Many diseases are caused by pathogenic expansion of microsatellite repeats. Longread sequencing allows evaluation of the content of such expanded repeats. Friedreich ataxia patients are typically homozygous for an expanded GAA repeat in intron 1 of the FXN gene. Longread whole genome sequencing identified expanded composite alleles, consisting of substantial tracks of tandem GGA triplets within the expanded GAA repeat. In a prospective series of 112 unrelated patients, we found that...

Here, we present a detailed workflow for clustering and enhanced sampling of biomolecular conformations using the ShapeGMM methodology. This approach fits a probabilistic model of biomolecular conformations rooted in the idea that the free energy can be expressed in terms of local fluctuations in atomic positions around metastable states. We demonstrate using a single model system how to generate and fit equilibrium molecular dynamics simulation data. We then demonstrate how to use the resulting...

Cancer risk in children with VACTERL, a nonrandom co-occurrence of ≥ 3 defects (vertebral, anal, cardiac, tracheoesophogeal fistula, renal, and limb), remains unclear. We evaluated this association in a population-based study. We analyzed data from the Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Study, a US registry linkage cohort. VACTERL was defined as the presence of ≥ 3 associated defects. Cox regression was applied to estimate hazard ratios (HRs) and 95% confidence...

CONCLUSION: Mortality due to Alzheimer's disease in elderly patients with metabolic syndrome has shown a dramatic increase. The highest AAMRs were observed in women, NH Black/African Americans and residents of the West and metropolitan areas. An individualized approach to patient management is necessary moving forward to curb disease progression.

CONCLUSION: Caregivers with pre-existing high strain may be especially vulnerable to the adverse impacts of unexpected public health emergencies such as COVID-19 and could benefit most from targeted interventions to foster resilience.