medRxiv : the preprint server for health sciences最新文献

{"title":"HIV Transmission in a Declining African Epidemic.","authors":"Griffin J Bell, M Kate Grabowski, Josephine Mpagazi, Francesco Di Lauro, Aleya Khalifa, Anthony Ndyanabo, Hadijja Nakawooya, Joseph Kagaayi, Godfrey Kigozi, Gertrude Nakigozi, Ronald M Galiwango, Grace Kigozi, Michael A Martin, Luca Ferretti, Christophe Fraser, David Bonsall, Lucie Abeler-Dörner, Tanya Golubchik, Aaron Ar Tobian, Laura K Beres, Caitlin Kennedy, Justin Lessler, Thomas C Quinn, Steven J Reynolds, Maria J Wawer, Ronald H Gray, David Serwadda, Larry W Chang, Robert Ssekubugu","doi":"10.64898/2026.04.29.26350859","DOIUrl":"https://doi.org/10.64898/2026.04.29.26350859","url":null,"abstract":"<p><strong>Background: </strong>Novel HIV prevention interventions such as long-acting pre-exposure prophylaxis (PrEP) could substantially reduce HIV transmission in Africa. However, efficient implementation in high-prevalence settings where incidence has declined requires an understanding of the contemporary dynamics driving new infections.</p><p><strong>Methods: </strong>We identified incident HIV cases from a longitudinal, population-based cohort in Uganda. We individually matched cases to HIV-negative controls; traced and enrolled reported sexual partners; and enrolled female sex workers (FSWs) from reported venues. Conditional logistic regression, transmission modeling, and phylogenetics were used to characterize transmission networks.</p><p><strong>Findings: </strong>From 2021-2024, 38,899 HIV tests among 22,255 people identified 187 people with incident infections (47.6% male); 164 (88%) were enrolled and matched to 164 HIV-negative controls. Overall, 593 non-sex-worker partners (371 enrolled,62.6%), 146 FSW partners (21 enrolled,14.4%), and 28 venues (208 FSWs enrolled) were reported. Incident infection was most strongly predicted by partnership with a FSW (odds ratio:15.5; 95%CI:3.7-64.8), identified in 43.0% of male cases versus 6.3% of controls. Men with FSW partners had larger sexual networks than men without (median:6 vs 2 partners), and 91.2% of men with FSW partners also had non-sex-worker partners. Transmission modeling attributed 34.4% (95%CI:31.5-36.8%) of all male infections and 80.0% (95%CI:73.2-84.4%) of infections among male clients to sex with FSWs. Oral PrEP use among HIV-negative partners of incident cases was low (8.9% in women; 2.1% in men).</p><p><strong>Interpretation: </strong>Men with FSW partners accounted for a substantial share of incident HIV infections and had markedly higher odds of infection than men without such partnerships. Together with the high potential for onward transmission within male client networks, these findings suggest that inclusion of male clients in long-acting HIV prevention strategies could be highly efficient and impactful.</p><p><strong>Funding: </strong>National Institutes of Health, United States; Gates Foundation; National Health and Medical Research Council, Australia.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848416","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":"Immune Subtypes and Survival in Patients with Primary Glioma.","authors":"Yu Fang, Jiwoong Kim, Zachary J Thompson, Youngchul Kim, Harshan Ravi, Asim Mazin, Carlos M Moran Segura, Jonathan V Nguyen, Robert J Macaulay, Filippo Veglia, Reid C Thompson, Sajeel A Chowdhary, Kathleen M Egan, Natarajan Raghunand","doi":"10.64898/2026.04.29.26351981","DOIUrl":"https://doi.org/10.64898/2026.04.29.26351981","url":null,"abstract":"<p><strong>Background: </strong>Gliomas are heterogeneous tumors with poor outcomes following current therapies, including immunotherapy. The tumor microenvironment (TME) is a critical determinant of therapeutic response in gliomas. We have classified the immune TME of gliomas by multiplex immunofluorescence (mIF).</p><p><strong>Methods: </strong>Tissue taken at initial resection from 354 patients with newly-diagnosed glioma grades 2-4 were analyzed using three mIF panels of markers for T, B, and myeloid cells. Tumor cores were characterized by the relative abundances of: (i) 15 primary immune phenotypes, (ii) 96 secondary immune phenotypes, and, (iii) 29 biologically meaningful multi-marker immune phenotypes.