Purpose
The Chang Gung Research Database (CGRD), the largest multi‐institutional electronic medical records (EMR) collection in Taiwan, provides good access for researchers to efficiently use the ...standardized patient‐level data. This study evaluates the capacity and representativeness of the CGRD to promote secondary use of EMR data for clinical research with more accurate estimates.
Methods
The National Health Insurance Research Database (NHIRD) which covers over 99.9% of the Taiwanese population served as the comparator in this study. We compare the data components of the CGRD with the NHIRD, including records for health care facilities, patients, diagnoses, drugs, and procedures. Using the chi‐square test, we compared the distributions of age categories and sex of patients, and the rates of their health conditions between NHIRD and CGRD based on the year 2015.
Results
The CGRD contains more clinical information such as pathological and laboratory results than the NHIRD. The CGRD includes 6.1% of outpatients and 10.2% of hospitalized patients from the NHIRD. We found the CGRD includes more elderly outpatients (23.5% vs 12.5%) and pediatric inpatients (19.7% vs 14.4%) compared with the NHIRD. We found patients' sex distributions were similar between CGRD and NHIRD, but coverage rates of severe conditions, such as cancer, were higher than other health conditions in CGRD.
Conclusions
The CGRD could serve as the basis for accurate estimates in medical studies. However, researchers should pay special attention to selection biases since patients' characteristics from CGRD differ from those of the national database.
Taiwan's National Health Insurance Research Database (NHIRD) exemplifies a population-level data source for generating real-world evidence to support clinical decisions and health care policy-making. ...Like with all claims databases, there have been some validity concerns of studies using the NHIRD, such as the accuracy of diagnosis codes and issues around unmeasured confounders. Endeavors to validate diagnosed codes or to develop methodologic approaches to address unmeasured confounders have largely increased the reliability of NHIRD studies. Recently, Taiwan's Ministry of Health and Welfare (MOHW) established a Health and Welfare Data Center (HWDC), a data repository site that centralizes the NHIRD and about 70 other health-related databases for data management and analyses. To strengthen the protection of data privacy, investigators are required to conduct on-site analysis at an HWDC through remote connection to MOHW servers. Although the tight regulation of this on-site analysis has led to inconvenience for analysts and has increased time and costs required for research, the HWDC has created opportunities for enriched dimensions of study by linking across the NHIRD and other databases. In the near future, researchers will have greater opportunity to distill knowledge from the NHIRD linked to hospital-based electronic medical records databases containing unstructured patient-level information by using artificial intelligence techniques, including machine learning and natural language processes. We believe that NHIRD with multiple data sources could represent a powerful research engine with enriched dimensions and could serve as a guiding light for real-world evidence-based medicine in Taiwan.
Support vector machine (SVM) is a popular pattern classification method with many diverse applications. Kernel parameter setting in the SVM training procedure, along with the feature selection, ...significantly influences the classification accuracy. This study simultaneously determines the parameter values while discovering a subset of features, without reducing SVM classification accuracy. A particle swarm optimization (PSO) based approach for parameter determination and feature selection of the SVM, termed PSO
+
SVM, is developed.
Several public datasets are employed to calculate the classification accuracy rate in order to evaluate the developed PSO
+
SVM approach. The developed approach was compared with grid search, which is a conventional method of searching parameter values, and other approaches. Experimental results demonstrate that the classification accuracy rates of the developed approach surpass those of grid search and many other approaches, and that the developed PSO
+
SVM approach has a similar result to GA
+
SVM. Therefore, the PSO
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SVM approach is valuable for parameter determination and feature selection in an SVM.
