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Background/Aims Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P

Background/Aims Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Abstract Introduction Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). Methods The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. Results A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. Conclusion Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Abstract Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p

Background/Aims Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background: Treating marginalized populations with HCV infection for elimination is faced with the challenge for the integration of HCV screening service offered for patients often moving across multiple settings. We envisaged a novel collaborative care approach to identify to what extent HCV patients overlapped between and within these multiple institutions and reported the findings of treatment coverage of these marginalized populations after HCV care cascades. Methods: We enrolled 7765 patients residing in the Changhua County, Taiwan offered with HCV screening from correctional institutions, HIV clinics, methadone clinics, and the existing HIV surveillance program (four subgroups including police-arrested people, probationers, non-injection drug user, and high-risk behavior people) between 2019 and 2020. The collaborative care and information were integrated through a teamwork of gastroenterologists, psychologists, infectious disease specialists, and nursing coordinators under the auspices of local health authority. Results: The overall participation rate in HCV screening was 92.65% (7194/7765). The prevalence rate was the highest in methadone clinics (90.17%) followed by correctional institutions (37.67%), HIV clinics (34.60%), and the surveillance program (18.14%). We found 25.41% (77/303) of methadone clinic patients, 17.65% (129/731) of HIV clinic patients, and various proportions for 44.09% (41/93) of deferred prosecuted or probationers under surveillance program were also recruited into other settings. Individuals' patient flow within setting was more frequent than that between setting. After calibrating the overlap of patient flow, a total of 1700 anti-HCV positives out of 4074 after screening were traced with available follow-up information to complete 92.52% treatment coverage of 1177 RNA-positives (77.23%) diagnosed from 1524 undergoing RNA testing with similar findings across multiple settings. Conclusion: A new collaborative integrated care was adopted for elucidating patient flow between and within multiple settings in order to calibrate the accurate demand for HCV care cascades and enhance HCV treatment coverage in marginalized populations.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of one trabecular microbypass stent (first generation iStent) combined with phacoemulsification cataract surgery (phaco) in eyes with open-angle glaucoma (OAG) in a Taiwanese population. MATERIALS AND METHODS: One trabecular microbypass stent was implanted after phacoemulsification cataract surgery by one surgeon. Intraocular pressure (IOP), medications, corrected distance visual acuity, complications, and adverse events were evaluated. RESULTS: This case series included 28 eyes of 25 patients with OAG (19 primary open-angle glaucoma [POAG] and 9 normal tension glaucoma [NTG]). None had previous trabeculectomy or laser trabeculoplasty. At 1 year, the mean IOP decreased from 19.34 ± 3.92 mmHg to 15.84 ± 3.05 mmHg, and the mean number of glaucoma medications decreased from 1.82 ± 1.12 to 0.79 ± 1.17 (both P < 0.001). Longer survival was observed in the NTG eyes (NTG: 11.67 ± 1.00 months, POAG: 9.53 ± 3.78 months, P = 0.031). iStent reposition was performed in one eye, and four eyes received laser treatment for stent occlusion. None had secondary glaucoma surgery. CONCLUSION: Combined phacoemulsification and iStent implantations are a safe and effective way in reducing IOP and medication burden in patients with OAG, especially NTG.

Background/purpose: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. Methods: Patients enrolled in TACR from 2017–2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). Results: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P

Abstract The risks of misdiagnosing a healthy individual as glaucomatous or vice versa may be high in a population with a large majority of highly myopic individuals, due to considerable morphologic variability in high myopic fundus. This study aims to compare the diagnostic ability of the regular and long axial length databases in the RS-3000 Advance SD-OCT (Nidek) device to correctly diagnose glaucoma with high myopia. Patients with high myopia (axial length ≥ 26.0 mm) in Chang Gung Memorial Hospital, Taiwan between 2015 and 2020 were included. Glaucoma was diagnosed based on glaucomatous discs, visual field defects and corresponding retinal nerve fiber layer defects. The sensitivity, specificity, diagnostic accuracy and likelihood ratios of diagnosing glaucoma via mGCC thickness in both superior/inferior and GChart mapping using the regular and long axial length normative databases. The specificity and diagnostic accuracy of mGCC thickness for distinguishing glaucomatous eyes from nonglaucomatous eyes among highly myopic eyes were significantly improved using the long axial length database (p = 0.046). There were also significant proportion changes in S/I mapping as well as GChart mapping (37.3% and 48.0%, respectively; p

