bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic Digital Analysis of Chromogenic Media for Vancomycin-Resistant-Enterococcus Screens Using Copan WASPLab
Authors: Faron Matthew L. , Buchan Blake W. , Coon Christopher , Liebregts Theo , van Bree Anita , Jansz Arjan R. , Soucy Genevieve , Korver John , Ledeboer Nathan A. 
Published: July 2016

ABSTRACT

Vancomycin-resistant enterococci (VRE) are an important cause of health care-acquired infections (HAIs). Studies have shown that active surveillance of high-risk patients for VRE colonization can aid in reducing HAIs; however, these screens generate a significant cost to the laboratory and health care system. Digital imaging capable of differentiating negative and “nonnegative” chromogenic agar can reduce the labor cost of these screens and potentially improve patient care. In this study, we evaluated the performance of the WASPLab Chromogenic Detection Module (CDM) (Copan, Brescia, Italy) software to analyze VRE chromogenic agar and compared the results to technologist plate reading. Specimens collected at 3 laboratories were cultured using the WASPLab CDM and plated to each site's standard-of-care chromogenic media, which included Colorex VRE (BioMed Diagnostics, White City, OR) or Oxoid VRE (Oxoid, Basingstoke, United Kingdom). Digital images were scored using the CDM software after 24 or 40 h of growth, and all manual reading was performed using digital images on a high-definition (HD) monitor. In total, 104,730 specimens were enrolled and automation agreed with manual analysis for 90.1% of all specimens tested, with sensitivity and specificity of 100% and 89.5%, respectively. Automation results were discordant for 10,348 specimens, and all discordant images were reviewed by a laboratory supervisor or director. After a second review, 499 specimens were identified as representing missed positive cultures falsely called negative by the technologist, 1,616 were identified as containing borderline color results (negative result but with no package insert color visible), and 8,234 specimens were identified as containing colorimetric pigmentation due to residual matrix from the specimen or yeast (
Candida
). Overall, the CDM was accurate at identifying negative VRE plates, which comprised 84% (87,973) of the specimens in this study.
Evaluation of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identification of KPC-Producing Klebsiella pneumoniae
Authors: Gaibani Paolo , Galea Anna , Fagioni Marco , Ambretti Simone , Sambri Vittorio , Landini Maria Paola 
Published: July 2016

ABSTRACT

We evaluated a real-time single-peak (11.109-Da) detection assay based on matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for the identification of
Klebsiella pneumoniae
carbapenemase (KPC)-producing
K. pneumoniae
. Our results demonstrated that the 11.109-Da peak was detected in 88.2% of the KPC producers. Analysis of
bla
KPC
-producing
K. pneumoniae
showed that the gene encoding the 11.109-Da protein was commonly (97.8%) associated with the Tn
4401
a isoform.
Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance
Authors: Kempf Brian J. , Peersen Olve B. , Barton David J. 
Published: July 2016

ABSTRACT

RNA recombination is important in the formation of picornavirus species groups and the ongoing evolution of viruses within species groups. In this study, we examined the structure and function of poliovirus polymerase, 3D
pol
, as it relates to RNA recombination. Recombination occurs when nascent RNA products exchange one viral RNA template for another during RNA replication. Because recombination is a natural aspect of picornavirus replication, we hypothesized that some features of 3D
pol
may exist, in part, to facilitate RNA recombination. Furthermore, we reasoned that alanine substitution mutations that disrupt 3D
pol
-RNA interactions within the polymerase elongation complex might increase and/or decrease the magnitudes of recombination. We found that an L420A mutation in 3D
pol
decreased the frequency of RNA recombination, whereas alanine substitutions at other sites in 3D
pol
increased the frequency of recombination. The 3D
pol
Leu420 side chain interacts with a ribose in the nascent RNA product 3 nucleotides from the active site of the polymerase. Notably, the L420A mutation that reduced recombination also rendered the virus more susceptible to inhibition by ribavirin, coincident with the accumulation of ribavirin-induced G→A and C→U mutations in viral RNA. We conclude that 3D
pol
Leu420 is critically important for RNA recombination and that RNA recombination contributes to ribavirin resistance.

