Basic Science and Pathogenesis.

Progranulin is a secreted pro-protein that is necessary for maintaining lysosomal function and exerts anti-inflammatory and neurotrophic effects in the brain. Loss-of-function GRN mutations, most of which cause progranulin haploinsufficiency, are a major autosomal dominant cause of frontotemporal dementia (FTD). Other GRN variants are associated with risk for FTD, Alzheimer's disease (AD) and Parkinson's disease.

Nursing home staff's experiences with the implementation of an automated blister packaging system for solid, orally ingestible drugs: a qualitative study in Northern Italy.

Objectives: To explore nursing home (NH) staff's experiences implementing an automated blister packaging system for solid, orally ingestible drugs.

Design: This was a descriptive qualitative study. Semistructured interviews were used for data collection, and qualitative content analysis was applied for data analysis.

Allogeneic haematopoietic stem-cell transplantation for children with refractory systemic juvenile idiopathic arthritis and associated lung disease: outcomes from an international, retrospective cohort study.

Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.

Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT.

Pan-KRAS inhibitors BI-2493 and BI-2865 display potent anti-tumor activity in tumors with KRAS wild-type allele amplification.

KRASG12C selective inhibitors, such as sotorasib and adagrasib, have raised hopes of targeting other KRAS mutant alleles in cancer patients. We report that KRAS wild-type amplified tumor models are sensitive to treatment with the small molecule KRAS inhibitors BI-2493 and BI-2865. These pan-KRAS inhibitors directly target the "OFF" state of KRAS and result in potent anti-tumor activity in pre-clinical models of cancers driven by KRAS mutant proteins.

Cytosolic S100A8/A9 promotes Ca supply at LFA-1 adhesion clusters during neutrophil recruitment.

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions.