Diverse Roles of the Exon Junction Complex Factors in the Cell Cycle, Cancer, and Neurodevelopmental Disorders-Potential for Therapeutic Targeting.

The exon junction complex (EJC) plays a crucial role in regulating gene expression at the levels of alternative splicing, translation, mRNA localization, and nonsense-mediated decay (NMD). The EJC is comprised of three core proteins: RNA-binding motif 8A (RBM8A), Mago homolog (MAGOH), eukaryotic initiation factor 4A3 (eIF4A3), and a peripheral EJC factor, metastatic lymph node 51 (MLN51), in addition to other peripheral factors whose structural integration is activity-dependent. The physiological and mechanistic roles of the EJC in contribution to molecular, cellular, and organismal level function continue to be explored for potential insights into genetic or pathological dysfunction. The EJC's specific role in the cell cycle and its implications in cancer and neurodevelopmental disorders prompt enhanced investigation of the EJC as a potential target for these diseases. In this review, we highlight the current understanding of the EJC's position in the cell cycle, its relation to cancer and developmental diseases, and potential avenues for therapeutic targeting.

Intrasaccular Flow Disruption: Examining Global Access and Research Trends.

The Woven EndoBridge (WEB) and other intrasaccular flow disruptors show promise in treating intracranial aneurysms. We performed a bibliometric analysis to provide novel insights into the trends and trajectory of these devices. We systematically assessed bibliometric data such as citations, journals, study designs, open access status, and multi-institutional involvement for the top-cited articles on WEB and other disruptors. The top 100 cited studies on the WEB had citations from 7 to 144 (mean ± standard deviation 35.6 ± 29.5), while only 33 studies were published for other intrasaccular flow disruptors (4.24 ± 8.45). Of the other devices, the Contour has the most publications (n = 21). Retrospective reviews were the most common study design for both WEB and other intrasaccular devices. France published the most studies in the top 100 WEB papers (n = 35), while Germany led for other flow disruptors (n = 10). In all studies analyzed, no senior authors from Africa are present. The top 100 WEB publications had a higher mean citation count (35.6 vs. 4.24, P<0.001), higher mean citations per year (5.24 vs. 1.03, P<0.01), and a higher proportion of multi-institutional collaborations (44.0% vs. 12.1%, P<0.01) than other intrasaccular flow disruptors. In conclusion, countries with the most publications on WEB are not necessarily the ones leading the way with newer intrasaccular devices, while study designs remain similar. There is a limited contribution to the literature outside of Europe and North America. Our findings identify notable collaborators and trends, providing a snapshot of the field and a roadmap for future research.

Readability of cerebrovascular diseases online educational material from major cerebrovascular organizations.

INTRODUCTION: The internet is an essential resource for patients and their loved ones to understand their medical conditions, and professional medical organizations have taken great strides to develop educational material targeting patients. The average American reads at a seventh to eighth grade reading level, hence it is important to understand the readability of this medical information to ensure patients comprehend what is being presented. METHODS: In January 2023, online patient education material was downloaded from major cerebrovascular healthcare organizations and assessed using eight assessments, including Bormuth Cloze Mean, Bormuth Grade Placement, Coleman-Liau (grade levels), Coleman-Liau (predictive cloze scores), Flesch Reading Ease (FRE), and Fry. RESULTS: A total of 32 files were extracted from six organizations and analyzed across 15 readability measures. None of the organizations met the federal government guidelines for grade-level readability. This held constant across all measured tests. Two organizations had above a postgraduate level. The FRE graphs do not identify any organizations with material below a ninth grade reading level, while the American Association of Neurological Surgeons (AANS) and the Society of Interventional Radiology (SIR) have a postgraduate readability level. The Fry graphs show similar results, with AANS/CNS Cerebrovascular Section, Society of NeuroInterventional Surgery (SNIS), SIR, and AANS having college-level readability. The lowest readability across all measures is only at an early seventh grade reading level. CONCLUSIONS: Current health literacy content for cerebrovascular patients is far above the recommended readability level. We provide straightforward suggestions for how major professional organizations should improve their informational material on cerebrovascular diseases to improve patient understanding.

Advancing endovascular neurosurgery training with extended reality: opportunities and obstacles for the next decade.

