medRxiv : the preprint server for health sciences最新文献

{"title":"Sibling Control Analysis of Perinatal Health and Family Environment Factors Related to Childhood ADHD Symptoms.","authors":"Michael A Mooney, Peter Ryabinin, Elizabeth Nousen, Jessica Tipsord, Nathan F Dieckmann, Sarah L Karalunas, Megan M Herting, Molly Nikolas, Joel T Nigg, Stephen V Faraone","doi":"10.1101/2025.06.16.25329516","DOIUrl":"10.1101/2025.06.16.25329516","url":null,"abstract":"<p><strong>Background: </strong>Numerous studies have reported associations between environmental exposures and ADHD. However, whether environmental effects are causal or due to confounding with other familial factors, such as genetic risk, is still unclear. A more complete understanding of which environmental risk factors are causal remains crucial.</p><p><strong>Methods: </strong>Using one population (ABCD cohort, N=11646) and one case-control cohort (Oregon ADHD-1000, N=744), we conducted both full-cohort and sibling-control analyses (770 and 152 families in ABCD and Oregon ADHD-1000, respectively) to assess the association of family environment and perinatal risk factors with ADHD symptoms. Within-family effects were compared to effects estimated in the full cohorts. We also assessed the impact of gene-environment correlation using child polygenic risk scores and measures of maternal mental health.</p><p><strong>Results: </strong>For both cohorts, full-cohort analyses yielded significant associations between child ADHD symptoms and family conflict, perinatal health factors, and breastfeeding duration (p-values <0.001). These associations were non-significant after accounting for family-level confounds (e.g., genetic risk and shared family environment) in exposure-discordant sibling-control analyses. In the full cohorts, effect sizes were substantially reduced (an average 43.7% decrease in effect size across all exposures tested in the ABCD cohort; average 47.6% decrease in Oregon ADHD-1000) after adjusting for child ADHD polygenic risk and measures related to maternal mental health.</p><p><strong>Conclusions: </strong>The full-cohort associations between child ADHD symptoms and environmental risks confirm associations from prior research, but current findings do not indicate direct causal effects. Instead, much or all of the observed risk appears due to confounding with family-level factors, likely including genetic factors. Our results underscore the importance of accounting for familial risk factors that may confound relationships between behavioral traits and environmental exposures by using multiple study designs.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532329","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":"Quantifying the impact of early-life growth adversity on later-life health.","authors":"Raphael Goldman-Pham, Matthew P Alter, Rebecca Bao, Sophie É Collins, Catherine L Debban, James P Allinson, Antony Ambler, Alain G Bertoni, Avshalom Caspi, Stephanie Lovinsky-Desir, Magnus P Ekstrom, James C Engert, David R Jacobs, Daniel Malinsky, Ani Manichaikul, Erin D Michos, Terrie E Moffitt, Elizabeth C Oelsner, Sandhya Ramrakha, Stephen S Rich, Coralynn Sack, Sanja Stanojevic, Padmaja Subbarao, Karen Sugden, Reremoana Theodore, Karol E Watson, Benjamin Williams, Bin Yang, Josée Dupuis, Seif O Shaheen, R Graham Barr, Robert J Hancox, Benjamin M Smith","doi":"10.1101/2025.06.16.25327714","DOIUrl":"10.1101/2025.06.16.25327714","url":null,"abstract":"<p><strong>Background: </strong>Early-life growth adversity is important to later-life health, but precision assessment in adulthood is challenging. We evaluated whether the difference between attained and genotype-predicted adult height (\"height-GaP\") would associate with prospectively ascertained early-life growth adversity and later-life all-cause and cardiovascular mortality.</p><p><strong>Methods: </strong>Data were first analyzed from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UKBiobank. Genotype-predicted height was calculated using a multi-ancestry polygenic height score. Height-GaP was calculated as the difference between measured and genotype-predicted adult height. Early-life growth conditions were ascertained prospectively via standardized procedures (ALSPAC) and mortality via death register (UKBiobank). Regression models adjusted for age, sex, genotype-predicted height and genetic ancestry. Analyses were replicated in the Dunedin Multidisciplinary Health and Development Study (DMHDS) and the Multi-Ethnic Study of Atherosclerosis (MESA).