bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectivity and Transmissibility of Avian H9N2 Influenza Viruses in Pigs
Authors: Wang Jia , Wu Maocai , Hong Wenshan , Fan Xiaohui , Chen Rirong , Zheng Zuoyi , Zeng Yu , Huang Ren , Zhang Yu , Lam Tommy Tsan-Yuk , Smith David K. , Zhu Huachen , Guan Yi 
Published: January 2016

ABSTRACT
The H9N2 influenza viruses that are enzootic in terrestrial poultry in China pose a persistent pandemic threat to humans. To investigate whether the continuous circulation and adaptation of these viruses in terrestrial poultry increased their infectivity to pigs, we conducted a serological survey in pig herds with H9N2 viruses selected from the aquatic avian gene pool (Y439 lineage) and the enzootic terrestrial poultry viruses (G1 and Y280 lineages). We also compared the infectivity and transmissibility of these viruses in pigs. It was found that more than 15% of the pigs sampled from 2010 to 2012 in southern China were seropositive to either G1 or Y280 lineage viruses, but none of the sera were positive to the H9 viruses from the Y439 lineage. Viruses of the G1 and Y280 lineages were able to infect experimental pigs, with detectable nasal shedding of the viruses and seroconversion, whereas viruses of the Y439 lineage did not cause a productive infection in pigs. Thus, adaptation and prevalence in terrestrial poultry could lead to interspecies transmission of H9N2 viruses from birds to pigs. Although H9N2 viruses do not appear to be continuously transmissible among pigs, repeated introductions of H9 viruses to pigs naturally increase the risk of generating mammalian-adapted or reassorted variants that are potentially infectious to humans. This study highlights the importance of monitoring the activity of H9N2 viruses in terrestrial poultry and pigs.

IMPORTANCE
H9N2 subtype of influenza viruses has repeatedly been introduced into mammalian hosts, including humans and pigs, so awareness of their activity and evolution is important for influenza pandemic preparedness. However, since H9N2 viruses usually cause mild or even asymptomatic infections in mammalian hosts, they may be overlooked in influenza surveillance. Here, we found that the H9N2 viruses established in terrestrial poultry had higher infectivity in pigs than those from aquatic birds, which suggests that adaptation of the H9N2 viruses in terrestrial poultry might have increased the infectivity of the virus to mammals. Therefore, monitoring the prevalence and evolution of H9 viruses prevalent in terrestrial birds and conducting risk assessment of their threat to mammals are critical for evaluating the pandemic potential of this virus.
Involvement of the N-Terminal Deubiquitinating Protease Domain of Human Cytomegalovirus UL48 Tegument Protein in Autoubiquitination, Virion Stability, and Virus Entry
Authors: Kim Young-Eui , Oh Se Eun , Kwon Ki Mun , Lee Chan Hee , Ahn Jin-Hyun 
Published: January 2016

ABSTRACT

Human cytomegalovirus (HCMV) protein pUL48 is closely associated with the capsid and has a deubiquitinating protease (DUB) activity in its N-terminal region. Although this DUB activity moderately increases virus replication in cultured fibroblast cells, the requirements of the N-terminal region of pUL48 in the viral replication cycle are not fully understood. In this study, we characterized the recombinant viruses encoding UL48(ΔDUB/NLS), which lacks the DUB domain and the adjacent nuclear localization signal (NLS), UL48(ΔDUB), which lacks only the DUB, and UL48(Δ360–1200), which lacks the internal region (amino acids 360 to 1200) downstream of the DUB/NLS. While ΔDUB/NLS and Δ360–1200 mutant viruses did not grow in fibroblasts, the ΔDUB virus replicated to titers 100-fold lower than those for wild-type virus and showed substantially reduced viral gene expression at low multiplicities of infection. The DUB domain contained ubiquitination sites, and DUB activity reduced its own proteasomal degradation in
trans
. Deletion of the DUB domain did not affect the nuclear and cytoplasmic localization of pUL48, whereas the internal region (360–1200) was necessary for cytoplasmic distribution. In coimmunoprecipitation assays, pUL48 interacted with three tegument proteins (pUL47, pUL45, and pUL88) and two capsid proteins (pUL77 and pUL85) but the DUB domain contributed to only pUL85 binding. Furthermore, we found that the ΔDUB virus showed reduced virion stability and less efficiently delivered its genome into the cell than the wild-type virus. Collectively, our results demonstrate that the N-terminal DUB domain of pUL48 contributes to efficient viral growth by regulating its own stability and promoting virion stabilization and virus entry.

