Applying the OMOP Common Data Model to Facilitate Benefit-Risk Assessments of Medicinal Products Using Real-World Data from Singapore and South Korea

Hui Xing Tan,Desmond Chun Hwee Teo,이동윤,김청수,Jing Wei Neo,Cynthia Sung,Haroun Chahed,Pei San Ang,Doreen Su Yin Tan,박래웅,Sreemanee Raaj Dorajoo 대한의료정보학회 2022 Healthcare Informatics Research Vol.28 No.2

Objectives: The aim of this study was to characterize the benefits of converting Electronic Medical Records (EMRs) to acommon data model (CDM) and to assess the potential of CDM-converted data to rapidly generate insights for benefitriskassessments in post-market regulatory evaluation and decisions. Methods: EMRs from January 2013 to December 2016were mapped onto the Observational Medical Outcomes Partnership-CDM (OMOP-CDM) schema. Vocabulary mappingswere applied to convert source data values into OMOP-CDM-endorsed terminologies. Existing analytic codes used in a priorOMOP-CDM drug utilization study were modified to conduct an illustrative analysis of oral anticoagulants used for atrialfibrillation in Singapore and South Korea, resembling a typical benefit-risk assessment. A novel visualization is proposed torepresent the comparative effectiveness, safety and utilization of the drugs. Results: Over 90% of records were mapped ontothe OMOP-CDM. The CDM data structures and analytic code templates simplified the querying of data for the analysis. Intotal, 2,419 patients from Singapore and South Korea fulfilled the study criteria, the majority of whom were warfarin users. After 3 months of follow-up, differences in cumulative incidence of bleeding and thromboembolic events were observable viathe proposed visualization, surfacing insights as to the agent of preference in a given clinical setting, which may meaningfullyinform regulatory decision-making. Conclusions: While the structure of the OMOP-CDM and its accessory tools facilitatereal-world data analysis, extending them to fulfil regulatory analytic purposes in the post-market setting, such as benefit-riskassessments, may require layering on additional analytic tools and visualization techniques.

A novel design method for improving collapse resistances of multi-story steel frames with unequal spans using steel braces

Zheng Tan,Wei-hui Zhong,Bao Meng,Shi-chao Duan,Hong-chen Wang3,Xing-You Yao,Yu-hui Zheng 국제구조공학회 2023 Steel and Composite Structures, An International J Vol.47 No.2

The bearing capacities resisted by the two-bay beams of multi-story planar frames with unequal spans under column removal scenarios differ considerably owing to the asymmetric stress on the left and right beams connected to the failed column and cause the potential for beams with larger span-to-depth ratios to be unable to exert effectively, which is disadvantageous for resisting the vertical load in unequal-span frame structures. To address this problem, the structural measure of adding braces to the weak bays of multi-story unequal-span frames was proposed, with the objective of achieving a coordinated stress state in two-bay beams with unequal spans, thereby improving the collapse resistance of unequal-span frame structures. Before conducting the numerical simulation, the modeling methods were verified by previous experimental results of two multi-story planar frames with and without steel braces. Thereafter, the effects of the tensile and compressive braces on the collapse behavior of the frame structures were elucidated. Then, based on the mechanical action laws of the braces throughout the collapse process, a detailed design method for improving the collapse resistance of unequal-span frame structures was proposed. Finally, the proposed design method was verified by using sufficient example models, and the results demonstrated that the design method has good application prospects and high practical value.

