tbuckley/cabot-search huggingface dataset:
Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers
Authors: Sarah C. Moser, Jos Jonkers
Journal: Cancer Discovery (2025)

Abstract Thirty years ago, the cloning of the first breast cancer susceptibility gene, BRCA1, marked a milestone in our understanding of hereditary breast and ovarian cancers. This discovery initiated extensive research into DNA repair mechanisms, BRCA1-associated tumorigenesis, and therapeutic interventions. Despite these advances, critical questions remain unanswered, such as the evolution of BRCA1-associated tumors and their tissue specificity. These issues hinder the development of effective treatment and prevention strategies, which ultimately aim to improve the quality of life for BRCA1 mutation carriers. In this review, we discuss current knowledge, identify existing gaps, and suggest possible avenues to tackle these challenges. Significance: Here, we explore the impact of three decades of BRCA1 research on the lives of mutation carriers and propose strategies to improve the prevention and treatment of BRCA1-associated cancer.
The Role of Ultrasound Diagnosis of Traumatic Arteriovenous Fistula of the Brachial Artery
Authors: V. N. Troyan, G. V. Golovushkina
Journal: Radiology - Practice (2025)

Objective . To demonstrate the importance and necessity of ultrasound diagnostics in case of traumatic injury of the upper extremities of various types on the example of a clinical case of detection of volumetric formation of soft tissues of the right upper limb of a false aneurysm and arteriovenous fistula of the brachial artery during ultrasound scanning. Materials and Methods . Information about the patient's medical history, protocols, laboratory and radiation examination methods. Results . In a victim with a combined gunshot wound to the chest, abdomen, limbs, and a closed craniocerebral injury in the lower third of the right shoulder, a volumetric pulsating formation measuring 10 × 8 × 8 cm was visually determined, during ultrasound scanning of soft tissues and main vessels of the right limb, defects in the walls of the brachial and radial arteries were revealed with the formation of a pulsating hematoma in the soft tissues of the right shoulder and forearms, defects in the walls of the brachial artery and vein at the level of the lower third of the right shoulder with the formation of an arteriovenous junction between them. The presence of an arteriovenous fistula and pseudoaneurysm were also confirmed during CT angiography. Due to the timely and high–quality radiation diagnosis, the patient underwent successful surgical treatment — resection of the brachial artery aneurysm of the right upper limb, separation of the arteriovenous fistula. Conclusion . Ultrasound scanning of soft tissues and main vessels of the extremities in case of their traumatic damage, unlike other methods of radiation diagnostics, allows noninvasively, without radiation load, timely and mobile assessment of the state of blood flow in the affected limb, to identify the presence of hematomas, false aneurysms and arteriovenous fistulas and distinguish them from each other based on the spectral characteristics of blood flow and vascular staining in the mode of color Doppler mapping, which was carried out to a wounded man with damage to the right upper limb, who was suspected of having a soft tissue hematoma at the initial examination, and during an ultrasound scan was diagnosed as a false aneurysm and arteriovenous fistula of the brachial artery.
Extracellular vesicles of <i>Limosilactobacillus fermentum</i> SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism
Authors: Hyejin Choi, Min-Jin Kwak, Youbin Choi, An Na Kang, Daye Mun, Ju Young Eor, Mi Ri Park, Sangnam Oh, Younghoon Kim
Journal: Gut Microbes (2025)

Atopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of the interaction between AD and gut microbiome. In this study, we investigated the effects of probiotic-derived extracellular vesicles on AD. Initially, we isolated and characterized extracellular vesicles from Limosilactobacillus fermentum SLAM 216 (LF216EV) and characterized their composition through multi-omics analysis. Gene ontology (GO) and pathway analysis classified LF216EV proteins into biological processes, molecular functions, and cellular components. Importantly, specific abundance in linoleic, oleic, palmitic, sebacic, and stearic acids indicating upregulated fatty acid metabolism were observed by metabolomic analysis. Furthermore, featured lipid profiling including AcylGlcADG and ceramide were observed in LF216EV. Importantly, in an atopic dermatitis-like cell model induced by TNFα/IFNγ, LF216EV significantly modulated the expression of immune regulatory genes (TSLP, TNFα, IL-6, IL-1β, and MDC), indicating its potential functionality in atopic dermatitis. LF216EV alleviated AD-like phenotypes, such as redness, scaling/dryness, and excoriation, induced by DNCB. Histopathological analysis revealed that LF216EV decreased epidermal thickness and mast cell infiltration in the dermis. Furthermore, LF216EV administration reduced mouse scratching and depression-related behaviors, with a faster onset than the classical treatment with dexamethasone. In the quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significant increase in the expression levels of htrb2c, sert, and tph-1, genes associated with serotonin, in the skin and gut of the LF216EV-treated group, along with a significant increase in the total serum serotonin levels. Gut microbiome analysis of the LF216EV-treated group revealed an altered gut microbiota profile. Correlation analysis revealed that the genera Limosilactobacillus and Desulfovibrio were associated with differences in the intestinal metabolites, including serotonin. Our findings demonstrate that LF216EV mitigates AD-like symptoms by promoting serotonin synthesis through the modulation of gut microbiota and metabolome composition.
STModule: identifying tissue modules to uncover spatial components and characteristics of transcriptomic landscapes
Authors: Ran Wang, Yan Qian, Xiaojing Guo, Fangda Song, Zhiqiang Xiong, Shirong Cai, Xiuwu Bian, Man Hon Wong, Qin Cao, Lixin Cheng, Gang Lu, Kwong Sak Leung
Journal: Genome Medicine (2025)

Abstract Here we present STModule, a Bayesian method developed to identify tissue modules from spatially resolved transcriptomics that reveal spatial components and essential characteristics of tissues. STModule uncovers diverse expression signals in transcriptomic landscapes such as cancer, intraepithelial neoplasia, immune infiltration, outcome-related molecular features and various cell types, which facilitate downstream analysis and provide insights into tumor microenvironments, disease mechanisms, treatment development, and histological organization of tissues. STModule captures a broader spectrum of biological signals compared to other methods and detects novel spatial components. The tissue modules characterized by gene sets demonstrate greater robustness and transferability across different biopsies. STModule: https://github.com/rwang-z/STModule.git .
Implications of gene × environment interactions in post-traumatic stress disorder risk and treatment
Authors: Carina Seah, Anne Elizabeth Sidamon-Eristoff, Laura M. Huckins, Kristen J. Brennand
Journal: Journal of Clinical Investigation (2025)

Exposure to traumatic stress is common in the general population. Variation in the brain's molecular encoding of stress potentially contributes to the heterogeneous clinical outcomes in response to traumatic experiences. For instance, only a minority of those exposed to trauma will develop post-traumatic stress disorder (PTSD). Risk for PTSD is at least partially heritable, with a growing number of genetic factors identified through GWAS. A major limitation of genetic studies is that they capture only the genetic component of risk, whereas PTSD by definition requires an environmental traumatic exposure. Furthermore, the extent, timing, and type of trauma affects susceptibility. Here, we discuss the molecular mechanisms of PTSD risk together with gene × environment interactions, with a focus on how either might inform genetic screening for individuals at high risk for disease, reveal biological mechanisms that might one day yield novel therapeutics, and impact best clinical practices even today. To close, we discuss the interaction of trauma with sex, gender, and race, with a focus on the implications for treatment. Altogether, we suggest that predicting, preventing, and treating PTSD will require integrating both genotypic and environmental information.
Injectable hydrogel with miR-222-engineered extracellular vesicles ameliorates myocardial ischemic reperfusion injury via mechanotransduction
Authors: Yongtao Wang, Danni Meng, Xiaohui Shi, Yan Hou, Shihui Zang, Lei Chen, Michail Spanos, Guoping Li, Dragos Cretoiu, Qiulian Zhou, Junjie Xiao
Journal: Cell Reports Medicine (2025)

