bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Treatment against Hepatitis C Virus on Overall Survival of Naive Patients with Advanced Liver Disease
Authors: Kutala Blaise K. , Guedj Jeremie , Asselah Tarik , Boyer Nathalie , Mouri Feryel , Martinot-Peignoux Michelle , Valla Dominique , Marcellin Patrick , Duval Xavier 
Published: November 2014

ABSTRACT

The beneficial effect of achieving a sustained virological response (SVR) after antiviral treatment against hepatitis C virus is well established. However, it remains unclear whether unsuccessful treatment (non-SVR) also improves patient survival, especially in patients with advanced liver fibrosis. We retrospectively evaluated the incidence of death or liver transplantation in the 427 naive patients with a Child-Pugh score of A and advanced fibrosis newly admitted to the Hospital Beaujon between 2000 and 2010. Patients were followed for a median time of 5.5 years. The baseline characteristics of untreated (
n
= 102) and treated (
n
= 325) patients were largely similar, and there was no evidence of a bias of indication. Treated patients received a combination of interferon and ribavirin and had an SVR rate of 32%. The incidence of death or liver transplantation per 100 person-years was 1.00, 3.20, and 5.44 in SVR, non-SVR, and untreated patients, respectively. After adjusting for baseline characteristics, the risk of death or liver transplantation was significantly lower in SVR than in non-SVR patients and in non-SVR than in untreated patients (hazard ratios, 0.35 and 0.51, respectively;
P
= 0.019 and 0.038, respectively). The effect of treatment in non-SVR patients was higher in patients who had a virological or a biochemical response than in those who did not have a virological or a biochemical response. The risk of death or liver transplantation was significantly lower in treated than in untreated patients. Moreover, there was a gradient of mortality between patients with SVRs, virological or biochemical responders, and untreated patients, suggesting that treatment, even in the absence of viral eradication, has a beneficial effect on survival.
Radioiodinated DPA-713 Imaging Correlates with Bactericidal Activity of Tuberculosis Treatments in Mice
Authors: Ordonez Alvaro A. , Pokkali Supriya , DeMarco Vincent P. , Klunk Mariah , Mease Ronnie C. , Foss Catherine A. , Pomper Martin G. , Jain Sanjay K. 
Published: November 2014

ABSTRACT

Current tools for monitoring response to tuberculosis treatments have several limitations. Noninvasive biomarkers could accelerate tuberculosis drug development and clinical studies, but to date little progress has been made in developing new imaging technologies for this application. In this study, we developed pulmonary single-photon emission computed tomography (SPECT) using radioiodinated DPA-713 to serially monitor the activity of tuberculosis treatments in live mice, which develop necrotic granulomas and cavitary lesions. C3HeB/FeJ mice were aerosol infected with
Mycobacterium tuberculosis
and administered either a standard or a highly active bedaquiline-containing drug regimen. Serial
125
I-DPA-713 SPECT imaging was compared with
18
F-fluorodeoxyglucose (
18
F-FDG) positron emission tomography (PET) and standard microbiology.
Ex vivo
studies were performed to characterize and correlate DPA-713 imaging with cellular and cytokine responses. Pulmonary
125
I-DPA-713 SPECT, but not
18
F-FDG PET, was able to correctly identify the bactericidal activities of the two tuberculosis treatments as early as 4 weeks after the start of treatment (
P
< 0.03). DPA-713 readily penetrated the fibrotic rims of necrotic and cavitary lesions. A time-dependent decrease in both tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels was observed with treatments, with
125
I-DPA-713 SPECT correlating best with tissue TNF-α levels (ρ = 0.94;
P
< 0.01).
124
I-DPA-713 was also evaluated as a PET probe and demonstrated a 4.0-fold-higher signal intensity in the infected tuberculous lesions than uninfected controls (
P
= 0.03). These studies provide proof of concept for application of a novel noninvasive imaging biomarker to monitor tuberculosis treatments, with the potential for application for humans.
Complete Nucleotide Sequence of
cfr
-Carrying IncX4 Plasmid pSD11 from Escherichia coli
Authors: Sun Jian , Deng Hui , Li Liang , Chen Mu-Ya , Fang Liang-Xing , Yang Qiu-E , Liu Ya-Hong , Liao Xiao-Ping 
Published: November 2014

