tbuckley/cabot-search huggingface dataset:
Swimming Exercise Pretreatment Attenuates Postoperative Delirium‐Like Behavior in Type 2 Diabetic Rats by Enhancing Mitochondrial Biogenesis Through Activation of SIRT2 Deacetylation
Authors: Kaixi Liu, Lei Chen, Xinning Mi, Qian Wang, Yitong Li, Jingshu Hong, Xiaoxiao Wang, Yue Li, Yanan Song, Yi Yuan, Jie Wang, Dengyang Han, Taotao Liu, Ning Yang, Xiangyang Guo, Zhengqian Li
Journal: MedComm (2025)

Postoperative delirium (POD) is a common postsurgical complication that seriously affects patients' prognosis and imposes a heavy burden on families and society. Type 2 diabetes mellitus (T2DM) is a major risk factor for POD. The susceptibility mechanisms of POD in T2DM individuals and the role of exercise preconditioning remain unclear. Adult rats with and without T2DM were used to assess the promotive effect of diabetes on postoperative delirium-like behavior. The diabetic rats were also subjected to a swimming exercise program before surgery. The potential beneficial effect of exercise preconditioning on postoperative cognition was evaluated by examining neurobehavior, hippocampal neuroinflammation, mitochondrial morphology, and function in diabetic rats. Finally, underlying mechanisms were further analyzed by exploring the role of the sirtuin family in vivo and in vitro. We found that performing tibial fracture surgery resulted in delirium-like behavior and inhibited hippocampal mitochondrial biogenesis in diabetic rats but not in healthy rats. Preoperative swimming exercise was beneficial in attenuating delirium-like behavior, inhibiting neuroinflammation, and improving mitochondrial biogenesis and function. Preoperative swimming exercise achieved these positive effects by upregulating SIRT2-mediated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) deacetylation and activating mitochondrial biogenesis in T2DM rats.
Mitigating Early Phosphatidylserine Exposure in a Tmem30a‐Dependent Way Ameliorates Neuronal Damages After Ischemic Stroke
Authors: Chuanjie Wu, Jiaqi Guo, Yunxia Duan, Jiachen He, Shuaili Xu, Guiyou Liu, Chen Zhou, Yuchuan Ding, Xianjun Zhu, Xunming Ji, Di Wu
Journal: MedComm (2025)

ABSTRACT Phosphatidylserine (PS) exposes to the outer plasma membrane after a pathological insult (e.g., stroke) but not under normal conditions whereby PS remains within the inner plasma membrane. However, the reversibility and translational potential of PS exposure in damaged cells after stroke are still unknown. Here, we demonstrated that plasma Annexin V, which has a high affinity to membranes bearing PS, was increased in patients with salvage penumbra after endovascular therapy, and associated with early neurological improvement. Moreover, Annexin V treatment could decrease PS exposure and mitigate neurological impairments in transient ischemia/reperfusion mouse models, but not in permanent ischemia. Furthermore, we used a combination of cell, rodent, and nonhuman primate ischemia/reperfusion models and found that transmembrane protein 30A (Tmem30a) was increased in the ischemic penumbra after stroke and imperative for less PS exposure and better neurological functions. Mechanistically, mitigation of PS exposure mediated by Tmem30a/Annexin V connection led to decreased expression of apoptosis and necroptosis markers in neurons of penumbra. Overall, our findings reveal a previously unappreciated role of reducing PS exposure by Annexin V treatment in protecting the penumbra in a clinically relevant ischemia/reperfusion model. Tmem30a is essential for reducing PS exposure in the penumbra after ischemic stroke.
Nanomedicines for cardiovascular diseases: lessons learned and pathways forward
Authors: Yi-An Mao, Xiaozhou Shi, Pingyuan Sun, Michail Spanos, Liyun Zhu, Hang Chen, Xiya Wang, Chanyuan Su, Yanjia Jin, Xu Wang, Xuerui Chen, Junjie Xiao
Journal: Biomaterials (2025)
Consternation as Congress proposal for autonomous prescribing AI coincides with the haphazard cuts at the FDA
Authors: Stephen Gilbert, Tinglong Dai, Rebecca Mathias
Journal: npj Digital Medicine (2025)

