bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reassortment between Swine H3N2 and 2009 Pandemic H1N1 in the United States Resulted in Influenza A Viruses with Diverse Genetic Constellations with Variable Virulence in Pigs
Authors: Rajão Daniela S. , Walia Rasna R. , Campbell Brian , Gauger Phillip C. , Janas-Martindale Alicia , Killian Mary Lea , Vincent Amy L. 
Published: December 2016

ABSTRACT
Repeated spillovers of the H1N1 pandemic virus (H1N1pdm09) from humans to pigs resulted in substantial evolution of influenza A viruses infecting swine, contributing to the genetic and antigenic diversity of influenza A viruses (IAV) currently circulating in swine. The reassortment with endemic swine viruses and maintenance of some of the H1N1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. Here, we performed a whole-genome phylogenetic analysis of 368 IAV circulating in swine from 2009 to 2016 in the United States. We identified 44 different genotypes, with the most common genotype (32.33%) containing a clade IV-A HA gene, a 2002-lineage NA gene, an M-pdm09 gene, and remaining gene segments of triple reassortant internal gene (TRIG) origin. To understand how different genetic constellations may relate to viral fitness, we compared the pathogenesis and transmission in pigs of six representative genotypes. Although all six genotypes efficiently infected pigs, they resulted in different degrees of pathology and viral shedding. These results highlight the vast H3N2 genetic diversity circulating in U.S. swine after 2009. This diversity has important implications in the control of this disease by the swine industry, as well as a potential risk for public health if swine-adapted viruses with H1N1pdm09 genes have an increased risk to humans, as occurred in the 2011-2012 and 2016 human variant H3N2v cases associated with exhibition swine.

IMPORTANCE
People continue to spread the 2009 H1N1 pandemic (H1N1pdm09) IAV to pigs, allowing H1N1pdm09 to reassort with endemic swine IAV. In this study, we determined the 8 gene combinations of swine H3N2 IAV detected from 2009 to 2016. We identified 44 different genotypes of H3N2, the majority of which contained at least one H1N1pdm09 gene segment. We compared six representative genotypes of H3N2 in pigs. All six genotypes efficiently infected pigs, but they resulted in different degrees of lung damage and viral shedding. These results highlight the vast genetic diversity of H3N2 circulating in U.S. swine after 2009, with important implications for the control of IAV for the swine industry. Because H1N1pdm09 is also highly adapted to humans, these swine viruses pose a potential risk to public health if swine-adapted viruses with H1N1pdm09 genes also have an increased risk for human infection.
Amino Acid Mutations in the NS4A Region of Hepatitis C Virus Contribute to Viral Replication and Infectious Virus Production
Authors: Murayama Asako , Sugiyama Nao , Suzuki Ryosuke , Moriyama Masaki , Nakamura Noriko , Mochizuki Hidenori , Wakita Takaji , Kato Takanobu 
Published: December 2016

ABSTRACT
Hepatitis C virus (HCV) strain JFH-1, which belongs to genotype 2a, replicates autonomously in cultured cells, whereas another genotype 2a strain, J6CF, does not. Previously, we found that replacement of the NS3 helicase and NS5B-to-3′X regions of J6CF with those of JFH-1 confers J6CF replication competence. In this study, we aimed to identify the minimum modifications within these genomic regions needed to establish replication-competent J6CF. We previously identified 4 mutations in the NS5B-to-3′X region that could be used instead of replacement of this region to confer J6CF replication competence. Here, we induced cell culture-adaptive mutations in J6CF by the long-term culture of J6CF/JFH-1 chimeras composed of JFH-1 NS5B-to-3′X or individual parts of this but not the NS3 helicase region. After 2 months of culture, efficient HCV replication and infectious virus production in chimeric RNA-transfected cells were observed, and several amino acid mutations in NS4A were identified in replicating HCV genomes. The introduction of NS4A mutations into the J6CF/JFH-1 chimeras enhanced viral replication and infectious virus production. Immunofluorescence microscopy demonstrated that some of these mutations altered the subcellular localization of the coexpressed NS3 protein and affected the interaction between NS3 and NS4A. Finally, introduction of the most effective NS4A mutation, A1680E, into J6CF contributed to its replication competence in cultured cells when introduced in conjunction with four previously identified adaptive mutations in the NS5B-to-3′X region. In conclusion, we identified an adaptive mutation in NS4A that confers J6CF replication competence when introduced in conjunction with 4 mutations in NS5B-to-3′X and established a replication-competent J6CF strain with minimum essential modifications in cultured cells.

