medRxiv : the preprint server for health sciences最新文献

{"title":"Amplification parameters of the alpha-synuclein seed amplification assay on CSF predict the clinical subtype of Parkinson's Disease at 10-year follow-up.","authors":"Piergiorgio Grillo, Giulietta Maria Riboldi, Antonio Pisani, Un Jung Kang, Seyed-Mohammad Fereshtehnejad","doi":"10.1101/2025.03.27.25324778","DOIUrl":"https://doi.org/10.1101/2025.03.27.25324778","url":null,"abstract":"<p><strong>Importance: </strong>Data-driven approaches identified Mild Motor Predominant (MMP), Intermediate (IM) and Diffuse Malignant (DM) as subtypes of Parkinson's Disease (PD) with a different degree of motor and non-motor impairment at time of diagnosis. It is not clear whether subtypes remain stable over time nor whether they represent distinct biological substrates. The recent introduction of alpha-synuclein seed amplification assay on CSF (CSF-αSyn-SAA) might provide further insights.</p><p><strong>Objective: </strong>To assess the association between the parameters of CSF-αSyn-SAA collected at baseline and the clinical evolution of PD subtypes for 10 years.</p><p><strong>Design: </strong>Retrospective, longitudinal, cohort study.</p><p><strong>Setting: </strong>Data were collected from the Parkinson's Progression Marker Initiative (PPMI) cohort.</p><p><strong>Participants: </strong>Subjects with a sporadic form of PD and positivity on CSF-αSyn-SAA (n=323) were included.</p><p><strong>Exposure: </strong>clinical and biochemical data available in the PPMI dataset.</p><p><strong>Main outcome and measure: </strong>PD participants were classified as MMP, IM and DM at baseline (n=323) and 10-year follow-up (n=146), based on previously published motor summary score and three non-motor features (cognitive impairment, RBD and dysautonomia). CSF-αSyn-SAA parameters were collected at baseline, including Fmax (maximum fluorescence), T50 (time to reach 50% of Fmax), TTT (time to threshold), Slope, and AUC (area under the curve). CSF Aβ1-42, tTau, pTau181, CSF and serum NfL were also collected at baseline.</p><p><strong>Results: </strong>Times of reaction <b>(</b> T50 and TTT) and AUC respectively were shorter and larger in DM subtype compared to IM/MMP subtype. The difference in amplification parameters at baseline was more evident when comparing subtypes based on the 10-year clinical features (T50, η2=0.036; TTT, η2=0.031; AUC, η2=0.033; all p values < 0.05) than when comparing subtypes based on the baseline clinical features (T50, η2=0.012; TTT, η2=0.012; AUC, η2=0.013; all p<0.05). Shorter T50 and TTT assessed at baseline were associated with a greater risk of DM subtype versus MMP at 10-year follow-up (T50, OR=3.286, p=0.010; TTT, OR=4.586, p=0.001). CSF Aβ1-42, tTau, pTau181, CSF and Serum NfL did not differ between groups.</p><p><strong>Conclusions and relevance: </strong>CSF-αSyn-SAA parameters collected at baseline predicted the long-term progression of PD. In detail, faster reactions were associated with a severer 10-year phenotype of PD considering motor, cognitive, sleep and dysautonomia features.</p><p><strong>Key points: </strong><b>Question:</b> Can the parameters of alpha-synuclein seed amplification assay on CSF (CSF-αSyn-SAA) predict the long-term evolution of Parkinson's Disease (PD) clinical subtypes?<b>Findings:</b> In this retrospective, longitudinal study including 323 PD subjects from the PPMI cohort, we found that faster CSF-","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association meta-analysis identifies 126 novel loci for diverticular disease and implicates connective tissue and colonic motility.","authors":"Christopher J Neylan, Michael G Levin, Katherine Hartmann, Katherine Beigel, Sam Khodursky, John S DePaolo, Sarah Abramowitz, Emma E Furth, Robert O Heuckeroth, Scott M Damrauer, Lillias H Maguire","doi":"10.1101/2025.03.27.25324777","DOIUrl":"https://doi.org/10.1101/2025.03.27.25324777","url":null,"abstract":"<p><p>Diverticular disease is a common and morbid complex phenotype influenced by both innate and environmental risk factors. We performed the largest genome-wide association study meta-analysis for diverticular disease, identifying 126 novel loci. Employing multiple downstream analytic strategies, including tissue and pathway enrichment, statistical fine-mapping, allele-specific expression, protein quantitative trait loci and drug-target investigations, and linkage disequilibrium score regression, we prioritized causal genes and produced several lines of evidence linking diverticular disease to connective tissue biology and colonic motility. We substantiated these findings by integrating single-cell RNA sequencing data, showing that prioritized diverticular disease-associated genes are enriched for expression in colonic smooth muscle, fibroblasts, and interstitial cells of Cajal. In quantitative analysis of surgical specimens, we found a substantial reduction in the density of elastin present in the sigmoid colon in severe diverticulitis.