Absorptivity Is an Important Determinant in the Toxicity Difference between Aristolochic Acid I and Aristolochic Acid II.

Inadvertent exposure to aristolochic acids (AAs) is causing chronic renal disease worldwide, with aristolochic acid I (AA-I) identified as the primary toxic agent. This study employed chemical methods to investigate the mechanisms underlying the nephrotoxicity and carcinogenicity of AA-I. Aristolochic acid II (AA-II), which has a structure similar to that of AA-I, was investigated with the same methods for comparison.

Longer-term survival, quality of life, and cost-effectiveness of conservative versus liberal oxygenation targets in critically ill children: a pre-specified analysis from Oxy-PICU, a multicentre, open, parallel-group, randomised controlled trial.

Background: Peripheral oxygen saturation (SpO) above 94% is typical in children in paediatric intensive critical care units (PICUs) who are receiving invasive ventilation and supplemental oxygen. In a previous report from the Oxy-PICU trial, we showed that lower (conservative) oxygenation targets (SpO 88-92%) are beneficial, showing small but statistically significant differences in duration of organ support and large but non-significant cost reductions at 30 days. In this pre-specified analysis of the Oxy-PICU trial, we compare longer-term outcomes and cost-effectiveness of conservative versus liberal (SpO >94%) oxygenation targets in children with emergency PICU admission.

UniVar: A variant interpretation platform enhancing rare disease diagnosis through robust filtering and unified analysis of SNV, INDEL, CNV and SV.

Background: Interpreting the pathogenicity of genetic variants associated with rare diseases is a laborious and time-consuming endeavour. To streamline the diagnostic process and lighten the burden of variant interpretation, it is crucial to automate variant annotation and prioritization. Unfortunately, currently available variant interpretation tools lack a unified and comprehensive workflow that can collectively assess the clinical significance of these types of variants together: small nucleotide variants (SNVs), small insertions/deletions (INDELs), copy number variants (CNVs) and structural variants (SVs).

Recommendations for the optimal introduction of novel antibiotics to treat uncomplicated gonorrhoea in the face of increasing antimicrobial resistance: a case study with zoliflodacin.

New, first-in-class oral antibiotics like zoliflodacin, developed in a public-private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase.