bluuebunny/crossref_metadata_2025_split huggingface dataset:
233 Evolutionary Analysis Identifies Early Responsive Macrophage Representing as Anti-tumor Myeloid Cell in Glioblastoma
Authors: Zeng Ailiang , Huntoon Kristin , Kim Betty Y.S. , Hu Jian 
Published: March 2024

INTRODUCTION:
Glioblastoma (GBM) has no effective treatments. Although immunotherapy has shown promise in certain cancer types, it has not been effective against GBM, largely due to its highly immunosuppressive tumor microenvironment (TMEs), which is rich in tumor-associated macrophages/microglia (TAMs). TAMs in late-stage GBM contribute to T-cell exhaustion and worsen prognosis, but the role of TAMs in earlier stages of tumor development is unclear.

METHODS:
By employing genetically engineered mouse models and human samples, we used spatiotemporal single-cell transcriptomics to investigate TAM evolution during GBM progression.

RESULTS:
We identified a previously unknown macrophage state, termed early responsive macrophage (ERM), that exhibited antitumoral activity. ERMs were found to be abundant in the early stages of GBM progression and spatially enriched in the invading edges of GBMs. ERMs are characterized by upregulated immune response signatures, particularly pathways related to antigen processing and presentation, as well as genes associated with phagocytosis and chemotaxis. Mechanistically, we identified QKI, a transcriptional co-activator, as a key player that activates antigen processing and presentation and MHCII expression in ERMs. Loss of QKI in TAMs is associated with the transformation of ERMs into exhausted tumor-infiltrating macrophages (TIMs), which promote an immune-suppressive TME. Therapeutically, enhancement of QKI's transcriptional co-factor activity greatly improved the efficacy of immune checkpoint blockade.

CONCLUSIONS:
Our study sheds light on the evolutionary trajectory of TAMs in GBM and presents a novel therapeutic approach to enhance their antitumoral activity, thereby constraining tumor growth.
237 SeeMe: An Automated Methodology to Detect Early Signs of Recovery After Acute Brain Injury
Authors: Mofakham Sima , Cheng Xi , Cleri Nathaniel , Saadon Jordan Raphael , Wang Cassie , Kleyner Robert , Zheng Xuwen , Swarna Sujith , Forohar Ariana , Mikell Charles B. 
Published: March 2024

INTRODUCTION:
Assessing the functional state of the brain and predicting recovery after acute brain injury (ABI) remains a major unsolved problem. At present, physicians make predictions using clinical examination, traditional scoring systems, and statistical models, which have significant shortcomings and lack the ability to forecast recovery on an individual basis.

METHODS:
SeeMe is based on analyzing subtle facial expressions in response to auditory commands (i.e., “open your eyes,” “make a smile”) over time and compares the results to a pre-stimulus baseline. These subtle motions are often not detectable by the naked eye. We enrolled 26 comatose ABI patients and 16 healthy volunteers to test this tool. Command-evoked eye-opening movements were compared to clinical observation and the JFK Coma Recovery Scale-Revised (CRS-R).

RESULTS:
In our study, 22 of 26 (85%) patients recovered consciousness during hospitalization after ABI. On average, SeeMe detected command-evoked eye opening ∼9 days before clinical assessment using the CRS-R and ∼3 days before blinded human raters who observed the recorded videos using the naked eye.Using the optimally identified decision threshold, SeeMe demonstrated the following performance metrics on ABI patients with no eye opening to command (auditory CRS subscale = 2): sensitivity = 74.1%, specificity = 66.6%, positive predictive value = 16.8%, and negative predictive value = 96.6%.

CONCLUSIONS:
These findings demonstrate the high predictive performance of SeeMe in assessing consciousness in ABI patients and provide a quantitative tool for studying neural circuits and developing novel therapeutic approaches. SeeMe's ability to detect low-amplitude motor movements opens new avenues for understanding and facilitating recovery of consciousness in patients with ABI.
242 Beyond the Stereotypes: Nurturing Success and Retaining Black Women Neurosurgeons
Authors: Charles Antoinette Jasmine , Duvall Julia , Green Destiny , Umoye Alexis , Flowers Jasmine , Woods GaResia , Potter Tamia , Goodwin C. Rory , Corley Jacquelyn , Williamson Theresa 
Published: March 2024

INTRODUCTION:
The underrepresentation of African American women in clinical neurosurgery, with fewer than 50 practicing neurosurgeons in the United States, highlights the significant barriers they face due to the intersection of race and gender. These challenges underscore the need for targeted efforts to recruit, retain, and support Black women in neurosurgery.

