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Abstract Polyhydroxyalkanoates (PHAs) could be used to make sustainable, biodegradable plastics. However, the precise and accurate mechanistic modeling of PHA biosynthesis, especially medium-chain-length PHA (mcl-PHA), for yield improvement remains a challenge to biology. PHA biosynthesis is typically triggered by nitrogen limitation and tends to peak at an optimal carbon-to-nitrogen (C/N) ratio. Specifically, simulation of the underlying dynamic regulation mechanisms for PHA bioprocess is a bottleneck owing to surfeit model complexity and current modeling philosophies for uncertainty. To address this issue, we proposed a quantum-like decision-making model to encode gene expression and regulation events as hidden layers by the general transformation of a density matrix, which uses the interference of probability amplitudes to provide an empirical-level description for PHA biosynthesis. We implemented our framework modeling the biosynthesis of mcl-PHA in Pseudomonas putida with respect to external C/N ratios, showing its optimization production at maximum PHA production of 13.81% cell dry mass (CDM) at the C/N ratio of 40:1. The results also suggest the degree of P. putida’s preference in channeling carbon towards PHA production as part of the bacterium’s adaptative behavior to nutrient stress using quantum formalism. Generic parameters (kD, kN and theta θ) obtained based on such quantum formulation, representing P. putida’s PHA biosynthesis with respect to external C/N ratios, was discussed. This work offers a new perspective on the use of quantum theory for PHA production, demonstrating its application potential for other bioprocesses.

Leucaena leucocephala, an invasive toxic tree species, has threatened the survival of native plants in the Hengchun Peninsula, southern Taiwan. Due to the small-to-medium diameter, the utilization and processing of L. leucocephala is highly restricted, while its discarding accelerates carbon dioxide emission to the atmosphere. Biochar, produced from the pyrolysis of biomass under an inert atmosphere, is considered an effective carbon sequestration technique with high stability, which is important for long-term carbon storage and soil improvement. L. leucocephala biomass and montmorillonite were co-pyrolyzed under inert conditions, aiming to investigate the effects of different pyrolysis temperatures and montmorillonite blending ratios on biochar yield and carbon retention. Results showed improved biochar yield and carbon retention with increasing montmorillonite addition. Thermogravimetric analysis, nuclear magnetic resonance spectroscopy, and Fourier-transform infrared spectroscopy demonstrated enhanced stability of the modified biochars. The production of modified L. leucocephala biochar represents a promising technique for carbon dioxide sequestration and biochar stabilization, enabling the development of L. leucocephala utilization approaches.

A quick and reliable test of vocabulary knowledge is a vital component of many studies looking at a range of language processing skills. Recent proliferation of online (web-based) research has generated a growing need for reliable open-access vocabulary tests that can be administered online. This data report presents the newly developed 30-item Web-based Open-access Reliable Decision on Synonyms (WORDS) English Vocabulary Test. In Experiment 1, we tested 109 participants (age range: 18–69 years) on an initial set of 51 potential multiple-choice test items in which participants read a target word (e.g., ubiquitous) and selected a (near-)synonym (e.g., omnipresent) from among three semantically unrelated foils (e.g., interpersonal, catatonic, voluminous). We conducted an item response theory analysis of participants’ accuracy data to select an optimal subset of 30 items to include in the final version of the test. In Experiment 2, we verified the reliability of this 30-item version in a different sample (N = 121; 18–79 years); reliability (internal consistency) was good (Cronbach’s α = 0.82). We confirmed that, consistent with numerous previous studies, (1) responses were more accurate and quicker for more frequent compared to less frequent words, and (2) older adults showed greater vocabulary knowledge compared to younger adults. The WORDS test takes on average 4 minutes (5 minutes 40 seconds including consent/debrief) to complete. It can be freely accessed via Gorilla Open Materials (https://app.gorilla.sc/openmaterials/694887), allowing ease of use and for useful comparisons between data collected by different researchers.

