Hypodense cerebellar tuberculoma on CT scan masquerading low grade glioma

We report a case of hypodense cerebellar tuberculoma in a 26 year old postpartum lady who presented with one episode of generalized tonic-clonic seizures and discuss the histopathology findings where on CT scan the lesion was suspected as low grade glioma.She was started on isoniazid,rifampicin,pyrazinamide,ethambutol and pyridoxine.She is asymptomatic and had no neurological deficits at follow up.

ABCC8 is correlated with immune cell infiltration and overall survival in lower grade glioma

ATP binding cassette subfamily C member 8(ABCC8)encodes a protein regulating the ATP-sensitive potassium channel.Whether the level of ABCC8 mRNA in lower grade glioma(LGG)correlates with immune cell infiltration and patient outcomes has not been evaluated until now.Comparisons of ABCC8 expression between different tumors and normal tissues were evaluated by exploring publicly available datasets.The association between ABCC8 and tumor immune cell infiltration,diverse gene mutation characteristics,tumor mutation burden(TMB),and survival in LGG was also investigated in several independent datasets.Pathway enrichment analysis was conducted to search for ABCC8-associated signaling pathways.Through an online database,we found that ABCC8 expression in LGG was lower than in normal tissues.Then,the association of ABCC8 expression and immune cell infiltration in LGG was discussed.As we expected,the ABCC8 mRNA levels were negatively associated with non-T immune cell infiltration levels in all datasets.Consistently,TCGA_LGG RNA-seq data revealed that ABCC8 downregulated several non-T immune cell-associated signaling pathways in gene set enrichment analysis.Different ABCC8 expression groups showed diverse gene mutation characteristics and TMB.The high expression of ABCC8 was linked to improved survival of LGG patients.A pathway enrichment analysis of ABCC8-associated genes indicated that the GABAergic synapse signaling pathway might be involved in regulating immunity in LGG.Our findings show that ABCC8 reflects LGG tumor immunity and is an ideal prognostic biomarker for LGG.

Plasticity of language pathways in patients with low-grade glioma A diffusion tensor imaging study

Knowledge of the plasticity of language pathways neurosurgeons to achieve maximum resection wh n patients with low-grade glioma is important for e preserving neurological function. The current study sought to investigate changes in the ventral language pathways in patients with low-grade glioma located in regions likely to affect the dorsal language pathways. The results revealed no significant difference in fractional anisotropy values in the arcuate fasciculus between groups or between hemispheres. However, fractional anisotropy and lateralization index values in the left inferior longitudinal fasciculus and lateralization index values in the left inferior fronto-occpital fasciculus were higher in patients than in healthy subjects. These results indicate plasticity of language pathways in patients with low-grade glioma. The ventral language pathways may perform more functions in patients than in healthy subjects. As such, it is important to protect the ventral language pathways intraoperatively.

Repeated operations for infiltrative low - grade gliomas without intervening therapy.

OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.

Genomic profiling of lower-grade gliomas uncovers cohesive disease groups:implications for diagnosis and treatment

Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas,oligodendrogliomas,or oligoastrocytomas.Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century,it suffers from high intra-and inter-observer variability and does not adequately predict clinical outcomes.Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas,lower-grade gliomas have been found to segregate into three cohesive,clinically relevant molecular classes.Molecular classes were closely aligned with the status of isocitrate dehydrogenase(IDH)mutations,tumor protein 53 mutations and the co-deletion of chromosome arms 1 p and 19q,but were not closely aligned with histologic classes.These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.

Adaptability of language-related brain network in a low-grade glioma patient

Because functional magnetic resonance imaging can be used for dynamic observation of functional cortical changes after brain injuries, we followed up functional magnetic resonance imaging manifestations of a language-related brain network in a low-grade glioma patient. Disease progression and therapy during a 3-year period were followed up at different time points： before and after reoperation, after radiation therapy, and 1 year after irradiation. During the whole 3-year follow-up period, the patient exhibited no neurological deficits while functional magnetic resonance imaging revealed different topologies of the language-related brain network. During disease progression and after irradiation, the language-related brain network was extended or completely transferred to the nondominant （right） hemisphere. In addition, after reoperation and 1 year after irradiation, language areas were primarily found in the language dominant （left） hemisphere. Our results suggest a high level of adaptability of the language-related cortical network of the bilateral hemispheres in this low-grade glioma patient.

