Precision Medicine for High-Risk Gene Fusions in Pediatric AML: a focus on KMT2A, NUP98, and GLIS2 Rearrangements.

Robust genetic characterization of paediatric AML has demonstrated that fusion oncogenes are highly prevalent drivers of AML leukemogenesis in young children. Identification of fusion oncogenes associated with adverse outcomes has facilitated risk stratification of patients, although successful development of precision medicine approaches for most fusion-driven AML subtypes have been historically challenging. This knowledge gap has been in part due to difficulties in targeting structural alterations involving transcription factors and in identification of a therapeutic window for selective inhibition of the oncofusion without deleterious effects upon essential wild-type proteins.

Outcomes following resective and disconnective strategies in the treatment of epileptic spasms: a systematic review of the literature and individual patient data meta-analysis.

Epileptic spasms (ES) are a unique seizure type typically presenting in the form of infantile epileptic spasms syndrome (IESS) with characteristic hypsarrhythmia on scalp EEG and a preponderance with developmental delay or regression. While pharmacotherapy is the mainstay of treatment, surgical options, including disconnective or resective procedures, are increasingly recognized as viable therapeutic options for recurrent or persistent ES. However, limited data on safety, effectiveness, and prognostic factors hinder informed decision-making regarding surgery indications, timing, and intervention type.

Negative Staining Electron Microscopy of a Highly Flexible Sec1/Munc18 Protein Complex Stabilized by Glutaraldehyde Crosslinking.

Negative staining electron microscopy is one of the easiest ways to determine the shape and dimensions of multimeric protein complexes over 100 kDa molecular weight. This method requires small volumes (< 10 μL) of dilute protein (0.01-0.

Glycogen synthase GYS1 overactivation contributes to glycogen insolubility and malto-oligoglucan-associated neurodegenerative disease.

Polyglucosans are glycogen molecules with overlong chains, which are hyperphosphorylated in the neurodegenerative Lafora disease (LD). Brain polyglucosan bodies (PBs) cause fatal neurodegenerative diseases including Lafora disease and adult polyglucosan body disease (ABPD), for which treatments, biomarkers, and good understanding of their pathogenesis are currently missing. Mutations in the genes for the phosphatase laforin or the E3 ubiquitin ligase malin can cause LD.

The birth of the virtual clinic: welcome to the Mediverse.

The COVID-19 pandemic triggered a global pivot to virtual care (VC) technologies. While there has been considerable academic work exploring the "how" of VC, few studies have explored the impact of this pivot, its unintended consequences, and its governing rationales. This study addresses this gap in relation to care, professional identity and the evolving requirements for health professions education.

Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing.

Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling.

Validity of the Diabetic Wound Assessment Learning Tool.

Purpose: The development of the Diabetic Wound Assessment Learning Tool (DiWALT) has previously been described. However, an examination of its application to a larger, more heterogeneous group of participants is lacking. In order to allow for a more robust assessment of the psychometric properties of the DiWALT, we applied it to a broader group of participants.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

Effects of Food Processing on Allergenicity.

Purpose Of Review: There is an increasing awareness among clinicians that industrial and household food processing methods can increase or decrease the allergenicity of foods. Modification to allergen properties through processing can enable dietary liberations. Reduced allergenicity may also allow for lower risk immunotherapy approaches.

Cardiac growth patterns and metabolism before and after birth in swine: Role of miR in proliferation, hypertrophy and metabolism.

The adult mammalian heart is unable to undergo cardiac repair, limiting potential treatment options after cardiac damage. However, the fetal heart is capable of cardiac repair. In preparation for birth, cardiomyocytes (CMs) undergo major maturational changes that include exit from the cell cycle, hypertrophic growth, and mitochondrial maturation.

Impact of obesity on outcome in children diagnosed with cancer in Canada: A report from Cancer in Young People in Canada.

Background: Childhood obesity can result in adverse health outcomes. The objectives of this study were to describe the prevalence of obesity and determine the association between obesity at cancer diagnosis and event-free survival (EFS) and overall survival (OS) in children diagnosed with cancer in Canada.

Methods: The authors conducted a retrospective cohort study using the Cancer in Young People in Canada database, including all children with newly diagnosed cancer aged 2-18 years across Canada from 2001 to 2020.

Staged Approach: The Role of Delayed Repair Following Complete Unifocalization of Major Aortopulmonary Collateral Arteries with Ventricular Septal Defect and Pulmonary Atresia.

