Small molecule protein assembly modulators with pan-cancer therapeutic efficacy.

Two structurally unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against Mpox virus (formerly known as monkeypox virus) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity with reasonable pharmacokinetics. Non-toxicity is demonstrated in a non-cancer cell line and in mice at doses achieving drug exposure at active concentrations.

LGBTQ+ Health Inequities in a Rural, Conservative Context: Alabama Compared with Other Southern States.

Objectives: There are no statewide statistics regarding the health of lesbian, gay, bisexual, transgender, and queer (LGBTQ+) Alabamians. To fill this gap, we used data collected by the Southern Equality Research and Policy Center to compare Alabama with other southern US states regarding the health and well-being of LGBTQ+ people.

Methods: We tested for unadjusted differences between Alabama and other southern states using χ tests for dichotomous outcomes and the Wilcoxon rank-sum test for ordinal outcomes.

Toward defining the Anthropocene onset using a rapid increase in anthropogenic fingerprints in global geological archives.

One of the remaining issues regarding the Anthropocene is the lack of stratigraphic evidence indicating when the cumulative human pressure from the early Holocene began to fundamentally change the Earth system. Herein, we compile anthropogenic fingerprints from various high-precision-dated proxy records for 137 global sites to determine the age of the unprecedented surge in these records over the last 7700 y. The cumulative number of fingerprints revealed an unprecedented surge in diverse anthropogenic fingerprints starting in 1952 ± 3 CE, corresponding to the onset of the Great Acceleration.

Non-Operative Management of Uncomplicated Appendicitis in Children: Can Patients Be Discharged From the Emergency Department?

Introduction: Non-operative management of uncomplicated appendicitis in children is a safe alternative to laparoscopic appendectomy. The purpose of this study is to determine the feasibility of nonoperative outpatient management of uncomplicated appendicitis in pediatric patients.

Methods: A standardized pathway for non-operative outpatient management of uncomplicated appendicitis in children (NOMA-C) was implemented in a university pediatric surgery practice starting October 2021.

Use of Janus kinase inhibitors before and after European Medicines Agency safety recommendations: a retrospective study.

Background: Safety recommendations for Janus kinase inhibitors (JAKi) issued by the European Medical Agency (EMA) in 2023 could potentially influence treatment patterns for rheumatoid arthritis (RA) drugs, but little is known about the impact of these recommendations in routine clinical care.

Methods: We retrospectively analyzed the German RHADAR rheumatology database for adult patients with RA and documentation of a new therapy with a JAKi, tumor necrosis factor inhibitor (TNFi), or interleukin-6 receptor inhibitor (IL-6Ri). Data were grouped into half-yearly intervals from quarter (Q)2/2020 to Q3/2023.