Objective To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. Methods A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. Results Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. Conclusion New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.

Glioblastoma ranks among the most lethal of all human cancers. Glioblastomas display striking cellular heterogeneity, with stem-like glioblastoma stem cells (GSCs) at the apex. Although the original identification of GSCs dates back more than a decade, the purification and characterization of GSCs remains challenging. Despite these challenges, the evidence that GSCs play important roles in tumor growth and response to therapy has grown. Like normal stem cells, GSCs are functionally defined and distinguished from their differentiated tumor progeny at core transcriptional, epigenetic, and metabolic regulatory levels, suggesting that no single therapeutic modality will be universally effective against a heterogenous GSC population. Glioblastomas induce a systemic immunosuppression with mixed responses to oncoimmunologic modalities, suggesting the potential for augmentation of response with a deeper consideration of GSCs. Unfortunately, the GSC literature has been complicated by frequent use of inferior cell lines and a lack of proper functional analyses. Collectively, glioblastoma offers a reliable cancer to study cancer stem cells to better model the human disease and inform improved biologic understanding and design of novel therapeutics.

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Glioblastoma (World Health Organization grade IV glioma) represents the most common primary, intrinsic brain tumor with inevitable recurrence, limiting the median survival of patients to little more than a year ( 1, 2 ). Glioblastomas display cellular hierarchies with self-renewing glioblastoma stem cells (GSC) at the apex, with contributions of GSCs to therapeutic resistance and tumor recurrence ( 3-5 ). Standard-of-care therapy includes surgical resection followed by combined radiotherapy and chemotherapy, and then adjuvant chemotherapy, but treatment remains palliative ( 6 ). Given the roles of GSCs in therapeutic resistance, angiogenesis, immune escape, and invasion, clinical and preclinical observations suggest that targeting GSCs may improve tumor outcome ( 7 ). SIGNIFICANCE:Epitranscriptomics promotes cellular heterogeneity in cancer. RNA m6A landscapes of cancer and NSCs identifi ed cell type-specifi c dependencies and therapeutic vulnerabilities. The m6A reader YTHDF2 stabilized MYC mRNA specifi cally in cancer stem cells. Given the challenge of targeting MYC, YTHDF2 presents a therapeutic target to perturb MYC signaling in glioblastoma.Research.

Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.