We live in interesting regulatory times. In January, a bill was introduced to the US Congress proposing that AI "can qualify as a practitioner eligible to prescribe drugs" if overseen by the States and FDA. This a bold and contentious move. Even proponents of AI's swift integration into medicine must recognize the deep paradox: this proposal emerges even as the FDA's world-leading infrastructure for AI oversight faces dismantling.
Sex Differences in B Cells from the Joints of Children with Oligoarticular Juvenile Idiopathic Arthritis
Authors: Ki Pui Lam, Claudia Harris, Maria L Taylor, Daniela Fernandez‐Salinas, Jing Cui, Biju Issac, Liang Sun, Indu Raman, Chengsong Zhu, Maryrose Hahn, Maryam Ashoor, Ahmad Bakhsh, Maria C Bryant, Siobhan Case, Mia Chandler, Joyce C Chang, Ezra Cohen, Fatma Dedeoglu, Olha Halyabar, Jonathan S Hausmann, Melissa Hazen, Daniel Ibanez, Liyoung Kim, Jeffrey Lo, Mindy S Lo, Esra Meidan, Megan Perron, Helene Powers, Mary Beth Son, Holly Wobma, Erin Janssen, Pui Y Lee, Peter A Nigrovic, Laurie Ohlms, A Eliot Shearer, Margaret H Chang, Maria Gutierrez‐Arcelus, Lauren A Henderson
Journal: Arthritis & Rheumatology (2025)

Objective Disordered T peripheral helper (Tph)‐B cell interactions have been implicated in several forms of inflammatory arthritis, including oligoarticular juvenile idiopathic arthritis (oligo JIA). We sought to evaluate the Tph‐B cell axis in oligo JIA through an analysis of intra‐articular B cells. Methods B cells from the blood and synovial fluid (SF) of 44 children with oligo JIA were compared to those from the blood and tonsils of controls. Flow cytometry, B cell receptor (BCR) repertoire analysis, and autoantibody profiling were used to characterize B cells. Results Memory B (Bmem) cells and heterogeneous subsets of CD21 lo B cells were enriched in oligo JIA SF vs. blood of patients and controls. Compared to male patients, females with oligo JIA had greater proportions of intra‐articular Tph cells that expressed B cell help factors as well as Bmem, plasmablasts, and age/autoimmune‐associated B cells. The sex differences in B cells were observed only in the joints and not found in the blood or tonsil nor were they explained by other disease features such as age of onset, ANA status, or severity. Bmem cells in female SF displayed characteristics of autoreactivity, including longer CDR3 lengths and increased usage of autoreactive BCR gene segments, which were not found in blood Bmem cells. A diverse array of autoantibodies accumulated in the SF of females with oligo JIA compared to blood of JIA patients and controls. Conclusions These findings demonstrate prominent B cell dysregulation in oligo JIA and implicate sex as an important biologic factor in B cell responses in this disease.
Efficacy and Tolerability of Low-Dose Versus High-Dose Doxycycline in the Management of Lymphocytic Scarring Alopecias
Authors: Carli Needle, Anna Brinks, Akshay Pulavarty, Caitlin Kearney, Ambika Nohria, Deesha Desai, Jerry Shapiro, Kristen Lo Sicco
Journal: Journal of the American Academy of Dermatology (2025)
Upfront lipid-lowering combination therapy in high cardiovascular risk patients: a route to effective atherosclerotic cardiovascular disease prevention
Authors: Maciej Banach, Stanisław Surma, Tomasz J Guzik, Peter E Penson, Michael J Blaha, Fausto J Pinto, Laurence S Sperling
Journal: Cardiovascular Research (2025)