IMPORTANCE
The HCV cell culture system using the JFH-1 strain and HuH-7 cells can be used to assess the complete HCV life cycle in cultured cells. This cell culture system has been used to develop direct-acting antivirals against HCV, and the ability to use various HCV strains within this system is important for future studies. In this study, we aimed to establish a novel HCV cell culture system using another HCV genotype 2a strain, J6CF, which replicates in chimpanzees but not in cultured cells. We identified an effective cell culture-adaptive mutation in NS4A and established a replication-competent J6CF strain in cultured cells with minimum essential modifications. The described strategy can be used in establishing a novel HCV cell culture system, and the replication-competent J6CF clone composed of the minimum essential modifications needed for cell culture adaptation will be valuable as another representative of genotype 2a strains.
High Prevalence of Infectious Adeno-associated Virus (AAV) in Human Peripheral Blood Mononuclear Cells Indicative of T Lymphocytes as Sites of AAV Persistence
Authors: Hüser Daniela , Khalid Dina , Lutter Timo , Hammer Eva-Maria , Weger Stefan , Heßler Melanie , Kalus Ulrich , Tauchmann Yvonne , Hensel-Wiegel Karin , Lassner Dirk , Heilbronn Regine 
Published: December 2016

ABSTRACT

Seroepidemiology shows that infections with adeno-associated virus (AAV) are widespread, but diverse AAV serotypes isolated from humans or nonhuman primates have so far not been proven to be causes of human disease. In view of the increasing success of AAV-derived vectors in human gene therapy, definition of the
in vivo
sites of wild-type AAV persistence and the clinical consequences of its reactivation is becoming increasingly urgent. Here, we identify the presumed cell type for AAV persistence in the human host by highly sensitive AAV PCRs developed for the full spectrum of human AAV serotypes. In genomic-DNA samples from leukocytes of 243 healthy blood donors, 34% were found to be AAV positive, predominantly AAV type 2 (AAV2) (77%), AAV5 (19%), and additional serotypes. Roughly 11% of the blood donors had mixed AAV infections. AAV prevalence was dramatically increased in immunosuppressed patients, 76% of whom were AAV positive. Of these, at least 45% displayed mixed infections. Follow-up of single blood donors over 2 years allowed repeated detection of the initial and/or additional AAV serotypes, suggestive of fluctuating, persistent infection. Leukocyte separation revealed that AAV resided in CD3
+
T lymphocytes, perceived as the putative
in vivo
site of AAV persistence. Moreover, infectious AAVs of various serotypes could be rescued and propagated from numerous samples. The high prevalence and broad spectrum of human AAVs in leukocytes closely follow AAV seroepidemiology. Immunosuppression obviously enhances AAV replication in parallel with activation of human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6), reminiscent of herpesvirus-induced AAV activation.

IMPORTANCE
Adeno-associated virus is viewed as apathogenic and replication defective, requiring coinfection with adenovirus or herpesvirus for productive infection.
In vivo
persistence of a defective virus requires latency in specialized cell types to escape the host immune response until viral spread becomes possible. Reactivation from latency can be induced by diverse stimuli, including infections, typically induced upon host immunosuppression. We show for the first time that infectious AAV is highly prevalent in human leukocytes, specifically T lymphocytes, and that AAV is strongly amplified upon immunosuppression, along with reactivation of latent human herpesviruses. In the absence of an animal model to study the AAV life cycle, our findings in the human host will advance the understanding of AAV latency, reactivation, and
in vivo
pathogenesis.
Late Quaternary climatic control of Lake Baikal (Russia) turbidite systems: Implications for turbidite systems worldwide
Authors: Evangelinos Dimitris , Nelson C. Hans , Escutia Carlota , De Batist Marc , Khlystov Oleg 
Published: December 2016