</p><p><strong>Findings: </strong>Among 4,582 ALSPAC participants (median [IQR] age: 24[18-25] years at height-GaP assessment), lower gestational age at birth, greater pre- and post-natal deprivation indices, tobacco smoke exposure and less breastfeeding were associated with larger adult height-GaP deficit (p<0.01). Among 483,385 UKBiobank participants (mean±SD age: 56±8 years at height-GaP assessment), height-GaP deficit was associated with death from all-causes (adjusted hazard ratio comparing highest-to-lowest height-GaP deficit quartile [aHR]:1.25 95%CI:1.21-1.29), atherosclerotic cardiovascular disease (aHR:1.33 95%CI:1.24-1.43) and coronary heart disease (aHR:1.68 95%CI:1.52-1.86). Early- and later-life height-GaP associations replicated in DMHDS and MESA.</p><p><strong>Interpretation: </strong>This study introduces a simple index of early-life growth adversity deployable in adulthood to investigate the developmental origins of longevity and improve health equity across the life course.</p><p><strong>Funding: </strong>Federal agencies and academic institutions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532324","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":"Creatine-weighted imaging in patients with Parkinson's disease.","authors":"Kexin Wang, Nirbhay Narayan Yadav, Zijiang Yang, Ted M Dawson, Peter van Zijl, Kelly A Mills, Jiadi Xu, Jannik Prasuhn","doi":"10.1101/2025.06.15.25329644","DOIUrl":"https://doi.org/10.1101/2025.06.15.25329644","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder involving impaired bioenergetics and mitochondrial dysfunction. Creatine (Cr) supplementation has been suggested as a pathophysiology-targeted therapy, yet human studies have yielded heterogeneous results. This study employs guanidino chemical exchange saturation transfer (GuanCEST) magnetic resonance imaging (MRI), a novel Cr-weighted imaging technique, to evaluate Cr level changes in patients with PD (PwPD) compared to healthy controls (HCs).</p><p><strong>Methods: </strong>25 PwPD and 24 age- and sex-matched HCs underwent standardized clinical assessments and GuanCEST MRI. Region-of-interest (ROI) and voxel-wise analyses were conducted to assess group differences. Kendall's correlation and ANCOVA were used to explore associations between GuanCEST signals, disease presence, and clinical severity.</p><p><strong>Results: </strong>GuanCEST signals in the caudate nucleus were significantly lower in PwPD (1.67 ± 0.26%) than in HCs (1.82 ± 0.16%; p = 0.023). Signal reduction correlated with increasing PD severity, particularly in thalamic subregions. In the internal medullary lamina, GuanCEST values negatively correlated with MDS-UPDRS-III scores (r = -0.44, p = 0.03) and a trend was also seen in the lateral thalamic nuclei (r = -0.39, p = 0.06). ANCOVA indicated GuanCEST values in the internal medullary lamina decreased by ∼0.01% per point increase in MDS-UPDRS-III (p = 0.007), adjusted for age and sex.</p><p><strong>Conclusion: </strong>GuanCEST MRI shows promise as a non-invasive tool for detecting Cr alterations in PD. This technique may enhance our understanding of Cr metabolism in PD and support the development of targeted therapeutic strategies.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532293","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":"Practice effects persist over two decades of cognitive testing: Implications for longitudinal research.","authors":"Jeremy A Elman, Erik Buchholz, Rouhui Chen, Mark Sanderson-Cimino, Tyler R Bell, Nathan Whitsel, Katherine J Bangen, Alice Cronin-Golomb, Anders M Dale, Lisa T Eyler, Christine Fennema-Notestine, Nathan A Gillespie, Eric L Granholm, Daniel E Gustavson, Donald J Hagler, Richard L Hauger, Diane M Jacobs, Amy J Jak, Mark W Logue, Michael J Lyons, Ruth E McKenzie, Michael C Neale, Robert E Rissman, Chandra A Reynolds, Rosemary Toomey, Arthur Wingfield, Hong Xian, Xin M Tu, Carol E Franz, William S Kremen, Matthew S Panizzon","doi":"10.1101/2025.06.16.25329587","DOIUrl":"https://doi.org/10.1101/2025.06.16.25329587","url":null,"abstract":"<p><strong>Background: </strong>Repeated cognitive testing can boost performance due to practice effects (PEs), yet it remains unclear whether PEs persist across multiple follow-ups and long durations. We examined PEs across 17 years from midlife to old age in a nonclinical sample.</p><p><strong>Method: </strong>Men (N=1,608) in the Vietnam Era Twin Study of Aging (VETSA) completed neuropsychological batteries comprising 30 measures across 4 waves over 20 years. We leveraged age-matched replacement participants to estimate PEs at each wave. We compared cognitive trajectories and MCI prevalence using unadjusted versus PE-adjusted scores.