bluuebunny/crossref_metadata_2025_split huggingface dataset:
140 Muscle Accelerometry as a Novel Marker of Axonal Injury in Chronic Entrapment Neuropathy
Authors: Javeed Saad , Xu Yameng , Benedict Braeden Christopher , Yan Ying , Birenbaum Nathan , Zhang Justin , Dibble Christopher , Greenberg Jacob K , Faraji Amir H. , Spinner Robert J. , Brogan David , MacEwan Matthew R. , Ray Wilson Zachary 
Published: March 2024

INTRODUCTION:
Chronic entrapment neuropathy results in a clinical syndrome ranging from mild-pain to debilitating atrophy. There remains a lack of objective metrics that quantify nerve dysfunction and guide surgical decision-making. Muscle accelerometry quantify mechanical-motor-activity after stimulation of neuromuscular tissue and may enable evaluation of underlying nerve function.

METHODS:
Experimental Lewis-rats underwent compressions at proximal- and distal-sites of sciatic nerves using silicone-conduits. To simulate chronic-entrapment, sciatic nerves were compressed for 2-, 3-, and 4-months (n = 6 in each month) and were serially evaluated by accelerometry, compound-muscle-action-potential (CMAP), and compound-neural-action-potential (CNAP). To simulate recovery, sciatic nerves were decompressed at 3-months and tracked for additional 2-months with accelerometry, CMAP, and CNAP. In each group, the left-side served as control nerve and right-side served as experimental nerve. Accelerometry was acquired by custom-built-device after direct electrical-nerve-stimulation from 0.1-mA to 1.5-mA current. The accelerometry was quantified by composite magnitude of muscle movement in x-, y-, and z-axis. At each endpoint, histomorphometry analysis was performed to evaluate nerve injury and recovery.

RESULTS:
After each month of nerve compression, there was a trend in worsening of nerve function indicated by decline in accelerometry at higher stimulation current of 1.5-mA .This finding was correlated with CMAP and CNAP.At each endpoint of 2-, 3-, and 4-month, there was significant worsening in g-ratio of compressed nerve as compared to the control nerves. After decompression at 3-months, muscle accelerometry at 0.5 mA current indicated a clear trend in recovery of nerve function. This finding was correlated with CNAP, however, CMAP results were variable.

CONCLUSIONS:
The muscle accelerometry may serve as a quantitative marker of axonal function and neuromuscular reinnervation in chronic entrapment neuropathy.
143 Individual Vagus Nerve Sensory Neurons Respond Distinctly to Specific Pro-inflammatory Cytokines
Authors: Huerta Tomas , Chen Adrian , Chang Eric H. 
Published: March 2024

INTRODUCTION:
The peripheral nervous system (PNS) communicates with the immune system in response to injury or infection. In the case of inflammation, sensory signals travel up to the brain via the vagus nerve, which is a major pathway for neuro-immune communication. While our previous work showed that systemic cytokine administration was associated with specific patterns of vagus nerve activity, we did not know how individual vagal sensory neurons encoded this immune information. Here, we use invivo calcium imaging to monitor the neural activity of individual vagal sensory neurons in response to specific inflammatory mediators.

METHODS:
Using mice that express the calcium sensor GCaMP6f in glutamatergic neurons, we imaged neurons of the nodose ganglion in-vivo using a 1-photon miniature microscope (Miniscope). During imaging, the inflammatory mediator tumor necrosis factor (TNF) and interleukin 1β (IL-1β) were applied directly to the vagus nerve. The fluorescence data were analyzed with Python-based calcium imaging analysis (CaImAn) software and customized pipelines to output the neural activity as the normalized change in fluorescence (DFF) individually detected neurons.

RESULTS:
Our results reveal that specific vagal sensory neurons respond differentially to specific immune mediators. The average amplitude, and integral of TNF-responsive neurons were significantly higher than IL-1β-responsive cells (TNF vs IL-1β, p < 0.01). This result suggests that TNF application triggers higher firing rates for a more prolonged time in TNF-responsive neurons compared to IL-1β specific responses. Neuronal responses to IL-1β had a significantly higher number of peaks when compared to TNF responses (IL-1β vs TNF, p < 0.05).

