bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Insights into the Human Metapneumovirus Glycoprotein Ectodomain
Authors: Leyrat Cedric , Paesen Guido C. , Charleston James , Renner Max , Grimes Jonathan M. 
Published: July 2014

ABSTRACT
Human metapneumovirus is a major cause of respiratory tract infections worldwide. Previous reports have shown that the viral attachment glycoprotein (G) modulates innate and adaptive immune responses, leading to incomplete immunity and promoting reinfection. Using bioinformatics analyses, static light scattering, and small-angle X-ray scattering, we show that the extracellular region of G behaves as a heavily glycosylated, intrinsically disordered polymer. We discuss potential implications of these findings for the modulation of immune responses by G.
Phosphorylation of Hepatitis C Virus RNA Polymerases Ser29 and Ser42 by Protein Kinase C-Related Kinase 2 Regulates Viral RNA Replication
Authors: Han Song-Hee , Kim Seong-Jun , Kim Eun-Jung , Kim Tae-Eun , Moon Jae-Su , Kim Geon-Woo , Lee Seung-Hoon , Cho Kun , Yoo Jong Shin , Son Woo Sung , Rhee Jin-Kyu , Han Seung Hyun , Oh Jong-Won 
Published: July 2014

ABSTRACT

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase (RdRp), is the key enzyme for HCV RNA replication. We previously showed that HCV RdRp is phosphorylated by protein kinase C-related kinase 2 (PRK2). In the present study, we used biochemical and reverse-genetics approaches to demonstrate that HCV NS5B phosphorylation is crucial for viral RNA replication in cell culture. Two-dimensional phosphoamino acid analysis revealed that PRK2 phosphorylates NS5B exclusively at its serine residues
in vitro
and
in vivo
. Using
in vitro
kinase assays and mass spectrometry, we identified two phosphorylation sites, Ser29 and Ser42, in the Δ1 finger loop region that interacts with the thumb subdomain of NS5B. Colony-forming assays using drug-selectable HCV subgenomic RNA replicons revealed that preventing phosphorylation by Ala substitution at either Ser29 or Ser42 impairs HCV RNA replication. Furthermore, reverse-genetics studies using HCV infectious clones encoding phosphorylation-defective NS5B confirmed the crucial role of these PRK2 phosphorylation sites in viral RNA replication. Molecular-modeling studies predicted that the phosphorylation of NS5B stabilizes the interactions between its Δ1 loop and thumb subdomain, which are required for the formation of the closed conformation of NS5B known to be important for
de novo
RNA synthesis. Collectively, our results provide evidence that HCV NS5B phosphorylation has a positive regulatory role in HCV RNA replication.

IMPORTANCE
While the role of RNA-dependent RNA polymerases (RdRps) in viral RNA replication is clear, little is known about their functional regulation by phosphorylation. In this study, we addressed several important questions about the function and structure of phosphorylated hepatitis C virus (HCV) nonstructural protein 5B (NS5B). Reverse-genetics studies with HCV replicons encoding phosphorylation-defective NS5B mutants and analysis of their RdRp activities revealed previously unidentified NS5B protein features related to HCV replication and NS5B phosphorylation. These attributes most likely reflect potential structural changes induced by phosphorylation in the Δ1 finger loop region of NS5B with two identified phosphate acceptor sites, Ser29 and Ser42, which may transiently affect the closed conformation of NS5B. Elucidating the effects of dynamic changes in NS5B phosphorylation status during viral replication and their impacts on RNA synthesis will improve our understanding of the molecular mechanisms of NS5B phosphorylation-mediated regulation of HCV replication.
Propionibacterium
-Produced Coproporphyrin III Induces Staphylococcus aureus Aggregation and Biofilm Formation
Authors: Wollenberg Michael S. , Claesen Jan , Escapa Isabel F. , Aldridge Kelly L. , Fischbach Michael A. , Lemon Katherine P. 
Published: July 2014

