Background and Aims Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. Approach and Results To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n = 17) of tumors and microvascular invasion in 25% (n = 94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC‐driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P = 1.7 × 10−11; human FN1, P = 1.5 × 10−4) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n = 153; P < 0.001). Lastly, we showed that plasma fibronectin levels were significantly elevated in patients with HCC (n = 35; mean = 307.7 μg/mL; SEM = 35.9) when compared to cirrhosis (n = 10; mean = 41.8 μg/mL; SEM = 13.3; P < 0.0001). Conclusions Our study evaluates the molecular landscape of tumors with VI, identifying distinct transcriptional, epigenetic, and proteomic changes driven by the MYC oncogene. We show that MYC up‐regulates fibronectin expression, which promotes HCC invasiveness. In addition, we identify fibronectin to be a promising noninvasive proteomic biomarker of VI in HCC.

Background and Objective Children with a history of acute provoked neonatal seizures are at high risk for disability, often requiring developmental services. The COVID-19 pandemic has led to widespread changes in how healthcare is delivered. Our objective was to determine the magnitude of service interruption of services among children born between 10/2014-12/2017 and enrolled in the Neonatal Seizure Registry (NSR) , a nine-center collaborative of pediatric centers in the US. Design /Methods Prospective cohort study of children with acute provoked seizures with onset 44 weeks gestation and evaluated at age 3-6 years. Parents of children enrolled in the NSR completed a survey about their child’s access to developmental services between June 2020 and April 2021. Results Among 144 children enrolled, 72 children (50%) were receiving developmental services at the time of assessment. Children receiving services were more likely to be male, born preterm, and have seizure etiology of infection or ischemic stroke. Of these children, 64 (89%) experienced a disruption in developmental services due to the pandemic, with the majority of families (n=47, 73%) reporting that in-person services were no longer available. Conclusion Half of children with acute provoked neonatal seizures were receiving developmental services at ages 3-6 years. The COVID-19 pandemic has led to widespread changes in delivery of developmental services. Disruptions in services have the potential to impact long term outcomes for children who rely on specialized care programs to optimize mobility and learning.

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BACKGROUND/PURPOSE: Therapeutic hypothermia (TH) initiated within the fi rst 6 hours after birth, is proven to decrease brain tissue injury in moderate to severe neonatal encephalopathy (NE) and improve 18-24 month neurological outcomes. Recently, a correlation between the resistive index (RI) of the anterior cerebral artery on head ultrasound (HUS) performed after rewarming and severity of injury on MRI was reported. It remains unknown whether early RI anomalies (before rewarming) may be associated with severity of injury on MRI and as such, might have prognostic value for infants too unstable to undergo an MRI within the optimal time window. The aim of this study was to evaluate: (i) the association between a low anterior cerebral artery RI on HUS obtained during active TH and the severity of brain injury on MRI, and to examine the association between the RI value and outcomes at 48 months of age.