Citations

Background Recent studies have disputed the association between bisphenol A (BPA) and endometriosis. This updated meta-analysis was conducted to investigate the impact of BPA exposure on endometriosis. Methods This study evaluated BPA exposure and endometriosis risk, analyzing studies from Web of Science, PubMed, Embase, Cochrane Library, and Chinese databases (CNKI, CBM, Wanfang, VIP) through August 2025. Methodological quality was assessed via the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality Tool (AHRQ). Heterogeneity was quantified using I 2 statistics. Pooled odds ratios (ORs) and 95% CIs were calculated using fixed- or random-effects models according to heterogeneity. Subgroup analysis, sensitivity analysis, and publication bias assessment were supplemented to validate the overall finding. Results Seven studies comprising 2,488 participants were included in quantitative synthesis. The meta-analyses demonstrated that BPA exposure was associated with a statistically significant increase in endometriosis risk (OR = 1.36, 95% CI = 1.13–1.63, p = 0.008). Additionally, subgroup analysis indicated that BPA exposure may further elevate endometriosis risk in cases with different regions, populations, and measurement methods. Sensitivity analysis confirmed that the results of these meta-analyses were relatively robust. No publication bias was detected. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251019552 , identifier PROSPERO (CRD420251019552).

Abstract We present chromosome-level, phased diploid genome assemblies of two widely used human fibroblast cell lines: BJ (46,XY) and IMR-90 (46,XX). Using Oxford Nanopore, PacBio HiFi, and Hi-C sequencing data, we generated assemblies spanning 5.9 and 6.0 Gbp with diploid quality values exceeding QV 60. To validate structural integrity, we developed KaryoScope, an alignment-free tool for generating computational karyograms from k-mer feature databases. We identify >50 000 structural variants relative to T2T-CHM13v2.0, the majority of which are heterozygous and cell-line-specific. Combining reference-based and de novo gene annotation, we uncover a previously unreported 1 Mbp homozygous duplication at the 16p11.2 locus in BJ, demonstrating that even karyotypically normal cell lines can harbor clinically relevant submicroscopic rearrangements. We show that mapping publicly available short-read, RNA-seq, and ChIP-seq data to sample-matched diploid assemblies substantially improves read alignment and enables haplotype phasing of 23%–28% of short reads. The BJ and IMR-90 assemblies and associated variant calls are publicly available as a resource for the research community.

Background: The Spinal Cord Injury Model Systems (SCIMS) began studying traumatic SCI (TSCI) in 1970. The National Institute of Disability, Independent Living and Rehabilitation Research (NIDILRR) provided pilot funding during the 2021-2026 SCIMS funding cycle to perform an initial study of individuals with nontraumatic spinal cord injury (NTSCI). Objectives: To describe the demographic and etiological profiles and inpatient rehabilitation outcomes of the SCIMS NTSCI pilot cohort. Methods: This was a descriptive study of adults with NTSCI admitted to SCIMS centers who consented to medical records abstraction and completed survey questionnaires near the completion of inpatient rehabilitation. Results: One hundred eighty-seven people with NTSCI consented to participate and provided data. The etiology of patients’ NTSCI was degenerative vertebral causes ( n = 67), tumor-malignant ( n = 29), tumor-benign/unknown ( n = 16), vascular ( n = 28), infection ( n = 26), and other NTSCI causes ( n = 21). The average age was 59.2 years. Over 40% of the population was age 60-74 years. The population was 35% female, 59.5% non-Hispanic White, 21.6% non-Hispanic Black, and 11.4% Hispanic. Age, sex, race, and ethnicity distributions did not differ significantly across etiology groups. Only symptom onset time ( P = .002) and marital status ( P = .005) were significantly different between groups. Vascular disorders onset was less than a day in 60% of cases. Greater than 60% of tumor-malignant, vascular, and other NTSCI individuals were married or living with a partner. Conclusion: The US SCIMS program can recruit a population of NTSCI research participants that is consistent with previously published results. Ongoing study of NTSCI through the US SCIMS could provide important data akin to that available regarding TSCI.

