bluuebunny/crossref_metadata_2025_split huggingface dataset:
454 Utilization of Adipose-Derived Stem Cells in Cranial Nerve Regeneration: A Systematic Review
Authors: Aguirre Alexander Otilio , Chee Keanu , Harris Mark , Himstead Alexander Scott , Dzihich Ermin , Brown Nolan James , Musmar Basel , Kuo Cathleen , Bui Nicholas , Kortz Michael 
Published: March 2024

INTRODUCTION:
Large peripheral nerve injuries may require surgical reconnection. Cell-based therapies have also been investigated for nerve regeneration.

METHODS:
PubMed and Embase databases were used to search for primary studies reporting the use ADSCs in the regeneration of cranial nerves. A total of 12 studies were included which all presented data on specific neural injury, therapy, and functional outcomes.

RESULTS:
Eight studies focused on the facial nerve (66.7%), two on the optic nerve (16.7%), one on the olfactory nerve (8.3%), and one on the hypoglossal nerve (8.3%). One study applied ADSCs to human cranial nerve injuries, while the remainder studied animal models. In these studies, ADSC groups had higher numbers of myelinated fibers, increased myelin thickness and diameter of muscle fibers as well as greater magnitude of compound muscle action potentials (CMAP) when compared to controls. In studies focused on optic nerve regeneration, significant improvements across visual tests were observed.

CONCLUSIONS:
ADSCs demonstrate potential utility in regard to their ability to facilitate functional recovery of cranial nerves in humans as well as animal models. Further investigation into the use of ADSC should be pursued in both animal and early human studies to validate the findingsof previous literature.
457 Timing of Surgery as an Outcome Predictor in Brachial Plexus Injury: A Systematic Review and Meta-Analysis
Authors: Hanna Amgad , Moscote-Salazar Luis Rafael , Florez-Perdomo William , Moriones Natalia Guevara 
Published: March 2024

INTRODUCTION:
Injuries that affect the brachial plexus are considered to have a high impact on the quality of life of patients. Brachial plexus injuries in adults require reconstruction using microsurgical techniques. At least, there is still controversy about the impact of the timing of surgical reconstruction and its effect on outcome.

METHODS:
We searched PubMed, EMBASE, Cochrane Library, SCOPUS, and MEDLINE, up to March 2023, for published studies on evidence of timing of surgery in Brachial plexus injury and neurological outcome. Primary outcome Good motor functional Recovery (MRC).

RESULTS:
In this meta-analysis, it was found that early surgical treatment before 6 months post-injury increases motor recovery (MRC) three times more than late intervention (after 6 months) with adequate statistical significance and good homogeneity (OR 3,115 [95% CI 2,248–4,317] p = <0.0001; I2 = <0.00001%).

CONCLUSIONS:
The available evidence suggests that performing brachial plexus surgery in less than 6 months can be associated with a better outcome. Further research is needed to characterize various subgroups of BPI patients. It is necessary to improve the quality of the evidence, so we suggest the creation of a multicenter database in the United States that allows us to obtain better conclusions.
462 Stem Cell-Loaded Implantable Intrathecal Bioreactors for the Treatment of Spinal Cord Injury: A Porcine Model Pilot Study
Authors: Jiang Kelly , Saberi Amir , Weber-Levine Carly , Bhimreddy Meghana , Menta Arjun , Routkevich Denis , Davidar Daniel , Quiroz Victor , Hersh Andrew , Luksik Andrew , Khalsa Siri , Liu Ann , Judy Brendan F. , Manbachi Amir , Doloff Joshua , Theodore Nicholas 
Published: March 2024

INTRODUCTION:
Stem cells promote spinal cord injury (SCI) recovery by secreting paracrine factors that orchestrate endogenous healing mechanisms. However, effects in clinical trials are modest and there are no approved stem cell therapies to treat SCI. Major barriers include cell washout, immune attack, and oncogenic potential.

METHODS:
ITBs were implanted in three pigs. One pig received a cell-loaded ITB without injury (Cells), another received a cell-loaded ITB with injury (Cells + SCI), and another received a sham ITB with injury (SCI). SCIs were induced by weight drop at T5. ITBs were implanted cranial to the injury and sutured under the dura then loaded with human mesenchymal stem cells or sham cell media. Cerebrospinal fluid (CSF) was collected for 6 days following surgery through a lumbar drain. Cytokines in the CSF were measured by ELISA and the ITB was retrieved for cell viability staining.

