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OBJECTIVELower-grade gliomas (LGGs) are often observed within eloquent regions, which indicates that tumor resection in these areas carries a potential risk for neurological disturbances, such as motor deficit, language disorder, and/or neurocognitive impairments. Some patients with frontal tumors exhibit severe impairments of neurocognitive function, including working memory and spatial awareness, after tumor removal. The aim of this study was to investigate neurocognitive and functional outcomes of frontal LGGs in both the dominant and nondominant hemispheres after awake brain mapping.METHODSData from 50 consecutive patients with diffuse frontal LGGs in the dominant and nondominant hemispheres who underwent awake brain surgery between December 2012 and September 2018 were retrospectively analyzed. The goal was to map neurocognitive functions such as working memory by using working memory tasks, including digit span testing and N-back tasks.RESULTSDue to awake language mapping, the frontal aslant tract was frequently identified as a functional boundary in patients with left superior frontal gyrus tumors (76.5%). Furthermore, functional boundaries were identified while evaluating verbal and spatial working memory function by stimulating the dorsolateral prefrontal cortex using the digit span and visual N-back tasks in patients with right superior frontal gyrus tumors (7.1%). Comparing the preoperative and postoperative neuropsychological assessments from the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III) and Wechsler Memory Scale–Revised (WMS-R), significant improvement following awake surgery was observed in mean Perceptual Organization (Z = −2.09, p = 0.04) in WAIS-III scores. Postoperative mean WMS-R scores for Visual Memory (Z = −2.12, p = 0.03) and Delayed Recall (Z = −1.98, p = 0.04) were significantly improved compared with preoperative values for every test after awake surgery. No significant deterioration was noted with regard to neurocognitive functions in a comprehensive neuropsychological test battery. In the postoperative course, early transient speech and motor disturbances were observed in 30.0% and 28.0% of patients, respectively. In contrast, late permanent speech and motor disturbances were observed in 0% and 4.0%, respectively.CONCLUSIONSIt is noteworthy that no significant postoperative deterioration was identified compared with preoperative status in a comprehensive neuropsychological assessment. The results demonstrated that awake functional mapping enabled favorable neurocognitive and functional outcomes after surgery in patients with diffuse frontal LGGs.

There are no accurate mass screening methods for early detection of central nervous system (CNS) tumors. Recently, liquid biopsy has received a lot of attention for less-invasive cancer screening. Unlike other cancers, CNS tumors require efforts to find biomarkers due to the blood–brain barrier, which restricts molecular exchange between the parenchyma and blood. Additionally, because a satisfactory way to collect urinary biomarkers is lacking, urine-based liquid biopsy has not been fully investigated despite the fact that it has some advantages compared to blood or cerebrospinal fluid-based biopsy. Here, we have developed a mass-producible and sterilizable nanowire-based device that can extract urinary microRNAs efficiently. Urinary microRNAs from patients with CNS tumors (n = 119) and noncancer individuals (n = 100) were analyzed using a microarray to yield comprehensive microRNA expression profiles. To clarify the origin of urinary microRNAs of patients with CNS tumors, glioblastoma organoids were generated. Glioblastoma organoid-derived differentially expressed microRNAs (DEMs) included 73.4% of the DEMs in urine of patients with parental tumors but included only 3.9% of those in urine of noncancer individuals, which suggested that many CNS tumor-derived microRNAs could be identified in urine directly. We constructed the diagnostic model based on the expression of the selected microRNAs and found that it was able to differentiate patients and noncancer individuals at a sensitivity and specificity of 100 and 97%, respectively, in an independent dataset. Our findings demonstrate that urinary microRNAs extracted with the nanowire device offer a well-fitted strategy for mass screening of CNS tumors.

The µ-η 2 :η 2 -peroxodicopper(II) (Cu 2 (µ-η 2 :η 2 -O 2 )) and bis(µoxo)dicopper(III) (Cu 2 (µ-O) 2 ) species have been investigated in the model studies of type III copper proteins, and these structures are also considered as important motifs for O 2 -activating metalloproteins in biological systems. 1,2 The interconversion between these species in solution was found to depend on organic solvents and counteranions. 2,3 Recent studies of the interconversion equilibrium in copper-aliphatic diamine complex systems strongly suggested that coordination of counteranions promotes the conversion of Cu 2 (µ-O) 2 to Cu 2 (µ-η 2 :η 2 -O 2 ) species. 2b,3b,c However, direct evidence for formation of the anion-coordinating structure is yet to be presented. Here, we report the formation and crystal structure of a new Cu 2 (µ-η 2 :η 2 -O 2 ) complex with a bridging carboxylate ligand. 4a Structural studies and density functional theory (DFT) calculations suggested factors regulating stepwise-activation of dioxygen by bridging-carboxylate ligation to the dicopper core.

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