bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production
Authors: Jeong Yun Hee , Hur Yun-Gyoung , Lee Hyejon , Kim Sunghyun , Cho Jang-Eun , Chang Jun , Shin Sung Jae , Lee Hyeyoung , Kang Young Ae , Cho Sang-Nae , Ha Sang-Jun 
Published: November 2014

ABSTRACTMycobacterium tuberculosisis the major causative agent of tuberculosis (TB). The gamma interferon (IFN-γ) release assay (IGRA) has been widely used to diagnose TB by testing cell-mediated immune responses but has no capacity for distinguishing between active TB and latent TB infection (LTBI). This study aims to identify a parameter that will help to discriminate active TB and LTBI. Whole-blood samples from 33 active TB patients, 20 individuals with LTBI, and 26 non-TB controls were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and plasma samples were analyzed for interleukin-2 (IL-2), IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNF-α), IFN-γ, monokine induced by IFN-γ (MIG), interferon gamma inducible protein 10 (IP-10), interferon-inducible T cell alpha chemoattractant (I-TAC), and monocyte chemoattractant protein 1 (MCP-1) by using a commercial cytometric bead array. TheMycobacterium tuberculosisantigen-specific production of most of the assayed cytokines and chemokines was higher in the active TB than in the LTBI group. The mitogen-induced responses were lower in the active TB than in the LTBI group. When the ratio of TB-specific to mitogen-induced responses was calculated, IL-2, IL-6, IL-10, IL-13, TNF-α, IFN-γ, MIG, and IP-10 were more useful in discriminating active TB from LTBI. In particular, most patients showed higher IP-10 production toMycobacterium tuberculosisantigens than to mitogen at the individual level, and the ratio for IP-10 was the strongest indicator of active infection versus LTBI with 93.9% sensitivity and 90% specificity. In conclusion, the ratio of the TB-specific to the mitogen-induced IP-10 responses showed the most promising accuracy for discriminating active TB versus LTBI and should be further studied to determine whether it can serve as a biomarker that might help clinicians administer appropriate treatments.
Development of a Rapid Multiplex PCR Assay To Genotype Pasteurella multocida Strains by Use of the Lipopolysaccharide Outer Core Biosynthesis Locus
Authors: Harper Marina , John Marietta , Turni Conny , Edmunds Mark , St. Michael Frank , Adler Ben , Blackall P. J. , Cox Andrew D. , Boyce John D. 
Published: November 2014

ABSTRACT

Pasteurella multocida
is a Gram-negative bacterial pathogen that is the causative agent of a wide range of diseases in many animal species, including humans. A widely used method for differentiation of
P. multocida
strains involves the Heddleston serotyping scheme. This scheme was developed in the early 1970s and classifies
P. multocida
strains into 16 somatic or lipopolysaccharide (LPS) serovars using an agar gel diffusion precipitin test. However, this gel diffusion assay is problematic, with difficulties reported in accuracy, reproducibility, and the sourcing of quality serovar-specific antisera. Using our knowledge of the genetics of LPS biosynthesis in
P. multocida
, we have developed a multiplex PCR (mPCR) that is able to differentiate strains based on the genetic organization of the LPS outer core biosynthesis loci. The accuracy of the LPS-mPCR was compared with classical Heddleston serotyping using LPS compositional data as the “gold standard.” The LPS-mPCR correctly typed 57 of 58 isolates; Heddleston serotyping was able to correctly and unambiguously type only 20 of the 58 isolates. We conclude that our LPS-mPCR is a highly accurate LPS genotyping method that should replace the Heddleston serotyping scheme for the classification of
P. multocida
strains.
Multisite Clinical Evaluation of a Rapid Test for Entamoeba histolytica in Stool
Authors: Verkerke Hans P. , Hanbury Blake , Siddique Abdullah , Samie Amidou , Haque Rashidul , Herbein Joel , Petri William A. 
Published: November 2014

