Research square最新文献

{"title":"HPV co-infection burden, vaginal microbiota restructuring, and host context are associated with Cervical precancer risk in a racially restricted observational cohort.","authors":"Katherine Y Tossas, Bin Zhu, Katarzyna M Tyc, Ciara Rhodes, Jerome F Strauss, Myrna G Serrano, Gregory A Buck","doi":"10.21203/rs.3.rs-11028378/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11028378/v1","url":null,"abstract":"<p><p>Background High-risk human papillomavirus (HPV) infection is necessary for cervical carcinogenesis, but HPV detection alone does not distinguish transient infection from lesions at greatest risk of progression. We evaluated whether HPV burden, vaginal microbiota structure, and host-context variables jointly characterize cervical intraepithelial neoplasia grade 3 (CIN3) in a Black/African American and White analytic cohort from the Vaginal Microbiome Health Project (VaMHP), integrating L1-based HPV typing, 16S rRNA vaginal microbiota profiling, and linked clinical metadata. Results Among 1181 participants, 75 had CIN3. CIN3 was associated with HPV positivity (55/75, 73.3% vs 431/1106, 39.0%; odds ratio [OR] 4.31, 95% CI 2.55-7.29; Fisher exact p = 7.9 x 10^-9) and with multiple HPV infection among HPV-positive participants (35/55, 63.6% vs 176/431, 40.8%; OR 2.54, 95% CI 1.42-4.54; p = 0.0022). HPV communities in CIN3-positive samples showed higher Shannon diversity, greater observed strain richness, higher evenness, and significant beta-diversity separation. In vaginal microbiota analyses, alpha diversity did not differ by CIN3 status, but community composition did, and Lactobacillus crispatus was the only taxon depleted in CIN3 after multiple-testing correction. Race, age, and metronidazole exposure were central nodes in the host-factor network. In predictive modeling, a full integrated model combining metadata, HPV, and vaginal microbiota features (auROC = 0.745) outperformed both HPV + vaginal microbiota (auROC = 0.670) and HPV-only (auROC = 0.440) models. Conclusions CIN3 in this cohort was associated with coordinated shifts in virologic burden, vaginal community structure, and host social-clinical context. The results support a structure-function interpretation in which loss of Lactobacillus crispatus-dominant states and enrichment of dysbiosis-associated communities define a host-microbiome context that is more permissive to HPV persistence and precancer. These findings move beyond descriptive omics by showing that microbiome and host-context features add nonredundant discriminatory signal beyond HPV-only models.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280215","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":"Diversity, Distribution, and Plasmodium falciparum Sporozoite Infectivity of Anopheles Mosquitoes in Flood-Prone Communities of Kasese District, Western Uganda: A Cross- Sectional Household Entomological Study.","authors":"Rogers Kalyetsi, Kaylin Lewandowski, Ronnie Ndizeye, Raquel Reyes, Mbusa Rapheal, Abel Bwambale, Emmanuel Baguma, Liao Huipeng, Dana A Giandomenico, Bonnie E Shook-Sa, Moses Ntaro, Peter Chris Kawungezi, Hope Mudondo, Charles Nkubi Bagenda, Paul E Alele, Jerome Kabakyenga, Gertrude N Kiwanuka, Edgar M Mulogo, Ross M Boyce, Michael H Reiskind","doi":"10.21203/rs.3.rs-11062919/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11062919/v1","url":null,"abstract":"<p><p>Background Malaria poses an ongoing public health challenge for children in Uganda, especially in climate-vulnerable, flood-prone communities. Understanding malaria vector species diversity and transmission measures is vital to guide vector control in these unique environments. We sought to determine the vector species diversity, distribution, and <i>Plasmodium falciparum</i> sporozoite infectivity in flood-prone villages in the Kasese district, Uganda. Methods We conducted a cross-sectional study in which we collected adult mosquitoes indoors and outdoors from 154 consented sentinel households using unbaited CDC light traps. Mosquitoes were identified morphologically to genus and species. Adult female <i>Anopheles</i> spp. were tested for <i>P</i> . <i>falciparum</i> circumsporozoite antigen by ELISA. We estimated associations between entomological outcomes and covariates of interest, including place of residence, net ownership, household location and construction materials, and reported history of floods in the previous year. Results Between 19th February and 22nd May 2025, a total of 1,772 mosquitoes were collected in 136/154 (88.3%) households. Adult <i>Anopheles</i> mosquitoes were collected in 54/154 households (prevalence 35.1% (95% CI: 27.9-43.0)). The highest presence of <i>Anopheles</i> mosquitoes was in Karusandara (58%), and the lowest in the more urban municipality area (22%). We documented diversity in known malaria vectors, with <i>Anopheles gambiae s.l.