ABSTRACT

We report the complete nucleotide sequence of a plasmid carrying the multiresistance gene
cfr
. This plasmid was isolated from an
Escherichia coli
strain of swine origin in 2011. This 37,672-bp plasmid, pSD11, had an IncX4 backbone similar to those of the IncX4 plasmids obtained from the United States and Australia, in which the
cfr
gene was flanked by two copies of IS
26
and a truncated Tn
1331
was inserted.
Inappropriate Continued Empirical Vancomycin Use in a Hospital with a High Prevalence of Methicillin-Resistant Staphylococcus aureus
Authors: Kim Nak-Hyun , Koo Hei Lim , Choe Pyeong Gyun , Cheon Shinhye , Kim Moon Suk , Lee Myung Jin , Jung Young Hee , Park Wan Beom , Song Kyoung-Ho , Kim Eu Suk , Bang Ji Hwan , Kim Hong Bin , Park Sang Won , Kim Nam Joong , Oh Myoung-don , Kim Eui Chong 
Published: November 2014

ABSTRACT
Vancomycin is frequently inappropriately prescribed, especially as empirical treatment. The aim of this study was to evaluate (i) the amount of inappropriate continued empirical vancomycin use as a proportion of total vancomycin use and (ii) the risk factors associated with inappropriate continued empirical vancomycin use. We reviewed the medical records of adult patients who had been prescribed at least one dose of parenterally administered vancomycin between January and June 2012, in a single tertiary care hospital. When empirically prescribed vancomycin treatment was continued after 96 h without documentation of beta-lactam-resistant Gram-positive microorganisms in clinical specimens with significance, the continuation was considered inappropriate, and the amount used thereafter was considered inappropriately used. We identified risk factors associated with inappropriate continued empirical vancomycin use by multiple logistic regression. During the study period, the amount of parenterally administered vancomycin prescribed was 34.2 defined daily doses (DDDs)/1,000 patient-days (1,084 prescriptions for 971 patients). The amount of inappropriate continued empirical vancomycin use was 8.5 DDDs/1,000 patient-days, which represented 24.9% of the total parenterally administered vancomycin used (8.5/34.2 DDDs/1,000 patient-days). By multivariate analyses, inappropriate continued empirical vancomycin use was independently associated with the absence of any documented etiological organism (adjusted odds ratio [aOR], 1.60 [95% confidence interval {CI}, 1.06 to 2.41]) and suspected central nervous system (CNS) infections (aHR, 2.33 [95% CI, 1.20 to 4.50]). Higher Charlson's comorbidity index scores were inversely associated with inappropriate continued empirical vancomycin use (aHR, 0.90 [95% CI, 0.85 to 0.97]). Inappropriate continued empirical vancomycin use represented 24.9% of the total amount of vancomycin prescribed, which indicates room for improvement.
IL12Rβ1ΔTM Is a Secreted Product ofil12rb1That Promotes Control of Extrapulmonary Tuberculosis
Authors: Ray Aurelie A. , Fountain Jeffrey J. , Miller Halli E. , Cooper Andrea M. , Robinson Richard T. 
Published: November 2014