Cardiac ischemic reperfusion injury (IRI) significantly exacerbates cardiac dysfunction and heart failure, causing high mortality. Despite the severity of IRI, effective therapeutic strategies remain elusive. Acellular cardiac patches have shown considerable efficacy in delivering therapeutics directly to cardiac tissues. Herein, we develop injectable GelMA (GEL) hydrogels with controlled mechanical properties. Targeting miR-222-engineered extracellular vesicles (TeEVs), tailored with cardiac-ischemia-targeting peptides (CTPs), are developed as ischemic TeEV therapeutics. These TeEVs are encapsulated within mechanical hydrogels to create injectable TeEV-loaded cardiac patches, enabling minimal invasiveness to attenuate IRI. The injectable patches facilitate the precise targeting of TeEVs for the efficient rescue of damaged cells. Persistent delivery of TeEVs into the infarcted region alleviates acute IRI and mitigated remodeling post IRI. This is linked to focal adhesion activation, cytoskeleton force enhancement, and nuclear force-sensing preservation. These findings may pave the way for force-sensing approaches to cardiac therapy using bioengineered therapeutic patches.
Inflammatory reprogramming of the solid tumor microenvironment by infiltrating clonal hematopoiesis is associated with adverse outcomes
Authors: Marco M. Buttigieg, Caitlyn Vlasschaert, Alexander G. Bick, Robert J. Vanner, Michael J. Rauh
Journal: Cell Reports Medicine (2025)

Clonal hematopoiesis (CH)-the expansion of somatically mutated hematopoietic cells-is common in solid cancers. CH is associated with systemic inflammation, but its impact on tumor biology is underexplored. Here, we report the effects of CH on the tumor microenvironment (TME) using 1,550 treatment-naive patient samples from the Clinical Proteomics Tumor Analysis Consortium (CPTAC) cohort. CH is present in 18.3% of patients, with one-third of CH mutations also detectable in tumor-derived DNA from the same individual (CH-Tum), reflecting CH-mutant leukocyte infiltration. Across cancers, the presence of CH-Tum is associated with worse survival outcomes. Molecular analyses reveal an association between CH-Tum and an immune-rich, inflammatory TME that is notably distinct from age-related gene expression changes. These effects are most prominent in glioblastoma, where CH correlates with pronounced macrophage infiltration, inflammation, and an aggressive, mesenchymal phenotype. Our findings demonstrate that CH shapes the TME, with potential applications as a biomarker in precision oncology.
Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein
Authors: Daniel Hansen, Jasmin E R Jensen, Christian A T Andersen, Peter R Jakobsgaard, Jesper Havelund, Line Lauritsen, Samuel Mandacaru, Majken Siersbaek, Oliver L Shackleton, Hiroshi Inoue, Jonathan R Brewer, Robert F Schwabe, Blagoy Blagoev, Nils J Færgeman, Marko Salmi, Kim Ravnskjaer
Journal: Cell Metabolism (2025)

The liver is essential for normal fatty acid utilization during fasting. Circulating fatty acids are taken up by hepatocytes and esterified as triacylglycerols for either oxidative metabolization and ketogenesis or export. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, the uptake and retention of non-esterified fatty acids by hepatocytes is not. Here, we show that murine hepatic stellate cells (HSCs) and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic substrate preference for fasting energy metabolism. HSC-specific ablation of PLVAP in mice elevated hepatic insulin signaling and improved glucose tolerance. Fasted HSC PLVAP knockout mice showed suppressed hepatic fatty acid esterification into di- and triacylglycerols, shifting fasting metabolism from fatty acid oxidation to reliance on carbohydrates. By super-resolution microscopy, we localized HSC PLVAP to caveolae residing along the sinusoidal lumen, supporting a role for HSCs and PLVAP-diaphragmed caveolae in normal fasting metabolism of the liver.
Realigned transsulfuration drives BRAF-V600E-targeted therapy resistance in melanoma
Authors: Klaudia Borbényi-Galambos, Katalin Erdélyi, Tamás Ditrói, Eszter Petra Jurányi, Noémi Szántó, Réka Szatmári, Ágnes Czikora, Edward E Schmidt, Dorottya Garai, Mihály Cserepes, Gabriella Liszkay, Erika Tóth, József Tóvári, Péter Nagy
Journal: Cell Metabolism (2025)
Pathogen-derived glyoxylate inhibits Tet2 DNA dioxygenase to facilitate bacterial persister formation
Authors: Zhou-Li Cheng, Shuyuan Zhang, Zhenning Wang, Aixia Song, Chao Gao, Jun-Bin Song, Pu Wang, Lei Zhang, Yue Zhou, Wenyan Shan, Chen Zhang, Jinye Zhang, Yiping Sun, Yanhui Xu, Fei Lan, Ming Zhong, Liang-Dong Lyu, Guanghua Huang, Fei Xavier Chen, Gang Li, Zixin Wang, Faying Chen, Jianhuang Xue, Jiejun Shi, Yujun Liu, Zihao Lin, Duojiao Wu, Jim Na, Lei-Lei Chen, Kun-Liang Guan, Yue Xiong, Dan Ye
Journal: Cell Metabolism (2025)
Breastfeeding Support Provided by Lactation Consultants
Authors: Curtis J. D’Hollander, Victoria A. McCredie, Elizabeth M. Uleryk, Michaela Kucab, Rosella M. Le, Ofri Hayosh, Charles D. G. Keown-Stoneman, Catherine S. Birken, Jonathon L. Maguire
Journal: JAMA Pediatrics (2025)

