bluuebunny/crossref_metadata_2025_split huggingface dataset:
287 What is the Velocity of Return-to-work After Circumferential Minimally-Invasive Surgery Versus Open Correction for Adult Spinal Deformity?
Authors: Macki Mohamed , Bess Shay , Uribe Juan S. , Mundis Gregory M. , Nunley Pierce D. , Le Vivian , Jamieson Alysha , Fu Kai-Ming G. , Wang Michael Y. , Anand Neel , Okonkwo David O. , Park Paul , Passias Peter G. 
Published: March 2024

INTRODUCTION:
While faster recovery is a touted benefit of minimally-invasive spinal operations, these differences have been poorly described for return-to-work after larger fusion constructs for adult spinal deformity.

METHODS:
Adult spinal deformity (ASD) patients =18 yr were queried from a multicenter, prospective database across the USA. To ensure equal cohorts for comparing the impact of MIS vs. open correction technique, propensity score matched gender, age, BMI, pelvic incidence-lumbar lordosis mismatch, and sagittal vertical axis. Of 190 patients with baseline surveys, 173 respondents (91.0%) had both baseline employment and 2-year follow-up. The open and cMIS cohorts were compared with a chi-squared test. The rate of return-to-work was calculated via discrete-time proportional hazards model—reporting an adjusted odds ratio (ORadj)—at three follow-up intervals: 6 weeks, 1-year, and 2-years.

RESULTS:
Of 173 patients, baseline employment status was nearly equal between open (n = 85) vs cMIS (n = 88) cohorts: employed (20.0% vs 21.5%), unemployed (3.5% vs 4.5%), disabled (4.7% vs 6.8%), and retired (71.7% vs 67.0%) (p = 0.888). The number of employed patients between the open vs cMIS cohort statistically significantly differed at 1-year (10.5% vs 21.5%, p = 0.049), but not at 6 weeks (14.1% vs 15.9%, p = 0.741) or 2-years (14.1% vs 19.3%, p = 0.277). The velocity of return-to-work did not differ (OR = 1.2, p = 0.549). In a sub-analysis of 36 patients who were employed at baseline, the number of employed patients between the open vs cMIS cohort statistically significantly differed at 1-year (47.0% vs 89.4%, p = 0.006), but not at 6 weeks (70.5% vs 73.6%, p = 0.636) or 2-years (58.8% vs 78.9%, p = 0.191). The velocity of return-to-work was also similar (ORadj = 1.57, p = 0.481).

CONCLUSIONS:
Despite an equivalent baseline employment status, more patients in the cMIS cohort were employed at 1-year; however, there was no difference at 2-years. Similar trends were appreciated in a sub-analysis of patients who were employed at baseline.
294 Multi-omic Screening of Invasive GBM Cells in Engineered Biomaterials and Patient Biopsies Reveals Targetable Transsulfuration Pathway Alterations
Authors: Choudhary Nikita , Garcia Joseph , Akins Erin , Jain Saket , Wolf Kayla , Zhang Jason , Lad Meeki , Shukla Poojan , Gill Sabraj , Carette Luis , Zheng Allison , Kumar Sanjay , Aghi Manish Kumar 
Published: March 2024

INTRODUCTION:
The poor prognosis of glioblastoma (GBM) is driven by tumor invasion; however, little is known of the metabolic alterations that drive invasion in glioblastoma.

METHODS:
We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multi-omics analyses to define metabolic drivers of invasive glioblastoma cells. A CRISPR metabolic gene screen was utilized to identify metabolic genes crucial for GBM invasion. We further targeted an identified hit from our high-throughput screens by utilizing a sgRNA to generate a knockdown cell line and assessing invasion in vitro and in vivo in a patient-derived xenograft orthotopic mouse model.

RESULTS:
Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Amongst oncologic ROS, hydrogen peroxide specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine gamma lyase (CTH), an enzyme which converts cystathionine to the non-essential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo.

