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Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas (‘early glioblastoma’). Methodology: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers—MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Results: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2–90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. Conclusion: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes.

Abstract Background Advances in molecular diagnostics accomplished the discovery of two malignant glioma entities harboring alterations in the H3 histone: diffuse midline glioma, H3 K27-altered and diffuse hemispheric glioma, H3 G34-mutant. Radiogenomics research, which aims to correlate tumor imaging features with genotypes, has not comprehensively examined histone-altered gliomas (HAG). The aim of this research was to synthesize the current published data on imaging features associated with HAG. Methods A systematic search was performed in March 2022 using PubMed and the Cochrane Library, identifying studies on the imaging features associated with H3 K27-altered and/or H3 G34-mutant gliomas. Results Forty-seven studies fulfilled the inclusion criteria, the majority on H3 K27-altered gliomas. Just under half (21/47) were case reports or short series, the remainder being diagnostic accuracy studies. Despite heterogeneous methodology, some themes emerged. In particular, enhancement of H3 K27M-altered gliomas is variable and can be less than expected given their highly malignant behavior. Low apparent diffusion coefficient values have been suggested as a biomarker of H3 K27-alteration, but high values do not exclude this genotype. Promising correlations between high relative cerebral blood volume values and H3 K27-alteration require further validation. Limited data on H3 G34-mutant gliomas suggest some morphologic overlap with 1p/19q-codeleted oligodendrogliomas. Conclusions The existing data are limited, especially for H3 G34-mutant gliomas and artificial intelligence techniques. Current evidence indicates that imaging-based predictions of HAG are insufficient to replace histological assessment. In particular, H3 K27-altered gliomas should be considered when occurring in typical midline locations irrespective of enhancement characteristics.

Primary Central Nervous System Lymphoma (PCNSL) is a highly malignant brain tumour. We investigated dynamic changes in tumour volume and apparent diffusion coefficient (ADC) measurements for predicting outcome following treatment with MATRix chemotherapy in PCNSL. Patients treated with MATRix (n = 38) underwent T1 contrast-enhanced (T1CE) and diffusion-weighted imaging (DWI) before treatment, after two cycles and after four cycles of chemotherapy. Response was assessed using the International PCNSL Collaborative Group (IPCG) imaging criteria. ADC histogram parameters and T1CE tumour volumes were compared among response groups, using one-way ANOVA testing. Logistic regression was performed to examine those imaging parameters predictive of response. Response after two cycles of chemotherapy differed from response after four cycles; of the six patients with progressive disease (PD) after four cycles of treatment, two (33%) had demonstrated a partial response (PR) or complete response (CR) after two cycles. ADCmean at baseline, T1CE at baseline and T1CE percentage volume change differed between response groups (0.005 < p < 0.038) and were predictive of MATRix treatment response (area under the curve: 0.672–0.854). Baseline ADC and T1CE metrics are potential biomarkers for risk stratification of PCNSL patients early during remission induction therapy with MATRix. Standard interim response assessment (after two cycles) according to IPCG imaging criteria does not reliably predict early disease progression in the context of a conventional treatment approach.

Introduction: Gliomatosis cerebri describes a rare growth pattern of diffusely infiltrating glioma. The treatment options are limited and clinical outcomes remain poor. To characterise this population of patients, we examined referrals to a specialist brain tumour centre. Methods: We analysed demographic data, presenting symptoms, imaging, histology and genetics, and survival in individuals referred to a multidisciplinary team meeting over a 10-year period. Results: In total, 29 patients fulfilled the inclusion criteria with a median age of 64 years. The most common presenting symptoms were neuropsychiatric (31%), seizure (24%) or headache (21%). Of 20 patients with molecular data, 15 had IDH wild-type glioblastoma, with an IDH1 mutation most common in the remainder (5/20). The median length of survival from MDT referral to death was 48 weeks (IQR 23 to 70 weeks). Contrast enhancement patterns varied between and within tumours. In eight patients who had DSC perfusion studies, five (63%) had a measurable region of increased tumour perfusion with rCBV values ranging from 2.8 to 5.7. A minority of patients underwent MR spectroscopy with 2/3 (66.6%) false-negative results. Conclusions: Gliomatosis imaging, histological and genetic findings are heterogeneous. Advanced imaging, including MR perfusion, could identify biopsy targets. Negative MR spectroscopy does not exclude the diagnosis of glioma.

