Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

多维价值框架推动思政教学——药事法规课程思政建设探索

目的： 探究药事法规课程思政建设的思路与实施路径，为高等学校药学相关专业本科药事法规课程思政建设提供参考方法： 基于《高等学校课程思政建设指导纲要》的文件要求，汇总分析药事法规课程思政建设要点与思政元素，结合课堂内外资源，提出课程思政建设多维价值框架，并应用于药事法规课程思政教学中。结果与结论： 在课程思政教学中，可遵循“三结合，两巩固，一推动”的多维价值框架，将社会主义核心价值观、职业使命感、民族自豪感、中医药文化自信、家国情怀等思政元素融入其中。专业课程需起到良好的思政教学作用，但应注意坚持以学生为中心，做到“润物细无声”，有效把握不同课程思政元素的应用，并重视任课教师的言传身教，还需要对课程思政建设效果进行评价与反思，以使课程建设不断完善。     

国内健康信息研究作者合著网络及研究主题分析

目的分析核心作者、作者合著网络特征,推测国内健康信息研究的发展阶段、主要研究力量及主要研究主题。方法以CNKI期刊库为数据源,以"健康信息"及相关词为主题词,检索2000—2018年的相关文献,基于普莱斯定律及综合指数法确定核心作者,使用数据统计软件Excel及社会网络分析软件Vcinet,利用综合指数以及社会网络分析法计算作者间联系合作紧密度,并离析高产合作子网。结果文献量以较快指数型速率增长。作者合作率较高且信息传输渠道较通畅,2000—2018年国内研究的合著率稳定在80%,但学者的合作关系较为单一,多集中在同一机构或同一师门,阻碍了跨机构学者的交流合作。主要合作团队活跃度较高且核心成员多为研究领域的核心作者,科研产出量较大且被引频次较高。结论国内研究正处于旺盛发展期,但未形成稳定的核心作者群体。学者间因同机构或师门关系产生固定合作,健康信息管理、公众健康行为、健康教育等为核心作者或活跃团队研究的主要主题。     

Two-year results after combined phacoemulsification and iris-fixated phakic intraocular lens removal

Graefe's Archive for Clinical and Experimental Ophthalmology - To describe and present results after a technique for cataract surgery combined with explantation of an iris-fixated phakic...     

A Coupled FEM-BEM Approach for the Solution of the Free-Boundary Axi-Symmetric Plasma Equilibrium Problem

In this paper we present a coupled Finite Element Method – Boundary Element Method (FEM-BEM) approach for the solution of the free-boundary axi-symmetric plasma equilibrium problem. The proposed method, obtained from an improvement of the Hagenow-Lackner coupling method, allows to efficiently model the equilibrium problem in unbounded domains by discretizing only the plasma region; the external conductors can be modelled either as 2D or 3D models, according to the problem of interest. The paper explores different iterative methods for the solution of the nonlinear Grad-Shafranov equation, such as Picard, Newton-Raphson and Newton-Krylov, in order to provide a robust and reliable tool, able to handle large-scale problems (e.g. high resolution equilibria). This method has been implemented in the FRIDA code (FRee-boundary Integro-Differential Axisimmetric – https://github. om/matteobonotto/ FRIDA), together with a suitable Adaptive Integration Technique (AIT) for the computation of the source term. FRIDA has been successfully tested and validated against experimental data from RFX-mod device, and numerical equilibria of an ITER-like device.