Commissioning and clinical implementation of an Autoencoder based Classification-Regression model for VMAT patient-specific QA in a multi-institution scenario.

BACKGROUND AND PURPOSE: To commission and implement an Autoencoder based Classification-Regression (ACLR) model for VMAT patient-specific quality assurance (PSQA) in a multi-institution scenario. MATERIALS AND METHODS: 1835 VMAT plans from seven institutions were collected for the ACLR model commissioning and multi-institutional validation. We established three scenarios to validate the gamma passing rates (GPRs) prediction and classification accuracy with the ACLR model for different delivery equipment, QA devices, and treatment planning systems (TPS). The prediction performance of the ACLR model was evaluated using mean absolute error (MAE) and root mean square error (RMSE). The classification performance was evaluated using sensitivity and specificity. An independent end-to-end test (E2E) and routine QA of the ACLR model were performed to validate the clinical use of the model. RESULTS: For multi-institution validations, the MAEs were 1.30-2.80% and 2.42-4.60% at 3%/3 mm and 3%/2 mm, respectively, and RMSEs were 1.55-2.98% and 2.83-4.95% at 3%/3 mm and 3%/2 mm, respectively, with different delivery equipment, QA devices, and TPS, while the sensitivity was 90% and specificity was 70.1% at 3%/2 mm. For the E2E, the deviations between the predicted and measured results were within 3%, and the model passed the consistency check for clinical implementation. The predicted results of the model were the same in daily QA, while the deviations between the repeated monthly measured GPRs were all within 2%. CONCLUSIONS: The performance of the ACLR model in multi-institution scenarios was validated on a large scale. Routine QA of the ACLR model was established and the model could be used for VMAT PSQA clinically.

Deacetylation of metabolic enzymes by Sirt2 modulates pyruvate homeostasis to extend insect lifespan.

Diapause in insects is akin to dauer in Caenorhabditis elegans and hibernation in vertebrates. Diapause causes a profound extension of lifespan by low metabolic activity. However, the detailed regulatory mechanisms for low metabolic activity remain unknown. Here, we showed that low pyruvate levels are present in the brains of diapause-destined pupae of the cotton bollworm Helicoverpa armigera, and three enzymes pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and phosphoglycerate mutase (PGAM) are closely correlated with pyruvate homeostasis. Notably, Sirt2 can deacetylate the three enzymes to increase their activity in vitro. Thus, low Sirt2 expression in the brains of diapause individuals decreases PK and PEPCK protein levels as well as PGAM activity, resulting in low pyruvate levels and low tricarboxylic acid cycle activity and eventually inducing diapause initiation by low metabolic activity. These findings suggest that pyruvate is a checkpoint for development or lifespan extension, and Sirt2 is a negative regulator to extend lifespan in insects.