Immune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.

Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.

Osteoporotic fracture risks of thiazides and dihydropyridines in angiotensin modulator users.

Unlabelled: This study examined the impact of thiazide and RAAS antihypertensive medications vs DHP-RAAS medications on fracture risk. The close alignment of such settings with clinical use, combined with the potential bone benefits of ACEis and ARBs, provides enhanced accuracy in bone health evidence.

Purpose: To determine whether thiazides, combined with either angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), offer bone-protective benefits compared with dihydropyridine (DHP) drugs combined with ACEi or ARB.

Structural evolution and nanodomain formation in blend films of a block copolymer and homopolymer.

This study explores the concurrent formation of surface perforations, parallel cylinders, and double gyroids in symmetric PS--PMMA/hPS blend films during isothermal annealing at 205 and 240 °C. By controlling the weight fraction ratio of PS--PMMA to hPS at 75/25, we systematically examined the impact of film thickness and annealing temperature on nanodomain development. Using GISAXS and SEM, we observed that thin films rapidly formed surface perforations and underlying parallel cylinders at both annealing temperatures.

Homozygous variant in translocase of outer mitochondrial membrane 7 leads to metabolic reprogramming and microcephalic osteodysplastic dwarfism with moyamoya disease.

Background: Impaired mitochondrial protein import machinery leads to phenotypically heterogeneous diseases. Here, we report a recurrent homozygous missense variant in the gene that encodes the translocase of outer mitochondrial membrane 7 (TOMM7) in nine patients with microcephaly, short stature, facial dysmorphia, atrophic macular scarring, and moyamoya disease from seven unrelated families.

Methods: To prove the causality of the TOMM7 variant, mitochondrial morphology, proteomics, and respiration were investigated in CRISPR/Cas9-edited iPSCs-derived endothelial cells.