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Showing papers by "Fu Jen Catholic University published in 2019"



Journal ArticleDOI
01 Feb 2019-Gut
TL;DR: HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.
Abstract: Objective The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota. Design High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis. Results Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii, a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1’s anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance. Conclusions HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.

439 citations


Journal ArticleDOI
E. Kou, Phillip Urquijo1, Wolfgang Altmannshofer2, F. Beaujean3  +558 moreInstitutions (140)
TL;DR: The Belle II detector as mentioned in this paper is a state-of-the-art detector for heavy flavor physics, quarkonium and exotic states, searches for dark sectors, and many other areas.
Abstract: The Belle II detector will provide a major step forward in precision heavy flavor physics, quarkonium and exotic states, searches for dark sectors, and many other areas. The sensitivity to a large number of key observables can be improved by about an order of magnitude compared to the current measurements, and up to two orders in very clean search measurements. This increase in statistical precision arises not only due to the increased luminosity, but also from improved detector efficiency and precision for many channels. Many of the most interesting observables tend to have very small theoretical uncertainties that will therefore not limit the physics reach. This book has presented many new ideas for measurements, both to elucidate the nature of current anomalies seen in flavor, and to search for new phenomena in a plethora of observables that will become accessible with the Belle II dataset. The simulation used for the studiesinthis book was state ofthe artat the time, though weare learning a lot more about the experiment during the commissioning period. The detector is in operation, and working spectacularly well.

247 citations


Journal ArticleDOI
TL;DR: The strategy used to optimally implant the effective prebiotics, probiotics and the derived postbiotics for amelioration of the diseases is presented and the effectiveness of these agents seems promising.
Abstract: Dysbiosis of gut microbiota is closely related to occurrence of many important chronic inflammations-related diseases. So far the traditionally prescribed prebiotics and probiotics do not show significant impact on amelioration of these diseases in general. Thus the development of next generation prebiotics and probiotics designed to target specific diseases is urgently needed. In this review, we first make a brief introduction on current understandings of normal gut microbiota, microbiome, and their roles in homeostasis of mucosal immunity and gut integrity. Then, under the situation of microbiota dysbiosis, development of chronic inflammations in the intestine occurs, leading to leaky gut situation and systematic chronic inflammation in the host. These subsequently resulted in development of many important diseases such as obesity, type 2 diabetes mellitus, liver inflammations, and other diseases such as colorectal cancer (CRC), obesity-induced chronic kidney disease (CKD), the compromised lung immunity, and some on brain/neuro disorders. The strategy used to optimally implant the effective prebiotics, probiotics and the derived postbiotics for amelioration of the diseases is presented. While the effectiveness of these agents seems promising, additional studies are needed to establish recommendations for most clinical settings.

222 citations


Journal ArticleDOI
TL;DR: The important roles of next generation probiotics and gut microbiota normobiosis on the maintenance of intestinal integrity and homeostasis are emphasized.

175 citations


Journal ArticleDOI
TL;DR: This study ascertained CR availability, volumes and its drivers, and density globally, finding that capacity is grossly insufficient, such that most patients will not derive the benefits associated with participation.

123 citations


Journal ArticleDOI
TL;DR: Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC, and older age, male sex, and cirrhosis use was correlated with a decreased HCC risk.
Abstract: Importance Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited. Objective To investigate the association of daily aspirin therapy with HBV-related HCC risk. Design, Setting, and Participants In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018. Exposures Daily aspirin therapy during the study period. Main Outcomes and Measures Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event. Results Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%;P Conclusions and Relevance Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.

116 citations


Journal ArticleDOI
TL;DR: An AI- and cloud-based telemedicine interaction tool for diagnosis and proposed treatment of AMD is presented and a website for realistic cloud computing based on this AI platform, available at https://www.ym.edu.tw/~AI-OCT/.
Abstract: Artificial intelligence (AI) based on convolutional neural networks (CNNs) has a great potential to enhance medical workflow and improve health care quality. Of particular interest is practical implementation of such AI-based software as a cloud-based tool aimed for telemedicine, the practice of providing medical care from a distance using electronic interfaces. Methods: In this study, we used a dataset of labeled 35,900 optical coherence tomography (OCT) images obtained from age-related macular degeneration (AMD) patients and used them to train three types of CNNs to perform AMD diagnosis. Results: Here, we present an AI- and cloud-based telemedicine interaction tool for diagnosis and proposed treatment of AMD. Through deep learning process based on the analysis of preprocessed optical coherence tomography (OCT) imaging data, our AI-based system achieved the same image discrimination rate as that of retinal specialists in our hospital. The AI platform's detection accuracy was generally higher than 90% and was significantly superior (p < 0.001) to that of medical students (69.4% and 68.9%) and equal (p = 0.99) to that of retinal specialists (92.73% and 91.90%). Furthermore, it provided appropriate treatment recommendations comparable to those of retinal specialists. Conclusions: We therefore developed a website for realistic cloud computing based on this AI platform, available at https://www.ym.edu.tw/~AI-OCT/. Patients can upload their OCT images to the website to verify whether they have AMD and require treatment. Using an AI-based cloud service represents a real solution for medical imaging diagnostics and telemedicine.

116 citations


Journal ArticleDOI
TL;DR: Long-term outcomes were assessed (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status.
Abstract: Summary Background In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4–86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7–88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6–92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters. Methods This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov , NCT01906879 . Findings Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 [33%] per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p Interpretation Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy. Funding National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

113 citations


Journal ArticleDOI
Andrew P. Morris1, Andrew P. Morris2, Thu H Le3, Haojia Wu4, Artur Akbarov5, Peter J. van der Most6, Gibran Hemani7, George Davey Smith, Anubha Mahajan2, Kyle J. Gaulton8, Girish N. Nadkarni9, Adan Valladares-Salgado10, Niels Wacher-Rodarte10, Josyf C. Mychaleckyj3, Nicole Dueker11, Xiuqing Guo12, Yang Hai12, Jeff Haessler13, Yoichiro Kamatani, Adrienne M. Stilp14, Gu Zhu15, James P. Cook1, Johan Ärnlöv16, Johan Ärnlöv17, Susan H. Blanton11, Martin H. de Borst6, Erwin P. Bottinger9, Thomas A. Buchanan18, Sylvia Cechova3, Fadi J. Charchar19, Fadi J. Charchar20, Fadi J. Charchar21, Pei-Lun Chu22, Jeffrey Damman23, James Eales5, Ali G. Gharavi24, Vilmantas Giedraitis25, Andrew C. Heath4, Eli Ipp26, Eli Ipp12, Krzysztof Kiryluk24, Holly Kramer27, Michiaki Kubo, Anders Larsson25, Cecilia M. Lindgren2, Cecilia M. Lindgren28, Yingchang Lu9, Pamela A. F. Madden4, Grant W. Montgomery29, George Papanicolaou, Leslie J. Raffel30, Ralph L. Sacco11, Ralph L. Sacco31, Elena Sanchez24, Holger Stark32, Johan Sundström25, Kent D. Taylor12, Anny H. Xiang33, Aleksandra Zivkovic32, Lars Lind25, Erik Ingelsson34, Erik Ingelsson25, Nicholas G. Martin15, John Whitfield15, Jianwen Cai35, Cathy C. Laurie14, Yukinori Okada36, Koichi Matsuda37, Charles Kooperberg13, Yii-Der Ida Chen12, Tatjana Rundek11, Stephen S. Rich3, Ruth J. F. Loos9, Esteban J. Parra38, Miguel Cruz10, Jerome I. Rotter12, Harold Snieder6, Maciej Tomaszewski5, Benjamin D. Humphreys4, Nora Franceschini35 
TL;DR: Trans-ethnic genome-wide meta-analyses for eGFR in 312,468 individuals are performed and novel loci and downstream putative causal genes are identified, offering insight into clinical outcomes and routes to CKD treatment development.
Abstract: Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

111 citations


Journal ArticleDOI
TL;DR: The results indicate that product quality, perceived price, perceived promotions, and e-WOM can be added to the e-commerce system success model to form a mobile catering app success model and show that perceived value influences eWOM more strongly than does user satisfaction while user satisfaction affects intention to reuse more strong than does perceived value.