RESULTS:
Upon retrieval, stem cells were alive on viability staining of the ITB. CSF levels of the pro-inflammatory cytokines IFNy and IL-1a were increased in the SCI condition compared to the Cells and Cells + SCI conditions. Pro-inflammatory cytokines peaked on post-operative day 5 and remained high. Anti-inflammatory cytokines IL-1ra, VEGF, and TGFβ were elevated in the SCI + Cells condition and depressed in the SCI condition compared to the Cells condition. Anti-inflammatory cytokines peaked on post-operative day 3 and decreased by day 6.

CONCLUSIONS:
In this pilot study, stem cells survived in an implantable ITB and altered cytokine levels in the CSF of pigs with SCI. Cell-loaded ITBs reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. Implantable ITBs warrant further study as they may represent a potential new delivery option for stem cell therapy.
483 Network Analysis of the Thalamic RNS in Patients With Drug Resistant Epilepsy: Insights to Improve Surgical Targeting
Authors: Subramaniam Varun Ramanan , Avecillas-Chasin Josue Moises , Marcuse Lara , Panov Fedor 
Published: March 2024

INTRODUCTION:
Approximately 30% of epilepsy patients are refractory to pharmacotherapy. Patients with drug-resistant epilepsy (DRE) with seizure foci located bilaterally or in the eloquent cortex may be ineligible for resective surgery. For such cases, responsive neurostimulation (RNS) is a viable treatment strategy.

METHODS:
Retrospective analysis of 23 patients treated with thalamic RNS of the centromedian (CM) and anterior nuclei of the thalamus (ANT) from 2015-2022. Clinical features and seizure outcomes were recorded. RNS electrodes were used to model the electrical field using the parameters at last follow up. Patient-specific probabilistic tractography was used to define the network of the seizure onset zone (SOZ) and its thalamic involvement. Each patient’s probabilistic map was used to define the area of highest connectivity of the thalamus with the seizure network. Each of these patient-specific thalamic areas demonstrating highest connectivity with the seizure network were correlated with electrode position, stimulation modeling, and seizure outcomes.

RESULTS:
Seizure network from neocortical areas were highly connected to the CM and from limbic cortical areas to the ANT, MD, and parafascicularis nuclei. Results of the correlation analysis between connectivity, stimulation modelling of the RNS electrode, and seizure outcomes will be presented along with illustrative cases of patient-specific targeting using tractography for RNS placement.

CONCLUSIONS:
Probabilistic tractography is useful to define the networks associated with improved seizure control in thalamic RNS. The identification of these networks prior to surgery could help to identify specific corticothalamic connections and their anatomical trajectories to optimize the implantation of the leads for better and more predictable seizure control.
490 Unilateral Subthalamic Nucleus Deep Brain Stimulation Improves Motor Symptoms Without Neurocognitive Worsening in Parkinsons Disease
Authors: Rogowski Brandon , Salazar Claudia , Rowland Nathan Christopher 
Published: March 2024

INTRODUCTION:
Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical intervention for patients with medically refractory Parkinson’s disease (PD). Numerous reports have described adverse nonmotor side effects, such as declines in verbal fluency and working memory, following bilateral implantation. Unilateral STN DBS is a possible alternative; however, it remains unclear whether unilateral implantation meaningfully reduces harmful effects on cognition.

METHODS:
This retrospective cohort study utilized chart review to collect pre- and postoperative Unified Parkinson’s Disease Rating Scale (UPDRS)-III, Levodopa Equivalent Daily Dosage (LEDD), imaging, and neurocognitive test results from 32 patients (unilateral, n = 12; bilateral, n = 20). For all statistical comparisons, p-values less than or equal to 0.05 were considered statistically significant. Student’s unpaired and paired T-tests were used to assess for differences between groups and within groups, respectively.

