bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune response profiling of primary monocytes and oral keratinocytes to different Tannerella forsythia strains and their cell surface mutants
Authors: Bloch S. , Zwicker S. , Bostanci N. , Sjöling Å. , Boström E.A. , Belibasakis G.N. , Schäffer C. 
Published: December 2017

SummaryThe oral pathogen Tannerella forsythia possesses a unique surface (S‐) layer with a complex O‐glycan containing a bacterial sialic acid mimic in the form of either pseudaminic acid or legionaminic acid at its terminal position. We hypothesize that different T. forsythia strains employ these stereoisomeric sugar acids for interacting with the immune system and resident host tissues in the periodontium. Here, we show how T. forsythia strains ATCC 43037 and UB4 displaying pseudaminic acid and legionaminic acid, respectively, and selected cell surface mutants of these strains modulate the immune response in monocytes and human oral keratinocytes (HOK) using a multiplex immunoassay. When challenged with T. forsythia, monocytes secrete proinflammatory cytokines, chemokines and vascular endothelial growth factor (VEGF) with the release of interleukin‐1β (IL‐1β) and IL‐7 being differentially regulated by the two T. forsythia wild‐type strains. Truncation of the bacteria's O‐glycan leads to significant reduction of IL‐1β and regulates macrophage inflammatory protein‐1. HOK infected with T. forsythia produce IL‐1Ra, chemokines and VEGF. Although the two wild‐type strains elicit preferential immune responses for IL‐8, both truncation of the O‐glycan and deletion of the S‐layer result in significantly increased release of IL‐8, granulocyte‐macrophage colony‐stimulating factor and monocyte chemoattractant protein‐1. Through immunofluorescence and confocal laser scanning microscopy of infected HOK we additionally show that T. forsythia is highly invasive and tends to localize to the perinuclear region. This indicates, that the T. forsythia S‐layer and attached sugars, particularly pseudaminic acid in ATCC 43037, contribute to dampening the response of epithelial tissues to initial infection and hence play a pivotal role in orchestrating the bacterium's virulence.
Time‐resolved identification of mechanical loadings on plates using the virtual fields method and deflectometry measurements
Authors: O'Donoughue P. , Robin O. , Berry A. 
Published: December 2017

AbstractThis paper describes an approach for identifying the magnitude and location of both stationary and transient mechanical loadings applied to a thin rectangular simply supported plate. Full‐field deflectometry measurements and the virtual fields method are used with the local equilibrium equation of the plate in the time domain to solve the force reconstruction problem, whereas previous work by the authors used this last equation in the frequency domain. As a result, it is possible to reconstruct load time history in addition to magnitude and location. Experimental results of this complete identification are presented for two different instrumented mechanical exciters: electrodynamic shaker and impact hammer for stationary and transient excitations, respectively. The approach is then applied to determine the location and time of multiple unknown transient excitations produced by a set of impacting metal marbles.
Species-Wide Collection of Escherichia coli Isolates for Examination of Genomic Diversity
Authors: Gangiredla Jayanthi , Mammel Mark K. , Barnaba Tammy J. , Tartera Carmen , Gebru Solomon T. , Patel Isha R. , Leonard Susan R. , Kotewicz Michael L. , Lampel Keith A. , Elkins Christopher A. , Lacher David W. 
Published: December 2017

ABSTRACT

Pathogenic and nonpathogenic
Escherichia coli
strains present a vast genomic diversity. We report the genome sequences of 2,244
E. coli
isolates from multiple animal and environmental sources. Their phylogenetic relationships and potential risk to human health were examined.
Complete Genome Sequence of Roe Deer Picobirnavirus Strain PBV/roe_deer/SLO/D38-14/2014
Authors: Kuhar Urska , Vengust Gorazd , Jamnikar-Ciglenecki Urska 
Published: December 2017