Journal ArticleDOI
TL;DR: This first-ever survey of CR around the globe suggests CR quality is high, however, there is significant regional variation, which could impact patient outcomes.

Journal ArticleDOI
TL;DR: An overview of various nanoemulsion and nanoliposome systems reported recently for enhancing stability, bioavailability, and bioactivity of anthocyanins is presented.
Abstract: Background: Anthocyanins, a flavonoid class of water-soluble pigments, are reported to possess several biological activities, including antioxidant, anti-inflammatory, and anti-cancer. However, anthocyanins are highly susceptible to degradation in high pH, light, heat, and oxygen during processing and storage. Conventional microencapsulation techniques fail to provide stability to anthocyanins under physiological environments mainly because of their large particle size as well as low zeta potential and encapsulation efficiency. Methods: Nanotechnology provides novel strategies for preparing nanoformulations to enhance the physicochemical stability of anthocyanins. Nanoemulsion and nanoliposome are the two most commonly used nanosystems in pharmaceutical and food-related fields. In this review, an overview of various nanoemulsion and nanoliposome systems reported recently for enhancing stability, bioavailability, and bioactivity of anthocyanins is presented. Results: Anthocyanin nanoemulsions with different oil, water, surfactant, and cosurfactant ratios were prepared from extracts of mangosteen peel, purple sweet potato, cranberry, red cabbage, blueberry, jaboticaba peel, and acai berry and evaluated for their antioxidant activity, enhancement of physicochemical stability, topical skin application, and urinary tract infection. Likewise, unilamellar and multilamellar nanoliposomes were prepared using different types and levels of lecithin without or with cholesterol from anthocyanin standards and extracts of Hibiscus sabdariffa, mulberry, elderberry, black carrot, and pistachio green hull for the evaluation of physicochemical and oxidative stability, in vitro bioaccessibility, and melanogenic activity, as well as protective effects against diabetes mellitus and cataract. Conclusion: This review provides an insight into the current nanotechnology updates on enhancement of anthocyanin stability and biological activity.

Journal ArticleDOI
TL;DR: A novel algorithm based on deep convolutional neural network (DCNN), which classifies the stages of DR into five categories, labeled with an integer ranging between zero and four, and can achieve a recognition rate up to 86.17%, which is higher than previously reported in the literature.
Abstract: Diabetic retinopathy (DR) is a complication of long-standing diabetes, which is hard to detect in its early stage because it only shows a few symptoms. Nowadays, the diagnosis of DR usually requires taking digital fundus images, as well as images using optical coherence tomography (OCT). Since OCT equipment is very expensive, it will benefit both the patients and the ophthalmologists if an accurate diagnosis can be made, based solely on reading digital fundus images. In the paper, we present a novel algorithm based on deep convolutional neural network (DCNN). Unlike the traditional DCNN approach, we replace the commonly used max-pooling layers with fractional max-pooling. Two of these DCNNs with a different number of layers are trained to derive more discriminative features for classification. After combining features from metadata of the image and DCNNs, we train a support vector machine (SVM) classifier to learn the underlying boundary of distributions of each class. For the experiments, we used the publicly available DR detection database provided by Kaggle. We used 34,124 training images and 1,000 validation images to build our model and tested with 53,572 testing images. The proposed DR classifier classifies the stages of DR into five categories, labeled with an integer ranging between zero and four. The experimental results show that the proposed method can achieve a recognition rate up to 86.17%, which is higher than previously reported in the literature. In addition to designing a machine learning algorithm, we also develop an app called “Deep Retina.” Equipped with a handheld ophthalmoscope, the average person can take fundus images by themselves and obtain an immediate result, calculated by our algorithm. It is beneficial for home care, remote medical care, and self-examination.

Journal ArticleDOI
01 Mar 2019
TL;DR: Mortality associated with tobacco smoking continued to increase among Asian men in recent birth cohorts, indicating that tobacco smoking will remain a major public health problem in most Asian countries in the coming decades.
Abstract: Importance Understanding birth cohort–specific tobacco smoking patterns and their association with total and cause-specific mortality is important for projecting future deaths due to tobacco smoking across Asian populations. Objectives To assess secular trends of tobacco smoking by countries or regions and birth cohorts and evaluate the consequent mortality in Asian populations. Design, Setting, and Participants This pooled meta-analysis was based on individual participant data from 20 prospective cohort studies participating in the Asia Cohort Consortium. Between September 1, 2017, and March 31, 2018, a total of 1 002 258 Asian individuals 35 years or older were analyzed using Cox proportional hazards regression analysis and random-effects meta-analysis. The pooled results were presented for mainland China; Japan; Korea, Singapore, and Taiwan; and India. Exposures Tobacco use status, age at starting smoking, number of cigarettes smoked per day, and age at quitting smoking. Main Outcomes and Measures Country or region and birth cohort–specific mortality and the population attributable risk for deaths from all causes and from lung cancer. Results Of 1 002 258 participants (51.1% women and 48.9% men; mean [SD] age at baseline, 54.6 [10.4] years), 144 366 deaths (9158 deaths from lung cancer) were ascertained during a mean (SD) follow-up of 11.7 (5.3) years. Smoking prevalence for men steadily increased in China and India, whereas it plateaued in Japan and Korea, Singapore, and Taiwan. Among Asian male smokers, the mean age at starting smoking decreased in successive birth cohorts, while the mean number of cigarettes smoked per day increased. These changes were associated with an increasing relative risk of death in association with current smoking in successive birth cohorts of pre-1920, 1920s, and 1930 or later, with hazard ratios for all-cause mortality of 1.26 (95% CI, 1.17-1.37) for the pre-1920 birth cohort, 1.47 (95% CI, 1.35-1.61) for the 1920s birth cohort, and 1.70 (95% CI, 1.57-1.84) for the cohort born in 1930 or later. The hazard ratios for lung cancer mortality were 3.38 (95% CI, 2.25-5.07) for the pre-1920 birth cohort, 4.74 (95% CI, 3.56-6.32) for the 1920s birth cohort, and 4.80 (95% CI, 3.71-6.19) for the cohort born in 1930 or later. Tobacco smoking accounted for 12.5% (95% CI, 8.4%-16.3%) of all-cause mortality in the pre-1920 birth cohort, 21.1% (95% CI, 17.3%-24.9%) of all-cause mortality in the 1920s birth cohort, and 29.3% (95% CI, 26.0%-32.3%) of all-cause mortality for the cohort born in 1930 or later. Tobacco smoking among men accounted for 56.6% (95% CI, 44.7%-66.3%) of lung cancer mortality in the pre-1920 birth cohort, 66.6% (95% CI, 58.3%-73.5%) of lung cancer mortality in the 1920s birth cohort, and 68.4% (95% CI, 61.3%-74.4%) of lung cancer mortality for the cohort born in 1930 or later. For women, tobacco smoking patterns and lung cancer mortality varied substantially by countries and regions. Conclusions and Relevance In this study, mortality associated with tobacco smoking continued to increase among Asian men in recent birth cohorts, indicating that tobacco smoking will remain a major public health problem in most Asian countries in the coming decades. Implementing comprehensive tobacco-control programs is warranted to end the tobacco epidemic.

