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.

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.

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.

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.

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.

Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma.

Glioblastoma (GBM) is an aggressive primary CNS malignancy and clinical outcomes have remained stagnant despite introduction of new treatments. Understanding the tumor microenvironment (TME) in which tumor associated macrophages (TAMs) interact with T cells has been of great interest. Although previous studies examining TAMs in GBM have shown that certain TAMs are associated with specific clinical and/or pathologic features, these studies used an outdated M1/M2 paradigm of macrophage polarization and failed to include the continuum of TAM states in GBM. Perhaps most significantly, the interactions of TAMs with T cells have yet to be fully explored. Our study uses single-cell RNA sequencing data from adult IDH-wildtype GBM, with the primary aim of deciphering the cellular interactions of the 7 TAM subtypes with T cells in the GBM TME. Furthermore, the interactions discovered herein are compared to IDH-mutant astrocytoma, allowing for focus on the cellular ecosystem unique to GBM. The resulting ligand-receptor interactions, signaling sources, and global communication patterns discovered provide a framework for future studies to explore methods of leveraging the immune system for treating GBM.

Genomic subtypes of cutaneous melanoma have distinct metabolic profiles: A single-cell transcriptomic analysis.

OBJECTIVE: Genomic profiling previously classified melanoma into distinct subtypes based on the presence or absence of mutations in driver genes, but metabolic differences between and within these groups have yet to be thoroughly analyzed. Thus, the objective of the present study is to provide the first effort to holistically characterize the metabolic landscape of qualified melanoma genomic subtypes at single-cell resolution. METHODS: Expression data for a total of 1145 malignant cells sourced from NRAS(Q61L), BRAF(V600E), and NRAS/BRAF WT melanomas were retrieved from the Broad Single Cell Portal. Metabolic activity was interrogated by pathway scoring and gene set enrichment analysis. RESULTS: A total of 53 metabolic pathways were differentially regulated in at least one melanoma genomic subtype. Some notable findings include: BRAF/NRAS WT cells were enriched for fatty acid biosynthesis and depleted for metabolism of alanine, aspartate, and glutamate; BRAF(V600E) melanoma cells were enriched for beta-alanine metabolism and depleted for phenylalanine metabolism; NRAS(Q61L) melanoma cells were enriched for steroid biosynthesis and depleted for linoleic acid metabolism. CONCLUSION: Primary limitations include the total quantity of single cells and breadth of available genomic subtypes plus inherent noisiness of the applied methodologies. Nonetheless, these findings nominate novel, testable therapeutic targets.

Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review.

Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supplementation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 55 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases.

Single Cell Metabolic Landscape of Pituitary Neuroendocrine Tumor Subgroups and Lineages.

Pituitary neuroendocrine tumors (PitNETs) are common intracranial tumors comprising numerous subtypes whose metabolic profiles have yet to be fully examined. The present in silico study analyzed single-cell expression profiles from 2311 PitNET cells from various lineages and subtypes to elucidate differences in metabolic activities. Gonadotroph tumors exhibited high activities with histidine metabolism, whose activity is low in lactotroph tumors. Somatotroph tumors enriched for sulfur and tyrosine metabolism, while lactotroph tumors were enriched metabolism of nitrogen, ascorbate, and aldarate. PIT-1 lineage tumors exhibited high sulfur and thiamine metabolism. These results set precedence for further translational studies for subgroup/lineage specific targeted therapies.

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.

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.

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.

Primary and Metastatic Cutaneous Melanomas Discriminately Enrich Several Ligand-Receptor Interactions.

INTRODUCTION: Cutaneous melanoma remains a leading cancer with sobering post-metastasis mortality rates. To date, the ligand-receptor interactome of melanomas remains weakly studied despite applicability to anti-cancer drug discovery. Here we leverage established crosstalk methodologies to characterize important ligand-receptor pairs in primary and metastatic cutaneous melanoma. METHODS: Bulk transcriptomic data, representing 470 cutaneous melanoma samples, was retrieved from the Broad Genome Data Analysis Center Firehose portal. Tumor and stroma compartments were computationally derived as a function of tumor purity estimates. Identification of preferential ligand-receptor interactions was achieved by relative crosstalk scoring of 1380 previously established pairs. RESULTS: Metastatic cutaneous melanoma uniquely enriched PTH2-PTH1R for tumor-to-stroma signaling. The Human R-spondin ligand family was involved in 4 of the 15 top-scoring stroma-to-tumor interactions. Receptor ACVR2B was involved in 3 of the 15 top-scoring tumor-to-tumor interactions. CONCLUSIONS: Numerous gene-level differences in ligand-receptor crosstalk between primary and metastatic cutaneous melanomas. Further investigation of notable pairings is warranted.

