bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Detection of KPC, NDM, and OXA-48-Like Carbapenemases by Real-Time PCR from Rectal Swab Surveillance Samples
Authors: Lee Tracy D. , Adie Kathleen , McNabb Alan , Purych Dale , Mannan Kulvinder , Azana Robert , Ng Corrinne , Tang Patrick , Hoang Linda M. N. 
Published: May 2015

ABSTRACT

We describe a multiplex real-time PCR assay for use on the ABI 7500 Fast TaqMan platform to detect all currently described
Klebsiella pneumoniae
carbapenemases (KPC), New Delhi metallo-β-lactamases (NDM), and the OXA-48-like family of carbapenemases from bacterial culture lysates or sample enrichment broth lysates.
Protective Efficacy of Recombinant Modified Vaccinia Virus Ankara Delivering Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein
Authors: Volz Asisa , Kupke Alexandra , Song Fei , Jany Sylvia , Fux Robert , Shams-Eldin Hosam , Schmidt Jörg , Becker Christin , Eickmann Markus , Becker Stephan , Sutter Gerd 
Published: May 2015

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans. We tested a recombinant modified vaccinia virus Ankara (MVA) vaccine expressing full-length MERS-CoV spike (S) glycoprotein by immunizing BALB/c mice with either intramuscular or subcutaneous regimens. In all cases, MVA-MERS-S induced MERS-CoV-specific CD8
+
T cells and virus-neutralizing antibodies. Vaccinated mice were protected against MERS-CoV challenge infection after transduction with the human dipeptidyl peptidase 4 receptor. This MERS-CoV infection model demonstrates the safety and efficacy of the candidate vaccine.
Local Virus Extinctions following a Host Population Bottleneck
Authors: Kapusinszky Beatrix , Mulvaney Usha , Jasinska Anna J. , Deng Xutao , Freimer Nelson , Delwart Eric 
Published: May 2015

ABSTRACT
A small number of African green monkeys (AGMs) were introduced into the Caribbean from West Africa in the 1600s. To determine the impact of this population bottleneck on the AGM virome, we used metagenomics to compare the viral nucleic acids in the plasma of 43 wild AGMs from West Africa (Gambia) to those in 44 AGMs from the Caribbean (St. Kitts and Nevis). Three viruses were detected in the blood of Gambian primates: simian immunodeficiency virus (SIVagm; in 42% of animals), a novel simian pegivirus (SPgVagm; in 7% of animals), and numerous novel simian anelloviruses (in 100% of animals). Only anelloviruses were detected in the Caribbean AGMs with a prevalence and levels of viral genetic diversity similar to those in the Gambian animals. A host population bottleneck therefore resulted in the exclusion of adult-acquired SIV and pegivirus from the Caribbean AGMs. The successful importation of AGM anelloviruses into the Caribbean may be the result of their early transmission to infants, very high prevalence in African AGMs, and frequent coinfections with as many as 11 distinct variants.

IMPORTANCE
The extent to which viruses can persist in small isolated populations depends on multiple host, viral, and environmental factors. The absence of prior infections may put an immunologically naive population at risk for disease outbreaks. Isolated populations originating from a small number of founder individuals are therefore considered at increased risk following contact with populations with a greater variety of viruses. Here, we compared the plasma virome of West African green monkeys to that in their descendants after importation of a small number of animals to the Caribbean. A lentivirus and a pegivirus were found in the West African population but not in the Caribbean population. Highly diverse anelloviruses were found in both populations. A small founder population, limited to infants and young juvenile monkeys, may have eliminated the sexually transmitted viruses from the Caribbean AGMs, while anelloviruses, acquired at an earlier age, persisted through the host population bottleneck.
The V1V2 Region of HIV-1 gp120 Forms a Five-Stranded Beta Barrel
Authors: Pan Ruimin , Gorny Miroslaw K. , Zolla-Pazner Susan , Kong Xiang-Peng 
Published: May 2015

ABSTRACT

The region consisting of the first and second variable regions (V1V2) of gp120 plays vital roles in the functioning of the HIV-1 envelope (Env). V1V2, which harbors multiple glycans and is highly sequence diverse, is located at the Env apex and stabilizes the trimeric gp120 spike on the virion surface. It shields V3 and the coreceptor binding sites in the prefusion state and exposes them upon CD4 binding. Data from the RV144 human HIV-1 vaccine trial suggested that antibody responses targeting the V1V2 region inversely correlated with the risk of infection; thus, understanding the antigenic structure of V1V2 can contribute to vaccine design. We have determined a crystal structure of a V1V2 scaffold molecule (V1V2
ZM109
-1FD6) in complex with 830A, a human monoclonal antibody that recognizes a V1V2 epitope overlapping the integrin-binding motif in V2. The structure revealed that V1V2 assumes a five-stranded beta barrel structure with the region of the integrin-binding site (amino acids [aa] 179 to 181) included in a “kink” followed by an extra beta strand. The complete barrel structure naturally presents the glycans on its outer surface and packs into its core conserved hydrophobic residues, including the Ile at position 181 which was highly correlated with vaccine efficacy in RV144. The epitope of monoclonal antibody 830A is discontinuous and composed of three segments: (i) Thr
175
, Tyr
177
, Leu
179
, and Asp
180
at the kink overlapping the integrin-binding site; (ii) Arg
153
and Val
154
in V1; and (iii) Ile
194
at the C terminus of V2. This report thus provides the atomic details of the immunogenic “V2i epitope.”

IMPORTANCE
Data from the RV144 phase III clinical trial suggested that the presence of antibodies to the first and second variable regions (V1V2) of gp120 was associated with the modest protection afforded by the vaccine. V1V2 is a highly variable and immunogenic region of HIV-1 surface glycoprotein gp120, and structural information about this region and its antigenic landscape will be crucial in the design of an effective HIV-1 vaccine. We have determined a crystal structure of V1V2 in complex with human MAb 830A and have shown that MAb 830A recognizes a region overlapping the α4β7 integrin-binding site. We also showed that V1V2 forms a 5-stranded beta barrel, an elegant structure allowing sequence variations in the strand-connecting loops while preserving a conserved core.
Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen
Authors: Tsouchnikas Georgios , Zlatkovic Juergen , Jarmer Johanna , Strauß Judith , Vratskikh Oksana , Kundi Michael , Stiasny Karin , Heinz Franz X. 
Published: May 2015

ABSTRACTThe antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as an immunogen. TBE virus occurs in Europe and Asia and—together with the yellow fever, dengue, West Nile, and Japanese encephalitis viruses—represents one of the major human-pathogenic flaviviruses. Mice were immunized with a dimeric soluble form of E (sE) alone or in complex with monoclonal antibodies specific for each of the three domains of E, and the antibody response induced by these ICs was compared to that seen after immunization with sE alone. Immunoassays using recombinant domains and domain combinations of TBE virus sE as well as the distantly related West Nile virus sE allowed the dissection and quantification of antibody subsets present in postimmunization sera, thus generating fine-specificity patterns of the polyclonal responses. There were substantially different responses with two of the ICs, and the differences could be mechanistically related to (i) epitope shielding and (ii) antibody-mediated structural changes leading to dissociation of the sE dimer. The phenomena described may also be relevant for polyclonal responses upon secondary infections and/or booster immunizations and may affect antibody responses in an individual-specific way.IMPORTANCEInfections with flaviviruses such as yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitis (TBE) viruses pose substantial public health problems in different parts of the world. Antibodies to viral envelope protein E induced by natural infection or vaccination were shown to confer protection from disease. Such antibodies can target different epitopes in E protein, and the fine specificities of polyclonal responses can differ between individuals. We conducted a mouse immunization study with TBE E protein alone or complexed to monoclonal antibodies specific for each of the three protein domains. We demonstrated that phenomena such as epitope shielding and antibody-induced structural changes can profoundly influence the fine specificity of antibody responses to the same immunogen. The study thus provided important new information on the potential immunomodulatory role of preexisting antibodies in a flavivirus system that can be relevant for understanding individual-specific factors influencing antibody responses in sequential flavivirus infections and/or immunizations.
Antigenic and molecular characterisation of Border disease virus associated with high mortality in lambs in Spain
Authors: Vega S. , Rosell R. , Orden J. A. , Pérez T. , Marín C. , González S. , Marco I. , Cabezón O. , de la Fuente R. 
Published: May 2015

