings will inform the development of future clinical trials where ALT pre-treatment can be combined with T cell-activating therapies.
Disruption of Ataxia-telangiectasia mutated kinase enhances radiation therapy efficacy in spatially-directed diffuse midline glioma models
Authors: Avani Mangoli, Vennesa Valentine, Spencer Maingi, Sophie R Wu, Harrison Q Liu, Michael Aksu, Vaibhav Jain, Bronwen E Foreman, Joshua A Regal, Loren B Weidenhammer, Connor E Stewart, Maria E Guerra Garcia, Emily Hocke, Karen Abramson, Tal Michaeli, Nerissa T Williams, Lixia Luo, Megan Romero, Katherine Deland, Samantha Gadd, Eita Uchida, Laura Attardi, Kouki Abe, Rintaro Hashizume, David M Ashley, Oren J Becher, David G Kirsch, Simon G Gregory, Zachary J Reitman
Journal: Journal of Clinical Investigation (2025)

Diffuse midline gliomas (DMGs) are lethal brain tumors characterized by p53-inactivating mutations and oncohistone H3.3K27M mutations that rewire the cellular response to genotoxic stress. We used RCAS/tv-a retroviruses and Cre recombinase to inactivate p53 and induce native H3.3K27M mutations in a lineage- and spatially-directed manner. We generated primary mouse tumors that recapitulate human DMG. Disrupting ataxia-telangiectasia mutated kinase (ATM) enhanced the efficacy of radiation therapy in murine and patient-derived DMG models which increased survival. Microscopy-based in situ sequencing was used to spatially resolve transcriptional profiles in >750,000 single cells with or without ATM disruption and radiation therapy, revealing altered immune-neoplastic and endothelial cell interactions after treatment. An allelic series of primary murine DMG models with different p53 mutations confirmed that transactivation-independent p53 activity is a key mediator of radiosensitivity after ATM disruption. Our findings contribute primary DMG mouse models with deep profiling and reveal the mechanisms of treatment response to an actionable therapeutic strategy.
Long-Term Outcomes in Nephrotic Syndrome by Kidney Biopsy Diagnosis and Proteinuria
Authors: David Pitcher, Fiona Braddon, Bruce Hendry, Alex Mercer, Jonathan Barratt, Retha Steenkamp, Katie Wong, A. Neil Turner, Wu Gong, Daniel P. Gale, Moin A. Saleem
Journal: Journal of the American Society of Nephrology (2025)

Background: The UK Registry of Rare Kidney Diseases (RaDaR) Idiopathic Nephrotic Syndrome cohort includes adults and children with genetic nephrotic syndrome, Focal Segmental Glomerulosclerosis (FSGS) and minimal change disease. This study examines long-term patient outcomes as a function of kidney biopsy diagnosis and proteinuria control. Methods: 2467 adults and 1599 children were followed to establish outcomes including eGFR slope and kidney survival by diagnosis, analysed as a function of proteinuria from disease onset for FSGS and minimal change disease. Enrollment began in 2010, with follow-up to September 2023. Index date for the survival analyses was date of disease onset. Results: The cohort had median [IQR] follow up of 8.2 [4.3-13.1] years; 30% of patients reached kidney failure or died. 1303 patients had FSGS, 1153 minimal change disease, 105 monogenic nephrotic syndrome. Children showed relatively preserved mean kidney function at disease onset (eGFR&gt;100 ml/min/1.73m 2 ), compared to adults (FSGS 61ml/min/1.73m 2 ; minimal change disease 76ml/min/1.73m 2 ). Kidney survival probability (95% CI) at 10 years varied with diagnosis: Genetic 29% (20-38), FSGS 58% (55-61), minimal change disease 87% (85-89) with mean (SD) rates of eGFR loss -26.5 (34.7), -6.2 (14.3), and -1.9 (10.2) ml/min/1.73m 2 per year respectively. FSGS 10-year kidney survival (95% CI) for 6-12 months lowest proteinuria value in complete remission (&lt;0.3g/g), partial remission (0.3-3.5g/g) and no remission (&gt;3.5g/g) was 88% (70-96). 65% (50-76) and 37% (26-48), respectively. Time-averaged proteinuria of &lt;1.5g/g over 6-24 months from disease onset was associated with 90% 10-year kidney survival. For minimal change disease, patients’ 10-year kidney survival (95% CI) stratified by 6-12 months lowest proteinuria value was: complete remission 89% (79-94), partial remission 75% (51-89), and no remission 64% (41-81). In FSGS and minimal change disease 10-year eGFR slope was strongly correlated with absolute levels of proteinuria. Conclusions: Kidney outcomes were poor in genetic nephrotic syndrome; in FSGS outcomes were strongly associated with proteinuria level. Minimal change disease patients had better proteinuria control than FSGS and had better outcomes at each proteinuria level.
Loss of MRAP2 in MC4R neurons protect from obesity-associated autonomic and cardiovascular dysfunctions
Authors: Deng Fu Guo, Paul A Williams, Alexis Olson, Donald A Morgan, Hussein Herz, Jon Resch, Deniz Atasoy, Harald M Stauss, Julien A Sebag, Kamal Rahmouni
Journal: Cardiovascular Research (2025)

