Allele-specific silencing of a dominant mutation in familial amyotrophic lateral sclerosis type 4.

Amyotrophic lateral sclerosis 4 (ALS4) is an autosomal dominant motor neuron disease that is molecularly characterized by reduced R-loop levels and caused by pathogenic variants in (). encodes an RNA/DNA helicase that resolves three-stranded nucleic acid structures called R-loops. Currently, there are no disease-modifying therapies available for ALS4.

Optimizing Precision Medicine for Breast Cancer Brain Metastases with Functional Drug Response Assessment.

Unlabelled: The development of novel therapies for brain metastases is an unmet need. Brain metastases may have unique molecular features that could be explored as therapeutic targets. A better understanding of the drug sensitivity of live cells coupled to molecular analyses will lead to a rational prioritization of therapeutic candidates.

BMS-986158, a Small Molecule Inhibitor of the Bromodomain and Extraterminal Domain Proteins, in Patients with Selected Advanced Solid Tumors: Results from a Phase 1/2a Trial.

This phase 1/2a, open-label study (NCT02419417) evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of BMS-986158, a selective bromodomain and extraterminal domain (BET) inhibitor. Dose escalation was performed with 3 BMS-986158 dosing schedules: A (5 days on, 2 days off; range, 0.75-4.

Relationship of Physical Examination Technique to Associated Clinical Skills: Results from a Direct Observation Assessment.

Background: The purpose of this research was to use direct observation of the physical examination to elucidate the role physical examination technique plays in diagnostic accuracy. Physical examination is important for quality clinical care and requires multiple interrelated skills. The relationship of physical examination technique to related skills is poorly understood.