tbuckley/cabot-search huggingface dataset:
Looking Back, Moving Forward—Reflecting on a Career in Psychiatric Research
Authors: Charles F. Reynolds
Journal: JAMA Psychiatry (2025)

The arc of my career has focused on the integration of clinical care, mentoring, and research, leading to meaningful research questions and intervention trials advancing the field. In this Special Communication, I first offer a brief synopsis of my work as an academic psychiatrist, highlighting mission, themes and publications, sponsors, and collaborators. I then discuss activities as a mentor, focusing on 2 National Institute of Mental Health (NIMH)–funded research career development programs. As the past recipient of K01, K02, and K05 awards from the NIMH (1980-2000), I have taken to heart the obligation to pay it forward: to support, advise, instruct, and guide younger colleagues, challenging them academically and professionally. For 20 years, my P30 infrastructure center grant provided a platform for institutional training grants (T32s) and psychiatric research education grants (R25s) to serve as a foundation for training the next generation of clinical scientists in late life mood disorders, as well as a nidus for interdisciplinary collaboration. I have benefitted greatly from having had mentors and wise friends, particularly David Kupfer, MD; Ellen Frank, PhD; and Thomas Detre, MD, of the University of Pittsburgh School of Medicine; colleagues in the Aging Branch of NIMH throughout my 40-year career as a physician scientist; Dilip Jeste, MD, University of California at San Diego; Daniel Blazer, MD, PhD, Duke University School of Medicine; George Alexopoulos, MD, Weill Cornell School of Medicine; John Rush, MD, University of Texas Southwestern School of Medicine; Alan Schatzberg, MD, Stanford University School of Medicine; M. Katherine Shear, MD, Columbia University Schools of Social Work and of Medicine; Helena Kraemer, PhD, Stanford University School of Medicine; and Edmund Ricci, PhD, University of Pittsburgh Graduate School of Public Health. These colleagues are good listeners, flexible, diverse in perspectives, knowledgeable, nonjudgmental, and able to give constructive feedback, network, and help find resources. I have sought to do likewise with many younger colleagues, both men and women, physicians and PhDs, and persons of different professional, racial, and ethnic backgrounds—totaling about 25 K awardees. I conclude with recommendations for future clinical practice and research in late-life depression, describing a broad spectrum of approaches aiming both to reduce its public health burden and to enhance wisdom, resilience, and well-being in later life.
National Incidence of Physician Suicide and Associated Features
Authors: Hirsh Makhija, Judy E. Davidson, Kelly C. Lee, Arianna Barnes, Amanda Choflet, Sidney Zisook
Journal: JAMA Psychiatry (2025)

Importance Previous reports regarding comparative suicide incidence among US physicians vs nonphysicians have been inconclusive. Objective To estimate the national incidence of male and female physician suicide and analyze associated factors, comparing findings to the general population. Design, Setting, and Participants This retrospective cohort study investigated suicides among physicians and nonphysicians aged 25 years and older in the US from January 2017 to December 2021. The analysis took place from November 2023 to September 2024. National Violent Death Reporting System data from 30 US states and Washington, DC, were used. Decedents with missing age or sex were excluded for incidence, and missing race, ethnicity, or marital status for further analyses. Exposure Physician occupation. Main Outcome and Measures Suicide incidence rate ratios (IRRs) and odds ratios (aORs) adjusted by age, sex, race, ethnicity, and marital status were used to compare preceding circumstances, primary method, and substances. Results A total of 448 physician (354 [79%] male and 94 [21%] female; mean [SD] age, 60 [16] years) and 97 467 general population (76 697 [79%] male and 20 770 [21%] female; mean [SD] age, 51 [17] years) suicides were identified. Female physicians had higher rates of suicide than female nonphysicians in 2017 (IRR, 1.88; 95% CI, 1.19-2.83) and 2019 (IRR, 1.75; 95% CI, 1.09-2.65), with overall higher 2017 to 2021 suicide risk (IRR, 1.53; 95% CI, 1.23-1.87). Male physicians had lower 2017 to 2021 suicide risk than male nonphysicians (IRR, 0.84; 95% CI, 0.75-0.93). Compared to the general population and including all available jurisdiction data, physicians had higher odds of depressed mood (aOR, 1.35; 95% CI, 1.14-1.61; P &amp;amp;lt; .001) as well as mental health (aOR, 1.66; 95% CI, 1.39-1.97; P &amp;amp;lt; .001), job (aOR, 2.66; 95% CI, 2.11-3.35; P &amp;amp;lt; .001), and legal (aOR, 1.40, 95% CI, 1.06-1.84; P = .02) problems preceding suicide as well as use of poisoning (aOR, 1.85; 95% CI, 1.50-2.30; P &amp;amp;lt; .001) and sharp instruments (aOR, 4.58; 95% CI, 3.47-6.06; P &amp;amp;lt; .001). Physicians also had higher odds of positive toxicology for caffeine; poison; cardiovascular agents; benzodiazepines; anxiolytics, nonbenzodiazepines, or hypnotics; and drugs not prescribed for home use. Conclusion and Relevance These findings show a higher incidence of suicide for US female physicians compared to female nonphysicians. Comprehensive and multimodal suicide prevention strategies remain warranted.
