The landscape of current research on pediatric diffuse midline glioma: a quantitative analysis of shifts, leaders, and future avenues.

PURPOSE: Diffuse midline glioma (DMG) has seen a surge of research interest in recent years with the growth in knowledge of new avenues for potential treatments. However, no bibliometric review of the field has been conducted to visualize the current state of the field. Here, we use bibliometric mapping to visualize the knowledge structure, collaborations, and trends in the field. METHODS: A total of 1079 original and review articles from 1996 to 2023 on diffuse midline glioma were extracted from the Web of Science Core Collection on June 3, 2023. These files were analyzed with R and VOSviewer to construct bibliometric visualizations. RESULTS: Research interest in DMG has continued to grow, driven by publications of original research. Molecular characterization of DMG has been a key focus of recent literature, and terms relating to novel small molecules, mutations, immunotherapy, the blood-brain barrier, and liquid biopsy may be areas for future growth in the literature. Collaborating nations have generally been the North American and European nations, but other nations have begun to make their mark in the field. Leading and rising institutions and journals are described. CONCLUSION: Research in DMG may continue to focus on molecular characterization and new therapeutics based on this knowledge. Novel collaborations between rising nations and institutions in the field may aid in accelerating this research.

Biopsy of diffuse midline glioma is safe and impacts targeted therapy: a systematic review and meta-analysis.

PURPOSE: To quantify the safety and utility of biopsy of pediatric diffuse midline glioma (DMG). METHODS: This study was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Web of Science were queried for relevant articles from inception until June 2023. Two reviewers identified all articles that included diagnostic yield, morbidity, and mortality rates for pediatric DMG patients. Studies that did not present original data or were not in English or peer-reviewed were excluded. Meta-analysis was conducted in R using Freeman-Tukey or logit transformation and DerSimonian-Laird random-effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. A protocol for this review was not registered. RESULTS: We identified 381 patients from ten studies that met all criteria. DMG biopsy is safe overall (0% mortality, 95% CI: 0-0.6%; 11.0% morbidity, 95% CI: 4.8-18.9%) and has a high diagnostic yield (99.9%, 95% CI: 98.5-100%). The use of stereotactic biopsy is a significant moderator of morbidity (p = 0.0238). Molecular targets can be identified in approximately 53.4% of tumors (95% CI: 37.0-69.0%), although targeted therapies are only delivered in about 33.5% of all cases (95% CI: 24.4-44.1%). Heterogeneity was high for morbidity and identification of targets. The risk of bias was low for all studies. CONCLUSION: We conducted the first meta-analysis of DMG biopsy to show that it is safe, effective, and able to identify relevant molecular targets that impact targeted therapy.

Characterization hiPSC-derived neural progenitor cells and neurons to investigate the role of NOS1AP isoforms in human neuron dendritogenesis.

Abnormal dendritic arbor development has been implicated in a number of neurodevelopmental disorders, such as autism and Rett syndrome, and the neuropsychiatric disorder schizophrenia. Postmortem brain samples from subjects with schizophrenia show elevated levels of NOS1AP in the dorsolateral prefrontal cortex, a region of the brain associated with cognitive function. We previously reported that the long isoform of NOS1AP (NOS1AP-L), but not the short isoform (NOS1AP-S), negatively regulates dendrite branching in rat hippocampal neurons. To investigate the role that NOS1AP isoforms play in human dendritic arbor development, we adapted methods to generate human neural progenitor cells and neurons using induced pluripotent stem cell (iPSC) technology. We found that increased protein levels of either NOS1AP-L or NOS1AP-S decrease dendrite branching in human neurons at the developmental time point when primary and secondary branching actively occurs. Next, we tested whether pharmacological agents can decrease the expression of NOS1AP isoforms. Treatment of human iPSC-derived neurons with d-serine, but not clozapine, haloperidol, fluphenazine, or GLYX-13, results in a reduction in endogenous NOS1AP-L, but not NOS1AP-S, protein expression; however, d-serine treatment does not reverse decreases in dendrite number mediated by overexpression of NOS1AP isoforms. In summary, we demonstrate how an in vitro model of human neuronal development can help in understanding the etiology of schizophrenia and can also be used as a platform to screen drugs for patients.