Uncovering of Key Pathways and miRNAs for Intracranial Aneurysm Based on Weighted Gene Co-Expression Network Analysis

<b><i>Background:</i></b> Intracranial aneurysm (IA) is a serious cerebrovascular disease. The identification of key regulatory genes can provide research directions for early diagnosis and treatment of IA. <b><i>Methods:</i></b> Initially, the miRNA and mRNA data were downloaded from the Gene Expression Omnibus database. Subsequently, the limma package in R was used to screen for differentially expressed genes. In order to investigate the function of the differentially expressed genes, a functional enrichment analysis was performed. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to identify the hub module and hub miRNAs. The correlations between miRNAs and mRNAs were assessed by constructing miRNA-mRNA regulatory networks. In addition, in vitro validation was performed. Finally, diagnostic analysis and electronic expression verification were performed on the GSE122897 dataset. <b><i>Results:</i></b> In the present study, 955 differentially expressed mRNAs (DEmRNAs, 480 with increased and 475 with decreased expression) and 46 differentially expressed miRNAs (DEmiRNAs, 36 with increased and 10 with decreased expression) were identified. WGCNA demonstrated that the yellow module was the hub module. Moreover, 16 hub miRNAs were identified. A total of 1,124 negatively regulated miRNA-mRNA relationship pairs were identified. Functional analysis demonstrated that DEmRNAs in the targeted network were enriched in vascular smooth muscle contraction and focal adhesion pathways. In addition, the area under the curve of 16 hub miRNAs was &#x3e;0.8. It is implied that 16 hub miRNAs may be used as potential diagnostic biomarkers of IA. <b><i>Conclusion:</i></b> Hub miRNAs and key signaling pathways were identified by bioinformatics analysis. This evidence lays the foundation for understanding the underlying molecular mechanisms of IA and provided potential therapeutic targets for the treatment of this disease.

The Involvement of miRNAs in Pituitary Adenomas Pathogenesis and the Clinical Implications

Pituitary adenomas (PAs) account for the top three primary intracranial tumors in terms of total incidence rate. PAs can cause severe endocrine disorders and even malignant features, such as invasion, metastasis, and recurrence. Therefore, the early diagnosis and accurate prognosis would be greatly beneficial for clinical treatment of PAs. MicroRNAs (miRNAs) are small, protein-noncoding RNAs that regulate gene expression posttranscriptionally. They regulate essential physiological processes, including proliferation, growth, and apoptosis, and also they involve in the invasion and metastasis of malignant tumors. At the tissue level, differential miRNA expression in endocrine malignancies including PAs has been reported. When miRNAs have been successfully detected in various biofluids and cell-free environments, their important roles as potential screening or prognostic biomarkers have been extensively investigated. The current work reviews recent studies on the emerging roles of miRNAs in PAs and the clinical significance.

From Discipline to Quality of Care: How Neurologists Can Learn from Decisions of Disciplinary Tribunals

<b><i>Background:</i></b> One of the primary aims of medical disciplinary law is to improve the quality of care. However, the decisions of disciplinary tribunals are not sufficiently analysed to identify the learning elements. <b><i>Aim:</i></b> This study aimed to investigate the frequency and nature of complaints for the specialty neurology which were upheld by the disciplinary tribunals and to learn from disciplinary law through an analysis of which factors contributed to complaints being upheld. <b><i>Design:</i></b> This is a retrospective, observational study. <b><i>Methods:</i></b> All upheld complaints in the field of neurology were collected for the period of January 1, 2010, to January 1, 2020. A qualitative analysis of the decisions was conducted using the usual characteristics set out by disciplinary tribunals in their annual reports. The relevant factors which potentially played a role in the complaint being upheld were identified for more detailed analysis. <b><i>Results:</i></b> In the 10-year period, a complaint was submitted to the disciplinary tribunals against 299 neurologists. Forty-four complaints were upheld (15%). The most common sanction was a warning (70%). A large majority of cases were directly related to patient care, such as decisions about the patient’s diagnosis and the treatment. Recordkeeping (50%), interpretation and discussion of imaging (30%), and involvement of several consultants of one or more specialties (34%) frequently played a role in the successful complaints. <b><i>Conclusion:</i></b> Medical disciplinary cases in the field of neurology are usually about diagnosis- and treatment-related aspects. Recordkeeping, interpretation of neuroimaging, and involvement of several consultants frequently play a role in a complaint being upheld. It is important that specialties evaluate disciplinary decisions on a structural and continuous basis.

