Iron Overload, Oxidative Stress, and Somatic Mutations in MDS: What Is the Association?

Introduction: Iron overload (IOL) accumulates in myelodysplastic syndromes (MDS) from expanded erythropoiesis and transfusions. Somatic mutations (SM) are frequent in MDS and stratify patient risk. MDS treatments reversing or limiting transfusion dependence are limited.

Allogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a second-line treatment with curative potential for leukemia patients. However, the prognosis of allo-HSCT patients with disease relapse or graft-versus-host disease (GvHD) is poor. CD4 or CD8 conventional T (Tconv) cells are critically involved in mediating anti-leukemic immune responses to prevent relapse and detrimental GvHD.

Cytisine compared to combination nicotine replacement therapy to reduce cigarette consumption in relapsed smokers: protocol for a pilot randomized controlled trial.

Background: Cigarette smoking is a leading cause of death and disease, including those related to the cardiovascular system. Cytisine is a plant-based medication, which works in a similar mechanism to varenicline. It is safe, efficacious, and cost-effective for smoking cessation.

Knowledge translation initiatives at the Transitional Pain Service: insights from healthcare provider outreach and patient education.

Evidence-based treatment of chronic pain requires a multidisciplinary approach grounded in the biopsychosocial model. Implementing this approach within health systems relies on its acceptance by both healthcare providers and patients. While pioneering multidisciplinary pain clinics can serve as a model for implementation, a systematic effort is needed to share knowledge effectively and broadly.

Which combination of medical expulsive therapy is more effective for treatment of distal ureteral stone in adults? A systematic review and network meta-analysis.

Background: Medical Expulsive Therapy (MET) has been recommended as an established modality for the treatment of distal ureteral stones due to its clearance rate, pain control, and patient satisfaction while having minimal morbidity in comparison to other urologic interventions. In some studies, a combination of medications has been used, which we assessed in this network meta-analysis (NMA).

Methods: We conducted systematic searches in PubMed, Scopus, and Web of Science to identify relevant trials published between 2001 and 2024.

Identification of patient demographic, clinical, and SARS-CoV-2 genomic factors associated with severe COVID-19 using supervised machine learning: a retrospective multicenter study.

Background: Drivers of COVID-19 severity are multifactorial and include multidimensional and potentially interacting factors encompassing viral determinants and host-related factors (i.e., demographics, pre-existing conditions and/or genetics), thus complicating the prediction of clinical outcomes for different severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants.

Community benefits of mass distribution of three types of dual-active-ingredient long-lasting insecticidal nets against malaria prevalence in Tanzania: evidence from a 3-year cluster-randomized controlled trial.

Background: Long-lasting insecticidal nets (LLINs) were once fully effective for the prevention of malaria; however, mosquitoes have developed resistance to pyrethroids, the main class of insecticides used on nets. Dual active ingredient LLINs (dual-AI LLINs) have been rolled out as an alternative to pyrethroid (PY)-only LLINs to counteract this. Understanding the minimum community usage at which these LLINs elicit an effect that also benefits non-users against malaria infection is important.

Development and validation of a minimal SNP genotyping panel for the differentiation of Cannabis sativa cultivars.

Background: Due to its previously illicit nature, Cannabis sativa had not fully reaped the benefits of recent innovations in genomics and plant sciences. However, Canada's legalization of C. sativa and products derived from its flower in 2018 triggered significant new demand for robust genotyping tools to assist breeders in meeting consumer demands.

Rationale and design of APOLLO: a personalized rehAbilitation PrOgram in aLLOgeneic bone marrow transplantation.

Background: Hematopoietic stem cell transplantation (HSCT) is a common therapy for many hematologic malignancies. While advances in transplant practice have improved cancer-specific outcomes, multiple and debilitating long term physical and psychologic effects remain. Patients undergoing allogeneic bone marrow transplantation (allo-BMT) are often critically ill at initial diagnosis and with necessary sequential treatments become increasingly frail and deconditioned.

Leveraging Model Master Files for Long-Acting Injectables.

The U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a public workshop on May 2-3, 2024, titled "Considerations and Potential Regulatory Applications for a Model Master File (Lachaine et al Can J Psychiatry.

Molecular Therapeutics in Development to Treat Hyperlipoproteinemia.

Clinical endpoints caused by hyperlipoproteinemia include atherosclerotic cardiovascular disease and acute pancreatitis. Emerging lipid-lowering therapies targeting proprotein convertase subtilisin/kexin 9 (PCSK9), lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 represent promising advances in the management of patients with hyperlipoproteinemia. These therapies offer novel approaches for lowering pathogenic lipid and lipoprotein species, particularly in patients with serious perturbations who are not adequately controlled with conventional treatments or who are unable to tolerate them.

Description of STRIVE-ON Study Protocol: Safety and Tolerability of GTX-104 (Nimodipine Injection for IV Infusion) Compared with Oral Nimodipine in Patients Hospitalized for Aneurysmal Subarachnoid Hemorrhage (aSAH): A Prospective, Randomized, Phase III Trial (STRIVE-ON).

Oral nimodipine is the only drug approved in North America for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is variable and frequently poor, leading to fluctuations in peak plasma concentrations that cause dose-limiting hypotension. Furthermore, administration is problematic in patients who cannot swallow.

Intramyocellular lipid use is altered with exercise in males with childhood-onset obesity despite no differences in substrate oxidation.

Objective: Compared to adulthood-onset obesity (AO), those with childhood-onset obesity (CO) are at greater risk of metabolic disease. However, the differences between these two obesity phenotypes are not clear. The aim of this study is to investigate how the age of obesity onset (CO vs.

A cross sectional investigation of the development of rhythmic preferences with motor and perceptual tests.

The preferred period hypothesis posits a slowing down of motor and perceptual rhythmic preferences with age, both reflecting an increase in the common internal oscillation period. This study further investigates the preferred period hypothesis by improving the measurement of perceptual rhythmic preferences through two tasks, tempo adjustment and tempo judgment, conducted in auditory and visual modalities. The study was conducted with three groups of children (5-6, 8-9, and 11-12 years old), and a group of young adults (21 to 30 years old) during the same time of the day.

Machine learning models for predicting interaction affinity energy between human serum proteins and hemodialysis membrane materials.

Membrane incompatibility poses significant health risks, including severe complications and potential fatality. Surface modification of membranes has emerged as a pivotal technology in the membrane industry, aiming to improve the hemocompatibility and performance of dialysis membranes by mitigating undesired membrane-protein interactions, which can lead to fouling and subsequent protein adsorption. Affinity energy, defined as the strength of interaction between membranes and human serum proteins, plays a crucial role in assessing membrane-protein interactions.

Comparative analysis of salivary cytokine profiles in newly diagnosed pediatric patients with cancer and healthy children.

Salivary cytokines have the potential to serve as biomarkers for evaluating cancer progression and treatment response in specific cancer types. This study explored salivary cytokine profiles in pediatric cancer patients and healthy controls, examining changes during chemotherapy. We conducted a prospective study involving newly diagnosed cancer patients and healthy controls under 19 years old.

Dilated SE-DenseNet for brain tumor MRI classification.

In the field of medical imaging, particularly MRI-based brain tumor classification, we propose an advanced convolutional neural network (CNN) leveraging the DenseNet-121 architecture, enhanced with dilated convolutional layers and Squeeze-and-Excitation (SE) networks' attention mechanisms. This novel approach aims to improve upon state-of-the-art methods of tumor identification. Our model, trained and evaluated on a comprehensive Kaggle brain tumor dataset, demonstrated superior performance over established convolution-based and transformer-based models: ResNet-101, VGG-19, original DenseNet-121, MobileNet-V2, ViT-L/16, and Swin-B across key metrics: F1-score, accuracy, precision, and recall.

Enantioselective Borylcupration/Cyclization of Alkene-Tethered Oxime Esters.

A copper-catalyzed enantioselective synthesis of borylated 1-pyrrolines from γ,δ-unsaturated oxime esters is reported. Twenty-four novel 1-pyrroline derivatives are reported in yields ranging from 26% to 96% and enantioselectivities from 74.5:25.

Community and Hospital Healthcare Use by Adults With and Without Intellectual and Developmental Disabilities in Ontario, Canada, During the First 2 Years of the COVID-19 Pandemic.

Background: This study describes the proportion of Ontario adults with and without intellectual and developmental disabilities (IDD) who used community- and hospital-based healthcare in the first 2 years of the pandemic compared with the year pre-COVID-19.

Methods: Linked health administrative databases identified 87 341 adults with IDD and also adults without IDD living in Ontario, Canada. For each cohort, counts and proportions of adults who used different types of healthcare services were reported for the pre-COVID-19 year (16 March 2019 to 14 March 2020) and the first two COVID-19 years (15 March 2020 to 14 March 2021 and 15 March 2021 to 14 March 2022).

'I wish I had been better prepared': a mixed-methods study of psychological reactions, perceptions and opinions of cardiovascular preparticipation screening among young competitive athletes.

Objective: To evaluate the psychological reactions, perceptions and opinions of cardiovascular preparticipation screening (PPS) among young competitive athletes.

Methods: This convergent parallel mixed-methods study recruited 222 athletes (mean age: 18.7 years) who underwent PPS at a Canadian university.

Chronic disease prevalence and preventive care among Ontario social housing residents compared with the general population: a population-based cohort study.

Background: Older adults living in social housing report poor health and access to healthcare services. This study aimed to estimate the prevalence of chronic diseases, influenza vaccination and cancer screenings among social housing residents versus non-residents in Ontario, Canada.

Methods: We conducted a population-based cohort study for all health-insured Ontarians alive and aged 40 or older as of 1 January 2020.

Impact of changes in primary care attachment: a scoping review.

Objectives: Primary care attachment represents an inclusive, equitable and cost-effective way of enhancing health outcomes globally. However, the growing shortage of family physicians threatens to disrupt patient-provider relationships. Understanding the consequences of these disruptions is essential for guiding future research and policy.

Understanding patient safety during earthquakes: a phenomenological study of disaster response.

Background: Natural hazards, such as earthquakes, pose a significant risk to both the public and healthcare professionals, jeopardising patient safety due to the disruption of healthcare systems and services. This study aimed to explore the lived experiences of healthcare professionals concerning patient safety during natural hazards, specifically earthquakes.

Methods: Employing a descriptive phenomenological approach, the study followed the Consolidated Criteria for Reporting Qualitative Research guidelines.

Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.