IMPORTANCE
HCMV pUL48 and its herpesvirus homologs play key roles in virus entry, regulation of immune signaling pathways, and virion assembly. The N terminus of pUL48 contains the DUB domain, which is well conserved among all herpesviruses. Although studies using the active-site mutant viruses revealed that the DUB activity promotes viral growth, the exact role of this region in the viral life cycle is not fully understood. In this study, using the mutant virus lacking the entire DUB domain, we demonstrate that the DUB domain of pUL48 contributes to viral growth by regulating its own stability via autodeubiquitination and promoting virion stability and virus entry. This report is the first to demonstrate the characteristics of the mutant virus with the entire DUB domain deleted, which, along with information on the functions of this region, is useful in dissecting the functions associated with pUL48.
Influenza A Viruses Expressing Intra- or Intergroup Chimeric Hemagglutinins
Authors: Chen Chi-Jene , Ermler Megan E. , Tan Gene S. , Krammer Florian , Palese Peter , Hai Rong 
Published: January 2016

ABSTRACT
A panel of influenza A viruses expressing chimeric hemagglutinins (cHA) with intragroup or intergroup head/stalk combinations was generated. Viruses were characterized for growth kinetics and preservation of stalk epitopes. With a few notable exceptions, cHA viruses behaved similarly to wild-type viruses and maintained stalk epitopes, which indicated their potential as vaccine candidates to induce stalk-specific antibodies.
Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop
Authors: Patil Shilpa , Kumar Rajesh , Deshpande Suprit , Samal Sweety , Shrivastava Tripti , Boliar Saikat , Bansal Manish , Chaudhary Nakul Kumar , Srikrishnan Aylur K. , Murugavel Kailapuri G. , Solomon Suniti , Simek Melissa , Koff Wayne C. , Goyal Rajat , Chakrabarti Bimal K. , Bhattacharya Jayanta 
Published: January 2016

ABSTRACT
Broadly neutralizing antibodies isolated from infected patients who are elite neutralizers have identified targets on HIV-1 envelope (Env) glycoprotein that are vulnerable to antibody neutralization; however, it is not known whether infection established by the majority of the circulating clade C strains in Indian patients elicit neutralizing antibody responses against any of the known targets. In the present study, we examined the specificity of a broad and potent cross-neutralizing plasma obtained from an Indian elite neutralizer infected with HIV-1 clade C. This plasma neutralized 53/57 (93%) HIV pseudoviruses prepared with Env from distinct HIV clades of different geographical origins. Mapping studies using gp120 core protein, single-residue knockout mutants, and chimeric viruses revealed that G37080 broadly cross-neutralizing (BCN) plasma lacks specificities to the CD4 binding site, gp41 membrane-proximal external region, N160 and N332 glycans, and R166 and K169 in the V1-V3 region and are known predominant targets for BCN antibodies. Depletion of G37080 plasma with soluble trimeric BG505-SOSIP.664 Env (but with neither monomeric gp120 nor clade C membrane-proximal external region peptides) resulted in significant reduction of virus neutralization, suggesting that G37080 BCN antibodies mainly target epitopes on cleaved trimeric Env. Further examination of autologous circulating Envs revealed the association of mutation of residues in the V1 loop that contributed to neutralization resistance. In summary, we report the identification of plasma antibodies from a clade C-infected elite neutralizer that mediate neutralization breadth via epitopes on trimeric gp120 not yet reported and confer autologous neutralization escape via mutation of residues in the V1 loop.

