bluuebunny/crossref_metadata_2025_split huggingface dataset:
182 Purification and Characterization of Human Neural Stem and Progenitor Cells
Authors: He Joy , Liu Daniel , Sinha Rahul , Eastman Anna , Toland Angus , Morri Maurizio , Neff Norma , Vogel Hannes , Uchida Nobuko , Weissman Irving 
Published: March 2024

INTRODUCTION:
The human brain undergoes rapid development at mid-gestation from a pool of neural stem and progenitor cells (NSPCs) that give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. Functional study of these cell types has been hampered by a lack of precise purification methods.

METHODS:
We combine high-dimensional flow cytometry with single cell transcriptomics to comprehensively purify and functionally characterize NSPCs from the developing human brain during mid-gestation. We utilize index sorting based on the combinatorial expression of cell-surface markers (immunophenotype) to directly link surface-marker expression to the expressed transcriptomes of single cells, allowing for rigorous validation of sort purity. We further demonstrate the functional properties of each identified cell type in vitro and in vivo.

RESULTS:
CD24-THY1-/lo cells were enriched for radial glia, which robustly engrafted and differentiated into all three neural lineages in the mouse brain.THY1hi cells marked unipotent oligodendrocyte precursors committed to an oligodendroglial fate, and CD24+ THY1-/lo cells marked committed excitatory and inhibitory neuronal lineages. Notably, we identify and functionally characterize a novel transcriptomically distinct THY1hiEGFRhiPDGFRA- bipotent glial progenitor cell, which is lineage-restricted to astrocytes and oligodendrocytes, but not to neurons.

CONCLUSIONS:
The results presented here are strong proof-of-concept that distinct cell types from the developing brain can be prospectively isolated based on the expression of multiple surface markers. The combined results from scRNA-seq, in vitro differentiation, and in vivo transplantation offers the most rigorous interrogation of NSPCs’ transcriptomic identities and functional behavior. The modular nature of our antibody panel allows for the easy expansion or simplification of the panel, based on the cell-type of interest, thus providing a valuable tool for future investigation of both molecular and functional NSPC heterogeneity.
187 Achondroplasia Natural History Study (CLARITY): 60-Year Experience With Hydrocephalus in Achondroplasia From Four Skeletal Dysplasia Centers
Authors: Campbell Jeffrey , Piatt Joseph , Hoover-Fong Julie Elizabeth , Bober Michael , Lagare Janet M. 
Published: March 2024

INTRODUCTION:
This study is the largest to date to look at the treatment of hydrocephalus in achondroplasia.

METHODS:
CLARITY (The Achondroplasia Natural History Study) is a registry for clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2017. Data included surgeries with indications and complications, medical diagnoses, and radiographic information.

RESULTS:
1374 patients with achondroplasia were included in this study. 124 (9%) of these patients underwent treatment of hydrocephalus at a median age of 14.6 months. There was wide variation by center and decade of birth, with treatment ranging from 0% to 28% of patients, although in the most recent decade, it fell to 3.4% of patients. Requiring cervicomedullary decompression (CMD) predicted treatment of hydrocephalus with an odds ratio of 5.8 (95% CI 3.9-8.4), although that association has disappeared in those born since 2010 with an odd’s ratio of 1.1 (95% CI 0.2-5.7). In patients born since 1990, treatment of hydrocephalus with an ETV has become more common. Kaplan Meier analysis suggests a single ETV will treat hydrocephalus in roughly half of these patients.

