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A Genetics-guided Integrative Framework for Drug Repurposing: Identifying Anti-hypertensive Drug Telmisartan for Type 2 Diabetes.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.22.25324223
Xue Zhong, Qiang Wei, Anshul Tiwari, Quan Wang, Yuting Tan, Rui Chen, Yan Yan, Nancy J Cox, Bingshan Li
{"title":"A Genetics-guided Integrative Framework for Drug Repurposing: Identifying Anti-hypertensive Drug Telmisartan for Type 2 Diabetes.","authors":"Xue Zhong, Qiang Wei, Anshul Tiwari, Quan Wang, Yuting Tan, Rui Chen, Yan Yan, Nancy J Cox, Bingshan Li","doi":"10.1101/2025.03.22.25324223","DOIUrl":"https://doi.org/10.1101/2025.03.22.25324223","url":null,"abstract":"<p><p>Drug development is a long and costly process, and repurposing existing drugs for use toward a different disease or condition may serve as a cost-effective alternative. As drug targets with genetic support have a doubled success rate, genetics-informed drug repurposing holds promise in translating genetic findings into therapeutics. In this study, we developed a Genetics Informed Network-based Drug Repurposing via in silico Perturbation (GIN-DRIP) framework and applied the framework to repurpose drugs for type-2 diabetes (T2D). In GIN-DRIP for T2D, it integrates multi-level omics data to translate T2D GWAS signals into a genetics-informed network that simultaneously encodes gene importance scores and a directional effect (up/down) of risk genes for T2D; it then bases on the GIN to perform signature matching with drug perturbation experiments to identify drugs that can counteract the effect of T2D risk alleles. With this approach, we identified 3 high-confidence FDA-approved candidate drugs for T2D, and validated telmisartan, an anti-hypertensive drug, in our EHR data with over 3 million patients. We found that telmisartan users were associated with a reduced incidence of T2D compared to users of other anti-hypertensive drugs and non-users, supporting the therapeutic potential of telmisartan for T2D. Our framework can be applied to other diseases for translating GWAS findings to aid drug repurposing for complex diseases.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757115","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}
引用次数: 0
The association of umbilical cord blood neurofilament light with non-reassuring fetal status: a prospective observational study.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.01.23.25320706
David Zalcberg, Kaitlin Kramer, Emma Payne, Thomas Payne, Shreeya Marathe, Neha Mahajan, Ashly Liu, Jessica Barry, Andrew Duckworth, Mitchell Brookes, Bradley de Vries, Fernando Gonzalez-Ortiz, Kaj Blennow, Henrik Zetterberg, Adrienne Gordon, Benjamin Moran, Helen Manning, Robert D Sanders
{"title":"The association of umbilical cord blood neurofilament light with non-reassuring fetal status: a prospective observational study.","authors":"David Zalcberg, Kaitlin Kramer, Emma Payne, Thomas Payne, Shreeya Marathe, Neha Mahajan, Ashly Liu, Jessica Barry, Andrew Duckworth, Mitchell Brookes, Bradley de Vries, Fernando Gonzalez-Ortiz, Kaj Blennow, Henrik Zetterberg, Adrienne Gordon, Benjamin Moran, Helen Manning, Robert D Sanders","doi":"10.1101/2025.01.23.25320706","DOIUrl":"10.1101/2025.01.23.25320706","url":null,"abstract":"<p><strong>Objective: </strong>Early detection of hypoxic-ischaemic encephalopathy (HIE) in neonates is critical. We conducted a pilot cohort study to determine the feasibility of collecting umbilical cord blood samples for neurofilament light (NfL) and to assess the association of NfL with non-reassuring fetal status and other cord biomarkers.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Setting: </strong>A single, large tertiary and quaternary referral hospital.</p><p><strong>Patients: </strong>108 maternal participants consenting to donate cord blood.</p><p><strong>Intervention: </strong>Umbilical cord venous blood plasma NfL levels.</p><p><strong>Main outcome measures: </strong>(1) Feasibility of cord NfL sample collection and analysis; (2) Association of NfL with non-reassuring fetal status (CTG changes and/or documented non-reassuring fetal status), NICU admission and length of stay; (3) Correlation of NfL with other cord biomarkers.</p><p><strong>Results: </strong>Cord NfL was higher in preterm neonates, and was correlated with cord lactate, pH, and base excess. After controlling for mode of delivery and gestational age, NfL (OR = 2.29, 95%CI: 1.15 to 5.57), but not pH (OR = 0.78, 95%CI: 0.42 to 1.41), base excess (OR = 0.83, 95%CI: 0.37 to 1.86), or lactate (OR = 1.06, 95%CI: 0.51 to 2.12) was associated with non-reassuring fetal status. NfL levels were higher in neonates admitted to NICU (median (IQR): 11.3 (7) versus 8.5 (5.1)).</p><p><strong>Conclusions: </strong>Cord blood NfL analysis was feasible and provided correlates of adverse outcomes. Higher venous cord blood NfL levels were associated with non-reassuring fetal status. Further research is needed to validate these findings and establish the role of NfL, if any, in clinical practice.</p><p><strong>What is already known on this topic: </strong>Umbilical cord blood NfL is a promising biomarker of neuronal injury in neonates with overt HIE. Whether cord NfL may improve diagnosis of mild-moderate HIE via identification of in utero hypoxia is unknown.</p><p><strong>What this study adds: </strong>We found that cord NfL is associated with non-reassuring fetal status, and outperforms other cord biomarkers.</p><p><strong>How this study might affect research practice or policy: </strong>This study lays the groundwork for future research into the use of cord NfL for HIE diagnosis and risk stratification. It supports ongoing development of a point-of-care scalp NfL assay.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11838990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461539","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}
引用次数: 0
Skin-to-skin holding in relation to white matter connectivity in infants born preterm.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.21.25324424
Katherine E Travis, Molly F Lazarus, Melissa Scala, Virginia A Marchman, Lisa Bruckert, Rocio Velasco Poblaciones, Sarah Dubner, Heidi M Feldman
{"title":"Skin-to-skin holding in relation to white matter connectivity in infants born preterm.","authors":"Katherine E Travis, Molly F Lazarus, Melissa Scala, Virginia A Marchman, Lisa Bruckert, Rocio Velasco Poblaciones, Sarah Dubner, Heidi M Feldman","doi":"10.1101/2025.03.21.25324424","DOIUrl":"https://doi.org/10.1101/2025.03.21.25324424","url":null,"abstract":"<p><strong>Background and objectives: </strong>Preterm birth is associated with altered white matter development and long-term neurodevelopmental impairments. Skin-to-skin care (kangaroo care) has well-documented benefits for physiological stability and bonding, but its association with neonatal brain structure remains unclear. This study explored the association between in-hospital skin-to-skin care and neonatal white matter microstructure in frontal and limbic pathways that are linked to stress regulation and socio-emotional development, processes potentially influenced by affective touch during skin-to-skin care.</p><p><strong>Methods: </strong>This retrospective study analyzed electronic medical records and diffusion MRI data collected from 86 preterm infants (<32 weeks gestational age) in a single NICU. Skin-to-skin care exposure was quantified as total duration (minutes/instance) and rate (minutes/day) of sessions. Diffusion MRI scans obtained before hospital discharge assessed mean diffusivity (MD) and fractional anisotropy (FA) in the cingulate, anterior thalamic radiations (ATR), and uncinate fasciculus. Hierarchical regression models examined associations between skin-to-skin care and white matter microstructure, adjusting for gestational age, health acuity, postmenstrual age at scan, and MRI coil type. Sensitivity analyses controlled for socioeconomic status and NICU visitation frequency.</p><p><strong>Results: </strong>Skin-to-skin care duration was positively associated with MD in the cingulate (B = 0.002, p = 0.016) and ATR (B = 0.002, p = 0.020). Skin-to-skin care rate was also positively linked to MD in the ATR (B = 0.040, p = 0.041). Skin-to-skin care duration and rate were not associated with FA in the cingulate but skin-to-skin duration and rate were negatively associated with FA in the ATR (duration: B =-0.001, <i>p</i> = 0.020; rate: B =-0.017, p = 0.008). No significant associations were found for the uncinate fasciculus. Findings remained robust after adjusting for socioeconomic status and visitation frequency.</p><p><strong>Discussion: </strong>This study provides novel evidence linking in-hospital experiences of skin-to-skin care to neonatal white matter development. These findings have important implications for understanding how family-centered neuroprotective practices, such as skin-to-skin care, may affect brain development to improve long-term developmental outcomes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757108","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}