Conditional protein degradation is a powerful tool for controlled protein knockdown. The auxin-inducible degron (AID) technology uses a plant auxin to induce depletion of degron-tagged proteins, and it has been shown to be functional in several non-plant eukaryotes. In this study, we demonstrated AID-based protein knockdown in an industrially important oleaginous yeast Yarrowia lipolytica. Using the mini-IAA7 (mIAA7) degron derived from Arabidopsis IAA7, coupled with an Oryza sativa TIR1 (OsTIR1) plant auxin receptor F-box protein (expressed from the copper-inducible MT2 promoter), C-terminal degron-tagged superfolder GFP could be degraded in Yarrowia lipolytica upon addition of copper and the synthetic auxin 1-Naphthaleneacetic acid (NAA). However, leaky degradation of the degron-tagged GFP in the absence of NAA was also noted. This NAA-independent degradation was largely eliminated by replacing the wild-type OsTIR1 and NAA with the OsTIR1F74A variant and the auxin derivative 5-Ad-IAA, respectively. Degradation of the degron-tagged GFP was rapid and efficient. However, Western blot analysis revealed cellular proteolytic cleavage within the mIAA7 degron sequence, leading to the production of a GFP sub-population lacking an intact degron. The utility of the mIAA7/OsTIR1F74A system was further explored in controlled degradation of a metabolic enzyme, β-carotene ketolase, which converts β-carotene to canthaxanthin via echinenone. This enzyme was tagged with the mIAA7 degron and expressed in a β-carotene producing Y. lipolytica strain that also expressed OsTIR1F74A controlled by the MT2 promoter. By adding copper and 5-Ad-IAA at the time of culture inoculation, canthaxanthin production was found to be reduced by about 50% on day five compared to the control culture without adding 5-Ad-IAA. This is the first report that demonstrates the efficacy of the AID system in Y. lipolytica. Further improvement of AID-based protein knockdown in Y. lipolytica may be achieved by preventing proteolytic removal of the mIAA7 degron tag.

Abstract The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

Background/Aims Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for end-stage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P

ABSTRACT Background and Aim Ropeginterferon alfa‐2b (P1101) is a novel long‐acting mono‐PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N‐terminus, allowing every‐two‐week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia vera in 2019 and 2020, respectively. This phase 2 study aimed to evaluate the pharmacokinetics, safety, and preliminary efficacy of ropeginterferon alfa‐2b as compared with PEG‐IFN‐α2a in patients with chronic hepatitis C virus genotype 1 infection. Methods One hundred six treatment naive patients were enrolled in this phase 2 study and randomized to four treatment groups: subcutaneous weekly PEG‐IFN‐α2a 180 μg (group 1), weekly ropeginterferon alfa‐2b 180 μg (group 2), weekly ropeginterferon alfa‐2b 270 μg (group 3), or biweekly ropeginterferon alfa‐2b 450 μg (group 4) plus ribavirin for 48 weeks. Results After multiple weekly administration, serum exposure (AUC0‐τ) in ropeginterferon alfa‐2b 180 μg was approximately 41% greater and the accumulation ratio of 2‐fold greater than PEG‐IFN‐α2a 180 μg. The incidences of flu‐like symptoms were 66.7% (18/27), 53.3% (16/30), 55.0% (11/20), and 48.3% (14/29), anxiety were 14.8% (4/27), 6.7% (2/30), 0%, and 0%, and depression were 25.9% (7/27), 13.3% (4/30), 0%, and 3.4% (1/29), for groups 1–4, respectively. Two grade 2 of 3 depression were noted in PEG‐IFN‐α2a arm, but none in ropeginterferon arms. The SVR24 rates were 77.8% (21/27), 66.7% (20/30), 80% (16/20), and 69% (20/29), respectively. Conclusions Ropeginterferon alfa‐2b showed longer effective half‐life and superior safety profile than PEG‐IFN‐α2a. Biweekly injection of ropeginterferon alfa‐2b will be studied in larger viral hepatitis patient population.

