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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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Impact of covid-19 restrictions on western Australian children’s physical activity and screen timePhysical activity is essential for children’s healthy development, yet COVID-19 physical distancing restrictions such as school closures and staying at home, playground closures, and the cancelling of organised community sport have dramatically altered children’s opportunities to be physically active. This study describes changes in levels of physical activity and screen time from February 2020 (i.e., before COVID-19 restrictions were introduced in Western Australia) to May 2020 (i.e., when COVID-19 restrictions were in place). Parents of children aged 5 to 9 years from Western Australia were eligible to participate and recruited through convenience sampling.
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Barriers and Considerations for Diagnosing Rare Diseases in Indigenous PopulationsAdvances in omics and specifically genomic technologies are increasingly transforming rare disease diagnosis. However, the benefits of these advances are disproportionately experienced within and between populations, with Indigenous populations frequently experiencing diagnostic and therapeutic inequities. The International Rare Disease Research Consortium (IRDiRC) multi-stakeholder partnership has been advancing toward the vision of all people living with a rare disease receiving an accurate diagnosis, care, and available therapy within 1 year of coming to medical attention. In order to further progress toward this vision, IRDiRC has created a taskforce to explore the access barriers to diagnosis of rare genetic diseases faced by Indigenous peoples, with a view of developing recommendations to overcome them.
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Romidepsin enhances the efficacy of cytarabine in vivo, revealing HDAC inhibition as a therapeutic strategy for KMT2A-rearranged acute lymphoblastic leukemiaIn this study, we investigate the in vivo synergy between romidepsin and cytarabine
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Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironmentOur results identify a pretreatment tumor microenvironment that predicts response to immune checkpoint blockade, which can be therapeutically attained
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Exposure to Solar UVR Suppresses Cell-Mediated Immunization Responses in Humans: The Australian Ultraviolet Radiation and Immunity StudyHigher UVR exposure at antigen sensitization was associated with a reduced delayed-type hypersensitivity response and altered T helper type 17 kinetics
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Overcrowded housing: One of a constellation of vulnerabilities for child sexual abuseThe findings suggest that overcrowded living conditions are associated with an increased risk of sexual abuse for some children
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Immunogenicity and Safety of a Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine 6 Years After MenC Priming as ToddlersOne dose of MenACWY-TT boosts protection against MenC in primed children, is safe and extends protection against MenA, MenW and MenY
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Gamifying Breastfeeding for Fathers: Process Evaluation of the Milk Man Mobile AppThe Milk Man app was an acceptable source of breastfeeding information and support that fathers and fathers-to-be are prepared to use throughout the perinatal period