Search

This article discusses the findings of a study on moyamoya disease (MMD), a condition characterized by the occlusion of the intracranial internal carotid artery and the formation of collateral vessels. The study focuses on the differential protein metabolism among different subtypes of MMD and the role of WNT4 (wingless‐type MMTV integration site family member 4) in causing cellular impairments by reducing microtubule stability. The researchers used proteomic profiling and in vitro experiments to identify the differences in protein metabolism and explore the potential mechanisms of haemorrhagic MMD. The study suggests that overexpression of WNT4 may lead to decreased stability of cellular microtubules, which could contribute to the rupture and hemorrhage of moyamoya vessels. These findings provide new insights into the biomarkers and mechanisms of haemorrhagic MMD. [Extracted from the article]

Indirect bypass surgery is an effective treatment for moyamoya disease (MMD), but the success of the surgery depends on the formation of spontaneous collateral vessels, which cannot be accurately predicted before surgery. Developing a prediction nomogram model for neoangiogenesis in patients after indirect revascularization surgery can aid surgeons in identifying suitable candidates for indirect revascularization surgery. This retrospective observational study enrolled patients with MMD who underwent indirect bypass surgery from a multicenter cohort between December 2010 and December 2018. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis identifying potential predictors of good neoangiogenesis. A total of 263 hemispheres of 241 patients (mean ± SD age 24.38 ± 15.78 years, range 1–61 years) were reviewed, including 168 (63.9%) hemispheres with good postoperative collateral formation and 95 (36.1%) with poor postoperative collateral formation. Based on multivariate analysis, a nomogram was formulated incorporating four predictors, including age at operation, abundance of ICA moyamoya vessels, onset type, and Suzuki stage. The C-index for this nomogram was 0.80. Calibration curve and decision-making analysis validated the fitness and clinical application value of this nomogram. The nomogram developed in this study exhibits high accuracy in predicting good neoangiogenesis after indirect revascularization surgery in MMD patients. This model can be very helpful for clinicians when making decisions about surgical strategies for MMD patients in clinical practice. [ABSTRACT FROM AUTHOR]

The greater amberjack is a very important fishery species with high commercial value, and it is distributed worldwide. Transcriptome-based studies on S. dumerili have been limited by an inadequate reference genome and a lack of well-annotated full-length transcripts. In this study, a total of 12 tissues from juvenile and adult fish both sexes were collected for next-generation RNA sequencing (RNA-seq) and full-length isoform sequencing (Iso-seq). For Iso-seq, a total of 163,218, 149,716, and 189,169 high-quality unique transcript sequences were obtained, with an N50 of 5,441, 5,255, and 5,939, from juvenile, adult male and adult female S. dumerili, respectively. We integrated the Iso-seq and RNA-seq data to construct a comprehensive gene annotation and systematically profiled the dynamics of gene expression across the 12 tissues. Our gene models had greater detail and accuracy than those from NCBI and Ensembl, with more precise polyA locations. These resources serve as a foundation for functional genomic studies and provide valuable insights into the molecular mechanisms underlying the development, reproduction and commercial traits of amberjack. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to explore whether preoperative hemoglobin levels could serve as a prospective biomarker for early brain injury in patients with aneurysmal subarachnoid hemorrhage (aSAH). This investigation seeks to discern its association with postoperative complications and unfavorable clinical outcomes. Methods: We conducted a comprehensive analysis of data derived from the LongTeam registry, including patients with aSAH diagnosed between January 2015 and September 2021. These patients were stratified into three distinct groups based on their hemoglobin levels: anemic, standard, and elevated HGB. We employed logistic models featuring spline transformations to assess the relationship between HGB levels and in‐hospital complications. Furthermore, a multivariate Cox proportional hazard model was employed to estimate the impact of elevated hemoglobin levels on the hazard function, which was elucidated through Kaplan–Meier curves. Results: Our study comprised a total of 988 patients, among whom 115 (11.6%) presented preoperative anemia, and 63 (6.4%) exhibited elevated preoperative HGB levels. Following adjustments for potential confounding factors, no significant disparity in risk was evident between anemic patients and those with standard HGB levels. However, individuals with elevated HGB levels displayed a heightened incidence and an increased risk of developing deep vein thrombosis (DVT, odds ratio [OR] = 2.39, 95% confidence interval [CI] = 1.16–4.91, p = 0.018; hazard ratio [HR] = 2.05, 95% CI 1.08–3.92, p = 0.015). Aberrant HGB concentrations did not demonstrate an association with other clinical outcomes. Conclusion: Our findings emphasize that abnormal HGB levels show no association with adverse outcomes at the 90 days mark after accounting for clinical confounding factors in patients with aSAH. Simultaneously, the study illuminates the potential of HGB as an early indicator for identifying patients at a heightened risk of developing DVT. [ABSTRACT FROM AUTHOR]

Glioma is the most common malignant brain tumor in adults with a high mortality and recurrence rate. Integrin alpha 2 (ITGA2) is involved in cell adhesion, stem cell regulation, angiogenesis and immune cell function. The role of ITGA2 in glioma malignant invasion remains unknown. The function and clinical relevance of ITGA2 were analysed by bioinformatics databases. The expression of ITGA2 in parent cells and GSCs was detected by flow cytometry and immunofluorescence double staining. The role of ITGA2 on the malignant phenotype of GSCs and epithelial–mesenchymal transition (EMT) was identified by stem cell function assays and Western blot. The effect of ITGA2 on glioma progression in vivo was determined by the intracranial orthotopic xenograft model. Immunohistochemistry, Spearman correlation and Kaplan–Meier were used to analyse the relationship of ITGA2 with clinical features and glioma prognosis. Biological analysis showed that ITGA2 might be related to cell invasion and migration. ITGA2, enriched in GSCs and co-expressed with SOX2, promoted the invasion and migration of GSCs by activating STAT3 phosphorylation and enhancing EMT. ITGA2 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice. In addition, the expression level of ITGA2 was significantly correlated to the grade of malignancy, N-cadherin and Ki67. High expression of ITGA2 indicated a worse prognosis of glioma patients. As a biomarker for the prediction of prognosis, ITGA2 promotes the malignant invasion of GSCs by activating STAT3 phosphorylation and enhancing EMT, leading to tumor recurrence and poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression. Methods: The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy. Results: DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights. Conclusions: We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker. [ABSTRACT FROM AUTHOR]

This article discusses a study on moyamoya disease (MMD), a rare cerebrovascular condition characterized by narrowing of the intracranial internal carotid arteries. The study aims to identify specific metabolomic changes and biomarkers that can distinguish between different subtypes of MMD for clinical diagnosis. The researchers used metabolomics analysis to identify differential metabolite features in patients with MMD compared to healthy controls. They found that LPC 16:1-2, a type of lipid, was significantly lower in patients with ischaemic MMD and could potentially serve as a biomarker for this subtype. Additionally, the study explored the effects of LPC supplementation on cell viability and angiogenesis in MMD. The findings suggest that LPC supplementation may have therapeutic potential for managing MMD. [Extracted from the article]

Objective: Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post‐operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. Results: Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p < 0.001). The ROC curve eloquently manifested the predictive capacity of right IC Hu in relation to NCI (AUC = 0.650, 95%CI, 0.591–0.709, p < 0.001). Further subgroup analysis revealed significant interactions between right IC Hu and factors such as age, history of heart disease, and Graeb 5–12 score. Sensitivity analysis further upheld the results' significant (p = 0.002). The discrepancy in NCI incidence between the two groups, both prior (p < 0.002) and post (p = 0.039) PSM, exhibited statistical significance. After PSM implementation, the likelihood of NCI displayed an ascending trend with increasing right IC Hu values, from the Hu1 cohort onward, receding post the Hu4 cohort. Conclusion: This study definitively establishes an elevated right IC Hu value in the early stages of emergency admission as an autonomous predictor for ensuing NCI subsequent to aSAH. [ABSTRACT FROM AUTHOR]

Purpose: Intracranial vertebral artery dissecting aneurysm (IVADA) is a rare type of aneurysm with high morbidity and mortality. Recently, the application of pipeline embolization devices (PEDs) has been extended to IVADAs. Here, we aim to investigate the safety and effectiveness of PEDs for IVADAs. Method: We retrospectively reviewed the PLUS database to identify patients who had IVADAs and were treated with PEDs from 2014 to 2019 at 14 centers across China. Data including patient and aneurysm characteristics, procedure details, angiographic and clinical results, relationship with the ipsilateral posterior inferior cerebellar artery (PICA), and patency of the PICA following PED coverage were analyzed. Results: In this study 52 consecutive patients with 52 IVADAs were included. The mean age was 52.33 years and 82.7% were male. With a median follow-up of 10.5 months, the complete occlusion rate was 93.8% (45/48) and no recurrence or in-stent stenosis was detected. The total postoperative complication rate and mortality were 11.5% and 1.9%, respectively. Complications occurred in 9.6% (5/52) of patients within 30 days after the operation, including ischemic stroke in 3 and hemorrhagic stroke in 2. Another patient suffered an ischemic stroke at follow-up, 78.8% (41/52) PICAs were covered by PEDs, 1 case (2.4%) had a functional disability due to PICA occlusion, while 39.0% (16/41) had reduced flow during follow-up but hardly caused any obvious neurological deficits. Patients with IVADA involving PICA had a trend towards more complications (66.7% vs. 51.1%; P = 1). Conclusion: Treating IVADAs with PEDs may be a safe and effective option, with favorable clinical and angiographic outcomes; however, complications associated with this treatment should not be ignored. Registration: http://www.clinicaltrials.gov. Unique identifier: NCT03831672 [ABSTRACT FROM AUTHOR]

