medRxiv : the preprint server for health sciences最新文献

{"title":"Psychometric Properties and Prognostic Value of the UCSD Shortness of Breath Questionnaire in Hypersensitivity Pneumonitis: A Prospective Cohort Study.","authors":"Jeffrey J Swigris, Teng Moua, Sachin Chaudhary, Tracy N Adams, Ayodeji Adegunsoye, Mary Beth Scholand, Namita Sood, Brian Vestal, Evans R Fernández Pérez","doi":"10.1101/2025.09.24.25336538","DOIUrl":"https://doi.org/10.1101/2025.09.24.25336538","url":null,"abstract":"<p><strong>Rationale: </strong>Dyspnea is a prominent symptom of hypersensitivity pneumonitis (HP), limiting patients' activity and impairing their quality of life. The University of California San Diego Shortness of Breath questionnaire (UCSD) is a 24-item instrument used to assess dyspnea severity in patients with various respiratory conditions.</p><p><strong>Objective: </strong>To examine the psychometric properties of the UCSD and assess the validity of its scores as measures of dyspnea severity and prognostic value in a prospective cohort with HP.</p><p><strong>Methods: </strong>We evaluated the reliability, validity, and responsiveness of UCSD scores and assessed the association between score change and survival in a cohort of patients with HP who completed the UCSD and other HP severity metrics at baseline, 6 and 12 months. We introduce the reliable change index (RCI) and the likely change index (LCI) as ways to assess the statistical significance of within-individual change in UCSD scores and conducted analyses to provide context.</p><p><strong>Results: </strong>At baseline, internal consistency (Cronbach's coefficient alpha) was 0.97; there were significant, moderately strong correlations between UCSD scores and percent predicted forced vital capacity (FVC%) r = -0.39, percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) r = -0.33), and Borg dyspnea scores (0.55). UCSD scores were significantly different between the lowest and highest FVC%, 64.9 ± 18.9 vs. 36.2 ± 22.9. A 10- point worsening in the UCSD score was associated with a nearly 15-fold increase in time-to-death over the follow-up period.</p><p><strong>Conclusion: </strong>The UCSD has acceptable psychometric properties for assessing dyspnea severity in patients with HP. Worsening dyspnea is associated with shortened survival.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214952","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":"Reduced central alpha power at rest is associated with risk of alcohol-related blackout and frequency of non-REM parasomnia episodes.","authors":"Grace M Elliott, Madeline M Robertson, Celine E Locklear, Donita L Robinson, Margaret A Sheridan, Charlotte A Boettiger","doi":"10.1101/2025.09.25.25336484","DOIUrl":"https://doi.org/10.1101/2025.09.25.25336484","url":null,"abstract":"<p><p>People who report experiencing alcohol-related blackouts (ARBs) are at increased risk of alcohol-related injury and even death. Blackout susceptibility is heritable and blackouts are not experienced by all who engage in hazardous drinking. Blackout is defined by anterograde amnesia, but a person in the blackout state also maintains consciousness and motor control at high levels of intoxication, which is behaviorally similar to episodes seen in individuals with a history of sleepwalking or related parasomnias. Spectral analysis of resting-state electroencephalograms (EEG) can provide insight into individual differences in baseline neurophysiology which may predict blackout susceptibility in otherwise healthy individuals. The current study investigated potential neurophysiological phenotypes present in the resting-state EEG spectra of individuals with a history of blackout, sleepwalking, or related parasomnias. In Experiment 1, adult females with a history of alcohol-related blackout had reduced resting-state alpha peak power over the primary motor cortex compared to those with no such history, while aperiodic slope over the right primary motor cortex was negatively correlated with lifetime blackout score in males. In Experiment 2, increased frequency of parasomnia episodes was associated with reduced resting-state alpha peak power across males and females. Together, these findings provide the first support for the existence of common neurophysiological phenotypes between specific parasomnias and alcohol-related blackout.