IntroductionBorder disease virus (BDV) causes congenital disorders in sheep and results in severe, but underestimated, economic losses worldwide. However, information about BDV strains affecting several ruminants worldwide is scarce. Therefore, antigenic and genetic classification of isolates from different geographical regions is important to enhance the knowledge of the epidemiology of BDV.Materials and methodsFive pestiviruses isolated from lambs in an epidemic outbreak with an unusually high mortality in Spain in 1997 were characterised antigenically with a panel of monoclonal antibodies and genetically by sequencing within the 50 untranslated (50UTR) region of the genome.ResultsAll the isolates were classified as BDV and showed a high homology with the Aveyron strain (Av), which was associated with an epidemic reported in sheep from the Aveyron region of France in 1984.ConclusionsClassification of the isolates from this study provides valuable information on the molecular epidemiology of BDV.
Conditions for mafic magma storage beneath fissure zones at oceanic islands. The case of São Miguel Island (Azores archipelago)
Authors: Zanon Vittorio 
Published: May 2015

Abstract

Ponding conditions of basalts erupted from fissure zones at São Miguel Island (Azores) were investigated through microthermometry of fluid inclusions, hosted in olivines and clinopyroxenes, and whole-rock and mineral chemistry. The Região dos Picos and Achada das Furnas fissure zones formed between central volcanoes and erupted geochemically similar magmas for the last 30 kyr. Hydrocarbonic fluid inclusions that survived to diffusion and re-equilibration recorded a maximum density value of 1000 kg m
−3
(29.3 km) at both fissure zones, at the intersection with the feeding systems of older central volcanoes. The maximum density decreases to 875 kg m
−3
(23.5 km) towards the central segment of Região dos Picos. Further trapping of low-density fluids is occasional and limited to a few samples. While the deepest event is interpreted to mark the vertical variation of the Moho at each location, all other events are only representative of short-time ponding with fluid re-equilibration. The deepening of the Moho towards the central volcanoes might be the effect of long-lasting underplating. However, the periodic stretching of the lithosphere, in response to the differential stress field acting at central volcanoes, would have been responsible for the thinning of the crust at the central segment of the fissure zone.

Supplementary material:

Whole-rock geochemistry with international standard used, and representative analyses of selected mineral phases from the two segments of the Região dos Picos fissure zone is available at
www.geolsoc.org.uk/SUP18818
Evidence Suggesting That Discontinuous Dosing of ALK Kinase Inhibitors May Prolong Control of ALK+ Tumors
Authors: Amin Amit Dipak , Rajan Soumya S. , Liang Winnie S. , Pongtornpipat Praechompoo , Groysman Matthew J. , Tapia Edgar O. , Peters Tara L. , Cuyugan Lori , Adkins Jonathan , Rimsza Lisa M. , Lussier Yves A. , Puvvada Soham D. , Schatz Jonathan H. 
Published: May 2015

Abstract
The anaplastic lymphoma kinase (ALK) is chromosomally rearranged in a subset of certain cancers, including 2% to 7% of non–small cell lung cancers (NSCLC) and ∼70% of anaplastic large cell lymphomas (ALCL). The ALK kinase inhibitors crizotinib and ceritinib are approved for relapsed ALK+ NSCLC, but acquired resistance to these drugs limits median progression-free survival on average to ∼10 months. Kinase domain mutations are detectable in 25% to 37% of resistant NSCLC samples, with activation of bypass signaling pathways detected frequently with or without concurrent ALK mutations. Here we report that, in contrast to NSCLC cells, drug-resistant ALCL cells show no evidence of bypassing ALK by activating alternate signaling pathways. Instead, drug resistance selected in this setting reflects upregulation of ALK itself. Notably, in the absence of crizotinib or ceritinib, we found that increased ALK signaling rapidly arrested or killed cells, allowing a prolonged control of drug-resistant tumors in vivo with the administration of discontinuous rather than continuous regimens of drug dosing. Furthermore, even when drug resistance mutations were detected in the kinase domain, overexpression of the mutant ALK was toxic to tumor cells. We confirmed these findings derived from human ALCL cells in murine pro-B cells that were transformed to cytokine independence by ectopic expression of an activated NPM–ALK fusion oncoprotein. In summary, our results show how ALK activation functions as a double-edged sword for tumor cell viability, with potential therapeutic implications. Cancer Res; 75(14); 2916–27. ©2015 AACR.
Association between statin use and plasma D-dimer levels
Authors: Mikhailidis Dimitri , Undas Anetta , Lip Gregory , Muntner Paul , Bittner Vera , Ray Kausik , Watts Gerald , Hovingh G. Kees , Rysz Jacek , Kastelein John , Sahebkar Amirhossein , Serban Corina , Banach Maciej ,   Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
Published: May 2015

