medRxiv : the preprint server for health sciences最新文献

{"title":"Racial and ethnic and sex differences in at-home estimates of sleep-disordered breathing parameters among Mexican American, Black, and Non-Hispanic White adults.","authors":"Yue Leng, Clémence Cavaillès, Carrie Peltz, Sid E O'Bryant, Susan Redline, Kristine Yaffe","doi":"10.1101/2024.10.23.24315996","DOIUrl":"https://doi.org/10.1101/2024.10.23.24315996","url":null,"abstract":"<p><p>Background Racial and ethnic and sex differences in sleep may exist, but there are limited data directly comparing objective estimates of sleep-disordered breathing (SDB), particularly in rapid eye movement (REM) versus non-rapid eye movement (NREM) sleep, among Black, Mexican American (MA) and non-Hispanic White (NHW) men and women. Our goal is to investigate health disparities in SDB in a new, diverse cohort of older adults. Research Question Do SDB parameters during REM and NREM sleep differ by race and ethnicity or sex in community-dwelling older adults?. Methods The Dormir Study conducted a comprehensive sleep examination among eligible participants enrolled in the ongoing community-based Health and Aging Brain Study-Health Disparities (HABS-HD) cohort (2020-4), among Black, MA, and NHW adults aged 50 years and older. Here we characterize racial and ethnic and sex differences in SDB indices assessed by an FDA-approved Peripheral Arterial Tonometry (PAT)-based home sleep testing system. Results We examined 821 participants, including 543 (66.1%) women, and 284 (34.6%) MA and 174 (21.2%) Black individuals, with a mean age of 66.6±8.5 years. Around half (50.5%) of the participants had moderate to severe SDB as defined by the respiratory event index (REI based on 3% desaturations) of ≥15/ hour, 72.7% with moderate to severe REM SDB (REM-REI ≥ 15/hour) and 39.5% with moderate to severe NREM SDB (NREM-REI ≥15/hour). The prevalence of SDB did not differ by race or sex. However, significant racial and ethnic and sex differences were observed for REM-specific SDB metrics. Overall, Black women had the highest REM REI, and NHW men had the lowest REM REI and REM ODI. After controlling for age, sex, education, income, employment status, cognitive status, BMI, history of hypertension, diabetes, stroke, and coronary heart disease, and sleep medication use, Black participants had a REM-REI that was 3 events per hour higher than that of NHW adults, while NREM-REI were similar. MA individuals had similar REM or NREM SDB parameters compared to NHW adults but exhibited higher average blood oxygen levels. Conclusions In this community-based cohort of middle- to older-aged NHW, MA, and Black adults, PAT-based measures of in-home sleep indicate a higher prevalence of REM SDB in Black adults, particularly Black women, compared to their NHW counterparts; this contrasts with the similar NREM parameters observed across racial and ethnic groups. Given the close link between REM SDB and adverse health outcomes, clinicians should pay more attention to this sleep apnea phenotype, especially in minoritized populations.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585441","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":"Extreme precipitation, exacerbated by anthropogenic climate change, drove Peru's record-breaking 2023 dengue outbreak.","authors":"Mallory J Harris, Jared T Trok, Kevin S Martel, Mercy J Borbor Cordova, Noah S Diffenbaugh, César V Munayco, Andrés G Lescano, Erin A Mordecai","doi":"10.1101/2024.10.23.24309838","DOIUrl":"https://doi.org/10.1101/2024.10.23.24309838","url":null,"abstract":"<p><p>Anthropogenic forcing is increasing the likelihood and severity of certain extreme weather events, which may catalyze outbreaks of climate-sensitive infectious diseases. Extreme precipitation events can promote the spread of mosquito-borne illnesses by creating vector habitat, destroying infrastructure, and impeding vector control. Here, we focus on Cyclone Yaku, which caused heavy rainfall in northwestern Peru from March 7th - 20th, 2023 and was followed by the worst dengue outbreak in Peru's history. We apply generalized synthetic control methods to account for baseline climate variation and unobserved confounders when estimating the causal effect of Cyclone Yaku on dengue cases across the 56 districts with the greatest precipitation anomalies. We estimate that 67 (95% CI: 30 - 87) % of cases in cyclone-affected districts were attributable to Cyclone Yaku. The cyclone significantly increased cases for over six months, causing 38,209 (95% CI: 17,454 - 49,928) out of 57,246 cases. The largest increases in dengue incidence due to Cyclone Yaku occurred in districts with a large share of low-quality roofs and walls in residences, greater flood risk, and warmer temperatures above 24° <i>C</i> . Analyzing an ensemble of climate model simulations, we found that extremely intense March precipitation in northwestern Peru is 42% more likely in the current era compared to a preindustrial baseline due to climate forcing. In sum, extreme precipitation like that associated with Cyclone Yaku has become more likely with climate change, and Cyclone Yaku caused the majority of dengue cases across the cyclone-affected districts.