ABSTRACTIL12RB1is a human gene that is important for resistance toMycobacterium tuberculosisinfection.IL12RB1is expressed by multiple leukocyte lineages, and encodes a type I transmembrane protein (IL12Rβ1) that associates with IL12p40 and promotes the development of host-protective TH1cells. Recently, we observed thatil12rb1—the mouse homolog ofIL12RB1—is alternatively spliced by leukocytes to produce a second isoform (IL12Rβ1ΔTM) that has biological properties distinct from IL12Rβ1. Although the expression of IL12Rβ1ΔTM is elicited byM. tuberculosisin vivo, and its overexpression enhances IL12p40 responsivenessin vitro, the contribution of IL12Rβ1ΔTM to controllingM. tuberculosisinfection has not been tested. Here, we demonstrate that IL12Rβ1ΔTM represents a secreted product ofil12rb1that, when absent from mice, compromises their ability to controlM. tuberculosisinfection in extrapulmonary organs. Furthermore, elevatedM. tuberculosisburdens in IL12Rβ1ΔTM-deficient animals are associated with decreased lymph node cellularity and a decline in TH1 development. Collectively, these data support a model wherein IL12Rβ1ΔTM is a secreted product ofil12rb1that promotes resistance toM. tuberculosisinfection by potentiating THcells response to IL-12.
Chemical Biology Applied to the Study of Bacterial Pathogens
Authors: Anthouard Rebecca , DiRita Victor J. 
Published: November 2014

ABSTRACTIn recent years, chemical biology and chemical genomics have been increasingly applied to the field of microbiology to uncover new potential therapeutics as well as to probe virulence mechanisms in pathogens. The approach offers some clear advantages, as identified compounds (i) can serve as a proof of principle for the applicability of drugs to specific targets; (ii) can serve as conditional effectors to explore the function of their targetsin vitroandin vivo; (iii) can be used to modulate gene expression in otherwise genetically intractable organisms; and (iv) can be tailored to a narrow or broad range of bacteria. This review highlights recent examples from the literature to illustrate how the use of small molecules has advanced discovery of novel potential treatments and has been applied to explore biological mechanisms underlying pathogenicity. We also use these examples to discuss practical considerations that are key to establishing a screening or discovery program. Finally, we discuss the advantages and challenges of different approaches and the methods that are emerging to address these challenges.
IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction
Authors: Swierstra Jasper , Debets Stephanie , de Vogel Corné , Lemmens-den Toom Nicole , Verkaik Nelianne , Ramdani-Bouguessa Nadjia , Jonkman Marcel F. , van Dijl Jan Maarten , Fahal Ahmed , van Belkum Alex , van Wamel Willem 
Published: November 2014

ABSTRACTIgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses againstStaphylococcus aureusmight generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 differentS. aureusvirulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alpha-toxin, chemotaxis inhibitory protein ofS. aureus(CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistentS. aureuscarriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with highS. aureuscarriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.
Edwardsiella tarda MliC, a Lysozyme Inhibitor That Participates in Pathogenesis in a Manner That Parallels Ivy
Authors: Li Mo-Fei , Wang Chong , Sun Li 
Published: November 2014

ABSTRACT

Edwardsiella tarda
, a bacterial pathogen to farmed fish as well as humans, possesses the genes of two lysozyme inhibitors,
ivy
and
mliC
(

ivy
Et

and

mliC
Et

). We recently studied Ivy
Et
and found it to be implicated in
E. tarda
virulence. In the present study, we characterized MliC
Et
in comparison with Ivy
Et
in a turbot model. MliC
Et
contains the FWSKG motif and two cysteines (C33 and C98) that are highly conserved in subgroup 1 MliCs but are of unknown functional importance. To examine the essentialness of these conserved structural features, recombinant MliC
Et
(rMliC) and its mutants bearing C33S and W79A (of the FWSKG motif) substitutions were prepared. Subsequent analysis showed that rMliC (i) inhibited lysozyme-induced lysis of a Gram-positive bacterium, (ii) reduced serum-facilitated lysozyme killing of
E. tarda
, and (iii) when introduced into turbot, promoted bacterial dissemination in fish tissues. The C33S mutation had no influence on the activity of rMliC, while the W79A mutation slightly but significantly enhanced the activity of rMliC. Knockout strains of either

