tbuckley/cabot-search huggingface dataset:
Gender Disparities and Lung Cancer Screening Outcomes Among Individuals Who Have Never Smoked
Authors: Yeon Wook Kim, Dong-Hyun Joo, So Yeon Kim, Young Sik Park, Sowon Jang, Jong Hyuk Lee, Gerard A. Silvestri, Marjolein A. Heuvelmans, Jihang Kim, Hyeontaek Hwang, Choon-Taek Lee
Journal: JAMA Network Open (2025)

Importance Lung cancer in individuals who have never smoked (INS) is a growing global concern, with a rapidly increasing incidence and proportion among all lung cancer cases. Particularly in East Asia, opportunistic lung cancer screening (LCS) programs targeting INS have gained popularity. However, the sex-specific outcomes and drawbacks of screening INS remain unexplored, with data predominantly focused on women. Objective To compare LCS outcomes between Asian women and men with no smoking history. Design, Setting, and Participants This multicenter cohort study was conducted at health checkup centers in South Korea from 2009 to 2021. Participants included individuals aged 50 to 80 years with no smoking history who underwent low-dose computed tomography (LDCT) screening. Data were retrospectively analyzed from November 2023 to June 2024. Exposures Opportunistic LDCT screening for lung cancer. Main Outcomes and Measures Participants were followed up until December 2022 for the outcome of death. Lung cancer diagnosis, diagnostic characteristics, clinical course, and lung cancer–specific deaths (LCSD) were compared between women and men. Results A total of 21 062 participants (16 133 [76.6%] women and 4929 [23.4%] men) with a mean (SD) age of 59.8 (7.2) years were included. From baseline screening, 176 participants (139 women [0.9%] and 37 men [0.8%]) were diagnosed with lung cancer (screen-detected); 131 of 139 women (94.3%) and 33 of 37 men (89.2%) were diagnosed with stage 0 to I disease, with 133 of 139 women (95.7%) and 36 of 37 men (97.3%) having adenocarcinoma. There were no significant sex-based differences in stage or histologic type distribution. Among the 21 062 screened individuals, LCSD was reported in 8 women and 3 men during a mean (SD) follow-up of 83.8 (41.7) months. Multivariable analyses found no significant association between sex and cumulative hazards of lung cancer diagnosis (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.64-1.26] for men vs women) or LCSD (aHR, 1.06 [95% CI, 0.28-4.00] for men vs women). The estimated 5-year lung cancer–specific survival rate was 97.7% for women and 100% for men with screen-detected lung cancer, showing no significant sex differences. Conclusions and Relevance In this cohort study of Asian individuals with no smoking history who underwent LDCT screening, no significant sex-based differences were detected in lung cancer diagnosis, stage distribution, or LCSD. These findings suggest that men and women who have never smoked would experience similar risks of overdiagnosis with little to no benefit when exposed to indiscriminate screening.
Sometimes Saying Less Is More—Poetry and Effective Patient-Centered Communication
Authors: Rafael Campo
Journal: JAMA (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Triple Bypass
Authors: Wendy Wisner
Journal: JAMA (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Scabies Infestations
Authors: Jaimie Oldham, Edel O’Toole, Malvina Cunningham
Journal: JAMA (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Multicomponent Deimplementation Strategy to Reduce Low-Value Preoperative Testing
Authors: Alexis G. Antunez, Ruby J. Kazemi, Caroline Richburg, Cecilia Pesavento, Andrew Vastardis, Erin Kim, Abigail L. Kappelman, Devak Nanua, Hiba Pediyakkal, Faelan Jacobson-Davies, Shawna N. Smith, James Henderson, Valerie Gavrila, Anthony Cuttitta, Hari Nathan, Lesly A. Dossett
Journal: JAMA Surgery (2025)