</p><p><strong>New & noteworthy: </strong>Research on blackout often focuses on hippocampal suppression by alcohol because anterograde amnesia is a salient and definitional aspect of alcohol-related blackout. We focused here instead on the resilience of motor function to suppression by alcohol during the blackout state. We identified a sex-specific EEG marker associated with blackout history, and then found that the same marker was related to the frequency of episodes of certain non-REM parasomnias in both sexes. These findings suggest that these pathological states may share underlying dysfunction of motor inhibition, allowing for coordinated motor activity to persist during intoxication or sleep.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214997","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":"Pain Treatment Strategy and Readmission Rates for Medicare Beneficiaries Post-Acute Ischemic Stroke.","authors":"Madhav Sankaranarayanan, Rebeka Bustamante Rocha, Julianne D Brooks, Maria A Donahue, Shuo Sun, Sonia Hernandez Diaz, Alexander Tsai, Joseph P Newhouse, Sebastien Haneuse, Lidia M V R Moura","doi":"10.1101/2025.09.25.25336638","DOIUrl":"https://doi.org/10.1101/2025.09.25.25336638","url":null,"abstract":"<p><strong>Purpose: </strong>Stroke is highly prevalent and commonly presents with pain. Primary care providers generally manage follow-up care, although ideal pain management strategies remain unclear. Treatment options include gabapentinoids, tricyclic antidepressants, and various antiseizure medications. We aim to analyze differences in hospital readmissions, a quality metric, for those initiating gabapentin in contrast to other medicines for post-stroke pain in older adults.</p><p><strong>Methods: </strong>In this matched cohort study, we analyzed a 20% sample of U.S. Medicare beneficiaries aged 65 and over hospitalized for acute ischemic stroke (AIS) between December 31, 2016, and December 31, 2021, who were discharged home. Individuals met insurance coverage criteria and did not take pain medications before hospitalization. We matched individuals on days from discharge to medication initiation. Individuals who initiated Gabapentin within 90 days of discharge (N = 1,546) were matched to individuals who initiated first-line pharmacological treatments for nerve pain other than Gabapentin within 90 days of discharge (N = 285). We investigated the time to re-admissions using a semi-competing risk framework.</p><p><strong>Results: </strong>The matched cohort of 1,831 initiators had a median age of 76 (IQR 11) and was 57.2% female and 81.3% Non-Hispanic White. Using the semi-competing risk framework, the hazard of readmissions, given that death had not occurred, was not different for Gabapentin initiators, compared to if they had initiated other medications, hazard ratio 0.871 (95% CI: 0.517, 1.466).</p><p><strong>Conclusion: </strong>We found no significant difference in hospital readmission rates between gabapentin and other post-stroke pain treatment strategies. Our findings contribute to the pharmacosurveillance of gabapentin in real-world Medicare beneficiaries.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214911","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":"CSF Hypo-Inflammation Drives Mortality in HIV-Associated Tuberculous Meningitis.","authors":"Anna L Wilt, David B Meya, Fiona V Cresswell, Abduljewad Wele, Mable Kabahubya, Enock Kagimu, Jane Gakuru, Timothy Mugabi, Sarah Kimuda, Suzan Namombwe, Asmus Tukundane, Elizabeth C Okafor, Biyue Dai, Nicole Engen, Nathan C Bahr, David R Boulware, Tyler D Bold","doi":"10.1101/2025.09.24.25336544","DOIUrl":"https://doi.org/10.1101/2025.09.24.25336544","url":null,"abstract":"<p><strong>Background: </strong>Excessive CNS inflammation is associated with poor outcomes in tuberculous meningitis (TBM). Anti-inflammatory corticosteroid therapy improves survival in HIV-negative TBM, but not in people with HIV. In people with HIV, TBM is fatal in 40-50% of cases. Therefore, we investigated how mortality is associated with the local immune dynamics in people with HIV-associated TBM.