ABSTRACT
Picobirnaviruses (PBVs) have been detected in feces from various animal species and humans. Here, we report the complete genome sequence of the PBV/roe_deer/SLO/D38-14/2014 strain, which is the first PBV detected in roe deer, providing additional knowledge about the high diversity and host range of PBVs.
First Report of a Whole-Genome Shotgun Sequence of a Clinical Enterococcus faecalis Sequence Type 6 Strain from South Africa
Authors: Mbelle Nontombi Marylucy , Maningi Nontuthuko Excellent , Tshisevhe Vhudzani , Modipane Lesedi , Amoako Daniel Gyamfi , Osei Sekyere John 
Published: December 2017

ABSTRACT

Enterococcus faecalis
is a lactic acid-producing Gram-positive bacterium commonly found in the intestinal tract of humans and animals; it is implicated in multidrug-resistant nosocomial infections. The draft genome of this
E. faecalis
sequence type 6 (ST6) strain consists of 3,215,228 bp, with 37.20% GC content, 3,048 predicted coding sequences, and 61 RNA genes.
Nucleic Acid Amplification Test Quantitation as Predictor of Toxin Presence in Clostridium difficile Infection
Authors: Crobach M. J. T. , Duszenko N. , Terveer E. M. , Verduin C. M. , Kuijper E. J. 
Published: December 2017

ABSTRACT

Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) is among the most accurate methods for
Clostridium difficile
infection (CDI) diagnosis. The obvious shortcoming of this approach is that multiple tests must be performed to establish a CDI diagnosis, which may delay treatment. Therefore, we sought to determine whether a preliminary diagnosis could be made on the basis of the quantitative results of the first test in algorithmic testing, which provide a measure of organism burden. To do so, we retrospectively analyzed two large collections of samples (
n
= 2,669 and
n
= 1,718) that were submitted to the laboratories of two Dutch hospitals for CDI testing. Both hospitals apply a two-step testing algorithm in which a NAAT is followed by a toxin A/B EIA. Of all samples, 208 and 113 samples, respectively, tested positive by NAAT. Among these NAAT-positive samples, significantly lower mean quantification cycle (

C
q

) values were found for patients whose stool eventually tested positive for toxin, compared with patients who tested negative for toxin (mean

C
q

values of 24.4 versus 30.4 and 26.8 versus 32.2;
P
< 0.001 for both cohorts). Receiver operating characteristic curve analysis was performed to investigate the ability of

C
q

values to predict toxin status and yielded areas under the curve of 0.826 and 0.854. Using the optimal

C
q

cutoff values, prediction of the eventual toxin A/B EIA results was accurate for 78.9% and 80.5% of samples, respectively. In conclusion,

C
q

values can serve as predictors of toxin status but, due to the suboptimal correlation between the two tests, additional toxin testing is still needed.
Low Yield of FilmArray GI Panel in Hospitalized Patients with Diarrhea: an Opportunity for Diagnostic Stewardship Intervention
Authors: Hitchcock Matthew M. , Gomez Carlos A. , Banaei Niaz 
Published: December 2017

ABSTRACT

The FilmArray GI panel (BioFire Diagnostics, Salt Lake City, UT) is a multiplex, on-demand, sample-to-answer, real-time PCR assay for the syndromic diagnosis of infectious gastroenteritis that has become widely adopted and, in some instances, has replaced conventional stool culture and parasite exams. Conventional testing has historically been restricted among hospitalized patients due to low diagnostic yield, but it is not known whether use of the FilmArray GI panel should be circumscribed. Cary-Blair stool samples submitted for FilmArray GI panel in adult patients admitted to an academic hospital from August 2015 to January 2017 were included in this study. Of 481 tests performed >72 h after admission, 29 (6.0%) were positive, all for a single target, excluding
Clostridium difficile
. When follow-up tests beyond the first positive per hospitalization were excluded, 20 (4.8%) of 414 tests were positive. There was no difference in yield by immune status. Most targets detected were viral (79% of all positives [
n
= 23] and 70% in unique patients [
n
= 14]). All four cases positive for a bacterial target could not be confirmed and presentation was atypical, suggesting possible false positives. After removing potential false positives and chronic viral shedders, the yield was 3.0% (12/406). Repeat testing performed >72 h after admission and following a negative result within the first 72 h was done in 19 patients and 100% (22/22) remained negative. The FilmArray GI panel has low yield in adult patients hospitalized for >72 h, similar to conventional stool microbiology tests, and it is reasonable to restrict its use in this population.
Evaluation of a Novel Single-Tube Method for Extended Genotyping of Human Papillomavirus
Authors: Bhatia R. , Serrano I. , Wennington H. , Graham C. , Cubie H. , Boland E. , Fu G. , Cuschieri K. 
Published: December 2017

