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Genotype E:The neglected genotype of hepatitis B virus

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World Journal of Hepatology 2021年第12期13卷 1875-1891页

作者： Luicer Anne Olubayo Ingasia Constance Wose Kinge anna kramvis Hepatitis Virus Diversity Research Unit Department of Internal MedicineSchool of Clinical MedicineFaculty of Health SciencesUniversity of the WitwatersrandJohannesburg 2193GautengSouth Africa Department of Implementation Science Right to CareJohannesburg 0046GautengSouth Africa

Hepatitis B virus(HBV)(sub)genotypes A1,D3 and E circulate in sub-Saharan Africa,the region with one of the highest incidences of HBV-associated hepatocellular carcinoma *** genotype E was identified more than 20 years ago,and is the most widespread genotype in Africa,it has not been extensively *** current knowledge status and gaps in its origin and evolution,natural history of infection,disease progression,response to antiviral therapy and vaccination are *** E is an African genotype,with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African *** low prevalence of this genotype in the African descendant populations in the New World,phylogeographic analyses,the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent reintroduction into the *** is scarcity of information on the clinical and virological characteristics of genotype E-infected patients,disease progression and outcomes and efficacy of anti-HBV *** infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha.A minority of genotype E-infected participants have been included in studies in which treatment response was *** concern is that current guidelines do not consider patients infected with genotype ***,there is an urgent need for further large-scale investigations into genotype E,the neglected genotype of HBV.

关键词： Hepatitis B virus Genotype E Evolution Clinical significance Antiviral therapy Vaccination

Follow up of infection of chacma baboons with inoculum containing a and non-a genotypes of hepatitis B virus

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World Journal of Gastroenterology 2003年第4期9卷 731-735页

作者： Marina Baptista anna kramvis Saffie Jammeh Jocelyn Naicker Jacqueline S. Galpin Michael C. Kew University Molecular Hepatology Research Unit Department of MedicineUniversity of the WitwatersrandJohannesburgSouth Africa School of Statistics and Actuarial Sciences University of the WitwatersrandJohannesburgSouth Africa University Molecular Hepatology Research Unit Department of Medicine University of the Witwatersrand JohannesburgSouth Africa

AIM: To determine whether one genotype (A or non-A genotypes of HBV) predominated over the other during the course of HBV ***: Four baboons were inoculated with HBV. DNA was extracted from serum obtained at monthly intervals postinoculation for 52 weeks and HBV DNA was amplified using primers specific for the core region containing an insert characteristic of genotype A (nt 2 354-2 359, numbering from the EcoRI site). The amplicons were cloned into PCRScriptTM and a minimum of 15 clones per time point were sequenced in both ***: Both genotypes persisted for the entire followup period of 52 weeks. Genotype non-A predominated in two baboons and genotype A in one baboon. Neither genotype predominated in the fourth baboon, as shown at a 5 % level of ***: No conclusions concerning the dominance of either genotype or the natural progression or replication rates of HBV could be drawn because the pattern of the genotypes found may have been caused by sampling fluctuations at the time of DNA extraction and cloning as a result of the very low viral loads in the baboon sera.

关键词： Animals Base Sequence DNA Primers DNA, Viral Disease Models, Animal Genotype Hepatitis B Hepatitis B virus Papio Polymerase Chain Reaction Research Support, Non-U.S. Gov't

The roles and mechanisms of miRNA in HBV-HCC carcinogenesis:Why no therapeutic agents after 30 years?