Race and Ethnicity, Lifestyle, Diet, and Survival in Patients With Prostate Cancer
Authors: Anqi Wang, Erin L. Van Blarigan, Iona Cheng, June M. Chan, Peggy Wan, Song-Yi Park, Wei Xiong, Ann S. Hamilton, Fei Chen, Loic Le Marchand, Lynne R. Wilkens, David V. Conti, Stacey A. Kenfield, Christopher A. Haiman
Journal: JAMA Network Open (2025)

Importance Prostate cancer (PCa) remains a leading cause of cancer-related death among men in the US. Objective To evaluate the association of healthy lifestyle and dietary behaviors with survival after a nonmetastatic PCa diagnosis in a multiethnic population. Design, Setting, and Participants This prospective cohort study was conducted among men aged 45 to 75 years enrolled between 1993 and 1996 in the Multiethnic Cohort study. Participants with nonmetastatic PCa completed a questionnaire after diagnosis (2003-2008) and were followed up until death or loss to follow-up. Data were analyzed from January 10, 2023, to May 20, 2024. Exposures Lifestyle and dietary patterns were assessed after diagnosis using 3 PCa behavior scores and 13 dietary indices (4 prioritized scores: the Healthy Eating Index–2015, Healthful Plant-Based Diet Index, Dietary Inflammatory Index, and Empirical Dietary Index for Hyperinsulinemia). Main Outcomes and Measures Cox proportional hazards models were used to evaluate multivariable-adjusted associations of each PCa behavior score with all-cause, cardiovascular disease (CVD), and PCa-specific mortality. Results A total of 2603 men with nonmetastatic PCa (mean [SD] age, 69.6 [7.1] years) were followed up, and 1346 deaths were documented, including 356 (24.6%) from CVD and 197 (14.6%) from PCa. The median (IQR) follow-up was 10.9 (IQR, 6.8-12.7) years from questionnaire return and 14.5 (IQR, 11.8-18.0) years from diagnosis. The 2021 PCa Behavior Score was associated with reduced risks of all-cause (hazard ratio [HR] per point, 0.69; 95% CI, 0.63-0.77) and CVD-related (HR, 0.67; 95% CI, 0.56-0.79) mortality. This score was also associated with a lower risk of PCa-specific mortality among African American men (HR, 0.46; 95% CI, 0.24-0.88) but not in the other racial and ethnic groups. Comparing quintile 5 (highest score) with 1 (lowest score), the Empirical Dietary Index for Hyperinsulinemia was positively associated with all-cause (HR, 1.37; 95% CI, 1.02-1.84) and CVD-related (HR, 1.96; 95% CI, 1.15-3.33) mortality, whereas the Healthful Plant-Based Diet Index was associated with a reduced risk of all-cause (HR, 0.75; 95% CI, 0.58-0.97); findings for CVD-related mortality were not statistically significant (HR, 0.67; 95% CI, 0.44-1.03). No associations were found between lifestyle or dietary patterns and PCa mortality. Conclusions and Relevance In this multiethnic cohort of patients with nonmetastatic PCa, healthier lifestyles were associated with improved overall survival but not with PCa-specific survival. Given the predominance of non–PCa-specific deaths, these findings support the need for health behavior counseling to treat comorbidities in men with PCa.