METHODS:
The study employed a comprehensive identification process to recruit Black women who identified as neurosurgical trainees or clinical neurosurgeons. Virtual interviews were conducted from January 2021 to May 2021, using structured questions to explore various aspects of the participants' experiences navigating neurosurgery as Black women. A thematic analysis was performed on the recorded and transcribed interviews to identify overarching themes.

RESULTS:
The thematic analysis identified key findings regarding Black women in neurosurgery. Mentorship was crucial, with mentors shaping career paths and fostering confidence. Residency program culture, encompassing faculty diversity, family-oriented values, and gender-specific challenges, significantly influenced experiences. Positive and negative experiences underscored the importance of representation, challenges related to racial biases, and the need for a supportive network. Building an equitable and diverse workplace was deemed vital, requiring actions to improve retention, promote Black women to leadership roles, and reduce hierarchical boundaries. Recommendations included diverse leadership, educational initiatives, and programs supporting aspiring neurosurgeons to enhance Black women's representation.

CONCLUSIONS:
The achievements of trailblazing Black women in neurosurgery showcase progress, yet significant disparities persist due to the intersection of race and gender. By addressing these challenges, support can be provided to enhance representation. The study highlights the importance of diverse leadership, comprehensive initiatives, and recognizing the impact of intersectionality in promoting Black women to leadership roles in neurosurgery.
256 The Neuropathological Basis of Elevated Serum Neurofilament Light Following Experimental Concussion
Authors: Arena John , Smith Douglas , Diaz-Arrastia Ramon , Cullen D. Kacy , Xiao Rui , Harris Danielle , Lynch Cillian , Johnson Victoria 
Published: March 2024

INTRODUCTION:
Mild traumatic brain injury (mTBI), or concussion, is a substantial health problem, with up to 15% of patients experiencing persisting symptoms. Identifying patients at risk for a poor outcome or protracted recovery remains challenging. Axonal damage caused by rotational forces is now recognized as an important consequence of injury. Moreover, serum measurement of the neurofilament light (NfL) protein has emerged as a potentially promising biomarker of injury.

METHODS:
A gyrencephalic, porcine model of head rotational acceleration scaled to human mTBI was performed with survival of 48 hr (n = 2), 72 hr (n = 6) and 14 days (n = 4) and compared with shams at 72 hr (n = 1) and 14 days (n = 1). Serum NfL was measured pre-injury and at 40 min, 1.5 hr, 3-4 hr, 8 hr, 18 hr, 24 hr, 2 days, 3 days and 14 days post-injury. Detailed neuropathological assessment was performed including staining for markers of cell death (Fluoro-Jade-C), axonal injury (amyloid precursor protein and NfL), and blood-brain barrier (BBB) disruption (fibrinogen).

RESULTS:
Significant elevations in serum-NfL were identified following mTBI, with a peak at 72hr post-injury. Moreover, increased serum-NfL was detectable out to 2 weeks post-injury. Subsequent quantitative histological examinations demonstrated that axonal pathology was the likely source of elevated serum-NfL. However, the extent of axonal pathology quantified via multiple markers did not correlate strongly with the extent of serum-NfL. Interestingly, the extent of BBB permeability offered more robust correlations with serum-NfL measured at multiple time points, suggesting BBB disruption is an important determinant of serum biomarker dynamics after mTBI.

CONCLUSIONS:
These data provide novel insights to the temporal course and pathological basis of serum NfL measurements that inform its utility as a biomarker in mTBI. The ability of NfL to measure underlying pathology will be critical for future clinical and translational research.
275 Absence of Hindbrain Herniation in Myelomeningocele Myeloschisis: A Closer Look at Patients Who Progress to Hindbrain Herniation in the Prenatal and Postnatal Period
Authors: Flanders Tracy Ma , Punchak MSCE; Maria , Land Sierra , Flohr Sabrina , Reynolds Tom , Schmidt Katie , Ertz Danielle , Moldenhauer Julie , Adzick N. Scott , Heuer Gregory G. 
Published: March 2024

INTRODUCTION:
Prenatal repair is the gold standard for appropriate patients with fetal myelomeningocele/myeloschisis. Hindbrain herniation is a prerequisite for fetal repair; however, there is a subset of patients without herniation on initial imaging and then progress to herniation on subsequent prenatal/postnatal imaging.