IMPORTANCE
A preventive vaccine to protect against HIV-1 is urgently needed. HIV-1 envelope glycoproteins are targets of neutralizing antibodies and represent a key component for immunogen design. The mapping of epitopes on viral envelopes vulnerable to immune evasion will aid in defining targets of vaccine immunogens. We identified novel conformational epitopes on the viral envelope targeted by broadly cross-neutralizing antibodies elicited in natural infection in an elite neutralizer infected with HIV-1 clade C. Our data extend our knowledge on neutralizing epitopes associated with virus escape and potentially contribute to immunogen design and antibody-based prophylactic therapy.
The influence of a school-based intervention programme regarding adherence to a healthy diet in children and adolescents from disadvantaged areas in Greece: the DIATROFI study
Authors: Kastorini Christina Maria , Lykou Anastasia , Yannakoulia Mary , Petralias Athanassios , Riza Elena , Linos Athena 
Published: January 2016

BackgroundTo evaluate the effects, via a cohort study, of a food aid and promotion of healthy nutrition programme, implemented in areas of low socioeconomic status (SES) in Greece, on students’ diet quality.MethodsFrom a total of 162 schools participating in the programme during the 2012–2013 school year, we collected 3941 individually linked questionnaires at baseline and at the end of the intervention, recording sociodemographic characteristics, lifestyle parameters and dietary habits of the students. For the assessment of diet quality, the KIDMED score was computed, along with food frequency consumption data regarding milk, fruits, vegetables and whole grain products. Pre–post intervention values were compared using non-parametric tests. Generalised estimating equations were used to explore the factors that influence changes in dietary habits.ResultsBy the end of the intervention, favourable changes were observed regarding healthy eating; KIDMED increased statistically significantly in adolescent girls (p=0.042), while the consumption frequency of all foods promoted by the intervention, namely, milk, fruits, vegetables and whole grain products, increased for children and adolescents, boys and girls (p≤0.002). Factors indicating lower SES, such as foreign country of birth, lower education level, no income source and high levels of food insecurity, were associated with lower diet quality.ConclusionsAs low SES groups tend to adopt unhealthier dietary choices, it is of the outmost importance to take action for the promotion of healthy eating, directed especially to these at risk populations. School-based nutritional programmes can be considered as an effective policy measure towards this direction.
GOVERNANCE OF INNOVATION AND GROWTH IN SME NETWORKS
Authors: BRINK TOVE 
Published: January 2016

The aim of this article is to reveal what organising of innovation and growth can be enabled in small and medium-sized enterprise (SME) networks. This is especially interesting for the governance of loosely coupled networks. The research is conducted in the Danish food industry with three food-producing firm networks. The posed hypotheses are tested in a structural equation modelling (SEM) approach with the available data of 60 SMEs.The findings show that the governance of preferred behaviours of SMEs has a considerable significant positive impact on product and systematic innovation, which have a significant impact on growth. Governance of network connections is also found to have a significant positive impact on growth. The findings contribute to an understanding of how both governance of preferred SME behaviour and network connections enable innovation. This study provides SMEs, SME network organisations and policy bodies with an enhanced understanding of governance approaches.
Incorporation of Next-Generation Sequencing into Routine Clinical Care to Direct Treatment of Head and Neck Squamous Cell Carcinoma
Authors: Chau Nicole G. , Li Yvonne Y. , Jo Vickie Y. , Rabinowits Guilherme , Lorch Jochen H. , Tishler Roy B. , Margalit Danielle N. , Schoenfeld Jonathan D. , Annino Don J. , Goguen Laura A. , Thomas Tom , Becker Hailey , Haddad Tyler , Krane Jeffrey F. , Lindeman Neal I. , Shapiro Geoffrey I. , Haddad Robert I. , Hammerman Peter S. 
Published: January 2016

