medRxiv : the preprint server for health sciences最新文献

{"title":"Inflammatory reactivity is unrelated to childhood adversity or provoked modulation of nociception.","authors":"Gillian J Bedwell, Luyanduthando Mqadi, Peter R Kamerman, Mark R Hutchinson, Romy Parker, Victoria J Madden","doi":"10.1101/2024.12.16.24319079","DOIUrl":"10.1101/2024.12.16.24319079","url":null,"abstract":"<p><p>Adversity in childhood is robustly associated with persistent pain in adulthood. Neuro-immune interactions are a candidate mechanistic link between childhood adversity and persistent pain, given that both childhood adversity and persistent pain are associated with neural and immune upregulation in adulthood. As such, we aimed to clarify whether immune reactivity is associated with provoked differences in nociceptive processing in humans. Pain-free adults (n=96; 61 female; median (range) age: 23 (18-65) years old) with a history of mild to severe childhood adversity underwent psychophysical assessments before and after in vivo neural provocation (high-frequency electrical stimulation) and then, separately, in vivo immune provocation (influenza vaccine administration). Psychophysical assessments included the surface area of secondary hyperalgesia after neural provocation and change in conditioned pain modulation (test stimulus: pressure pain threshold; conditioning stimulus: cold water immersion) after immune provocation. Immune reactivity was assessed as IL-6 and TNF-alpha expression after in vitro lipopolysaccharide provocation of whole blood. We hypothesised associations between immune reactivity and (1) childhood adversity, (2) induced secondary hyperalgesia, and (3) vaccine-associated change in conditioned pain modulation. We found that provoked expression of pro-inflammatory cytokines was not statistically associated with childhood adversity, induced secondary hyperalgesia, or vaccine-associated change in conditioned pain modulation. The current findings from a heterogenous sample cast doubt on two prominent ideas: that childhood adversity primes the inflammatory system for hyper-responsiveness in adulthood and that nociceptive reactivity is linked to inflammatory reactivity. This calls for the broader inclusion of heterogeneous samples in fundamental research to unpack the psychoneuroimmunological mechanisms underlying vulnerability to persistent pain.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960985","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":"Prompts to Table: Specification and Iterative Refinement for Clinical Information Extraction with Large Language Models.","authors":"David Hein, Alana Christie, Michael Holcomb, Bingqing Xie, A J Jain, Joseph Vento, Neil Rakheja, Ameer Hamza Shakur, Scott Christley, Lindsey G Cowell, James Brugarolas, Andrew R Jamieson, Payal Kapur","doi":"10.1101/2025.02.11.25322107","DOIUrl":"10.1101/2025.02.11.25322107","url":null,"abstract":"<p><p>Extracting structured data from free-text medical records at scale is laborious, and traditional approaches struggle in complex clinical domains. We present a novel, end-to-end pipeline leveraging large language models (LLMs) for highly accurate information extraction and normalization from unstructured pathology reports, focusing initially on kidney tumors. Our innovation combines flexible prompt templates, the direct production of analysis-ready tabular data, and a rigorous, human-in-the-loop iterative refinement process guided by a comprehensive error ontology. Applying the finalized pipeline to 2,297 kidney tumor reports with pre-existing templated data available for validation yielded a macro-averaged F1 of 0.99 for six kidney tumor subtypes and 0.97 for detecting kidney metastasis. We further demonstrate flexibility with multiple LLM backbones and adaptability to new domains utilizing publicly available breast and prostate cancer reports. Beyond performance metrics or pipeline specifics, we emphasize the critical importance of task definition, interdisciplinary collaboration, and complexity management in LLM-based clinical workflows.