IMPORTANCE
Recombination contributes to the formation of picornavirus species groups and the emergence of circulating vaccine-derived polioviruses (cVDPVs). The recombinant viruses that arise in nature are occasionally more fit than either parental strain, especially when the two partners in recombination are closely related, i.e., members of characteristic species groups, such as enterovirus species groups A to H or rhinovirus species groups A to C. Our study shows that RNA recombination requires conserved features of the viral polymerase. Furthermore, a polymerase mutation that disables recombination renders the virus more susceptible to the antiviral drug ribavirin, suggesting that recombination contributes to ribavirin resistance. Elucidating the molecular mechanisms of RNA replication and recombination may help mankind achieve and maintain poliovirus eradication.
Relative Contributions of Herpes Simplex Virus 1 ICP0 and vhs to Loss of Cellular IFI16 Vary in Different Human Cell Types
Authors: Orzalli Megan H. , Broekema Nicole M. , Knipe David M. 
Published: July 2016

ABSTRACT

The herpes simplex virus 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase that promotes the degradation of several host cell proteins. Most studies have found that ICP0 promotes the loss of IFI16 in infected cells, but one study reported that ICP0 was not necessary or sufficient for loss of IFI16 in a tumor-derived cell line. Therefore, in this study, we examined the requirement for ICP0 in promoting the loss of IFI16 in several normal and tumor-derived cell lines. HSV-1 infection resulted in an observable decrease of IFI16 protein levels in normal human foreskin fibroblasts (HFFs), normal oral keratinocytes (NOKs), and HeLa cells but not in U2OS cells. During infection with an ICP0-null virus, we observed a reduced loss of IFI16 in HFFs and NOKs but not in HeLa cells. Ectopic expression of ICP0 from a transfected plasmid was sufficient to promote the loss of IFI16 in HFFs and NOKs. In the absence of ICP0, we observed a delayed reduction of IFI16 protein that correlated with a reduction in the steady-state levels of
IFI16
mRNA. In addition, we show that the ICP0-independent loss of IFI16 in HeLa cells is dependent in part on the activity of the viral virion host shutoff (vhs) tegument protein. Together, these results demonstrate that HSV-1 promotes the loss of IFI16 through at least two mechanisms: (i) by ICP0-dependent degradation of IFI16 and (ii) by vhs-dependent turnover of
IFI16
mRNA. In addition, this study highlights a potential intrinsic difference between normal and tumor-derived cells for the activities of IFI16 and HSV-1 ICP0.

IMPORTANCE
HSV-1 is a ubiquitous virus that establishes a lifetime persistent infection in humans. The relative success of HSV-1 as a pathogen is, in part, dependent on the expression of viral proteins that counteract host intrinsic defense mechanisms and that modulate immune responses during viral infection. In this study, we examined the relative roles of two viral gene products for the ability to promote loss of the antiviral IFI16 DNA sensor. We demonstrate that the viral immediate early ICP0 protein plays a dominant role in the loss of IFI16 in normal, but not tumor-derived, human cell lines. In contrast, viral vhs-mediated loss of IFI16 by mRNA destabilization is revealed to be dominant in tumor-derived cells in which ICP0 is nonfunctional. Together, these results contribute to our understanding of how HSV-1 modulates IFI16 protein levels and highlight cell-type-dependent differences between normal and tumor-derived cells.
Myristoylation of the Arenavirus Envelope Glycoprotein Stable Signal Peptide Is Critical for Membrane Fusion but Dispensable for Virion Morphogenesis
Authors: York Joanne , Nunberg Jack H. 
Published: July 2016

