Research square最新文献

{"title":"The Association of Resilience with Psychiatric Morbidity, Sleep Quality and Antiretroviral Therapy Adherence among Older Adults Living with HIV in Nigeria.","authors":"Olufisayo Oluyinka Elugbadebo, Lisa M Kuhns, Lauren Brittany Beach, Bibilola D Oladeji, Chiamaka Egbuna, Olutosin Awolude, Olayinka Omigbodun, Philip B Gorelick","doi":"10.21203/rs.3.rs-11290080/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11290080/v1","url":null,"abstract":"<p><p>Advances in antiretroviral therapy (ART) have increased survival among people living with HIV, resulting in a growing population of older adults who often face persistent psychological challenges. However, limited evidence exists on how in the face of these challenges, resilience may interact with psychiatric morbidity and HIV treatment adherence in African countries. This study therefore examined resilience among older adults living with HIV in Ibadan, Nigeria and its association with psychiatric morbidity and ART adherence. In this cross-sectional study, resilience, psychiatric morbidity and HIV treatment adherence were assessed among 400 older adults aged ≥ 50 years living with HIV. Resilience, depression, anxiety and sleep quality were measured using the 25-item Wagnild and Young resilience scale, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item scale (GAD-7) and the Pittsburgh Sleep Quality Index (PSQI) respectively. Antiretroviral medication adherence was self-reported for the prior 30-days. Associations between resilience levels, psychiatric morbidity, and medication adherence outcomes were investigated using multivariable logistic regression controlling for demographic and clinical factors. The mean age of participants was 58.2 ± 6.5 years. Low resilience was common, affecting approximately 89.7% of the cohort. The prevalence of psychiatric morbidity was 7.8% for depression, 6.0% for anxiety, and 15.2% for poor sleep quality. Overall, ART adherence was relatively high, with 85.5% of participants reporting adequate adherence. Higher resilience scores were associated with lower odds of depression (adjusted [aOR] = 0.958, 95% CI: 0.939-0.977), anxiety (aOR = 0.971, 95% CI: 0.950-0.993, p = 0.010) and an increased odds of at least 95% antiretroviral therapy adherence (aOR = 1.033, 95% CI: 1.008-1.058, p = 0.009). In this study of older adults living with HIV in Nigeria, the level of resilience was low but was protective for psychiatric morbidity and medication adherence. Promoting resilience may improve well-being among aging populations living with HIV.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280278","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":"Profiling Transcriptomic Changes Across Frontal Cortical Subregions in Major Depressive Disorder.","authors":"Artemis Iatrou, Adrien Gigliotta, Vijetha Balakundi, Rahul Bharadwaj, Chris Chatzinakos, Natalie Matosin, Corina Nagy, Clara Snijders, Gustavo Turecki, Boyan Leng, PsychENCODE Ptsd Brainomics Project, Daniel Weinberger, Thomas Hyde, Charles Nemeroff, Kerry Ressler, Joel Kleinman, Nikolaos Daskalakis","doi":"10.21203/rs.3.rs-7349413/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-7349413/v1","url":null,"abstract":"<p><p>Major depressive disorder (MDD) involves frontal cortical dysfunction, with emerging evidence implicating gliovascular and immune mechanisms, yet its transcriptional signatures across subregions, cell-types, and molecular layers remain poorly defined. Here, we integrated bulk-tissue RNA-seq data from dlPFC, mPFC, and dACC (n = 286) to identify a conserved core transcriptional profile, anchored in downregulated interneuron markers, and upregulated immune and vascular genes, spatially enriched in leptomeninges and white matter. Concordantly, multiomic factor analysis revealed immune activation, stress-response, and accelerated aging in MDD. Analysis of snRNA-seq data from dlPFC, mPFC, and oFC (863,511 nuclei; n = 204) revealed most pronounced MDD signatures in excitatory neurons, accompanied by coordinated disruption of glucocorticoid receptor machinery across cell-types, including <i>FKBP5</i> upregulation. Glial, immune, and perivascular populations exhibited signatures of oxidative stress, ECM remodeling, and reduced neuronal support, and greater concordance with bulk-tissue MDD signals than neurons. A global reduction in cell-to-cell communications in MDD revealed a shift from homeostatic neuronal signaling toward endothelial and myelination-associated pathways. Ephrin-Eph signaling was consistently dysregulated, implicating disrupted axonal guidance, synaptic remodeling, and neurovascular integrity. Notably, MDD signatures were shared between MDD-only and PTSD comorbid cases at bulk-tissue analyses, while diverging at single-cell resolution. Together, these findings reframe MDD as a distributed frontal cortex disorder, driven by disrupted neuroglial and neurovascular communication.