SummaryD-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors, but their effect on plasma D-dimer levels is controversial. Therefore, the aim of this meta-analysis was to evaluate the association between statin therapy and plasma D-dimer levels. We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to September 25, 2014) to identify randomised controlled trials (RCTs) investigating the impact of statin therapy on plasma D-dimer levels. Two independent reviewers extracted data on study characteristics, methods and outcomes. Meta-analysis of data from nine RCTs with 1,165 participants showed a significant effect of statin therapy in reducing plasma D-dimer levels (standardised mean difference [SMD]: –0.988 µg/ml, 95 % confidence interval [CI]: –1.590 – –0.385, p=0.001). The effect size was robust in sensitivity analysis and omission of no single study significantly changed the overall estimated effect size. In the subgroup analysis, the effect of statins on plasma D-dimer levels was significant only in the subsets of studies with treatment duration ≥ 12 weeks (SMD: –0.761 µg/ml, 95 %CI: –1.163– –0.360; p< 0.001), and for lipophilic statins (atorvastatin and simvastatin) (SMD: –1.364 µg/ml, 95 % CI: –2.202– –0.526; p=0.001). Hydrophilic statins (pravastatin and rosuvastatin) did not significantly reduce plasma D-dimer levels (SMD: –0.237 µg/ml, 95 %CI: –1.140–0.665, p=0.606). This meta-analysis of RCTs suggests a decrease of plasma D-dimer levels after three months of statin therapy, and especially after treatment with lipophilic statins. Well-designed trials are required to validate these results.Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.
Classic thrombophilic gene variants
Authors: Franchini Massimo , Mannucci Pier Mannuccio 
Published: May 2015

SummaryThrombophilia is defined as a condition predisposing to the development of venous thromboembolism (VTE) on the basis of a hypercoagu-lable state. Over the past decades, great advances in the pathogenesis of VTE have been made and nowadays it is well established that a thrombophilic state may be associated with acquired and/or inherited factors. The rare loss-of-function mutations of the genes encoding natural anticoagulant proteins (i. e. protein C, protein S and antithrombin) and the more common gain-of-function polymorphisms factor V Leiden and prothrombin G20210A are the main genetic determinants of thrombophilia. In addition, non-O blood group has been consistently demonstrated to be the most frequent inherited marker of an increased risk of VTE. The mechanism role of these inherited thrombophilia markers will be discussed in this narrative review.
Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: De Ferrari Gaetano M. , Dusi Veronica , Spazzolini Carla , Bos J. Martijn , Abrams Dominic J. , Berul Charles I. , Crotti Lia , Davis Andrew M. , Eldar Michael , Kharlap Maria , Khoury Asaad , Krahn Andrew D. , Leenhardt Antoine , Moir Christopher R. , Odero Attilio , Olde Nordkamp Louise , Paul Thomas , Rosés i Noguer Ferran , Shkolnikova Maria , Till Jan , Wilde Arthur A.M. , Ackerman Michael J. , Schwartz Peter J. 
Published: May 2015

Background—
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder causing life-threatening arrhythmias whenever sympathetic activity increases. β-Βlockers are the mainstay of therapy; when they fail, implantable cardioverter-defibrillators (ICDs) are used but often cause multiple shocks. Preliminary results with flecainide appear encouraging. We proposed left cardiac sympathetic denervation (LCSD) as useful additional therapy, but evidence remains anecdotal.

Methods and Results—

We report 63 patients with CPVT who underwent LCSD as secondary (n=54) or primary (n=9) prevention. The median post-LCSD follow-up was 37 months. The 9 asymptomatic patients remained free of major cardiac events. Of the 54 patients with prior major cardiac events either on (n=38) or off (n=16) optimal medical therapy, 13 (24%) had at least 1 recurrence: 0 patients had an aborted cardiac arrest, 2 patients had syncope only, 10 patients had ≥1 appropriate ICD discharges, and 1 patient died suddenly. The 1- and 2-year cumulative event-free survival rates were 87% and 81%. The percentage of patients with major cardiac events despite optimal medical therapy (n=38) was reduced from 100% to 32% (
P
<0.001) after LCSD, and among 29 patients with a presurgical ICD, the rate of shocks dropped by 93% from 3.6 to 0.6 shocks per person per year (
P
<0.001). Patients with an incomplete LCSD (n=7) were more likely to experience major cardiac events after LCSD (71% versus 17%;
P
<0.01) than those with a complete LCSD.