引用次数: 0
The Healthy Brain 9 (HB9): A New Instrument to Characterize Subjective Cognitive Decline, and Detect Anosognosia in Mild Cognitive Impairment.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.23.25324480
James E Galvin, Katherine C Almonte, Andrea Buehler, Yolene M Caicedo, Conor B Galvin, Willman Jimenez, Mahesh S Joshi, Nicole Mendez, Mary Lou A Riccio, Marcia I Walker, Michael J Kleiman
{"title":"The Healthy Brain 9 (HB9): A New Instrument to Characterize Subjective Cognitive Decline, and Detect Anosognosia in Mild Cognitive Impairment.","authors":"James E Galvin, Katherine C Almonte, Andrea Buehler, Yolene M Caicedo, Conor B Galvin, Willman Jimenez, Mahesh S Joshi, Nicole Mendez, Mary Lou A Riccio, Marcia I Walker, Michael J Kleiman","doi":"10.1101/2025.03.23.25324480","DOIUrl":"https://doi.org/10.1101/2025.03.23.25324480","url":null,"abstract":"<p><strong>Objectives: </strong>Subjective cognitive decline (SCD) affects 10% of older adults and may be a risk factor for future mild cognitive impairment (MCI) and dementia. Some individuals with MCI have anosognosia, the denial or lack of awareness of their cognitive deficits. We developed and tested the Healthy Brain 9 (HB9), a self-reported assessment of cognitive performance and everyday functioning, in a diverse community-based cohort of older adults in South Florida.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Setting: </strong>Community-based longitudinal study of brain health.</p><p><strong>Participants: </strong>A total of 344 participants (mean age of 68.5±9.3y, 70% were female, 62% with 16 or less years of education, 39% ethnoracial minorities) completed the study. The sample included 42% normal cognition, 27% SCD and 30% MCI. Within the MCI group, 62% demonstrated awareness of cognitive deficits and 38% had MCI with anosognosia.</p><p><strong>Measurements: </strong>The psychometric properties of the HB9 were examined and the performance of the HB9 was compared to Gold Standard comprehensive clinical-cognitive-functional-behavioral evaluations and biomarkers evaluations from the Healthy Brain Initiative at the University of Miami.</p><p><strong>Results: </strong>The HB9 had strong psychometric properties with a Cronbach α of 0.898 (95%CI: 0.882-0.913) and low floor and ceiling effects. The HB9 performed well across different sociodemographic groups. Lower HB9 scores were associated with greater resilience, better physical performance, and less physical frailty. Higher HB9 scores were associated with more comorbid medical conditions, more mood symptoms, lower resilience, and more functional impairment. A cut-off score of 4 on the HB9 provided a 15-fold ability to detect SCD in cognitively normal individuals, and a 14-fold ability to detect anosognosia in MCI.</p><p><strong>Conclusions: </strong>The use of the HB9 as an assessment of subjective cognitive complaints may help identify SCD for potential interventions and enrollment into clinical trials. The HB9 may also identify anosognosia which could lead to worse outcomes in MCI.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757177","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}
引用次数: 0
Subjective Response to Opioids Predicts Risk for Opioid Use Disorder.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.21.25324409
Jean Gonzalez, Vinh Tran, John Meredith, Ivonne Xu, Ritviksiddha Penchala, Laura Vilar Ribo, Natasia S Courchesne-Krak, Daniel Zoleikhaeian, Matt McIntyre, Pierre Fontanillas, Katelyn Kukar Bond, Eric Otto Johnson, Alvin Jeffery, James MacKillop, Carla Marienfeld, Harriet de Wit, Abraham A Palmer, Sandra Sanchez-Roige