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280166","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":"\"Why can't they come up with a program that teaches people how to get high and go to work\": Structural vulnerability, personal substance use and recovery goals, and substance use treatment among sexual and gender minority persons (SGMP) in Los Angeles, California.","authors":"Sid S Ganesh, Rebecca P Smeltzer, Gilbert A Orta Portillo, Natalie Jefferson, Julia J Koerber, Jacklynn Pham, Moranda L Tate, Pamina M Gorbach, Ricky N Bluthenthal","doi":"10.21203/rs.3.rs-10320093/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10320093/v1","url":null,"abstract":"<p><p><b>Introduction</b> Sexual and gender minority persons (SGMP) report disproportionately high rates of substance use in the United States, yet relatively low rates of treatment access and initiation. In this study, we examined substance use treatment experiences among SGMP who inject drugs in Los Angeles, California. <b>Methods</b> We conducted 15 one-on-one qualitative semi-structured interviews with self-identified SGMP assigned male at birth. Eligibility included being assigned male at birth, reporting sex with men, and meeting at least one of the following: being a participant in either the NIH-funded mSTUDY or CANOP cohorts or reporting any opioid or injection drug use within the past two years. Data were collected at a community site associated with a syringe services program and LGBT+ service provider in Los Angeles, CA between May 2022 - February 2023. We employed inductive and deductive coding, using the intersectional risk environment framework and life course theory to develop our codebook and guide our thematic analysis. <b>Results</b> Participants described motivations to decrease their substance use in order to use drugs more intentionally and reduce stigma. Disordered use was linked to financial and material insecurity, which participants perceived as inadequately addressed by treatment programs. Experiences of shame, punishment, conditionality, and loss of support were common in treatment settings. However, patients reported positive experiences with programs that addressed structural vulnerabilities (such as social isolation and financial hardship) and integrated multiple therapeutic modalities into care. <b>Discussion</b> We found that participants view substance use recovery on a continuum that included reducing frequency and type of substance use and modifying routes of administration to reduce infection risk. These findings support integrating harm reduction-based therapeutic modalities into substance use treatment settings. Furthermore, our results emphasize how substance use treatment may be delivered to improve efficacy by 1) co-delivering structurally competent services, that address housing instability, social isolation, unemployment/underemployment, and professional development, 2) prioritizing patient directed, and centered care that incorporates harm reduction and shared decision making, and 3) providing integrated treatment that combines various treatment and therapeutic modalities to meet patients' most pertinent needs.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280153","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":"Contracting Skeletal Muscle Releases Antioxidant-Enriched Extracellular Vesicles and Non-vesicular Extracellular Nanoparticles.","authors":"Sarah Pribil Pardun, Li Yu, Saadyeh Rashidi, Chittibabu Guda, Lie Gao","doi":"10.21203/rs.3.rs-10978006/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10978006/v1","url":null,"abstract":"<p><p>While the benefits of exercise are well-documented, the underlying molecular mechanisms remain to be fully elucidated. Previous research in our lab demonstrated that electrical pulse stimulation (EPS) of cultured C2C12 myotubes activates the Nrf2/antioxidant pathway. In the study presented in this manuscript, we hypothesized that these upregulated antioxidant enzymes are secreted into the conditioned medium (CdM) <i>via</i> extracellular vesicles (EVs) and non-vesicular extracellular nanoparticles (nvEPs). We also hypothesized that these antioxidant-enriched particles protect H9c2 cardiomyocytes from H ₂ O ₂ -induced damage. EVs/nvEPs were isolated from the CdM of EPS-treated C2C12 cells and compared to those from non-stimulated (NS) cells using differential ultracentrifugation. Transmission electron microscopy (TEM) revealed that the isolated particles displayed a typical morphology, with EVs showing a cup-shaped structure and lipid bilayer membrane, and nvEPs exhibiting a pill-like and amembranous structure with high electron density. Western blot analysis demonstrated that EVs/nvEPs from EPS-C2C12 myotubes contained higher levels of antioxidant proteins (NQO1 and GSTA2) than those isolated from non-stimulated myotubes. Using a CCK-8 viability assay, we found that H9c2 cells pretreated with C2C12-derived nvEPs showed varying degrees of survival following H ₂ O ₂ challenge. Our findings demonstrate that the EVs/nvEPs released from EPS-C2C12 myotubes contain enriched antioxidant enzymes, which protect cardiomyocytes from oxidative stress.