tbuckley/cabot-search huggingface dataset:
Predicting Diagnostic Progression to Schizophrenia or Bipolar Disorder via Machine Learning
Authors: Lasse Hansen, Martin Bernstorff, Kenneth Enevoldsen, Sara Kolding, Jakob Grøhn Damgaard, Erik Perfalk, Kristoffer Laigaard Nielbo, Andreas Aalkjær Danielsen, Søren Dinesen Østergaard
Journal: JAMA Psychiatry (2025)

Importance The diagnosis of schizophrenia and bipolar disorder is often delayed several years despite illness typically emerging in late adolescence or early adulthood, which impedes initiation of targeted treatment. Objective To investigate whether machine learning models trained on routine clinical data from electronic health records (EHRs) can predict diagnostic progression to schizophrenia or bipolar disorder among patients undergoing treatment in psychiatric services for other mental illness. Design, Setting, and Participants This cohort study was based on data from EHRs from the Psychiatric Services of the Central Denmark Region. All patients aged 15 to 60 years with at least 2 contacts (at least 3 months apart) with the Psychiatric Services of the Central Denmark Region between January 1, 2013, and November 21, 2016, were included. Analysis occurred from December 2022 to November 2024. Exposures Predictors based on EHR data, including medications, diagnoses, and clinical notes. Main Outcomes and Measures Diagnostic transition to schizophrenia or bipolar disorder within 5 years, predicted 1 day before outpatient contacts by means of elastic net regularized logistic regression and extreme gradient boosting (XGBoost) models. The area under the receiver operating characteristic curve (AUROC) was used to determine the best performing model. Results The study included 24 449 patients (median [Q1-Q3] age at time of prediction, 32.2 [24.2-42.5] years; 13 843 female [56.6%]) and 398 922 outpatient contacts. Transition to the first occurrence of either schizophrenia or bipolar disorder was predicted by the XGBoost model, with an AUROC of 0.70 (95% CI, 0.70-0.70) on the training set and 0.64 (95% CI, 0.63-0.65) on the test set, which consisted of 2 held-out hospital sites. At a predicted positive rate of 4%, the XGBoost model had a sensitivity of 9.3%, a specificity of 96.3%, and a positive predictive value (PPV) of 13.0%. Predicting schizophrenia separately yielded better performance (AUROC, 0.80; 95% CI, 0.79-0.81; sensitivity, 19.4%; specificity, 96.3%; PPV, 10.8%) than was the case for bipolar disorder (AUROC, 0.62, 95% CI, 0.61-0.63; sensitivity, 9.9%; specificity, 96.2%; PPV, 8.4%). Clinical notes proved particularly informative for prediction. Conclusions and Relevance These findings suggest that it is possible to predict diagnostic transition to schizophrenia and bipolar disorder from routine clinical data extracted from EHRs, with schizophrenia being notably easier to predict than bipolar disorder.
Health Care Staffing Shortages and Potential National Hospital Bed Shortage
Authors: Richard K. Leuchter, Benjo A. Delarmente, Sitaram Vangala, Yusuke Tsugawa, Catherine A. Sarkisian
Journal: JAMA Network Open (2025)

This cross-sectional study assesses several possible US hospital bed occupancy scenarios arising from an aging US population over the next decade, based on varying hospitalization rates and staffed hospital bed supply.
Comparing International Revision Incidence of Commonly Used Breast Implants
Authors: J. Juliët Vrolijk, Babette E. Becherer, Patrick Garduce, Ahmad Reza Pourghaderi, Danny A. Young-Afat, René R. J. W. van der Hulst, Gillian Farrell, Melanie Walker, Patrick Tansley, Marc A. M. Mureau, Arul Earnest, Susannah Ahern, Hinne A. Rakhorst
Journal: JAMA Surgery (2025)

Importance Despite the widespread use of breast implants, to date, no large-scale international studies on long-term revision incidence of different implant types have been conducted. Objective To determine whether international data could be combined using a harmonized dataset to increase power and investigate clinically relevant differences in complication-related revision incidence between breast implant types. Design, Setting, and Participants This multicenter, population-based cohort study used data from the Australian Breast Device Registry and the Dutch Breast Implant Registry from 2016 to 2021. Time-to-event analysis was performed using a frailty Cox proportional hazards regression model with pooled data. The study included all permanent breast implants that were inserted for primary postmastectomy or benign breast reconstruction or cosmetic augmentation. Data were analyzed from January 1, 2016, through December 31, 2021. Exposure Permanent breast implants grouped based on implant shape, shell, and fill. Main outcomes and measures Complication-related revision incidence between breast implant types. Results Data exchange between registries was successful. In total, 21 115 reconstructive and 129 854 cosmetic breast implants inserted in patients with a median (IQR) age of 47 (38-55) years and 31 (25-38) years, respectively, were included. Overall complication-related revision was 6.3% for reconstructive and 1.2% for cosmetic implants. For reconstructive implants, hazard ratios (HRs) for implant types showed no significant differences compared with anatomical textured-silicone implants. For cosmetic implants, anatomical polyurethane-silicone implants showed a lower risk of revision (HR, 0.38; 95% CI, 0.22-0.64) compared with anatomical-textured-silicone implants. At 5 years, no significant differences in cumulative revision incidence were observed between implant types for either reconstructive or cosmetic implants. Conclusions and relevance This study showed that international datasets can be pooled to assess real-world incidence of breast implant revision, which is anticipated to generate a foundation on which future breast implant studies can be based.
Early vs Delayed Bypass Surgery in Patients With Acute Coronary Syndrome Receiving Ticagrelor
Authors: Derek Y. F. So, George A. Wells, Marie Lordkipanidzé, Aun Yeong Chong, Marc Ruel, Louis P. Perrault, Michel R. Le May, Louise Sun, Diem Tran, Marino Labinaz, Christopher Glover, Juan Russo, Mélanie Welman, Vincent Chan, Lily Chen, Jordan Bernick, Fraser Rubens, Jean-Francois Tanguay, Gerri Salapang, Poppy MacPhee, Tanya Abarbanel, Carol Mitchell, Kendra Racine, Rima Amche, Richard Davies, Darryl Davis, Anthony Poulin, Girish Nair, Sophie De Roock, My-Linh Tran
Journal: JAMA Surgery (2025)

Importance Perioperative bleeding is a major concern in patients receiving ticagrelor for acute coronary syndromes (ACS) when coronary artery bypass graft (CABG) surgery is required. Objective To evaluate whether early CABG surgery at 2 to 3 days after ticagrelor cessation is noninferior to waiting 5 to 7 days. Design, Setting, and Participants RAPID CABG was a noninferiority, open-label randomized trial with 6 months of follow-up. Participants were patients with ACS who had received ticagrelor and required CABG. Patients were enrolled in tertiary centers in Canada between January 2016 and March 2021. Data were analyzed from March 2021 to December 2023. Intervention Early or delayed CABG. Main Outcomes and Measures The primary outcome was based on noninferiority comparison of class 3 or 4 universal definition of perioperative bleeding (UDPB). Noninferiority was prespecified as 8% between groups. Twelve-hour chest tube drainage was reported as a noninferiority comparison. Other bleeding, ischemic, and length-of-stay outcomes were assessed