Conclusions—
LCSD is an effective antifibrillatory intervention for patients with CPVT. Whenever syncope occurs despite optimal medical therapy, LCSD could be considered the next step rather than an ICD and could complement ICDs in patients with recurrent shocks.
Geographic Variations in Cardiovascular Health in the United States: Contributions of State‐ and Individual‐Level Factors
Authors: Gebreab Samson Y. , Davis Sharon K. , Symanzik Jürgen , Mensah George A. , Gibbons Gary H. , Diez‐Roux Ana V. 
Published: May 2015

BackgroundImproving cardiovascular health (CVH) of all Americans by 2020 is a strategic goal of the American Heart Association. Understanding the sources of variation and identifying contextual factors associated with poorCVHmay suggest important avenues for prevention.Methods and ResultsCross‐sectional data from the Behavioral Risk Factor Surveillance System for the year 2011 were linked to state‐level coronary heart disease and stroke mortality data from the National Vital Statistics System and to state‐level measures of median household income, income inequality, taxes on soda drinks and cigarettes, and food and physical activity environments from various administrative sources. PoorCVHwas defined according to the American Heart Association definition using 7 self‐reportedCVHmetrics (current smoking, physical inactivity, obesity, poor diet, hypertension, diabetes, and high cholesterol). Linked micromap plots and multilevel logistic models were used to examine state variation in poorCVHand to investigate the contributions of individual‐ and state‐level factors to this variation. We found significant state‐level variation in the prevalence of poorCVH(median odds ratio 1.32,P<0.001). Higher rates of poorCVHand cardiovascular disease mortality were clustered in the southern states. Minority and low socioeconomic groups were strongly associated with poorCVHand explained 51% of the state‐level variation in poorCVH; state‐level factors explained an additional 28%. State‐level median household income (odds ratio 0.89; 95%CI0.84–0.94), taxes on soda drinks (odds ratio 0.94; 95% CI 0.89–0.99), farmers markets (odds ratio 0.91; 95% CI 0.85–0.98), and convenience stores (odds ratio 1.09; 95% CI 1.01–1.17) were predictive of poorCVHeven after accounting for individual‐level factors.ConclusionsThere is significant state‐level variation in poorCVHthat is partly explained by individual‐ and state‐level factors. Additional longitudinal research is warranted to examine the influence of state‐level policies and food and physical activity environments on poorCVH.
The Crucial Role of Internal Variability in Modulating the Decadal Variation of the East Asian Summer Monsoon–ENSO Relationship during the Twentieth Century
Authors: Song Fengfei , Zhou Tianjun 
Published: May 2015

Abstract
This study investigates the role of internal variability in modulating the East Asian summer monsoon (EASM)–ENSO relationship using Twentieth-Century Reanalysis (20CR) data and simulations from phase 5 of CMIP (CMIP5). Analysis of 20CR data reveals an unstable EASM–ENSO relationship during the twentieth century. During the high-correlation periods of 1892–1912 and 1979–99, an evident western Pacific anticyclone (WPAC) and dipole sea level pressure (SLP) pattern are present in the decaying El Niño summer, accompanied by Indian Ocean warming and a tropospheric temperature Matsuno–Gill pattern. However, these are weaker or absent during low-correlation periods (1914–34 and 1958–78). After removing the external forcings based on historical simulations from 15 CMIP5 models, all the above features remain almost unchanged, suggesting the crucial role of internal variability. In a 501-yr preindustrial control (piControl) simulation without external forcing variation from CCSM4, the EASM–ENSO relationship also shows significant decadal variation, with a magnitude comparable to the 20CR data. The analysis demonstrates that the EASM–ENSO relationship’s variation is modulated by the interdecadal Pacific oscillation (IPO). Compared to negative IPO phases, the warmer East China Sea in positive IPO phases weakens the western North Pacific subtropical high (WNPSH), inducing more precipitation. Thus, the Kelvin wave–induced interannual divergence suppresses more mean-state precipitation and leads to a stronger WPAC. Hence, the IPO modulates the EASM–ENSO relationship through the WNPSH, which is evident in both 20CR and the piControl simulation.