In Taiwan, approximately 379,000 automobiles and 588,000 motorcycles were recycled in 2019. Rigid polyurethane foam is one of the principal components of auto shredder residue. The amount of rigid polyurethane foam from the recycling of waste vehicles is 8,000 to 10,000 tons/year. In this study, waste Cryptomeria wood was mixed with waste rigid polyurethane foam to form derived fuels. The oxidation behaviors of the wood mixed with waste rigid polyurethane foam-derived fuels were investigated. The characteristics of the derived fuel made from wood mixed with waste rigid polyurethane foam showed that the ash content was less than 2.5% and its calorific value reached 21.9 MJ/kg. According to the Friedman equation, the activation energies of the wood mixed with 5%, 15%, and 30% of waste rigid polyurethane foam pellets were 212, 220, and 188 kJ/mol, respectively. The thermal conversion efficiencies of the wood mixed with 5%, 15%, and 30% of waste rigid polyurethane foam pellets were 30.2% to 48.1% by a water boiling test. The results showed that waste Cryptomeria mixed with waste rigid polyurethane foam-derived fuels is suitable for use as an alternative renewable energy fuel.

Abstract Direct interspecies electron transfer (DIET) has been identified as an efficient metabolism between symbiotically interacting organisms. One method of DIET uses conductive materials (e.g., granular activated carbon (GAC)) as a medium to shuttle electrons from electron donating organisms (eg., Geobacter metallireducens) to electron accepting organisms (e.g., Geobacter sulfurreducens and Methanosarcina barkeri). Conductive materials such as GAC, become negatively charged in DIET processes due to reduction by electron donating organisms. This high excess electron density in GAC leads to quantum tunnelling of electrons being a significant electron transfer mechanism for DIET. Thus, a theoretical model obeying the Wentzel–Kramers–Brillouin (WKB) approximation and Fermi–Dirac statistics was developed and simulated. In the model, the electron tunnelling transfer barrier was described by an effective rectangular barrier. The result of our 1D tunnelling simulations indicates that within 29.4 nm of the GAC, tunnelling can sufficiently supply electrons from GAC to G. sulfurreducens and M. barkeri. The phenomenon of tunnelling may also have significance as a stimulant of chemotaxis for G. sulfurreducens and other electron accepting microbes when attempting to adsorb onto GAC. This study sheds light on quantum tunnelling’s significant potential in both bacterium and archaeon DIET-centric processes.

Kawasaki disease (KD) is a form of acute systemic vasculitis that primarily affects children and has become the most common cause of acquired heart disease. While the etiopathogenesis of KD remains unknown, the diagnostic criteria of KD have been well established. Nevertheless, the diagnosis of KD is currently based on subjective clinical symptoms, and no molecular biomarker is yet available. We have previously performed and combined methylation array (Illumina HumanMethylation450 BeadChip) and transcriptome array (Affymetrix GeneChip Human Transcriptome Array 2.0) to identify genes that are differentially methylated/expressed in KD patients compared with control subjects. We have found that decreased methylation levels combined with elevated gene expression can indicate genes (e.g., toll-like receptors and CD177) involved in the disease mechanisms of KD. In this study, we constructed a database called KDmarkers to allow researchers to access these valuable potential KD biomarkers identified via methylation array and transcriptome array. KDmarkers provides three search modes. First, users can search genes differentially methylated and/or differentially expressed in KD patients compared with control subjects. Second, users can check the KD patient groups in which a given gene is differentially methylated and/or differentially expressed. Third, users can explore the DNA methylation levels and gene expression levels in all samples (KD patients and controls) for a particular gene of interest. We further demonstrated that the results in KDmarkers are strongly associated with KD immune responses. All analysis results can be downloaded for downstream experimental designs. KDmarkers is available online at https://cosbi.ee.ncku.edu.tw/KDmarkers/.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan had established a management consensus guideline in 2016. The current recommendations focus on updating critical issues regarding the management of HCC, including surveillance, diagnosis, and systemic treatment. For surveillance, the updated guideline suggests the role of dynamic computed tomography or magnetic resonance imaging and contrast-enhanced ultrasound (CEUS) in selected patients. For diagnosis, this update incorporates CEUS and recognizes the role of gadoxetic acid–enhanced magnetic resonance imaging. For systemic therapy, the updated guideline summarizes the multiple choices of targeted therapy, immune checkpoint inhibitors, and the combination of both. Through this update of the management consensus guideline, patients with HCC can benefit from receiving optimal diagnostic and therapeutic modalities.