</p><p><strong>Results: </strong>Using unsupervised cluster analysis of WHO grade 4 gliomas we identified four subtypes α, β, γ, and δ that were internally reproducible. Immune subtype α was characterized by high abundance of antigen-presenting cells (APCs) and low levels of MHC II- monocytes. Subtype β was high in regulatory T cells and myeloid cells, but low in lymphocytes with effector functions. Subtype γ displayed high abundance of immune cell phenotypes, particularly lymphocytes with effector or helper functions. Subtype δ was low in lymphoid and myeloid immune phenotypes and APCs, with poorer outcomes. Grade 3 tumors could also be classified into α, β, γ, and δ subtypes, indicating generalizability of these immune TME subtypes across high grade gliomas.</p><p><strong>Conclusions: </strong>We have identified internally reproducible criteria for classifying gliomas according to the immune microenvironment, findings that could aid our understanding of the natural progression of low- and high-grade gliomas and inform the rational application of immune-oncologic therapeutic interventions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848348","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":"Analytic Choices Shape Genomic Risk Estimates from Electronic Health Records: Coronary Heart Disease in eMERGE IV.","authors":"Jingheng H Chen, Sarah A Knerr, David L Veenstra, Noura S Abul-Husn, Sarah C Hanks, Eimear E Kenny, Nita A Limdi, Josh B Cortopassi, David Crosslin, Gail P Jarvik, Iftikhar J Kullo","doi":"10.64898/2026.04.28.26352002","DOIUrl":"https://doi.org/10.64898/2026.04.28.26352002","url":null,"abstract":"<p><strong>Background: </strong>Electronic health records (EHR) are an important data source for genomic studies, but challenges exist in ascertaining cases and observation start time. We used data derived from the Electronic Medical Records and Genomics (eMERGE) IV study to examine how analytic assumptions regarding case ascertainment and EHR entry time influence estimation of monogenic and polygenic risks for coronary heart disease (CHD).</p><p><strong>Methods: </strong>We assessed agreement between CHD cases ascertained from EHR phenotyping and survey. Associations of monogenic variants and high (top 5%) PRS of CHD were evaluated using multivariate relative risk (RR) regression under three alternative case definitions: EHR-algorithm-defined, self-reported, and combined. Time-to-event analyses (Kaplan-Meier method and Cox proportional hazards models) were conducted under three entry time specifications: (1) entry at the first EHR record, (2) entry at the start of the latest consecutive observation period, and (3) no left truncation.</p><p><strong>Results: </strong>The agreement between CHD cases ascertained by the EHR-based algorithm versus self-report was 37.2% among individuals identified as cases by at least one source, with the EHR algorithm demonstrating higher accuracy. The adjusted RR [95% confidence interval (CI)] associated with high PRS was 2.05 [1.50, 2.81] for EHR-defined, 1.49 [1.04, 2.13] for self-reported, and 1.66 [1.27, 2.18] for combined CHD. Estimated cumulative incidence by age 75 was 0.188 using the first EHR code as left truncation and 0.225 using the most recent observation period. Hazard ratio (HR) estimates were similar across the three left truncation scenarios.</p><p><strong>Conclusion: </strong>The choice of case definition meaningfully influenced RR estimates, whereas alternative specifications of EHR entry time affected absolute cumulative incidence estimates but has minimal impact on HR. These findings highlight the impact of analytical choices in EHR and survey-data-based studies that are applicable beyond the context of CHD.