</p><p><strong>Result: </strong>We found significant PEs for multiple tests at all waves, especially in episodic memory and visuospatial domains. Adjusting for PEs resulted in greater cognitive decline and earlier detection of MCI, with up to 20% increased prevalence.</p><p><strong>Conclusion: </strong>PEs persist across multiple assessments and decades, even with long testing intervals, underscoring the importance of accounting for PEs in longitudinal studies and clinical trials.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532318","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":"Utility of 18F-Flurpiridaz PET Relative Flow Reserve in Differentiating Obstructive from Nonobstructive Coronary Artery Disease.","authors":"Diana M Lopez, Dan Huck, Sanjay Divakaran, Jenifer M Brown, Brittany Weber, Mark Lemley, Valerie Builoff, Aakash Shanbhag, Zhou Lan, Christopher Buckley, Mouaz H Al-Mallah, Sharmila Dorbala, Ron Blankstein, Piotr Slomka, Marcelo F Di Carli","doi":"10.1101/2025.06.11.25329454","DOIUrl":"https://doi.org/10.1101/2025.06.11.25329454","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Absolute quantification of myocardial blood flow (MBF) on PET perfusion imaging improves the identification of coronary artery disease (CAD). However, distinguishing MBF impairment due to obstructive CAD from nonobstructive CAD remains challenging. We aimed to evaluate the incremental diagnostic value of PET-derived relative flow reserve (RFR) in the diagnosis of obstructive CAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This is a post hoc analysis of the multicenter phase-III trial of &lt;sup&gt;18&lt;/sup&gt; F-flurpiridaz PET ( NCT01347710 ). Patients with available MBF quantification were included. Reduced stress MBF (sMBF) was defined as sMBF below the median (2.2 mL/min/g). Obstructive CAD on quantitative invasive coronary angiography (ICA) was defined as &gt; 70% stenosis. RFR was calculated as a ratio of the minimal segment sMBF over the highest reference vascular territory sMBF. RFR performance for predicting obstructive CAD was evaluated through Receiver Operating Characteristic (ROC) analysis and the net reclassification index (NRI) of multivariable regression models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study included 231 patients (71% male; 56% with established CAD) drawn from the original cohort of 755 trial participants. No patients had three-vessel CAD. In a per vessel-based analysis, 82% of vessels with reduced sMBF had no obstructive CAD on ICA. RFR was significantly lower for vessels with obstructive CAD (0.55 vs 0.80, p&lt;0.0001). In vessels with reduced sMBF, RFR was independently associated with obstructive CAD even after accounting for sTPD and MFR (OR 3.08, 95% CI: 1.49-6.38; p = 0.002). While the addition of RFR did not significantly improve discrimination (AUC 0.806 vs. 0.822, p = 0.11), it significantly improved reclassification of vessels with and without obstructive CAD (NRI: 0.93, p &lt; 0.0001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;RFR provides complementary diagnostic information beyond existing PET parameters and may help refine the diagnosis of obstructive CAD in patients with reduced flows.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical perspective: &lt;/strong&gt;A major diagnostic dilemma in cardiac PET/CT perfusion imaging is determining whether reductions in stress myocardial blood flow and/or myocardial flow reserve are caused by obstructive or nonobstructive coronary artery disease (CAD), leading to uncertainty about whether invasive angiography is needed. Our study demonstrates that incorporating PET-derived relative flow reserve (RFR) adds meaningful diagnostic information beyond existing PET perfusion and flow parameters. RFR does not substantially increase overall discrimination between obstructive and nonobstructive CAD, but it significantly improves reclassification of individual cases, indicating that RFR can help refine decision-making, particularly in borderline cases. These data suggest that selective integration of RFR with existing PET metrics could improve patient selection for invasive procedures and guide more targeted m","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532351","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":"Chest binding practices and health impacts for transmasculine individuals: A mixed methods analysis.","authors":"Theo G Beltran, Ashleigh J Rich, Mannat Malik, Erin Cooney, Jean-Michel Brevelle, Katherine Croft, Rachel Bluebond-Langner, Zach Reilly, Tonia Poteat","doi":"10.1101/2025.06.14.25327031","DOIUrl":"https://doi.org/10.1101/2025.06.14.25327031","url":null,"abstract":"<p><strong>Background: </strong>There is a large knowledge gap among health care providers regarding the importance of chest-binding among transmasculine people. With increased passage of anti-transgender laws denying rights and health care services for transgender youth, it is more important than ever to document their experiences within healthcare settings.