RetroFun-RVS: A Retrospective Family-Based Framework for Rare Variant Analysis Incorporating Functional Annotations.

A large proportion of genetic variations involved in complex diseases are rare and located within noncoding regions, making the interpretation of underlying biological mechanisms a daunting task. Although technical and methodological progress has been made to annotate the genome, current disease-rare-variant association tests incorporating such annotations suffer from two major limitations. First, they are generally restricted to case-control designs of unrelated individuals, which often require tens or hundreds of thousands of individuals to achieve sufficient power.

Virtual reality-based interventions improve balance skills in children with developmental coordination disorder: systematic review and meta-analysis.

Purpose: Virtual reality-based interventions (VRBI) are a gamified approach to therapy that can improve balance and motor skills in children diagnosed with Developmental Coordination Disorder (DCD). The aim was to investigate the effectiveness of VRBI in improving balance and motor skills in children with DCD.

Methods: According to PRISMA guidelines, meta-analyses were conducted by searching randomized controlled trials (RCTs) that investigated the effect of VRBI on balance and motor skills in children with DCD.

Context-specific eQTLs provide deeper insight into causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

Approach to autologous stem cell transplantation in a patient with severe cold agglutinin disease, a case report.

Background: Cold agglutinin disease (CAD) or syndrome (CAS) can be particularly challenging when autologous stem cell transplant (ASCT) is needed. Standard peripheral blood stem cell (PBSC) collection and manipulation involve ex vivo blood manipulations at lower than body temperature, predisposing to agglutination during graft collection, handling, processing, and infusion.

Study Design And Methods: We describe the first case of ASCT for relapsing lymphoma in a patient with high-titer CAD requiring anti-complement therapy and chronic transfusion.

Coexisting with large carnivores based on the Volterra principle.

Coexistence with large carnivores represents one of the world's highest profile conservation challenges. Ecologists have identified ecological benefits derived from large carnivores (and large herbivores), yet livestock depredation, perceived competition for shared game, risks to pets and humans, and social conflicts often lead to demands for reduction of predator numbers from a range of stakeholder groups. Nearly 100 years ago, Vito Volterra predicted that increased mortality on both prey and predators results in increased abundance of prey and decreased abundance of predators.

Dissolved organic carbon from "white" waters in Amazon basin (Brazil) and the osmoregulatory responses of tambaqui (Colossoma macropomum) in neutral and acidic environments.

Optical characterization of dissolved organic carbon (DOC) freshly collected from the circumneutral "white water" of the Rio Solimoes revealed that it had lower aromaticity, lower molecular weight, and a greater autochthonous content than DOC from the acidic "black water" of the Rio Negro. The tambaqui (Colossoma macropomum), a characid member of the Serrasalmidae, is a model neotropical fish that migrates annually between the two rivers. We analysed ionoregulatory responses of the tambaqui over 24 h in ion-poor water at pH 7.

Language Mapping With rTMS in Healthy Pediatric Patients.

Purpose: Repetitive transcranial magnetic stimulation (rTMS) is a potentially effective, noninvasive tool for language mapping. However, there is a paucity of data in pediatric patients. In this study, we aimed to map language sites in healthy pediatric participants with navigated rTMS.

Molecular Profiling of Odontoclasts during Physiological Tooth Replacement.

The odontoclast is a rarely studied cell type that is overly active in many dental pathologies, leading to tooth loss. It is difficult to find diphyodont mammals in which either physiological or pathological root resorption can be studied. Here we use the adult leopard gecko, which has repeated cycles of physiological tooth resorption and shedding.

Estimating greenhouse gas emissions from the health sector in Canada: Mind the gap.

Healthcare is a surprisingly large contributor to climate change, responsible for a significant quantity of global Greenhouse Gas (GHG) emissions. Global commitments to achieve "net zero" health systems, including by the federal government in Canada, suggest a growing need to understand and mobilize capacity for GHG emissions estimation across Canada's health sector. Our analysis highlights efforts by public sector healthcare organizations in Canada to estimate an increasingly broad scope of GHG emissions, building on longstanding efforts to report or reduce energy-related emissions from facilities.

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.

Residency training programs to support residents working in First Nations, Inuit, and Métis communities.

Background: To gain culturally appropriate awareness of First Nations, Inuit and/or Métis Health, research suggests that programs focus on sending more trainees to First Nations, Inuit and/or Métis communities Working within this context provides experiences and knowledge that build upon classroom education and support trainees' acquisition of skills to engage in culturally safe healthcare provision. This study examines residents' and faculty members' perceptions of how residency training programs can optimize First Nations, Inuit and/or Métis health training and support residents in gaining the knowledge, skills, and experiences for working in and with First Nations, Inuit and/or Métis communities.

Methods: A qualitative approach was used, guided by a relational lens for collecting data and a constructivist grounded theory for data interpretation.

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.

Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8).

Background: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder with dysregulated glyoxylate metabolism in the liver. Oxalate over-production leads to renal stones, progressive kidney damage and renal failure, with potentially life-threatening systemic oxalosis. Nedosiran is a synthetic RNA interference therapy, designed to reduce hepatic lactate dehydrogenase (LDH) to decrease oxalate burden in PH.

Hilbert transform analysis of the mouse scotopic electroretinogram reveals two distinct bursts of oscillatory potentials with progressively dimmer flashes.

Purpose: Study the scotopic oscillatory potentials (OPs) in mice over a wide range of flash luminance levels using the Hilbert transform (HT) to extract new features of the high frequency components of the electroretinogram (ERG).

Methods: Scotopic ERGs [Intensity: - 6.3 to 0.