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280111","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":"Immunoproteasome Deficiency Impairs Microglial Clearance and Worsens Tau and Amyloid Pathology.","authors":"Malavika Srikanth, Shan Jiang, Steven M Wellman, Shrita Sarkar, Daniella E Lorman, Timothy Lantin, Avery M Runyan, Mayank Kumar, Eric Sydney, Helen Y Figueroa, Mu Yang, Qi Wang, Natura Myeku","doi":"10.21203/rs.3.rs-11129729/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11129729/v1","url":null,"abstract":"<p><p><b>Background</b> Immunoproteasome induction is prominent in Alzheimer's disease (AD), but whether this response protects proteostasis or amplifies neuroinflammation remains unresolved. Microglia must engage, internalize and degrade pathological protein cargo, yet uptake alone may not indicate successful clearance. We investigated how loss of inducible immunoproteasome function affects AD-related protein pathology and microglial processing of pathological cargo. <b>Methods</b> We crossed L7M1 mice, which lack the immunoproteasome catalytic subunits β2i/MECL-1/PSMB10 and β5i/LMP7/PSMB8, with PS19 tauopathy mice and APP/human tau double-knock-in mice. Tau and amyloid pathology, glial reactivity, constitutive proteasome activity and behavior were evaluated in vivo. Microglial uptake and processing of tau aggregate-bearing material were examined using primary microglial cultures, live-cell imaging and longitudinal in vivo two-photon microscopy. Mouse single-nucleus RNA sequencing and reanalysis of two human single-nucleus transcriptomic datasets were used to define associated cellular programs. Isolated brain mitochondrial respiration was also assessed. <b>Results</b> Immunoproteasome deficiency increased phospho-tau burden and microglial reactivity in PS19 mice and exacerbated tau and amyloid-β pathology in APP/human tau double-knock-in mice. These pathological changes occurred without detectable suppression of constitutive 26S proteasome activity. Although immunoproteasome-deficient microglia engaged and engulfed tau aggregate-bearing material, live-cell imaging showed inefficient resolution of internalized cargo. Longitudinal two-photon imaging similarly demonstrated retention or accumulation of microglia-associated tau in immunoproteasome-deficient mice, identifying a post-engulfment degradative defect in vivo. Single-nucleus transcriptomics revealed a remodeled P2ry12low/Trem2high microglial state accompanied by altered phagolysosomal cargo-processing and mitochondrial programs. In two human datasets, lower microglial immunoproteasome expression was associated with cargo-processing gene-program changes that overlapped with those observed in immunoproteasome-deficient mouse microglia. Despite transcriptional suppression of mitochondrial programs, no detectable impairment of isolated brain mitochondrial respiration was observed. <b>Conclusions</b> These findings support immunoproteasome biogenesis as a protective glial stress response that facilitates post-engulfment processing of pathological cargo and restrains tau and amyloid accumulation in AD-relevant brain environments. They further distinguish microglial engagement and uptake from successful intracellular resolution, identifying immunoproteasome function as an important component of aggregate clearance in AD.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280177","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":"Credential farming in the age of generative AI: relocating trust from outputs to communities.","authors":"Gift Osei Agyemang, Rawad Al-Louzi, Melat Mezgebu Bawoke, Connor Bender, Leo Anthony Celi, Nishita Chavan, Rahul Gorijavolu, Diego Halac, Nikhil Jaiswal, Sofiya Mikolutskaya, Anthony Nguyen, Raul Ignacio Rojas Sillery, Sparsh Roy, Dharaa Suresha, Alexa Xiang, Boya Zhang","doi":"10.21203/rs.3.rs-10944586/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10944586/v1","url":null,"abstract":"<p><p>Publications, affiliations and authorship positions began as proxies for qualities that cannot be observed directly: judgement, understanding and the capacity to contribute to shared inquiry. Generative artificial intelligence has weakened the inference those proxies depend on. Polished research outputs can now be produced by people who do not understand them, yet admissions committees and hiring panels still read an output as evidence of the competence that producing it once required. The result is faster credential farming, the extraction of the social trust held in credentials without contribution to the enterprise that gives them meaning. Better detection of machine-generated text will not repair this. What has to change is where epistemic trust sits. Work in the sociology of credentials, in social epistemology and on situated learning points to where it should move: scientific formation, how communities shape people and teach them what to value, carries the evidential weight that credentials only summarised. Three commitments follow. Select members for depth rather than legibility. Build small relational structures in which judgement can be formed and witnessed. Refuse to convert those structures into new metrics. The argument matters most for researchers in low-resource settings, whose learning happens in informal spaces that credentialing systems do not see, and who are asked to make themselves legible in a vocabulary nobody taught them.