bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life
Authors: Willemse S. B. , Baak L. C. , Kuiken S. D. , van der Sluys Veer A. , Lettinga K. D. , van der Meer J. T. M. , Depla A. C. T. M. , Tuynman H. , van Nieuwkerk C. M. J. , Schinkel C. J. , Kwa D. , Reesink H. W. , van der Valk M. 
Published: July 2016

SummaryChronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver‐related death. Recently, multiple regimens of different direct‐acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real‐life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon‐based treatment, and one was treatment naive. In this real‐life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment‐experienced patients as recommended in guidelines.
Anti‐envelope antibody responses in individuals at high risk of hepatitis C virus who resist infection
Authors: Swann R. E. , Mandalou P. , Robinson M. W. , Ow M. M. , Foung S. K. H. , McLauchlan J. , Patel A. H. , Cramp M. E. 
Published: July 2016

SummaryInjection drug users uninfected by hepatitis C virus (HCV) despite likely repeated exposure through high‐risk behaviour are well documented. Factors preventing infection in these individuals are incompletely understood. Here, we looked for anti‐HCV‐envelope antibody responses in a cohort of repeatedly exposed but uninfected subjects. Forty‐two hepatitis C diagnostic antibody‐ and RNA‐negative injection drug users at high risk of exposure were studied and findings compared to healthy controls and cases with chronic HCV infection. Purified IgGs from sera were tested by ELISA for binding to genotype 1a and 3a envelope glycoproteins E1E2 with further testing for IgG and IgM reactivity against soluble E2. Virus‐neutralizing activity was assessed using an HCV pseudoparticle system. Uninfected subjects demonstrated significantly greater IgG and IgM reactivities to envelope glycoproteins than healthy controls with IgG from 6 individuals additionally showing significant neutralization. This study is the first to describe humoral immunological responses targeting the HCV envelope, important for viral neutralization, in exposed uninfected individuals. A subset of these cases also had evidence of viral neutralization via anti‐envelope antibodies. In addition to confirming viral exposure, the presence of specific anti‐envelope antibodies may be a factor that helps these individuals resist HCV infection.
A Pedagogical Model for Computational Linguistics across Curricular Boundaries
Authors: Alm Cecilia Ovesdotter , Womack Kathryn , Haake Anne , Engström Timothy 
Published: July 2016

AbstractAs techniques in computational linguistics become more widely used in scholarship and application in diverse fields, strategies for attracting students and practitioners to this area, for collaborating across disciplinary boundaries, as well as the pedagogical approaches to teaching it, will also shift. This pedagogical concept paper reports on an educational example providing a high‐level introduction of computational linguistics to students across curricular levels and disciplines. Specifically, it focuses on an interdisciplinary summer workshop in which the topic of computational natural language processing (NLP) was a key theme, illustrating the workshop's provision of exposure to computational linguistics for students in both technical and non‐technical majors. Including NLP modules as a major theme could bring together students from various backgrounds, encourage intellectual curiosity beyond their respective fields of study, and foster critical thinking about modeling practices and computational epistemologies. The interdisciplinary approach provided opportunities to reach out to emerging scholars and practitioners across fields, to expose them to NLP concepts, and to let them consider the benefits of considering natural language data in their own work or in future interdisciplinary collaborations.
Enhanced Memory as a Common Effect of Active Learning
Authors: Markant Douglas B. , Ruggeri Azzurra , Gureckis Todd M. , Xu Fei 
Published: July 2016

ABSTRACTDespite widespread consensus among educators thatactive learningleads to better outcomes than comparatively passive forms of instruction, it is often unclear why these benefits arise. In this article, we review research showing that the opportunity to control the information experienced while learning leads to improved memory relative to situations where control is absent. By integrating findings from a wide range of experimental paradigms, we identify a set of distinct mechanisms that mediate these effects, including the formation of distinctive sensorimotor associations, elaborative encoding due to goal‐directed exploration, improved co‐ordination of selective attention and encoding, adaptive selection of material based on existing memory, and metacognitive monitoring. Examining these mechanisms provides new insights into the effects of active learning, including how different forms of active control lead to improved outcomes relative to more traditional, passive instruction.
Visions of Albion: ancient landscapes, Glastonbury and alternative forms of nationalism
Authors: Gemie Sharif 
Published: July 2016

