Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Interaction between the leg recovery test and subjective measures of fatigue in handball players: short-, mid-, and long-term assessment.

Background: The physical and mental demands of handball during training or competition often lead to fatigue which can impair performance. Many attempts have been made to assess the level of fatigue in athletes either by objective (neuromuscular performance) or subjective (questionnaires) measures, however, their interplay over short-, mid-, and long-term periods is currently unknown. Knowledge about both types of assessments is important as load management by coaches is traditionally based on direct adjustments following a training session, adjustments of content structure of training weeks between games, as well as adjustments of load management over the entire competitive season.

Evaluation of Pelvic MRI-to-CT Deformable Registration for Adaptive MR-Guided Particle Therapy.

Purpose: We aim to assess the magnetic resonance imaging (MRI)-to-CT deformable image registration (DIR) quality of our treatment planning system in the pelvic region as the first step of an online MRI-guided particle therapy clinical workflow.

Materials And Methods: Using 2 different DIR algorithms, ANAtomically CONstrained Deformation Algorithm (ANACONDA), the DIR algorithm incorporated in RayStation, and Elastix, an open-source registration software, we retrospectively assessed the quality of the deformed CT (dCT) generation in the pelvic region for 5 patients. T1- and T2-weighted daily control MRI acquired prior to treatment delivery were used for the DIR.

Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.

Development of an understanding of membrane nanodomains colloquially known as "lipid rafts" has been hindered by a lack of pharmacological tools to manipulate rafts and protein affinity for rafts. We screened 24,000 small molecules for modulators of the affinity of peripheral myelin protein 22 (PMP22) for rafts in giant plasma membrane vesicles (GPMVs). Hits were counter-screened against another raft protein, MAL, and tested for impact on raft , leading to two classes of compounds.