CONCLUSIONS:
Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.
296 Towards Nose-to-brain Inhibition of NFB: Activity of a Novel p65 Inhibitor in Glioblastoma and Feasibility of Intranasal Delivery With a Near-infrared Fluorescent HMC-Chitosan Nanoparticle
Authors: Tusa Lavieri Miguel Eduardo , Michel Michelot , Mohyeddinipour Sarah , Israel Liron , Wang Hongqiang , Miyaguchi Ken , Rajiv Subashni , Chatterjee Avradip , Watanabe Junji , Murali Ramachandran , Yu John 
Published: March 2024

INTRODUCTION:
Constitutive NFκB inflammatory signaling is a driving force of tumor progression, immune evasion, and therapeutic resistance in glioblastoma (GBM). CRL1101 is a novel small molecule inhibitor of RelA (p65), a transcription factor of NFκB-mediated gene expression. Previously, we have shown that heptamethine carbocyanine (HMC) conjugated nanoparticles target GBM tumor sites via organic anion transporter proteins. The activity of CRL1101 in GBM has not been explored. Poor blood-brain barrier (BBB) penetration and theoretical toxicities related to p65 inhibition pose challenges to its implementation in vivo.

METHODS:
GBM transcriptomic analysis was performed using Gene Profiling Interactive Analysis. In vitro cytotoxicity and migration assays were performed in U87 and GL261. Western blot was used to confirm the mechanism of CRL1101. Quantitative PCR was used to assess the relative expression of NFκB-regulated genes. HMC-chitosan-CRL1101 nanoparticles were synthesized by cross-linking chitosan with HMC and their uptake was visualized using immunocytochemistry. For survival analysis, we implanted GL261 cells into immunocompetent mice and treated intranasally with HMC-chitosan-CRL1101.

RESULTS:
RelA is overexpressed in GBM relative to normal brain tissue. CRL1101 alone effectively kills U87 cells (IC50 = 16.0 uM) and prevents migration in vitro (p < 0.0001) by disabling the nuclear translocation of RelA. Treatment with CRL1101 was associated with a decrease in IL-8 (p = 0.01) and PD-L1 (p = 0.44) expression. HMC-chitosan-CRL1101 demonstrated an IC50 of 25.23 uM in U87. Near-infrared imaging confirmed intranasal delivery of HMC-chitosan-CRL1101 across the BBB in vivo.

CONCLUSIONS:
RelA-targeted NFκB inhibition with CRL1101 is a promising immunotherapeutic strategy in GBM. Intranasal nanoparticle delivery is a practical route to bypass the BBB and minimize systemic toxicities in mouse models of GBM, with expected survival benefit in vivo.
306 Endothelial Infiltrating Regulatory B Cells and NK T Cells Precipitate Inflammatory Cascade That Leads to Aneurysmal Rupture
Authors: Antonios Joseph Paul , Barak Tanyeri , Gultekin Batur , Yalcin Kanat , Adenu-Mensah Nana , Sujijantarat Nanthiya , Koo Andrew B. , Haynes Joseph , Hebert Ryan Matthew , Matouk Charles Christian , Gunel Murat 
Published: March 2024

INTRODUCTION:
Current literature examining the mechanisms delineating intracranial aneurysm development and subsequent rupture is sparse. Studies from decades prior defined the aneurysm model as being one largely driven by flow changes. However, the scope of these models is limited and does not fully explain why only a subset of patients with existing intracranial aneurysms subsequently go on to rupture.

METHODS:
We obtained aneurysm endothelial lining from 20 patients with ruptured, unruptured, sentinel hemorrhage, and recurrent aneurysms during endovascular coil embolization, which were processed and analyzed using mass spectrometry.

RESULTS:
Compared to unruptured aneurysms, ruptured aneurysms had significantly increased infiltrating populations of NK cells (5.5% vs 1.4%, p < 0.01), regulatory B cells (27.6% vs 16.0%, p < 0.05), and cytotoxic CD8 T cells (23.7% vs 13.5%, p < 0.05). To understand whether these cells were recruited at the time of rupture or whether they were present prior to the ictus event, we examined aneurysms that were treated after presenting with sentinel hemorrhages – again these patients had that same population of early-NK cells (7.5%, p = 0.2), suggesting that these cells were present at the nexus point immediately prior to rupture. Further, the regulatory B cells were even more prominent in the sentinel population, (45.6%, p < 0.01).

CONCLUSIONS:
These findings all point to a complex, coordinated immune response that is driving the remodeling of the aneurysm vessel wall. We interpret the results to suggest that regulatory B cell driven destabilization of the aneurysmal wall leads to a series of events; namely the recruitment of NK cells, subsequent inflammatory cascade, and ultimate rupture. While there remains much to be understood about this multi-faceted picture, these findings provide the basis for further studies looking at targets for adjunctive immune therapies in both our unruptured and ruptured patient populations.
333 Financial Toxicity in Malignant Brain Tumors
Authors: Terrell Danielle , Camarano Joseph Gayle , Whipple Stephen Garrett , Guthikonda Bharat , Newman W. Christopher 
Published: March 2024

INTRODUCTION:
As costs for cancer care continue to rise, ongoing development of novel therapeutics have increased the number of patients living with cancer. Cancer survivors are at increased risk of having high medical debt burdens, bankruptcy, delayed treatments, poor compliance with therapy, and even death as a result of financial toxicity.

