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Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastomaMedulloblastoma (MB) consists of four core molecular subgroups with distinct clinical features and prognoses. Treatment consists of surgery, followed by radiotherapy and cytotoxic chemotherapy. Despite this intensive approach, outcome remains dismal for patients with certain subtypes of MB, namely, MYC-amplified Group 3 and TP53-mutated SHH. Using high-throughput assays, six human MB cell lines were screened against a library of 3208 unique compounds. We identified 45 effective compounds from the screen and found that cell cycle checkpoint kinase (CHK1/2) inhibition synergistically enhanced the cytotoxic activity of clinically used chemotherapeutics cyclophosphamide, cisplatin, and gemcitabine.
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Congenital anomalies in children with postneonatally acquired cerebral palsy: an international data linkage studyTo describe the major congenital anomalies present in children with postneonatally acquired cerebral palsy (CP), and to compare clinical outcomes and cause of postneonatally acquired CP between children with and without anomalies.
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Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescenceEpigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.
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A Single-Centre Retrospective Review of Modified Blalock-Taussig Shunts: A 22-Year ExperienceThis single-centre retrospective study explores demographics and outcomes of patients who underwent a modified Blalock-Taussig shunt (MBTS) over a 22-year period. The predominant surgical approach in this study is a lateral thoracotomy, in contrast to a midline sternotomy. Risks and outcomes of this approach are compared with national and international literature.
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Impact of ventilation tube insertion on long-term language outcomes at 6 and 10 years of age: A prospective pregnancy cohort studyInvestigating the impact of early childhood ventilation tube insertion (VTI) on long-term language outcomes.
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Gene dysregulation in acute HIV-1 infection – early transcriptomic analysis reveals the crucial biological functions affectedTranscriptomic analyses from early human immunodeficiency virus (HIV) infection have the potential to reveal how HIV causes widespread and lasting damage to biological functions, especially in the immune system. Previous studies have been limited by difficulties in obtaining early specimens.
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Maternal antibiotic exposure during pregnancy and hospitalization with infection in offspring: a population-based cohort studyAntibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections
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Physical and mental health of mothers caring for a child with Rett syndromeThis study compared the behavior profile of cases in the Australian Rett Syndrome Database (ARSD) with those in a British study using the Rett Syndrome...
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Characterizing the risk of respiratory syncytial virus in infants with older siblings: a population-based birth cohort studyOur results lend support to a vaccination strategy which includes family members in order to provide maximum protection for newborn babies.
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Reproducibility of the plasma glucose response to moderate-intensity exercise in adolescents with Type 1 diabetesThe plasma glucose response to moderate-intensity exercise can be reproducible in adolescents with Type 1 diabetes