ABSTRACT
Arenaviruses are responsible for severe and often fatal hemorrhagic disease. In the absence of effective antiviral therapies and vaccines, these viruses pose serious threats to public health and biodefense. Arenaviruses enter the host cell by fusion of the viral and endosomal membranes, a process mediated by the virus envelope glycoprotein GPC. Unlike other class I viral fusion proteins, GPC retains its stable signal peptide (SSP) as an essential third subunit in the mature complex. SSP spans the membrane twice and is myristoylated at its cytoplasmic N terminus. Mutations that abolish SSP myristoylation have been shown to reduce pH-induced cell-cell fusion activity of ectopically expressed GPC to ∼20% of wild-type levels. In order to examine the role of SSP myristoylation in the context of the intact virus, we used reverse genetics to generate Junín viruses (Candid #1 isolate) in which the critical glycine-2 residue in SSP was either replaced by alanine (G2A) or deleted (ΔG2). These mutant viruses produced smaller foci of infection in Vero cells and showed an ∼5-fold reduction in specific infectivity, commensurate with the defect in cell-cell fusion. However, virus assembly and GPC incorporation into budded virions were unaffected. Our findings suggest that the myristate moiety is cryptically disposed in the prefusion GPC complex and may function late in the fusion process to promote merging of the viral and cellular membranes.

IMPORTANCE
Hemorrhagic fever arenaviruses pose significant threats to public health and biodefense. Arenavirus entry into the host cell is promoted by the virus envelope glycoprotein GPC. Unlike other viral envelope glycoproteins, GPC contains a myristoylated stable signal peptide (SSP) as an essential third subunit. Myristoylation has been shown to be important for the membrane fusion activity of recombinantly expressed GPC. Here, we use reverse genetics to study the role of SSP myristoylation in the context of the intact virion. We find that nonmyristoylated GPC mutants of the Candid #1 strain of Junín virus display a commensurate deficiency in their infectivity, albeit without additional defects in virion assembly and budding. These results suggest that SSP myristoylation may function late in the fusion process to facilitate merging of the viral and cellular membranes. Antiviral agents that target this novel aspect of GPC membrane fusion may be useful in the treatment of arenavirus hemorrhagic fevers.
Linking e-health records, patient-reported symptoms and environmental exposure data to characterise and model COPD exacerbations: protocol for the COPE study
Authors: Moore Elizabeth , Chatzidiakou Lia , Jones Roderic L , Smeeth Liam , Beevers Sean , Kelly Frank J , K Quint Jennifer , Barratt Benjamin 
Published: July 2016

IntroductionRelationships between exacerbations of chronic obstructive pulmonary disease (COPD) and environmental factors such as temperature, humidity and air pollution are not well characterised, due in part to oversimplification in the assignment of exposure estimates to individuals and populations. New developments in miniature environmental sensors mean that patients can now carry a personal air quality monitor for long periods of time as they go about their daily lives. This creates the potential for capturing a direct link between individual activities, environmental exposures and the health of patients with COPD. Direct associations then have the potential to be scaled up to population levels and tested using advanced human exposure models linked to electronic health records.Methods and analysisThis study has 5 stages: (1) development and deployment of personal air monitors; (2) recruitment and monitoring of a cohort of 160 patients with COPD for up to 6 months with recruitment of participants through the Clinical Practice Research Datalink (CPRD); (3) statistical associations between personal exposure with COPD-related health outcomes; (4) validation of a time-activity exposure model and (5) development of a COPD prediction model for London.Ethics and disseminationThe Research Ethics Committee for Camden and Islington has provided ethical approval for the conduct of the study. Approval has also been granted by National Health Service (NHS) Research and Development and the Independent Scientific Advisory Committee. The results of the study will be disseminated through appropriate conference presentations and peer-reviewed journals.
Delayed infarction following aneurysmal subarachnoid hemorrhage: Can the role of severe angiographic vasospasm really be dismissed?
Authors: Mortimer Alex M , Steinfort Brendan , Faulder Ken , Harrington Timothy 
Published: July 2016

