bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site
Authors: Koel Björn F. , van der Vliet Stefan , Burke David F. , Bestebroer Theo M. , Bharoto Eny E. , Yasa I. Wayan W. , Herliana Inna , Laksono Brigitta M. , Xu Kemin , Skepner Eugene , Russell Colin A. , Rimmelzwaan Guus F. , Perez Daniel R. , Osterhaus Albert D. M. E. , Smith Derek J. , Prajitno Teguh Y. , Fouchier Ron A. M. 
Published: June 2014

ABSTRACT
Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are genetically highly variable and have diversified into multiple phylogenetic clades over the past decade. Antigenic drift is a well-studied phenomenon for seasonal human influenza viruses, but much less is known about the antigenic evolution of HPAI H5N1 viruses that circulate in poultry. In this study, we focused on HPAI H5N1 viruses that are enzootic to Indonesia. We selected representative viruses from genetically distinct lineages that are currently circulating and determined their antigenic properties by hemagglutination inhibition assays. At least six antigenic variants have circulated between 2003, when H5N1 clade 2.1 viruses were first detected in Indonesia, and 2011. During this period, multiple antigenic variants cocirculated in the same geographic regions. Mutant viruses were constructed by site-directed mutagenesis to represent each of the circulating antigenic variants, revealing that antigenic differences between clade 2.1 viruses were due to only one or very few amino acid substitutions immediately adjacent to the receptor binding site. Antigenic variants of H5N1 virus evaded recognition by both ferret and chicken antibodies. The molecular basis for antigenic change in clade 2.1 viruses closely resembled that of seasonal human influenza viruses, indicating that the hemagglutinin of influenza viruses from different hosts and subtypes may be similarly restricted to evade antibody recognition.

IMPORTANCE
Highly pathogenic avian influenza (HPAI) H5N1 viruses are responsible for severe outbreaks in both commercial and backyard poultry, causing considerable economic losses and regular zoonotic transmissions to humans. Vaccination is used increasingly to reduce the burden of HPAI H5N1 virus in poultry. Influenza viruses can escape from recognition by antibodies induced upon vaccination or infection through genetic changes in the hemagglutinin protein. The evolutionary patterns and molecular basis of antigenic change in HPAI H5N1 viruses are poorly understood, hampering formulation of optimal vaccination strategies. We have shown here that HPAI H5N1 viruses in Indonesia diversified into multiple antigenic variants, that antigenic differences were due to one or a very few substitutions near the receptor binding site, and that the molecular basis for antigenic change was remarkably similar to that for seasonal human influenza viruses. These findings have consequences for future vaccination and surveillance considerations and contribute to the understanding of the antigenic evolution of influenza viruses.
A Histone Deacetylase Complex Mediates Biofilm Dispersal and Drug Resistance in Candida albicans
Authors: Nobile Clarissa J. , Fox Emily P. , Hartooni Nairi , Mitchell Kaitlin F. , Hnisz Denes , Andes David R. , Kuchler Karl , Johnson Alexander D. 
Published: June 2014

ABSTRACTBiofilms are resilient, surface-associated communities of cells with specialized properties (e.g., resistance to drugs and mechanical forces) that are distinct from those of suspension (planktonic) cultures. Biofilm formation by the opportunistic human fungal pathogenCandida albicansis medically relevant becauseC. albicansinfections are highly correlated with implanted medical devices, which provide efficient substrates for biofilm formation; moreover, biofilms are inherently resistant to antifungal drugs. Biofilms are also important forC. albicansto colonize diverse niches of the human host. Here, we describe four core members of a conserved histone deacetylase complex inC. albicans(Set3, Hos2, Snt1, and Sif2) and explore the effects of their mutation on biofilm formation. We find that these histone deacetylase complex members are needed for proper biofilm formation, including dispersal of cells from biofilms and multifactorial drug resistance. Our results underscore the importance of the physical properties of biofilms in contributing to drug resistance and dispersal and lay a foundation for new strategies to target biofilm dispersal as a potential antifungal intervention.IMPORTANCEThrough the formation of biofilms—surface-associated communities of cells—microorganisms can establish infections, become drug resistant, and evade the host immune system. Here we investigate how four core members of a conserved histone deacetylase complex mediate biofilm formation byCandida albicans, the major fungal pathogen of humans. We show that this histone deacetylase complex is required for biofilm dispersal, a process through which cells leave the biofilm to establish new infections. We also show that the deacetylase complex mediates biofilm drug resistance. This work provides new insight into how the physical properties of biofilms affect dispersal and drug resistance and suggests new potential antifungal strategies that could be effective against biofilms.
Incidence, prevalence and outcomes of rheumatic heart disease in South Africa: a systematic review protocol
Authors: Zühlke Liesl , Watkins David , Engel Mark E 
Published: June 2014

