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Synthetic lethality in homologous recombination (HR)-deficient cancers caused by Poly (ADP-ribose) polymerase inhibitors (PARPi) has been classically attributed to its role in DNA repair. The mode of action of PARPi and resistance thereof are now believed to be predominantly replication associated. Therefore, effective combinatorial approaches of targeting replication fork processing along with HR-downregulation to target HR-proficient and possibly PARPi-resistant tumors are warranted.
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Sci Rep
March 2025
Sports Medicine Outpatient Clinic, University Leipzig, Leipzig, Germany.
The American Heart Association (AHA) guidelines assess heart failure (HF) via comorbidities, laboratory markers, and echocardiography, while the New York Heart Association (NYHA) classification evaluates functional capacity. The primary objective of this study was to investigate the correlation between objectified HF-related symptoms and cardiac and muscular exercise capacity in Stage B HF patients with non-reduced ejection fraction. As secondary endpoints, we stratified this analysis for subgroups of NYHA classes to evaluate the primary endpoint for different levels of impairment and for sex to address for differences between men and women.
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Background: Long-term patterns of depressive symptoms among patients with heart failure, specifically those with a preserved ejection fraction (HFpEF), and their relationship with prognoses are not well studied.
Methods: This analysis included 609 participants from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) at baseline and at 1-year, 2-year and 3-year intervals.
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Bioorg Chem
March 2025
State Key Laboratory Base for Eco-Chemical Engineering in College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, #1 Ningde Road, Qingdao 266073, China. Electronic address:
Natural cytotoxic peptides (NCPs) are emerging sources of novel anticancer chemotherapeutics. Especially, Melittin, which is the major component of bee venom and the first-in-class NCP, has been considered as a promising anticancer scaffold. Nevertheless, as a classical linear, cationic, amphipathic, and membrane-lytic peptide, Melittin may be easily degraded by proteases, suffering from poor stability, moderate anticancer durability, and severe hemolysis.
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Res Dev Disabil
March 2025
Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth PL6 8BU, UK. Electronic address:
Background: A high proportion of adults with intellectual disabilities receive psychotropic medicines, often in the absence of a mental illness but primarily off-licence for behaviours that challenge.
Aim: To provide a cross-sectional view of the pattern of psychotropic medicine prescriptions with the reasons for their use among adults with intellectual disabilities in community settings in the UK.
Method: We collected psychotropic prescription data on 112 adults with intellectual disabilities who lived in community homes or supported accommodations in the UK.
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