bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Vertical Linkages Limit Protectionism? Switzerland in the Multifibre Arrangement
Authors: Weder Rolf , Wyss Simone 
Published: March 2013

AbstractThe multifibre arrangement (MFA) heavily restricted the world trade in textiles and clothing (T&C) from 1974 to 1994. Switzerland joined the MFA as one of 44 signatory economies in 1974, but never applied its discriminatory instruments. To explain this peculiar behaviour, we apply international trade theory as well as files gathered from the Swiss Federal Archives. Our analysis suggests that Switzerland used the MFA, first, as an instrument to seek better market access, and second, as an option to protect its T&C industry if required. Switzerland refrained, however, from exercising the option mainly because of the existence of an important vertically related export industry, that is the Swiss textile machinery industry.
Comparison of mitotic index and Ki67 index in the prognostication of canine cutaneous mast cell tumours
Authors: Berlato D. , Murphy S. , Monti P. , Stewart J. , Newton J. R. , Flindall A. , Maglennon G. A. 
Published: March 2013

AbstractProliferation markers are commonly used for prognostication of mast cell tumours. The aim of the study is to compare the relative abilities of Ki67 and mitotic index to predict survival in the same cohort of dogs with cutaneousMCTs. Histological grade, mitotic index and Ki67 index were performed in all samples and clinical information was obtained by a follow‐up questionnaire. Ninety‐five dogs were included in the study with a median follow‐up of 1145 days. Survival times varied significantly between categories of histological grade, mitotic index and Ki67 index. Multivariable analyses showed that the risk of dying due toMCTwas similar in dogs with increased Ki67 index [hazard ratio,HR: 3.0 (95% CI 1.3–6.8)] or increased mitotic index [HR: 2.7 (95% CI 1.1–6.5)]. In conclusion, both mitotic index and Ki67 index were able to independently differentiateMCTswith worse prognosis. This distinction is particularly meaningful in selecting intermediate gradeMCTsthat may benefit from more aggressive local or systemic treatment.
Adaptive Evolution of Multiple Traits Through Multiple Mutations at a Single Gene
Authors: Linnen Catherine R. , Poh Yu-Ping , Peterson Brant K. , Barrett Rowan D. H. , Larson Joanna G. , Jensen Jeffrey D. , Hoekstra Hopi E. 
Published: March 2013

Additive EffectsAlthough specific genes involved in animal coloration have been identified, the underlying selection for genetic variation in color-specific adaptation is not well understood. Examining theAgoutigene and other loci in the deer mice of Nebraska, where predation selects for light-colored mice in light environments and dark-colored mice in dark environments,Linnenet al.(p.1312) find evidence of multiple genetic variants under selection affecting coloration. The light color of Sand Hills mice is not the result of a single large-effect mutation, but is because of many accumulated mutations, each with a smaller phenotypic effect.
Sensitive Cell-Based Assay for Determination of Human Immunodeficiency Virus Type 1 Coreceptor Tropism
Authors: Weber Jan , Vazquez Ana C. , Winner Dane , Gibson Richard M. , Rhea Ariel M. , Rose Justine D. , Wylie Doug , Henry Kenneth , Wright Alison , King Kevin , Archer John , Poveda Eva , Soriano Vicente , Robertson David L. , Olivo Paul D. , Arts Eric J. , Quiñones-Mateu Miguel E. 
Published: March 2013