Abstract
Purpose: The clinical impact of next-generation sequencing (NGS) in patients with head and neck squamous cell carcinoma (HNSCC) has not been described. We aimed to evaluate the clinical impact of NGS in the routine care of patients with HNSCC and to correlate genomic alterations with clinical outcomes.
Experimental Design: Single-center study examining targeted NGS platform used to sequence tumor DNA obtained from 213 HNSCC patients evaluated in outpatient head and neck oncology clinic between August 2011 and December 2014. We correlated tumor genomic profiling results with clinical outcomes.
Results: PI3K/RTK pathway activation occurred frequently [activating PIK3CA mutation or amplification (13%), PTEN inactivation (3%), RAS activation (6%), EGFR or ERBB2 activation (9%)]. Alterations in pathways affecting cell-cycle regulation [CCND1 amplification (9%), CDKN2A inactivation (17%), BRCA2 inactivation (2%)] and squamous differentiation [NOTCH1 inactivation (8%) andEP300 inactivation (6%)] were identified. PIK3CA amplification (n = 43), not PIK3CA mutation, was associated with significantly poorer progression-free survival (P = 0.0006). Oncogenic RAS mutations (n = 13) were associated with significantly poorer progression-free survival (P = 0.0001) and lower overall survival (P = 0.003). Eight patients with advanced, treatment-refractory HNSCC enrolled on clinical trials matched to tumor profiling results, and 50% achieved a partial response.
Conclusions: Incorporation of NGS clinical assays into the routine care of patients with HNSCC is feasible and may readily facilitate enrollment into clinical trials of targeted therapy with a higher likelihood of success. Data can be utilized for discovery of genomic biomarkers of outcome. PIK3CA amplification and RAS mutations were frequently identified and associated with poorer prognosis in this cohort. Clin Cancer Res; 22(12); 2939–49. ©2016 AACR.
Diagnostic accuracy of rapid immunoassays for heparin-induced thrombocytopenia
Authors: Sun Lova , Gimotty Phyllis A. , Lakshmanan Suvasini , Cuker Adam 
Published: January 2016

SummaryThe platelet factor 4/heparin ELISA has limited specificity for heparininduced thrombocytopenia (HIT) and frequently does not provide same-day results. Rapid immunoassays (RIs) have been developed which provide results in 30 minutes or less. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of RIs for HIT. We searched the literature for studies in which samples from patients with suspected HIT were tested using a RI and a functional assay against which the performance of the RI could be measured. We performed sensitivity analyses of studies that directly compared different RIs with each other and with ELISAs. Estimates of sensitivity and specificity for each RI were calculated. Twenty-three articles, collectively involving six different RIs, met eligibility criteria. All RIs exhibited high sensitivity (0.96 to 1.00); there was wider variability in specificity (0.68 to 0.94). Specificity of the IgG-specific chemiluminescent assay (IgG-CA) was greater than the polyspecific chemiluminescent assay [0.94 (95 %CI 0.89–0.99) vs 0.82 (0.77–0.87)]. The particle gel immunoassay demonstrated greater specificity than the polyspecific ELISA [0.96 (0.95–0.97) vs 0.91 (0.89–0.92)]. The IgG-CA and lateral flow immunoassay [0.94 (0.91–0.97)] exhibited greater specificity than the IgG-specific ELISA [0.86 (0.82–0.90)]. Given their high sensitivity and rapid turnaround time, RIs are a reliable means of excluding HIT at the point-of-care in patients with low or intermediate clinical probability. Additionally, some RIs have greater specificity than HIT ELISAs. In summary, IgG-specific RIs appear to have improved diagnostic accuracy compared with ELISAs in patients with suspected HIT and may reduce misdiagnosis and overtreatment.
A projeção especular da imagem do artista e o jogo de enunciação
Authors: Tomasi Carolina , Schwartzmann Saulo Nogueira 
Published: January 2016

<p>Bastam apenas as categorias de enunciação, enunciva e enunciativa, como estratégias de produção de sentido de pinturas e de fotografias? Este artigo objetiva discutir exatamente essa questão. A ideia de modernidade se impõe não como um saber, nem como ciência, mas como modo de reflexão do próprio fazer artístico. Temos a partir de então a explicitação do enunciador (o artista) no enunciado, um<br />simulacro do criador na criatura. Configura-se como objeto deste trabalho a análise da foto de Helmut Newton Autorretrato com esposa e modelos para explicitar estratégias de enunciação enunciativa e enunciação enunciva quando são postas em jogo. Analisaremos ainda a projeção da imagem dos artistas na produção de seus enunciados, primeiramente na pintura, e em um segundo momento na fotografia.</p>
Alternative Strategies to Achieve Cardiovascular Mortality Goals in China and India
Authors: Basu Sanjay , Yudkin John S. , Sussman Jeremy B. , Millett Christopher , Hayward Rodney A. 
Published: January 2016

Background—
The World Health Organization aims to reduce mortality from chronic diseases including cardiovascular disease (CVD) by 25% by 2025. High blood pressure is a leading CVD risk factor. We sought to compare 3 strategies for treating blood pressure in China and India: a treat-to-target (TTT) strategy emphasizing lowering blood pressure to a target, a benefit-based tailored treatment (BTT) strategy emphasizing lowering CVD risk, or a hybrid strategy currently recommended by the World Health Organization.

