tbuckley/cabot-search huggingface dataset:
Risk Factors for Health Care–Associated Bloodstream Infections in NICUs
Authors: Julia Johnson, Sudhir Malwade, Sharad Agarkhedkar, Bharat Randive, Uday C. Rajput, Chhaya Valvi, Aarti Kinikar, Tushar B. Parikh, Umesh Vaidya, Abhay Kadam, Basma Ouddi, Rachel M. Smith, Matthew Westercamp, Vidya Mave, Christina Schumacher, Susan E. Coffin, Matthew L. Robinson, Amita Gupta, Yukari C. Manabe, Aaron M. Milstone
Journal: JAMA Network Open (2025)

Importance Neonates requiring intensive care are at high risk of health care–associated infections. In neonatal intensive care units (NICUs) in low-resource settings, the identification of modifiable risk factors can inform targeted prevention strategies to reduce the global burden of neonatal morbidity and mortality. Objective To describe the incidence of and the risk factors associated with health care–associated bloodstream infections (BSIs) in NICUs in Pune, India. Design, Setting, and Participants This multicenter prospective cohort study enrolled all neonates admitted to 3 NICUs in Pune, India, from May 1, 2017, to July 31, 2019. Neonates were followed up from admission until discharge, transfer, or death. This secondary data analysis included neonates admitted for 3 days or more and was completed on January 31, 2024. Main Outcomes and Measures The primary outcome was health care–associated BSIs, defined as a positive blood culture on or after admission day 3. Summary statistics, incidence of health care–associated BSIs, and hazard rate by characteristics of interest were generated. Among neonates admitted for 7 days or longer, the association between antibiotic exposure and infection risk was assessed. Results A total of 6410 neonates were admitted for 3 days or longer. The median gestational age was 34 weeks (IQR, 32-37 weeks), and 3560 (55.5%) were male. The incidence of health care–associated BSIs was 6.09 per 1000 patient-days. Most isolates were gram-negative organisms (n = 273 [66.3%]), of which 85.5% (202 of 236 isolates tested) were resistant to third- or fourth-generation cephalosporins and 44.8% (117 of 261 isolates tested) were resistant to carbapenems. The hazard rate of health care–associated BSIs was higher among neonates with central venous catheters, respiratory support, or urinary catheters within 3 days preceding infection. Of 3229 neonates admitted for 7 days or longer, 190 (5.8%) had health care–associated BSIs on or after hospital day 7, with an incidence of 3.22 per 1000 patient-days. Antibiotic exposure during the first week of admission was associated with a nearly 3-fold increase in the risk of health care–associated BSIs (adjusted hazard ratio, 2.82 [95% CI, 1.26-6.32]). Conclusions and Relevance In this cohort study of 6410 neonates admitted to 3 NICUs in Pune, India, the risk of health care–associated BSIs was associated with the presence of indwelling devices and prior antibiotic exposure. Future efforts should focus on mitigating the risks associated with indwelling devices and strengthening infection prevention and control and antimicrobial stewardship programs to prevent health care–associated infections.
Modified endoscopic hand-suturing without scope reinsertion for an ileocecal defect after endoscopic submucosal dissection
Authors: Lizhou Dou, Shibo Song, Chen Zhang, Yumeng Liu, Ying Lv, Guiqi Wang
Journal: Endoscopy (2025)

We present a modified endoscopic hand-suturing (EHS) technique that effectively and safely closed an ileocecal defect following endoscopic submucosal dissection (ESD) without requiring reinsertion of the endoscope. A 59-year-old woman underwent ESD for a laterally spreading tumor measuring approximately 3.5 × 3.0 cm in the ileocecum. The steps of the modified EHS procedure are detailed below ([Video 1Video 1]).
Doxycycline to prevent bacterial sexually transmitted infections in the USA: final results from the DoxyPEP multicentre, open-label, randomised controlled trial and open-label extension
Authors: Anne F Luetkemeyer, Deborah Donnell, Stephanie E Cohen, Julia C Dombrowski, Cole Grabow, Grace Haser, Clare Brown, Chase Cannon, Cheryl Malinski, Rodney Perkins, Melody Nasser, Carolina Lopez, Robert J Suchland, Eric Vittinghoff, Susan P Buchbinder, Hyman Scott, Edwin D Charlebois, Diane V Havlir, Olusegun O Soge, Connie Celum
Journal: The Lancet Infectious Diseases (2025)
Bacterial vaginosis associates with dysfunctional T cells and altered soluble immune factors in the cervicovaginal tract
Authors: Finn MacLean, Adino Tesfahun Tsegaye, Jessica B. Graham, Jessica L. Swarts, Sarah C. Vick, Nicole B. Potchen, Irene Cruz Talavera, Lakshmi Warrier, Julien Dubrulle, Lena K. Schroeder, Ayumi Saito, Corinne Mar, Katherine K. Thomas, Matthias Mack, Michelle C. Sabo, Bhavna H. Chohan, Kenneth Ngure, Nelly Rwamba Mugo, Jairam R. Lingappa, Jennifer M. Lund
Journal: Journal of Clinical Investigation (2025)

