Blunted CD40-responsive enhancer activation in CREBBP-mutant lymphomas can be restored by enforced CD4 T-cell engagement.

The CREBBP lysine acetyltransferase (KAT) is frequently mutated in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and has been studied using gene knock-out (KO) in murine and human cells. However, the majority of CREBBP mutations encode amino acid substitutions within the catalytic KAT domain (CREBBP KAT-PM) that retain an inactive protein and have not been extensively characterized. Using CRISPR gene editing and extensive epigenomic characterization of lymphoma cell-lines, we found that CREBBP KAT-PM lead to unloading of CREBBP from chromatin, loss of enhancer acetylation and prevention of EP300 compensation.

Using Mixed Methods to Evaluate Risk Minimisation Programs in Europe and the USA: An Innovative Blueprint.

Background: Significant methodological shortcomings have been documented to date in risk minimisation program evaluations for medicinal products, including overreliance on survey methods alone. Recently updated guidances from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recommend the use of frameworks and mixed methods designs to improve the rigor of these assessments.

Objective: The purpose of this paper was to exemplify how a mixed methods approach, guided by an implementation science framework, can be used to design the evaluation of a risk minimisation program.

Improved Post-Operative Outcomes and Reduced Narcotic Use With ERAS Protocol in a Pediatric Ambulatory Surgery Setting.

Compared to the adult literature, there are few enhanced recovery after surgery (ERAS) protocols standardized in the pediatric population. The objective of the current study is to determine if the implementation of an ERAS protocol would improve patient outcomes in the ambulatory pediatric urologic population. A retrospective analysis was performed on pediatric patients who underwent urologic procedures (circumcision, orchiopexy, hypospadias correction, and urethroplasty) in the ambulatory surgical setting affiliated with a tertiary pediatric hospital.

Assessing the Impact of Advanced Cooling Technology in Firefighting Gear during Live Burn Scenario.

Objective: A firefighter wears a standard safety coat, its model unchanged for many years, when tackling a fire. We designed a new cooling system coat with carbon nano tube-based fabric and pouches inside the coat for coolants and fans. The coats, one standard and the other still evolving, are compared on several metrics including core body temperature and thermal comfort.

Characterizing the Cellular Constituents of Proximal Airway Disease in Granulomatosis With Polyangiitis.

Objective: Granulomatosis with polyangiitis (GPA) is a rare multisystem autoimmune vasculitis. 10-20% of patients suffer life-threatening obstruction of their proximal airways. Although progress has been made in the treatment of systemic disease, ameliorating airway disease in GPA remains an unmet need arising from limited understanding of disease pathogenesis.