ABSTRACT

The majority of bacteria detected in the nostril microbiota of most healthy adults belong to three genera:
Propionibacterium
,
Corynebacterium
, and
Staphylococcus
. Among these staphylococci is the medically important bacterium
Staphylococcus aureus
. Almost nothing is known about interspecies interactions among bacteria in the nostrils. We observed that crude extracts of cell-free conditioned medium from
Propionibacterium
spp. induce
S. aureus
aggregation in culture. Bioassay-guided fractionation implicated coproporphyrin III (CIII), the most abundant extracellular porphyrin produced by human-associated
Propionibacterium
spp., as a cause of
S. aureus
aggregation. This aggregation response depended on the CIII dose and occurred during early stationary-phase growth, and a low pH (~4 to 6) was necessary but was not sufficient for its induction. Additionally, CIII induced plasma-independent
S. aureus
biofilm development on an abiotic surface in multiple
S. aureus
strains. In strain UAMS-1, CIII stimulation of biofilm depended on
sarA
, a key biofilm regulator. This study is one of the first demonstrations of a small-molecule-mediated interaction among medically relevant members of the nostril microbiota and the first description of a role for CIII in bacterial interspecies interactions. Our results indicate that CIII may be an important mediator of
S. aureus
aggregation and/or biofilm formation in the nostril or other sites inhabited by
Propionibacterium
spp. and
S. aureus
.

IMPORTANCE
Very little is known about interspecies interactions among the bacteria that inhabit the adult nostril, including
Staphylococcus aureus
, a potential pathogen that colonizes about a quarter of adults. We demonstrated that coproporphyrin III (CIII), a diffusible small molecule excreted by nostril- and skin-associated
Propionibacterium
spp., induces
S. aureus
aggregation in a manner dependent on dose, growth phase, and pH. CIII also induces
S. aureus
to form a plasma-independent surface-attached biofilm. This report is the first description of a role for CIII in bacterial interspecies interactions at any human body site and a novel demonstration that nostril microbiota physiology is influenced by small-molecule-mediated interactions.
Detection of the Middle East Respiratory Syndrome Coronavirus Genome in an Air Sample Originating from a Camel Barn Owned by an Infected Patient
Authors: Azhar Esam I. , Hashem Anwar M. , El-Kafrawy Sherif A. , Sohrab Sayed Sartaj , Aburizaiza Asad S. , Farraj Suha A. , Hassan Ahmed M. , Al-Saeed Muneera S. , Jamjoom Ghazi A. , Madani Tariq A. 
Published: July 2014

ABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV.

IMPORTANCE
This work clearly highlights the importance of continuous surveillance and infection control measures to control the global public threat of MERS-CoV. While current MERS-CoV transmission appears to be limited, we advise minimal contact with camels, especially for immunocompromised individuals, and the use of appropriate health, safety, and infection prevention and control measures when dealing with infected patients. Also, detailed clinical histories of any MERS-CoV cases with epidemiological and laboratory investigations carried out for any animal exposure must be considered to identify any animal source.
Health information technology interventions enhance care completion, engagement in HIV care and treatment, and viral suppression among HIV-infected patients in publicly funded settings
Authors: Shade Starley B , Steward Wayne T , Koester Kimberly A , Chakravarty Deepalika , Myers Janet J 
Published: July 2014

Abstract
Background The National HIV/AIDS Strategy (NHAS) emphasizes the use of technology to facilitate coordination of comprehensive care for people with HIV. We examined the effect of six health information technology (HIT) interventions in a Ryan White-funded Special Projects of National Significance (SPNS) on care completion services, engagement in HIV care, and viral suppression.
Methods Interventions included use of surveillance data to identify out-of-care individuals, extending access to electronic health records to support service providers, use of electronic laboratory ordering and prescribing, and development of a patient portal. Data from a sample of electronic patient records from each site were analyzed to assess changes in utilization of comprehensive care (prevention screening, support service utilization), engagement in primary HIV medical care (receipt of services and use of antiretroviral therapy), and viral suppression. We used weighted generalized estimating equations to estimate outcomes while accounting for the unequal contribution of data and differences in the distribution of patient characteristics across sites and over time.
Results We observed statistically significant changes in the desired direction in comprehensive care utilization and engagement in primary care outcomes targeted by each site. Five of six sites experienced statistically significant increases in viral suppression.
Discussion These results provide additional support for the use of HIT as a valuable tool for achieving the NHAS goal of providing comprehensive care for all people living with HIV. HIT has the potential to increase utilization of services, improve health outcomes for people with HIV, and reduce community viral load and subsequent transmission of HIV.
A randomised controlled trial for the evaluation of risk for type 2 diabetes in hypertensive patients receiving thiazide diuretics: Diuretics In the Management of Essential hypertension (DIME) study
Authors: Ueda Shinichiro , Morimoto Takeshi , Ando Shin-ichi , Takishita Shu-ichi , Kawano Yuhei , Shimamoto Kazuaki , Ogihara Toshio , Saruta Takao ,   for the DIME Investigators
Published: July 2014