The presentation of pulmonary vasculature in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCA) is highly variable-as is the number, size and position of the MAPCAs and their relationship with the native pulmonary artery system. The priority in the management of this disease should be attaining timely and complete unifocalization, as opposed to single-stage full repair in every case. The merit of early unifocalization is that it secures the pulmonary vascular bed by (a) avoiding loss of lung segments from progressive stenosis/atresia of MAPCA origins, (b) preventing lung injury from high pressure/flow in areas fed by large, unobstructed MAPCAs, and (c) restoring central continuity of the pulmonary vasculature.

Does using the Lung Clearance Index (LCI) inform clinical decisions in children with cystic fibrosis?

Introduction: The Lung Clearance Index (LCI) is an established research test, but its role in clinical decision-making is not well defined. This study estimated the proportion of treatment decisions that are changed or supported by the added information provided by LCI.

Methods: A mixed methods prospective observational study was conducted in North America.

Right ventricular remodeling in complex congenital heart disease.

In congenital heart diseases (CHD) of moderate to great complexity involving the right ventricle (RV), the morphologic RV can be exposed to significant stressors across the lifespan either in a biventricular circulation in a sub-pulmonary or sub-aortic position, or as part of a univentricular circulation. These include pressure and/or volume overload, hypoxia, ischemia, and periprocedural surgical stress leading to remodeling, maladaptation, dilation hypertrophy and dysfunction. This review examines the macroscopic remodeling of the RV in various forms of CHD and explores remodeling trajectories, along with the effects of surgeries and residual lesion repair, in tetralogy of Fallot, Ebstein anomaly, congenitally corrected transposition of the great arteries, transposition of the great arteries with atrial switch surgery, and single ventricle palliated by Fontan.

Home oxygen therapy for Thai preterm infants with bronchopulmonary dysplasia. What are the predictive factors for successful weaning: a 20-year review.

Background: Consequences of lung injury and inflammation in preterm infants with bronchopulmonary dysplasia (BPD) contribute to prolonged oxygen requirements. Home oxygen therapy (HOT) is an alternative way of respiratory support in infant with BPD. However, there is no consensus on weaning guidelines.

The association between self-reported total gestational weight gain by pre-pregnancy body mass index and moderate to late preterm birth.

Background: Inadequate and excessive gestational weight gain (GWG) defined by the Institute of Medicine (IOM) has been associated with preterm birth. However, studies demonstrate inconsistent associations.

Objectives: We examined the associations between categorical and continuous total GWG and moderate to late preterm birth (32-<37 weeks), and evaluated differences in these associations by pre-pregnancy BMI.

Systematic Analysis of the Design, Methodology and Patient Population Characteristics of the Pediatric Direct Oral Anticoagulant (DOAC) Trials of Venous Thromboembolism Treatment.

Introduction: The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.

Objective: To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.

Methods: Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.

Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain.

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes anteriorly past the left.

LINE1 elements at distal junctions of rDNA repeats regulate nucleolar organization in human embryonic stem cells.

The nucleolus is a major subnuclear compartment where ribosomal DNA (rDNA) is transcribed and ribosomes are assembled. In addition, recent studies have shown that the nucleolus is a dynamic organizer of chromatin architecture that modulates developmental gene expression. rDNA gene units are assembled into arrays located in the p-arms of five human acrocentric chromosomes.

From Cellular to Metabolic: Advances in Imaging of Inherited Retinal Diseases.

: Inherited retinal diseases (IRDs) are a genetically complex group of disorders, usually resulting in progressive vision loss due to retinal degeneration. Traditional imaging methods help in structural assessments, but limitations exist in early functional cellular-level detection that are crucial for guiding new therapies. : This review includes a systematic search of PubMed and Google Scholar for studies on advanced imaging techniques for IRDs.

Extracorporeal Membrane Oxygenation in Pediatric Patients with Congenital Heart Disease: Surgical Considerations.

The use of extracorporeal membrane oxygenation (ECMO) in the pediatric population has increased over time, with the ability to rescue pulmonary and cardiovascular deterioration. ECMO can be utilized by neonates and children with congenital heart disease in both the preoperative and post-operative setting to improve survival and minimize morbidity. ECMO cannulation strategy must be tailored to age, weight and physiological state of the patient.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Flexed-Neck Flexible Nasolaryngoscopy for Evaluation of the Subglottis and Trachea in Children.

Objective: Determine if a flexed-neck posture during flexible nasolaryngoscopy (FNL) improves visualization of the subglottis.

Study Design: Retrospective review of children undergoing FNL in the neutral (FNL) and flexed-neck (FN-FNL) positions.

Setting: Tertiary children's hospital.