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848269","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":"<i>Shortkit-ML</i> : A Unified Multi-Perspective Framework for Detecting Shortcut Learning in Medical Imaging Embeddings.","authors":"Sebastian Cajas, Aldo Marzullo, Sahil Kapadia, Filipe Santos, Felipe Ocampo Osorio, Qingpeng Kong, Alessandro Quarta, Po-Chih Kuo, Milit Patel, Raul Ignacio Rojas Sillery, Leo Anthony Celi","doi":"10.64898/2026.04.29.26352053","DOIUrl":"https://doi.org/10.64898/2026.04.29.26352053","url":null,"abstract":"<p><p>Shortcut learning poses a significant challenge in clinical artificial intelligence, as models may rely on spurious signals rather than clinically relevant features, leading to biased predictions and poor generalization. Existing detection methods are fragmented and lack systematic evaluation across datasets and model architectures. To address this issue, we propose <i>ShortKit-ML</i> , an open-source Python framework for unified shortcut analysis in embedding spaces. The framework integrates over 20 detection methods and six mitigation strategies within a modular pipeline, encompassing embedding analysis, fairness metrics, training dynamics, causal methods, explainability, and representation analysis. We evaluate the framework on chest X-ray datasets (CheXpert and MIMIC-CXR), synthetic benchmarks, and an out-of-domain dataset (CelebA). Experimental results demonstrate that multi-method auditing provides more stable and interpretable evidence than individual methods, while detector disagreement reveals meaningful representational differences. The proposed framework offers automated reporting, interactive visualization, and is available as a pip-installable package. The source code and documentation are publicly available at https://github.com/criticaldata/ShortKit-ML and https://criticaldata.github.io/ShortKit-ML/ .</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848271","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":"Optimization of head and neck cancer peripheral blood mononuclear cell processing for robust downstream functional immune analysis.","authors":"Margaret Nelson, Katelyn Jansen, Farah Sagin, Maria Lehn, Hani Alrefai, Claire Girten, Joanna Khoury, Marina Rodriguez, Jacob Garner, Carolyn Schroeder, Melissa Meyer, Pravin Mishra, Dalia El-Gamal, Kelsey Dillehay McKillip, Trisha M Wise-Draper","doi":"10.64898/2026.04.29.26351856","DOIUrl":"https://doi.org/10.64898/2026.04.29.26351856","url":null,"abstract":"<p><p>The current \"gold standard\" for diagnosing and assessing treatment response is tumor biopsy; however, biopsies are not always feasible, safe or easily repeated during treatment. Utilization of peripheral blood mononuclear cells (PBMCs) as a surrogate for tumor biopsy allows for longitudinal sampling and is a safer, more readily available option. However, collection conditions, sample transfer time across multiple clinical sites, and PBMC processing conditions are external pre-analytical factors that must be understood and controlled to mitigate bias in downstream functional analyses. This study aims to systematically evaluate the pre-analytical variables affecting PBMC integrity and functional immune readouts as a prerequisite for downstream translational biomarker applications. Peripheral blood samples were collected from 80 treatment-naive patients with a diagnosis of head and neck squamous cell carcinoma. Blood was collected in cell preparation tubes (BD Vacutainer ^® CPT™), potassium ethylenediaminetetraacetic acid (EDTA), or sodium heparin (SH) tubes and diluted 1:1 with sterile PBS or remained undiluted. PBMCs were processed and cryopreserved immediately or held for 8- and 24-hours before processing. PBMC viability was measured at cryopreservation and upon thawing. CD8+ T cells or natural killer (NK) cells derived from PBMCs were subjected to cytotoxicity assays using flow cytometry. CPT™ tubes provided lower cell viability and yield at cryopreservation and upon thaw compared to EDTA and SH tubes while dilution had no effect on viability. NK cell cytotoxicity was similar between EDTA and SH tubes irrespective of dilution. However, diluted EDTA tubes resulted in lower T cell cytotoxicity after 24-hour hold. Viability and NK and T cell cytotoxicity were equivalent between cryopreserved PBMCs that were processed immediately or processed after 8- or 24-hour hold. Here we report cryopreservation methods for reproducibility of viable cells that maintain functional immunological capacity even after significant delay in processing allowing flexibility and feasibility for collection from multiple clinical sites for deferred processing.