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BIOCELL 2024年第11期48卷 1543-1567页

作者： KURT SARTORIUS BENN SARTORIUS CHERIE WINKLER ANIL CHUTURGOON anna kramvis PING AN WEIGANG ZHANG YUNJIE LU Hepatitis Diversity Research Unit School of Internal MedicineUniversity of the WitwatersrandJohannesburg2050South Africa School of Laboratory Medicine and Molecular Sciences University of KwaZulu-NatalDurban4041South Africa Africa HepatoPancreatoBiliary Cancer Consortium(AHPBCC) Mayo ClinicJacksonvilleMN 55902USA Centre for Clinical Research(UQCCR) Faculty of MedicineUniversity of QueenslandBrisbaneNSW2580Australia Basic Research Laboratory Centre for Cancer ResearchNational Cancer InstituteLeidos Biomedical ResearchInc.Frederick Nat.Lab.for Cancer ResearchFrederickMD 240USA Department of Hepatobiliary and Pancreatic Surgery The First Afﬁliated Hospital of Soochow UniversitySuzhou215100China Department of General Surgery Wujin Hospital Afﬁliated with Jiangsu UniversityZhenjiang212013China

Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic *** (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major ﬁndings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.

关键词： miRNA Molecular mechanisms HBV-HCC Pathogenesis Cellular-processes Epigenetic Im-mune-response Therapeutics Diagnostics

Hepatitis B virus(HBV)and hepatocellular carcinoma(HCC)in sub-Saharan Africa:no room for complacency

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Hepatoma Research 2022年第1期8卷 207-211页

作者： Philippa C.Matthews anna kramvis The Francis Crick Institute Midland RoadLondon NW14ATUK Division of Infection and Immunity University College LondonLondon WC1E 6BTUK Department of Infectious Diseases University College London NHS Foundation TrustLondon NW12PGUK Hepatitis Virus Diversity Research Unit School of Clinical MedicineFaculty of Health SciencesUniversity of the WitwatersrandJohannesburg 2050South Africa

The increasing incidence and mortality of hepatocellular carcinoma(HCC)driven by hepatitis B virus(HBV)infection is a global public health concern[1].Despite World Health Organization(WHO)targets for the elimination of hepatitis as a public health problem by 2030,death attributable to viral hepatitis has continued to rise over the past decade[2],in contrast to the reduction seen in the comparable threats of human immunodeficiency virus(HIV),tuberculosis(TB)and malaria.

关键词： hepatocellular mortality (HBV)

Hepatitis B virus subgenotype A1 predominates in liver disease patients from Kerala,India

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World Journal of Gastroenterology 2013年第48期19卷 9294-9306页

作者： Deepak Gopalakrishnan Mark Keyter Kotacherry Trivikrama Shenoy Kondarappassery Balakumaran Leena Lakshmikanthan Thayumanavan Varghese Thomas KR Vinayakumar Charles Panackel Arun T Korah Ramesh Nair anna kramvis Hepatitis Virus Diversity Research Programme Department of Internal Medicine School of Clinical Medicine Faculty of Health Sciences University of the Witwatersrand Parktown Johannesburg 2193 South Africa Department of Gastroenterology Medical College Trivandrum 695011 India Population Health and Research Institute Trivandrum 695011 India Government Rajaji Hospital Madurai Medical College Madurai 625002 India Department of Gastroenterology Calicut Medical College PO Calicut 673008 India

AIM:To molecularly characterize hepatitis B virus(HBV)isolates from Kerala and to relate them to the clinical manifestation of ***:Sera and clinical data were collected from91 patients diagnosed with chronic HBV infection and HBV-related hepatocellular carcinoma(HCC).HBV from44 HCC,22 cirrhotic and 25 chronic hepatitis patients were genotyped by sequencing of the complete S region or by restriction fragment length polymorphism *** basic core promoter/precore region was *** complete surface DNA sequences were assembled and aligned manually,and then compared with the sequences of HBV of genotypes(A-J)from *** evolutionary history was inferred using the Neighbor-Joining method and the evolutionary distances computed using the Kimura 2-parameter *** was performed using 1000 *** TaqMan BS-1 probe was used to quantify HBV DNA at a lower detection limit of approximately20 IU/*** variables were compared using an independent Student’s t ***χ2test or Fisher’s exact test was used to compare categorical *** differences were considered statistically significant at P<***:Irrespective of disease status,the predominant genotype was A(72%);95%belonging to subgenotype A1,followed by genotypes D(27%)and C(1%).HCC patients infected with subgenotype A1were significantly younger than those infected with *** A1762T/G1764A was significantly associated with HCC in both genotypes A and *** G1862T was more frequent in subgenotype A1(P<0.0001),and in combination with A1762T/G1764A,it was significantly associated with HBV from HCC *** C1766T/T1768A was significantly associated with genotype A(P=0.05)and HCC(P=0.03).The preS2start codon M1T/I mutation was unique to genotype A strains(15.6%)from all disease groups and occurred at a higher frequency in isolates from HCC patients(P=0.076).A higher frequency of preS deletion mutants(33.3%)was observed in genotype A from HC