</p><p><strong>Methods: </strong>This mixed methods study integrated quantitative and qualitative data. Participants were transmasculine individuals who completed surveys (N=44) or in-depth interviews (N=21) in Baltimore or Towson metropolitan areas in 2016.</p><p><strong>Results: </strong>The majority of transmasculine survey participants bound in their lifetime (n=36, 82%). Among them, 43% (n=19) reported binding seven days per week and 52% (n=23) bound eight or more hours per day on average. Of survey participants, 39% felt healthcare providers were not comfortable with transgender people. Interview themes included physical health challenges of binding, provider de-prioritization of binding, gender affirmation as a facilitator of safety, need for safer binding education, and binding as mental health promotion.</p><p><strong>Conclusion: </strong>Binding is an important part of gender affirmation for many transmasculine people, with social, safety and mental health benefits. However, many transmasculine people report barriers to social and healthcare provider support around binding. Healthcare providers should understand the benefits of binding and be prepared to discuss safer binding practices with transmasculine patients.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532270","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":"Healthcare utilization and cost of care for a multidisciplinary integrated practice unit model of spine rehabilitation compared to standard or no physical therapy.","authors":"Bahar Shahidi, Connor Richards, Lissa Taitano, Armin Zavareh, Kamshad Raiszadeh","doi":"10.1101/2025.06.10.25327236","DOIUrl":"https://doi.org/10.1101/2025.06.10.25327236","url":null,"abstract":"<p><strong>Objective: </strong>To compare healthcare utilization and cost in individuals with spine pain who undergo no physical therapy, standard physical therapy, or physical therapy in an integrated practice unit model.</p><p><strong>Design: </strong>A cost-effectiveness analysis.</p><p><strong>Setting: </strong>Multi-site outpatient physical therapy clinics within a single metropolitan region.</p><p><strong>Participants: </strong>Individuals with de-identified claims data from a single insurance provider under Medicare Advantage with a spine-pain related diagnosis from January 2019-December 2021.</p><p><strong>Interventions: </strong>Patients were categorized into three cohorts: No physical therapy (NoPT), standard physical therapy (SPT), and physical therapy within an integrated practice unit model (IPUPT) based on their physical therapy history during the data collection period.</p><p><strong>Main outcome measures: </strong>Number and percentage of patients reporting claims, number of claims/patient per year, paid amount, and number of RVUs were compared across groups using chi-square or one-way ANOVA with multiple comparisons corrections.</p><p><strong>Results: </strong>Data from 13,569 patients was included in this study. The number of patients with spine-related inpatient claims was highest in the SPT group (2.8%) compared to the IPUPT (1.5%) and NoPT (1.3%) groups (p=0.004). Outpatient care utilization was driven by radiology (54.7%) and laboratory (22.1%) claims and was lowest in the IPUPT group (N=1,096; 56.8%) compared to the SPT group (N=1,654; 68.3%) and NoPT group (N=9,150; 99.3%, p<0.001). The SPT group was most costly per person ($2,243.66(11,048.94)) followed by the NoPT ($1,352.01(6,419.2), p<0.001) and the IPUPT ($1,259.88(9,061.23), p<0.001) groups. The greatest contributor to cost was outpatient procedures, averaging $142.39(1,046.26) per person.</p><p><strong>Conclusion: </strong>An integrated multidisciplinary rehabilitation model may be a cost-effective method of multimodal care in individuals with spine pain.