Small molecule modulators of B56-PP2A restore 4E-BP function to suppress eIF4E-dependent translation in cancer cells.

Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1.

Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).

Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).

Continental influx and pervasive matrilocality in Iron Age Britain.

Roman writers found the relative empowerment of Celtic women remarkable. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male.

A Metastable State Facilitates Low Temperature CO Oxidation over Pt Nanoparticles.

The dynamic response of heterogeneous catalytic materials to their environment opens a wide variety of possible surface states which may have increased catalytic activity. In this work, we find that it is possible to generate a surface state with increased catalytic activity over metallic 2 nm Pt nanoparticles by performing a thermal treatment of the CO*-covered Pt catalyst. This state is characterised by its ability to oxidise CO to CO at room temperature.

Partial PdAu nanoparticle embedding into TiO support accentuates catalytic contributions from the Au/TiO interface.

Despite the broad catalytic relevance of metal-support interfaces, controlling their chemical nature, the interfacial contact perimeter (exposed to reactants), and consequently, their contributions to overall catalytic reactivity, remains challenging, as the nanoparticle and support characteristics are interdependent when catalysts are prepared by impregnation. Here, we decoupled both characteristics by using a raspberry-colloid-templating strategy that yields partially embedded PdAu nanoparticles within well-defined SiO or TiO supports, thereby increasing the metal-support interfacial contact compared to nonembedded catalysts that we prepared by attaching the same nanoparticles onto support surfaces. Between nonembedded PdAu/SiO and PdAu/TiO, we identified a support effect resulting in a 1.

Hip Adduction and Abduction Strength Reference Values of Gaelic Football and Rugby Union Players: A Cross-Sectional Study.

Purpose: The purpose of this research was to report isometric hip adduction and abduction strength reference values of men's and women's Gaelic football and rugby union players and compare values between sexes and between sports.

Methods: This cross-sectional cohort study consisted of 331 club-level athletes. Maximum isometric hip adduction squeeze and abduction press strength values were measured with a ForceFrame across several testing positions.

Exploring the association between moral injury and posttraumatic stress symptoms among Canadian public safety personnel.

Public safety personnel (PSP), such as police officers, firefighters, correctional workers, and paramedics, routinely face work stressors that increase their risk of developing posttraumatic stress disorder (PTSD). PSP may additionally face moral transgressions in the workplace (e.g.

Safe and effective anticoagulation use: case studies in anticoagulation stewardship.

Anticoagulant use is prevalent and associated with significant potential for harm. Anticoagulation stewardship practice has emerged to address care gaps and promote safe, effective, and cost-conscious anticoagulation use across health care systems. We present 4 patient cases describing common challenges in anticoagulation management: inappropriate dosing of direct oral anticoagulants, the diagnosis and management of heparin-induced thrombocytopenia, periprocedural anticoagulation management, and heavy menstrual bleeding on anticoagulation.

analysis of gas dependent redistribution kinetics in bimetallic Au-Pd nanoparticles.

The catalytic and plasmonic properties of bimetallic gold-palladium (Au-Pd) nanoparticles (NPs) critically depend on the distribution of the Au and Pd atoms inside the nanoparticle bulk and at the surface. Under operating conditions, the atomic distribution is highly dynamic. Analyzing gas induced redistribution kinetics at operating temperatures is therefore key in designing and understanding the behavior of Au-Pd nanoparticles for applications in thermal and light-driven catalysis, but requires advanced characterization strategies.

Accuracy and confidence of Irish general practitioners in diagnosing skin disease in patients with darkly pigmented skin.

Managing skin conditions in patients with darkly pigmented skin (DPS) can be challenging due to inadequate exposure to dermatology in DPS in clinical training. In this study, Irish GPs were less likely to correctly diagnose common skin conditions in patients with DPS ( < 0.001) and had lower confidence levels in diagnosis in DPS ( < 0.

Maximum Isometric Hip Adduction Squeeze and Abduction Press Strength Values in Men's Rugby Union Players at Select Timepoints Throughout a Competitive Season.

