Histone H3.3 mutations are a hallmark of pediatric gliomas, but their core oncogenic mechanisms are not well-defined. To identify major effectors, we used CRISPR-Cas9 to introduce H3.3K27M and G34R mutations into previously H3.3-wildtype brain cells, while in parallel reverting the mutations in glioma cells back to wildtype. ChIP-seq analysis broadly linked K27M to altered H3K27me3 activity including within super-enhancers, which exhibited perturbed transcriptional function. This was largely independent of H3.3 DNA binding. The K27M and G34R mutations induced several of the same pathways suggesting key shared oncogenic mechanisms including activation of neurogenesis and NOTCH pathway genes. H3.3 mutant gliomas are also particularly sensitive to NOTCH pathway gene knockdown and drug inhibition, reducing their viability in culture. Reciprocal editing of cells generally produced reciprocal effects on tumorgenicity in xenograft assays. Overall, our findings define common and distinct K27M and G34R oncogenic mechanisms, including potentially targetable pathways.

Ultrasound and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value. © 2017 John Wiley & Sons, Ltd.

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Purpose: The purpose of this systematic review is to examine the effectiveness of music therapy for adolescents and young adults with anxiety disorders. Methods: PRISMA guidelines were followed in performing this systematic review. Studies published in the last 25 years from September 1997 to September 2022 were identified through the use of the Medline, PsycInfo, PubMed, and Google Scholar databases, using the keywords: music* AND anxi*. Two authors independently conducted a focused analysis and reached a final consensus on six studies that met the specific selection criteria and passed the study quality checks. Results: All six studies included showed significant improvement as measured by anxiety symptom severity measures for adolescents and young adults receiving music therapy. Conclusion: While music therapy has shown to be promising as a stand-alone or adjunctive treatment for anxiety disorders in adolescents and young adults, more research is needed to establish music therapy as an effective treatment.

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