Citations

Abstract Background/Purpose Diagnosing wrist ligament injuries is challenging; early detection and treatment are important to prevent osteoarthritis progression. Interosseous proximity maps, a proxy measure for joint space, can be generated from volumetric imaging data and may provide important information about wrist health. Artificial intelligence (AI) could enhance accuracy of noninvasive diagnosis based on imaging-derived metrics. This work demonstrates feasibility of AI training using synthetic proximity map data generated from finite element models (FEMs). Methods Personalized wrist FEMs for two asymptomatic participants were created from four-dimensional computed tomography-derived anatomic and kinematic data. Monte Carlo sampling varied 22 ligament material properties and simulated 7,500 unique injury scenarios generating 9,000,000 labeled red, green, and blue (RGB) images of interosseous proximity vector fields from FEM-derived motions. Images were associated with 17 descriptive metrics, including gross wrist angles and bone surface pairs, and used to develop mixed-input convolutional neural networks (CNNs). Model performance was evaluated for identifying specific ligament injuries. Results Average area under receiver operating characteristic curve (AUROC) for CNNs was 0.757 across all injury types and kinematics. In a subset with clinically-relevant functional angles, the average AUROC was 0.824. Best-performing individual ligament AUROCs ranged from 0.807 to 0.999. Sensitivities and specificities exceeded 0.99 for some ligament injury simulations under specific wrist angles and bone surface pairs. Conclusion This study demonstrates the feasibility of using synthetic data from FEMs to train AI models for classifying wrist ligament injuries. Proximity-based RGB images may be a relevant biomarker of ligamentous injury.

Abstract The Tau Global Conference 2025, hosted by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation, convened international experts from academia, industry, government, and philanthropy to explore advances and challenges in tauopathy research. The meeting highlighted progress across tau biology, including emerging models of tau regulation, degradation, and propagation; advances in biomarker development for the diagnosis and staging of tauopathies; and evolving therapeutic strategies targeting diverse aspects of tau pathophysiology. Discussions also emphasized the importance of cross‐sector collaboration, and global initiatives to address disparities in tau research. This report synthesizes key insights from the conference and underscores the critical role of interdisciplinary, biomarker‐driven, and globally inclusive approaches in accelerating the translation of tau research into effective clinical applications.

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type–specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced lysosomal biogenesis contributed to the observed neuroprotection. These findings reveal potentially novel roles for microglial VRAC in regulating seizure outcomes and microglia-neuron interactions.

Abstract Senescent cells accumulate with age and contribute to tissue dysfunction, yet their identification in tissues is challenging due to low abundance, heterogeneous phenotypes, and the lack of specific markers. Senescence-associated features span multiple subcellular compartments, including nuclear DNA damage foci, cytosolic protein changes, and perinuclear alterations, each requiring tailored detection strategies. To overcome these challenges, we developed SenoQuant ( https://github.com/HaamsRee/senoquant ), a versatile software designed for comprehensive, accurate, and unbiased spatial quantification and prediction of senescence markers across diverse tissue contexts. Utilizing AI models, SenoQuant enables precise nuclear and cytoplasmic segmentation and detection of senescence markers across low- and high-plex imaging modalities, applicable to cultured cells and tissue sections from mice and humans. The platform also supports custom AI models; for example, we built SenCeption, a proof-of-concept predictor of single-cell p21 status from DAPI-stained nuclei in human skin. Available as a free napari plugin, SenoQuant is widely accessible to researchers. By providing a unified approach to senescence analysis and prediction, SenoQuant opens new opportunities for exploring the complex biology of senescence and its impacts on aging and disease.

ABSTRACT Purpose Substantial endothelial cell loss (∼80%) occurs after keratoplasty. Corneal rigid and scleral lenses are frequently prescribed to manage irregular astigmatism and high refractive error, but lens wear may contribute to hypoxic stress. The relationship between various lens wear and corneal stress after penetrating keratoplasty remains unclear. This study characterizes cell density distribution in post‐keratoplasty corneas and evaluates its influence on swelling during lens wear. Methods Participants ≥5 years post‐surgery, with or without habitual lens wear, were enrolled. Specular microscopy measured endothelial cell density in central, superior, inferior, superotemporal, and superonasal corneal quadrants (@3 mm). Baseline corneal thickness maps (>2 h after waking without lens wear) were acquired using Scheimpflug imaging (Pentacam). Wearers applied habitual lenses and all participants returned 6–8 h later for imaging. Nonparametric tests assessed cell density variation by quadrant and lens designs. Linear mixed models evaluated associations between endothelial parameters and corneal swelling while accounting for within‐subject correlation, repeated measures, lens type, location, and interactions. Results Twenty‐five participants (31 eyes) from three centers were included; 90% had keratoconus preoperatively. Four wore large‐diameter scleral lenses (13%), nine wore small‐diameter scleral lenses (29%), 12 wore corneal rigid lenses (39%), and six did not wear lenses (19%). Cell density across quadrants averaged 780 ± 240 cells/mm 2 . Central thickness decreased slightly in non‐lens‐wearing eyes (−0.3%) but increased in lens‐wearing eyes (1.9% ± 3.1%). Central cell density showed a weak negative correlation with swelling ( r = −0.39, p = 0.03). Compared with non‐lens wearers, corneal rigid ( p = 0.02) and large diameter scleral lenses ( p = 0.05) generated greater swelling; smaller diameter scleral lenses did not. Conclusions Although all eyes fitted with various lens designs were clear, lower central cell density correlated with increased swelling during lens wear, except when smaller diameter scleral lenses were worn. Clinically, however, cell density does not seem to be a robust predictor of corneal swelling induced by lens wear post‐keratoplasty.