RESULTS:
There was no difference across 17 preoperative neurocognitive tests. Both unilateral and bilateral STN DBS resulted in significant decreases in postoperative UPDRS-III and LEDD (unilateral: p < 0.0001; bilateral: p < 0.0001) scores. There were no differences in the absolute decreases in UPDRS (p=0.055) and LEDD (p=0.120) scores between the groups. The bilateral STN DBS group had a significant deterioration in verbal fluency (COWAT FAS, p = 0.002; COWAT Animals, p = 0.014) and attention/executive function (Trails A, p=0.049 and Trails B, p = 0.011) compared to the unilateral group.

CONCLUSIONS:
Unilateral STN DBS is an effective and safe treatment option for patients with advanced PD. Particularly for patients with asymmetric motor symptoms, unilateral implantation provides a meaningful improvement in motor symptoms and reductions in dopaminergic medications without the risk of neurocognitive decline seen in bilateral implantation.
506 Deep Learning-Based Image-to-Image Translation to Identify Macrophage Infiltration in High-Grade Glioma Using Label-Free Stimulated Raman Histology
Authors: Alber Daniel Alexander , Lee Sangwon Karl , Smith Andrew , Lock Emily Katherine , Movah-Ezazi; Todd Charles Hollon Misha , Oermann Eric Karl , Orringer Daniel A. 
Published: March 2024

INTRODUCTION:
5-Aminolevulinic acid (5-ALA) is the most widely used fluorophore in image-guided glioma surgery, and previous work at our institution demonstrated that 5-ALA highlights tumor-associated macrophages (TAMs) in two-photon microscopy images of brain tumor tissue. Using a unique, paired dataset of stimulated Raman histology (SRH) and two-photon images that share one-to-one spatial resolution, we propose a deep-learning approach to identify macrophages from intraoperative SRH images without requiring fluorescent labels.

METHODS:
We compiled a dataset of 9,554 non-overlapping, 300-by-300 pixel fields of view from paired SRH and two-photon images representing 40 cases of high-grade glioma. A deep generative adversarial network (pix2pix), consisting of a U-Net generator and PatchGAN discriminator, was trained to generate synthetic two-photon images from each SRH patch. The model was trained for 200 epochs, and similarity between the synthetic and real distributions was assessed qualitatively while training and quantitatively using FrÉchet inception distance (FID).

RESULTS:
Our model was successfully trained to generate synthetic two-photon images nearly indistinguishable from ground truth examples. The FID between a held-out test set of real and synthetic images was 8.58, compared to a mean FID of 9.26 ± 0.24 between randomly sampled sets of real images. Our model consistently inferred the location of brightly fluorescing TAMs in held-out, previously unseen test images.

CONCLUSIONS:
We used deep learning to visualize TAMs in label-free SRH images. Analysis of TAM infiltration has the potential to identify patients most likely to benefit from immunotherapy clinical trials. Ongoing work will leverage additional deep-learning approaches to automatically identify and quantify TAM infiltration with SRH, enabling rapid patient-specific analysis of the glioma immune microenvironment.
510 Dopaminergic Neuronal Cell Therapy for Parkinson’s Disease: Results From a Phase 1 Study of Bemdaneprocel
Authors: Tabar Viviane S. , Yu Kenny , Lozano Andres M. , Brennan Cameron Walter , Kalia Suneil K. , Fasano Alfonso , Sarva Harini , Henchcliffe Claire , Yountz Marcus , Enayetellah Ahmed , Lampron Antoine 
Published: March 2024

INTRODUCTION:
None of the available therapies for PD directly address the loss of dopaminergic neurons. Bemdaneprocel is an investigational cellular therapy composed of midbrain dopaminergic neuronal cells derived from human embryonic stem cells.

METHODS:
In this open-label study 12 subjects have received 1 of 2 doses of bemdaneprocel to the putamen bilaterally, along with a 1-year immunosuppression regimen. Safety and tolerability have been assessed, along with assessments of engraftment and clinical impact.

RESULTS:
At screening, the average age was 66.4 yrs and the mean time since diagnosis was 9.1 yrs. All subjects presented at screening with a Hoehn and Yahr stage of 2 in the on-medication state. The mean MDS-UPDRS part III score was 46.6 (15-73) when assessed in the off-medication state, and patients presented with 4.3 (1.4-6.2) average daily hours of OFF time as assessed by PD diaries. In both cohorts, the safety profile is favorable with the vast majority of reported treatment-emergent AEs being mild to moderate. All but one AE deemed potentially related to the intervention were attributed to the immunosuppression regimen. There were no AEs reported as possibly related to the cell therapy. Patients enrolled in both cohorts to date have demonstrated clinical improvement as measured by the MDS-UPDRS, PD diaries, PDQ-39, and others. F-DOPA PET imaging supports evidence of engraftment, survival and functionality of the cells at 1 year.