</p><p><strong>Significance statement: </strong>Anthropogenic climate change is increasing the risk of extreme events that can lead to infectious disease epidemics, but few studies have directly measured this health cost of climate change. We do so by focusing on Cyclone Yaku, which affected northwestern Peru in March 2023, and was immediately followed by a dengue epidemic. Cyclone Yaku caused 67% of cases reported over six months in the affected region. Industrial-era climate forcing has increased the likelihood of extreme March precipitation like that associated with Cyclone Yaku by 42%. Assessing the linkages between climate change, extreme weather, and outbreaks of dengue and other infectious diseases is crucial for understanding the impact that climate change has already had and preparing for future health risks.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585387","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":"Accelerated epigenetic aging and prospective morbidity and mortality among U.S. veterans.","authors":"Kyle J Bourassa, Livia Anderson, Sandra Woolson, Paul A Dennis, Melanie E Garrett, Lauren Hair, Michelle Dennis, Karen Sugden, Benjamin Williams, Renate Houts, Patrick S Calhoun, Jennifer C Naylor, Allison E Ashley-Koch, Jean C Beckham, Avshalom Caspi, Gregory A Taylor, Katherine S Hall, Terrie E Moffitt, Nathan A Kimbrel","doi":"10.1101/2024.10.23.24315691","DOIUrl":"https://doi.org/10.1101/2024.10.23.24315691","url":null,"abstract":"<p><p>Epigenetic measures of aging derived from DNA methylation are promising biomarkers associated with prospective morbidity and mortality, but require validation in real-world medical settings. Using data from 2,216 post-9/11 veterans, we examined whether accelerated DunedinPACE aging scores were associated with chronic disease morbidity, predicted healthcare costs, and mortality assessed over an average of 13.1 years of follow up in VA electronic health records. Veterans with faster DunedinPACE aging scores developed more chronic disease and showed larger increases in predicted healthcare costs over the subsequent 5, 10, and 15 years. Faster aging was associated with incident myocardial infarction, stroke, diabetes, cancer, liver disease, and renal disease, as well greater risk of mortality due to all-causes and chronic disease. These findings provide evidence that accelerated epigenetic aging is associated with worsening prospective health across multiple chronic diseases and organ systems assessed using electronic health records from an integrated healthcare system.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585384","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 role of the microbiota in respiratory virus-bacterial pathobiont relationships in the upper respiratory tract.","authors":"Matthew S Kelly, Pixu Shi, Sefelani C Boiditswe, Emily Qin, Andrew P Steenhoff, Tiny Mazhani, Mohamed Z Patel, Coleen K Cunningham, John F Rawls, Kathy Luinstra, Jodi Gilchrist, Julia Maciejewski, Jillian H Hurst, Patrick C Seed, David Bulir, Marek Smieja","doi":"10.1101/2024.10.22.24315478","DOIUrl":"https://doi.org/10.1101/2024.10.22.24315478","url":null,"abstract":"<p><p>The mechanisms by which respiratory viruses predispose to secondary bacterial infections remain poorly characterized. Using 2,409 nasopharyngeal swabs from 300 infants in Botswana, we performed a detailed analysis of factors that influence the dynamics of bacterial pathobiont colonization during infancy. We quantify the extent to which viruses increase the acquisition of <i>Haemophilus influenzae</i> , <i>Moraxella catarrhalis</i> , and <i>Streptococcus pneumoniae</i> . We provide evidence of cooperative interactions between these pathobionts while identifying host characteristics and environmental exposures that influence the odds of pathobiont colonization during early life. Using 16S rRNA gene sequencing, we demonstrate that respiratory viruses result in losses of putatively beneficial <i>Corynebacterium</i> and <i>Streptococcus</i> species that are associated with a lower odds of pathobiont acquisition. These findings provide novel insights into viral-bacterial relationships in the URT of direct relevance to respiratory infections and suggest that the URT bacterial microbiota is a potentially modifiable mechanism by which viruses promote bacterial respiratory infections.