BackgroundRheumatic heart disease (RHD) is the principal cause of acquired heart disease affecting people living largely in poverty and deprived conditions. Sub-Saharan Africa was long thought to be the hotspot of the disease but recent reports suggest that this is no longer the case. South Africa is the leading economic force within this region yet contends with continued extreme income disparities. It is of interest to ascertain whether the strides that have been made in healthcare since the democratic transition in South Africa have translated into decreased RHD burden. We therefore propose to review the current best estimates of incidence of newly diagnosed RHD and prevalence of existing RHD within the past two decades. We also propose to characterise the fatal and non-fatal outcomes of RHD and identify any trends in this period.Methods and designWe plan to search electronic databases and reference lists of relevant articles published from April 1994 to April 2014. Studies will be included if they estimated one of the following epidemiological measures: incidence, prevalence, remission rate, relative risk of mortality or cause-specific mortality. For studies deemed eligible for inclusion, we will assess overall study quality, reliability and risk of bias using design-specific criteria. We will extract data using a standardised form and perform descriptive and quantitative analysis to assess RHD prevalence, mortality and morbidity. This review protocol is registered in the PROSPERO International Prospective Register of systematic reviews, registration number CRD42014007072.DisseminationOur planned review will provide healthcare providers, public health officials and policymakers with pooled contemporary data regarding RHD, in particular regarding the effect the new political dispensation has had on the burden of this preventable disease within South Africa. In addition, these important country-specific data could influence policy decisions regarding prevention, management and control of RHD.
Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of long-term randomised controlled trials
Authors: Esposito Katherine , Chiodini Paolo , Maiorino Maria Ida , Bellastella Giuseppe , Capuano Annalisa , Giugliano Dario 
Published: June 2014

ObjectivesTo evaluate glycaemic durability with dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes.DesignA systematic review and meta-analysis of long-term randomised trials of DPP-4 inhibitors on haemoglobin A1c (HbA1c) was conducted. Electronic searches were carried out on the following databases: MEDLINE, EMBASE, Scopus and Web of Knowledge to December 2013. Searches were supplemented by a review of trial registries and references from identified trials. Trials were included if they lasted at least 76 weeks, and had intermediate and final assessments of HbA1c. Citations and full-text articles were screened by two reviewers. A random effect model was used to pool data.ParticipantsAdults with type 2 diabetes.InterventionsAny DPP-4 inhibitor (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin).Outcome measuresThe difference between final and intermediate HbA1c assessment was the primary outcome.ResultsWe screened 461 citations and reviewed 12 articles reporting 12 trials in 14 829 participants. All trials were of 76 weeks duration at least. The difference in HbA1c changes between final and intermediate points averaged 0.22% (95% CI 0.15% to 0.29%), with high heterogeneity (I2=91%, p<0.0001). Estimates of differences were not affected by the analysis of six extension trials (0.24%, 0.02 to 0.46), or five trials in which a DPP-4 inhibitor was added to metformin (0.24%, 0.16 to 0.32).ConclusionsThere is evidence that the effect of DPP-4 inhibitors on HbA1c in type 2 diabetes significantly declines during the second year of treatment. Future research should focus on the characteristics of patients that benefit most from DPP-4 inhibitors in terms of glycaemic durability.
The association between objectively measured sitting and standing with body composition: a pilot study using MRI
Authors: Smith L , Thomas E L , Bell J D , Hamer M 
Published: June 2014

ObjectiveTo investigate the association between objectively measured sitting and standing, using a postural allocation technique, with MRI-assessed body composition.DesignThe present study was a cross-sectional pilot study.SettingParticipants were examined at one centre located in London, UK.ParticipantsNormal weight Caucasian women (30.9±6.1 years; body mass index (BMI), 22.9±3.4 kg/m2) with desk-bound occupations were recruited to minimise variability in body composition outcomes. A convenience sample of 12 women was recruited in January 2014 from University College London.Outcome measuresFor each participant a number of body composition variables were attained from a single whole-body MRI session. Main outcome variables included: total and liver adiposity, visceral/subcutaneous fat ratio and BMI. Main exposure variables included: average sitting time, standing:sitting ratio and step count. Pearson correlations were carried out to examine associations between different activity categories and body composition variables.ResultsThere were significant correlations between average daily sitting and liver adiposity and visceral/subcutaneous abdominal fat ratio (r=0.66 and 0.64, respectively); standing:sitting ratio was moderately correlated with liver adiposity and visceral/subcutaneous abdominal fat ratio (r=−0.53 and −0.45); average daily step count was moderately correlated with liver adiposity, total adiposity and visceral/subcutaneous abdominal fat ratio (r=−0.45, −0.46 and −0.51, respectively).ConclusionsThis pilot study has provided preliminary evidence of relationships between objectively measured sitting and standing and precise measures of body composition.
Factors influencing unspecified chest pain admission rates in England
Authors: Bidmead Tom , Goodacre Steve , Maheswaran Ravi , O'Cathain Alicia 
Published: June 2014