Spatial Mapping of Genes Implicated in SARS-CoV-2 Neuroinvasion to Dorsolateral Prefrontal Cortex Gray Matter.

Introduction: SARS-CoV-2 is the newest beta coronavirus family member to demonstrate neuroinvasive capability in severe cases of infection. Despite much research activity in the SARS-CoV-2/COVID-19 space, the gene-level biology of this phenomenon remains poorly understood. In the present analysis, we leveraged spatial transcriptomics methodologies to examine relevant gene heterogeneity in tissue retrieved from the human prefrontal cortex. Methods: Expression profiles of genes with established relations to the SARS-CoV-2 neuroinvasion process were spatially resolved in dorsolateral prefrontal cortex tissue (N = 4). Spotplots were generated with mapping to six (6) previously defined gray matter layers. Results: Docking gene BSG, processing gene CTSB, and viral defense gene LY6E demonstrated similar spatial enrichment. Docking gene ACE2 and transmembrane series proteases involved in spike protein processing were lowly expressed across DLPFC samples. Numerous other findings were obtained. Conclusion: Efforts to spatially represent expression levels of key SARS-CoV-2 brain infiltration genes remain paltry to date. Understanding the sobering history of beta coronavirus neuroinvasion represents a weak point in viral research. Here we provide the first efforts to characterize a motley of such genes in the dorsolateral prefrontal cortex.

Neuro-oncology authorship trends in gender since 1944: a systematic review of 14,020 articles from five top-tier academic journals.

OBJECTIVE: This study was performed to compare authorship trends, by gender, in the neurosurgical oncology literature. METHODS: Complete author listings for neurosurgical oncology articles published between 1944 and 2021 in five top neuro-oncology journals were extracted from the PubMed database and journal websites on December 2, 2021. Author gender was characterized with the web application programming interface (API) genderize.io. The statistical significance (p < 0.05) of time-, journal-, and gender-based differences was determined by independent-samples t-test, chi-square test, and/or Fisher's exact test. RESULTS: A total of 14,020 articles were written by 67,115 unique authors occupying 97,418 authorship spots. The gender for 80,030 authorship positions (82.2%) was successfully characterized. Male authors were significantly more likely than the female authors to have a first-author publication, have a last-author publication, and have authored multiple articles within the data set. Among authors who published in multiple different years (n = 11,532), women had a shorter time window of publishing (5.46 vs 6.75 years between first and last publication: mean difference [MD] 1.28 [95% CI 1.06-1.50] years, p < 0.001). During this window, however, they were slightly more productive than the men, based on the mean number of publications per year (1.06 vs 1.01 articles: MD 0.05 [95% CI 0.02-0.09] articles, p = 0.002). The percentage of female authors on each neuro-oncology research team has increased by 3.3% (95% CI 2.6%-3.9%) per decade to a mean of 26.5% in the 2020s. Having a female last author was positively associated with having a female first author (OR 2.57 [95% CI 2.29-2.89]) and a higher proportion of women on the research team overall. The percentages of female first and last authors increased at significantly higher rates in medically oriented journals than in surgically oriented journals (first authors: 0.72% [95% CI 0.58%-0.87%] vs 0.36% [95% CI 0.30%-0.42%] per year, p < 0.001; and last authors: 0.50% [95% CI 0.38%-0.62%] vs -0.03% [95% CI -0.10% to 0.05%] per year, p < 0.001). CONCLUSIONS: Female authorship in top neuro-oncology journals has increased since the 1940s, with female-led teams showing greater gender diversity. However, female researchers lag behind their male counterparts in quantity of published research and are less likely to hold first or last authorship positions. This difference is more pronounced in the three neurosurgical oncology journals than in the two medical neuro-oncology journals, which may reflect the relatively low female representation in neurosurgery relative to medical oncology. Collectively, these trends have meaningful implications for career advancement, which is often dependent on academic productivity.