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485381","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":"Directed exploration is reduced by an aversive interoceptive state induction in healthy individuals but not in those with affective disorders.","authors":"Ning Li, Claire A Lavalley, Ko-Ping Chou, Anne E Chuning, Samuel Taylor, Carter M Goldman, Taylor Torres, Rowan Hodson, Robert C Wilson, Jennifer L Stewart, Sahib S Khalsa, Martin P Paulus, Ryan Smith","doi":"10.1101/2024.06.19.24309110","DOIUrl":"10.1101/2024.06.19.24309110","url":null,"abstract":"<p><p>Elevated anxiety and uncertainty avoidance are known to exacerbate maladaptive choice in individuals with affective disorders. However, the differential roles of state vs. trait anxiety remain unclear, and underlying computational mechanisms have not been thoroughly characterized. In the present study, we investigated how a somatic (interoceptive) state anxiety induction influences learning and decision-making under uncertainty in individuals with clinically significant levels of trait anxiety. A sample of 58 healthy comparisons (HCs) and 61 individuals with affective disorders displaying elevated anxiety symptoms (iADs; i.e., anxiety and/or depression) completed a previously validated explore-exploit decision task, with and without an added breathing resistance manipulation designed to induce state anxiety. Computational modeling revealed a significant group-by-condition interaction, such that information-seeking (i.e., directed exploration) in HCs was reduced by the anxiety induction (Cohen's d=.47, p=.013), while no change was observed in iADs. The iADs also showed slower learning rates than HCs across conditions (Cohen's d=.52, p=.003), suggesting their uncertainty decreased more slowly over time. These findings highlight a complex interplay between trait anxiety and state anxiety. Specifically, state anxiety may attenuate reflection on uncertainty in healthy individuals, while familiarity with anxious states in those with high trait anxiety may create an insensitivity to this effect.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474291","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":"Effects of emotional arousal on amygdala neural response and cigarette craving reduction during repeated exposure to graphic warning labels.","authors":"Astrid P Ramos-Rolón, Daniel D Langleben, Kevin G Lynch, Corinde E Wiers, Zhenhao Shi","doi":"10.1101/2025.03.27.25324796","DOIUrl":"https://doi.org/10.1101/2025.03.27.25324796","url":null,"abstract":"<p><p>Graphic warning labels (GWLs) have been implemented on cigarette packaging worldwide. In the U.S., GWLs have encountered legal obstacles based on the tobacco industry arguments that their aversive imagery unnecessarily triggers strong emotional arousal. This longitudinal study evaluated the effect of the high-arousal GWLs on cigarette craving and the neural substrates of emotional processing. 158 adult smokers were exposed to either high-arousal (n=79) or low-arousal (n=79) GWLs that were attached to their own cigarette packs for 4 weeks. Craving and brain activity in response to GWLs and control stimuli were measured using functional magnetic resonance imaging before and after the 4-week exposure. The amygdala, which plays a key role in emotional processing, served as the a priori region of interest. Results indicate that, at baseline, high-arousal GWLs elicited a larger reduction in craving and stronger amygdala neural response compared to low-arousal GWLs; however, at week 4, GWL-induced craving reduction and amygdala response became comparable between the high-arousal and low-arousal groups. Amygdala response mediated GWLs' effects on craving reduction, which was moderated by arousal and time in such a way that the amygdala's mediating role was more pronounced for high-arousal than low-arousal GWLs at baseline but did not differ between groups at week 4. Together, the results suggest that the impact of emotional arousal on cigarette cravings decreases over time, potentially due to the amygdala's diminishing responsivity to repeated presentations of high-arousal imagery. Low-arousal GWLs may represent a more feasible approach for tobacco control efforts in the U.S.