We report an efficient method to synthesize undoped and K-doped rare cubic tungsten trioxide nanowires through the thermal evaporation of WO3 powder without a catalyst. The WO3 nanowires are reproducible and stable with a low-cost growth process. The thermal evaporation processing was conducted in a three-zone horizontal tube furnace over a temperature range of 550–850 °C, where multiple substrates were placed at different temperature zones. The processing parameters, including pressure, temperature, type of gas, and flow rate, were varied and studied in terms of their influence on the morphology, aspect ratio and density of the nanowires. The morphologies of the products were observed with scanning electron microscopy. High resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction studies were conducted to further identify the chemical composition, crystal structure and growth direction of the nanostructures. Additionally, the growth mechanism has been proposed. Furthermore, we investigated the potassium doping effect on the physical properties of the nanostructures. Photoluminescence measurements show that there were shorter emission bands at 360 nm and 410 nm. Field emission measurements show that the doping effect significantly reduced the turn-on electric field and increased the enhancement factor. Furthermore, as compared with related previous research, the K-doped WO3 nanowires synthesized in this study exhibited excellent field emission properties, including a superior field enhancement factor and turn-on electric field. The study reveals the potential of WO3 nanowires in promising applications for sensors, field emitters and light-emitting diodes.

Transcript isoforms regulated by alternative splicing can substantially impact carcinogenesis, leading to a need to obtain clues for both gene differential expression and malfunctions of isoform distributions in cancer studies. The Cancer Genome Atlas (TCGA) project was launched in 2008 to collect cancer-related genome mutation raw data from the population. While many repositories tried to add insights into the raw data in TCGA, no existing database provides both comprehensive gene-level and isoform-level cancer stage marker investigation and survival analysis. We constructed Cancer DEIso to facilitate in-depth analyses for both gene-level and isoform-level human cancer studies. Patient RNA-seq data, sample sheets, patient clinical data, and human genome datasets were collected and processed in Cancer DEIso. And four functions to search differentially expressed genes/isoforms between cancer stages were implemented: (i) Search potential gene/isoform markers for a specified cancer type and its two stages; (ii) Search potentially induced cancer types and stages for a gene/isoform; (iii) Expression survival analysis on a given gene/isoform for some cancer; (iv) Gene/isoform stage expression comparison visualization. As an example, we demonstrate that Cancer DEIso can indicate potential colorectal cancer isoform diagnostic markers that are not easily detected when only gene-level expressions are considered. Cancer DEIso is available at http://cosbi4.ee.ncku.edu.tw/DEIso/.

Abstract Background Current understanding of the carbon cycle in methanogenic environments involves trophic interactions such as interspecies H2 transfer between organotrophs and methanogens. However, many metabolic processes are thermodynamically sensitive to H2 accumulation and can be inhibited by H2 produced from co-occurring metabolisms. Strategies for driving thermodynamically competing metabolisms in methanogenic environments remain unexplored. Results To uncover how anaerobes combat this H2 conflict in situ, we employ metagenomics and metatranscriptomics to revisit a model ecosystem that has inspired many foundational discoveries in anaerobic ecology—methanogenic bioreactors. Through analysis of 17 anaerobic digesters, we recovered 1343 high-quality metagenome-assembled genomes and corresponding gene expression profiles for uncultured lineages spanning 66 phyla and reconstructed their metabolic capacities. We discovered that diverse uncultured populations can drive H2-sensitive metabolisms through (i) metabolic coupling with concurrent H2-tolerant catabolism, (ii) forgoing H2 generation in favor of interspecies transfer of formate and electrons (cytochrome- and pili-mediated) to avoid thermodynamic conflict, and (iii) integration of low-concentration O2 metabolism as an ancillary thermodynamics-enhancing electron sink. Archaeal populations support these processes through unique methanogenic metabolisms—highly favorable H2 oxidation driven by methyl-reducing methanogenesis and tripartite uptake of formate, electrons, and acetate. Conclusion Integration of omics and eco-thermodynamics revealed overlooked behavior and interactions of uncultured organisms, including coupling favorable and unfavorable metabolisms, shifting from H2 to formate transfer, respiring low-concentration O2, performing direct interspecies electron transfer, and interacting with high H2-affinity methanogenesis. These findings shed light on how microorganisms overcome a critical obstacle in methanogenic carbon cycles we had hitherto disregarded and provide foundational insight into anaerobic microbial ecology. Video Abstract