Tumors are influenced by a microenvironment rich in inflammatory cytokines, growth factors and chemokines, which may promote tumor growth. Interleukin‐6 (IL‐6) is a multifunctional cytokine and known ...as a regulator of immune and inflammation responses. IL‐6 has also been reported to be associated with tumor progression and chemoresistance in different types of cancers. In our study, we demonstrated that IL‐6 enriches the properties of lung cancer stem‐like cells in A549 lung cancer cells cultured in spheroid medium. IL‐6 also promotes sphere formation and stem‐like properties of A549 cells by enhancing cell proliferation. Methylation‐specific polymerase chain reaction (PCR) was performed and revealed that IL‐6 increased methylation of p53 and p21 in A549 cancer cells. Western blot analysis and quantitative real‐time PCR demonstrated that IL‐6 increased the expression of DNA methyltransferase 1 (DNMT1) in A549 cells cultured in spheroid medium, but not the expression of DNMT3a or DNMT3b. Knockdown of DNMT1 eliminated IL‐6‐mediated hypermethylation of cell cycle regulators and enrichment of lung cancer stem‐like properties. In conclusion, our study, for the first time, shows that the IL‐6/JAK2/STAT3 pathway upregulates DNMT1 and enhances cancer initiation and lung cancer stem cell (CSC) proliferation by downregulation of p53 and p21 resulting from DNA hypermethylation. Upon blockage of the IL‐6/JAK2/STAT3 pathway and inhibition of DNMT1, the proliferation of lung CSCs was reduced and their formation of spheres and ability to initiate tumor growth were decreased. These data suggest that targeting of the IL‐6/JAK2/STAT3 signaling pathway and DNMT1 may become important strategies for treating lung cancer.
What's new?
Dysregulation of interleukin‐6 is implicated in the progression of lung cancer, but the mechanisms by which IL‐6 may facilitate disease progression are not fully known. Here, in cell and tumor sphere models, cancer initiation and lung cancer stem cell (CSC) proliferation were enhanced by upregulation of DNA methyltransferase 1 (DNMT1) as a consequence of IL‐6/JAK2/STAT3 pathway activity. DNMT1 upregulation resulted in DNA hypermethylation and downregulation of p53 and p21. Upon blockage of the IL‐6/JAK2/STAT3 pathway and inhibition of DNMT1, the proliferation of lung CSCs, their formation of spheres, and their ability to initiate tumor growth decreased.
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•Carbon-coated V2O5 nanoparticles are prepared using MOF as template and precursor.•The carbon coating layer can enhance the electronic conductivity and dimensional stability of ...V2O5.•Compared with the bare V2O5, carbon-coated V2O5 exhibits excellent electrochromic performance.
In this study we synthesized a vanadium (V)-containing metal–organic framework (MOF) and used it as a template to prepare V2O5 NPs. We used MIL-47, a V-containing MOF having uniform C and V distributions, as a precursor for the preparation of carbon-coated V2O5 (C@V2O5) samples through annealing. The C@V2O5 structures were readily dispersed in poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) to form stable solutions, allowing the deposition of C@V2O5 on various substrates through simple low-temperature solution-based processes. The uniform coating of carbon on V2O5 was useful for two reasons: (i) the outer layer enhanced the electronic conductivity of a V2O5 electrode and its corresponding electrochemical properties and (ii) based on the electrochemical quartz crystal microbalance (EQCM) analysis, the carbon coating served as a buffer layer that allowed Li+ ion transport, but blocked migration of solvent into the V2O5 electrode, thereby improving the dimensional and electrochemical stability. Compared with the bare V2O5, C@V2O5 exhibited excellent electrochromic (EC) performance, with an EC contrast of 45.8%, a mean response time of 3.4 s, and a coloration efficiency of 89.3 cm2/C. C@V2O5 also displayed higher cycling stability (80.6% retention after 5000 cycles) and highly reversible ionic transport during redox reactions, compared with those of the bare V2O5.
