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Biology subjects

Miller, E. Y.

Publications and source records attributed to Miller, E. Y..

2 recordsLinked to original sources

Integrating Machine Learning with Musculoskeletal Simulation Improves OpenCap Video-Based Dynamics Estimation

ObjectiveMusculoskeletal dynamics influence the progression and rehabilitation of many movement-related conditions. However, accurately estimating whole-body dynamics using accessible tools, like smartphone video, remains challenging. Physics-based and machine learning (ML)-based dynamic predictions each offer advantages, but both approaches struggle to achieve both high accuracy and physical realism. Here, we created a hybrid ML-simulation framework to improve estimates of ground reaction forces, joint moments, and joint contact forces from smartphone video kinematics. MethodsWe used machine learning models to predict ground reaction forces and centers of pressure from video-based kinematics. The hybrid framework generates a dynamic simulation that tracks predicted forces and kinematics while enforcing dynamic consistency. We compared the hybrid models performance with a simulation-only approach and with ML forces applied through inverse dynamics. We evaluated mean absolute error from lab-based reference data (inverse dynamics from marker and force plate data) from 10 individuals walking. ResultsThe hybrid model had 29% lower joint moment errors compared to simulations (p<0.001) and 45% lower errors compared to the ML-only approach (p<0.001). It also reduced vertical ground force error by 40% compared to simulations. The hybrid approach improved key metrics of joint loading related to knee osteoarthritis progression by 13-30% compared to simulations. ConclusionOur hybrid model outperforms purely physics-based and ML approaches for estimating dynamics from smartphone video during walking. SignificanceThese methods move us closer to fast, accurate, and scalable assessments of whole-body musculoskeletal dynamics, which will enable large out-of-lab biomechanics studies and precision treatment of gait-related conditions.

physiology↗

Lactate cannot replace glucose for maintaining the viability of mouse and human glioma cells

ObjectivesAerobic lactic acid fermentation (the "Warburg effect") is associated with OxPhos insufficiency and altered energy metabolism in most cancers. Whether lactate is a major fuel in cancer cells remains debated. This study investigated whether lactate could serve as a metabolic fuel in glioma cells and replace glucose to support viability. MethodsA bioluminescence ATP assay and calcein-AM/EthD-III double-staining were used to measure ATP content and viability in mouse (VM-M3, CT-2A) and human (U-87MG) glioma cells differing in cell biology and genetic background. Viability was assessed in thioglycollate-elicited peritoneal macrophages (TPMs) from VM/Dk and C57BL/6J mice, used as syngeneic non-neoplastic controls for VM-M3 and CT-2A gliomas, respectively. Oxygen consumption rate (OCR) was determined using the Resipher system. ResultsLactate alone failed to sustain ATP content and viability in all glioma cell lines. ATP content and viability were lower in cancer cells cultured in glutamine and lactate than in glucose and glutamine. In contrast, lactate alone sustained over 45% viability in both TPM models. Moreover, viability was similar between TPMs cultured in glutamine and lactate and in glucose and glutamine. In human U-87MG, lactate addition under severe glucose restriction increased OCR and viability. A low dose of the glycolysis inhibitor 2-deoxy-D-glucose abolished both increases. ConclusionsOur results suggest non-neoplastic mouse TPMs utilize lactate more effectively than mouse glioma cells. In U-87MG, lactate utilization appears glycolysis-dependent, given its sensitivity to 2-deoxy-D-glucose. In conclusion, our data does not support lactate as a major oxidative fuel for viability in mouse and human glioma cells.

cancer biology↗