bluuebunny/crossref_metadata_2025_split huggingface dataset:
A virtual trial framework for quantifying the detectability of masses in breast tomosynthesis projection data
Authors: Young Stefano , Bakic Predrag R. , Myers Kyle J. , Jennings Robert J. , Park Subok 
Published: April 2013

Purpose:Digital breast tomosynthesis (DBT) is a promising breast cancer screening tool that has already begun making inroads into clinical practice. However, there is ongoing debate over how to quantitatively evaluate and optimize these systems, because different definitions of image quality can lead to different optimal design strategies. Powerful and accurate tools are desired to extend our understanding of DBT system optimization and validate published design principles.Methods:The authors developed a virtual trial framework for task‐specific DBT assessment that uses digital phantoms, open‐source x‐ray transport codes, and a projection‐space, spatial‐domain observer model for quantitative system evaluation. The authors considered evaluation of reconstruction algorithms as a separate problem and focused on the information content in the raw, unfiltered projection images. Specifically, the authors investigated the effects of scan angle and number of angular projections on detectability of a small (3 mm diameter) signal embedded in randomly‐varying anatomical backgrounds. Detectability was measured by the area under the receiver‐operating characteristic curve (AUC). Experiments were repeated for three test cases where the detectability‐limiting factor was anatomical variability, quantum noise, or electronic noise. The authors also juxtaposed the virtual trial framework with other published studies to illustrate its advantages and disadvantages.Results:The large number of variables in a virtual DBT study make it difficult to directly compare different authors’ results, so each result must be interpreted within the context of the specific virtual trial framework. The following results apply to 25% density phantoms with 5.15 cm compressed thickness and 500 μm3 voxels (larger 500 μm2 detector pixels were used to avoid voxel‐edge artifacts): 1. For raw, unfiltered projection images in the anatomical‐variability‐limited regime, AUC appeared to remain constant or increase slightly with scan angle. 2. In the same regime, when the authors fixed the scan angle, AUC increased asymptotically with the number of projections. The threshold number of projections for asymptotic AUC performance depended on the scan angle. In the quantum‐ and electronic‐noise dominant regimes, AUC behaviors as a function of scan angle and number of projections sometimes differed from the anatomy‐limited regime. For example, with a fixed scan angle, AUC generally decreased with the number of projections in the electronic‐noise dominant regime. These results are intended to demonstrate the capabilities of the virtual trial framework, not to be used as optimization rules for DBT.Conclusions:The authors have demonstrated a novel simulation framework and tools for evaluating DBT systems in an objective, task‐specific manner. This framework facilitates further investigation of image quality tradeoffs in DBT.
Integrating the Xpert MTB/RIF Assay into a Diagnostic Workflow for Rapid Detection of Mycobacterium tuberculosis in a Low-Prevalence Area
Authors: Deggim Vanessa , Somoskovi Akos , Voit Antje , Böttger Erik C. , Bloemberg Guido V. 
Published: April 2013

ABSTRACT

The Xpert MTB/RIF assay is a rapid and fully automated real-time PCR assay. The performance of the Xpert MTB/RIF assay as a primary screening test for urgent clinical specimens was evaluated during a 2-year period. The results showed that replacing smear microscopy with the Xpert MTB/RIF assay facilitates laboratory handling and improves the sensitivity and specificity of
Mycobacterium tuberculosis
detection.
Endemic Genotypes of Candida albicans Causing Fungemia Are Frequent in the Hospital
Authors: Escribano Pilar , Rodríguez-Créixems Marta , Sánchez-Carrillo Carlos , Muñoz Patricia , Bouza Emilio , Guinea Jesús 
Published: April 2013

ABSTRACT

Genotyping of
Candida albicans
strains causing candidemia can uncover the presence of endemic genotypes in the hospital. Using a highly reproducible and discriminatory microsatellite marker panel, we studied the genetic diversity of 217
C. albicans
isolates from the blood cultures of 202 patients with candidemia (from January 2007 to December 2011). Each isolate represented 1 candidemia episode. Multiple episodes were defined as the isolation of
C. albicans
in further blood cultures taken ≥7 days after the last isolation in blood culture. Of the 202 patients, 188 had 1 episode, 13 had 2 episodes, and 1 had 3 episodes. Identical genotypes showed the same alleles for all 6 markers. The genotypes causing both episodes were identical in most patients with 2 episodes (11/13; 84.6%). In contrast, 2 different genotypes were found in the patient with 3 episodes, one causing the first and second episodes and the other causing the third episode (isolated 6 months later). We found marked genetic diversity in 174 different genotypes: 155 were unique, and 19 were endemic and formed 19 clusters (2 to 6 patients per cluster). Up to 25% of the patients were infected by endemic genotypes that infected 2 or more different patients. Some of these endemic genotypes were found in the same unit of the hospital, mainly neonatology, whereas others infected patients in different wards.
Epitopes of the Highly Immunogenic Trichomonas vaginalis α-Actinin Are Serodiagnostic Targets for Both Women and Men
Authors: Neace Calvin J. , Alderete J. F. 
Published: April 2013