ABSTRACT

Rapid point-of-care detection of enteric protozoa in diarrheal stool is desirable in clinical and research settings to efficiently determine the etiology of diarrhea. We analyzed the ability of the third-generation
E. histolytica
Quik Chek assay developed by Techlab to detect amebic antigens in fecal samples collected from independent study populations in South Africa and Bangladesh. We compared the performance of this recently released rapid test to that of the commercially available ProSpecT
Entamoeba histolytica
microplate assay from Remel and the
E. histolytica
II enzyme-linked immunosorbent assay (ELISA) from Techlab, using real-time and nested-PCR for
Entamoeba
species to resolve any discrepant results. After discrepant resolution, The
E. histolytica
Quik Chek assay exhibited sensitivity and specificity compared to the
E. histolytica
II ELISA of 98.0% (95% confidence interval [CI], 92.9% to 99.8%) and 100% (95% CI, 99.0% to 100%), respectively. Compared to the ProSpecT microplate assay, the
E. histolytica
Quik Chek (Quik Chek) assay exhibited 97.0% sensitivity (95% CI, 91.5% to 99.4%) and 100% specificity (95% CI, 99.0% to 100%). Our results indicate that the Quik Chek is a robust assay for the specific detection of
E. histolytica
trophozoites in unfixed frozen clinical stool samples.
First Human Systemic Infection Caused by Spiroplasma
Authors: Aquilino Ana , Masiá Mar , López Pilar , Galiana Antonio J. , Tovar Juan , Andrés María , Gutiérrez Félix 
Published: November 2014

ABSTRACT

Spiroplasma
species are organisms that normally colonize plants and insects. We describe the first case of human systemic infection caused by
Spiroplasma
bacteria in a patient with hypogammaglobulinemia undergoing treatment with biological disease-modifying antirheumatic agents.
Spiroplasma
turonicum
was identified through molecular methods in several blood cultures. The infection was successfully treated with doxycycline plus levofloxacin.
An Atypical Outbreak of Food-Borne Botulism Due to Clostridium botulinum Types B and E from Ham
Authors: Mazuet Christelle , Sautereau Jean , Legeay Christine , Bouchier Christiane , Bouvet Philippe , Popoff Michel R. 
Published: November 2014

ABSTRACT

An outbreak of human botulism was due to consumption of ham containing botulinum neurotoxins B and E. A
Clostridium botulinum
type E strain isolated from ham was assigned to a new subtype (E12) based on
bont
/
E
gene sequencing and belongs to a new multilocus sequence subtype, as analyzed by whole-genome sequencing.
Gordonia Species as Emerging Causes of Continuous-Ambulatory-Peritoneal-Dialysis-Related Peritonitis Identified by 16S rRNA and
secA1
Gene Sequencing and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS)
Authors: Lam Jimmy Y. W. , Wu Alan K. L. , Leung Wai-Shing , Cheung Ingrid , Tsang Chi-Ching , Chen Jonathan H. K. , Chan Jasper F. W. , Tse Cindy W. S. , Lee Rodney A. , Lau Susanna K. P. , Woo Patrick C. Y. 
Published: November 2014

ABSTRACT

We report here four cases of continuous ambulatory peritoneal dialysis-related peritonitis caused by three different species of
Gordonia
. The portal of entry was likely through Tenckhoff catheters. 16S rRNA and s
ecA1
gene sequencing are so far the most reliable methods for the accurate identification of
Gordonia
species.
Trends in Secondary Antibiotic Resistance of Helicobacter pylori from 2007 to 2014: Has the Tide Turned?
Authors: Boltin Doron , Ben-Zvi Haim , Perets Tsachi Tsadok , Kamenetsky Zvi , Samra Zmira , Dickman Ram , Niv Yaron 
Published: November 2014

