Investigating the origins of the mutational signatures in cancer.

Most of the risk factors associated with chronic and complex diseases, such as cancer, stem from exogenous and endogenous exposures experienced throughout an individual's life, collectively known as the exposome. These exposures can modify DNA, which can subsequently lead to the somatic mutations found in all normal and tumor tissues. Understanding the precise origins of specific somatic mutations has been challenging due to multitude of DNA adducts (i.

Generation of BT-Amide, a Bone-Targeted Pyk2 Inhibitor, Effective Oral Administration, for the Prevention of Glucocorticoid-Induced Bone Loss.

Glucocorticoid-induced osteoporosis (GIOP) is the leading cause of iatrogenic osteoporosis due to the widespread clinical use of glucocorticoids (GC) as immunosuppressants. Previous research identified the proline-rich tyrosine kinase 2, Pyk2, as a critical mediator of GC-induced bone loss, and that blocking Pyk2 could protect the skeleton from adverse GC actions. However, systemic administration of current Pyk2 inhibitors causes harmful side effects, such as skin lesions.

Stimulating ambulance specialist nurse students' ethical reflections by high-fidelity simulation.

Ethical competence in professional practice can be considered essential among nurses and nurses in ambulance care encounter ethical dilemmas frequently. To enhance ethical competence among students in the ambulance specialist nursing program, high-fidelity simulation scenarios including ethical dilemmas were introduced as a learning activity. The research aim was to investigate the usefulness of high-fidelity simulation in ambulance specialist nurse education to teach ethical reasoning when caring for children.

Hybrid emergency care at the home for patients - A multiple case study.

Introduction: Healthcare systems worldwide are facing numerous challenges, such as an aging population, reduced availability of hospital beds, staff reductions and closure of emergency departments (ED). These issues can exacerbate crowding and boarding problems in the ED, negatively impacting patient safety and the work environment. In Sweden a hybrid of prehospital and intrahospital emergency care has been established, referred to in this article as Medical Emergency Team (MET), to meet the increasing demand for emergency care.

Liquid Biopsy in Progressing Prostate Cancer Patients Starting Docetaxel with or Without Enzalutamide: A Biomarker Study of the PRESIDE Phase 3b Trial.

Background And Objective: The PRESIDE (NCT02288247) randomized trial demonstrated prolonged progression-free survival (PFS) with continuing enzalutamide beyond progression in metastatic castration-resistant prostate cancer (mCRPC) patients starting docetaxel. This study aims to test the associations of PFS and circulating tumor DNA (ctDNA) prior to and after one cycle (cycle 2 day 1 [C2D1]) of docetaxel and with a liquid biopsy resistance biomarker (LBRB; plasma androgen receptor [AR] gain and/or circulating tumor cells [CTCs] expressing AR splice variant 7 [CTC-AR-V7]) prior to continuation of enzalutamide/placebo.

Methods: Patients consenting to the biomarker substudy and donating blood before starting docetaxel with enzalutamide/placebo (N = 157) were included.