Background: Isocitrate Dehydrogenase 1/2 (IDH 1/2)-wildtype (WT) astrocytomas constitute a heterogeneous group of tumors and have undergone a series of diagnostic reclassifications over time. This study aimed to investigate molecular markers, clinical, imaging, and treatment factors predictive of outcomes in WHO grade 2/3 IDH-WT astrocytomas ('early glioblastoma'). Methodology: Patients with WHO grade 2/3 IDH-WT astrocytomas were identified from the hospital archives. They were cross-referenced with the electronic medical records systems, including neuroimaging. The expert neuro-pathology team retrieved data on molecular markers—MGMT, TERT, IDH, and EGFR. Tumors with a TERT mutation and/or EGFR amplification were reclassified as glioblastoma. Results: Fifty-four patients were identified. Sixty-three percent of the patients could be conclusively reclassified as glioblastoma based on either TERT mutation, EGFR amplification, or both. On imaging, 65% showed gadolinium enhancement on MRI. Thirty-nine patients (72%) received long-course radiotherapy, of whom 64% received concurrent chemotherapy. The median follow-up of the group was 16 months (range: 2–90), and the median overall survival (OS) was 17.3 months. The 2-year OS of the whole cohort was 31%. On univariate analysis, older age, worse performance status (PS), and presence versus absence of contrast enhancement on diagnostic MRI were statistically significant for poorer OS. Conclusion: IDH-WT WHO grade 2/3 astrocytomas are a heterogeneous group of tumors with poor clinical outcomes. The majority can be reclassified as glioblastoma, based on current WHO classification criteria, but further understanding of the underlying biology of these tumors and the discovery of novel targeted agents are needed for better outcomes. [ABSTRACT FROM AUTHOR]

The rapid and unplanned change to teaching and learning in the online format brought by COVID-19 has likely impacted many, if not all, aspects of university students' lives worldwide. To contribute to the investigation of this change, this study focuses on the impact of the pandemic on student well-being, which has been found to be as important to student lifelong success as their academic achievement. Student well-being has been linked to their engagement and performance in curricular, co-curricular, and extracurricular activities, intrinsic motivation, satisfaction, meaning making, and mental health. The purpose of this study was to examine how student perceptions of their degree completion and future job prospects during the pandemic impact their well-being and what role university support plays in this relationship. We used the conservation of resources theory to frame our study and to develop five hypotheses that were later tested via structural equation modeling. Data were collected from 2,707 university students in France, Germany, Russia, and UK via an online survey. The results showed that university support provided by instructors and administration plays a mediating role in the relationship between the perceived impact of COVID-19 on degree completion and future job prospects and levels of student well-being. Student well-being is decreased by their concerns for their degree completion but not by their concerns for future job prospects. In turn, concerns for future job prospects affect student well-being over time. These results suggest that in a “new normal,” universities could increase student well-being by making support to student studies a priority, especially for undergraduates. Also, universities should be aware of the students' changing emotional responses to crisis and ensure visibility and accessibility of student support.

