Disadvantaged Neighborhoods Continue to Bear the Burden of Gun Violence.

INTRODUCTION: Gun violence is a pervasive and dynamic public health crisis causing substantial burden on communities and healthcare systems in the United States. Risk factor and outcome analyses are crucial to develop effective interventions. The aim of this study was to assess firearm injury in a diverse community setting as it relates to neighborhood socioeconomic disadvantage and changes over time following large-scale local interventions. METHODS: All county residents with firearm injury presenting to a Level 1 Trauma Center from January 2012 to December 2021 were retrospectively reviewed. Area Deprivation Index (ADI) was used to measure neighborhood socioeconomic disadvantage based on a nine-digit zip code at patients' home address. Injuries were also stratified by 5-year time periods, 2012-2016 and 2017-2021. Demographics and clinical data were analyzed including injury severity, hospital course, and discharge location. Data were compared by ADI quintile and between time periods using chi-squared, one-way analysis of variance, and Cochran-Armitage test. RESULTS: A total of 1044 injuries were evaluated. Patients were 93% male with mean age of 29 y (standard deviation 10.2) and were concentrated in the most disadvantaged neighborhoods (74% ADI Q5). Black or African American race was greater in the most disadvantaged ADI groups (76% versus 47%-66%; P <0.001). Percentage of total injuries in the most disadvantaged ADI group rose from 71% to 78% over time (P = 0.006). Mortality occurred in 154 (15%) patients overall, while most (71%) were discharged to home. Mortality declined from 18% to 11% over time (P <0.001). Medicaid utilization rose from 42% to 77% alongside a decrease in self-pay status from 44% to 4% (P <0.001). There were no clinically significant group differences in injury severity or clinical characteristics. CONCLUSIONS: Firearm injury remains concentrated in the most socioeconomically disadvantaged neighborhoods, and this disparity is increasing over time. Medicaid utilization rose and mortality decreased in this population over time. This research presents a method to inform and monitor local gun violence interventions using ADI to address public health equity.

Predictors of inpatient admission likelihood and prolonged length of stay among cerebrovascular disease patients: A nationwide emergency department sample analysis.

PURPOSE: To examine the hospital- and patient-related factors associated with increased likelihood of inpatient admission and extended hospitalization. METHODS: We applied multivariate logistic regression to a subset of ED hospital and patient characteristics linearly extrapolated from the 2019 National Emergency Department Sample database (n=626,508). Patient characteristics with 10 or fewer ED visits after national extrapolation were not reported in the current study to maintain patient confidentiality, in accordance with the HCUP Data Use Agreement. All selected ED visits represented a primary diagnosis of CVD (ICD-10 codes 160-168). All reported hospital and patient characteristics were subject to adjustment for covariates. P-values < 0.05 were considered statistically significant. MAIN FINDINGS: Medicare beneficiaries report higher inpatient admission rates than uninsured OR 0.81 (0.73-0.91) and privately insured OR 0.86 (0.79-0.94) individuals. Black and Native-American patients were 37% and 55% more likely to be hospitalized long (>75th percentile) (OR 1.37 [1.25-1.50], OR 1.55 [1.14-2.10]). Northeast emergency departments reported an increased odds of admission compared to the Midwest OR (0.40-0.62), South OR 0.79 (0.63-0.98) and West OR 0.52 (0.39-0.69). Patients with multiple comorbidities (mCCI = 3+) were 226% more likely to have a longer stay OR 3.26 (3.09-3.45) than patients presenting with zero or few comorbidities. Level I, II, and III trauma centers report distinctly high odds of inpatient admission (OR 3.54 [2.84-4.42], OR 2.68 [2.14-3.35], OR 1.51 [1.25-1.84]). PRINCIPAL CONCLUSIONS: Likelihoods of inpatient admission and long hospital stays were observably stratified through multiple, independently acting hospital and patient characteristics. Significant associations were stratified by race/ethnicity, location, and clinical presentation, among others. Attention to the factors reported here may serve well to mitigate emergency department crowding and its sobering impact on United States healthcare systems and patients.