Abstract Background Liver cirrhosis is one of the main causes of the morbidity and mortality in liver diseases. Chinese herbal medicine (CHM) has long been used for the clinical treatment of liver diseases. This study was designed to explore the usage frequency and prescription patterns of CHM for patients with decompensated liver cirrhosis and to evaluate the long-term effects of CHM on overall mortality. Methods Two thousand four hundred sixty-seven patients with decompensated liver cirrhosis (ICD-9-CM code: 571.2, 571.5, and 571.6) diagnosed between 2000 and 2009 in Taiwan were identified from the registry for catastrophic illness patients. Of these, 149 CHM users and 298 CHM non-users were matched for age, gender, and Charlson comorbidity index score. The chi-squared test, paired Student’s t-test, Cox proportional hazard model, and Kaplan–Meier method were applied for various comparisons between these groups of patients. Results CHM-treated patients showed a lower overall mortality risk compared with non-treated patients (Multivariable: p

Background: For chronic hepatitis C (CHC) patients completing pegylated interferon (PegIFN)-α/ribavirin therapy, long-term liver histological changes remain largely unexplored. Methods: This observational cohort study included 85 CHC patients completing PegIFN-α/ribavirin therapy with liver biopsies performed at baseline and the end of surveillance (EOS). Median years between paired biopsies were 6.75 (interquartile range: 5.63–7.54). Results: In patients with baseline METAVIR fibrosis stages (F) 70% at EOS compared with baseline (OR = 9.013, p = 0.038). For non-SVR cases among the entire cohort, baseline AST levels >80 U/l and glucose levels ⩽ 105 mg/dl independently predicted significant fibrosis (F2/F3/F4) at EOS (OR = 12.558, p = 0.049) and activity response (OR = 17.741, p = 0.047), respectively. Conclusions: Among CHC patients completing PegIFN-α/ribavirin therapy, SVR lowers the risk of liver histological progression but does not guarantee fibrosis clearance. For SVR cases, those with baseline F ⩾ 2 or without significantly declined follow-up AST levels should be specifically monitored. As for non-SVR cases, those with a higher baseline AST or glucose level should preferentially receive retreatment.

Aims. Long-term risk stratification using combined liver stiffness (LS) and clinically relevant blood tests acquired at the baseline further beyond the sustained virologic response (SVR) visit for chronic hepatitis C (CHC) has not been thoroughly investigated. This study retrospectively investigated the prognostics of liver-related events (LREs) further beyond the SVR visit. Methods. Cox regression and random forest models identified the key factors, including longitudinal LS and noninvasive test results, that could predict LREs, including hepatocellular carcinoma, during prespecified follow-ups from 2010 to 2021. Kaplan–Meier survival analysis estimated the significance of between-group risk stratification. Results. Of the entire eligible cohort (n = 520) of CHC patients with SVR to antiviral therapy, 28 (5.4%) patients developed post-SVR LREs over a median follow-up period of 6.1 years (interquartile range = 3.5–8.7). The multivariate Cox regression analysis identified two significant predictors of LREs after the year 3 post-SVR (Y3PSVR) baseline (LRE, n = 15 of 28, 53.6%, median follow-up = 4.1 [1.6–6.4] years after Y3PSVR): LS at Y3PSVR (adjusted hazard ratio [aHR] = 3.980, 95% confidence interval [CI] = 2.085–7.597, P