Reference gene selection for transcriptional profiling by RT-qPCR in the 28-spotted larger potato ladybird

Zhang Yu-Xing,Tan Qiao,Shen Chen-Hui,Wu Jian-Jian,Wu Yi-Kuan,Li Wen-Ze,Jin Lin,Li Guo-Qing 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.2

Henosepilachna vigintioctomaculata is one of the most serious defoliates attacking potatoes. However, studies on functional genes have greatly been limited due to the insufficiency of effective and stable endogenous references to normalize RT-qPCR data. In this report, nine housekeeping genes (RPL4, RPL6, RPL13, RPL32, RPS18, ACT, EF1α, GAPDH and α-TUB) involved in different biological processes were selected. Their expression levels under diverse experimental conditions including developmental stages, tissues, temperatures and host plants were determined using RT-qPCR technology. The tested candidate genes were comprehensively ranked based on five alternative stability analysis methods (Ct value, geNorm, NormFinder, BestKeeper and ReFinder). The results revealed that the optimal internal reference genes varied under different experimental conditions. Any gene pair among the five candidates (RPL4, RPL13, RPL32, RPS18 and EF1α) was a suitable reference gene set under different temperatures and on different host plants. A combination of RPL6 and RPL13 was recommended as the best reference gene set across different developmental stages. A pair of RPS18 and EF1α was ranked as the optimal reference gene combination within different tissues. The most suitable reference genes were RPS18 and RPL13 under four different experimental conditions. Our findings not only establish an accurate and reliable normalization of RT-qPCR data, but also lay a solid foundation for further functional gene researches in H. vigintioctomaculata

Elevated PIVKA-II is Associated with Early Recurrence and Poor Prognosis in BCLC 0-A Hepatocellular Carcinomas

Wang, Bei-Li,Tan, Qi-Wen,Gao, Xing-Hui,Wu, Jiong,Guo, Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection. Materials and Methods: Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013. ELISA was used to detect the serum concentrations of preoperative PIVKA-II. The prognostic value of PIVKA-II and other clinicopathological factors was analyzed by the Kaplan-Meier method and the multivariate Cox proportional hazards model. Results: During follow-up, 39 of 140 patients suffered recurrence and the 1-year recurrence rate was 27.9%. The high-PIVKA-II expression group had lower 1-year time to progression (TTP) compared with the low-expression group (54.8% vs 20.2%, p<0.001). Patients with high preoperative PIVKA-II expression showed a relatively higher risk of developing postoperative recurrence than those with low expression in the low-recurrence-risk subgroups, including ${\alpha}$-fetoprotein ${\leq}400ng/mL$ (45.4% vs 16.7%; p=0.006), tumor size ${\leq}5cm$ (54.2% vs 18.1%; p<0.001), single tumor (56.0% vs 19.1%; p<0.001), absence of satellite lesions (53.3% vs 19.8%; p=0.001), absence of vascular invasion (52.6% vs 14.9%; p=0.002), and Edmondson stage I/II (60.9% vs 20.3%; p<0.001). PIVKA-II was the strongest independent prognostic factor for TTP (hazard ratio, 2.877; 95% CI 1.524-5.429; p=0.001). Conclusions: Elevated PIVKA-II is associated with early recurrence of BCLC 0-A HCC after curative resection and can be considered a novel prognostic predictor.

Upregulation and biological function of transmembrane protein 119 in osteosarcoma

Zhen-Huan Jiang,Jun Peng,Hui-Lin Yang,Xing-Li Fu,Jin-Zhi Wang,Lei Liu,Jian-Nong Jiang,Yong-Fei Tan,Zhi-Jun Ge 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in osteosarcoma tissues to be positively correlated with cell cycle, apoptosis, metastasis and TGF-β signaling. We then knocked down TMEM119 expression in U2OS and MG63 cells using small interfering RNA, which revealed that downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that TMEM119 knockdown significantly inhibited cell migration and invasion, and decreased the expression of TGF-β pathway-related factors (BMP2, BMP7 and TGF-β). TGF-β application rescued the inhibitory effects of TMEM119 knockdown on osteosarcoma cell migration and invasion. Further in vitro experiments with a TGF-β inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that TMEM119 significantly promotes cell migration and invasion, partly through TGF-β/BMP signaling. In conclusion, our data support the notion that TMEM119 contributes to the proliferation, migration and invasion of osteosarcoma cells, and functions as an oncogene in osteosarcoma.