Methods and Results—
We developed a microsimulation model of adults aged 30 to 70 years in China and in India to compare the 2 treatment approaches across a 10-year policy-planning horizon. In the model, a BTT strategy treating adults with a 10-year CVD event risk of ≥10% used similar financial resources but averted ≈5 million more disability-adjusted life-years in both China and India than a TTT approach based on current US guidelines. The hybrid strategy in the current World Health Organization guidelines produced no substantial benefits over TTT. BTT was more cost-effective at $205 to $272/disability-adjusted life-year averted, which was $142 to $182 less per disability-adjusted life-year than TTT or hybrid strategies. The comparative effectiveness of BTT was robust to uncertainties in CVD risk estimation and to variations in the age range analyzed, the BTT treatment threshold, or rates of treatment access, adherence, or concurrent statin therapy.

Conclusions—
In model-based analyses, a simple BTT strategy was more effective and cost-effective than TTT or hybrid strategies in reducing mortality.
Association of Digoxin With Interstage Mortality: Results From the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Dataset
Authors: Oster Matthew E. , Kelleman Michael , McCracken Courtney , Ohye Richard G. , Mahle William T. 
Published: January 2016

Background
Mortality for infants with single ventricle congenital heart disease remains as high as 8% to 12% during the interstage period, the time between discharge after the Norwood procedure and before the stage II palliation. The objective of our study was to determine the association between digoxin use and interstage mortality in these infants.

Methods and Results

We conducted a retrospective cohort study using the Pediatric Heart Network Single Ventricle Reconstruction Trial public use dataset, which includes data on infants with single right ventricle congenital heart disease randomized to receive either a Blalock‐Taussig shunt or right ventricle‐to‐pulmonary artery shunt during the Norwood procedure at 15 institutions in North America from 2005 to 2008. Parametric survival models were used to compare the risk of interstage mortality between those discharged to home on digoxin versus those discharged to home not on digoxin, adjusting for center volume, ascending aorta diameter, shunt type, and socioeconomic status. Of the 330 infants eligible for this study, 102 (31%) were discharged home on digoxin. Interstage mortality for those not on digoxin was 12.3%, compared to 2.9% among those on digoxin, with an adjusted hazard ratio of 3.5 (95% CI, 1.1–11.7;
P
=0.04). The number needed to treat to prevent 1 death was 11 patients. There were no differences in complications between the 2 groups during the interstage period.

Conclusions
Digoxin use in infants with single ventricle congenital heart disease is associated with significantly reduced interstage mortality.
Disruption of Broca's Area Alters Higher-order Chunking Processing during Perceptual Sequence Learning
Authors: Alamia Andrea , Solopchuk Oleg , D'Ausilio Alessandro , Van Bever Violette , Fadiga Luciano , Olivier Etienne , Zénon Alexandre 
Published: January 2016

Abstract
Because Broca's area is known to be involved in many cognitive functions, including language, music, and action processing, several attempts have been made to propose a unifying theory of its role that emphasizes a possible contribution to syntactic processing. Recently, we have postulated that Broca's area might be involved in higher-order chunk processing during implicit learning of a motor sequence. Chunking is an information-processing mechanism that consists of grouping consecutive items in a sequence and is likely to be involved in all of the aforementioned cognitive processes. Demonstrating a contribution of Broca's area to chunking during the learning of a nonmotor sequence that does not involve language could shed new light on its function. To address this issue, we used offline MRI-guided TMS in healthy volunteers to disrupt the activity of either the posterior part of Broca's area (left Brodmann's area [BA] 44) or a control site just before participants learned a perceptual sequence structured in distinct hierarchical levels. We found that disruption of the left BA 44 increased the processing time of stimuli representing the boundaries of higher-order chunks and modified the chunking strategy. The current results highlight the possible role of the left BA 44 in building up effector-independent representations of higher-order events in structured sequences. This might clarify the contribution of Broca's area in processing hierarchical structures, a key mechanism in many cognitive functions, such as language and composite actions.