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Meningiomas account for one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system there remains considerable uncertainty in predicting tumor behavior. Here, we analyzed 160 tumors from all 3 World Health Organization (WHO) grades (I through III) using clinical, gene expression, and sequencing data. Unsupervised clustering analysis identified 3 molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which classifies more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell-cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.

The nature of astrocyte diversity in the adult brain has remained poorly defined. The authors identify five astrocyte subpopulations in the brain that exhibit extensive molecular and functional diversity. They uncover correlative populations in malignant glioma, providing insight into how diverse astrocyte populations contribute to synaptogenesis, tumor pathophysiology and neurological disease. Astrocytes are the most abundant cell type in the brain, where they perform a wide array of functions, yet the nature of their cellular heterogeneity and how it oversees these diverse roles remains shrouded in mystery. Using an intersectional fluorescence-activated cell sorting–based strategy, we identified five distinct astrocyte subpopulations present across three brain regions that show extensive molecular diversity. Application of this molecular insight toward function revealed that these populations differentially support synaptogenesis between neurons. We identified correlative populations in mouse and human glioma and found that the emergence of specific subpopulations during tumor progression corresponded with the onset of seizures and tumor invasion. In sum, we have identified subpopulations of astrocytes in the adult brain and their correlates in glioma that are endowed with diverse cellular, molecular and functional properties. These populations selectively contribute to synaptogenesis and tumor pathophysiology, providing a blueprint for understanding diverse astrocyte contributions to neurological disease.

The object recognition concept is being widely used a result of increasing CCTV surveillance and the need for automatic object or activity detection from images or video. Increases in the use of various sensor networks have also raised the need of lightweight process frameworks. Much research has been carried out in this area, but the research scope is colossal as it deals with open-ended problems such as being able to achieve high accuracy in little time using lightweight process frameworks. Convolution Neural Networks and their variants are widely used in various computer vision activities, but most of the architectures of CNN are application-specific. There is always a need for generic architectures with better performance. This paper introduces the Dimension-Based Generic Convolution Block (DBGC), which can be used with any CNN to make the architecture generic and provide a dimension-wise selection of various height, width, and depth kernels. This single unit which uses the separable convolution concept provides multiple combinations using various dimension-based kernels. This single unit can be used for height-based, width-based, or depth-based dimensions; the same unit can even be used for height and width, width and depth, and depth and height dimensions. It can also be used for combinations involving all three dimensions of height, width, and depth. The main novelty of DBGC lies in the dimension selector block included in the proposed architecture. Proposed unoptimized kernel dimensions reduce FLOPs by around one third and also reduce the accuracy by around one half; semi-optimized kernel dimensions yield almost the same or higher accuracy with half the FLOPs of the original architecture, while optimized kernel dimensions provide 5 to 6% higher accuracy with around a 10 M reduction in FLOPs.

To the Editor: The review of protein-losing enteropathy (PLE) by Ozen and Lenardo (Aug. 24 issue) 1 provides a vivid depiction of the two principal pathologic mechanisms — namely, intestinal mucosa damage and microcirculation drainage failure (Fig. 2 of their article). The list of potential causes, however, seems to neglect a common condition. Specifically, major surgery involves intraoperative stresses that divert blood from the enteric circulation. 2 The decreased perfusion can lead to mucosal ischemia, reduced cellular integrity, and abnormal physiological characteristics (e.g., postoperative lactose intolerance). 3 In addition, postoperative atelectasis may indirectly impair microcirculation and lymphatic drainage. 4,5 Major surgery, therefore, could provoke . . .

Background RNA-sequencing has become a standard tool for analyzing gene activity in bulk samples and at the single-cell level. By increasing sample sizes and cell counts, this technique can uncover substantial information about cellular transcriptional states. Beyond quantification of gene expression, RNA-seq can be used for detecting variants, including single nucleotide polymorphisms, small insertions/deletions, and larger variants, such as copy number variants. Notably, joint analysis of variants with cellular transcriptional states may provide insights into the impact of mutations, especially for complex and heterogeneous samples. However, this analysis is often challenging due to a prohibitively high number of variants and cells, which are difficult to summarize and visualize. Further, there is a dearth of methods that assess and summarize the association between detected variants and cellular transcriptional states. Results Here, we introduce XCVATR (e X pressed C lusters of V ariant A lleles in T ranscriptome p R ofiles), a method that identifies variants and detects local enrichment of expressed variants within embedding of samples and cells in single-cell and bulk RNA-seq datasets. XCVATR visualizes local “clumps” of small and large-scale variants and searches for patterns of association between each variant and cellular states, as described by the coordinates of cell embedding, which can be computed independently using any type of distance metrics, such as principal component analysis or t-distributed stochastic neighbor embedding. Through simulations and analysis of real datasets, we demonstrate that XCVATR can detect enrichment of expressed variants and provide insight into the transcriptional states of cells and samples. We next sequenced 2 new single cell RNA-seq tumor samples and applied XCVATR. XCVATR revealed subtle differences in CNV impact on tumors. Conclusions XCVATR is publicly available to download from https://github.com/harmancilab/XCVATR .