Arteriovenous fistulas (AVFs) at the craniocervical junction (CCJ) are uncommon conditions with complex angioarchitecture. The objective of this study was to identify the angioarchitectural features of CCJ-AVF that were predictive of clinical presentation and neurological function. The study encompassed a total of 68 consecutive patients with CCJ-AVF at two neurosurgical centers between 2014 and 2022. Additionally, a systematic review was conducted, including 68 cases with detailed clinical data obtained via PubMed database spanning 1990 to 2022. Clinical and imaging data were collected and pooled together to analyze factors associated with subarachnoid hemorrhage (SAH), myelopathy, and modified Rankin scale (mRS) at presentation. The mean age of the patients was 54.5 ± 13.1 years, with 76.5% of them being male. The most common feeding arteries were V3-medial branches (33.1%), and drainage was frequently through the anterior or posterior spinal vein/perimedullary vein (72.8%). SAH was the most common presentation (49.3%), and an associated aneurysm was identified as a risk factor for SAH (adjusted OR, 7.44; 95%CI, 2.89–19.15). Anterior or posterior spinal vein/perimedullary vein (adjusted OR, 2.78; 95%CI, 1.00–7.72) and male gender (adjusted OR, 3.76; 95%CI, 1.23–11.53) were associated with higher risk for myelopathy. Myelopathy at presentation was an independent risk factor for unfavorable neurological status (adjusted OR per score, 4.73; 95%CI, 1.31–17.12) in untreated CCJ-AVF. The present study identifies risk factors associated with SAH, myelopathy, and unfavorable neurological status at presentation in patients with CCJ-AVF. These findings may help treatment decisions for these complex vascular malformations. [ABSTRACT FROM AUTHOR]

This study aims to investigate the correlation between AVM size and rupture by examining natural history, angioarchitecture characteristics, and quantitative hemodynamics. A retrospective review of 90 consecutive AVMs from the MATCH registry was conducted. Patients were categorized into small nidus (< 3 cm) and large nidus (≥ 3 cm) groups based on the Spetzler-Martin grading system. Natural history analysis used prospective cohort survival data, while imaging analysis examined angioarchitecture characteristics and quantitative hemodynamic parameters measured with QDSA. The small-nidus group had a significantly higher annualized rupture risk (2.3% vs. 1.0%; p = 0.011). Cross-sectional imaging revealed independent hemorrhagic risk factors, including small nidus (OR, 4.801; 95%CI, 1.280–18.008; p = 0.020) and draining vein stenosis (OR, 6.773; 95%CI, 1.179–38.911; p = 0.032). Hemodynamic analysis identified higher stasis index in the feeding artery (OR, 2.442; 95%CI, 1.074–5.550; p = 0.033), higher stasis index in the draining vein (OR, 11.812; 95%CI, 1.907–73.170; p = 0.008), and lower outflow gradient in the draining vein (OR, 1.658; 95%CI, 1.068–2.574; p = 0.024) as independent predictors of AVM rupture. The small nidus group also showed a higher likelihood of being associated with hemorrhagic risk factors. Small AVM nidus has a higher risk of rupture based on natural history, angioarchitecture, and hemodynamics. Clinical Trial Registration-URL:http://www.clinicaltrials.gov. Unique identifier: NCT04572568. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a chronic and progressive cerebrovascular stenosis or occlusive disease that occurs near Willis blood vessels. The aim of this study was to investigate the mutation of DIAPH1 in Asian population, and to compare the angiographic features of MMD patients with and without the mutation of the DIAPH1 gene. Blood samples of 50 patients with MMD were collected, and DIAPH1 gene mutation was detected. The angiographic involvement of the posterior cerebral artery was compared between the mutant group and the non-mutant group. The independent risk factors of posterior cerebral artery involvement were determined by multivariate logistic regression analysis. DIAPH1 gene mutation was detected in 9 (18%) of 50 patients, including 7 synonymous mutations and 2 missense mutations. However, the incidence of posterior cerebral artery involvement in mutation positive group was very higher than that in mutation negative group (77.8% versus 12%; p = 0.001). There is an association between DIAPH1 mutation and PCA involvement (odds ratio 29.483, 95% confidence interval 3.920–221.736; p = 0.001). DIAPH1 gene mutation is not a major genetic risk gene for Asian patients with moyamoya disease but may play an important role in the involvement of posterior cerebral artery. [ABSTRACT FROM AUTHOR]

The association of exosomal RNA profiling and pathogenesis of moyamoya disease (MMD) and intracranial Atherosclerotic disease (ICAD) is unknown. In this study, we investigated the RNA profiles of sEV (small extracellular vesicles)/exosomes in patients with MMD and ICAD. Whole blood samples were collected from 30 individuals, including 10 patients with MMD, 10 patients with ICAD, and 10 healthy individuals. Whole transcriptome analysis was performed using the GeneChip WT Pico Reagent kit. Transcriptional correlation was verified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between functional dysregulation and candidate RNAs was studied in vitro. In total, 1,486 downregulated and 2,405 upregulated RNAs differed significantly between patients with MMD and healthy controls. Differential expression of six circRNAs was detected using qPCR. Among these significantly differentially expressed RNAs, IPO11 and PRMT1 circRNAs were upregulated, whereas CACNA1F circRNA was downregulated. This is the first study showing that the differential expression of exosomal RNAs associated with MMD pathogenesis, such as overexpression of IPO11 and PRMT1 circRNAs, may be related to angiogenesis in MMD. The downregulation of CACNA1F circRNA may be related to vascular occlusion. These results propose the utility of exosomal RNAs as biological markers in MMD. [ABSTRACT FROM AUTHOR]

Background: Several pharmacological pathways have revealed statin to have a positive role in patients with for intracranial aneurysms. However, prior studies regarding the association between statin use and patients' outcomes after pipeline embolization device (PED) treatment were not completely supportive. Objectives: To investigate whether statin medication following PED treatment would improve the outcomes of intracranial aneurysm patients in a real-world setting. Design: A retrospective multicenter cohort study. Methods: Patients were selected from the PLUS registry study conducted from November 2014 to October 2019 across 14 centers in China. The population was divided into two groups: those who received statin medication after the PED treatment and those who did not receive statin medication after PED treatment. Study outcomes included angiographic evaluation of aneurysm occlusion, parent arteries stenosis, ischemic and hemorrhage complications, all-cause mortality, neurologic mortality, and functional outcome. Results: 1087 patients with 1168 intracranial aneurysms were eligible; 232 patients were in the statin user group and the other 855 were in the non-statin user group. For the statin user group versus the non-statin user group, no significant difference was found for the primary outcomes of complete occlusion of aneurysm (82.4% versus 84.2%; p = 0.697). Of the secondary outcomes, none had a significant difference including stenosis of parent arteries ≥ 50% (1.4% versus 2.3%; p = 0.739), total subarachnoid hemorrhage (0.9% versus 2.5%; p = 0.215), all-cause mortality (0.0% versus 1.9%; p = 0.204), neurologic mortality (0.0% versus 1.6%; p = 0.280), excellent (95.5% versus 97.2%; p = 0.877), and favorable (98.9% versus 98.4%; p = 0.933) functional outcomes. The total ischemic complication rate (9.0% versus 7.1%; p = 0.401) was higher but not significant in the statin user group. The propensity score-matched cohort showed similar results. Results of binary multivariable logistic regression analysis and propensity score-matched analysis both showed that statin usage was not independently associated with an increased rate of complete occlusion or any other secondary outcomes. Subgroup analysis found the same result in patients who did not use statin before the procedure. Conclusion: Among patients with intracranial aneurysms, statin use after the PED treatment was not significantly associated with better angiographic and clinical outcomes. Well-designed studies are needed to further confirm this finding. [ABSTRACT FROM AUTHOR]