CONCLUSIONS:
Results from at least 1 year of follow-up in this phase 1 study will be presented. An acceptable safety profile, evidence of sustained engraftment, and positive exploratory clinical outcomes in this study support further investigation of bemdaneprocel for the treatment of PD. Unpublished data, will be partly shown in a poster at MDS
698 Animal Model of a Common HFE Mutation Modifies Recovery Following Intracerebral Hemorrhage
Authors: Helmuth Timothy , Kumari Rashmi , Palsa Kondaiah , Neely Elizabeth , Slagle-Webb Becky , Simon Scott , Connor James 
Published: March 2024

INTRODUCTION:
Intracerebral hemorrhage (ICH) is a devastating disease with a one-year mortality rate of 45%. In the setting of an ICH, the breakdown of blood releases iron into the brain parenchyma. This excess iron contributes to stroke-induced neurodegeneration as it creates a cytotoxic environment through increased oxidative stress. Genetic variations in iron metabolism such as the H63D HFE mutation have been shown to modify disease progression in neurodegenerative diseases such as Parkinson’s, but have not been studied in ICH.

METHODS:
An autologous blood infusion model was utilized to create an ICH in the right caudate of H67D (human homolog of the H63D HFE mutation) and WT mice. Motor recovery was assessed using latency to fall from rotarod. 3-days post-ICH, the extent of neurodegeneration and mitochondrial damage in glial cells in the perihematomal area were measured using Fluorojade-B (FJB) and Cytochrome-C (CytC) immunofluorescent staining respectively. Levels of key regulatory proteins in the antioxidant and iron storage systems (Nrf2, GPX4, and FTH1) were evaluated using immunoblotting.

RESULTS:
H67D mice demonstrated significantly increased motor recovery at two- and three-days post-ICH compared to WT. H67D mice displayed significantly decreased degenerated neurons and CytC+ glial cells in the perihematomal region compared to WT. Furthermore, levels of Nrf2, GPX4, and FTH1 were significantly increased in the ICH-affected hemisphere of H67D mice.

CONCLUSIONS:
Our data suggest that the H67D HFE mutation modifies ICH recovery through significant improvements in motor recovery and decreases in damaged cells in the perihematomal region. The mechanism appears to be an upregulation of the endogenous antioxidant systems. These data suggest that a study determining the impact of HFE mutations on clinical outcomes in ICH is warranted. Given the prevalence of the H63D HFE mutation in humans, the impact of this mutation on ICH could be highly significant.
701 A Modified Frailty Index to Predict Adverse Outcomes After Decompressive Hemicraniectomy for Acute Ischemic Stroke
Authors: Joshi Krishna C. , Munich Stephan , Kolb Bradley 
Published: March 2024

INTRODUCTION:
Surgical decision-making for decompressive hemicraniectomy (DHC) is challenging because of the heterogeneity of health status and the paucity of tools for predicting the operative risk of DHC for malignant edema following acute infarction.

METHODS:
The 2008–2018 National Surgical Quality Improvement Program (NSQIP) data set was accessed for patients undergoing DHC for Acute ischemic stroke (AIS) based on Current Procedural Terminology (CPT) codes. We used a modified frailty index (mFI) based on eleven preoperative clinical NSQIP variables. The outcomes assessed were 30-day occurrences of adverse events.

RESULTS:
A total of 394 patients were identified in the database, there were 55 (14%) patients with mFI 0, 118 patients (30%) with mFI 0.09, 115(29.2 %) with mFI 0.18 and 106 (27%) patients with mFI = 0.27. The rate of return to the operating room for a second procedure significantly increased from 4/55 (7.3%) in patients with mFI 0 to 23/106 (31.1%) in patients with mFI = 0.27. The discharge disposition was significantly different in patients with higher mFI (mFI > 0.27), with only 6/106 (5.7%) discharged to home versus 8/55 (14.5%) with mFI 0. Multivariate logistic regression analysis showed that compared to age, gender, ASA class, and pre albumin levels, mFI was a better predictor of the development of pneumonia (OR 6.278, 95 % CI 1.8, 22.0, p = 0.004) and return to the operating room (OR 4.0, 95 % CI 1.2 ,13.4, p = 0.02).