AbstractNationalist visions are often connected with a cult of the land. This article considers some of the cultural‐nationalist ideas linked to the Somerset town of Glastonbury, a prominent New Age centre. It discusses the legacy of British pastoralism as shown in the work of H. V. Morton and Cecil Sharp. It considers the evolution of an English–Celtic tradition, drawing on the legacy of the Arthurian legend, but being re‐formulated in the late twentieth century as a vehicle for New Age conceptions of British society. The article concludes by evaluating the political values inherent in the New Age.
Can evolutionary constraints explain the rarity of nitrogen‐fixing trees in high‐latitude forests?
Authors: Menge Duncan N. L. , Crews Timothy E. 
Published: July 2016

SummaryThe rarity of symbiotic nitrogen (N)‐fixing trees in temperate and boreal (‘high‐latitude’) forests is curious. One explanation – the evolutionary constraints hypothesis – posits that high‐latitude N‐fixing trees are rare because few have evolved. Here, we consider traits necessary for high‐latitude N‐fixing trees. We then use recent developments in trait evolution to estimate that > 2000 and > 500 species could have evolved from low‐latitude N‐fixing trees and high‐latitude N‐fixing herbs, respectively. Evolution of N‐fixing from nonfixing trees is an unlikely source of diversity. Dispersal limitation seems unlikely to limit high‐latitude N‐fixer diversity. The greater number of N‐fixing species predicted to evolve than currently inhabit high‐latitude forests suggests a greater role for ecological than evolutionary constraints.

Contents

Summary
1195

I.
Introduction
1196

II.
The role of diversity
1196

III.
An evolutionary framework for the success of high‐latitude N‐fixing woody symbioses
1196

IV.
Conclusions
1200

Acknowledgements
1200

References
1200
Gap expansion in old‐growth subarctic forests: the climate–pathogen connection
Authors: Vézeau Corinne , Payette Serge 
Published: July 2016

Summary

We tested the hypothesis considering old‐growth subarctic woodlands, free of fire, insect and stand‐scale blowdown disturbances, to be at equilibrium with the climate. To do so, we explored the status of Hudsonian woodlands based on the natality/mortality ratio.

The gap history of the woodland was reconstructed based on mapping and dating of dead gap‐spruces (Picea mariana). Among the 25 gaps studied, 763 dead trees and only 14 saplings were recorded. The center of some gaps remained treeless over the last 1000 yr, and gap area doubled over the last 100 yr. The status of the tree population is in a demographic disequilibrium caused by the small replacement of dead spruces in all of the gaps.

Episodes of ‘mass’ mortality occurred during several decades corresponding to years of favorable tree‐ring growth. The natural process of gap‐filling appears to be ineffective under current conditions. Good tree‐ring growth of dying trees suggests abundant precipitation during the mortality episodes, but precipitation appears to be involved indirectly in the mortality process.

The main cause of the widespread tree mortality during the last centuries of gap expansion appears to be biotic in origin. The impact of pathogenic fungal disease linked to late‐lying snow cover is proposed for the mortality events.
Effect of plant‐based diets on obesity‐related inflammatory profiles: a systematic review and meta‐analysis of intervention trials
Authors: Eichelmann F. , Schwingshackl L. , Fedirko V. , Aleksandrova K. 
Published: July 2016

SummaryPlant‐based dietary interventions have been proposed to reduce obesity induced chronic low‐grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta‐analysis of intervention trials aimed to assess the effect of plant‐based diets on obesity‐related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C‐reactive protein (CRP), interleukin‐6 (IL‐6), tumour necrosis factor‐alpha (TNF‐ɑ), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta‐analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant‐based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, −0.55 mg/l, 95% confidence intervals (CI): −0.78; −0.32, I2 = 94.4%], IL‐6 [effect size, −0.25 ng/l, 95% CI: −0.56; 0.06, I2 = 74%], and, to some degree, sICAM (−25.07 ng/ml [95% CI: −52.32; 2.17, I2 = 93.2%]). No substantial effects were revealed for TNF‐ɑ, resistin, adiponectin and leptin. Plant‐based diets are associated with an improvement in obesity‐related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk.
Inhibition of FGF Signalling Pathway Augments the Expression of Pluripotency and Trophoblast Lineage Marker Genes in Porcine Parthenogenetic Blastocyst
Authors: Li LY , Li MM , Yang SF , Zhang J , Li Z , Zhang H , Zhu L , Zhu X , Verma V , Liu Q , Shi D , Huang B 
Published: July 2016

ContentsThe consistent failure to isolate bona fide pluripotent cell lines from livestock indicates that the underlying mechanisms of early lineage specification are poorly defined. Unlike other species, the contrivances of segregation have been comprehensively studied in the mouse. In mouse, FGF/MAPK signalling pathway dictates the segregation of hypoblast (primitive endoderm). However, it is not evident whether this mechanism is also conserved in livestock. Here, in this study, we examined the roles of FGF/MAP kinase signalling pathways in porcine parthenogenetic embryos during the early development. Porcine parthenogenetic embryos were cultured in the medium addition with FGFR inhibitor BGJ398 (10 μm) or DEMOS. Pluripotency‐ and lineage‐related gene expressions in the early porcine embryos were determined. Compared to control, total cell numbers on day 7 were significantly higher (55 ± 5.96 vs 47 ± 1.97, p < 0.05) in embryos cultured in the presence of BGJ398, but had no significant effect on the rate of blastocyst development (47% vs 44%, p > 0.05). Nonetheless, BGJ398 treatment significantly augmented the expression of pluripotency and trophoblast marker genes (SOX2, OCT4, KLF4 and CDX2), but did not significantly change the expression of NANOG and hypoblast marker gene (GATA4). Furthermore, the addition of FGF signalling agonist (FGF2) during the embryo development significantly decreased the expression of pluripotency and trophoblast marker genes (SOX2, NANOG, KLF4 and CDX2), but no significant effect on the expression of OCT4 and GATA4 was observed. Here, we exhibit that inhibition of FGF signalling could improve the quality of the porcine embryo and escalate the chance to capture pluripotency. Besides, it also promotes the trophoblast development of porcine parthenogenetic embryo. In addition, the data suggested that FGF signalling pathway is dispensable for the segregation of hypoblast and epiblast lineages in porcine embryo during the early development.
Recognition criteria, characteristics and implications of the fluvial to marine transition zone in ancient deltaic deposits (Lajas Formation, Argentina)
Authors: Gugliotta Marcello , Flint Stephen S. , Hodgson David M. , Veiga Gonzalo D. 
Published: July 2016

AbstractThe seaward end of modern rivers is characterized by the interactions of marine and fluvial processes, a tract known as the fluvial to marine transition zone, which varies between systems due to the relative strength of these processes. To understand how fluvial and tidal process interactions and the fluvial to marine transition zone are preserved in the rock record, large‐scale outcrops of deltaic deposits of the Middle Jurassic Lajas Formation (Neuquén Basin, Argentina) have been investigated. Fluvial–tidal indicators consist of cyclically distributed carbonaceous drapes in unidirectional, seaward‐oriented cross‐stratifications, which are interpreted as the result of tidal modulation of the fluvial current in the inner part of the fluvial to marine transition zone. Heterolithic deposits with decimetre‐scale interbedding of coarser‐grained and finer‐grained facies with mixed fluvial and tidal affinities are interpreted to indicate fluvial discharge fluctuations (seasonality) and subordinate tidal influence. Many other potential tidal indicators are argued to be the result of fluvial–tidal interactions with overall fluvial dominance or of purely fluvial processes. No purely tidal or tide‐dominated facies were recognized in the studied deposits. Moreover, fluvial–tidal features are found mainly in deposits interpreted as interflood (forming during low river stage) in distal (delta front) or off‐axis (interdistributary) parts of the system. Along major channel axes, the interpreted fluvial to marine transition zone is mainly represented by the fluvial‐dominated section, whereas little or no tide‐dominated section is identified. The system is interpreted to have been hyposynchronous with a poorly developed turbidity maximum. These conditions and the architectural elements described, including major and minor distributary channels, terminal distributary channels, mouth bars and crevasse mouth bars, are consistent with an interpretation of a fluvial‐dominated, tide‐influenced delta system and with an estimated short backwater length and inferred microtidal conditions. The improved identification of process interactions, and their preservation in ancient fluvial to marine transition zones, is fundamental to refining interpretations of ancient deltaic successions.
Double red blood cell collection: comparison of three apheresis systems
Authors: Burgstaler Edwin A. , Duffy Kimberly J. , Gandhi Manish J. 
Published: July 2016

