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Vagus nerve stimulation (VNS) has been suggested to be an effective method for regulating seizures in patients with drug-resistant epilepsy. This study aims to investigate the effects of VNS on the directed brain networks of patients with drug-resistant epilepsy, offering new insights into the clinical treatment of epilepsy using VNS. We analyzed EEG data from drug-resistant epilepsy patients who underwent VNS treatment between 2017 and 2021. We used the directed phase transfer entropy (dPTE) to evaluate effective connectivity in various frequency bands (delta, theta, alpha, beta, gamma) among scalp EEG channels. We computed mean dPTE values for each node to assess changes in information flow, in-degree, and out-degree as indicators of node properties. Statistical analyses have been performed to compare conditions before and after VNS treatment. The results showed that before VNS treatment, the primary information flow was from the anterior to the posterior regions. However, after VNS treatment, this flow shifted to a posterior-to-anterior direction. Significant changes in directed network nodes and edges were found to be frequency-dependent, with the most prominent changes occurring in the frontal and parietal-occipital regions. In-degree, out-degree, and directed edges also exhibited remarkable changes after VNS treatment. Notably, weakened edges were mainly observed in the frontal lobe, while enhanced edges were predominantly from the parietal-occipital region to the frontal lobe. In summary, VNS treatment alters the brain network in patients with drug-resistant epilepsy, promoting forward information flow, and contributing to our better understanding of VNS as an epilepsy treatment. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of intracranial aneurysm (IA) is arduous in the current situation, and no biomarker is available for the screening of IA. We here systematically evaluate the diagnostic value of circulating non-coding RNA (ncRNA) for the diagnosis of IA.Methods: We searched PubMed, Web of Science, Embase, Scopus and Cochrane Library databases from inception to June 2020. We included studies that investigated the diagnostic performance of circulating ncRNAs for the diagnosis of IA. We performed Random-effect meta-analyses for the diagnostic test accuracy to calculate pooled estimates. Subgroup analyses and sensitivity analyses were conducted to explore the source of heterogeneity.Results: Thirteen studies, including 1,105 patients and 28 ncRNAs, were included. The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.76-0.83) and 0.80 (95% CI, 0.76-0.84), respectively, and the area under the hierarchical summary receiver operating characteristic curve was 0.87 (95% CI, 0.84-0.89). The pooled positive and negative likelihood ratios were 3.97 (95% CI, 3.17-4.98) and 0.25 (95% CI, 0.21-0.31), corresponding with a diagnostic odds ratio of 15.63 (95% CI, 10.41-23.47). Subgroup analyses revealed that the diagnostic accuracy of miRNA, lncRNA and circRNA were not significantly different (p > 0.05). Circulating ncRNAs showed higher diagnostic accuracy for patients with unruptured IA than those with ruptured IA (p = 0.0122).Conclusion: Current evidence suggests that the circulating ncRNA test could be an effective method for universal IA screening. Future clinical studies need to confirm the diagnostic role of specific ncRNAs. [ABSTRACT FROM AUTHOR]

Abstract: A simple and accurate method has been developed to simultaneously separate and determine 10 bioactive compounds in citrus fruits by high-performance liquid chromatography coupled with diode array detection and electrospray ionisation mass spectrometry (HPLC-DAD–ESI/MS). This HPLC assay was performed on a reversed-phase C18 column with acetonitrile and 0.1% (v/v) aqueous formic acid as mobile phase. DAD has been performed at 273, 283 and 324nm for quantification of the alkaloids, flavanones and hydroxycinnamic acids. MS was also employed to identify the each analyte. Ten analytes (naringin, hesperidin, neohesperidin, ferulic acid, p-coumaric acid, chlorogenic acid, caffeic acid, octopamine, synephrine and tyramine) demonstrated good linearity (r ⩾0.9990) in a relatively wide concentration range. The method revealed high average recovery (range, 92.1–97.9%) and good precision with interday and intraday variations with less than 4.71%. The limits of detection (LODs) ranged from 0.02 to 0.11μg/ml, while the limits of quantification (LOQs) were defined in the range of 0.08–0.39μg/ml. The proposed method has been successfully applied to analyse three types of bioactive constituents in eight citrus hybrids pulps and eight citrus hybrids peels, which has been successfully cultivated in China. [Copyright &y& Elsevier]

NY-ESO-1 TCR T (GSK3377794) are autologous polyclonal T cells transduced by a self-inactivating lentiviral vector to express an affinity-enhanced TCR recognizing NY-ESO-1 or LAGE-1a antigenic peptides in complex with HLA-A2. NY-ESO-1 and LAGE-1a are immunogenic cancer/testis antigens overexpressed in mutiple myeloma (MM) and linked to poor clinical outcome. Patients (pts) with MM who received GSK3377794 after autologous stem cell transplant (ASCT) showed encouraging clinical activity. PD-1 expression on CD8 T cells can occur in GSK3377794-treated MM pts and may limit adaptive immune response; this is a mechanism of resistance/relapse in CD19 CAR T-cell trials. Combining GSK3377794 with an anti-PD1 inhibitor (pembrolizumab) may have synergistic antitumor activity. Evaluate safety and efficacy of GSK3377794 alone or in combination with pembrolizumab in pts with relapsed MM. This is an open-label, pilot study (NCT03168438) of GSK3377794 in pts who are HLA-A*02:01, 05, ± 06 positive and have NY-ESO-1+/LAGE-1a+ relapsed/refractory MM. Twenty pts who have received ≥3 prior therapies containing ≥1 (separately or combined; including ASCT) of an IMiD, PI, alkylator, CD38 monoclonal antibody, and glucocorticoid, will be assigned to 1 of 2 arms: GSK3377794 as a single infusion (Arm 1, n=10) or GSK3377794 as a single infusion + pembrolizumab 200 mg IV every 3 wk (Arm 2, n=10). Arm 1 enrollment will complete before enrolling Arm 2. Pembrolizumab treatment will start from Wk 3 (Wk 6 if precluded by toxicity). Each patient will undergo leukapheresis to obtain cells for autologous NY-ESO-1-specific T-cell manufacturing, followed by lymphodepleting chemotherapy with fludarabine + cyclophosphamide, then GSK3377794 infusion of 1−8 × 109 transduced T cells. Study objectives are to assess safety and tolerability (primary) and antitumor activity (secondary) of GSK3377794 treatment (± pembrolizumab). At each visit, pts will be monitored for AEs and treatment-limiting toxicities, efficacy (using IMWG criteria), and biomarkers. Arm 2 enrollment will pause for a 3-wk safety review period after the first 3 pts receive their first pembrolizumab dose. Treatment will continue until disease progression or 108 wk after GSK3377794 infusion. After completing treatment, pts will transfer to long-term follow-up (NCT03391778) to continue safety/survival monitoring for up to 15 years. As of Jan 27, 2019, 50 pts have been screened. Half have tested positive for HLA-A*02:01, 05, ± 06; bone marrow samples from 12/21 (57%) tested positive for NY-ESO-1 ± LAGE-1a. To date, 3 pts have received GSK3377794. Further work is ongoing to enhance patient eligibility. These data are presented on behalf of the original authors with their permission. A similar presentation will be presented at the ASH Annual Meeting, Orlando, FL, USA, Dec 7-10, 2019. This study (NCT03168438) is funded by GSK. [ABSTRACT FROM AUTHOR]