CONCLUSIONS:
While children with achondroplasia have enlarged intracranial CSF spaces and macrocephaly, treatment of hydrocephalus has become relatively unusual in the last twenty years. Historically there was a significant association between symptomatic foramen magnum (FM) stenosis and treatment of hydrocephalus, although concurrent treatment of both has fallen out of favor since CMD alone will treat hydrocephalus in some patients. While understood as communicating hydrocephalus, endoscopic third ventriculostomy (ETV) appears to be reasonably successful in certain patients and should be considered an option in selected patients.
194 Responsive Neurostimulation Targeting the Centromedian Nucleus of the Thalamus Improves Seizure Control in Idiopathic Generalized Epilepsy and Select Multifocal Disease
Authors: Nanda Pranav , Walton Ashley , Sisterson Nathaniel , Richardson Robert Mark 
Published: March 2024

INTRODUCTION:
Although more than 30% of epilepsy patients are drug resistant, many have not traditionally been considered surgical candidates due to generalized or multifocal disease. However, responsive neurostimulation (RNS) of the centromedian nucleus (CM) of the thalamus appears promising for this patient population. We present outcomes following CM RNS for patients with idiopathic generalized epilepsy (IGE) or multifocal disease, with subgroup analyses of patients’ seizure types and targeting methodology.

METHODS:
21 patients with drug resistant epilepsy underwent bilateral CM RNS implantation. Electrodes were localized and volumes of tissue activation (VTAs) were modeled in Lead-DBS. Outcome measures were extracted from electronic medical records. Clinical outcomes over time were compared between patients’ seizure types and RNS recorded long-episodes, and VTA overlap with thalamic nuclei was compared between patients with direct and indirect targeting methodologies.

RESULTS:
For patients with at least 1-year of follow up, average seizure reduction from pre-operative baseline was 81.3%, with 3 Engel class 1 patients, 5 Engel class 2, 8 Engel class 3, and 0 Engel class 4. Average seizure reduction was greatest for non-lesional multifocal patients. Average time to worthwhile seizure reduction was 217 days, and was shortest for myoclonic IGE patients. Long-episodes were associated with seizure reduction in IGE patients only. Direct targeting led to more anterior and medial electrodes with greater VTA overlap with CM.

CONCLUSIONS:
CM RNS may provide significant relief for IGE and multifocal epilepsy patients. Subsets of these patient populations may particularly benefit from CM RNS. Direct targeting may facilitate more selective stimulation of the CM. The refinement of stimulation targeting, tuning of RNS system parameters, and deliberate patient selection are ongoing areas of investigation.
200 DWI and ADC Changes in Patients With Glioblastoma IDH-Wild Type Following Surgical Tumor Resection
Authors: Rojas Pavel Pichardo , Bandopadhay Josh , Nunez Luis C. , Esquenazi Yoshua , Dono Ostorga Antonio Gabriel , Rodriguez Andres , Tandon Nitin , Riascos Roy 
Published: March 2024

INTRODUCTION:
Current standard of care for glioblastoma (GBM) entails maximal tumor resection to achieve better outcomes while preserving neurological function. Early postoperative DWI has elucidated that peritumoral ischemia is common following glioma resection, but radiographic characteristics, risk factors, and outcomes have not been well described.

METHODS:
This retrospective cohort included 324 patients (18-86 years) who underwent surgical resection for glioblastoma IDH-wildtype between 2005 and 2022. All patients had structural MRI and DWI acquired preoperatively and within 72 hrs after resection. Areas of restricted diffusion on postoperative DWI were classified as rim, sector, mixed, or remote.

RESULTS:
Areas of restricted diffusion on postoperative DWI were found in 173 (53%) patients. 55 (32%) were rim-shaped, 103 (59%) sector-shaped, 10 (6%) mixed, and 5 (3%) remote. Preoperative tumor volume was positively correlated with areas of ischemia (p = 0.048), but peritumoral DWI was not correlated with decreased overall survival (OS) or Karnofsky Performance Score (KPS). In the full cohort analysis, gross total resection (GTR) correlated with improved OS compared to subtotal total resection (STR) (p = 0.016); however, subgroup analysis revealed that this survival benefit was exclusively found in patients without peritumoral infarction on DWI (21 months vs. 13 months, p = 0.043).