{"title":"Subjective Response to Opioids Predicts Risk for Opioid Use Disorder.","authors":"Jean Gonzalez, Vinh Tran, John Meredith, Ivonne Xu, Ritviksiddha Penchala, Laura Vilar Ribo, Natasia S Courchesne-Krak, Daniel Zoleikhaeian, Matt McIntyre, Pierre Fontanillas, Katelyn Kukar Bond, Eric Otto Johnson, Alvin Jeffery, James MacKillop, Carla Marienfeld, Harriet de Wit, Abraham A Palmer, Sandra Sanchez-Roige","doi":"10.1101/2025.03.21.25324409","DOIUrl":"https://doi.org/10.1101/2025.03.21.25324409","url":null,"abstract":"<p><p>Exposure to prescription opioids can lead to opioid use disorder (OUD) in some individuals, but we lack scalable tools to predict who is at risk. We collected retrospective data on the initial subjective effects of prescription opioids from 117,508 research participants, 5.3% of whom self-reported OUD. Positive subjective effects, particularly \"Like Overall\", \"Euphoric\", and \"Energized\", were the strongest predictors of OUD. For example, the odds-ratio for individuals responding \"Extremely\" for \"Like Overall\" was 36.2. The sensitivity and specificity of this single question was excellent (ROC=0.87). Negative effects and analgesic effects were much less predictive. We present a two-step decision tree that can identify a small high-risk subset with 77.4% prevalence of OUD and a much larger low-risk subset with 1.7% prevalence of OUD. Our results demonstrate that positive subjective responses are predictive of future misuse and suggest that vulnerable individuals may be identified and targeted for preventative interventions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757145","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}
引用次数: 0
Network-based Molecular Constraints on in vivo Synaptic Density Alterations in Schizophrenia.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.22.25324465
Sidhant Chopra, Patrick D Worhunsky, Mika Naganawa, Xi-Han Zhang, Ashlea Segal, Edwina Orchard, Vanessa Cropley, Stephen Wood, Gustavo A Angarita, Kelly Cosgrove, David Matuskey, Nabeel B Nabulsi, Yiyun Huang, Richard E Carson, Irina Esterlis, Patrick D Skosnik, Deepak C D'Souza, Avram J Holmes, Rajiv Radhakrishnan
{"title":"Network-based Molecular Constraints on in vivo Synaptic Density Alterations in Schizophrenia.","authors":"Sidhant Chopra, Patrick D Worhunsky, Mika Naganawa, Xi-Han Zhang, Ashlea Segal, Edwina Orchard, Vanessa Cropley, Stephen Wood, Gustavo A Angarita, Kelly Cosgrove, David Matuskey, Nabeel B Nabulsi, Yiyun Huang, Richard E Carson, Irina Esterlis, Patrick D Skosnik, Deepak C D'Souza, Avram J Holmes, Rajiv Radhakrishnan","doi":"10.1101/2025.03.22.25324465","DOIUrl":"https://doi.org/10.1101/2025.03.22.25324465","url":null,"abstract":"<p><p>Converging neuroimaging, genetic, and post-mortem evidence show a fundamental role of synaptic deficits in schizophrenia pathogenesis. However, the underlying molecular and cellular mechanisms that drive the onset and progression of synaptic pathology remain to be established. Here, we used synaptic density positron emission tomography (PET) imaging using the [11C]UCB-J radiotracer to reveal a prominent widespread pattern (p_FWE<0.05) of lower synaptic density in individuals with schizophrenia (n=29), compared to a large sample of healthy controls (n=93). We found that the spatial pattern of lower synaptic density in schizophrenia is spatially aligned (r_cca = 0.67; p<0.001) with higher normative distributions of GABAA/BZ, 5HT1B, 5HT2A, and 5HT6, and lower levels of CB1 and 5HT1A. Competing neighborhood deformation network models revealed that regional synaptic pathology strongly correlated with estimates predicted using a model constrained by both interregional structural connectivity and molecular similarity (.42 < r < .61; p_FWE<0.05). These data suggest that synaptic pathology in schizophrenia is jointly constrained by both global axonal connectivity and local molecular vulnerability. Simulation-based network diffusion models were used to identify regions that may represent the initial sources of pathology, nominating left prefrontal areas (p_FWE<0.05) as potential foci from which synaptic pathology initiates and propagates to molecularly similar areas. Overall, our findings provide in vivo evidence for widespread deficit in synaptic density in schizophrenia that is jointly constrained by axonal connectivity and molecular similarity between regions, and that synaptic deficits spread from initial source regions to axonally connected and molecularly similar territories.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757146","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}
引用次数: 0
HIV seroprevalence, incidence, and viral suppression among Ugandan female bar workers: a population-based study.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.22.25324404
Xinyi Feng, Gertrude Nakigozi, Eshan U Patel, Caitlin E Kennedy, Slisha Shrestha, Fred Nalugoda, Godfrey Kigozi, Robert Ssekubugu, Larry W Chang, Andrea L Wirtz, Hadijja Nakawooya, Grace Kigozi, Ronald M Galiwango, Steven J Reynolds, Joseph Kagaayi, Aaron A R Tobian, M Kate Grabowski