关键词： Hepatocellular carcinoma Cirrhosis Chronic hepatitis Phylogenetic analysis Genotype India

HBV/HIV共感染与单纯感染HBV 1762T/1764A突变及前S基因缺失的比较研究

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应用预防医学 2017年第2期23卷 113-118页

作者：李开文梁淑家陈钦艳王学燕杨庆利何翔胡丽萍贾蕙华 anna kramvis 方钟燎广西医科大学基础医学院广西壮族自治区疾病预防控制中心广西病毒性肝炎防治研究重点实验室广东省疾病预防控制中心南非金山大学

目的比较分析HBV/HIV共感染者与HBV单纯感染者肝癌相关HBV 1762T/1764A突变及前S基因缺失突变率。方法根据病例对照研究原理,收集未接受HBV及HIV抗病毒治疗的HBV/HIV共感染者和HBV单纯感染者血清标本,用分子生物学技术对血清HBV核心基... 详细信息

目的比较分析HBV/HIV共感染者与HBV单纯感染者肝癌相关HBV 1762T/1764A突变及前S基因缺失突变率。方法根据病例对照研究原理,收集未接受HBV及HIV抗病毒治疗的HBV/HIV共感染者和HBV单纯感染者血清标本,用分子生物学技术对血清HBV核心基因启动子（BCP）和前S基因进行分析。结果病例-对照共61对,平均年龄为（44.9±2.1）岁,共发现3个HBV基因型:基因型B、C和I。共感染者和单纯感染者的主要基因型均为B基因型,分别占63.4%（39/61）和50.8%（31/61）。共感染者肝癌相关HBV基因突变总率（52.5%）显著高于HBV单纯感染者（23.0%）,差异有统计学意义（χ;=11.307,P<0.05）。共感染者BCP的1762T/1764A双突变率（44.3%）显著高于HBV单纯感染者（χ;=7.290,P<0.05）。同样,共感染者前S基因缺失率也显著高于HBV单纯感染者（χ;=8.270,P<0.05）。随机从两组中各抽20例进行对比分析,结果显示共感染与高病毒载量有关,但是高病毒载量与肝癌相关HBV基因突变无关。肝癌相关HBV基因突变率不随CD;细胞计数变化而变化。多因素分析结果表明,合并HIV感染与肝癌相关HBV基因突变（包括BCP双突变与前S缺失突变）有关。结论 HBV/HIV共感染可增加肝癌相关HBV基因突变率。

关键词：乙型肝炎病毒人类免疫缺陷病毒共感染基因变异流行率

Cyclicity of the Lower Buntsandstein in the eastern part of the Central European Basin:implications for Early Triassic palaeogeography and for geochronological calibration

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Journal of Palaeogeography 2024年第2期13卷 252-292页

作者： anna Becker Polish Geological Institute-National Research Institute 4 Rakowiecka str.00-975 WarsawPoland