Journal ArticleDOI
05 Apr 2019
TL;DR: The study’s findings suggest the urgent need for developing diabetes management programs that are tailored to Asian populations and the subsequent strong implementation of these programs in Asia.
Abstract: Importance Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations. Objectives To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants’ age, sex, education level, body mass index, and smoking status. Design, Setting, and Participants This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018. Exposures Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status. Main Outcomes and Measures All-cause and cause-specific mortality. Results Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (Pfor interaction Conclusions and Relevance This study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.

Journal ArticleDOI
TL;DR: In this article, the authors explore how service quality and brand awareness influence customer satisfaction and loyalty in the business-to-business (B2B) technology service industry and propose a study to explore how these factors influence the customer satisfaction.
Abstract: The main purpose of this study is to explore how service quality and brand awareness influence customer satisfaction and loyalty in the business-to-business (B2B) technology service industry. Most ...

Journal ArticleDOI
TL;DR: There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB).
Abstract: Background There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB). Aim To investigate if hepatitis B core-related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation. Methods This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2 months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score. Results During a median follow-up of 25.9 months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5-year cumulative incidence of 56.1% (95% CI 46.7-66.0%) and 8.8% (95% CI 4.3-17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE-B) was calculated by the equation of 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2*age (year) + ALT (U/L) + 40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5 years, respectively. Moreover, HBsAg loss occurred exclusively in low-risk patients predicted by the score. Conclusions Serum HBcrAg and HBsAg levels were independent predictors of off-NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.

Journal ArticleDOI
TL;DR: The number of the massive open online courses (MOOCs) around the globe is on the rise as mentioned in this paper. But despite the popularity of MOOCs, they have received less attention from faculty members around the world.
Abstract: The number of the massive open online courses (MOOCs) around the globe is on the rise. Despite the popularity of MOOCs, they have received less attention from faculty members around the glo...

Journal ArticleDOI
TL;DR: This work utilizes the virtual CH formation and flow graph modeling to efficiently tolerate the failures of CHs and achieves fault tolerance with the minimum total energy consumption among all failure-free CHs in the IoT WSNs.
Abstract: In the Internet of Things (IoT), a wireless sensor network (WSN) is deployed for collecting the interesting data of an application field. Sensor nodes in an IoT WSN are usually with the heterogeneous property. Some nodes have more power (energy) and additional functionality (e.g., data aggregation) than others. Cluster-based routing is usually used in WSNs for data transmissions due to efficiently routing consideration. Based on cluster-based routing, the cluster heads (CHs) act as the sensed data forwarding role. Once one or more CHs fail, the faulty CHs cannot forward the sensed data of their serving sensor nodes. As a result, the sink node (gateway) has not sufficient sensed data of the IoT application field. This will deeply affect the information processing of the IoT applications. We utilize the virtual CH formation and flow graph modeling to efficiently tolerate the failures of CHs. First, the available resources of all failure-free CHs are logically organized as a virtual CH to be the common backup of all faulty CHs. Then, the flow graph modeling is used to achieve fault tolerance with the minimum total energy consumption among all failure-free CHs. Finally, we perform extensive experiments to demonstrate the effectiveness of our approach in the fault-tolerant routing of the IoT WSNs.

