Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding of pathogenetic mechanisms and patient stratification. Concurrently, the role of immune cells in the tumor microenvironment has received increasing attention, especially T cells and tumor-associated macrophages (TAM). The latter are a mixed population of activated brain-resident microglia and infiltrating monocytes/monocyte-derived macrophages, both of which express ionized calcium-binding adapter molecule 1 (IBA1). This study investigated differences in immune cell subpopulations among distinct transcriptional subtypes of GBM. Human GBM samples were molecularly characterized and assigned to Proneural, Mesenchymal or Classical subtypes as defined by NanoString nCounter Technology. Subsequently, we performed and analyzed automated immunohistochemical stainings for TAM as well as specific T cell populations. The Mesenchymal subtype of GBM showed the highest presence of TAM, CD8+, CD3+ and FOXP3+ T cells, as compared to Proneural and Classical subtypes. High expression levels of the TAM-related gene AIF1, which encodes the TAM-specific protein IBA1, correlated with a worse prognosis in Proneural GBM, but conferred a survival benefit in Mesenchymal tumors. We used our data to construct a mathematical model that could reliably identify Mesenchymal GBM with high sensitivity using a combination of the aforementioned cell-specific IHC markers. In conclusion, we demonstrated that molecularly distinct GBM subtypes are characterized by profound differences in the composition of their immune microenvironment, which could potentially help to identify tumors amenable to immunotherapy.

Global health education in Germany: an analysis of current capacity, needs and barriers.

BACKGROUND: In times of increasing global challenges to health, it is crucial to create a workforce capable of tackling these complex issues. Even though a lack of GHE in Germany is perceived by multiple stakeholders, no systematic analysis of the current landscape exists. The aim of this study is to provide an analysis of the global health education (GHE) capacity in Germany as well as to identify gaps, barriers and future strategies. METHODS: An online search in combination with information provided by student representatives, course coordinators and lecturers was used to create an overview of the current GHE landscape in Germany. Additionally, a semi-structured questionnaire was sent to GHE educators and students engaged in global health (GH) to assess the capacity of German GHE, its barriers and suggested strategies for the future. RESULTS: A total of 33 GHE activities were identified at 18 German universities. Even though medical schools are the main provider of GHE (42%), out of 38 medical schools, only 13 (34%) offer any kind of GHE. Modules offered for students of other health-related professions constitute 27% of all activities. Most survey respondents (92%, n = 48) consider current GHE activities in Germany insufficient. Suggested formats were GHE as part of medical curricula (82%, n = 45) and dual degree MD/MPH or PhD programs. Most important barriers mentioned were low priority of GH at faculties and academic management levels (n = 41, 75%) as well as lack of necessary institutional structures (n = 33, 60%). CONCLUSIONS: Despite some innovative academic approaches, there is clearly a need for more systematic GHE in Germany. GHE educators and students can take an important role advocating for more awareness at university management level and suggesting ways to institutionalize GHE to overcome barriers. This study provides key evidence, relevant perceptions and suggestions to strengthen GHE in Germany.

Improvement of image quality using BLADE sequences in brain MR imaging.

The purpose of this study is to compare two types of sequences in brain magnetic resonance (MR) examinations of uncooperative and cooperative patients. For each group of patients, the pairs of sequences that were compared were two T2-weighted (T2-W) fluid attenuated inversion recovery sequences with different k-space trajectories (conventional Cartesian and BLADE) and two T2-TSE weighted with different k-space trajectories (conventional Cartesian and BLADE). Twenty-three consecutive uncooperative patients and 44 cooperative patients, who routinely underwent brain MR imaging examination, participated in the study. Both qualitative and quantitative analyses were performed based on the signal-to-noise ratio, contrast-to-noise ratio (CNR), and relative contrast (ReCon) measures of normal anatomic structures. The qualitative analysis was performed by experienced radiologists. Also, the presence of motion, other (e.g., Gibbs, susceptibility artifacts, phase encoding from vessels) artifacts and pulsatile flow artifacts was evaluated. In the uncooperative group of patients, BLADE sequences were superior to the corresponding conventional sequences in all the cases. Furthermore, the differences were found to be statistically significant in almost all the cases. In the cooperative group of patients, BLADE sequences were superior to the conventional sequences with the differences of the CNR and ReCon values in nine cases being statistically significant. Furthermore, BLADE sequences eliminated motion and other artifacts and T2 FLAIR BLADE sequences eliminated pulsatile flow artifacts. BLADE sequences (T2-TSE and T2 FLAIR) should be used in brain MR examinations of uncooperative patients. In cooperative patients, T2-TSE BLADE sequences may be used as part of the routine protocol and orbital examinations. T2 FLAIR BLADE sequences may be used optionally in examinations of AVM, orbits, haemorrhages, ventricular lesions, lesions in the frontal lobe, periventricular lesions, lesions in regions close to artifacts and lesions in posterior fossa.