Age-associated Ligand-receptor Interactions Imputed from Nasopharyngeal Transcriptomes of COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exhibited different clinical manifestations amongst various age cohorts. As the immune microenvironment may play a role in clinical progression, it is crucial to examine molecular interactions to gain insight into host response. Therefore, to elucidate any differences in host response related to age, the present study imputed ligand-receptor interactions within the nasopharyngeal immune microenvironment in patients affected with SARS-COV-2. Tissue purities, the proportion of non-immune cells in the tissue sample, of 467 nasopharyngeal transcriptome profiles were estimated using known mRNA expression signatures of stromal/immune cells. Using the purity estimates and bulk tissue expression values, non-negative linear regression was used to estimate average expression of each gene in the tissue/stroma compartments. The inferred expression profiles were annotated with a curated database of ligand-receptor interactions and assumed as reasonable proxies for the law of mass action, allowing for quantification of directional ligand-receptor complex concentrations under equilibrium. It was found that older patients (>60 years) exhibited decreased interactions with receptors selectin L receptor SELL and increased interactions with pro-inflammatory chemokine receptors CXCR2 and CCR1. Younger patients showed increased interactions with various members of the TNF receptor super family (TNFRSF). The interactions were further related to immune cell subtypes, with older patients predicted to have less CD8+ and CD4+ resting T cells but increased neutrophil proportions. Collectively, the results suggest certain ligand-receptor interactions of the nasopharyngeal immune microenvironment are age-associated in response to SARS-CoV-2.

A Review of Applications of Machine Learning in Mammography and Future Challenges.

BACKGROUND: The aim of this study is to systematically review the literature to summarize the evidence surrounding the clinical utility of artificial intelligence (AI) in the field of mammography. Databases from PubMed, IEEE Xplore, and Scopus were searched for relevant literature. Studies evaluating AI models in the context of prediction and diagnosis of breast malignancies that also reported conventional performance metrics were deemed suitable for inclusion. From 90 unique citations, 21 studies were considered suitable for our examination. Data was not pooled due to heterogeneity in study evaluation methods. SUMMARY: Three studies showed the applicability of AI in reducing workload. Six studies demonstrated that AI can aid in diagnosis, with up to 69% reduction in false positives and an increase in sensitivity ranging from 84 to 91%. Five studies show how AI models can independently mark and classify suspicious findings on conventional scans, with abilities comparable with radiologists. Seven studies examined AI predictive potential for breast cancer and risk score calculation. Key Messages: Despite limitations in the current evidence base and technical obstacles, this review suggests AI has marked potential for extensive use in mammography. Additional works, including large-scale prospective studies, are warranted to elucidate the clinical utility of AI.

Imbalance of tyrosine by modulating TyrA arogenate dehydrogenases impacts growth and development of Arabidopsis thaliana.

l-Tyrosine is an essential aromatic amino acid required for the synthesis of proteins and a diverse array of plant natural products; however, little is known on how the levels of tyrosine are controlled in planta and linked to overall growth and development. Most plants synthesize tyrosine by TyrA arogenate dehydrogenases, which are strongly feedback-inhibited by tyrosine and encoded by TyrA1 and TyrA2 genes in Arabidopsis thaliana. While TyrA enzymes have been extensively characterized at biochemical levels, their in planta functions remain uncertain. Here we found that TyrA1 suppression reduces seed yield due to impaired anther dehiscence, whereas TyrA2 knockout leads to slow growth with reticulate leaves. The tyra2 mutant phenotypes were exacerbated by TyrA1 suppression and rescued by the expression of TyrA2, TyrA1 or tyrosine feeding. Low-light conditions synchronized the tyra2 and wild-type growth, and ameliorated the tyra2 leaf reticulation. After shifting to normal light, tyra2 transiently decreased tyrosine and subsequently increased aspartate before the appearance of the leaf phenotypes. Overexpression of the deregulated TyrA enzymes led to hyper-accumulation of tyrosine, which was also accompanied by elevated aspartate and reticulate leaves. These results revealed that TyrA1 and TyrA2 have distinct and overlapping functions in flower and leaf development, respectively, and that imbalance of tyrosine, caused by altered TyrA activity and regulation, impacts growth and development of Arabidopsis. The findings provide critical bases for improving the production of tyrosine and its derived natural products, and further elucidating the coordinated metabolic and physiological processes to maintain tyrosine levels in plants.

Analysis of Transcriptomic Similarity between Osteosarcoma Cell Lines and Primary Tumors.

BACKGROUND: Osteosarcoma (OS) cell lines are commonly used to mimic tumors for in vitro experiments. The present study explores the resemblance of OS cell lines to OS primary tumors in regard to gene expression. METHODS: Transcriptomic data were retrieved from published data sets for 18 primary tumor samples and 13 commonly used OS cell lines. Tumor purity was accounted for when correlating tumor and cell line gene expression. Differentially expressed genes between tumors and cell lines were discovered and gene ontology analysis was performed. RESULTS: Certain commonly used cell lines, including NY, NOS1, and U2OS, display less resemblance to OS tumors than do other cell lines. For genes overexpressed in tumors, and consequently underexpressed in cell lines, gene ontology analysis enriched pathways related to cell-cell adhesion and stimulus detection. CONCLUSION: The pathways dysregulated between cell lines and tumors have been implicated in OS pathogenesis. Therefore, the findings suggest that the transcriptome of OS cell lines may not be completely representative of OS primary tumors' gene expression and the disease process.