</i> (73.7%), and <i>An. funestus</i> (9.4%) being most common, but also <i>An. pretoriensis, An. rivulorum, An. mouchetti, An. nili, and An. marshalli</i> were identified. <i>Plasmodium falciparum</i> circumsporozoite antigen was detected from three female <i>An. funestus</i> demonstrating a mosquito sporozoite infectivity rate of 1.49% (03/202) (95% CI: 0.48-4.53), and a household positivity rate of 1.95% (3/154) (95% CI: 0.62-5.91) across the study area. Conclusion The varied species diversity may sustain malaria transmission in this region of rapidly changing ecological conditions as a result of flooding. The sporozoite infectivity and household positivity emphasize ongoing transmission of malaria, albeit at a low levels, even during an atypically dry period. There is a need to strengthen implementation of targeted vector control interventions with a focus on flood-prone and low-altitude communities within Kasese District, western Uganda.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280070","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":"Trust, place, and polysubstance use shape the feasibility of community-based drug checking in the Southern United States: A mixed-methods implementation study.","authors":"Sarah Febres-Cordero, Roesheen McGilvery, Daniel J Smith, Lydia Vlachou, Abigail Gale Pires, Fawaz Shanun, Nadiah Cunningham, Hannah L Nelson, Mojgan Zare, Lisa M Thompson, Athena D F Sherman, Beatrice King","doi":"10.21203/rs.3.rs-10359475/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10359475/v1","url":null,"abstract":"<p><p>Background The unregulated drug supply in the United States (US) is increasingly volatile, with rising contamination by fentanyl and xylazine, contributing to overdose and drug-related morbidity and mortality. Drug checking is a promising harm reduction strategy; yet, little is known about how social trust, place, and patterns of polysubstance use influence the feasibility and implementation of community-based drug checking in the Southern US, where punitive drug policies and institutional mistrust remain prominent. Methods We conducted a multiphase, sequential, exploratory, and explanatory mixed-methods, community-engaged implementation study in Fulton County, Georgia. The theoretical framework COM-B (Capability, Opportunity, Motivation-Behavior) was used to examine individual- and community-level determinants of engagement among people who use drugs. Quantitative surveys were administered to people who use drugs (PWUD; N = 164), recruited from syringe services programs, nightlife settings, festivals, and informal housing environments, to assess drug use contexts, drug-checking behaviors, and trust in drug sources, and a subset of participants completed semi-structured qualitative interviews (n = 16). Survey findings were analyzed descriptively and used iteratively to inform qualitative data collection. Qualitative data were analyzed using rapid thematic analysis and integrated across frameworks. Results Nearly two-thirds of PWUD in the quantitative sample (62%) reported never testing their drugs despite high awareness of overdose risk. Trust in known drug sources was a central theme reducing the perceived need for testing, while distrust of law enforcement and institutions constrained engagement with formal drug-checking services. Polysubstance use was widespread and intentional, complicating the perceived utility of single-analyte testing tools. Conclusions This study demonstrates that while community drug checking is urgently needed in Fulton County, its successful implementation is constrained by stigma, trust in source, and limited drug education. Legal reforms and expanded access to testing tools alone are insufficient to ensure uptake of drug checking.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280304","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":"α-Synuclein Seeding Activity in Fixed Antemortem Skin Biopsies From Patients With Synucleinopathies.","authors":"Zerui Wang, Maria Gerasimenko, Tricia Gilliland, Bailey Bellaire, Todd Levine, Christopher Gibbons","doi":"10.21203/rs.3.rs-10953905/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10953905/v1","url":null,"abstract":"<p><p>α-Synuclein seed amplification assays can detect seed-competent pathological α-synuclein in fresh and frozen biospecimens, but their performance in fixed antemortem skin biopsies is less well defined. We applied an optimized real-time quaking-induced conversion assay to paraformaldehyde-fixed skin biopsy sections from participants with Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and controls. Fixed tissue retained measurable α-synuclein seeding activity, although amplification was delayed and the apparent 50% seeding dose was lower than in unfixed or autopsy skin. In this selected proof-of-concept cohort, SAA positivity was observed in 70% of PD, 80% of DLB, 80% of MSA, and 20% of control samples; exploratory ROC analysis yielded an AUC of 0.86. Seeding readouts correlated with Hoehn and Yahr stage but not significantly with MoCA score or pS129 α-synuclein burden. Fixed skin biopsies can therefore provide complementary morphological and functional measures of peripheral α-synuclein pathology.