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machine to classify SOZs, PZs, and non-involved regions and was able to significantly increase model accuracy by incorporating local structurefunction coupling.CONCLUSIONS: SOZs and PZs demonstrate a distinct local structure-function coupling to that of non-involved regions and each other. This distinct coupling profile can be used to accurately classify SOZs, PZs and non-involved regions.

Synaptic connectivity between gliomas and adjacent brain was recently implicated in tumorigenesis. However, the interaction of synapse-related genes (SRGs) with patient survival and with established clinical and molecular glioma subtypes merit further study in a large patient cohort. We characterized differential expression of SRGs in gliomas and investigated SRG expression as putative clinical biomarkers in a large glioma cohort. Expression of 1189 SRGs was interrogated via RNA sequencing analysis in 603 gliomas (LGG n=451, GBM n=152) of The Cancer Genome Atlas. SRG expression patterns partitioned gliomas into two clusters that were more distinctive than priorly identified glioma subtypes. The two glioma clusters showed significantly low (14.9 months) or high median survival (105.1 months; Hazard Ratio = 7.1, 95% CI: [5.32, 9.78], p = 1.29e-46 using a log-rank test). The high survival cluster showed overrepresentation of known pro-neural and neural subtypes and IDH-mutated gliomas (p<0.00001). The mesenchymal and classic GBMs and IDH-wild type gliomas were overrepresented in the low survival cluster (p < 0.00001). In addition, an Elastic Net Cox Regression model identified 34 SRGs whose expression significantly predicted differential survival and a prognostic Synapse Gene Score (SGS) was created. Using an accelerated failure time model, SGS predicted survival in the overall gliomas after adjusting for IDH-1 mutation (HR = 2.51, 95% CI: [2.27, 2.7496], p<0.00001), and in the IDH-1 mutant cohort after adjusting for 1p/19q co-deletion (HR = 2.05, 95% CI: [1.73, 2.37], p<0.00001). Our analysis shows that gliomas can be distinctively clustered by differential SRGs expression, suggesting that synapse-related proteins may contribute to tumorigenesis via multiple mechanisms. Furthermore, the potential utility of SRGs as clinical glioma biomarkers is supported by our creation of a prognostic SGS. Future studies elucidating interactions between tumorigenesis and synaptic mechanisms may reveal additional insights for glioma biology and therapeutic targeting.

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Background: Alagille syndrome is a rare genetic syndrome, which arises due to defects in the Notch signaling pathway, resulting in liver, cardiopulmonary, renal, skeletal, and ophthalmologic problems, among others. Epidermoid cysts are rare congenital benign lesions that develop from ectopic ectodermal cell rests formed during neurulation. Case Description: A 24-year-old Alagille syndrome patient presented with hearing loss and was found to have a sizable posterior fossa mass. He underwent craniotomy for uneventful resection of the lesion, which was found to be an epidermoid cyst. Conclusion: While our case may represent a coincidental occurrence of two pathologies presenting together, given that epidermoid cysts arise from aberrant neurulation, and in light of the crucial role of the Notch signaling pathway both in normal neurogenesis and in the pathogenesis of Alagille syndrome, we hypothesize a possible association between these entities.