ObjectivesThiazide diuretics are one of the first choice antihypertensives but not optimally utilised because of concerns regarding their adverse effects on glucose metabolism. The Diuretics In the Management of Essential hypertension (DIME) study was designed, for the first time, to assess the risk for type 2 diabetes mellitus in patients with essential hypertension during antihypertensive treatment with low-dose thiazide diuretics compared to those not treated with diuretics.DesignMulticentre, unblinded, pragmatic, randomised, controlled trial with blinded assessment of end points and intention-to-treat analysis that was started in 2004 and finished in 2012.SettingHypertension clinics at 106 sites in Japan, including general practitioners’ offices and teaching hospitals.ParticipantsNon-diabetic patients with essential hypertension.InterventionsAntihypertensive treatment with low-dose thiazide diuretics at 12.5 mg/day of hydrochlorothiazide or equivalent (Diuretics group) or that without thiazide diuretics (No-diuretics group).Main outcomeThe primary outcome was new onset of type 2 diabetes diagnosed according to WHO criteria and the criteria of Japanese Society of Diabetes.Results1130 patients were allocated to Diuretics (n=544) or No-diuretics group (n=586). Complete end point information was collected for 1049 participants after a median follow-up of 4.4 years. Diabetes developed in 25 (4.6%) participants in the Diuretics group, as compared with 29 (4.9%) in the No-diuretics group (HR 0.93; 95% CI 0.55 to 1.58; p=0.800).ConclusionsAntihypertensive treatment with thiazide diuretics at low doses may not be associated with an increased risk for new onset of type 2 diabetes. This result might suggest safety of use of low doses of thiazide diuretics.Trial registration numberClinicalTrials.govNCT00131846.
Comparison of two anterior fusion methods in two-level cervical spondylosis myelopathy: a meta-analysis
Authors: Huang Zhe-Yu , Wu Ai-Min , Li Qing-Long , Lei Tao , Wang Kang-Yi , Xu Hua-Zi , Ni Wen-Fei 
Published: July 2014

ObjectiveThe aim of this study was to evaluate the efficacy and safety of anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) for treating two-adjacent-level cervical spondylosis myelopathy (CSM).DesignA meta-analysis of the two anterior fusion methods was conducted. The electronic databases of PubMed, the Cochrane Central Register of Controlled Trials, ScienceDirect, CNKI, WANFANG DATA and CQVIP were searched. Quality assessment of the included studies was evaluated using the Cochrane Risk of Bias Tool and the Methodological Index for Non-Randomised Studies criteria. Pooled risk ratios of dichotomous outcomes and standardised mean differences (SMDs) of continuous outcomes were generated. Using the χ2and I2tests, the statistical heterogeneity was assessed. Subgroup and sensitivity analyses were also performed.ParticipantsNine eligible trials with a total of 631 patients and a male-to-female ratio of 1.38:1 were included in this meta-analysis.Inclusion criteriaRandomised controlled trials (RCTs) and non-randomised controlled trials that adopted ACCF and ACDF to treat two-adjacent-level CSM were included.ResultsNo significant differences were identified between the two groups regarding hospital stay, the Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) scores for neck and arm pain, total cervical range of motion (ROM), fusion ROM, fusion rate, adjacent-level ossification and complications, while ACDF had significantly less bleeding (SMD=1.14, 95% CI (0.74 to 1.53)); a shorter operation time (SMD=1.13, 95% CI (0.82 to 1.45)); greater cervical lordosis, total cervical (SMD=−2.95, 95% CI (−4.79 to −1.12)) and fused segment (SMD=−2.24, 95% CI (−3.31 to −1.17)); higher segmental height (SMD=−0.68, 95% CI (−1.03 to −0.34)) and less graft subsidence (SMD=0.40, 95% CI (0.06 to 0.75)) compared to ACCF.ConclusionsThe results suggested that ACDF has more advantages compared to ACCF. However, additional high-quality RCTs and a longer follow-up duration are needed.
Increased homocysteine levels in valproate-treated patients with epilepsy: a meta-analysis
Authors: Ni Guanzhong , Qin Jiaming , Fang Ziyan , Chen Yishu , Chen Ziyi , Zhou Jueqian , Zhou Liemin 
Published: July 2014