The comorbidity of aneurysmal subarachnoid hemorrhage (aSAH) with intracranial atherosclerotic stenosis (ICAS) has been suggested to increase the risk of postoperative ischemic stroke. Logistic regression models were established to explore the association between computed tomography perfusion (CTP) parameters and 3-month neurological outcomes and delayed cerebral ischemia (DCI). Prognostic-related perfusion parameters were added to the existing prognostic prediction models to evaluate model performance improvement. Tmax > 4.0 s volume > 0 mL was significantly associated with 3-month unfavorable neurological outcomes after adjusting for potential confounders (OR 3.90, 95% CI 1.11–13.73), whereas the stenosis degree of ICAS was not. Although the cross-validated area under the curve (AUC) was similar after the addition of the Tmax > 4.0 s volume > 0 mL (SAHIT: p = 0.591; TAPS: p = 0.379), the continuous net reclassification index (cNRI) and integrated discrimination index (IDI) showed that the perfusion parameters significantly improved the performance of the two models (p < 0.001 for all comparisons). Patients with coexistent aSAH and ICAS, Tmax > 4.0 s volume > 0 mL is an independent factor of 3-month neurological outcomes. A quantitative assessment of cerebral perfusion may help accurately screen patients with poor outcomes due to the coexistence of aSAH and ICAS. [ABSTRACT FROM AUTHOR]

An inflammatory response after an aneurysmal subarachnoid hemorrhage (aSAH) has always been in the spotlight. However, few studies have compared the prognostic impact of inflammatory biomarkers. Moreover, why these inflammatory biomarkers contribute to a poor prognosis is also unclear. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The 90-day unfavorable functional outcome was defined as a modified Rankin scale (mRS) of ≥ 3. Independent inflammatory biomarker-related risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cut-off value of inflammatory biomarkers. Then, patients were divided into two groups according to each biomarker's cut-off value. To eliminate the imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of each biomarker on in-hospital complications. A total of 543 patients were enrolled in this study and 96 (17.7%) patients had unfavorable 90-day outcomes. A multivariate analysis showed that the white blood cell (WBC) count, the systemic inflammation response index, the neutrophil count, the neutrophil-to-albumin ratio, the monocyte count, and the monocyte-to-lymphocyte ratio were independently associated with 90-day unfavorable outcomes. The WBC count showed the best predictive ability (area under the curve (AUC) = 0.710, 95% CI = 0.652–0.769, p < 0.001). After PSM, almost all abnormal levels of inflammatory biomarkers were associated with a higher incidence of pneumonia during hospitalization. The WBC count had the strongest association with poor outcomes. Similar to nearly all other inflammatory biomarkers, the cause of poor prognosis may be the higher incidence of in-hospital pneumonia. [ABSTRACT FROM AUTHOR]

Background: Small multiple intracranial aneurysms (SMIAs) are known to be more prone to rupture than are single aneurysms. However, specific recommendations for patients with small MIAs are not included in the guidelines of the American Heart Association and American Stroke Association. In this study, we aimed to evaluate the feasibility of machine learning-based cluster analysis for discriminating the risk of rupture of SMIAs. Methods: This multi-institutional cross-sectional study included 1,427 SMIAs from 660 patients. Hierarchical cluster analysis guided patient classification based on patient-level characteristics. Based on the clusters and morphological features, machine learning models were constructed and compared to screen the optimal model for discriminating aneurysm rupture. Results: Three clusters with markedly different features were identified. Cluster 1 (n = 45) had the highest risk of subarachnoid hemorrhage (SAH) (75.6%) and was characterized by a higher prevalence of familiar IAs. Cluster 2 (n = 110) had a moderate risk of SAH (38.2%) and was characterized by the highest rate of SAH history and highest number of vascular risk factors. Cluster 3 (n = 505) had a relatively mild risk of SAH (17.6%) and was characterized by a lower prevalence of SAH history and lower number of vascular risk factors. Lasso regression analysis showed that compared with cluster 3, clusters 1 (odds ratio [OR], 7.391; 95% confidence interval [CI], 4.074–13.150) and 2 (OR, 3.014; 95% CI, 1.827–4.970) were at a higher risk of aneurysm rupture. In terms of performance, the area under the curve of the model was 0.828 (95% CI, 0.770–0.833). Conclusions: An unsupervised machine learning-based algorithm successfully identified three distinct clusters with different SAH risk in patients with SMIAs. Based on the morphological factors and identified clusters, our proposed model has good discrimination ability for SMIA ruptures. [ABSTRACT FROM AUTHOR]

High-frequency activity (HFA) in intracranial electroencephalography recordings are diagnostic biomarkers for refractory epilepsy. Clinical utilities based on HFA have been extensively examined. HFA often exhibits different spatial patterns corresponding to specific states of neural activation, which will potentially improve epileptic tissue localization. However, research on quantitative measurement and separation of such patterns is still lacking. In this paper, spatial pattern clustering of HFA (SPC-HFA) is developed. The process is composed of three steps: (1) feature extraction: skewness which quantifies the intensity of HFA is extracted; (2) clustering: k-means clustering is applied to separate column vectors within the feature matrix into intrinsic spatial patterns; (3) localization: the determination of epileptic tissue is performed based on the cluster centroid with HFA expanding to the largest spatial extent. Experiments were conducted on a public iEEG dataset with 20 patients. Compared with existing localization methods, SPC-HFA demonstrates improvement (Cohen’s d $>0.2$) and ranks top in 10 out of 20 patients in terms of the area under the curve. In addition, after extending SPC-HFA to high-frequency oscillation detection algorithms, corresponding localization results also improve with effect size Cohen’s d $\geq 0.48$. Therefore, SPC-HFA can be utilized to guide clinical and surgical treatment of refractory epilepsy. [ABSTRACT FROM AUTHOR]

Background: Glioma is the most common intracranial malignancy in adults with a high degree of malignancy and poor prognosis, which is largely attributed to the existence of glioma stem cells (GSCs). Previous evidence indicated that the matrix metalloproteinase ADAMTS1 was implicated in the process of tumor invasion, but the involvement of ADAMTS1 in glioma malignant invasion remains poorly understood. Methods: The expression and prognosis values of ADAMTS1 were investigated in patients with glioma based on ONCOMINE and GEPIA databases. ADAMTS1 expression of different malignancy grade tissues was determined by immunohistochemistry. The effects of ADAMTS1 on cell proliferation and invasion were determined by clone formation assay and Transwell migration assay. The animal experiment was performed in an intracranial orthotopic xenograft model by knockout of ADAMTS1. Stemness properties and Notch1-SOX2 pathway were examined in stable ADAMTS1 knockdown GSCs. Results: The expression levels of ADAMTS1 were significantly higher in glioma tissues and significantly correlated with the grade of malignancy and prognosis of glioma. Elevated ADAMTS1 expression was associated with SOX2, N-cadherin and the resistance of chemoradiotherapy of glioma patients. ADAMTS1 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice in vivo. Mechanistically, we found a blockade of the migration and invasiveness of GSCs and the expression levels of Notch1 and SOX2 in absence of ADAMTS1. Conclusion: As a biomarker for prediction of prognosis, ADAMTS1 may affect the invasive phenotype of GSCs by regulating Notch1-SOX2 signaling pathway, thereby promoting the invasive growth of glioma. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the relationship between white blood cells (WBCs) at admission and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients and Methods: We analyzed data from patients with aSAH between January 2015 and September 2021 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. WBC is classified into four groups according to the quartile. We used the logistic model for in-hospital complications, mortality, modified Rankin scale (mRS) at discharge and 90 days to examine the relationship between WBC and clinical outcomes. We used WBC levels near odds ratio (OR) = 1 (Q1) in restricted cubic splines as the reference to evaluate whether there is a nonlinear relationship between WBC and clinical outcomes. Another Kaplan–Meier method was used to analyze the relationship between WBC levels and the risk of developing pneumonia. Results: Of the 988 patients included, the results showed that compared with patients in the Q1 group, patients in the highest quartile (Q4) had an increased incidence of 90-day unfavorable outcomes after adjusting the confounders (adjusted OR = 1.81, 95% CI = 1.02– 3.20, p = 0.042), which may be caused by the increased incidence and risk of pneumonia (adjusted OR = 2.06, 95% CI = 1.30– 3.29, p = 0.002; adjusted hazard ratio [HR]=1.63, 95% CI = 1.13– 2.36, p < 0.001). The restricted cubic spline indicated that the incidence of developing pneumonia and 90-day unfavorable outcomes rises with increasing WBC levels (p for nonlinear = 0.135 and 0.113). Conclusion: Patients with higher WBC at admission were associated with an increased incidence of 90-day unfavorable outcomes, which might be related to pneumonia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the angioarchitectural factors associated with postoperative cerebral infarction in ischemic moyamoya disease. Methods: Data on patients who underwent surgery for ischemic MMD from 1 October 2015 to 31 October 2020, at Peking University International Hospital were collected and retrospectively analyzed. General conditions such as patient sex, age, site of surgery, preoperative manifestations such as TIA attack and old cerebral infarction, and seven angioarchitectural factors of the MMD based on DSA were selected and measured. Statistical analysis was performed by the Pearson chi-square statistic, analysis of variance (ANOVA), and multifactor logistic regression analysis. Results: Age (OR, 0.969; 95%CI, 0.939–1.000; p = 0.049), A1stenosis (OR, 5.843; 95%CI, 1.730–19.732; p = 0.004), M1stenosis (OR, 6.206; 95%CI, 2.079–18.526; p = 0.001), PCA anomalies (OR, 4.367; 95%CI, 1.452–13.129; p = 0.049), Unstable compensation (OR, 5.335; 95%CI, 1.427–19.948; p = 0.013), TIA (OR, 4.264; 95%CI, 1.844–9.863; p = 0.001), Old cerebral infarction (OR, 2.972; 95%CI, 1.194–7.397; p = 0.019). The above seven factors can be used in the regression equation to predict the probability of postoperative cerebral infarction. The prediction accuracy is 90.2%. Conclusions: Age, TIA attack, old cerebral infarction, and five angioarchitectural factors of MMD are strongly associated with postoperative cerebral infarction. Seven factors, including age, TIA attack, old infarction, and four angioarchitectural factors, can be taken to quantify the probability of surgical cerebral infarction in MMD. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations (AVMs) are the most common types of cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. The dysfunction of endothelial cells has been postulated to play a role in the pathogenesis of brain AVMs. mTOR-FABP4 signal enhances the angiogenic responses of endothelial cells and is not activated in the normal cerebral vasculature. Herein, we investigated the hypothesis that the mTOR-FABP4 signal may be activated in brain AVMs. The abundance of molecules in mTOR-FABP4 signal expression was detected by immunohistochemistry and Western blotting; special expressing cells were further characterized by double immunofluorescence using antibodies against various cell-specific markers. Next, several functional assays were performed to analyze the influence of the mTOR-FABP4 signal on proliferation, apoptosis, migration, and vascular tube formation of endothelial cells in human umbilical vein endothelial cells (HUVECs) using rapamycin and L-leucine. The expression of mTOR, p-mTOR, and FABP4 was increased in endothelial cells of human brain AVMs. Endothelial cell mTOR and p-mTOR expression were present in 70% and 55% of brain AVMs, respectively. Moreover, a population of FABP4-positive endothelial cells was detected in 80% of brain AVMs. The mTOR-FABP4 signal was activated and inhibited by L-leucine and rapamycin in HUVECs. The proliferation, apoptosis, migration, and vascular tube formation of endothelial cells could be inhibited by rapamycin. The mTOR-FABP4 signal was activated in human brain AVMs, and the mTOR-FABP4 signal was involved in proliferation, apoptosis, migration, and the vascular tube formation of endothelial cells. Taken together, whether rapamycin has therapeutic potential for treating human brain AVMs is worthy of further study. Key messages: We confirmed that the mTOR- FABP4 pathway is activated in human brain arteriovenous malformations. We confirmed that mTOR signaling pathway affects endothelial cell function by regulating proliferation, migration, apoptosis, and tube formation of endothelial cell. Our study can provide theoretical support for mTOR pathway inhibitors in the treatment of human brain arteriovenous malformations. [ABSTRACT FROM AUTHOR]

