Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell.

Shatavari supplementation during eight weeks of resistance training increases training load, enhances skeletal muscle contractility and alters the skeletal muscle proteome in older women.

Introduction: Shatavari is a herbal dietary supplement that may increase skeletal muscle strength in younger and older adults. Shatavari contains compounds with both estradiol-like and antioxidant properties, which could enhance muscle function. Postmenopausal women may derive the greatest benefit, as estrogen deficiency adversely impacts skeletal muscle function.

Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases.

Background: Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is often not specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants.

Methods: Using dedicated pipelines to address the technical challenges posed by the mtDNA - circular genome, variant heteroplasmy, and nuclear misalignment - single nucleotide variants, small indels, and large mtDNA deletions were called from exome and genome sequencing data, in addition to RNA-sequencing when available.

Donor site morbidity of upper extremity flaps in head and neck reconstruction.

Objective: This retrospective cohort study aims to compare donor site morbidity of three commonly used upper extremity flaps used in head and neck reconstructive surgery: scapular tip free flap (STFF), radial forearm free flap (RFFF), and pectoralis major pedicled flap (PMPF).

Methods: The billing database of an urban, academic, tertiary otolaryngology practice was queried to identify patients who underwent STFF, RFFF, and PMPF from 2020 to 2023. The primary outcome was identification of donor site pain and need for physical therapy (PT) referral after undergoing reconstruction.