BackgroundThe recent literature pertaining to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage has downplayed the role of angiographic vasospasm. However, it is our hypothesis that angiographic vasospasm has a significant pathophysiological role in this disease. We undertook an observational radiographic study of patients who presented in a delayed manner (>72 h from ictus) with evidence of severe angiographic vasospasm on initial angiography in order to describe an apparent association between vasospasm and infarct location.MethodsThis was a retrospective study of consecutive patients treated at our unit. Initial, subsequent, and follow-up cross-sectional imaging with CT or MRI was analyzed in conjunction with initial angiography. Sites of angiographic narrowing, angiographic hypoperfusion, and subsequent sites of infarction were assessed.ResultsThirteen patients (6 women, 7 men) of mean age 49 years were assessed. Mean time to presentation was 6 days. All had severe angiographic vasospasm. Nine of the 13 patients suffered infarction; the infarcts in seven of the nine patients were large. There was correlation between sites of angiographic narrowing and infarction in all cases and eight of the nine cases showed angiographic hypoperfusion in a location corresponding to eventual infarct location.ConclusionsSevere angiographic vasospasm may be linked to infarction in patients who present late. These infarcts are mostly large despite maximal treatment. We question the notion that proximal vasospasm has a minor role in delayed ischemia.
Deflection of the progradational axis and asymmetry in tidal seaway and strait deltas: insights from two outcrop case studies
Authors: Longhitano Sergio G. , Steel Ron J. 
Published: July 2016

Abstract
Deltas represent the major sediment source for tectonically confined, tide-dominated seaways or straits. Modern examples show how along-shore tidal currents are able to modify the impinging delta shape, generating asymmetrical coastal plains, deflected delta fronts and elongate sandbanks. Seaway or strait deltas can become become tide-influenced or tide-dominated, assuming physical attributes that may depart from classical models. Ancient deltas in seaways and straits can also reveal unexpected facies stacking and stratigraphies, which can be misinterpreted or attributed to different depositional settings. Two ancient analogues of deltas that prograded into elongate basins dominated by amplified tidal currents are presented here. A common element in these deltas is the progressive-upwards change in the dominant process of sediment dispersion recorded in the delta facies. Early stages of progradation are dominated by river- and wave-influenced lithofacies, whereas late deltaic advancements occur with a dominance of tidal current circulation on the delta fronts and the consequent morphologies are deflected/elongated in the direction of tidal flow. This study provides the basis for a preliminary stratigraphic framework for the depositional style of these types of delta. The studied deposits also suggest analogies with the spatial distribution of many hydrocarbon reservoirs investigated along the margins of confined, narrow, linear basins, the interpretation of which is still debated.
Moho and basement depth in the NE Atlantic Ocean based on seismic refraction data and receiver functions
Authors: Funck Thomas , Geissler Wolfram H. , Kimbell Geoffrey S. , Gradmann Sofie , Erlendsson Ögmundur , McDermott Kenneth , Petersen Uni K. 
Published: July 2016

Abstract

Seismic refraction data and results from receiver functions were used to compile the depth to the basement and Moho in the NE Atlantic Ocean. For interpolation between the unevenly spaced data points, the kriging technique was used. Free-air gravity data were used as constraints in the kriging process for the basement. That way, structures with little or no seismic coverage are still presented on the basement map, in particular the basins off East Greenland. The rift basins off NW Europe are mapped as a continuous zone with basement depths of between 5 and 15 km. Maximum basement depths off NE Greenland are 8 km, but these are probably underestimated. Plate reconstructions for Chron C24 (
c.
54 Ma) suggest that the poorly known Ammassalik Basin off SE Greenland may correlate with the northern termination of the Hatton Basin at the conjugate margin. The most prominent feature on the Moho map is the Greenland–Iceland–Faroe Ridge, with Moho depths >28 km. Crustal thickness is compiled from the Moho and basement depths. The oceanic crust displays an increased thickness close to the volcanic margins affected by the Iceland plume.
ATM Mutations in Cancer: Therapeutic Implications
Authors: Choi Michael , Kipps Thomas , Kurzrock Razelle 
Published: July 2016

AbstractActivation of checkpoint arrest and homologous DNA repair are necessary for maintenance of genomic integrity during DNA replication. Germ-line mutations of the ataxia telangiectasia mutated (ATM) gene result in the well-characterized ataxia telangiectasia syndrome, which manifests with an increased cancer predisposition, including a 20% to 30% lifetime risk of lymphoid, gastric, breast, central nervous system, skin, and other cancers. Somatic ATM mutations or deletions are commonly found in lymphoid malignancies, as well as a variety of solid tumors. Such mutations may result in chemotherapy resistance and adverse prognosis, but may also be exploited by existing or emerging targeted therapies that produce synthetic lethal states. Mol Cancer Ther; 15(8); 1781–91. ©2016 AACR.
Microparticles reveal cell activation during IVF – a possible early marker of a prothrombotic state during the first trimester
Authors: Mobarrez Fariborz , Wallen Håkan , Westerlund Eli , Hovatta Outi , Henriksson Peter , Olausson Nina 
Published: July 2016

SummaryCell-derived microparticles (MPs) are known to be elevated in a number of diseases related to arterial and venous thromboembolism (VTE), such as acute myocardial infarction, VTE (deep-vein thrombosis and pulmonary embolism) and peripheral arterial disease. IVF-associated pregnancies have previously been shown to be associated with an increased incidence of VTE, mechanisms behind being unknown and sparsely studied. Our objective was to assess cell activation during IVF through analysis of MP levels and phenotype following ovarian stimulation. Thirty-one women undergoing IVF were included and blood samples were collected at down regulation of oestrogen and at high level stimulation with 10- to 100-fold increased endogenous oestrogen levels. MPs were analysed by flow cytometry and phenotyped according to size and protein expression. We found that overall phosphatidylserine positive platelet-, endothelial- and monocyte-derived MPs significantly increased following ovarian stimulation with increased levels of platelet activation markers CD40 ligand and P-selectin. Furthermore, there was an increase in endothelial-derived MPs exposing activation marker E-selectin and monocyte-derived MPs, while neutrophil-derived MPs decreased slightly. In conclusion we found a major increase in MPs and markers indicating cell activation in parallel with the profound oestrogen boost during IVF. To assess whether these changes in MPs are associated with thromboembolic events requires extended longitudinal studies.
Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction
Authors: Srivaratharajah Kajenny , Coutinho Thais , deKemp Robert , Liu Peter , Haddad Haissam , Stadnick Ellamae , Davies Ross A. , Chih Sharon , Dwivedi Girish , Guo Ann , Wells George A. , Bernick Jordan , Beanlands Robert , Mielniczuk Lisa M. 
Published: July 2016

Background—
There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. The aim of this study was to determine whether abnormalities exist in MFR in patients with HFpEF without epicardial coronary artery disease.

Methods and Results—

A total of 376 patients with ejection fraction ≥50%, no known history of obstructive coronary artery disease, and a confirmed diagnosis of heart failure (n=78) were compared with patients with no evidence of heart failure (n=298), further stratified into those with (n=186) and without (n=112) hypertension. Global and regional left ventricular MFR was calculated as stress/rest myocardial blood flow using Rb-82 positron emission tomography. Patients with HFpEF were more likely to be older, female, and have comorbid hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, anemia, and renal dysfunction. HFpEF was associated with a significant reduction in global MFR (2.16±0.69 in HFpEF versus 2.54±0.80 in hypertensive controls;
P
<0.02 and 2.89±0.70 in normotensive controls;
P
<0.001). A diagnosis of HFpEF was associated with 2.62 times greater unadjusted odds of having low global MFR (defined as <2.0) and remained a significant predictor of reduced global MFR after adjusting for comorbidities.

Conclusions—
HFpEF, in the absence of known history for obstructive epicardial coronary artery disease, is associated with reduced MFR independent of other risk factors.