Importance Breast milk offers numerous health benefits, yet breastfeeding recommendations are met less than half of the time in high-income countries. Objective To evaluate the effect of lactation consultant (LC) interventions on breastfeeding, maternal breastfeeding self-efficacy, and infant growth compared to usual care. Data Sources The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, Scopus, Web of Science, and the gray literature were searched for articles published between January 1985 and July 2024. The search took place on July 10, 2024, and data analysis was performed from July to August 2024. Study Selection Randomized clinical trials of LC interventions in high-income countries published in any language were eligible for inclusion. Data Extraction and Synthesis Data extracted included study design, participant and intervention characteristics, and outcome data. To account for studies that reported outcomes at multiple time points, effect estimates were pooled with 3-level correlated and hierarchical effects models. Meta-regression was performed for clinically important characteristics, such as the time point when the outcome was measured, intervention intensity, and participant income. Main Outcomes and Measures The primary outcome was stopping exclusive breastfeeding. Secondary outcomes included stopping any breastfeeding, exclusive breastfeeding and any breastfeeding duration, maternal breastfeeding self-efficacy, infant overweight and obesity, and infant growth. Results The search yielded 6476 records, of which 40 studies were included involving 8582 participants. Studies were published between 1992 and 2024, and most studies (n = 22) were conducted in the US. Compared to usual care, LC interventions reduced the risk of stopping exclusive breastfeeding (risk ratio [RR], 0.96; 95% CI, 0.94-0.99) and any breastfeeding (RR, 0.92; 95% CI, 0.87-0.96) and increased any breastfeeding duration by 3.63 weeks (95% CI, 0.13-7.12). There was weak evidence that LC interventions increased exclusive breastfeeding duration (mean difference [MD], 1.44 weeks; 95% CI, −2.73 to 5.60), maternal breastfeeding self-efficacy (MD, 2.83; 95% CI, −1.23 to 6.90), or the risk of infant overweight and obesity (RR, 1.52; 95% CI, 0.94-2.46). Meta-regression showed that LC interventions were more effective at reducing the risk for stopping exclusive breastfeeding ( P = .01) and any breastfeeding ( P &amp;amp;lt; .001) the earlier that breastfeeding was measured in the postpartum period. LC interventions with a higher intensity (ie, number of LC visits) were more effective at reducing the risk for stopping any breastfeeding ( P = .04). Conclusions and Relevance According to the results of this systematic review and meta-analysis, LC interventions are a promising intervention for improving exclusive breastfeeding and any breastfeeding in high-income countries.
Hospital-Physician Integration and Cardiac Rehabilitation Following Major Cardiovascular Events
Authors: Ngoc H. Thai, Brady Post, Gary Young, Md. Noor-E-Alam
Journal: JAMA Network Open (2025)