Objective: We aimed to develop a deep learning (DL)–based algorithm for early glaucoma detection based on color fundus photographs that provides information on defects in the retinal nerve fiber layer (RNFL) and its thickness from the mapping and translating relations of spectral domain OCT (SD-OCT) thickness maps. Design: Developing and evaluating an artificial intelligence detection tool. Subjects: Pretraining paired data of color fundus photographs and SD-OCT images from 189 healthy participants and 371 patients with early glaucoma were used. Methods: The variational autoencoder (VAE) network training architecture was used for training, and the correlation between the fundus photographs and RNFL thickness distribution was determined through the deep neural network. The reference standard was defined as a vertical cup-to-disc ratio of ≥0.7, other typical changes in glaucomatous optic neuropathy, and RNFL defects. Convergence indicates that the VAE has learned a distribution that would enable us to produce corresponding synthetic OCT scans. Main Outcome Measures: Similarly to wide-field OCT scanning, the proposed model can extract the results of RNFL thickness analysis. The structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) were used to assess signal strength and the similarity in the structure of the color fundus images converted to an RNFL thickness distribution model. The differences between the model-generated images and original images were quantified. Results: We developed and validated a novel DL-based algorithm to extract thickness information from the color space of fundus images similarly to that from OCT images and to use this information to regenerate RNFL thickness distribution images. The generated thickness map was sufficient for clinical glaucoma detection, and the generated images were similar to ground truth (PSNR: 19.31 decibels; SSIM: 0.44). The inference results were similar to the OCT-generated original images in terms of the ability to predict RNFL thickness distribution. Conclusions: The proposed technique may aid clinicians in early glaucoma detection, especially when only color fundus photographs are available.

The reported prevalence of non-alcoholic fatty liver disease in studies of lean individuals ranges from 7.6% to 19.3%. The aim of the study was to develop machine-learning models for the prediction of fatty liver disease in lean individuals. The present retrospective study included 12,191 lean subjects with a body mass index < 23 kg/m2 who had undergone a health checkup from January 2009 to January 2019. Participants were divided into a training (70%, 8533 subjects) and a testing group (30%, 3568 subjects). A total of 27 clinical features were analyzed, except for medical history and history of alcohol or tobacco consumption. Among the 12,191 lean individuals included in the present study, 741 (6.1%) had fatty liver. The machine learning model comprising a two-class neural network using 10 features had the highest area under the receiver operating characteristic curve (AUROC) value (0.885) among all other algorithms. When applied to the testing group, we found the two-class neural network exhibited a slightly higher AUROC value for predicting fatty liver (0.868, 0.841–0.894) compared to the fatty liver index (FLI; 0.852, 0.824–0.81). In conclusion, the two-class neural network had greater predictive value for fatty liver than the FLI in lean individuals.