Objective Immunohistochemically (IHC) measured transactive response DNA‐binding protein 43 (TDP‐43) inclusions are observed in Alzheimer's disease (AD) and are associated with medial temporal lobe atrophy. Accumulation of cryptic exons occurs in AD in response to TDP‐43 pathology. We aimed to assess relationships between IHC and biochemically measured insoluble TDP‐43 and cryptic exons and assess associations with hippocampal and amygdala volume loss and atrophy rates on magnetic resonance imaging (MRI). Methods Eighty‐one neuropathologically diagnosed AD cases were analyzed. For biochemistry, insoluble TDP‐43 was quantified using a Meso‐scale discovery (MSD) immunoassay. IHC‐TDP burden was quantified with digital histopathology. Cryptic RNAs were assessed via quantitative real‐time polymerase chain reaction (qRT‐PCR). Thirty‐eight cases had serial brain MRI. Hippocampal and amygdala volumes were calculated using FreeSurfer. Regression models were used to investigate associations among IHC‐TDP‐43 status/burden, MSD‐TDP status/levels, cryptic RNAs, and hippocampal and amygdala volumes and atrophy rates. Results IHC‐TDP(+) cases exhibited elevated levels of MSD‐TDP and cryptic RNAs ( KCNQ2 , STMN2 , and UNC13A ) and increased MSD‐TDP levels were associated with increased cryptic RNA levels, in the hippocampus and amygdala. IHC‐TDP(+) cases had smaller hippocampal and amygdala volumes compared to IHC‐TDP(−) cases. MSD‐TDP(+) cases had smaller hippocampal volumes and faster amygdala rates of atrophy compared with MSD‐TDP(−) cases. Higher KCNQ2 and UNC13A levels were associated with smaller amygdala volumes. Interpretation MSD‐TDP level is a reliable surrogate for IHC‐based TDP‐43 status. Both TDP‐43 and cryptic RNA levels are associated with reduced medial temporal volumes, suggesting cryptic exons may be playing a role in brain volume loss in AD. ANN NEUROL 2026;100:193–205

Abstract Amyotrophic lateral sclerosis (ALS) affects approximately 1.5 per 100,000 person-years in the United States, with a point prevalence of 3.8-5.6 per 100,000. ALS arises from the intersection of diverse pathogenic mechanisms spanning genetic mutations (C9orf72, SOD1, FUS, TARDBP), protein misfolding, RNA-metabolism defects, nucleocytoplasmic transport failure, prion-like propagation, mitochondrial dysfunction, and neuroinflammation. Increasing evidence from plasma proteomics and machine-learning studies indicates that these perturbations emerge years prior to clinical onset, highlighting an urgent need for mechanistically grounded patient stratification. At the same time, epidemiologic and molecular studies suggest unexpected parallels between ALS and cancer—including dysregulated DNA-damage responses, cell-cycle control, metabolic rewiring, and aberrant immune signaling—yet these cross-disease links remain fragmented and poorly mapped. We developed a multi-scale ALS-cancer knowledge graph integrating genetic, transcriptomic, proteomic, neuropathological, and longitudinal clinical datasets. Knowledge-graph completion approaches, including link prediction, graph embeddings, and embedding-based reasoning, were applied to infer missing edges and reveal latent modules connecting ALS-associated genetic lesions to oncogenic pathways implicated in genome instability, altered proliferation, metabolic remodeling, and immune dysregulation. This approach enables systematic interrogation of shared molecular programs across ALS and cancer, exposing under-characterized immune, metabolic, and axonal-transport circuits whose dual roles have been suggested but never comprehensively mapped. Predicted associations were evaluated using enrichment for established ALS genes, overlap with curated oncogenic and neurodegenerative pathways, and their ability to stratify patients by site of onset, progression rate, and biomarker signatures. These analyses generated patient-specific pathway fingerprints that (i) resolve dominant biological mechanisms across clinical subgroups, (ii) illuminate mechanistic intersections between neurodegeneration and malignancy, and (iii) prioritize repurposed oncology targets with potential relevance to ALS. This knowledge-graph framework provides a scalable and mechanistically informed strategy for classifying ALS patients, uncovering ALS-cancer pathway convergence, and supporting targeted therapeutic discovery across traditionally siloed disease domains. Citation Format: Vasileios Alevizos, Sabrina Edralin, Clark Xu, George A. Papakostas, Zongliang Yue. Mapping convergent neurodegenerative and oncogenic pathways in ALS using a multi-scale knowledge-graph framework [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6875.