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585446","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":"Prolonged dry seasons lengthen coccidioidomycosis transmission seasons: implications for a changing California.","authors":"Simon K Camponuri, Jennifer R Head, Philip A Collender, Amanda K Weaver, Alexandra K Heaney, Kate A Colvin, Abinash Bhattachan, Gail Sondermeyer-Cooksey, Duc J Vugia, Seema Jain, Justin V Remais","doi":"10.1101/2024.10.22.24315941","DOIUrl":"https://doi.org/10.1101/2024.10.22.24315941","url":null,"abstract":"<p><p>Coccidioidomycosis, a fungal disease caused by soil-borne <i>Coccidioides</i> spp., exhibits pronounced seasonal transmission, with incidence in California typically peaking in the fall. However, the influence of climate on the timing and duration of transmission seasons remains poorly understood. Using weekly data on reported coccidioidomycosis cases in California from 2000-2023, we developed a distributed-lag Markov state-transition model to estimate the effects of temperature and precipitation on the timing of transmission season onset and end. We found that transitions from cooler, wetter conditions to hotter, drier conditions accelerate season onset. Dry conditions (10 ^th percentile of precipitation) in the spring shifted season onset an average of 2.8 weeks (95% CI: 0.43-3.58) earlier compared to wet conditions (90 ^th percentile of precipitation). Conversely, transitions back to cooler, wetter conditions hastened season end, with dry fall conditions extending the season by an average of 0.69 weeks (95% CI: 0.37-1.41) compared to wet conditions. When dry conditions occurred in the spring and fall, the transmission season extended by 3.70 weeks (95% CI: 1.23-4.22). As California is expected to experience prolonged dry seasons with climate change, our findings suggest this shift may lengthen the time at which populations are at elevated coccidioidomycosis risk.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585440","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 whole food, plant-based diet reduces amino acid levels in patients with metastatic breast cancer.","authors":"TashJaé Q Scales, Bradley Smith, Lisa M Blanchard, Nellie Wixom, Emily T Tuttle, Brian J Altman, Luke J Peppone, Joshua Munger, Thomas M Campbell, Erin K Campbell, Isaac S Harris","doi":"10.1101/2024.10.09.24315165","DOIUrl":"10.1101/2024.10.09.24315165","url":null,"abstract":"<p><strong>Background: </strong>Amino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels. Further, a plant-based diet is reported to contain fewer amino acids than an animal-based diet. The extent to which a plant-based diet lowers the serum levels of amino acids in patients with cancer is unclear.</p><p><strong>Methods: </strong>Patients with metastatic breast cancer (n=17) were enrolled in a clinical trial with an ad libitum whole food, plant-based diet for 8 weeks without calorie or portion restriction. Dietary changes by participants were monitored using a three-day food record. Serum was collected from participants at baseline and 8 weeks. Food records and serum were analyzed for metabolic changes.</p><p><strong>Results: </strong>We found that a whole food, plant-based diet resulted in a lower intake of calories, fat, and amino acids and higher levels of fiber. Additionally, body weight, serum insulin, and IGF were reduced in participants. The diet contained lower levels of essential and non-essential amino acids, except for arginine (glutamine and asparagine were not measured). Importantly, the lowered dietary intake of amino acids translated to reduced serum levels of amino acids in participants (5/9 essential amino acids; 4/11 non-essential amino acids).</p><p><strong>Conclusions: </strong>These findings provide a tractable approach to limiting amino acid levels in persons with cancer. This data lays a foundation for studying the relationship between amino acids in patients and tumor progression. Further, a whole-food, plant-based diet has the potential to synergize with cancer therapies that exploit metabolic vulnerabilities.</p><p><strong>Trial registration: </strong>The clinical trial was registered with ClinicalTrials.gov identifier NCT03045289 on 2017-02-07.