CONCLUSIONS:
Larger tumor volume was a risk factor for larger peritumoral infarction. The survival benefit of GTR was only seen in patients who did not experience postoperative peritumoral infarction, underscoring the importance of maximal safe tumor resection. Future study on specific causes of postoperative peritumoral infarctions may improve surgical management and outcomes in glioblastoma patients.
207 Intraoperative Functional Re-mapping Unveils Evolving Patterns of Cortical Plasticity
Authors: Ng Sam , Valdes Pablo Andres , Moritz-Gasser Sylvie , Lemaitre Anne-Laure , Duffau Hugues , Herbet Guillaume 
Published: March 2024

INTRODUCTION:
Diffuse low-grade gliomas (DLGG) induce a compensatory modulation of the anatomo-functional architecture, making this kind of brain tumours an ideal lesion model to study the dynamics of neuroplasticity. Direct electrostimulation (DES) mapping is a well-tried procedure used during awake resection surgeries to spare cortical epicenters which are critical for a range of functions. Because DLGG is a chronic disease, it inevitably relapses years after the initial surgery, and thus requires a second surgery to reduce tumour volume again.

METHODS:
We capitalized on a series of 101 DLGG patients who benefited from two DES-guided neurosurgeries usually spaced several years apart, resulting in a DES dataset of 2082 cortical sites. We used a multi-step approach to generate probabilistic neuroplasticity maps that reflected the dynamic rearrangements of cortical mappings from one surgery to another, both at the population and individual-level.

RESULTS:
Voxel-wise neuroplasticity maps revealed regions with a high potential of evolving reorganizations, including the supplementary motor area (SMA), the dorsolateral prefrontal cortex (dlPFC), the anterior ventral premotor cortex (vPMC) and the middle superior temporal gyrus (STG). Parcel-wise neuroplasticity maps confirmed this potential for the dlPFC, the anterior and the ventral precentral gyrus. A series of clustering analyses revealed a topological migration of clusters, especially within the left dlPFC and STG (language sites); the left vPMC (speech arrest/dysarthria sites) and the right SMA (negative motor response sites). At the individual level, these dynamic changes were confirmed for the dlPFC (bilateral), the left vPMC and the anterior left STG (threshold free cluster enhancement, 5000 permutations, family-wise-error-corrected).

CONCLUSIONS:
Our results provide a critical insight into the dynamic potential of DLGG-induced continuing rearrangements of the cerebral cortex, with considerable implications for re-operations.
215 Reexamining Nimodipine's Effect on Neurological Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis
Authors: Derrico Nicholas , Lucas Kathryn , Washington Chad W. 
Published: March 2024

INTRODUCTION:
Nimodipine therapy is a guideline-directed treatment to improve neurological outcomes after ruptured aneurysmal subarachnoid hemorrhage (aSAH).

METHODS:
We performed a systematic review and meta-analysis of ruptured aSAH trials reporting ‘good’ neurological outcomes, defined as Modified Rankin Scale 0-2 or the study’s own criteria. ‘Pre-nimodipine’ studies included those prior to the use of nimodipine. ‘Nimodipine’ studies gave nimodipine as an investigational drug, leading to its widespread acceptance. ‘Post-nimodipine’ studies gave nimodipine as standard-of-care to controls. 172 studies were screened, 122 were evaluated in full for eligibility, and 52 were included. Rates of ‘good’ outcomes were aggregated and compared with respect to era and nimodipine status.

RESULTS:
‘Nimodipine’ era nimodipine recipients had exceptionally high rates of ‘good’ neurological outcome at 81% (95% CI 68-92%). ‘Post-nimodipine’ era nimodipine recipients had a 67% (95% CI 64-70%) rate of ‘good’ neurological outcome. When subcategorized by decade, this was stable at 68% (95% CI 62-73%), 64% (95% CI 58-69%), and 70% (95% CI 64-73%). Those not receiving nimodipine in the ‘pre-nimodipine’ and ‘nimodipine’ eras also had a similar chance of ‘good’ neurological outcome at 60% (95% CI 49-71%) and 69% (95% CI 55-82%) respectively. ‘Nimodipine’ era studies were too heterogeneous to be statistically different, however 5 of the 7 are outside 95% confidence intervals when compared to any other group.

