Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response.

The DNA-damaging agent Gemcitabine (GEM) is a first-line treatment for pancreatic cancer, but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs, including kinase inhibitors, but the experimental evidence for such rationale is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines.

Infants with Excessive Weight Gain while Exclusively Breastfeeding: Follow-Up at 36 Months.

Rapid weight gain in infancy is associated with an increased risk of later adiposity. Very rarely, however, exclusively breastfed infants experience excessive weight gain (EWG) during the period of exclusive breastfeeding (EBF) when breast milk is the only source of nutrition. We investigated growth and body composition at 36 months in children experiencing EWG during EBF.

Circulating lipocalin-2 across the adult lifespan.

Lipocalin-2 (LCN2), a hormone produced by adipocytes, osteoblasts, and renal tubular cells, is implicated in age-related diseases, including cardio-metabolic disease. To understand the role LCN2 may play in pathological states, we first need to elucidate the relationship between circulating LCN2 with indices of cardio-metabolic health during "normal" aging. This study examined the relationship between serum levels of LCN2, age, and cardio-metabolic measures across the adult lifespan in males and females.

First-line osimertinib compared to earlier generation TKIs in advanced EGFR-mutant NSCLC: A real-world survival analysis.

Objectives: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies.

PROTOCOL: Non-criminal justice interventions for countering cognitive and behavioural radicalisation amongst children and adolescents: A systematic review of effectiveness and implementation.

This is the protocol for a Campbell systematic review. The objectives are as follows. (1) Examine whether secondary and tertiary interventions delivered outside of the criminal justice system are effective at countering the cognitive and behavioural radicalisation of children and adolescents by synthesising evidence relating to relevant primary and secondary outcomes of effectiveness.