Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential.

The fungal Bromodomain and Extra-Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on-target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4.

Psychological mechanisms underlying the biased interpretation of numerical scientific evidence.

Do people use their statistical expertise selectively to reach preferred conclusions when evaluating scientific evidence, with those more expert showing more preferential bias? We investigated this motivated numeracy account of evidence evaluation but came to a different account for biased evaluation. Across three studies ( = 2,799), participants interpreted numerical data from gun control intervention studies. In Studies 1 and 2, participants reached accurate conclusions more frequently from scientific data when those data aligned with their political preferences than when they did not, an attitude congeniality effect.

Association Between the Sequence of β-lactam and Vancomycin Administration and Mortality in Patients with Suspected Sepsis.

Background: Timely antibiotic initiation is critical to sepsis management, but there are limited data on the impact of giving β-lactams first vs vancomycin first amongst patients prescribed both agents.

Methods: We retrospectively analyzed all adults admitted to 5 US hospitals from 2015-2022 with suspected sepsis (blood culture collected, antibiotics administered, and organ dysfunction) treated with vancomycin and a broad-spectrum β-lactam within 24h of arrival. We estimated associations between β-lactam vs vancomycin first strategies and in-hospital mortality using inverse probability weighting (IPW) to adjust for potential confounders.