The Psychosocial Impact of the COVID-19 Pandemic on Adolescent and Young Adult Cancer Survivors in the United States: An Integrative Review.

Adolescent and young adult cancer survivors (AYAs) are uniquely challenged with navigating health care systems during an important developmental phase of life. During the Coronavirus disease 2019 (COVID-19) pandemic, many people experienced social isolation, mental health symptoms, and schooling and employment changes, which may have affected vulnerable AYA cancer survivors. The purpose of this integrative review is to explore the psychosocial impact of the COVID-19 pandemic on AYA cancer survivors in the United States. A literature search was conducted in November 2022 using PubMed, Web of Science, and SCOPUS databases with the following search terms: distress*, depress*, lonel*, anx*, insomnia*, cancer*, neoplasm, COVID-19, coronavirus, young adult, AYA, teen*, and adolescen*. The initial search yielded 468 articles. Inclusion criteria required that studies were conducted in the United States, published in English, with a sample of patients diagnosed with cancer between ages 15 and 39. After review and appraisal of each relevant article, eight were included. Through comparative analysis of eight articles, including qualitative and quantitative studies, three themes emerged: mental health impact, health care impact, and financial impact. Mental health impact included increased anxiety, worsening depression and social isolation, and sleep disturbances. Changes in health care included delays in care, medical cost-coping and benefits of virtual care. Financial difficulties included employment changes and benefits of remote work. The COVID-19 pandemic had an immense impact on the psychosocial health of AYA cancer survivors. It is essential that oncology providers and health care teams consider specific interventions to best serve the psychosocial needs of their AYA patients.

Spatial analysis of recurrent glioblastoma reveals perivascular niche organization.

Tumor evolution is driven by genetic variation; however, it is the tumor microenvironment (TME) that provides the selective pressure contributing to evolution in cancer. Despite high histopathological heterogeneity within glioblastoma (GBM), the most aggressive brain tumor, the interactions between the genetically distinct GBM cells and the surrounding TME are not fully understood. To address this, we analyzed matched primary and recurrent GBM archival tumor tissues with imaging-based techniques aimed to simultaneously evaluate tumor tissues for the presence of hypoxic, angiogenic, and inflammatory niches, extracellular matrix (ECM) organization, TERT promoter mutational status, and several oncogenic amplifications on the same slide and location. We found that the relationships between genetic and TME diversity are different in primary and matched recurrent tumors. Interestingly, the texture of the ECM, identified by label-free reflectance imaging, was predictive of single-cell genetic traits present in the tissue. Moreover, reflectance of ECM revealed structured organization of the perivascular niche in recurrent GBM, enriched in immunosuppressive macrophages. Single-cell spatial transcriptomics further confirmed the presence of the niche-specific macrophage populations and identified interactions between endothelial cells, perivascular fibroblasts, and immunosuppressive macrophages. Our results underscore the importance of GBM tissue organization in tumor evolution and highlight genetic and spatial dependencies.

An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Nonciliated Neurons.

Regulatory Factor X (RFX) transcription factors (TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans, the sole RFX gene, daf-19, encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons, whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is downregulated in the presence of DAF-19, primarily in nonsensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for downregulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform (tm5562) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. Thus, we have identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects that daf-19 exerts on nervous system function.