ABSTRACTCCR5 antagonists are a powerful new class of antiretroviral drugs that require a companion assay to evaluate the presence of CXCR4-tropic (non-R5) viruses prior to use in human immunodeficiency virus (HIV)-infected individuals. In this study, we have developed, characterized, verified, and prevalidated a novel phenotypic test to determine HIV-1 coreceptor tropism (VERITROP) based on a sensitive cell-to-cell fusion assay. A proprietary vector was constructed containing a near-full-length HIV-1 genome with the yeast uracil biosynthesis (URA3) gene replacing the HIV-1envcoding sequence. Patient-derived HIV-1 PCR products were introduced by homologous recombination using an innovative yeast-based cloning strategy. Theenv-expressing vectors were then used in a cell-to-cell fusion assay to determine the presence of R5 and/or non-R5 HIV-1 variants within the viral population. Results were compared with (i) the original version of Trofile (Monogram Biosciences, San Francisco, CA), (ii) population sequencing, and (iii) 454 pyrosequencing, with the genotypic data analyzed using several bioinformatics tools, i.e., the 11/24/25 rule, Geno2Pheno (2% to 5.75%, 3.5%, or 10% false-positive rate [FPR]), and webPSSM. VERITROP consistently detected minority non-R5 variants from clinical specimens, with an analytical sensitivity of 0.3%, with viral loads of ≥1,000 copies/ml, and from B and non-B subtypes. In a pilot study, a 73.7% (56/76) concordance was observed with the original Trofile assay, with 19 of the 20 discordant results corresponding to non-R5 variants detected using VERITROP and not by the original Trofile assay. The degree of concordance of VERITROP and Trofile with population and deep sequencing results depended on the algorithm used to determine HIV-1 coreceptor tropism. Overall, VERITROP showed better concordance with deep sequencing/Geno2Pheno at a 0.3% detection threshold (67%), whereas Trofile matched better with population sequencing (79%). However, 454 sequencing using Geno2Pheno at a 10% FPR and 0.3% threshold and VERITROP more accurately predicted the success of a maraviroc-based regimen. In conclusion, VERITROP may promote the development of new HIV coreceptor antagonists and aid in the treatment and management of HIV-infected individuals prior to and/or during treatment with this class of drugs.
Neutralization of Antimicrobial Substances in New BacT/Alert FA and FN Plus Blood Culture Bottles
Authors: Mitteregger Dieter , Barousch Wolfgang , Nehr Marion , Kundi Michael , Zeitlinger Markus , Makristathis Athanasios , Hirschl Alexander M. 
Published: March 2013

ABSTRACT

Time to detection (TTD) in automated blood culture systems is delayed for sensitive microorganisms in the presence of antimicrobial substances and has been associated with worse outcomes for sepsis patients on inadequate empirical therapy. While resin addition removes antimicrobial substances to various degrees from blood culture media, media formulations and the blend of resins may influence performance. The BacT/Alert 3D system (bioMérieux) was investigated using the new resin-containing medium types FA Plus (aerobic) and FN Plus (anaerobic). TTD was compared between control and test bottles containing relevant bacteria or
Candida albicans
, with and without defined concentrations of antimicrobials. Failure of neutralization was defined as a negative blood culture on day 3. In general, growth delay was nonlinear, concentration dependent, bottle type specific, and reciprocally associated with MICs. Substance-specific serum drug concentrations corresponding to a predefined, clinically relevant 3-h delay of TTD were calculated. Where appropriate, a time interval allowing for drug elimination below this critical level was obtained by pharmacokinetic modeling. Clarithromycin, clindamycin, gentamicin, linezolid, tigecycline, vancomycin, and fluconazole were neutralized. For ciprofloxacin and piperacillin-tazobactam, which were only incompletely neutralized in combination with the most sensitive test strains, a maximum waiting time for blood draw of 1 h was determined based on pharmacokinetics. One or more test strains did not grow in bottles containing either amoxicillin-clavulanate, cefepime, cefotaxime, meropenem, or metronidazole, and we thus recommend particular caution in timing of blood draws if patients have been pretreated with these agents.
Serial Testing from a 3-Day Collection Period by Use of the Bartonella Alphaproteobacteria Growth Medium Platform May Enhance the Sensitivity of Bartonella Species Detection in Bacteremic Human Patients
Authors: Pultorak Elizabeth L. , Maggi Ricardo G. , Mascarelli Patricia E. , Breitschwerdt Edward B. 
Published: March 2013

ABSTRACTPatients with infection from bacteremicBartonellaspp., tested usingBartonella Alphaproteobacteriagrowth medium (BAPGM), were retrospectively categorized into one of two groups that included those whose blood was collected once (group 1;n= 55) or three times (group 2;n= 36) within a 1-week period. Overall, 19 patients (20.8%) were PCR positive for one or moreBartonellaspp. using the BAPGM platform. Seven patients (12.7%) in group 1 tested positive, and 12 patients (33.3%) in group 2 tested positive. Detection was improved when the patients were tested three times within a 1-week period (odds ratio, 3.4 [95% confidence interval, 1.2 to 9.8];P= 0.02). Obtaining three sequential blood samples during a 1-week period should be considered a diagnostic approach when bartonellosis is suspected.
Next-Generation Antimicrobial Susceptibility Testing
Authors: van Belkum Alex , Dunne W. Michael 
Published: March 2013

ABSTRACT
Antimicrobial resistance has emerged as one of the most-significant health care problems of the new millennium, and the clinical microbiology laboratory plays a central role in optimizing the therapeutic management of patients with infection. This minireview explores the potential value of innovative methods for antimicrobial susceptibility testing of microorganisms that could provide valuable alternatives to existing methodologies in the very near future.
Comparison of the Abbott
m
2000 RealTi
m
e CT Assay and the Cepheid GeneXpert CT/NG Assay to the Roche Amplicor CT Assay for Detection of Chlamydia trachomatis in Ocular Samples from Tanzania
Authors: Dize Laura , West Sheila , Williams James A. , Van Der Pol Barbara , Quinn Thomas C. , Gaydos Charlotte A. 
Published: March 2013