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848472","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":"Implementation strategy modifications: An applied multi-site comparison using ERIC and FRAME-IS for the \"Fluoroquinolone Restriction for the Prevention of <i>Clostridioides difficile</i> infection Trial\" (FIRST).","authors":"Vishala Parmasad, Demetrius Solomon, Douglas Wiegmann, Marin Schweizer-Looby, Nasia Safdar","doi":"10.64898/2026.04.28.26351921","DOIUrl":"https://doi.org/10.64898/2026.04.28.26351921","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Implementation strategies are dynamic techniques used to apply evidence-based practices (EBPs) to diverse contexts. Despite their importance, context-specific selection and modification of implementation strategies remain underreported, limiting understanding of how to optimize strategy deployment across heterogeneous healthcare settings. We describe a systematic method to document and analyze modifications to implementation strategies using four diverse hospital sites from the Fluoroquinolone Restriction for the Prevention of &lt;i&gt;Clostridioides difficile&lt;/i&gt; infection (FIRST) trial as case studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;FIRST was a multisite fluoroquinolone pre-prescription restriction intervention delivered via the electronic health record. We partnered with multidisciplinary stakeholders at each site to co-design and adapt the intervention using pre-planned implementation strategies. Multiple data sources (interviews, meeting notes, implementation diaries) collected iteratively over two years were analyzed to identify strategy modifications. Strategies were coded using Expert Recommendations for Implementing Change (ERIC) conceptual clusters, and modifications were documented using the Framework for Reporting Adaptations and Modifications to Evidence-Based Implementation Strategies (FRAME-IS). Modified strategies were categorized as planned or unplanned and contextualized via thematic content analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Across 458 total modifications, the most modified strategies focused on facilitating stakeholder engagement, adapting to local contexts, and using evaluative approaches to improve EBP uptake/sustainment. Planned modifications (n=330, 72%) outnumbered unplanned modifications (n=157, 34%). Rural and community hospitals required more unplanned modifications (average 41 vs. 31 for academic centers), while sites with prior restrictive intervention experience had higher planned-to-unplanned ratios (3.1:1 vs. 1.6:1). Academic hospitals with trainee rotations required ongoing education and higher strategy modifications. All modifications maintained EBP core fidelity. Site-specific patterns organizational characteristics were linked to modification intensity and type, including absorptive capacity, prior experience, relational coordination, rurality, and educational requirements.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Integrating ERIC and FRAME-IS enabled systematic documentation of implementation strategy modifications across diverse settings. Planned:unplanned modification ratios provided novel insights into organizational absorptive capacity and implementation preparedness. Standardized implementation approaches inadequately address critical organizational differences, requiring context-sensitive strategy selection and intensity calibration. This work advances implementation science methodology by demonstrating how systematic modification documentation can inform tailored implementa","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848439","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":"Performance of Human and Computer-aided Evaluation of Digital Chest Radiography for Community-based Screening of Asymptomatic Tuberculosis.","authors":"Sarah Nyangu, Humphrey Mulenga, Simon C Mendelsohn, Tahlia Perumal, Michele Tameris, Tumelo Moloantoa, Stephanus T Malherbe, Firdows Noor, Justin Shenje, Nicolette Tredoux, Angelique Kany Kany Luabeya, Fernanda