bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Combination Vaccine Consisting of Three Live Attenuated Enterotoxigenic Escherichia coli Strains Expressing a Range of Colonization Factors and Heat-Labile Toxin Subunit B Is Well Tolerated and Immunogenic in a Placebo-Controlled Double-Blind Phase I Trial in Healthy Adults
Authors: Harro Clayton , Sack David , Bourgeois A. Louis , Walker R. , DeNearing Barbara , Feller Andrea , Chakraborty Subhra , Buchwaldt Charlotte , Darsley Michael J. 
Published: October 2011

ABSTRACT

Immune responses against colonization factors (CFs) and the nontoxic B component of the enterotoxigenic
Escherichia coli
(ETEC) heat-labile toxin (LTB) are considered to be important for immunity against diarrhea caused by ETEC. Individual live attenuated ETEC derivatives that have had their toxin genes removed and whose
aroC
,
ompC
, and
ompF
genes are deleted have shown promise as vaccines against ETEC. The development of such strains has culminated in the testing of a three-strain-combination live attenuated vaccine known as ACE527, comprised of strains ACAM2025 expressing colonization factor antigen I (CFA/I) and LTB; ACAM2022, expressing CS5, CS6, and LTB; and ACAM2027, expressing CS1, CS2, CS3, and LTB. The recombinant CF and LTB genes expressed in the three strains were inserted into the bacterial chromosome to ensure their stable inheritance and expression without the requirement for any selection. ACE527 has been tested in a randomized placebo-controlled, double-blind, phase I safety and immunogenicity study in healthy adult volunteers and proved to be well tolerated and immunogenic at dose levels of 10
10
and 10
11
total CFU. There was no indication of strain interference on the basis of fecal shedding patterns, with all three being detected in the feces of 50% and 83% of low- and high-dose vaccine recipients, respectively. Similarly, strong immune responses to LTB and to CFs expressed on all three constituent strains were induced, with at least 50% of subjects in the high-dose group responding to LTB, CFA/I, CS3, and CS6.
Clinical Performance of the (1,3)-β-
d
-Glucan Assay in Early Diagnosis of Nosocomial Candida Bloodstream Infections
Authors: Del Bono Valerio , Delfino Emanuele , Furfaro Elisa , Mikulska Malgorzata , Nicco Elena , Bruzzi Paolo , Mularoni Alessandra , Bassetti Matteo , Viscoli Claudio 
Published: October 2011

ABSTRACT

Microbiological diagnosis of nosocomial candidemia is negatively affected by suboptimal culture yield. Alternative methods are not fully reliable as an aid in candidemia diagnosis. Recently, the detection of (1,3)-β-
d
-glucan (BG) has been shown to be very promising in this setting. We carried out a prospective study on the clinical usefulness of BG detection in early diagnosis of candidemia. BG detection was performed in patients with fever unresponsive to antibacterial agents and risk factors for candidemia. BG detection was done with the Fungitell test. A total of 152 patients were included in the study; 53 were proven to have candidemia, while in 52 patients candidemia was excluded on microbiological and clinical bases. The remaining 47 patients were considered to have possible candidemia. In summary, 41 of 53 candidemia patients (77.3%), 9 of 52 patients without candidemia (17.3%), and 38 of 47 patients with possible candidemia (80.8%) were positive in the BG assay. With these results, the sensitivity and the specificity of the assay were 77% and 83%, respectively. BG levels of >160 pg/ml were highly predictive of candidemia. In 36 of 41 patients with candidemia and positive BG testing, the BG assay was performed within 48 h from when the first
Candida-
positive blood sample for culture was drawn, thus allowing a possible earlier start of antifungal therapy. Based on these results, the BG assay may be used as an aid in the diagnosis of nosocomial candidemia. The timing of assay performance is critical for collecting clinically useful information. However, the test results should be associated with clinical data.
Comparison of the FilmArray Respiratory Panel and Prodesse Real-Time PCR Assays for Detection of Respiratory Pathogens
Authors: Loeffelholz M. J. , Pong D. L. , Pyles R. B. , Xiong Y. , Miller A. L. , Bufton K. K. , Chonmaitree T. 
Published: October 2011