CONCLUSIONS:
Our findings demonstrate that individual vagal sensory neurons encode information about distinct inflammatory stimuli and provide insight into the neural sensing of inflammation. Further investigation into neuro-immune signaling may identify novel neural targets for the treatment of inflammatory disorders.
144 Use of Intraoperative Sodium Fluorescein During Nerve Tumor Surgery: A Systematic Review
Authors: Venero Carmelo , Asfour Mohamed Zaky , Palmisciano Paolo 
Published: March 2024

INTRODUCTION:
Nerve tumors are categorized into various classifications based on location, origin, and malignant potential. Symptoms and signs of nerve tumors result from direct infiltration of the nerve, compression on adjacent tissues, or the mass effect of the tumor. The primary treatment approach for nerve tumors is complete surgical resection. This should be achieved while preserving the function of the nerve. Sodium fluorescein holds promise in achieving this objective.

METHODS:
PubMed, EMBASE, Web-of-Science, and SCOPUS were searched to include studies reporting the use of sodium fluorescein in nerve tumors surgery. Intervention-related outcomes were systematically reviewed following the PRISMA guidelines.

RESULTS:
Our review comprised 5 studies encompassing 177 patients with a total of 179 tumors. Of these patients, 98 (55.4%) were female, and 101 (69.1%) had sporadic (non-syndromic) tumors. Histopathological examination revealed that 125 (69.8%) tumors were schwannoma WHO grade 1. No post-operative complications were reported in 149 (88.7%) patients. Gross total resection was achieved in 152 (84.9%) tumors. High tumor fluorescence was reported in 150 (94.3%) tumors, while absent and low parent nerve fluorescence was reported in 121 (79.6%) and 27 (17.8%) tumors, respectively. No side effects of the fluorescent dye were reported among the 179 tumor cases. The median latency period was 30 (range: 7-95) minutes, and the median duration of surgery was 51.5 (range: 24-92) minutes.

CONCLUSIONS:
Intraoperative sodium fluorescein shows promise as an aid in nerve tumor surgery, facilitating differentiation between the tumor, parent nerve, and surrounding soft tissue. Future prospective studies are necessary to determine its effect on surgical duration, postoperative complication rates, and extent of resection in comparison to current standard of care.
148 Ventral Mammillo-tegmental Tract Atrophies With Normal Aging
Authors: Skandalakis Georgios P. , Courville Evan , Owodunni Oluwafemi , Kazim Syed Faraz , Hadjipanayis Constantinos G. , Kalyvas Aristotelis , Yeh Fang-Cheng , Kogan Michael 
Published: March 2024

INTRODUCTION:
We recently characterized the Ventral Mammillo-tegmental tract (VMTT) throug Klingler’s microdissections and fiber tractography using an averaged template generated from diffusion MRI (dMRI) data of 1065 human healthy subjects acquired from the Human Connectome Project (HCP) and the 50/200 μm cadaveric brainstem dMRI Duke database. The VMTT interconnects the ventral tegmental area with mammillary bodies, regions that are profoundly affected in dementia. We hypothesize that his tract is involved in memory which is inherently affected by normal brain aging and thus atrophy over time.

METHODS:
We performed fiber tractography of the VMTT and the corticospinal tract (CST), using individual subject data from multiple HCP databases spanning neonatal, developmental, healthy adult, and aging populations. These data were generated using an averaged template from diffusion MRI (dMRI) data of 1065 healthy human subjects acquired from the Human Connectome Project (HCP) and the Duke database of cadaveric brainstem dMRI. The CST served as a control in this study. Tract diameter, volume, and fractional anisotropy were measured using DSI Studio developed by FCY. Trends analysis was performed evaluating diameter changes by age.

RESULTS:
The tract was reconstructed in total of 20 subjects for ages ranging from 9 to 100 years old. Our analysis revealed a significant age-related atrophy of the VMTT (p < 0.0001) while no age-related atrophy was observed in the CST (p = 0.161).

CONCLUSIONS:
Our findings indicate that the VMTT experiences disproportionate atrophy with normal aging as compared to CST which served as a control tract. This highlights the distinct age-related changes in the VMTT. Future dMRI studies on this tract across diverse patient populations will shed light on its potential role as a biomarker for early diagnosis of dementia disorders and its utility as a deep brain stimulation (DBS) target.
149 Dynamical Network State Sequences for Human Language Production
Authors: Forseth Kiefer , Pitkow Xaq , Fischer-Baum Simon , Tandon Nitin 
Published: March 2024

INTRODUCTION:
Speech requires the selection of a conceptual representation, the construction of a word form, and the execution of a complex articulatory plan. Investigating this global system requires high-resolution recordings with an analytic approach to resolve discrete cognitive states. We integrated autoregressive hidden Markov models to resolve trial-by-trial state transition sequences in distributed networks derived from a large-scale electrocorticographic dataset with complete coverage of language-dominant cortex.

