medRxiv : the preprint server for health sciences最新文献

{"title":"Psychotherapy remains a human endeavor: Human therapy is valued more than AI-integrated therapy.","authors":"Colin Xu, Thomas T Kim","doi":"10.64898/2026.09.29.26364234","DOIUrl":"https://doi.org/10.64898/2026.09.29.26364234","url":null,"abstract":"<p><p>While Artificial intelligence (AI) is increasingly being integrated into psychotherapy, little is known about how prospective patients evaluate different levels of AI involvement. Participants (n = 1,003) with depression evaluated vignettes describing psychotherapy options, from treatment delivered without AI integration (Human therapist) to treatments involving different degrees of AI integration (Assistive, Collaborative, Fully Autonomous AI). Participants consistently evaluated Human therapists more favorably, reporting a greater likelihood of seeking treatment, less hesitancy, and greater treatment acceptability. Economically, compared with a Human therapist, participants were willing to pay 31.6% less for therapists using Assistive or Collaborative AI and 57.2% less for Fully Autonomous AI. 18-19% of participants indicated that they would refuse treatment involving Assistive or Collaborative AI, compared with 31% for Fully Autonomous AI. Preference for Human over AI therapists was particularly pronounced at higher levels of therapist experience (doctoral/masters vs. peer/trainee). Overall, participants valued psychotherapy delivered by Human therapists more highly than AI integrated psychotherapy. These findings suggest that, despite increasing AI integration in mental health care, prospective patients continue to view psychotherapy as a distinctly human endeavor.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169501","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":"Declining Adherence to Dietary Approaches to Stop Hypertension (DASH) Diet Among US Adults with Hypertension: NHANES 2003-2018.","authors":"Vijaya Parameswaran, Anjali Phalke, Christopher Gardner, David J Maron","doi":"10.64898/2026.09.28.26364241","DOIUrl":"https://doi.org/10.64898/2026.09.28.26364241","url":null,"abstract":"<p><strong>Background: </strong>Data from National Health and Nutrition Examination Survey (NHANES) cycles 1988-1994 and 1999-2004 show a declining trend in the adherence to Dietary Approaches to Stop Hypertension (DASH) among adults. Since then, DASH evidence, dietary guidelines, and public-facing dietary resources have advanced, but whether national DASH adherence has improved is uncertain.</p><p><strong>Methods: </strong>We extended the Mellen et al. NHANES analysis among 14,163 adults with self-reported hypertension (N=6,914, 2003-2010, N=7,249, 2011-2018). DASH score included 9 nutrient components: total fat, saturated fat, protein, cholesterol, fiber, calcium, magnesium, potassium, and sodium, with adherence defined as a score ≥4.5. Survey-weighted multivariable models compared DASH score, adherence, and nutrient-threshold attainment across periods.</p><p><strong>Results: </strong>In 2011-2018, U.S. adults with self-reported hypertension represented 76.2 million individuals (33.8%). Multivariable-adjusted DASH adherence declined from 22.1% in 2003-2010 to 18.6% in 2011-2018 (p=0.003), and mean DASH score declined from 2.98 to 2.85 (p=0.007). Adjusted odds of adherence were lower in 2011-2018 compared with 2003-2010 (OR, 0.78; 95% CI, 0.67-0.91; p=0.002). Adherence was lower among non-Hispanic Black adults (OR, 0.70; 95% CI, 0.59-0.84), adults with BMI ≥30 kg/m² (OR, 0.61; 95% CI, 0.51- 0.73), and adults with prior stroke (OR, 0.71; 95% CI, 0.56-0.89). Total fat and sodium threshold attainment declined from 20.9% to 18.7% and 13.8% to 11.8%, respectively.</p><p><strong>Conclusions: </strong>DASH adherence among U.S. adults with self-reported hypertension declined from 2003-2011 to 2011-2018. Implementation strategies should identify barriers to adoption and address the full DASH dietary pattern.