</p><p><strong>Methods: </strong>We measured baseline concentrations of immune signaling mediators in cerebrospinal fluid (CSF) of 149 adults with HIV in Uganda, who presented with definite or probable TBM. Participants received both antimycobacterial and corticosteroid therapy.</p><p><strong>Results: </strong>Non-survivors had more severe TBM disease stage and lower blood CD4 T cells than survivors at baseline. Mortality at 90 days was strongly associated with CSF hypo-inflammation. CSF interferon gamma (IFN-γ) was the cytokine most differentially expressed by survivors (2.2 log ₂ -fold change higher, p=.003), and 90-day mortality was lower with increasing concentrations (Tertile-1=50%, Tertile-2=41%, Tertile-3=18%; p=.006). Even among people who successfully mounted a CSF cellular immune response (>5 white cells/μL CSF), those with low CSF IFN-γ had higher risk of death (Hazard Ratio =3.10 (1.44- 6.68). In contrast, people with intermediate CSF interleukin-13 had lower mortality than extreme (Tertile-1=45%, Tertile-2=22%, Tertile-3=40%; p=.017). Of all sub-groups, those with both peripheral CD4 depletion and low CSF IFN-γ had the highest mortality (63%).</p><p><strong>Conclusions: </strong>In adults with HIV-associated TBM receiving dexamethasone, mortality was strongly associated with CSF hypo-inflammation. Although steroids may be appropriate in those with high inflammation, personalized approaches to immunotherapy are likely necessary to improve outcomes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214967","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":"Comparing Five Generative AI Chatbots' Answers to LLM-Generated Clinical Questions with Medical Information Scientists' Evidence Summaries.","authors":"Mallory N Blasingame, Taneya Y Koonce, Annette M Williams, Jing Su, Dario A Giuse, Poppy A Krump, Nunzia B Giuse","doi":"10.1101/2025.09.24.25336199","DOIUrl":"10.1101/2025.09.24.25336199","url":null,"abstract":"<p><strong>Objective: </strong>To compare answers to clinical questions between five publicly available large language model (LLM) chatbots and information scientists.</p><p><strong>Methods: </strong>LLMs were prompted to provide 45 PICO (patient, intervention, comparison, outcome) questions addressing treatment, prognosis, and etiology. Each question was answered by a medical information scientist and submitted to five LLM tools: ChatGPT, Gemini, Copilot, DeepSeek, and Grok-3. Key elements from the answers provided were used by pairs of information scientists to label each LLM answer as in Total Alignment, Partial Alignment, or No Alignment with the information scientist. The Partial Alignment answers were also analyzed for the inclusion of additional information.</p><p><strong>Results: </strong>The entire LLM set of answers, 225 in total, were assessed as being in Total Alignment 20.9% of the time (n=47), in Partial Alignment 78.7% of the time (n=177), and in No Alignment 0.4% of the time (n=1). Kruskal-Wallis testing found no significant performance difference in alignment ratings between the five chatbots (<i>p</i>=0.46). An analysis of the partially aligned answers found a significant difference in the number of additional elements provided by the information scientists versus the chatbots per Wilcoxon-Rank Sum testing (<i>p</i>=0.02).</p><p><strong>Discussion: </strong>Five chatbots did not differ significantly in their alignment with information scientists' evidence summaries. The analysis of partially aligned answers found both chatbots and information scientists included additional information, with information scientists doing so significantly more often. An important next step will be to assess the additional information both from the chatbots and the information scientists for validity and relevance.