Comparative profiling of immune genes improves the prognoses of lower grade gliomas

Objective:Lower grade gliomas(LGGs),classified as World Health Organization(WHO)grade II and grade III gliomas,comprise a heterogeneous group with a median survival time ranging from 4–13 years.Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice.Methods:We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts.The comparative profile of immune genes was analyzed for signature identification and validation.In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas(CGGA)dataset were used as training and internal validation cohorts,respectively.The samples from The Cancer Genome Atlas(TCGA)and GSE16011 cohorts were used as external validation cohorts,and the real-time PCR of frozen LGG tissue samples(n=36)were used for clinical validation.Results:A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs(IGPs).A total of 402 IGPs were identified with prognostic values for LGGs.The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses.An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups,exhibiting different clinical outcomes.A nomogram,combining immune signature,1p/19q status,and tumor grade,was able to predict the overall survival(OS)with c-indices of 0.85,0.80,0.80,0.79,and 0.75 in the training,internal validation,external validation,and tissue sample cohorts,respectively.Conclusions:This study was the first to report a comparative profiling of immune genes in large LGG cohorts.A promising individualized immune signature was developed to estimate the survival time for LGG patients.

Magnetic Resonance Perfusion Imaging in the Diagnosis of High-Grade Glioma Progression and Treatment-Related Changes: A Systematic Review

In patients with high grade gliomas (HGGs), progression after treatment can be difficult to diagnose due to treatment-related effects, which overlap in appearance with tumour progression on conventional magnetic resonance imaging (MRI) sequences. Specialised imaging methods have been studied for this purpose, though most institutions currently use histopathology or clinicoradiological follow-up for diagnosis. This publication aims to review the evidence for perfusion MRI techniques. The databases of Pubmed, MEDLINE, EMBASE and Scopus were searched using combinations of the subject headings high grade glioma and MRI perfusion. 41 articles fulfilled the inclusion criteria. Dynamic Susceptibility Contrast (DSC) MRI was the most extensively studied, with several studies achieving high sensitivities and specificities. Other techniques exhibiting potential include Dynamic Contrast Enhanced (DCE) MRI, Arterial Spin Labelling (ASL). However, these techniques are not widely used or available for clinical practice. Composite measures combining results from multiple techniques tended to achieve higher accuracies. Some publications compared processing software used or looked at machine learning with relative success. An issue common to the literature is the lack of standardisation in the reference standard and acquisition/processing methods. Furthermore, many had small sample sizes, and further consideration needs to be given with regards to timing of imaging, and treatment regimens received in such studies.

Temozolomide resistance in high grade gliomas

High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy. Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment. This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas. This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O^6-methylguanine-DNA methyltransferase(MGMT) methylation, mismatch repair mutation and epigenetic regulation consisting of p21, chromatin and histone, Y-box binding protein-1 and micro RNAs.

Fractionated resection on low grade gliomas involving Broca＇s area and insights to brain plasticity

Background Resent advances on functional mapping have enabled us to conduct surgery on gliomas within the eloquent area. The objective of the article is to discuss the feasibility of a planned fractionated strategy of resection on low-grade gliomas （LGGs） involving Broca＇s area. We report the first surgical series of planned fractionated resections on LGGs within Broca＇s area, focusing on language functional reshaping. Methods Four patients were treated with fractionated operations for LGGs involving Broca＇s area. All cases underwent conventional magnetic resonance （MR） scanning, language functional MR and diffusion tensor imaging （DTI） before operation. The resections were then performed on patients under awake anesthesia using intraoperative electrical stimulation （IES） for functional mapping. Pre- and post-operative neuro-psychological examinations were evaluated.Results Total resections were achieved in all cases as confirmed by the postoperative control MR. After transient language worsening, all patients recovered to normal 3-6 months later. Language functional MR scannings have shown language functional cortical and subcortical pathway reorganization （in the perilesion or contra-lateral hemisphere） after the operation. All patients returned to a normal socioprofessional life. Conclusions By utilizing the dynamic interaction between brain plasticity and fractionated resections, we can totally remove the tumor involving Broca＇s structure without inducing permanent postoperative deficits and even improve the quality of life.