Background: Extended reality (XR) includes augmented reality (AR), virtual reality (VR), and mixed reality (MR). Endovascular neurosurgery is uniquely positioned to benefit from XR due to the complexity of cerebrovascular imaging. Given the different XR modalities available, as well as unclear clinical utility and technical capabilities, we clarify opportunities and obstacles for XR in training vascular neurosurgeons. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Studies were critically appraised using ROBINS-I. Results: 19 studies were identified. 13 studies used VR, while 3 studies used MR, and 3 studies used AR. Regarding specific educational applications, VR was used for simulation in 10 studies and anatomical modeling in 3 studies. AR was only used for live intra-operative guidance (n = 3 studies). MR was only used for modeling and intra-operative teaching. Considering disease-specific uses, XR enhanced trainee understanding of intracranial aneurysms (n = 12 studies) and stroke (n = 7). XR trained surgeons in diverse neurosurgical procedures, including aneurysm coiling (n = 5 studies), diagnostic angiography (n = 5), and thrombectomy (n = 5). Conclusions: Anatomical modeling with VR and MR enhances neurovascular anatomy education with patient-specific, 3-D models from imaging data. AR and MR enable live intra-operative guidance, allowing experienced surgeons to remotely instruct novices, potentially improving patient care and reducing geographic disparities. AR overlays enhance instruction by allowing the surgeon to highlight key procedural aspects during training. Inaccurate tracking of surgical tools is an XR technological barrier for modeling and intra-operative training. Importantly, the most reported application of XR is VR for simulation-using platforms like the Mentice VIST and Angio Mentor. 10 studies examine VR for simulation, showing enhanced procedural performance and reduced fluoroscopy use after short training, although long-term outcomes have not been reported. Early-stage trainees benefited the most. Simulation improved collaboration between neurosurgeons and the rest of the surgical team, a promising role in interprofessional teamwork. Given the strength of VR for simulation, MR for simulation is an important gap in the literature for future studies. In conclusion, XR holds promise for transforming neurosurgical education and practice for simulation, but technological research is needed in modeling and intra-procedural training.

Extended Length of Stay After Mechanical Thrombectomy for Stroke: A Single-Center Analysis of 703 Patients.

BACKGROUND AND OBJECTIVES: Mechanical thrombectomy (MT) is crucial for improving functional outcomes for acute ischemic stroke. Length of stay (LOS) is a reimbursement metric implemented to incentivize value-based care. Our study aims to identify predictors of LOS in patients undergoing MT at a high-volume center in the United States. METHODS: This was a retrospective study of patients who underwent MT at a single institution from 2017 to 2023. Patients who experienced mortality during their course of hospital stay were excluded from this study. Extended LOS (eLOS) was defined as the upper quartile (≥75th) of the median duration of hospital stay. Univariate and multivariate analyses were performed, with P values < .05 denoting statistical significance. RESULTS: Seven hundred three patients met criteria for inclusion. The median age of the cohort was 72 years (IQR: 61-82), and 57.2% was female. The median LOS was 6, IQR: 4-10. A total of 28.9% of the cohort (n = 203) patients experienced eLOS. The multivariate regression model identified age (odds ratio [OR]: 0.98, 95% CI: 0.97-0.99), diabetes mellitus (OR: 1.68, 95% CI: 1.15-2.44), and hemorrhagic transformation of stroke (OR: 2.89, 95% CI: 0.39-0.90) as predictors of eLOS, whereas antiplatelet use before admission (OR: 0.55, 95% CI: 0.34-0.89) and higher baseline modified Rankin Scale before stroke were associated with lower odds (OR: 0.59 [0.39-0.90]; P < .05) of eLOS. CONCLUSION: By identifying predictors of eLOS, we provide a foundation for targeted interventions aimed at optimizing post-thrombectomy care pathways and improving patient outcomes. The implications of our study extend beyond clinical practice, offering insights into healthcare resource utilization, reimbursement strategies, and value-based care initiatives.

The Physiological Roles of the Exon Junction Complex in Development and Diseases.

The exon junction complex (EJC) becomes an increasingly important regulator of early gene expression in the central nervous system (CNS) and other tissues. The EJC is comprised of three core proteins: RNA-binding motif 8A (RBM8A), Mago homolog (MAGOH), eukaryotic initiation factor 4A3 (EIF4A3), and a peripheral EJC factor, metastatic lymph node 51 (MLN51), together with various auxiliary factors. The EJC is assembled specifically at exon-exon junctions on mRNAs, hence the name of the complex. The EJC regulates multiple levels of gene expression, from splicing to translation and mRNA degradation. The functional roles of the EJC have been established as crucial to the normal progress of embryonic and neurological development, with wide ranging implications on molecular, cellular, and organism level function. Dysfunction of the EJC has been implicated in multiple developmental and neurological diseases. In this review, we discuss recent progress on the EJC's physiological roles.