METHODS:
Hospital billing database was queried for patients with ICD code C71 who had a bad debt discharge (unpaid balance) on record from 2020-2022. The corresponding hospital chart was then queried for demographic data, patient factors, and clinical factors.

RESULTS:
43 total patients had data available for analysis. The patient diagnoses were GBM (50%), Other (45.2%), followed by metastatic disease (4.7%). White patients had an average bad debt of $2742.10, while Black patients averaged $9851.6 (p = 0.017). 38.5% of White patients had more than $2000 in bad debt, compared to 81.8% of Black patients in that category (p = 0.014). The amount of debt differed significantly between tumor types; with 66.7% of GBM patients having more than $2000 in bad debt (p = 0.052). Difference in debt amount based on pre-operative employment status trended towards significance but fell short (p = 0.08). Most patients were unemployed (58.9%), followed by employed patients (33%), and retired patients (7.6%). 61.5% of employed patients had greater than $2000 in bad debt, compared with 56.5% of unemployed patients. 40% of patients had a pre-operative deficit, and of those patients, 54% had a bad debt amount in excess of $2000. 71% of patients without a pre-operative deficit had more than $2000 in bad debt.

CONCLUSIONS:
Bad debt is a major contributor to financial toxicity in patients with malignant brain tumors.
348 Comparison of Brain Functional Imaging of Pain States Using Resting-State fMRI and Multi-Delay pCASL to Clinical Scores of Pain in Chronic Low Back Pain Patients Implanted With Thoracic Spinal Cord Stimulation
Authors: Ashok Arjun Balaji , Oghli Yazan Shamli , Ailes Isaiah , Syed Mashaal , Kang KiChang , Naghizadehkashani Sara , Fayed Islam , Matias Caio M. , Mohamed Feroze , Krisa Laura , Alizadeh Mahdi 
Published: March 2024

INTRODUCTION:
Thoracic spinal cord stimulation (tSCS) is an interventional option for patients with refractory chronic low back pain (cLBP). The use of functional imaging of brain regions involved in pain as a quantitative method to evaluate treatment effectiveness has not yet been studied.

METHODS:
pCASL data using 5 post-label delays (0.5-2.5s) alongside rs-fMRI data was gathered from five patients (4 M, 1F) post-tSCS with cLBP post-implantation with the SCS device turned off at a 3.0T scanner. Arterial transit time (ATT), cerebral blood flow (CBF), and cerebral blood volume (CBV) were derived from pCASL data. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), degree of centrality (DC) and regional homogeneity (ReHo) were derived from rs-fMRI data. These data were registered against a pain-ROI atlas. The following clinical pain scores were assessed in the same five patients: Numerical Pain Rating Scale (NPRS), Visual Analogue Scale (VAS), Central Sensitization Inventory (CSI), Oswestry Disability Index (ODI), Pain Catastrophizing Scale (PCS), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS). Predictive linear associations between pain ROIs and clinical scores were investigated using linear regression.

RESULTS:
Significant linear associations (p-value < 0.001) were found between pCASL-derived ATT to the dorsolateral prefrontal cortex (DLPC) and the NPRS; CBF to the ventral posterolateral thalamus (VPL) and the VAS, and of the posterior cingulate cortex (PCC) and the VAS; CBV of the posterior short gyrus (PS) and the VAS; and rs-fMRI-derived fALFF of the amygdala and the CSI.

CONCLUSIONS:
A comparison of functional imaging results and clinical pain scores suggest predictive relationships between resting-state function/brain perfusion in regions involved in pain perception and processing and various clinical pain assessments.
357 Postoperative Outcomes and Decreases in Pain Medication Utilization Following Nucleus Caudalis DREZ Lesioning for Painful Trigeminal Neuropathy: A Case Series
Authors: Venkatraman Vishal , Futch Brittany Grace , Padron Kevin Bode , Parente Beth , Rahimpour Shervin , Lad Nandan P. 
Published: March 2024

INTRODUCTION:
Painful trigeminal neuropathy is characterized by treatment-resistant trigeminal pain. Nucleus Caudalis Dorsal Root Entry Zone lesioning (NC-DREZ) has been utilized to treat this condition, but changes in medication utilization has not been studied in this population.

METHODS:
We retrospectively reviewed patients who underwent NC-DREZ at an academic medical center for the treatment of painful trigeminal neuropathy between March 2014 and December 2022, with a minimum 30-day follow-up. Postoperative complications, emergency department visits, readmissions, reoperations, changes in patients' subjective pain, and the longitudinal dosage of pain medications were collected as outcomes. The Fisher's exact and Kruskal-Wallis tests, with alpha set at 0.05, were used to compare the proportion and doses of medications used at each timepoint.

RESULTS:
Thirty-nine patients were included (mean age 55.7 years, 66.7% female) Prior interventions included trigeminal ablation (35.9%), microvascular decompression (59.0%), and stereotactic radiosurgery (41.0%).Twelve patients (30.8%) had postoperative complications, including five with transient ataxia and two with pseudomeningocele. Nine patients (23.1%) visited the ED after surgery, and 7 (17.9%) were readmitted. The rate of opioid use decreased from 56.4% at baseline to 32.3% six months following surgery (p = 0.03). Additionally, the use of carbamazepine, gabapentin, pregabalin, duloxetine, and amitriptyline decreased. One year after surgery, 11/26 patients (42.3%) reported sustained pain relief.

CONCLUSIONS:
In this case series of NC-DREZ patients, we demonstrated that postoperative complications and subjective pain outcomes were comparable to those previously reported in the literature. Importantly, we demonstrated a reduction in the use of opioids six months after surgery. This study's findings support the use of NC-DREZ as an alternative treatment for painful trigeminal neuropathy. Large scale prospective studies are needed to confirm these results.
363 Anatomic Study of Cervical Neural Foraminal Dimensions, Interpedicular Distance, and Disc Space Height From C2-T1 Using Computed Tomography of 1,000 Patients
Authors: Razzouk Jacob Anees , Case Trevor , Sajdak Grant , Kricfalusi Mikayla , Nguyen Kai , Taylor Rachel , Vyhmeister Ethan , Kagabo Whitney , Carter Mei , Carter Davis , Ramos Omar , Cheng Wayne K. , Danisa Olumide A. 
Published: March 2024

INTRODUCTION:
The normative relationships among cervical neuroforaminal dimensions (NFD), interpedicular distance (IPD), and disc space height (DSH) remain unknown.

METHODS:
We reviewed CT imaging of 1,000 patients between 18 and 35 years of age without spinal pathology to measure cervical NFD, defined as follows: foraminal height, sagittal anterior-to-posterior width, and area. Anterior, middle, and posterior DSH, and IPD were also measured. Interobserver reliability was assessed via the intraclass correlation coefficient (ICC) two-way mixed model on absolute agreement.

RESULTS:
Bilateral NFD followed bimodal distribution patterns moving caudally from C2-T1, whereas DSH measurements exhibited multimodal distribution patterns and IPD demonstrated a unimodal distribution clustered at the lower cervical spine. Significant differences were observed in NFD, DSH, and IPD measurements with respect to patient sex and race taking into consideration patient demographic and anthropometric characteristics. The African American cohort demonstrated the smallest NFD, DSH, and IPD measurements, followed by the Hispanic cohort, followed by the Caucasian cohort. Weak-to-moderate correlations were observed among NFD, DSH, and IPD measurements across all levels.

CONCLUSIONS:
This study describes 70,800 DSH, NFD, and IPD measurements from C2-T1 using CT imaging of young patients without spinal pathology. Findings from this study may provide normative guidelines necessary to establish the foundation for diagnosis of cervical neuroforaminal stenosis. Surprisingly, this study found no strong, or even moderate, correlations between normative NFD, DSH, and IPD measurements across all levels from C2-T1. Patient sex, ethnicity, and height are associated with NFD, DSH, and IPD, though patient weight is not.
380 2021 WHO Grading Scheme Provides Minimal Incremental Improvement in Prognostic Stratification of a Retrospective IDH-Mutant Astrocytoma Cohort Compared to 2016 WHO Grading Scheme
Authors: Kalluri Anita , Myneni Saket , Parker Megan , Weber-Levine Carly , Arshad Umar , Shaw Jacob , Sarlin Samantha , Rempert Ashley , Dunseath Chloe , Materi Joshua , Raj Divyaansh , Rincon Torroella Jordina N. , Ye Xiaobu , Lucas Calixto-Hope , Bettegowda Chetan 
Published: March 2024

INTRODUCTION:
The 2021 WHO Classification of CNS Tumors introduced prognostically relevant molecular alterations (ex. CDKN2A homozygous deletion) into grading criteria for select tumors.