Alternative splicing is an important way of regulating gene functions in eukaryotes. Several key genes involved in sex determination and gonadal differentiation, such as nr5a1 and ddx4, have sex-biased transcripts between males and females, suggesting a potential regulatory role of alternative splicing in gonads. Currently, the sex-specific alternative splicing events and genes have not been comprehensively studied at the genome-wide level in zebrafish. In this study, through global splicing analysis on three independent sets of RNA-seq data from matched zebrafish testes and ovaries, we identified 120 differentially spliced genes shared by the three datasets, most of which haven't been reported before. Functional enrichment analysis showed that the GO terms of mRNA processing, mRNA metabolism and microtubule-based process were strongly enriched. The testis- and ovary-biased alternative splicing genes were identified, and part of them (tp53bp1, tpx2, mapre1a, kif2c, and ncoa5) were further validated by RT-PCR. Sequence characteristics analysis suggested that the lengths, GC contents, and splice site strengths of the alternative exons or introns may have different influences in different types of alternative splicing events. Interestingly, we identified an unexpected high proportion (over 70%) of non-frameshift exon-skipping events, suggesting that in these cases the two protein isoforms derived from alternative splicing may both have functions. Furthermore, as a representative example, we found that the alternative splicing of ncoa5 causes the loss of a conserved RRM domain in the short transcript predominantly produced in testes. Our study discovers novel sex-specific alternative splicing events and genes with high reliabilities in zebrafish testes and ovaries, which would provide attractive targets for follow-up studies to reveal the biological significances of alternative splicing events and genes in sex determination and gonadal differentiation. [ABSTRACT FROM AUTHOR]

Controlling blood pressure levels is critical to preventing intracranial aneurysm rupture, and a summary review of induced rupture events allows better health education for patients. We retrospectively reviewed all medical records of consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH) admitted to Beijing Tiantan Hospital from 2015 to 2020. We collected patients' demographic information, aneurysm morphology, blood pressure level on admission, time to onset, and events at the time of aneurysm rupture to analyze the factors precipitating aneurysmal rupture. A total of 764 patients were enrolled for analysis, including 461 (60.3%) female patients and 303 (39.7%) male patients. The mean age of onset in this cohort was 55, and 465 (60.9%) patients had hypertension history. Autumn (245/764 [32.1%]) was the most frequent season for aneurysm rupture, and 07:00–12:59 (277/764 [36.3%]) was the most frequent time frame for aneurysm rupture. The five most prevalent events when aneurysm rupture happened were: (1) daily behaviors that may induce hypertension (181/764 [23.7%]), especially defecation or micturition (116/181 [64.1%]); (2) sporting (162/764 [21.2%]), especially high‐intensity sports (108/162 [66.7%]); (3) mood and mental factors (112/764 [14.7%]), especially arguing or quarreling (61/112 [54.5%]); (4) sudden postural changes (93/764 [12.2%]), especially getting up (69/93 [74.2%]); and (5) sleeping (72/764 [9.4%]). Patients should avoid behaviors that may cause fluctuations in blood pressure, including keeping warm during seasonal alternation, keeping their urine and defecation unobstructed, avoiding high intensity physical exercise, maintaining a happy mood, avoiding sudden postural changes, and should not bathe with too cold or too hot water. [ABSTRACT FROM AUTHOR]

HLA‐C*14:02:01:33 differs from HLA‐C*14:02:01:01 by one nucleotide substitution in intron 2. [ABSTRACT FROM AUTHOR]

Various bacterial diseases have caused great economic losses to the high-density and intensive aquaculture industry; however, the pathogenic mechanism underlying the large-scale challenged to caused by many bacteria remain unclear, making the prevention and treatment of these diseases difficult. In the present study, we isolated a bacterial strain from Cyprinus carpio having a typical bacterial disease and named it Cc2021. Through subsequent morphological observations, a regression challenge, biochemical identification, and 16S rRNA gene sequence analysis, we determined Cc2021 to be Plesiomonas shigelloides. Subsequently, we comprehensively investigated the pathogenicity of P. shigelloides in C. carpio through a regression challenge and assessed the underlying the pathogenic mechanism. Mortality results revealed that P. shigelloides is highly pathogenic and infects various tissues throughout the body, resulting in edema of the liver, spleen, and body and head kidneys. Histopathological analysis revealed obvious inflammation, bleeding, and necrosis in the intestine, spleen, and head kidney. The body's immune tissues actively produce complement C3, superoxide dismutase, and lysozyme after a challenge to resist bacterial invasion. With regard to the underlying pathogenesis of P. shigelloides , comparative transcriptome analysis revealed 876 upregulated genes and 828 downregulated genes in the intestine of C. carpio after the challenge. Analysis of differentially expressed unigenes revealed the involvement of major immune pathways, particularly the TNF signaling pathway, interleukin (IL)-17 signaling pathway, and Toll-like receptor signaling pathway. The present study provides new valuable information on the immune system and defense mechanisms of P. shigelloides. [ABSTRACT FROM AUTHOR]

