Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.

Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).

A Randomized Controlled Feasibility Study to Evaluate the Online Delivery of Storytelling Through Music With Oncology Nurses.

Background: Oncology nurses frequently contend with intense work-related emotions stemming from their roles, which include bearing witness to suffering, managing end-of-life care, and navigating ethical dilemmas. These emotional challenges can lead to burnout, compassion fatigue, and overall psychological distress.

Objective: To determine the feasibility, acceptability, and preliminary effect of implementing Storytelling Through Music (STM) online with oncology nurses.

Acute and chronic toxicity of cationic polyquaterniums of varying charge density and molecular weight to Daphnia magna and Ceriodaphnia dubia.

Cationic polymers have the unique ability to neutralize negative charge with practical applications in personal care products, such as shampoos, conditioners, contact lens solutions, and as flocculants in wastewater treatment processes. Cationic polymers are a diverse class of materials varying in structural composition, cationic charge density (CD), and molecular weight (MW). In this study, we investigated three classes of polyquaternium cationic polymers (PQ-6, PQ-10, PQ-16) of varying CD and MW to characterize their toxicity to aquatic invertebrates.

Consistent differences in tissue oxygen levels across 15 insect species reflect a balance between oxygen supply and demand and highlight a hitherto unknown adaptation for extracting sufficient oxygen from water.

Animals, including insects, need oxygen for aerobic respiration and eventually asphyxiate without it. Aerobic respiration, however, produces reactive oxygen species (ROS), which contribute to dysfunction and aging. Animals appear to balance risks of asphyxiation and ROS by regulating internal oxygen relatively low and stable, but sufficient levels.

Divergent folding-mediated epistasis among unstable membrane protein variants.

Many membrane proteins are prone to misfolding, which compromises their functional expression at the plasma membrane. This is particularly true for the mammalian gonadotropin-releasing hormone receptor GPCRs (GnRHR). We recently demonstrated that evolutionary GnRHR modifications appear to have coincided with adaptive changes in cotranslational folding efficiency.

Resource allocation strategies and mechanical constraints drive the diversification of stick and leaf insect eggs.

The diversity of insect eggs is astounding but still largely unexplained. Here, we apply phylogenetic analyses to 208 species of stick and leaf insects, coupled with physiological measurements of metabolic rate and water loss on five species, to evaluate classes of factors that may drive egg morphological diversification: life history constraints, material costs, mechanical constraints, and ecological circumstances. We show support for all three classes, but egg size is primarily influenced by female body size and strongly trades off with egg number.

Evaluation of potency and metabolic stability of diphyllin-derived Vacuolar-ATPase inhibitors.

Diphyllin is a naturally occurring lignan comprised of an aryl naphthalene lactone scaffold that demonstrates beneficial biological activities in disease models of cancer, obesity, and viral infection. A target of diphyllin and naturally occurring derivatives is the vacuolar ATPase (V-ATPase) complex. Although diphyllin-related natural products are active with in vitro models for viral entry, the potencies and unknown pharmacokinetic properties limit well-designed in vivo evaluations.

Diagnosis and pharmacological management of attention deficit hyperactivity disorder in adults with and without intellectual disability: cohort study using electronic health records.

Background: Attention deficit hyperactivity disorder (ADHD) is increasingly diagnosed in adults. People with intellectual disability have higher rates of ADHD yet there is little evidence on the presentation and pharmacological treatment of ADHD in this population or how this differs from the general population.

Methods: Retrospective cohort study using data from electronic health records.

Exploring patient and staff member views on a 'consent for contact' system for sexual health research: A mixed methods study.

Background: Recruitment in sexual health research is challenging. This study explores the potential of a Consent for Contact system (C4C) - generic consent for research contact - to improve participant recruitment and engagement in sexual health research. Our objectives were to understand patient and staff understanding of research, their views on a separate C4C system, and their preferences for its acceptability in a sexual health clinic setting.

How to improve scientific peer review: Four schools of thought.

Peer review plays an essential role as one of the cornerstones of the scholarly publishing system. There are many initiatives that aim to improve the way in which peer review is organized, resulting in a highly complex landscape of innovation in peer review. Different initiatives are based on different views on the most urgent challenges faced by the peer review system, leading to a diversity of perspectives on how the system can be improved.