BackgroundUnspecified chest pain is an important and potentially avoidable cause of emergency hospital admission. We aimed to examine inter-hospital variation in admission rates with unspecified chest pain and identify population characteristics, services and technologies that might explain this variation.MethodsWe used Hospital Episodes Statistics data from 152 acute trusts in England to calculate a direct standardised annual admission rate per 100 000 population for each trust. Regression analysis was used to identify factors explaining variation, first, using routinely available data relating to the hospital catchment area and service and then using responses to a survey of emergency department (ED) management.ResultsThe best predictors of admission rate using routine data were total beds per 1000 population (p=0.001), rapid access chest pain clinic (RACPC) attendances per year (p<0.001) and percentage of households in poverty (p=0.01). Including data from 105/142 (74%) survey responses, the best predictors of admission rate were total beds (p<0.001), RACPC attendances (p=0.001), mean ED waiting time (p=0.049) and percentage of households in poverty (p<0.001). All associations were positive (higher variable predicts higher rate) except ED waiting time. We found no significant associations between factors relating to acute chest pain management and admission rate.ConclusionsHospitals with higher admission rates for unspecified chest pain have greater bed provision, more RACPC attendances and serve populations with a higher percentage of households in poverty. These findings may be explained by services responding to demand in populations with greater need. We found no evidence that chest pain management influenced admission rates.
ATV riding and helmet use among youth aged 12–17 years, USA, 2011: results from the YouthStyles survey
Authors: Shults Ruth A , West Bethany A 
Published: June 2014

BackgroundNational estimates of all-terrain vehicle (ATV) riding patterns among youth in the USA are lacking.MethodsWe analysed the 2011 YouthStyles survey to estimate the proportion of 12–17 year olds in the USA who had ridden an ATV at least once during the past 12 months and summarise their patterns of helmet use.ResultsOf the 831 youth respondents, an estimated 25% reported riding an ATV at least once during the past year. The proportion of youth living outside of a Metropolitan Statistical Area who reported riding an ATV was twice that of those living inside of a Metropolitan Statistical Area. Males and females reported similar proportions of riding at least once during the past year, but among riders, the proportion of males who rode ≥6 times was triple that of females. Only 45% of riders reported always wearing a helmet, and 25% reported never wearing a helmet. The most frequent riders had the lowest consistent helmet use, with 8 of 10 youth who rode ≥6 times during the past year not always wearing a helmet.ConclusionsATV riding appears to remain popular among youth in the USA, particularly in rural areas, and consistent helmet use while riding is low. A more thorough understanding of gender differences in ATV riding patterns among youth and perceived risks and benefits of both safe and unsafe riding practices might help inform future ATV injury prevention efforts.
Conventional and novel peripheral blood iron markers compared against bone marrow in Malawian children
Authors: Jonker Femkje A M , Boele van Hensbroek Michael , Leenstra Tjalling , Vet Raymond J W M , Brabin Bernard J , Maseko Nelson , Gushu Montfort B , Emana Mercy , Kraaijenhagen Rob , Tjalsma Harold , Swinkels Dorine W , Calis Job C J 
Published: June 2014

AimIron deficiency is an important child health problem. Its diagnosis in areas of high infection exposure remains complicated as inflammation may interfere with the accuracy of peripheral iron markers. With this study, we aimed to validate the conventional iron markers and two novel iron markers, hepcidin and Red blood cell Size Factor (RSf), against the reference standard of iron status, bone marrow iron, in children living in an infectious setting.MethodsWe compared ferritin, soluble transferrin receptor, Soluble Transferrin Log-Ferritin Index (sTfR-F), mean cellular volume, mean cellular haemoglobin concentration, hepcidin and RSf, against bone marrow iron in 87 healthy Malawian children (6–66 months) scheduled for elective surgery.ResultsOf all children, 44.8% had depleted bone marrow iron stores. Using optimised cut-offs, ferritin (<18 µg/L) and sTfR-F (>1.85) best predicted depleted iron stores with a sensitivity/specificity of 73.7%/77.1% and 72.5%/75.0%, respectively. Hepcidin (<1.4 nmol/L) was a moderate sensitive marker (73.0%) although specificity was 54.2%; RSf poorly predicted depleted iron stores.ConclusionsWe provide the first bone marrow-validated data on peripheral iron markers in African children, and showed ferritin and sTfR-F best predicted iron status. Using appropriately defined cut-offs, these indicators can be applied in surveillance and research. As their accuracy is limited for clinical purposes, more reliable iron biomarkers are still required in African children.
Combined sputum hypermethylation and eNose analysis for lung cancer diagnosis
Authors: Hubers A Jasmijn , Brinkman Paul , Boksem Remco J , Rhodius Robert J , Witte Birgit I , Zwinderman Aeilko H , Heideman Daniëlle A M , Duin Sylvia , Koning Remco , Steenbergen Renske D M , Snijders Peter J F , Smit Egbert F , Sterk Peter J , Thunnissen Erik 
Published: June 2014