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805139","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":"The Therapeutic Impact of Genetic Evaluation in an Atrial Fibrillation Precision Medicine Clinic.","authors":"J Lukas Laws, Mahsima Shabani, Hollie L Williams, Dakota D Grauherr, Wendy M Kilbourne, Diane M Crawford, Isaac Ogunmola, Lili Sun, Zain Virk, Brianna Cathey, Majd A El-Harasis, Cassady J Pelphrey, Joseph A Quintana, Brittany S Murphy, Giovanni E Davogustto, M Edward Ponder, Omeed M Irani, J Michael Daw, Bibin T Varghese, Pablo Saavedra, Robert L Abraham, Juan C Estrada, Katherine T Murray, Walter K Clair, Sharon T Shen, Arvindh N Kanagasundram, Jay A Montgomery, Christopher R Ellis, Frank Fish, Travis D Richardson, George H Crossley, Rebecca R Hung, Jeffrey M Dendy, Adam Wright, Quinn S Wells, Fei Ye, Harikrishna Tandri, William G Stevenson, Megan Lancaster, Prince J Kannankeril, Lynne W Stevenson, Dan M Roden, Zachary T Yoneda, M Benjamin Shoemaker","doi":"10.1101/2025.03.28.25324544","DOIUrl":"https://doi.org/10.1101/2025.03.28.25324544","url":null,"abstract":"<p><strong>Background and aims: </strong>Genetic testing is recommended for select patients with atrial fibrillation (AF). The aims of this study were to define the results of genetic evaluation and its therapeutic impact for patients referred to a dedicated AF precision medicine clinic.</p><p><strong>Methods: </strong>Patients diagnosed with AF before age 60 were candidates for referral. In addition to standard evaluation with history, physical exam, and ECG, genetic evaluation included a 3-generation pedigree, cardiac imaging, ambulatory monitoring, and clinical genetic testing with a cardiomyopathy/arrhythmia panel.</p><p><strong>Results: </strong>264 participants were referred: the median age was 47 years (Q1, Q3: 38, 55), 77 (29%) were female, and 236 (89%) were White. Median age at AF diagnosis was 39 years (Q1, Q3: 31, 48) and median time from AF diagnosis to evaluation was 3.7 years (Q1, Q3: 0.9, 10). 242 patients (92%) underwent genetic testing, which identified a pathogenic or likely pathogenic variant in 48 (20%). The strongest predictors of positive genetic testing were history of cardiomyopathy, infranodal conduction disease, and elevated T1 or late gadolinium enhancement on cardiac MRI (all p<0.05). The strongest predictors of negative genetic testing were obstructive sleep apnea and a normal 12-lead ECG (both p<0.04). Overall, genetic testing changed clinical management in 52% of patients with positive genetic testing, highlighted by 7 new ICD placements and initiation of disease modifying therapy in 16 patients.</p><p><strong>Conclusions: </strong>Genetic testing was positive in 20% of patients with early-onset AF referred to a dedicated AF precision medicine clinic. Genetic testing results changed clinical management in approximately half of genotype-positive patients.</p><p><strong>Structured graphical abstract: </strong><b>Key Question:</b> Does genetic evaluation of patients with early-onset atrial fibrillation (AF) change their clinical management?<b>Key Finding:</b> Among 246 participants that completed genetic evaluation in a dedicated AF precision medicine clinic, 20% had positive genetic testing with identification of a pathogenic cardiomyopathy or channelopathy variant. These findings led to changes in clinical management in 52% of patients with positive genetic testing.<b>Take-home Message:</b> Genetic evaluation of patients with early-onset AF consists of detailed phenotyping and genetic testing to identify previously undiagnosed genetic disorders. This facilitates earlier diagnosis and clinical intervention.