bluuebunny/crossref_metadata_2025_split huggingface dataset:
305 Extracellular Vesicular mRNA and miRNA Biomarkers in Patients With Glioblastoma
Authors: Huntoon Kristin , Hong Li , Zhnag Jingjing , Kim Betty Y.S. , Jiang Wen , Lee James , Reategui Eduardo 
Published: March 2024

INTRODUCTION:
Glioblastoma (GBM) is a highly lethal primary brain cancer that is resistant to conventional immunotherapies. However, currently, there is a lack of reliable biomarkers for clinical practice. Extracellular vesicles (EVs) present in biofluids are a potential biomarker for GBM diagnosis.

METHODS:
EVs from cell culture medium, healthy donor and GBM patient serum were purified using tangential flow filtration (TFF). Morphology, size, and numbers of EVs were characterized by TEM and qNano, respectively. EVs from healthy donor and GBM patient serum were compared against other cancer EV samples using bulk mRNA and miRNA sequencing analysis. Selected mRNA and miRNA name are not mentioned due to patents being drafted. mRNA and miRNA expression in EVs were quantified by a fluorescent nucleic acid detection method using a biochip platform at a single-EV level. Fluorescence images were recorded using high-resolution total internal reflection fluorescence (TIRF) microscopy.

RESULTS:
From bulk mRNA and miRNA sequencing and bioinformatics analysis, three miRNA and two mRNA were selected as potential candidate biomarkers for GBM. Subsequently, EVs from the serum of GBM patients (n = 39) were evaluated through our biochip platform. mRNA and miRNA expression of these biomarkers were positive in single EVs, for which we detected colocalization of protein/RNAs or multiple RNAs in subpopulations of EVs. Our platform was benchmarked with a standard PCR method showing 100X more sensitivity. Moreover, levels of expression of the different RNAs were compared to a cohort of serum from healthy donors (n=20), and showing significant differences between the two groups.

CONCLUSIONS:
Our non-invasive biochip assay outperformed qRT-PCR for EV RNA detection. Selected mRNAs and miRNAs in subpopulations of EVs could be used as potential GBM biomarkers.
308 Improvement in Cranial Nerve Neuropathies Following Treatment of Intracranial Aneurysms With Flow Diverters: Institutional Outcomes and Meta-analysis of Literature
Authors: Sujijantarat Nanthiya , Antonios Joseph Paul , Koo Andrew B. , Haynes Joseph , Renedo Daniela , Hebert Ryan Matthew , Sheth Kevin , King Joseph , Christian Matouk Charles 
Published: March 2024

INTRODUCTION:
Cranial nerve (CN) neuropathies are rare presenting symptoms of intracranial aneurysms. Ophthalmological outcomes for symptomatic aneurysms treated with flow diversion are not well established.

METHODS:
We conducted a retrospective review of our institutional database for patients with intracranial aneurysms presenting with CN neuropathies who underwent treatment with flow diversion between 2015 and 2023. Systematic review of the literature was performed using Medline, EMBASE, Cochrane, and manual citation searches. Random effects meta-analysis was used.

RESULTS:
Twelve out of 136 studies were included in this meta-analysis, totaling 261 patients. The results were combined with our institutional data. The pooled rate of improvement in any CN neuropathies following flow diversion was 76% (95% CI, 67%-84%, n = 272). Patients presenting with CNII deficits were less likely to improve following treatment compared to other CN neuropathies (pooled OR [pOR] 0.32, 95% CI, 0.16-0.63, n = 224). The pooled rate of clinical improvement was 53% in CNII deficits (95% CI, 42%-65%, n = 80) and 80% in other CN deficits (95% CI, 71%-88%, n = 106). Intervention within one month of presentation was associated with improvement (pOR 6.53, 95% CI, 1.34-31.81, n = 33). Adjunctive coiling did not demonstrate effect on the improvement rate (pOR 0.38, 95% CI, 0.07-2.13, n = 31). Near total occlusion (Raymond Roy Occlusion Classification of 1 or 2, or O'Kelly-Marotta scale of C or D) was associated with symptomatic improvement (pOR 5.29, 95% CI, 1.66-16.90, n = 118), but not total occlusion (pOR 2.83, 95% CI, 0.97-8.23, n = 118).

