Improving the Measurement of Environmental Sensitivity in Children and Adolescents: The Highly Sensitive Child Scale-21 Item Version

Children differ in their sensitivity to positive and negative environmental influences, which can be measured with the Highly Sensitive Child (HSC) scale. The present study introduces the HSC-21, an adaptation of the original 12 item scale with new items and factor structure that are meant to be more informative than the original ones. The psychometric properties of the HSC-21 were investigated in 1,088 children across Belgium and the Netherlands, including child and mother reports. Results showed evidence for (a) bifactor model with a general sensitivity factor and two specific factors (i.e., Ease of Excitation–Low Sensory Threshold and Aesthetic Sensitivity); (b) (partial) measurement invariance across gender, developmental stage, country, and informants; (c) moderate child–mother agreement; (d) good reliability; (e) normally distributed item scores; and (f) meaningful associations with personality and temperament across both samples. No evidence was found for HSC-21 as a moderator in the relationship between parenting and problem behaviors

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Precision medicine approaches for the management of Ewing sarcoma: current perspectives

Victoria T Rizk,1 Christine M Walko,2 Andrew S Brohl3,41University of South Florida Hematology/Oncology Fellowship, 2DeBartolo Family Personalized Medicine Institute, 3Sarcoma Department, 4Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Advancements in molecular and genetic techniques have significantly furthered our biological understanding of Ewing sarcoma (ES). ES is typified by a driving TET–ETS fusion with an otherwise relatively quiet genome. Detection of one of several characteristic fusions, most commonly EWSR1–FLI1, is the gold standard for diagnosis. We discuss the current role of precision medicine in the diagnosis, treatment, and monitoring of ES. Continued efforts toward molecularly guided approaches are actively being pursued in ES to better refine prognosis, identify germline markers of disease susceptibility, influence therapeutic selection, effectively monitor disease activity in real time, and identify genetic and immunotherapeutic targets for therapeutic development. Keywords: Ewing sarcoma, next generation sequencing, genomics, liquid biopsy, targeted therap