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating Health Insurance Selection for in Vitro Fertilization (IVF) Benefits: A Study Protocol.","authors":"Olumayowa Dayo, Victoria Turcotte, Breanna Reyes, Ricardo E Flores Ortega, Bonnie N Kaiser, Gregory A Aarons, Sara B McMenamin, H Irene Su, Sally A D Romero","doi":"10.1101/2025.03.27.25324807","DOIUrl":"https://doi.org/10.1101/2025.03.27.25324807","url":null,"abstract":"<p><strong>Introduction: </strong>A large public university added health insurance coverage of 50% co-insurance for up to two cycles of in vitro fertilization (IVF) to eligible faculty and staff.</p><p><strong>Methods: </strong>We describe the design and conduct of a randomized controlled trial to evaluate the effectiveness of a health insurance educational intervention on health insurance literacy and IVF benefit utilization. The intervention materials included 1) Key insurance terms; 2) Examples of premiums and deductibles across the insurance plan options; 3) Examples of how premiums and deductibles affect out-of-pocket costs; and 4) A guide to find in-network providers/facilities. The primary outcome is health insurance literacy. Secondary outcomes are IVF services and insurance benefit utilization, out-of-pocket costs, and financial hardship related to fertility care. We collected validated patient-reported outcomes at three timepoints over 1 year. We will integrate mixed methods data to explore whether the intervention was effective, feasible, acceptable, and appropriate.</p><p><strong>Results: </strong>Among 394 faculty and staff screened, 217 (55%) reproductive-aged (18 to 50 years) employees consented, completed the baseline survey and were randomized in a 2:1 fashion. Participants were female (81%), married (63%), and worked as a staff employee (72%). Approximately 39% reported an infertility diagnosis, and 28% had undergone prior IVF treatment. Participants reported feeling slightly confident when using their health insurance plans and moderately confident being proactive when using their health insurance plans.</p><p><strong>Discussion: </strong>Our goal is to improve health insurance literacy and utilization of health insurance benefits for IVF care, thereby expanding family-building options for reproductive-aged individuals.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transdiagnostic Polygenic Risk Models for Psychopathology and Comorbidity: Cross-Ancestry Analysis in the <i>All of Us</i> Research Program.","authors":"Phil H Lee, Jae-Yoon Jung, Brandon T Sanzo, Rui Duan, Tian Ge, Irwin Waldman, Jordan W Smoller, Ted Schwaba, Elliot M Tucker-Drob, Andrew D Grotzinger","doi":"10.1101/2025.03.26.25324720","DOIUrl":"https://doi.org/10.1101/2025.03.26.25324720","url":null,"abstract":"<p><p>Psychiatric disorders exhibit substantial genetic overlap, raising questions about the utility of transdiagnostic genetic risk models. Using data from the <i>All of Us</i> Research Program (N=102,091), we evaluated common psychiatric genetic (CPG) factor-based polygenic risk scores (PRSs) compared to standard disorder-specific PRSs. The CPG PRS consistently outperformed disorder-specific scores in predicting individual disorder risk, explaining 1.07 to 24.6 times more phenotypic variance across 11 psychiatric conditions. Meanwhile, many disorder-specific PRSs retained independent but smaller contributions, highlighting the complementary nature of shared and disorder-specific genetic risk. While alternative multi-factor models improved model fit, the CPG PRS provided comparable or superior predictive performance across most disorders, including overall comorbidity burden. Cross-ancestry analyses however revealed notable limitations of European-centric GWAS datasets for other populations due to ancestral differences in genetic architecture. These findings underscore the potential value of transdiagnostic PRSs for psychiatric genetics while highlighting the need for more equitable genetic risk models.