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ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation,Regardless of HBV Genotype

Journal of Clinical and Translational Hepatology 2022年第6期10卷 1068-1076页

作者： Luisa Roade mar Riveiro-Barciela Adriana Palom francisco Rodríguez-frías mar.a Bes Ariadna Rando mar.a Teresa Salcedo Rosario Casillas Elena Vargas-Accarino David Tabernero Silvia Sauleda Rafael Esteban mar.a Buti Liver Unit Internal Medicine DepartmentHospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Universitat Autònoma de Barcelona(UAB) Department of MedicineBarcelonaSpain Universitat Au-tònoma de Barcelona(UAB) Department of Biochemistry and Molecular BiologyBarcelonaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadridSpain Liver Pathology Lab Biochemistry and Microbiology Departments(Clinical Laboratories)Hospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Vall d’Hebron Institut de Recerca(VHIR) Liver Diseases GroupBarcelonaSpain Transfusion Safety Laboratory Banc de Sang i TeixitsServei Catalàde la SalutBarcelonaSpain De-partment of Pathology Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelonaSpain

Background and Aims:Hepatitis B virus(HBV)biomark-ers have been used for a better categorization of patients,even though the lack of simple algorithms and the impact of genotypes limit their *** aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers(ICs)in a single-point evaluation and to design a predictive model for their ***-ods:This retrospective-prospective study included 343 consecutive HBeAg-negative ***,analytical,and virological data were collected,and a liver biopsy was performed if *** were classified at the end of follow-up as ICs,chronic hepatitis B and gray zone.A pre-dictive model was constructed,and validated by 1000-boot-strap ***:After 39 months of follow-up,298 subjects were ICs,36 were chronic hepatitis B CHB,and nine were gray ***-nine(25.9%)individuals re-quired a liver *** HBV DNA hazard ratio(HR)6.0,p<0.001),HBV core-related antigen(HBcrAg)(HR 6.5,p<0.001),and elastography(HR 4.6,p<0.001)were inde-pendently associated with the IC *** ACE score(HBV DNA,HBcrAg,elastography),obtained by bootstrapping,yielded an area under the receiver operating characteris-tics(AUROC)of 0.925(95%CI:0.880-0.970,p<0.001)for identification of *** AUROC for genotype D was 0.95,0.96 for A,0.90 for E,and 0.88 for H/*** ACE score of<1 had a positive predictive value of 99.5%,and a score≤12 points had a diagnostic accuracy of 93.8%.Conclusions:Low baseline HBV DNA,HBcrAg,and liver stiffness were in-dependently associated with the IC phase.A score including those variables identified ICs at a single-point evaluation,and might be applied to implement less intensive follow-up strategies.

关键词： Hepatitis B virus Inactive carrier Liver stiffness HBV DNA Quan-titative HBsAg Core-related antigen.

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Influence of the operating temperature on the ageing and interfaces of double layer polymer electrolyte solid state Li metal batteries

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Nano Research 2023年第6期16卷 8377-8384页

作者： Mikel Arrese-Igor mar.a martinez-Ibañez Ander Orue Ekaterina Pavlenko Erwan Dumont Michel Armand frédéric Aguesse Pedro López Aranguren Centre for Cooperative Research on Alternative Energies(CIC energiGUNE) Basque Research and Technology Alliance(BRTA)Alava Technology ParkAlbert Einstein 48Vitoria-Gasteiz 01510Spain University of the Basque Country(UPV/EHU) Barrio Sarrienas/nLeioa 48940Spain Saft 111 Boulevard Alfred DaneyBordeaux Cedex 33074France

Solid-state lithium metal batteries(SSLMBs)are considered an auspicious technology to develop high energy density and safe energy storage *** double layer polymer electrolyte(DLPE)is a rational approach for engineering high-performance SSLMBs addressing electrolyte requirements with specifically designed polymers at the positive electrode and as *** this work,SSLMBs were assembled with poly(propylene carbonate)(PPC),offering stability toward oxidation at the positive electrode,and a gel polymer electrolyte with polyethyleneglycol dimethylether(PEGDME)as separator,offering high ionic conductivity at low temperature and sufficient interfacial stability with Li *** electrochemical properties and performance of cells with LiFePO_(4) and Li[Ni_(0.6)Mn_(0.2)Co_(0.2)]O_(2) positive electrodes are thoroughly investigated as function of the operating temperature by using a host of characterization ***-voltage cells with an areal capacity of 0.7 mAh·cm^(−2)cycled at 40℃ exhibit a higher capacity retention than the cells cycled at 70℃.To understand such differences,a three-electrode setup is applied to discriminate anodic processes from cathodic as function of the *** elucidate the ageing and interfacial evolution for DLPE cells with gel polymer electrolytes paving the way for building performance solid state batteries.

