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DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3DYRK1A is a serine/threonine kinase encoded on human chromosome 21 (HSA21) that has been implicated in several pathologies of Down syndrome (DS), including cognitive deficits and Alzheimer's disease. Although children with DS are predisposed to developing leukemia, especially B cell acute lymphoblastic leukemia (B-ALL), the HSA21 genes that contribute to malignancies remain largely undefined. Here, we report that DYRK1A is overexpressed and required for B-ALL. Genetic and pharmacologic inhibition of DYRK1A decreased leukemic cell expansion and suppressed B-ALL development in vitro and in vivo.
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The role of fit testing N95/FFP2/FFP3 masks: a narrative reviewFor healthcare workers performing aerosol-generating procedures during the COVID-19 pandemic, well fitted filtering facepiece respirators, for example, N95/FFP2 or N99/FFP3 masks, are recommended as part of personal protective equipment. In this review, we evaluate the role of fit checking and fit testing of respirators, in addition to airborne protection provided by respirators. Filtering facepiece respirators are made of material with sufficient high filter capacity to protect against airborne respiratory viruses.
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The Role of Cannabinoids as Anticancer Agents in Pediatric OncologyCannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant Cannabis sativa L. Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects, including memory, pain, reproduction, bone remodeling or immunity, to name a few. Unsurprisingly, given these broad physiological effects, alterations of the ECS have been found in different diseases, including cancer.
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Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in AustraliaEmpyema is a serious complication of pneumonia frequently caused by Streptococcus pneumoniae (SP). We assessed the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema after inclusion in the Australian National Immunisation Program.
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Zika Virus Changes Methylation of Genes Involved in Immune Response and Neural Development in Brazilian Babies Born With Congenital MicrocephalyThe recent increase in babies born with brain and eye malformations in Brazil is associated with Zika virus (ZIKV) infection in utero. ZIKV alters host DNA methylation in vitro. Using genome-wide DNA methylation profiling we compared 18 babies born with congenital ZIKV microcephaly with 20 controls. We found ZIKV-associated alteration of host methylation patterns, notably at RABGAP1L which is important in brain development, at viral host immunity genes MX1 and ISG15, and in an epigenetic module containing the causal microcephaly gene MCPH1. Our data support the hypothesis that clinical signs of congenital ZIKV are associated with changes in DNA methylation.
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Pulmonary Gas Exchange Improves over the First Year in Preterm Infants with and without Bronchopulmonary DysplasiaRight shift of the peripheral oxyhaemoglobin saturation (SpO2) versus inspired oxygen pressure (PIO2) curve is a sensitive marker of pulmonary gas exchange. The aim of this study was to assess the impact of prematurity and bronchopulmonary dysplasia (BPD) on gas exchange and right-to-left shunt in the neonatal period, and its evolution over the first year of life.
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Exposomes and metabolic health through a physical activity lens: a narrative reviewIn this narrative review, we provide an overview of the role of physical activity as part of differing exposomes (our combined non-genetic exposures from conception onwards) and environmental influences on metabolic health. We discuss 'beneficial' exposomes (green/natural outdoor spaces, sun exposure, healthy diets and features of built environments) that could synergise with physical activity to prevent metabolic dysfunction, particularly that related to lifestyle diseases of obesity, type 2 diabetes and metabolic syndrome.
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Australia needs a prioritised national research strategy for clinical trials in a pandemic: lessons learned from COVID-19The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sparking a global pandemic, has driven an imperative to quickly design and conduct treatment studies. We strongly propose a national, coordinated approach for randomised controlled trials (RCTs) for coronavirus disease 2019 (COVID-19), future pandemics and inter-pandemic periods in Australia.
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OmicsVolcano: software for intuitive visualization and interactive exploration of high-throughput biological dataAdvances in omics technologies have generated exponentially larger volumes of biological data; however, their analyses and interpretation are limited to computationally proficient scientists. We created OmicsVolcano, an interactive open-source software tool to enable visualization and exploration of high-throughput biological data, while highlighting features of interest using a volcano plot interface. In contrast to existing tools, our software and user-interface design allow it to be used without requiring any programming skills to generate high-quality and presentation-ready images.
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Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail FormulationAntimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials.