This abstract has been withheld from publication.

Cerebral palsy (CP) is a neurological disorder caused by early brain damage, often leading to spasticity, an involuntary muscle contraction, and is a major cause of childhood disability. This study focuses on spastic CP, the most common subtype, to investigate muscle tissue abnormalities at the cellular level. The goal is to compare regional stiffness differences and distributions between control and CP skeletal muscle. This study will utilize a combination of Atomic Force Microscopy (AFM) with Two-Photon imaging processed in Leica’s AI Image Analysis Software (AIVIA) with the goal of uncovering disease mechanisms and informing less invasive treatments. Data is processed into images via pixel-point calculations and aligned with manually assisted software. Overlaid AFM and Two-Photon images are segmented into distinct objects based on tissue components. Images are quantified by object using built-in AIVIA software and data is exported for further comparison. Initial analysis reveals differences in young’s modulus (YM) values between control and CP sample myofiber and endomysium. Further, coefficients of variance show a normalized difference in deviation within components of control and CP images. Ongoing analysis aims to further characterize these differences and their implications for muscle function in CP. Identifying these physiological changes will improve understanding of CP pathology and may support the development of therapies best suited to treat contracture.

NK-92, an IL-2-dependent human natural killer (NK) cell line, is known for its broad cytotoxic potential and emergence as a novel immunotherapy across a range of cancers. Yet, its role in hepatocellular carcinoma (HCC) remains largely unexplored. To better understand the functional capacity of NK-92 cells against HCC, we evaluated NK-92–mediated cytotoxicity against SNU-423 tumor cells across three E:T ratios (1:1, 2.5:1, and 5:1) and assessed viability at 24, 48, and 72 hours. NK-92 cells demonstrated potent time- and dose-dependent cytotoxicity against SNU-423 cells, with near-complete elimination of tumor cells at 2.5:1 and 5:1 E:T ratios by 48 hours, with no further reduction at 72 hours, indicating a cytotoxic plateau. Cytotoxic efficiency was statistically indistinguishable between the 2.5:1 and 5:1 E:T ratios at all time points, indicating 2.5:1 as the threshold for maximal NK-92–mediated killing. These findings establish NK-92 cells as a viable cytotoxic effector against HCC in vitro. Future characterization of perforin and granzyme B expression and cytokine production will help understand the mechanisms underlying NK-92–mediated cytotoxicity and establish its potential as an immunotherapeutic strategy for hepatocellular carcinoma.

Obesity, type 2 diabetes mellitus (T2DM), and weight loss are associated with increased fragility fracture risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed, yet their effects on skeletal outcomes remain uncertain. Our objective is to evaluate the association between GLP-1 RA initiation and 3-year fragility fracture risk compared with dipeptidyl peptidase-3 inhibitor (DPP-4i) initiation among adults with T2DM. This retrospective target trial emulation used the TriNetX Research Network, a multicenter US electronic health record database. Adults aged 50-90 years with T2DM who newly initiated a GLP-1 RA or DPP-4i were followed up for 3 years. The primary outcome was incident fragility fracture, defined as fractures after low-energy trauma. Cohorts were propensity-score matched. Time-varying mediation analyses evaluated the contribution of change in body mass index (BMI) and hemoglobin A1c (HbA1c). After matching,133,606 patients were included, with 66,803 per group. GLP-1 RA initiation was associated with lower fragility fracture risk compared with DPP-4i initiation (HR, 0.79, 95% CI, 0.76-0.83; ARR 0.79%; NNT 126). Mediation analyses showed that cumulative BMI loss was associated with increased fracture risk, while the direct association between GLP-1 RA use and lower fracture risk persisted. Among adults with T2DM, GLP-1 RA initiation was associated with lower 3-year fragility fracture risk compared with DPP-4i initiation, independent of changes in BMI and HbA1c.