Abstract
Lake Baikal (Russia) contains a variety of turbidite systems in different tectonic and depositional settings that provide tests for the role of Quaternary climatic change on turbidite system growth. During Pleistocene glacial climates, all types of systems exhibit increased sediment supply (high sedimentation rates, high net sand percent, thick sand turbidites) and progradation. During Holocene interglacial climate, all systems exhibit reduced sediment supply and retreat. Seismic profiles from the large Selenga Fan and small Tompuda Fan show (1) maximum fan growth during the late Pleistocene glacial melt time, where lobes and large channels reached the distal outer fan, and (2) fan retreat during the transition to the fully developed Holocene interglacial climate. For example, the Selenga Fan surface lobes backstepped ∼55 km from the distal outer fan to the distal inner fan, and the large outer fan surface channel (∼750 m wide, ∼20 m levee relief) evolved to a smaller surface channel (∼450 m wide, ∼13 m levee relief) that extended only to the end of the inner fan. These results show that Quaternary climate controls the growth of the Lake Baikal turbidite systems in a setting where there are no significant water-level changes, which often are cited as the main control on turbidite system growth. The Lake Baikal and other marine turbidite systems suggest that climatic control of sediment supply, unrelated to sea-level lowering and tectonic effects, may have been a much more important control for turbidite systems than previously believed, not only during the Pleistocene, but perhaps also for ancient systems.
Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol
Authors: English Shane W , Fergusson D , Chassé M , Turgeon A F , Lauzier F , Griesdale D , Algird A , Kramer A , Tinmouth A , Lum C , Sinclair J , Marshall S , Dowlatshahi D , Boutin A , Pagliarello G , McIntyre L A 
Published: December 2016

IntroductionAnaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months.MethodsDesignThis is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres.PopulationWe are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L).RandomisationCentral computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L.InterventionPatients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L).OutcomePrimary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate.Ethics and disseminationThe study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH.Trial registration numberNCT02483351; Pre-results.
Ethnic disparities in the prevalence of metabolic syndrome and its risk factors in the Suriname Health Study: a cross-sectional population study
Authors: Krishnadath Ingrid S K , Toelsie Jerry R , Hofman Albert , Jaddoe Vincent W V 
Published: December 2016

BackgroundThe metabolic syndrome (MetS) indicates increased risk for cardiovascular disease and type 2 diabetes. We estimated the overall and ethnic-specific prevalence of MetS and explored the associations of risk factors with MetS among Amerindian, Creole, Hindustani, Javanese, Maroon and Mixed ethnic groups.MethodWe used the 2009 Joint Interim Statement (JIS) to define MetS in a subgroup of 2946 participants of the Suriname Health Study, a national survey designed according to the WHO Steps guidelines. The prevalences of MetS and its components were determined for all ethnicities. Hierarchical logistic regressions were used to determine the associations of ethnicity, sex, age, marital status, educational level, income status, employment, smoking status, residence, physical activity, fruit and vegetable intake with MetS.ResultsThe overall estimated prevalence of MetS was 39.2%. From MetS components, central obesity and low high-density lipoprotein cholesterol (HDL-C) had the highest prevalences. The prevalence of MetS was highest for the Hindustanis (52.7%) and lowest for Maroons (24.2%). The analyses showed that in the overall population sex (women: OR 1.4; 95% CI 1.2 to 1.6), age (OR 5.5 CI 4.3 to 7.2), education (OR 0.7 CI 0.6 to 0.9), living area (OR 0.6 CI 0.5 to 0.8), income (OR 0.7 CI 0.5 to 0.9) and marital status (OR 1.3 CI 1.1 to 1.6) were associated with MetS. Variations observed in the associations of the risk factors with MetS in the ethnic groups did not materially influence the associations of ethnicities with MetS.ConclusionsThe prevalence of MetS was high and varied widely among ethnicities. Overall, central obesity and low HDL-C contributed most to MetS. Further studies are needed to assess the prospective associations of risk factors with MetS in different ethnic groups.
What affects response rates in primary healthcare-based programmes? An analysis of individual and unit-related factors associated with increased odds of non-response based on HCV screening in the general population in Poland
Authors: Parda Natalia , Stępień Małgorzata , Zakrzewska Karolina , Madaliński Kazimierz , Kołakowska Agnieszka , Godzik Paulina , Rosińska Magdalena 
Published: December 2016