Abstract Aims The melanocortin receptor accessory protein 2 (MRAP2), which is abundantly expressed in the brain including the hypothalamus, has emerged as a key regulator of melanocortin-4 receptor (MC4R) activity. We sought to delineate the physiological significance of MRAP2 in MC4R neurons, with a particular focus on autonomic and cardiovascular functions. Methods and Results Selective deletion of MRAP2 in MC4R neurons causes obesity that was associated with hyperphagia and impairment in glucose homeostasis and insulin sensitivity. MC4R agonist Melatonan II (MTII)-induced anorectic effects were blunted in mice lacking MRAP2 in MC4R neurons, whereas Celastrol retained its efficacy in reducing food intake and body weight. MRAP2 deletion also reduced baseline sympathetic nerve activity (SNA), particularly the SNA subserving the kidney. This was associated with reduced innervation of the kidney. In addition, MTII-induced increases in renal and brown adipose tissue (BAT) SNA as well as hepatic vagal nerve activity were significantly attenuated in MC4R neuron MRAP2-deficient mice. Anatomical tracing revealed that MC4R neurons projecting to BAT and kidneys were localized to specific brain nuclei including the paraventricular nucleus of the hypothalamus, providing anatomical substrate for MRAP2 regulation of sympathetic outflow. Although loss of MRAP2 in MC4R neurons did not affect arterial pressure, it caused a significant decrease in heart rate and baroreflex sensitivity. Finally, MRAP2 deficiency in MC4R neurons attenuated MTII-induced increase in arterial pressure and heart rate. Conclusion These findings demonstrate that in addition to its role in energy balance and glucose homeostasis MRAP2 in MC4R neurons is crucial for cardiovascular autonomic regulation and is required for the development of obesity-associated hypertension and autonomic dysfunction.
Combined circulating microRNA and peptide biomarkers for prognostication in heart failure
Authors: Lee Lee Wong, Hiromi W L Koh, Hyungwon Choi, Ruiyang Zou, Lihan Zhou, Jia Yuen Lim, Dominic C Y Phua, Oi Wah Liew, Jenny P C Chong, Jessica Y X Ng, Siew Pang Chan, Yei-Tsung Chen, Poh Shuan D Yeo, Lieng H Ling, David Sim, Kui Toh G Leong, Hean Y Ong, Fazlur Jaufeerally, Raymond Wong, Ping Chai, Adrian F Low, Mayanna Lund, Gerry Devlin, Richard Troughton, Robert N Doughty, Carolyn S P Lam, Heng Phon Too, Arthur Mark Richards
Journal: Cardiovascular Research (2025)
Radiologic Imaging Aids Management of High-risk Cutaneous Squamous Cell Carcinoma: A Retrospective Cohort Study
Authors: Angela H Wei, Lydia Cassard, Cong Fan, Sokhna Seck, Marla Rodriguez Vazquez, Jim Bena, Todd Stultz, Shlomo A Koyfman, Allison T Vidimos
Journal: Journal of the American Academy of Dermatology (2025)
Bioengineered Bilayered Grafts for Structural and Functional Posterior Lamellar Eyelid Reconstruction
Authors: Qiumei Ji, Xingran Liu, Ruize Tang, Jing Yang, Yan Zeng, Rehanguli Aimaier, Xiangqi Liu, Valeriya V Kardumyan, Anna B Solovieva, Qingfeng Li, Ru-Lin Huang
Journal: Biomaterials (2025)