O' Connor, C, Mc Intyre, M, Delahunt, E, and Thorborg, K. Maximum isometric hip adduction squeeze and abduction press strength values in men's rugby union players at select timepoints throughout a competitive season. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this research was to report hip adduction and abduction strength values in men's rugby union players at select timepoints throughout a competitive season and to examine if differences exist between time of season and hip-testing positions.

Exploring Social Preferences for Health and Well-Being Across the Digital Divide: A Qualitative Investigation Based on Tasks Taken From an Online Discrete Choice Experiment.

Objectives: Increasingly, discrete choice experiments (DCEs) are conducted online, with little consideration of the digitally excluded, who are unable to participate. Policy makers or others considering online research data need clarity about how views might differ across this "digital divide." We took tasks from an existing online DCE designed to elicit social preferences for health and well-being outcomes.

Treatment of Critical Bleeds in Patients With Immune Thrombocytopenia: A Systematic Review.

Objectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.

Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.

Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer.

Uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) tumors are uniquely aggressive, suggesting that the primary tumor is intrinsically equipped to disseminate and metastasize. Previous work identified mutational hotspots within PPP2R1A, which encodes the Aα scaffolding subunit of protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine phosphatase. Two recurrent heterozygous PPP2R1A mutations, P179R and S256F, occur exclusively within high-grade subtypes of uterine cancer and can drive tumorigenesis and metastasis.

Embracing innovation and advancing care: integrating learning health system principles into Inova Schar Heart and Vascular.

Inova Schar Heart and Vascular has an unwavering commitment to delivering excellent cardiovascular care and has integrated principles of a learning health care system to develop our system of continuous process improvement and innovation. A learning health system integrates its internal experiences with external research to enhance patient outcomes, support the discovery of new treatments and care pathways, and deliver safer, more efficient, and more personalized care. Leveraging learning across health systems maximizes the impact, allowing cardiovascular teams to gain insights into the effectiveness of different treatment strategies.

Artificial Intelligence in Cardiovascular Clinical Trials.

Randomized clinical trials are the gold standard for establishing the efficacy and safety of cardiovascular therapies. However, current pivotal trials are expensive, lengthy, and insufficiently diverse. Emerging artificial intelligence (AI) technologies can potentially automate and streamline clinical trial operations.

Research needs of higher specialist trainees in psychiatry in Ireland: mixed methods study.

Aims And Method: Higher specialist trainees (HSTs) in psychiatry in Ireland were recruited to complete a 21-item online questionnaire anonymously. Questions were designed to establish the research experience of HSTs in various years of training, identify perceived barriers to participation and generate potential strategies to overcome these barriers.

Results: Of 165 HSTs surveyed, 50 (30%) responded.

"Nobody Knew . . . What Was Gonna Happen": Indigenous Loss and Grief During the COVID-19 Pandemic.

Indigenous peoples have experienced higher rates of loss and death compared to the general population, partly due to historical loss. This qualitative inquiry focused on understanding Indigenous women's experiences of loss, grief, and death during the COVID-19 pandemic, involving 31 head-of-household Native American women from a southeastern US tribe. Reconstructive analysis of data from a community-based critical ethnography identified the following themes spanning the ecological levels of the FHORT: (a) loss of finances, (b) loss of structure and loss of self, (c) death due to COVID-19, (d) disrupted mourning and burial rituals, and (e) grief and extensive losses.

Perinatal deaths in twin and singleton infants in Ireland: A comparison of characteristics and causes.

Introduction: Twin pregnancies are associated with significantly higher perinatal mortality (PM) rates compared to singletons, primarily due to complications like fetal growth restriction, preterm birth, and congenital anomalies. This study aimed to compare the characteristics associated with PM in twin pregnancies and compare maternal and obstetric factors and cause of death among twins and singletons in the Republic of Ireland.

Materials And Methods: Data spanning 2011 to 2022 from the National Perinatal Epidemiology Centre's annual perinatal mortality clinical audit included 4494 perinatal deaths.