Warehouse accidents have become of wide concern to the public because they often cause heavy economic losses and heavy casualties. Therefore, it is critical to foster the safety and reliability of warehouse facilities to reduce accidents. However, in the relevant literature, the increased safety of warehouse facilities has seldom been researched. This is a main research gap that the authors would like to supplement with the aim of enhancing warehouse facility reliability to improve risk management in a comprehensive and reliable way. The objectives of this research article are to collect the critical risks from the relevant literature and interviewees, to calculate the weights of four critical indicators (O, S, D, and E) by the BWM approach, and to rank the critical risks of picking and material-handling accidents in a warehouse facility through GRA, the HFACS model, and the FMEA approach. The ranking results show that cost is the most essential element and the expected cost > detection > severity > occurrence, according to the average value of experts’ comprehensive consideration of importance. Next, GRA is used to prioritize the critical risks of picking and material-handling accidents. The main contribution is that we identify 18 major critical risk accidents of the HFACS risk categories and make up for the insufficiency of past research that lacks an empirical analysis of the risks of picking and material-handling accidents in warehouse facilities.

Abstract Background Studies on temporal changes in noninvasive fibrosis indices and liver stiffness measurement (LSM) in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral agents (DAAs) are limited. Methods We retrospectively enrolled consecutive patients with CHC who had received DAAs. Results In total, we recruited 395 consecutive patients, of which 388 (98.2%) achieved a sustained virologic response (SVR) at 12 weeks after therapy. In patients who received DAA therapy and achieved SVR 12 weeks after therapy (n = 388), the median aspartate aminotransferase/platelet ratio index (APRI) value decreased from 1.19 (0.62–2.44) at baseline to 0.50 (0.32–0.95), 0.51 (0.31–0.92), 0.48 (0.31–0.88), and 0.52 (0.33–0.92) at week 2, week 4, end of therapy, and PW12, respectively (all P

Objectives To explore the risk factors for fragility fractures in rheumatoid arthritis (RA) patients using a 3-year longitudinal, observational cohort study. Methods This RA registry study included consecutive RA patients in the outpatient clinic of Chang Gung Memorial Hospital since September 1, 2014. The demographics, clinical characteristics, lifestyle, evidence of previous fracture, risk factors according to the Fracture Risk Assessment Tool (FRAX®), and the FRAX score of each participant were recorded. The participants were categorized into the new incident fracture (group A) and no incident fracture (group B) groups based on evidence or absence of new incident fractures and propensity score matching (age and gender, 1:2). Results Overall, 477 participants completed the 3-year observation period. After matching, 103 and 206 participants were allocated to groups A and B, respectively. The non-adjusted model revealed, presented as hazard ratio (HR) (95% confidence interval [CI]), that the presence of co-morbidity (1.80 [1.17–2.78], p = 0.008), Health Assessment Questionnaire Disability Index (1.35 [1.07–1.69], p = 0.010), lower baseline hip bone mineral density (0.11 [0.02–0.48], p = 0.004), longer disease duration (1.02 [1.00–1.04], p = 0.026), higher FRAX score of major fracture (1.03 [1.02–1.04], pConclusions In addition to aging and disease-related factors, previous fracture history is the most important risk factor for fragility fractures in RA patients.

Background & aimsIt remains limited whether diabetes mellitus (DM) and hypertension (HTN) affect the prognosis of advanced hepatocellular carcinoma (HCC) treated with sorafenib. Our study attempted to elucidate the roles of DM/HTN and the effects of diabetes medications among advanced HCC patients receiving sorafenib.MethodsFrom August 2012 to February 2018, 733 advanced HCC patients receiving sorafenib were enrolled at China Medical University, Taichung, Taiwan. According to the presence/absence of DM or HTN, they were divided into four groups: control [DM(-)/HTN(-), n = 353], DM-only [DM(+)/HTN(-), n = 91], HTN-only [DM(-)/HTN(+), n = 184] and DM+HTN groups [DM(+)/HTN(+), n = 105]. Based on the types of diabetes medications, there were three groups among DM patients (the combined cohort of DM-only and DM+HTN groups), including metformin (n = 63), non-metformin oral hypoglycemic agent (OHA) (n = 104) and regular insulin (RI)/neutral protamine hagedorn (NPH) groups (n = 29). We then assessed the survival differences between these groups.ResultsDM-only and DM+HTN groups significantly presented longer overall survival (OS) than control group (control vs. DM-only, 7.70 vs. 11.83 months, p = 0.003; control vs. DM+HTN, 7.70 vs. 11.43 months, p = 0.008). However, there was no significant OS difference between control and HTN-only group (7.70 vs. 8.80 months, p = 0.111). Besides, all groups of DM patients showed significantly longer OS than control group (control vs. metformin, 7.70 vs. 12.60 months, p = 0.011; control vs. non-metformin OHA, 7.70 vs. 10.80 months, p = 0.016; control vs. RI/NPH, 7.70 vs. 15.20 months, p = 0.026).ConclusionsRather than HTN, DM predicts better prognosis in advanced HCC treated with sorafenib. Besides, metformin, non-metformin OHA and RI/NPH are associated with longer survival among DM-related advanced HCC patients receiving sorafenib.

