tbuckley/cabot-search huggingface dataset:
Sex-Specific Factors Influencing Obesity in Women: Bridging the Gap Between Science and Clinical Practice
Authors: Hazem Ayesh, Samar A. Nasser, Keith C. Ferdinand, Barbara Gisella Carranza Leon
Journal: Circulation Research (2025)

Obesity in women is a significant public health issue with serious implications for cardiovascular-kidney-metabolic syndrome and cardiovascular disease. This complex challenge is influenced by physiological, hormonal, socioeconomic, and cultural factors. Women face unique weight management challenges due to hormonal changes during pregnancy, perimenopause, and menopause, which affect fat distribution and increase cardiovascular-kidney-metabolic syndrome risk. Current clinical guidelines often overlook these sex-specific factors, potentially limiting the effectiveness of obesity management strategies in women. This review explores the sex-specific aspects of obesity’s pathophysiology, epidemiological trends, and associated comorbidities, focusing on cardiovascular and metabolic complications. This review synthesizes literature on obesity in women, emphasizing sex-specific factors influencing its development and progression. It examines the limitations of body mass index as an obesity measure and explores alternative classification methods. Additionally it investigates the relationship between obesity and comorbidities such as diabetes, hypertension, and dyslipidemia, with a focus on postmenopausal women. Obesity in women is linked to increased risks of cardiovascular-kidney-metabolic syndrome and cardiovascular disease. Hormonal fluctuations throughout life contribute to weight gain and fat distribution patterns specific to women, increasing cardiovascular disease risk. Effective obesity management strategies in women must account for these sex-specific variations. Postmenopausal women are particularly affected by obesity-related complications. Lifestyle interventions, pharmacotherapy, and bariatric surgery have shown efficacy in weight management, though success rates vary. Addressing obesity in women requires a comprehensive approach that considers sex-specific physiological factors, life-stage challenges, and sociocultural barriers. Integrating precision medicine and emerging therapies offers potential for more personalized and effective interventions. Personalized strategies that consider women’s biological and life-stage challenges can enhance obesity management and improve cardiovascular outcomes. Future research and clinical practice should focus on developing tailored strategies that address women’s unique vulnerabilities to obesity and its associated health risks and on validating sex-specific interventions to improve obesity management in women.
Lifelong Care of Females With Congenital Heart Disease
Authors: Rose Tompkins, Prashanth Venkatesh, Adam J. Small, Dan G. Halpern
Journal: Circulation Research (2025)

Medical and surgical advancements of the past 70 years have resulted in a remarkable shift in the natural history of congenital heart disease (CHD) such that survival to adulthood is expected for &gt;90% of children born with congenital heart defects, including those with complex CHD. There are now more adults than children living with CHD, a majority of them are female. As significant strides have been made in the management of adult patients with CHD, there has been an evolving understanding of the important role inherent sex-specific differences play in impacting long-term outcomes for females with CHD including differences in sexual and reproductive health, risk and incidence of acquired cardiovascular disease, and health surveillance. Notably, care for the female CHD patient is a continuum that is not isolated to discrete stages but cumulative of health exposures and experiences over a lifetime. This review aims to provide a brief overview of the current understanding of the unique health needs and considerations for females with CHD over their lifetime for both the pediatric and adult provider to help identify opportunities for care optimization, continue to raise awareness of the necessity of lifelong care and advocate for the critical need of research that prospectively evaluates pregnancy and other health-related exposures on long-term quality of life and survival for females with CHD.
Strategies for Overcoming Barriers in Access to Cardiovascular Care for Women
Authors: Deirdre J. Mattina, Michael C. Honigberg, Zainab Mahmoud, Karen E. Joynt Maddox
Journal: Circulation Research (2025)