Deep brain stimulation (DBS) of the fimbria–fornix—a region that provides input to the hippocampus—is shown to restore hippocampus-dependent memory and hippocampal long-term potentiation and neurogenesis in a mouse model of Rett syndrome, suggesting that DBS, which is already used in the treatment of several neurological conditions, could be a viable approach to mitigating cognitive impairment in Rett syndrome and other disorders of childhood intellectual disability. Deep brain stimulation in Rett syndrome Rett syndrome is a genetic disorder that causes profound intellectual disability and other impairments. Huda Zoghbi and colleagues now show that in a mouse model of the disorder, a two-week course of daily deep-brain stimulation of the fimbria-fornix — part of the brain that provides input to the hippocampus — restored hippocampal-dependent memory when tested three weeks after the end of the treatment. It also restored hippocampal long-term potentiation and neurogenesis. These findings indicate that deep-brain stimulation, which is already used in the treatment of motor diseases such as Parkinson's disease and dystonia, could be a viable approach to mitigating cognitive impairment in Rett syndrome and other disorders of childhood intellectual disability. Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnesic rats have demonstrated that DBS targeted to the fimbria–fornix 1 , 2 , 3 , the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory 3 , 4 , 5 . Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder. Such disorders are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We proposed that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP2 (ref. 6 ), RTT appears by the second year of life in humans, causing profound impairment in cognitive, motor and social skills, along with an array of neurological features 7 . RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity 8 , 9 , 10 , 11 . Here we show that forniceal DBS in RTT mice rescues contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restores in vivo hippocampal long-term potentiation and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq ( n  = 6) and exome sequencing ( n  = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted. Vestibular schwannomas are benign tumours which can lead to neurological symptoms and morbidity. Here, the authors use single cell RNA-seq and ATAC-seq to identify Schwann cell subtypes in the tumour microenvironment which mimic a nerve injury phenotype.

Background Non-Hispanic blacks bear a disproportionate burden of the growing obesity epidemic. Bariatric surgery is an effective treatment for morbid obesity. We sought to assess for racial disparities in short-term outcomes following bariatric surgery. Methods Patients undergoing bariatric surgery were extracted from the Nationwide Inpatient Sample between 1999 and 2007. In-hospital mortality and length of stay were compared between different racial groups undergoing bariatric surgery after stratification by gender, and multivariate analysis was conducted to adjust for demographic, surgery year, and clinical and hospital characteristics. Results There were 115,507 bariatric surgeries. Overall mortality rate was 2.5 deaths per 1,000 and was higher among non-Hispanic blacks compared to non-Hispanic whites (3.7 vs. 2.3 per 1,000; P  = 0.007). Racial mortality disparities were most pronounced among males and at hospitals with lowest surgical volumes. In multivariate analysis, predictors of mortality were non-Hispanic black race (odds ratio [OR], 1.73; 95 % confidence interval [CI], 1.22–2.45), increasing age, increasing Charlson index (OR, 1.26; 95 % CI, 1.16–1.37), Medicare (OR, 2.13; 95 % CI, 1.57–2.91), and Medicaid (OR, 3.35; 95 % CI, 2.29–4.91) insurance. Incremental calendar year had reduced odds of mortality (OR, 0.80; 95 % CI, 0.76–0.83). Above national median neighborhood income (OR, 0.59; 95 % CI, 0.42–0.83) was protective in males, while teaching hospital status conveyed greater mortality (OR, 2.12; 95 % CI, 1.40–3.22). Conclusions Non-Hispanic blacks undergoing bariatric surgery demonstrate higher in-hospital mortality than their racial counterparts. It is unclear if this disparity is due to susceptibility to obesity-related mortality or suboptimal delivery of healthcare in the perioperative setting.

ObjectiveTo determine sex-based differences in risk of a second ACL injury (overall and by laterality) following primary ACL reconstruction in athletes who are attempting to return to sport.DesignSystematic review with meta-analysis.Data sourcesSystematic search of five databases conducted in August 2019.Eligibility criteria for selecting studiesStudies reporting sex-based differences in the incidence of second ACL injury in athletes attempting to return-to-sports and who were followed for at least 1 year following primary ACL reconstruction.ResultsNineteen studies were included in this review, with seven studies excluded from the primary meta-analysis due to high risk of bias. The remaining 12 studies (n=1431 females, n=1513 males) underwent meta-analysis, with all 19 studies included in a sensitivity analysis. Total second ACL injury risk was 21.9% (females: 22.8%, males: 20.3%). Females were found to have 10.7% risk of an ipsilateral ACL injury and 11.8% risk of a contralateral ACL injury. Males were found to have 12.0% risk of an ipsilateral ACL injury and 8.7% risk of a contralateral ACL injury. No statistically significant differences were observed for total second ACL injury risk (risk difference=−0.6%, 95% CI −4.9 to 3.7, p=0.783, I2=41%) or contralateral ACL injury risk (risk difference=1.9%, 95% CI −0.5% to 4.4%, p=0.113, I2=15%) between sexes. Females were found to have a 3.4% absolute risk reduction in subsequent ipsilateral ACL injury risk compared with males (risk difference=−3.4%, 95% CI −6.7% to −0.02%, p=0.037, I2=35%).ConclusionBoth sexes have >20% increased risk of experiencing a second ACL injury. Any difference in the absolute risk of either a subsequent ipsilateral or contralateral ACL injury between sexes appears to be small.RegistrationPROSPERO (CRD42020148369)

The safety and efficacy of various pharmacotherapeutic regimens on refractory meningiomas have been the focus of investigations. We present a comprehensive review of the previous efforts and the current state of ongoing clinical trials. A PRISMA-compliant review of the MEDLINE and ClinicalTrial.gov databases of the National Library of Medicine were performed. The primary outcomes of interest for included articles were radiographic response, overall survival, progression-free survival, six-month progression-free survival, and adverse events. Overall, 34 completed trials and 27 ongoing clinical trials were eligible. Six-month progression-free survival was reported in 6–100% of patients in the completed studies. Hematological disorders were the most common adverse events. Of the ongoing clinical trials identified, nine studies are phase I clinical trials, eleven are phase II trials, two are phase I and II trials, one is phase II and III, and two trials do not have a designated phase. Currently, there is no effective chemotherapy for refractory or recurrent meningiomas. Several promising targeted agents have been developed and are currently being investigated in the hope of identifying novel therapeutic strategies for the treatment of this pathology.