Importance Routine preoperative blood tests and electrocardiograms before low-risk surgery do not prevent adverse events or change management but waste resources and can cause patient harm. Given this, multispecialty organizations recommend against routine testing before low-risk surgery. Objective To determine whether a multicomponent deimplementation strategy (the intervention) would reduce low-value preoperative testing before low-risk general surgery operations. Design, Setting, and Participants This study had a pre-post quality improvement interventional design using interrupted time series and difference-in-difference analytic approaches. The setting was a single academic, quaternary referral hospital with 2 freestanding ambulatory surgery centers and a central preoperative clinic. Included in the study were adult patients undergoing nonurgent outpatient inguinal hernia repairs, lumpectomy, or laparoscopic cholecystectomy between June 2022 and August 2023. Eligible clinicians included those treating at least 1 patient during both the preintervention and postintervention periods. Interventions All clinicians were exposed to the multicomponent deimplementation intervention, and their testing practices were compared before and after the intervention. The strategy components were evidenced-based decisional support, multidisciplinary stakeholder engagement, educational sessions, and consensus building with surgeons and physician assistants staffing a preoperative clinic. Main Outcomes and Measures The primary end point of the trial was the rate of unnecessary preoperative tests across each trial period. Results A total of 1143 patients (mean [SD] age, 58.7 [15.5] years; 643 female [56.3%]) underwent 261 operations (23%) in the preintervention period, 510 (45%) in the intervention period, and 372 (33%) in the postintervention period. Unnecessary testing rates decreased over each period (intervention testing rate, −16%; 95% CI, −4% to −27%; P = .01; postintervention testing rate, −27%; 95% CI, −17% to −38%; P = .003) and within each test category. The decrease in overall testing was not observed at other hospitals in the state on adjusted difference-in-difference analysis. Conclusions and Relevance In this quality improvement study, a multicomponent deimplementation strategy was associated with a reduction in unnecessary preoperative testing before low-risk general surgery operations. The resulting changes in testing practice patterns were not associated with temporal trends within or outside the study hospital. Results suggest that this intervention was effective, applicable to common general surgery operations, and adaptable for expansion into appropriate clinical settings.
Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study
Authors: Philippe Moreau, Thierry Facon, Saad Z. Usmani, Nizar Bahlis, Noopur Raje, Torben Plesner, Robert Z. Orlowski, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael O’Dwyer, Aurore Perrot, Christopher P. Venner, Katja Weisel, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, George Wang, Huiling Pei, Maria Krevvata, Robin Carson, Fredrik Borgsten, Shaji K. Kumar
Journal: Leukemia (2025)
John Launer: Losing touch with NHS reality
Authors: John Launer
Journal: BMJ (2025)

A wonderfully absurdist NHS fantasy has been doing the rounds on social media.It stemmed from a case vignette in a government document, Reforming Elective Care for Patients, 1 in a text box illustrating how patients can be empowered by accessing their results on the NHS App.I'm a great fan of patient empowerment and have nothing against the NHS App.But the illustrative story (which has since been removed) was so hilarious that it deserves to be widely shared.
The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial
Authors: Jianfeng Wu, Fei Pei, Lixin Zhou, Weiqin Li, Renhua Sun, Yimin Li, Zheng Wang, Zhijie He, Xiaofei Zhang, Xiaodong Jin, Yun Long, Wei Cui, Chunting Wang, Erzhen Chen, Jun Zeng, Jing Yan, Qinhan Lin, Feihu Zhou, Lei Huang, You Shang, Meili Duan, Wei Zheng, Duming Zhu, Qiuye Kou, Shihong Zhang, Yin Liu, Chen Yao, Meixia Shang, Sui Peng, Qian Zhou, Kar Keung Cheng, Xiangdong Guan
Journal: BMJ (2025)

Abstract Objective To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis. Design Multicentre, double blinded, placebo controlled phase 3 trial. Setting 22 centres in China, September 2016 to December 2020. Participants 1106 adults aged 18-85 years with a diagnosis of sepsis according to sepsis-3 criteria and randomly assigned in a 1:1 ratio to receive thymosin α1 (n=552) or placebo (n=554). A stratified block method was used for randomisation, and participants were stratified by age (&lt;60 and ≥60 years) and centre. Interventions Subcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent. Main outcome measure The primary outcome was 28 day all cause mortality after randomisation. All analyses were based on a modified intention-to-treat set, including participants who received at least one dose of study drug. Results Of 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treat analyses (thymosin α1 group n=542, placebo group n=547). 28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93 with log-rank test). No secondary or safety outcome differed statistically significantly between the two groups. The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (&lt;60 years: hazard ratio 1.67, 1.04 to 2.67; ≥60 years: 0.81, 0.61 to 1.09; P for interaction=0.01) and diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04). Conclusions This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis. Trial registration ClinicalTrials.gov NCT02867267 .
A rare haplotype of the GJD3 gene segregating in familial Meniere’s disease interferes with connexin assembly
Authors: Alba Escalera-Balsera, Paula Robles-Bolivar, Alberto M. Parra-Perez, Silvia Murillo-Cuesta, Han Chow Chua, Lourdes Rodríguez-de la Rosa, Julio Contreras, Ewa Domarecka, Juan Carlos Amor-Dorado, Andrés Soto-Varela, Isabel Varela-Nieto, Agnieszka J. Szczepek, Alvaro Gallego-Martinez, Jose A. Lopez-Escamez
Journal: Genome Medicine (2025)

