A therapeutic window for preventive therapy in NF1-associated optic pathway glioma.

Pediatric low-grade gliomas (pLGGs) are almost universally driven by abnormal activation of RAS-mediated MEK-ERK/MAPK signaling pathway. pLGGs predominantly occur in children, suggesting that they originate in an ERK-dependent neural stem/progenitor population(s) transiently present in the developing brain. Our recent preclinical study reveals a cell-lineage-of-origin and develops a chemopreventative therapeutic strategy.

Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors.

The mechanism of vulnerability to pediatric low-grade gliomas (pLGGs)-the most common brain tumor in children-during development remains largely unknown. Using mouse models of neurofibromatosis type 1 (NF1)-associated pLGGs in the optic pathway (NF1-OPG), we demonstrate that NF1-OPG arose from the vulnerability to the dependency of Mek-Erk/MAPK signaling during gliogenesis of one of the two developmentally transient precursor populations in the optic nerve, brain-derived migrating glial progenitors (GPs), but not local progenitors. Hyperactive Erk/MAPK signaling by Nf1 loss overproduced GPs by disrupting the balance between stem-cell maintenance and gliogenesis of hypothalamic ventricular zone radial glia (RG).

Immigration Detention in the United States: Identifying Alternatives That Comply With Human Rights and Advance Public Health.

Under international law, the United States is obligated to uphold noncitizens' fundamental rights, including their rights to health. However, current US immigration laws-and their enforcement-not only fail to fulfill migrants' health rights but actively undermine their realization and worsen the pandemic's spread. Specifically, the US immigration system's reliance on detention, which precludes effective social distancing, increases risks of exposure and infection for detainees, staff, and their broader communities.

Murine models of IDH-wild-type glioblastoma exhibit spatial segregation of tumor initiation and manifestation during evolution.

Recent characterization of spatiotemporal genomic architecture of IDH-wild-type multifocal glioblastomas (M-GBMs) suggests a clinically unobserved common-ancestor (CA) with a less aggressive phenotype, generating highly genetically divergent malignant gliomas/GBMs in distant brain regions. Using serial MRI/3D-reconstruction, whole-genome sequencing and spectral karyotyping-based single-cell phylogenetic tree building, we show two distinct types of tumor evolution in p53-mutant driven mouse models. Malignant gliomas/GBMs grow as a single mass (Type 1) and multifocal masses (Type 2), respectively, despite both exhibiting loss of Pten/chromosome 19 (chr19) and PI3K/Akt activation with sub-tetraploid/4N genomes.

Sox2 cells in Sonic Hedgehog-subtype medulloblastoma resist p53-mediated cell-cycle arrest response and drive therapy-induced recurrence.

Background: High-intensity therapy effectively treats most wild-type (-WT) Sonic Hedgehog-subgroup medulloblastomas (SHH-MBs), but often cause long-term deleterious neurotoxicities in children. Recent clinical trials investigating reduction/de-escalation of therapy for -WT SHH-MBs caused poor overall survival. Here, we investigated whether reduced levels of p53-pathway activation by low-intensity therapy potentially contribute to diminished therapeutic efficacy.

Umbilical cord milking at birth for term newborns with acidosis: neonatal outcomes.

Objective: To determine if umbilical cord milking is detrimental in compromised term/near-term infants.

Study Design: A retrospective analysis of infants with abnormal cord gases (cord arterial or venous pH of ≤ 7.1 or base deficit > -12).