METHODS:
We retrospectively identified 176 adult IDHmAstro patients with available next-generation sequencing (NGS). All tumors were regraded based on the 2021 and 2016 WHO grading schema using relevant histopathological (mitotic rate, microvascular proliferation, necrosis) and molecular (CDKN2A) features. The prognostic ability of each grading schema was evaluated with Kaplan-Meier and multivariate Cox Regression analyses.

RESULTS:
The cohort consisted of 76 grade 2 (43.2%), 45 grade 3 (25.6%), and 55 grade 4 (31.3%) IDHmAstro cases using the 2021 grading schema. Only four patients (2%) had a grade change from the 2016 WHO grading scheme - one prior 2016 WHO grade II and three grade III tumors, all regraded to Grade 4 based on present CDKN2A homozygous deletion. When assessed based on both classification schemas, WHO Grade 4/IV tumors were associated with lower OS than Grade 2/II tumors (HR [95% CI]: 4.20 [1.09–16.22], P = 0.037 per 2016 and 3.82 [1.04–14.09], P = 0.044 per 2021). There were no significant differences in OS between Grade 2/II and Grade 3/III tumors or Grade 3/III and Grade 4/IV tumors within either grading schema.

CONCLUSIONS:
Only four patients had a change in grade, implying the majority of IDHmAstro patients would have received similar treatment using either grading schema. Interestingly, outcomes for grade 3/III IDHmAstro were not significantly different from grade 2/II or grade 4/IV IDHmAstro in either schema, suggesting that grade 3/III tumors represent a biologically heterogeneous group. These results should be validated in other series but underscore a continued unmet need for novel biomarkers to improve IDHmAstro risk-stratification.
381 Glioma Three-Dimensional Shape Predicts Underlying Genetic Mutations
Authors: Warman Pranav , Adil Syed M. , Seas Andreas , Sexton Daniel , Calabrese Evan , Lad Nandan P. , Kolls Brad , Fuller Anthony , Dunn Timothy , Friedman Allan H. , Hasan David M. , Komisarow Jordan M. , Cook Steven H. , Codd Patrick James , Zomorodi Ali R. , Fecci Peter Edward , Patel Anoop , Grant Gerald A. , Tralie Christopher 
Published: March 2024

INTRODUCTION:
Phenotype is the detectable expression of genotype. Despite this, little is known about how the three-dimensional structure of brain tumors correlates with their genetic biomarkers.

METHODS:
The UCSF-PDGM dataset was filtered for histopathologically-proven gliomas. Segmentation masks of the enhancing tumor, non-enhancing/necrotic tumor, and surrounding FLAIR abnormality were obtained from each patient’s preoperative brain MRI. All tumors were evaluated for IDH mutations and 1p/19q codeletion; all grade III and IV tumors were tested for MGMT methylation status. The segmentation masks were processed to create topological features describing the tumor’s 3D shape. These features, without other clinical variables, were used in a custom machine learning pipeline to predict the presence of IDH mutations, 1p/19q codeletion, and MGMT methylation.

RESULTS:
After filtration, 103 of 494 gliomas tested had an IDH mutation, 29 of 494 had a 1p/19q codeletion, and 247 of 409 had methylation of MGMT. On the blinded test-subset, the machine learning model, using only features describing shape, rendered an AUROC of 0.902 (95% CI: 0.875-0.929), specificity of 90.3% (83.9%-96.6%), and sensitivity of 75.7% (68.0%-83.3%) for IDH mutation. For 1p/19q codeletion, we found an AUROC of 0.949 (0.908-0.990), specificity of 94.5% (84.3%-100%), and sensitivity of 86.6% (79.6%-93.6%). For MGMT methylation, the performance was poor with an AUROC of 0.445 (0.385-0.504).

CONCLUSIONS:
The three-dimensional shape of a glioma may be used to predict the presence of some key underlying genetic mutations before biopsy. Additional research is needed to validate this, improve its fidelity, and generalize it to other biomarkers.