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X-ray diffraction/scattering computed tomography (XRS-CT) was used to create two-dimensional images, with 20 µm resolution, of passivated Co/TiO2/Mn Fischer-Tropsch catalyst extrudates postreaction after 300 h on stream under industrially relevant conditions. This combination of scattering techniques provided insights into both the spatial variation of the different cobalt phases and the influence that increasing Mn loading has on this. It also demonstrated the presence of a wax coating throughout the extrudate and its capacity to preserve the Co/Mn species in their state in the reactor. Correlating these findings with catalytic performance highlights the crucial phases and active sites within Fischer-Tropsch catalysts required for understanding the tunability of the product distribution between saturated hydrocarbons or oxygenate and olefin products. In particular, a Mn loading of 3 wt % led to an optimum equilibrium between the amount of hexagonal close-packed Co and Co2C phases resulting in maximum oxygenate selectivity. XRS-CT revealed Co2C to be located on the extrudates' periphery, while metallic Co phases were more prevalent toward the center, possibly due to a lower [CO] ratio there. Reduction at 450 °C of a 10 wt % Mn sample resulted in MnTiO3 formation, which inhibited carbide formation and alcohol selectivity. It is suggested that small MnO particles promote Co carburization by decreasing the CO dissociation barrier, and the Co2C phase promotes CO nondissociative adsorption leading to increased oxygenate selectivity. This study highlights the influence of Mn on the catalyst structure and function and the importance of studying catalysts under industrially relevant reaction times.
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Glioblastoma, an aggressive brain tumor prevalent in adults, exhibits heterogeneity in its microstructures and vascular patterns. The delineation of its subregions could facilitate the development of region-targeted therapies. However, current unsupervised learning techniques for this task face challenges in reliability due to fluctuations of clustering algorithms, particularly when processing data from diverse patient cohorts. Furthermore, stable clustering results do not guarantee clinical meaningfulness. To establish the clinical relevance of these subregions, we will perform survival predictions using radiomic features extracted from them. Following this, achieving a balance between outcome stability and clinical relevance presents a significant challenge, further exacerbated by the extensive time required for hyper-parameter tuning. In this study, we introduce a multi-objective Bayesian optimization (MOBO) framework, which leverages a Feature-enhanced Auto-Encoder (FAE) and customized losses to assess both the reproducibility of clustering algorithms and the clinical relevance of their outcomes. Specifically, we embed the entirety of these processes within the MOBO framework, modeling both using distinct Gaussian Processes (GPs). The proposed MOBO framework can automatically balance the trade-off between the two criteria by employing bespoke stability and clinical significance losses. Our approach efficiently optimizes all hyper-parameters, including the FAE architecture and clustering parameters, within a few steps. This not only accelerates the process but also consistently yields robust MRI subregion delineations and provides survival predictions with strong statistical validation.
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In the dynamic landscape of glioblastoma, the 2021 World Health Organization Classification of Central Nervous System tumours endeavoured to establish biological homogeneity, yet isocitrate dehydrogenase-wild-type (IDH-wt) glioblastoma persists as a tapestry of clinical and molecular diversity. Intertumoural heterogeneity in IDH-wt glioblastoma presents a formidable challenge in treatment strategies. Recent strides in genetics and molecular biology have enhanced diagnostic precision, revealing distinct subtypes and invasive patterns that influence survival in patients with IDH-wt glioblastoma. Genetic and molecular biomarkers, such as the overexpression of neurofibromin 1, phosphatase and tensin homolog and/or cyclin-dependent kinase inhibitor 2A, along with specific immune cell abundance and neurotransmitters, correlate with favourable outcomes. Conversely, increased expression of epidermal growth factor receptor tyrosine kinase, platelet-derived growth factor receptor alpha and/or vascular endothelial growth factor receptor, coupled with the prevalence of glioma stem cells, tumour-associated myeloid cells, regulatory T cells and exhausted effector cells, signifies an unfavourable prognosis. The methylation status of O6-methylguanine-DNA methyltransferase and the influence of microenvironmental factors and neurotransmitters further shape treatment responses. Understanding intertumoural heterogeneity is complemented by insights into intratumoural dynamics and cellular interactions within the tumour microenvironment. Glioma stem cells and immune cell composition significantly impact progression and outcomes, emphasizing the need for personalized therapies targeting pro-tumoural signalling pathways and resistance mechanisms. A successful glioblastoma management demands biomarker identification, combination therapies and a nuanced approach considering intratumoural variability. These advancements herald a transformative era in glioblastoma comprehension and treatment.