Granulocytic myeloid-derived suppressor cells to prevent and treat murine immune-mediated bone marrow failure.

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that originate in the bone marrow (BM) and have immunoregulatory functions. MDSCs have been implicated in the pathogenesis of several autoimmune diseases but have not been investigated in immune aplastic anemia (AA). We examined the roles of granulocytic-MDSCs (G-MDSCs) in murine models of human AA and BM failure (BMF). As both prophylaxis and therapy, BM-derived G-MDSCs improved pancytopenia and BM cellularity and suppressed BM T-cell infiltration in major histocompatibility complex (MHC)-matched C.B10 BMF mice. These effects were not obtained in the MHC-mismatched CByB6F1 AA model, likely because of MHC disparity between G-MDSCs and donor T cells. Single-cell RNA sequencing demonstrated that G-MDSCs downregulated cell cycle-related genes in BM-infiltrated T cells, consistent with suppression of T-cell proliferation by G-MDSCs through reactive oxygen species pathways. Clearance of G-MDSCs in the MHC-mismatched CByB6F1 model using anti-Ly6G antibody facilitated T cell-mediated BM destruction, suggesting an intrinsic immunosuppressive property of G-MDSCs. However, the same anti-Ly6G antibody in the MHC-matched C.B10 AA model mildly mitigated BMF, associated with expansion of an intermediate Ly6G population. Our results demonstrate that G-MDSC eradication and therapeutic efficacy are immune context-dependent.

Tyrosine kinase inhibitors versus radiation therapy in unresectable dermatofibrosarcoma protuberans (DFSP): A narrative systematic review.

BACKGROUND: In unresectable dermatofibrosarcoma protuberans (DFSP), no clear guideline exists regarding the use of tyrosine kinase inhibitors (TKI) versus radiotherapy. This study reviews current literature regarding TKI and radiotherapy in unresectable DFSP. METHODS: Following PROSPERO registration (CRD42021232508), a systematic literature search was performed including all studies reporting clinical results of TKI and/or radiotherapy in the treatment of unresectable DFSP. A narrative synthesis was used to compare patient characteristics, outcomes, and adverse effects. RESULTS: Of 1345 screened studies, 14 were included for review. Patient age ranged 18-77 years and 55% were male. Radiotherapy patients exhibited lower grade disease than TKI patients. Overall clinical benefit following TKI ranged from 70% to 96%. Radiotherapy patients exhibited control or resolution on last follow-up in 90% of cases. Radiotherapy adverse effects were mild, while TKI adverse effects were more severe and managed with dose reduction. CONCLUSION: TKI may be employed in unresectable DFSP of all histology types whereas radiation alone may be limited to low-grade and classic-type DFSP. TKI may cause more severe adverse effects compared to radiation alone.

In Silico Binding Analysis of Cannabinoids with Eph Receptors for Therapeutic Use in Gliomas.

Background: Accumulating evidence suggests overexpression of Eph receptors is associated with malignant human gliomas. Inhibiting interactions of Eph receptors with their ephrin ligands may improve clinical outcomes in glioma patients. The present study investigated the potential of cannabinoids to bind Eph receptors and block Eph/ephrin interactions. Methods: Twelve major cannabinoids were computationally docked with ligand binding domains from six glioma-associated Eph receptors through Auto Dock Vina to measure their potential binding affinities. The molecular structures and residue interactions of the most favorable poses for each receptor binding domain were further visually examined. Results: Cannabichromene (CBC) exhibited the most favorable binding with EphA2, EphA3, and EphB4 receptor ligand binding domains while tetrahydrocannabinol (THC) was predicted to bind favorably with EphB2 and EphB3 receptor ligand binding domains. EphA4 showed the best potential binding affinity with cannabidivarin (CBDV). Further analysis revealed that these cannabinoids bind to specific locations on Eph receptors required for Eph/ephrin interactions. Conclusion: The findings suggest that certain cannabinoids can effectively bind to hydrophobic pockets required for ephrin binding and thereby be used to block subsequent Eph/ephrin interactions.