ABSTRACT

There is a need for a point-of-care serodiagnostic test for women and men for sexually transmitted infections (STIs) caused by
Trichomonas vaginalis
. Sera from women with this STI and sera from men that were analyzed in studies showing a relationship between serostatus and prostate cancer are highly seropositive in response to trichomonad α-actinin and its truncated protein (ACT-P2) (positive control sera). Epitope mapping experiments showed that positive control sera from women had antibodies to 13 distinct epitopes, 5 of which were detected by positive control sera from men. Sera from women and men that were unreactive with α-actinin (negative control sera) failed to detect any of the epitopes or other α-actinin amino acid sequences. The
T. vaginalis
α-actinin amino acid sequence and the sequences of the epitopes showed little or no identity with those of other proteins of microbial pathogens or the human α-actinin 1 (HuACTN1) homolog. Immunoassays such as dot blot, immunoblot, and enzyme-linked immunosorbent assays were used. Positive control sera did not detect HuACTN1 in immunoassays, and the range of levels of identity of α-actinin epitopes with HuACTN1 was 0% to 50%. Comparison of the
T. vaginalis
α-actinin epitopes with proteins in data banks, such as
Tritrichomonas suis
,
Candida albicans
, and
Saccharomyces cerevisiae
proteins, gave a range of identity levels of 0% to 22%. Specific 15-mer peptide epitopes of α-actinin with low to no identity with other proteins were synthesized and were reactive with positive control sera only. These findings identify epitopes of α-actinin as candidate serodiagnostic targets and suggest strongly that a highly seropositive reaction to α-actinin suggests exposure to
T. vaginalis
.
Sequencing Assays for Failed Genotyping with the Versant Hepatitis C Virus Genotype Assay (LiPA), Version 2.0
Authors: Larrat Sylvie , Poveda Jean-Dominique , Coudret Camille , Fusillier Katia , Magnat Nelly , Signori-Schmuck Anne , Thibault Vincent , Morand Patrice 
Published: April 2013

ABSTRACT
For optimal antiviral therapy, the hepatitis C virus (HCV) genotype needs to be determined, as it remains a strong predictor of sustained viral response. In this study, we assessed the number of HCV genotyping results that could not be determined using the commercially available line probe assay (LiPA) (Versant hepatitis C virus genotype 2.0 assay) in a large international panel of samples from 9,874 HCV-positive patients. In-house sequencing assays targeting the 5′ untranslated region (UTR), core region, NS3 region, and NS5B region of the HCV genome and phylogenetic analyses were used to resolve these LiPA failures. Among all cases, the genotypes of 51 samples (0.52%) could not be determined with the LiPA. These undetermined results were observed more frequently among samples from non-European regions (mainly the Arabian Peninsula). The use of sequencing assays coupled with phylogenetic analysis provided reliable genotype results for 86% of the LiPA failures, which exhibited higher rates of genotypes 4, 5, and 6 than did LiPA-resolved genotypes. As expected, the 5′ UTR was not sufficiently variable for clear discrimination between genotypes 1 and 6, but it also resulted in errors in classification of some genotype 3 and 4 cases using well-known Web-based BLAST programs. This study demonstrates the low frequency of genotyping failures with the Versant hepatitis C virus genotype 2.0 assay (LiPA) and also underlines the need for a complex combination of sequences and phylogenetic analyses in order to genotype these particular HCV strains correctly.
Molecular Analysis of an Outbreak of Lethal Postpartum Sepsis Caused by Streptococcus pyogenes
Authors: Turner Claire E. , Dryden Matthew , Holden Matthew T. G. , Davies Frances J. , Lawrenson Richard A. , Farzaneh Leili , Bentley Stephen D. , Efstratiou Androulla , Sriskandan Shiranee 
Published: April 2013