ABSTRACT

The GeneXpert CT/NG assay (GeneXpert) and the Abbott
m
2000 RealTi
m
e CT (
m
2000) assay were compared to Amplicor for detecting ocular
Chlamydia trachomatis
. Discordant specimens were tested by the Aptima CT assay. The
m
2000 assay sensitivity was 100% (95% confidence interval [CI], 90% to 100%), and specificity was 98.46% (95% CI, 95.2% to 99.2%); GeneXpert sensitivity was 100% (95% CI, 90% to 100%), and specificity was 100% (95% CI, 98.1% to 100%). The
m
2000 and GeneXpert assays appear to perform as well as the Amplicor assay.
Nasopharyngeal Carriage of Klebsiella pneumoniae and Other Gram-Negative Bacilli in Pneumonia-Prone Age Groups in Semarang, Indonesia
Authors: Farida Helmia , Severin Juliëtte A. , Gasem M. Hussein , Keuter Monique , van den Broek Peterhans , Hermans Peter W. M. , Wahyono Hendro , Verbrugh Henri A. 
Published: March 2013

ABSTRACT

Gram-negative bacilli (GNB) cause many cases of pneumonia in Indonesia. We investigated nasopharyngeal carriage of GNB in Semarang, Indonesia.
Klebsiella pneumoniae
carriage in adults (15%) was higher than in children (7%) (
P
= 0.004), while that of other GNB was comparable. Poor food and water hygiene are determinants of carriage of these bacteria.
Multilaboratory Study of the Biomic Automated Well-Reading Instrument versus MicroScan WalkAway for Reading MicroScan Antimicrobial Susceptibility and Identification Panels
Authors: Fader Robert C. , Weaver Emily , Fossett Rhonda , Toyras Michele , Vanderlaan John , Gibbs David , Wang Andrew , Thierjung Nikolaus 
Published: March 2013

ABSTRACT
This study compared the Biomic automated well reader results to the MicroScan WalkAway results for reading MicroScan antimicrobial susceptibility and identification panels at four different sites. Routine fresh clinical isolates and quality control (QC) organisms were tested at each study site. A total of 46,176 MicroScan panel drug-organism combinations were read. The Biomic category agreement for 3,117 Gram-negative bacteria was 98.4%, with 1.4% minor and 0.2% major discrepancies. The Biomic category agreement for 5,233 Gram-positive bacteria was 98.7%, with 0.9% minor, 0.3% major, and 0.1% very major errors. Essential agreement, defined as Biomic results that were within ±1 2-fold dilution of the MicroScan results, was 99.3% for Gram-negative bacteria and 98.3% for Gram-positive bacteria. Biomic reading of MicroScan identification panels provided an overall agreement (first- and second-choice organism match) of 99.5% with 846 Gram-negative isolates and 99.5% with 430 Gram-positive isolates. These results suggest that the Biomic automated reader can provide accurate reading of MicroScan panels and has the capability of a visual panel read for manual adjustment of results.
Comparison of the Biofire FilmArray RP, Genmark eSensor RVP, Luminex xTAG RVPv1, and Luminex xTAG RVP Fast Multiplex Assays for Detection of Respiratory Viruses
Authors: Popowitch Elena B. , O'Neill Stacey S. , Miller Melissa B. 
Published: March 2013

ABSTRACT

There are several U.S. FDA-cleared molecular respiratory virus panels available today, each with advantages and disadvantages. This study compares four multiplex panels, the BioFire Diagnostics FilmArray RP (
r
espiratory
p
anel), the GenMark Dx eSensor RVP (
r
espiratory
v
iral
p
anel), the Luminex xTAG RVPv1, and the Luminex xTAG RVP fast. Three hundred specimens (200 retrospective and 100 consecutive) were tested using all four platforms to determine performance characteristics. The overall sensitivity and specificity, respectively, and 95% confidence interval (CI; in parentheses) for each panel were as follows: FilmArray RP, 84.5% (79.2, 88.6) and 100% (96.2, 100); eSensor RVP, 98.3% (95.5, 99.5) and 99.2% (95.4, 100); xTAG RVPv1, 92.7% (88.5, 95.4) and 99.8% (96.0, 100); and xTAG RVP fast, 84.4% (78.5, 88.9) and 99.9% (96.1, 100). The sensitivity of each assay fluctuated by viral target, with the greatest discrepancies noted for adenovirus and influenza virus B detection. Hands-on time and time to result were recorded and ease of use was assessed to generate a complete profile of each assay.
Comparative Epidemiology of Staphylococcus epidermidis Isolates from Patients with Catheter-Related Bacteremia and from Healthy Volunteers
Authors: Cherifi S. , Byl B. , Deplano A. , Nonhoff C. , Denis O. , Hallin M. 
Published: March 2013