mliC
Et

or

ivy
Et

were severely attenuated for the ability of tissue invasion, host lethality, serum survival, and intracellular replication. The lost virulence of the
mliC
transformant (TXΔ
mliC
) was restored by complementation with an introduced

mliC
Et

gene. Compared to the Δ

ivy
Et

or Δ

mliC
Et

single-knockout strains, the Δ

mliC
Et

Δ

ivy
Et

double-knockout strain was significantly impaired in most of the virulence features. Together, these results provide the first evidence that the conserved cysteine is functionally dispensable to a subgroup 1 MliC and that as a virulence factor, MliC
Et
most likely works in a concerted and parallel manner with Ivy.
An Inducible and Secreted Eukaryote-Like Serine/Threonine Kinase of Salmonella enterica Serovar Typhi Promotes Intracellular Survival and Pathogenesis
Authors: Theeya Nagaraja , Ta Atri , Das Sayan , Mandal Rahul S. , Chakrabarti Oishee , Chakrabarti Saikat , Ghosh Amar N. , Das Santasabuj 
Published: November 2014

ABSTRACT

Eukaryote-like serine/threonine kinases (eSTKs) constitute an important family of bacterial virulence factors. Genome analysis had predicted putative eSTKs in
Salmonella enterica
serovar Typhi, although their functional characterization and the elucidation of their role in pathogenesis are still awaited. We show here that the primary sequence and secondary structure of the
t4519
locus of
Salmonella
Typhi Ty2 have all the signatures of eukaryotic superfamily kinases.
t4519
encodes a ∼39-kDa protein (T4519), which shows serine/threonine kinase activities
in vitro
. Recombinant T4519 (rT4519) is autophosphorylated and phosphorylates the universal substrate myelin basic protein. Infection of macrophages results in decreased viability of the mutant (Ty2Δ
t4519
) strain, which is reversed by gene complementation. Moreover, reactive oxygen species produced by the macrophages signal to the bacteria to induce T4519, which is translocated to the host cell cytoplasm. That T4519 may target a host substrate(s) is further supported by the activation of host cellular signaling pathways and the induction of cytokines/chemokines. Finally, the role of T4519 in the pathogenesis of
Salmonella
Typhi is underscored by the significantly decreased mortality of mice infected with the Ty2Δ
t4519
strain and the fact that the competitive index of this strain for causing systemic infection is 0.25% that of the wild-type strain. This study characterizes the first eSTK of
Salmonella
Typhi and demonstrates its role in promoting phagosomal survival of the bacteria within macrophages, which is a key determinant of pathogenesis. This, to the best of our knowledge, is the first study to describe the essential role of eSTKs in the
in vivo
pathogenesis of
Salmonella
spp.
Morphological and hemodynamic analysis of posterior communicating artery aneurysms prone to rupture: a matched case–control study
Authors: Duan Guoli , Lv Nan , Yin Jianhua , Xu Jinyu , Hong Bo , Xu Yi , Liu Jianmin , Huang Qinghai 
Published: November 2014

ObjectivesWe evaluated the correlation between posterior communicating artery (PcomA) aneurysm rupture and morphological and hemodynamic parameters to assess related rupture risk indices.MethodsSix patients with PcomA aneurysms that ultimately ruptured (cases) were studied after initially being included in a prospective database including their three-dimensional (3D) imaging before rupture. For each case, four incidental stable unruptured aneurysms (controls) were randomly selected and matched based on clinical factors. The 3D images from all patients were reconstructed to establish the patient-specific model. Six morphologic parameters and three hemodynamic parameters were measured and calculated. A conditional logistic regression analysis was used to assess the individual risk of rupture.ResultsThe analysis demonstrated a larger aneurysm size (p=0.001), higher aspect ratio (p=0.018), ellipticity index (p<0.001), undulation index (p=0.005), percentage of low wall shear stress (WSS) area (LSA%) (p=0.010), and a lower normalized WSS (p=0.005) in the case group. The multivariate conditional logistic regression analysis demonstrated that only normalized WSS was significantly associated with the rupture of PcomA aneurysms (OR 0.151; 95% CI 0.025 to 0.914; p=0.040).ConclusionsHemodynamics and morphology are closely associated with aneurysm rupture, and WSS may be a more reliable parameter characterizing the rupture status of PcomA aneurysms.
Carotid sacrifice with a single Penumbra occlusion device: a feasibility study in a swine model
Authors: Spiotta Alejandro M , Turner Raymond D , Chaudry M Imran , Turk Aquilla S , Hui Ferdinand K , Schonholz Claudio 
Published: November 2014