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280255","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":"Depressive and PTSD symptoms are associated with regional differences in light-evoked brain responses in chronic ocular pain.","authors":"Eric Moulton, Ema Karakoleva, David Valdes-Arias, Pradip Pattany, Vanda Faria, Elizabeth Helix, Anat Galor","doi":"10.21203/rs.3.rs-11053966/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11053966/v1","url":null,"abstract":"<p><strong>Background/objectives: </strong>Chronic ocular pain (COP) often co-occurs with depression or post-traumatic stress disorder (PTSD), but whether these comorbidities confer a distinct biological signature is unknown. Thus, we compared light-evoked blood oxygen level-dependent (BOLD) responses in individuals with COP, stratified by the presence or absence of clinically relevant depressive and/or PTSD symptoms.</p><p><strong>Subjects/methods: </strong>43 individuals with COP (pain intensity ≥ 1/10 for ≥ 3 months) underwent event-related functional magnetic resonance imaging using bright-light. Thirty participants were classified as COP with mental health comorbidity (COP + MHC+) based on a Patient Health Questionnaire-9 (PHQ-9) score ≥ 5 and/or a PTSD Checklist-Military Version (PCL-M) ≥ 33; 13 were classified as COP without MHC (COP + MHC-). BOLD responses exceeding an exploratory voxelwise threshold of Z > 2.3 were compared within predefined bilateral regions of interest (ROIs) comprising the anterior cingulate cortex (ACC), anterior mid-cingulate cortex (aMCC), anterior insula, and amygdala. Regional parameter estimates were correlated with clinical symptoms. Result Demographics were similar between groups. Participants with COP + MHC+ reported greater dry-eye symptom burden and non-ocular pain, whereas measured ocular surface signs and in-scanner eye-pain and unpleasantness ratings did not differ significantly between groups. In exploratory ROI analyses, COP + MHC+ participants demonstrated greater light-evoked BOLD responses in the right ACC and caudal right aMCC, whereas COP + MHC- participants demonstrated greater responses in the rostral right aMCC and right anterior insula. Conclusions These findings suggest that depressive and PTSD symptoms may contribute to heterogeneity in central pain processing among individuals with COP. If confirmed, such differences could help refine COP phenotyping and inform more targeted, mechanism-based treatment strategies.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280094","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":"Stage at Presentation and Clinical Characteristics of Breast Cancer Patients at the Butaro Cancer Centre of Excellence, Rwanda: A Retrospective Chart Review.","authors":"Jean Paul Majyambere, Betel Amdeslassie Fenta, Naol Belema Gemechu, Phillip J Hsu, Anteneh Gadisa Belachew, Anne Niyigena, Alexandra Fehr, Alex Y Z Huang, Mulugeta Tenna, Yuval Cohen, Nefti Bempong-Ahun, Wendy Williams, Robert Riviello, Abebe Bekele, Geoff Ibbotson, Barnabas Tobi Alayande","doi":"10.21203/rs.3.rs-11308254/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11308254/v1","url":null,"abstract":"<p><p>Background Breast cancer is the leading cancer among women in sub-Saharan Africa, where late-stage presentation contributes to poor outcomes. Understanding the risk-factor profile, comorbidity burden, and functional status of patients at presentation is essential to guide early-detection and management strategies in resource-limited settings. Methods We conducted a retrospective chart review of patients who underwent surgery for breast cancer at the Butaro Cancer Center of Excellence (BCCOE), Rwanda, between 2018 and 2023. From 422 patients identified, 300 charts were selected through simple random sampling and reviewed using a pretested REDCap tool drawing on electronic and paper-based records. Data was analyzed in IBM SPSS Statistics (version 29), and disease was staged according to the AJCC TNM system. Results The mean age