Women face unique barriers to equitable health care. To ensure access to quality cardiovascular care across the lifespan of women, several systemic and social challenges need to be addressed. With the understanding that women often direct health care decisions, not only for themselves but for their family unit as well, a holistic approach to address health care barriers is warranted. This review aims to highlight key barriers to equitable health care access for women and propose potential strategies to overcome these barriers. This review is structured around 5 key areas in which there are gender- or sex-specific barriers to optimal outcomes: (1) insurance-related barriers, (2) geographic and social barriers, (3) health care delivery capacity and workforce issues, (4) quality and accountability measures, and (5) global health challenges. More research is needed on the sustainability, costs, and sex- and gender-specific outcomes of these solutions to drive transformative change.
Influence of Primary Neurologic Disease on Cardiovascular Health in Females
Authors: Khadija Awais Ali, Deborah L.G. Kerrigan, Jillian Molli Berkman
Journal: Circulation Research (2025)

Neurocardiology is an interdisciplinary field that examines the complex interactions between the nervous and the cardiovascular systems, exploring how neurological processes, such as autonomic nervous system regulation and brain-heart communication impact heart function and contribute to cardiovascular health and disease. Although much of the focus on cardiovascular health has centered on traditional risk factors, the influence of the nervous system, especially in females, is increasingly recognized as a key determinant of cardiovascular outcomes. This article reviews existing literature on the neurological mechanisms that impact cardiovascular function in females. Specifically, we analyze how primary neurological disorders including cerebrovascular disease, headache disorders, and multiple sclerosis have specific downstream effects on cardiac function. By understanding the complex relationship between neurological and cardiovascular health, this review highlights the need for sex-specific approaches to prevention, diagnosis, and treatment of cardiovascular disease in females, ultimately encouraging the discovery of more effective care strategies and improving health outcomes.
Advances in Our Understanding of Cardiovascular Diseases After Preeclampsia
Authors: Malamo E. Countouris, Natalie A. Bello
Journal: Circulation Research (2025)

Preeclampsia is a syndrome of hypertension in association with target organ dysfunction, including proteinuria, which manifests during pregnancy and the immediate postpartum period. The pathophysiology of preeclampsia originates from impaired trophoblastic invasion of the placental resulting in malperfusion and involves multiple mechanistic pathways that include anti-angiogenic factors, endothelial dysfunction, and immune dysregulation. Preeclampsia caries an increased risk of subclinical cardiovascular disease including left ventricular remodeling, diastolic dysfunction, coronary artery calcification, peripheral vascular abnormalities, and microvascular dysfunction and clinical cardiovascular disease including stroke, heart failure, myocardial infarction, and death from a cardiovascular cause. This review will highlight several common mechanistic pathways shared between preeclampsia and cardiovascular diseases that provide insight into potential targets for risk reduction and disease process mitigation that can be examined in future trials.
Understanding Thoracic Aortic Disease in Women
Authors: Bana Samman, Mimi X. Deng, Jennifer C.Y. Chung, Maral Ouzounian
Journal: Circulation Research (2025)

Multifaceted disparities exist between men and women with thoracic aortic aneurysm and dissection. Despite a higher prevalence of thoracic aortic aneurysm and dissection among men, women experience disproportionately accelerated aneurysmal expansion, greater risks of rupture or dissection, and acute aortic syndromes that occur at relatively smaller diameters. In the context of acute type A aortic dissection, they also experience more complications, increased out-of-hospital mortality, delays in presentation and diagnosis, and worse postoperative survival. These gaps are largely driven by sex differences in vascular aging and remodeling, which include arterial stiffening associated with the hormonal changes that occur during menopause. Furthermore, the increased risk of acute type A aortic dissection during pregnancy in women with thoracic aortic disease necessitates a multidisciplinary approach to peripartum counseling and surveillance. Despite significant recent improvements in early postoperative outcomes, other disparities persist, emphasizing the need for sex-specific research, patient counseling, routine monitoring, and surgical thresholds to bridge the gap in outcomes of thoracic aortic care between sexes. Elucidating the underlying mechanisms of aortic aging and its difference between men and women, as well as moving toward personalized management protocols, will give rise to improved outcomes in the treatment of thoracic aortopathy.
The 2024 US Medical Eligibility Criteria for Contraceptive Use: Application to Practice in the Care of Patients With Cardiac Disease
Authors: Kayle Shapero, Tessa Madden
Journal: Circulation Research (2025)