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171768","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":"Comparing epigenetic puberty and epigenetic clocks as biomarkers of adult biological aging and health.","authors":"Q Wu, S F P Gibbs, A J de Steiguer, S Zarandooz, Y E Willems, T Smith, J A Goode, C Mitchell, E M Crimmins, K P Harden, R E Marioni, L Raffington","doi":"10.64898/2026.09.29.26364286","DOIUrl":"10.64898/2026.09.29.26364286","url":null,"abstract":"<p><p>Recent lifespan frameworks of aging theorize that pubertal development and cellular aging are governed by overlapping pathways, but the time lag between adolescence and older adulthood complicates the study of shared molecular mechanisms. Here we compare a DNA-methylation-based epigenetic index of pubertal development to epigenetic clocks, which were designed to measure biological aging, as a putative biomarker of adult aging and health in two adult cohorts: 3,642 older Americans in the Health and Retirement Study (HRS; age range, 56 to 100 years; 2,106 females) and 18,676 adults from Generation Scotland (GS; age range, 18 to 98 years; 10,974 females). Epigenetic puberty was correlated with chronological age in both cohorts, moderately in the older HRS sample (r = 0.51 in females, r = 0.51 in males) and strongly across the wider adult age range of GS (r = 0.82 in females, r = 0.86 in males). In both cohorts, age-residualized epigenetic puberty was associated with accelerated biological aging as measured by epigenetic clocks and other aging biomarkers (standardized coefficients: HRS, 0.13 to 0.47, all P < 0.005; GS, 0.05 to 0.40, all P < 0.001). Epigenetic puberty was linked with multiple health outcomes: mortality in HRS in both sexes (ORs, 1.39 and 1.46, both P ≤ 0.001) and in GS among females (HR, 1.12, P = 0.003); 10-year onset of diabetes, any cancer and lung disease in GS (HRs, 1.12 to 1.19, all P < 0.005); and with multimorbidity, functional limitations and BMI in females in HRS (standardized coefficients, 0.10 to 0.16, all P < 0.001). It also accounted for a unique, albeit smaller, proportion of variance in aging-related outcomes beyond that explained by epigenetic clocks. These findings indicate that the epigenetic puberty index reflects pro-aging underlying biology, showing overlapping molecular pathways between pubertal development and cellular aging, and support a lifespan-based approach to studying biological aging.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171648","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":"Neuropsychiatric Symptom Associations with <i>NOTCH3</i> Genotype in the United States CADASIL Consortium.","authors":"Megan R Caruso, Barbara L Fischer, William H Adams, Deven K Burks, Bianca Le, Arash Salardini, Jennifer J Majersik, Stephen P Salloway, Jamie L Elliott, H Jeremy Bockholt, Suman Jayadev, Michael D Geschwind, José Biller, Helmi L Lutsep, Sara J Doyle, Jason D Hinman, David S Liebeskind, Imama A Naqvi, Kelsey Eklund, Sudha Seshadri, Lisa C Krishnamurthy, Myriam Fornage, Jane S Paulsen, Edward D Huey","doi":"10.64898/2026.09.24.26363718","DOIUrl":"10.64898/2026.09.24.26363718","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common monogenic cerebral small vessel disease. Though neuropsychiatric symptoms (NPS) of CADASIL profoundly impact function and quality of life, these symptoms remain understudied. This analysis characterizes the prevalence, severity, and profile of NPS among individuals with CADASIL-causing <i>NOTCH3</i> variants and non-carrier biological family controls in the United States CADASIL Consortium (USCC).</p><p><strong>Methods: </strong>This cross-sectional analysis used multimodal baseline data from 12 enrollment sites across the country. Statistical analyses used nonparametric tests and regression models to compare clinical and neuropsychiatric outcomes across CADASIL risk tiers and controls, adjusting for age, sex, race, and education where appropriate. The primary outcome measure was the Neuropsychiatric Inventory Questionnaire (NPI-Q), an informant-reported measure which assesses 12 categories of NPS. NPI-Q item severity and distress were evaluated for individuals with confirmed cysteine-altering pathogenic <i>NOTCH3</i> variants and compared with controls.</p><p><strong>Results: </strong>Four hundred fifty-nine USCC participants were included in the analytic cohort: 343 cases [256 high-risk (HR); 63 medium-risk (MR); 24 low-risk (LR)]; and 116 controls. Among participants with available NPI-Q data, at least one neuropsychiatric symptom was reported by 72.6% (n = 228/314) of cases compared with 53.2% (n = 58/109) of controls. Reported symptoms were more common among CADASIL cases than controls, occurring in 75.0%, 71.2%, and 72.7% of participants in the LR, MR, and HR groups, respectively, compared with 53.2% of controls. Compared with controls, participants in the MR group and HR group had higher NPI-Q severity scores. HR participants also had higher NPI-Q distress scores than controls.