at presentation was 50.8 years (SD = 11.8; range 28-82); 98% of patients were female, 94% had health insurance, and 74% were farmers. At least one risk factor was present in 65% of patients, with alcohol consumption (55.3%) and tobacco smoking (21.7%) the most common modifiable factors, followed by family history (5.3%) and nulliparity (3.7%). Comorbidities were frequent, affecting 60.3% of patients; hypertension (25.7%) and HIV/AIDS (7.0%) predominated. Most patients had good functional status at diagnosis (ECOG 0, 81.5%; ECOG 1, 16.4%). Of 281 staged patients (19 of 300 lacked complete TNM staging data), Stage III (38.4%) and Stage II (37.0%) were most common, and late-stage disease (Stage III-IV) accounted for 47.3% of cases. Conclusion Breast cancer patients at BCCOE are diagnosed at a younger age than the global average and carry a high burden of modifiable risk factors and comorbidities. The substantial proportion presenting at late stage may complicate treatment and compromise survival, emphasizing the need for strengthened awareness and early-detection efforts. By centering on a rural referral hospital, this study adds to the limited literature on breast cancer presentation in Rwanda.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280276","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":"Thrombotic Risk of Targeted Therapies in Breast Cancer: A Real-World Cohort Study.","authors":"Wesley Boland, Gregory Guzik, Eduarda Grinsztejn, Jaime A Perez, Keri Plevniak, Bethany Samuelson Bannow, Lalitha Nayak, James Martin","doi":"10.21203/rs.3.rs-10813538/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10813538/v1","url":null,"abstract":"<p><p>Purpose Targeted therapies for breast cancer, including CDK4/6, PARP, mTOR, and PI3K inhibitors, have raised concerns regarding thrombosis risk, but real-world data comparing these agents remain limited. We investigated thrombosis incidence and risk factors in a large national cohort of breast cancer patients. Methods In this retrospective cohort study using the TriNetX national database, we evaluated the thrombotic risk and associated factors among patients with breast cancer treated with these therapies. The primary outcome was any arterial or venous thrombotic event. Results Among 4,165 patients on targeted therapy, treatment with CDK4/6i was associated with increased risk of any thrombosis (HR 3.36, 95% CI 2.89-3.92) and venous thrombosis (HR 4.45, 95% CI 3.68-5.39). PARPi (HR 3.78, 95% CI 1.82-7.85; venous HR 5.79, 95% CI 2.52-13.3) and everolimus (HR 6.59, 95% CI 3.82-11.4; venous HR 9.67, 95% CI 5.29-17.7) showed similar associations. Within CDK4/6i, palbociclib carried the highest hazard for any thrombosis (HR 3.64, 95% CI 3.02-4.39) and venous thrombosis (HR 5.11, 95% CI 4.05-6.45). Nicotine dependence (HR 2.01, 95% CI 1.91-2.12), brain metastases (HR 4.20, 95% CI 2.98-5.93), and higher BMI (HR 1.03, 95% CI 1.03-1.03) were independent risk factors. Conclusion This real-world analysis demonstrates that CDK4/6i and everolimus were associated with increased risk of both arterial and venous thrombosis, while PARPi was specifically associated with venous thrombosis. Similar risk was seen across CDK4/6 inhibitor agents. These results support risk stratification tools incorporating both agent and patient-level factors to better inform clinical management.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between cross-reactive Plasmodium vivax antibody responses and P. knowlesi parasitaemia and clearance.","authors":"Jeyamalar T Thurai Rathnam, Megha Rajasekhar, Rhea J Longley, Anju Abraham, Timothy William, Sitti Saimah Sakam, Daniel J Cooper, Giri S Rajahram, Bridget E Barber, Nicholas M Anstey, Matthew J Grigg, Julie A Simpson","doi":"10.21203/rs.3.rs-11044112/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11044112/v1","url":null,"abstract":"<p><p>Background Pre-existing antibodies to <i>Plasmodium vivax</i> may cross-react with <i>P. knowlesi</i> and influence infection outcomes. We investigated whether baseline <i>P. vivax</i> antibody levels affect parasitaemia and clearance in knowlesi malaria. Methods Total IgG to 21 <i>P. vivax</i> antigens was quantified in pre-treatment plasma from patients in three Malaysian clinical trials. Parasitaemia was assessed 6-hourly by microscopy and clearance half-life estimated. Antibody associations with <i>P. knowlesi</i> baseline parasitaemia and clearance were identified using regression and machine learning approaches (elastic net regression and random forests). Results Data were available for 134 patients (median age 37 years, 37% with prior malaria). Five antibodies were associated with reduced baseline <i>P. knowlesi</i> parasitaemia (0.75-0.90-fold lower per two-fold increase, 95% CIs ranging from 0.65-1.00). Median <i>P. knowlesi</i> parasite clearance half-life was 2.6 hours (IQR 2.1-3.2). Two antibodies were associated with slightly slower parasite clearance (1.04-fold increases in mean clearance half-life per two-fold antibody level). Within-group correlation analyses revealed widespread, positive antibody associations in <i>P. knowlesi</i> infections, with weaker but coordinated (RBP and DBP family) responses in malaria-negative endemic controls. Conclusions Cross-reactive <i>P. vivax</i> antibodies may partially constrain <i>P. knowlesi</i> parasitaemia, but functional studies are needed to clarify their role in immunity and zoonotic transmission.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280336","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":"Social well-being is associated with slower multisystem aging estimated from a single brain MRI scan: prospective evidence from MIDUS.","authors":"Minwoo Lee, Sara M Garza-Gonzalez, Stacey M Schaefer, Kyle Bourassa, Casey K Brown","doi":"10.21203/rs.3.rs-11292832/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11292832/v1","url":null,"abstract":"<p><p>Subjective well-being is increasingly recognized as critical for health across the adult lifespan. Yet, it is unclear whether separable dimensions of well-being are differentially associated with biological aging. Using data from the Midlife in the United States (MIDUS) study ( <i>N</i>  = 213; age = 56.2 ± 13.6), we modeled the multifaceted structure of subjective well-being (i.e., private/eudaimonic, social, and hedonic well-being) and examined its prospective association with DunedinPACNI, a novel brain MRI-derived biomarker trained to estimate the pace of biological aging. We found that the social dimension of well-being was consistently associated with a slower pace of aging after sequentially controlling for demographic, health, lifestyle, and social covariates. Associations with private/eudaimonic well-being and hedonic well-being were rendered non-significant once health and lifestyle factors were accounted for. Data-driven variable selection further identified social well-being as the most stable predictor of DunedinPACNI among the well-being dimensions. Lastly, using community volunteering as an illustrative example of a modifiable, health-promoting behavior, we found an indirect association with a slower pace of aging via social well-being that was not detected when well-being was modeled as a broader construct. These findings suggest that a fine-grained characterization of subjective well-being may yield novel insights into the psychosocial mechanisms supporting healthy aging. They also provide the first evidence that psychosocial correlates of the pace of aging can be detected from a single structural MRI scan, which may extend the evidence base for aging research to cohorts that lack biospecimens.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280244","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":"Novel Screening Methods for Binary Outcomes with Rare Events.","authors":"Mohammad Nahian Ferdous Abrar, Hongmei Zhang, Meredith Ray, Yuanjin Liu, Hasan Arshad, Yu Jiang","doi":"10.21203/rs.3.rs-10925760/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10925760/v1","url":null,"abstract":"<p><strong>Background: </strong>Epigenome-wide association studies often involve high-dimensional DNA methylation data. Efficient methods are needed to screen CpG sites associated with binary outcomes, particularly when the event rate is below 5%. Existing screening methods, such as ttScreening, are effective for filtering out unimportant variables, such as CpG sites, in epigenome-wide studies when event rates are moderate. However, ttScreening and many other screening approaches face challenges in handling rare events. Therefore, we proposed two novel methods, Rare-Screening and Firth-ttScreening , designed specifically for binary outcomes with rare events.</p><p><strong>Results: </strong>We evaluated the performance of the proposed approaches and benchmark methods, including FDR-based and Bonferroni approaches for multiple testing correction, through extensive simulations across varying sample sizes and numbers of independent variables.</p><p><strong>Conclusions: </strong>The Rare-Screening and Firth-ttScreening methods outperformed FDR and Bonferroni methods with higher sensitivities. The proposed functions have been incorporated into the ttScreening R package, which is available through the Comprehensive R Archive Network (CRAN).</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280234","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}