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532275","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":"Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.","authors":"Joel Sanchez Mendez, Bryan Queme, Yubo Fu, John Morrison, Juan P Lewinger, Eric Kawaguchi, Huaiyu Mi, Mireia Obón-Santacana, Ferran Moratalla-Navarro, Vicente Martín, Victor Moreno, Yi Lin, Stephanie A Bien, Conghui Qu, Yu-Ru Su, Emily White, Tabitha A Harrison, Jeroen R Huyghe, Catherine M Tangen, Polly A Newcomb, Amanda I Phipps, Claire E Thomas, David V Conti, Jun Wang, Elizabeth A Platz, Temitope O Keku, Christina C Newton, Caroline Y Um, Anshul Kundaje, Anna Shcherbina, Neil Murphy, Marc J Gunter, Niki Dimou, Nikos Papadimitriou, Stéphane Bézieau, Franzel Jb van Duijnhoven, Satu Männistö, Gad Rennert, Alicja Wolk, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Yu Tian, Loïc Le Marchand, Michelle Cotterchio, Konstantinos K Tsilidis, D Timothy Bishop, Yohannes Adama Melaku, Brigid M Lynch, Daniel D Buchanan, Cornelia M Ulrich, Jennifer Ose, Anita R Peoples, Andrew J Pellatt, Li Li, Matthew Am Devall, Peter T Campbell, Demetrius Albanes, Stephanie J Weinstein, Sonja I Berndt, Stephen B Gruber, Edward Ruiz-Narvaez, Mingyang Song, Amit D Joshi, David A Drew, Jessica L Petrick, Andrew T Chan, Marios Giannakis, Li Hsu, Ulrike Peters, W James Gauderman, Mariana C Stern","doi":"10.1101/2025.06.13.25329599","DOIUrl":"10.1101/2025.06.13.25329599","url":null,"abstract":"<p><strong>Background: </strong>High intake of red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported 204 variants (G) associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways and constructed pathway-based Polygenic Risk Scores (pPRS) to model pPRS x environment (E) interactions.</p><p><strong>Methods: </strong>A pooled sample of 30,812 cases and 40,504 CRC controls of European ancestry from 27 studies were analyzed. Quantiles for red and processed meat intake were constructed. The 204 GWAS variants were annotated to genes with AnnoQ and assessed for overrepresentation in PANTHER-reported pathways. pPRS's were constructed from significantly overrepresented pathways. Covariate-adjusted logistic regression models evaluated pPRSxE interactions with red or processed meat intake in relation to CRC risk.</p><p><strong>Results: </strong>A total of 30 variants were overrepresented in four pathways: Alzheimer disease-presenilin, Cadherin/WNT-signaling, Gonadotropin-releasing hormone receptor, and TGF-β signaling. We found a significant interaction between TGF-β-pPRS and red meat intake (p = 0.003). When variants in the TGF-β pathway were assessed, significant interactions with red meat for rs2337113 (intron <i>SMAD7</i> gene, Chr18), and rs2208603 (intergenic region <i>BMP5</i>, Chr6) (p = 0.013 & 0.011, respectively) were observed. We did not find evidence of pPRS x red meat interactions for other pathways or with processed meat.</p><p><strong>Conclusions: </strong>This pathway-based interaction analysis revealed a significant interaction between variants in the TGF-β pathway and red meat consumption that impacts CRC risk.</p><p><strong>Impact: </strong>These findings shed light into the possible mechanistic link between CRC risk and red meat consumption.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500051","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":"Differential DNA Methylation of the Brain-Derived Neurotrophic Factor Gene is Observed after Pediatric Traumatic Brain Injury Compared to Orthopedic Injury.","authors":"Lacey W Heinsberg, Aboli Kesbhat, Bailey Petersen, Lauren Kaseman, Zachary Stec, Nivinthiga Anton, Patrick M Kochanek, Keith Owen Yeates, Daniel E Weeks, Yvette P Conley, Amery Treble-Barna","doi":"10.1101/2025.06.16.25329571","DOIUrl":"https://doi.org/10.1101/2025.06.16.25329571","url":null,"abstract":"<p><strong>Importance: </strong>Pediatric traumatic brain injury (TBI) triggers biological changes that may differ from those observed in non-brain injuries. <i>BDNF</i> DNA methylation (DNAm) may serve as a novel, dynamic biomarker of the brain's response and help identify TBI-specific epigenetic patterns relevant to later recovery.</p><p><strong>Objective: </strong>To determine whether <i>BDNF</i> DNAm differed between children with TBI and those with orthopedic injury (OI, comparison group) acutely and over time.</p><p><strong>Design: </strong>The Epigenetic Effects on TBI Recovery (EETR) study is a prospective, longitudinal, cohort study with phenotype data and peripheral blood collection at approximately 24 hours, 6 months, and 12 months post-injury.</p><p><strong>Setting: </strong>Single-site study conducted at UPMC Children's Hospital of Pittsburgh.