bluuebunny/crossref_metadata_2025_split huggingface dataset:
787 Higher County-Level Socioeconomic Status Is Associated With Increased Meningioma Survival But Does Not Impact Likelihood of Surgical Treatment: A CBTRUS Analysis
Authors: Pugazenthi Sangami , Price Mackenzie , De La Vega Gomar Rodrigo , Kruchko Carol , Waite Kristin , Barnholtz-Sloan Jill , Walsh Kyle , Kim Albert H. , Ostrom Quinn 
Published: March 2024

INTRODUCTION:
Prior literature suggests that individual socioeconomic status (SES) may influence access to treatment and outcomes for primary brain tumors. To date, no population-level studies have assessed the correlation between meningioma treatment and outcome with county-level SES.

METHODS:
Incidence data were extracted from the Central Brain Tumor Registry of the United States(CBTRUS), a combined dataset including the CDC’s National Program of Cancer Registries (NPCR) and NCI’s Surveillance, Epidemiology, and End Results Program data, for diagnosis years 2006-2019, and survival data were extracted from the NPCR survival analytic dataset from 2006-2018. SES quintiles were created using American Community Survey data. Logistic regression and Cox proportional hazards models were used to assess the relationship the odds of receiving treatment and overall survival and SES and the individual SES factors.

RESULTS:
There were 409,681 meningioma cases available from CBTRUS. Asian/Pacific-Islander non-Hispanic individuals (odds ratio [OR] = 1.28, p < 0.001) were more likely and Black non-Hispanic (BNH) individuals (OR = 0.90, p < 0.001) were less likely to receive surgery than White non-Hispanic (WNH) individuals. Female sex (OR = 1.31, p < 0.001), living in a metropolitan area (OR = 0.96, p < 0.001), and increased age at diagnosis (OR = 0.96, p < 0.001) were associated with decreased likelihood of surgery. There was no association between SES and likelihood to receive surgery. Overall median survival was 137 months and survival was higher in higher SES counties, which held true for both WNH and BNH. Age at diagnosis(hazard ratio [HR] = 1.01, p < 0.001), male sex (HR = 1.51, p < 0.001), BNH (HR = 1.31, p < 0.001), subtotal resection (HR = 1.38, p < 0.001), and malignant behavior(HR = 1.64, p < 0.001) were associated with increased hazard of death.

CONCLUSIONS:
In the US, county-level SES did not impact treatment patterns, but higher SES was associated with increased survival. These findings provide valuable insight into socioeconomic factors influencing treatment and outcomes in meningioma patients.
788 Impact of Preoperative Mental Health State on Perioperative Surgical Outcomes After Lumbar Spine Fusions: An Analysis of the National Inpatient Sample (2009-2020)
Authors: Aguirre Alexander Otilio , Soliman Mohamed A.R. , Elbayomy Ahmed , Baig Rehman , Kuo Cathleen , Khan Ali , Burns Evan , Khan Asham , Levy Hannon , Ghannam Moleca M. , Pollina John , Mullin Jeffrey Paul 
Published: March 2024

INTRODUCTION:
The intersection of mental health and patient reported outcomes after various neurosurgical procedures has been well published. Although there is paucity in the literature focused on the surgical outcomes of patients after spinal fusion and their relationship with the patient’s mental state before surgery.

METHODS:
The National Inpatient Sample (NIS) database was utilized, with a search identifying all patients who underwent a spinal fusion in all years between 2009-2020. Once patients were identified, diagnosis codes for major psychiatric disorders (depression, anxiety, bipolar disorder) were utilized to separate sample into a psychiatric disorder cohort, and a control sample. Univariate and multivariate linear/logistic regression models were utilized to analyze data.

RESULTS:
A total of 2,877,241 patients were identified from this database, of which 647,951 (22.5%) of patients had a preoperative diagnosis of at least one of the psychiatric disorders. Univariate analysis of patient demographics in the psychiatric disorder cohort demonstrated that these patients were more likely to be female (67.26% vs. 50.74%, P < .001), and younger (58.88 years vs. 59.11 years, P < .001) when compared to control cohort. Increased rates of respiratory (P < .001), urinary (P < .001), cardiac (P < .001) complications were seen in the psychiatric disorder cohort. On multivariate analysis patients had increased odds of fusion disorders (OR, 1.62; 95% CI, 1.55-1.70, P < .001), mechanical injuries (OR, 1.27; 95% CI, 1.20-1.35, P < .001), and postoperative hematomas (OR, 1.29; 95% CI, 1.26-1.33; P < .001).

