medRxiv : the preprint server for health sciences最新文献

{"title":"Androgen Deprivation Therapy (ADT) and Radiotherapy (RT) with Imaging Evaluation Longitudinally (ARIEL) trial: protocol, early results, and implications of neoadjuvant ADT for focal RT boost in prostate cancer.","authors":"Yuze Song, Mariluz Rojo Domingo, Lily Nguyen, Christopher C Conlin, Nitin Dhillon, Son Do, Anna Dornisch, Michael E Hahn, Roshan Karunamuni, Joshua Kim, Kang-Lung Lee, Jasmine Liu, Rana R McKay, Loren K Mell, Arno J Mundt, Rakesh Patel, Edmund M Qiao, Brent Rose, Rhea Rupareliya, Hadley Schaub, Armin Schwartzman, Tyler Stewart, Anders M Dale, Tyler M Seibert","doi":"10.64898/2026.04.22.26351215","DOIUrl":"https://doi.org/10.64898/2026.04.22.26351215","url":null,"abstract":"<p><strong>Background: </strong>Men with aggressive, localized prostate cancer (PC) undergo definitive radiotherapy (RT) with androgen deprivation therapy (ADT). The prospective, phase II ARIEL trial evaluates a quantitative MRI biomarker, Restriction Spectrum Imaging restriction score (RSIrs), at three time points (before treatment, after ADT and after RT) for treatment response assessment. RSIrs highlights intracellular restricted diffusion and is correlated with high-grade PC.</p><p><strong>Design: </strong>Participants are men with unfavorable-intermediate-risk or high-risk localized PC undergoing definitive RT with neoadjuvant and concurrent ADT, and MRI-RSI acquisitions at three time points: before therapy, after neoadjuvant ADT but before RT, and after RT. The primary aim is to evaluate performance of RSIrs for identifying patients who will experience early biochemical recurrence. Change in RSIrs within visible tumors after ADT and RT is the primary independent variable.</p><p><strong>Results: </strong>97 patients met inclusion criteria and received ≥1 MRI. On central review, visible PI-RADS lesions were identified in 88 patients: 80 patients had one lesion, and 8 patients had two lesions. After neoadjuvant ADT, 40% of lesions were not clearly visible. Those still visible had shrank by median 55.8% (IQR: 42.8-69.0%), much more than the prostate volume decrease of 21.5% (11.9-31.6%). RSIrs maximum within visible lesions decreased from mean 329 (SD:185) pre-ADT to 209 (SD:125) pre-RT ( <i>p</i> <0.01), and to 107 (SD:61) post-RT ( <i>p</i> <0.01). Conventional apparent diffusion coefficient (ADC) changes were less consistent. Follow-up is ongoing to assess whether imaging response is related to future recurrence risk.</p><p><strong>Conclusion: </strong>ARIEL has completed accrual and preliminary results demonstrate changes in RSIrs after treatment, which may indicate tumor response. Primary results will be presented when the primary endpoint is reached. With neoadjuvant ADT, both pre- and post-ADT MRI are likely necessary for accurate focal RT boost targeting. Concurrent commencement of ADT and RT simplifies workflows and facilitates accurate gross tumor volume delineation.</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/PMC13142587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848290","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":"Polygenic predisposition modifies the associations of fish oil supplementation with circulating omega-3 fatty acids: a cross-sectional gene-diet interaction study in UK Biobank.","authors":"Huifang Xu, Ge Yu, Yueqi Lu, Harriett Fuller, Suhang Song, Ye Shen, Charleston W K Chiang, Burcu F Darst, Kaixiong Ye","doi":"10.64898/2026.04.29.26352078","DOIUrl":"https://doi.org/10.64898/2026.04.29.26352078","url":null,"abstract":"<p><strong>Background: </strong>Several genetic variants have been identified to modify the effects of fish oil supplementation (FOS) on increasing circulating omega-3 fatty acids, but it remains unexplored whether polygenic predisposition to low circulating omega-3 fatty acids modifies these effects.</p><p><strong>Objective: </strong>To test if polygenic scores (PGS) for circulating omega-3 fatty acids modify the associations of FOS with corresponding circulating concentrations.