CONCLUSIONS:
A higher mFI was associated with an increased risk of return to the operating room and worse discharge disposition. The mFI is based on easily identifiable patient characteristics and can be an additional tool to improve perioperative risk stratification in elderly patients considered for DHC after AIS.
727 Trends Between Males and Females in Public and Private Neurosurgical Research Funding From 2015 to 2021
Authors: Shah Varunil Nilesh , Das Nikita , Shah Aakash , Kelly Michael L. 
Published: March 2024

INTRODUCTION:
Open Payments Database (OPD) is a public database established by the Centers for Medicare and Medicaid Services under the 2010 Physician Payments Sunshine Act. It is a national program that reports all financial relationships between physicians and healthcare manufacturers, including pharmaceutical and medical device companies. OPD aims to promote transparency and help patients make informed decisions about their healthcare providers.

METHODS:
All the Principal Investigators from 2015 to 2021 who received research payments as neurosurgeons or payments tagged with the keyword "neurosurgery" in the OPD and NIH RePORTER, respectively, were subclassified according to the neurosurgical subspecialty of their research and their identified gender; Python and R were used to compute descriptive statistics for the public and private research payments.

RESULTS:
The total difference between males and females in public and private neurosurgical research funding from 2015 to 2021 was $674,715,146.00 and $148,361,648.45, respectively. The difference in funding has a growth rate of 54.63% and 32.33% from 2015–2021 in private and public funding, respectively. The Permutation Test showed a significant difference in total private funding between males and females in 2018 (p = 0.03). Besides this, there were no significant differences between gender payments in the public and private sectors.

CONCLUSIONS:
These findings suggest a significant difference in total funding for neurosurgery, with males receiving significantly more public and private funding than females. The difference in funding has also grown over time, particularly in private funding. However, the difference in funding per researcher between the two groups is similar; the discrepancy between funding is largely due to gender disparity in the number of neurosurgical researchers.
786 An Analysis of Artificial Intelligence Responses to Common Patient and Family Questions in Cranial Neurosurgery
Authors: Cassimatis Nicholas , O'Malley Geoffrey R. , Janezcko Patrick , Adams David , Kumar Rohit Prem , Patel Nitesh Vijay , Roth Patrick , Meyer Scott A. 
Published: March 2024

INTRODUCTION:
In recent decades, the internet has revolutionized how patients receive and navigate medical information. The development of artificial intelligence (AI) may provide patients and their families with the next landmark development in information transfer.

METHODS:
ChatGPT was asked 3 questions (pertaining to risks & benefits, length of operation, and length of recovery) about each of these 3 surgeries: transphenoidal resection of pituitary adenoma, deep brain stimulation for Parkinson’s tremor, and hemicraniectomy for a subdural hematoma. Neurosurgeons were asked to appraise the quality of AI responses from 1 (low) to 5 (high), 3 being a threshold that they would be satisfied with a patient reading. The reviewing neurosurgeons were unaware that responses were AI generated, to limit potential bias. To gauge patient accessibility, responses were also graded using readability tools.

RESULTS:
Quality ratings were collected from 5 neurosurgeons on 3 AI responses for each of the 3 questions, totaling 45 quality ratings. 44 of 45 ratings (97.8%) indicated that the AI generated response was of a high enough quality to show to patients (quality rating > or = to 3). 14 of 45 ratings (31.1%) indicated that AI generated responses were 5 out of 5 quality. AI response readability averaged a Flesch-Kincaid Grade Level of 15.12, and a reach of 46.9% of the English-reading population.

CONCLUSIONS:
While readability was not optimal, our trials produced physician satisfaction scores which were high enough to warrant further investigation. Furthermore, the readability scores were comparable to many other patient resources. As artificial intelligence grows in technological sophistication, its utilization will no-doubt continue to increase among patients. It will be the duty of medical professionals to optimize this resource for patient use, and increase access to quality patient and family healthcare information.