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Glioma represents the most common central nervous system neoplasm in adults. Current classification scheme utilizes molecular alterations, particularly IDH1.R132H, to stratify lesions into distinct prognostic groups. Identification of the single nucleotide variant through traditional tissue biopsy assessment poses procedural risks and does not fully reflect the heterogeneous and evolving tumor landscape. Here, we introduce a liquid biopsy assay, mt- IDH1 dx . The blood-based test allows minimally invasive detection of tumor-derived extracellular vesicle RNA using only 2 ml plasma volume. We perform rigorous, blinded validation testing across the study population ( n  = 133), comprising of IDH1.R132H patients ( n  = 80), IDH1 wild-type gliomas ( n  = 44), and age matched healthy controls ( n  = 9). Results from our plasma testing demonstrate an overall sensitivity of 75.0% (95% CI: 64.1%–84.0%), specificity 88.7% (95% CI: 77.0%–95.7%), positive predictive value 90.9%, and negative predictive value 70.1% compared to the tissue gold standard. In addition to fundamental diagnostic applications, the study also highlights the utility of mt- IDH1 dx platform for blood-based monitoring and surveillance, offering valuable prognostic information. Finally, the optimized workflow enables rapid and efficient completion of both tumor tissue and plasma testing in under 4 hours from the time of sampling. Efficient and non-invasive, liquid biopsy methods could greatly improve the molecular classification of gliomas. Here, the authors develop an RNA-based Droplet Digital PCR assay to detect the key IDH1.R132H mutation in plasma-derived extracellular vesicles from glioma patients with high sensitivity, allowing accurate diagnosis, prognostication and longitudinal monitoring.

Characterizing the m6A epigenetic landscape is essential for understanding glioma biology, yet transcriptome-wide mapping of these modifications at isoform resolution across specific tumor subtypes has remained limited. Conventional short-read approaches lack the capacity to resolve full-length transcript isoforms or assign m6A modifications to individual transcripts, representing a critical gap in glioma where alternative splicing is pervasive. We performed direct RNA nanopore sequencing and transcriptome-wide m6A analysis in 14 glioma tumor tissues, including IDH1-mutant astrocytoma, oligodendroglioma, and IDH1 wild-type glioblastoma, enabling isoform-resolved profiling not accessible by conventional short-read approaches. m6A sites were predicted computationally using the m6Anet deep learning framework, which has been independently benchmarked against MeRIP-seq-derived sites, and high-confidence calls were defined at a probability threshold of ≥0.9 and required detection across multiple patients within each subtype. IDH1-mutant gliomas showed a higher overall burden of computationally inferred m6A-modified sites, transcripts, and genes than IDH1 wild-type glioblastoma, along with variation in transcript biotypes, regional distribution of m6A sites, and extent of isoform methylation. Differential methylation analysis identified subtype-specific patterns of m6A localization, many of which were observed without corresponding changes in gene-level expression, indicating that m6A variation represents a post-transcriptional regulatory layer not captured by gene-level analysis alone. Integration of gene expression, isoform usage, and m6A status further identified variation in isoform composition and transcript features between astrocytoma and glioblastoma. Analysis of m6A regulators showed subtype-associated expression patterns among readers, writers, and erasers, and exploratory analyses identified isoform-level associations with survival that were not apparent at the gene level. Overall, these data describe subtype-specific patterns of m6A marking and isoform architecture across glioma tissues, derived from computational inference using direct RNA sequencing in a modestly sized cohort and warrant validation by orthogonal methods in larger studies. These findings are consistent with concurrent independent evidence that isoform-specific m6A deposition is evolutionarily conserved across mammals and that long-read isoform resolution reveals transcript diversity in glioma not captured by gene-level analysis. While cohort size and the absence of orthogonal site-level validation suggest that the data require cautious interpretation, this work provides a hypothesis-generating resource and methodological framework for future mechanistic and translational investigation of the glioma epitranscriptome.

Abstract m6AnetAnalyzer is an R package that streamlines post-processing and interpretation of site-level m6A predictions from m6Anet. It summarizes m6A distributions across transcripts, genes, biotypes, and transcript regions, and enables functional annotation using user-provided BED files or built-in datasets, including RNA-binding proteins and SNPs. Condition-specific changes in m6A methylation are quantified using the log2-transformed weighted modification ratio, with statistical tests applied when appropriate to identify significant differential methylation. By integrating differential gene expression data, m6AnetAnalyzer links methylation changes with expression differences, offering biotype- and region-specific insights into how m6A localization patterns relate to transcriptional regulation. Availability  and implementation m6AnetAnalyzer is freely available at https://github.com/hannalee809/m6AnetAnalyzer. It is compatible with Linux, macOS, and Windows platforms. Detailed installation instructions, example input and output files, and a step-by-step analysis workflow are provided in the package vignette.