ABSTRACT

The current guidelines recommend culture and antibiotic susceptibility testing of
Helicobacter pylori
following two failed eradication attempts. Where testing is unavailable, epidemiological data for secondary
H. pylori
resistance are essential to allow for the rational use of antibiotics. The aim of this study was to describe the temporal changes in antibiotic resistance among adults previously treated for
H. pylori
infections and to identify predictors of resistance. Between 2007 and 2014, consecutive patients undergoing gastroscopy with
H. pylori
culture and susceptibility testing at our institution following at least two treatment failures were retrospectively identified. Antibiotic susceptibilities were recorded and linked to the demographic data. A total of 1,042 patients were identified, including 739 (70.9%) males, aged 39.3 ± 18.9 years. Resistance to clarithromycin, metronidazole, and levofloxacin was found in 57.2%, 64.4%, and 5.1% of isolates, respectively. Dual resistance to clarithromycin and metronidazole was seen in 39.9%. Over the study period, clarithromycin resistance increased annually in a linear manner (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03 to 1.14;
P
< 0.01), levofloxacin resistance decreased annually (OR, 0.78; 95% CI, 0.61 to 0.92;
P
< 0.01), and metronidazole resistance was nonlinear. Age was an independent predictor of resistance to all antibiotics. Time elapsed predicted resistance for clarithromycin and levofloxacin and dual resistance for clarithromycin-metronidazole. Secondary resistance of
H. pylori
to clarithromycin and metronidazole remains high. The low secondary resistance to levofloxacin makes it an attractive treatment option in our region for patients following two failed eradication attempts.
Genomic Dissection of Travel-Associated Extended-Spectrum-Beta-Lactamase-Producing Salmonella enterica Serovar Typhi Isolates Originating from the Philippines: a One-Off Occurrence or a Threat to Effective Treatment of Typhoid Fever?
Authors: Hendriksen Rene S. , Leekitcharoenphon Pimlapas , Mikoleit Matthew , Jensen Jacob Dyring , Kaas Rolf Sommer , Roer Louise , Joshi Heena B. , Pornruangmong Srirat , Pulsrikarn Chaiwat , Gonzalez-Aviles Gladys D. , Reuland E. Ascelijn , Al Naiemi Nashwan , Wester Astrid Louise , Aarestrup Frank M. , Hasman Henrik 
Published: November 2014

ABSTRACT

One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing
Salmonella enterica
serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of
S
. Typhi. The reported strain was similar to a previously published strain harboring
bla
SHV-12
from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing
S
. Typhi.
Clinical Performance Evaluation of the Sofia RSV FIA Rapid Antigen Test for Diagnosis of Respiratory Syncytial Virus Infection
Authors: Jang Jin Woo , Cho Chi Hyun , Nam Myung-Hyun , Yoon Soo Young , Lee Chang Kyu , Lim Chae Seung , Kim Woo Joo 
Published: November 2014

ABSTRACT
A recently introduced Sofia respiratory syncytial virus (RSV) fluorescent immunoassay (FIA) was evaluated against the BinaxNOW RSV card and the SD Bioline RSV test using 348 respiratory samples. The Sofia, BinaxNOW, and SD Bioline kits showed sensitivities of 66%, 65%, and 64%, respectively, for detecting RSV-A, and 71%, 63%, and 65% for detecting RSV-B, respectively.
Hydrophobic and Charged Residues in the C-Terminal Arm of Hepatitis C Virus RNA-Dependent RNA Polymerase Regulate Initiation and Elongation
Authors: Cherry Amy L. , Dennis Caitriona A. , Baron Andrew , Eisele Leslie E. , Thommes Pia A. , Jaeger Joachim 
Published: November 2014

ABSTRACT

The RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV) is essential for viral genome replication. Crystal structures of the HCV RdRp reveal two C-terminal features, a β-loop and a C-terminal arm, suitably located for involvement in positioning components of the initiation complex. Here we show that these two elements intimately regulate template and nucleotide binding, initiation, and elongation. We constructed a series of β-loop and C-terminal arm mutants, which were used for
in vitro
analysis of RdRp
de novo
initiation and primer extension activities. All mutants showed a substantial decrease in initiation activities but a marked increase in primer extension activities, indicating an ability to form more stable elongation complexes with long primer-template RNAs. Structural studies of the mutants indicated that these enzyme properties might be attributed to an increased flexibility in the C-terminal features resulting in a more open polymerase cleft, which likely favors the elongation process but hampers the initiation steps. A UTP cocrystal structure of one mutant shows, in contrast to the wild-type protein, several alternate conformations of the substrate, confirming that even subtle changes in the C-terminal arm result in a more loosely organized active site and flexible binding modes of the nucleotide. We used a subgenomic replicon system to assess the effects of the same mutations on viral replication in cells. Even the subtlest mutations either severely impaired or completely abolished the ability of the replicon to replicate, further supporting the concept that the correct positioning of both the β-loop and C-terminal arm plays an essential role during initiation and in HCV replication in general.

