Publications by Year: 2026

OBJECTIVES: While sexual dimorphism of knee osteoarthritis (KOA) is well established, sex-specific clinical manifestations-particularly involving peri-articular tissues undetectable by radiography-remain underexplored. This study aimed to define female-specific alterations in joint integrity, peri-articular muscle quality, symptom presentation, and the transcriptomic landscape of peri-articular muscles, with the goal of uncovering the mechanistic contributions of each to KOA pathophysiology.

METHODS: Forty-nine participants (32 females, 17 males; Kellgren-Lawrence grade 1-2) underwent clinical assessment, including (1) quantitative ultrasound assessment of the vastus medialis (VM) and rectus femoris (RF) muscles; (2) MRI to assess joint integrity; and (3) patient-reported outcomes. Principal component analysis (PCA) followed by receiver operating characteristic curve analysis were conducted to identify discriminative sex-specific imaging and symptom features. Correlation-based network analysis examined sex-specific interdependencies among clinical variables. Publicly available transcriptomic datasets were analyzed to identify molecular drivers underlying female-specific muscle quality changes.

RESULTS: Despite similar radiographic severity and symptom presentation across the sexes, female individuals exhibited greater cartilage degeneration and higher fatty infiltration in the VM and RF. These features were central to sex separation in the PCA, with both features identified as network hubs in female individuals, indicating interconnected muscle-joint degeneration. Transcriptomic analysis revealed enrichment of adipogenic reprogramming in female individuals, suggesting aberrant intramuscular fat programming.

DISCUSSIONS: Our findings uncover a distinct female-specific musculoskeletal phenotype in early-stage KOA, characterized by muscle degeneration and cartilage deterioration undetectable by radiography. These female-specific clinical manifestations may be due, at least partly, to aberrant adipogenic programming in muscle. These findings provide mechanistic and clinical insight into sexual dimorphism in KOA.

Repetitive head impacts (RHIs) in soccer have been associated with long-term risk for neurodegenerative disease. The pathophysiology is largely unknown. This study aims to investigate alterations in cerebral blood flow (CBF) in athletes exposed to RHI compared with athlete controls (CTL). Given that females are known to exhibit higher CBF than males, we also explore sex-specific differences. Finally, we investigate the relationship between CBF and neuropsychological functioning and RHI measures. This study includes 82 amateur athletes (mean age 22.8 ± 1.6 years; 48.9% female). Participants underwent 3T magnetic resonance imaging and completed neuropsychological testing, including questionnaires on stress, resilience, and sleep quality, and computerized assessment of executive function, memory, and processing speed. CBF was assessed using MR pulsed arterial spin labeling. Analysis of covariance was applied to assess the effect of RHI exposure and sex on CBF. Associations between CBF and neuropsychological functioning were analyzed using linear regression models. The analysis was conducted hierarchically, beginning with global gray matter CBF (level 1), followed by cortical and deep gray matter (level 2), and finally brain lobes (level 3). Correction for multiple comparisons was applied at each hierarchical level using false discovery rate, with a significance threshold set at p < 0.05 after correction. We found higher CBF in athletes with RHI exposure (RHI group) compared with athletes with <5 years of exposure to RHI (CTL group; Δ 95% confidence interval [95% CI] = 3.9 [0.5, 7.3] mL/100g/min, p = 0.027). Female athletes with RHI exposure exhibited higher CBF in the global gray matter compared with female CTL (Δ[95% CI] = 6.6 [1.6, 11.5] mL/100g/min, p = 0.013). Among males, individuals with RHI exposure demonstrated higher CBF in the occipital lobe compared with male CTL (Δ[95% CI] = 4.9 [0.3, 9.5] mL/100g/min, p = 0.047). There were no statistically significant associations between CBF and neuropsychological functioning. In the RHI group, years of soccer play were positively associated with whole-brain CBF. Results from this study suggest an association between RHI exposure and higher CBF, a measure of brain activity. Furthermore, we report sex-specific patterns of higher CBF in individuals exposed to RHI, with more widespread elevated CBF in women and more localized higher CBF in men. While these findings highlight the importance of investigating sex-specific effects, there were no associations between CBF and neuropsychological functioning. Future studies are warranted to determine the clinical relevance of the observed sex-specific effects to RHI.

Background/Objectives: Although cross-sectional muscle quality has shown prognostic relevance, the impact of temporal changes in muscle composition in septic shock has not been fully explored. This study aimed to investigate whether deterioration in muscle quality on serial computed tomography (CT) scans is associated with mortality in patients with septic shock. Methods: We conducted a retrospective single-center study using a prospectively collected registry of adult patients with septic shock between May 2016 and May 2022. Patients who underwent CT on the day of emergency department (ED) presentation and had a CT performed more than 180 days earlier were included. Muscle quality maps were generated and segmented based on CT attenuation values into normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA), and intramuscular adipose tissue area. Differences between the ED and prior CT scans were also calculated. The primary outcome was the 28-day mortality. Results: Among the 768 enrolled patients, the 28-day mortality was 18.0%. Both survivors and non-survivors showed a significantly greater increase in LAMA (20.8 vs. 9.8 cm2) and a greater decrease in NAMA (-26.0 vs. -18.8 cm2). Multivariate analysis identified increased LAMA as an independent risk factor for 28-day mortality (adjusted OR 1.03; 95% CI: 1.01-1.04; p < 0.01). Conclusions: An increase in LAMA on serial CT scans was associated with higher short-term mortality in patients with septic shock, suggesting that temporal degradation of skeletal muscle quality may serve as a potential prognostic marker.