AimsThe aim of this study is to explore DNA hypermethylation analysis in sputum and exhaled breath analysis for their complementary, non-invasive diagnostic capacity in lung cancer.MethodsSputum samples and exhaled breath were prospectively collected from 20 lung cancer patients and 31 COPD controls (Set 1). An additional 18 lung cancer patients and 8 controls only collected exhaled breath as validation set (Set 2). DNA hypermethylation of biomarkersRASSF1A, cytoglobin,APC,FAM19A4,PHACTR3,3OST2andPRDM14was considered, and breathprints from exhaled breath samples were created using an electronic nose (eNose).ResultsBoth DNA hypermethylation markers in sputum and eNose were independently able to distinguish lung cancer patients from controls. The combination ofRASSF1Aand3OST2hypermethylation had a sensitivity of 85% with a specificity of 74%. eNose had a sensitivity of 80% with a specificity of 48%. Sensitivity for lung cancer diagnosis increased to 100%, whenRASSF1Ahypermethylation was combined with eNose, with specificity of 42%. Both methods showed to be complementary to each other (p≤0.011). eNose results were reproducible in Set 2.ConclusionsWhen used in concert,RASSF1Ahypermethylation in sputum and exhaled breath analysis are complementary for lung cancer diagnosis, with 100% sensitivity in this series. This finding should be further validated.
Does waist circumference uncorrelated with BMI add valuable information?
Authors: Ngueta Gerard , Laouan-Sidi Elhadji A , Lucas Michel 
Published: June 2014

BackgroundEstimation of relative contribution of Body Mass Index (BMI) and waist circumference (WC) on health outcomes requires a regression model that includes both obesity metrics. But, multicollinearity could yield biased estimates.MethodsTo address the multicollinearity issue between BMI and WC, we used the residual model approach. The standard WC (Y-axis) was regressed on the BMI (X-axis) to obtain residual WC. Data from two adult population surveys (Nunavik Inuit and James Bay Cree) were analysed to evaluate relative effect of BMI and WC on four cardiometabolic risk factors: insulin, triglycerides, systolic blood pressure and high-density lipoprotein levels.ResultsIn multivariate models, standard WC and BMI were significantly associated with cardiometabolic outcomes. Residual WC was not linked with any outcomes. The BMI effect was weakened by including standard WC in the model, but its effect remained unchanged if residual WC was considered.ConclusionsThe strong correlation between standard WC and BMI does not allow assessment of their relative contributions to health in the same model without a risk of making erroneous estimations. By contrast with BMI, fat distribution (residual WC) does not add valuable information to a model that already contains overall adiposity (BMI) in Inuit and Cree.
Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up
Authors: Schoindre Yoland , Jallouli Moez , Tanguy Marie-Laure , Ghillani Pascale , Galicier Lionel , Aumaître Olivier , Francès Camille , Le Guern Véronique , Lioté Frédéric , Smail Amar , Limal Nicolas , Perard Laurent , Desmurs-Clavel Hélène , Thi Huong Du Le , Asli Bouchra , Kahn Jean-Emmanuel , Sailler Laurent , Ackermann Félix , Papo Thomas , Sacré Karim , Fain Olivier , Stirnemann Jérôme , Cacoub Patrice , Leroux Gaëlle , Cohen-Bittan Judith , Hulot Jean-Sébastien , Lechat Philippe , Musset Lucile , Piette Jean-Charles , Amoura Zahir , Souberbielle Jean-Claude , Costedoat-Chalumeau Nathalie 
Published: June 2014

ObjectivesGrowing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups.MethodsSerum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov numberNCT00413361).ResultsThe mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22).ConclusionsWe found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.
Ornamental stone in the history of St Petersburg architecture
Authors: Bulakh A. G. 
Published: June 2014

Abstract
St Petersburg was founded in 1703. Between 1703 and the 1830s, buildings of baroque and classicism styles were faced with stones from the NW part of the Russian Empire. In 1840s–1910s, many new types of ornamental stones from different European countries were added to the faces of buildings of so-called eclecticism and modernism styles. The map of deposits shows 32 main sources of stone. This report gives a chronological review of the use of natural stone in the architecture of St Petersburg, Russia, in 1703–2009. The map of deposits and a list of rock types are given.