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contamination rates in serially sampled sputum specimens obtained during tuberculosis treatment to capture culture conversion.","authors":"N Niemand, J A Rooney, S Malatesta, N Rawoot, T C Bouton, E J Ragan, T Carney, L F White, M Farhat, C R Horsburgh, B Myers, R M Warren, K R Jacobson","doi":"10.1101/2025.03.26.25324668","DOIUrl":"https://doi.org/10.1101/2025.03.26.25324668","url":null,"abstract":"<p><p>Sputum cultures are the gold standard for tuberculosis (TB) diagnosis and treatment monitoring. However, cultures in MGIT liquid media are susceptible to microbial contamination, often rendering them uninterpretable. Research has shown that maintaining strict cold chains and supervised sample collection can reduce contamination rates, but few longitudinal studies with weekly sampling have explored this. Here we evaluated whether (1) the time between specimen collection and laboratory processing and (2) unsupervised specimen collection are associated with contamination rates. Additionally, we estimated contamination rates over the first 12 weeks of treatment and assessed clinical and behavioral predictors of contamination. We collected 3155 sputum specimens from 301 participants undergoing TB treatment. Contamination was lowest (12.3%) at treatment initiation, increased over the first few weeks, and stabilized around 30% from week 8 onwards. Samples collected without supervision were more likely to be contaminated at treatment initiation (p=0.048) and over the 12 weeks (p=0.028). We observed an inverse relationship between smear grade and contamination risk throughout the sampling period. These findings underscore the importance of supervised sputum collection to reduce contamination and provide ways to enhance the clinical and research value of weekly cultures, particularly those collected later in treatment. This is especially relevant for community-collected specimens used in monitoring treatment response.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory risk loci link disrupted androgen response to pathophysiology of Polycystic Ovary Syndrome.","authors":"Jaya Srivastava, Ivan Ovcharenko","doi":"10.1101/2025.03.26.25324630","DOIUrl":"https://doi.org/10.1101/2025.03.26.25324630","url":null,"abstract":"<p><p>A major challenge in deciphering the complex genetic landscape of Polycystic Ovary Syndrome (PCOS) is the limited understanding of the molecular mechanisms driven by susceptibility loci, necessitating investigation into the regulatory pathways that contribute to the diverse phenotypic manifestations of PCOS. In this study, we integrated molecular and epigenomic annotations across proposed pathogenic cell types and employed a deep learning (DL) model to infer the cell type specific effects of risk variants. Our analysis revealed the role of these variants in brain and endocrine cell types affecting the binding sites of key transcription factors (TFs): FOXA1, FOXL1, WT1, SALL4, and CPEB1, which regulate ovarian development, folliculogenesis, and steroid hormone signaling, contributing to disease-associated transcriptomic profiles. Our DL model, which is strongly correlated with MPRA data, identified enhancer-disrupting activity in 20% of the risk variants, particularly affecting TFs involved in androgen-mediated signaling, shedding light on the molecular consequences of hyperandrogenemia. Using the FTO/IRX3 locus as a case study, we explored the potential cell-type-specific regulatory effects of risk variants in the fetal brain, pancreas, adipocytes, and an endothelial cell line, which suggest that disruptions in IRX3 regulation (previously linked to obesity) may contribute to PCOS pathogenesis through diverse mechanisms, including neuronal development, metabolic regulation, and folliculogenesis. Our findings underscore the value of integrating DL models with epigenomic annotations to identify disease relevant variants, explore the pleiotropic impact of disease risk loci, and gain novel insights into cross cell type regulatory interactions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infant Subcortical Brain Volumes Associated with Maternal Obesity and Diabetes: A Large Multicohort Study.","authors":"Ann M Alex, Jerod M Rasmussen, Jetro J Tuulari, Julie Nihouarn Sigurðardottir, Claudia Buss, Kirsten A Donald, A David Edwards, Sonja Entringer, John H Gilmore, Nynke A Groenewold, Hasse Karlsson, Linnea Karlsson, Katherine E Lawrence, Inka Mattilla, Dan J Stein, Martin Styner, Paul M Thompson, Pathik D Wadhwa, Heather J Zar, Xi Zhu, Gustavo de Los Campos, Rebecca C Knickmeyer, Shan Luo","doi":"10.1101/2025.03.25.25324641","DOIUrl":"https://doi.org/10.1101/2025.03.25.25324641","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Maternal diabetes (MD) and maternal obesity (MO) have been robustly established to confer health risks in offspring. Additionally, mounting evidence suggests that these fetal programming effects vary by sex, but whether these factors independently or interactively influence infant brain development remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To characterize interactions between MD, MO, and sex on offspring subcortical brain volumes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design setting and participants: &lt;/strong&gt;This was a cross-sectional study of 1,966 infants from six international cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;MD and MO.