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280120","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":"PathVista Integrates Cellular Foundation Models with Multiscale Histopathology for Colorectal Cancer Prognosis and Molecular Stratification.","authors":"Usama Sajjad, Abdul Rehman Akbar, Tianyang Wang, Wendy L Frankel, Metin N Gurcan, Wei Chen, Muhammad Khalid Khan Niazi","doi":"10.21203/rs.3.rs-11037299/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11037299/v1","url":null,"abstract":"<p><p>Personalized management of colorectal cancer (CRC) requires accurate risk stratification and identification of clinically actionable molecular alterations. However, standard clinicopathologic features often fail to capture the cellular and tumor microenvironmental heterogeneity driving disease behavior. Although routine hematoxylin and eosin (H&E) whole-slide images (WSIs) reflect these patterns, patch-level foundation models may obscure fine-grained cellular morphology and spatial organization. We present <b>PathVista</b> , a cell-centered framework that integrates cellular and tissue-level representations for prognostic and molecular stratification. PathVista incorporates <b>CellSwAV</b> , a cellular foundation model pretrained on more than 160 million CRC cells and combines spatially aggregated cellular features with broader tissue context. Across <b>2,568 CRC patients</b> , PathVista risk scores were significantly associated with <b>overall survival (HR = 6.65, 95% CI: 3.53-12.51)</b> , <b>disease-free survival (HR = 3.15, 95% CI: 1.82-5.45)</b> , and <b>recurrence-free survival (HR = 3.04, 95% CI: 1.76-5.26)</b> , with risk scores remaining independently associated with outcomes after clinicopathologic adjustment. Locked models also generalized to external <b>TCGA (HR = 5.25, 95% CI: 2.29-12.05)</b> and <b>SURGEN (HR = 2.89, 95% CI: 1.86-4.49)</b> cohorts. PathVista predicted <b>microsatellite instability (AUC = 0.91)</b> and <i><b>BRAF</b></i> <b>mutation status (AUC = 0.83)</b> . Across <b>4,667 patients</b> spanning CRC, lung, and breast cancers, PathVista demonstrated the potential of cell-centered histopathology for prognostic, molecular, and tumor characterization.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280149","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":"Prevalence, Clinical Presentation Antifungal Susceptibility Profiles and Factors Associated with Chronic Pulmonary Aspergillosis among Pulmonary Tuberculosis Suspects in Uganda: A Cross- sectional study.","authors":"Allen Rhoda Nankya, Richard Kwizera, Priscilla Apio, Moses Ssemwanga, Fiona Mutesi Magololo, Lorna Atikoro, Tonny Luggya, Amelia Margaret Namiiro, Moses Joloba, Willy Ssengoba, Beatrice Achan","doi":"10.21203/rs.3.rs-11293911/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11293911/v1","url":null,"abstract":"<p><strong>Background: </strong>Chronic pulmonary aspergillosis (CPA) is a possible diagnosis in patients evaluated for pulmonary tuberculosis (PTB), especially in resource limited settings with high TB burden. Its clinical presentation closely mimics PTB, often resulting in missed diagnosis and delayed initiation of treatment. This study aimed to describe the prevalence, clinical presentation, antifungal susceptibility profiles and factors associated with CPA among PTB suspects in Mulago National Referral Hospital.</p><p><strong>Methods: </strong>This was a cross-sectional study conducted between February and May 2025 at Mulago National Referral Hospital, Kampala, Uganda. We consecutively enrolled adult patients with persistent respiratory symptoms, suspected to have PTB. All participants underwent Gene Xpert MTB/RIF testing of sputum and fungal culture using Sabouraud dextrose agar. CPA was diagnosed based on the presence of compatible symptoms lasting two weeks or more, positive Aspergillus culture, and radiological findings. Antifungal susceptibility testing was done using gradient strips to determine minimum inhibitory concentrations. Multivariable logistic regression was used to identify predictors of CPA.