CONCLUSIONS:
Preoperative diagnosis of various psychiatric conditions have notable effects on postoperative outcomes after spinal fusion and should be evaluated preoperatively.
814 Results and Opinions on the Implementation of a Preference Signaling System in Neurosurgical Residency Applications
Authors: Jonzzon Soren , Roth Steven G. , Lee Benjamin , Carlstrom Lucas P. , Graffeo Christopher Salvatore , Chambless Lola Blackwell 
Published: March 2024

INTRODUCTION:
The 2022-2023 neurosurgery residency application cycle employed an optional preference signaling system that indicated a focused interest in a particular program. During this first iteration, applicants could signal interest in up to eight participating programs.

METHODS:
A survey consisting of 28 questions pertaining to the signaling process was distributed via email to all neurosurgery applicants participating in the 2022-2023 cycle. Results were compiled, and descriptive statistics were used to generate results.

RESULTS:
Of the 361 total applicants, 82 (22.7%) completed the survey; 84.1% attend a US MD program, 1.2% a DO program, 12.2% are international medical graduates, and 2.4% are post-graduates. The mean number of programs applied to was 78 (range 21-116 (all). The median number of interviews received was 17 (range 0 to 57). Notably, 14.6% of individuals signaled their home programs, and 63.4% signaled at least one externship program. 90.2% of applicants utilized all eight signals. Applicants averaged 3.5 interviews from programs they signaled, and 15.6% of applicants matched at a program they signaled. Sixty-five percent of applicants were unsatisfied with the application process, but 53.1% indicated preference signaling should continue. Regarding the number of available signals, 43.75% felt eight was appropriate, 32.5% felt it was too few, 13.75% thought it was too many, and 10% were indifferent.

CONCLUSIONS:
Preference signaling was implemented in the 2022-2023 applicant cycle to improve interview efficiency and equity. Applicant opinions were mixed about this first iteration. Two consistently noted themes were the desire for improved home and away rotation signaling standardization and the perceived lack of impact on match outcome.
924 Corpus Callosotomy for Intractable Epilepsy: A Contemporary Series of Operative Factors and Overall Complication Rate
Authors: Motiwala Mustafa , Tambi Sandra , Blum Deke M. , Dacus Mallory , Troy Christopher , Klimo Paul , Boop Frederick A. , Wheless James , Einhaus Stephanie L. 
Published: March 2024

INTRODUCTION:
Corpus callosotomy is an effective treatment for atonic seizures in medically refractory epilepsy. Recently, laser interstitial thermal therapy has been adapted as a less invasive method to achieve similar results, yet technical challenges associated with this nascent approach persist. A modern series of corpus callosotomies performed by open craniotomy is lacking in the literature, a fact which highlights the importance of establishing contemporary complication rates for this operation to compare with newer methodologies.

METHODS:
We retrospectively reviewed institutional data for patients who underwent first time open callosotomy from 2005 to 2022. Demographic and clinical variables were collected and analyzed with a focus on operative factors and complication rates.

RESULTS:
105 patients were included in the study with a mean age of 9.39 years (0.67-24.17 years). 58.1% of patients were male (61), and one surgeon performed a majority (76.20%, 80) of the operations with two other surgeons performing the remainder (21.9% and 1.90%, respectively). In total, 63 complete, 31 subtotal (anterior 70-99%), and 1 posterior (40%) callosotomies were performed. Blood loss was available for 102/105 patients with a mean of 96.67 mL (10-500 mL), and mean operative time was calculated as 226.76 minutes (45-504 minutes) from 76/105 patients by excluding those patients who underwent concurrent vagal nerve stimulator placement or revision. Operative complication rate was determined to be 6.67% and was comprised of 3 pseudomeningoceles, 3 superficial wound infections, and 1 delayed intraparenchymal hemorrhage. No venous infarcts were observed on postoperative MRI.

CONCLUSIONS:
This the largest single center series of open callosotomy patients describes important updated metrics to help evaluate new techniques being developed for the surgical treatment of atonic seizures in medically intractable epilepsy.
928 Autologous Rib Graft for Posterior Cervical Fusion in Pediatrics: Efficacy and Complications
Authors: Snyder Rita , Bauer David F. 
Published: March 2024

INTRODUCTION:
Cervical instability in the pediatric population presents unique challenges. Indication for fusion include instability or deformity from multiple causes. A recent meta-analysis showed high failure rate of successful arthrodesis after pediatric craniocervial fusion (over 30%). We describe use of autologous rib graft with BMP to augment fusion, evaluating efficacy and complication from this technique.

