Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma.

Group 3 medulloblastoma (G3 MB) carries the worst prognosis of all MB subgroups. MYC oncoprotein is elevated in G3 MB tumors; however, the mechanisms that support MYC abundance remain unclear. Using metabolic and mechanistic profiling, we pinpoint a role for mitochondrial metabolism in regulating MYC. Complex-I inhibition decreases MYC abundance in G3 MB, attenuates the expression of MYC-downstream targets, induces differentiation, and prolongs male animal survival. Mechanistically, complex-I inhibition increases inactivating acetylation of antioxidant enzyme SOD2 at K68 and K122, triggering the accumulation of mitochondrial reactive oxygen species that promotes MYC oxidation and degradation in a mitochondrial pyruvate carrier (MPC)-dependent manner. MPC inhibition blocks the acetylation of SOD2 and oxidation of MYC, restoring MYC abundance and self-renewal capacity in G3 MB cells following complex-I inhibition. Identification of this MPC-SOD2 signaling axis reveals a role for metabolism in regulating MYC protein abundance that has clinical implications for treating G3 MB.

Integrative Neuroinformatics for Precision Prognostication and Personalized Therapeutics in Moderate and Severe Traumatic Brain Injury.

Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the "one-treatment fits all" approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex "-omics" data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.

Automated Detection of Helium Bubbles in Irradiated X-750.

Imaging nanoscale features using transmission electron microscopy is key to predicting and assessing the mechanical behavior of structural materials in nuclear reactors. Analyzing these micrographs is often a tedious and labour intensive manual process. It is a prime candidate for automation. Here, a region-based convolutional neural network is adapted to detect helium bubbles in micrographs of neutron-irradiated Inconel X-750 reactor spacer springs. We demonstrate that this neural network produces analyses of similar accuracy and reproducibility to that produced by humans. Further, we show this method as being four orders of magnitude faster than manual analysis allowing for generation of significant quantities of data. The proposed method can be used with micrographs of different Fresnel contrasts and magnification levels.

Pneumoretroperitoneum in two patients with Clostridium perfringens necrotizing pancreatitis.

Pancreatic gas gangrene is an uncommon and often fatal complication of acute pancreatitis, due to the sporulating anaerobe Clostridium perfringens. C. perfringens is a normal constituent of colonic flora, but infects the pancreas by either transmural spread from the colon or via the biliary tree. Only three reported cases in the world literature describe acute pancreatitis with pneumoretroperitoneum and clostridial infection. Two separate cases, at the same institution, of acute pancreatitis complicated by C. perfringens were analyzed. The records of patients were reviewed for admission history, laboratory and radiology results, intensive care support, surgical intervention, and outcome. Retroperitoneal air was visualized early in the clinical course of both patients by computed tomography. Early surgical debridement, drainage, parental antibiotics, and reexploration resulted in an uncomplicated recovery. Early computed tomography in patients with suspected necrotizing pancreatitis contributes to early intervention and may advantageously enhance survival.