This paper presents a two-phased tracking that forms a photovoltaic (PV) power-increment-aided incremental-conductance (PI-INC) maximum power point tracking (MPPT) to improve the tracking behavior of ...the conventional INC MPPT. The PI-INC MPPT performs, using either variable-frequency constant-duty control (VFCD) or constant-frequency variable-duty control (CFVD), with reference to a collectively called threshold-tracking zone (TTZ), beyond which a power-increment (PI) tracking along the P pv -V pv curve executes and within which an INC tracking along the I pv -V pv curve toward maximum power point (MPP) does. Delay tracking due to ambiguous conductance-increment detection in the flat portion of the left-hand side of the MPP along the I pv -V pv curve will not appear in the PI-INC MPPT by using the PI tracking with clear and correct power-increment detection along the P pv - V pv curve. In addition, the merit of INC MPPT to accurately track against the random solar insolation change still retains in the PI-INC MPPT that uses INC tracking toward MPP along the I pv -V pv curve when tracking in the TTZ. Modeling and analysis of two typical PV power converters with VFCD and CFVD controls are addressed for implementing the tracking of the PI-INC MPPT in design and experiment. The tracking behavior of PI-INC MPPT and the conventional INC MPPT is assessed and compared through elaborate experimental tests.
Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and ...severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5.
191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR
) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed.
The SVR
rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR
rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR
rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR
were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations.
SOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.
Summary
Background
While direct‐acting antivirals have been approved for treating hepatitis C, the guidelines highlight the importance of considering potential drug‐drug interactions between DAAs and ...concomitant medications.
Aim
To assess comorbidity prevalence, concomitant medication use and potential drug‐drug interactions between DAAs and concomitant medications for hepatitis C patients in Taiwan.
Methods
This cross‐sectional study enrolled 822 patients from May to August 2016 in Taiwan. Patient demographics, comorbidities and concomitant medications were evaluated by physician surveys.
Results
A total of 709 (86.3%) patients had ≥1 comorbidity; the most prevalent comorbidity categories were diseases of the digestive system (40.1%), circulatory system (38.7%) and endocrine/nutritional/metabolic diseases (35.2%). Elderly patients had more comorbidities. A total of 622 (75.7%) patients received ≥1 concomitant medication; the average number of concomitant medications was 3.2. The most common concomitant medication classes were cardiovascular (34.4%), gastrointestinal (25.7%) and central nervous system drugs (22.7%). Among patients without cirrhosis or with compensated cirrhosis, contraindications were most prevalent with paritaprevir/ritonavir/ombitasvir plus dasabuvir, daclatasvir/asunaprevir and glecaprevir/pibrentasvir (13.3%, 6.0% and 5.4% respectively), and least prevalent with sofosbuvir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir and sofosbuvir/velpatasvir (0.8%, 1.3%, 1.4% and 2.1% respectively). Sofosbuvir‐based regimens had no contraindications in patients with decompensated cirrhosis.
Conclusion
Our population represented an elderly demographic, with a high prevalence of comorbidities and widespread use of concomitant medications. The potential drug‐drug interactions between these concomitant medications and DAA regimens differed, with the fewest potential interactions with sofosbuvir‐based regimens.
Background & Aims
Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long‐term entecavir therapy in ...reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB‐related cirrhosis patients.
Methods
The C‐TEAM (Cirrhosis‐Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective–prospective cohort study in Taiwan. We enrolled treatment‐naïve patients with CHB‐related cirrhosis and baseline HBV‐DNA≥2000 IU/mL receiving long‐term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort.
Results
In total, 1315 entecavir‐treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow‐up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28‐0.57. Additionally, an older age, the male gender, HBeAg positivity, alpha‐fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver‐related and all‐cause mortality. These findings were confirmed by propensity score‐matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1‐year virological response were predictive of HCC development.
Conclusions
Four‐year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB‐related cirrhosis.
See Editorial on Page 1752
An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that ...facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon‐induced signaling, demonstrating that this metabolite transporter is an interferon‐stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS‐CoV‐2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro‐viral ISG co‐opted by some viruses to gain a survival advantage.
Synopsis
ENT3 is an IFN‐stimulated metabolite transporter in macrophages that facilitates viral genome release. Suppression of ENT3 expression is sufficient to decrease viral replication both in vitro and in vivo.
ENT3 is a fast‐responding metabolite transporter upon pathogen insults.
ENT3 is an interferon‐stimulated gene whose expression is regulated by the type I IFN‐IFNAR axis.
Viruses have co‐evolved with the host and take advantage of ENT3 for their genome release and their replication.
ENT3 is an IFN‐stimulated metabolite transporter in macrophages that facilitates viral genome release. Suppression of ENT3 expression is sufficient to decrease viral replication both in vitro and in vivo.