CONCLUSIONS:
Flow diversion improves CN outcomes in patients with symptomatic intracranial aneurysms. These results support the theory that CN neuropathies depend more on the pulsatility of the aneurysm sac rather than mass effect. The inferior rate of improvement in CNII deficits compared to other CN symptoms may imply an additional, more irreversible mechanism contributing to CNII visual deficits.
309 High Glutamine Associated With the Risk of Stroke by Inducing Endothelial to Mesenchymal Transition Through ITGB4 MAPK-ERK Smad in Moyamoya Disease
Authors: Yang Yi , Ge Peicong , Zhao Jizong , He Qiheng 
Published: March 2024

INTRODUCTION:
Previous studies have suggested potential association between glutamine and stroke. The role of glutamine in moyamoya disease (MMD) manifestation and pathological process remains unknown.

METHODS:
A prospective cohort of 360 adult MMD patients between September 2020 to December 2021 was established. Human brain microvascular endothelial cells (HBMECs) were utilized for rt-qPCR, western blot, immunofluorescence, and functional assays including CCK8, Edu for proliferation and wound healing for migration. HBMECs were transfected with ITGB4 adenovirus, ITGB4 siRNA or Smad4 siRNA to explore the downstream alterations. Atorvastatin was used to treat HBMECs and the mechanism was explored. Finally, the expression of ITGB4 was validated in databases and immunofluorescence staining of superficial temporal artery in MMD patients.

RESULTS:
After fully adjusted, the risk of stroke increased with each increment of glutamine level (OR = 1.599, 95% CI = 1.071 – 2.387, p = 0.022). Consistently, compared with patients in the lower tertiles of serum glutamine levels, a significantly higher risk of complete stroke was found in those in highest glutamine tertile (OR = 2.752, 95% CI = 1.556 – 4.868, p = 0.001). After treated with glutamine, HBMECs showed increased proliferation, migration, and endothelial-mesenchymal transition (EndMT) which was reversed by ITGB4 knockdown. In ITGB4-transfected HBMECs, MAPK-ERK-TGF-β/BMP pathway was activated and Smad4 knockdown could reverse the EndMT. Atorvastatin alleviated the EndMT by inhibiting Smad2/3 phosphorylation in ITGB4-transfected HBMECs. The upregulated ITGB4 expression was validated in the superficial temporal artery of MMD patients.

CONCLUSIONS:
High glutamine was independently associated with the risk of stroke in MMD. Glutamine promotes the proliferation, migration, and EndMT by ITGB4 through MAPK-ERK-TGFβ/BMP-Smad pathway. Atorvastatin could alleviate the EndMT by inhibiting Smad2/3 phosphorylation and promoting Smad4 ubiquitination and thus may be a potential drug for MMD patients.
310 The Derivo 2 Heal Embolization Device in the Treatment of Ruptured and Unruptured Intracranial Aneurysms: A Retrospective Multicenter Analysis
Authors: Nordmeyer Hannes , Schwab Roland , Behme Daniel 
Published: March 2024

INTRODUCTION:
The Derivo 2 Flow diverter has been previously described for the treatment of intracranial aneurysms. To overcome the risk of in-stent thrombosis and thrombo-embolism as a well-known risk of intracranial flow diverter implantation, the device was modified by adding an antithrombogenic fibrin-heparin coating. The fibrin network aims at surface passivation, reduction of inflammatory reactions and building a scaffold for endothelial cells. The covalently bound heparin reduces the thrombogenicity by locally reducing platelet activation and inhibtion of the coagulation cascade.

METHODS:
We perform a retrospective multicenter, single-arm trial at seven neurovascular centers. Patients treated with the D2H for unruptured or ruptured intracranial aneurysms are included in the study. The primary endpoint is angiographic aneurysm occlusion at six months as assessed by the O’Kelly-Marotta (OKM) grading scale. Clinical outcome is evaluated after intervention and at six months with major morbidity defined as modified Rankin Scale scores (mRS) of 3-5.

RESULTS:
Between October 2021 and March 2023 56 patients with ruptured and unruptered intracranial aneurysms were treated with the D2H embolization device and included in our analysis. All patients were subjected to the regular antiplatelet pre- and post-treatment medication as per standard of care in the respective institutions with no deviations being reported. No differences in terms of technical device properties were observed. By the time of the conference, data evaluation will be completed and clinical as well as safety results including angiographic follow-up will be available.