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484841","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":"Local activity alterations in autism spectrum disorder correlate with neurotransmitter properties and ketamine induced brain changes.","authors":"Pascal Grumbach, Jan Kasper, Joerg F Hipp, Anna Forsyth, Sofie L Valk, Suresh Muthukumaraswamy, Simon B Eickhoff, Leonhard Schilbach, Juergen Dukart","doi":"10.1101/2024.10.20.24315801","DOIUrl":"https://doi.org/10.1101/2024.10.20.24315801","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition (E/I) ratio is discussed as a potential pathomechanism but in-vivo evidence of disturbed neurotransmission underlying these functional alterations remains scarce. We compared rs-fMRI local activity (LCOR) between ASD (N=405, N=395) and neurotypical controls (N=473, N=474) in two independent cohorts (ABIDE1 and ABIDE2). We then tested how these LCOR alterations co-localize with specific neurotransmitter systems derived from nuclear imaging and compared them with E/I changes induced by GABAergic (midazolam) and glutamatergic medication (ketamine). Across both cohorts, ASD subjects consistently exhibited reduced LCOR, particularly in higher-order default mode network nodes, alongside increases in bilateral temporal regions, the cerebellum, and brainstem. These LCOR alterations negatively co-localized with dopaminergic (D1, D2, DAT), glutamatergic (NMDA, mGluR5), GABAergic (GABAa) and cholinergic neurotransmission (VAChT). The NMDA-antagonist ketamine, but not GABAa-potentiator midazolam, induced LCOR changes which co-localize with D1, NMDA and GABAa receptors, thereby resembling alterations observed in ASD. We find consistent local activity alterations in ASD to be spatially associated with several major neurotransmitter systems. NMDA-antagonist ketamine induced neurochemical changes similar to ASD-related alterations, supporting the notion that pharmacological modulation of the E/I balance in healthy individuals can induce ASD-like functional brain changes. These findings provide novel insights into neurophysiological mechanisms underlying ASD.</p><p><strong>One sentence summary: </strong>Local activity alterations in ASD co-localize with glutamatergic and GABAergic neurotransmission and were similar to ketamine-induced brain changes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585388","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":"Loss of Peripheral Retinal Vessels in Retinitis Pigmentosa.","authors":"Hossein Ameri, Alexander T Hong, Jason Chwa","doi":"10.1101/2024.10.18.24315764","DOIUrl":"10.1101/2024.10.18.24315764","url":null,"abstract":"<p><strong>Objective: </strong>Retinitis pigmentosa (RP) is the most common inherited retinal disease and a major cause of irreversible vision loss. The purpose of this study was to assess peripheral retinal vessels in RP.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Subjects: </strong>Patients with RP and age-matched controls.</p><p><strong>Methods: </strong>Using ultra-wide field fundus images, the retina was divided into three zones: posterior, mid periphery, and far periphery. To evaluate vascularity of the retina, the vessels were counted at the border of posterior and mid peripheral zones (Z1/2) and the border of mid peripheral and far peripheral zones (Z2/3).</p><p><strong>Main outcome measures: </strong>Vessel counts at Z1/2 and Z2/3.</p><p><strong>Results: </strong>181 eyes of 107 RP patients and 130 eyes of 84 controls were included. In the RP group, the median vessel counts at Z1/2 and Z2/3 were 8 and 3, respectively. These were strikingly lower than the control group with the median vessels of 42 and 43.5 at Z1/2 (p<0.001) and Z2/3 (p<0.001), respectively. 22% of RP eyes were entirely avascular in the far periphery and 7% were avascular in the mid periphery and far periphery. Only 5% of RP eyes had more than 25 vessels at Z2/3. There were significantly fewer vessels in the temporal retina at both Z1/2 (p=0.01) and Z2/3 (p<0.001) in RP eyes. Furthermore, eyes with visual acuity of 20/200 or worse had significantly fewer vessels at Z1/2 (p<0.001) and Z2/3 (p<0.001). There were no significant differences in the number of vessels at Z1/2 and 2/3 between the right and left eyes of RP patients with both eyes included in the study.</p><p><strong>Conclusions: </strong>This study provides compelling evidence of substantial symmetrical peripheral retinal vascular loss in RP. This finding may aid in clinical diagnosis of the disease and have significant therapeutic implications.