CONCLUSIONS:
Approximately 60-70% of patients in randomized studies of ruptured aSAH have ‘good’ neurologic outcomes regardless of nimodipine status or era of treatment. The studies that examined nimodipine as an intervention, leading to its acceptance as the standard of care, are historical outliers. This raises concerns about nimodipine’s overall efficacy in treating aSAH, and the validity of its recommendation in the ruptured aSAH management guidelines.
230 Machine Learning for Automated and Real-time 2D-3D Registration of the Spine Using Only a Single Radiograph
Authors: Abumoussa Andrew , Gopalakrishnan Vivek , Succop Benjamin Sterling , Galgano Michael Anthony , Jaikumar Sivakumar , Lee Yueh , Bhowmick Deb A. 
Published: March 2024

INTRODUCTION:
Authors present a 2-dimensional to 3-dimensional (2D-3D) registration algorithm that identifies the position of a C-arm relative to a 3D volume.

METHODS:
This work utilizes digitally reconstructed radiographs (DRR) which are synthetic radiographic images generated by simulating the x-ray projections as they would pass through a CT volume. To evaluate our algorithm, we used cone-beam CT data from 127 patients obtained from a de-identified registry of cervical, thoracic, and lumbar scans. We systematically evaluated and tuned a self-supervised algorithm, quantified the limitations and convergence rate of our model by simulating C-arm registrations with 80 randomly simulated DRRs for each CT volume. The endpoints for this study were the time to convergence, accuracy of convergence for each of the C-arm's degrees of freedom (DoF), and overall registration accuracy based on a voxel-by-voxel measurement.

RESULTS:
10,160 unique fluoroscopic images were simulated from 127 CT scans. Our algorithm successfully converged to the correct solution 81% of the time with an average of 1.97 seconds of computation. The fluoroscopic images for which the algorithm converged to the solution achieved 99.9% registration accuracy despite only utilizing single-precision computation for speed. Our algorithm was found to be optimized for convergence when the search space was limited to a ± 45° offset in the RAO/LAO, cranial/caudal and receiver rotation angles with the radiographic isocenter contained within 8000cm3 of the volumetric center of the CT volume.

CONCLUSIONS:
The machine learning algorithm we present has the potential to aid surgeons with many aspects of spine surgery through an automated 2D-3D registration process. Future work will focus on algorithmic optimizations adn deep-learning to improve the convergence rate and speed profile.
235 IL-4/13 Blocking Peptide (KROS-401) Inhibits M2 Macrophage Polarization in vitro and Demonstrates Anti-tumor Activity in a Murine Model of Glioblastoma
Authors: Michel Michelot , Israel Liron , Tusa Lavieri Miguel Eduardo , Wang Hongqiang , Miyaguchi Ken , Mohyeddinipour Sarah , Watanabe Junji , Black Keith L. , Murali Ramachandran , Yu John 
Published: March 2024

INTRODUCTION:
Glioblastoma (GBM) is the most aggressive primary brain malignancy with a median survival of 14 months. Tumor-associated macrophages (TAMs) comprise up to 40% of the GBM tumor mass and are significant enablers of an immunosuppressive tumor microenvironment (TME), limiting immunotherapeutic efficacy. TAMs are generally classified as M2 macrophages that demonstrate a pro-tumor phenotype and increased CD206 surface marker expression. Reducing the M2 macrophage population in tumors has shown benefit in preclinical studies across various cancers. Interleukins (IL)-4 and -13 both play a role in polarizing macrophages to an M2 state. We developed a peptide inhibitor (KROS-401) that targets the shared IL-4Ra subunit of the IL-4 and -13 receptor complex to inhibit macrophage polarization to an M2 phenotype and reprogram the immunosuppressive TME.