CONCLUSIONS:
The Derivo 2 heal Flow Diverter is a promising antithrombogenic coated device for the treatment of ruptured and unruptured intracranial aneurysms. Early post-interventional and long-term results will provide further insight into the effect of antithrombogenicity and endothelial healing.
313 Development and Validation of a Scoring System for Hemorrhage Risk in Brain Arteriovenous Malformations
Authors: Chen Xiaolin 
Published: March 2024

INTRODUCTION:
The dilemma between natural rupture risk and adverse outcomes of intervention is of major concern for patients with unruptured arteriovenous malformations (AVMs). The existing risk score for AVM rupture includes factors that are controversial and lacks prospective validation.

METHODS:
This prognostic study developed a prediction model derived from a single-center cohort (derivation cohort) and validated in a multicenter external validation cohort and a conservative treatment validation cohort. Patients were recruited from a nationwide multicenter prospective collaboration registry in China. A total of 4135 patients were enrolled. 3962 patients were included (3585 in the derivation cohort and 377 in the multicenter external validation cohort); 1028 patients from the derivation cohort who had time-to-event data and prerupture imaging results were included in the conservative treatment validation cohort.

RESULTS:
Four risk factors were used to develop the scoring system: ventricular system involvement, venous aneurysm, deep location, and exclusively deep drainage (VALE). The VALE scoring system performed well in all 3 cohorts, with areas under the receiver operating characteristic curve of 0.77 (95% CI, 0.75-0.78) in the derivation cohort, 0.85 (95% CI, 0.81-0.89) in the multicenter external validation cohort, and 0.73 (95% CI, 0.65-0.81) in the conservative treatment validation cohort. The 10-year hemorrhage-free rate was 95.5% (95% CI, 87.1%-100%) in the low-risk group, 92.8% (95% CI, 88.8%-97.0%) in the moderate-risk group, and 75.8% (95% CI, 65.1%-88.3%) in the high-risk group; the model discrimination was significant when comparing these rates between the high-risk group and the low- and moderate-risk groups (p < .001 for both comparisons).

CONCLUSIONS:
In this prognostic study, the VALE scoring system was developed to distinguish rupture risk among patients with AVMs. The stratification of unruptured AVMs may enable patients with low risk of rupture to avoid unnecessary interventions.
317 Automated Diffusion Tensor Tractography: Quantitative Tract Counts Predict 90-Day Change in Motor Function by Baseline Deficit in Acute Ischemic Stroke Patients Undergoing Mechanical Thrombectomy
Authors: Jaquish Rigel , Abraham Benjamin , Spivak Sarah , Tobin Matthew Kyle , Troja Weston C. , Bohnstedt Bradley N. 
Published: March 2024

INTRODUCTION:
Ischemic stroke causes persistent motor deficits in roughly half of survivors. Although mechanical thrombectomy (MT) optimizes stroke outcomes, not all patients improve. Commercially available diffusion tensor tractography (DTT) software increases access to robust tractometric software. Automation and seamless clinical integration of diffusion tensor imaging (DTI) and tractography protocols standardizes data acquisition in high-throughput and high-resolution manners.

METHODS:
Between June 2020 and 2021, a total of 28 patients with M1 and M2 ischemic strokes underwent a standardized DTT protocol following MT. Patients were stratified by their baseline deficits, defined as the averaged upper and lower extremity motor testing scores at the time of initial presentation (MTS severe = 0, intermediate = 0.5–3.5, and mild = 4+). Multivariable linear regression analysis included demographics, clinical characteristics, and tractometrics of the lesioned CST with MTS at 90-days as the outcome.

RESULTS:
There were 12 patients with severe, 12 with intermediate, and 4 with mild baseline deficits. Stratification by baseline deficits revealed no significant difference between mean effected tract counts (5.20, 5.08, and 5.78 in the severe, intermediate, and mild groups, respectively, p = 0.377). When controlling for demographics and clinical characteristics, baseline deficits (β = -0.838, SE = 0.913, p < 0.001) and effected mean tract count (β = 1.755, SE = 0.407, p = 0.001) of the CST significantly predicted the change in MTS at 90-day follow-up (adjusted R2 = 0.727 p = 0.002).