METHODS:
Intracranial electrodes (n = 25810, 134 patients), including both surface grids and stereotactic depths, were implanted for the evaluation of epilepsy. Patients performed picture naming of common objects and underwent systematic cortical stimulation mapping of language function. We used cross-validated autoregressive hidden Markov models – combining the interpretability of multivariate autoregressive analysis with the nonlinear embedding of the switching Markov characteristic – to distinguish cognitive states defined by causal interactional motifs of distributed cortical substrates and to simulate in silico lesions of dynamical network structures.

RESULTS:
We created a detailed spatiotemporal atlas of word production spanning the entire language-dominant cortex. From this map, we resolved network dynamics comprising sequences of state space transitions for each word articulated. This identified five essential states for speech production, each defined by a unique pattern of directed interactions within the language network. We then derived a computational lesion model for state dynamics and compared its predictions with causal perturbation by direct cortical stimulation. We assembled a global dynamical state model for language production and resolved the fine-scale interregional dynamics of conceptualization and lexical access.

CONCLUSIONS:
The distributed network dynamics detailed within this comprehensive interactional map of speech production advance our understanding of how both local and disconnection injuries yield complex neurological deficits, facilitating the development of novel therapeutic approaches for aphasia.
153 Spatial Transcriptomic Profiling of T Cell Exhaustion Markers in Atypical Teratoid Rhabdoid Tumor Subtypes
Authors: Lucke-Wold Brandon 
Published: March 2024

INTRODUCTION:
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in pediatric populations. Despite advances in treatment, overall survival remains poor and novel effective therapies are needed.

METHODS:
Tumor purities of 49 atypical ATRT tumors, encompassing 3 epigenetic subtypes (MYC, SHH, TYR) were estimated using known mRNA expression signatures of stromal and immune cells. Using the purity estimates and bulk tumor expression values, non-negative linear regression was implemented to estimate the average expression of each gene in the stromal and tumor compartments for each subtype.

RESULTS:
Compared to other subtypes, SHH-ATRTs expressed relatively higher levels of T-cell immunoglobulin domain and mucin domain protein 3 (TIM-3) and its ligand GAL9. MYC-ATRTs expressed higher levels of numerous T cell inhibitory receptors including lymphocyte activation gene 3 protein (LAG-3), band T lymphocyte attenuator (BTLA), cytotoxic T lymphocyte antigen-4 (CTLA-4), and programmed cell death protein 1 (PD-1).

CONCLUSIONS:
The predicted stromal and tumor compartment deconvolution yielded previously unrecognized expression patterns of T cell exhaustion markers which should be evaluated further to develop effective targeted therapies for ATRT.
154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery
Authors: Robert Stephanie , Kiziltug Emre , Lu Benjamin , Arnal-Estape Anna , Nguyen Don , Chiang Veronica 
Published: March 2024

INTRODUCTION:
Radiation necrosis (RN), a common and morbid side effect of radiosurgical treatment of brain metastasis, is becoming more prevalent as immunotherapy options and patient survival improve. Thought to be immunologically driven, the pathophysiology of RN remains poorly defined. Further, RN is often indistinguishable from regrowing metastases after stereotactic radiosurgery (SRS), requiring invasive brain biopsy for diagnosis.

METHODS:
We collected 20 intraoperative samples from patients undergoing craniotomy for RN and/or metastatic tumor, as well as time-matched blood and CSF. We created a tissue bank, processed samples, and using fluorescence-activated cell sorting (FACS) and 10x Genomics single cell RNA sequencing, analyzed the cellular immune profile of lesional tissue, blood, and CSF.

RESULTS:
RN tissue demonstrates a robust, detectable expression of immune cells, including CD8+ and CD4+ T cells, natural killer (NK) and myeloid cells. Importantly, clustering of RN-derived immune cells (including T cells, myeloid cells, and NK cells) is reflected in the blood and CSF, with similar immune profiles. We demonstrate a subpopulation of myeloid cells with a microglia signature (CD14+, LYZ-, MS4A7+), and a separate population expressing interferon-stimulated gene (ISG). Supporting these findings, pathway analysis of top blood markers reveals pathways involved in innate and inflammatory immune responses in the blood of RN patients.

