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BackgroundImmune checkpoint inhibition holds promise as a novel treatment for pancreatic ductal adenocarcinoma (PDAC). The clinical significance of soluble immune checkpoint (ICK) related proteins have not yet fully explored in PDAC.MethodsWe comprehensively profiled 14 soluble ICK-related proteins in plasma in 70 PDAC patients and 70 matched healthy controls. Epidemiological data of all subjects were obtained through structured interviews, and patients’ clinical data were retrieved from electronical health records. We evaluated the associations between the biomarkers with the risk of PDAC using unconditional multivariate logistic regression. Consensus clustering (k-means algorithm) with significant biomarkers was performed to identify immune subtypes in PDAC patients. Prediction models for overall survival (OS) in PDAC patients were developed using multivariate Cox proportional hazards regression. Harrell’s concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve and calibration curve were utilized to evaluate performance of prediction models. Gene expressions of the identified ICK-related proteins in tumors from TCGA were analyzed to provide insight into underlying mechanisms.ResultsSoluble BTLA, CD28, CD137, GITR and LAG-3 were significantly upregulated in PDAC patients (all q < 0.05), and elevation of each of them was correlated with PDAC increased risk (all p < 0.05). PDAC patients were classified into soluble immune-high and soluble immune-low subtypes, using these 5 biomarkers. Patients in soluble immune-high subtype had significantly poorer OS than those in soluble immune-low subtype (log-rank p = 9.7E-03). The model with clinical variables and soluble immune subtypes had excellent predictive power (C-index = 0.809) for the OS of PDAC patients. Furthermore, the immune subtypes identified with corresponding genes’ expression in PDAC tumor samples in TCGA showed an opposite correlation with OS to that of immune subtypes based on blood soluble ICK-related proteins (log-rank p =0.02). The immune-high subtype tumors displayed higher cytolytic activity (CYT) score than immune-low subtype tumors (p < 2E-16).ConclusionFive soluble ICK-related proteins were identified to be significantly associated with the risk and prognosis of PDAC. Patients who were classified as soluble immune-low subtype based on these biomarkers had better overall survival than those of the soluble immune-high subtype.

A digital rights management (DRM) system provides the function of packaging raw content into an appropriate distribution form, protection for content temper-proof transmission and circumvention of unauthorized use. The digital rights contents in DRM system improve people’s spiritual quality and create huge market value. However, in the sharing of digital contents, malicious adversaries could bring security and privacy issues even cause infringement of copyright. To solve these problems, valid user identity authentication and secret key distribution to legal users is an efficient method. Nevertheless, the existing authentication schemes for DRM system have problems of security weakness or efficiency to be enhanced. Thereby, we cryptanalyze these protocols’ vulnerabilities and propose a new lightweight anonymous authentication protocol called Eland that can be efficiently applied to DRM system. We compare our protocol with six DRM-related authentication protocols from the aspects of security properties, computation expense and communication cost. Comparisons results indicate that our protocol achieves a well trade-off between security and performance. Specifically, our protocol reduces 37.5% communication cost and satisfies more security requirements than Yu et al.’s scheme. &nbsp

The traditional TRIZ(Teoriya Resheniya Izobretatelskikh Zadatch, Theory of Inventive Problem Solving) ideality level algorithm is improved, on the basis of interpretation of the meaning of ideality level, the concept of ideality level is redefined, the expression, range, domain, and application range of ideality level are explored; by adding weight parameters in the ideality level calculation formula, the relative importance of specific functions is reflected, the concept of idealized innovation is proposed, the correlations among each innovation stage in the total innovation system are established, and the specific application of ideality level is illustrated with the technological evolution process of washing machine as an example.