Abstract Background T1‐weighted dynamic contrast‐enhanced (DCE) perfusion magnetic resonance imaging (MRI) has been broadly utilized in the evaluation of brain tumors. We aimed at assessing the diagnostic accuracy of DCE‐MRI in discriminating between low‐grade gliomas (LGGs) and high‐grade gliomas (HGGs), between tumor recurrence and treatment‐related changes, and between primary central nervous system lymphomas (PCNSLs) and HGGs. Methods We performed this study based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis of Diagnostic Test Accuracy Studies criteria. We systematically surveyed studies evaluating the diagnostic accuracy of DCE‐MRI for the aforementioned entities. Meta‐analysis was conducted with the use of a random effects model. Results Twenty‐seven studies were included after screening of 2945 possible entries. We categorized the eligible studies into three groups: those utilizing DCE‐MRI to differentiate between HGGs and LGGs (14 studies, 546 patients), between recurrence and treatment‐related changes (9 studies, 298 patients) and between PCNSLs and HGGs (5 studies, 224 patients). The pooled sensitivity, specificity, and area under the curve for differentiating HGGs from LGGs were 0.93, 0.90, and 0.96, for differentiating tumor relapse from treatment‐related changes were 0.88, 0.86, and 0.89, and for differentiating PCNSLs from HGGs were 0.78, 0.81, and 0.86, respectively. Conclusions Dynamic contrast‐enhanced‐Magnetic resonance imaging is a promising noninvasive imaging method that has moderate or high accuracy in stratifying gliomas. DCE‐MRI shows high diagnostic accuracy in discriminating between HGGs and their low‐grade counterparts, and moderate diagnostic accuracy in discriminating recurrent lesions and treatment‐related changes as well as PCNSLs and HGGs.

Primary central nervous system lymphoma (PCNSL) has variable imaging appearances, which overlap with those of glioblastoma (GBM), thereby necessitating invasive tissue diagnosis. We aimed to investigate whether a rapid filtration histogram analysis of clinical MRI data supports the distinction of PCNSL from GBM. Ninety tumours (PCNSL n = 48, GBM n = 42) were analysed using pre-treatment MRI sequences (T1-weighted contrast-enhanced (T1CE), T2-weighted (T2), and apparent diffusion coefficient maps (ADC)). The segmentations were completed with proprietary texture analysis software (TexRAD version 3.3). Filtered (five filter sizes SSF = 2–6 mm) and unfiltered (SSF = 0) histogram parameters were compared using Mann-Whitney U non-parametric testing, with receiver operating characteristic (ROC) derived area under the curve (AUC) analysis for significant results. Across all (n = 90) tumours, the optimal algorithm performance was achieved using an unfiltered ADC mean and the mean of positive pixels (MPP), with a sensitivity of 83.8%, specificity of 8.9%, and AUC of 0.88. For subgroup analysis with >1/3 necrosis masses, ADC permitted the identification of PCNSL with a sensitivity of 96.9% and specificity of 100%. For T1CE-derived regions, the distinction was less accurate, with a sensitivity of 71.4%, specificity of 77.1%, and AUC of 0.779. A role may exist for cross-sectional texture analysis without complex machine learning models to differentiate PCNSL from GBM. ADC appears the most suitable sequence, especially for necrotic lesion distinction.

We have demonstrated sub-Angstrom TEM to a resolution of 0.78 Angstrom with the one-Angstrom microscope (OAM) project at the National Center for Electron Microscopy. The OAM combines a modified CM300FEG-UT with computer software able to generate sub-Angstrom images from experimental image series. We achieved sub-Angstrom resolution with the OAM by paying close attention to detail. We placed the TEM in a favorable environment. We reduced its three-fold astigmatism A2 from 2.46mm to 300 Angstrom (corresponding to transfer of 0.68 Angstrom spacings at a pi/4 phase limit). We improved its information limit by minimizing high-voltage and lens current ripple. Energy spread of 0.93eV FWHH gave a focus spread of 20 Angstrom and an information limit of 0.78 Angstrom, allowing successful resolution of the 0.89 Angstrom (400) atom spacings in [110] diamond. As a further test, we reduced the electron gun extraction voltage to 3kV to improve our information limit to 0.75 Angstrom, and then imaged 0.7 Angstrom (444) atom spacings in [112] silicon as distinct pairs of 'white atoms' near an alpha-null defocus of -3783 Angstrom.