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804953","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":"Whole-Genome Sequencing Reveals Individual and Cohort Level Insights into Chromosome 9p Syndromes.","authors":"Yingxi Wang, Eleanor I Sams, Rachel Slaugh, Sandra Crocker, Emily Cordova Hurtado, Sophia Tracy, Ying-Chen Claire Hou, Christopher Markovic, Kostandin Valle, Victoria Tate, Khadija Belhassan, Elizabeth Appelbaum, Titilope Akinwe, Rodrigo Starosta Tzovenos, Yang Cao, Amber Neilson, Yu Liu, Nathaniel Jensen, Reza Ghasemi, Tina Lindsay, Juana Manuel, Sophia Couteranis, Milinn Kremitzki, Jack Ustanik, Thomas Antonacci, Jeffrey K Ng, Andrew Emory, Laura Metz, Tracie DeLuca, Katherine N Lyons, Toni Sinnwell, Brianne Thomeczek, Kymme Wang, Nick Sisneros, Megha Muraleedharan, Anantha Kethireddy, Marco Corbo, Harsha Gowda, Katherine King, Christina A Gurnett, Susan K Dutcher, Catherine Gooch, Yang E Li, Matthew W Mitchell, Kevin A Peterson, Amjad Horani, Jill A Rosenfeld, Weimin Bi, Pawel Stankiewicz, Hsiao-Tuan Chao, Jennifer Posey, Christopher M Grochowski, Zain Dardas, Erik Puffenberger, Christopher E Pearson, Frank Kooy, Dale Annear, A Micheil Innes, Michael Heinz, Richard Head, Robert Fulton, Stephan Toutain, Lucinda Antonacci-Fulton, Xiaoxia Cui, Robi D Mitra, F Sessions Cole, Julie Neidich, Patricia I Dickson, Jeffrey Milbrandt, Tychele N Turner","doi":"10.1101/2025.03.28.25324850","DOIUrl":"https://doi.org/10.1101/2025.03.28.25324850","url":null,"abstract":"<p><p>Previous genomic efforts on chromosome 9p deletion and duplication syndromes have utilized low resolution strategies (i.e., karyotypes, chromosome microarrays). We present the first large-scale whole-genome sequencing (WGS) study of 100 individuals from families with 9p-related syndromes including 85 unrelated probands through the 9P-ARCH ( <b>A</b> dvanced <b>R</b> esearch in <b>C</b> hromosomal <b>H</b> ealth: Genomic, Phenotypic, and Functional Aspects of <b>9p</b> -Related syndromes) research network. We analyzed the genomic architecture of these syndromes, highlighting fundamental features and their commonalities and differences across individuals. This work includes a machine-learning model that predicts 9p deletion syndrome from gene copy number estimates using WGS data. Two Late Replicating Regions (LRR1 [a previously un-named human fragile site], LRR2) were identified that contain most structural variant breakpoints in 9p deletion syndrome pointing to replication-based issues in structural variant formation. Furthermore, we show the utility of using WGS information to obtain a comprehensive understanding of 9p-related variation in an individual with complex structural variation where chromothripsis is the likely mechanism. Genes on 9p were prioritized based on statistical assessment of human genomic variation. Furthermore, through application of spatial transcriptomics to embryonic mouse tissue we examined 9p-gene expression in craniofacial and brain development. Through these strategies, we identified 24 important genes for the majority (83%) of individuals with 9p deletion syndrome including <i>AK3, BRD10, CD274, CDC37L1, DMRT1, DMRT2, DMRT3, DOCK8, GLIS3, JAK2, KANK1, KDM4C, PLPP6, PTPRD, PUM3, RANBP6, RCL1</i> , <i>RFX3</i> , <i>RIC1</i> , <i>SLC1A1</i> , <i>SMARCA2</i> , <i>UHRF2</i> , <i>VLDLR</i> , and <i>ZNG1A</i> . Two genes ( <i>AK3</i> , <i>ZNG1A</i> ) are involved in mitochondrial function and testing of the mitochondrial genome revealed excess copy number in individuals with 9p deletion syndrome. This study presents the most comprehensive genomic analysis of 9p-related syndromes to date, with plans for further expansion through our 9P-ARCH research network.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805132","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":"Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study.","authors":"Bingyu Zhang, Qiong Wu, Ravi Jhaveri, Ting Zhou, Michael J Becich, Yuriy Bisyuk, Frank Blanceró, Elizabeth A Chrischilles, Cynthia H Chuang, Linday G Cowell, Daniel Fort, Carol R Horowitz, Susan Kim, Nathalia Ladino, David M Liebovitz, Mei Liu, Abu S M Mosa, Hayden T Schwenk, Srinivasan Suresh, Bradley W Taylor, David A Williams, Jeffrey S Morris, Christopher B Forrest, Yong Chen","doi":"10.1101/2025.03.28.25324858","DOIUrl":"https://doi.org/10.1101/2025.03.28.25324858","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Post-acute sequelae of SARS-CoV-2 infection (PASC) remains a major public health challenge. While previous studies have focused on characterizing PASC and identifying its subphenotypes in children and adolescents following an initial SARS-CoV-2 infection, the risks of PASC with Omicron-variant reinfections remain unclear. Using a real-world data approach, this study investigates the risks of PASC following reinfections during the Omicron phase in the pediatric population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the risks of PASC diagnosis and 24 PASC symptoms and conditions after reinfection of SARS-CoV-2 during Omicron period in the pediatric population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design setting and participants: &lt;/strong&gt;This retrospective cohort study used data from the RECOVER consortium comprising 40 children's hospitals and health institutions in U.S. between January 2022 and October 2023.