Familial Meniere's disease (FMD) is a rare polygenic disorder of the inner ear. Mutations in the connexin gene family, which encodes gap junction proteins, can also cause hearing loss, but their role in FMD is largely unknown. We retrieved exome sequencing data from 94 individuals in 70 Meniere's disease (MD) families. Through gene burden analysis, we calculated the enrichment of rare variants (allele frequency < 0.05) in connexins genes in FMD individuals compared with the reference population. The connexin monomer and the homomeric connexon structural models were predicted using AlphaFold2 and HDOCK. RT-qPCR and immunofluorescence were done in mice cochleae to identify expression of the mouse ortholog candidate gene Gjd3. We found an enrichment of rare missense variants in the GJD3 gene when comparing allelic frequencies in FMD (N = 94) with the Spanish reference population (OR = 3.9[1.92–7.91], FDR = 2.36E-03). In the GJD3 sequence, we identified a rare haplotype (TGAGT) composed of two missense, two synonymous, and one downstream variant. This haplotype was found in five individuals with FMD, segregating in three unrelated families with a total of ten individuals; and in another eight MD individuals. GJD3 encodes the gap junction protein delta 3, also known as human connexin 31.9 (Cx31.9). The protein model predicted that the NP_689343.3:p.(His175Tyr) missense variant could modify the interaction between connexins and the connexon assembly, affecting the homotypic GJD3 gap junction between cells. Our studies in mice revealed that Gjd3—encoding Gjd3 or mouse connexin 30.2 (Cx30.2)—was expressed in the organ of Corti and vestibular organs, particularly in the tectorial membrane, the base of inner and outer hair cells and the nerve fibers. The present results describe a novel association between GJD3 and FMD, providing evidence that FMD is related to changes in the inner ear channels, and supporting a new role of tectorial membrane proteins in MD.
Inhibition of aortic CX3CR1+ macrophages mitigates thoracic aortic aneurysm progression in Marfan syndrome in mice
Authors: Jiaqi Huang, Hao Liu, Zhujiang Liu, Zhenting Wang, Hanshi Xu, Zhuofan Li, Shan Huang, Xueyuan Yang, Yicong Shen, Fang Yu, Yulin Li, Junming Zhu, Wei Li, Li Wang, Wei Kong, Yi Fu
Journal: Journal of Clinical Investigation (2025)

The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients. Specific elimination of CX3CR1+ cells by diphtheria toxin in Cx3cr1-CreERT2iDTRF/+Fbn1C1041G/+ mice efficiently ameliorated TAA progression. Administering the monoclonal antibodies to respectively neutralize TNF-α and IGF1 produced by CX3CR1+ cells from MFS patients greatly suppressed the cocultured MFS patient-specific induced pluripotent stem cell-derived VSMC inflammation. BM transplantation and parabiosis revealed that CX3CR1+ macrophages are mainly originated from BM-derived monocytes. Targeting TNF-α and IGF1 in CX3CR1+ macrophages via shRNA lentivirus transduction in BM cells efficiently suppressed TAA development in BM-transplanted Fbn1C1041G/+ mice. Application of the CCR2 antagonist RS504393 to inhibit monocyte infiltration markedly reduced the accumulation of CX3CR1+ macrophages and subsequently alleviated TAA progression in Fbn1C1041G/+ mice. In summary, CX3CR1+ macrophages mainly located in aortic intima mediate TAA formation by paracrinally causing VSMC inflammation, and targeting them offers a potential antiinflammatory therapeutic strategy for MFS-related TAA.
Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity
Authors: Khaled Ezzedine, Rim Tannous, Todd F Pearson, John E Harris
Journal: Journal of Clinical Investigation (2025)