ABSTRACT

Sepsis is now the leading direct cause of maternal death in the United Kingdom, and
Streptococcus pyogenes
is the leading pathogen. We combined conventional and genomic analyses to define the duration and scale of a lethal outbreak. Two postpartum deaths caused by
S. pyogenes
occurred within 24 h; one was characterized by bacteremia and shock and the other by hemorrhagic pneumonia. The women gave birth within minutes of each other in the same maternity unit 2 days earlier. Seven additional infections in health care and household contacts were subsequently detected and treated. All cluster-associated
S. pyogenes
isolates were genotype
emm
1 and were initially indistinguishable from other United Kingdom
emm
1 isolates. Sequencing of the virulence gene
sic
revealed that all outbreak isolates had the same unique
sic
type. Genome sequencing confirmed that the cluster was caused by a unique
S. pyogenes
clone. Transmission between patients occurred on a single day and was associated with casual contact only. A single isolate from one patient demonstrated a sequence change in
sic
consistent with longer infection duration. Transmission to health care workers was traced to single clinical contacts with index cases. The last case was detected 18 days after the first case. Following enhanced surveillance, the outbreak isolate was not detected again. Mutations in bacterial regulatory genes played no detectable role in this outbreak, illustrating the intrinsic ability of
emm
1
S. pyogenes
to spread while retaining virulence. This fast-moving outbreak highlights the potential of
S. pyogenes
to cause a range of diseases in the puerperium with rapid transmission, underlining the importance of immediate recognition and response by clinical infection and occupational health teams.
Exposure to Human and Bovine Noroviruses in a Birth Cohort in Southern India from 2002 to 2006
Authors: Menon Vipin Kumar , George Santosh , Shanti Aruna A. , Saravanabavan Anuradha , Samuel Prasanna , Ramani Sasirekha , Estes Mary K. , Kang Gagandeep 
Published: April 2013

ABSTRACT
Human and bovine norovirus virus-like particles were used to evaluate antibodies in Indian children at ages 6 and 36 months and their mothers. Antibodies to genogroup II viruses were acquired early and were more prevalent than antibodies to genogroup I. Low levels of IgG antibodies against bovine noroviruses indicate possible zoonotic transmission.
Analysis of Mutations in Streptomycin-Resistant Strains Reveals a Simple and Reliable Genetic Marker for Identification of the Mycobacterium tuberculosis Beijing Genotype
Authors: Villellas Cristina , Aristimuño Liselotte , Vitoria María-Asunción , Prat Cristina , Blanco Silvia , García de Viedma Darío , Domínguez José , Samper Sofía , Aínsa José A. 
Published: April 2013

ABSTRACT

The
Mycobacterium tuberculosis
pandemic is a major health problem, further complicated by an increasing incidence of drug-resistant isolates and the existence of highly transmissible strains, such as those in the Beijing family. Streptomycin (STR)-resistant
M. tuberculosis
clinical isolates have been analyzed to look for mutations in the
rpsL
,
rrs
, and
gidB
genes. In addition, the
Rv1258c
gene, which encodes Tap, an efflux pump that transports STR, has been sequenced. Mutations affecting codons 43 and 88 of the
rpsL
gene were found in 44.4% of the strains, and 16.7% of the strains carried mutations in the
rrs
gene, both of which probably contribute to STR resistance. Many strains presented with mutations in the
gidB
gene, but the implication of those mutations in STR resistance remains unclear. Interestingly, a cytosine nucleotide insertion between positions 580 and 581 (denominated Tap
580
) in the
Rv1258c
gene has been found in all Beijing isolates included in this study, suggesting that it might be a novel polymorphism specific to the Beijing family of
M. tuberculosis
. A simple and fast restriction fragment length polymorphism (RFLP)-PCR method for detecting the Tap
580
insertion has been developed and used to screen a collection of 220 DNA samples obtained from cultures of
M. tuberculosis
isolates and 30 respiratory specimens. In all cases, the Beijing and non-Beijing representative samples were identified correctly. Tap
580
is a novel polymorphism specific to the highly transmissible Beijing family, which allows for fast detection of these strains even at the very early stages of infection.
Quantitative and Qualitative Involvement of P3N-PIPO in Overcoming Recessive Resistance against Clover Yellow Vein Virus in Pea Carrying the
cyv1
Gene
Authors: Choi Sun Hee , Hagiwara-Komoda Yuka , Nakahara Kenji S. , Atsumi Go , Shimada Ryoko , Hisa Yusuke , Naito Satoshi , Uyeda Ichiro 
Published: April 2013