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;A second SARS-CoV-2 infection, confirmed by a positive polymerase-chain-reaction (PCR) or antigen tests, or a diagnose of COVID-19, occurring at least 60 days after the initial infection, compared to the initial infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;PASC was identified using two approaches: (1) the ICD-10- CM diagnosis code U09.9 and (2) a symptom-based definition including 24 physician-identified symptoms and conditions. Absolute risks of incident PASC were reported, and relative risks (RRs) were calculated by comparing the second infection episode with the first infection episode groups using a modified Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through exact matching and propensity scoring matching.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 465,717 individuals under 21 years old (mean [SD] age 8.17 [6.58] years; 52% male) were included. Compared to the first infection, a second infection was associated with significantly increased risk of an overall PASC diagnosis (RR, 2.08; 95% confidence interval [CI], 1.68-2.59), and with many specific conditions including: myocarditis (RR, 3.60; 95% CI, 1.46-8.86); changes in taste and smell (RR, 2.83; 95% CI, 1.41-5.67); thrombophlebitis and thromboembolism (RR, 2.28; 95% CI, 1.71-3.04); heart disease (RR, 1.96; 95% CI, 1.69 to 2.28); acute kidney injury (RR, 1.90; 95% CI, 1.38 to 2.61); fluid and electrolyte (RR, 1.89; 95% CI, 1.62 to 2.20); generalized pain (RR, 1.70; 95% CI, 1.48 to 1.95); arrhythmias (RR, 1.59; 95% CI, 1.45-1.74); abnormal liver enzyme (RR, 1.56; 95% CI, 1.24 to 1.96); fatigue and malaise (RR, 1.50; 95% CI, 1.38 to 1.64); musculoskeletal pain (RR, 1.45; 95% CI, 1.37 to 1.54); abdominal pain (RR, 1.42; 95% CI, 1.34 to 1.50); postural orthostatic tachycardia syndromes (POTS)/dysautonomia (RR, 1.35; 95% CI, 1.20 to 1.51); cognitive functions (RR, 1.32; 95% CI, 1.15 to 1.50); and respiratory signs and symptoms (RR, 1.29; 95% CI, 1.25 to 1.33). The risks were","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805277","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":"Real-World Type 2 Diabetes Second-Line Treatment Allocation Among Patients.","authors":"Jaysón Davidson, Rohit Vashisht, Kendra Radtke, Ayan Patel, Suneil K Koliwad, Atul J Butte","doi":"10.1101/2025.03.26.25324631","DOIUrl":"https://doi.org/10.1101/2025.03.26.25324631","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the impact of socioeconomic disparities on the allocation of second-line treatments among patients with type 2 diabetes (T2D).</p><p><strong>Materials and methods: </strong>We conducted an observational study using real-world data from over 9 million patients across five University of California Health centers. The study included patients who initiated a second-line T2D medication after metformin, with hemoglobin A1c (HbA1c) measurements within ±7 days of treatment initiation from 2012 through September 2024. Multinomial regression models assessed the association between socioeconomic status and second-line treatment choices. Additionally, we used the GPT-4 large language model with a zero-shot learning approach to analyze 270 clinical notes from 105 UCSF patients. GPT-4 identified adverse social determinants of health (SDOH) across six domains: transportation, housing, relationships, patients with children, support, and employment.