Journal ArticleDOI
TL;DR: Empagliflozin significantly changed Ca2+ regulation, late Na+ and Na+/hydrogen-exchanger currents and electrophysiological characteristics in DM cardiomyopathy, which may contribute to its cardioprotective benefits in DM patients.
Abstract: Diabetes mellitus (DM) has significant effects on cardiac calcium (Ca2+) and sodium (Na+) regulation. Clinical studies have shown that empagliflozin (Jardiance™) has cardiovascular benefits, however the mechanisms have not been fully elucidated. This study aimed to investigate whether empagliflozin modulates cardiac electrical activity as well as Ca2+/Na+ homeostasis in DM cardiomyopathy. Electrocardiography, echocardiography, whole-cell patch-clamp, confocal microscopic examinations, and Western blot, were performed in the ventricular myocytes of control and streptozotocin-induced DM rats, with or without empagliflozin (10 mg/kg for 4 weeks). The results showed that the control and empagliflozin-treated DM rats had smaller left ventricular end-diastolic diameters and shorter QT intervals than the DM rats. In addition, the prolonged action potential duration in the DM rats was attenuated in the empagliflozin-treated DM rats. Moreover, the DM rats had smaller sarcoplasmic reticular Ca2+ contents, intracellular Ca2+ transients, L-type Ca2+, reverse mode Na+-Ca2+exchanger currents, lower protein expressions of sarcoplasmic reticulum ATPase, ryanodine receptor 2 (RyR2), but higher protein expressions of phosphorylated RyR2 at serine 2808 than the control and empagliflozin-treated DM rats. The incidence and frequency of Ca2+ sparks, cytosolic and mitochondrial reactive oxygen species, and late Na+ current and Na+/hydrogen-exchanger currents were greater in the DM rats than in the control and empagliflozin-treated DM rats. Empagliflozin significantly changed Ca2+ regulation, late Na+ and Na+/hydrogen-exchanger currents and electrophysiological characteristics in DM cardiomyopathy, which may contribute to its cardioprotective benefits in DM patients.

Journal ArticleDOI
11 Jun 2019-Sleep
TL;DR: Sleep disturbances, particularly insomnia, should be considered an influencing factor when developing preventive strategies against adolescent suicidal ideation, and potential moderators of these associations are explored.
Abstract: Study objectives To systematically review and meta-analyze the associations between sleep disturbances and suicidal ideation, plans, and attempts in adolescents and explore potential moderators of these associations. Methods Embase, PubMed, ProQuest, and the China Knowledge Resource Integrated Database were searched from their inception dates to October 19, 2018. We selected cross-sectional, prospective, or retrospective studies without time or language restrictions. Results Nine cross-sectional studies, four prospective studies, and one retrospective report that, respectively, involved 37 536, 9295, and 80 adolescents were included in the meta-analysis. Cross-sectional analyses revealed that adolescents with sleep disturbances were at higher risks of suicidal ideation, plans, and attempts (pooled odds ratios [ORs] = 2.35, 1.58, and 1.92) than those without sleep disturbances. Prospective reports indicated that sleep disturbances in adolescents significantly predicted the risk of suicidal ideation but not suicide attempts (pooled ORs = 1.79 and 1.98, 95% confidence intervals = 1.36-2.36 and 0.62-6.29, respectively). The retrospective study did not support the association between sleep disturbances and suicide attempts. Depression did not moderate the associations between sleep disturbances and suicidal ideation or attempts in adolescents. Adolescents with insomnia complaints had a higher risk of suicidal ideation than those with other sleep complaints. Age, the female percentage, and reliable sleep measures were significant moderators (all p Conclusions Sleep disturbances, particularly insomnia, should be considered an influencing factor when developing preventive strategies against adolescent suicidal ideation. Additional prospective studies are warranted to establish causality of sleep disturbances in youth suicide plans and attempts.

Journal ArticleDOI
TL;DR: In this paper, a plasmonic perfect absorber (PPA) based on metal nanorod arrays with the connected veins was proposed for ultra-sensitive refractive index (RI) sensing applications in the near-infrared region.
Abstract: We propose a plasmonic perfect absorber (PPA) based on metal nanorod arrays with the connected veins for ultra-sensitive refractive index (RI) sensing applications in the near-infrared region. The physical origin is explained through the absorptance/reflectance spectra, distribution of electric/magnetic field intensity, surface charge density, height and gap distance. The designed PPA can constitute a cavity resonance center and serve as a plasmonic sensor. There is a huge difference of absorptance and reflectance between the case with and without veins due to the vein effect has a dominant influence on plasmon resonance in the proposed PPA. Simulation results show that the absorptance (A) of the proposed PPA is nearly perfect (A = 99.67%) which is about 1332.49 times enhancement compared to its counterpart without the connected veins (A = 0.075%). The calculated sensitivity, figure of merit and quality factor can be achieved up to 800.00 nm/RIU (RIU is the refractive index unit), 12.17 (RIU−1) and 14.78, respectively.

