Investigation of the prevalence and clinical implications of ERBB2 exon 16 skipping mutations in Chinese pan-cancer patients

BackgroundAlthough rare, ERBB2 exon 16 skipping mutations (ERBB2ΔEx16) have been implicated in resistance to anti-HER2 and anti-EGFR targeted agents. Our study investigated the prevalence and clinical significance of ERBB2ΔEx16 in Chinese pan-cancer patients.MethodsWe retrospectively screened 40996 patients, spanning 19 cancer types, who had available genomic profiles acquired with DNA-based next-generation sequencing (NGS). We characterized the clinical and molecular features of the ERBB2ΔEx16-positive patients. Furthermore, we also analyzed a pan-cancer dataset from the Cancer Genome Atlas (TCGA; n=8705).ResultsA total of 22 patients were detected with ERBB2ΔEx16, resulting in an overall prevalence rate of 0.054% (22/40996). Of them, 16 patients had lung cancer (LC; 0.05%, 16/30890), five patients had gastric cancer (GC; 0.35%, 5/1448), and one patient had ovarian cancer (0.12%, 1/826). Among the 16 LC patients, ERBB2ΔEx16 was detected in four treatment-naïve EGFR/ALK-negative patients and 12 EGFR-positive patients after the onset of resistance to EGFR tyrosine kinase inhibitors (TKIs). The treatment-naïve patients harbored no LC-associated oncogenic drivers except ERBB2 amplification, suggesting a potential oncogenic role for ERBB2ΔEx16. Consistently, ERBB2ΔEx16+ patients from TCGA data also carried no known drivers despite various concurrent alterations. In the 12 EGFR TKI-resistant LC patients, relative variant frequencies for ERBB2ΔEx16 were lower than in untreated patients, suggesting ERBB2ΔEx16 as secondary alterations following TKI treatment and thereby implicating ERBB2ΔEx16 in mediating therapeutic resistance.ConclusionsOur study identified an overall ERBB2ΔEx16 prevalence rate of 0.054% and provided insights into the clinical implications of ERBB2ΔEx16 in Chinese pan-cancer patients

A Support Vector Machine Model with Hyperparameters Optimised by Mind Evolutionary Algorithm for Assessing Permeability of Rock

In this paper, a database developed from the existing literature about permeability of rock was established. Based on the constructed database, a Support Vector Machine (SVM) model with hyperparameters optimised by Mind Evolutionary Algorithm (MEA) was proposed to predict the permeability of rock. Meanwhile, the Genetic Algorithm- (GA-) and Particle Swarm Algorithm- (PSO-) SVM models were constructed to compare the improving effects of MEA on the foretelling accuracy of machine learning models with those of GA and PSO, respectively. The following conclusions were drawn. MEA can increase the predictive accuracy of the constructed machine learning models remarkably in a few iteration times, which has better optimisation performance than that of GA and PSO. MEA-SVM has the best forecasting performance, followed by PSO-SVM, while the estimating precision of GA-SVM is lower than them. The proposed MEA-SVM model can accurately predict the permeability of rock indicating the model having a satisfactory generalization and extrapolation capacity

Investigation of Anisotropic Permeability and Porosity of CJRM considering Different Confinement Loading Pressures

An innovative method is proposed to prepare artificial columnar jointed rock masses (CJRM) with different columnar dip angles, and laboratory physical model tests are conducted to investigate anisotropic permeability and porosity characteristics of the prepared artificial CJRM. In the physical model experiment, permeability and porosity of artificial CJRM with different columnar dip angles is measured during three times cyclic loading and unloading of confinement pressure. Based on the results of the laboratory model tests, the Equivalent Continuum Media Model was applied to analyse anisotropic permeability of CJRM. The main conclusions are summarized as follows. In the first loading phase of confinement pressure, the impacts of confinement pressure on the anisotropic permeability of artificial CJRM, porosity, and the major and minor principle permeability coefficients (PPCs) are significant, while in the following stages of confinement pressure loading and unloading, the change of them is small, with stable value. Permeability of artificial CJRM gradually increases with rise of columnar dip angle, and the permeability anisotropy of artificial CJRM under low confinement pressure is higher than that under low confinement pressure

Efficacy and safety of Sofosbuvir-containing regimens in patients co-infected with chronic hepatitis C virus and human immunodeficiency virus: a meta-analysis

Abstract Background The treatment of hepatitis C virus (HCV) in HCV/human immunodeficiency virus (HIV) co-infected patients remains complex. This present meta-analysis evaluated the efficacy and safety of Sofosbuvir (SOF) for treatment in HCV/HIV co-infected patients using the most recent and available data. Methods A systematic search of the published data was conducted in PubMed Medline, EMBASE and Cochrane databases. Eligible studies were clinical trials, case-control studies or prospective cohort studies aiming at assessing the efficacy and safety of the SOF-containing regimens in patients co-infected with HCV and HIV. Heterogeneity of results was assessed and a pooled analysis was performed using random effects model with maximum likelihood estimate and 95% confidence intervals (95%CI). Subgroup analysis and assessment of publication bias through Egger’s test were also performed. STATA 13.0 software was used to analyze the data. Results Seven studies (n = 1167 co-infected patients) were included in this analysis. The pooled estimate of sustained virological response at 12 weeks (SVR12) was 94.0% (95%CI: 92.0%–95.0%). Subgroup analysis showed that the treatment-naïve patients had higher SVR12 compared with patients that were treated before (χ2 = 21.39, P < 0.01). The pooled incidence of any adverse events (AEs) was 79.6% (95%CI: 77.1%–82.1%). Publication bias did not exist. Conclusion The results of this study showed that the treatment response of SOF-containing regimens in patients co-infected with HIV and HCV was satisfied. Attention should be paid to the high rates of AEs