PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma.

PAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. Here we show that PAX3-FOXO1 RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved in pyrimidine synthesis, including dihydrofolate reductase (DHFR). Consequently, PAX3-FOXO1 cells display increased sensitivity to inhibition of DHFR by the chemotherapeutic drug methotrexate, and this dependence is rescued by provision of pyrimidine nucleotides.

Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection.

Background: Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC populations. Variations in MSCs' secretory and proliferation profiles, and their proteomic and transcriptional characteristics significantly influence their therapeutic potency, highlighting the need for enhanced characterization methods to better predict their efficacy. This study aimed to evaluate the biological characteristics of MSCs from different tissue origins, selecting the most promising line for further validation in a K18-hACE2 mouse model of SARS-CoV-2 infection.

Decrease in Fracture Rate with Mandatory Bone-protecting Agents in the EORTC 1333/PEACE-3 Trial Comparing Radium-223 Combined with Enzalutamide Versus Enzalutamide Alone: A Safety Analysis.

Bone health is central to the management of patients with metastatic castration-resistant prostate cancer (mCRPC). International guidelines recommend giving a bone-protecting agent (BPA) to patients with mCRPC and bone metastases. However, the data supporting these recommendations were generated before androgen receptor pathway inhibitors (ARPIs) were available.

Androgen Receptor Pathway Inhibitor Therapy for Advanced Prostate Cancer: Secondary Analysis of a Randomized Clinical Trial.

Importance: The open-label randomized phase 2 LACOG0415 trial evaluated 3 treatment strategies for patients with advanced castration-sensitive prostate cancer (CSPC): androgen deprivation therapy (ADT) plus abiraterone acetate and prednisone (AAP), apalutamide (APA) alone, or APA plus AAP.

Objective: To investigate the association of ADT plus AAP, APA alone, or APA plus AAP with health-related quality of life (HRQOL) in patients with advanced CSPC in the LACOG0415 trial.

Design, Setting, And Participants: The LACOG0415 randomized clinical trial comprised 128 patients with advanced CSPC who were randomized (1:1:1) to 1 of 3 treatment arms from October 16, 2017, to April 23, 2019.

Optimizing Management of Acute Respiratory Distress Syndrome in Critically Ill Surgical Patients: A Systematic Review.

Introduction: This systematic review aims to evaluate the optimal management of acute respiratory distress syndrome (ARDS) in critically ill surgical patients, specifically focusing on positioning, extracorporeal membrane oxygenation (ECMO) use, ventilation, fluid resuscitation, and pharmacological treatments.

Methods: A systematic review was conducted utilizing four databases including PubMed, Google Scholar, EMBASE, and ProQuest. This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with The International Prospective Register of Systematic Reviews.