METHODS:
A retrospective study was performed between 2020 and 2023 of all pediatric patients (age 0-18) who underwent autologous rib grafting with extra-small BMP-2 for posterior craniocervical arthrodesis at a single institution. Patients with less than 3 month post-operative follow-up and no post operative CT were excluded. Primary outcomes include presence of fusion on CT, perioperative complication, and complication from rib harvest.

RESULTS:
Twenty-one patients met inclusion criteria. Ten were male, with average age 10 years (range 2 to 18). 87 total levels were fixated and fused, with no fixation screws misplaced on post operative CT. There were no surgical site infections, post operative seroma, or unplanned return to OR. All patients had solid fusion on postoperative CT. Average follow up was 268 days, with range of 45 days to 3 years. No patient had pain at the rib harvest on any post operative visit, and all rib incisions healed without complication.

CONCLUSIONS:
Our preliminary results suggest that autologous rib graft with extra-small BMP-2 is an effective strategy to achieve a high rate of fusion in pediatric patients undergoing posterior instrumented craniocervical fusion. In our series, we found an acceptable safety profile, with no seroma, surgical site infection, return to the OR, or rib harvest complication.
936 YouTube and Pudendal Neuralgia: Is It a Good Source of Information for Patients?
Authors: Hanna Amgad S. , Reyes Bello Juan Sebastian , Moscote-Salazar Luis Rafael , Restrepo-Lugo Claudia Marcela , Florez-Perdomo William 
Published: March 2024

INTRODUCTION:
Pudendal neuralgia (PN) is a disabling condition characterized by chronic pain in the distribution area of the pudendal nerve (perineum, anus, and genital region) which is originated from the sacral plexus and contains sensory fibers located in the dorsal root ganglia of the sacrum S2-S4. Patients suffering from pudendal neuralgia use the internet to learn more about their medical condition.YouTube has become a popular source of information, but little is known about the quality of material offered to patients.

METHODS:
A search was conducted (April 2023) on YouTube using the words “pudendal neuralgia physical therapy," "medications for pudendal neuralgia," "pudendal nerve block," "pudendal neuralgia surgery," and "alternative treatments for pudendal neuralgia." The results were analyzed based on the source, general descriptive statistics, the intended audience, and five content areas.The DISCERN scoring system was used to evaluate the quality of videos.

RESULTS:
After the search, 73 videos met the inclusion criteria for further analysis.The majority of these videos (61.64%) were intended to target the general population, whereas a smaller percentage were identified as professional (41.10%) or targeted for physicians (35.62%). From the videos included, 10 (13.70%) described treatment options in a balanced and evidence-based manner. The higher DISCERN score positively correlated with the presence of this last content criterion. With a total DISCERN mean score of 35.42, a significant proportion of the videos (41.10%) were rated very poor. The remaining videos were classified as poor (23.29%), fair (19.18%), good (8.22%), and excellent (8.22%).

CONCLUSIONS:
The quality of the information included in YouTube videos regarding pudendal neuralgia treatment was considered generally poor. Healthcare providers must recognize the potential influence of this platform on patients’ understanding of pudendal neuralgia treatment.
Analysis of DNA and RNA Genomic Profiles from Phase-II Clinical Trial NCT03398694 Showed Distinct Transcriptomic Profile for Patients With Local Failure
Authors: Dey Mahua , Shireman Jack , Kendziorski Christina 
Published: March 2024

INTRODUCTION:
Stereotactic radiosurgery (SRS) has become a standard of care for brain metastasis (BM). In the setting of lesions needing surgical intervention, it is typically delivered to the resection cavity after surgical resection to strike a balance between adverse effect from the dose of radiation and tumor recurrence. Pre-operative SRS is now being examined because of its ability to deliver radiation to all cells before surgical disruption and dispersion with added advantage of treating larger lesions with radiation.

METHODS:
We designed a phase II trial for patients with up to 4 BM and at least one resectable lesion. All lesions were treated with SRS and symptomatic lesions were resected. We examined both the clinical and biological outcomes.