Background: The Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial primarily demonstrated the safety and efficacy of the implantation of multiple pipeline embolization devices (multi-PEDs) for large/giant intracranial aneurysms. However, no study has focused on when, why, or how to apply multi-PEDs. Objective: The purpose of this study was to investigate the indications and strategies of using multi-PEDs for complex intracranial aneurysms. Methods: Patients who had been treated with two or more PEDs were included in the post-market multicenter registry study from 2014 to 2019, across 14 centers in China. Indications, strategies, perioperative safety, and clinical outcomes were retrospectively analyzed. The modified Rankin scale (mRS) score was used to evaluate clinical outcomes comprehensively, and the O'Kelly–Marotta (OKM) grading scale was used to evaluate aneurysm healing results. Results: A total of 55 intracranial aneurysms were treated with multi-PEDs. There were 20 fusiform aneurysms with a large range, 25 large/giant saccular aneurysms, six aneurysms with failed treatment, and four aneurysms with greatly varied diameters of the parent artery. The strategies included telescope techniques in 40 patients and overlap techniques in 15 patients. In total, 120 stents were deployed in 55 patients. The operation styles included 25 patients (55.6%) with two PEDs, 21 patients (38.2%) with two PEDs combined with coiling, four patients (7.3%) with three PEDs, four patients (7.3%) with three PEDs combined with coiling, and one patient (1.8%) with four PEDs. Angiography revealed OKM D in two, OKM C in seven, and OKM A and B in 46 cases after surgery. During the perioperative period, eight patients developed neurological dysfunction, three of whom died. A total of thirty-four patients were followed up with digital subtraction angiography for 2–45 (8.2 ± 8.0) months. Angiography revealed OKM D in 26, OKM C in five, and OKM B in three. At the last follow-up, the mRS score was 0–1 in 52 patients. Conclusion: The treatment of anterior circulation aneurysms with multi-PEDs is safe and effective. The implantation of multi-PEDs could be considered for large-scale fusiform aneurysms, large/giant saccular aneurysms with a jet-sign, salvage of failed PED treatments, and in cases where the diameter of the parent artery varies greatly. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this work was to summarize the real-world safety and efficacy of Pipeline Embolization Device (PED) therapy for small and medium-sized intracranial aneurysms in China. Methods: Patients from the PED in China post-market multi-center registry study (PLUS) with aneurysms smaller than 12 mm were selected. Radiographic outcomes were assessed using digital subtraction angiography. Clinical outcomes included functional outcomes (modified Rankin Scale, MRS) in the early postoperative period (≤ 30 days) and early postoperative complications associated with PED therapy. Results: A total of 652 patients with a combined 754 aneurysms were included in this study (mean age of 53.9 ± 10.3 years, 68.7% women). Mean aneurysm diameter was 6.78 ± 2.67 mm. Of the 687 stents deployed, 99.7% (685/689) were successfully deployed. In this study, 64.7% (488/754) of aneurysms were treated with only the PED, whereas 35.3% (266/754) were subjected to PED-assisted therapy. Radiographic outcome at the last follow-up (median time: seven months) was available for 64.3% (485/754) of the aneurysms. 82.5% (400/485) of aneurysms demonstrated complete occlusion (Raymond Roy Grade I). 81.4% (395/485) of aneurysms were found to meet the study's primary effectiveness outcome. At the early postoperative period, the mRS score was determined to be 0–2 vs. 3-6 in 98.2% (640/652) vs. 1.8% (12/652) of the cases, respectively. The combined major morbidity and mortality rate was 3.2% (21/652). Conclusion: In the largest study of PED therapy for small and medium-sized intracranial aneurysms to date, pipeline-assisted coil embolization was chosen more often than multiple stent implantation for aneurysm treatment, demonstrating good results, high surgical success rates, high occlusion rates, and low morbidity and mortality. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03831672. [ABSTRACT FROM AUTHOR]

Rapid formation of innovative, inexpensive, personalized, and quickly reproducible artery bioresorbable stents (BRSs) is significantly important for treating dangerous and sometimes deadly cerebrovascular disorders. It is greatly challenging to give BRSs excellent mechanical properties, biocompatibility, and bioabsorbability. The current BRSs, which are mostly fabricated from poly-l-lactide (PLLA), are usually applied to coronary revascularization but may not be suitable for cerebrovascular revascularization. Here, novel 3D-printed BRSs for cerebrovascular disease enabling anti-stenosis and gradually disappearing after vessel endothelialization are designed and fabricated by combining biocompatible poly (p-dioxanone) (PPDO) and 3D printing technology for the first time. We can control the strut thickness and vessel coverage of BRSs by adjusting the printing parameters to make the size of BRSs suitable for small-diameter vascular use. We added bis-(2,6-diisopropylphenyl) carbodiimide (commercial name: stabaxol®-1) to PPDO to improve its hydrolytic stability without affecting its mechanical properties and biocompatibility. In vitro cell experiments confirmed that endothelial cells can be conveniently seeded and attached to the BRSs and subsequently demonstrated good proliferation ability. Owing to the excellent mechanical properties of the monofilaments fabricated by the PPDO, the 3D-printed BRSs with PPDO monofilaments support desirable flexibility, therefore offering a novel BRS application in the vascular disorders field. [ABSTRACT FROM AUTHOR]

The mechanism by which ubiquitin-specific protease 18 (USP18) (enzyme commission: 3.4.19.12) inhibition in cancer promotes cell pyroptosis via the induction of interferon (IFN)-stimulated genes has been recently demonstrated. It is also known that USP18 influences the epithelial-mesenchymal transition of glioma cells. In the present study, the upregulation of USP18 in glioma was revealed through bulk transcriptome analysis, which was associated with poor prognosis in patients with glioma. Furthermore, USP18 levels affected the response to immunotherapy in patients with glioma. Single-cell transcriptome and enrichment analyses demonstrated that USP18 was associated with type 1 IFN responses in glioma T cells. To demonstrate the effect of USP18 expression levels on glioma cells, USP18 expression was knocked down in U251 and U87MG ATCC cell lines. A subsequent Cell Counting Kit-8 assay revealed that glioma cell viability was significantly decreased 4 days after USP18 knockdown. In addition, the knockdown of USP18 expression significantly inhibited the clonogenicity of U251 and U87MG ATCC cells. In conclusion, the present study demonstrated that knockdown of USP18 expression inhibited the proliferation of glioma cells, which may be mediated by the effect of USP18 on the IFN-I response. [ABSTRACT FROM AUTHOR]

Objective: Elevated ICP is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Delayed cerebral ischemia (DCI) is the most important reason for a poor clinical outcome after a subarachnoid hemorrhage. DCI is understood as a multifactorial process that evolves over time, largely caused by the sequelae of increased intracranial pressure (ICP). The study aimed to assess how to better define the association between ICP and DCI, and whether rational ICP management can improve the outcome of aSAH patients. Methods: We prospectively reviewed patients diagnosed with aSAH and received microsurgery clipping at our department from December 2019 to January 2021. Subdural ICP monitoring devices were kept to monitor the ICP. The ICP values were recorded every 1-h epochs. ICP -guided dehydration treatments were routinely performed to control the ICP level of patients after surgery. To evaluate whether the subdural ICP-directed management improved the prognosis of the aSAH patients, we compared the outcome data of the patients in our cohort with those treated at another ward of our hospital at the same period. Results: In total, 144 consecutive aSAH patients received microsurgery clipping at our department, 68 of whom underwent ICP monitoring. A total of 11,424 1-h ICP measurements were recorded for the included patients (1.30 years of recordings). Of 68 patients with ICP monitoring, 27 (27/68, 39.7%) patients developed DCI. Univariate analysis showed that higher Hunt-Hess grade (OR 2.138, 95% CI 1.025–4.459, p = 0.043), higher preoperative modified Rankin Scale score (OR 1.534, 95% CI 1.033–2.276, p = 0.034), and the max ICP value of each day value >28.5 mmHg (OR 4.442, 95% CI 1.509–13.082, p = 0.007) were associated with DCI. Also, patients with ICP-directed treatment showed a significantly lower DCI incidence than patients without ICP monitoring. Conclusion: Our study suggests that I less than 15 mmHg possibly constitute normal values and that 28.5 mmHg is the ICP threshold most strongly associated with the occurrence of DCI in aSAH patients. Patients who received the ICP-directed treatment presented a lower incidence of DCI. Our findings provide a basis for the recommendation of ICP-directed treatment after aSAH. Trial Registration Number: NCT04785976. [ABSTRACT FROM AUTHOR]

Objective: Paediatric aneurysms are rare and difficult to treat. Studies on the long-term angiographic and clinical outcomes conducted within the past decade are lacking. We aimed to investigate the clinical and radiographic outcomes of paediatric aneurysms treated with different strategies in a contemporary series. Methods: We performed a retrospective medical record review of paediatric patients examined at our institution between 2011 and 2018. Patient charts were retrospectively reviewed for age, presentation, type and location of the aneurysm, modalities of treatment, complications, and clinical and angiographic outcomes. The rates of aneurysm recurrence and de novo formation were determined. Results: We evaluated 61 patients (mean age, 11.6 years; 23 females, 38 males) with 69 intracranial aneurysms. Their presentations included headache, neurological deficits, aneurysmal subarachnoid haemorrhage, incidental aneurysm, and traumatic subarachnoid haemorrhage. Of the aneurysms, 30 (49.2%) were giant. Forty-five (73.8%) patients underwent treatment for their aneurysms, and 16 (26.2%) patients were managed conservatively. The perioperative morbidity rate was 17.8%. There were no deaths. The long-term morbidity rate was 4.6%. The clinical outcomes were favourable in 82.2 and 95.3% at discharge and follow-up, respectively (mean, 41.5 months; range, 1.5–9 years). For treated aneurysms, 2/43 (4.6%) risk of aneurysm recurrence, 1/43 (2.3%) risk of aneurysm bleeding, 1/43 (2.3%) risk of de novo aneurysm formation. The annual bleeding, recurrence, and de novo formation or growth risk were 0.7, 1.4, and 0.7%, respectively. Conclusions: In neurovascular centres where microsurgical and endovascular options are available, most children with intracranial aneurysms can be successfully treated with low morbidity and mortality. However, they have higher rates of recurrence and a greater risk of de novo formation or growth than their adult counterparts, which mandates lifelong follow-up. [ABSTRACT FROM AUTHOR]