ObjectiveTo determine whether valproate (VPA) monotherapy influences homocysteine metabolism in patients with epilepsy.DesignSystematic review and meta-analysis.Data sourcesWe searched all articles in English through PubMed, Web of Science and EMBASE published up to August 2013 concerning the homocysteine levels in VPA monotherapeutic patients with epilepsy.ParticipantsVPA-treated patients with epilepsy (n=266) and matched healthy controls (n=489).Outcome measuresHeterogeneity between studies was assessed using I2statistics. Pooled standardised mean difference (SMD) and 95% CIs were calculated using a random effect model.ResultsA total of eight eligible studies were enrolled in our meta-analysis. We compared the plasma levels of homocysteine in VPA-treated patients with epilepsy and healthy controls. There was significant heterogeneity in the estimates according to the I2test (I2=65.6%, p=0.005). Plasma homocysteine levels in VPA-treated patients with epilepsy were significantly higher than in healthy controls under a random effect model. (SMD, 0.62; 95% CI 0.32 to 0.92). Further subgroup analyses suggested that no signiﬁcant differences were present when grouped by ethnicity and age, but the risk of heterogeneity in the West Asian group (I2=47.4%, p=0.107) was diminished when compared with that of the overall group (I2=65.6%, p=0.005).ConclusionsOur meta-analysis indicates that VPA monotherapy is associated with the increase in plasma homocysteine levels in patients with epilepsy. Whether this association is influenced by ethnicity needs further research.
Estimating smoking prevalence in general practice using data from the Quality and Outcomes Framework (QOF)
Authors: Honeyford Kate , Baker Richard , Bankart M John G , Jones David R 
Published: July 2014

ObjectivesTo determine to what extent underlying data published as part of Quality and Outcomes Framework (QOF) can be used to estimate smoking prevalence within practice populations and local areas and to explore the usefulness of these estimates.DesignCross-sectional, observational study of QOF smoking data. Smoking prevalence in general practice populations and among patients with chronic conditions was estimated by simple manipulation of QOF indicator data. Agreement between estimates from the integrated household survey (IHS) and aggregated QOF-based estimates was calculated. The impact of including smoking estimates in negative binomial regression models of counts of premature coronary heart disease (CHD) deaths was assessed.SettingPrimary care in the East Midlands.ParticipantsAll general practices in the area of study were eligible for inclusion (230). 14 practices were excluded due to incomplete QOF data for the period of study (2006/2007–2012/2013). One practice was excluded as it served a restricted practice list.MeasurementsEstimates of smoking prevalence in general practice populations and among patients with chronic conditions.ResultsMedian smoking prevalence in the practice populations for 2012/2013 was 19.2% (range 5.8–43.0%). There was good agreement (mean difference: 0.39%; 95% limits of agreement (−3.77, 4.55)) between IHS estimates for local authority districts and aggregated QOF register estimates. Smoking prevalence estimates in those with chronic conditions were lower than for the general population (mean difference −3.05%), but strongly correlated (Rp=0.74, p<0.0001). An important positive association between premature CHD mortality and smoking prevalence was shown when smoking prevalence was added to other population and service characteristics.ConclusionsPublished QOF data allow useful estimation of smoking prevalence within practice populations and in those with chronic conditions; the latter estimates may sometimes be useful in place of the former. It may also provide useful estimates of smoking prevalence in local areas by aggregating practice based data.
Psychosocial and behavioural factors in the explanation of socioeconomic inequalities in adolescent health: a multilevel analysis in 28 European and North American countries
Authors: Moor Irene , Rathmann Katharina , Stronks Karien , Levin Kate , Spallek Jacob , Richter Matthias 
Published: July 2014