Journal ArticleDOI
TL;DR: 3D organoids are established as a valid disease model for X-linked juvenile retinoschisis and it is shown that the C625T mutation can be repaired precisely and efficiently using a base-editing approach.
Abstract: Summary X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model.

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TL;DR: It is suggested that Lactobacillus plantarum TWK10 has the potential to be an ergogenic aid to improve aerobic endurance performance via physiological adaptation effects and change in body composition shifted in the healthy direction for TWK 10 administration groups.
Abstract: Probiotics have been rapidly developed for health promotion, but clinical validation of the effects on exercise physiology has been limited. In a previous study, Lactobacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage as a probiotic, was demonstrated to improve exercise performance in an animal model. Thus, in the current study, we attempted to further validate the physiological function and benefits through clinical trials for the purpose of translational research. The study was designed as a double-blind placebo-controlled experiment. A total of 54 healthy participants (27 men and 27 women) aged 20–30 years without professional athletic training were enrolled and randomly allocated to the placebo, low (3 × 1010 colony forming units (CFU)), and high dose (9 × 1010 CFU) TWK10 administration groups (n = 18 per group, with equal sexes). The functional and physiological assessments were conducted by exhaustive treadmill exercise measurements (85% VO2max), and related biochemical indices were measured before and after six weeks of administration. Fatigue-associated indices, including lactic acid, blood ammonia, blood glucose, and creatinine kinase, were continuously monitored during 30 min of exercise and a 90 min rest period using fixed intensity exercise challenges (60% VO2max) to understand the physiological adaptation. The systemic inflammation and body compositions were also acquired and analyzed during the experimental process. The results showed that TWK10 significantly elevated the exercise performance in a dose-dependent manner and improved the fatigue-associated features correlated with better physiological adaptation. The change in body composition shifted in the healthy direction for TWK10 administration groups, especially for the high TWK10 dose group, which showed that body fat significantly decreased and muscle mass significantly increased. Taken together, our results suggest that TWK10 has the potential to be an ergogenic aid to improve aerobic endurance performance via physiological adaptation effects.

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TL;DR: At normal or high levels, uric acid is associated with a reduction in bone mineral density and protects against bone fracture, but in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation.
Abstract: Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.

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TL;DR: Melatonin suppresses lung cancer stemness by inhibiting the PLC, ERK/p38, β‐catenin, and Twist signaling pathways, and it is found CD133 expression is positively correlated with Twist expression in lung cancer specimens.
Abstract: Lung cancer is one of the most common cancer in cancer-related deaths worldwide, which is characterized by its strong metastatic potential. The melatonin hormone secreted by the pineal grand has an antioxidant effect and protects cells against carcinogenic substances. However, the effects of melatonin in lung cancer stemness are largely unknown. We found that melatonin reduces CD133 expression by ~50% in lung cancer cell lines, while results of a sphere formation assay showed that melatonin inhibits lung cancer stemness. These effects of melatonin were reversed when the cell lines were incubated with phospholipase C (PLC), ERK/p38, and a β-catenin activator. Transfection with Twist siRNA augmented the inhibitory effects of melatonin, indicating that melatonin suppresses lung cancer stemness by inhibiting the PLC, ERK/p38, β-catenin, and Twist signaling pathways. We also found CD133 expression is positively correlated with Twist expression in lung cancer specimens. Melatonin shows promise in the treatment of lung cancer stemness and deserves further study.

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TL;DR: It is demonstrated that T SP-2 expression is highly correlated with lung cancer tumor stage and that the TSP-2 neutralizing antibody reduces osteoclast formation in conditioned medium obtained from lung cancer cells.