Pulmonary fibrosis is characterized by fibroblast proliferation and extracellular matrix remodelling, leading to respiratory insufficiency. The mechanisms underlying this progressive and devastating ...disease remain unclear. Conditions that can impair the function of the endoplasmic reticulum (ER) cause accumulation of unfolded or misfolded proteins, resulting in ER stress and activation of the unfolded protein response (UPR). ER stress has been implicated in many conditions including cancer, diabetes, obesity, and inflammation. It is also involved in lung fibrosis, through myofibroblastic differentiation of fibroblasts; however, the precise role of ER stress in lung fibrosis is unknown. The current study aimed to investigate the underlying mechanisms of ER stress inhibitors in the treatment of bleomycin-induced lung fibrosis. We demonstrated that bleomycin can activate ER stress associated proteins, including GRP78, CHOP, and ATF-4, both in vitro and in vivo. PI3K/AKT acts upstream of ER stress to affect lung fibroblast proliferation, resulting in bleomycin-induced pulmonary fibrosis. Treatment with ER stress inhibitors or a PI3K inhibitor caused a reduction in fibroblast proliferation and improved pulmonary function. The relationship between PI3K/AKT/mTOR and ER stress in pulmonary fibrosis, and the application of PI3K inhibitors and ER stress inhibitors in the treatment of pulmonary fibrosis require further investigation.
Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic ...reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition. Normally, such hypoxic response will cease when oxygen level is restored. However, the situation becomes complicated if hypoxic stress persists (chronic hypoxia) or cyclic normoxia-hypoxia phenomenon occurs (intermittent hypoxia). A series of chain reaction-like gene expression cascade, termed hypoxia-mediated gene regulatory network, will be initiated under such prolonged or intermittent hypoxic conditions and subsequently leads to alteration of cellular function and/or behaviors. As a result, irreversible processes occur that may cause physiological disorder or even pathological consequences. A growing body of evidence implicates that hypoxia plays critical roles in the pathogenesis of major causes of mortality including cancer, myocardial ischemia, metabolic diseases, and chronic heart and kidney diseases, and in reproductive diseases such as preeclampsia and endometriosis. This review article will summarize current understandings regarding the molecular mechanism of hypoxia in these common and important diseases.
Tumor progression with chemoresistance and local recurrence is commonly happened during treatment of esophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSC) may respond for tumor ...progression. However, there are few reports regarding metabolism of esophageal CSCs with clinical correlation. In this work, we demonstrated that ESCC cell lines in spheroid culture display CSC phenotypes, including increased ALDH activity, chemoresistance and tumor initiation, which are dependent on Hsp27 activation. Esophageal CSCs also exhibit reprogrammed metabolic features particularly higher glycolysis and oxidative phosphorylation, which are regulated via the Hsp27–AKT–HK2 pathway. Moreover, HK2 is required for maintenance of CSC phenotypes. Inhibition of CSC metabolism reduces cell growth and tumor formation. Clinically, patients who underwent surgical resection for esophageal cancer, and displayed overexpression of both Hsp27 and HK2, had the worst prognosis of all expression types. In conclusion, stem cells features and aberrant metabolic reprogramming of esophageal CSCs depend on the Hsp27–AKT–HK2 pathway. Targeting Hsp27 and HK2 could be novel therapeutic strategy for treating esophageal cancer and warrants further investigation.
What's new?
Cancer stem cells (CSC) are suspected of contributing to chemoresistance in esophageal cancer, a role likely made possible by CSC metabolic plasticity and rapid adaptation to changes in tumor microenvironment. Here, human esophageal squamous cancer cells in spheroid culture were found to exhibit key CSC features, including elevated ALDH activity, glycolysis, and oxidative phosphorylation. Hsp27‐AKT‐HK2 pathway upregulation was required for CSC phenotype maintenance. In vivo, inhibition of CSC metabolism successfully blocked tumor growth. While Hsp27 and HK2 upregulation correlates with poor prognosis in patients, the data suggest that Hsp27‐AKT‐HK2 targeting and metabolic inhibition can potentially be used against esophageal cancer.
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