Importance Cardiac rehabilitation (CR) is a medically supervised program designed to improve heart health after a cardiac event. Despite its demonstrated clinical benefits, CR participation among eligible patients remains poor due to low referral rates and individual barriers to care. Objectives To evaluate CR participation by patients who receive care from hospital-integrated physicians compared with independent physicians, and subsequently, to examine CR and recurrent cardiac hospitalizations. Design, Setting, and Participants This retrospective cohort study evaluated Medicare Part A and Part B claims data from calendar years 2016 to 2019. All analyses were conducted between January 1 and April 30, 2024. Patients were included if they had a qualifying event for CR between 2017 and 2018, and qualifying events were identified using diagnosis codes on inpatient claims and procedure codes on outpatient and carrier claims. Eligible patients also had to continuously enroll in fee-for-service Medicare for 12 months or more before and after the index event. Physicians’ integration status and patients’ CR participation were determined during the 12-month follow-up period. The study covariates were ascertained during the 12 months before the index event. Exposure Hospital-integration status of the treating physician during follow-up. Main Outcomes and Measures Postindex CR participation was determined by qualifying procedure codes on outpatient and carrier claims. Results The study consisted of 28 596 Medicare patients eligible for CR. Their mean (SD) age was 74.0 (9.6) years; 16 839 (58.9%) were male. A total of 9037 patients (31.6%) were treated by a hospital-integrated physician, of which 2995 (33.1%) received CR during follow-up. Logistic regression via propensity score weighting showed that having a hospital-integrated physician was associated with an 11% increase in the odds of receiving CR (odds ratio [OR], 1.11; 95% CI, 1.05-1.18). Additionally, CR participation was associated with a 14% decrease in the odds of recurrent cardiovascular-related hospitalizations (OR, 0.86; 95% CI, 0.81-0.91). Conclusions and Relevance The findings of this cohort study suggest that hospital integration has the potential to facilitate greater CR participation and improve heart care. Several factors may help explain this positive association, including enhanced care coordination and value-based payment policies. Further research is needed to assess the association of integration with other appropriate high-quality care activities.
Levels of Satisfaction and Regret Are Far From Settled—Reply
Authors: Kristina R. Olson, G. F. Raber, Natalie M. Gallagher
Journal: JAMA Pediatrics (2025)

In Reply Sinai et al raised a series of questions and concerns about our article1 and the broader field of gender-affirming medical care (GAMC). We respond to as many of these concerns here as space permits.
Integrating Tobacco Treatment Into Lung Cancer Screening
Authors: Elyse R. Park, Jennifer S. Haas, Nancy A. Rigotti, Jordan M. Neil, Caylin J. Marotta, Amy J. Wint, Irina Gonzalez, Sydney E. McGovern, Yuchiao Chang, Douglas E. Levy, Efren J. Flores, Vanessa L. Merker, Elise Noonan, Cayley C. Bliss
Journal: JAMA Internal Medicine (2025)

Importance Integrating tobacco treatment into lung cancer screening (LCS) could increase smoking cessation among older smokers by leveraging a teachable moment and treatment access. Objective To identify effective evidence-based tobacco treatment components for individuals undergoing LCS. Design, Setting, and Participants A 2 × 2 × 2 factorial randomized clinical trial offered to adults aged 50 to 80 years who spoke English or Spanish and were scheduled for LCS at 11 outpatient imaging sites from April 2019 to June 2023. Interventions Individuals were randomized to 8 groups of a multicomponent intervention with 3 treatment factors: duration of telehealth counseling offered (4 sessions over 4 weeks vs 8 sessions over 12 weeks), duration of free nicotine replacement therapy (NRT) provided (2 vs 8 weeks), offer of screening for social determinants of health (SDOH), and referral to community-based resources (yes or no). Main Outcomes and Measures Primary outcome was self-reported 7-day tobacco abstinence at 6-month follow-up. Results A total of 642 individuals were randomized (mean [SD] age, 64 [6.5] years; 358 [55.8%] female; 67 (10.4%) identified as Black, 47 (7.3%) identified as Hispanic, 540 (84.1%) identified as White; 207 [32.3%] had high school education or less; 36.3 [19.4] mean [SD] pack-years; mean [SD] 16.2 [8.2] cigarettes per day; 484 [75.4%] smoked within 30 minutes after waking). At 6 months, 7-day abstinence was higher for individuals offered 8 vs 4 counseling sessions (17.3% vs 11.7%; risk difference, 5.6; 95% CI, 0.1-11.0; P = .045) but was not significantly different by duration of NRT provision or offer of SDOH screening or referral. In exit interviews, individuals expressed support for more counseling and medication choice and identified barriers to SDOH screening uptake. Conclusions and Relevance In this randomized clinical trial among current smokers undergoing LCS, an integrated, centralized tobacco treatment program offering a longer duration of counseling produced greater tobacco abstinence at 6 months, but providing a longer duration of NRT or offering SDOH screening and referral in this context did not. In future work, strategies to expand medication usage and promote SDOH screening might be explored. Trial Registration ClinicalTrials.gov Identifier: NCT03611881