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TL;DR: It is suggested that increased levels of IL-6 and IL-33 in the serum of mice with BLM-induced lung injury may cause lung fibrosis with thickened interstitial lung tissue accompanied by reduced lung function and muscle mass through the activation of STAT3 and AMPK signals.
Abstract: Weight loss due to skeletal muscle atrophy in patients with chronic pulmonary disease is negatively correlated with clinical outcome. Pulmonary fibrosis is a chronic and progressive interstitial lung disease characterized by the dysregulated deposition of the extracellular matrix (ECM) with the destruction of normal tissue, resulting in end-stage organ failure. BLM-induced fibrosis is one of several different experimental models of pulmonary fibrosis, characterized by inflammation and excessive ECM deposition. We directly induced mouse lung injury by the intratracheal administration of bleomycin and monitored the physiological and biochemical changes in lung and skeletal muscle tissues by using lung function testing, ELISA, Western blotting, and immunohistochemistry. Here, we found that BLM-induced lung fibrosis with thickened interstitial lung tissue, including fibronectin and collagen, was correlated with the increased serum concentrations of IL-6 and IL-33 and accompanied by reduced lung function, including FRC (functional residual capacity), C chord (lung compliance), IC (inspiratory capacity), VC (vital capacity), TLC (total lung capacity), and FVC (forced vital capacity) (p < 0.05). The activity of AKT in lung tissue was suppressed, but conversely, the activity of STAT3 was enhanced during lung fibrosis in mice. In addition, we found that the amount of sST2, the soluble form of the IL-33 receptor, was dramatically decreased in lung fibrosis tissues. The skeletal muscle tissue isolated from lung injury mice increased the activation of STAT3 and AMPK, accompanied by an increased amount of Atrogin-1 protein in BLM-induced lung fibrosis mice. The mouse myoblast cell-based model showed that IL-6 and IL-33 specifically activated STAT3 and AMPK signaling, respectively, to induce the expression of the muscle-specific proteolysis markers MuRF1 and Atrogin-1. These data suggested that increased levels of IL-6 and IL-33 in the serum of mice with BLM-induced lung injury may cause lung fibrosis with thickened interstitial lung tissue accompanied by reduced lung function and muscle mass through the activation of STAT3 and AMPK signals.

Journal ArticleDOI
15 Dec 2019
TL;DR: Comprehensive understandings of effectiveness on amelioration of diseases, safety, physiological, genomic, and metabolomics characteristics, the drug susceptibility pattern and transfer of drug resistance genes, and potential virulence factors are mandatory.
Abstract: The roles of newly identified, non-conventional, native gut microbiota bacteria for promotion of health and even therapeutic purposes have rapidly attracted much more attention in contrast to the traditional probiotics. Detailed physiological and molecular evidences on isolation, identification and functional characterization of these various bacteria are rapidly gathering. These potentially beneficial bacteria are gradually grouped to form the next generation probiotics (NGP). Many bacterial species and strains belonging to Actinobacteria, Bacteroidetes, Firmicutes and Verrucomicrobia are gradually highlighted. Notably, NGP may have the potential of being treated as drugs (live biotherapeutic products, LBP); therefore, the requirements for grouping of NGP are much more stringent than traditional probiotics. Comprehensive understandings of effectiveness on amelioration of diseases, safety, physiological, genomic, and metabolomics characteristics, the drug susceptibility pattern and transfer of drug resistance genes, and potential virulence factors are mandatory. Besides, how NPG interact with the host to maintain intestinal integrity and host homeostasis has to be addressed. While most NGP products are currently not commercially available yet, this present review emphasizes the requirements of grouping newly identified microbiota bacteria as NGP. Furthermore, selection of specific functional bacteria to the strain level is essential. We also provide an overview of the potential NGP candidates that could be applied for targeted therapy on specific inflammation related diseases.