The common carp (Cyprinus carpio) accounts for approximately 10% of the annual freshwater aquaculture production and is an ideal model to study cyprinidae reproduction. Female common carp grow faster than the males; therefore, related research presents an opportunity with high application value. Although we have a detailed understanding of common carp's early gonadal differentiation process, information about genome-wide gene expression, regulation, and underlying molecular mechanisms during this process remain limited. Here, time-course data comprising six key stages during testicular differentiation and maturation were investigated to further understand the molecular mechanisms underlying the testicular development in cyprinid species. After integrating these time-series data sets, common carp genome, including 98,345 novel transcripts and 3,071 novel genes were re-annotated and precisely updated. Gene co-expression network analysis revealed that the ubiquitin-mediated proteolysis pathway was essential for metabolism during testicular differentiation in the endocrine system of C. carpio. Functional enrichment analyses indicated that genes mainly related to amino acid metabolism and steroid hormone synthesis were relatively highly expressed at the testicular undifferentiation stages, whereas genes associated with cell cycle and meiosis were expressed from the beginning of testicular differentiation until maturation. The dynamics of alternative splicing events demonstrated that exon skipping accounted for majority of the alternative splicing events in the testis and the brain during gonad development. Notably, several potential male-specific genes (fanci and sox30) and brain-specific genes (oxt , gad2 , and tac1 , etc.) were identified. Importantly, we traversed beyond the level of transcription to test for stage- and gonad-specific alternative splicing patterns between the brain and testis. This study is the first to describe a comprehensive landscape of alternative splicing events and gene expression patterns during gonadogenesis in common carp. This work is extremely valuable to elucidate the mechanisms underlying gonadal differentiation in Cyprinidae as well as other fish species. [ABSTRACT FROM AUTHOR]

Background: Unruptured small aneurysms with a size of <7 mm were often followed conservatively. However, it is unknown whether unruptured small multiple intracranial aneurysms (MIAs) are better to be prophylactically treated or conservatively followed. Objective: We aim to compare the effectiveness of different strategies regarding their management. Methods: A decision-analytic Markov model was built over a entire life cycle. The compared strategies include natural history, treat one aneurysm, treat both aneurysms, annual follow-up, biennial follow-up, and follow-up every 5 years. The inputs for the model were obtained from real-world data and related medical literature. Outcomes were measured in terms of quality-adjusted life-years (QALYs). Results: Treat both aneurysms had the highest effectiveness of 15.36 QALYs and treat one aneurysm had the second-highest effectiveness of 15.11 QALYs. Probabilistic sensitivity analysis with 10,000 iterations showed that treat both aneurysms and treat one aneurysm were optimal in 67.28 and 17.91% of all cases, respectively. One-way and two-way sensitivity analyses showed that the result was sensitive to the proportion of moderate to severe disability after treating two aneurysms, mortality after treating two aneurysms, proportion of moderate to severe disability after treating one aneurysm, and rupture rate of small growing aneurysm. Either treat both aneurysms or treat one aneurysm would be the optimal strategy under most of the circumstances with the variations of these parameters. Conclusion: For patients with small unruptured MIAs, prophylactic coiling was superior to conservative management and at least one aneurysm should be treated. [ABSTRACT FROM AUTHOR]

Purpose: Endovascular coil occlusion is a successful and rapidly evolving strategy used to treat patients who present with intracranial aneurysms. This study aimed to compare the safety and efficacy of the Avenir® and AxiumTM passive mechanically detachable coil systems. Methods: A prospective, multicenter, randomized controlled study was carried out at ten medical centers from March 2018 to December 2019. A series of consecutive patients diagnosed with intracranial aneurysms were randomly assigned to undergo endovascular treatment with either the Avenir® or the AxiumTM mechanically detachable coil systems. The short-term outcomes from the two groups were compared with a focus on treatment efficacy and safety. Results: A total of 162 and 161 patients were enrolled in the Avenir and Axium groups, respectively. The rate of successful coil detachment was 100% for the Avenir group and 99.38% for the Axium group. At the six-month follow-up visit, the overall aneurysm occlusion rate was 94.66% for the Avenir group and 96.95% for the Axium group (p > 0.05). We observed no statistically significant differences in clinical condition (as per the modified Rankin Scale) or the degree of aneurysm occlusion (as determined by digital subtraction angiography [DSA] and Raymond-Roy Occlusion Classification). Surgical complications were reported in 27 subjects in the Avenir group and 22 in the Axium group (p > 0.05). DSA performed at 6 months revealed complete aneurysm occlusion in 84 and 86% of patients in the Avenir and Axium groups, respectively. Conclusion: We observed no significant short-term differences with respect to efficacy or safety when using either Avenir® or AxiumTM coils for the treatment of intracranial aneurysms. [ABSTRACT FROM AUTHOR]

MiR-143-3p is aberrantly expressed in patients with ischemic stroke and associated with ischemic brain injury. However, the underlying mechanisms are largely unknown. Here, we confirmed circ_0025984 and TET1 as a sponge and target of miR-143-3p, respectively, by luciferase reporter assay. In astrocytes, OGD significantly decreased circ_0025984 and TET1 levels but increased miR-143-3p levels, which was also observed in brains of mice with MCAO. Treatment with miR-143-3p inhibitor or circ_0025984 significantly decreased astrocyte apoptosis and autophagy, as well as cerebral injury and neuron loss in mice with MCAO. Notably, TET1 overexpression decreased astrocyte apoptosis and autophagy and induced promoter hypomethylation and expression of ORP150. Our results demonstrated for the first time that circ_0025984 protects astrocytes from ischemia-induced autophagy and apoptosis by targeting the miR-143-3p/TET1 pathway and might inhibit cerebral injury induced by ischemic stroke. Furthermore, our data revealed the important positive regulation of ORP150 by TET1, which could be associated with its neuroprotective role. [ABSTRACT FROM AUTHOR]

Phthalate esters (PAEs) are prone to migrate from the plastic containers into oil during production and storage process. Owing to the trace amount of PAEs and complex sample matrix, it is of great importance to explore a facile and sensitive way to extract and detect PAEs from oil samples. In this work, magnetic covalent organic framework nanospheres (Fe3O4@COF(TbBD)) were fabricated by the aldehyde-amine condensation between benzidine (BD) and 1,3,5-triformylbenzene (Tb) on the surface of Fe3O4 nanoparticles with the help of ultrasonic treatment. The new type nanomaterials were firstly used to the magnetic solid-phase extraction (MSPE) of seven PAEs in edible vegetable oils prior to high performance liquid chromatography coupled with a diode array detector (HPLC–DAD). In order to achieve the best extraction efficiency, several key parameters were optimized. Under optimal conditions, the proposed Fe3O4@COF(TbBD)-MSPE-HPLC–DAD method possessed high sensitivity (0.55–0.95 µg/kg for LODs and 1.80–3.10 µg/kg for LOQs), good linearity (R2 ≥ 0.9983), and satisfactory recoveries (80.2–102.9%). The RSDs for intra-day was less than 6.1%, and inter-day was less than 7.9%. This work not only proposed a rapid and reliable approach for determining PAEs in edible vegetable oils but also broadened the application of magnetic COFs in food determination. [ABSTRACT FROM AUTHOR]

Objective: Whether partial embolization could facilitate the post-stereotactic radiosurgery (SRS) obliteration for brain arteriovenous malformations (bAVMs) remains controversial. We performed this study to compare the outcomes of SRS with and without prior embolization for bAVMs. Methods: We retrospectively reviewed the Beijing Tiantan AVMs prospective registration research database from September 2011 to October 2014. Patients were categorized into two groups, combined upfront embolization and SRS (Em+SRS group) and SRS alone (SRS group), and we performed a propensity score matching analysis based on pre-embolization baseline characteristics; the matched groups each comprised 76 patients. Results: The obliteration rate was similar between SRS and Em+SRS (44.7 vs. 31.6%; OR, 1.754; 95% CI, 0.905–3.401; p = 0.096). However, the SRS group was superior to the Em+SRS group in terms of cumulative obliteration rate at a follow-up of 5 years (HR,1.778; 95% CI, 1.017–3.110; p = 0.033). The secondary outcomes, including functional state, post-SRS hemorrhage, all-cause mortality, and edema or cyst formation were similar between the matched cohorts. In the ruptured subgroup, the SRS group could achieve higher obliteration rate than Em+SRS group (56.5 vs. 31.9%; OR, 2.773; 95% CI, 1.190–6.464; p = 0.018). The cumulative obliteration rate at 5 years was also higher in the SRS group (64.5 vs. 41.3%; HR, 2.012; 95% CI, 1.037–3.903; p = 0.038), and the secondary outcomes were also similar between the matched cohorts. Conclusion: Although there was no significant difference in the overall obliteration rate between the two strategies, this study suggested that pre-SRS embolization may have a negative effect on post-SRS obliteration. Furthermore, the obliteration rates of the SRS only strategy was significantly higher than that of the Em+SRS strategy in the ruptured cohort, while no such phenomenon was found in the unruptured cohort. [ABSTRACT FROM AUTHOR]