关键词： double layer polymer electrolyte solid-state lithium metal battery gel polymer electrolyte high voltage interfacial study

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Relationship of Food Craving Behavior with Body Mass Index and Body Composition in Reproductive Age Females

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Food and Nutrition Sciences 2017年第7期8卷 699-713页

作者： mar.a-De-Los-Remedios Moreno-frías Sonya Chaudhari mar.a-Raquel Huerta-franco Department of Applied Sciences to Work Division of Health Sciences Campus Leon University of Guanajuato Leon Mexico Department of Biomedical and Health Informatics University of Missouri-Kansas City School of Medicine Kansas City Missouri USA

Objective: To estimate the relationship of Food Craving (FC) behavior with females’ Body Mass Index (BMI), and body-composition. Design, setting and participants: A cross-sectional study of 302 reproductive-age women from middle-socioeconomic class was conducted at the Health & Occupational-Environmental Laboratory. Variable Measures: A FC behavior questionnaire (FCQ) was designed and validated in 151 female subjects. This questionnaire evaluated five dimensions: FC-leisure, FC-psychological reactance, FC-depression, FC-anxiety/stress, and FC-anger. Dependent variables were Body Mass Index (BMI, kg/m2) and the body fat mass. Interventions: A second group of 151 women completed the FCQ. Anthropometrical variables were recorded using the International Society for the Advancement of Kinanthropometry procedure. Analysis: A multiple regression-analysis using STAT- ISTICS version 7 was performed to determine the relationship of FC behavior with anthropometrical variables described. Results: We demonstrated that 98.7% of women had FC behavior. Women with higher BMI had higher scores of FC-depressions (p = 0.02) and FC-anger (p = 0.007). Food craving behavior (p < 0.0008), and food psychological-reactance (p = 0.006), were positive predictors of BMI;food psychological reactance was also a positive predictor of upper and lower-body fat mass (p = 0.005) and (p = 0.008), respectively. Conclusion and Implications: The food craving behavior is a common problem in the female population. Food psychological reactance, in addition to another affective alteration that present the population of women are predictor variables for the increase in BMI and in body-fat mass. It is important that health professionals are aware of the affective states of their patients.

关键词： Food Craving Behavior Body Mass Index Body Composition Reproductive Age Females

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Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection

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World Journal of Gastroenterology 2019年第13期25卷 1566-1579页

作者： Cristina Godoy David Tabernero Sara Sopena Josep Gregori mar.a francesca Cortese Carolina González Rosario Casillas mar.al Yll Ariadna Rando Rosa López-martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban mar Riveiro-Barciela mar.a Buti francisco Rodríguez-frías Liver Pathology Unit Departments of Biochemistry and Microbiology Hospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona Liver Unit Liver Disease Laboratory-Viral Hepatitis Vall d’Hebron Institut Recerca-Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Instituto de Salud Carlos Ⅲ Roche Diagnostics SL Centro de Investigación Médica Aplicada (CIMA) Universidad de Navarra Liver Unit Department of Internal MedicineHospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona (UAB)

Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two *** To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected *** Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA *** HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies *** CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed

关键词： Hepatitis B virus Hepatitis delta virus Hepatitis B X gene Next-generation sequencing Viral quasispecies Hepatitis B virus-hepatitis delta virus interaction

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Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

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World Journal of Gastroenterology 2018年第6期24卷 680-692页

作者： Rosario Casillas David Tabernero Josep Gregori Irene Belmonte mar.a francesca Cortese Carolina González mar Riveiro-Barciela Rosa mar.a López Josep Quer Rafael Esteban mar.a Buti francisco Rodríguez-frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve *** The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any ***

关键词： Hepatitis B virus Hepatitis B virus preS1 region sodium-taurocholate co-transporting polypeptide NTCP-interacting domain virion morphogenesis domain SNP rs2296651 next-generation sequencing real-time PCR melting curves

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Elastic Smart Contracts in Blockchains

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IEEE/CAA Journal of Automatica Sinica 2021年第12期8卷 1901-1912页

作者： Schahram Dustdar Pablo Fernández Josémar.a García Antonio Ruiz-Cortés Distributed Systems Group Vienna University of TechnologyWien 1040Austria Smart Computer Systems Research and Engineering Lab Research Institute of Computer EngineeringUniversity of SevillaSevilla 41012Spain

In this paper,we deal with questions related to blockchains in complex Internet of Things(IoT)-based *** ecosystems are typically composed of IoT devices,edge devices,cloud computing software services,as well as people,who are decision makers in scenarios such as smart *** decisions related to analytics can be based on data coming from IoT sensors,software services,and ***,they are typically based on different levels of abstraction and *** poses a number of challenges when multiple blockchains are used together with smart *** work proposes to apply our concept of elasticity to smart contracts and thereby enabling analytics in and between multiple blockchains in the context of *** propose a reference architecture for Elastic Smart Contracts and evaluate the approach in a smart city scenario,discussing the benefits in terms of performance and self-adaptability of our solution.

关键词： Blockchain elasticity Internet of Things(IoT) smart cities smart contracts virtual chains

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Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy

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World Journal of Gastroenterology 2018年第19期24卷 2095-2107页

作者： Carolina González David Tabernero mar.a francesca Cortese Josep Gregori Rosario Casillas mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando mar.al Yll Rosa Lopez-martinez Josep Quer Rafael Esteban mar.a Buti francisco Rodríguez-frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene *** The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also *** NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like *** Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

关键词： Hepatitis B virus Hepatitis B X gene Hepatitis B X protein Gene therapy Next-generation sequencing HBV conserved regions Small interference RNA

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An uneasy alliance:a nesting association between aggressive ants and equally fierce social wasps

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Insect Science 2020年第1期27卷 122-132页

作者： Pablo Servigne Jerome Orivel frederic Azemar James Carpenter Alain Dejean Bruno Corbara Ecologie Sociale CP 231 Universite Libre de Bruxelles(ULB)Campus PlaineBoulevard du TriompheBrusselsBelgium CNRS UMR EcoFoGAgroParisTechCiradINRAUniversite des AntillesUniversite de GuyaneKourouFrance EcoLabf CNRS INPTUPSUniversite de ToulouseToulouseFrance Division of Invertebrate Zoology American Museum of Natural HistoryNew YorkNew YorkUSA CNRS LMGEUniversite Clermont AuvergneClermont-FerrandFrance

Although the Neotropical territorially dominant arboreal ant Azteca chartifex Forel is very aggressive towards any intruder,its populous colonies tolerate the close presence of the fierce polistine wasp Polybia rejecta(F.).In french Guiana,83.33%of the 48 *** nests recorded were found side by side with those of *** nesting association results in mutual protection from predators(i.e.,the wasps protected from army ants;the ants protected from birds).We conducted field studies,laboratorybased behavioral experiments and chemical analyses to elucidate the mechanisms allowing the persistence of this *** to differences in the cuticular profiles of the two species,we eliminated the possibility of chemical ***,analyses of the carton nests did not reveal traces of marking on the *** ant forager flows were not perturbed by extracts from the wasps’Dufour’s and venom glands,we rejected any hypothetical action of repulsive ***,we noted that the wasps"scraped"the surface of the upper part of their nest envelope using their mandibles,likely removing the ants'scent trails,and an experiment showed that ant foragers were perturbed by the removal of their scent *** leads us to use the term"erasure hypothesis."Thus,this nesting association persists thanks to a relative tolerance by the ants towards wasp presence and the behavior of the wasps that allows them to"contain"their associated ants through the elimination of their scent trails,direct attacks,"wing-buzzing"behavior and ejecting the ants.