NF2-related Schwannomatosis (NF2-SWN) remains a disorder with few effective treatment options. Patients develop vestibular schwannomas (VSs) on both auditory nerves, which gradually impair hearing and often result in significant communication difficulties, social withdrawal, and higher rates of depression. Progress in understanding NF2-SWN biology and translating discoveries into therapies has been slowed by the absence of robust animal models that faithfully reproduce both tumor behavior and the associated neurological deficits. In this review, we summarized the development of animal models that not only reproduce tumor growth in the peripheral nerve microenvironment but also reproduce tumor-induced neurological symptoms, such as hearing loss and ataxia. We further highlight the currently available organotypic models for NF2-SWN. Together, these systems provide an essential foundation for advancing mechanistic studies and accelerating the development of effective therapies for this devastating disorder.

Background/Objectives: Early and accurate characterization of endometrial cancer (EC) is crucial for patient management, but current imaging modalities lack in diagnostic accuracy and ability to assess molecular profiles. The aim of this study is to evaluate hybrid [18F]FDG PET/MRI's diagnostic accuracy in EC staging and role in predicting tumor aggressiveness, molecular characterization, and recurrence. Methods: A prospective study (ClinicalTrials.gov, ID:NCT04212910) evaluating EC patients undergoing [18F]FDG PET/MRI before surgery (2018-2024). Histology, immunohistochemistry, and patients' follow-up (mean FU time: 3.13y) were used as the reference standard. [18F]FDG PET/MRI, PET only, and MRI only were independently reviewed to assess the diagnostic accuracy (ACC), sensitivity (SN), specificity (SP), and positive/negative predictive value (PPV, NPV). Imaging parameters were extracted from [18F]FDG PET and pcT1w, T2w, DWI, and DCE MRI. Spearman's correlations, Fisher's exact test, ROC-AUC analysis, Kaplan-Meier survival curves, log-rank tests and Cox proportional hazards models were applied. Results: Eighty participants with primary EC (median age 63 ± 12 years) were enrolled, with 17% showing LN involvement. [18F]FDG PET/MRI provided ACC = 98.75%, SN = 98.75%, and PPV = 100% for primary tumor detection, and ACC = 92.41%, SN = 84.62%, SP = 93.94%, PPV = 73.33%, and NPV = 96.88% for LN detection. PET/MRI parameters predicted LN involvement (AUC = 79.49%), deep myometrial invasion (79.78%), lymphovascular space invasion (82.00%), p53abn (71.47%), MMRd (74.51%), relapse (82.00%), and postoperative administration of adjuvant therapy (79.64%). Patients with a tumor cranio-caudal diameter ≥ 43 mm and MTV ≥ 13.5 cm3 showed increased probabilities of recurrence (p < 0.001). Conclusions: [18F]FDG PET/MR showed exceptional accuracy in EC primary tumor and LN detection. Derived parameters demonstrated potential ability in defining features of aggressiveness, molecular alterations, and tumor recurrence.

Background/Objectives: To identify the barriers and facilitators to accessing healthcare following intimate partner violence (IPV)-related brain injury (BI). Methods: Sixteen adult women participated in interviews about their experience of accessing healthcare following IPV-related BI. Interviews were transcribed verbatim and analyzed using the interpretative descriptive (ID) approach to identify themes and subthemes in the data. Results: Two themes, each with six subthemes related to healthcare seeking for IPV-related BI were identified: Theme 1-Deciding to seek and ability to access healthcare, comprising (a) severity of injury; (b) impact of injury; (c) ability to access medical services; (d) self-blame, fear, shame, and guilt; (e) contextual influences on healthcare seeking; and (f) previous negative interactions; and Theme 2-Complexity in identifying IPV-related BI, comprising (a) trauma can affect recall of events; (b) inability to distinguish IPV-related trauma or aging outcomes from BI sequelae; (c) the importance of trust in disclosure; (d) healthcare professionals need to ask the right questions and respond in the right way; (e) the complex nature of disclosure creates challenges for diagnosis; and (f) fear of being dismissed or judged. Conclusions: Many context-related factors influence whether women can seek treatment for IPV-related BIs. These factors need to be understood by first responders and medical professionals to improve the likelihood and speed of treatment seeking. Furthermore, challenges and fears associated with disclosure of IPV prevent women from seeking proper treatment. IPV training could be helpful in ensuring women feel safe with disclosure.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated clinical success in hematologic malignancies but has limited efficacy in solid tumors due to tumor microenvironment (TME) barriers that impede CAR T cell recognition, infiltration, and sustained function. Traditional 2D assays inadequately recapitulate these constraints, necessitating improved in vitro models. This study validated a 3D tumor spheroid platform using an agarose microwell system to generate uniform B7-H3-positive spheroids from multiple solid tumor cell lines, enabling the evaluation of CAR T cell activity. TME-relevant immune modulation under 3D conditions was analyzed by flow cytometry for B7-H3, MHC I/II, and antigen processing machinery (APM), followed by co-culture with B7-H3 CAR T cells to assess cytotoxicity, spheroid integrity, tumor viability, and CAR T cell activation, exhaustion, and cytokine production. Two human cancer-cell-line-derived spheroids, DU 145 (prostate cancer) and SUM159 (breast cancer), retained B7-H3 expression, while MC38 (mouse colon cancer)-derived spheroids served as a B7-H3 negative control. Under 3D culture conditions, DU 145 and SUM159 spheroids acquire TME-like immune evasion characteristics and specifically downregulated MHC-I and APM (TAP1, TAP2, LMP7) with concurrent upregulation of MHC-II and calreticulin. Co-culture showed effective spheroid infiltration, cytotoxicity, and structural disruption, with infiltrating CAR T cells displaying higher CD4+ fraction, activation, exhaustion, effector/terminal differentiation, and IFN-γ/TNF-α production. This 3D platform recapitulates critical TME constraints and provides a cost-effective, feasible preclinical tool to assess CAR T therapies beyond conventional 2D assays.