IMPORTANCE
HCV RNA polymerase is a key target for the development of directly acting agents to cure HCV infections, which necessitates a thorough understanding of the functional roles of the various structural features of the RdRp. Here we show that even highly conservative changes, e.g., Tyr→Phe or Asp→Glu, in these seemingly peripheral structural features have profound effects on the initiation and elongation properties of the HCV polymerase.
Unraveling the Web of Viroinformatics: Computational Tools and Databases in Virus Research
Authors: Sharma Deepak , Priyadarshini Pragya , Vrati Sudhanshu 
Published: November 2014

ABSTRACT
The beginning of the second century of research in the field of virology (the first virus was discovered in 1898) was marked by its amalgamation with bioinformatics, resulting in the birth of a new domain—viroinformatics. The availability of more than 100 Web servers and databases embracing all or specific viruses (for example, dengue virus, influenza virus, hepatitis virus, human immunodeficiency virus [HIV], hemorrhagic fever virus [HFV], human papillomavirus [HPV], West Nile virus, etc.) as well as distinct applications (comparative/diversity analysis, viral recombination, small interfering RNA [siRNA]/short hairpin RNA [shRNA]/microRNA [miRNA] studies, RNA folding, protein-protein interaction, structural analysis, and phylotyping and genotyping) will definitely aid the development of effective drugs and vaccines. However, information about their access and utility is not available at any single source or on any single platform. Therefore, a compendium of various computational tools and resources dedicated specifically to virology is presented in this article.
Nipah Virus Attachment Glycoprotein Stalk C-Terminal Region Links Receptor Binding to Fusion Triggering
Authors: Liu Qian , Bradel-Tretheway Birgit , Monreal Abrrey I. , Saludes Jonel P. , Lu Xiaonan , Nicola Anthony V. , Aguilar Hector C. 
Published: November 2014

ABSTRACT
Membrane fusion is essential for paramyxovirus entry into target cells and for the cell-cell fusion (syncytia) that results from many paramyxoviral infections. The concerted efforts of two membrane-integral viral proteins, the attachment (HN, H, or G) and fusion (F) glycoproteins, mediate membrane fusion. The emergent Nipah virus (NiV) is a highly pathogenic and deadly zoonotic paramyxovirus. We recently reported that upon cell receptor ephrinB2 or ephrinB3 binding, at least two conformational changes occur in the NiV-G head, followed by one in the NiV-G stalk, that subsequently result in F triggering and F execution of membrane fusion. However, the domains and residues in NiV-G that trigger F and the specific events that link receptor binding to F triggering are unknown. In the present study, we identified a NiV-G stalk C-terminal region (amino acids 159 to 163) that is important for multiple G functions, including G tetramerization, conformational integrity, G-F interactions, receptor-induced conformational changes in G, and F triggering. On the basis of these results, we propose that this NiV-G region serves as an important structural and functional linker between the NiV-G head and the rest of the stalk and is critical in propagating the F-triggering signal via specific conformational changes that open a concealed F-triggering domain(s) in the G stalk. These findings broaden our understanding of the mechanism(s) of receptor-induced paramyxovirus F triggering during viral entry and cell-cell fusion.

