Rapid and scalable personalized ASO screening in patient-derived organoids.

Personalized antisense oligonucleotides (ASOs) have achieved positive results in the treatment of rare genetic disease. As clinical sequencing technologies continue to advance, the ability to identify patients with rare disease harbouring pathogenic genetic variants amenable to this therapeutic strategy will probably improve. Here we describe a scalable platform for generating patient-derived cellular models and demonstrate that these personalized models can be used for preclinical evaluation of patient-specific ASOs.

Comparison of Kinetic, Automated, Tangent Screen, and Novel Disposable Perimetry for the Evaluation of Dermatochalasis and Blepharoptosis.

Purpose: To compare a novel disposable ptosis visual field device to conventional perimetry devices for the evaluation of dermatochalasis and/or blepharoptosis.

Methods: Forty patients from a single academic center participated in this prospective, observational study. Patients with dermatochalasis (skin resting on the eyelashes) and/or blepharoptosis (marginal reflex distance 1 ≤2 mm) were included.

Strongyloides Hyperinfection Syndrome (SHS) in a Patient With Prolonged Intensive Care Unit (ICU) Exposure: A Case Report.

Strongyloides hyperinfection syndrome (SHS) is a severe manifestation of the Strongyloides parasite, often occurring in immunocompromised patients due to the inability to subdue larvae autoinfection. As the parasitic burden increases, the patient can develop worsening respiratory symptoms that mimic common pathologies such as chronic obstructive pulmonary disease (COPD). The parasite is endemic to the Appalachian region as well as subtropical and tropical areas worldwide.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests.

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.

Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell transcription factor, MECOM, underlies one key driver mechanism in largely incurable AMLs. How MECOM results in such aggressive AML phenotypes remains unknown.