Background: Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually-acquired HIV, yet the immunological mechanisms underlying this association are not well understood. Methods: To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, Kinga Study participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples. Results: High-parameter flow cytometry revealed an increased frequency of cervical conventional CD4+ T cells (Tconv) expressing CCR5. However, we found no difference in number of CD3+CD4+CCR5+ cells in the CX or VT of BV+ versus BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV have an increased frequency of dysfunctional CX and VT CD39+ Tconv and CX tissue-resident CD69+CD103+ Tconv, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations. Conclusion: Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.
Association Between Use of Sodium–Glucose Cotransporter 2 Inhibitors and Epilepsy: A Population-Based Study Using Target Trial Emulation
Authors: Houyu Zhao, Baixue Zhang, Lin Zhuo, Yueqi Yin, Yexiang Sun, Peng Shen, Zhiqin Jiang, Siyan Zhan
Journal: Diabetes Care (2025)

OBJECTIVE Preclinical studies in animals have suggested potential neuroprotective effects of sodium–glucose cotransporter 2 inhibitors (SGLT-2is), but no epidemiological study has investigated the potential effects of SGLT-2is on epilepsy risk. We aimed to assess the association between use of SGLT-2is and epilepsy incidence. RESEARCH DESIGN AND METHODS We emulated a target trial comparing SGLT-2is and dipeptidyl peptidase 4 inhibitors (DPP-4is) based on the Yinzhou Regional Health Care Database. Cohorts of patients with type 2 diabetes mellitus who were new users of an SGLT-2i or a DPP-4i were assembled. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards regression modeling were applied to estimate the hazard ratio (HR) and 95% CI of the association between use of SGLT-2is and incidence of epilepsy. RESULTS The final cohort included 24,930 new users of SGLT-2is and 28,924 initiators of DPP-4is. A total of 243 patients with incident epilepsy were found during a median follow-up of 2.0 (interquartile range 0.8–3.3) years, with the incidence of epilepsy being 174.2 and 231.5 per 100,000 person-years in users of SGLT-2is and DPP-4is, respectively. After controlling for potential confounding using IPTW, SGLT-2i use was associated with a lower incidence of epilepsy, with an HR of 0.71 (95% CI 0.52–0.97). Various subgroup analyses and sensitivity analyses supported the results in primary analyses. CONCLUSIONS SGLT-2is were associated with a reduced incidence of epilepsy in the study population. More studies are needed to confirm and replicate the study results.
Targeting legumain-mediated cell-cell interaction sensitizes glioblastoma to immunotherapy in preclinical models
Authors: Lizhi Pang, Songlin Guo, Yuyun Huang, Fatima Khan, Yang Liu, Fei Zhou, Justin D. Lathia, Peiwen Chen
Journal: Journal of Clinical Investigation (2025)

Tumor-associated macrophages (TAMs) are the most prominent immune cell population in the glioblastoma (GBM) tumor microenvironment (TME) and play critical roles in promoting tumor progression and immunosuppression. Here we identified that TAM-derived legumain (LGMN) exhibited a dual role in regulating the biology of TAMs and GBM cells. LGMN promoted macrophage infiltration in a cell-autonomous manner by activating the GSK3b-STAT3 pathway. Moreover, TAM-derived LGMN activated the integrin aV-AKT-P65 signaling to drive GBM cell proliferation and survival. Targeting LGMN-directed macrophage (inhibiting GSK3b and STAT3) and GBM cell (inhibiting integrin aV) mechanisms resulted in an anti-tumor effect in immunocompetent GBM mouse models that was further enhanced when combined with anti-PD1 therapy. Our study reveals a paracrine and autocrine mechanism of TAM-derived LGMN in promoting GBM progression and immunosuppression, providing effective therapeutic targets for improving immunotherapy in GBM.
Induced clustering of SHP2-depleted tumor cells in vascular islands restores sensitivity to MEK/ERK inhibition
Authors: Yuyi Wang, Hidetaka Ohnuki, Andy D. Tran, Dunrui Wang, Taekyu Ha, Jing-Xin Feng, Minji Sim, Raymond Barnhill, Claire Lugassy, Michael R. Sargen, Emanuel Salazar-Cavazos, Michael Kruhlak, Giovanna Tosato
Journal: Journal of Clinical Investigation (2025)