Abstract Despite three decades of using statin therapy, 20 years of experience with ezetimbe, and availability of innovative non-statin lipid lowering therapies (LLT), there are still about 70% patients over the low-density lipoprotein cholesterol (LDL-C) goal, with every 5-6th being over the target from the group of very high and extremely high cardiovascular disease (CVD) risk patients. Adding another even every 5th patient at very high CVD risk without any LLT, makes this situation highly frustrating, especially lipid disorders are the most common CVD risk factor with the prevalence of over 60%, with the worst awareness within all cardiovascular risk factors (only about 15% people knows their LDL-C level). To answer this since 2021 there is an approach to apply upfront (immediate) lipid lowering combination therapy of statin and ezetimibe in very high and extremely high-risk patients to be on the LDL-C target as low as possible, but especially as early as possible, enabling to introduce the third line therapy (i.e., bempedoic acid and/or PCSK9 targeted therapy) already after 4-6 weeks. This review discusses the current stage of knowledge and recent data on the group of patients that might benefit the most from the upfront combination LLT, when it should be optimally implemented, and the recent data on its role on LDL-C reduction, cardiovascular and mortality outcomes as well as safety issues.
Unusual 131I Uptake in the Right Sternocleidomastoid Muscle After Parathyroid Transplantation on 131I Whole-Body Scintigraphy
Authors: Qiaoqiao Shu, Yaofeng Xiao, Yanyao Han, Maoxue Deng, Liang Cai
Journal: Clinical Nuclear Medicine (2025)

A 29-year-old woman with papillary thyroid cancer underwent thyroidectomy and parathyroid auto-transplantation. One month after surgery, the patient received radioiodine therapy. Two days after 131 I administration, localized 131 I uptake in the right sternocleidomastoid muscle was detected by post-therapy 131 I whole-body scintigraphy. We found that the 131 I uptake area was colocalized at the site of parathyroid transplantation.
Thyroid Tuberculosis Depicted by 18F-FAPI PET/CT
Authors: Yuhua Wang, Lei Zhang, Feifei Qiao, Wanchun Zhang
Journal: Clinical Nuclear Medicine (2025)

Thyroid tuberculosis is a rare condition that is difficult to diagnose and may be suspected of being a malignant tumor. We report a case of thyroid tuberculosis in a 54-year-old woman that mimicked thyroid cancer on ultrasound, with a 18 F-FAPI PET/CT scan showing intense 18 F-FAPI uptake in the thyroid lobe, right neck lymph node, and celiac lymph nodes.
Increased 68Ga-DOTATATE Uptake in Brown Adipose Tissue in a Case of Head and Neck Paraganglioma
Authors: Hongyuan Dai, Xiaohui Li, Minggang Su, Rui Huang
Journal: Clinical Nuclear Medicine (2025)

68 Ga-DOTATATE uptake in brown adipose tissue is rarely documented. Herein, we report a case of increased 68 Ga-DOTATATE uptake in brown adipose tissue at multiple locations, including mesenteric region, in a young woman with head and neck paraganglioma.
18F-FDG-avid Myelophthisis
Authors: Pipitsa N. Valsamaki, Konstantinos Liapis, Savvas Deftereos
Journal: Clinical Nuclear Medicine (2025)

Disseminated 18 F-FDG-avid intraosseous lesions and clumps of malignant signet-ring cells on subsequent bone marrow aspirate were detected upon investigation of a 58-year-old man with intolerable bone pain, normocytic anemia, and elevated serum ﻿alkaline phosphatase. Immunohistochemistry and gastroscopic biopsy confirmed mucin-rich signet-ring cell adenocarcinoma [signet-ring cell gastric carcinoma (SRGC)]. Intriguingly, synchronous bone secondaries from SRGC tend to be hypermetabolic, regardless of the primary tumor 18 F-FDG-negativity, insinuating a reverse heterogeneity of tumor molecular biology. The identification of 18 F-FDG-avid myelophthisis on the setting of bone pain constitutes a caveat for suspicion of cancerous lesions from SRGC and should urge for bone marrow biopsy to improve treatment implications.
Historical aspects of testicular function: virility, androgen production and spermatogenesis
Authors: Alan D Rogol, Marco Cappa
Journal: Endocrine Reviews (2025)