Implicit Racial Bias and Unintentional Harm in Vascular Care
Authors: Corey A. Kalbaugh, Erika T. Beidelman, Kerry A. Howard, Brian Witrick, Ashley Clark, Katharine L. McGinigle, Samantha Minc, Olamide Alabi, Caitlin W. Hicks, Andrew A. Gonzalez, Crystal W. Cené, Samuel Cykert
Journal: JAMA Surgery (2025)

Importance Implicit bias may influence physician treatment decisions and contribute to Black-White health disparities. There are limited data linking implicit bias with actual care delivery and outcomes. Objective To determine whether implicit racial bias is associated with potentially harmful surgical treatment selection for a cohort of patients with peripheral artery disease–related claudication. Design, Setting, and Participants This survey study, linked with observational registry data, included eligible clinicians who participate in the Vascular Quality Initiative (VQI) among 960 centers. The VQI includes academic medical centers, teaching hospitals, community hospitals, and private practices. Eligible participants included all vascular specialist VQI members (N = 2512), of whom 218 completed the race implicit association test (IAT) and were linkable to procedure-level data. The study was conducted between October 2021 and October 2022. Exposure Race IAT. Main Outcomes and Measures Clinician-level implicit bias results were linked to patient-level registry data of peripheral revascularization procedures performed for claudication. The adjusted odds of performance of any infrapopliteal procedure by specialist implicit bias and patient race were measured via mixed-effects logistic regression models. Implicit bias as a moderator of the association of infrapopliteal procedures for claudication and patient race with 1-year amputation was assessed as a secondary outcome. Results Among 218 vascular specialists (mean [SD] age, 46 [9] years; 160 [73%] male), 157 (72%) had a pro-White bias. Black patients treated by a physician with pro-White bias had a significant increase in the odds of receiving an infrapopliteal procedure compared with the total sample (adjusted odds ratio [AOR], 1.67; 95% CI, 1.12-2.48). When treated by a specialist with pro-White bias, Black patients had increased odds of 1-year amputation, regardless of anatomic location treated, compared with White patients (AOR, 2.34; 95% CI, 1.20-4.55). Conversely, Black patients treated by a specialist with no bias had similar odds of an infrapopliteal procedure (AOR, 0.93; 95% CI, 0.68-1.26) as the full patient sample and similar odds of 1-year amputation (AOR, 1.29; 95% CI, 0.33-4.99) as White patients. Conclusions and Relevance These findings indicate that implicit bias is associated with potentially harmful infrapopliteal procedures for Black patients and contributes to Black-White outcome disparities in the US. These results suggest the need for system-level interventions that transparently identify and warn of procedures not aligned with best practices to reduce the negative influence of implicit bias.