Identification of Novel Biomarkers in Platelets for Diagnosing Parkinson’s Disease

<b><i>Background:</i></b> Parkinson’s disease (PD) is a common neurodegenerative disease affecting the elderly, but there is no blood test for PD diagnosis in the clinic currently. This study aimed to explore promising biomarkers in platelets (PLTs) for PD diagnosis. <b><i>Methods:</i></b> PLTs were isolated from whole blood samples of PD patients and healthy controls (HCs), and RNA was extracted for sequencing. RNA-seq was performed on the Illumina HiSeq platform. <b><i>Results:</i></b> A total of 2,221 genes with differential transcript levels (GDTLs) were identified between PD patients and HCs, 1,041 of which are upregulated genes and 1,180 of which are downregulated genes. <i>WASH5P</i> was the most upregulated gene and <i>AC114491.1</i> was the most downregulated gene. Among the top 12 most relevant genes, metastasis-associated lung adenocarcinoma transcript 1 (<i>MALAT1</i>), eukaryotic elongation factor 1A (<i>EEF1A1</i>), and cathepsin S (<i>CTSS</i>) were reported to be associated with PD. Furthermore, gene ontology analysis showed that the most significant term in biological processes was neutrophil degranulation; the most enriched term in cellular components was cytoplasmic vesicle lumen; and tumor necrosis factor receptor superfamily binding was the most significant term in molecular functions. In the Kyoto Encyclopedia of Genes and Genomes enrichment analysis, inflammation-related pathway accounts for the majority. <b><i>Conclusion:</i></b> Our findings demonstrated <i>WASH5P</i>, <i>MALAT1</i>, <i>EEF1A1,</i> and <i>CTSS</i> may be promising biomarkers in PD, which may contribute to improving the effectiveness and accuracy of diagnosis for PD in the future.

Efficacy of Intra-Arterial Thrombolysis for Acute Central Retinal Artery Occlusion: A Meta-Analysis

<b><i>Introduction:</i></b> The best management strategy still remains strong controversy for acute nonarteritic central retinal artery occlusion (CRAO). We thus performed a meta-analysis to determine the efficacy of intra-arterial thrombolysis (IAT) for visual improvement according to different times from symptom onset. <b><i>Methods:</i></b> We searched EMBASE, PubMed, and Web of Science for relevant studies assessing efficiency of IAT in patients with CRAO compared with standard therapy. Fixed-effects and random-effects models were performed. <b><i>Results:</i></b> Five eligible studies including 459 patients with acute CRAO were pooled in the meta-analysis. In all, 219 (47.7%) received IAT, and the mean time from symptom onset to IAT was 13 h. The pooled analysis demonstrates odds ratio (OR) for the procedure of IAT and any visual improvement to be 1.520 (95% confidence intervals [CIs] 1.258–1.837; <i>p</i> &#x3c; 0.001). Subgroup analyses further indicated that the CRAO patients who received IAT achieved any visual improvement more easily within 6 h from symptom onset (OR = 1.703, 95% CI 1.219–2.381; <i>p</i> = 0.002), but not those beyond 6 h (OR = 1.260, 95% CI 0.973–1.632; <i>p</i> = 0.080). <b><i>Conclusion:</i></b> Our meta-analysis of available published data supports IAT to be an alternative treatment option for CRAO patients within 6 h from symptom onset.