ABSTRACT

In pea carrying
cyv1
, a recessive gene for resistance to
Clover yellow vein virus
(ClYVV), ClYVV isolate Cl-no30 was restricted to the initially infected cells, whereas isolate 90-1 Br2 overcame this resistance. We mapped the region responsible for breaking of
cyv1
-mediated resistance by examining infection of
cyv1
pea with chimeric viruses constructed from parts of Cl-no30 and 90-1 Br2. The breaking of resistance was attributed to the P3 cistron, which is known to produce two proteins: P3, from the main open reading frame (ORF), and P3N-PIPO, which has the N-terminal part of P3 fused to amino acids encoded by a small open reading frame (ORF) called PIPO in the +2 reading frame. We introduced point mutations that were synonymous with respect to the P3 protein but nonsynonymous with respect to the P3N-PIPO protein, and vice versa, into the chimeric viruses. Infection of plants with these mutant viruses revealed that both P3 and P3N-PIPO were involved in overcoming
cyv1
-mediated resistance. Moreover, P3N-PIPO quantitatively affected the virulence of Cl-no30 in
cyv1
pea. Additional expression in
trans
of the P3N-PIPO derived from Cl-no30, using
White clover mosaic virus
as a vector, enabled Cl-no30 to move to systemic leaves in
cyv1
pea. Susceptible pea plants infected with chimeric ClYVV possessing the P3 cistron of 90-1 Br2, and which were therefore virulent toward
cyv1
pea, accumulated more P3N-PIPO than did those infected with Cl-no30, suggesting that the higher level of P3N-PIPO in infected cells contributed to the breaking of resistance by 90-1 Br2. This is the first report showing that P3N-PIPO is a virulence determinant in plants resistant to a potyvirus.
The Four and a Half LIM Family Members Are Novel Interactants of the Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein
Authors: McCabe Áine , Hashimoto Kenichi , Hall William W. , Sheehy Noreen 
Published: April 2013

ABSTRACT

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). The viral regulatory protein Tax1 plays a pivotal role in T-cell transformation and ATL development. Previous studies in our laboratory, using the yeast 2-hybrid approach to screen a T-cell library for Tax1-interacting partners, identified the cellular Four and a Half Lim domain protein 3 (FHL3) as a possible Tax1-interacting candidate. FHL3 is a member of the FHL family of proteins, which function as transcriptional coactivators and cytoskeleton regulators and have a role in cancer progression and development. The aim of this study was to investigate the physical and functional interaction between Tax1 and members of the FHL family of proteins. We show that Tax1 and FHL3 interact both
in vitro
and
in vivo
. Furthermore, both FHL1 and -2 also interact with Tax1. We have demonstrated that FHL3 enhances Tax1-mediated activation of the viral long terminal repeat (LTR) without affecting basal activity and that FHL1 to -3 regulate NF-κB activation by Tax1 in a cell-specific manner. In addition, we have found that the interaction between Tax1 and FHL1 to -3 affects the localization of these proteins, leading to their redistribution in cells. Tax1 also affected FHL3 cytoskeleton function by increasing FHL3-mediated cell spreading. Overall, our results suggest that the interaction between Tax1 and the FHL family alters both the transactivating activity and the subcellular localization of Tax1 and provide new insights into molecular mechanisms that underlie the oncogenic nature of this HTLV-1 protein.
The Cytokine Response of U937-Derived Macrophages Infected through Antibody-Dependent Enhancement of Dengue Virus Disrupts Cell Apical-Junction Complexes and Increases Vascular Permeability
Authors: Puerta-Guardo Henry , Raya-Sandino Arturo , González-Mariscal Lorenza , Rosales Victor H. , Ayala-Dávila José , Chávez-Mungía Bibiana , Martínez-Fong Daniel , Medina Fernando , Ludert Juan E. , del Angel Rosa María 
Published: April 2013