BACKGROUNDWe compared three instruments for double red blood cell (DRBC) collection to efficiently optimize our RBC inventory.STUDY DESIGN AND METHODSInstruments compared were the TerumoBCT Trima Accel (Trima), the Fenwal Alyx (Alyx), and the Haemonetics MCS+ 8150 (MCS+). Forty consecutive collections (80 products) per instrument were evaluated for hemoglobin (Hb) content, leukoreduction, collection time, instrument efficiency, donor acceptance, and reactions. The total number of whole blood donors who could be eligible for DRBC collection was analyzed. All collections were as per the manufacturer recommendations with target volume of 360 or 400mL. Leukoreduction was integral to the collection procedure for the Alyx and Trima, while it was a separate process for the MCS+.RESULTSThe total numbers of whole blood donors who could be eligible for DRBC collection were 10,116 for the MCS+, 9378 for the Alyx, and 8573 for the Trima. All units collected had more than 42.5 g of Hb. Mean Hb levels were as follows: Trima, 59.2 g; Alyx, 56.8 g; and MCS+, 51.5 g. Donor times for the Trima, Alyx, and MCS+ were 52, 45, and 52 minutes, respectively. Technician times for the Trima, Alyx, and MCS+ (without filtration) were 87, 73, and 64 minutes. All collected products had fewer than 5 × 106 white blood cells.CONCLUSIONSAll three instruments would be capable of collecting an acceptable leukoreduced DRBC product. The Alyx was most portable, with the shortest donor time and total technician time (considering filtration time) and highest collection efficiency and would collect from more donors than the Trima. We thus chose the Alyx as it best fits the specific needs of our center.
Does therapeutic plasma exchange have a role in the treatment of prosthetic hip–associated cobalt toxicity? A case report and literature review
Authors: Grant Michelle L. , Karp Julie K. , Palladino Michele , Le Nguyet , Hall Nancy , Herman Jay H. 
Published: July 2016

BACKGROUNDProsthetic hip–associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal‐on‐metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels.CASE REPORTA 61‐year‐old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 µg/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two‐thirds of measurable cobalt, but levels rebounded to pre‐TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 µg/L and clinical symptoms improved.DISCUSSIONTPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment.CONCLUSIONTPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated.
Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins
Authors: Ielasi Francesco S. , Alioscha-Perez Mitchel , Donohue Dagmara , Claes Sandra , Sahli Hichem , Schols Dominique , Willaert Ronnie G. 
Published: July 2016

ABSTRACTThe first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy—based on the construction of a lectin-glycan interaction (LGI) network—to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulentEscherichia coli(FimH adhesin), and the fungal pathogensCandida albicans(Als1p and Als3p adhesins) andC. glabrata(Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity.IMPORTANCEMicrobial pathogens may express a wide range of carbohydrate-specific adhesion proteins that mediate adherence to host tissues. Pathogen attachment to host cells is achieved through the binding of these lectin-like adhesins to glycans on human glycoproteins. In only a few cases have the human receptors of pathogenic adhesins been described. We developed a new strategy to predict these interacting receptors. Therefore, we developed a novel LGI network that would allow the mapping of potential adhesin binding receptors in the host with prioritization, based on the experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins (bacterial uroepithelial FimH fromE. coliand fungal Epa and Als adhesins fromC. glabrataandC. albicans) were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with human-pathogenic viruses and to discover whether FimH adhesin has anti-HIV activity.
Transfer of DNA from Bacteria to Eukaryotes
Authors: Lacroix Benoît , Citovsky Vitaly 
Published: July 2016

ABSTRACT

Historically, the members of the
Agrobacterium
genus have been considered the only bacterial species naturally able to transfer and integrate DNA into the genomes of their eukaryotic hosts. Yet, increasing evidence suggests that this ability to genetically transform eukaryotic host cells might be more widespread in the bacterial world. Indeed, analyses of accumulating genomic data reveal cases of horizontal gene transfer from bacteria to eukaryotes and suggest that it represents a significant force in adaptive evolution of eukaryotic species. Specifically, recent reports indicate that bacteria other than
Agrobacterium
, such as
Bartonella henselae
(a zoonotic pathogen),
Rhizobium etli
(a plant-symbiotic bacterium related to
Agrobacterium
), or even
Escherichia coli
, have the ability to genetically transform their host cells under laboratory conditions. This DNA transfer relies on type IV secretion systems (T4SSs), the molecular machines that transport macromolecules during conjugative plasmid transfer and also during transport of proteins and/or DNA to the eukaryotic recipient cells. In this review article, we explore the extent of possible transfer of genetic information from bacteria to eukaryotic cells as well as the evolutionary implications and potential applications of this transfer.