Modeling membrane geometries implicitly in Rosetta.

Interactions between membrane proteins (MPs) and lipid bilayers are critical for many cellular functions. In the Rosetta molecular modeling suite, the implicit membrane energy function is based on a "slab" model, which represent the membrane as a flat bilayer. However, in nature membranes often have a curvature that is important for function and/or stability.

Energetic costs of raising brood in honey bee colonies are high, but heater bees are cheap.

Little is known about the energetic costs to insects of raising young. Honey bees collectively raise young, or brood, through a series of complex behaviors that appear to accelerate and synchronize the timing of brood maturation. These include maintaining the brood nest at warmer and consistent temperatures (33-36 °C) and the exceptional activity of heater bees.

Gender and racialisation of pharmaceutical sector leaders in Canada: a cross-sectional study.

Objective/design: Lacking diversity in pharmaceutical leadership positions could contribute to inequities in medicine access. The objective of this cross-sectional study was to determine the gender and racial identities of individuals who hold leadership positions in the Canadian pharmaceutical sector.

Participants: We compiled a list of all Canadian governmental bodies, pharmaceutical companies and insurance providers.

Essential cancer medicines and cancer outcomes: Cross-sectional study of 124 countries.

Background: Cancer is the second leading cause of death worldwide. Alongside other interventions, access to certain medicines may decrease cancer-associated mortality. Listing medicines on national essential medicines lists may improve health outcomes.

Preventive care recommendations to promote health equity.

Background: Avoidable disparities in health outcomes persist in Canada despite substantial investments in a publicly funded health care system that includes preventive services. Our objective was to provide preventive care recommendations that promote health equity by prioritizing effective interventions for people experiencing disadvantages.

Methods: The guideline was developed by a primary care provider-patient panel, with input from a patient-partner panel with diverse lived experiences.

Where next for partial randomisation of research funding? The feasibility of RCTs and alternatives.

We outline essential considerations for any study of partial randomisation of research funding, and consider scenarios in which randomised controlled trials (RCTs) would be feasible and appropriate. We highlight the interdependence of target outcomes, sample availability and statistical power for determining the cost and feasibility of a trial. For many choices of target outcome, RCTs may be less practical and more expensive than they at first appear (in large part due to issues pertaining to sample size and statistical power).

Divergent Folding-Mediated Epistasis Among Unstable Membrane Protein Variants.

Many membrane proteins are prone to misfolding, which compromises their functional expression at the plasma membrane. This is particularly true for the mammalian gonadotropin-releasing hormone receptor GPCRs (GnRHR). We recently demonstrated that evolutionary GnRHR modifications appear to have coincided with adaptive changes in cotranslational folding efficiency.

Computational modeling and prediction of deletion mutants.

In-frame deletion mutations can result in disease. The impact of these mutations on protein structure and subsequent functional changes remain understudied, partially due to the lack of comprehensive datasets including a structural readout. In addition, the recent breakthrough in structure prediction through deep learning demands an update of computational deletion mutation prediction.

An overview of innovations in the external peer review of journal manuscripts.

There are currently numerous innovations in peer review and quality assurance in scholarly publishing. The Research on Research Institute conducted a programme of co-produced projects investigating these innovations. This literature review was part of one such project 'Experiments in peer review' which created an inventory and framework of peer review innovations.

Mechanisms underlying thermal breadth differ by species in insects from adjacent but thermally distinct streams - A test of the climate variability hypothesis.

The Climate Variability Hypothesis (CVH) predicts that ectotherms from thermally variable climates should have wider thermal tolerances than their counterparts living in stable climates. Although the CVH has been widely supported, the mechanisms underlying wider tolerance traits remain unclear. We test the CVH along with three mechanistic hypotheses that may explain how differences in tolerance limits arise: 1) Short-term Acclimation Hypothesis (mechanism: rapid, reversible plasticity), 2) Long-term Effects Hypothesis (mechanisms: developmental plasticity, epigenetics, maternal effects, or adaptation), and 3) Trade-off Hypothesis (mechanism: trade-off between short- and long-term responses).