Abstract From antiquity, Man has been fascinated by at least two processes of testicular function: virility and reproduction; their biological basis was uncovered beginning in the mid-19th century. We have divided the search into 3 epochs: the speculative and observational, the experimental, and the biochemical/physiological. The first begins with Susruta, approximately 3,000 years ago and winds its way through the Greek, Roman, the Christian Bible, Arabic, Chinese, and Indian pathways before coalescing in Europe at the dawn of the Renaissance. The second began withThomas Willis who postulated a virilizing factor from the testis. A century later de Bordeu hypothesized a neurosecretory function for the hypothalamus/pituitary. After John Hunter began to study testis implantation, it was Berthold who showed a secretory function of the testis following implantation. Charles-Éduard Brown-Séquard focused the medical and lay communities on the testis secretion with self-experimentation with animal testis extracts leading to more than four decades of uncertainty in the newly-launched science of endocrinology. Multiple series of testicular implants and vas deferens ligations for the purposes of rejuvenation of older men followed. The medical experimentation continued in the biochemical/physiological epoch where androgenic steroids were isolated, purified, identified, synthesized and used in clinical trials. The effects of castration, some known from antiquity were placed on a modern scientific basis with studies of the Skoptzy, a self-castrating sect from Russia and the castrati opera singers. Details of hypothalamic-pituitary-gonadal axis function as well as the embryology of male sexual differentiation and spermatogenesis were defined during this epoch.
Adherence to Follow-Up Lung Cancer Screening—A Critical Target for Intervention
Authors: Francesca C. Duncan, Matthew Triplette
Journal: JAMA Network Open (2025)

Roger Y. Kim, MD, MSCE; Katharine A. Rendle, PhD, MSW, MPH; Nandita Mitra, PhD; Christine Neslund-Dudas, PhD; Robert T. Greenlee, PhD, MPH; Stacey A. Honda, MD, PhD; Marilyn M. Schapira, MD, MPH; Michael J. Simoff, MD; Jihyoun Jeon, PhD, MS; Rafael Meza, PhD; Debra P. Ritzwoller, PhD; Anil Vachani, MD, MSCE
Phase I study of the mutant IDH1 inhibitor ivosidenib: long-term safety and clinical activity in patients with conventional chondrosarcoma
Authors: William D. Tap, Gregory M. Cote, Howard Burris, Lia Gore, Anthony Elias, Murali Beeram, Anthony P. Conley, Diego A. Gianolio, Zhe Qu, Susan Pandya, Jonathan C. Trent
Journal: Clinical Cancer Research (2025)