METHODS:
From July 2016 to July 2022, patients seen at the Center of Fetal Diagnosis and Treatment for myelomeningocele/myeloschisis were evaluated for hindbrain herniation. The osseous lesion level was defined as the bony defect level on prenatal ultrasound. Prenatal sac volume was measured on MRI. Prenatal ventricular size was determined on US. The fronto-occipital horn ratio was measured on the first postnatal US.

RESULTS:
Of 422 patients identified with a prenatal diagnosis of myelomeningocele/myeloschisis, 73 were identified who initially had negative hindbrain herniation; of these, 9 and 11 patients progressed to herniation on subsequent prenatal and postnatal imaging, respectively; 32 remained without herniation throughout the prenatal/postnatal period. Sac volume was significant (p = 0.04) for those whose hindbrain herniation was detected on subsequent prenatal visits but not for those diagnosed in the postnatal period (p = 0.10). The majority of patients with hindbrain herniation progression had L1-2 lesions. A subset of patients ultimately underwent permanent CSF diversion (no herniation: 21.8%, prenatal herniation: 33.3%, postnatal herniation: 36.3%).

CONCLUSIONS:
Patients who initially exhibit no hindbrain herniation and then ultimately progress to herniation in subsequent prenatal or postnatal evaluation are more likely to have higher levels of osseous defect. Sac volume was determined as significant for delayed prenatal progression of hindbrain herniation. Further long-term outcomes are necessary to better characterize this unique cohort of patients.
288 Impact of Disc Degeneration on Clinical Outcomes After Fusion for Grade 1 Spondylolisthesis: A 5-year QOD Study
Authors: Yee Timothy Joseph , Upadhyaya Cheerag D. , Coric Domagoj , Potts Eric A. , Bisson Erica Fay , Turner Jay D. , Knightly Jack , Fu Kai-Ming G. , Foley Kevin T. , Tumialan Luis Manuel , Shaffrey Mark Edwin , Bydon Mohamad , Mummaneni Praveen V. , Chou Dean , Kai-Hong Chan Andrew , Meyer Scott A. , Asher Anthony L. , Shaffrey Christopher I. , Gottfried Oren N. , Than Khoi Duc , Wang Michael Y. , Lee Buchholz Avery , Haid Regis W. , Glassman Steven D. , Park Paul 
Published: March 2024

INTRODUCTION:
Disc degeneration with loss of disc height can be an indication to fuse patients with lumbar spondylosis. However, its relevance for spondylolisthesis is unknown.

METHODS:
The Quality Outcomes Database was queried for adult patients who underwent fusion for single-level degenerative grade 1 lumbar spondylolisthesis. Pfirrmann grade at the level to be fused was assessed on preoperative sagittal T2-weighted MRI. VAS-back pain (BP-VAS), VAS-leg pain (LP-VAS), and ODI were collected preoperatively and at 3, 12, 24, 36, and 60 months postoperatively.

RESULTS:
The query returned 395 patients. Mean age (95% CI) was 60 (58.9-61.1) years; 39.5% were male. None had a Pfirrmann grade 1 disc. One (0.3%) had a grade 2 disc, 53 (13.4%) had a grade 3 disc, 245 (62%) had a grade 4 disc, and 96 (24.3%) had a grade 5 disc. Posterior-only approach was performed in 92.6%; interbody graft was placed in 92.7%. Mean BP-VAS (95% CI) at baseline, 3 months, 12 months, 24 months, 36 months, and 60 months were 7.1 (6.8-7.3) (n = 343), 3.1 (2.8-3.3) (n = 353), 2.9 (2.6-3.2) (n = 305), 3.2 (2.8-3.5) (n = 283), 3.5 (2.9-4.1) (n = 107), and 3.7 (3.3-4.0) (n = 324). Mean LP-VAS (95% CI) were 6.7 (6.4-7.0) (n = 392), 2.3 (2.0-2.6) (n = 353), 2.2 (1.9-2.6) (n = 306), 2.6 (2.2-2.9) (n = 284), 2.8 (2.2-3.4) (n = 107), and 2.8 (2.4-3.1) (n = 322). Mean ODI (95% CI) were 49.4 (47.8-51.1) (n = 392), 27.4 (25.3-29.5) (n = 347), 22.9 (20.6-25.2) (n = 313), 22.4 (20.1-24.8) (n = 291), 22.4 (18.3-26.4) (n = 97), and 25.9 (23.7-28.2) (n = 325). Utilizing linear regression, Pfirrmann grade was not associated with improvements in VAS-BP, VAS-LP, or ODI at any time point in unadjusted and adjusted analyses (p > 0.05).