ABSTRACT

Severe dengue (SD) is a life-threatening complication of dengue that includes vascular permeability syndrome (VPS) and respiratory distress. Secondary infections are considered a risk factor for developing SD, presumably through a mechanism called antibody-dependent enhancement (ADE). Despite extensive studies, the molecular bases of how ADE contributes to SD and VPS are largely unknown. This work compares the cytokine responses of differentiated U937 human monocytic cells infected directly with dengue virus (DENV) or in the presence of enhancing concentrations of a humanized monoclonal antibody recognizing protein E (ADE-DENV infection). Using a cytometric bead assay, ADE-DENV-infected cells were found to produce significantly higher levels of the proinflammatory cytokines interleukin 6 (IL-6), IL-12p70, and tumor necrosis factor alpha (TNF-α), as well as prostaglandin E
2
(PGE
2
), than cells directly infected. The capacity of conditioned supernatants (conditioned medium [CM]) to disrupt tight junctions (TJs) in MDCK cell cultures was evaluated. Exposure of MDCK cell monolayers to CM collected from ADE-DENV-infected cells (ADE-CM) but not from cells infected directly led to a rapid loss of transepithelial electrical resistance (TER) and to delocalization and degradation of apical-junction complex proteins. Depletion of either TNF-α, IL-6, or IL-12p70 from CM from ADE-DENV-infected cells fully reverted the disrupting effect on TJs. Remarkably, mice injected intraperitoneally with ADE-CM showed increased vascular permeability in sera and lungs, as indicated by an Evans blue quantification assay. These results indicate that the cytokine response of U937-derived macrophages to ADE-DENV infection shows an increased capacity to disturb TJs, while results obtained with the mouse model suggest that such a response may be related to the vascular plasma leakage characteristic of SD.
Identification of Multiple Novel Viruses, Including a Parvovirus and a Hepevirus, in Feces of Red Foxes
Authors: Bodewes Rogier , van der Giessen Joke , Haagmans Bart L. , Osterhaus Albert D. M. E. , Smits Saskia L. 
Published: April 2013

ABSTRACT

Red foxes (
Vulpes vulpes
) are the most widespread members of the order of
Carnivora
. Since they often live in (peri)urban areas, they are a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. Here we evaluated the fecal viral microbiome of 13 red foxes by random PCR in combination with next-generation sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses, and picobirnaviruses, were identified.
The Small Molecules AZD0530 and Dasatinib Inhibit Dengue Virus RNA Replication via Fyn Kinase
Authors: de Wispelaere Melissanne , LaCroix Amy J. , Yang Priscilla L. 
Published: April 2013

ABSTRACT

In this study, we characterized the antiviral mechanism of action of AZD0530 and dasatinib, two pharmacological inhibitors of host kinases, that also inhibit dengue virus (DV) infection. Using Northern blot and reporter replicon assays, we demonstrated that both small molecules inhibit the DV2 infectious cycle at the step of steady-state RNA replication. In order to identify the cellular target of AZD0530 and dasatinib mediating this anti-DV2 activity, we examined the effects of RNA interference (RNAi)-mediated depletion of the major kinases known to be inhibited by these small molecules. We determined that Fyn kinase, a target of both AZD0530 and dasatinib, is involved in DV2 RNA replication and is probably a major mediator of the anti-DV activity of these compounds. Furthermore, serial passaging of DV2 in the presence of dasatinib led to the identification of a mutation in the transmembrane domain 3 of the NS4B protein that overcomes the inhibition of RNA replication by AZD0530, dasatinib, and Fyn RNAi. Although we observed that dasatinib also inhibits DV2 particle assembly and/or secretion, this activity does not appear to be mediated by Src-family kinases. Together, our results suggest that AZD0530 and dasatinib inhibit DV at the step of viral RNA replication and demonstrate a critical role for Fyn kinase in this viral process. The antiviral activity of these compounds
in vitro
makes them useful pharmacological tools to validate Fyn or other host kinases as anti-DV targets
in vivo
.
Adaptation of Avian Influenza A Virus Polymerase in Mammals To Overcome the Host Species Barrier
Authors: Mänz Benjamin , Schwemmle Martin , Brunotte Linda 
Published: April 2013

ABSTRACT
Avian influenza A viruses, such as the highly pathogenic avian H5N1 viruses, sporadically enter the human population but often do not transmit between individuals. In rare cases, however, they establish a new lineage in humans. In addition to well-characterized barriers to cell entry, one major hurdle which avian viruses must overcome is their poor polymerase activity in human cells. There is compelling evidence that these viruses overcome this obstacle by acquiring adaptive mutations in the polymerase subunits PB1, PB2, and PA and the nucleoprotein (NP) as well as in the novel polymerase cofactor nuclear export protein (NEP). Recent findings suggest that synthesis of the viral genome may represent the major defect of avian polymerases in human cells. While the precise mechanisms remain to be unveiled, it appears that a broad spectrum of polymerase adaptive mutations can act collectively to overcome this defect. Thus, identification and monitoring of emerging adaptive mutations that further increase polymerase activity in human cells are critical to estimate the pandemic potential of avian viruses.