Abstract Purpose: A phase I study demonstrated that ivosidenib, a mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, showed manageable toxicity and durable disease control in patients with mIDH1 conventional chondrosarcoma (CS). Here we present long-term follow-up data on the safety and clinical activity of ivosidenib in patients with mIDH1 conventional CS from this phase I study. Patients and Methods: This phase I open-label dose-escalation and expansion study assessed ivosidenib monotherapy in patients with advanced mIDH1 solid tumors, including CS. An ivosidenib dose of 500 mg/day was identified in the dose-escalation phase and used for the expansion phase. The primary outcome was safety and tolerability. Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). The database lock date for this analysis was 18 March 2024. Results: Of 168 patients with advanced mIDH1 solid tumors receiving ivosidenib in this study, 21 patients had CS, of which 13 had conventional histology. Six (46.2%), 4 (30.8%) and 3 (23.1%) patients with conventional CS continued ivosidenib treatment for &amp;gt;1 year, &amp;gt;6 years and &amp;gt;7 years, respectively. Of the 21 patients with CS, 71.4% and 28.6% had treatment-related and serious adverse events (SAEs), respectively, but no SAEs were considered related to ivosidenib. The ORR for patients with conventional CS was 23.1% and median duration of response was 53.5 months. The median PFS of patients with conventional CS treated with ivosidenib was 7.4 months. Conclusions: Ivosidenib demonstrated long-term disease control and manageable toxicity for some patients with mIDH1 conventional CS and is under further investigation (NCT06127407).
Sex differences in cardiac remodelling in ischaemic cardiomyopathy and functional mitral regurgitation: impact on prognosis
Authors: Duygu Kocyigit Burunkaya, Nancy A Obuchowski, Natalie Ho, Zoran B Popovic, David Chen, Christopher Nguyen, W H Wilson Tang, Deborah H Kwon
Journal:  (2025)

Sex differences in prognosis of functional mitral regurgitation (FMR) associated with ischaemic cardiomyopathy (ICM) demonstrate the need to identify sex differences in cardiac remodelling. This study aimed to characterize sex differences in cardiac remodelling associated with FMR in the setting of ICM, sex interactions with cardiac remodelling and FMR severity, and predictors of all-cause mortality or heart transplantation using cardiac magnetic resonance (CMR) imaging. Consecutive patients with ICM referred to CMR between 2002 and 2017 were reviewed. Eligible 790 patients [mean age: 62.0 (standard deviation = 11.2] years and 24.7% females] were evaluated over a median follow-up of 5.8 years. There were 773 subjects with complete data for survival analysis, with 449 primary events. Coronary artery disease risk factors, medications, and previous coronary revascularization were similar in females and males (all P > 0.05). Indexed left ventricular and right ventricular (LV and RV) volumes were larger in males (P < or =0.005 for all comparisons) with similar slope of increasing LV and RV volumes in the setting of increasing FMR (all P > 0.05, for interactions). However, indexed left atrial volume was similar in males and females (P = 0.696), after adjusting for FMR severity. After adjusting for medical risk factors and post-CMR procedural interventions, females demonstrated increased risk of primary clinical composite point with enlarging LV volumes [hazard ratio: 1.04 (95% confidence interval: 1.01-1.06), P = 0.034]. Because females with increasing LV size and FMR severity demonstrated significantly increased risk of adverse outcomes, our findings suggest the importance of deriving sex-specific CMR selection criteria for therapeutic management of FMR in the setting of ICM.
Biologically engineered valved conduits for right ventricular outflow tract repair evaluated for 52 weeks in growing lambs
Authors: Zeeshan H Syedain, Matthew Lahti, James Berry, John P Carney, Jill Schappa Faustich, Bee Haynie, Jack Maher, Richard Bianco, Gurumurthy Hiremath, John E Mayer, Robroy MacIver, Robert T Tranquillo
Journal: Cardiovascular Research (2025)