Background: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. Methods: Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg–IFN–α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). Results: SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg–IFN–α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. Conclusion: Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg–IFN–α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

Among various eye diseases, glaucoma is one of the leading causes of blindness. Glaucoma is also one of the most common eye diseases in Taiwan. Glaucoma screenings can use optical coherence tomography (OCT) to locate areas in which the retinal nerve fiber layer is thinning. However, because OCT equipment is costly, only large hospitals with well-equipped facilities will have OCT, and regular eye clinics cannot afford such expensive equipment. This has caused many glaucoma patients to worsen because they cannot get an early diagnosis in regular eye clinics in time. This paper proposes a method of using a generative adversarial network (GAN) to generate corresponding OCT images from fundus images to assist family doctors in judging whether further examination is needed based on the generated OCT images to achieve early detection and treatment of glaucoma. In addition, in order to improve the classification accuracy of the system deployed in different hospitals or clinics, this paper also proposes to use the incremental training method to fine-tune the model. The model can be quickly applied by adding a small number of images from a specific clinic or hospital. Experimental results show that the cosine similarity between the generated OCT image and the real OCT image is 97.8%. Combined with the proposed transfer learning method, the classification accuracy of the classification model reaches 83.17%. As well as the use of the incremental method, the accuracy of identifying glaucoma is approximately 78.94%, which is 8.77% higher than the 70.17% accuracy of the initial model. Experimental results show the effectiveness and feasibility of our proposed method.

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.

Background Tenofovir alafenamide (TAF) has good viral suppression efficacy and less adverse effect than tenofovir disoproxil fumarate (TDF). Real-world studies on the antiviral efficacy and safety of switching from TDF to TAF in patients with chronic hepatitis B (CHB) are limited. Methods This retrospective study included 167 nucleos(t)ide analogue (NA)-naive patients with CHB. All the patients received TDF at least 12 months before switching and TAF at least 12 months after switching at a single medical center. The Friedman test with Dunn–Bonferroni post hoc tests and repeated-measures analysis of variance was used to analyze the effect of complete viral suppression, alanine aminotransferase (ALT) level normalization, renal function changes, body weight, and body mass index in the periods before and after switching. Results The mean age and TDF treatment duration were 52 ± 11 years and 2.8 years (interquartile range, 1.51–5.15 years), respectively. The complete viral suppression rate was similar between the time of switching and 48 weeks after switching to TAF (77.8% vs 76%, P = 1.000). The percentage of alanine aminotransferase (ALT) normalization increased from 26.3% at TDF start to 81.4% (P < 0.001) at time of switching and 89.2% at 48 weeks after switching to TAF (P = 0.428). The median estimated glomerular filtration rate decreased from 100.09 mL/min/1.73 m² at TDF start to 91.97 mL/min/1.73 m² (P < 0.001) at the time of switching and stabilized at 48 weeks after switching to TAF (93.47 mL/min/1.73m², P = 1.000). The body weight decreased from 69.2 ± 12.2 kg at TDF start to 67.4 ± 12.1 kg (P < 0.001) at the time of switching to TAF and returned to 68.7 ± 12.7 kg (P < 0.001) 48 weeks thereafter. The body mass index (BMI) decreased from 25 ± 3.3 kg/m² at TDF start to 24.5 ± 3.3 kg/m² (P = 0.002) at the time of switching to TAF and returned to 25.1 ± 3.6 kg/m² (P < 0.001) 48 weeks thereafter. Conclusions Our study showed that switching to TAF from TDF had good antiviral effectiveness and stabilized renal function. The body weight and BMI decreased during TDF therapy and regained after switching to TAF.

PURPOSE: The purpose of this study is to evaluate the rate of progression of Humphrey visual field before and after the cataract surgery in patients with angle-closure glaucoma. MATERIAL AND METHODS: Patients with angle-closure glaucoma who underwent regular visual field (VF) examination and received cataract surgery during the follow-up periods were retrospectively reviewed. The visual field rate of progression, visual acuity (VA), intraocular pressure (IOP), and number of glaucoma medication before and after cataract surgery were compared. RESULTS: A total of 26 eyes were included. The mean follow-up duration before and after the cataract surgery were 5.14 ± 3.31 years and 5.97 ± 2.35 years. After cataract surgery, the IOP and VA improved significantly. The visual field rate of progression significantly slowed down after cataract surgery from − 1.39 ± 1.31 dB/year preoperatively to − 0.34 ± 0.64 dB/year postoperatively (P = 0.003). CONCLUSION: The ACG eyes had rapid VF decline before cataract extraction, which was slowed down significantly after cataract removal.