ObjectivesResponse rate in public health programmes may be a limiting factor. It is important to first consider their delivery and acceptability for the target. This study aimed at determining individual and unit-related factors associated with increased odds of non-response based on hepatitis C virus screening in primary healthcare.DesignPrimary healthcare units (PHCUs) were extracted from the Register of Health Care Centres. Each of the PHCUs was to enrol adult patients selected on a random basis. Data on the recruitment of PHCUs and patients were analysed. Multilevel modelling was applied to investigate individual and unit-related factors associated with non-response. Multilevel logistic model was developed with fixed effects and only a random intercept for the unit. Preliminary analysis included a random effect for unit and each of the individual or PHCU covariates separately. For each of the PHCU covariates, we applied a two-level model with individual covariates, unit random effect and a single fixed effect of this unit covariate.SettingThis study was conducted in primary care units in selected provinces in Poland.ParticipantsA total of 242 PHCUs and 24 480 adults were invited. Of them, 44 PHCUs and 20 939 patients agreed to participate. Both PHCUs and patients were randomly selected.ResultsData on 44 PHCUs and 24 480 patients were analysed. PHCU-level factors and recruitment strategies were important predictors of non-response. Unit random effect was significant in all models. Larger and private units reported higher non-response rates, while for those with a history of running public health programmes the odds of non-response was lower. Proactive recruitment, more working hours devoted to the project and patient resulted in higher acceptance of the project. Higher number of personnel had no such effect.ConclusionsPrior to the implementation of public health programme, several factors that could hinder its execution should be addressed.
Epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma: a systematic review protocol
Authors: Nieto T , Tomlinson C L , Dretzke J , Bayliss S , Dilworth M , Beggs A D , Tucker O 
Published: December 2016

IntroductionBarrett's oesophagus (BO), a metaplastic condition affecting the lower oesophagus due to long-standing gastro-oesophageal reflux and chronic inflammation, is a precursor lesion for oesophageal adenocarcinoma (OADC). There is no clinical test to predict which patients with BO will progress to OADC. The British Society of Gastroenterology recommends endoscopic surveillance of patients with BO. Epigenetic changes have been well characterised in the neoplastic progression of ulcerative colitis to colonic carcinoma, another gastrointestinal cancer associated with chronic inflammation. This systematic review protocol aims to identify and evaluate studies which examine epigenetic biomarkers in BO and their association with progression to OADC.Methods and analysisAll prospective and retrospective primary studies, and existing systematic reviews investigating epigenetic markers including DNA methylation, histone modification, chromatin remodelling, micro and non-coding RNAs of all types will be eligible for inclusion. Eligible patients are those over the age of 18 with BO, BO with dysplasia, OADC or unspecified oesophageal cancer. A comprehensive search of bibliographic databases using combinations of text and index words relating to the population, prognostic markers and outcome will be undertaken with no language restrictions. Results will be screened by 2 independent reviewers and data extracted using a standardised proforma. The quality and risk of bias of individual studies will be assessed using the Quality in Prognostic Studies (QUIPS) tool. A narrative synthesis of all evidence will be performed with key findings tabulated. Meta-analysis will be considered where studies and reported outcomes are considered sufficiently homogeneous, both clinically and methodologically. Findings will be interpreted in the context of the quality of included studies. The systematic review will be reported according to PRISMA guidelines.Ethics and disseminationThis is a systematic review of completed studies and no ethical approval is required. Findings from the full systematic review will be submitted for publication and presentation at national and international conferences which will inform future research on risk stratification in patients with BO.Review registration numberCRD42016038654.
Getting it Right: study protocol to determine the diagnostic accuracy of a culturally-specific measure to screen for depression in Aboriginal and/or Torres Strait Islander people
Authors: Hackett Maree L , Farnbach Sara , Glozier Nick , Skinner Timothy , Teixeira-Pinto Armando , Askew Deborah , Gee Graham , Cass Alan , Brown Alex 
Published: December 2016

IntroductionA freely available, culturally valid depression screening tool is required for use by primary care services across Australia to screen for depression in Aboriginal and/or Torres Strait Islander populations. This is the protocol for a study aiming to determine the validity, sensitivity and specificity of the culturally adapted 9-item Patient Health Questionnaire (aPHQ-9).Methods and analysisCross-sectional validation study. A total of 500 people who self-identify as Aboriginal and/or Torres Strait Islander, are ≥18 years of age, attending 1 of 10 primary healthcare services or service events across Australia and able to communicate sufficiently to answer study questions will be recruited. All participants will complete the aPHQ-9 and the criterion standard MINI International Neuropsychiatric Interview (MINI) 6.0.0. The primary outcome is the criterion validity of the aPHQ-9. Process outcomes related to acceptability and feasibility of the aPHQ-9 will be analysed only if the measure is found to be valid.Ethics and disseminationLead ethical approval was obtained jointly from the University of Sydney Human Research Ethics Committee (project 2014/361) and the Aboriginal Health and Medical Research Council of New South Wales (project 1044/14). Results will be disseminated via the usual scientific forums, including peer-reviewed publications and presentations at international conferences following presentation to, discussion with and approval by participating primary healthcare service staff and community.Trial registration numberACTRN12614000705684.