for superiority. Results Among 143 randomized patients, the median (IQR) age was 65 (58-72) years; there were 117 male patients (82%) and 26 female (18%). Of these, 123 patients (86.0%) underwent surgery in the allocated time frame (per protocol). The median (IQR) time to surgery was 3 (2-3) days in the early group and 6 (5-7) days in the delayed group ( P &amp;amp;lt; .001). In a per-protocol analysis, severe or massive UDPB occurred in 3 of 65 early-group patients (4.6%) and 3 of 58 patients (5.2%) in the delayed group (between-group difference, −0.6%; 95% CI, −8.3% to 7.1%; P = .03 for noninferiority). Median (IQR) chest tube drainage was 470 (330-650) mL vs 495 (380-610) mL (between-group difference −25 mL; 95% CI, −111.25 to 35; P = .01 for noninferiority). Median (IQR) hospital stay was 9 (7-13) days and 12 (10-15) days for the early and delayed groups ( P &amp;amp;lt; .001). Conclusion and Relevance This study found that an early surgical strategy, 2 to 3 days after ticagrelor cessation, was noninferior in incurring perioperative bleeding. The data support a reduction in the delay between ticagrelor cessation and CABG surgery and may decrease hospital length of stay. Trial Registration ClinicalTrials.gov Identifier: NCT02668562
Maternal RSVpreF and Infant Nirsevimab Immunizations Uptake During Respiratory Syncytial Virus Season
Authors: Ethan A. Litman, Tina Yi Jin Hsieh, Anna M. Modest, Kathleen Clarke, Melissa Dzinoreva, Valerie Perrinez, Esther Apraku Bondzie, Lydia Gallup, Eleanor Schonberg, Marjorie Rowe, K’ara Locke, Oluwaseyi Oginni, Robert Jones, Chloe A. Zera, Ai-ris Y. Collier
Journal: JAMA Network Open (2025)

This cohort study evaluates the use rate of respiratory syncytial virus (RSV) vaccines to prevent RSV-related lower respiratory tract disease among infants.
Long-Term Outcomes of Laparoscopic Roux-en-Y Gastric Bypass vs Laparoscopic Sleeve Gastrectomy for Obesity
Authors: Marko Kraljević, Julian Süsstrunk, Bettina Karin Wölnerhanssen, Thomas Peters, Marco Bueter, Daniel Gero, Bernd Schultes, Adisa Poljo, Romano Schneider, Ralph Peterli
Journal: JAMA Surgery (2025)

Importance Reports on long-term outcomes from randomized clinical trials comparing laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are scarce. Objective To compare long-term weight and metabolic outcomes, reoperation rates, and quality of life for patients undergoing SG vs RYGB at 10 years and beyond. Design, Setting, and Participants The SM-BOSS (Swiss Multicenter Bypass or Sleeve Study) randomized clinical trial was conducted from January 2007 to November 2011 at 4 bariatric centers in Switzerland. (The last follow-up was obtained in July 2023.) A total of 3971 patients with severe obesity were assessed, and 217 patients were enrolled and randomized to undergo SG or RYGB. Interventions Laparoscopic SG or RYGB. Main Outcomes and Measures The primary outcome of the SM-BOSS trial was the percentage excess body mass index loss (%EBMIL) at 5 years. The present study reports on the long-term weight and metabolic outcomes at 10 years and beyond, including changes in weight and obesity-related diseases, reoperation rates, and quality of life. Results Of 217 patients randomized to undergo SG or RYGB, mean (SD) age was 42.5 (11.1) years, mean (SD) baseline BMI was 43.9 (5.3), and 156 patients (71.9%) were female. Of 217 patients, 110 patients were randomized to RYGB and 107 to SG. Complete 10-year follow-up is available for 65.4% of patients. In the intention-to-treat population, mean (SD) %EBMIL was 60.6% (25.9) after SG and 65.2% (26.0) after RYGB ( P = .29). Patients who underwent SG had significantly higher conversion rates because of insufficient weight reduction or reflux compared to RYGB (29.9% vs 5.5%; P &amp;amp;lt; .001). Patients undergoing RYGB had significantly higher mean (SD) %EBMIL compared to SG after 10 years in the per-protocol (PP) population (65.9% [26.3] vs 56.1% [25.2]; P = .048). However, mean (SD) percentage total weight loss was not significantly different between groups (RYGB: 27.7% [10.8]; SG: 25.5% [15.1]; P = .37). SG patients had significantly more de novo gastroesophageal reflux (GERD) compared with RYGB ( P = .02). Conclusions and Relevance In the SM-BOSS randomized clinical trial, RYGB led to significantly higher %EBMIL in the PP population compared with SG beyond 10 years of follow-up, with better results for GERD. Patients undergoing SG experienced a significantly higher number of conversions to different anatomy compared with RYGB. Trial Registration ClinicalTrials.gov Identifier NCT00356213