Purpose: To report the application of LUXIE and validate its reliability by comparing the test results with those of Humphrey Field Analyzer 3 (HFA3). Methods: In this pilot study, we prospectively recruited participants who had received HFA3 SITA standard 30-2 perimetry and tested them with LUXIE on the same day. LUXIE is a software designed for visual field testing cooperating with HTC Vive Pro Eye, a head-mounted virtual reality device with an eye-tracking system. The test stimuli were synchronized with eye movements captured by the eye-tracking system to eliminate fixation loss. The global, hemifields, quadrants, glaucoma hemifield test (GHT) sectors, and point-by-point retinal sensitivities were compared between LUXIE and HFA3. All participants were asked to fill out a post-test user survey. Results: Thirty-eight participants with 65 eyes were enrolled. LUXIE demonstrated good correlations with HFA3 in global (r = 0.81), superior hemifield (r = 0.77), superonasal, superotemporal, and inferonasal quadrants (r = 0.80, 0.78, 0.80). The user survey showed that participants were more satisfied with LUXIE in operating difficulty, comfortability, time perception, concentration, and overall satisfaction. Conclusions: LUXIE demonstrated good correlations with HFA3. Fixation loss could be eliminated in LUXIE with the eye-tracking system. The application of virtual reality devices such as the HTC Vive Pro Eye makes telemedicine and even home-based self-screening visual field tests possible. Key Messages: 1. Virtual reality perimetry is a developing technology that has the potential in telemedicine, and home self-screening visual field tests. 2. LUXIE demonstrated good correlations with Humphrey Field Analyzer 3 in visual field retinal sensitivities.

Abstract Background Age, obesity, and metabolic syndrome are known risk factors for gallstones; however, the combined impact of these different risk factors on gallstone formation has not yet been examined. Methods This retrospective, cross-sectional study involved 3190 participants, including 207 participants (6.5%) with gallstones and 986 (30.9%) with metabolic syndrome. Participants were divided into four phenotypes according to metabolic syndrome and obesity status: 1378 participants were metabolically healthy and non-obese (MHNO); 826 were metabolically healthy but obese (MHO); 185 were metabolically abnormal but not obese (MANO); and 801 participants were metabolically abnormal and obese (MAO). Results The MAO and MANO phenotypes had more gallstones than the MHO and MHNO phenotypes, regardless of age (

Background/Purpose: While direct-acting antiviral regimens have been approved for chronic hepatitis C (CHC) patients in Taiwan, reimbursement is limited to certain populations. Thus, pegylated interferon plus ribavirin (PEG-IFN/RBV) remains the standard of care for many patients. The aim of this study was to investigate the percentage of CHC patients who were recommended and willing to receive PEG-IFN/RBV, and to identify reasons why patients were not recommended or unwilling to receive treatment. Methods: 822 Taiwanese CHC patients were enrolled from May–August 2016 in this cross-sectional study. PEG-IFN/RBV recommendation and patient willingness to receive treatment were evaluated through surveys. Patient characteristics associated with treatment recommendation and willingness were assessed. Results: 311 (37.8%) patients were recommended PEG-IFN/RBV while 102 (12.4%) were willing to follow treatment recommendation. Rates of recommendation and willingness were lower in treatment-experienced, hepatitis C virus genotype 1 (GT1) and cirrhotic patients, and those treated in Northern Taiwan. Multivariate analyses found factors such as prior treatment experience, GT1, cirrhosis and low hemoglobin levels to be associated with lower recommendation rates while advanced age, GT1 and low baseline viral loads were associated with lower willingness rates. Physicians' top reasons for not recommending PEG-IFN/RBV included the wish to wait for better treatment options (60.3%), prior treatment failure (21.3%) and patients’ advanced age (20.9%). Patients were unwilling to receive treatment mainly due to concerns about side effects (91.4%), the wish to wait for better treatment options (71.3%) and inconvenience (25.4%). Conclusion: A minority of Taiwanese CHC patients were recommended PEG-IFN/RBV, of which few were willing to receive treatment. Keywords: Hepatitis C, Pegylated interferon, Ribavirin, Direct acting antiviral, Taiwan