Lower Buntsandstein small—scale cycles recognized in the Central European Basin(CEB) are readily used for astrochronological calibration of the Early Triassic time scales,although they are not well studied *** borehole sections from the eastern part of the CEB,forming a south-north transect perpendicular to the basin axis,were studied in terms to better understand the depositional history of the Lower Buntsandstein developed as the Baltic Formation in the studied Polish part of the *** sedimentary facies were recognized,based on lithological and sedimentological investigations of 655.7 m of drill cores from the Otyń IG 1,Gorzów Wielkopolski IG 1 and Kamień Pomorski IG 1 *** facies can be grouped according to a lithological criterion into facies of predominantly siliciclastic lithology(including 9facies types) and facies of predominantly carbonate lithology(including 2 facies types).Facies analysis allowed to distinguish 8 facies associations of:1) alluvial fan,2) playa,3) sandy-muddy coastal plain,4)embayment and distal delta,5) lagoon,6) sand bars or shoals,7) ooidal shoals or bars,and 8) ***-upward(DC) and shallowing-upward(SC) sedimentary cycles were recognized in parts of the Baltic Formation,with DCs dominating in the southernmost located Otyń IG 1,and SCs dominating in Gorz ow Wielkopolski IG 1,located in the axial part of the *** cycles are very *** statistical significance of the sedimentary cycles is relatively low according to Markov-chain analysis conducted with the phpSedistat software of Stanova et al.(2009).Analysis of small—scale cycles performed on well logs of investigated boreholes and additional boreholes in the vicinity of Otyń IG 1,implementing the earlier study of Becker(2005),showed that the correlation of well-log cycles(GR cycles) and sedimentary cycles is not *** cycles can be roughly correlated with lithological carbonate—siliciclastic cycles(c-s cycles),refle

关键词： Triassic Lower Buntsandstein Cyclicity Central European Basin

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Cornea modelling

Eye and Vision 2020年第1期7卷 11-25页

作者： anna Pandolfi Department of Civil and Environmental Engineering Politecnico di MilanoPiazza Leonardo da Vinci 3220133 MilanoItaly

Background:Biomechanics introduces numerous technologies to support clinical practice in ophthalmology,with the goal of improving surgical outcomes and to develop new advanced technologies with minimum impact on clinical ***,a few misconceptions on the way that computational methods should be applied to living tissues contributes to a lack of confidence towards computer-based ***:Corneal biomechanics relies on sound theories of mechanics,including concepts of equilibrium,geometrical measurements,and complex material *** peculiarities of biological tissues require the consideration of multi-physics,typical of the eye environment,and to adopt customized geometrical models constructed on the basis of advanced optical imaging and in-vivo ***:Patient-specific models are able to predict the outcomes of refractive surgery and to exploit the results of in-vivo test to characterize the material properties of the corneal ***:Corneal biomechanics can become an important support to clinical practice,provided that methods are based on the actual multi-physics and use customized geometrical and mechanical models.

关键词： Corneal biomechanics Physiologic configuration Tonometry modelling Refractive surgery modelling

Joint power and spectrum allocation algorithm in cognitive radio networks

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Journal of Systems Engineering and Electronics 2011年第4期22卷 691-701页

作者： anna Auguste Anghuwo Communication Research Center Harbin Institute of Technology

The spectrum sharing problem between primary and cognitive users is mainly investigated. Since the interference for primary users and the total power for cognitive users are constrained, based on the well-known water-filling theorem, a novel one-user water-filling algorithm is proposed, and then the corresponding simulation results are given to analyze the feasibility and validity. After that this algorithm is used to solve the communication utility optimization problem subject to the power constraints in cognitive radio network. First, through the gain to noise ratio for cognitive users, a subcarrier and power allocation algorithm based on the optimal frequency partition is proposed for two cognitive users. Then the spectrum sharing algorithm is extended to multiuser conditions such that the greedy and parallel algorithms are proposed for spectrum sharing. Theory and simulation analysis show that the subcarrier and power allocation algorithms can not only protect the primary users but also effectively solve the spectrum and power allocation problem for cognitive users.

关键词： cognitive radio spectrum sharing water-filling algo-rithm interference constraint communication overhead.