Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Electrical Heterogeneity in Hispanic Background Subpopulations: The HCHS/SOL.

Background: The Hispanic/Latino population is not uniform. Prevalence and clinical outcomes of cardiac arrhythmias in ethnic background subgroups are variable, but the reasons for differences are unclear. Vectorcardiographic Global Electrical Heterogeneity (GEH) has been shown to be associated with adverse cardiovascular outcomes.

Molecular Pharmacology of Dasatinib Provides Unique Insights into the Mechanistic Basis of Success and Failure of Targeted Cancer Therapy.

Despite the enthusiasm for targeted cancer therapies in preclinical studies and the success of a select few drugs, many promising drug candidates fail in clinical trials. The gap between preclinical promise and clinical outcomes underscores the need to investigate factors influencing the success or failure of targeted therapies. Dasatinib, an inhibitor of Abl and Src protein tyrosine kinases, is highly effective toward chronic myeloid leukemia (CML) by targeting BCR-Abl, but it is ineffective against solid tumors when targeting Src kinases.

Cardiomyocyte S1PR1 promotes cardiac regeneration via AKT/mTORC1 signaling pathway.

Lower vertebrates and some neonatal mammals are known to possess the ability to regenerate cardiomyocyte and fully recover after heart injuries within a limited period. Understanding the molecular mechanisms of heart regeneration and exploring new ways to enhance cardiac regeneration hold significant promise for therapeutic intervention of heart failure. Sphingosine 1-phospahte receptor 1 (S1PR1) is highly expressed in cardiomyocytes and plays a crucial role in heart development and pathological cardiac remodeling.

in enhancing the effect of defactinib on gastric cancer cells via the inhibition of FAK phosphorylation.

Background: Chromosome segregation 1 like () overexpression can promote proliferation and migration in cancer. In previous study, we found that CSE1L expression was higher in gastric cancer (GC) tissues compared to normal tissues. However, the biological function and molecular mechanism of CSE1L in GC remains unclear.

Barriers to Research Faced by High-Income Versus Low- and Middle-Income Country Otolaryngologists and Otolaryngology Residents.

Objective: This study aims to compare research productivity and barriers to research between high-income countries (HICs) and low- and middle-income countries (LMICs) otolaryngologists.

Study Design: Cross-sectional survey.

Setting: International survey.

Increased usage of doxycycline for young children with Lyme disease.

Background: The 2018 Infectious Disease Committee of the American Academy of Pediatrics stated that up to 3 weeks or less of doxycycline is safe in children of all ages. Our goal was to examine trends in doxycycline treatment for children with Lyme disease.

Methods: We assembled a prospective cohort of children aged 1 to 21 years with Lyme disease who presented to one of eight participating Pedi Lyme Net centers between 2015 and 2023.

Adaptive Cost-Benefit Control Fueled by Striatal Dopamine.

The twenty-first century has brought forth a deluge of theories and data shedding light on the neural mechanisms of motivated behavior. Much of this progress has focused on dopaminergic dynamics, including their signaling properties (how do they vary with expectations and outcomes?) and their downstream impacts in target regions (how do they affect learning and behavior?). In parallel, the basal ganglia have been elevated from their original implication in motoric function to a canonical circuit facilitating the initiation, invigoration, and selection of actions across levels of abstraction, from motor to cognitive operations.

Orthopaedic Surgery in the Jehovah's Witness Patient: Clinical, Ethical, and Legal Considerations.

➢ Jehovah's Witnesses refuse allogeneic blood products based on religious beliefs that create clinical, ethical, and legal challenges in orthopaedic surgery, requiring detailed perioperative planning and specific graft selection.➢ Detailed perioperative planning is particularly important for procedures with high intraoperative blood loss.➢ Graft selection must align with Jehovah's Witnesses patients' religious beliefs, with options including autografts, allografts, and synthetic materials; this requires shared decision-making between the patient and surgeon.

Iliopsoas Injections: A Systematic Review of Patient Outcomes and Progression to Surgery.

Background: Iliopsoas injuries are a common cause of anterior hip and groin pain and can be successfully managed with conservative treatment. Corticosteroid and local anesthetic injections can also be offered in conjunction with nonoperative management. Given the variability in reported injection guidelines, composition, and techniques, the purpose of this study was to systematically review the literature to assess progression to surgery and patient outcomes following iliopsoas injections.

HIV pre-exposure prophylaxis prescription initiation and maintenance among homeless-experienced people who use drugs.

Background: HIV pre-exposure prophylaxis (PrEP) remains particularly underutilized among homeless-experienced people who use drugs (PWUD).

Setting: Boston Health Care for the Homeless Program, a Federally Qualified Health Center serving homeless-experienced individuals in Boston, Massachusetts.