Allosteric inhibitors of the tyrosine phosphatase SHP2 hold therapeutic promise in cancers with overactive RAS/ERK signaling but "adaptive resistance" to SHP2 inhibitors may limit benefits. Here, we utilized tumor cells that proliferate similarly with or without endogenous SHP2 to explore means to overcome this growth-independence from SHP2. We found that SHP2 depletion profoundly alters output of vascular regulators, cytokines, chemokines, and other factors from SHP2 growth-resistant cancer cells. Tumors derived from inoculation of SHP2-depleted, but SHP2 growth-independent, mouse melanoma and colon carcinoma cell lines display a typically subverted architecture where proliferative tumor cells cluster in distinct "vascular islands" centered by remodeled vessels, each limited by surrounding hypoxic and dead tumor tissue, where inflammatory blood cells are limited. Although vascular islands generally reflect protected sanctuaries for tumor cells, we found that vascular island-resident, highly proliferative, SHP2-depleted tumor cells acquire an increased sensitivity to blocking MEK/ERK signaling resulting in reduced tumor growth. Our results show that response to targeted therapies in resistant tumor cells is controlled by tumor cell-induced vascular changes and tumor architectural reorganization providing a compelling approach to eliciting tumor response by exploiting tumor and endothelial-dependent biochemical changes.
Long non-coding RNA BCYRN1 promotes cardioprotection by enhancing human and murine regulatory T cell dynamics
Authors: Ke Liao, Jiayi Yu, Akbarshakh Akhmerov, Zahra Mohammadigoldar, Liang Li, Weixin Liu, Natasha Anders, Ahmed G.E. Ibrahim, Eduardo Marbán
Journal: Journal of Clinical Investigation (2025)

Regulatory T (Treg) cells modulate immune responses and attenuate inflammation. Extracellular vesicles from human cardiosphere-derived cells (CDC-EVs) enhance Treg proliferation and IL10 production, but the mechanisms remain unclear. Here we focus on BCYRN1, a long noncoding RNA (lncRNA) highly abundant in CDC-EVs, and its role in Treg cell function. BCYRN1 acts as a "microRNA sponge," inhibiting miR-138, miR-150, and miR-98. Suppression of these miRs leads to increased Treg cell proliferation via ATG7-dependent autophagy, CCR6-dependent Treg migration, and enhanced Treg IL10 production. In a mouse model of myocardial infarction, CDC-EVs, particularly those overexpressing BCYRN1, were cardioprotective, reducing infarct size and troponin I levels even when administered after reperfusion. Underlying the cardioprotection, we verified that CDC-EVs overexpressing BCYRN1 increased cardiac Treg infiltration, proliferation, and IL10 production in vivo. These salutary effects were negated when BCYRN1 levels were reduced in CDC-EVs, or when Tregs were depleted systemically. Thus, we have identified BCYRN1 as a booster of Treg number and bioactivity, rationalizing its cardioprotective efficacy. While here we studied BCYRN1 overexpression in the context of ischemic injury, the same approach merits testing in other disease processes (e.g., autoimmunity or transplant rejection) where increased Treg activity is a recognized therapeutic goal.
Improving Exome Sequencing for Neurodevelopmental Disorders
Authors: Seth I. Berger
Journal: JAMA Network Open (2025)