METHODS:
Human peripheral blood mononuclear cell (PBMC)-derived macrophages were isolated and treated with KROS-401 in the presence of IL-4 and IL-13 cytokines. M2 (CD206) surface markers were assessed by flow cytometry. The efficacy of KROS-401 peptide was examined using an intracranially implanted syngeneic murine model with luciferase-expressing GL261, a glioma cell line. Mice were inspected daily for survival and tumor growth was tracked by non-invasive in vivo bioluminescent imaging (BLI).

RESULTS:
Human PBMC-derived macrophages treated with KROS-401 displayed a dose-dependent decrease in M2 (CD206) cell surface markers. KROS-401 peptide inhibitor demonstrated anti-tumor activity in GL261 glioma-bearing mice with a significantly increased probability of survival compared to control (p = 0.0046) with a median survival of >40 days versus 27 days, respectively.

CONCLUSIONS:
KROS-401 inhibits M2 polarization of human macrophages in vitro and tumor growth in vivo. These findings highlight this IL-4/IL-13 peptide inhibitor as a potential immunomodulator of the TME for the treatment of GBM.
238 Quality of Life After Chronic Subdural Hematoma Surgery—GET-UP Randomized Clinical Trial's 1 Year Results
Authors: Sousa Sérgio , Pinto Vasco Sá , Grande Ana , Fernandes Armindo Picão , Batata Rodrigo , Costa Tiago , Silva João Fernandes , Rangel Rui , Calheiros Alfredo 
Published: March 2024

INTRODUCTION:
Timing for mobilization after chronic subdural hematoma (cSDH) surgery is highly heterogeneous among neurosurgical centers around the world. Nonetheless, there is a scarcity of high-quality evidence addressing this question.

METHODS:
A total of 208 patients were randomized to either an early mobilization group (EMG), where mobilization is required within the first 12 hours post-op; or to a bed rest group (BRG) where they remain recumbent for 48 hours after surgery. All 208 patients were interviewed by telephone one year after surgery. A score of 16 or more in the Mini Mental State Examination was mandatory for study inclusion. Quality of life was assessed by applying the 36-Item Short Form Health Survey (SF-36).

RESULTS:
A total of 134 patients (73 in the EMG and 61 in the BRG) were included. EMG patients performed significantly better in six of the eight domains of SF-36 questionnaire. The mean scores obtained were, in the EMG and in the BRG, respectively, 73.4 and 61.7 in the Physical Functioning (p = 0.017); 88.6 and 75.8 in the Social Functioning (p = 0.004); 67.6 and 61.4 in Mental Health (p = 0.029); 87.4 and 78.6 in Emotional Performance (p = 0.036); 61.2 and 50.4 in Vitality (p = 0.011); and 58.5 and 47.1 in General Health (p = 0.007). In the two remaining dimensions, Physical Performance and Body Pain, results were also superior in the EMG but without statistical significance. Quality of life was negatively impacted by the occurrence of medical complications, with the Physical Performance domain reaching statistical significance (p = 0.016).

CONCLUSIONS:
GET-UP trial’s results argue strongly towards an early mobilization protocol, as this strategy leads to a significant improvement in the quality of life of patients after cSDH surgery.
246 Algorithmic CT Scan Analysis for Prognosticating Brain Injury: A Preliminary Effort
Authors: Broadbent Charles , Sridhar Sharada Kadaba , Gupta Rishabh , Sterk Brett , Koller Michael , Kuang Rui , Samadani Uzma 
Published: March 2024

INTRODUCTION:
Predicting which trauma patients will progress to brain death is currently based on history, physical examination and radiographic findings.