</p><p><strong>Discussion: </strong>Our findings support the notion that NPS are an important clinical manifestation of CADASIL. Beyond previously reported symptoms, additional neuropsychiatric manifestations were identified. Given the higher burden and variability in the neuropsychiatric presentation of CADASIL, the relationships among neuropsychiatric, neurological, and patient-reported outcomes merit further investigation. The NPS profile may enhance the evaluation of the safety and efficacy of different treatments to target these symptoms for CADASIL patients. Trial Registration Information: The study is registered at ClinicalTrials.gov ( NCT05677880 , 12/12/2022).</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171700","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":"Predicting PANSS symptoms in schizophrenia spectrum disorders using speech only: an international, multi-centre, computational secondary analysis across multiple languages.","authors":"Rui He, Maryia Kirdun, Claudio Palominos, Lara Navarrete Orejudo, Sophie Barthelemy, Simran Bhola, Silvia Ciampelli, Amandine Decker, Cemal Demirlek, Riccardo Fusaroli, José Tomás García-Molina, Guy Gimenez, Roya Hüppi, Katja Koelkebeck, Amandine Lecomte, Renxiang Qiu, Arndis Simonsen, Vincent Tourneur, Burcu Verim, Huiling Wang, Berna Yalincetin, Sandy Yin, Yuan Zhou, Maxime Amblard, Rosa Ayesa Arriola, Emre Bora, Janna de Boer, Alicia I Figueroa-Barra, Sanne Koops, Michel Musiol, Lena Palaniyappan, Alberto Parola, Filip Spaniel, Sunny X Tang, Iris E Sommer, Philipp Homan, Wolfram Hinzen","doi":"10.64898/2026.02.20.26345632","DOIUrl":"10.64898/2026.02.20.26345632","url":null,"abstract":"<p><strong>Background: </strong>Speech carries cues to variation in mental state in schizophrenia, typically indexed with clinician-rated scales such as Positive and Negative Syndrome Scale (PANSS). In this study, we aggregate multi-centre recordings to assemble a large corpus and assess symptom-prediction models at scale, to enable rater-independent, efficient, and reproducible assessments for early detection of relapse-related signals from speech.</p><p><strong>Methods: </strong>In this computational secondary analysis, we compiled data from 453 patients with schizophrenia spectrum disorders, recruited between 2005 and 2026 from ten global sites in the Czech Republic, United States, Spain, Chile, France, Switzerland, the Netherlands, Türkiye, Germany, and China, and clipped their speech recordings into 6,664 segments. Across three featuresets, acoustic-prosodic profile, pretrained multilingual embeddings, and their concatenation, we compared 16 algorithms in separate item-specific models to predict eight relapse-related PANSS items, including three positive (P1, P2, P3), three negative (N1, N4, N6), and two general (G5, G9) items, on speaker-disjoint splits. Performance was assessed by root-mean-squared-error (RMSE) at both segment and participant (median-aggregation) levels. Best model per item underwent bias checks for age, sex, education, and symptom severity.</p><p><strong>Findings: </strong>Best-performing models predicted symptoms with prediction errors of 1·5 or lower: P1 1·544/1·527, P2 1·318/1·107, P3 1·487/1·542, N1 1·071/1·030, N4 1·521/1·430, N6 0·869/0·855, G5 0·951/0·882, G9 1·298/1·282 (segment/participant). Performance of pretrained embeddings surpassed acoustic-prosodic features and concatenation. Results were comparable in languages or language variants with fewer available speech and language computational resources. We found no bias by age, sex, or education, aside from reduced N4 accuracy in males; but performance degraded with higher symptom severity.</p><p><strong>Interpretation: </strong>Speech can support automatic assessment of schizophrenia symptoms using pretrained embeddings, even without transcripts. Such models show promise as clinically meaningful, efficient, and low-burden tools for real-time monitoring of symptom trajectories. Future work should validate these models prospectively in higher-severity samples and improve clinical interpretability.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169459","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":"Evolving clinical roles in the era of genomic medicine: Insights from rapid genome sequencing in the neonatal intensive care unit.","authors":"Peter Taber, Chelsea Solorzano, L Weaver, Kelsey A Simek, Rachel Palmquist, Jorie Butler, Tanner Ellsworth, Mickey Bolyard, Martin Tristani-Firouzi, Paul Estabrooks, Sabrina Malone Jenkins","doi":"10.64898/2026.09.28.26363665","DOIUrl":"https://doi.org/10.64898/2026.09.28.26363665","url":null,"abstract":"<p><strong>Background: </strong>Rapid genome sequencing (rGS) is a first-tier test in the neonatal intensive care unit (NICU). Implementation strategies to scale rGS for clinical care may change clinician roles. We analyzed the NICU rGS workflow to understand challenges rGS poses for clinical roles and responsibilities.</p><p><strong>Methods: </strong>The study took a qualitative approach to understanding the rGS workflow in Level III and Level IV NICUs. The five workflow phases studied included: i) identification of a patient with a suspected genetic disorder, ii) subspecialist consultation, iii) test selection and ordering, iv) return of results, and v) disclosure. Data were collected via job task journals, interviews, and workflow diagram construction with clinicians involved in rGS. Analysis included participant-guided workflow diagram refinement, qualitative thematic analysis, and identification of rGS workflow challenges.</p><p><strong>Results: </strong>We documented issues related to decision-making authority and scope of responsibility for clinicians, with the majority relating to complexities of subspecialist consultations. Issues included differences in: criteria for triggering consultations, expectations of consulted subspecialists' roles, test selection preferences, and responsibility for documenting clinical interpretations and disclosure.</p><p><strong>Conclusion: </strong>Subspecialist consultations in clinical rGS involved significant role ambiguity and communication challenges, requiring intentional implementation efforts to ensure clear clinical roles and responsibilities.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","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/PMC13648811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171976","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":"Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson's Disease Spectrum.","authors":"Mikaela Rosen, J Oriol Narcis Majos, Daniele Mattei, Elena Mejia, Carlos Perez Mandry, Beomjin Jang, Kailash Bp, Tatsuhiko Naito, Amanda Allan, Tarek Khashan, Charlie Argyrou, Mengxi Yang, Deborah Raymond, Casey Young, Kelly Astudillo, Aloysius Domingo, Steven Frucht, Susan Bressman, Anna Tocheva, Giulietta Riboldi, Rachel Saunders-Pullman, Towfique Raj","doi":"10.64898/2026.09.23.26363800","DOIUrl":"10.64898/2026.09.23.26363800","url":null,"abstract":"<p><p>The role of peripheral immunity in Parkinson's disease (PD) remains incompletely understood. Here, we performed paired single-cell RNA sequencing (scRNA-seq) and T-cell receptor (TCR) profiling of 630k peripheral blood mononuclear cells (PBMCs) from 168 donors spanning idiopathic and genetic PD, prodromal PD, and healthy controls. We identify broad changes in immune-cell composition across the disease spectrum, including decreased naive B cells and increased naive CD8+ T cells in idiopathic PD. Transcriptional profiling reveals disease stage-dependent remodeling of mitochondrial and oxidative phosphorylation programs, with increased activity in prodromal disease followed by reduced activity in manifest PD, consistent with a transition in peripheral immune state during disease progression. High-resolution T cell analysis further identifies sex-dependent changes in cytotoxic CD8+ T-cell states and TCR clonal diversity. TCR motif analysis reveals disease-associated receptor groups with predicted specificities spanning PD-related, viral and autoimmune antigens. Together, these findings provide a comprehensive single-cell map of peripheral immune dysregulation in PD, defining dynamic and sex-dependent remodeling of peripheral immunity across the PD spectrum.