Maruri, Ravindre Panchia, Khuthadzo Hlongwane, Kim Stanley, Yuri F van der Heijden, Kate Hadley, Neil Martinson, Keertan Dheda, Al Leslie, Bernard Fourie, Gerhard Walzl, Thomas J Scriba, Timothy R Sterling, Mark Hatherill","doi":"10.64898/2026.04.29.26351560","DOIUrl":"https://doi.org/10.64898/2026.04.29.26351560","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The World Health Organisation (WHO) recommends digital chest radiography (dCXR) with computer-aided detection (CAD) for tuberculosis (TB) screening of individuals &gt;15 years of age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methodology: &lt;/strong&gt;Adults (≥18 years) were enrolled (March 2021-December 2022) in South Africa into a community-based Screening Cohort (household contacts) and a facility-based Triage Cohort (symptomatic clinic attendees). Microbiologically-confirmed pulmonary TB required positive sputum culture and/or Xpert Ultra. Asymptomatic TB was diagnosed in participants without TB symptoms. dCXR were read by blinded human readers and qXR CAD (0.5 threshold; Qure.AI, India).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;dCXR from 1,353 participants (886 Screening Cohort; 467 Triage Cohort) were analysed. Microbiologically-confirmed TB occurred in 48 (5.4%) Screening Cohort [9 symptomatic (19%) and 39 asymptomatic (81%)]; and 116 (24.8%) Triage Cohort (all symptomatic) participants. dCXR sensitivity (human readers) for asymptomatic TB in the Screening Cohort was 56.4%, vs. 72.4% for symptomatic TB in the Triage Cohort (difference -16%; 95%CI -2.9 to -29.1); with specificities 94.1% and 81.2%, respectively. Corresponding qXR CAD sensitivities were 69.2% vs. 83.6% (difference -14.4%; 95%CI -26 to -2.8), with specificities 89.3% and 73.5%, respectively. The difference in dCXR sensitivity and specificity for asymptomatic TB between qXR CAD and human readers was 12.8% (95%CI -0.48 to 26.1) and -4.8% (95%CI -12.4 to 28.2), respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Sensitivity of community-based dCXR screening for microbiologically-confirmed asymptomatic TB among household contacts was lower than for facility-based triage of symptomatic TB, but approached 70% with CAD. Neither human reader nor qXR CAD evaluation met WHO targets for a TB screening test (90% sensitivity; 80% specificity).&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; The World Health Organisation (WHO) recommends digital chest radiography (dCXR) with computer-aided detection (CAD) for tuberculosis (TB) screening of individuals &gt;15 years of age, based on data from prevalence surveys and facility-based studies. Performance data for community-based screening of asymptomatic TB are lacking. We searched PubMed for literature published in English between January 1, 2000, and November 1, 2025, for community-based, active case-finding studies of adolescents and adults aged 15 years and older that used dCXR CAD for asymptomatic TB screening. We used the following search terms: \"Tuberculosis\" AND (\"asymptomatic\" OR \"subclinical\") AND (\"computer aided diagnosis\" OR \"artificial intelligence\") AND \"community-based screening\" AND \"chest radiography\" AND (\"diagnostic performance\" OR \"sensitivity\"). We identified five studies reporting on microbiologically-confirmed asymptomatic TB and dCXR CAD performance. Three of five studies tested sputum only in those who were","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848213","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":"Reliability of TRUST ASL for measuring cerebral blood flow and blood-brain barrier water exchange: a scan-rescan pilot study in healthy subjects and patients with epilepsy.","authors":"Ning Hua, Lena Václavů, Joseph Sisto, Chad Farris, Osamu Sakai, Janine Barrett, Maria Stefanidou, Abrar Al-Faraj, Matthew Belisle, Muhammad M Qureshi, Ali Guermazi, Lee Goldstein, Sara K Inati, Meher Juttukonda, Bruce Rosen, William Theodore, Matthias Jp van Osch, Myriam Abdennadher","doi":"10.64898/2026.04.21.26350807","DOIUrl":"https://doi.org/10.64898/2026.04.21.26350807","url":null,"abstract":"<p><strong>Objective: </strong>Water exchange across the blood-brain barrier (BBB) sustains tissue homeostasis; BBB dysfunction can raise neuronal excitability and promote seizures. Noninvasive imaging of water exchange probes BBB function. T2l1lrelaxation underl1lspinl1ltagging (TRUST) arterial spin labeling (ASL) separates intravascular and extravascular labeled water. We tested TRUSTl1lASL feasibility and scan-rescan reliability.