</p><p><strong>Participants: </strong>Consecutive sampling of children aged 3-18 years hospitalized for a minimum of overnight for complicated mild to severe non-penetrating TBI (n=189) or OI without evidence of head trauma (n=105). Participants were excluded for pre-existing neurological or psychiatric conditions, sensory or motor impairments precluding study participation, and prior hospitalization for TBI.</p><p><strong>Exposure: </strong>The primary exposure was injury type (TBI vs. OI), with severity examined as a secondary exposure within the TBI group.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was <i>BDNF</i> DNAm measured via pyrosequencing at seven sites (five retained for analysis) acutely (mean=31.6 hours post-injury) and 6 (mean=216.9 days) and 12 months (mean=405.9 days post-injury). Primary covariates included age, sex, and race; secondary covariates included age-adjusted body mass index, non-head injury severity score, pubertal status, socioeconomic status, and psychosocial adversity. Outcomes, covariates, and hypotheses were prespecified.</p><p><strong>Results: </strong>Participants were 66.3% male, 82.3% White, and had a mean age of 11.7 (±4.2) years. Acutely, children with TBI showed significantly lower DNAm at three of five sites (1.8%-8.7% lower; p=0.0042 to 5.76E-06). One site remained significantly lower at 12 months (p=0.0038); no significant differences were observed at 6 months. TBI severity (measured via Glasgow Coma Scale) was not associated with DNAm at any time point.</p><p><strong>Conclusions and relevance: </strong><i>BDNF</i> DNAm appears to differ in children with TBI vs OI, particularly in the acute period. <i>BDNF</i> DNAm differences may reflect early biological responses that are specific to TBI.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532255","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":"Project CLEAR (ChemicaL Exposure and Awareness Research): A protocol for assessing the availability and chemical composition of skin-lightening products in Northern Manhattan.","authors":"Adana A M Llanos, Alexis A Schaefer, Andrew Turner, Jaia Wingard, Nia Jenkins, Mila Cordero, Jasmine McDonald, Ami R Zota, Randolph R Singh, Jessica Contreras, Dustin T Duncan","doi":"10.1101/2025.06.13.25329600","DOIUrl":"10.1101/2025.06.13.25329600","url":null,"abstract":"<p><strong>Introduction: </strong>Skin lightening products (SLPs) are widely used in communities of color and often contain toxic chemicals such as mercury and hydroquinone, posing serious health risks. Despite regulations, these products remain accessible through illegal sales and deceptive labeling. Targeted marketing in marginalized areas raises environmental justice and public health equity concerns.</p><p><strong>Objectives: </strong>This study employs a novel spatial sampling approach to audit retail stores in Northern Manhattan, assessing the availability of SLPs in relation to neighborhood context. Products will be screened for harmful substances-including per- and polyfluoroalkyl substances (PFAS), parabens, and heavy metals-with results compared to ingredient labels.</p><p><strong>Methods: </strong>Conducted in Northern Manhattan, New York City, this study focuses on neighborhoods with high proportions of Black and Latinx residents. Phase 1 involves a structured audit of 50 retail stores, including beauty supply shops and ethno-cultural retailers. Store selection is guided by spatial sampling and demographic data. Trained research assistants collect detailed information on store environments and individual SLPs. In Phase 2, 20 products will be purchased for laboratory analysis using advanced targeted and non-targeted methods. Analyses will include descriptive statistics, GIS mapping, and comparisons across neighborhoods.</p><p><strong>Results: </strong>We expect beauty supply stores to carry a greater variety and volume of SLPs than ethno-cultural retailers, such as African markets, which are anticipated to sell mostly imported products. Chemical testing is expected to show that a substantial portion of SLPs contain hazardous chemicals, including some not disclosed on product labels.</p><p><strong>Conclusions: </strong>Project CLEAR combines spatial methods and laboratory science to map SLP availability and assess chemical risks in Northern Manhattan. By linking store-level data with neighborhood demographics, the study highlights structural inequities and environmental racism. Findings will support future research, inform policy and regulatory efforts, and strengthen community advocacy for safer, transparent skincare products.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532322","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}