ABSTRACT

We compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the FilmArray Respiratory Panel (RP) multiplex PCR assay (Idaho Technology, Inc., Salt Lake City, UT) with those of the Food and Drug Administration (FDA)-cleared Prodesse ProFlu+, ProFAST+, ProParaflu+, Pro hMPV+, and ProAdeno+ real-time PCR assays (Gen-Probe, San Diego, CA). The assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children under 1 year of age with upper respiratory tract symptoms. To resolve discordant results and confirm pathogens detected only by the larger FilmArray panel, we performed laboratory-developed real-time PCR assays. Among viruses detectable by both commercial assays (adenovirus, human metapneumovirus, influenza A virus, influenza B virus, parainfluenza viruses 1 to 3, and respiratory syncytial virus), the FilmArray and Prodesse assays showed good overall agreement (181/192 [94.3%]; kappa = 0.87; 95% CI, 0.79 to 0.94). FilmArray RP detected more parainfluenza viruses 1 and 3 than ProParaflu+ (18 versus 13) while ProAdeno+ detected more adenoviruses (11 versus 6), but these differences were not statistically significant. Additionally, FilmArray RP detected 138 pathogens (confirmed as true positives) not included in the Prodesse assays (rhinovirus [RV]/enterovirus [EV], 118; bocavirus, 8; coronavirus, 7; parainfluenza virus 4, 4;
Mycoplasma pneumoniae
, 1). FilmArray RP was cleared by the FDA following the completion of this study. The FDA-cleared version includes the following targets: adenovirus, coronaviruses HKU1 and NL63, human metapneumovirus (hMPV), influenza A virus (to type level only), influenza A H1 seasonal virus, influenza A H3 seasonal virus, influenza A virus H1-2009, influenza B virus, parainfluenza viruses 1 to 4, respiratory syncytial virus (RSV), and RV/EV (no differentiation). The larger panel in the FilmArray RP assay allowed the detection of additional respiratory pathogens compared to the Prodesse assays. In this population of young children with upper respiratory tract infection, RV/EV accounted for the majority of the additional pathogens detected by FilmArray RP.
Characterization of Genetic Diversity of Bacillus anthracis in France by Using High-Resolution Melting Assays and Multilocus Variable-Number Tandem-Repeat Analysis
Authors: Derzelle S. , Laroche S. , Le Flèche P. , Hauck Y. , Thierry S. , Vergnaud G. , Madani N. 
Published: October 2011

ABSTRACT

Using high-resolution melting (HRM) analysis, we developed a cost-effective method to genotype a set of 13 phylogenetically informative single-nucleotide polymorphisms (SNPs) within the genome of
Bacillus anthracis
. SNP discrimination assays were performed in monoplex or duplex and applied to 100
B. anthracis
isolates collected in France from 1953 to 2009 and a few reference strains. HRM provided a reliable and cheap alternative to subtype
B. anthracis
into one of the 12 major sublineages or subgroups. All strains could be correctly positioned on the canonical SNP (canSNP) phylogenetic tree, except the divergent Pasteur vaccine strain ATCC 4229. We detected the cooccurrence of three canSNP subgroups in France. The dominant B.Br.CNEVA sublineage was found to be prevalent in the Alps, the Pyrenees, the Auvergne region, and the Saône-et-Loire department. Strains affiliated with the A.Br.008/009 subgroup were observed throughout most of the country. The minor A.Br.001/002 subgroup was restricted to northeastern France. Multiple-locus variable-number tandem-repeat analysis using 24 markers further resolved French strains into 60 unique profiles and identified some regional patterns. Diversity found within the A.Br.008/009 and B.Br.CNEVA subgroups suggests that these represent old, ecologically established clades in France. Phylogenetic relationships with strains from other parts of the world are discussed.
Xpert MTB/RIF Assay for Diagnosis of Pleural Tuberculosis
Authors: Friedrich Sven O. , von Groote-Bidlingmaier Florian , Diacon Andreas H. 
Published: October 2011

ABSTRACT

We prospectively investigated the diagnostic utility of the Xpert MTB/RIF (
Mycobacterium tuberculosis
/rifampin [RIF] resistance) assay in 20 cases with confirmed tuberculous pleural effusion. The sensitivity and specificity of the Xpert assay in pleural fluid were 25% and 100%, respectively. All cases positive by the Xpert assay were also positive by pleural fluid culture.
Circulating MicroRNAs in Patients with Active Pulmonary Tuberculosis
Authors: Fu Yurong , Yi Zhengjun , Wu Xiaoyan , Li Jianhua , Xu Fuliang 
Published: October 2011