Effect of ultraviolet mutagenesis on heterotrophic strain mutation and bioleaching of low grade copper ore

The effect of ultraviolet mutagenesis on a heterotrophic strain(Providencia JAT-1) mutation was studied and bioleaching of low grade copper ore with mutant bacteria was investigated. The results show that the activity of bacteria was improved after ultraviolet mutagenesis; the best irradiation time was 120 s. Compared to the original bacteria, the cells density of mutant bacteria at stationary phase increased by 26% and ammonia produced by mutant bacteria increased by 12%. Higher activity of bacteria leads to a higher copper extraction rate. The bioleaching performance of Providencia JAT-1 was improved after UV mutagenesis. The copper extraction rate with mutant bacteria increased by 10.6% compared to the original bacteria. The ore surface was corroded and the fine particles were absent after bioleaching. Free copper oxide and copper silicates could be leached out easily by using JAT-1; a small part of the copper sulfide can also be leached out. Bioleaching using JAT-1 is more effective than ammonia leaching and copper extraction rate with mutant bacteria was 21.1% higher than that by ammonia leaching under the same condition.

Comparison of selective flocculation of low grade goethitic iron ore fines using natural and synthetic polymers and a graft copolymer

This study aims to beneficiate low grade goethitic iron ore fines using a selective flocculation process. Selective flocculation studies were conducted using different polymers such as starch amylopectin(AP), poly acrylic acid(PAA), and a graft copolymer(AP-g-PAA). The obtained results were analyzed; they indicate the enhancement of the iron ore grade from 58.49% to 67.52% using AP-g-PAA with a recovery of 95.08%. In addition, 64.45% Fe with a recovery of 88.79% was obtained using AP. Similarly, using PAA, the grade increased to 63.46% Fe with a recovery of 82.10%. The findings are also supported by characterizing concentrates using X-ray diffraction(XRD) and electron probe microanalysis(EPMA) techniques.

Reductive Acid Leaching of Low Grade Manganese Ores

Manganese recoveries from low-grade ores using organic acids as reducing agents were investigated in the present work. The acid leaching potential of both oxalic acid and citric acid were estimated. Manganese leaching amount were measured by using standard manganese curve and estimated by titration method. Effects of various acid concentrations on leaching efficiency were studied. The observed result suggested prominent manganese recovery of 66% by oxalic acid at 2 M concentration whereas citric acid had less effect on leaching showing leaching percentage upto 40% in 6 days. Acid leaching of manganese ore with both the acids gave a comparative data stating that oxalic acid leached better than citric acid.

Radiotherapy of high-grade gliomas: current standards and new concepts, innovations in imaging and radiotherapy, and new therapeutic approaches

The current standards in radiotherapy of high-grade gliomas(HGG) are based on anatomic imaging techniques, usually computed tomography(CT) scanning and magnetic resonance imaging(MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma(AG) or a grade 4 glioblastoma multiforme(GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume(GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume(CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase(CTV1) including any T2 hyperintensity area(edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in < 10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators(LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density(diffusion MRI), angiogenesis(perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography(PET) and magnetic resonance spectroscopy(MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non- contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost(SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines(and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software applications, the simultaneous acquisition of anatomic and functional images(PET-MRI machines), the combination of complementary imaging tools(perfusion and diffusion MRI), and the concomitant addition of some ad hoc targeted drugs against angiogenesis and invasiveness to chemoradiotherapy. The integration of these hybrid data will construct new synthetic metrics for fully individualized treatments.

Enhanced copper recovery from low grade copper sulfide ores through bioleaching using residues produced by fermentation of agricultural wastes

Effects of residues produced by agricultural wastes fermentation(AWF)on low grade copper sulfide ores bioleaching,copper recovery,and microbial community were investigated.The results indicated that adding appropriate bulk of AWF made contributions to low grade copper sulfide ores bioleaching,which may be mainly realized through reducing the passivation layer formed by Fe3+hydrolysis.Improved copper recovery(78.35%)and bacteria concentration(9.56×10^(7)cells·mL^(−1))were yielded in the presence of 5 g·L^(−1)AWF.The result of 16S rDNA analysis demonstrated that microbial community was differentiated by adding AWF.Bacteria proportion,such as Acidithiobacillus ferrooxidans,Moraxella osloensis,and Lactobacillus acetotolerans changed distinctly.Great difference between samples was showed according to beta diversity index,and the maximum value reached 0.375.Acidithiobacillus ferrooxidans accounted for the highest proportion throughout the bioleaching process,and that of sample in the presence of 5 g·L^(−) AWF reached 28.63%.The results should show reference to application of agricultural wastes and low grade copper sulfide ores.