The underlying immunopathogenesis of inflammatory arthritis (IA) immune-related adverse event (irAE) remains obscure. Unlike rheumatoid arthritis (RA), where autoantibodies and B cell dysfunction are central features, the contribution of humoral immunity to IA-irAE is unclear. Here, we performed immunophenotyping of peripheral blood from patients with IA-irAE and compared them with patients with seronegative RA, immune checkpoint inhibition–treated patients without irAE, and healthy controls. IA-irAE was marked with increased cytotoxic gene expression and metabolic activation in T cells and reduced CXCR3 and CCR6 expression in CD4 + T cells. Contrary to seronegative RA, patients with IA-irAE displayed no substantial elevation in autoantibody levels or atypical CD11c + CD21 − B cells. IA-irAE was further characterized by elevated levels of interleukin-6 (IL-6), IL-12, and type I interferon, which correlated with the T cell activation phenotypes. Together, our findings define IA-irAE as a disease with certain immunological features distinctive from RA, representing a potentially T cell–driven, autoantibody-independent autoimmunity. These results offer insights into immune tolerance breakdown and therapeutic targeting in irAEs.

ABSTRACT Behavioral and social factors (BSFs) substantially influence the risk, onset, and progression of Alzheimer’s disease and related dementias (ADRD), yet BSF-related knowledge remains scattered across heterogeneous sources, posing critical challenges for data harmonization and evidence synthesis. To address this gap, we present the B ehavioral S ocial Data and Knowledge O ntology for AD RD (BSO-AD), a FAIR-compliant semantic resource for representing and harmonizing BSFs and ADRD-related knowledge. BSO-AD was developed following established ontology design principles with reuse of existing ontologies and controlled terminologies, including the Social Determinants of Health Ontology, Drug Repurposing-Oriented Alzheimer’s Disease Ontology, AD-Onto, ICD-9-CM, and ICD-10-CM. Relationships between BSFs and ADRD were derived through literature mining. BSO-AD contains 1,690 classes, 152 object properties, 49 data properties, and 40 annotation properties. Ontology evaluation through Hootation-based domain expert review and a scalable LLM-assisted ontology assessment framework demonstrated high domain coverage and strong semantic coherence. BSO-AD provides a semantic foundation for data harmonization and knowledge integration in BSF-related ADRD research, while the LLM-assisted evaluation framework supports scalable and automated ontology assessment.

Variants in TMEM106B and GRN , which encode lysosomal proteins, interact through unknown mechanisms to increase the risk of age-related cognitive decline and neurodegeneration. Here, we show that these variants converge on a single molecular intermediate: the cleaved intra-lysosomal fibril core of TMEM106B, a precursor to amyloid fibrils that accumulate in the aging brain. A protein-coding TMEM106B risk variant (p.T185) drives fibril core accumulation by impairing its degradation and GRN risk variants amplify this effect. Mice over-expressing the fibril core develop hallmarks of neurodegeneration, and cryo-electron tomography reveals intra-lysosomal fibrils in cultured neurons, mice, and diseased human brain. In GRN -mutation carriers, in whom fibril burden is greatest, fibrils extrude through ruptured lysosomal membranes. These findings identify intra-lysosomal TMEM106B fibrillization as a convergent neurodegeneration mechanism and potential therapeutic target.