Background: Diffusion-weighted magnetic resonance has a well-defined role in differentiating between important intracranial lesions. Sometimes, the surgeon is faced with a dilemma of how to diagnose an infectious versus malignant lesion. Case Description: A 28-year-old male presented to the neurosurgery clinic with complaints of headache and left-sided weakness for 2 weeks. Neurological examination was intact. Magnetic resonance imaging (MRI) scan showed a large infiltrating heterogeneous mass involving the right parietal lobe. On further reviewing, there was homogenous diffusion restriction in the center of lesion. In addition, its aggressive behavior confirmed it to be a fungal abscess. Conclusions: Correctly identifying an infectious versus tumor etiology is important. Research has been carried out to employ diffusion-weighted imaging (DWI) in differentiating the variable radiological findings. The role of DWI in diagnosing bacterial abscess is more commonly seen in comparison to fungal abscess. DWI has a high diagnostic potential, but more works need to be done.

m6ASeqTools is an R package designed to streamline the post-processing and interpretation of site-level m6A predictions from m6Anet. It provides descriptive summaries of m6A distribution across transcripts, genes, biotypes, and transcript regions, and enables condition comparisons through a calculated weighted modification ratio. By integrating differential gene expression data, the package links methylation changes with expression differences, providing biotype-specific and region-specific insights into how m6A localization patterns relate to transcriptional regulation.

N6-methyladenosine (m6A) is the most prevalent internal mRNA modification, enriched in the CNS yet poorly characterized in glioma. Using long-read RNA sequencing, we mapped m6A in an glioma model following knockdown (KD) of the reader IGF2BP2, writer METTL3, and eraser ALKBH5, with naive glioma cells and astrocytes as controls. Glioma cells exhibited a two-fold reduction in global m6A, suggesting progressive loss from healthy to malignant states. Integrated analysis revealed that m6A mediated control of gene expression is influenced by modification topology (CDS:3'UTR), transcript biotype, and length. Regulator KD, particularly ALKBH5 induced redistribution of m6A toward 3'UTR with consequent gene upregulation. We also identified m6A-mediated isoform switching, with a higher usage of retained intron and nonsense-mediated decay isoforms. Structural and splicing alterations at the isoform level were identified unique to each KD condition indicating m6A driven aberrant alternative splicing. At the functional level, KD specific remodeling of oncogenic signaling was also observed. ALKBH5 KD suppressed MYC targets and pro-apoptotic signaling while METTL3 KD enhanced mTOR and PI3K-AKT signaling. Collectively, these results demonstrate that m6A mediated regulation in glioma is highly context-dependent, defining distinct clinically relevant phenotypes. This has implications for future biomarker discovery and development of targeted therapeutics.

Background Eustachian tube dysfunction (ETD) and laryngopharyngeal reflux disease (LPRD) are under-recognized conditions that significantly impact quality of life. LPRD may contribute to ETD via gastric refluxate-induced mucosal damage. While proton pump inhibitors (PPIs) are commonly used for reflux management, their role in alleviating ETD symptoms remains controversial. This study investigates the association between LPRD and ETD and evaluates the efficacy of PPI therapy in ETD management. Methods A prospective study was conducted on patients diagnosed with ETD and LPRD. A total of 126 patients were included using consecutive non-randomized sampling. The participants underwent an eight-week regimen of twice-daily 40 mg oral omeprazole. ETD severity was assessed using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7), while LPRD severity was measured via the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS), both pre- and post-intervention. Independent t-tests and correlation analyses were performed to evaluate treatment outcomes. Results Significant reductions were observed in ETDQ-7 (16.20±10.47 to 10.40±5.47, p<0.001), RSI (11.42±7.65 to 4.50±2.65, p<0.001), and RFS (22.56±10.14 to 4.84±2.45, p<0.001) scores following PPI therapy, suggesting symptomatic improvement in both ETD and LPRD. Correlation analysis revealed a moderate association between both ETDQ-7 and RSI (0.346-0.391, p<0.001), and ETDQ-7 and RFS (0.437-0.515, p<0.001) scores respectively. However, residual symptoms in some patients suggest that additional pathophysiological factors may contribute to ETD beyond the reflux-mediated inflammation. Conclusion This study provides evidence supporting the link between LPRD and ETD and suggests that PPI therapy may alleviate ETD symptoms in a subset of patients. However, given the multifactorial nature of ETD, further studies are needed to explore alternative therapies (such as potassium channel blockers, Eustachian tube dilation, etc.) and long-term treatment outcomes.