Robust detection of pathogenic variants that cause primary ciliary dyskinesia using RNA-seq of nasal mucosa.

Primary ciliary dyskinesia (PCD, OMIM 244400) is a rare genetic disorder that affects motile cilia and is characterised by impaired mucociliary clearance of the airway epithelium, which results in chronic upper and lower airway infections. While short-read next-generation sequencing technology has been used for the genetic testing of PCD, its effectiveness is limited in identifying variants in the gene because of the nearly identical pseudogene As we confirmed that the gene was not expressed in airway cells, we obtained nasal mucosa biopsy specimens for total RNA sequencing (RNA-seq) with library enrichment using exome oligos. Among the 34 nasal samples from patients suspected of having PCD, three aberrant splicing patterns in were identified in two samples.

KOnezumi-AID: Automation Software for Efficient Multiplex Gene Knockout Using Target-AID.

With the groundbreaking advancements in genome editing technologies, particularly CRISPR-Cas9, creating knockout mutants has become highly efficient. However, the CRISPR-Cas9 system introduces DNA double-strand breaks, increasing the risk of chromosomal rearrangements and posing a major obstacle to simultaneous multiple gene knockout. Base-editing systems, such as Target-AID, are safe alternatives for precise base modifications without requiring DNA double-strand breaks, serving as promising solutions for existing challenges.

Successful granulocyte-macrophage colony-stimulating factor inhalation therapy for recurrent autoimmune pulmonary alveolar proteinosis after lung transplantation: A case report.

Sargramostim, a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy, was recently approved for pharmaceutical use in Japan and shows promise as a treatment for autoimmune pulmonary alveolar proteinosis (APAP). For APAP patients with severe respiratory failure due to advanced lung fibrosis, lung transplantation is also a treatment option; however, APAP may recur after the procedure. Here, we report a case of successful sargramostim inhalation therapy for post-transplant APAP relapse in a patient who underwent living lung transplantation owing to severe fibrosis.

Cough and sputum symptoms reduce physical activity in patients with NTM pulmonary disease.

Although physical activity is an important outcome in patients with chronic respiratory disease, it has not been characterised in those with non-tuberculous mycobacterial pulmonary disease (NTM-PD). This study aimed to evaluate physical activity and its associated factors in patients with NTM-PD.This prospective observational study measured daily step counts using an accelerometer to assess physical activity (steps per day).

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.