Citations

This study presents the first in vivo intraoperative measurement of the kinetic properties of spastic human muscle. Despite slower relaxation in spastic biceps, the force-frequency relationship was similar to that of the healthy gracilis muscle. This suggests that spasticity does not substantially alter frequency-dependent force summation, possibly due to similar fiber-type compositions and limited changes in calcium handling or myosin isoforms in human spastic muscle.

Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

Abstract With the increasing volume of biomedical experimental data, standardizing, sharing, and integrating heterogeneous experimental data across domains has become a major challenge. To address this challenge, we have developed an ontology-supported Study-Experiment-Assay (SEA) common data model (CDM), which includes 10 core and 3 auxiliary classes based on object-oriented modeling. SEA CDM uses interoperable ontologies for data standardization and knowledge inference. Building on the SEA CDM, we developed the Ontology-based SEA Network (OSEAN) relational database and knowledge graph, along with a set of ETL (Extract, Transform, Load) and query tools, and further applied them to represent 1,278 immune studies with over two million samples from three resources: VIGET, ImmPort, and CELLxGENE. Using simple, robust queries and analyses, our research identified multiple scientific insights into sex-specific immune responses, such as neutrophil degranulation and TNF binding to physiological receptors, following live attenuated and trivalent inactivated influenza vaccination. The novel SEA CDM system lays a foundation for establishing an integrative biodata ecosystem across biological and biomedical domains.

Abstract Background Breast cancer genome-wide association studies (GWAS) have identified more than 200 susceptibility loci, but most studies are dominated by European and East Asian populations. Methods We analyzed breast cancer GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR), and Hispanic/Latina (H/L) samples (159,297 cases and 212,102 controls). We estimated logit-scale SNP-based heritability, polygenicity, and cross-ancestry genetic correlation, partitioned heritability across functional annotations, and integrated GWAS results with the Tabula Sapiens single-cell atlas using scDRS+. Results The logit-scale heritability of breast cancer ranged from ℎ 2 =0.47 (SE = 0.07) in EAS to AFR ℎ 2 =0.61 (SE = 0.10), with no significant differences across ancestries (p=0.63). The estimated number of susceptibility markers in a sparse normal-mixture effects model also varied from 4,446 (SE = 3,100) in EAS to 8,308 (SE = 2,751) in AFR, but differences were not significant across ancestries (p=0.55). Cross-sample genetic correlations varied, with the strongest correlation between EUR and EAS (𝜌 = 0.79, SE = 0.08) and weakest between AFR and H/L (𝜌 = 0.26, SE = 0.24). Regulatory annotations were enriched for breast cancer heritability across samples. Integration with single-cell expression profiles implicated ancestry-shared associations with innate immune, secretory epithelial, and stromal cell types. Conclusion These results indicate substantial cross-ancestry sharing of breast cancer polygenic architecture, highlight a consistent contribution of regulatory variation, and identify convergent cellular contexts that motivate functional follow-up and inform expectations for the transferability and attainable performance of common-variant risk prediction across populations.

Increasing evidence strongly links neuroinflammation to Alzheimer’s disease (AD) pathogenesis. Peripheral monocytes are crucial components of the human immune system, but their contribution to AD pathogenesis is still largely understudied partially due to limited human models. Here, we introduce human cortical organoid microphysiological systems (hCO-MPSs) to study AD monocyte-mediated neuroinflammation. By culturing doughnut-shape organoids on 3D-printed devices within standard 96-well plates, we generate hCO-MPSs with reduced necrosis, minimized hypoxia, and improved viability. Using these models, we found that monocytes from AD patients exhibit increased infiltration ability, decreased amyloid-β clearance capacity, and stronger inflammatory response than monocytes from age-matched control donors. Moreover, we observed that AD monocytes induce pro-inflammatory effects such as elevated astrocyte activation and neuronal apoptosis. Furthermore, the marked increase in IL1B and CCL3 expression underscores their pivotal role in AD monocyte-mediated neuroinflammation. Our findings provide insight into understanding monocytes’ role in AD pathogenesis, and our lab-compatible MPS models may offer a promising way for studying various neuroinflammatory diseases.

Abstract Background Cabozantinib is indicated for hepatocellular carcinoma (HCC) following first-line (1L) sorafenib, but the 1L standard has shifted to immuno-oncology (IO)-based regimens. This study evaluated real-world outcomes among patients with advanced HCC receiving second-line (2L) cabozantinib following 1L therapies, including newer regimens. Patients and Methods US claims data were used to identify adults with advanced HCC initiating 2L cabozantinib monotherapy (index date). Patients were stratified into three 1L treatment cohorts: IO monotherapy/IO + IO combination therapy; IO + non–IO combination therapy; or tyrosine kinase inhibitor (TKI) monotherapy. Real-world time to treatment discontinuation (rwTTD), real-world time to next treatment or death (rwTNTD), real-world overall survival (rwOS), and cabozantinib dosing were assessed collectively and by cohort. Adverse events were assessed before/after cabozantinib initiation. Results Among 148 patients who received 2L cabozantinib, 28 were in the IO monotherapy/IO + IO combination therapy cohort, 54 in the IO + non–IO combination therapy cohort, and 66 in the TKI monotherapy cohort. Median rwTTD among all patients was 3.2 months; median rwTNTD was 7.6 months; 12-month rwOS rate was 61.6%. There were no significant differences in these outcomes among the three cohorts. Overall, 44.6% of patients initiated 2L cabozantinib at 60 mg/day, of whom 39.4% required a dose reduction; 37.8% initiated at 40 mg/day, of whom 16.1% had a dose reduction. Adverse event rates were similar before/after cabozantinib initiation. Conclusions Cabozantinib shows consistent effectiveness and safety in the 2L HCC setting following prior TKIs or IO-based regimens in real-world clinical practice. These findings may inform 2L treatment decisions.

The objective is to create an automated knowledge extraction tool for cancer research that builds high-quality academic corpora for LLM fine-tuning while investigating its effectiveness in interleukin-6 and bladder cancer domains. To address the current gap in knowledge retrieval techniques for cancer research data collection, we propose KnowledgePipeline, a novel automated tool that incorporates diverse aspects of academic papers and metadata. Our tool integrates content, co-citations, and co-authorship networks to construct domain-specific academic corpora suitable for fine-tuning LLMs. We leverage two LLMs (GPTJ-6.7B and Galactica30B) trained on domain-specific question-answer pairs from the refined data. The system’s evaluation focuses on both the quality of extracted knowledge and the performance of fine-tuned models in open-ended question-answering tasks. We see that KnowledgePipeline offers a scalable, automated framework for domain-specific knowledge retrieval and fine-tuned applications in cancer research, advancing literature discovery and addressing critical biomedical challenges. It achieved high relevance scores of 68% for IL-6 and 74.5% for bladder cancer, with a fine-tuned Galactica-30B model demonstrating promising capabilities.

Abstract Objective Determine relationship between frailty and hospital mortality, length of stay, cost, and medical and surgical complications in Zenker diverticulum surgery. Study Design Retrospective cross‐sectional. Setting National database. Methods Data from the National Inpatient Sample for 712 patients who underwent surgery for Zenker diverticulum 2016 to 2021 were analyzed using multivariate regressions. Frailty was defined as at least 1 frailty‐defining diagnosis from the Johns Hopkins ACG® Frailty Indicator. Elixhauser Comorbidity Index was calculated to quantify comorbidity burden. Results 12.2% of patients were identified as frail, 77.0% of whom had a weight loss or malnutrition diagnosis. Frailty predicted increased length of stay (mean, 4.09 days [95% CI: 2.98‐5.20]) and increased costs (mean, $10,500.36 [95% CI: $6885.76‐$14,114.95]). Frail patients were more likely to have medical complications compared to non‐frail patients (OR = 2.84 [95% CI: 1.66‐4.84]). Elixhauser Comorbidity Index was predictive of hospital mortality (OR = 1.78 [95% CI: 1.27‐2.51]) and likelihood of endoscopic surgical complications (OR = 1.25 [95% CI: 1.05‐1.47]), but frailty was not predictive of either. Conclusion Frailty is not associated with increased risk of surgical complications or mortality and is not an absolute contraindication to Zenker diverticulum surgery. Frailty predicts length of stay, costs, and medical complications in Zenker diverticulum surgery and should be used with comorbidity to stratify patient risk for surgery. Prospective studies involving frail patients could help develop a standardized method for assessing surgical fitness, potentially expanding treatment options and improving outcomes for this population. Level of Evidence 2.

Importance Women diagnosed with breast cancer at a young age are felt to have a higher risk for locoregional recurrence (LRR) regardless of type of local therapy. Objective To assess the long-term incidence of isolated LRR by molecular subtype in a modern multicenter cohort of young women. Design, Setting, and Participants This cohort study, a multicenter prospective study named the Young Women’s Breast Cancer Study, enrolled 1302 women diagnosed with breast cancer at 40 years or younger from 2006 to 2016. Treatment information and incident LRR (ipsilateral breast/chest or lymph node recurrence) were self-reported on study surveys and confirmed with medical record review; molecular subtype was determined by record review. Analysis was reported from February 2023 to May 2025. Main Outcomes and Measures Cumulative incidence of isolated LRR was calculated using the Kaplan-Meier method; hazard ratios were estimated by Cox proportional hazards regression. Results The cohort included 1135 women with stage I through III breast cancer who had a median follow-up of 10.1 years (range, 0.4-16.3 years). The age at diagnosis was younger than 30 years for 145 patients (12.8%), 31 to 35 years for 318 patients (28.0%), and 36 to 40 years for 672 patients (59.2%). There were 59 isolated local recurrences (5.2%) and 4 isolated regional recurrences (0.4%). Among patients with local therapy and subtype data available (n = 1128), 366 (32%) had luminal A–like tumors; 240 (21%), luminal B–like tumors; 231 (20%) luminal ERBB2 positive (+)–like (formerly HER2 positive); 90 (8%) ERBB2 +-like; and 201 (18%) triple negative. A total of 346 women (30%) had breast-conserving therapy (BCT) (98% of whom had radiation), 296 (26%) unilateral mastectomy, and 487 (43%) bilateral mastectomy. Of women who had mastectomy, 425 (54%) had radiation. The cumulative incidence of LRR at 10.1 years by subtype was as follows: luminal A, 4.4% (range, 1.0%-6.9%); luminal B, 4.7% (range 1.8%-7.7%); luminal ERBB2 +, 6.1% (range, 3.1%-8.3%); ERBB2 +, 2.2% (range, 0%-6.3%); and triple negative, 6.5% (range, 4.2%-10.1%). The cumulative incidence of LRR by locoregional treatment type at 10.1 years was 6.7% after BCT (range, 4.3%-10.1%), 6.5% after mastectomy without radiation (range, 0%-7.7%), and 2.4% after mastectomy with radiation (range, 1%-4.2%). Although mastectomy with radiation was associated with the lowest risk of LRR on multivariable analysis, when examined within molecular subtype, there were no differences seen. Conclusions and Relevance In this contemporary cohort of women diagnosed with breast cancer at age 40 years or younger, risk of isolated LRR was relatively low (5.6%) at a median follow-up of 10.1 years, and significant differences were not seen by tumor subtype. Concerns for long-term risk of LRR should not influence surgical decision-making with young women, irrespective of molecular subtype.