Background The wide reach and unique short audiovisual nature of TikTok make it a potential modality for disseminating information about orthopaedic surgery to both patients and medical professionals. However, only a few recent studies have assessed the purpose and creators of orthopaedic surgery content on TikTok. Methods The top 100 most-liked TikTok videos about orthopaedic surgery topics were included for analysis. Data reflecting video and creator account characteristics were collected. Video validity was determined by three reviewers according to the DISCERN criteria and Kruskal-Wallis H tests were performed to correlate validity to creator and video type. Results The majority of videos were created by orthopaedic surgeons (n=57/100) and for entertainment purposes (n=82/100). Orthopaedic surgeons had the highest DISCERN score (34.7) and greater video reliability compared to all other creator types (H = 59.0-67.1, all p<0.001). Videos made for educational and procedural purposes had the highest DISCERN scores (38.9 and 40.5, respectively) while entertainment videos had lower reliability (H=-56.7 to -113.5, all p<0.05). Conclusion The most popular orthopaedic surgery-related videos on the TikTok platform are primarily being created by orthopaedic surgeons for entertainment purposes. Less frequently were videos made to educate, describe procedures, and explain the lifestyle of an orthopaedic surgeon. Potential applications of utilizing the platform by orthopaedic surgeons include case or research discussions, educational videos on different pathologies, recruitment of prospective students to the field, and entertainment highlighting a day in the life of an orthopaedic surgeon.

ABSTRACT Background Men with castration‐resistant prostate cancer (CRPC) who have a pre‐existing history of cardiovascular disease (CVD) or other comorbidities are often excluded from clinical trials involving oral androgen receptor pathway inhibitors (ARPi). In this study, we compared all‐cause and prostate cancer‐specific mortality among CRPC patients, with and without a pre‐existing history of CVD, receiving ARPi compared to chemotherapy. Methods Men with CRPC were identified using the Surveillance, Epidemiology, and End Results‐Medicare Linked Database from 2004 to 2015. Patients were grouped into two analytical cohorts by drug use. Inverse probability treatment weights (IPTW)‐adjusted Cox models and Fine‐Gray subdistribution hazards models were used to evaluate associations between ARPi and chemotherapy, and between ENZ and AA for all‐cause mortality and cancer‐specific mortality separately. Results The study cohort included 1438 men with CRPC. Nearly 54.4% of patients had a pre‐existing history of CVD. Patients with a pre‐existing history of CVD had a higher incidence of all‐cause and prostate cancer‐specific mortality compared to patients without a history of CVD (all‐cause mortality: 69.7% vs. 59.3%, prostate cancer‐specific mortality: 56.0% vs. 49.5%, respectively). In the pre‐existing history of CVD cohort, the IPTW‐adjusted Cox model showed a significantly lower all‐cause mortality in patients who received APRi, enzalutamide, and abiraterone, versus chemotherapy (IPTW‐adjusted hazard ratio [AHR], 0.56; 95% Confidence Interval [CI], 0.48–0.64; p ‐value < 0.001). Further, the IPTW‐adjusted competing risk model showed significantly lower prostate cancer‐specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW‐AHR, 0.48; 95% CI, 0.41 to 0.57; p ‐value < 0.001). In the without pre‐existing history of CVD cohort, the adjusted Cox model showed significantly lower all‐cause mortality in patients who received APRi than those who received chemotherapy (IPTW‐AHR, 0.49; 95% CI, 0.41–0.60; p ‐value < 0.001). Whereas the IPTW‐adjusted competing risk model showed significantly lower prostate cancer‐specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW‐AHR, 0.52; 95% CI, 0.42–0.64; p ‐value < 0.001). Conclusion In this population‐based cohort of older men with castration‐resistant prostate cancer, treatment with oral androgen receptor pathway inhibitors was associated with lower estimated risks of all‐cause and prostate cancer–specific mortality compared with chemotherapy in patients with and without pre‐existing CVD. These findings add real‐world comparative effectiveness evidence for patient populations not well represented in randomized clinical trials; however, given the observational design and limitations of administrative data, residual confounding and unmeasured clinical differences may have influenced the results.

Abstract Brief inhalation of carbon dioxide (CO 2 ) has been proposed to counteract transient hypocapnia by enhancing oxygen unloading, vasodilation, and sympathetic modulation. Despite these potential ergogenic mechanisms, CO 2 has rarely been investigated in the exercise context. The present study investigated whether brief CO 2 inhalation (iCO 2 ) influences performance and recovery during high‐intensity interval exercise. Nine healthy adults completed two randomized, single‐blinded crossover trials of repeated cycling intervals at 85% peak work rate until volitional exhaustion or cadence dropped below 60 rpm, with a minimum 2‐min interval duration required and 3‐min active recovery between bouts. Participants inhaled 5% CO 2 or room air (15 breaths) before and after each exercise bout. Gas exchange, cardiovascular responses, and perceived exertion were assessed. Total exercise time was similar between trials; however, participants completed more intervals with iCO 2 . During the first interval, iCO 2 increased exercise duration and VO 2 . At matched exercise time, perceived exertion and dyspnea were lower with iCO 2 . During recovery, systolic blood pressure was lower and heart rate was higher following iCO 2 . Brief iCO 2 improved first‐interval performance, altered cardiovascular recovery, and reduced perceptual strain but did not extend overall exercise duration. These findings suggest iCO 2 may transiently modulate tolerance and autonomic‐vascular responses during high‐intensity interval exercise.