High-grade gliomas: reality and hopes

In this issue of the Chinese Journal of Cancer, European experts review current standards, trends, and future prospects in the difficult domain of high-grade glioma. In all fields covered by the different authors, the progress has been impressive. For example, discoveries at the molecular level have already impacted imaging, surgery, radiotherapy, and systemic therapies, and they are expected to play an increasing role in the management of these cancers. The European Organization for Research and Treatment of Cancer(EORTC) has pioneered new treatment strategies and contributed to new standards. The articles in this issue will cover basic molecular biological principles applicable today, novel surgical approaches, innovations in radiotherapy planning and delivery, evidence-based standards for radiotherapy alone or combined with chemotherapy, current standards and novel approaches for systemic treatments, and the important but often neglected field of health-related quality of life. Despite the advances described in these articles, the overall prognosis of high-grade glioma, especially glioblastoma, remains poor, and more research is needed to address this problem.

Dissolution kinetics of low grade complex copper ore in ammonia-ammonium chloride solution

The leaching kinetics of Tang-dan refractory low grade complex copper ore was investigated in ammonia-ammonium chloride solution.The concentration of ammonia and ammonium chloride,the ore particle size,the solid-to-liquid ratio and the temperature were chosen as parameters in the experiments.The results show that temperature,concentration of ammonia and ammonium chloride have favorable influence on the leaching rate of copper oxide ores.But,leaching rate decreases with increasing particle size and solid-to-liquid ratio.The leaching process is controlled by the diffusion of the lixiviant and the activation energy is determined to be 23.279 kJ/mol.An equation was also proposed to describe the leaching kinetics.

Molecular biology of high-grade gliomas: what should the clinician know?

The current World Health Organization classification system of primary brain tumors is solely based on morphologic criteria. However, there is accumulating evidence that tumors with similar histology have distinct molecular signatures that significantly impact treatment response and survival. Recent practice-changing clinical trials have defined a role for routine assessment of O-6-methylguanine-DNA methyltransferase(MGMT) promoter methylation in glioblastoma patients, especially in the elderly, and 1p and 19q codeletions in patients with anaplastic glial tumors. Recently discovered molecular alterations including mutations in IDH-1/2, epidermal growth factor receptor(EGFR), and BRAF also have the potential to become targets for future drug development. This article aims to summarize current knowledge on the molecular biology of high-grade gliomas relevant to daily practice.

Leaching kinetics of low grade zinc oxide ore in NH_3-NH_4Cl-H_2O system

The leaching kinetics of low grade zinc oxide ore in NH3-NH4Cl-H2O system was studied. The effects of ore particle size, reaction temperature and the sum concentration of ammonium ion and ammonia on the leaching efficiency of zinc were examined. The leaching kinetics of low-grade zinc oxide ore in NH3-NH4Cl-H2O system follows the kinetic law of shrinking-core model. The results show that diffusion through the inert particle pores is the leaching kinetics rate controlling step. The calculated apparent activation energy of the process is about 7.057 kJ/mol. The leaching efficiency of zinc is 92.1% under the conditions of ore particle size of 69 μm, holding at 80 ℃ for 60 min, sum ammonia concentration of 7.5 mol/L, the molar ratio of ammonium to ammonia being 2-1, and the ratio (g/mL) of solid to liquid being 1-10.

Beneficiation of a low grade limestone sample

Pilot scale column flotation studies were conducted on a low grade siliceous limestone ore. Silica content was reduced to less than 1% in the concentrate so that it became satisfactory for use in the paper or rub- ber industries. The limestone sample was crystalline and constituted primarily of calcite that contained quartz, feldspar, pyroxene, and biotite as gangue minerals. Quartz is the major silicate gangue whereas feldspar, pyroxene, and biotite exist in minor to trace quantities. Traces of pyrite were also observed within the sample. A reverse flotation process was adopted where the silicate gangue minerals were floated using two different commercial cationic collectors: Chem-750 F or Floatamine-D. The studies clearly suggest it is possible to produce a limestone concentrate assaying around 96-97% CaCO3 contain- ing less than 1% SiO2. The effect of feed flow rate, percent solids, froth depth, and wash water on the grade and recovery of the CaCO3 concentrate is discussed.