</p><p><strong>Methods: </strong>We developed PGS models for absolute circulating concentrations of total omega-3 fatty acids (Omega-3), docosahexaenoic acid (DHA), and their relative percentages in total fatty acids (Omega-3% and DHA%), using a multi-ethnic genome-wide association study (N=136,016). PGS models were validated in 437,803 UK Biobank participants of European (EUR), Central/South Asian (CSA), African, and East Asian genetic ancestries. Linear models tested PGS-by-FOS interactions on corresponding observed circulating concentrations. Discovery analysis was performed separately in 237,380 EUR participants and each non-EUR group. Replication analyses were performed using oily fish intake and in another 178,935 EUR participants.</p><p><strong>Results: </strong>In EUR participants, PGS explained 5.3-11.1% of the phenotypic variance, and significant PGS-by-FOS interactions were detected across all four circulating omega-3 traits. Among participants in the bottom 5% of the PGS distribution, FOS was significantly associated with a 0.40 SD (95% CI: 0.39-0.44) increase in Omega-3. This association effect was 11.1% larger than the population average (β = 0.36; 95% CI: 0.35-0.37; P _Int = 0.016) and 42.8% larger than that in participants in the top 5% of the PGS distribution (β = 0.28 SD; 95% CI: 0.25-0.32; P _Int = 4.03X10 ^-10 ). These interaction patterns were consistently observed in CSA ancestry and confirmed in replication and sensitivity analyses.</p><p><strong>Conclusions: </strong>PGS modify the associations of FOS with circulating omega-3 fatty acids in EUR and CSA populations, with larger FOS effects in participants with lower PGS. These findings support the development of genome-informed precision nutrition.</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/PMC13142608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848299","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":"Associations of vegetarianism with circulating lipids across varying genetic capacity: a cross-sectional Polygenic Score-by-Vegetarianism interaction study in UK Biobank.","authors":"Angela Ge, Yitang Sun, Alexandra Huong Chiang, Aryaman Singh, Huifang Xu, Kaixiong Ye","doi":"10.64898/2026.04.29.26352068","DOIUrl":"https://doi.org/10.64898/2026.04.29.26352068","url":null,"abstract":"<p><strong>Background: </strong>Circulating lipid levels are influenced by both genetic and environmental factors. While vegetarianism has been linked to improved lipid profiles, it remains unclear whether these beneficial effects persist across individuals with varying genetic capacity for lipid metabolism.</p><p><strong>Objective: </strong>We hypothesized that genetic capacity and vegetarianism interact to influence the circulating levels of four lipids, including total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG).</p><p><strong>Methods: </strong>Our study included UK Biobank participants of European (EUR, n = 182,300), Central/South Asian (CSA, n = 2,627), African (n = 2,143), and East Asian (n = 1,031) ancestry. Utilizing polygenic scores (PGS) for four circulating lipids, we employed multivariable regression models to assess PGS-by-vegetarianism interactions for each lipid.</p><p><strong>Results: </strong>Vegetarianism is associated with reduced levels of TC, LDL cholesterol, and HDL cholesterol, and with elevated levels of TG in the EUR cohort (p-value < 0.001). The same significant association patterns were observed for HDL cholesterol and TG in the CSA cohort. We did not detect significant PGS-by-vegetarianism interactions for any lipid traits (Interaction p-value > 0.05). There is a lack of evidence supporting that PGS modifies the associations between vegetarianism and lipid levels, nor that vegetarianism alters the effects of PGS on lipid levels.</p><p><strong>Conclusions: </strong>Vegetarianism is associated with reduced TC, LDL cholesterol, and HDL cholesterol, as well as elevated TG among EUR participants, with similar patterns for HDL cholesterol and TG in CSA participants. These association effects of vegetarianism on circulating lipids are similar across individuals with varying genetic capacity for lipid metabolism.