ABSTRACT
Emerging evidence shows that microRNAs (miRNAs) play an important role in pathogen-host interactions. Circulating miRNAs have been repeatedly and stably detected in blood and hold promise to serve as molecular markers for diverse physiological and pathological conditions. To date, the relationship between circulating miRNAs and active pulmonary tuberculosis (TB) has not been reported. Using microarray-based expression profiling followed by real-time quantitative PCR validation, the levels of circulating miRNAs were compared between patients with active pulmonary tuberculosis and matched healthy controls. The receiver operating characteristic curve was used to evaluate the diagnostic effect of selected miRNA. Bioinformatic analysis was used to explore the potential roles of these circulating miRNAs in active pulmonary tuberculosis infection. Among 92 miRNAs significantly detected, 59 miRNAs were downregulated and 33 miRNAs were upregulated in the TB serum compared to their levels in the control serum. Interestingly, only two differentially expressed miRNAs were increased not only in the serum but also in the sputum of patients with active pulmonary tuberculosis compared to the levels for the healthy controls. Upregulated miR-29a could discriminate TB patients from healthy controls with reasonable sensitivity and specificity. A number of significantly enriched pathways regulated by these circulating miRNAs were predicted, and most of them were involved in acute-phase response, inflammatory response, and the regulation of the cytoskeleton. In all, for the first time our results revealed that a number of miRNAs were differentially expressed during active pulmonary tuberculosis infection, and circulating miR-29a has great potential to serve as a marker for the detection of active pulmonary tuberculosis infection.
Species Identification of Clinical Isolates of Anaerobic Bacteria: a Comparison of Two Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Systems
Authors: Justesen Ulrik Stenz , Holm Anette , Knudsen Elisa , Andersen Line Bisgaard , Jensen Thøger Gorm , Kemp Michael , Skov Marianne Nielsine , Gahrn-Hansen Bente , Møller Jens Kjølseth 
Published: October 2011

ABSTRACT

We compared two matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) systems (Shimadzu/SARAMIS and Bruker) on a collection of consecutive clinically important anaerobic bacteria (
n
= 290). The Bruker system had more correct identifications to the species level (67.2% versus 49.0%), but also more incorrect identifications (7.9% versus 1.4%). The system databases need to be optimized to increase identification levels. However, MALDI-TOF MS in its present version seems to be a fast and inexpensive method for identification of most clinically important anaerobic bacteria.
Performance of the MGIT TBc Identification Test and Meta-Analysis of MPT64 Assays for Identification of the Mycobacterium tuberculosis Complex in Liquid Culture
Authors: Brent Andrew J. , Mugo Daisy , Musyimi Robert , Mutiso Agnes , Morpeth Susan , Levin Michael , Scott J. Anthony G. 
Published: October 2011

ABSTRACT

Rapid MPT64-based immunochromatographic tests (MPT64 ICTs) have been developed to detect
Mycobacterium tuberculosis
complex (MTBC) in culture. We demonstrated the noninferiority of one commercial MTP64 ICT, the MGIT TBc identification (TBcID) test, to GenoType line probe assays for MTBC identification in positive MGIT cultures. Meta-analysis of MPT64 ICT performance for identification of MTBC in liquid culture confirmed similar very high sensitivities and specificities for all three commercial MPT64 assays for which sufficient data were available.
Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation
Authors: Nam Jeong-Hyun , Kim Eun-Ha , Song Daesub , Choi Young Ki , Kim Jeong-Ki , Poo Haryoung 
Published: October 2011

ABSTRACT
The migratory waterfowl of the world are considered to be the natural reservoir of influenza A viruses. Of the 16 hemagglutinin subtypes of avian influenza viruses, the H6 subtype is commonly perpetuated in its natural hosts and is of concern due to its potential to be a precursor of highly pathogenic influenza viruses by reassortment. During routine influenza surveillance, we isolated an unconventional H6N5 subtype of avian influenza virus. Experimental infection of mice revealed that this isolate replicated efficiently in the lungs, subsequently spread systemically, and caused lethality. The isolate also productively infected ferrets, with direct evidence of contact transmission, but no disease or transmission was seen in pigs. Although the isolate possessed the conserved receptor-binding site sequences of avian influenza viruses, it exhibited relatively low replication efficiencies in ducks and chickens. Our genetic and molecular analyses of the isolate revealed that its PB1 sequence showed the highest evolutionary relationship to those of highly pathogenic H5N1 avian influenza viruses and that its PA protein had an isoleucine residue at position 97 (a representative virulence marker). Further studies will be required to examine why our isolate has the virologic characteristics of mammalian influenza viruses but the archetypal receptor binding profiles of avian influenza viruses, as well as to determine whether its potential virulence markers (PB1 analogous to those of H5N1 viruses or isoleucine residue at position 97 within PA) could render it highly pathogenic in mice.
A Virion-Associated Protein Kinase Induces Apoptosis
Authors: Chitnis Nilesh S. , Paul Eric R. , Lawrence Paulraj K. , Henderson Curtis W. , Ganapathy Saranya , Taylor Patrick V. , Virdi Kamaldeep S. , D’Costa Susan M. , May Ashley R. , Bilimoria Shan L. 
Published: October 2011