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559959","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":"HIGHLY ADAPTIVE LASSO: MACHINE LEARNING THAT PROVIDES VALID NONPARAMETRIC INFERENCE IN REALISTIC MODELS.","authors":"Zachary Butzin-Dozier, Sky Qiu, Alan E Hubbard, Junming Seraphina Shi, Mark J van der Laan","doi":"10.1101/2024.10.18.24315778","DOIUrl":"10.1101/2024.10.18.24315778","url":null,"abstract":"<p><p>Understanding treatment effects on health-related outcomes using real-world data requires defining a causal parameter and imposing relevant identification assumptions to translate it into a statistical estimand. Semiparametric methods, like the targeted maximum likelihood estimator (TMLE), have been developed to construct asymptotically linear estimators of these parameters. To further establish the asymptotic efficiency of these estimators, two conditions must be met: 1) the relevant components of the data likelihood must fall within a Donsker class, and 2) the estimates of nuisance parameters must converge to their true values at a rate faster than <math> <msup><mrow><mi>n</mi></mrow> <mrow><mo>-</mo> <mn>1</mn> <mo>/</mo> <mn>4</mn></mrow> </msup> </math> . The Highly Adaptive LASSO (HAL) satisfies these criteria by acting as an empirical risk minimizer within a class of <i>càdlàg</i> functions with a bounded sectional variation norm, which is known to be Donsker. HAL achieves the desired rate of convergence, thereby guaranteeing the estimators' asymptotic efficiency. The function class over which HAL minimizes its risk is flexible enough to capture realistic functions while maintaining the conditions for establishing efficiency. Additionally, HAL enables robust inference for non-pathwise differentiable parameters, such as the conditional average treatment effect (CATE) and causal dose-response curve, which are important in precision health. While these parameters are often considered in machine learning literature, these applications typically lack proper statistical inference. HAL addresses this gap by providing reliable statistical uncertainty quantification that is essential for informed decision-making in health research.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559967","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":"Digital phenotyping from wearables using AI characterizes psychiatric disorders and identifies genetic associations.","authors":"Jason J Liu, Beatrice Borsari, Yunyang Li, Susanna Liu, Yuan Gao, Xin Xin, Shaoke Lou, Matthew Jensen, Diego Garrido-Martin, Terril Verplaetse, Garrett Ash, Jing Zhang, Matthew J Girgenti, Walter Roberts, Mark Gerstein","doi":"10.1101/2024.09.23.24314219","DOIUrl":"https://doi.org/10.1101/2024.09.23.24314219","url":null,"abstract":"<p><p>Psychiatric disorders are complex and influenced by both genetic and environmental factors. However, studying the full spectrum of these disorders is hindered by practical limitations on measuring human behavior. This highlights the need for novel technologies that can measure behavioral changes at an intermediate level between diagnosis and genotype. Wearable devices are a promising tool in precision medicine, since they can record physiological measurements over time in response to environmental stimuli and do so at low cost and minimal invasiveness. Here we analyzed wearable and genetic data from a cohort of the Adolescent Brain Cognitive Development study. We generated >250 wearable-derived features and used them as intermediate phenotypes in an interpretable AI modeling framework to assign risk scores and classify adolescents with psychiatric disorders. Our model identifies key physiological processes and leverages their temporal patterns to achieve a higher performance than has been previously possible. To investigate how these physiological processes relate to the underlying genetic architecture of psychiatric disorders, we also utilized these intermediate phenotypes in univariate and multivariate GWAS. We identified a total of 29 significant genetic loci and 52 psychiatric-associated genes, including ELFN1 and ADORA3. These results show that wearable-derived continuous features enable a more precise representation of psychiatric disorders and exhibit greater detection power compared to categorical diagnostic labels. In summary, we demonstrate how consumer wearable technology can facilitate dimensional approaches in precision psychiatry and uncover etiological linkages between behavior and genetics.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484850","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}