Abstract Aims Replacement heart valves that grow with children remain an unmet need. We previously reported valves fabricated from tubes of fibroblast-derived collagenous matrix increased in size while functioning with low systolic gradients and less than moderate regurgitation over 52 weeks in most cases, when implanted as interpositional grafts in the pulmonary artery of lambs. Here, we evaluated valved conduits fabricated by including an inflow segment to the tri-tube valve allowing for myocardial anastomosis as done in a typical right ventricular outflow tract (RVOT) surgical repair, in the same growing lamb model. Methods and results In this pilot study, 19 mm valved conduits fabricated from resorbable suture were implanted into Dorset lambs (n = 3), sutured to the pulmonary annulus and distal pulmonary artery with resorbable suture after dissection of the pulmonary valve leaflets and resection of an arterial segment. Valve function and dimensions were measured with longitudinal transthoracic echocardiography. All animals exhibited an increase in valve diameter (18.2 ± 1.8 mm at 1 week to 25.1 ± 2.4 mm at 52 weeks) and leaflet free-edge length (21.1 ± 2.4 mm at 1 week to 26.2 ± 3.9 mm at 52 weeks) while functioning with at most mild regurgitation over 52 weeks. The inflow segment of the conduit grew somatically based on its unchanged thickness and increased diameter (38%) and collagen content (128%). In all three explanted conduits, the leaflets contained interstitial cells, new collagen and elastin primarily around the base, a developing endothelium on the surfaces, and they remained thin and pliable without macroscopic calcification. There was interdigitating integration of the conduit with the myocardium at the pulmonary annulus. Further, a stent was successfully placed in a valved conduit at term to evaluate feasibility of a prospective clinical intervention. Conclusion This valved conduit grows in lambs based on this pilot study and thus has clinical potential for RVOT reconstruction and long-term valve growth in children.
An in-depth look at lung lymphatics
Authors: David G. Jackson
Journal: The Journal of Experimental Medicine (2025)

In this issue of JEM, Cleary et al. (https://doi.org/10.1084/jem.20241359) present a new intravital imaging technique using a 3D-printed window device that enables lung lymphatics and their participation in immune cell trafficking events to be visualized in action for the first time in mechanically ventilated mice.
Association of thigh intramuscular fat infiltration with incident knee and hip osteoarthritis: a longitudinal cohort study
Authors: Qianlin Weng, Ting Jiang, Tuo Yang, Yuqing Zhang, Weiya Zhang, Michael Doherty, Jie Wei, Yilun Wang, Guanghua Lei, Chao Zeng
Journal: Arthritis & Rheumatology (2025)

Objectives Intramuscular fat infiltration (IMFI) in the thigh is linked to metabolic inflammation and muscle dysfunction, which could contribute to osteoarthritis development. However, no longitudinal studies have examined the associations between thigh IMFI and incident knee and hip osteoarthritis. Methods We conducted a cohort study using UK Biobank data, including participants with baseline IMFI in thigh muscle assessed by magnetic resonance imaging and no history of knee or hip osteoarthritis. A total of 24,224 and 24,221 participants were included in analyses of IMFI of anterior and posterior thigh muscle with knee osteoarthritis, respectively, while 24,767 and 24,764 were included for hip osteoarthritis. Cox Proportional‐hazard models were used to estimate hazard ratios (HRs) for incident clinically diagnosed knee or hip osteoarthritis, adjusting for potential confounders. Results During a mean follow‐up of 4.8 years, 472 participants developed knee osteoarthritis, and 387 developed hip osteoarthritis. IMFI in the anterior thigh was significantly associated with incident knee osteoarthritis, with adjusted HRs of 1.78 (1.19‐2.65), 2.00 (1.34‐2.99), and 2.34 (1.53‐3.59) across the second to fourth quartiles, respectively ( P for trend &lt;0.01). Both anterior and posterior thigh IMFI were significantly associated with hip osteoarthritis (both Ps for trend &lt;0.01). Dose‐response relationships were observed in restricted spline models. The interaction and subgroup analyses support that the effect of IMFI is independent of body mass index and sex. Conclusions Elevated thigh IMFI is significantly associated with increased incidence of both knee and hip osteoarthritis. Interventions targeting IMFI reduction may help prevent osteoarthritis and mitigate its impact.
AI-driven framework to map the brain metabolome in three dimensions
Authors: Xin Ma, Cameron J Shedlock, Terrymar Medina, Roberto A Ribas, Harrison A Clarke, Tara R Hawkinson, Praveen K Dande, Hari K R Golamari, Lei Wu, Borhane Ec Ziani, Sara N Burke, Matthew E Merritt, Craig W Vander Kooi, Matthew S Gentry, Nirbhay N Yadav, Li Chen, Ramon C Sun
Journal: Nature Metabolism (2025)