A prospective trial comparing programmable targeted long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia.

The cerebellar ataxias (CAs) are a heterogeneous group of disorders characterized by progressive incoordination. Seventeen repeat expansion (RE) loci have been identified as the primary genetic cause and account for >80% of genetic diagnoses. Despite this, diagnostic testing is limited and inefficient, often utilizing single gene assays.

Posterior Inferior Cerebellar Artery Double Reimplantation Bypass for Treatment of a Dolichoectatic Posterior Inferior Cerebellar Artery Aneurysm: A Technical Report.

Background And Importance: The surgical management of posterior inferior cerebellar artery (PICA) aneurysms often poses a challenge because of tight surgical corridors, proximity to the lower cranial nerves, and the presence of perforators supplying the medulla. This report describes an excision and double reimplantation bypass for treatment of a dolichoectatic PICA aneurysm found on familial screening in a young man with a family history of aneurysmal subarachnoid hemorrhage.

Clinical Presentation: The patient underwent a right far-lateral craniotomy with excision of the dolichoectatic right PICA aneurysm with an additional outflow branch.

Epithelial outgrowth through mesenchymal rings drives lung alveologenesis.

Determining how alveoli are formed and maintained is critical to understanding lung organogenesis and regeneration after injury. To study the cellular dynamics of this critical stage of lung development, we have used scanned oblique-plane illumination microscopy of living lung slices to observe alveologenesis in real time at high resolution over several days. Contrary to the prevailing notion that alveologenesis occurs by airspace subdivision via ingrowing septa, we found that alveoli form by ballooning epithelial outgrowth supported by contracting mesenchymal ring structures.

Optimization of Potent and Selective Cyclohexyl Acid ERAP1 Inhibitors Using Structure- and Property-Based Drug Design.

Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves the -terminal amino acids of peptides, which can then bind onto major histocompatibility class I (MHC-I) molecules for presentation onto the cell surface, driving the activation of adaptive immune responses. In cancer, overtrimming of mature antigenic peptides can reduce cytotoxic T-cell responses, and ERAP1 can generate self-antigenic peptides which contribute to autoimmune cellular responses. Therefore, modulation of ERAP1 activity has potential therapeutic indications for cancer immunotherapy and in autoimmune disease.

Managing End of Life Care for the Critically Ill: A Novel Program to Deliver Bedside Critical Care Without Transfer to the Intensive Care Unit.

Navigating medical care at the end of life can be a challenging experience for patients. There are also significant resource burdens, including intensive care unit (ICU) admissions, accompanying terminal illness. For actively dying patients, developing a care plan based on patient goals and delivering care at the bedside can enhance patient well-being, avoid inappropriate transfers or interventions, and improve resource management.