CONCLUSIONS:
These findings demonstrate the feasibility of extracting live cells from RN tissue for scRNAseq analysis and suggest that there are unique signatures of RN that can be detected in the blood and CSF of patients. This work has the potential to open new avenues for improved diagnostic and therapeutic approaches to allow earlier detection and more effective treatment of RN in patients with metastatic brain tumors.
155 Safety and Efficacy of Endovascular Versus Microsurgical Treatment of Unruptured Wide-necked Middle Cerebral Artery Aneurysms: A Propensity-Matched Analysis of the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD)
Authors: Padmanaban Varun , Zhu Junjia , Zhou Shouhao , Ansari Sameer , Howington Jay , Sahlein Daniel , Tejada Juan , Wilkinson D. Andrew , Simon Scott Douglas , Cockroft Kevin M. , Church Ephraim W. 
Published: March 2024

INTRODUCTION:
There is clinical equipoise regarding the best treatment for unruptured wide-necked middle cerebral artery (WN-MCA) aneurysms.

METHODS:
The NVQI-QOD registry was queried for patients with unruptured WN-MCA aneurysms. Wide-neck was defined as aneurysm neck = 4 mm or dome:neck ratio = 2. Demographics, aneurysm characteristics, and safety data were queried. Aneurysm occlusion status and modified Rankin score (mRS) at discharge and last follow up were evaluated. Propensity score matching was utilized to match aneurysm size, number of aneurysms treated, patient age and aneurysm status (asymptomatic or symptomatic).

RESULTS:
Of 670 unruptured MCA aneurysms, 319 were wide-necked. Thirty operations were excluded as the aneurysm was previously treated. 289 operations in 282 patients were assessed (203 EVT, 86 MS). After propensity score matching, there were 86 operations in each group. The median aneurysm size was 5.6 mm (EVT) versus 5.3 mm (MS), p = 0.243. Patients who underwent MS were more likely to have complete occlusion at discharge (90.4% vs. 58.8%, p < 0.001). The median follow up was 404 days in the EVT group versus 157.5 days in the MS group (p = 0.241). Patients who underwent EVT were more likely to have a mRS of zero at discharge (50/59 (84.8%) versus 29/54 (53.7%), p < 0.0003) and last follow up (36/55 (65.5%) versus 13/36 (36.1%), p = 0.006). Safety data showed similar intra-operative (7% EVT vs. 3.5% MS, p = 0.496) and post-operative (4.7% EVT vs. 7% MS, p = 0.750) complication rates.

CONCLUSIONS:
This report describes the largest-to-date, modern cohort of propensity matched patients undergoing treatment of unruptured WN-MCA aneurysms. Patients undergoing EVT had better functional outcomes at discharge and last follow up though there was significant loss to follow up. Patients undergoing MS were more likely to have complete aneurysm occlusion. Safety data was similar in both groups.
162 The New Military Neurosurgeon Readiness Metric to Assess Surgical Readiness and Deployability
Authors: Woodle Samuel , Dewar Callum , Hooten Kristopher G. 
Published: March 2024

INTRODUCTION:
The US Military Health System includes military treatment facilities (MTFs) and deployable medical providers that have a dual mission to provide a “medically ready force and a ready medical force”. During wartime, the surge in casualties provides abundant surgical case volume to train and sustain a ready medical force. In contrast, peacetime poses a major challenge to military provider readiness, where lessons learned are quickly forgotten and advancements in trauma and combat surgical care decelerate; a phenomenon coined the “Walker dip”. As such, the Defense Health Agency in 2019 mandated critical wartime specialties develop specialty-specific readiness metrics to measure and maintain skills and competencies, named Knowledge, Skills, and Abilities (KSA). The neurosurgery KSA metric was released in early 2023.

METHODS:
Case counts and associated KSA values were obtained for active duty (AD) military neurosurgeons and neurosurgery-capable MTFs over the last 12 months.

RESULTS:
The neurosurgery KSA metric is a point-based system that assigns case valuations based on five categories: cranial (70 points), spine (45), peripheral (15), endovascular (5) and minor (5). The threshold KSA value per provider is set at 8000 points annually, or 667 monthly. Threshold was selected as the average between the KSA of a typical level II trauma center annual case volume and initial ABNS certification caseload requirements. Of 51 AD neurosurgeons from 16 MTFs over a 12-month period, only three providers have monthly KSA values above threshold; all of which have duty assignments at civilian institutions.

