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Disruption of cotranscriptional splicing suggests that RBM39 is a therapeutic target in acute lymphoblastic leukemiaThere are few options for patients with relapse/refractory B-cell acute lymphoblastic leukemia, thus this is a major area of unmet medical need. Here, we reveal that inclusion of a poison exon in RBM39, which could be induced both by CDK9 or CDK9 independent CMGC (cyclin-dependent kinases, mitogen-activated protein kinases, glycogen synthase kinases, CDC-like kinases) kinase inhibition, is recognized by the nonsense-mediated mRNA decay pathway for degradation.
Research
B cell epitope mapping: The journey to better vaccines and therapeutic antibodiesB-cell epitope mapping is an approach that can identify and characterise specific antigen binding sites of B-cell receptors and secreted antibodies. The ability to determine the antigenic clusters of amino acids bound by B-cell clones provides unprecedented detail that will aid in developing novel and effective vaccine targets and therapeutic antibodies for various diseases.
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Transcriptional rewiring in CD8+ T cells: implications for CAR-T cell therapy against solid tumoursT cells engineered to express chimeric-antigen receptors (CAR-T cells) can effectively control relapsed and refractory haematological malignancies in the clinic. However, the successes of CAR-T cell therapy have not been recapitulated in solid tumours due to a range of barriers such as immunosuppression, poor infiltration, and tumour heterogeneity.
Research
Mesothelioma survival prediction based on a six-gene transcriptomic signatureMesothelioma is a lethal cancer. Despite promising outcomes associated with immunotherapy, durable responses remain restricted to a minority of patients, highlighting the need for improved strategies that better predict outcome. Here, we described the development of a mesothelioma-specific gene signature that accurately predicts survival.
Research
Dog Ownership, Physical Activity, and Mental Health in Mid-to-Older Aged Adults: Findings From the HABITAT Cohort StudyDog ownership is a potential strategy for maintaining physical activity levels and supporting healthy aging. This study examined longitudinal effects of dog ownership and dog walking on physical activity and mental health in mid-to-older aged adults.
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Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS studyAim: To describe the real-world effects of trofinetide in individuals with Rett syndrome (RTT) using the 18-month follow-up analysis of the LOTUS study.
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Pathways to Adolescent Pregnancy in Southeast Asia: Qualitative Evidence From Lived Experiences of Girls in Four CountriesHistorically, adolescent pregnancy has been conceptualized as an outcome of child marriage, but in Southeast Asia, the contexts and drivers of adolescent pregnancy are less well-understood. This study examines the relationship between adolescent pregnancy and child marriage and explores the drivers of pregnancy in Cambodia, Indonesia, Lao People's Democratic Republic and Malaysia among adolescents who have experienced pregnancy.
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Pain and recovery profiles following common orthopaedic surgeries in childrenLittle evidence exists on the postoperative trajectory after paediatric orthopaedic surgery. Pain and behavioural disturbance can have short- and long-term impacts on children and their families. An improved understanding of procedure-specific postoperative trajectories can enhance recovery. The primary outcome was to examine the duration and severity of postoperative pain experienced by children undergoing 10 commonly performed orthopaedic procedures.
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Automated Insulin Delivery Is Associated with Reduced Hospital Admissions and Costs for Acute Diabetes Complications in Children with Type 1 DiabetesThis study evaluated the association between insulin regimen, hospitalization for acute diabetes complications, and related health care costs in children with type 1 diabetes (T1D). Hospital admissions for diabetic ketoacidosis or hypoglycemia between January 5, 2022, and April 30, 2024, were analyzed in Western Australian children with T1D. Admissions due to newly diagnosed T1D were excluded. Incidence rate ratios were calculated using generalized estimating equations, adjusted for age, diabetes duration, and socioeconomic status.
Research
Intranasal phage therapy overcomes antibody neutralization challenges in pulmonary Pseudomonas aeruginosa infectionsPhage therapy is a promising approach against multidrug-resistant infections, yet systemic administration can lead to incomplete cures. We investigated the distribution, immune responses, and efficacy of the therapeutic phage KPP10 delivered via intranasal or intraperitoneal routes in murine Pseudomonas aeruginosa lung infection models.