METHODS:
38 trauma subjects, 18 which progressed to brain death (BD), who suffered from high-velocity trauma with presumed diffuse axonal injury, cardiopulmonary/respiratory arrest, and/or found down were included. BLAST-CT was used to identify four lesion types: intraparenchymal hemorrhage, extra-axial hemorrhage, perilesional oedema, and intraventricular hemorrhage. Cerebrospinal fluid volumes were extracted using SimpleITK. These two sets of features were obtained from whole head CT scans and within 117 standardized brain atlas regions. Five ROC curves for classifying BD versus non-BD were generated using a support vector machine trained on (1) BLAST-CT (4 features), (2) Regional BLAST-CT (468 features), (3) Regional CSF volumes (117), (4) BLAST-CT + Regional CSF volumes (121 features), and (5) Regional BLAST-CT + Regional CSF volumes (585 features).

RESULTS:
For BLAST-CT alone, area under the curve (AUC), sensitivity, specificity, and accuracy in classifying BD were 0.7806, 61.11%, 95.00%, and 78.95% respectively. For regional BLAST CT, they were 0.7611, 55.56%, 100%, and 78.95% respectively. For regional CSF volume, they were 0.7056, 94.44%, 50.00%, and 71.05%. For BLAST-CT + regional CSF volumes, they were 0.8389, 94.44%, 65.00%, and 79.85%. For regional BLAST-CT + regional CSF volumes, they were 0.9083, 83.33%, 100%, 92.11%.

CONCLUSIONS:
Results indicate that the present model using regional BLAST-CT + regional CSF volumes is able to classify brain death with a large specificity, sensitivity, and accuracy above 90%. Given the clinical value of a tool to assist physicians in predicting progression to BD, additional prospective trials with larger samples and testing cohorts should be conducted.
255 Frailty Is Associated With Decreased 365-day Survival in Adult Patients With Operative and Nonoperative Traumatic Subdural Hemorrhage
Authors: Courville Evan , Owodunni Oluwafemi , Courville Jordyn , Kassicieh Alex James , Hynes Allison , Schmidt Meic H. , Bowers Christian Andrew 
Published: March 2024

INTRODUCTION:
Traumatic subdural hematoma (tSDH) is observed frequently in traumatic brain injury (TBI) patients and is one of the commonest neurosurgical emergencies. tSDH patients require rapid evaluation and treatment in order to achieve the best possible results. There is a paucity of literature on frailty’s impact in TBI patients.

METHODS:
We performed a retrospective review of tSDH patients in the ACS-TQIP® database between 2007-2020. We employed multivariable regression models to examine the independent relationship of frailty, identified by the modified frailty index-5 (mFI-5) with the endpoints of major complications, length of stay (LOS), mortality, and discharge to a higher level of care. Additionally, we employ Kaplan-Meier (K-M) plots to examine the probability of survival following tSDH across the various mFI-5 frailty risk strata.

RESULTS:
340,096 patients were managed nonoperatively and 41,658 operatively. The median age of the patients was 70.0 (IQR: 54.0, 81.0) nonoperative, and 71.0 (57.0, 80.0) operative cohorts. Multivariate analysis demonstrates a stepwise dose response relationship with outcomes p < 0.001. In both cohorts, there was an 18-86% in mortality i.e. nonoperative: frail (OR: 1.18 [95% CI 1.13, 1.23]), very frail (OR: 1.75 [95% CI 1.65, 1.86]); and operative: frail (OR: 1.21 [95% CI 1.12, 1.32]), very frail (OR: 1.86 [95% CI 1.66, 2.09]). Survival probability markedly decreased across frailty strata within the first 100 days.

CONCLUSIONS:
Frailty was associated with major complications, LOS, mortality, and discharge to a higher-level care facility in patients with tSDH. Rapid deployment of point of care frailty risk-assessment allows clinicians to improve prognostication for patients and their families and allocate resources more precisely in order to try to achieve better outcomes.