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Brain tumour microstructure is potentially predictive of changes following treatment to cognitive functions subserved by the functional networks in which they are embedded. To test this hypothesis, intra-tumoural microstructure was quantified from diffusion-weighted MRI to identify which tumour subregions (if any) had a greater impact on participants' cognitive recovery after surgical resection. Additionally, we studied the role of tumour microstructure in the functional interaction between the tumour and the rest of the brain. Sixteen patients (22-56 years, 7 females) with brain tumours located in or near speech-eloquent areas of the brain were included in the analyses. Two different approaches were adopted for tumour segmentation from a multishell diffusion MRI acquisition: the first used a two-dimensional four group partition of feature space, whilst the second used data-driven clustering with Gaussian mixture modelling. For each approach, we assessed the capability of tumour microstructure to predict participants' cognitive outcomes after surgery and the strength of association between the BOLD signal of individual tumour subregions and the global BOLD signal. With both methodologies, the volumes of partially overlapped subregions within the tumour significantly predicted cognitive decline in verbal skills after surgery. We also found that these particular subregions were among those that showed greater functional interaction with the unaffected cortex. Our results indicate that tumour microstructure measured by MRI multishell diffusion is associated with cognitive recovery after surgery.
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Neoplasias Encefálicas , Disfunção Cognitiva , Feminino , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Cognição , Imagem de Difusão por Ressonância Magnética/métodos , Córtex Cerebral/patologia , Encéfalo/patologiaRESUMO
BACKGROUND: Surgical site infections after craniotomy (SSI-CRANs) are a serious adverse event given the proximity of the wound to the central nervous system. SSI-CRANs are associated with substantial patient morbidity and mortality. Despite the importance and recognition of this event in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to SSI-CRAN specifically in patients after brain tumor surgery. METHODS: Systematic searches of Medline, Embase, and Cochrane Central were undertaken. The primary outcome was the incidence of SSI-CRAN at 30 and 90 days. Secondary outcomes were risk factors for SSI-CRAN. RESULTS: Thirty-seven studies reporting 91,907 patients with brain tumors who underwent cranial surgery were included in the meta-analysis. Pooled incidence of SSI-CRAN at 30 and 90 days was 4.03% (95% CI: 2.94%-5.28%, I2 = 97.3) and 6.17% (95% CI: 3.16%-10.07%, I2 = 97.3), respectively. Specifically, incidence of SSI-CRAN following surgery for posterior fossa tumors was the highest at 9.67% (95% CI: 5.98%-14.09%, I2 = 75.5). Overall pooled incidence of readmission within 30 days and reoperation due to SSI-CRAN were 13.9% (95% CI: 12.5%-15.5%, I2 = 0.0) and 16.3% (95% CI: 5.4%-31.3%, I2 = 72.9), respectively. Risk factors for SSI-CRAN included reintervention (risk ratio [RR] 1.58, 95% CI: 1.22-2.04, I2 = 0.0), previous radiotherapy (RR 1.69, 95% CI: 1.20-2.38, I2 = 0.0), longer duration of operation (mean difference 64.18, 95% CI: 3.96-124.40 minutes, I2 = 90.3) and cerebrospinal fluid (CSF) leaks (RR 14.26, 95% CI: 2.14-94.90, I2 = 73.2). CONCLUSIONS: SSI-CRAN affects up to 1 in 14 patients with brain tumors. High-risk groups include those with reintervention, previous radiotherapy, longer duration of operation, and CSF leaks. Further prospective studies should focus on bundles of care that will reduce SSI-CRAN.
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Neoplasias Encefálicas , Craniotomia , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Neoplasias Encefálicas/cirurgia , Fatores de Risco , Incidência , Craniotomia/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversosRESUMO
The extent to which tumour-infiltrated brain tissue contributes to cognitive function remains unclear. We tested the hypothesis that cortical tissue infiltrated by diffuse gliomas participates in large-scale cognitive circuits using a unique combination of intracranial electrocorticography (ECoG) and resting-state functional magnetic resonance (fMRI) imaging in four patients. We also assessed the relationship between functional connectivity with tumour-infiltrated tissue and long-term cognitive outcomes in a larger, overlapping cohort of 17 patients. We observed significant task-related high gamma (70-250 Hz) power modulations in tumour-infiltrated cortex in response to increased cognitive effort (i.e., switch counting compared to simple counting), implying preserved functionality of neoplastic tissue for complex tasks probing executive function. We found that tumour locations corresponding to task-responsive electrodes exhibited functional connectivity patterns that significantly co-localised with canonical brain networks implicated in executive function. Specifically, we discovered that tumour-infiltrated cortex with larger task-related high gamma power modulations tended to be more functionally connected to the dorsal attention network (DAN). Finally, we demonstrated that tumour-DAN connectivity is evident across a larger cohort of patients with gliomas and that it relates to long-term postsurgical outcomes in goal-directed attention. Overall, this study contributes convergent fMRI-ECoG evidence that tumour-infiltrated cortex participates in large-scale neurocognitive circuits that support executive function in health. These findings underscore the potential clinical utility of mapping large-scale connectivity of tumour-infiltrated tissue in the care of patients with diffuse gliomas.