CONCLUSIONS:
Patients who undergo fusion for single-level grade 1 spondylolisthesis are likely to experience significant and sustained improvements in pain and function regardless of severity of disc degeneration.
299 Predictors of Unplanned Readmission in Patients Undergoing Intracranial Tumor Resection: A Multi-center Analysis of 31,776 Patients
Authors: Zohdy Youssef M. , Skandalakis Georgios P. , Kassicieh Alex James , Rumalla Kavelin , Kazim Syed Faraz , Schmidt Meic H. , Bowers Christian 
Published: March 2024

INTRODUCTION:
Although unplanned readmission is a postoperative outcome metric associated with significant morbidity and financial burden, precise assessment tools for its prediction are yet to be developed. The Revised Risk Analysis Index (RAI) has been recently endorsed as a robust frailty index for predicting surgical outcomes. Hence, the RAI could potentially be utilized to help improve prediction unplanned readmission in patients undergoing intracranial tumor resection (ITR).

METHODS:
Data of patients undergoing ITR were obtained from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database from the years 2012-2019 using the ICD-9 and ICD-10 codes, indicating ITR. Baseline characteristics, preoperative clinical status, and outcomes were compared between patients with and without unplanned readmission. Frailty, as a measure of baseline physiological reserve, was calculated using the RAI. Univariate and multivariate logistic regression analyses were performed to identify independent associations between unplanned readmissions and patient characteristics.

RESULTS:
The unplanned readmission rate of this cohort (N = 31,776) was 10.8% (N = 3,420). Among the readmitted patients, 958 required unplanned reoperation. Multiple characteristics were significantly different between the readmitted and non-readmitted patients, including age, BMI, comorbidities, and RAI groups (p < 0.05). The most common causes of unplanned readmission were infection (9.4%), seizures (6%), and pulmonary embolism (4%). Patient characteristics identified as reliable predictors of unplanned readmission, included age, body mass index (BMI), functional status, diabetes, hypertension, hyponatremia, and their RAI score (p < 0.05). In multivariate analysis, RAI “frail” patients had an unplanned readmission odds ratio (OR) of 1.3(95%CI; 1.2-1.4), and RAI “severely frail” patients had an OR of 1.6 (95%CI; 1.3-2.1) (p < 0.001).

CONCLUSIONS:
The RAI is a reliable pre-operative frailty index for predicting unplanned readmission following ITR. Utilizing the RAI to identify high risk patients may decrease unplanned readmission through implementation of appropriate management guidelines.
301 Even Heterozygous Loss of CDKN2A B Greatly Accelerates Recurrence in Aggressive Meningioma
Authors: Basit Khan A. Basit , English Collin , Chen William , Athukuri Prazwal , Bayley James , Brandt Vicky , Shetty Arya , Hadley Caroline , Choudhury Abrar , Lu Hsiang-Chih , Harmanci Arif , Harmanci Akdes , Magill Stephen T. , Raleigh David R. , Klisch Tiemo , Patel Akash J. 
Published: March 2024

INTRODUCTION:
In the WHO 2021 criteria, homozygous deletion of cyclin-dependent kinase-inhibitor 2A and/or B (CDKN2A/B) qualifies meningiomas as Grade 3. We assessed the effect of heterozygous CDKN2A/B loss, which was not addressed by the WHO, on recurrence-free survival (RFS), and evaluated the relationship of CDKN2A/B losses with our MenG classification.

METHODS:
Methylation and RNA-profiling were used to assign MenG. Methylation data identified heterozygous or homozygous loss of CDKN2A/B in 776 meningiomas. Clinical data for 659 tumors were used for survival analysis.

RESULTS:
Of the 776 tumors, 738 (95.1%) had intact CDKN2A/B, 20 (2.5%) had heterozygous loss of both CDKN2A/B, 3 (0.4%) had homozygous CDKN2A and heterozygous CDKN2B loss, and 15 (1.9%) had homozygous loss of both CDKN2A/B. Of the 659 tumors with clinical data, 28 (4.2%) showed any CDKN2A/B loss. RFS was based on concordant CDKN2A/B status. Tumors with intact CDKN2A/B (n = 631, mRFS not reached) had improved RFS compared to those with heterozygous loss (n = 15, mRFS = 29.1 mo) and homozygous loss (n = 11, mRFS = 10.5mo; p < 0.0001 all groups, homozygous vs. heterozygous p = 0.4, Log-rank). Nearly all tumors with CDKN2A/B loss (27/28) were MenG C, the most aggressive group. Among MenG C tumors, presence of either homozygous (n = 11, mRFS 10.5mo) or heterozygous (n = 14, mRFS 25.1 mo) CDKN2A/B loss led to shortened RFS than those with intact CDKN2A/B (n = 198, mRFS 61.4 mo; p < 0.0001 Log-rank). Median RFS was not reached in MenG A (n = 173) or MenG B (n = 259). Tumors with any CDKN2A/B loss had worse survival when controlling for WHO Grade (Grade: 2 p < 0.0001, 3 p = 0.035, Log-rank).