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214815","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 multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations.","authors":"Nuzulul Kurniansyah, Shinya Tasaki, Habbibur Rehman, Congcong Zhu, John Farrell, Richard Sherva, Richard Hauger, Victoria C Merritt, Matthew Panizzon, Rui Zhang, J Michael Gaziano, Jungsoo Gim, Kunho Lee, Dong Yong Lee, Kwansik Nho, Ricardo A Vialle, Shubhabrata Mukherjee, Emily H Trittschuh, Annie J Lee, Adam M Brickman, Carlos Cruchaga, Shannon Risacher, Douglas N Greve, Paul Crane, Eden Martin, William Bush, Richard Mayeux, Jonathan L Haines, Margaret A Pericak-Vance, Mark Logue, David A Bennett, Lisa L Barnes, Andrew Saykin, Timothy Hohman, Li-San Wang, Gerard C Schellenberg, Ting Fang Alvin Ang, Rhoda Au, Jesse Mez, Kathryn L Lunetta, Xiaoling Zhang, Lindsay A Farrer","doi":"10.1101/2025.09.24.25336555","DOIUrl":"https://doi.org/10.1101/2025.09.24.25336555","url":null,"abstract":"<p><p>Alzheimer disease (AD) has a strong genetic basis, yet previously derived polygenic risk scores (PRS) are heavily weighted by the <i>APOE</i> locus and perform inconsistently across diverse ancestries. We developed an <i>APOE</i> -independent multi-ancestry AD PRS using genome-wide association study summary statistics from cohorts in the United States, Europe and East Asia that were applied to European ancestry (EA), African American (AA), Caribbean Hispanic (CH), and East Asian cohorts from the Alzheimer's Disease Genetics Consortium. PRS performance was evaluated in the multi-ancestry Alzheimer's Disease Sequencing Project (ADSP) dataset and validated in several additional multi-ancestry cohorts. The PRS was significantly associated with AD in the ADSP EA, AA, CH, and Native American Hispanic groups with adjusted odds ratios (ORs) between 1.14 and 1.52 per standard deviation of the PRS. PRS performance was validated in the replication cohorts (ORs 1.21-1.65). The PRS was also associated with poorer memory, executive function, and language performance; greater AD-related neuropathological burden (including CERAD, Braak stage, and Thal phase scores); reduced hippocampal volume; lower CSF Aβ42; and elevated total tau and phosphorylated tau (p-tau), with stronger p-tau associations observed in women. Longitudinal analyses revealed that individuals in the highest PRS decile exhibited the steepest cognitive decline, particularly among those who progressed to AD. Our findings demonstrate the utility of an ancestry-aware and APOE-independent PRS for advancing understanding of the genetic basis of AD across diverse populations. Associations observed with early biological and cognitive changes and potential sex-specific differences support the incorporation of a PRS in clinical trials and personalized intervention and prevention strategies.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214810","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":"Evaluating the causal effect of mitochondrial dysfunction on Alzheimer's and Parkinson's disease using Polygenic Risk Scores and Mendelian Randomization.","authors":"Aadrita Chatterjee, Brian Alvarez, Rakshya U Sharma, Caroline Jonson, Heather M Wilkins, Judy Pa, Russell H Swerdlow, Alison Goate, Kristine Yaffe, Shea J Andrews","doi":"10.1101/2025.09.25.25336251","DOIUrl":"https://doi.org/10.1101/2025.09.25.25336251","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial DNA copy number (mtDNAcn), a measure of mitochondrial genomes per nucleated cell, has an unclear causal relationship with AD and PD. We integrate genetic correlation, Polygenic Risk Scores (PRS), and Mendelian Randomization (MR) to assess whether mtDNAcn influences the risk of AD and PD, and evaluate how study-specific factors in mtDNAcn genome-wide association studies (GWAS) may distort these causal estimates.</p><p><strong>Methods: </strong>Using GWAS of four mtDNAcn measures, AD, AD/dementia, and PD, we evaluated genetic correlations, generated ancestry-normalized PRS in the AD Genetics Consortium (N=27,383), and applied MR methods including Latent Heritable Confounder MR (LHC-MR).</p><p><strong>Results: </strong>Across the four mtDNAcn GWAS, only one was consistently associated with AD/dementia and PD, with genetic correlations and PRS analysis showing negative correlations and MR indicating that higher mtDNAcn reduced AD/dementia and PD risk.</p><p><strong>Discussion: </strong>Higher blood-based mtDNAcn was causally associated with reduced risk of AD/dementia and PD, with limited evidence to suggest a bidirectional effect.