Background and Purpose: The utilization of flow diversion for ruptured intracerebral aneurysms (IAs) is still limited. We aimed to demonstrate our multicenter experience using the pipeline embolization device (PED) for ruptured IAs that were difficult to treat by clipping and coiling. Methods: Thirty-eight patients with ruptured IAs who underwent PED treatment from 2015 to 2020 were retrospectively reviewed. Factors associated with procedure-related stroke (ischemic and hemorrhagic) and clinical and angiography outcomes were analyzed. Results: There were 14 (36.8%) saccular IAs, 12 (31.6%) blister-like IAs, and 12 (31.6%) dissecting IAs. Perforator involvement was noted in 10 (26.3%) IAs. Early PED placement (≤ 15 days) and adjunctive coiling treatment were performed in 27 (71.1%) and 22 (57.9%) cases, respectively. The overall rate of stroke-related complications was 31.6% (12/38) (including rates of 10.5% for procedure-related hemorrhagic complications and 15.8% for procedure-related infarction). The mortality rate was 13.2% (5/38), and 84.2% of patients (32/38) had favorable outcomes. Thirty-two (84.2%) patients underwent follow-up angiographic evaluations; of these, 84.4% (27 patients) had complete occlusion and 15.6% had incomplete obliteration. Multivariate analysis revealed that early PED placement was not associated with a high risk of procedure-related stroke or an unfavorable outcome. Adjunctive coiling exhibited an association with procedure-related stroke (p = 0.073). Procedure-related hemorrhagic complications were significantly associated with an unfavorable outcome (p = 0.003). Immediate contrast stasis in the venous phase was associated with complete occlusion during follow-up (p = 0.050). Conclusion: The PED is a feasible and effective treatment to prevent rebleeding and achieve aneurysm occlusion, but it is associated with a substantial risk of periprocedural hemorrhage and ischemic complications in acute ruptured IAs. Therefore, the PED should be used selectively for acutely ruptured IAs. Additionally, adjunctive coiling might increase procedure-related stroke; however, it may reduce aneurysm rebleeding in acutely ruptured IAs. Patients with immediate contrast stasis in the venous phase were more likely to achieve total occlusion. A prospective study with a larger sample size should be performed to verify our results. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted in order to investigate the association of matrix metalloproteinase (MMP)-9 levels with phenotypes of moyamoya disease (MMD). Methods: This study included plasma samples from 84 MMD patients. The clinical variables of these patients were reviewed from the medical record. The serum concentration of tight junction, adherens junction proteins, and MMPs (MMP-2 and MMP-9) was determined using the ELISA method. Patients with hemorrhagic-onset MMD were compared with those with ischemic-onset MMD. Results: Compared with pediatric patients, the expression of MMP-9 was significantly higher, while the MMP-2 and vascular endothelial-cadherin were lower in adult patients. In adult subgroup analysis, hemorrhagic MMD patients exhibited significantly higher serum concentrations of MMP-9 compared with ischemic MMD patients. The ROC curve identified that a baseline serum MMP-9 level >1,011 ng/ml may be associated with spontaneous hemorrhage in adult MMD patients with 70.37% sensitivity and 71.88% specificity [area under curve (AUC), 0.73; 95% CI 0.597–0.864; P = 0.003]. A late Suzuki stage (>4) (OR 4.565, 95% CI 1.028–20.280, P = 0.046) and serum concentrations of MMP-9 >1,011 ng/ml (OR 7.218, 95% CI 1.826–28.533, P = 0.005) are risk predictors of hemorrhages in MMD patients. Hemorrhagic-type MMD patients had higher serum levels of MMP-9 and BBB permeability compared with ischemic-type MMD patients. Adult MMD patients had higher serum levels of MMP-9 and BBB permeability compared with pediatric patients. Conclusions: MMP-9 might serve as a biomarker for hemorrhage prediction in MMD. Serum MMP-9 level >1,011 ng/ml is an independent risk factor of MMD hemorrhagic strokes. [ABSTRACT FROM AUTHOR]

Background and purpose: Although grading scales for angiography outcomes following cerebral aneurysm treatment with flow diversion have been published, physicians have not widely adopted these scales in practice. The aim of this study is to propose and validate a novel Flow diversion Predictive Score (4F-FPS) grading scale based on previously established scales that is simple and reliable. Methods: We retrospectively analyzed consecutive patients who underwent endovascular treatment for cerebral aneurysms with flow diversion between January 2014 and September 2019. The included patients were randomly divided into the derivation and validation group in a 70/30 ratio, respectively. Aneurysms were classified as incomplete or complete occlusion based on final angiography outcomes. 4F-FPS was derived to predict aneurysm occlusion from multivariate logistic regression analyses in the derivation group and validated with previously published grading scales in the validation group. Results: Overall, 662 patients [mean age, 53.8 years; 72.5% (480/662) female] with 662 aneurysms treated with the PipelineTM flow diverter were included [69.9% (463/662) derivation group, 30.1% (199/662) validation group]. The incidence of aneurysm occlusion was 82.7%. 4F-FPS demonstrated significant discrimination in 10-fold cross validation [mean receiver operating characteristic (ROC) area, 0.862 ± 0.055] and calibration (Cox & Snell R 2, 0.251; Nagelkerke R 2, 0.413) in the derivation group. The ROC area of 4F-FPS score in both the derivation and validation groups is the largest compared with previously published grading scales/scores (p < 0.05), which shows better sensitivity and specificity. The 4F-FPS score showed excellent prediction, discrimination, and calibration properties. Conclusion: The 4F-FPS score is a simple and reliable tool to predict angiography outcome after flow diversion treatment. If widely adopted, it may provide a common language to be used in future reporting of flow diversion results for clinical trials and daily practice. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT03831672 [ABSTRACT FROM AUTHOR]

This study aims to investigate the long-term outcomes of unruptured giant intracranial aneurysms (GIAs) with different treatment modalities and to analyze the factors affecting prognosis. We performed a retrospective medical record review of patients with unruptured GIAs treated at our institution from 2011 to 2018. Prognosis was compared to the best medical treatment without intervention (conservative treatment, CT) and surgical (ST) or endovascular (ET) treatment. Risk factors for mortality were investigated. A total of 276 patients were included in this study. Patients received CT in 16.3%, ST in 30.1%, and ET in 53.6% of cases. After an average 7-year follow-up, the rupture rate after CT was 22.2%, accounting for an annual rupture rate of 7.3%. The postoperative complication rate was 30.1% and 8.1% after ST and ET, respectively. The recurrence rate after ET was 10.1%, compared with ST which was 1.2%. The follow-up mortality in unruptured GIAs was 26.7% after CT, 7.2% after ST, and 5.4% after ET. Older age (50~59, HR 5.877; 60~69, HR 8.565), size ≥ 40 mm (HR 3.916), and posterior circulation location (HR 6.411) were associated with increased mortality. ET significantly decreased mortality (HR 0.191). Unruptured GIAs warrant treatment if feasible due to the high rupture rate and mortality of the natural history. Older age, posterior circulation location, and larger size are risk factors for poor prognosis. Both ST and ET showed a lower mortality rate than CT. ST showed less likely recurrence compared to ET, while ET had a lower complication rate than ST. [ABSTRACT FROM AUTHOR]