Cardiovascular disease is the leading cause of maternal mortality in the United States, with the majority of deaths stemming from preventable causes. Contraception is one of the tools that can be utilized to prevent mortality and morbidity associated with unplanned pregnancy in patients with underlying congenital or acquired heart disease. There are a wide range of contraceptive methods available. While some methods, especially those containing estrogen, may be associated with increased risks in certain cardiac disease states, intrauterine devices, implants, and progestin-only methods may be safely used by the vast majority of patients with cardiac disease. Furthermore, intrauterine devices and implants are the most effective reversible contraceptive methods available. This review provides a summary of the US Centers for Disease Control and Prevention 2024 Medical Eligibility Criteria for Contraceptive Use as it applies to cardiac disease states. This review emphasizes the importance of contraceptive counseling and aims to familiarize the reader with the various forms of contraception available to patients, as well as the risks and benefits of each method in patients with different types of cardiac disease.
The High Expression of PD-1 Defines A Subpopulation of Tfh Cells Responding to COVID-19 Vaccine in Humans
Authors: Jingxin Guo, Zhangfan Fu, Yi Zhang, Mengyuan Xu, Jinhang He, Haocheng Zhang, Qiran Zhang, Jieyu Song, Ke Lin, Mingxiang Fan, Zhangyufan He, Guanmin Yuan, Ning Jiang, Huang Huang, Chao Qiu, Jingwen Ai, Wenhong Zhang
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract Inactivated coronavirus disease 2019 (COVID-19) vaccines and receptor binding domain subunit (RBD-subunit) booster vaccination can induce effective humoral immune response. CD4+ T helper cells are essential in helping B cells and antibody response. However, the response of CD4+ T cells to booster vaccination, especially the virus-induced T follicular helper (Tfh) cells, needs to be better characterized. In this study, it was investigated using tools of single-cell sequencing and flow cytometry. Additionally, a customized analysis algorithm was applied to identify virus-induced T cell receptor (VI-TCR) which is useful to explore the activation and persistence of virus-induced CD4+ T cell response. We identified a subset of classic Tfh (cTfh) cells with high expression of PD-1 and IFN-γ. They were notably activated following booster vaccination, and their proportion was correlated with the antibody titer level. We used trajectory analysis to analyze the dynamic changes of activated and found that a subset of virus-induced cTfh cells might maintain immune responses beyond 90 days post-vaccination. In summary, we found a group of PD-1high cTfh cells in COVID-19 vaccination, which can enhance the humoral response and show the persistence of immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We also provided a method for single-cell immune data analysis to understand the virus-induced responses. Understanding how cTfh cells help antibody production will provide essential insights into the rational design of new vaccine strategies to optimize long-term immunity.
Cutaneous Granulomas: Mechanisms, Cellular Interactions, and Therapeutic Insights
Authors: Satoshi Nakamizo, Kenji Kabashima
Journal: British Journal of Dermatology (2025)

Abstract Granulomas are specialized biological defense mechanisms that form in response to infections with pathogens, foreign bodies, or specific stimuli such as antimicrobials or fungi. These structures function to isolate foreign materials and pathogens that cannot be eliminated by immune cells, primarily through macrophage activity. In the skin, granulomas are a hallmark of several conditions, including sarcoidosis, granuloma annulare, tuberculosis and leprosy, each exhibiting distinct pathological and immunological features. Granulomas can also arise from lipid accumulation, as observed in xanthogranuloma, or be triggered by inflammatory processes associated with unidentified antigens. Among their cellular components, Langhans-type multinucleated giant cells play a pivotal role in granuloma structure and function, contributing to pathogen containment and tissue remodeling, though their precise mechanisms of action remain an area of active investigation. In addition to these giant cells, recent studies have identified TREM2-positive macrophages as key contributors to granuloma formation and maintenance. These macrophages are involved in extracellular degradation of foreign substances and play a role in adapting to the hypoxic and nutrient-poor microenvironment of granulomas through metabolic reprogramming, including the pentose phosphate pathway. Recent advances in molecular biology, such as single-cell RNA sequencing, have provided unprecedented insights into the cellular heterogeneity and molecular pathways involved in granuloma formation. These techniques have revealed disease-specific differences in immune cell profiles and activation states, offering new perspectives on the underlying mechanisms of granulomatous diseases. Despite these advances, the precise processes driving granuloma formation and their functional significance remain largely unclear. This review addresses the central question, “What is a granuloma? ” by synthesizing recent findings, with a particular focus on cutaneous granulomas, and presenting interpretations grounded in the current body of literature. Furthermore, we discuss the implications of these findings for the development of novel therapeutic strategies, including targeted immunomodulation and cytokine blockade, which hold promise for treating granulomatous diseases while preserving host defense.
Letter to the Editor - Survival Among Patients Treated with Total Mesorectal Excision or Selective Watch-and-Wait After Total Neoadjuvant Therapy: A Pooled Analysis of the CAO/ARO/AIO-12 and OPRA Randomized Phase II Trials
Authors: R O Perez, B B Vailati, G P São Julião, L E Corbi
Journal: Annals of Oncology (2025)
MuCST: restoring and integrating heterogeneous morphology images and spatial transcriptomics data with contrastive learning
Authors: Yu Wang, Zaiyi Liu, Xiaoke Ma
Journal: Genome Medicine (2025)