ABSTRACT

Staphylococcus epidermidis
is a major cause of catheter-related bloodstream infections (CRBSIs). Recent studies suggested the existence of well-adapted, highly resistant, hospital-associated
S. epidermidis
clones. The molecular epidemiology of
S. epidermidis
in Belgian hospitals and the Belgian community has not been explored yet. We compared a set of 33
S. epidermidis
isolates causing CRBSI in hospitalized patients with a set of 33 commensal
S. epidermidis
isolates. The factors analyzed included resistance to antibiotics and genetic diversity as determined by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and SCC
mec
typing. Additionally, the presence of virulence-associated mobile genetic elements, the
ica
operon and the arginine catabolic mobile element (ACME), was assessed and compared against clinical data. CRBSI
S. epidermidis
isolates were significantly resistant to more antibiotics than commensal
S. epidermidis
isolates. The two populations studied were very diverse and genetically distinct as only 23% of the 37 PFGE types observed were harbored by both CRBSI and commensal isolates. ACME was found in 76% of
S. epidermidis
strains, regardless of their origin, while the
ica
operon was significantly more prevalent in CRBSI isolates than in commensal isolates (
P
< 0.05). Nine patients presented a clinically severe CRBSI, eight cases of which were due to an
ica
-positive multiresistant isolate belonging to sequence type 2 (ST2) or ST54.
S. epidermidis
isolates causing CRBSI were more resistant and more often
ica
positive than commensal
S. epidermidis
isolates, which were genetically heterogeneous and susceptible to the majority of antibiotics tested. Clinically severe CRBSIs were due to isolates belonging to two closely related MLST types, ST2 and ST54.
Human Cytomegalovirus Inhibits Apoptosis by Proteasome-Mediated Degradation of Bax at Endoplasmic Reticulum-Mitochondrion Contacts
Authors: Zhang Aiping , Hildreth Richard L. , Colberg-Poley Anamaris M. 
Published: March 2013

ABSTRACTHuman cytomegalovirus (HCMV) encodes the UL37 exon 1 protein (pUL37x1), which is the potent viral mitochondrion-localized inhibitor of apoptosis (vMIA), to increase survival of infected cells. HCMV vMIA traffics from the endoplasmic reticulum (ER) to ER subdomains, which are physically linked to mitochondria known as mitochondrion-associated membranes (MAM), and to mitochondria. The antiapoptotic function of vMIA is thought to primarily result from its ability to inhibit Bax-mediated permeabilization of the outer mitochondrial membrane (OMM). Here, we establish that vMIA retargets Bax to the MAM as well as to the OMM from immediate early through late times of infection. However, MAM localization of Bax results in its increased ubiquitination and proteasome-mediated degradation. Surprisingly, HCMV infection does not increase OMM-associated degradation (OMMAD) of Bax, even though the ER and mitochondria are physically connected at the MAM. It was recently found that lipid rafts at the plasma membrane can connect extrinsic and intrinsic apoptotic pathways and can serve as sites of apoptosome assembly. In transfected permissive human fibroblasts, vMIA mediates, through its cholesterol affinity, association of Bax and apoptosome components with MAM lipid rafts. While Bax association with MAM lipid rafts was detected in HCMV-infected cells, association of apoptosome components was not. These results establish that Bax recruitment to the MAM and its MAM-associated degradation (MAMAD) are a newly described antiapoptotic mechanism used by HCMV infection to increase cell survival for its growth.
Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis
Authors: Belser Jessica A. , Davis C. Todd , Balish Amanda , Edwards Lindsay E. , Zeng Hui , Maines Taronna R. , Gustin Kortney M. , Martínez Irma López , Fasce Rodrigo , Cox Nancy J. , Katz Jacqueline M. , Tumpey Terrence M. 
Published: March 2013