In silico Analysis of the Immunological Landscape of Hippocampi in Alzheimer's Disease.

INTRODUCTION: Accumulating evidence suggests a relationship between neuroinflammation and neurodegenerative pathologies such as Alzheimer's disease (AD). This study sought to investigate the immunological composition of hippocampi in patients afflicted with AD. METHODS: CIBERSORTx RNA deconvolution was applied on gene expression data developed from hippocampi of 38 AD patients and 17 controls to infer the relative proportions of 22 subsets of immune cells. RESULTS: AD-afflicted hippocampi were found to have greater relative abundances of M2 macrophages and CD8 T cells. AD-afflicted hippocampi were also composed of significantly more active dendritic cells and significantly fewer resting dendritic cells than control samples. CONCLUSION: AD-afflicted hippocampi present with a distinct immune signature and dendritic cells may play a critical role in the pathogenesis of AD in this brain component.

Progressive Multiple Sclerosis Transcriptome Deconvolution Indicates Increased M2 Macrophages in Inactive Lesions.

Accumulating evidence suggests M2 macrophages contribute to tissue reparation and limit inflammation in multiple sclerosis (MS). However, most studies have focused on murine models without substantial support through human MS observations. The present study aimed to quantify the relative abundances of M2 macrophages in different lesion types excised from human MS patients. CIBERSORTx, an established RNA deconvolution algorithm, was applied on bulk RNA-sequencing data developed from 98 lesions from 10 progressive MS patients and 5 neuropathological control donors. A validated gene signature matrix for 22 human hematopoietic cell subsets was used to infer the relative proportions of immune cells that were present in the original lesion. Deconvolution of the bulk gene expression data showed that inactive lesions contained significantly more M2 macrophages compared to normal white matter control samples. The findings suggest that M2 macrophages may play a role during lesion inactivity in MS.

Prefrontal Cortex Transcriptomic Deconvolution Implicates Monocyte Infiltration in Parkinson's Disease.

INTRODUCTION: Although not considered a primary cause, neuroinflammation is associated with many neurodegenerative disorders, including Parkinson's disease (PD). METHODS: To elucidate potential immune involvement in PD, the present study imputed immune cell abundances from bulk RNA-sequencing transcriptomic data of PD postmortem prefrontal cortices. CIBERSORTx, an RNA deconvolution algorithm that implements support vector regression, was used to measure the relative abundances of immune cells from a previously published gene expression dataset. Through this machine-learning approach, relative proportions of 22 immune cell subtypes present in the original brain tissue were estimated. RESULTS: Prefrontal cortices from PD patients exhibited significantly higher relative abundances of monocytes compared to neuropathologically normal controls (p value = 0.0005). The relative proportions of the other 21 immune subtypes showed no significant differences between control and PD samples. CONCLUSION AND DISCUSSION: The findings corroborate previous reports and suggest monocytes may be involved in PD pathogenesis.

Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine learning algorithm on ENB transcriptomic profiles. METHODS: The authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine learning pipeline on RNA sequencing data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB. RESULTS: No differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (P > 0.05). Also, no difference in median overall survival was appreciated (52.0 ± 13.1 months vs. 50.0 ± 43.2 months, P = 0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B cells (13%) and CD4 memory resting T cells (12%). No gross differences in CD20, CD4, or CD8 cells/mm2 were apparent on gross histology (P > 0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB, but did suggest immunoprofile differences. CONCLUSIONS: Basal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.

Transcriptome-Derived Ligand-Receptor Interactome of Major PitNET Subgroups.