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;MRI-based subcortical brain volumes (thalamus, amygdala, hippocampus, pallidum, putamen, caudate) were segmented and mixed effects models were used to examine associations, controlling for age at scan, prematurity, birthweight, maternal education, and intracranial volume. Backward elimination regression was used to identify the best fitting model (3-way interaction, 2-way interaction, no interaction) for each region and false discovery rate (FDR) corrections were applied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 1,966 infants, 46% were female (N=909), 9% were exposed to MD (N=172), and 21% were exposed to MO (N=386). MRI scans were performed at (mean±SD) 25.9±18.8 days of age. There was a significant interaction between MD, MO and sex in the thalamus (standardized β=-0.32, 95%CI -0.54 to -0.11, FDR corrected &lt;i&gt;P&lt;/i&gt; =0.014). In female infants, MD (standardized β=-0.10, 95%CI -0.02 to -0.003, &lt;i&gt;P&lt;/i&gt; =0.04) and MO (standardized β =-0.09, 95%CI -0.14 to -0.03, &lt;i&gt;P&lt;/i&gt; =0.003) were independently and negatively associated with thalamic volume. In males, a significant interaction between MD and MO was observed (standardized β =-0.20, 95%CI -0.34 to -0.06, &lt;i&gt;P&lt;/i&gt; =0.005), with post hoc analysis showing that males with combined exposure to MD and MO had lower thalamic volume compared to those with one or neither exposure (all &lt;i&gt;Ps&lt;/i&gt; &lt;0.05). In the hippocampus, an interaction between MO and infant sex was identified (standardized β =0.15, 95%CI 0.05 to 0.26, FDR corrected &lt;i&gt;P&lt;/i&gt; =0.015), whereby MO (independent of MD) was associated with lower offspring hippocampal volume in females only (standardized β =-0.12, 95%CI -0.2 to -0.05, &lt;i&gt;P&lt;/i&gt; =0.002).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion and relevance: &lt;/strong&gt;Our results suggest independent, interactive associations of intrauterine exposure to MD and MO with infant subcortical brain volumes, varying by sex. This has implications for future metabolic disorders, among other health risks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This study aims to investigate how sex modulates the influence of intrauterine exposure to maternal diabetes (MD) and maternal obesity (MO) on infant subcortical brain volumes. We observed sex-specific associations of gestational exposure to MD or MO with infant brain volumes in regions critical for mo","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mining Social Media Data for Influenza Vaccine Effectiveness Using a Large Language Model and Chain-of-Thought Prompting.","authors":"Dongfang Xu, Guillermo López García, Karen O'Connor, Haily Holston, Ari Z Klein, Ivan Flores Amaro, Matthew Scotch, Graciela Gonzalez-Hernandez","doi":"10.1101/2025.03.26.25324701","DOIUrl":"https://doi.org/10.1101/2025.03.26.25324701","url":null,"abstract":"<p><p>Influenza vaccine effectiveness (VE) estimation plays a critical role in public health decision-making by quantifying the real-world impact of vaccination campaigns and guiding policy adjustments. Current approaches to VE estimation are constrained by limited population representation, selection bias, and delayed reporting. To address some of these gaps, we propose leveraging large language models (LLMs) with few-shot chain-of-thought (CoT) prompting to mine social media data for real-time influenza VE estimation. We annotated over 4,000 tweets from the 2020-2021 flu season using structured guidelines, achieving high inter-annotator agreement. Our best prompting strategy achieves F ₁ scores above 87% for identifying influenza vaccination status and test outcomes, outperforming traditional supervised fine-tuning methods by large margins. These findings indicate that LLM-based prompting approaches effectively identify relevant social media information for influenza VE estimation, offering a valuable real-time surveillance tool that complements traditional epidemiological methods.