Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany To maximize profit by growing user engagement and participation, social media companies have created sophisticated tools which filter information and place people in virtual echo chambers. These confirm or even radicalize the users’ world views. Currently, the algorithms underlying social media platforms’ business model amplify the angry and divisive voices which drive engagement, pushing users towards ever more extreme content. First, the use of long peptides, such as the 27-mer H3K27M-vac, is safe irrespective of concomitant anti-PD-1 therapy and suitable to induce mutation-specific CD4 + T cell responses in patients with H3K27M + DMG. The induction of CD4 + T cell-dominated immune responses by long mutation-specific peptide vaccines is similar to that observed in 28 of 30 patients in a first-in-human phase I trial of the long peptide vaccine IDH1-vac in patients with newly diagnosed astrocytomas 20, 21. Notably, CD4 + T cell phenotyping following H3K27M-vac revealed no evidence of induction of immunosuppressive regulatory T cells. While the immunogenicity of the short peptide vaccine H3.3K27M 26-35 is restricted to HLA-A*02 + patients 17, we provide evidence of presentation of H3K27M neoepitope on MHC class II on tumor cells and on APCs across multiple HLA types (Fig. 4). While killing activity of H3K27M-specific CD8 + T cells against HLA-A*02 + tumor cells with endogenous H3.3K27M expression remains controversial 17, 18, 19 we have recently demonstrated that CD4 + T cell interaction with peptide MHC class II in glioma-infiltrating myeloid cells is critical for the fitness of glioma-infiltrating CD8 + T cells 22. Further analyses in a larger clinical trial cohort will assess the suitability of MHC class II expression and neoepitope presentation in DMG as predictive markers for response to H3K27M-vac. Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).

Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nature Methods 9, 357–359 (2012). Waitkus, M. S., Diplas, B. H. & Yan, H. Isocitrate dehydrogenase mutations in gliomas. Neuro Oncol. 18, 16–26 (2016). Losman, J. A. & Kaelin, W. G.Jr. What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev. 27, 836–852 (2013). Max Eder Junior Group on Low Grade Gliomas, Heidelberg University Medical Center, Heidelberg, GermanyInstitute of Neurology (Edinger Institute), University Hospital and Medical Faculty, Goethe University, Frankfurt, Germany

Poretsky, R. S. et al. Comparative day/night metatranscriptomic analysis of microbial communities in the North Pacific subtropical gyre. Environ. Microbiol. 11, 1358–1375 (2009).peacebuilding practitioners to use social media technology much more strategically and systematically for analysis of conflict actors, early warning, counter-messaging and the defence of democracy and human rights; Grassian, A. R. et al. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism. Cancer Res. 74, 3317–3331 (2014). Passariello, C. L. et al. Evidence that AMP-activated protein kinase can negatively modulate ornithine decarboxylase activity in cardiac myoblasts. Biochim. Biophys. Acta 1823, 800–807 (2012). Karlstaedt, A. et al. Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart. Proc. Natl Acad. Sci. USA 113, 10436–10441 (2016).

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

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Vuong, H. G., Ngo, T. N. M., Le, H. T. & Dunn, I. F. The prognostic significance of HIST1H3B/C and H3F3A K27M mutations in diffuse midline gliomas is influenced by patient age. J. Neurooncol. 158, 405–412 (2022).

The device in use today safely burns a continuous stream of a flammable gas such as natural gas (which is principally methane) or a liquefied petroleum gas such as propane, butane, or a mixture of both. L.B., S.P., and T.B. designed and performed experiments, analyzed data, and wrote the paper. F.S. and A.v.D. provided glioma tissue, determined IDH1 status, provided tissue stainings, and performed 850 k methylation arrays. K.S., M.F., M.Ki., A.v.L., and S.K.-B. performed in vitro experiments. J.K.S., M.Kr., and I.O. performed in vivo experiments. D.A. and B.A.N. performed calcium and respiration measurements. E.G., M.B., and R.H. performed genetic modification of cell lines. K.D. analyzed primary human tissue. C.N., M.L.S., S.U., and K.B. were involved in TIL processing. T.K. and D.S. analyzed RNA-seq data. A.S.B. and M.Pr. provided glioma tissue, determined IDH1 status, and provided immunohistochemistry stainings. K.M., M.S., D.Z., B.N., and M.D. performed metabolomics and interpreted data. B.W. performed statistical and TCGA analyses. M.O.B. performed magnetic resonance imaging. R.A.-A. and S.T. performed epigenetic profiling. J.M. and A.H. performed RNA-seq. G.P. performed adenosine phosphate and polyamine measurements. M.W. provided glioma tissues and was involved in data interpretation. M.N.-O., N.T., M.C.B., P.N.H., M.R., D.P.C., K.H.P., and D.H. provided glioma tissue. A.B. performed KEGG pathway analyses. J.E. and J.O. performed R-2-HG measurements. C.H.-M. provided the primary glioma cell line. S.K. and H.H.-S. interpreted data and provided BAY1436032. W.W. was involved in study design and data interpretation. M.Pl. conceptualized the study, interpreted data, and wrote the paper. Corresponding authorTyrakis, P. A. et al. S-2-hydroxyglutarate regulates CD8(+) T-lymphocyte fate. Nature 540, 236–241 (2016). Spilling, K. Dense sub-ice bloom of dinoflagellates in the Baltic Sea, potentially limited by high pH. J. Plankton Res. 29, 895–901 (2007).