Variants in <i>KLF4</i> affecting residue Asp441 cause an autosomal dominant syndromic ichthyosis
Authors: Zijuan Wang, Jun Liu, Oded Wechsberg, Lina Liang, Catherine E Keegan, Christina Sloan-Heggen, You Mo, Yangyang Luo, Huijun Wang, Zhimiao Lin
Journal: British Journal of Dermatology (2025)

Congenital ichthyoses comprise a group of skin scaling diseases with clinical and genetic heterogeneity. They can be subclassified into syndromic and nonsyndromic forms. Syndromic ichthyoses affect organs beyond the skin. An increasing number of causative genes has been identified. To identify the causative gene and the underlying pathogenesis of a previously unreported syndromic ichthyosis. Whole-exome sequencing (WES), combined with Sanger sequencing, was utilized to identify the genetic defect. Protein structural modeling and dual-luciferase reporter assays were employed to investigate the effects of the pathogenic variants on KLF4. A human embryonic stem cell-H9 line (hESC-H9) harboring the pathogenic variant was developed into a skin organoid for morphological observation and RNA sequencing analysis. The expression of candidate target genes was further validated in patients' skin samples using quantitative RT-PCR and immunofluorescence. We collected four unrelated sporadic patients with a syndromic ichthyosis, predominantly manifesting as ichthyosis, palmoplantar keratoderma, hypotrichosis, periorificial keratosis, nail dystrophy, and varying extracutaneous involvement. WES identified two heterozygous missense variants, c.1322A>G (p.Asp441Gly) and c.1323T>A (p.Asp441Glu), in the KLF4 gene in these patients. Protein modeling predicted that the substitutions of the affected residue, Asp441, were likely to affect the stability of the local α-helix structure. Both variants exhibited reduced transcriptional activity. Skin organoids derived from hESC-H9 cells harboring the heterozygous c.1323T>A variant displayed defects in epithelial morphogenesis and abnormal expression of keratinocyte differentiation-related genes and WNT signaling genes. Decreased expression of KLK7 and WNT10A, which are vital for skin desquamation and multi-organ development, respectively, was detected in the patients' skin lesions. Loss-of-function variants affecting residue Asp441 of KLF4 cause an autosomal dominant syndromic ichthyosis with multi-organ involvement. These variants impair KLF4 transcriptional activity, leading to the downregulation of multiple genes, particularly KLK7 and WNT10A. This may disrupt the skin desquamation process and affect multi-organ development in the patients.
Response to Coppinger et al., “Comment on ‘5α-reductase inhibitor exposure for dermatologic conditions does not increase the risk of female breast or gynecologic cancers: A population-based propensity score-matched cohort study’”
Authors: Li-Chi Chen, Tina Yi Jin Hsieh, Aubrey Martin, Maryanne M Senna
Journal: Journal of the American Academy of Dermatology (2025)
Assessing the Diagnostic Metrics of Cutaneous Leiomyomas in Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome: an Observational Study
Authors: Lydia Ouchene, Megha Udupa, Lorena A Mija, Sarah Moussa, May Chergui, Kevin A Watters, Tania Cruz-Marino, Simon Tanguay, Fadi Brimo, Lili Fu, Elham Rahme, Mohammed Kaouache, William D Foulkes, Elena Netchiporouk
Journal: Journal of the American Academy of Dermatology (2025)
Spatially resolved, multi-region proteomics for prediction of immunotherapy outcome in deficient mismatch repair metastatic colorectal cancer
Authors: Bahar Saberzadeh-Ardestani, Zhenglong Liu, Mariam I. Stein, Will A. Sherman, Christy E. Trussoni, Charles W. Abbott, Dongyao Yan, Skyler Smith, Kandavel Shanmugam, Rondell P. Graham, Alos Diallo, Joshua J. Levy, Tamas Ordog, Frank A. Sinicrope
Journal: Clinical Cancer Research (2025)