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","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/PMC13648675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171006","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":"Alterations in relative perfusion and synaptic patterns in Parkinson's disease using dynamic SV2A PET.","authors":"Praveen Honhar, Sule Tinaz, Faranak Ebrahimian Sadabad, Jean-Dominique Gallezot, Mika Naganawa, Mark Dias, Yunpeng Ye, Hong Gao, Nabeel Nabulsi, Yiyun Huang, Sophie E Holmes, Robert A Comley, Ansel T Hillmer, Sjoerd J Finnema, David Matuskey, Richard E Carson","doi":"10.64898/2026.09.28.26364237","DOIUrl":"10.64898/2026.09.28.26364237","url":null,"abstract":"<p><strong>Purpose: </strong>Dynamic [¹¹C]UCB-J PET can simultaneously provide information about synaptic density and relative perfusion in Parkinson's disease (PD). We investigated whether these complementary biomarkers could explain a higher percentage of motor symptom severity variation in PD and inform other PD-specific physiological alterations and symptomatology.</p><p><strong>Methods: </strong>Binding potential (<i>BP</i> _ND) and relative perfusion (<i>R</i> ₁) images were derived 30 PD and 30 controls imaged with [¹¹C]UCB-J PET. A spatial covariance analysis was used on <i>R</i> ₁ to derive PDRP-a known metabolic network alteration in PD. Linear models related PD-motor symptom severity to PDRP expression and nigral synaptic losses. Next, whole-brain cluster analyses identified physiological correlates for PD-tremor severity, a prominent motor symptom that does not correlate with dopaminergic losses. Lastly, inter-individual regional correlation alterations in PD were examined for both <i>BP</i> _ND and <i>R</i> ₁.</p><p><strong>Results: </strong>PDRP was identified from <i>R</i> ₁, with higher expression in PD (<i>p</i>=1.7×10^-5, Cohen's <i>d</i>=1.2), and its expression correlated with MDS-UPDRS III (<i>r</i>=0.57, <i>p</i>=0.0009). Combining PDRP expression scores with synaptic density in the substantia nigra explained 48% of the total variation in MDS-UPDRS Part III, twice as much as previously reported using nigral synaptic density alone. Two significant large clusters (<i>p</i> _k<1×10^-6) were identified in the occipital-parietal areas where <i>R</i> ₁ was negatively correlated with tremor severity (<i>r</i> ~ -0.65, <i>p</i><0.001). Extensive correlation alterations were observed in synaptic density (prominently involving pallidum) and perfusion (prominently involving thalamus).</p><p><strong>Conclusions: </strong>Combining synaptic and perfusion outcomes for [¹¹C]UCB-J PET explains more physiological alterations associated with PD.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","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/PMC13648810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171763","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":"Antiviral Antibody Fc Dysfunction Is Linked to Increased IgG1 Fucosylation in Long COVID.","authors":"Rahul Ukey, Ioannis E Michailidis, Patricia Greenberg, Tracy Andrews, Sung Yun Jung, Haiyan Zheng, William Honnen, Abraham Pinter, Lawrence C Kleinman, Natalie Bruiners, Maria Laura Gennaro","doi":"10.64898/2026.09.28.26364044","DOIUrl":"10.64898/2026.09.28.26364044","url":null,"abstract":"<p><strong>Background: </strong>Persistent SARS-CoV-2 antigen is a leading hypothesis for post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID. Impaired Fc-mediated antiviral antibody function could contribute to inefficient clearance of infected cells and viral antigen despite preserved antibody levels. Therefore, we tested whether PASC is associated with altered Fcγ receptor-mediated antibody function and differences in IgG1 Fc fucosylation, a major regulator of Fc effector function.</p><p><strong>Methods: </strong>Serum samples from RECOVER-Adult participants with prior SARS-CoV-2 infection (99 PASC, 139 non-PASC) were analyzed for anti-SARS-CoV-2 spike receptor-binding domain (RBD) IgG and subclasses, FcγRIIIa- and FcγRIIa-mediated reporter activity as surrogate measures of antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), anti-RBD IgG1 Fc glycosylation, and circulating fucose-modifying enzymes.