Carbonic anhydrase VIII (CAVIII) is a member of the CA family, while CA8 is the oncogene. Here we observed increased expression of CAVIII with high expression in colorectal cancer tissues. CAVIII is also expressed in more aggressive types of human colorectal cancer cells. Upregulated CAVIII expression in SW480 cell lines increased vascular endothelial growth factor (VEGF) and reduced miRNA16-5p. Conversely, knockdown of the CAVIII results in VEGF decline by up-regulated miRNA16-5p. Moreover, the collection of different grades of CAVIII expression CRC cells supernatant co-culture with endothelial progenitor cells (EPCs) promotes the ability of tube formation in soft agar and migration in the Transwell experiment, indicating that CAVIII might facilitate cancer-cell-released VEGF via the inhibition of miRNA16-5p signaling. Furthermore, in the xenograft tumor angiogenesis model, knockdown of CAVIII significantly reduced tumor growth and tumor-associated angiogenesis. Taken together, our results prove that the CAVIII/miR-16-5p signaling pathway might function as a metastasis suppressor in CRC. Targeting CAVIII/miR-16-5p may provide a strategy for blocking its metastasis.

Background/Aims In a recent study, attenuation imaging (ATI) with ultrasound was used as a new approach for detecting liver steatosis. However, although there are many studies on ATI and controlled attenuation parameter (CAP) that prove their practicability, there are few studies comparing these two methods. As such, this study compared CAP and ATI for the detection and evaluation of liver steatosis. Methods A prospective analysis of 28 chronic liver disease patients who underwent liver biopsy, FibroScan® imaging, and ATI with ultrasound was conducted. The presence and degree of steatosis, as measured with the FibroScan® device and ATI, were compared with the pathological results obtained using liver biopsy. Results The areas under the receiver operating characteristic curve (AUROC) of ATI and CAP for differentiating between normal and hepatic steatosis were 0.97 (95% confidence interval [CI] 0.83–1.00) and 0.96 (95% CI 0.81–0.99), respectively. ATI has a higher AUROC than CAP does in liver steatosis, at 0.99 (95% CI, 0.86–1.00) versus 0.91 (95% CI, 0.74–0.98) in grade ≥ 2 and 0.97 (95% CI, 0.82–1.00) versus 0.88 (95% CI, 0.70–0.97) in grade = 3, respectively. Conclusion The ATI and CAP results showed good consistency and accuracy for the steatosis grading when compared with the liver biopsy results. Moreover, ATI is even better than CAP in patients with moderate or severe steatosis. Therefore, ATI represents a non-invasive and novel diagnostic tool with which to support the diagnosis of liver steatosis in clinical practice.

Purpose. To evaluate Humphrey visual field (VF) progression rate before and after cataract surgery in patients with open-angle glaucoma (OAG) and angle-closure glaucoma (ACG). Methods. After reviewing all records in our Humphrey VF database from July 1, 2001, to December 31, 2018, eyes of OAG and ACG that had received uncomplicated phacoemulsification with intraocular lens implantation during the period and had been followed up regularly for more than one year with ≥3 reliable VF tests before and after cataract surgery, respectively, were enrolled. The VF progression rate, visual acuity, and intraocular pressure (IOP) before and after cataract surgery were compared. Results. Seventy-seven eyes (OAG: 51; ACG: 26) from 60 patients were enrolled. The mean preoperative and postoperative follow-up durations were 4.89 ± 2.70 and 5.48 ± 2.30 years in the OAG group and 5.14 ± 3.31 and 5.97 ± 2.35 years in the ACG group. IOP and visual acuity significantly improved postoperatively in both groups. In the OAG group, there was no significant change in the VF progression rate (pre-op: −0.39 ± 0.94 dB/year; post-op: −0.47 ± 0.72 dB/year) (P=0.619), whereas, in the ACG group, the rate significantly flattened after surgery from −1.39 ± 1.31 dB/year to −0.34 ± 0.64 dB/year (P=0.003). Conclusions. The VF progression rate did not differ between preoperative and postoperative eyes with OAG, but those with ACG exhibited rapid VF decline preoperatively, which was significantly flattened postoperatively.