ABSTRACT
H7 subtype influenza A viruses, responsible for numerous outbreaks in land-based poultry in Europe and the Americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. The emergence of a highly pathogenic avian influenza H7N3 virus in poultry throughout the state of Jalisco, Mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (A/Mexico/InDRE7218/2012 [MX/7218]) and related avian H7 subtype viruses in mouse and ferret models. Several high- and low-pathogenicity H7N3 and H7N9 viruses replicated efficiently in the respiratory tract of mice without prior adaptation following intranasal inoculation, but only MX/7218 virus caused lethal disease in this species. H7N3 and H7N9 viruses were also detected in the mouse eye following ocular inoculation. Virus from both H7N3 and H7N9 subtypes replicated efficiently in the upper and lower respiratory tracts of ferrets; however, only MX/7218 virus infection caused clinical signs and symptoms and was capable of transmission to naive ferrets in a direct-contact model. Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high titers in human bronchial epithelial cells, yet it downregulated numerous genes related to NF-κB-mediated signaling transduction. These findings indicate that the recently isolated North American lineage H7 subtype virus associated with human conjunctivitis is capable of causing severe disease in mice and spreading to naive-contact ferrets, while concurrently retaining the ability to replicate within ocular tissue and allowing the eye to serve as a portal of entry.
Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function
Authors: Kim Hangeun , Meyer Keith , Di Bisceglie Adrian M. , Ray Ranjit 
Published: March 2013

ABSTRACTHepatitis C virus (HCV) proteins inhibit complement component expression, which may attenuate immunity against infection. In this study, we examined whether HCV regulates the membrane attack complex (MAC) via complement component C9. MAC is composed of C5b to C9 (C5b-9) and mediates cell lysis of invaded pathogens. Liver biopsy specimens from chronically HCV-infected patients exhibited a lower level of C9 mRNA expression than liver biopsy specimens from unrelated disease or healthy control human liver RNA. Hepatocytes infected with cell culture-grown HCV or expressing HCV core protein also displayed significant repression of C9 mRNA and protein levels. Promoter analysis suggested that the T cell factor-4 (TCF-4E) transcription factor is responsible for HCV core-mediated C9 promoter regulation. Sera from chronically HCV-infected patients displayed a lower level of C5b-9 and a reduced antimicrobial effect on model organisms compared to unrelated patient sera or sera from healthy volunteers. Together, these results for C9 regulation by HCV core protein coupled with functional impairment of the membrane attack complex underscore HCV-mediated attenuation of immune mechanisms.
Directed Evolution of Mutator Adenoviruses Resistant to Antibody Neutralization
Authors: Myers Nicolle D. , Skorohodova Ksenia V. , Gounder Anshu P. , Smith Jason G. 
Published: March 2013

ABSTRACT
We incorporated a previously identified mutation that reduces the fidelity of the DNA polymerase into a human adenovirus vector. Using this mutator vector, we demonstrate rapid selection of resistance to a neutralizing anti-hexon monoclonal antibody due to a G434D mutation in hexon that precludes antibody binding. Since mutator adenoviruses can accumulate compound mutations that are unattainable using traditional random mutagenesis techniques, this approach will be valuable to the study of antivirals and host factor interactions.
Herpes Simplex Virus 2 Expresses a Novel Form of ICP34.5, a Major Viral Neurovirulence Factor, through Regulated Alternative Splicing
Authors: Tang Shuang , Guo Nini , Patel Amita , Krause Philip R. 
Published: March 2013

ABSTRACT
Herpes simplex virus 1 (HSV-1) and HSV-2, two closely related neurotropic human herpesviruses, achieve neurotropism through ICP34.5, a major viral neurovirulence factor. In this report, in addition to the full-length 38-kDa protein (ICP34.5α), we identified a 28-kDa novel form of ICP34.5 (ICP34.5β) in HSV-2-infected cells. ICP34.5β is translated from unspliced ICP34.5 mRNA, with the retained intron introducing a premature stop codon. Thus, ICP34.5β lacks the C-terminal conserved GADD34 domain but includes 19 additional amino acids encoded by the intron. Although a fraction of both HSV-2 ICP34.5 proteins are detected in the nucleolus, ICP34.5α is predominantly located in cytoplasm, and ICP34.5β is mainly detected more diffusely in the nucleus. ICP34.5β is unable to counteract PKR-mediated eIF2 phosphorylation but does not interfere with ICP34.5α's function in this process. Efficient expression of ICP34.5β in cell culture assays is dependent on viral infection or expression of ICP27, a multifunctional immediate-early gene. The effect of ICP27 on the ICP34.5β protein level is attributed to its selective inhibition of ICP34.5 splicing, which results in increased expression of ICP34.5β but a reduced level of ICP34.5α. The C- terminal KH3 domain but not the RNA binding domain of ICP27 is required for its specific inhibition of ICP34.5 splicing and promotion of ICP34.5β expression. Our results suggest that the expression of ICP34.5α and ICP34.5β is tightly regulated in HSV-2 and likely contributes to viral pathogenesis.