</p><p><strong>Research in context: </strong><b>Systematic Review:</b> Mitochondrial dysfunction, measured by mitochondrial DNA copy number (mtDNAcn), has been linked to Alzheimer's disease (AD) and Parkinson's disease (PD). However, Mendelian randomization (MR) studies on this relationship have shown inconsistent results, have not applied advanced MR methods that address prior limitations, or examined study-specific biases.<b>Interpretation:</b> Using genetic correlations, polygenic scores, and Mendelian Randomization, we triangulated evidence across complementary methods. We found that results varied depending on the dataset (e.g., clinically diagnosed AD vs. family history of AD) and study design factors such as mtDNAcn measurement techniques. Despite these biases, higher mtDNAcn was consistently associated with a lower risk of AD and PD, supporting a mitochondrial mechanism in both diseases.<b>Future directions:</b> Our findings highlight mtDNAcn as a potential biomarker for AD/PD, emphasizing the importance of measurement methods. Future research is needed to explore the biological pathways underlying this relationship.</p><p><strong>Highlights: </strong>Genetically predicted higher mtDNAcn is causally associated with lower AD and PD riskAD genetic liability is causally associated with higher mtDNAcn, possibly as a compensatory responsemtDNAcn is a potential early biomarker of mitochondrial dysfunction in AD/PD.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214890","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":"Omega-6 polyunsaturated fatty acids and adiposity in the UK Biobank Cohort: a cross-sectional and longitudinal prospective analysis.","authors":"Heidi T M Lai, Jason Westra, Evan De Jong, Nathan L Tintle, Martha A Belury, William S Harris","doi":"10.1101/2025.09.24.25336554","DOIUrl":"https://doi.org/10.1101/2025.09.24.25336554","url":null,"abstract":"<p><strong>Background: </strong>The role of omega-6 polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) in adiposity remains contested. While clinical interventions suggest improved body composition with higher LA intake, observational evidence is inconsistent, and few studies incorporate repeated measures to examine longitudinal change.</p><p><strong>Objective: </strong>To investigate associations of circulating LA, non-LA omega-6, and total omega-6 PUFAs with adiposity outcomes in the UK Biobank.</p><p><strong>Methods: </strong>Multivariable linear models evaluated cross-sectional and longitudinal associations between omega-6 fatty acid levels and waist circumference (WC), weight, and whole-body fat mass (FM) adjusting for relevant demographic, lifestyle and medical history covariates. Models considered FA levels per interquintile range and by quintiles.</p><p><strong>Results: </strong>Cross-sectionally, higher circulating LA was inversely associated with WC, weight, and FM. Participants in the highest versus lowest quintile of LA had significantly smaller WC [-11.04 (-11.17, -10.91) cm], lower weight [-11.77 (-11.92, -11.62) kg], and lower FM [-7.87 (-7.97, -7.77) kg]. Associations for total omega-6 were generally consistent with those for LA. Conversely, non-LA omega-6 was positively associated with WC [1.46 (1.32, 1.61) cm], weight [2.41 (2.25, 2.58) kg], and FM [1.81 (1.69, 1.92) kg]. Longitudinal analyses largely corroborated these patterns, with annual changes in WC, weight, and FM inversely associated with LA and positively associated with non-LA omega-6.</p><p><strong>Conclusions: </strong>Higher circulating LA, but not non-LA omega-6, was associated with lower WC, weight, and FM both cross-sectionally and longitudinally. Our findings support dietary recommendations to promote LA-rich oils. Divergent associations between LA and non-LA omega-6 caution against treating omega-6 PUFAs as a homogenous group, and there remains a need to examine the distinct health effects of individual non-LA omega-6.