This study employs biomass growth analyses and 13C-isotope tracing to investigate lipid feedstock utilization by Yarrowia lipolytica. Compared to glucose, oil-feedstock in the minimal medium increases the yeast's biomass yields and cell sizes, but decreases its protein content (

To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of 3/μL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/μL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99–1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06–1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58–0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98–0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71–0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.

Background: Little is known about the use of an electronic reminder system for HCV screening among patients with kidney disease. In this study, we tried to determine whether reminder systems could improve the HCV screening rate in patients with kidney disease. Methods: Patients with kidney disease were enrolled from August 2019 to December 2020 to automatically screen and order HCV antibody and RNA testing in outpatient departments. Results: A total of 19,316 outpatients with kidney disease were included, and the mean age was 66.5 years. The assessment rate of HCV antibody increased from 53.1% prior to the reminder system to 79.8% after the reminder system (p < 0.001), and the assessment rate of HCV RNA increased from 71% to 82.9%. The anti-HCV seropositivity rate decreased from 7.3% at baseline to 2.5% after the implementation of the reminder system (p < 0.001), and the percentage of patients with detectable HCV RNA among those with anti-HCV seropositivity decreased from 69.1% at baseline to 46.8% (p < 0.001). Conclusions: The feasibility of an electronic reminder system for HCV screening among patients with kidney disease in a hospital-based setting was demonstrated.

Purpose. To compare the effects of early phacoemulsification and intraocular lens implantation (phaco/IOL), delayed phaco/IOL after initial laser peripheral iridotomy (LPI), and conventional LPI alone in patients with acute primary angle-closure (PAC). Methods. Patients with acute PAC were included in the study, and those with secondary glaucoma, prior ocular trauma, or other ocular diseases and those who had undergone ocular surgeries previously were excluded. Patients were categorized into three groups: Group A, which underwent primary phaco/IOL after acute PAC; Group B, which underwent LPI initially after acute PAC, followed by phaco/IOL within 6 months; and Group C, which underwent LPI alone. The IOP control success at 12 months as well as changes in ocular characteristics and the number of antiglaucoma medications used after the treatment among the groups were evaluated. Results. Eighty-one eyes were included in the study: 24 eyes in Group A, 23 eyes in Group B, and 34 eyes in Group C. The linear mixed model analysis demonstrated considerable IOP control in Groups A and B. Visual acuity, anterior chamber depth (ACD), and angle width improved significantly in Groups A and B, but not in Group C. The number of antiglaucoma medications used was significantly higher in Group C than in Groups A and B. Conclusions. Patients who underwent phaco/IOL had better IOP control, improved vision, deeper ACD, and wider angle and required less antiglaucoma medications than those who underwent LPI alone. Performing phaco/IOL weeks to months after the initial LPI did not appear to adversely affect outcomes compared with those of early phaco/IOL.