Xiaoping Lan, PhD; Xiaojun Tang, MS; Wenhao Weng, PhD; Wuhen Xu, MS; Xiaozhen Song, PhD; Yongchen Yang, MS; Hong Sun, PhD; Haiyun Ye, MD, PhD; Hong Zhang, MS; Guangjun Yu, MD, PhD; Shengnan Wu, PhD
Author Correction: Origin and de novo domestication of sweet orange
Authors: Shengjun Liu, Yuantao Xu, Kun Yang, Yue Huang, Zhihao Lu, Shulin Chen, Xiang Gao, Gongao Xiao, Peng Chen, Xiuli Zeng, Lun Wang, Weikang Zheng, Zishuang Liu, Guanglian Liao, Fa He, Junjie Liu, Pengfei Wan, Fang Ding, Junli Ye, Wenbiao Jiao, Lijun Chai, Zhiyong Pan, Fei Zhang, Zongcheng Lin, Yanjun Zan, Wenwu Guo, Robert M. Larkin, Zongzhou Xie, Xia Wang, Xiuxin Deng, Qiang Xu
Journal: Nature Genetics (2025)
Evolving patterns of macrolide and fluoroquinolone resistance in Mycoplasma genitalium: an updated systematic review and meta-analysis
Authors: Teck-Phui Chua, Lenka A Vodstrcil, Gerald L Murray, Erica L Plummer, Jørgen S Jensen, Magnus Unemo, Eric P F Chow, Nicola Low, David M Whiley, Emma L Sweeney, Jane S Hocking, Jennifer A Danielewski, Suzanne M Garland, Christopher K Fairley, Lei Zhang, Catriona S Bradshaw, Dorothy A Machalek
Journal: The Lancet Microbe (2025)
Robotic-Assisted Cholecystectomy—for Whom?
Authors: David R. Urbach
Journal: JAMA Network Open (2025)

Cody Lendon Mullens, MD, MPH; Sarah Sheskey, BS; Jyothi R. Thumma, MPH; Justin B. Dimick, MD, MPH; Edward C. Norton, PhD; Kyle H. Sheetz, MD, MS
Long-Term Outcomes After Subarachnoid Hemorrhage—The Road to Recovery Is Longer Than Expected
Authors: Victor Volovici, Jose I. Suarez
Journal: JAMA Network Open (2025)

Ho Seok Lee, MD, PhD; Min Kyun Sohn, MD, PhD; Jongmin Lee, MD, PhD; Deog Young Kim, MD, PhD; Yong-Il Shin, MD, PhD; Gyung-Jae Oh, MD, PhD; Yang-Soo Lee, MD, PhD; Min Cheol Joo, MD, PhD; So Young Lee, MD, PhD; Min-Keun Song, MD, PhD; Junhee Han, PhD; Jeonghoon Ahn, PhD; Young-Hoon Lee, MD, PhD; Dae Hyun Kim, MD, PhD; Young-Taek Kim, PhD; Yun-Hee Kim, MD, PhD; Won Hyuk Chang, MD, PhD
Author Correction: Rare variant analyses in 51,256 type 2 diabetes cases and 370,487 controls reveal the pathogenicity spectrum of monogenic diabetes genes
Authors: Alicia Huerta-Chagoya, Philip Schroeder, Ravi Mandla, Jiang Li, Lowri Morris, Maheak Vora, Ahmed Alkanaq, Dorka Nagy, Lukasz Szczerbinski, Jesper G. S. Madsen, Silvia Bonàs-Guarch, Fanny Mollandin, Joanne B. Cole, Bianca Porneala, Kenneth Westerman, Josephine H. Li, Toni I. Pollin, Jose C. Florez, Anna L. Gloyn, David J. Carey, Inês Cebola, Uyenlinh L. Mirshahi, Alisa K. Manning, Aaron Leong, Miriam Udler, Josep M. Mercader
Journal: Nature Genetics (2025)
Local DIO2 Elevation Is an Adaption in Malformed Cerebrovasculature
Authors: Ruofei Li, Yushan Tang, Haiyue Wang, Pengyan Hu, Liang Yu, Cheng Lv, Yu Zhang, A. Martin Gerdes, Yibo Wang
Journal: Circulation Research (2025)