关键词： Azteca chartifex ants interspecific association mutualism Polybia rejecta wasps scent trail erasure

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Assessing Quality of Reclaimed Urban Wastewater from Algarrobo Municipality to Be Used for Irrigation

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Journal of Water Resource and Protection 2018年第11期10卷 1090-1105页

作者： Desiree Munoz-Sánchez Veronika Bogodist Vicente Manuel García-Canizares David frías-Gil mar.a Remedios López-Díaz Emilio Jaime-Fernández mar.a Remedios Romero-Aranda Department of Plant Breeding and Biotechnology IHSM-La MayoraCSICAlgarroboSpain

In the European Mediterranean area, the lack of available water resources had led to consider the reclaimed urban waters as an integral part of water resources. Reclaimed urban waters could mitigate water shortage, support agriculture sector and protect rivers and groundwater resources. This work is focused on the evaluation of reclaimed urban water (RW) from Algarrobo municipality, which is located in the Málaga province in the Mediterranean coast at South-East of Spain. Wastewater in the municipal waste water treatment plant, was treated by a membrane bioreactor (MBR) as a tertiary treatment. The main goal of this work was to determine the composition of RW to be compared with fresh local water (LW) from the Algarrobo River, in order to evaluate its suitability for irrigation. Electrical conductivity (EC), pH, sodium absorption ratio (SAR), and mineral content were weekly measured from September 2017 until June 2018. Assessment of RW quality was carried out considering the limit values for each parameter as stated by the current Spanish legislation RD 1620/2007 for reuse of reclaimed water and European Directive for water reuse (EU 91/271/EEC, Annex I). The MBR facility was also focused on preserving essential minerals for plant nutrition to use them for crop fertilization instead of commercial fertilizers. The average content of nitrogen, phosphorous and potassium were, respectively, 72%, 65% and 46% of the amount needed for the Hoagland 1/4 strength solution that was used in this study for irrigation of tomato, avocado and mango crops. from this study it appears that it is possible using membrane technology, to treat urban wastewater in order to supply a good quality of water for irrigation. Water analysis has also proved MBR to be efficient for removal of microbiological pollutants, inorganic compounds, some trace elements and heavy metals. The assessment of RW shows that the evaluated parameters of water-quality are within the range of values stated by Spanish

关键词： Reclaimed Urban Water MBR Electrical Conductivity SAR Nutrients Trace Elements Heavy Metals

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Conservation and variability of hepatitis B core at different chronic hepatitis stages

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World Journal of Gastroenterology 2020年第20期26卷 2584-2598页

作者： mar.al Yll mar.a francesca Cortese Mercedes Guerrero-Murillo Gerard Orriols Josep Gregori Rosario Casillas Carolina González Sara Sopena Cristina Godoy mar.a Vila David Tabernero Josep Quer Ariadna Rando Rosa Lopez-martinez Rafael Esteban mar Riveiro-Barciela mar.a Buti francisco Rodríguez-frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Department of Microbiology Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos ⅢMadrid 28029Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autónoma de BarcelonaBarcelona 08035Spain

BACKGROUND Since it is currently not possible to eradicate hepatitis B virus(HBV)infection with existing treatments,research continues to uncover new therapeutic *** core protein,encoded by the HBV core gene(HBC),intervenes in both structural and functional processes,and is a key protein in the HBV life *** this reason,both the protein and the gene could be valuable targets for new therapeutic and diagnostic ***,alterations in the protein sequence could serve as potential markers of disease *** To detect,by next-generation sequencing,HBC hyper-conserved regions that could potentially be prognostic factors and targets for new *** Thirty-eight of 45 patients with chronic HBV initially selected were included and grouped according to liver disease stage[chronic hepatitis B infection without liver damage(CHB,n=16),liver cirrhosis(LC,n=5),and hepatocellular carcinoma(HCC,n=17)].HBV DNA was extracted from patients’plasma.A region between nucleotide(nt)1863 and 2483,which includes HBC,was amplified and analyzed by next-generation sequencing(Illumina Mi Seq platform).Sequences were genotyped by distance-based discriminant *** and intergroup nt and amino acid(aa)conservation was determined by sliding window *** presence of nt insertion and deletions and/or aa substitutions in the different groups was determined by aligning the sequences with genotype-specific consensus *** Three nt(nt 1900-1929,2249-2284,2364-2398)and 2 aa(aa 117-120,159-167)hyper-conserved regions were shared by all the clinical *** groups showed a similar pattern of conservation,except for five nt regions(nt 1946-1992,2060-2095,2145-2175,2230-2250,2270-2293)and one aa region(aa 140-160),where CHB and LC,respectively,were less conserved(P<0.05).Some group-specific conserved regions were also observed at both nt(2306-2334 in CHB and 1935-1976 and 2402-2435 in LC)and aa(between aa 98-103 in CHB and 28-30 and 5

关键词： Hepatitis B virus Hepatitis B core gene Next-generation sequencing Genetic conservation Amino acid substitution Gene therapy Small interfering RNA

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