CONCLUSIONS:
Our study suggests automated tractometrics predict the change in motor function at 90 days when controlling for the patient’s baseline motor deficit. Although larger cohort studies should be conducted, commercially available DTI software could yield novel avenues into rehabilitation optimization for post-stroke patients with persistent motor deficits.
318 Profiling Long RNA Transcriptome From Circulating Extracellular Vesicles in Subarachnoid Hemorrhage for Biomarker Discovery
Authors: Batool Syeda , Escobedo Ana , Hsia Tiffaney , Khanna Sirena , Ekanayake Emil , Gamblin Austin , McLellan Rachel , Carter Bob S. , Patel Aman B. , Balaj Leonora 
Published: March 2024

INTRODUCTION:
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high mortality rate and permanent neurological deficits following acute brain injury. Previous studies have aimed at investigating CNS specific biomarkers that can predict the outcomes following aSAH. Liquid biopsy represents a promising minimally invasive approach for biomarker discovery using biofluids (plasma, CSF).

METHODS:
CSF was collected from patients (n = 10) during in-hospital stay at multiple time points via the external ventricular drain and EV RNA was sequenced using Oxford Nanopore Technologies.

RESULTS:
We detected different biotypes in EV RNA with minimal rRNA contamination (protein coding; 58.4%, pseudogene; 23.1%, LncRNA; 10%, rRNA; 1.7%). This is the first study reporting presence of long (>500 bp) RNA transcripts in CSF derived EVs. Approximately, 80% of the sequenced reads were up to 500 bp long and 20% reads 500-10,000 bp long. Principal Component Analysis demonstrated distinct clustering of samples based on location (anterior vs. posterior circulation) and type of aneurysm (saccular, dissecting, bilobed). A set of protein coding genes (S100A9, EEF1A1, SCARNA1, DMTN) were found to be differentially enriched in patients who developed cerebral vasospasm (n = 6). Furthermore, for each patient there was a unique population of biomarkers upregulated in acute (HBB, COX2) vs. chronic (SEPTIN7, PDK4) immune response following aSAH. Preliminary findings reveal potential candidate biomarkers providing insight into the pathogenesis and prognosis.

CONCLUSIONS:
There is an unmet need for inclusion of diagnostic and predictive biomarkers in clinical management of aSAH to decrease the overall mortality. In this study, we overcame challenges of analyzing low input RNA using a sensitive and optimized sequencing platform. Validation and testing in a larger study population offers new opportunities for biomarker discovery.
326 Factors Associated With the Maintenance of Cost-Effectiveness at 5 Years in Adult Spinal Deformity Corrective Surgery
Authors: Passias Peter G. , Mir Jamshaid M. , Dave Pooja , Tretiakov Peter S. , Smith Justin S. , Lafage Renaud , Gum Jeffrey Lynn , Line Breton G. , Diebo Bassel G. , Daniels Alan H. , Protopsaltis Themistocles , Hamilton D. Kojo 
Published: March 2024

INTRODUCTION:
Substantial increase of costs in the surgical treatment of adult spinal deformity has given precedence to scrutinize the value it can provide hence cost-effectiveness (CE) is a vital analytical constituent. The analysis of factors associated with the durability of cost-effectiveness at 5 years has not been previously evaluated.

METHODS:
Adult spinal deformity (ASD) patients with baseline (BL) to 5-year (5Y) data were included. Cost calculation using PearlDiver database and CMS.gov definitions was used. Cost analysis was based on average DRG reimbursement rates. ODI was converted to SF-6D, with a 3% discount applied for residual decline in life expectancy. Cost per QALY gained at 2Y and 5Y was calculated. Threshold value for cost per QALY was $100,000. Patients that met 2Y (CE2+) were grouped based on meeting CE at 5Y(CE5+) or not(CE5-). Analysis based on meeting cost-effectiveness (CE) at 2Y and 5Y was conducted. Conditional-inference-tree (CIT) established cutoffs values for HRQLs.

RESULTS:
299 patients with 5Y data were included. Major and minor complication rates were 11% and 47% respectively, while 26% underwent reoperation by 5Y. The mean cost of surgery was $91,095 ± $47,003, utility-gain of 0.091 ± 0.086, and QALY of 0.171 ± 0.183, CE of $118,976 ± $208,323. 85.5% of the cohort met CE at 2Y, 79.2% at 5Y, whereas 59.6% met both. Frailty was comparable at baseline but was worse in CE5- at 2Y. CIT depicted 2Y ODI < 18 and SRS-22r > 3.3 (both p < 0.03) being associated with higher rates of C5+. Multivariable-regression depicted higher baseline CCI and pelvic tilt (PT) to be the strongest baseline predictors of not maintaining CE at 5Y (CCI OR: 1.821, p = 0.009) (PT OR: 1.079, p = .030).