Abstract Purpose. Digital proteomic profiling was performed to identify spatial context in relationship to patient response and survival after anti-PD-1 therapy in metastatic colorectal cancer (CRC). Experimental Design. Primary CRCs with deficient mismatch repair (d-MMR) from patients treated with anti-PD-1 antibodies were analyzed (N=30) using Digital Spatial Profiling (GeoMx® nCounter). At the invasive margin, 71 proteins were profiled in 10 regions of interest /slide that were segmented into 3 compartments labeled with pan-cytokeratin (PanCK; epithelia), CD45 (stromal cells) and SYTO13 (nuclei). In an independent cohort (n=13), DSP data and single cell transcriptomic data were analyzed. Differential protein abundance, after Benjamini-Hochberg correction, was examined by response and progression-free survival (PFS) using multivariable Cox regression. Results. Protein abundance varied significantly between epithelial and stromal compartments. Nonresponders (NR) to anti-PD-1 showed higher fibronectin and smooth muscle actin (SMA) abundance in the epithelial compartment that were associated with significantly shorter PFS (HRadj: 6.49 and 4.52, respectively; p &amp;lt; 0.05). In CD45+ stroma, increased expression of proteins related to T-cells (CD3, CD4), NK cells (CD56), antigen presentation (CD40), immune activation (CD27, ICOS), and apoptosis (GZMA) were found in responders (vs NR) to anti-PD-1; each marker was significantly associated with longer patient PFS (0.02 &amp;lt;HRadj &amp;lt; 0.17; p &amp;lt; 0.05). In a separate cohort, consistent results by compartment were found for fibronectin and CD56. Gene expression data revealed that fibronectin and SMA were primarily derived from cancer-associated fibroblasts. Conclusions. Spatially resolved protein profiles within microenvironments of d-MMR CRCs can influence patient response and survival after anti-PD-1 highlighting their potential clinical significance.
Spatial Transcriptomics of Intraductal Papillary Mucinous Neoplasms Reveals Divergent Indolent and Malignant States
Authors: Matthew K. Iyer, Ashley Fletcher, Jude Ogechukwu. Okoye, Chanjuan Shi, Fengming Chen, Elishama Kanu, Austin M. Eckhoff, Matthew Bao, Marina Pasca di Magliano, Timothy L. Frankel, Arul M. Chinnaiyan, Daniel P. Nussbaum, Peter J. Allen
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Intraductal papillary mucinous neoplasms (IPMN) occur in 5-10% of the population, but only a small minority progress to pancreatic ductal adenocarcinoma (PDAC). The lack of accurate predictors of high-risk disease leads both to unnecessary operations for indolent neoplasms as well as missed diagnoses of PDAC. Digital spatial RNA profiling (DSP-RNA) provides an opportunity to define and associate transcriptomic states with cancer risk. Experimental Design: We performed whole-transcriptome DSP-RNA profiling on 10 IPMN specimens encompassing the spectrum of dysplastic changes from normal duct to cancer. Epithelial regions within each tissue were annotated as normal duct (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or invasive carcinoma (INV). The resulting digital gene expression data were analyzed with R/Bioconductor. Results: Our analysis uncovered three distinct epithelial transcriptomic states – “normal-like” (cNL), “low-risk” (cLR), and “high-risk” (cHR) – which were significantly associated with pathologic grade. Furthermore, the three states were significantly correlated with the exocrine, classical, and basal-like molecular subtypes described in PDAC. Specifically, exocrine function diminished in cHR, classical activation distinguished neoplasia (cLR and cHR) from cNL, and basal-like genes were specifically upregulated in cHR. Intriguingly, markers of cHR were detected in NL and LGD regions from specimens with PDAC but not low-grade IPMN. Conclusions: DSP-RNA of IPMN revealed low-risk (indolent) and high-risk (malignant) expression programs that correlated with the activity of exocrine and basal-like PDAC signatures, respectively, and distinguished pathologically low-grade from malignant specimens. These findings contextualize IPMN pathogenesis and have the potential to improve risk stratification.