</p><p><strong>Methods: </strong>Twelve participants (5 controls, 7 with epilepsy) underwent two 3T MRI sessions 2-4 weeks apart, acquiring T1, FLAIR, and TRUSTl1lASL. At each epilepsy visit we recorded seizure frequency, last seizure details, and medications. ASL images were processed in MATLAB to quantify CBF and water exchange time. Maps were registered to T1 and normalized to MNI space via FreeSurfer. Scan-rescan reliability across gray matter and regions (temporal cortex including amygdala/hippocampus, frontal, occipitoparietal, basal ganglia) used intraclass correlation coefficients. Individual agreement was evaluated with Bland-Altman plots and withinl1lsubject coefficient of variation. Statistical analyses used R.</p><p><strong>Results: </strong>Scan-rescan reliability was good for CBF (ICC = 0.79, 95% CI [0.28 - 0.94]) and excellent for water exchange time (ICC = 0.97, 95%CI [0.90-0.99]) across grey matter. Regional analyses revealed lower reliability in the basal ganglia compared to other subregions. Bland-Altman analysis demonstrated strong agreement between sessions, with mean differences near zero for CBF (limits of agreement: -20 to 20 ml/100g/min), and water exchange time (mean differences 0.17s; limits of agreement: -0.44 to 0.79 s).</p><p><strong>Significance: </strong>Our findings show TRUSTl1lASL reliably measures BBB water exchange. Tex has high relative reliability (ICC) but substantial withinl1lsubject variability (wCV), limiting sensitivity for small individual longitudinal changes. Groupl1llevel reliability is strong, supporting use in longitudinal epilepsy studies. BBB water exchange is a promising noninvasive biomarker of BBB dysfunction in epilepsy.</p><p><strong>Plain language summary: </strong>The blood-brain barrier protects the brain from harmful substances while letting nutrients pass from the blood. In epilepsy, this barrier can become disrupted and may make seizures worse. We tested a noninvasive MRI method (no injections) to measure how well the blood and brain exchange substances. Our results show the technique can clearly visualize these exchanges and can be repeated reliably, offering a safe tool to study barrier function in people with epilepsy.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848255","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":"Autism Sensory Profiles Predict Stimulus-Evoked Insula Connectivity.","authors":"Zachary Jacokes, Stefen Beeler-Duden, Sophie Lawson, Jeff Eilbott, John Darrell Van Horn, Kevin Pelphrey","doi":"10.64898/2026.04.29.26352062","DOIUrl":"https://doi.org/10.64898/2026.04.29.26352062","url":null,"abstract":"<p><p>Sensory processing is a common target in autism spectrum disorder (ASD) research, yet the latent structure of sensory experience is disputed. Researchers frequently explore the presence of \"subtypes\" to categorize sensory heterogeneity, but such discrete models can fail to capture the intrinsic geometry of phenotypic data. In this study, we aim to characterize heterogeneous sensory profiles in ASD and explore if the same characterization can describe neurobiological function. First, we apply unsupervised spectral manifold dimensionality reduction to item-level Sensory Profile data from a large cohort of autistic participants ( <i>n</i> =223) to compare categorical subtyping against continuous models. The behavioral results reveal unstable and irreproducible subtyping solutions; instead, sensory processing differences are best characterized as a continuous, non-linear manifold of sensory severity. To determine the neurobiological relevance of this sensory gradient, we employed voxel-wise linear mixed-effects modeling of insula-seeded functional connectivity ( <i>n</i> =63). We demonstrate that sensory severity predicts a significant decoupling between the insula and sensorimotor cortices during externally driven stimulation involving motion stimuli, but not during resting state. This finding supports the interpretation that sensory-related neural hypoconnectivity is context-dependent and not reflective of intrinsic traits. Further, we identify a significant sex-by-sensory gradient interaction, indicating heightened sensitivity of connectivity patterns to sensory severity in autistic males. These findings indicate that sensory atypicality in ASD points toward a continuous regulatory manifold linked to disrupted social-sensory integration.