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NONENDOSCOPIC DETECTION OF BARRETT'S ESOPHAGUS IN PATIENTS WITHOUT GERD SYMPTOMS.","authors":"Amitabh Chak, Komal Keerthy, Gi-Ming Wang, Wendy Brock, Beth Bednarchik, Rajesh Guptha, Suman Verma, Helen Moinova, Curtis Tatsuoka, John Dumot, Sapna Thomas, Joseph E Willis, Sanford Markowitz","doi":"10.1101/2025.03.26.25324651","DOIUrl":"https://doi.org/10.1101/2025.03.26.25324651","url":null,"abstract":"<p><strong>Background: </strong>Screening efforts for Barrett's Esophagus (BE) predominantly focus on performing upper endoscopy (EGD) on patients with gastroesophageal reflux disease (GERD) symptoms who have additional risk factors for BE. However, cost and invasiveness preclude EGD in those who have no prior GERD symptoms, despite having other risk factors, representing missed opportunities for BE screening in individuals who account for approximately 40% of the patients who eventually develop esophageal adenocarcinoma (EAC).</p><p><strong>Aim: </strong>The aim of this study was to evaluate if non-endoscopic methods can enable BE detection in an at-risk population without GERD symptoms.</p><p><strong>Methods: </strong>Patients presenting for colonoscopy who had not undergone previous EGD plus had ≥3 BE risk factors (from among age > 50 years, male sex, white race, smoking history, family history of BE/EAC, or central obesity) without chronic GERD symptoms were prospectively recruited for non-endoscopic screening. Trained nurses administered the EsoCheck (Lucid Diagnostics) encapsulated balloon. Samples were assayed with the EsoGuard BE detection methylated DNA marker panel (Lucid Diagnostics). Patients with a positive result were offered standard-of-care EGD, while patients with a negative EG result were offered free of cost research EGD. Positive predictive value (PPV), negative predictive value (NPV), and BE prevalence were calculated.</p><p><strong>Results: </strong>The mean age of the 132 study subjects was 60.7 years, 129 (98%) were white, 124 (94%) were male, 71 (54%) had a prior smoking history, 46 (35%) were centrally obese, and 5 (4%) reported a family history. EsoCheck was successfully administered in 124 (94%) and the EsoGuard methylated DNA marker panel could be assayed in 120 (97%) of the samples. Thirty-four assays were positive of which 27 underwent a follow-up EGD and BE was identified in 9, PPV = 33% [17%, 54%] subjects. EGD was also performed in 22 of the 86 subjects whose assays were negative and none of them had BE, NPV = 100% [85%, 100%]. A logistic regression model fitted to impute the presence of BE estimated the PPV as 27% [13%, 44%], NPV as 98% [92%, 100%], and BE prevalence as 8.4% [4.5%, 14.3%].</p><p><strong>Conclusion: </strong>Patients without chronic GERD who have ≥3 BE risk factors have a moderately high prevalence of BE. Non-endoscopic detection can effectively identify BE, enabling expansion of screening to this larger at-risk population. Those with a negative EG assay have a low likelihood of BE.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential of Large Language Models for Automated Safety Plan Scoring in Outpatient Mental Health Settings.","authors":"Hayoung K Donnelly, Gregory K Brown, Kelly L Green, Ugurcan Vurgun, Sy Hwang, Emily Schriver, Michael Steinberg, Megan Reilly, Haitisha Mehta, Christa Labouliere, Maria Oquendo, David Mandell, Danielle L Mowery","doi":"10.1101/2025.03.26.25324610","DOIUrl":"https://doi.org/10.1101/2025.03.26.25324610","url":null,"abstract":"<p><p>The Safety Planning Intervention (SPI) produces a plan to help manage patients' suicide risk. High-quality safety plans - that is, those with greater fidelity to the original program model - are more effective in reducing suicide risk. We developed the Safety Planning Intervention Fidelity Rater (SPIFR), an automated tool that assesses the quality of SPI using three large language models (LLMs)-GPT-4, LLaMA 3, and o3-mini. Using 266 deidentified SPI from outpatient mental health settings in New York, LLMs analyzed four key steps: warning signs, internal coping strategies, making environments safe, and reasons for living. We compared the predictive performance of the three LLMs, optimizing scoring systems, prompts, and parameters. Results showed that LLaMA 3 and o3-mini outperformed GPT-4, with different step-specific scoring systems recommended based on weighted F1-scores. These findings highlight LLMs' potential to provide clinicians with timely and accurate feedback on SPI practices, enhancing this evidence-based suicide prevention strategy.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}