Background: The optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse diameter (ETD) ratio have been proven to be correlated with intracranial pressure. This study aimed to evaluate the prognostic roles of ONSD and the ONSD/ETD ratio in comatose patients with supratentorial lesions and to determine the relationship of these two indices with the prognosis of such patients.Methods: A total of 54 comatose patients with supratentorial lesions and 50 healthy controls were retrospectively included in this study. ONSD and ETD were measured by unenhanced computed tomography (CT). The differences in ONSD and the ONSD/ETD ratio between the two groups were compared. The prognosis of comatose patients was scored using the Glasgow Outcome Scale (GOS) at the 3-month follow-up, and these patients were classified into good (GOS score ≥ 3) and poor (GOS score < 3) prognosis groups. The differences in ONSD and the ONSD/ETD ratio were compared between comatose patients with good prognoses and those with poor prognoses.Results: The ONSD and ONSD/ETD ratios in the comatose patients were 6.30 ± 0.60 mm and 0.27 ± 0.03, respectively, and both were significantly greater than those in the healthy controls (5.10 ± 0.47 mm, t = 11.426, P < 0.0001; 0.22 ± 0.02, t = 11.468, P < 0.0001; respectively). ONSD in patients with poor prognosis was significantly greater than that in patients with good prognosis (6.40 ± 0.56 vs. 6.03 ± 0.61 mm, t = 2.197, P = 0.032). The ONSD/ETD ratio in patients with poor prognosis was significantly greater than that in patients with good prognosis (0.28 ± 0.02 vs. 0.26 ± 0.03, t = 2.622, P = 0.011). The area under the receiver operating characteristic (ROC) curve, used to predict the prognosis of comatose patients, was 0.650 (95% confidence interval (CI): 0.486-0.815, P = 0.078) for ONSD and 0.711 (95% CI: 0.548-0.874, P = 0.014) for the ONSD/ETD ratio.Conclusions: The ONSD and ONSD/ETD ratios were elevated in comatose patients. The ONSD/ETD ratio might be more valuable than ONSD in predicting the prognoses of comatose patients with supratentorial lesions. [ABSTRACT FROM AUTHOR]

Object: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have an increased incidence of cardiac events and short-term unfavorable neurological outcomes during the acute phase of bleeding. We studied whether troponin I elevation after ictus can predict future major adverse cardiac events (MACEs) and long-term neurological outcomes after 2 years. Methods: Consecutive aSAH patients within 3 days of bleeding were eligible for review from a prospective observational cohort (ClinicalTrials.gov Identifier: NCT04785976). Potential predictors of future MACEs and unfavorable long-term neurological outcomes were calculated by Cox and logistic regression analyses. Additional Kaplan–Meier curves were performed. Results: A total of 213 patients were enrolled with an average follow-up duration of 34.3 months. Individuals were divided into two groups: elevated cTnI group and unelevated cTnI group. By the last available follow-up, 20 patients had died, with an overall all-cause mortality rate of 9.4% and an annual all-cause mortality rate of 3.8%. Patients with elevated cTnI had a significantly higher risk of future MACEs (10.6 vs. 2.1%, p = 0.024, and 95% CI: 1.256–23.875) and unfavorable neurological outcomes at discharge, 3-month, 1-, 2-years, and last follow-up (p = 0.001, p < 0.001, p = 0.001, p < 0.001, and p < 0.001, respectively). In the Cox analysis for future MACE, elevated cTnI was the only independent predictor (HR = 5.980; 95% CI: 1.428–25.407, and p = 0.014). In the multivariable logistic analysis for unfavorable neurological outcomes, peak cTnI was significant (OR = 2.951; 95% CI: 1.376–6.323; p = 0.005). Kaplan–Meier analysis indicated that the elevated cTnI was correlated with future MACE (log-rank test, p = 0.007) and subsequent death (log-rank test, p = 0.004). Conclusion: cTnI elevation after aSAH could predict future MACEs and unfavorable neurological outcomes. [ABSTRACT FROM AUTHOR]

Comparison in pediatric hemorrhagic arteriovenous malformations (AVMs) to clarify the long-term neurological outcomes and prognostic predictors after surgical intervention was relatively rare, especially in the selection of surgical timing. The objective of this study was to elucidate these points. The authors retrospectively reviewed the pediatric hemorrhagic AVMs resected in their neurosurgical department between March 2010 and June 2017. The natural history was represented by rupture risk. Neurological outcome was assessed with the modified Rankin Scale (mRS) for children. Multivariate logistic regression analyses were used to assess the risk factors for disability (mRS > 2). The hemorrhagic early phase was defined as less than 30 days after bleeding. The corresponding prognosis of different surgical timing (early intervention or delayed intervention) was compared after propensity-score matching (PSM). A total of 111 pediatric hemorrhagic AVM patients were evaluated. The average patient age was 11.1 ± 4.0 years, with a mean follow-up of 4.3 ± 2.1 years. The annualized rupture risk was 9.3% for the pediatric hemorrhagic AVMs, and the annualized re-rupture risk was 9.8%. 7.2% of the patients had disabilities (mRS > 2) and 82.0% achieved neurological deficit-free (mRS < 2) at the last follow-up. Pre-treatment mRS (P = 0.042) and flow-related aneurysms (P = 0.039) were independent factors for long-term disability. In terms of short-term outcomes, early intervention was better than delayed intervention (P = 0.033), but the long-term outcomes were similar between the two groups (P = 0.367). Surgical intervention for pediatric hemorrhagic AVMs is recommended, most of the patients can achieve good neurological outcomes. Moreover, early surgical intervention is preferred after the initial hemorrhage. [ABSTRACT FROM AUTHOR]

During intracranial aneurysm embolization with the Pipeline embolization device (PED), ischemic and hemorrhagic complications have been observed in cases among Western populations. The postmarket multicenter registry study on the embolization of intracranial aneurysms with the PED in China, i.e., the PLUS study, was performed to assess real-world predictors of complications and functional outcomes in patients treated with the PED in a Chinese population. All patients with intracranial aneurysms who underwent embolization using the PED between November 2014 and October 2019 across 14 centers in China were included. The study endpoints included preoperative and early postoperative (< 30 days) functional outcomes (modified Rankin scale [mRS] scores) and complications related to PED treatment at early postoperative and follow-up time points (3–36 months). Multivariate analysis was performed to identify risk factors for complications. A total of 1171 consecutive patients (mean age, 53.9 ± 11.4; female, 69.6% [813/1171]) with 1322 aneurysms were included in the study. Hypertension, basilar artery aneurysms, and successful deployment after adjustment or unsuccessful device deployment were found to be independent predictors of ischemic stroke, while the use of the Flex PED and incomplete occlusion immediately after treatment were protective factors. An aneurysm size > 10 mm, distal anterior circulation aneurysms, and adjunctive coiling were found to be independent predictors of delayed aneurysm rupture, distal intraparenchymal hemorrhage, and neurological compression symptoms, respectively. The rate of PED-related complications in the PLUS study was similar to that in Western populations. The PLUS study identified successful deployment after adjustment or unsuccessful device deployment and the degree of immediate postoperative occlusion as novel independent predictors of PED-related ischemic stroke in a Chinese population. ClinicalTrial.gov Identifier: NCT03831672 [ABSTRACT FROM AUTHOR]

Background: More and more elderly patients are being diagnosed with arteriovenous malformation (AVM) in this global aging society, while the treatment strategy remains controversial among these aging population. This study aimed to clarify the long-term outcomes of elderly AVMs after different management modalities. Methods: The authors retrospectively reviewed 71 elderly AVMs (>60 years) in two tertiary neurosurgery centers between 2011 and 2019. Patients were divided into four groups: conservation, microsurgery, embolization, and stereotactic radiosurgery (SRS). The perioperative complications, short-term and long-term neurological outcomes, obliteration rates, annualized rupture risk, and mortality rates were compared among different management modalities in the ruptured and unruptured subgroups. Kaplan-Meier survival analysis was employed to compare the death-free survival rates among different management modalities. Logistic regression analyses were conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CI) for predictors of long-term unfavorable outcomes (mRS > 2). Results: A total of 71 elderly AVMs were followed up for an average of 4.2 ± 2.3 years. Fifty-four (76.1%) presented with hemorrhage, and the preoperative annualized rupture risk was 9.4%. Among these patients, 21 cases (29.6%) received conservative treatment, 30 (42.3%) underwent microsurgical resection, 13 (18.3%) received embolization, and 7 (9.9%) underwent SRS. In the prognostic comparison, the short-term and long-term neurological outcomes were similar between conservation and intervention both in the ruptured and unruptured subgroups (ruptured: p = 0.096, p = 0.904, respectively; unruptured: p = 0.568, p = 0.306, respectively). In the ruptured subgroup, the intervention cannot reduce long-term mortality (p = 0.654) despite the significant reduction of subsequent hemorrhage than conservation (p = 0.014), and the main cause of death in the intervention group was treatment-related complications (five of seven, 71.4%). In the logistic regression analysis, higher admission mRS score (OR 3.070, 95% CI 1.559–6.043, p = 0.001) was the independent predictor of long-term unfavorable outcomes (mRS>2) in the intervention group, while complete obliteration (OR 0.146, 95% CI 0.026–0.828, p = 0.030) was the protective factor. Conclusions: The long-term outcomes of elderly AVMs after different management modalities were similar. Intervention for unruptured elderly AVMs was not recommended. For those ruptured, we should carefully weigh the risk of subsequent hemorrhage and treatment-related complications. Besides, complete obliteration should be pursued once the intervention was initiated. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT04136860 [ABSTRACT FROM AUTHOR]