Research square最新文献

{"title":"Machine-learning classification of documented pedophilic sexual interest from eye-tracking patterns.","authors":"David Popovic, Kirsten Jordan, Peter Fromberger, Isabel Müller, Clara Weyer, Clara Vetter, Peter Falkai, Nikolaos Koutsouleris, Norbert Nedopil, Kolja Schiltz, Jürgen Leo Müller","doi":"10.21203/rs.3.rs-11114979/v1","DOIUrl":"10.21203/rs.3.rs-11114979/v1","url":null,"abstract":"<p><p>Assessment of pedophilic sexual interest is often embedded in crucial clinical and forensic contexts and could therefore benefit from non-invasive measures that complement clinical interviews and self-report. We investigated whether multivariate eye-tracking and behavioral patterns could classify documented pedophilic sexual interest at the individual level. The discovery sample comprised 124 adult men from five German sites, including 34 with and 90 without a documented pedophilia diagnosis according to ICD-10. Participants completed the Initial Orientation Task (IOT), Sexual Distractor Task (SDT), and Sexual Stimulus Rating task. Linear support vector machines were trained within a repeated nested cross-validation framework to predict pedophilia strictly on these eye-tracking features. The best-performing main model combined IOT and SDT, achieving 88.01% balanced accuracy, 88.24% sensitivity, 87.78% specificity, and an area under the curve of 0.93 (95% confidence interval, 0.87-0.99). Exploratory sparse modeling using only five IOT and four SDT features still yielded 87.65% balanced accuracy. This sparse model further classified all 32 participants in an independent healthy-control cohort as negative (100% specificity). Predictive features reflected relative attention to child versus adult stimuli and allocation of attention between distractors and cognitive targets. These findings support further investigation of eye-tracking measures as potential adjuncts to clinical assessment, in potentially high-stakes clinical and forensic decision-making. Prospective validation in representative cohorts containing both positive and negative cases is required to further establish generalizability and clinical utility.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171952","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":"How does machine learning bias in prediction of behavioral phenotypes relate to individual characteristics?","authors":"Jianxiao Wu, Jingwei Li, Simon Eickhoff, B T Yeo, Sarah Genon","doi":"10.21203/rs.3.rs-10604176/v1","DOIUrl":"10.21203/rs.3.rs-10604176/v1","url":null,"abstract":"<p><p>Brain-based prediction of behavioral phenotypes is promising for precision medicine. However, predictive models in the field have commonly shown limited accuracy and individual bias. For instance, participants of ethnic/racial minority (e.g., African Americans) are more likely to be misclassified or show larger prediction errors, compared to white American participants. Addressing these limitations requires a better understanding of the sociodemographic and scan-related factors related to prediction biases. Here, we investigated the association between the prediction errors of brain-based models predicting over 100 behavioral measures and eight variables capturing sociodemographic and scan-related individual characteristics. These associations were examined in two developmental and one young adult cohorts (sample size = 4278, 432, and 784 respectively). We found that socioaffective and mental health phenotypes in developmental cohorts were particularly susceptible to bias associated with individual characteristics. In particular, head motion, head morphology, and sex/gender are consistently related to the machine learning biases in multiple behavioral measures. Our work highlights the multifactorial nature of the prediction errors generated by the brain-based predictive models. Overall, our results call for greater attention to model bias in developmental populations, particularly in the context of AI-based approaches for psychiatric risk prediction and early diagnosis.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170170","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":"CDKPredict: a clinicogenomic model for risk-adapted therapeutic intervention in breast cancer.","authors":"Luca Boscolo-Bielo, Francisco Sanchez-Vega, Subhiksha Nandakumar, Antonio Marra, Enrico Moiso, Emanuela Ferraro, Ino de Bruijn, Luc Cabel, Karl Pichotta, Bianca Malagutti, Anton Safonov, Michele Waters, Julia Ah-Reum An, Mark Donoghue, Yixiao Gong, Matthew Zatzman, Maureen Carey, Sameet Sreenivasan, Gráinne Long, Sajan Khosla, Ingrid Mayer, Maurizio Scaltriti, Nicola Fusco, Elisabetta Munzone, Fresia Pareja, Dara S Ross, Walid K Chatila, Michael F Berger, David B Solit, Shanu Modi, Nikolaus Schultz, Giuseppe Curigliano, Mark E Robson, Sohrab Shah, Sarat Chandarlapaty, Pedram Razavi","doi":"10.21203/rs.3.rs-10176871/v1","DOIUrl":"10.21203/rs.3.rs-10176871/v1","url":null,"abstract":"<p><p>Wide