Discovery of CHF-6523, an Inhaled Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease.

The design of inhaled selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors for the treatment of inflammatory lung diseases was pursued. Knowledge-based design of a novel isocoumarin scaffold that was able to adopt a topology ensured the desired PI3Kδ selectivity. Achievement of low nanomolar cellular potencies through hinge binder group optimization, reduction of intrinsic permeability through head group optimization to extend lung retention, and screening of crystalline forms suitable for administration as dry powders culminated in the identification of compound .

Corrigendum: CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder.

[This corrects the article DOI: 10.3389/fphar.2024.

NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML.

Control of stem cell-associated genes by Trithorax group (TrxG) and Polycomb group (PcG) proteins is frequently misregulated in cancer. In leukemia, oncogenic fusion proteins hijack the TrxG homolog KMT2A and disrupt PcG activity to maintain pro-leukemogenic gene expression, though the mechanisms by which oncofusion proteins antagonize PcG proteins remain unclear. Here, we define the relationship between NUP98 oncofusion proteins and the non-canonical polycomb repressive complex 1.

The pediatric DAV-expert algorithm: A GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access device in children.

In pediatric patients, the choice of the venous access device currently relies upon the operator's experience and preference and on the local availability of specific resources and technologies. Though, considering the limited options for venous access in children if compared to adults, such clinical choice has a great critical relevance and should preferably be based on the best available evidence. Though some algorithms have been published over the last 5 years, none of them seems fully satisfactory and useful in clinical practice.

Growing teratoma syndrome in children and adolescents: Prevalence and surgical outcome.

Introduction: Patients affected by metastatic germ cell tumors may occasionally experience enlargement of masses with concurrent normalization of tumor markers during or after chemotherapy. This phenomenon is described as growing teratoma syndrome (GTS). The aim of the pre sent study is to assess the prevalence of GTS in the pediatric population and its implications in terms of surgical outcome.