ABSTRACT
The use of high-risk human papillomavirus (HPV) testing for surveillance and clinical applications is increasing globally, and it is important that tests are evaluated to ensure they are fit for this purpose. In this study, the performance of a new HPV genotyping test, the Papilloplex high-risk HPV (HR-HPV) test, was compared to two well-established genotyping tests. Preliminary clinical performance was also ascertained for the detection of CIN2+ in a disease-enriched retrospective cohort. A panel of 500 cervical liquid-based cytology samples with known clinical outcomes were tested by the Papilloplex HR-HPV test. Analytical concordance was compared to two assays: a Linear Array (LA) HPV genotyping test and an Optiplex HPV genotyping test. The initial clinical performance for the detection for CIN2+ samples was performed and compared to that of two clinically validated HPV tests: a RealTime High-Risk HPV test (RealTime) and a Hybrid Capture 2 HPV test (HC2). High agreement for HR-HPV was observed between the Papilloplex and LA and Optiplex HPV tests (97 and 95%, respectively), with kappa values for HPV16 and HPV18 being 0.90 and 0.81 compared to the LA and 0.70 and 0.82 compared to the Optiplex test. The sensitivity, specificity, positive predictive value, and negative predictive value of the Papilloplex test for the detection of CIN2+ were 92, 54, 33, and 96%, respectively, and very similar to the values observed with RealTime and HC2. The Papilloplex HR-HPV test demonstrated a analytical performance similar to those of the two HPV genotyping tests at the HR-HPV level and the type-specific level. The preliminary data on clinical performance look encouraging, although further longitudinal studies within screening populations are required to confirm these findings.
Maintenance of AP-2-Dependent Functional Activities of Nef Restricts Pathways of Immune Escape from CD8 T Lymphocyte Responses
Authors: Schouest Blake , Weiler Andrea M. , Janaka Sanath Kumar , Myers Tereance A. , Das Arpita , Wilder Sarah C. , Furlott Jessica , Baddoo Melody , Flemington Erik K. , Rakasz Eva G. , Evans David T. , Friedrich Thomas C. , Maness Nicholas J. 
Published: December 2017

ABSTRACT

Nef-specific CD8
+
T lymphocytes (CD8TL) are linked to extraordinary control of primate lentiviral replication, but the mechanisms underlying their efficacy remain largely unknown. The immunodominant, Mamu-B*017:01
+
-restricted Nef
195-203
MW9 epitope in SIVmac239 partially overlaps a sorting motif important for interactions with host AP-2 proteins and, hence, downmodulation of several host proteins, including Tetherin (CD317/BST-2), CD28, CD4, SERINC3, and SERINC5. We reasoned that CD8TL-driven evolution in this epitope might compromise Nef's ability to modulate these important molecules. Here, we used deep sequencing of SIV from nine B*017:01
+
macaques throughout infection with SIVmac239 to characterize the patterns of viral escape in this epitope and then assayed the impacts of these variants on Nef-mediated modulation of multiple host molecules. Acute variation in multiple Nef
195-203
MW9 residues significantly compromised Nef's ability to downregulate surface Tetherin, CD4, and CD28 and reduced its ability to prevent SERINC5-mediated reduction in viral infectivity but did not impact downregulation of CD3 or major histocompatibility complex class I, suggesting the selective disruption of immunomodulatory pathways involving Nef AP-2 interactions. Together, our data illuminate a pattern of viral escape dictated by a selective balance to maintain AP-2-mediated downregulation while evading epitope-specific CD8TL responses. These data could shed light on mechanisms of both CD8TL-driven viral control generally and on Mamu-B*017:01-mediated viral control specifically.