Vitiligo is an autoimmune disease that has been recognized, stigmatized, and treated for millennia. Recent translational research has revealed key mechanisms of disease, including cellular stress, innate immune activation, T cell-mediated elimination of melanocytes from the skin resulting in clinically apparent white spots, as well as stem cell regeneration that reverses established lesions. Many of these pathways have been targeted therapeutically, leading to the first FDA-approved medication to reverse the disease, with many more in clinical trials. Despite these impressive advances, many questions remain, which will be answered through integration of additional basic, translational, and clinical research studies. This vitiligo revolution has led to great excitement for individuals with vitiligo, those who know them, and the dermatologists who care for their patients. But just as importantly, these advances have great potential to shed light on autoimmune diseases that are more difficult to study, possibly leading to treatment advances that could not be achieved otherwise.
Parkin activates innate immunity and promotes antitumor immune responses
Authors: Michela Perego, Minjeong Yeon, Ekta Agarwal, Andrew T. Milcarek, Irene Bertolini, Chiara Camisaschi, Jagadish C. Ghosh, Hsin-Yao Tang, Nathalie Grandvaux, Marcus Ruscetti, Andrew V. Kossenkov, Sarah Preston-Alp, Italo Tempera, Noam Auslander, Dario C. Altieri
Journal: Journal of Clinical Investigation (2025)
<i>Orthopedia</i> regulates melanocortin 4 receptor transcription and energy homeostasis
Authors: Baijie Xu, Katherine Lawler, Steven C. Wyler, Li Li, None Swati, Julia M. Keogh, Xiameng Chen, Rong Wan, Amanda G. Almeida, Susan Kirsch, Kathleen G. Mountjoy, Joel K. Elmquist, I. Sadaf Farooqi, Chen Liu
Journal: Science Translational Medicine (2025)

Disruption of hypothalamic melanocortin 4 receptors (MC4Rs) causes obesity in mice and humans. Here, we investigated the transcriptional regulation of MC4R in the hypothalamus. In mice, we show that the homeodomain transcription factor Orthopedia (OTP) is enriched in MC4R neurons in the paraventricular nucleus (PVN) of the hypothalamus and directly regulates Mc4r transcription. Deletion of Otp in PVN neurons during development or adulthood reduced Mc4r expression, causing increased food intake and obesity. In humans, four of the five carriers of rare predicted functional OTP variants in UK Biobank had obesity. To explore a causal role for human OTP variants, we generated mice with a loss-of-function OTP mutation identified in a child with severe obesity. Heterozygous knock-in mice exhibited hyperphagia and obesity, reversed by treatment with an MC4R agonist. Our findings demonstrate that OTP regulates mammalian energy homeostasis and enable the diagnosis and treatment of individuals with obesity due to OTP deficiency.
A population of c-kit <sup>+</sup> IL-17A <sup>+</sup> ILC2s in sputum from individuals with severe asthma supports ILC2 to ILC3 trans-differentiation
Authors: Xiaotian Ju, Nahal Emami Fard, Anurag Bhalla, Anna Dvorkin-Gheva, Maria Xiao, Katherine Radford, Kayla Zhang, Reina Ditta, John Paul Oliveria, Guillaume Paré, Manali Mukherjee, Parameswaran Nair, Roma Sehmi
Journal: Science Translational Medicine (2025)

In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear. Here, we found by flow cytometry that sputum ILC3s are increased in severe asthma with intense airway neutrophilia, whereas equivalently raised sputum ILC2s and ILC3s were found in severe asthma with mixed granulocytic inflammation. Unbiased clustering analyses identified an “intermediate-ILC2” population displaying markers of both ILC2s (prostaglandin D 2 receptor 2; CRTH2, IL-5, and IL-13) and ILC3s (c-kit and IL-17A) that were most abundant in severe asthma with mixed granulocytic airway inflammation. Intermediate ILC2s correlated with airway neutrophilia and were associated with increased amounts of IL-1β and IL-18 in sputum supernatants. Coculture of sort-purified canonical ILC2s with IL-1β and IL-18 in vitro up-regulated c-kit and IL-17A as well as gene expression profiles related to both type 2 and type 17 inflammatory pathways. Together, we have identified an intermediate-ILC2 phenotype in the airways of individuals with severe mixed granulocytic asthma, representing a candidate therapeutic target for controlling neutrophilic airway inflammation.