Corrosion under insulation is one of the most important issues in the petroleum industry. Ordinarily, in order to check the corrosion, inspectors remove the insulation of pipelines to measure the ...level of corrosion on each section of pipelines. This procedure may take weeks for a site which distinctly affects the financial aspect of oil and gas companies due to the pause production of its high-value products; therefore, in most cases, inspectors spot-check pipeline corrosion based on their experience. However, because the environments on sites are various, experience-based inspection may not be suitable for every site. On the other hand, even though inspectors want to access more data for better understanding of the site before the site trip, historical data sometimes are lost or scattered which leads to a hard situation for preparation of corrosion inspection. This paper utilises passive RFID sensors, which are smart sensing technologies, to collect site data and then integrate them into a Building Information Modeling (BIM) system. A uniform corrosion model is also adapted from the theories of corrosion to leverage both sensor data and BIM elements' properties. They serve as inputs to calculate the corrosion rate which is the key value of corrosion prediction. Then, the corrosion prediction results are colour-coded on a BIM model which helps inspectors intuitively understand the prediction and prepare for the site inspection. In result, the proposed research could provide a novel approach for corrosion management under insulation.
•Integrate BIM and sensors for corrosion prediction and visualisation.•A mathematical model has been developed for corrosion prediction.•A prototype has been developed to validate the efficiency of the proposed approach.
Activated hepatic stellate cells promote hepatocellular carcinoma (HCC) progression. Hepatic stellate cells play a key role in retinoid metabolism, and activation of stellate cells increases retinoic ...acid (RA) in the liver. However, the role of RA in HCC proliferation remains unclear. We aimed to analyse the mechanism of RA in HCC proliferation. Thirty‐eight patients who had undergone hepatic resection for HCCs were recruited. Paired non‐tumour tissues, adjacent and distal to HCCs, were collected, and the RA levels in the tissues were analysed. The mechanisms of RA and HCC proliferation were assessed in liver cancer cell lines by protein and gene expression analyses. Early recurrence of HCC was significantly higher in patients with a higher RA concentration than in those with a lower RA concentration in tissues adjacent to HCCs (61.1% vs. 20%, p = .010). RA promoted HCC cell proliferation and activated the expression of Amphiregulin, a growth factor in hepatocarcinogenesis. The promoter of Amphiregulin contained the binding sites of the RA receptor, RXRα. Wnt signalling also activated the expression of Amphiregulin, and the RA and Wnt pathways acted synergistically to increase the expression of Amphiregulin. Furthermore, RXRα interacted with β‐catenin and then translocated to the nucleus to activate Amphiregulin. An increased RA concentration in the tissues adjacent to the tumour was associated with an early recurrence of HCC. RA activated the expression of Amphiregulin, and then promoted HCC proliferation, which might partly contribute to early recurrence of HCC after hepatic resection.
An increase in the concentration of retinoic acid (RA) in the microenvironment of hepatocellular carcinoma (HCC) is associated with a higher recurrence rate after the curative hepatic resection. Our work suggests that RA concentration could be used as a potential marker for early recurrence.
Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain ...unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore‐specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV‐specific T cells. In line with Taiwanese dominant HLA‐alleles, we also evaluated ex vivo HBVcore‐specific T cells by pMHC‐tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD‐1. Our parallel study showed HBV‐specific CD8 T cells were more activated with greater PD‐1 expression than CMV‐specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD‐1 fluctuation pattern of HBVcore‐specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen‐mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD‐1 levels of HBVcore‐specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.
Abstract
The genus
Sorghum
consists of 25 species, including
Sorghum bicolor
(L.) Moench, one of the top five cereal crops cultivated globally, and
S
.
halepense
, one of the most noxious weeds. ...Weedy
Sorghum
possesses outstanding adaptability and drought tolerance thrives in diverse environments and becomes an invasive plant worldwide. Taiwan is a unique place possessing suitable habitats for four
Sorghum
taxa,
S
.
bicolor
ssp.
bicolor
, var.
technicum
, ssp.
verticilliflorum
and
S
.
halepense
, which were identified by key morphological features. The four
Sorghum
taxa showed distinct geographic distributions, revealing that invasiveness was influenced by their own characteristics and human activities. The sporadic distributions of cultivated
S
.
bicolor
ssp.
bicolor
and var.
technicum
may be attributed to human disturbance and agricultural activities. The rhizomatous
S
.
halepense
was widely distributed and showed the highest genetic diversity (He > 0.776) among the four taxa, with its strong adaptation to various environments threatening the agricultural practices and ecosystem in Taiwan. In contrast, the newly naturalised
S
.
bicolor
ssp.
verticilliflorum
was confined to and dominant in southern Taiwan, with the lowest genetic diversity (He < 0.272). Significant genetic differentiation (
F
ST
= 0.5207) between the two ssp.
verticilliflorum
subpopulations was associated with natural geographic isolation. This study concretely elucidated the geographic distributions, genetic diversity and relatedness of invasive and escaped
Sorghum
taxa, indicating the potential aggressiveness and hazard of weedy
Sorghum
in Taiwan.