Background: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. Methods: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. Results: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (−0.56 IU/mL, −0.60 IU/mL, and −0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Conclusion: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. Clinical trial ID: NCT: 00922207. Keywords: Chronic hepatitis B, Hepatitis B e antigen, Peginterferon alfa-2a, Adefovir, Entecavir

Purpose: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by facial cutaneous venous dilatation (port-wine stain), leptomeningeal angioma, and ocular abnormalities. Here we report a case of SWS who experienced acute primary angle-closure in the same side of the nevus flammeus. Observations: A 64-years-old female patient with SWS port wine stain on the left side of her face was referred to our ER for acute primary angle-closure (PAC). The IOP was 64 mmHg in the left eye (12 mmHg in OD) and the visual acuity was 20/100. The acute PAC was aborted after medical treatment with intravenous Mannitol and oral Acetazolamide, but laser iridotomy (LI) was not performed because of the risk of bleeding. After the acute episode, her IOP remained stable in midteen under 3 topical medications. However, the patient reported several subacute attacks in the following month. We arranged phacoemulsification and intraocular lens (IOL) implantation two months after the initial PAC attack. The post-op condition was smooth with 20/20 visual acuity, and the angle opened dramatically on anterior segment optical coherence tomography (AS-OCT). Her IOP was around 13 mmHg without medication and there was no more acute PAC attack. Conclusions: SWS with ipsilateral acute PAC has seldom been reported. Lens extraction and IOL implantation can be an option in treating such patients since conventional laser iridotomy may cause bleeding. Keywords: Sturge-Weber syndrome, Acute primary angle-closure glaucoma, Phacoemulsification, Intra-ocular lens implantation, Laser iridotomy

In recent years, ultrasound attenuation imaging (ATI) has emerged as a new method to detect liver steatosis. However, thus far, no studies have confirmed the clinical utility of this technology. Using a retrospective database analysis of 28 patients with chronic liver disease who underwent ultrasound liver biopsy and ATI, we compared the presence and degree of steatosis measured by ATI with the results obtained through liver biopsy. The area under the receiver operating characteristic curve (AUROC) of the ATI for differentiating between normal and hepatic steatosis was 0.97 (95% confidence interval: 0.83–1.00). The AUROC of the ATI was 0.99 (95% confidence interval: 0.86–1.00) in grade ≥2 liver steatosis and 0.97 (95% confidence interval: 0.82–1.00) in grade 3. ATI showed good consistency and accuracy for the steatosis grading of liver biopsy. Therefore, ATI represents a novel diagnostic measurement to support the diagnosis of liver steatosis in non-invasive clinical practice.

The lower limits of virus detection of hepatitis C virus (HCV) RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4th week viral load [rapid virological response (RVR)] in predicting sustained virological response (SVR) in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN) and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4th week viral load as follows: undetectable (n = 90) and detectable but not quantifiable (< 12 IU/mL, n = 27). All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA) HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4th week viral load, respectively. The between-group difference in SVR was significant (p

Purpose. To investigate visual field progression pattern and factors associated with progression in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and chronic angle-closure glaucoma (CACG). Methods. The raw data of the 30-2 Humphrey Field Analyzer from glaucoma patients with definite visual field progression were processed with pointwise linear regression (PLR) analysis. The rate of change of retinal threshold sensitivity in the ten glaucoma hemifield test (GHT) zones, the upper and the lower hemifields, and the whole field was evaluated and was correlated with patients’ basic demographic data. Results. An average follow-up of 6.94 ± 2.69 years that showed the rate of change of visual field threshold sensitivity was correlated with the peak posttreatment intraocular pressure (IOP) and the long-term IOP fluctuations in all GHT zones except in the inferior arcuate area. The baseline IOP, the trough posttreatment IOP, the refractive status, and the CCT were not correlated with VF progression. Conclusion. The rate of visual field progression was correlated with the peak posttreatment IOP and the long-term IOP fluctuation but with subfield differences.

Esophagus thermal injury is a rare case that can be easily overlooked by practitioners. We herein present a case of thermally induced diffuse corrosive esophagitis with complaints of dysphagia and retrosternal chest pain after having steamed pork. A thorough disease course was demonstrated by serials of endoscopy images and video. A comprehensive review of articles and a concise overview of esophageal thermal injury clinical manifestation, disease process, typical endoscopy features, pharmacomanagement option, and outcomes will be conducted in this article.