A phase II study of ramucirumab and somatostatin analog therapy in patients with advanced neuroendocrine tumors.

Objectives: Well-differentiated neuroendocrine tumors (NET) are highly vascular tumors characterized by their expression of vascular endothelial growth factor (VEGF). This trial investigated the activity of ramucirumab, a monoclonal antibody that targets VEGF receptor-2 (VEGFR-2) and inhibits activity of VEGF, in combination with somatostatin analog therapy in patients (pts) with advanced extra-pancreatic NET.

Methods: We conducted a single-arm phase II trial enrolling pts with advanced, progressive extra-pancreatic NET.

Diversity of Trauma and Orthopaedic Trainees and Workplace Culture of Orthopaedic Training in the United Kingdom: Insights From the 2022 British Orthopaedic Trainee Association (BOTA) Census.

The British Orthopaedic Trainee Association (BOTA) conducted its latest census in 2022 of its membership. The results of wellbeing, diversity, equity, inclusion and bullying are discussed here. This highlighted several key focuses for improvement.

Protein-ligand binding affinity prediction using multi-instance learning with docking structures.

Introduction: Recent advances in 3D structure-based deep learning approaches demonstrate improved accuracy in predicting protein-ligand binding affinity in drug discovery. These methods complement physics-based computational modeling such as molecular docking for virtual high-throughput screening. Despite recent advances and improved predictive performance, most methods in this category primarily rely on utilizing co-crystal complex structures and experimentally measured binding affinities as both input and output data for model training.

Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents that are capable of neutralizing both enzyme-and non-enzyme-derived immunosuppressive IDO1 effects is therefore of high interest.

Older adults exhibit lesser smoothness despite increased caution than younger adults when navigating turns during walking.

Straight line walking currently dominates research into mechanisms associated with walking-related instability; however, the dynamics of everyday walking behavior are far more complex. The figure-8 walk test (F8W) is a clinically-feasible activity that focuses on turning mobility and provides a convenient and relevant task for understanding age-related differences in walking beyond our present knowledge of steady-state behavior. Our purpose was to investigate the effects of age (n = 30 older versus n = 31 younger adults) on path characteristics and the "smoothness" of turning mobility - herein measured via normalized center of mass jerk - during the F8W.