BACKGROUND: Cerebrovascular malformations are a pivotal cause of hemorrhage and neurological disability alongside lacking effective medication. Thyroid hormones (THs), including thyroxine and triiodothyronine, are essential for vascular development, yet whether they participate in malformed cerebrovascular pathology remains elusive. METHODS: Single-cell transcriptome analysis characterized human cerebral cavernous malformations and brain arteriovenous malformations, 2 typical cerebrovascular malformation diseases. Adeno-associated virus–mediated DIO2 (iodothyronine deiodinase 2; an enzyme that converts thyroxine to active triiodothyronine) overexpression/knockdown or triiodothyronine/methimazole (an antithyroid drug) treatment was applied to mouse models of cerebral cavernous malformations (endothelial-specific Pdcd10 knockout mice, Pdcd10 KO) and brain arteriovenous malformations (endothelial-specific Kras G12D mutant mice, Kras G12D ) to evaluate the involvement of DIO2 and TH signaling in cerebrovascular malformations. RESULTS: TH signaling was markedly activated in fibroblasts of human cerebral cavernous malformation and arteriovenous malformation single-cell samples, accompanied by elevated DIO2 expression. Similar DIO2 upregulation was observed in cerebrovascular fibroblasts of Pdcd10 KO/ Kras G12D mice and patient brain sections. Exogenous DIO2 or triiodothyronine replenishment effectively reduced brain hemorrhage, excessive ECM (extracellular matrix) remodeling, and vascular leakage in juvenile and adult male and female Pdcd10 KO/ Kras G12D mice. In contrast, DIO2 silencing or TH inhibition deteriorated vascular anomalies. Mechanistically, transcription factor Foxk1 (forkhead box K1) was determined to interact with the DIO2 promoter region. The activation of fibroblast PI3K-Akt-mTOR signaling in Pdcd10 KO/ Kras G12D mice triggered Foxk1 nuclear translocation to promote DIO2 transcription. Triiodothyronine treatment mitigated inflammatory infiltration, normalized mitochondrial morphology, and restored mitochondrial biogenesis in malformed brain vessels by activating the Pgc1a (peroxisome proliferator-activated receptor gamma coactivator 1-alpha)-Sod2 (superoxide dismutase 2)/Prdx3 (peroxiredoxin 3)/Gpx1 (glutathione peroxidase 1) axis to reduce reactive oxygen species accumulation. We also determined that the vascular repair effects of triiodothyronine were Pgc1a-dependent. CONCLUSIONS: We delineate a novel DIO2-mediated adaption in malformed cerebrovasculature and conclude that targeting TH signaling may represent a potential therapy for cerebrovascular disorders.
Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease
Authors: Bryan Sun, Lulin Li, Odette A. Harris, Jian Luo
Journal: Translational Neurodegeneration (2025)

Abstract Traumatic brain injury (TBI) has emerged as a significant risk factor for Alzheimer’s disease (AD), a complex and devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Both conditions share a common feature: blood‒brain barrier (BBB) dysfunction, which is believed to play a pivotal role in linking TBI to the development of AD. This review delves into the intricate relationship between TBI and AD, with a focus on BBB dysfunction and its critical role in disease mechanisms and therapeutic development. We first present recent evidence from epidemiological studies highlighting the increased incidence of AD among individuals with a history of TBI, as well as pathological and animal model studies that demonstrate how TBI can accelerate AD-like pathology. Next, we explore the mechanisms by which BBB dysfunction may mediate TBI-induced AD pathology. Finally, we investigate the shared molecular pathways associated with BBB dysfunction in both TBI and AD conditions and discuss the latest findings on how targeting these pathways and employing regenerative approaches, such as stem cell therapy and pharmacological interventions, can enhance BBB function and mitigate neurodegeneration.
High-Potency Cannabis Use and Health: A Systematic Review of Observational and Experimental Studies
Authors: Stephanie Lake, Conor H. Murray, Brittany Henry, Liza Strong, Kendall White, Beau Kilmer, Ziva D. Cooper
Journal: American Journal of Psychiatry (2025)

Amid continuously rising concentrations of delta-9-tetrahydrocannabinol (THC) in cannabis (i.e., potency), high-potency cannabis is a major topic in contemporary cannabis policy discussions, yet its impact on health is not well understood. The authors conducted a systematic review of observational and experimental studies examining the relationship between high-potency cannabis use and a range of health outcomes. Records were obtained from a systematic search of five biomedical research databases. The authors developed ecologically relevant potency (percent THC) exposure-comparison categories (1%-9%, 10%-19%, 20%-30%, kief/resin [∼30%-50%], concentrates [≥60%]) and used a landmark scientific report on cannabis and cannabinoids to determine outcome eligibility. Two reviewers independently conducted article screening and selection, extraction, and quality assessment. Findings were synthesized using both quantitative (association direction, binomial test) and narrative approaches. Certainty in the evidence was determined via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Of 4,545 screened records, 42 were eligible. Most studies addressed outcomes in the mental health, "problem" cannabis use, and other substance use domains. Findings in the "problem" cannabis use domain were suggestive of an association with higher-potency cannabis use. Findings were less consistent in other domains but tended to favor poorer outcomes with higher-potency use. Therapeutic outcomes were limited and mixed. Overall, certainty in the evidence was "very low." Findings within the "problem" cannabis use domain were suggestive of an association with high-potency use. Research is largely limited to cross-sectional studies spanning few adverse health domains, underscoring the need for prospective studies probing therapeutic, cardiorespiratory, cancer, and pre- and perinatal outcomes. Policies to curb high-potency cannabis use may be warranted while the evidence base improves.