{"title":"HIV seroprevalence, incidence, and viral suppression among Ugandan female bar workers: a population-based study.","authors":"Xinyi Feng, Gertrude Nakigozi, Eshan U Patel, Caitlin E Kennedy, Slisha Shrestha, Fred Nalugoda, Godfrey Kigozi, Robert Ssekubugu, Larry W Chang, Andrea L Wirtz, Hadijja Nakawooya, Grace Kigozi, Ronald M Galiwango, Steven J Reynolds, Joseph Kagaayi, Aaron A R Tobian, M Kate Grabowski","doi":"10.1101/2025.03.22.25324404","DOIUrl":"https://doi.org/10.1101/2025.03.22.25324404","url":null,"abstract":"<p><strong>Background: </strong>Prior studies have linked female bar and sex work in Africa. However, population-level data on HIV burden among female bar workers (FBWs) in African settings are rare.</p><p><strong>Methods: </strong>We used five survey rounds of data collected between 2011 and 2020 from the Rakai Community Cohort Study, a population-based HIV surveillance cohort in 36 inland agrarian and trading communities (HIV prevalence ~12%) and four Lake Victoria fishing communities (~36%) in southern Uganda. Women reporting bar work as a primary or secondary occupation were identified and compared to non-FBWs. Primary outcomes included laboratory-confirmed HIV seropositivity, incident infection, viral suppression (<200 copies/ml) among women with HIV, and population prevalence of viremia. Prevalence ratios (PRs) and incidence rate ratios (IRRs) were estimated using Poisson regression models with 95% confidence intervals (95%CI).</p><p><strong>Findings: </strong>A total of 23,556 female participants contributed 52,708 person visits. Overall, 1,205 (5.1%) women self-identified as FBWs. FBWs had significantly higher baseline HIV seroprevalence compared to non-FBWs (51.9% vs. 18.5%,PR=2.81, 95%CI=2.64-2.95). 356 HIV incident events occurred over 39,228 years of participant follow-up. Incidence among FBWs was 2.49/100 person-years versus 0.87/100 person-years among non-FBWs (age-adjusted IRR=3.64,95%CI=2.33-5.42). While HIV viral suppression was similar among participants living with HIV regardless of FBW status, the population prevalence of HIV viremia among FBWs was 1.69 times higher compared to non-FBWs, adjusting for age and community type (95%CI=1.38-2.08). Among 179 HIV seronegative FBWs surveyed in 2018-20, 79.9% (143/179) were aware of PrEP, while only 13.4% (24/179) had ever used it, and just 2.8% (5/179) were current users.</p><p><strong>Interpretation: </strong>FBWs in Uganda experience substantially higher HIV burden and acquisition risk compared to the general population. Tailored prevention strategies like prioritizing their HIV service delivery may reduce HIV incidence among FBWs and their partners.</p><p><strong>Funding: </strong>National Institute of Allergy and Infectious Diseases, National Institutes of Health.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756835","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}
引用次数: 0
HIV seroprevalence, incidence, and viral suppression among Ugandan males with bar or sex worker partners: a population-based study.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.22.25324410
Xinyi Feng, Kate Grabowski, Fred Nalugoda, Godfrey Kigozi, Larry W Chang, Andrea Wirtz, Caitlin E Kennedy, Gertrude Nakigozi, Eshan U Patel, Anthony Ndyanabo, Hadijja Nakawooya, Thomas C Quinn, Ronald M Galiwango, David Serwadda, Victor Ssempijja, Steven J Reynolds, Aaron A R Tobian, Robert Ssekubugu
{"title":"HIV seroprevalence, incidence, and viral suppression among Ugandan males with bar or sex worker partners: a population-based study.","authors":"Xinyi Feng, Kate Grabowski, Fred Nalugoda, Godfrey Kigozi, Larry W Chang, Andrea Wirtz, Caitlin E Kennedy, Gertrude Nakigozi, Eshan U Patel, Anthony Ndyanabo, Hadijja Nakawooya, Thomas C Quinn, Ronald M Galiwango, David Serwadda, Victor Ssempijja, Steven J Reynolds, Aaron A R Tobian, Robert Ssekubugu","doi":"10.1101/2025.03.22.25324410","DOIUrl":"https://doi.org/10.1101/2025.03.22.25324410","url":null,"abstract":"<p><strong>Background: </strong>Female bar or sex workers (FBSWs) in Eastern Africa experience a high burden of HIV. However, there is limited population-level data on HIV seroprevalence, incidence, and viral suppression among their male partners.