Following the BBC’s Blue Planet II nature documentary series on marine ecosystems, plastic packaging has come under public fire, with consumers demanding greener alternatives. The biodegradable properties of some bioplastics have offered a potential solution to the global challenge of plastic pollution, while enabling the capture of food waste through anaerobic digestion as a circular and energy-positive waste treatment strategy. However, despite their increasing popularity, currently bioplastics are being tested in environments that do not reflect real-life waste management scenarios. Bioplastics find their most useful, meaningful and environmentally-sound application in food packaging—why is there so little interest in addressing their anaerobic co-digestion with food waste? Here, we provide a set of recommendations to ensure future studies on bioplastic end-of-life are fit for purpose. This perspective makes the link between the environmental sustainability of bioplastics and the role of food waste anaerobic digestion as we move towards an integrated food–energy–water–waste nexus. It shines light on a novel outlook in the field of bioplastic waste management while uncovering the complexity of a successful path forward. Ultimately, this research strives to ensure that the promotion of bioplastics within a circular economy framework is supported across waste collection and treatment stages.

Thalassemia and iron deficiency are the most common etiologies for microcytic anemia and there are indices discriminating both from common laboratory simple automatic counters. In this study a new classifier for discriminating thalassemia and non-thalassemia microcytic anemia was generated via combination of exciting indices with machine-learning techniques. A total of 350 Taiwanese adult patients whose anemia diagnosis, complete blood cell counts, and hemoglobin gene profiles were retrospectively reviewed. Thirteen prior established indices were applied to current cohort and the sensitivity, specificity, positive and negative predictive values were calculated. A support vector machine (SVM) with Monte-Carlo cross-validation procedure was adopted to generate the classifier. The performance of our classifier was compared with original indices by calculating the average classification error rate and area under the curve (AUC) for the sampled datasets. The performance of this SVM model showed average AUC of 0.76 and average error rate of 0.26, which surpassed all other indices. In conclusion, we developed a convenient tool for primary-care physicians when deferential diagnosis contains thalassemia for the Taiwanese adult population. This approach needs to be validated in other studies or bigger database.

Abstract This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P

Abstract We developed an optimal noninvasive index comprising routine laboratory parameters for predicting cirrhosis in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients. This study included 992 CHB patients and 1,284 CHC patients who received liver biopsy. We developed the new index, named modified Fibrosis-4 (mFIB-4) according to four independent variables of the model: age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The formula of the mFIB-4 index is 10 × Age(years) × AST(U/L)/Platelet count(109/L) × ALT(U/L). For predicting cirrhosis, the bootstrap areas under the receiver operating characteristic curve for platelet count, AST/ALT ratio (AAR), AAR/platelet ratio index (AARPRI), AST/platelet ratio index (APRI), FIB-4, Pohl score, age-platelet (AP) index, Lok index, fibrosis quotient (FibroQ), and mFIB-4 were 0.7680, 0.7400, 0.8070, 0.6090, 0.7690, 0.6990, 0.7850, 0.7960, 0.8110, and 0.8070 in CHB patients, and 0.8170, 0.7210, 0.8400, 0.7310, 0.8310, 0.6730, 0.8220, 0.8440, 0.8570, and 0.8480 in CHC patients, respectively. FibroQ and mFIB-4 exhibited the highest diagnostic performance levels for liver cirrhosis in CHB and CHC despite the inclusion of the international normalised ratio in the formulation of FibroQ. Thus, mFIB-4 is a simple, inexpensive, and readily available method for assessing the liver fibrosis stage of Asian patients with CHB or CHC.