BackgroundThe relative contribution of different pathways leading to health inequalities in adolescence was rarely investigated, especially in a cross-national perspective. The aim of the study is to analyse the contribution of psychosocial and behavioural factors in the explanation of inequalities in adolescent self-rated health (SRH) by family wealth in 28 countries.MethodsThis study was based on the international WHO ‘Health Behaviour in School-aged Children’ (HBSC) study carried out in 2005/2006. The total sample included 117 460 adolescents aged 11–15 in 28 European and North American countries. Socioeconomic position was measured using the Family Affluence Scale (FAS). Multilevel logistic regression models were conducted to analyse the direct (independent) and indirect contribution of psychosocial and behavioural factors on SRH.ResultsAcross all countries, adolescents from low affluent families had a higher risk of reporting fair/poor SRH (OR1.76, CI 1.69 to 1.84). Separate adjustments for psychosocial and behavioural factors reduced the OR of students with low family affluence by 39% (psychosocial) and 22% (behavioural). Together, both approaches explained about 50–60% of inequalities by family affluence in adolescent SRH. Separate analyses showed that relationship to father and academic achievement (psychosocial factors) as well as physical activity and consumption of fruits/vegetables (behavioural factors) were the most important factors in explaining inequalities in SRH.ConclusionsMore than half of the inequalities by family affluence in adolescent SRH were explained by an unequal distribution of psychosocial and behavioural factors. Combining both approaches showed that the contribution of psychosocial factors was higher due to their direct (independent) and indirect impact through behavioural factors.
Aneurysm permeability following coil embolization: packing density and coil distribution
Authors: Chueh Ju-Yu , Vedantham Srinivasan , Wakhloo Ajay K , Carniato Sarena L , Puri Ajit S , Bzura Conrad , Coffin Spencer , Bogdanov Alexei A , Gounis Matthew J 
Published: July 2014

BackgroundRates of durable aneurysm occlusion following coil embolization vary widely, and a better understanding of coil mass mechanics is desired. The goal of this study is to evaluate the impact of packing density and coil uniformity on aneurysm permeability.MethodsAneurysm models were coiled using either Guglielmi detachable coils or Target coils. The permeability was assessed by taking the ratio of microspheres passing through the coil mass to those in the working fluid. Aneurysms containing coil masses were sectioned for image analysis to determine surface area fraction and coil uniformity.ResultsAll aneurysms were coiled to a packing density of at least 27%. Packing density, surface area fraction of the dome and neck, and uniformity of the dome were significantly correlated (p<0.05). Hence, multivariate principal components-based partial least squares regression models were used to predict permeability. Similar loading vectors were obtained for packing and uniformity measures. Coil mass permeability was modeled better with the inclusion of packing and uniformity measures of the dome (r2=0.73) than with packing density alone (r2=0.45). The analysis indicates the importance of including a uniformity measure for coil distribution in the dome along with packing measures.ConclusionsA densely packed aneurysm with a high degree of coil mass uniformity will reduce permeability.
Fast Computation of Singular Oscillatory Fourier Transforms
Authors: Kang Hongchao , Shao Xinping 
Published: July 2014

We consider the problem of the numerical evaluation of singular oscillatory Fourier transforms ∫ab‍x-aαb-xβf(x)eiωxdx, whereα>-1  and  β>-1. Based on substituting the original interval of integration by the paths of steepest descent, iffis analytic in the complex regionGcontaining [a,b], the computation of integrals can be transformed into the problems of integrating two integrals on [0, ∞) with the integrand that does not oscillate and decays exponentially fast, which can be efficiently computed by using the generalized Gauss Laguerre quadrature rule. The efficiency and the validity of the method are demonstrated by both numerical experiments and theoretical results. More importantly, the presented method in this paper is also a great improvement of a Filon-type method and a Clenshaw-Curtis-Filon-type method shown in Kang and Xiang (2011) and the Chebyshev expansions method proposed in Kang et al. (2013), for computing the above integrals.