variation in outcomes is observed for patients with hormone-receptor-positive metastatic breast cancer (MBC) receiving first-line CDK4/6 inhibitors plus endocrine therapy (CDK4/6i+ET). Although front-line escalation strategies are beginning to enter clinical practice, assigning patients to intensified or de-intensified approaches remains challenging due to several mechanisms of resistance spanning tumor-intrinsic and host factors. To address this, we developed CDKPredict, an interpretable machine-learning model integrating baseline clinicopathologic and genomic features to predict outcomes from first-line CDK4/6i+ET. The model was trained on a densely annotated cohort of 1,264 patients and validated in a large multi-institutional external cohort (n=564, time-dependent AUC=0.74), stratifying patients into low-, intermediate-, and high-risk groups (median progression-free survival: 29.8, 14.7, and 8.0 months, respectively; hazard ratio [high vs low]=3.85, <i>P</i>=1.5×10^-17). The model retained robust prognostication across clinically relevant subgroups and biomarker-selected populations and outperformed the current escalation criterion of treatment-free interval ≤12 months. Notably, CDKPredict demonstrated strong clinical and biological plausibility, with high-risk tumors featuring genomic and transcriptomic programs mechanistically linked to CDK4/6i+ET resistance, and higher-risk strata progressively enriched for actionable alterations. Finally, we developed CDKPredict-S, a pragmatic and scalable model requiring a restricted number of features intended for resource-variable settings, which was validated across two independent external cohorts totaling 1,019 patients and made publicly available. Collectively, CDKPredict provides a foundation for the prospective evaluation of risk-adapted, biomarker-informed therapeutic strategies.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171150","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":"All Roads Lead to Rome: Resting-State Criticality as a Neurophysiological Marker of Brain-Computer Interface (BCI) Performance in People with Amyotrophic Lateral Sclerosis (ALS) and Healthy Participants.","authors":"Tomko Settgast, Oren Shriki, Georg Northoff, Federico Zilio, Seyyed Bahram Borgheai, Yalda Shahriari, Andrea Kübler","doi":"10.21203/rs.3.rs-10422321/v1","DOIUrl":"10.21203/rs.3.rs-10422321/v1","url":null,"abstract":"<p><p>This exploratory study investigates the relationship between resting-state brain dynamics (EEG) and subsequent brain-computer interface (BCI) performance in people with amyotrophic lateral sclerosis (ALS) and healthy participants. Grounded in the critical brain hypothesis, we examined whether neurophysiological markers of criticality in resting-state EEG correlate with subsequent BCI performance. We analyzed neuronal avalanche dynamics, multiscale criticality measures, the spectral slope, and Lempel-Ziv complexity across two datasets: a longitudinal single-case study of a person in the locked-in state after a disease history with ALS (Dataset 1) and longitudinal data from 5 people with ALS and single sessions from 6 healthy participants (Dataset 2). Neuronal avalanche dynamics, the spectral slope, and Lempel-Ziv complexity consistently correlated with subsequent BCI performance in people with ALS. Conversely, healthy participants showed inverted correlation patterns for the neuronal avalanche dynamics. While group comparisons were not statistically significant, effect size analyses indicated supercritical brain dynamics in people with ALS. We integrate these findings into the B-ARC (BCI-Aptitude through Resting-State Criticality) framework proposing an inverted U-shaped relationship between the proximity of resting-state brain activity to criticality and BCI control. In this framework, healthy participants approach the critical optimum from a subcritical regime, while people with ALS appear to approach it from a putatively supercritical regime characterized by cortical hyperexcitability. These findings and the proposed framework provide potential resting-state predictors of BCI aptitude in people with ALS and may inform the detection of so-called <i>Windows of Consciousness</i>.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171084","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 <i>FMR1</i> mRNA levels and clinical phenotypes in Fragile X syndrome.","authors":"Braeden S Heald, Walker S McKinney, Lauren Schmitt, Kelli C Dominick, Richard K Lacher, Sebastian Piloto, Christina Gross, Craig A Erickson","doi":"10.21203/rs.3.rs-11053577/v1","DOIUrl":"10.21203/rs.3.rs-11053577/v1","url":null,"abstract":"<p><strong>Background: </strong>Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the <i>FMR1</i> gene on chromosome X that leads to hypermethylation and reduces or completely silences the expression of <i>FMR1</i> mRNA and its protein product, Fragile X Messenger Ribonucleoprotein (FMRP). Since the clinical manifestations of FXS can be variable, there is interest in identifying molecular markers that reflect phenotypic severity. The extent of CGG repeat expansion and resulting hypermethylation varies substantially between patients, suggesting that <i>FMR1</i> gene silencing differs between individuals with FXS and could contribute to the phenotypic variability. Previous studies have identified <i>FMR1</i> mRNA as a highly reproducible, sensitive and quantitative measure of gene activity. This study builds on these previous studies and assesses the relationship between <i>FMR1</i> mRNA and clinical outcomes in FXS.