Precision Oncology: A Global Perspective on Implementation and Policy Development.

Despite the acknowledged merits of precision oncology (PO) and its increasing global implementation, its full potential for advancing care and prevention remains unrealized. The benefits are currently accessible to only limited patient segments because of multifaceted barriers. Successful implementation hinges on various factors-scientific complexities not limited to technical, clinical, regulatory, economic, administrative, and health care policy-related challenges.

Survival Outcomes for Adolescent and Young Adults With Cancer in Low- and Middle-Income Countries: A Systematic Review.

Purpose: Patients with adolescent and young adult (AYA) cancer are recognized as a vulnerable subpopulation in high-income countries (HICs). Although survival gaps between HIC and low- and middle-income country (LMIC) children with cancer are well described, LMIC AYAs have been neglected. We conducted a systematic review to describe cancer outcomes among LMIC AYAs.

Support for and likely impacts of endgame measures in the Smokefree Aotearoa Action Plan: findings from the 2020-2021 International Tobacco Control New Zealand (EASE) surveys.

Aim: In February 2024, the Aotearoa New Zealand Government repealed legislation to mandate very low nicotine cigarettes (VLNCs), greatly reduce the number of tobacco retailers and disallow sale of tobacco products to people born after 2008 (smokefree generation). We investigated acceptability and likely impacts of these measures among people who smoke or who recently (≤2 years) quit smoking.

Method: We analysed data from 1,230 participants from Wave 3 (conducted in late 2020 and early 2021) and 615 participants from Wave 3.

Single-Cell Multi-Omics Profiling of Immune Cells Isolated from Atherosclerotic Plaques in Male ApoE Knockout Mice Exposed to Arsenic.

Background: Millions worldwide are exposed to elevated levels of arsenic that significantly increase their risk of developing atherosclerosis, a pathology primarily driven by immune cells. While the impact of arsenic on immune cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is a substantial barrier to in-depth examinations of the cellular dynamics for varying immune cell populations.

Objectives: This study aimed to conduct single-cell multi-omics profiling of atherosclerotic plaques in apolipoprotein E knockout () mice to elucidate transcriptomic and epigenetic changes in immune cells induced by arsenic exposure.

A single gene orchestrates androgen variation underlying male mating morphs in ruffs.

Androgens are pleiotropic and play pivotal roles in the formation and variation of sexual phenotypes. We show that differences in circulating androgens between the three male mating morphs in ruff sandpipers are linked to 17-beta hydroxysteroid dehydrogenase 2 (HSD17B2), encoded by a gene within the supergene that determines the morphs. Low-testosterone males had higher expression in blood than high-testosterone males, as well as in brain areas related to social behaviors and testosterone production.

Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.

18F-DCFPyL PET/MRI Radiomics for Intraprostatic Prostate Cancer Detection and Metastases Prediction Using Whole-Gland Segmentation.

Objectives: To evaluate 18F-DCFPyL-PET/MRI whole-gland-derived radiomics for detecting clinically significant (cs) prostate cancer (PCa) and predicting metastasis.

Methods: Therapy-naïve PCa patients who underwent 18F-DCFPyL PET/MRI were included. Whole-prostate-segmentation was performed.

Influences of gonad developmental stage on ovary selenium concentrations in fish-implications for ovary selenium monitoring.

Monitoring selenium (Se) concentrations in fish ovaries is an important tool for evaluating the ecological risk posed by Se in aquatic systems. Most guidance recommends sampling fish ovaries as closely as possible to when fish spawn on the premise that Se is mobilized from the liver to the ovary during vitellogenesis, and therefore, sampling ovaries during the early phases of oocyte maturation may underestimate egg Se concentrations at the time of spawning. In this study, we evaluated ovary Se data from two species with synchronous oocyte development (Ptychocheilus oregonensis and Prosopium williamsoni), one species with asynchronous oocyte development (Richardsonius balteatus), and one where the mode of development is unclear (Mylocheilus caurinus).

Neonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) that begins in the first year of life. While most cases of DS are caused by variants in SCN1A, variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are also linked to DS or to the more severe early infantile DEE. Both disorders fall under the OMIM term DEE52.

Pharmacology of Intestinal Inflammation and Repair.

Chronic inflammation is a common trait in the pathogenesis of several diseases of the gut, including inflammatory bowel disease and celiac disease. Control of the inflammatory response is crucial in these pathologies to avoid tissue destruction and loss of intestinal function. Over the last 50 years, the identification of the mechanisms and mediators involved in the acute phase of the inflammatory response, which is characterized by massive leukocyte recruitment, has led to a number of therapeutic options.

