St. Jude Children's Research Hospital

Paediatric therapeutic development workshop on osteosarcoma

The fourth Paediatric Therapeutic Development Workshop focused on osteosarcoma, the most common primary bone cancer in children and young adults. Current treatment of osteosarcoma comprises surgery and chemotherapy. Outcome has shown very little improvement over the last four dec...

Decoding TnsC Filament Assembly in CRISPR-Associated Transposons Using Interpretable Deep Learning and Molecular Simulations

Abstract CRISPR-associated transposons (CASTs) enable programmable DNA integration, yet how the TnsC regulator forms processive filaments on DNA to coordinate RNA-guided transposition in type V-K CAST systems remains unknown. Here, we integrate large-scale molecular simulations,...

Splicing genes as main targets of differential splicing

Abstract Splicing of transcripts via the spliceosome machinery is a complex process involving a multitude of proteins and short noncoding RNAs. In addition to full-length transcripts with all exons in the genomically encoded order, alternatively spliced transcripts can also be pr...

Beyond the scaffold: Glia as architects of the neural extracellular matrix

Astrocytes, oligodendrocyte lineage cells, and microglia dynamically shape the neural extracellular matrix (ECM) across brain development and aging. Recent findings highlight the potential of glial regulation of the ECM as a framework for understanding circuit formation and ident...

Optimizing safety and efficacy of asparaginase and blinatumomab therapy in frontline acute lymphoblastic leukemia regimens in diverse health care settings—international expert consensus

Frontline blinatumomab combined with chemotherapy has resulted in improved outcomes in both pediatric and adult patients with acute lymphoblastic leukemia and is considered the new cornerstone of acute lymphoblastic leukemia treatment. The role of asparaginase in this new landsca...

Longitudinal evaluation of sleep disturbances in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

Abstract Purpose The current study examines longitudinal changes in sleep disturbances and the risks they pose for new-onset health conditions in survivors of childhood cancer. Methods Five-year survivors ( N = 1081; median [range] age 50.0 [45.2–55.0] years) and siblings ( N = 2...

MBNL1 hijacks a structured single-stranded distal DNA element to sustain FLT3 expression in KMT2A-rearranged leukemias

The molecular mechanisms by which KMT2A-rearranged (KMT2A-r) leukemias maintain the oncogenic FLT3 expression remain largely unclear, limiting therapeutic opportunities. Here, we identify the RNA binding protein MBNL1 as an unexpected positive regulator of FLT3 by DepMap dataset...

ZPY-CpG-Ch, a broad coverage vaccine against Streptococcus pneumoniae

Existing licensed pneumococcal vaccines, including Prevnar-13 and its higher-valency successors, have played a major role in reducing invasive pneumococcal disease worldwide. However, their effectiveness is increasingly threatened by the rise of multidrug-resistant strains and th...

Designing Reliable Care Through Clinical Pathways: A Human Factors Framework

Background/Objectives: Healthcare delivery systems are inherently complex, and efforts to improve quality and safety often fail to achieve sustained, system-wide impact because of misalignment between work system design, care processes, and clinical practice. This article present...