Hsa_circ_0125356 promotes gemcitabine resistance by modulating WNT canonical and non-canonical pathways via miR-582-5p/FGF9 axis in non-small cell lung cancer
Authors: Xinyue Du, Weijie Luo, Hongwu Li, Qi Gu, Ping Huang, Cheng Wang, Na Li, Fanglan Liu, Chunhua Xia
Journal: Molecular Cancer (2025)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide. The prognosis of patients has been significantly improved by chemotherapy, but acquired drug resistance remains a major obstacle to NSCLC treatment. Circular RNAs (circRNAs), which act as miRNA or protein sponges, are critically associated with the development and chemotherapy resistance of NSCLC. CircRNA sequencing was performed to analyze the differential expression of circRNAs between A549 and A549-GR cells. Chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) technologies were used to detect the expression of hsa_circ_0125356, miR-582-5p,and FGF9 in NSCLC tissues and para-carcinoma tissues. Fluorescence in situ hybridization (FISH), dual-luciferase reporter assays and RNA immunoprecipitation (RIP) were conducted to evaluate the expression and regulation of hsa_circ_0125356, miR-582-5p, and FGF9. Furthermore, the regulation of hsa_circ_0125356/miR-582-5p/FGF9 on gemcitabine sensitivity was confirmed by TUNEL, Transwell, EdU, CCK8 and immunohistochemistry. We identified a novel hsa_circ_0125356 as a therapeutic target against gemcitabine resistance. Hsa_circ_0125356 was significantly elevated in clinical samples of patients with NSCLC. Moreover, hsa_circ_0125356 overexpression promoted gemcitabine resistance to NSCLC by upregulating FGF9 via sponging miR-582-5p in vivo and in vitro. Notably, WNT canonical (ERK/GSK3β/β-catenin) and non-canonical (Daam1/RhoA/ROCK2) signaling pathways were activated due to hsa_circ_0125356 acting as an endogenous miR-582-5p sponge to regulate the expression of FGF9, and thereby enhancing gemcitabine resistance via promoting DNA damage repair and inhibition of apoptosis. The results were further confirmed by two small molecule antagonists, WAY 316606 and XAV-939,which could inhibit the activation of WNT signaling pathway induced by hsa_circ_0125356. We first demonstrated that hsa_circ_0125356 was significantly upregulated and served as a biomarker for gemcitabine resistance in NSCLC by sponging miR-582-5p/FGF9 axis to regulate the WNT canonical and non-canonical signaling pathways, which provided a new direction for identification of therapeutic targets for the treatment of gemcitabine resistance of NSCLC.
Global burden of malaria and neglected tropical diseases in children and adolescents, 1990–2019: a population-based, cross-sectional study
Authors: Jinxin Zheng, Daoqi Zhang, Shunxian Zhang, Muxin Chen, Zhaoyu Guo, Shiyang Guan, Yushu Liu, Robert Bergquist, Shizhu Li, Xiaonong Zhou, Xinyu Feng
Journal: Journal of the Royal Society of Medicine (2025)

Objectives To estimate the global burden of malaria and neglected tropical diseases (NTDs) in children and adolescents aged 0–19 years and to analyse trends to inform public health and policy decisions. Design Population-based, cross-sectional study. Setting Global analysis across 204 countries and territories. Participants Children and adolescents aged 0–19 years with malaria and NTDs, stratified by age, gender and location from 1990 to 2019. Main outcome measures Yearly incidence, prevalence, and disability-adjusted life years (DALYs) for malaria and NTDs, age-standardised incidence rates (ASIRs) and age-standardised DALY rates (ASDRs). Results The global burden of malaria and NTDs among children and adolescents aged 0–19 years remains substantial. In 2019, 195.6 million cases of malaria and NTDs were recorded globally, resulting in 43.9 million (95% Uncertainty Interval (UI): 25.0–70.4 million) DALYs. The incidence rate increased until 2005 and then declined. Sub-Saharan Africa had the highest ASDR, while high-income regions had the lowest. Significant ASDR reductions occurred in Andean Latin America and South Asia. The burden was highest in low-Socio-Demographic Index (SDI) regions, with malaria accounting for over 93% of DALYs among children under five. Females had slightly higher incidence rates, while DALYs were evenly distributed between genders. There was an inverse association observed between SDI and ASDRs. Conclusions Malaria and NTDs continue to disproportionately affect children and adolescents in low-SDI regions, especially sub-Saharan Africa. Sustaining gains while accelerating control efforts is the key to successful control progress and ambiguous elimination goals for both malaria and NTDs.
A bladder-blood immune barrier constituted by suburothelial perivascular macrophages restrains uropathogen dissemination
Authors: Lu Li, Qiancheng Jiao, Qianqian Yang, Haisen Lu, Xia Zhou, Qing Zhang, Futing Zhang, Hai Li, Zhigang Tian, Zhutian Zeng
Journal: Immunity (2025)

Urinary tract infections (UTIs) predominantly occur in the bladder and can potentially progress into life-threatening sepsis if uropathogens spread unconstrainedly into the bloodstream. Here, we identified a subset of suburothelial perivascular macrophages (suPVMs) in the bladder that exerted a pivotal barrier function to prevent systemic bacterial dissemination during acute cystitis. During the initial phase of uropathogenic Escherichia coli (UPEC) infection, suPVMs actively captured UPEC invading the laminal propria and maintained the integrity of inflamed vessels. They subsequently underwent METosis to expel macrophage extracellular DNA traps (METs) into the urothelium to sequester bacteria within this avascular compartment. Matrix metallopeptidase-13 was released along with METs to promote neutrophil transuroepithelial migration. Replenished suPVMs from monocytes following a prior infection were functionally competent to confer protection against recurrent UTIs. Our study thus uncovers a bladder-blood immune barrier in restraining uropathogen dissemination, which could have implications for the prevention and treatment of urosepsis.
Macrophage-derived CTSS drives the age-dependent disruption of the blood-CSF barrier
Authors: Yifan Chen, Yifei Zhou, Yaqing Bai, Kaiwen Jia, Hao Zhang, Qingxia Chen, Mengjiao Song, Yumin Dai, Jiantao Shi, Zhengjun Chen, Xiumin Yan, Yidong Shen
Journal: Neuron (2025)
EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis
Authors: Fanglin Ma, Miriam Longo, Marica Meroni, Dipankar Bhattacharya, Erika Paolini, Shama Mughal, Syed Hussain, Sumit Kumar Anand, Neha Gupta, Yiwei Zhu, Amaia Navarro-Corcuera, Kenneth Li, Satya Prakash, Bruno Cogliati, Shuang Wang, Xin Huang, Xiaobo Wang, Arif Yurdagul, Oren Rom, Liheng Wang, Susan K Fried, Paola Dongiovanni, Scott L Friedman, Bishuang Cai
Journal: Cell Metabolism (2025)
Engineering Nanoallergens to Investigate Origins of Immunogenicity and Cross-Reactivity in Cephalosporin Allergy
Authors: Emily K Bromley, Jenna N Sjoerdsma, Caitlin L Horgan, Scott A Smith, David A Khan, Elizabeth J Phillips, Kimberly G Blumenthal, Cosby A Stone, Basar Bilgicer
Journal: Journal of Allergy and Clinical Immunology (2025)
Hepatic sphingomyelin phosphodiesterase 3 promotes steatohepatitis by disrupting membrane sphingolipid metabolism
Authors: Jie Jiang, Yuqing Gao, Jiang Wang, Yan Huang, Rong Yang, Yongxin Zhang, Yuandi Ma, Yingquan Wen, Gongkai Luo, Shurui Zhang, Yutang Cao, Minjun Yu, Qinxue Wang, Shulei Hu, Kanglong Wang, Xiaozhen Guo, Frank J Gonzalez, Yameng Liu, Hong Liu, Qing Xie, Cen Xie
Journal: Cell Metabolism (2025)
Cutaneous Ceramide Synthesis is Dysregulated in Pediatric Eosinophilic Esophagitis
Authors: Elena Goleva, Donald Y Leung, Kira Chaiboonma, Wynnis Tom, Ranjan Dohil, Katherine Lyubchenko, Irina Bronova, Anna-Sofia Bronoff, Evgeny Berdyshev, Seema S Aceves
Journal: Journal of Allergy and Clinical Immunology (2025)
BACE1-dependent cleavage of GABAA receptor contributes to neural hyperexcitability and disease progression in Alzheimer’s disease
Authors: Danlei Bi, Hong Bao, Xiaoli Yang, Zujun Wu, Xiaoxu Yang, Guangwei Xu, Xiaoming Liu, Zhikun Wan, Jiachen Liu, Junju He, Lang Wen, Yuying Jing, Ruijie Zhu, Zhenyu Long, Yating Rong, Dongxu Wang, Xiaoqun Wang, Wei Xiong, Guangming Huang, Feng Gao, Yong Shen
Journal: Neuron (2025)
So Close, and Yet… Plasma HPV DNA Detection of Recurrent HPV Oropharynx Cancer
Authors: Joseph A. Califano
Journal: Clinical Cancer Research (2025)

Abstract Plasma human papilloma virus (HPV) DNA is a biomarker closely associated with HPV-mediated oropharynx cancer recurrence. This CCR Translations discusses the potential utility of plasma HPV DNA in predicting HPV oropharynx cancer recurrence, and the challenges of application to clinical practice.