</p><p><strong>Methods: </strong>Men who had sex with FBSWs in the past year were identified through longitudinal population-based HIV surveillance in southern Uganda between 2013 and 2020. Surveillance was conducted over four surveys in four Lake Victoria fishing communities (HIV seroprevalence∼40%) and 37 inland agricultural and trading communities (∼12%). Primary outcomes included laboratory-confirmed HIV seropositivity, incident infection, and viral suppression (<200 copies/mL). Prevalence and incidence rate ratios (PR, IRR) were estimated using univariable and multivariable Poisson regressions with 95% confidence intervals (95%CIs).</p><p><strong>Findings: </strong>17,438 male participants contributed 35,273 visits, with 2,420 (13.9%) reporting FBSW partners at ≥1 study visit. Men with FBSW partners tended to be older, have less education and lower incomes, and be previously married compared to those without. HIV seroprevalence was significantly higher among men with FBSW partners (vs. without FBSW partners) in both inland (21.0%vs.7.5%; PR=2.79,95%CI=2.41-3.23) and fishing communities (38.6%vs.23.0%; PR=1.67,95%CI=1.53-1.84). Overall, 154 HIV incident events occurred over 27,396 years of participant follow-up. HIV incidence was also higher among men with FBSW partners than those without (1.93vs.0.44/100 person-years; IRR=4.37,95%CI=3.04-6.16). Among men with HIV, viral suppression was similar among those with and without FBSW partners. However, the population prevalence of HIV viremia was 1.6 times higher (95%CI=1.41-1.84) among men with FBSW partners due to a higher background seroprevalence of HIV.</p><p><strong>Interpretation: </strong>Men in Uganda frequently report sex with FBSWs, which is associated with a significantly higher risk of HIV acquisition. Tailored HIV prevention strategies, including the promotion and uptake of PrEP, are essential to reduce the HIV burden in this population.</p><p><strong>Funding: </strong>National Institute of Allergy and Infectious Diseases, National Institutes of Health.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756843","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}
引用次数: 0
Peripheral blood somatic mosaicism and clonal hematopoiesis across ancestry backgrounds.
medRxiv : the preprint server for health sciences Pub Date : 2025-03-23 DOI: 10.1101/2025.03.21.25324408
Christelle Colin-Leitzinger, Yi-Han Tang, Mingxiang Teng, Nancy Gillis
{"title":"Peripheral blood somatic mosaicism and clonal hematopoiesis across ancestry backgrounds.","authors":"Christelle Colin-Leitzinger, Yi-Han Tang, Mingxiang Teng, Nancy Gillis","doi":"10.1101/2025.03.21.25324408","DOIUrl":"https://doi.org/10.1101/2025.03.21.25324408","url":null,"abstract":"<p><p>Somatic mosaicism (SM), the presence of somatic mutations, is classified as clonal hematopoiesis (CH) when it occurs in hematopoietic cells at an age-related rate. CH is associated with risk for hematologic malignancies and cardiovascular disease, but most studies are predominately based on individuals of European ancestry. Using peripheral blood whole exome sequencing data from 125,748 individuals of diverse genetic ancestries, we cataloged 503,703 SM mutations based on low variant allele frequency distributions and 89,361 CH variants based on age-skewing. We examined CH prevalence across ancestry groups, including commonly recognized pathogenic variants in myeloid (M-CHIP) and lymphoid (L-CHIP) malignancies. CH and M-CHIP variants had the highest prevalence in the European non-Finnish ancestry group, and males trended toward more M-CHIP variants. Ancestry differences in CH included more mutations in <i>NF1</i> in African/African American, <i>TP53</i> in European, and <i>CUX1</i> in Asian and Latino/Admixed American ancestry groups. Linking the identified CH variants to a cancer database, CH was detected in 14% (55,190/391,102) of patient tumors. Prevalence of CH variants in some solid tumors ranged from 25% - 40%. M-CHIP variants in solid tumors were associated with younger age (61 vs 63, p <0.001), while M-CHIP in hematologic malignancies were linked to older age (60 vs 50, p <0.001), suggesting differences in disease biology. This study provides a catalog of SM, CH, and CHIP variants across diverse ancestry groups, highlighting differences that are important to inform clinical care, drug discovery, and study design to maximize generalizability across individuals.</p><p><strong>Key points: </strong>Establish a large-scale catalog of somatic mosaicism and clonal hematopoiesis mutations across genetic ancestry groups.Mutation occurrences within clonal hematopoiesis genes vary across ancestry groups, with age, and across tumor types.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756927","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}
