Highly active, durable, and cost-effective electrocatalysts for water oxidation to evolve oxygen gas hold a key to a range of renewable energy solutions, including water-splitting and rechargeable ...metal–air batteries. Here, we report the synthesis of ultrathin nickel–iron layered double hydroxide (NiFe-LDH) nanoplates on mildly oxidized multiwalled carbon nanotubes (CNTs). Incorporation of Fe into the nickel hydroxide induced the formation of NiFe-LDH. The crystalline NiFe-LDH phase in nanoplate form is found to be highly active for oxygen evolution reaction in alkaline solutions. For NiFe-LDH grown on a network of CNTs, the resulting NiFe-LDH/CNT complex exhibits higher electrocatalytic activity and stability for oxygen evolution than commercial precious metal Ir catalysts.
Background
Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle and poses a significant morbidity for patients. While many exhibit benign behaviour, others have a more ...aggressive nature and pattern of growth. Predicting who will fall into which category consistently remains uncertain. There is a need for a better understanding of the molecular landscape, and important subgroups therein, of this disease.
Methods
We select all vestibular schwannomas from our tumour bank with both methylation and RNA profiling available. Unsupervised clustering methods were used to define two distinct molecular subgroups of VS which were explored using computational techniques including bulk deconvolution analysis, gene pathway enrichment analysis, and drug repurposing analysis. Methylation data from two other cohorts were used to validate our findings, given a paucity of external samples with available multi-omic data.
Results
A total of 75 tumours were analyzed. Consensus clustering and similarity network fusion defined two subgroups (“immunogenic” and “proliferative”) with significant differences in immune, stroma, and tumour cell abundance (p < 0.05). Gene network analysis and computational drug repurposing found critical differences in targets of immune checkpoint inhibition PD-1 and CTLA-4, the MEK pathway, and the epithelial to mesenchymal transition program, suggesting a need for subgroup-specific targeted treatment/trial design in the future.
Conclusions
We leverage computational tools with multi-omic molecular data to define two robust subgroups of vestibular schwannoma with differences in microenvironment and therapeutic vulnerabilities.
Magnetic Resonance Imaging (MRI) evidence of spinal cord compression plays a central role in the diagnosis of degenerative cervical myelopathy (DCM). There is growing recognition that deep learning ...models may assist in addressing the increasing volume of medical imaging data and provide initial interpretation of images gathered in a primary-care setting. We aimed to develop and validate a deep learning model for detection of cervical spinal cord compression in MRI scans. Patients undergoing surgery for DCM as a part of the AO Spine CSM-NA or CSM-I prospective cohort studies were included in our study. Patients were divided into a training/validation or holdout dataset. Images were labelled by two specialist physicians. We trained a deep convolutional neural network using images from the training/validation dataset and assessed model performance on the holdout dataset. The training/validation cohort included 201 patients with 6588 images and the holdout dataset included 88 patients with 2991 images. On the holdout dataset the deep learning model achieved an overall AUC of 0.94, sensitivity of 0.88, specificity of 0.89, and f1-score of 0.82. This model could improve the efficiency and objectivity of the interpretation of cervical spine MRI scans.
We investigate high-field transport in graphene nanoribbons (GNRs) on SiO(2), up to breakdown. The maximum current density is limited by self-heating, but can reach >3 mA/μm for GNRs ~15 nm wide. ...Comparison with larger, micron-sized graphene devices reveals that narrow GNRs benefit from 3D heat spreading into the SiO(2), which enables their higher current density. GNRs also benefit from lateral heat flow to the contacts in short devices (<~0.3 μm), which allows extraction of a median GNR thermal conductivity (TC), ~80 W m(-1)K(-1) at 20 °C across our samples, dominated by phonons. The TC of GNRs is an order of magnitude lower than that of micron-sized graphene on SiO(2), suggesting strong roles of edge and defect scattering, and the importance of thermal dissipation in small GNR devices.
Meningiomas are the most common primary intracranial tumour in adults
. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health ...Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas
. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified.
BRCA (BReast CAncer gene)-associated protein 1 (BAP1), encoded by the
gene, a tumour suppressor that is lost in several cancers. Importantly, such mutations have been shown to be susceptible to poly ...(ADP-ribose) polymerase (PARP) inhibition in preclinical studies, offering hope for targeted therapy. While rare, BAP1 loss has been observed in a subset of rhabdoid and papillary meningioma and is associated with earlier recurrence. We seek to add to the literature on this rare disease and advocate for more routine BAP1 testing.
We present a report of two cases of BAP1-deficient meningioma and review the available literature on this rare entity.
Both cases present with a distinct trabecular architecture without rhabdoid or papillary features. Interestingly, both also presented with radiographic and histopathological findings unusual for meningioma. While immunohistochemistry and genetic sequencing confirmed BAP1 loss, DNA methylation analysis was required to confirm the final diagnosis.
We suggest that BAP1-deficient meningioma should be considered in the differential diagnosis of extra-axial central nervous system (CNS) tumours with atypical imaging or histopathological features and that BAP1 loss may constitute a clinically important meningioma subtype with opportunities for targeted therapy.
Liquid biopsy, as a non-invasive technique for cancer diagnosis, has emerged as a major step forward in conquering tumors. Current practice in diagnosis of central nervous system (CNS) tumors ...involves invasive acquisition of tumor biopsy upon detection of tumor on neuroimaging. Liquid biopsy enables non-invasive, rapid, precise and, in particular, real-time cancer detection, prognosis and treatment monitoring, especially for CNS tumors. This approach can also uncover the heterogeneity of these tumors and will likely replace tissue biopsy in the future. Key components of liquid biopsy mainly include circulating tumor cells (CTC), circulating tumor nucleic acids (ctDNA, miRNA) and exosomes and samples can be obtained from the cerebrospinal fluid, plasma and serum of patients with CNS malignancies. This review covers current progress in application of liquid biopsies for diagnosis and monitoring of CNS malignancies.
Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. ...Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis.
MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients >60 years of age with histologically confirmed GBM were included. Primary outcome of interest was the pooled HR from randomized controlled trials (RCTs). Secondary outcomes of interest included pooled HR from studies controlling for MGMT promoter methylation status, and safety.
Fourteen studies, including 5 RCTs, reporting 4,561 patients were included. Using highest quality data from RCTs, our network-based approach demonstrated that standard radiotherapy (SRT) and temozolomide (TMZ) provided similar survival benefit when compared with hypofractionated radiotherapy (HRT) and TMZ HR = 0.90; 95% confidence interval (CI), 0.43-1.87, TMZ alone (HR 1.25; 95% CI, 0.69-2.26), HRT alone (HR = 1.34; 95% CI, 0.73-2.45), or SRT alone (HR = 1.43; 95% CI, 0.87-2.36). HRT-TMZ had the highest probability (85%) of improving survival in older patients with GBM followed by SRT-TMZ (72%). Pooled analysis of trials controlling for
promoter methylation status demonstrated that TMZ monotherapy confers similar survival benefit to combined chemoradiotherapy.
Statistical comparisons using a network approach demonstrates that the common treatment regimens for older patients with GBM in previous RCTs confer similar survival benefits. Adjustments for MGMT promoter methylation status demonstrated that radiotherapy alone was inferior to TMZ-based approaches. Head-to-head comparison of TMZ monotherapy to combined TMZ and radiation is warranted.
The role of surgery in recurrent glioblastoma multiforme (GBM) remains a controversial topic. The goal of this study was to perform a case control analysis including time to tumor recurrence as an ...additional prognostic factor in order to determine which patients benefit most from repeat surgery.
Our brain tumor database was reviewed over a 10-year period for all adult (≥18 years old) patients with primary isocitrate dehydrogenase wildtype GBM who received surgery for recurrent disease. These patients were then age, sex, and treatment matched to case controls from our institution who received medical therapy for recurrent disease.
A total of 174 adult patients with GBM were included in the study, 87 patients who received surgery for recurrent GBM (surgery cohort) and 87 patients who did not receive surgery for recurrent GBM (nonsurgery cohort). The surgery cohort had longer overall survival (P = 0.0003) and postrecurrence survival (P = 0.001) than the nonsurgery cohort. When the surgery cohort was split into 2 groups on the basis of time to tumor recurrence, the long time to recurrence group (>6 months) demonstrated significantly increased survival compared with the short time to recurrence group (P < 0.0001). Multivariate analysis of both cohorts demonstrated surgery for recurrent GBM was independently significant after adjusting for age, Karnofsky Performance Scale, and time to tumor recurrence (P < 0.0001).
Surgery for recurrent GBM leads to improved survival independent of age, Karnofsky Performance Scale, and time to tumor recurrence. Patients with time to tumor recurrence >6 months benefit most from additional surgery.
Investigating the cellular internalization pathways of single molecules or single nano objects is important to understanding cell-matter interactions, and to applications in drug delivery and ...discovery. Imaging and tracking the motion of single molecules on cell plasma membranes require high spatial resolution in three dimensions. Fluorescence imaging along the axial dimension with nanometre resolution has been highly challenging, but critical to revealing displacements in transmembrane events. Here, utilizing a plasmonic ruler based on the sensitive distance dependence of near-infrared fluorescence enhancement of carbon nanotubes on a gold plasmonic substrate, we probe ~10 nm scale transmembrane displacements through changes in nanotube fluorescence intensity, enabling observations of single nanotube endocytosis in three dimensions. Cellular uptake and transmembrane displacements show clear dependences to temperature and clathrin assembly on cell membrane, suggesting that the cellular entry mechanism for a nanotube molecule is via clathrin-dependent endocytosis through the formation of clathrin-coated pits on the cell membrane.
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