Mechanically Affected Lung and Progression of Emphysema
Authors: Surya P Bhatt, Sandeep Bodduluri, Joseph M Reinhardt, Arie Nakhmani
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Most emphysema is believed to arise from small airways disease, but recent data suggest emphysema begets more emphysema and that its progression may be due to the mechanical stress experienced by normal lung regions adjacent to existing emphysema. To determine whether new emphysema arises from this penumbra of mechanically affected lung (MAL) or from small airways disease. We co-registered inspiratory chest computed tomography (CT) scans acquired at enrollment and 5 years later in 4,972 participants enrolled in a multicenter cohort. Using adaptive Gaussian smoothing, we quantified the 3D effect of all emphysema clusters on adjacent normal voxels by assuming that the mechanical effect of each emphysema cluster on surrounding voxels depends on cluster size and decays with increasing distance. The cumulative mechanical effect on each voxel was used to calculate MAL. Based on the probability distribution of normal voxels progressing to emphysema, we classified voxels into High (≥10.5), Intermediate (>0 to <10.5), and Zero MAL. We co-registered baseline inspiratory and expiratory CT images to quantify functional small airways disease. We quantified the proportion of new emphysema arising from each risk region. In adjusted analyses, higher MAL was associated with faster FEV1 decline (-2.2 ml/year, 95%CI -2.6 to -1.7; p<0.001) and emphysema progression (-0.14 g/L/year, 95%CI -0.16 to -0.12; p<0.001), and greater all-cause mortality (adjusted hazards ratio = 1.07, 95%CI 1.05-1.09; p<0.001). The relative mean contributions of high and intermediate MAL to new emphysema were 60.5% and 37.1%, respectively, in contrast to zero MAL (2.4%) and small airways disease (4.8%). Most new emphysema arises from areas of high MAL and in substantially higher proportion than areas of small airways disease.
Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways
Authors: Meiyu Shang, Jingwen Ning, Caixia Zang, Jingwei Ma, Yang Yang, Zhirong Wan, Jing Zhao, Yueqi Jiang, Qiuzhu Chen, Yirong Dong, Jinrong Wang, Fangfang Li, Xiuqi Bao, Dan Zhang
Journal: Acta Pharmaceutica Sinica B (2025)
Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype
Authors: Chao Chen, Hongxia Zhang, Lingling Qi, Haoqi Lei, Xuefei Feng, Yingjie Chen, Yuanyuan Cheng, Defeng Pang, Jufeng Wan, Haiying Xu, Shifeng Cao, Baofeng Yang, Yan Zhang, Xin Zhao
Journal: Acta Pharmaceutica Sinica B (2025)
Thermal proteome profiling (TPP) reveals NAMPT as the anti-glioma target of phenanthroindolizidine alkaloid PF403
Authors: Fangfei Li, Zhaoxin Zhang, Qinyan Shi, Rubing Wang, Ming Ji, Xiaoguang Chen, Yong Li, Yunbao Liu, Shishan Yu
Journal: Acta Pharmaceutica Sinica B (2025)
Navigating the Brain: Harnessing Endogenous Cellular Hitchhiking for Targeting Neoplastic and Neuroinflammatory Diseases
Authors: Suraj S. Wagh, Paras Famta, Saurabh Shah, Ganesh Vambhurkar, Giriraj Pandey, Anupama Sikder, Gurpreet Singh, Shalini Shukla, Abhishek Sharma, Sajja Bhanu Prasad, Akshay Shinde, Rahul Kumar, Nitin Pal Kalia, Rajeev Singh Raghuvanshi, Saurabh Srivastava
Journal: Asian Journal of Pharmaceutical Sciences (2025)