</p><p><strong>Results: </strong>Of the 135 participants (median age 35 years, IQR: 28-49; 62.2% male), CPA was diagnosed in 13.3% (18/135), with 5.9% (8/135) having CPA with active PTB and 7.4% (10/135) having CPA without PTB. Additionally, 31.9% (43/135) had PTB without CPA, and 54.8% (74/135) had neither PTB nor CPA. The most common Aspergillus species isolated were A. fumigatus (38.1%), A. niger (38.1%), and A. flavus (28.6%). Common clinical presentations included productive cough, fever, hemoptysis, and chest pain in CPA cases. Pulmonary fibrosis (66%) was the most common radiological finding among CPA patients. Antifungal susceptibility testing revealed complete sensitivity to voriconazole while resistance to amphotericin B was observed in 31% of the isolates. Longer duration of symptoms (adjusted odds ratio [aOR]: 1.22 per week; 95% CI: 1.06-1.41; p=0.006), chest pain (aOR: 3.05; 95% CI: 1.02-9.96; p=0.052), and TB exposure (aOR: 3.57; 95% CI: 1.11-12.08; p=0.034) were independently associated with CPA, Conclusions: About 13.3% patients suspected to have PTB in Uganda have CPA with clinical presentation similar to PTB, mostly caused by A. fumigatus and A. niger. CPA should be screened among PTB suspects to improve early case detection and patient outcomes.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280212","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":"Radiomics-Based Muscle Quality Assessment from Multi-Site Multi-Vendor MRI.","authors":"Ozkan Cigdem, Eros Montin, Salim Bin Ghouth, Akshay Chaudhari, Donnie Cameron, Christopher M Bergeron, Jan Bergeron, Luigi Ferrucci, Garry E Gold, Riccardo Lattanzi, Cem M Deniz, Valentina Mazzoli","doi":"10.21203/rs.3.rs-10845667/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-10845667/v1","url":null,"abstract":"<p><p>Muscle strength is critical for mobility, and its decline with aging contributes to frailty, falls, and loss of independence. Muscle cross-sectional area (CSA), which can be measured on MRI, only reflects muscle quantity and may not fully capture age-related changes in muscle composition, which significantly contribute to loss of muscle strength in older adults. We investigated strength prediction using multi-center/multi-scanner Dixon MRI from 141 adults across three cohorts: 82 healthy adults (Philips, 22-94 years), 24 healthy adults (GE, 30-79 years), and 35 older adults (Siemens, 70-91 years), including healthy, pre-frail, and sarcopenic participants. CSA was a strong predictor of muscle strength in the healthy cohorts, but radiomics features provided additional value when older adults were included. Fat-fraction radiomics showed the strongest and most consistent performance across cohort combinations, with the best results in the full combined cohort (R²=0.64 versus 0.42 for CSA alone). Water-only radiomics also retained predictive value, although generally less strongly than fat-fraction features. The most informative radiomics features reflected muscle size, signal magnitude, and internal heterogeneity, and SHAP analysis linked higher intramuscular heterogeneity to reduced strength. Taken together, these findings suggest that radiomics can capture muscle quality features that affect muscle force-generating capacity beyond size alone, particularly in older adults, and support automated MRI-based assessment of muscle composition and function, which potentially help future sarcopenia screening and functional risk stratification.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280161","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":"TLR7-mediated autoimmunity targets Robo3 to drive astrogliosis in frontotemporal dementia.","authors":"Eric Huang, Rufei Lu, Jennifer Choi, Naznin Jahan, Isabella Imhof, Samuel Collo, Sofia Eguiguren, Jiasheng Zhang, Gavin Sowa, Colin Zamecnik, Juliet Chen, Jeffrey Hofmann, Mary Nakamura, Michael Wilson, Raymund Bueno, Yang Sun, Chun Ye, Christine Hsieh","doi":"10.21203/rs.3.rs-11236688/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11236688/v1","url":null,"abstract":"<p><p>Mutations in GRN and C9orf72 are common causes of frontotemporal dementia (FTD). While it is well-recognized that GRN or C9orf72 mutations also increase the risk of autoimmune diseases, the intersection of innate and adaptive immunity, neuroinflammation, and neurodegeneration in FTD remains unclear. Here we show that concurrent loss of Grn and C9orf72 breaks immune tolerance by activating the pattern recognition receptor, TLR7, leading to clonal expansion of age-associated B cells and activated B cells. Grn-/-;C9orf72-/- B cells exhibited heightened responses upon TLR7 activation and produced autoantibodies that target the axon guidance receptor Robo3 to promote astroglial pathology. Interestingly, immunization with Robo3 extracellular domain in young Grn-/-;C9orf72-/- mice accelerated astrogliosis. Conversely, TLR7 antagonist M5049 treatment rescued B cell defects, reduced anti-Robo3 autoantibodies, and mitigated astrogliosis and synaptic loss in Grn-/-;C9orf72-/- mice. Together, these results offer critical insights into how TLR7-mediated autoimmune dysfunction targets Robo3 to drive neuroinflammation and neurodegeneration in FTD.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280248","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}