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214802","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":"Optical blood flow monitoring in humans with SNSPDs and high-density SPADs.","authors":"Carsi Kim, Christopher H Moore, Chien-Sing Poon, Michael A Wayne, Paul Mos, Arin Ulku, Timothy M Rambo, Aaron J Miller, Claudio Bruschini, Edoardo Charbon, Ulas Sunar","doi":"10.1101/2025.06.08.25329202","DOIUrl":"10.1101/2025.06.08.25329202","url":null,"abstract":"<p><p>Continuous, noninvasive monitoring of cerebral blood flow (CBF) is vital for neurocritical care. Diffuse correlation spectroscopy (DCS) enables assessment of microvascular blood flow by analyzing speckle intensity fluctuations of near-infrared light. In this review, we summarize recent advances in TD-DCS using superconducting nanowire single-photon detectors (SNSPDs) at 1064 nm, as well as complementary developments in high-density CW-DCS systems using single-photon avalanche diode (SPAD) cameras. Time-gated photon detection improves depth sensitivity in TD-DCS, and the use of longer wavelengths provides advantages in tissue penetration, photon throughput, and safety margin under ANSI exposure limits. Clinically feasible SPAD-based implementations, while lacking time-of-flight resolution, enable large signal-to-noise ratio gains via massive pixel averaging and offer a room-temperature, scalable path to high-density optical tissue monitoring. Together, these developments highlight a growing set of technologies for clinical applications, including bedside brain monitoring in neurocritical care. We conclude with practical guidance on detector technologies, gating strategies, system packaging, and briefly discuss interferometric DCS and speckle contrast optical spectroscopy (SCOS) as synergistic extensions for high-resolution and high-coverage imaging.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532313","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 modular pipeline for natural language processing-screened human abstraction of a pragmatic trial outcome from electronic health records.","authors":"Robert Y Lee, Kevin S Li, James Sibley, Trevor Cohen, William B Lober, Janaki O'Brien, Nicole LeDuc, Kasey Mallon Andrews, Anna Ungar, Jessica Walsh, Elizabeth L Nielsen, Danae G Dotolo, Erin K Kross","doi":"10.1101/2025.06.23.25330134","DOIUrl":"10.1101/2025.06.23.25330134","url":null,"abstract":"<p><strong>Background: </strong>Natural language processing (NLP) allows efficient extraction of clinical variables and outcomes from electronic health records (EHR). However, measuring pragmatic clinical trial outcomes may demand accuracy that exceeds NLP performance. Combining NLP with human adjudication can address this gap, yet few software solutions support such workflows. We developed a modular, scalable system for NLP-screened human abstraction to measure the primary outcomes of two clinical trials.</p><p><strong>Methods: </strong>In two clinical trials of hospitalized patients with serious illness, a deep-learning NLP model screened EHR passages for documented goals-of-care discussions. Screen-positive passages were referred for human adjudication using a REDCap-based system to measure the trial outcomes. Dynamic pooling of passages using structured query language (SQL) within the REDCap database reduced unnecessary abstraction while ensuring data completeness.</p><p><strong>Results: </strong>In the first trial (N=2,512), NLP identified 22,187 screen-positive passages (0.8%) from 2.6 million EHR passages. Human reviewers adjudicated 7,494 passages over 34.3 abstractor-hours to measure the cumulative incidence and time to first documented goals-of-care discussion for all patients with 92.6% patient-level sensitivity. In the second trial (N=617), NLP identified 8,952 screen-positive passages (1.6%) from 559,596 passages at a threshold with near-100% sensitivity. Human reviewers adjudicated 3,509 passages over 27.9 abstractor-hours to measure the same outcome for all patients.</p><p><strong>Conclusion: </strong>We present the design and source code for a scalable and efficient pipeline for measuring complex EHR-derived outcomes using NLP-screened human abstraction. This implementation is adaptable to diverse research needs, and its modular pipeline represents a practical middle ground between custom software and commercial platforms.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644501","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}