Introduction Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors which can impart significant disability owing to their locally invasive potential. To date, the gamut of PitNET subtypes remains ill-understood at the ligand-receptor (LR) interactome level, potentially limiting therapeutic options. Here, we present findings from in silico analysis of LR complexes formed by PitNETs with clinical presentations of acromegaly, Cushing's disease, high prolactin production, and without symptoms of hormone hypersecretion. Methods Previously published PitNET gene expression data was acquired from ArrayExpress. These data represented all secretion types. LR interactions were analyzed via a crosstalk score approach. Results Cortisol (CORT) ligand was significantly involved in tumor-to-tumor signaling across all PitNET subtypes but prolactinomas, which evidenced active CORT depletion. Likewise, CCL25 ligand was implicated in 20% of the top LR complex interactions along the tumor-to-stroma signaling axis, but silent PitNETs reported unique depletion of the CCL25 ligand. Along the stroma-to-tumor signaling axis, all clinical PitNET subtypes enriched stromal vasoactive intestinal polypeptide ligand interactions with tumor secretin receptor. All clinical PitNET subtypes enriched stromal DEFB103B (human ß-defensin 103B) ligand interactions with stromal chemokine receptors along the stroma-to-stroma signaling axis. In PitNETs causing Cushing's disease, immune checkpoint ligand CD274 reported high stromal expression, and prolactinomas reported low stromal expression. Moreover, prolactinomas evidenced distinctly high stromal expression of immune-exhausted T cell response marker IL10RA compared with other clinical subtypes. Conclusion Relative crosstalk score analysis revealed a great diversity of LR complex interactions across clinical PitNET subtypes and between solid tumor compartments. More data are needed to validate these findings and exact clinical importance.

Trends in Volume and Charges of Retinal Tear Patients in the Emergency Department.

PURPOSE: To characterize retinal tears (RTs) and calculate the economic burden of RTs that present to the emergency department (ED) in the US. METHODS: We used a large national ED database to retrospectively analyze RTs that presented to the ED from 2006 to 2019. Using extrapolation methods, national of the RT patient ED volume, demographics, comorbidities, disposition, inpatient (IP) charges, and ED charges were calculated. RESULTS: During the period between 2006 and 2019, 15841 ED encounters had RT listed as the primary diagnosis. The average annual RT ED encounters was 2,640 ± 856 and comprised an average of 6.4 × 10-5% of all ED visits annually. The number and ED percentage of RT encounters did not change during this time period (p = .22, p = .67, respectively). Most patients were males, Caucasian, paid with private insurance, and admitted to EDs in the Northeast. The most common comorbidities were hypertension (19%), a history of cataracts (15%), and diabetes (7.2%). During this time period, RTs charges added up to more than $79 million and $33 million in the ED and IP settings, respectively. Mean per-encounter ED and IP charges increased by 145% (p = .0008) and 86% (p = .0047), respectively. CONCLUSION: Despite the stable number of RT patients presenting to the ED, RTs place a significant economic burden to the healthcare system, which increases yearly. We recommend physicians and policy makers to work together to pass laws that could prevent the increasing healthcare charges.

Hypoxic transcriptomes predict survival and tumor-infiltrating immune cell composition in cutaneous melanoma.

Hypoxia has established associations with aggressive tumor phenotypes in many cancers. However, it is not currently understood whether tumor hypoxia levels map to distinct immune infiltrates in cutaneous melanoma, potentially unveiling novel therapeutic targets. To this end, we leveraged a previously identified seven-gene hypoxia signature to grade hypoxia levels of 460 cutaneous melanomas obtained from the Broad Institute GDAC Firehose portal. CIBERSORTx ( https://cibersortx.stanford.edu/ ) was employed to calculate the relative abundance of 22 mature human hematopoietic populations. Clinical outcomes and immune cell associations were assessed by computational means. Results indicated that patients with high-hypoxia tumors reported significantly worse overall survival and correlated with greater Breslow depth, validating the in-silico methodology. High-hypoxia tumors demonstrated increased infiltration of activated and resting dendritic cells, resting mast cells, neutrophils, and resting NK cells, but lower infiltration of gamma-delta T cells. These data suggest that high tumor hypoxia correlates with lower survival probability and distinct population differences of several tumor-infiltrating leukocytes in cutaneous melanomas.

A Decade of Global Skull Base Researchers: Authorship Trends from 3,295 Abstracts in the Journal of Neurological Surgery Part B: Skull Base.

Objective The North American Skull Base Society (NASBS) multidisciplinary annual conference hosts skull base researchers from across the globe. We hypothesized that the work presented at the NASBS annual conference would reveal diverse authorship teams in terms of specialty and geography. Methods In this retrospective review, abstracts presented at the NASBS annual meeting and subsequently published in the Journal of Neurological Surgery Part B: Skull Base between 01/01/2011 and 12/31/2020 were collected. Variables extracted included year, type of presentation, and author names and affiliations. Statistical analyses were performed with SPSS V23.0 with p -values less than 0.05 considered significant. Geographic heat maps were created to assess author distribution, and a network analysis was performed to display authorship collaboration between geographic regions. Results Of 3,312 published abstracts, 731 (22.1%) had an author with an affiliation outside of the United States. Fifty-seven distinct countries were represented. Three-hundred twenty-four abstracts (9.8%) had authorship teams representing at least 2 different countries. The top five US states by abstract representation were Pennsylvania, California, New York, Ohio, and Minnesota. A majority of authors reported neurosurgery affiliations (56.7% first authors, 53.2% last authors), closely followed by otolaryngology (39.1% first authors, 41.5% last authors). No solo authors and very few (3.3%) of the first authors reported a departmental affiliation outside of otolaryngology or neurosurgery. Conclusions Authors from many countries disseminate their work through poster and oral presentations at the NASBS annual meeting. Ten percent of abstracts were the product of international collaboration. Most authors were affiliated with a neurosurgery or otolaryngology department.