Abstract This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p

Abstract Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is unclear. In this study, HSCs were activated by the conditioned medium derived from HCV replicon cells. Secretomic profiling of HCV replicon cells and the parental Huh7 cells revealed ubiquitin carboxy-terminal hydrolase L1 (UCHL1) as a novel secreted protein from HCV-infected hepatocytes. UCHL1 expression in hepatocytes was induced by HCV infection. UCHL1 was expressed in the liver and found in the plasma of patients with chronic hepatitis C. Molecular analysis by use of the anti-UCHL1 neutralization antibody and purified UCHL1 protein showed that secreted UCHL1 protein was bound to the cell surface of HSCs and activated JNK signaling leading to overexpression of alpha-smooth muscle actin and the activation of HSCs. These results provide further for understanding the underlying mechanism in HCV-mediated hepatic fibrogenesis.

The combined effect of acrylonitrile butadiene styrene (ABS) spherical beads and granular activated carbon (GAC) particles as fluidized media on the performance of anaerobic fluidized bed membrane bioreactor (AFMBR) was investigated. GAC particles and ABS beads were fluidized together in a single AFMBR to investigate membrane fouling and organic removal efficiency as well as energy consumption. The density difference between these two similarly sized media caused the stratified bed layer where ABS beads are fluidized above the GAC along the membrane. Membrane relaxation was effective to reduce the fouling and trans-membrane pressure (TMP) below 0.25 bar could be achieved at 6 h of hydraulic retention time (HRT). More than 90% of soluble chemical oxygen demand (SCOD) was removed after 80 d operation. Biogas consisting of 65% of methane was produced by AFMBR, suggesting that combined use of GAC and ABS beads did not have any adverse effect on methane production during the operational period. Scanning Electron Microscope (SEM) examinations showed the adherence of microbes to both media. However, 16S rRNA results revealed that fewer microbes attached to ABS beads than GAC. There were also compositional differences between the ABS and GAC microbial communities. The abundance of the syntrophs and exoelectrogens population on ABS beads was relatively low compared to that of GAC. Our result implied that syntrophic synergy and possible occurrence of direct interspecies electron transfer (DIET) might be facilitated in AFMBR by GAC, while traditional methanogenic pathways were dominant in ABS beads. The electrical energy required was 0.02 kWh/m3, and it was only about 13% of that produced by AFMBR.

Single-stage nitrite shunt denitrification (through nitrite rather than nitrate) with low dissolved oxygen (DO) supply is a better alternative in terms of energy-efficiency, short-footprint, and low C/N-ratio requirement. This study investigates the optimal DO level with temperature effect, with saline sewage at the fixed hydraulic and solids retention times of 8 h and 8 d, respectively. Moreover, 16S rRNA gene sequencing analysis corresponding with total nitrogen (TN) and chemical oxygen demand (COD) removals in each operating condition were performed. Results showed that DO of 0.3 mg/L at 20 °C achieved over 60.7% and over 97.9% of TN and COD removal, respectively, suggesting that such condition achieved effective nitrite-oxidizing bacteria inhibition and efficient denitrification. An unexpected finding was that sulfur-reducing Haematobacter and nitrogen-fixing Geofilum and Shinella were highly abundant with the copredominance of ammonia-oxidizing Comamonas and Nitrosomonas, nitrite-oxidizing Limnohabitans, and denitrifying Simplicispira, Castellaniella, and Nitratireductor. Further, canonical correspondence analysis (CCA) with respect to the operating conditions associated with phenotype prediction via R-based tool Tax4Fun was performed for a preliminary diagnosis of microbial functionality. The effects of DO, temperature, nitrite, and nitrate in various extents toward each predominant microbe were discussed. Collectively, DO is likely pivotal in single-stage nitrite shunt denitrification, as well as microbial communities, for energy-efficient saline sewage treatment.