RESULTS:
We performed whole genome DNA and RNA sequencing of the center and periphery of the resected lesion from the first 35 patients. We found that SRS causes significant and biologically observable damage to the tumor. Radiation induced DNA damage is qualitatively different between center and periphery of the tumor. Functionally distinct genetic profiles exist between both center and peripheral tumor locations as well as between different primary tumor types. Center of the tumor has higher functional mutation burden while peripheral samples initiate DNA repair pathways. Peripheral samples may interact more with surrounding environment when compared to central samples. Different radiation delivery modality has differential transcriptomic profile and patients who failed locally also had a distinct transcriptomic profile.

CONCLUSIONS:
In conclusion, radiation dosing fall-off has differential effect on the genomic landscape of the tumor and cells from the periphery are most likely gaining DNA repair abilities and that might explain tumor recurrence. Also, Gamma knife and LINAC as different genomic signature.
Matched Three-Dimensional Organoids and Two-Dimensional Cell Lines of Metastatic Melanoma to the Brain Mirrors Response to Targeted Molecular Therapy
Authors: Hicks William Harrison , El Shami Mohamad , Gattie Lauren , Dimeo Emma , Abdullah Kalil G. 
Published: March 2024

INTRODUCTION:
Metastatic melanoma to the brain (MMB) represents a significant treatment challenge. Limitations in preclinical models, namely the lack of heterogeneity in cell lines and low throughput of xenograft models, have thwarted novel therapeutic development. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional models that recapitulate genotypic and phenotypic features of parent tumors with minimal extracranial processing. We aim to develop the first known matched patient-derived SXO and cell line of BRAF-mutant MMB to investigate responses to targeted therapy.

METHODS:
MMB SXOs were created by a novel protocol incorporating techniques for creating glioma and cutaneous melanoma organoids. A BRAFV600K-mutant MMB sample was collected and processed within 30 minutes of resection. SXOs were created using a 1.0 mm biopsy punch. Organoids were cultured in low-adherence plates in an optimized culture medium under continuous orbital rotation without an artificial extracellular scaffold. Organoid media was changed every 48 hours. Concurrently, matched patient-derived cell lines were created and passaged weekly. Drug screens were conducted with the CellTiter-Glo Luminescence Viability Assay (cell line) and ReadyProbe Cell Viability Imaging Kit (SXOs).

RESULTS:
After an initial shedding period, organoid growth was observed within 3-4 weeks. MMB SXOs retained histological phenotypes of the parent tissue, including pleomorphic epithelioid cells with abundant cytoplasm, large nuclei, focal melanin accumulation, strong Sox10 positivity, and HMB45 positivity. After sufficient growth, organoids could be manually parcellated to increase the number of replicates. Matched SXOs and cell lines demonstrated sensitivity to BRAF-V600 and MEK inhibitors.

CONCLUSIONS:
Here, we outline the creation of the first known scaffold-free organoid model of MMB. Further study using SXOs will improve the translational relevance of preclinical studies and enable the study of the melanoma tumor microenvironment.
A Untethered Magnetic Micro-Robot for Local Therapeutic Delivery for Neurosurgical Oncology
Authors: Tony Wang , Ansari Azadeh , Hoang Kimberly Bojanowski 
Published: March 2024

INTRODUCTION:
Microrobots designed for biomedical applications have garnered significant research interest, offering advantages in drug delivery, microsurgery, and biopsies. Magnetic fields enabled by electromagnetic coils permit untethered nonlinear movement of these tiny robots within the brain on the surface, the cerebrospinal fluid, and parenchyma. Microdrillers (either individually or in swarms) are a promising tool for microsurgery, capable of drilling through viscoelastic media (brain tissue). However, challenges remain in scaling down the robot size and exploring diverse applications.

METHODS:
Parallelizable (batch) microfabrication involved 3D printing via two-photon lithography. The pH-sensitive hydrogel was synthesized through UV-initiated radical polymerization mixed with a tracer (fluorescein sodium salt). Imaging via photon-counting CT was performed for microbot tracking in preclinical models including hydrogel phantoms, large animal cadaveric fresh brain tissue, and human cadaveric tissue.

RESULTS:
Microbot speeds in various tissues were characterized with speeds up to 800 um/sec over magnetic field amplitudes of 5 to 55 mT while performing complex nonlinear trajectories via open-loop surgeon control via surgeon. Targeted hydrogel delivery of fluorescein label/nanoparticle drug over a pH range of 6.2 (tumor tissue) and 7.8 (normal tissue) over a time interval of 50 s is demonstrated as proof of concept with a rate of 2.4 times faster in acidic conditions. Lastly, we show state-of-the-art micromillmetric resolution for real time imaging via photon-counting spectral CT for implementation of closed loop control.

CONCLUSIONS:
A novel minimally invasive microrobotic platform technology capable of targeted local drug delivery in brain parenchyma is demonstrated.
Molecular Profiling to Understand Treatment Resistance and Response in Glioblastoma
Authors: Nikolopoulos Marina , Wu Megan , Bahcheli Alexander , Kellett Sorcha , Myrehaug Sten , Sahgal Arjun , Bayani Jane , Spears Melanie , Das Sunit 
Published: March 2024

INTRODUCTION:
Patients with glioblastoma experience a wide variation in response to standard treatment, with nearly 30% experiencing tumour progression during treatment, and nearly 6% surviving more than 5 years. To date, there are few non-invasive clinical biomarkers to predict response to firstline treatment. Chemical exchange saturation transfer (CEST) MRI may have the potential to fill this gap. CEST MRI is sensitive to treatment-induced changes and changes in tumor metabolism1. Our team has obtained CEST data for patients before, during and after standard chemoradiation treatment, and found that CEST provides markers of early response and can identify early, standard and late progressors before treatment initiation.2

METHODS:
Patients (n = 104) with primary, IDH wild-type glioblastoma were imaged with CEST-MRI at multiple time points throughout standard chemoradiation treatment. DNA and RNA were co-extracted from matched normal and tumour pairs and processed for whole genome sequencing and gene expression analysis using Nanostring. Clinical variables such as age, extent of resection, sex, ECOG status and MGMT promoter methylated were also collected. A survival analysis was conducted using the Kaplan-Meier method with log-rank tests. Univariate and multi-variate hazard ratios for clinical variables were calculated by fitting Cox Proportional Hazards Models.

RESULTS:
Early progressors reported a median progression-free survival (PFS) of 142 days compared to 296.5 in standard and 832 days in late progressors (p < 0.0001). Early progressors also harbored distinct and statistically significant differences in gene expression and genomic alterations, namely in DNA damage repair, glucose transport and arginine metabolism pathways. A gene signature was prognostic of PFS and overall survival in a Cox proportional hazards model.

CONCLUSIONS:
This data may serve as a radiogenomic biomarker to assess treatment response within early phases of treatment and allow for a personalized treatment plan.
Real-Time MRI Stereotaxis Aided Smartflow Convection Delivery of DNX-2401
Authors: Pino Isabela Pena , Chen Clark C. 
Published: March 2024

INTRODUCTION:
The Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE) study is a phase II clinical trial testing the efficacy of a recombinant adenovirus DNX-2401 combined with the immune checkpoint inhibitor pembrolizumab.

METHODS:
Prospective case series.

RESULTS:
Precise catheter placement was achieved in all patients treated, and no adverse events were noted. Average radial error from target was 0.9 mm. The average procedural time was 3 hours and 16 minutes, and comparable to other CED techniques. In two patients, delivery of DNX-2401 was visualized as T1-hypointensity using an MRI taken within 30 minutes of procedure completion. These patients exhibited partial response based on RANO assessment. Infusion associated T1-hypointensity in tumor core was not seen in the other patients, who showed no evidence of therapeutic response.

CONCLUSIONS:
Our pilot study supports the safety of MRI guided SmartFlow convection delivery of the DNX-2401 adenovirus in recurrent glioblastoma patients. Visualization of drug delivery may serve as an imaging biomarker for therapeutic response.
Direct Evidence of Bitcoin Wash Trading
Authors: Aloosh Arash , Li Jiasun 
Published: March 2024

We use the internal trading records of a major Bitcoin exchange leaked by hackers to detect and characterize wash trading—a type of market manipulation in which a single trader clears the trader’s own limit orders to “cook” transaction records. Our finding provides direct evidence for the widely suspected “fake volume” allegation against cryptocurrency exchanges, which has so far only been backed by indirect estimation. We then use our direct evidence to evaluate various indirect techniques for detecting the presence of wash trades and find measures based on Benford’s law, trade size clustering, lognormal distributions, and structural breaks to be useful, whereas ones based on power law tail distributions to give opposite conclusions. We also provide suggestions to effectively apply various indirect estimation techniques. This paper was accepted by Professor Bruno Biais, finance. Funding: J. Li acknowledges support by the U.S. Department of Homeland Security [Grant 205187] through the Criminal Investigations and Network Analysis Center. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2021.01448 .