Exit interviews from two randomised placebo-controlled phase 3 studies with caregivers of young children with autism spectrum disorder.

Introduction: Autism spectrum disorder (ASD) is characterised by difficulty with social communication and restricted, repetitive patterns of behaviour. This study aimed to improve understanding of the ASD patient experience with the treatment (bumetanide) regarding the changes in core symptoms and to assess changes considered as meaningful. To achieve this, qualitative interviews were conducted with caregivers of patients in two phase 3 clinical trials (NCT03715153; NCT03715166) of a novel ASD treatment.

Disturbed spatial WNT activation - a potential driver of the reticularized skin phenotype in Systemic Sclerosis (SSc).

Objectives: Little is known on the mechanisms necessary to maintain the physiological adult human skin integrity. This study aims to quantitatively describe anatomical changes in systemic sclerosis (SSc)-skin compared to controls and investigate the underlying mechanisms.

Methods: Skin morphology was histologically assessed in twenty-three SSc-patients, eighteen controls and fifteen patients with hypertrophic scars.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.