IMPORTANCE
The emergent deadly viruses Nipah virus (NiV) and Hendra virus belong to the
Henipavirus
genus in the
Paramyxoviridae
family. NiV infections target endothelial cells and neurons and, in humans, result in 40 to 75% mortality rates. The broad tropism of the henipaviruses and the unavailability of therapeutics threaten the health of humans and livestock. Viral entry into host cells is the first step of henipavirus infections, which ultimately cause syncytium formation. After attaching to the host cell receptor, henipaviruses enter the target cell via direct viral-cell membrane fusion mediated by two membrane glycoproteins: the attachment protein (G) and the fusion protein (F). In this study, we identified and characterized a region in the NiV-G stalk C-terminal domain that links receptor binding to fusion triggering via several important glycoprotein functions. These findings advance our understanding of the membrane fusion-triggering mechanism(s) of the henipaviruses and the paramyxoviruses.
Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node
Authors: Wu Yuet , Tu Wenwei , Lam Kwok-Tai , Chow Kin-Hung , Ho Pak-Leung , Guan Yi , Peiris Joseph S. Malik , Lau Yu-Lung 
Published: November 2014

ABSTRACT

Secondary
Streptococcus pneumoniae
infection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. In the lung, lethal coinfection significantly increased virus titers and bacterial cell counts and decreased the level of virus-specific IgG, IgM, and IgA, as well as the number of B cells, CD4 T cells, and plasma cells. Lethal coinfection significantly reduced the size and weight of spleen, as well as the number of B cells along the follicular developmental lineage. In mediastinal lymph nodes, lethal coinfection significantly decreased germinal center B cells, T follicular helper cells, and plasma cells. Adoptive transfer of influenza virus-specific immune serum to coinfected mice improved survival, suggesting the protective functions of anti-influenza virus antibodies. In conclusion, coinfection reduced the B cell response to influenza virus. This study helps us to understand the modulation of the B cell response to influenza virus during a lethal coinfection.

IMPORTANCE
Secondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection.
The nsp3 Macrodomain Promotes Virulence in Mice with Coronavirus-Induced Encephalitis
Authors: Fehr Anthony R. , Athmer Jeremiah , Channappanavar Rudragouda , Phillips Judith M. , Meyerholz David K. , Perlman Stanley 
Published: November 2014

ABSTRACT

All coronaviruses encode a macrodomain containing ADP-ribose-1″-phosphatase (ADRP) activity within the N terminus of nonstructural protein 3 (nsp3). Previous work showed that mouse hepatitis virus strain A59 (MHV-A59) with a mutated catalytic site (N1348A) replicated similarly to wild-type virus but was unable to cause acute hepatitis in mice. To determine whether this attenuated phenotype is applicable to multiple disease models, we mutated the catalytic residue in the JHM strain of MHV (JHMV), which causes acute and chronic encephalomyelitis, using a newly developed bacterial artificial chromosome (BAC)-based MHV reverse genetics system. Infection of mice with the macrodomain catalytic point mutant virus (N1347A) resulted in reductions in lethality, weight loss, viral titers, proinflammatory cytokine and chemokine expression, and immune cell infiltration in the brain compared to mice infected with wild-type virus. Specifically, macrophages were most affected, with approximately 2.5-fold fewer macrophages at day 5 postinfection in N1347A-infected brains. Tumor necrosis factor (TNF) and interferon (IFN) signaling were not required for effective host control of mutant virus as all N1347A virus-infected mice survived the infection. However, the adaptive immune system was required for protection since N1347A virus was able to cause lethal encephalitis in RAG1
−/−
(recombination activation gene 1 knockout) mice although disease onset was modestly delayed. Overall, these results indicate that the BAC-based MHV reverse genetics system will be useful for studies of JHMV and expand upon previous studies, showing that the macrodomain is critical for the ability of coronaviruses to evade the immune system and promote viral pathogenesis.

IMPORTANCE
Coronaviruses are an important cause of human and veterinary diseases worldwide. Viral processes that are conserved across a family are likely to be good targets for the development of antiviral therapeutics and vaccines. The macrodomain is a ubiquitous structural domain and is also conserved among all coronaviruses. The coronavirus macrodomain has ADP-ribose-1″-phosphatase activity; however, its function during infection remains unclear as does the reason that coronaviruses have maintained this enzymatic activity throughout evolution. For MHV, this domain has now been shown to promote multiple types of disease, including hepatitis and encephalitis. These data indicate that this domain is vital for the virus to replicate and cause disease. Understanding the mechanism used by this enzyme to promote viral pathogenesis will open up novel avenues for therapies and may give further insight into the role of macrodomain proteins in the host cell since these proteins are found in all living organisms.