</p><p><strong>Methods: </strong>We recruited 300 study participants, including males and females across the following diagnostic groups: FXS, fragile X premutation carriers (PMCs), typically developing controls (TDC), and (non-FXS) developmental disability controls (DD). Peripheral blood samples were used for quantifying both <i>FMR1</i> mRNA and FMRP (from a Luminex-based assay). IQ and adaptive behavior were evaluated with the Stanford-Binet 5 and Vineland-3 tests, respectively. Analyses examined group- and sex-level associations between <i>FMR1</i> mRNA and FMRP, IQ, adaptive behavior, and age across diagnostic groups.</p><p><strong>Results: </strong><i>FMR1</i> mRNA was substantially reduced in participants with FXS, particularly males, consistent with expected gene silencing. Within the FXS group, higher <i>FMR1</i> mRNA levels were associated with higher IQ and better adaptive behavior. These associations were not observed in the TDC or DD comparison groups, suggesting that the relationship is specific to FXS pathology rather than developmental impairment more broadly. <i>FMR1</i> mRNA also correlated positively with FMRP in FXS, supporting its validity as a molecular marker. Age-related increases in <i>FMR1</i> mRNA were also observed in females with FXS.</p><p><strong>Conclusions: </strong>Our findings that <i>FMR1</i> mRNA correlates with both FMRP levels and clinical outcomes in participants with FXS support its utility as a clinically meaningful molecular marker of phenotypic severity. As an accessible surrogate of disease severity, <i>FMR1</i> mRNA may help improve prognostic assessment and support more individualized treatment planning in FXS.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171004","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 miR-221-5p/RAD18/RAD51 Axis Regulates DNA Damage Tolerance and Homologous Recombination to Drive Platinum Resistance in Ovarian Cancer.","authors":"Tasmin Rahman Omy, Naresh Sah, Subash Kairamkonda, Chinnadurai Mani, Md Ariful Islam, Mark B Reedy, Kenneth P Nephew, Komaraiah Palle","doi":"10.21203/rs.3.rs-11040918/v1","DOIUrl":"10.21203/rs.3.rs-11040918/v1","url":null,"abstract":"<p><p>Platinum resistance remains a major barrier in epithelial ovarian cancer (EOC) treatment, while upregulation of the DNA damage response (DDR) is a hallmark of chemoresistance, and the underlying epigenetic mechanisms driving this adaptation remain poorly understood. Here, we identify a novel post-transcriptional regulatory axis involving miR-221-5p that governs two critical DDR effectors: RAD18, which mediates DNA damage tolerance through translesion synthesis (TLS), and RAD51, the central recombinase for homologous recombination (HR). Although the miR-221/222 cluster has been traditionally categorized as oncogenic, we demonstrated that the miR-221-5p arm functions as a potent tumor suppressor in EOC. Bioinformatics and luciferase reporter assays confirmed that miR-221-5p directly targets the 3'UTRs of both <i>RAD18</i> and <i>RAD51</i>. In EOC clinical specimens and cell lines, miR-221-5p downregulation inversely correlated with RAD18/RAD51 expression. Functionally, miR-221-5p restoration suppressed platinum-induced PCNA mono-ubiquitination and HR, inducing a \"functional BRCAness\" that sensitized both established and patient-derived primary EOC cells to carboplatin and PARP inhibition. Furthermore, in xenograft models, stable miR-221-5p expression significantly reduced the tumor burden. Collectively, our results reveal a previously unrecognized miR-221-5p/RAD18/RAD51 axis that may contribute to therapeutic responses in EOC and provide a rationale for therapeutic strategies targeting RAD18/RAD51-driven DNA repair pathways.