To compare on-treatment and off-treatment parameters acquired using acoustic radiation force impulse elastography, the Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index (APRI) in patients with chronic hepatitis C (CHC).Patients received therapies based on pegylated interferon or direct-acting antiviral agents. The changes in paired patient parameters, including liver stiffness (LS) values, the FIB-4 index, and APRI, from baseline to sustained virologic response (SVR) visit (24 weeks after the end of treatment) were compared. Multiple regression models were used to identify significant factors that explained the correlations with LS, FIB-4, and APRI values and SVR.A total of 256 patients were included, of which 219 (85.5%) achieved SVR. The paired LS values declined significantly from baseline to SVR visit in all groups and subgroups except the nonresponder subgroup (n = 10). Body mass index (P = 0.0062) and baseline LS (P < 0.0001) were identified as independent factors that explained the LS declines. Likewise, the baseline FIB-4 (P < 0.0001) and APRI (P < 0.0001) values independently explained the declines in the FIB-4 index and APRI, respectively. Moreover, interleukin-28B polymorphisms, baseline LS, and rapid virologic response were identified as independent correlates with SVR.Paired LS measurements in patients treated for CHC exhibited significant declines comparable to those in FIB-4 and APRI values. These declines may have correlated with the resolution of necroinflammation. Baseline LS values predicted SVR.

Nanaerobes are a newly described class of microorganisms that use a unique cytochrome bd oxidase to achieve nanaerobic respiration at

The aim of this study was to compare the diagnostic performances of the collagen proportionate area (CPA) and liver stiffness measurement (LSM) for liver fibrosis quantification in chronic hepatitis C (CHC).A total of 137 eligible consecutive Taiwanese patients (74 women and 63 men; age 21-80 years; median age 54 years), with CHC underwent LSM by using acoustic radiation force impulse (ARFI) elastography and an immediate percutaneous liver biopsy for METAVIR scoring. Liver tissue sections were stained using picrosirius red. Areas of the stained collagen and the tissue parenchyma were calculated in pixels. The ratio between the two areas was expressed as a CPA percentage. The result of LSM was presented as shear wave velocity (SWV).METAVIR fibrosis (F) stages were dichotomized using the CPA (%) and SWV (m/s), and the optimal cut-off values were 7.47 and 1.59 for F1 versus F2-4; 12.56 and 1.73 for F1, 2 versus F3, 4; 15.32 and 1.96 for F1-3 versus F4. To dichotomize F1 versus F2-4, the areas under receiver operating characteristic curves for the CPA was 0.9349 (95% confidence interval: 0.8943-0.9755) and for SWV was 0.8434 (0.7762-0.9105) (CPA versus SWV, P = 0.0063). For F1, 2 versus F3, 4, the CPA was 0.9436 (0.9091-0.9781); SWV was 0.8997 (0.8444-0.9551) (P = 0.1587). For F1-3 versus F4, the CPA was 0.8647 (0.7944-0.9349); SWV was 0.9036 (0.8499-0.9573) (P = 0.2585). The CPA could be predicted in a linear regression formula by using SWV and platelet count (R2 = 0.524).The CPA and ARFI elastography are promising tools for liver fibrosis evaluation. The CPA was superior to ARFI elastography in the diagnosis of significant fibrosis (≥ F2). The CPA may be independent of severe necroinflammation, which may augment liver stiffness.

Multipartite viruses contain more than one distinctive genome component, and the origin of multipartite viruses has been suggested to evolve from a non-segmented wild-type virus. To explore whether recombination also plays a role in the evolution of the genomes of multipartite viruses, we developed a systematic approach that employs motif-finding tools to detect conserved motifs from divergent genomic regions and applies statistical approaches to select high-confidence motifs. The information that this approach provides helps us understand the evolution of viruses. In this study, we compared our motif-based strategy with current alignment-based recombination-detecting methods and applied our methods to the analysis of multipartite single-stranded plant DNA viruses, including bipartite begomoviruses, Banana bunchy top virus (BBTV) (consisting of 6 genome components) and Faba bean necrotic yellows virus (FBNYV) (consisting of 8 genome components). Our analysis revealed that recombination occurred between genome components in some begomoviruses, BBTV and FBNYV. Our data also show that several unusual recombination events have contributed to the evolution of BBTV genome components. We believe that similar approaches can be applied to resolve the evolutionary history of other viruses.