Methods: To identify determinants of PrEP prescription initiation and continuation, we analyzed electronic medical records and pharmacy data between April 2018-March 2022.

Blood Culture Use in Medical and Surgical Intensive Care Units and Wards.

Importance: Blood culture (BC) use benchmarks in US hospitals have not been defined.

Objective: To characterize BC use in adult intensive care units (ICUs) and wards in US hospitals.

Design, Setting, And Participants: A retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted.

Sociodemographic Variables Associated with Self-reported Access to Mental Healthcare Among Brazilian Immigrant Women in the U.S.

Brazilians are a rapidly growing immigrant population in the United States (U.S.), yet little is known about their mental health and access to mental healthcare.

Advanced Care Planning for the Orthopaedic Patient.

➢ Advanced care planning most commonly refers to the act of planning and preparing for decisions with regard to end-of-life care and/or serious illness based on a patient's personal values, life goals, and preferences.➢ Over time, advanced care planning and its formalization through advanced directives have demonstrated substantial benefits to patients, their families and caregivers, and the larger health-care system.➢ Despite these benefits, advanced care planning and advanced directives remain underutilized.

Sexual minority stressors and disordered eating behaviors in daily life: a daily diary study of sexual minority cisgender female couples.

Young cisgender sexual minority women (e.g. lesbian, queer) in the U.

Identifying Predictors of Extended Intensive Care Unit Stay Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: An Analysis of 101 ACS NSQIP Pediatric Participating Centers.

Background: While prolonged operative time and increased levels fused have been shown to increase the risk of prolonged intensive care unit (ICU) length-of-stay (LOS), studies are limited in guiding decision-making regarding the need for intensive care postoperatively. This is especially the case among the cohort of adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF); associations between comorbidities and ICU LOS are not well-delineated.

Methods: AIS patients who underwent PSF from January 1st, 2016 to December 1st, 2016 at 101 participating centers were identified using the American College of Surgeons (ACS) National Surgical Quality Im-provement Project (NSQIP) Pediatric database.

Post-COVID Hypertension With Hyperreninemic Hyperaldosteronism in a Pediatric Patient.

COVID-19 infection may predispose patients to long-term renovascular complications. Early recognition and management are crucial for optimal outcomes. This case report underscores the importance of thorough follow-up care for children recovering from COVID-19, with a focus on monitoring blood pressure and renal function to mitigate long-term renovascular disease.

Recommendations for Specialty Palliative APRN Graduate Education.

Background: Advanced practice registered nurses (APRNs) are essential to care for the growing number of individuals with advanced illness given the shortage of palliative care clinicians.

Problem: Graduate education for specialty practice palliative APRNs lacks consistency in structure, content, and standardization of specialty palliative APRN education.

Approach: A workgroup of expert palliative APRNs and graduate faculty conducted focused discussions and a literature review to develop consensus recommendations based on national palliative APRN competencies and aligned with the 8 core concepts of the AACN Essentials.

Impacts, Adaptations, and Preparedness Among SNAP-Ed Implementers During the COVID-19 Pandemic: A Multistate Study.

Objective: The study examines: 1) impacts of COVID-19 on the work of Supplemental Nutrition Assistance Program - Education (SNAP-Ed) implementers, 2) facilitators and barriers experienced in making adaptations, and 3) factors that would have helped with preparedness to adapt.

Design, Setting, And Participants: A purposive sample of 181 SNAP-Ed program implementers from across five states completed a survey or interview based on the study aims. Quantitative data was summarized with descriptive statistics and qualitative data was analyzed thematically.

Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement.

Importance: Osteoporotic fractures are associated with psychological distress, subsequent fractures, loss of independence, reduced ability to perform activities of daily living, and death.

Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for osteoporosis to prevent fractures in adults 40 years or older with no known diagnosis of osteoporosis or history of fragility fracture.

Population: Adults 40 years or older without known osteoporosis or history of fragility fractures.

Heteroconfinement in Single CdTe Nanoplatelets.

Dimension-engineered synthesis of atomically thin II-VI nanoplatelets (NPLs) remains an open challenge. While CdSe NPLs have been made with confinement ranging from 2 to 11 monolayers (ML), CdTe NPLs have been significantly more challenging to synthesize and separate. Here we provide detailed mechanistic insight into the layer-by-layer growth kinetics of the CdTe NPLs.

Discovering genetic modulators of the protein homeostasis system through multilevel analysis.

Every protein progresses through a natural lifecycle from birth to maturation to death; this process is coordinated by the protein homeostasis system. Environmental or physiological conditions trigger pathways that maintain the homeostasis of the proteome. An open question is how these pathways are modulated to respond to the many stresses that an organism encounters during its lifetime.