CONCLUSIONS:
Less than 10% of AD military neurosurgeons are meeting readiness thresholds per the KSA metric. However, no internal/external validation has been performed. Future validation studies will be pivotal in determining metric accuracy and guide adjustments to ensure a medically capable military force.
166 Trans-radial Versus Trans-femoral Access Routes for Diagnostic Cerebral Angiograms: A Large Single-Center Comparative Cost-analysis Study
Authors: El Naamani Kareem , Atalla Elias , Momin Arbaz , Abbas Rawad , Jain Paarth , Hunt Adam , Sambangi Abhijeet , Carreras Angeleah , El Fadel Omar , Gooch Michael Reid , Tjoumakaris Stavropoula I. , Zarzour Hekmat , Schmidt Richard Frank , Herial Nabeel , Rosenwasser Robert H. , Jabbour Pascal 
Published: March 2024

INTRODUCTION:
Recently, the trans-radial approach has become a common alternative given its safety profile and increased patient satisfaction compared to the transfemoral route. Both routes are associated with their respective associated costs and differences typically emerge based on patients’ anatomy, operator expertise, and occurrence of complications.

METHODS:
This a retrospective single-center study of 926 elective diagnostic angiograms performed between December 2019 and March 2022.

RESULTS:
The study comprised of 314 and 612 angiograms done through the TF and TR routes respectively. Female patients were significantly higher in the TF cohort (79.3% vs 67.8%, p < .001), and most other demographic characteristics and baseline modified Rankin Scale score were comparable between both cohorts. The overall cost of patients utilizing the TR route was comparable to that of the TF route ($12591.8 ± 19128 vs $12789.5 ± 18424, p = .88). However, the median cost of catheters was significantly higher in TR group ($55.2 vs $12.4, p = .03), while the median cost of closure devices ($87 vs $20.2 p < .001), and sheaths ($44.6 ± 11.3 vs $41.1 ± 3.1, p < .001) was significantly higher in the TF group.

CONCLUSIONS:
Overall, our study shows that the TR approach can be less a less expensive option for patients undergoing diagnostic cerebral angiograms, especially if complications occur. Future studies can corroborate our findings and potentially lead to the adoption of TR as a low-cost, efficient, gold-standard technique for cerebral angiography.
169 Quantifying the Effect of Fracture Morphology on Nonunion for Traumatic, Isolated Odontoid Fractures Managed Nonoperatively: A Propensity Score Matched Analysis
Authors: Cloney Michael Brendan , Thirunavu Vineeth , Roumeliotis Anastasios , Azad Hooman , Shlobin Nathan A. , Swong Kevin , El Tecle Najib , Dahdaleh Nader S. 
Published: March 2024

INTRODUCTION:
Odontoid fractures disproportionately affect older patients who have high surgical risk, but also high rates of fracture nonunion.

METHODS:
We examined all patients with isolated odontoid fractures treated nonoperatively at our institution between 2010 and 2020. Multivariable regression and propensity score matching were used to quantify the effect of fracture type, angulation, comminution, and displacement on bony healing by 26 weeks from injury.

RESULTS:
303 consecutive traumatic odontoid fracture patients were identified, of whom 163 (53.8%) had isolated fractures that were managed nonoperatively. Selection for nonoperative management was more likely with older age (OR = 1.45 [1.14, 1.84], p = 0.003), and less likely with angulated fractures (OR = 0.31 [0.14, 0.65], p = 0.002), or higher presenting Nurick scores (OR = 0.78 [0.63, 0.97], p = 0.023). Factors associated with nonunion at 26 weeks were angulated morphology (OR = 16.14 [2.93, 89.00], p = 0.001) and Anderson-D’Alonzo Type II morphology (OR = 6.54 [2.16, 19.77], p = 0.001). Cox proportional hazards regression demonstrated slower healing time for angulated (HR 0.144 [0.044, 0.377], p = 0.0003) and type II fractures (HR = 0.380 [0.214, 0.673], p = 0.0009). Propensity score matching to assess the effect of type II fracture, fracture angulation, displacement, and comminution all yielded balanced models (Rubin's B < 25.0, 0.5 < Rubin's R < 2.0). By 26 weeks, controlling for confounders, 77.3% of type I or III fractures healed, compared to 38.3% of type II fractures (p = 0.001), and 56.3% of non-angulated fractures healed compared to 12.5% of angulated fractures (p = 0.015). Fracture displacement and comminution had no significant effect.

CONCLUSIONS:
Type II fracture morphology and fracture angulation significantly increase nonunion among nonoperatively managed isolated traumatic odontoid fractures, but fracture comminution and displacement do not.