Safety, Feasibility, and Diagnostic Yield of Invasive Coronary Function Testing
Authors: Caïa Crooijmans, Tijn P. J. Jansen, Joan G. Meeder, Janneke Woudstra, Martijn Meuwissen, Annemiek M.J. De Vos, Valeria Paradies, Els G. M. Olde Bijvank, Patty Winkler, Nicola S. Vos, Karin Arkenbout, Pier Woudstra, Martin G. Stoel, Tim P. Van de Hoef, Stijn C. H. Van den Oord, Jos W. M. G. Widdershoven, Wouter Remkes, Aysun Cetinyurek-Yavuz, Hester M. Den Ruijter, N. Charlotte Onland-Moret, Eric Boersma, Marcel A.M. Beijk, Yolande Appelman, Jan J. Piek, Regina E. Konst, Angela H. E. M. Maas, Niels Van Royen, Aukelien C. Dimitriu-Leen, Suzette E. Elias-Smale, Peter Damman, Wilbert H Aarnoudse, Jihane Bourich, Bibilotte Ellerström, Olaf Gietman, Thedde Kuijsters, Maribel I Madera, Koen MJ Marques, Krishan D Sjauw, Peter C Smits, Bastiaan J Sorgdrager, Dirk J van der Heijden, Kyra van Keeken, Arnoud van 't Hof, Tessel N Vossenberg
Journal: JAMA Cardiology (2025)

Patients with angina and no obstructive coronary artery disease frequently have coronary vasomotor dysfunction as underlying pathophysiological mechanism, comprising epicardial spasm, microvascular spasm, and/or microcirculatory dysfunction. These endotypes can be diagnosed by invasive coronary function testing which has previously shown to be safe in tertiary and expert centers. To determine the prevalence of vasomotor dysfunction in patients with angina and no obstructive coronary artery disease who were clinically referred for a coronary function test (CFT); and assess safety and feasibility of a CFT. This quality improvement study was performed using the Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT), a prospective, observational registry, in 15 participating hospitals (2 tertiary and 13 nontertiary). Patients with angina and no obstructive coronary artery disease who were referred for a clinically indicated CFT between December 2020 and January 2024 were included. A complete CFT consisted of acetylcholine spasm provocation testing and assessment of microcirculatory function. Prevalence of different endotypes based on test results and overall safety were assessed. Among a total of 1207 patients included, 978 (81%) were female; and the mean (SD) age was 60 (10) years. The prevalence of coronary vasomotor dysfunction was very high (78%). There were 11 (0.9%) major and 10 (0.8%) minor complications reported. Of them, 3 major and all minor were definitely related to the coronary function test. No procedural death, myocardial infarction, or stroke was observed. No differences were found in the occurrence of complications between tertiary and nontertiary centers. This study found that a CFT was feasible and safe to perform in both tertiary and nontertiary centers with a high diagnostic yield.
Intracardiac Flow Dynamics in Mitral Regurgitation: State of the Art
Authors: Lorenzo Serio, Riccardo Beccari, Stefano Nistri, Antonella Cecchetto, Gianni Pedrizzetti, Donato Mele
Journal:  (2025)

Abstract Intracardiac flow dynamics is a complex phenomenon interrelated with cardiac mechanics. Today, it can be evaluated non-invasively using various imaging modalities, including echocardiography, magnetic resonance imaging, and computed tomography. This review explores the effects of mitral regurgitation on blood flow dynamics inside the left ventricular and atrial cavities and emphasizes the disruption of normal flow dynamics caused by mitral regurgitation, leading to turbulent flow and increased energy dissipation. It further examines the consequences of mitral valve repair and replacement, noting that, while repair generally improves intracardiac flow dynamics compared with replacement, residual flow disturbances may persist. Finally, the implications of abnormal intracardiac vorticity on left ventricular wall stress, myocardial remodelling, and thromboembolic risk are discussed.