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848300","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":"An mHealth-based social support program to improve antenatal care engagement and facility-based births in Uganda: A type I hybrid effectiveness-implementation clinical trial.","authors":"Esther C Atukunda, Godfrey R Mugyenyi, Jessica Haberer, Van T Nghiem, Elly B Atuhumuza, Peter Waiswa, Angella Musiimenta, Micheal Kanyesigye, Celestino Obua, Mark J Siedner, Lynn T Matthews","doi":"10.64898/2026.04.28.26351943","DOIUrl":"https://doi.org/10.64898/2026.04.28.26351943","url":null,"abstract":"<p><strong>Background: </strong>Ugandan women and their children suffer from high maternal and perinatal mortality, often due to low antenatal care (ANC) and skilled birth usage. We partnered with community members, women and the Ugandan Ministry of Health to formatively develop an intervention ( <i>Support-Moms app</i> ) to improve health education, engage social support networks, and augment access to ANC and delivery by a formal health care provider (HCP) for pregnant women in rural Uganda.</p><p><strong>Methods: </strong>We conducted a type 1 hybrid effectiveness-implementation trial to test the effectiveness of the <i>Support-Moms</i> intervention. We enrolled 824 pregnant women (<20 weeks gestation) living in Southwestern Uganda and randomized them (1:1) to standard of care or <i>Support-Moms</i> intervention. The primary effectiveness outcome was completion of a HCP-led skilled birth (discharge card) and was analyzed as intention-to-treat. Secondary outcomes included number of ANC visits, institution-based delivery, social support, quality-of-life, mode of infant delivery, pre-term birth, birth weight, obstetric complications and deaths (maternal, fetal, newborn).</p><p><strong>Results: </strong>A total of 1,216 women were screened, and 824 pregnant women enrolled (mean age ∼28 years; gestation at enrolment ∼13 weeks). Complete outcomes were available for 818 (99%). The <i>Support-Moms</i> intervention increased HCP-led skilled births compared to standard of care (93% vs 84%; OR 2.51, 95% CI 1.57-4.03, p<0.001). Women in the intervention group were more likely to achieve ≥4 ANC visits (84.1% vs 75.1%; OR 1.76, 95% CI 1.24-2.50, p=0.001) and less likely experience postpartum hemorrhage (9.1% vs 22.7%, OR 0.34, 95% CI 0.22-0.52, p<0.001) or for their neonates to require resuscitation (9.8% vs 13.7%, OR 0.69, 95% CI 0.45-0.99, p=0.001). Initiation of breastfeeding within an hour was higher (97.1% vs 71.7%, OR 1.76, 95% CI 1.15-3.44, p=0.001) and postnatal depression decreased (20.1% vs 27.1%, OR 0.68, 95% CI 0.49-0.94, p=0.019). More intervention participants reported adequate support, were birth-prepared and had a birth companion. There were no maternal deaths or differences in term births, birthweight, mode of delivery, perinatal mortality or other obstetric complications.</p><p><strong>Conclusions: </strong>In rural Uganda, the Support-Moms mHealth-based, social-support intervention significantly increased HCP-led skilled births compared with routine care, while also improving ANC attendance, early breastfeeding initiation, birth preparedness, perceived social support and higher presence of companion at birth. Less women experienced PPH, neonatal resuscitation, and postnatal depression. Further evaluation should focus on the cost effectiveness and sustainability of this program.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT05940831.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848307","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}