</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/PMC13142561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848263","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":"Association between Weather Variables and Viral Gastroenteritis in the United States.","authors":"Natalya Alekhina, Paola Fonseca-Romero, Per H Gesteland, Ben J Brintz, Amy L Leber, Jami T Jackson, Jennifer Dien Bard, Neena Kanwar, Ara Festekjian, Chari Larsen, Kimberle C Chapin, Rangaraj Selvarangan, Sean Soisson, Andrew T Pavia, Daniel T Leung","doi":"10.64898/2026.04.29.26352095","DOIUrl":"https://doi.org/10.64898/2026.04.29.26352095","url":null,"abstract":"<p><p>Infectious gastroenteritis (IGE) is a major cause of pediatric morbidity globally, with viral pathogens accounting for a substantial proportion of cases. While seasonal patterns of viral IGE are well recognized, the association between specific environmental exposures, such as ambient temperature, and viral IGE has not been fully quantified. First, we performed a secondary analysis of data from a prospective, multisite study of children presenting to emergency departments at five medical centers across the continental United States, linking individual level laboratory data to environmental exposures, including temperature, humidity, and air pollutants, measured during the 14 days preceding symptom onset. Mixed-effects logistic regression was applied to evaluate the association between viral IGE and environmental exposures, adjusting for site-level clustering and patient age. Among 868 children with IGE, higher ambient temperature was inversely associated with viral etiology (OR 0.50, 95% CI 0.36-0.68, p < 0.001). We did not find statistically significant associations between other environmental variables and viral IGE. Then, to contextualize these individual-level findings in children, we examined all-ages population-level surveillance data from GermWatch, a regional laboratory testing-based infectious disease surveillance system, which demonstrated concordant declines in viral pathogen detection with increasing temperature. These findings support the association of weather with viral transmission patterns. Incorporating environmental context into clinical decision-making may improve diagnostic stewardship and support more effective resource allocation during periods of increased viral IGE prevalence.</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/PMC13142582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848329","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":"Epigenetic inflammation signatures and lung cancer risk among never-smoking women: a nested case-control study.","authors":"Mohammad L Rahman, Aishani Gargapati, Lauren M Hurwitz, Wei Hu, Alexander P Keil, Charles E Breeze, Anil Chaturvedi, Jianxin Shi, Qiuyin Cai, Gong Yang, Jirong Long, Yu-Tang Gao, David C Christiani, Nathaniel Rothman, Wei Zheng, Xiao-Ou Shu, Jason Y Y Wong, Qing Lan","doi":"10.64898/2026.04.27.26351864","DOIUrl":"https://doi.org/10.64898/2026.04.27.26351864","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic inflammation has been implicated in lung carcinogenesis. Prospective studies have linked higher circulating C-reactive protein (CRP), an acute-phase inflammation marker, to higher lung cancer risk in predominantly smoking populations but lower risk in never smokers. We evaluated DNA methylation-based inflammation risk scores (DNAm-IRSs), which may capture longer-term immune-inflammatory and exposure-related biology, with lung cancer risk among never smokers.</p><p><strong>Methods: </strong>We evaluated six DNAm-IRSs, including four CRP-based scores (IRS _Ligthart , IRS _Wielscher , IRS _{Linear_Hillary} , IRS _{Elnet_Hillary} ), in 683 risk-set-sampled case-control pairs nested in the Shanghai Women's Health Study (n=74,941). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using conditional logistic regression. We examined DNAm-derived leukocyte composition and circulating immune-inflammatory proteins to characterize DNAm-IRS biology.</p><p><strong>Results: </strong>Circulating CRP correlated positively with IRS _Ligthart (r=0.19), IRS _Wielscher (r=0.13), and IRS _{Elnet_Hillary} (r=0.30), but inversely with IRS _{Linear_Hillary} (r=-0.02). Per standard deviation increase, IRS _Ligthart was associated with lower lung cancer risk (HR=0.85, 95% CI: 0.76-0.95), and IRS _Wielscher with lower risks of lung cancer (HR=0.87, 95% CI: 0.77-0.97) and adenocarcinoma (HR=0.83, 95% CI: 0.71-0.97). Associations persisted after adjustment for leukocyte composition and strengthened after adjustment for DNAm pack-years, an epigenetic smoking index that may capture combustion-related exposures beyond active smoking. Inverse associations were more evident among women with lower DNAm pack-years, although formal interaction tests were not statistically significant. Both scores were positively associated with acute-phase inflammation, IFN-γ/effector trafficking, and higher CD8+ T-cell proportions.