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Pre-Clinical Evaluation of the Hypomethylating Agent Decitabine for the Treatment of T-Cell Lymphoblastic LymphomaT-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10-20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing.
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Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirementsInfant MLL-AF4-driven acute lymphoblastic leukemia (ALL) is a devastating disease with dismal prognosis. A lack of understanding of the unique biology of this disease, particularly its prenatal origin, has hindered improvement of survival. We perform multiple RNA sequencing experiments on fetal, neonatal, and adult hematopoietic stem and progenitor cells from human and mouse.
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Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 ProtocolInfant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).
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Haemophilus influenzae remains the predominant otitis media pathogen in Australian children undergoing ventilation tube insertion in the PCV13 eraUnderstanding patterns of bacterial carriage and otitis media (OM) microbiology is crucial for assessing vaccine impact and informing policy. The microbiology of OM can vary with geography, time, and interventions like pneumococcal conjugate vaccines (PCVs). We evaluated the microbiology of nasopharyngeal and middle ear effusions in children living in Western Australia, 11 years following the introduction of PCV13.
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Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomesNeonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism.
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Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in AdultsConventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling.
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Clinical Predictors of Longitudinal Respiratory Exacerbation Outcomes in Young Hospitalised ChildrenRespiratory infection and wheezing illness are leading causes of hospitalisation in childhood, placing a significant burden on families and healthcare systems. However, reliably distinguishing children at risk of developing persistent disease from those likely to outgrow their symptoms remains a clinical challenge. Earlier identification would allow clinicians to focus care and resources on those most likely to benefit from long-term management, while reducing anxiety and uncertainty about the future for families.
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Healthy skin for children and young people with skin of colour starts with clinician knowledge and recognitionSkin conditions most frequently encountered in paediatric practice include infections, infestations, atopic dermatitis, and acne. Skin of colour refers to skin with increased melanin and darker pigmentation, and reflects global racial and ethnic diversity.
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A population pharmacokinetic study of benzathine benzylpenicillin G administration in children and adolescents with rheumatic heart diseaseFew children and adolescents receiving BPG as secondary prophylaxis will achieve concentrations >0.02 mg/L for the majority of the time between injections
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Investigation of group A Streptococcus immune responses in an endemic setting, with a particular focus on J8We analysed the stimulation of J8 antibodies in response to infection, and the role of existing J8 antibodies in protection against subsequent infection