IMPORTANCE
A rare subset of humans infected with HIV-1 and macaques infected with SIV can control the virus without aid of antiviral medications. A common feature of these individuals is the ability to mount unusually effective CD8 T lymphocyte responses against the virus. One of the most formidable aspects of HIV is its ability to evolve to evade immune responses, particularly CD8 T lymphocytes. We show that macaques that target a specific peptide in the SIV Nef protein are capable of better control of the virus and that, as the virus evolves to escape this response, it does so at a cost to specific functions performed by the Nef protein. Our results help show how the virus can be controlled by an immune response, which could help in designing effective vaccines.
Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1
Authors: Shen Zhou , Ye Gang , Deng Feng , Wang Gang , Cui Min , Fang Liurong , Xiao Shaobo , Fu Zhen F. , Peng Guiqing 
Published: December 2017

ABSTRACT

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic
Alphacoronavirus
, has caused enormous economic losses in the pork industry. Nonstructural protein 1 (nsp1) is a characteristic feature of alpha- and betacoronaviruses, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses. However, the detailed structure and molecular mechanisms underlying the
Alphacoronavirus
nsp1 inhibition of host gene expression remain unclear. Here, we report the first full-length crystal structure of
Alphacoronavirus
nsp1 from PEDV. The structure displays a six-stranded β-barrel fold in the middle of two α-helices. The core structure of PEDV nsp1 shows high similarity to those of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite its low degree of sequence homology. Using ribopuromycylation and
Renilla
luciferase reporter assays, we showed that PEDV nsp1 can dramatically inhibit general host gene expression. Furthermore, three motifs (amino acids [aa] 67 to 71, 78 to 85, and 103 to 110) of PEDV nsp1 create a stable functional region for inhibiting protein synthesis, differing considerably from
Betacoronavirus
nsp1. These results elucidate the detailed structural basis through which PEDV nsp1 inhibits host gene expression, providing insight into the development of a new attenuated vaccine with nsp1 modifications.

IMPORTANCE
Porcine epidemic diarrhea virus (PEDV) has led to tremendous economic losses in the global swine industry. PEDV nsp1 plays a crucial role in inhibiting host gene expression, but its functional mechanism remains unclear. Here, we report the full-length structure of PEDV nsp1, the first among coronaviruses to be reported. The 1.25-Å resolution crystal structure of PEDV nsp1 shows high similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1
13–128
and transmissible gastroenteritis virus (TGEV) nsp1
1–104
, despite a lack of sequence homology. Structural and biochemical characterization demonstrated that PEDV nsp1 possesses a stable functional region for inhibition of host protein synthesis, which is formed by loops at residues 67 to 71, 78 to 85, and 103 to 110. The different functional regions in PEDV nsp1 and SARS-CoV nsp1 may explain their distinct mechanisms. Importantly, our structural data are conducive to understanding the mechanism of PEDV nsp1 inhibition of the expression of host genes and may aid in the development of a new attenuated vaccine.
Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins
Authors: Turkington Hannah L. , Juozapaitis Mindaugas , Tsolakos Nikos , Corrales-Aguilar Eugenia , Schwemmle Martin , Hale Benjamin G. 
Published: December 2017

ABSTRACT
Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs.

IMPORTANCE
The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The recent discovery of influenza A-like viruses in bats has raised questions over whether these entities could be a threat to humans. Understanding unique properties of the newly described bat influenza A-like viruses, such as their mechanisms to infect cells or how they manipulate host functions, is critical to assess their likelihood of causing disease. Here, we characterized the bat influenza A-like virus NS1 protein, a key virulence factor, and found unexpected functional divergence of this protein from counterparts in other influenza A viruses. Our study dissects the molecular changes required by bat influenza A-like virus NS1 to adopt classical influenza A virus properties and suggests consequences of bat influenza A-like virus infection, potential future evolutionary trajectories, and intriguing virus-host biology in bat species.
Investigating the effect of sociodemographic factors on 30-day hospital readmission among medical patients in Toronto, Canada: a prospective cohort study
Authors: Smith Robert W , Kuluski Kerry , Costa Andrew P , Sinha Samir K , Glazier Richard H , Forster Alan , Jeffs Lianne 
Published: December 2017

ObjectiveTo examine the influence of patient-level sociodemographic factors on the incidence of hospital readmission within 30 days among medical patients in a large Canadian metropolitan city.DesignProspective cohort study.Setting and participantsPatients admitted to the General Internal Medicine service of an urban teaching hospital in Toronto, Canada participated in a survey of sociodemographic information. Patients were not surveyed if deemed medically unstable, receiving care in medical/surgical step-down beds or were isolated for infection control. Included in the final analysis was a diverse cohort of 1427 adult, non-palliative, patients who were discharged home.MeasuresThirteen patient-level sociodemographic variables were examined in relation to time to unplanned all-cause readmission within 30 days. Illness level was accounted for by the following covariates: self-perceived health status, previous hospital utilisation, primary diagnosis case mix group, Charlson Comorbidity Index score and inpatient length of stay.ResultsApproximately, 14.4% (n=205) of patients experienced readmission within 30 days. Sociodemographic factors were not significantly associated with time to readmission in unadjusted and adjusted analyses. Indicators of illness level, namely, previous hospitalisations, were the strongest risk factors for readmission within this cohort. One previous admission (adjusted HR 1.78; 95% CI 1.22 to 2.59, P<0.01) and at least four previous emergency department visits (adjusted HR 2.33; 95% CI 1.46 to 4.43, P<0.01) were associated with increased hazard of readmission within 30 days.ConclusionsPatient-level sociodemographic factors did not influence the incidence of unplanned all-cause readmission within 30 days. Further research is needed to understand the generalisability of our findings and investigate whether contextual factors, such as access to universal health insurance coverage, attenuate the effects of sociodemographic factors.
Ineficiencia económia y deuda de transparencia en México
Authors: Martínez Rodríguez María Concepción , Garcia Morales Maria Isabel , Vera Martínez Martin C. 
Published: December 2017

El presente trabajo analiza como se da la relación del gasto improductivo y la corrupción en México. Es un estudio descriptivo-exploratorio sobre el marco regulatorio del presupuesto y el gasto público, su ejercicio y la transparencia; se describe cómo opera éste, y cuales han sido los resultados. Se citan algunos ejemplos sobre el gasto improductivo y se esboza algunas recomendaciones y conclusiones.
Significance of Inducible Nonsustained Ventricular Tachycardias After Catheter Ablation for Ventricular Tachycardia in Ischemic Cardiomyopathy
Authors: Fujii Akira , Nagashima Koichi , Kumar Saurabh , Tanigawa Shinichi , Baldinger Samuel H. , Michaud Gregory F. , John Roy M. , Koplan Bruce A. , Tokuda Michifumi , Inada Keiichi , Tedrow Usha B. , Stevenson William G. 
Published: December 2017

Background
Noninducibility of sustained monomorphic ventricular tachycardia (SMVT) postablation does not insure absence of later recurrence in patients with ischemic cardiomyopathy. This study aims to determine the relation between inducible nonsustained VT postablation and VT recurrences.

Methods and Results

One hundred sixty-five consecutive patients (156 male; age 68±9 years) underwent ablation for SMVT because of ischemic cardiomyopathy; 44 patients who did not have induction testing or in whom only ventricular fibrillation was induced after ablation were excluded. In 38 patients (23%), SMVT was inducible (group C). Of the 83 patients without inducible SMVT after ablation, nonsustained VT defined as ≥5 beats lasting for <30 s, was induced in 34 patients (group B, 21%), whereas the remaining 49 patients had no VT induced by the induction test (group A, 30%). Over a median follow-up of 18.7 months, freedom from recurrent VT at 24 months was 60% in group A, 45% in group B (
P
=0.017 versus group A), and 38% in group C (
P
=0.005 versus group A). In patients without inducible SMVT, inducible nonsustained VT and left ventricular ejection fraction was independently associated with VT recurrence (hazard ratio, 3.66 and 1.07; 95% CI, 1.3–11.1 and 1.01–1.14).

Conclusions
Inducible nonsustained VT postablation suggests the continued presence of functional arrhythmia substrate. Further trials are needed to assess whether additional ablation would improve outcome in this group.