</p><p><strong>Conclusions: </strong>Among never smokers, selected CRP-related DNAm-IRSs were associated with lower lung cancer risk and were linked to immune features consistent with antitumor activity.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848334","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":"Evaluation of the genome-informed risk assessment (GIRA) approach from eMERGE in an independent health system.","authors":"Sandra Lapinska, Xinzhe Li, Ravi Mandla, Zhuozheng Shi, Veronica Tozzo, Alexander Flynn-Carroll, Marylyn D Ritchie, Daniel J Rader, Bogdan Pasaniuc","doi":"10.64898/2026.02.25.26347123","DOIUrl":"https://doi.org/10.64898/2026.02.25.26347123","url":null,"abstract":"<p><p>The Genome Informed Risk Assessment (GIRA) from eMERGE is an ongoing pragmatic prospective study designed to implement and evaluate genomic precision medicine across diverse clinical settings. Here, we examine the utility of the high-risk criteria from GIRA in assessing health risk through a retrospective evaluation of 9 adult conditions in a health system independent of eMERGE using the Penn Medicine Biobank (PMBB, n=48,279). We find a large proportion of patients - 30.4% (n=14,676) - labeled as high-risk based on the genomic components (monogenic and polygenic) of GIRA. Stratifying by ancestry revealed significant differences in high-risk classification, with higher rates in African/African American (56.6% vs. 50.1%, p=7.43x10-36) and lower rates in East (42.0%) and South Asian (40.0%) ancestries when considering all three high-risk components of GIRA. Enrichments of high-risk individuals were observed in the highest quartile of social deprivation index highlighting contextual influences on high-risk measures. The polygenic component of GIRA was a good predictor of prevalent cases. GIRA predicted incident disease albeit with lower accuracies for some conditions. We find demographic compositions of high-risk patients differed from the incident cases for certain conditions; for example, high-risk AFIB individuals where enriched for European ancestries in contrast with incident AFIB cases that were enriched for AFR ancestries. Overall, our results show the accuracy of GIRA's high-risk criteria as a biomarker to stratify high-risk patients for precision medicine and highlight its potential impact on the health system if implemented at scale.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848322","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 reliability-screened thalamocortical control-network phenotype tracks cocaine-use history in cocaine use disorder.","authors":"Brice Edelman, Jeffrey Skolnick","doi":"10.64898/2026.04.28.26351962","DOIUrl":"https://doi.org/10.64898/2026.04.28.26351962","url":null,"abstract":"<p><strong>Background: </strong>A central goal in psychiatry is to move from symptom-defined diagnoses toward biologically interpretable and reliable phenotypes. In cocaine use disorder (CUD), many resting-state abnormalities have been reported, but few circuit-level findings have been explicitly screened for reliability. We tested whether prespecified thalamocortical features yield a reproducible phenotype in CUD and whether that phenotype reflects diagnosis, recent cocaine use, or longer-term illness history.</p><p><strong>Methods: </strong>Discovery analyses used resting-state data from 105 participants (46 healthy controls, 59 CUD). From a 13-region thalamocortical circuit, we derived an HC-trained LEiDA state model, generated 11 prespecified features, and advanced only those meeting split-half reliability criteria (ICC[3,1] ≥0.40). A separate paired TMS sample (n=44) was used for extension analyses.