ABSTRACT

Apoptosis and inhibition of host gene expression are often associated with virus infections. Many viral polypeptides modulate apoptosis by direct interaction with highly conserved apoptotic pathways. Some viruses induce apoptosis during late stages of the infection cycle, while others inhibit apoptosis to facilitate replication or maintain persistent infection. In previous work, we showed that Chilo iridescent virus (CIV) or CIV virion protein extract induces apoptosis in spruce budworm and cotton boll weevil cell cultures. Here, we characterize the product of a CIV gene (
iridovirus
serine/threonine kinase;
istk
) with signature sequences for S/T kinase and ATP binding. ISTK appears to belong to the superfamily, vaccinia-related kinases (VRKs). The
istk
gene was expressed in
Pichia pastoris
vectors. Purified ISTK (48 kDa) exhibited S/T kinase activity. Treatment with ISTK induced apoptosis in budworm cells. A 35-kDa cleavage product of ISTK retaining key signature sequences was identified during purification.
Pichia
-expressed 35-kDa polypeptide, designated iridoptin, induced apoptosis and inhibition of host protein synthesis in budworm and boll weevil cells. A mutation in the ATP-binding site eliminated both kinase and apoptosis activity of iridoptin, suggesting that kinase activity is essential for induction of apoptosis. Analysis with custom antibody confirmed that ISTK is a structural component of CIV particles. This is the first demonstration of a viral kinase inducing apoptosis in any virus-host system and the first identification of a factor inducing apoptosis or host protein shutoff for the family
Iridoviridae
.
Characterization of the Pleiotropic Effects of the Genotype G-Specific 36-Nucleotide Insertion in the Context of Other Hepatitis B Virus Genotypes
Authors: Gutelius Danielle , Li Jisu , Wands Jack , Tong Shuping 
Published: October 2011

ABSTRACT
The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves as the messenger for both core and P proteins, with the downstream P gene translated by ribosomal leaky scanning. HBV replication begins with packaging of the pgRNA and P protein into core protein particles, followed by conversion of RNA into DNA. Genotype G has a low replication capacity due to a low pgRNA level. It has a 36-nucleotide (nt) insertion in the 5′ end of the core gene, adding 12 residues to the core protein. The insertion is needed to maintain efficient core protein expression and genome replication but causes inefficient virion secretion yet high maturity of virion DNA. In the present study, we confirmed that the 36-nt insertion had similar effects on core protein expression and virion secretion when it was introduced into genotype A and D clones but no impact on virion genome maturity. Surprisingly, the insertion impaired genome replication in both genotypes. Transcomplementation assays suggest that increased efficiency of core protein translation diminishes ribosomal scanning toward the downstream P gene. Indeed, mutating the core gene Kozak sequence restored core protein to lower levels but increased replication of the insertion mutant. Similar mutations impaired replication in genotype G. On the other hand, replacement of the core promoter sequence of genotype G with genotype A sequence increased pgRNA transcription and genome replication, implicating this region in the low replication capacity of genotype G. Why the 36-nt insertion is present in genotype G but absent in other genotypes is discussed.
A Virus-Like Particle-Based Epstein-Barr Virus Vaccine
Authors: Ruiss Romana , Jochum Simon , Wanner Gerhard , Reisbach Gilbert , Hammerschmidt Wolfgang , Zeidler Reinhard 
Published: October 2011