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167955","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":"Boy Bi! The Association Between HIV Knowledge, PrEP Stigma, Bisexual Contact, and Binegativity in a Sample of Undergraduate Students.","authors":"Vincent Dang, Nathan Grant Smith","doi":"10.21203/rs.3.rs-10684472/v1","DOIUrl":"10.21203/rs.3.rs-10684472/v1","url":null,"abstract":"<p><strong>Background: </strong>Binegativity (negative attitudes and beliefs towards bisexual people) towards bisexual men includes inaccurate stereotypes of sexual promiscuity and serving as vectors of HIV to heterosexual women. College students' HIV knowledge has been negatively associated with homonegative attitudes towards gay men; however, limited studies have explored the link between HIV knowledge and binegativity towards bisexual men. Like bisexual men, people who take HIV prevention medications (i.e., PrEP) are also stigmatized as being sexually irresponsible and promiscuous. However, limited studies have examined the link between PrEP stigma and binegativity towards bisexual men. To reduce binegativity, bisexual contact (positive and meaningful interactions with bisexual people) has been linked to reduced prejudice against bisexual people. The goal of the study was to examine the link between HIV knowledge, dimensions of PrEP stigma, bisexual contact, and binegativity towards bisexual men among undergraduate students (<i>N</i> = 633).</p><p><strong>Method: </strong>Undergraduate students were recruited through the University of Houston's SONA system and answered self-report forms regarding demographic variables, bisexual contacts, HIV knowledge, dimensions of PrEP stigma, and attitudes towards bisexual men. Hierarchical multiple linear regression was used to test the relationship between HIV knowledge, dimensions of PrEP stigma, and bisexual contact with binegativity. Additionally, bisexual contact was tested as a potential moderator between HIV knowledge and binegativity, and between dimensions of PrEP stigma and binegativity.</p><p><strong>Results: </strong>HIV knowledge and bisexual contact were negatively associated with binegativity, while dimensions of PrEP stigma were positively associated with binegativity. Bisexual contact did not moderate the relationship between HIV knowledge and binegativity, and between dimensions of PrEP stigma and binegativity. These results suggest that LGBTQ inclusive sexual health education that includes accurate information about HIV, STIs, and PrEP may play a major role in reducing negative attitudes towards sexual minorities.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172037","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":"β2 Integrins Differentially Regulate Macrophage Polarization, Inflammatory Signaling, and Function: A Prominent Role for CD11d.","authors":"Fahd Alhamdan, Ganchimeg Bayarsaikhan, Sophia Koutsogiannaki, Koichi Yuki","doi":"10.21203/rs.3.rs-11007877/v1","DOIUrl":"10.21203/rs.3.rs-11007877/v1","url":null,"abstract":"<p><p>β2 integrins are leukocyte-specific adhesion receptors that regulate immune cell trafficking and outside-in signaling; however, the individual contributions of their four α subunits, CD11a, CD11b, CD11c, and CD11d, to macrophage activation remain incompletely understood. Here, we investigated the expression dynamics and functional roles of β2 integrins during macrophage polarization by integrating bulk and single-cell RNA-sequencing datasets with transcriptomic, pathway, and functional analyses of individual β2-integrin-deficient macrophages. The four β2-integrin subunits displayed distinct temporal expression patterns during lipopolysaccharide (LPS)-induced macrophage activation and differential expression across M0, M1, and M2 macrophage states. Deletion of individual β2 integrins generally enhanced the M1 transcriptional signature but produced distinct cytokine, chemokine, and functional phenotypes. CD11d deficiency induced one of the most pronounced transcriptional alterations, characterized by increased TNF, interferon, IL-10, JAK-STAT, p53, TGFβ, and WNT signaling, accompanied by reduced hypoxia, MAPK, and PI3K pathway activity. CD11b deficiency preferentially enhanced NF-κB, TNFα, and VEGF signaling while reducing phagocytosis. In contrast, CD11a and CD11c deficiency showed partially convergent transcriptional and MAPK-associated signaling profiles but distinct functional consequences. Analysis of inflammatory and functional signatures further demonstrated integrin-specific regulation of phagocytosis, macrophage activation, differentiation, chemotaxis, and MHC class II-associated programs. Moreover, deletion of individual β2-integrin subunits altered the expression of the remaining family members, revealing a dynamic network of compensatory and antagonistic interactions that became more complex following LPS stimulation. CD11d deficiency was associated with increased inflammatory infiltration during LPS-induced acute lung injury, providing an <i>in vivo</i> correlate of its enhanced inflammatory macrophage phenotype. Together these findings demonstrate that β2 integrins differentially regulate macrophage polarization, signaling, and effector functions rather than acting as functionally redundant adhesion receptors.