</p><p><strong>Results: </strong>Five features survived reliability screening. Within CUD, longer duration since beginning cocaine use was associated with greater occupancy of a control-like state (standardized β=0.37, q=0.005) and stronger whole-thalamus connectivity with control frontoparietal cortex (standardized β=0.30, q=0.018). Neither days since last use nor CUD vs. healthy diagnosis were associated with any reliable feature after correction. Joint-history models indicated that the signal was better explained by longer-term use history than by recent use. Localization analyses indicated the connectivity effect was concentrated in dorsal thalamic regions. TMS-interaction and effective-connectivity follow-ups were null.</p><p><strong>Conclusions: </strong>Reliability screening identified a thalamocortical control-network phenotype in CUD that tracks longer cocaine-use history rather than diagnosis or recent use. More broadly, this workflow offers a practical framework for screening candidate circuit-level psychiatric phenotypes for reliability.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848324","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":"Feasibility of Non-Sedated Multispectral Neuroimaging in Newly Diagnosed Children with Leukemia.","authors":"Mary-Kaylin Tran, Lauren Appell, Simon Chung, Madison Sanders, Amy Jones, Mandy Fenwick, Elizabeth Oest, Xiawei Ou, Jason Farrar, Andrew W Brown, Timothy R Koscik, Ellen van der Plas","doi":"10.64898/2026.04.21.26351310","DOIUrl":"https://doi.org/10.64898/2026.04.21.26351310","url":null,"abstract":"<p><strong>Introduction: </strong>Children with acute lymphoblastic leukemia (ALL) require neurotoxic treatment during critical periods of brain development. Multispectral magnetic resonance imaging (MRI) offers opportunities to characterize the impact of chemotherapy on the developing brain, but this has been constrained by concerns regarding feasibility of obtaining quality MRIs from these critically ill children at a young age. Our goal is to demonstrate a framework for improving the feasibility of non-sedated, multispectral MRI in newly diagnosed ALL patients.</p><p><strong>Methods: </strong>Participants were enrolled from August 2023 through February 2026, and included newly diagnosed ALL patients and controls recruited from the community ages 3-10 years old. Participants completed a series of three non-sedated MRI without contrast on a 3T scanner over 12 months. Sequences included anatomical T1-weighted and QALAS sequences for quantitative mapping, diffusion weighted MRI (DWI), MR Spectroscopy (MRS), and resting-state functional MRI (rs-fMRI). A sequence was considered complete if data quality was sufficient for successful image processing. Mixed-effects logistic regression models were used determine if group and study visit were associated with MRI success rates across sequences.</p><p><strong>Results: </strong>The sample included 17 ALL patients and 30 controls, who contributed to 38 and 75 observations, respectively. Of 113 attempted scans, 105 had ≥1 sequence completed (93%). Across assessments, ALL patients were less likely to complete a scan (31 of 38 attempts; raw rate: 82%) relative to controls (73 of 75; raw rate: 96%; model-estimated difference=-14.1%, 95%CI=-27.1%; -1.1%, p=0.033). Baseline success rate was 65% (11 of 17) for ALL patients and 93% (28 of 30) for controls (model-estimated difference=-26.8%, 95%CI=-52.7%; -0.9%, p=0.42); however, nearly all T1w scans in ALL patients were successful at follow-up visits (20 of 21; 95%), with no significant differences between groups (model-estimated difference at follow-up 1=-2.1%, 95%CI=-11.7%; 7.6%; model-estimated difference at follow-up 2=-8.3%, 95%CI=-26.3%; 9.6%). A similar pattern was observed for DWI, MRS and rs-fMRI sequences with relatively high completion rates at follow-up assessments.</p><p><strong>Discussion: </strong>Non-sedated multispectral MRI is feasible in young children with newly diagnosed ALL, particularly with repeated visits and structured behavioral preparation. These results highlight opportunities to capture the scope and depth of neurodevelopmental changes concurrent with ALL treatment.