</p><p><strong>Results: </strong>Despite higher anti-RBD IgG and IgG1 abundance, PASC sera showed lower ADCC- and ADCP-associated FcγR reporter activity, including after normalization for antibody abundance. Anti-RBD IgG1 showed greater fucosylation in PASC samples (30 PASC, 34 non-PASC). Serum FUCA2 was lower in PASC samples (24 PASC, 34 non-PASC), whereas FUCA1 and soluble CD16a levels did not differ between the two groups.</p><p><strong>Conclusion: </strong>PASC is associated with impaired antiviral IgG Fc function, increased IgG1 Fc fucosylation, and reduced circulating FUCA2, identifying a glycoimmune axis that may contribute to impaired Fc-dependent antigen clearance and represents a potentially targetable pathway in Long COVID.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","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/PMC13648791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Exposure Signatures Distinguish Early-Onset from Later-Onset Colorectal Cancer in a Racially Diverse US Cohort: Findings from the Disparities and Cancer Epidemiology (DANCE) Study.","authors":"Sarah M Lima, Jaeil Ahn, Chiranjeev Dash, Mei-Chin Hseih, Rena R Jones, Batsirai Mabvakure, Reem Muhsen, Siddhi Patil, Alina Peluso, Candy Promprasert, Tingting Qin, Julie J Ruterbusch, Maureen A Sartor, Ann G Schwartz, Angela S Wenzlaff, Rui Zhang, Elena M Stoffel, Kristen S Purrington, Laura S Rozek","doi":"10.64898/2026.09.28.26363311","DOIUrl":"https://doi.org/10.64898/2026.09.28.26363311","url":null,"abstract":"<p><strong>Background: </strong>The incidence of early-onset colorectal cancer (EOCRC), defined as CRC diagnosed age <50, is rising in the United States and is the leading cause of cancer death in among those with early-onset cancer. Epigenetic exposure signatures based on methylation risk scores (MRS) offer a novel approach to identify long-term exposures that may contribute to EOCRC risk. We sought to replicate findings from a recent study in a racially and geographically diverse CRC cohort.</p><p><strong>Methods: </strong>We computed weighted MRS across lifestyle, air pollution, and pesticide exposome traits in 146 participants from the Disparities and Cancer Epidemiology (DANCE) cohort, a diverse population-based CRC study, applying the Maas <i>et al</i> . (2026) framework to tumor tissue. Associations between MRS and age at CRC onset (EOCRC, n=29; intermediate-onset (IOCRC) 50-64 years, n=69; late-onset, ≥65 years, n=48) were evaluated using linear and polytomous regression, with adjustment and stratification for race, geography, Area Deprivation Index (ADI), and Multi-Environmental Exposure Index (MEEI). Spearman correlations were calculated between MRSes and observed exposures.</p><p><strong>Results: </strong>EOCRC cases were predominately Black (65.5% vs. 31.3% among LOCRC) and resided in higher-deprivation neighborhoods. We found higher odds of EOCRC associated with epigenetic exposure signatures for 2,4-D herbicide, heptachlor, coarse particulate matter (PM), Mediterranean Diet Score, and smoking, and borderline associations for fine PM and nitrogen dioxide. IOCRC was associated with signatures for 2,4-D, lindane, and obesity. Heterogeneity was observed by race and area-level factors, though associations were largely consistent across strata. ADI and MEEI were correlated with multiple pesticide and pollutant epigenetic signatures.</p><p><strong>Conclusions: </strong>In a diverse US cohort, epigenetic exposure signatures distinguish CRC cohorts, particularly EOCRC from later-onset disease, with associations consistent with but not identical to previous research. EOCRC in DANCE was characterized by higher epigenetic exposure signatures for air pollution, smoking, and distinct pesticide exposure profiles. IOCRC had overlapping characteristics with early- and late-onset and were the only group with a significant obesity signature. These findings support the hypothesis that exposome-driven epigenetic changes contribute to EOCRC risk and highlight the importance of studying diverse populations to characterize the full spectrum of environmental risk factors.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","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/PMC13648759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171393","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}