引用次数: 0
A comparative analysis of dengue, chikungunya, and Zika manifestations in a pediatric cohort over 18 years. 18年以上儿童队列中登革热、基孔肯雅热和寨卡表现的比较分析
medRxiv : the preprint server for health sciences Pub Date : 2025-03-22 DOI: 10.1101/2025.01.06.25320089
Fausto Andres Bustos Carrillo, Sergio Ojeda, Nery Sanchez, Miguel Plazaola, Damaris Collado, Tatiana Miranda, Saira Saborio, Brenda Lopez Mercado, Jairo Carey Monterrey, Sonia Arguello, Lora Campredon, Zijin Chu, Colin J Carlson, Aubree Gordon, Angel Balmaseda, Guillermina Kuan, Eva Harris
{"title":"A comparative analysis of dengue, chikungunya, and Zika manifestations in a pediatric cohort over 18 years.","authors":"Fausto Andres Bustos Carrillo, Sergio Ojeda, Nery Sanchez, Miguel Plazaola, Damaris Collado, Tatiana Miranda, Saira Saborio, Brenda Lopez Mercado, Jairo Carey Monterrey, Sonia Arguello, Lora Campredon, Zijin Chu, Colin J Carlson, Aubree Gordon, Angel Balmaseda, Guillermina Kuan, Eva Harris","doi":"10.1101/2025.01.06.25320089","DOIUrl":"10.1101/2025.01.06.25320089","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dengue, chikungunya, and Zika are diseases of major human concern. Differential diagnosis is complicated in children and adolescents by their overlapping clinical features (signs, symptoms, and complete blood count results). Few studies have directly compared the three diseases. We aimed to identify distinguishing pediatric characteristics of each disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were derived from laboratory-confirmed cases aged 2-17 years enrolled in a longitudinal cohort study in Managua, Nicaragua, and attending a primary health care center from January 2006 through December 2023. We collected clinical records and laboratory results across the first 10 days of illness. Data were analyzed with generalized additive models, generalized linear mixed models, and machine learning models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;We characterized 1,405 dengue, 517 chikungunya, and 522 Zika pediatric cases. The prevalence of many clinical features exhibited by dengue, chikungunya, and Zika cases differed substantially overall, by age, and by day of illness. Dengue cases were differentiated most by abdominal pain, leukopenia, nausea, vomiting, and basophilia; chikungunya cases were differentiated most by arthralgia and the absence of leukopenia and papular rash; and Zika cases were differentiated most by rash and the lack of fever and lymphocytopenia. Dengue and chikungunya cases exhibited similar temperature dynamics during acute illness, and their temperatures were higher than Zika cases. Sixty-two laboratory-confirmed afebrile dengue cases, which would not be captured by any widely used international case definition, presented very similarly to afebrile Zika cases, though some exhibited warning signs of disease severity. The presence of arthralgia, the presence of basophilia, and the absence of fever were the most important model-based distinguishing predictors of chikungunya, dengue, and Zika, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretations: &lt;/strong&gt;These findings substantially update our understanding of dengue, chikungunya, and Zika in children while identifying various clinical features that could improve differential diagnoses. The occurrence of afebrile dengue warrants reconsideration of current case definitions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;US National Institutes of Health R01AI099631, P01AI106695, U01AI153416, U19AI118610.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Research in context: &lt;/strong&gt;&lt;b&gt;Evidence before this study:&lt;/b&gt; Dengue, chikungunya, and Zika co-occur in tropical and subtropical settings and cause fever, rash, and other clinical features. We reviewed widely used international case definitions for the three diseases; the Pan American Health Organization's (PAHO) 2022 report on differential diagnosis of the diseases; and the 80 studies underlying PAHO's diagnostic recommendations. On March 15, 2025, we queried PubMed without restrictions for \"pediatric cohort\" AND \"dengue\" AND \"chikungunya\" AND \"Zika,\" revealing that no ","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019413","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}
引用次数: 0
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