G Protein-Coupled Receptor Heteromers in Brain: Functional and Therapeutic Importance in Neuropsychiatric Disorders.

G protein-coupled receptors (GPCRs) represent the largest family of plasma membrane proteins targeted for therapeutic development. For decades, GPCRs were investigated as monomeric entities during analysis of their pharmacology or signaling and during drug development. However, a considerable body of evidence now indicates that GPCRs function as dimers or higher-order oligomers.

Rehabilitation Interventions for Fear Avoidance Beliefs and Behaviors in Sudden Onset Musculoskeletal Conditions: A Scoping Review.

Fear avoidance (FA) describes beliefs and behaviors related to avoiding movements or activities after a painful event. FA is a prevalent issue that limits the recovery outcomes and social reintegration of burn survivors. However, as current literature focuses on chronic conditions, understanding the impact and treatment of FA within sudden onset musculoskeletal (MSK) conditions, specifically in the burn survivor population, is lacking.

Patient Experiences and Perspectives When MyChart is Introduced in a Large Community Hospital: Mixed Methods Study.

Background: Patient portals, or secure websites linked to electronic medical records, have emerged as tools to provide patients with timely access to their health information. To support the potential benefits of patient portals such as improved engagement in health care, it is essential to understand how patients and caregivers experience these portals.

Objective: This study aimed to explore patient and caregiver experiences, facilitators, and barriers to accessing and using a patient portal called MyChart during the initial stages of its implementation.

Identifying the Minimal Clinically Important Difference in Emotion Regulation Among Youth Using the JoyPop App: Survey Study.

Background: The minimal clinically important difference (MCID) is an important threshold to consider when evaluating the meaningfulness of improvement following an intervention. The JoyPop app is an evidence-based smartphone app designed to improve resilience and emotion regulation. Information is needed regarding the JoyPop app's MCID among culturally diverse youth.

Estimating the Effect of Adhering to the Recommendations of the 2019 Canada's Food Guide on Health Outcomes in Older Adults: Protocol for a Target Trial Emulation.

Background: The 2019 Canada's Food Guide provides universal recommendations to individuals aged ≥2 years. However, the extent to which these recommendations are appropriate for older adults is unknown. Although ideal, conducting a large randomized controlled trial is unrealistic in the short term.

The History and Advancement of Light, Lasers, and Energy-Based Devices in Dermatologic Surgery.

Background: From the theoretical foundations of laser and energy-based applications for the skin to the development of advanced medical devices, the field of dermatologic surgery has undergone transformative changes.

Objective: To review the scientific and clinical advancement of laser and energy-based therapies within dermatologic surgery.

Materials And Methods: A literature search was conducted to identify important scientific advancements and landmark studies on light, laser, and energy-based devices within the field of dermatologic surgery.

Governing in the face of a global crisis: When do voters punish and reward incumbent governments?

The recent COVID-19 pandemic offers a rare opportunity to understand how citizens attribute responsibility for governments' responses to unanticipated negative-and in this case, systemic-exogenous shocks. Classical accounts of responsibility are complicated when crises are pervasive, involve multiple valence dimensions, and where individuals can make relative assessments of performance. We fielded a conjoint experiment in 16 countries with 22,147 respondents.

Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials.

Introduction: Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE).

Retrospective Analyses of Stability and Variability in Relative Age Effects of Handball Talents Over Seventeen Years.

In the last thirty years research on relative age effects (RAEs) has exploded in numbers. However, the stability and variability of these effects have hardly been investigated. The three aims of this retrospective study were first to investigate the stability and variability of RAEs over 17 years, second to compare these effects for young female and male athletes, and third to compare these effects between selected and non-selected athletes relative to variability estimates from 17 years prior to assess possible changes in athlete development trends.

Attenuating hyperammonemia preserves protein synthesis and muscle mass via restoration of perturbed metabolic pathways in bile duct-ligated rats.

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD.

A Canadian real-world, multi-center, prospective, observational study assessing the treatment duration, the treatment sequence, and the overall survival for patients treated with endocrine therapy ± targeted therapy in HR + HER2-negative advanced breast cancer.

Purpose: Understanding real-world treatment patterns and their effectiveness in HR + HER2- advanced breast cancer (aBC) in Canadian patients.

Patient And Methods: This was a multi-center, observational, prospective cohort study including men and pre-/peri-/postmenopausal women with HR + HER2- aBC receiving endocrine therapy (ET) or ET + targeted therapy (ET + TT). The primary objective was duration of treatment (DOT) with ET and ET + TT.