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848409","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":"Estimated Impacts of Rotavirus Vaccine Recommendation Changes in the U.S.","authors":"Ernest O Asare, Jiye Kwon, Melanie H Chitwood, Stephanie Perniciaro, Gregg S Gonsalves, Virginia E Pitzer","doi":"10.64898/2026.04.27.26351857","DOIUrl":"https://doi.org/10.64898/2026.04.27.26351857","url":null,"abstract":"<p><p>In January 2026, the United States Department of Health and Human Services downgraded the recommendation for infant immunization with rotavirus vaccine to one of shared clinical decision-making. We use a validated model for the transmission dynamics of rotavirus to predict the magnitude and timing of increases in the number of rotavirus hospitalizations in the US and in representative states given possible decreases in vaccine coverage. Rotavirus hospitalizations are likely to increase within two to three years following a drop in vaccine coverage, resulting in over 200,000 hospitalizations between July 2026-June 2031 if coverage were to drop to 20%. The burden is likely to fall disproportionately on southern states that currently experience higher rates of rotavirus hospitalization.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848253","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":"Adverse childhood family environment is associated with altered cardiovascular regulation during exercise among young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.","authors":"Nathaniel D M Jenkins, Austin T Robinson, Bjoern Hornikel, Kara M Whitaker, David R Jacobs, Kiarri Kershaw, Kelley Pettee Gabriel","doi":"10.64898/2026.04.24.26351696","DOIUrl":"https://doi.org/10.64898/2026.04.24.26351696","url":null,"abstract":"<p><p>The purposes of this study were to determine whether adverse childhood family environment (ACFE) exposure is associated with altered hemodynamic responses to graded exercise in young adulthood, and whether this association was modified by sex and race in a large, population-based cohort. We hypothesized that ACFE exposure would be associated with an exaggerated exercise pressor response in young adulthood, independent of resting BP. We further hypothesized that the association between ACFE and the hemodynamic response to exercise would be stronger in females than males, and in Black versus White participants.</p><p><strong>Methods: </strong>Exercising blood pressure (BP) and heart rate (HR) responses were recorded during graded exercise testing and ACFE exposure was assessed among 3,417 young adults (mean age = 25 ± 4 y; 44% female; 46% Black). Linear mixed-effects models that included participant-specific random intercepts and random slopes were used to assess the relation between ACFE exposure and exercising systolic (SBP), diastolic, and mean BP, pulse pressure (PP), pulse pressure index (PPI), heart rate (HR), and rate pressure product (RPP). All models were adjusted for resting values of the hemodynamic outcome, as well as age, sex, race, study center, body mass index, current hypertension medication use, smoking status, and alcohol consumption.</p><p><strong>Results: </strong>Graded exercise hemodynamic responses were analyzed in 3,346-3,417 participants in the final models, providing 15,372-17,481 observations. Higher ACFE exposure was associated with lower SBP (β = -0.304 mmHg/ACFE, <i>p</i> = 0.033), HR (β = -0.485 bpm/ACFE, <i>p</i> <0.001), and RPP (β = -83.404 bpm·mmHg/ACFE, <i>p</i> =0.002) at the lowest workload, but steeper workload-related increases in SBP (interaction β = 0.044 mmHg·MET⁻¹·ACFE⁻¹, <i>p</i> =0.029), HR (β = 0.061 bpm·MET⁻¹·ACFE⁻¹, <i>p</i> <0.001), RPP (β = 10.16 bpm·mmHg·MET⁻¹·ACFE⁻¹, <i>p</i> =0.025), and PP (β = 0.052 mmHg·MET⁻¹·ACFE⁻¹, <i>p</i> =0.038) and PPI (β = 0.000232 units·MET⁻¹·ACFE⁻¹, <i>p</i> =0.018). These findings were robust to additional adjustment for central adiposity, exercise capacity, and maximal heart rate and heart rate recovery.</p><p><strong>Conclusion: </strong>Our findings add nuanced evidence revealing that early adversity is associated with a demand-dependent shift in cardiovascular regulation, with attenuated responses at low demand, but more dramatic increases in pulsatile and myocardial load responses during progressive physiological stress.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848342","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}