</p><p><strong>Results: </strong>Among 15,090 patients (56.7% male, 43.3% female; mean age 59.3 years; mean HbA1c 8.91%), second-line treatments included sulfonylureas (SUs; n = 6,732), DPP4 inhibitors (n = 2,918), GLP-1 receptor agonists (n = 2,736), and SGLT2 inhibitors (n = 2,704). Patients from lower socioeconomic neighborhoods were more likely to receive SUs over other medications: DPP4i (OR = 0.96, [95% CI, 0.95-0.98]), GLP-1RA (OR = 0.94, [95% CI, 0.92-0.96]), SGLT2i (OR = 0.95, [95% CI, 0.93-0.97]). In UCSF clinical notes, we identified adverse SDOH including housing (n=8), transportation (n=1), relationships (n=22), employment (n=12), support (n=1), and patients with children (n=25).</p><p><strong>Conclusions: </strong>Socioeconomic factors influence second-line T2D treatment choices. Addressing these disparities is essential to ensuring equitable access to advanced T2D therapies.</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/PMC11974982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805237","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":"A Unified Flexible Large Polysomnography Model for Sleep Staging and Mental Disorder Diagnosis.","authors":"Guifeng Deng, Mengfan Niu, Yuxi Luo, Shuying Rao, Junyi Xie, Zhenghe Yu, Wenjuan Liu, Sha Zhao, Gang Pan, Xiaojing Li, Wei Deng, Wanjun Guo, Tao Li, Haiteng Jiang","doi":"10.1101/2024.12.11.24318815","DOIUrl":"10.1101/2024.12.11.24318815","url":null,"abstract":"<p><p>Sleep quality is vital to human health, yet automated sleep staging faces challenges in cross-center generalization due to data scarcity and domain gaps. Traditional scoring is labor-intensive, while deep learning models often fail to generalize across datasets. Here, we present LPSGM, a unified and flexible large polysomnography (PSG) model designed to enhance cross-center generalization in sleep staging and enable fine-tuning for disease diagnosis. Trained on 220,500 hours of PSG data from 16 public datasets, LPSGM integrates domain-adaptive learning and supports variable-channel configurations, achieving performance comparable to models trained directly on target-center data. In a prospective clinical study, LPSGM matches expert-level accuracy with lower variability. When fine-tuned, it attains 88.01% accuracy in narcolepsy detection and 100% in depression detection. These results establish LPSGM as a scalable, plug-and-play solution for automated PSG analysis, bridging the gap between sleep staging and clinical deployment.</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/PMC11661386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879328","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":"Opioidergic pain relief in humans is mediated by beta and high-gamma modulation in limbic regions.","authors":"Jacob C Garrett, Sierra Wilson, Alexander Jessup, Michael G Brandel, Caleb S Nerison, Ahmed M Raslan, Sharona Ben-Haim, Eric Halgren","doi":"10.1101/2025.03.03.25323046","DOIUrl":"10.1101/2025.03.03.25323046","url":null,"abstract":"<p><p>The nature of the neurophysiological effects of opioids, especially those responsible for their analgesic properties, are unknown, hindering efforts to develop non-addictive alternatives. Fentanyl and hydromorphone were administered to patients experiencing semi-chronic, clinically-relevant pain after surgical implantation of electrodes for the localization of seizure onset. Opioids suppressed beta oscillations in lateral amygdala, ventral and dorsolateral prefrontal cortices, and increased beta in medial amygdala and hippocampus. Opioids also suppressed high gamma oscillations in insula and lateral amygdala, and increased high gamma in cingulate cortex and hippocampus. The amplitude of these beta effects in the ventral prefrontal cortex, medial amygdala and hippocampus, and of gamma effects in the insula, were positively correlated with the magnitude of pain relief in response to a constant dose. These findings identify electrophysiological events in a network of limbic structures that may participate in opioidergic pain relief through nociceptive gating and a decreased concerned fixation on pain, providing insights into the neural basis of pain relief and suggesting possible biomarkers for developing non-addictive opioid alternatives.</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/PMC11908309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653034","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}