Spatially resolved transcriptomics (SRT) simultaneously measure spatial location, histology images, and transcriptional profiles of cells or regions in undissociated tissues. Integrative analysis of multi-modal SRT data holds immense potential for understanding biological mechanisms. Here, we present a flexible multi-modal contrastive learning for the integration of SRT data (MuCST), which joins denoising, heterogeneity elimination, and compatible feature learning. MuCST accurately identifies spatial domains and is applicable to diverse datasets platforms. Overall, MuCST provides an alternative for integrative analysis of multi-modal SRT data ( https://github.com/xkmaxidian/MuCST ).
Plasma pharmacometabolomics of inhaled corticosteroid-related adrenal suppression in asthma
Authors: Dung T Tran, Yulu Chen, Lourdes G Ramirez, Jessica A Lasky-Su, Ann C Wu, Kelan G Tantisira, Michael J McGeachie, Scott T Weiss, Amber Dahlin
Journal: Journal of Allergy and Clinical Immunology (2025)

Inhaled corticosteroids (ICS) are frequently prescribed medications for asthma symptoms, but higher doses can increase risks of adrenal insufficiency through suppression of endogenous cortisol production. Understanding which patients may be at increased risk for developing adrenal suppression related to ICS use may help providers improve treatment regimens for asthma patients; however, the mechanisms underlying ICS-related adrenal insufficiency have not been clarified. This study identifies metabolite signatures and biochemical pathways associated with ICS-related adrenal insufficiency in asthma patients. Global metabolite profiling (metabolomics) was integrated with electronic medical records data including the development of adrenal suppression, in two independent asthma cohorts. The discovery cohort, Pharmacogenomics of Adrenal Suppression with Inhaled Corticosteroids (PhASIC), included 711 adult asthma patients on ICS. Untargeted metabolomic profiling identified 1,397 metabolites, of which 810 were selected for further analysis. Using plasma cortisol as a biomarker for adrenal status (outcome), linear regression models were implemented to identify associations between metabolites and plasma cortisol, adjusted for potential confounders. Metabolite associations were validated in an additional 575 patients on ICS. Pathway and network analyses were performed using bioinformatic approaches to identify altered metabolic pathways related to the outcome. Of 810 endogenous metabolites, 12 demonstrated significant associations with adrenal insufficiency after correction for multiple comparisons. In the validation cohort, three of these 12 replicated, including two steroid metabolites (tetrahydrocortisol glucuronide and tetrahydrocortisol glucuronide (5)) and homocitrulline. Pathway and network analyses revealed alterations in biochemical pathways related to the metabolism of steroids, bile acids, urea cycle and long-chain polyunsaturated fatty acids. We have identified specific metabolites within steroid and non-steroid metabolic pathways that are associated with adrenal insufficiency with ICS use.
Blood-brain barrier crossing biopolymer activates immunity in primary brain lymphoma by targeting c-Myc and α-PD-1: Artificial intelligence analysis
Authors: Vladimir A Ljubimov, Tao Sun, Jiawei Wang, Lian Li, Paul Z Wang, Alexander V Ljubimov, Eggehard Holler, Keith L Black, Jindřich Kopeček, Julia Y Ljubimova, Jiyuan Yang
Journal: Journal of Controlled Release (2025)
Simultaneous liver transplant and sleeve gastrectomy provides durable weight loss, improves metabolic syndrome and reduces allograft steatosis
Authors: Ellen L Larson, Samia D Ellias, Daniel J Blezek, Jason Klug, Robert P Hartman, Nickie Francisco Ziller, Heather Bamlet, Shennen A Mao, Dana K Perry, Induja R Nimma, Dilhana Badurdeen, Liu Yang, Michael D Leise, Kymberly D Watt, Tayyab S Diwan, Timucin Taner, Charles D Rosen, Enrique F Elli, James A Madura, Caroline C Jadlowiec, Blanca Lizaola-Mayo, Todd A Kellogg, Julie K Heimbach
Journal: Journal of Hepatology (2025)
Daratumumab-based quadruplet versus triplet induction regimens in transplant-eligible newly diagnosed multiple myeloma: a systematic review and meta-analysis
Authors: João Tadeu Damian Souto Filho, Lucas Oliveira Cantadori, Edvan de Queiroz Crusoe, Vania Hungria, Angelo Maiolino
Journal: Blood Cancer Journal (2025)