A Decade of Global Skull Base Researchers: Gender Data from over 2,700 Abstract Authors in the Journal of Neurological Surgery Part B: Skull Base.

Objective The North American Skull Base Society (NASBS) annual conference brings together skull base researchers from surgical and nonsurgical fields. Our objective was to quantify the contributions of the authors by gender, who presented their work at NASBS and were subsequently published in the Journal of Neurological Surgery Part B: Skull Base . Methods Oral and poster abstracts presented at the NASBS annual meeting from January 1, 2011 to December 31, 2020 were extracted from the Journal of Neurological Surgery Part B: Skull Base. The genderize.io Web application programming interface was utilized to determine authorship gender. A minority of first and last authors had departmental affiliations listed; a subgroup analysis was performed of these authors. Results Female gender was assigned to 498 (17.8%) of the 2,798 first authors and 269 (9.7%) of the 2,762 last authors. Female authorship has consistently increased over the last decade. Representation was higher in otolaryngology (23.3% of first authors, 12.1% of last authors; p = 0.018) than neurosurgery (13.5% of first authors, 4.3% of last authors; p = 0.004). Female researchers were not less likely than their male counterparts to receive prestigious oral presentations. Of the 52 total countries represented, 20 (38.5%) had at least one female first author. Representation varied dramatically between countries. Conclusion The NASBS' efforts have undoubtedly contributed to these impressive strides toward gender parity. More work is needed to ensure that the best and the brightest, regardless of background, continue to contribute to skull base surgery research.

Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data.

Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author's best knowledge, the present study represents a first-use case of the Interplanetary File Storage protocol for storing and retrieving spine imaging smart contracts. Methods: The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected. Results: It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records. Conclusions: The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data.

Membranome Similarity between Glioblastoma Multiforme Cell Lines and Primary Tumors.

Genes encoding for proteins associated with the plasma membrane, referred to as the membranome, have long been recognized to play an important role in the development and maintenance of glioblastoma multiforme (GBM). GBM cell lines are commonly used to mimic tumors for in vitro experiments, but the extent to which they resemble GBM tumors in relation to the membranome is unclear. The present study explores the resemblance of GBM cell lines to primary tumors regarding membranome expression. Gene expression data was retrieved from Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA). Membranomic genes were annotated and tumor purity was accounted for when correlating tumors and cell lines. The results suggest some commonly used cell lines, including AM38 and U87MG, display relatively little resemblance to tumors membranome. Differential gene expression analysis and subsequent gene set enrichment showed numerous genes related to neurexin/neuroligin, ion homeostasis, and synaptic signaling were downregulated in cell lines' membranomes compared to that of GBM tumors. The findings suggest that the membranome of GBM cell lines exhibit pronounced changes in gene expression compared to primary tumors and may not be completely representative of the disease process.

Spatial metabolic heterogeneity of oligodendrogliomas at single-cell resolution.

Oligodendrogliomas are a type of rare and incurable gliomas whose metabolic profiles have yet to be fully examined. The present study examined the spatial differences in metabolic landscapes underlying oligodendrogliomas and should provide unique insights into the metabolic characteristics of these uncommon tumors. Single-cell RNA-sequencing expression profiles from 4044 oligodendroglioma cells derived from tumors resected from four locations frontal, temporal, parietal, and frontotemporoinsular) and in which 1p/19q co-deletion and IDH1 or IDH2 mutations were confirmed were computationally analyzed through a robust workflow to elucidate relative differences in metabolic pathway activities among the different locations. Dimensionality reduction using metabolic expression profiles exhibited clustering corresponding to each location subgroup. From the 80 metabolic pathways examined, over 70 pathways had significantly different activity scores between location subgroups. Further analysis of metabolic heterogeneity suggests that mitochondrial oxidative phosphorylation accounts for considerable metabolic variation within the same locations. Steroid and fatty acid metabolism pathways were also found to be major contributors to heterogeneity. Oligodendrogliomas display distinct spatial metabolic differences in addition to intra-location metabolic heterogeneity.