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172008","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":"SQOR regulates H₂S detoxification and lipid metabolism to maintain glioblastoma metabolic fitness.","authors":"Andras K Ponti, Taylor Gatesman, Sarah Hatem, Jordyn Smith, Ishana Senthil, Arjun Akula, Lilly Stanley, Matthew Godwin, Kewal Asosingh, Isaac Ampong, Belinda Willard, Naseer Sangwan, Andrew Dhawan, Daniel J Silver, Sameer Agnihotri, Justin D Lathia, Christopher Hine","doi":"10.21203/rs.3.rs-11077727/v1","DOIUrl":"10.21203/rs.3.rs-11077727/v1","url":null,"abstract":"<p><p>Glioblastoma (GBM) adapts to metabolic stress through mitochondrial pathways that are not fully defined. Here, we show sulfide quinone oxidoreductase (SQOR) is upregulated in human GBM and functions as a mitochondrial checkpoint linking hydrogen sulfide (H₂S) clearance to electron transport chain activity. In patient-derived GBM cells and immunocompetent syngeneic tumors, SQOR channels H₂S-derived electrons into the ubiquinone pool to sustain oxidative phosphorylation during stress. Genetic or pharmacologic SQOR inhibition causes intracellular H₂S accumulation, collapse of mitochondrial respiration, tricarboxylic acid cycle dysfunction, and compensatory glycolytic engagement. SQOR loss also redirects carbon into lipid synthesis and storage while impairing lipid mobilization, thereby limiting metabolic flexibility and stem-like cell maintenance. Increasing endogenous H₂S production further exacerbates the bioenergetic defects caused by SQOR blockade. Functionally, genetic or pharmacologic SQOR inhibition suppresses tumor growth and prolongs survival <i>in vivo</i>. Together, these data identify SQOR-dependent sulfide oxidation as a mitochondrial liability that supports GBM metabolic plasticity.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171390","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":"Individual and neighborhood social determinants and high-risk behaviors among Puerto Rican young adults: A cross-sectional analysis of the PR-OUTLOOK Study.","authors":"Mary R Lee, Cynthia M Pérez, Milagros C Rosal, Sarah N Forrester","doi":"10.21203/rs.3.rs-10832018/v1","DOIUrl":"10.21203/rs.3.rs-10832018/v1","url":null,"abstract":"<p><strong>Background: </strong>Health-risk behaviors, including tobacco use, excessive alcohol consumption, and physical inactivity, contribute to chronic disease and are shaped by individual and neighborhood social conditions. However, little is known about how individual social disadvantage and neighborhood social vulnerability relate to health-risk behaviors among young adults residing in Puerto Rico. The objectives of this study were to examine associations between individual- and neighborhood-level social determinants of health and engagement in high-risk behaviors among Puerto Rican young adults residing in Puerto Rico.</p><p><strong>Methods: </strong>We analyzed baseline data (2020-2024) from the PR-OUTLOOK cohort, including 2,727 adults aged 18-29 years residing in Puerto Rico. Individual-level social determinants of health were analyzed using a latent factor score derived from ten indicators and categorized into tertiles (least, moderate, and most disadvantaged). Neighborhood-level social vulnerability was assessed using the census-tract level Social Vulnerability Index (continuous range: 0-1.0). Five binary high-risk behavior outcomes were analyzed: cigarette smoking, e-cigarette use, recreational marijuana use, binge drinking, and physical inactivity. Poisson regression with robust standard errors was used to estimate adjusted prevalence ratios (aPRs) for individual-level social determinant groups; models were subsequently stratified by sex to assess sex-specific associations. Fixed-effects logistic regression with cluster-robust standard errors at the census-tract level was used to estimate adjusted odds ratios (aORs) for individual-level social determinants of health and neighborhood-level social vulnerability.</p><p><strong>Results: </strong>Among participants, 33.7% reported one high-risk behavior, 25.1% reported two, and 18.5% reported three or more. Compared with the least disadvantaged group, individuals in the most disadvantaged social determinants of health tertile had a higher prevalence of cigarette smoking (aPR: 1.71) and physical inactivity (aPR: 1.24), with stronger and more consistent associations observed among female participants. At the neighborhood-level, higher social vulnerability score was associated with increased odds of binge drinking (aOR: 1.85) but lower odds of e-cigarette and marijuana use.</p><p><strong>Conclusions: </strong>In this cohort of Puerto Rican young adults, both individual-level and neighborhood-level social disadvantage were associated with selected high-risk health behaviors, particularly among female participants. Future longitudinal studies are needed to elucidate causal pathways and inform multi-level interventions aimed at reducing disparities in high-risk health behaviors in this population.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166334","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}