The treatment landscape for transplant-eligible patients with newly diagnosed multiple myeloma (TE-NDMM) has evolved with the introduction of daratumumab-based quadruplet regimens. Adding daratumumab to traditional triplet regimens has demonstrated improved response rates and progression-free survival (PFS). However, the impact on long-term outcomes, particularly overall survival (OS), remains uncertain. This systematic review and meta-analysis aimed to compare the survival outcomes of these quadruplet regimens with triplets. Conducted in adherence to Cochrane Collaboration and PRISMA guidelines and registered on PROSPERO (CRD42024571946), the study involved searching PubMed, Embase, and Cochrane databases, from inception to June 2024. We included randomized clinical trials (RCT) and non-randomized controlled studies (NRCS) that compared daratumumab-based quadruplet regimens to triplets, focusing on OS and PFS, with a minimum follow-up of 18 months. The meta-analysis included 3327 TE-NDMM patients from four studies, comprising three RCT and one NRCS. Daratumumab-based regimens were administered to 1328 (40%) patients. The analysis revealed that daratumumab-based quadruplet regimens significantly improved both OS (pooled HR 0.60; 95% CI 0.48–0.75; P < 0.00001; I² = 0%) and PFS (pooled HR 0.49; 95% CI 0.37–0.65; P < 0.00001; I² = 52%). A per-protocol subgroup analysis comparing D-VRD to VRD further confirmed these benefits, with significant improvements in both OS (pooled HR 0.68; 95% CI 0.48–0.97; P = 0.03; I² = 0%) and PFS (pooled HR 0.41; 95% CI 0.31–0.54; P < 0.00001; I² = 0%). This meta-analysis consolidates evidence that daratumumab-based quadruplet regimens significantly improve OS, compared to triplet regimens for TE-NDMM patients.
Reply to: “Risks of Organ Preservation in Rectal Cancer: Beyond Distant Metastases, Ultimate Local Failure Can Also Be a Problem,” “Organ Preservation in Rectal Cancer: Fear of Risks Versus the Risks of Fear,” and “Distant Metastases With Nonoperative Management in Rectal Cancer: Challenges in Defining Risk”
Authors: Laura M. Fernandez, Guilherme P. São Julião, Carlos Cerdan-Santacruz, Andrew G. Renehan, Geerard L. Beets, Amjad Parvaiz, Jose Azevedo, Bruna B. Vailati, Rodrigo O. Perez
Journal: Journal of Clinical Oncology (2025)
Bioactive Polymers as Stimulus-responsive Anti-metastatic Combination Agents to Treat Pancreatic Cancer
Authors: Sudipta Panja, Ekta Kapoor, Kasturi Siddhanta, Chinmay M Jogdeo, Diptesh Sil, Rubayat I Khan, Neha Kumari, Ling Ding, Howard E Gendelman, Amar B Singh, David Oupický
Journal: Biomaterials (2025)