CONCLUSIONS:
The majority that met cost-effectiveness at the 2 year went on to maintain it at 5 years. Lower baseline CCI and PT were strong predictive factors.
327 Sustained Improvement in Compliance With Use of Sequential Compression Devices in a Neurosurgery Patient Population of a Safety-Net Hospital
Authors: Windermere Sonora , Filippidis Aristotelis , Binello Emanuela 
Published: March 2024

INTRODUCTION:
Sequential Compression Devices (SCDs) are utilized in perioperative patients given increased risks of deep venous thrombosis from mobility reductions and post-operative inflammatory responses. Additionally, mechanical prophylaxis is crucial in patients where chemical prophylaxis is contraindicated. Previous work has found SCD compliance far less than expected.

METHODS:
Across a 9-month period (August-April), we tracked which neurosurgical patients in stepdown units had SCDs on and properly functioning. When not on or properly functioning, we documented the missing element. Compliance was calculated daily as the percentage of patients who were SCD compliant out of all patients with SCD orders, then averaged over the month, for each month. Most common barriers to compliance were identified. Together with nursing management, we designed and implemented a best practice alert to facilitate nursing education and supply chain management, at month 3. The impact was tracked over the next six months, with a 4-months break from November-February.

RESULTS:
Compliance averaged 19.7% (n = 95) during August, and 38.4% (n = 131) in September. After implementation of the best practice nursing alert and supply chain upgrades, compliance was 48.8% (n = 150) in October, 41.2% (n = 104) in March, and 45.9% (n = 76) in April. Residual barriers to compliance included patient behavior and equipment issues. Compliance was significantly increased from baseline in August to October (z = 5.042). The significant difference was sustained through March (z = 3.402) and April (z = 3.730).

CONCLUSIONS:
While initial improvement was attributed to a Hawthorne effect, implementation of the best practice nursing alert likely facilitated the sustained improvement in SCD compliance despite the break in surveillance. SCD compliance nonetheless remained below 50%. Further study is warranted to address the remaining barriers, such as improving patient engagement and minimizing equipment malfunction.
335 Federal Research Funding Trends for Cerebrovascular Neurosurgeons: The Decline of the Cerebrovascular Surgeon-Scientist?
Authors: Pugazenthi Sangami , Srienc Anja I. , Cantu Luke , Huguenard Anna , Eskandar Emad N. , Mack William J. , Amin-Hanjani Sepideh , Vellimana Ananth K. , Zipfel Gregory J. 
Published: March 2024

INTRODUCTION:
With the rise of endovascular neurosurgery, the number of cerebrovascular (CV) surgeons has grown. However, it is unclear whether the number of CV surgeon-scientists has concomitantly increased.

METHODS:
Publicly available data were collected on currently practicing academic CV surgeons in the US. Inflation-adjusted NIH funding between 2009-2021 was surveyed using NIH RePORTER. The K12 Neurosurgeon Career Development Program grant data were queried for CV-focused grants. Pearson R correlation was used for statistical analysis.

RESULTS:
From 2009-2021, NIH funding has increased: in total (p = 0.0318), to neurosurgeons (p < 0.0001), to CV research projects (p < 0.0001), and to CV surgeons (p = 0.0018). There has been an increase in the total number of CV surgeons (p < 0.0001), NIH-funded CV surgeons (p = 0.0034), and the percent of CV surgeons with NIH funding (p = 0.370). Additionally, active NIH grant dollars per CV surgeon (p = 0.0047) and number of NIH grants per CV surgeon (p = 0.0078) has increased. However, the percent of neurosurgeon-awarded NIH grants awarded specifically to CV surgeons has trended down over the past decade (p=0.3664). Analysis of early-career research grants showed a decline in the proportion of K12 applicants (p = 0.1840).

CONCLUSIONS:
Our data show that there are more CV surgeons than ever, and there has been a proportional increase in number of NIH-funded CV surgeons. However, there are fewer early-career neurosurgeons pursuing CV-focused projects, and the proportion of neurosurgeon-awarded NIH grants given to CV surgeons has trended down. These findings suggest a declining trend in CV surgeons pursuing research careers.