ABSTRACTEpstein-Barr Virus (EBV) is an ubiquitous human herpesvirus which can lead to infectious mononucleosis and different cancers. In immunocompromised individuals, this virus is a major cause for morbidity and mortality. Transplant patients who did not encounter EBV prior to immunosuppression frequently develop EBV-associated malignancies, but a prophylactic EBV vaccination might reduce this risk considerably. Virus-like particles (VLPs) mimic the structure of the parental virus but lack the viral genome. Therefore, VLPs are considered safe and efficient vaccine candidates. We engineered a dedicated producer cell line for EBV-derived VLPs. This cell line contains a genetically modified EBV genome which is devoid of all potential viral oncogenes but provides viral proteins essential for the assembly and release of VLPs via the endosomal sorting complex required for transport (ESCRT). Human B cells readily take up EBV-based VLPs and present viral epitopes in association with HLA molecules to T cells. Consequently, EBV-based VLPs are highly immunogenic and elicit humoral and strong CD8+and CD4+T cell responsesin vitroand in a preclinical murine modelin vivo. Our findings suggest that VLP formulations might be attractive candidates to develop a safe and effective polyvalent vaccine against EBV.
Pyrosequencing Reveals Restricted Patterns of CD8+T Cell Escape-Associated Compensatory Mutations in Simian Immunodeficiency Virus
Authors: Burwitz Benjamin J. , Sacha Jonah B. , Reed Jason S. , Newman Laura P. , Norante Francesca A. , Bimber Benjamin N. , Wilson Nancy A. , Watkins David I. , O'Connor David H. 
Published: October 2011

ABSTRACTCD8+T cells play a major role in the containment of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. CD8+T cell-driven variations in conserved regions under functional constraints result in diminished viral replicative capacity. While compensatory mutations outside an epitope can restore replicative capacity, the kinetics with which they arise remains unknown. Additionally, certain patterns of linked mutations associated with CD8+T cell epitope escape in these highly conserved regions may lead to variable levels of viral fitness. Here, we used pyrosequencing to investigate the kinetics and patterns of mutations surrounding the Mamu-A1*00101-bound Gag181-189CM9 CD8+T cell epitope. We obtained more than 400 reads for each sequencing time point, allowing us to confidently detect the emergence of viral variants bearing escape mutations with frequencies as low as 1% of the circulating virus. With this level of detail, we demonstrate that compensatory mutations generally arise concomitantly with Gag181-189CM9 escape mutations. We observed distinct patterns of linked flanking mutations, most of which were found downstream of Gag181-189CM9. Our data indicate that, whereas Gag181-189CM9 escape is much more complex that previously appreciated, it occurs in a coordinated fashion, with very specific patterns of flanking mutations required for immune evasion. This is the first detailed report of the ontogeny of compensatory mutations that allow CD8+T cell epitope escape in infected individuals.
CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells
Authors: Gumbi P. P. , Jaumdally S. Z. , Salkinder A. L. , Burgers W. A. , Mkhize N. N. , Hanekom W. , Coetzee D. , Williamson A. , Passmore J. S. 
Published: October 2011

ABSTRACT

In blood, the accumulation of terminally differentiated (TD) T cells during HIV infection is associated with CD4 T cell loss and HIV disease progression. Here, we investigated the maintenance and functional characteristics of memory T cells at the cervix. We found that CD4 T cell depletion at the cervix mirrors CD4 depletion in blood. In all women, depletion of CD4 T cells at the cervix was associated with significant reductions in CD45RA
−
CCR7
+
(central memory [CM]) T cells and the accumulation of CD45RA
+
CCR7
−
(TD T cells). We determined whether inflammation in the genital tract was associated with the local differentiation of T cells at the cervix. In uninfected women, genital tract inflammation was associated with the accumulation of CD45RA
−
CCR7
+
CM CD4 T cells and reduced frequencies of CD45RA
+
CCR7
−
TD cells at the cervix. This finding may reflect the fact that, in the absence of HIV infection, TD T cells may be slowly lost in the presence of genital inflammation, while CD45RA
−
CCR7
+
CM T cells are recruited to replenish the diminishing CD4 T cell pool. Following global stimulation with phorbol myristate acetate (PMA)-ionomycin, we noted a significant interleukin 2 (IL-2) deficit in both cervical and blood CD4 T cells from HIV-infected women compared to uninfected women, while gamma interferon (IFN-γ) production was similar, irrespective of HIV status. Few HIV-infected women had detectable IFN-γ and IL-2 HIV-specific T cell responses at the cervix, and these responses were significantly lower in magnitude than the corresponding responses in blood. These data suggest that CD4 depletion was associated with the accumulation of terminally differentiated T cell phenotypes at the cervical mucosa defective in their ability to produce IL-2. CD4 depletion and compromised immunity at the cervix may be accompanied by progressive decline of central memory-like T cells and development of T cells toward terminally differentiated phenotypes.