Multiplexed base editing identifies functional gene-variant-context interactions.

Human genome sequencing efforts in healthy and diseased individuals continue to identify a broad spectrum of genetic variants associated with predisposition, progression, and therapeutic outcomes for diseases like cancer . Insights derived from these studies have significant potential to guide clinical diagnoses and treatment decisions; however, the relative importance and functional impact of most genetic variants remain poorly understood. Precision genome editing technologies like base and prime editing can be used to systematically engineer and interrogate diverse types of endogenous genetic variants in their native context .

Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma.

Purpose: Survival for patients with multiple myeloma (MM) has improved but outcomes remain heterogeneous. Consistent diagnostic identification of high-risk disease is desirable to address unmet patient need. The aim was to investigate the consistency of association of co-occurrence of high-risk cytogenetic abnormalities (HRCAs) with prognosis in patients with newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM), and across a range of treatment modalities.

Unified force and motion adaptive-integral control of flexible robot manipulators.

In this paper, we propose an adaptive nonlinear strategy for the motion and force control of manipulators with flexible joints. Our approach provides force control when in contact and robust motion control in its absence, all without the need for a control switch. This self-tuning behaviour for mixed contact/non-contact scenarios results from a unified formulation of force and motion control, with an integral transpose-based inverse kinematics core and adaptive update laws to cope with the manipulator flexibility and the contact stiffnesses.

Polygenic Susceptibility to Diabetes and Poor Glycemic Control in Stroke Survivors.

Background And Objectives: Type 2 diabetes mellitus (T2DM) is highly genetically determined, and polygenic susceptibility to T2DM (PSD) increases the risk of worse glycemic control and adverse vascular outcomes. Its role in stroke patients remains unknown. We aim to determine whether higher PSD is associated with worse glycemic control in stroke survivors.

Pomalidomide, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Survival and Subgroup Analyses From the OPTIMISMM Trial.

Introduction: In the OPTIMISMM trial, pomalidomide/bortezomib/dexamethasone (PVd) significantly prolonged median progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) in lenalidomide-exposed relapsed and refractory multiple myeloma (RRMM). We report final overall survival (OS) and updated efficacy analyses.

Methods: Adults with RRMM who had 1-3 prior regimens, including lenalidomide (≥ 2 cycles), were assigned (1:1) to PVd or Vd.