CONCLUSIONS:
Heterozygous CDKN2A/B loss (not addressed in the 2021 WHO criteria) leads to poor outcome in meningioma even when controlling for molecular subgroup (MenG C) or WHO grade (2/3). All but 1 tumor (27/28) with any type of CDKN2A/B loss were MenG C.
322 A Cost Analysis of Medical Students Applying to Neurological Surgery Residency: An Analysis of the Texas STAR Database
Authors: Lucke-Wold Brandon 
Published: March 2024

INTRODUCTION:
Medical Students applying to competitive residencies such as neurosurgery incur substantial costs associated with interviews, away rotations, and application fees. Researchers in the past have examined the sources of expenses during the residency application cycle, but few studies have compared the expenses prior to and during the COVID-19 pandemic.

METHODS:
The TEXAS STAR database was surveyed for applicants of neurosurgical residency programs during the COVID-19 pandemic (2021) and post-pandemic (2022). In total, 66 applicants for the 2021 application cycle and 50 applicants for the 2022 application cycle completed the survey. We compared the application fees, away rotations cost, interview cost, and total expenses as reported by the neurosurgery applicants of the 2021 and 2022 application cycle. A Shapiro-Wilk test was used to test for data normality, and a Mann-Whitney U-Test was used to compare costs during the 2021 and 2022 neurosurgery application cycle.

RESULTS:
There was a statistically significant reduction in total expenses in 2021 vs 2022 ($3,934 vs $9,860). Interview expenses and away rotation expenses were also decreased in 2021 vs 2022 (interview expenses $786 vs $4511, away rotation $1,083 vs $3,000, p < 0.001). Application fee expenses were not different between the 2021 and 2022 application cycle. Regional stratification revealed the greatest reduction in cost, an $11,908 savings, in the South region for the year of 2021.

CONCLUSIONS:
Our study revealed that the COVID-19 pandemic caused a significant reduction in the total fees associated with the neurosurgical residency application. The use of virtual platforms in place of in-person interviews could lessen the financial burden on applicants and alleviate socioeconomic barriers in the neurosurgical application process even after COVID-19.
329 Same Day Discharge After Craniotomy for Brain Tumor Resection: Enhancing Patient Selection Through a Prognostic Scoring System
Authors: Levy Adam , Merenzon Martin Andres , Bhatia Shovan , Costello Meredith , Di Long , Lu Victor M. , Morell Alexis Andres , Chand Daggubati Lekhaj , Shah Ashish H. , Komotar Ricardo Jorge , Ivan Michael E. 
Published: March 2024

INTRODUCTION:
Neurosurgery, among other surgical fields, is in the midst of a shift in patient management with enhanced recovery and same day discharge protocols slowly becoming more popular and feasible. While such protocols reduce risk of nosocomial complications and improve patient satisfaction, appropriate patient selection remains an area of debate.

METHODS:
Three arms of analysis were carried out. First, clinical data of SDD patients was prospectively collected between August 2021 and August 2022. In parallel, a retrospective analysis of patients who qualified for SDD but were excluded at surgeon clinical discretion over the same period was performed. Third, a comparative analysis of the pilot and follow-up studies was done from which a clinical scoring system for patient selection was derived.

RESULTS:
Over the length of the study, 31 of 334 patients were selected for SDD while 59 qualified by previously defined criteria but were not selected at the surgeon’s discretion. There was no difference in outcomes between the two groups nor any post-operative complications among the SDD group within 30 days of surgery. Preoperative clinical characteristics found to be significantly different between the two cohorts (Left sided lesion, extra-axial pathology, prior treatment of brain tumor, and tumor volume < 11.75 cm3) were included in a predictive scoring system for successful SDD. The system was found to significantly predict high or low likelihood for successful SDD when tested on the mixedprospective cohort.

CONCLUSIONS:
This study provides a straightforward clinical scoring system for appropriate selection of candidates for SDD after craniotomy for brain tumor resection. The application of this clinical tool aims to aid clinicians in appropriate admission course selection and builds on the growing literature surrounding same-day and outpatient cranial neurosurgery.