Mechanical Thrombectomy with or without Intravenous Thrombolysis in Acute Ischemic Stroke: A Meta-Analysis for Randomized Controlled Trials

<b><i>Introduction:</i></b> The combination of mechanical thrombectomy (MT) and intravenous thrombolysis (IVT) is more effective than IVT alone in patients with large vessel occlusion, which has been proven in recent studies. However, there are still debates over whether IVT benefits patients treated with only direct mechanical thrombectomy (dMT). <b><i>Methods:</i></b> PubMed, Embase, and Cochrane Library were searched on June 15, 2021, for randomized controlled trials (RCTs). Seven RCTs with 2,143 patients were enrolled in our study. <b><i>Results:</i></b> MT combined with IVT had comparable efficacy and safety outcome compared with dMT in proximal anterior circulation occlusion at 90 days. For the primary outcome, pooled data showed no significant difference in the modified Rankin Scale (mRS) 0–2 at 90 days between the dMT and MT+IVT groups (pooled odds ratio 0.96, 95% confidence interval, 0.79, 1.17, <i>p</i> = 0.39). As for the mRS score 0–1 at 90 days, the degree of benefit conferred by dMT was substantial: for every 100 patients treated, the number of patients which had an excellent outcome in the dMT group was 10 higher than that of the MT+IVT group. <b><i>Conclusion:</i></b> In this meta-analysis including 7 RCTs, MT had comparable consequences to bridging treatment in efficacy and safety outcomes for patients with ischemic stroke caused by the occlusion of proximal anterior circulation, irrespective of geographical location. These findings support the adoption of dMT in acute ischemic stroke treatments and have higher cost-effectiveness in global applications.

Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis

<b><i>Introduction:</i></b> We aimed to develop and validate an Expanded Disability Status Scale (EDSS) model through clinical, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) measures. <b><i>Methods:</i></b> Sixty-four multiple sclerosis (MS) patients underwent peripapillary retinal nerve fiber layer and segmented macular layers evaluation through OCT (Spectralis, Heidelberg Engineering). Brain parenchymal fraction was quantified through Freesurfer, while cervical spinal cord (SC) volume was assessed manually guided by Spinal Cord Toolbox software analysis. EDSS, neuroradiological, and OCT assessment were carried out within 3 months. OCT parameters were calculated as the average of both nonoptic neuritis (ON) eyes, and in case the patient had previous ON, the value of the fellow non-ON eye was taken. Brain lesion volume, sex, age, disease duration, and history of disease-modifying treatment (1st or 2nd line disease-modifying treatments) were tested as covariables of the EDSS score. <b><i>Results:</i></b> EDSS values correlated with patient’s age (<i>r</i> = 0.543, <i>p</i> = 0.001), SC volume (<i>r</i> = −0.301, <i>p</i> = 0.034), and ganglion cell layer (GCL, <i>r</i> = −0.354, <i>p</i> = 0.012). Using these correlations, an ordinal regression model to express probability of diverse EDSS scores were designed, the highest of which was the most probable (Nagelkerke <i>R</i>² = 43.3%). Using EDSS cutoff point of 4.0 in a dichotomous model, compared to a cutoff of 2.0, permits the inclusion of GCL as a disability predictor, in addition to age and SC. <b><i>Conclusions:</i></b> MS disability measured through EDSS is an age-dependent magnitude that is partly conditioned by SC and GCL. Further studies assessing paraclinical disability predictors are needed.

Shell Shock: The Response of UK Neurology

The neurological and psychological manifestations of trauma, confinement, and terror became apparent throughout Europe as soldiers were evacuated from the trenches of the Western Front. The response in the UK evolved as a result of the experience of medical staff embedded with the troops in base hospitals and the philosophy of those treating returned soldiers in specialist establishment. There were widely disparate approaches to the management encompassing simple supportive care, a psychanalytic approach and radical electric shock therapy. The latter was partially driven by the Queen Square experience in the UK but was also concurrently widely pursued throughout Europe. With experience, care was increasingly undertaken close to the front lines using a philosophy of immediacy and expectation of recovery. Post-war analysis was startlingly unsympathetic, yet the experiences and management of <i>shell shock</i> have guided psychiatric and medical understanding of functional illness and post-traumatic stress over the subsequent century. In this historical review, we have sought to present features of the UK response to the neurological manifestations of trauma, the way in which these changed as the war proceeded and the political and medical response in the aftermath of war.