IntroductionCarotid sacrifice is a valuable tool in the treatment of select vascular lesions. Traditional coil embolization as the primary means of carotid sacrifice can be expensive, with high radiation exposure. We investigated the feasibility of a novel hybrid coil, the Penumbra occlusion device (POD), for carotid sacrifice in a swine model.MethodsA total of eight common carotid artery sacrifices were performed in fully heparinized pigs under fluoroscopic guidance. A single POD device was deployed within each vessel, and intermittent follow-up angiography was performed to assess flow.ResultsComplete carotid occlusion was achieved in all cases with a single POD (time range 2–15 min) without any coil migration or intraprocedural complications. Once the anchor zone was stable, no distal migrations were observed during either proximal soft coil packing or during hand injected angiography. Complete occlusion was verified between 2 and 15 min following POD deployment.ConclusionsCarotid artery sacrifice using a novel POD device is safe and effective, allowing for reduced radiation and material costs compared with any other described endovascular technique.
Using Interaction Data to Explain Difficulty Navigating Online
Authors: Thomas Paul 
Published: November 2014

A user's behaviour when browsing a Web site contains clues to that user's experience. It is possible to record some of these behaviours automatically, and extract signals that indicate a user is having trouble finding information. This allows for Web site analytics based on user experiences, not just page impressions.
A series of experiments identified user browsing behaviours—such as time taken and amount of scrolling up a page—which predict navigation difficulty and which can be recorded with minimal or no changes to existing sites or browsers. In turn, patterns of page views correlate with these signals and these patterns can help Web authors understand where and why their sites are hard to navigate. A new software tool, “LATTE,” automates this analysis and makes it available to Web authors in the context of the site itself.
Topology-constrained synthesis of vector patterns
Authors: Zhou Shizhe , Jiang Changyun , Lefebvre Sylvain 
Published: November 2014

Decorative patterns are observed in many forms of art, typically enriching the visual aspect of otherwise simple shapes. Such patterns are especially difficult to create, as they often exhibit intricate structural details and at the same time have to precisely match the size and shape of the underlying geometry. In the field of Computer Graphics, several approaches have been proposed to automatically synthesize a decorative pattern along a curve, from an example. This empowers non expert users with a simple brush metaphor, allowing them to easily paint complex structured decorations.
We extend this idea to the space of design and fabrication. The major challenge is to properly account for the topology of the produced patterns. In particular, our technique ensures that synthesized patterns will be made of exactly one connected component, so that once printed they form a single object. To achieve this goal we propose a two steps synthesis process, first synthesizing the topology of the pattern and later synthesizing its exact geometry. We introduce topology descriptors that efficiently capture the topology of the pattern synthesized so far.

We propose several applications of our method, from designing objects using synthesized patterns along curves and within rectangles, to the decoration of surfaces with a dedicated smooth frame interpolation. Using our technique, designers
paint
structured patterns that can be fabricated into solid, tangible objects, creating unusual and surprising designs of lamps, chairs and laces from examples.
TrackCam
Authors: Liu Shuaicheng , Wang Jue , Cho Sunghyun , Tan Ping 
Published: November 2014

Panning and tracking shots are popular photography techniques in which the camera tracks a moving object and keeps it at the same position, resulting in an image where the moving foreground is sharp but the background is blurred accordingly, creating an artistic illustration of the foreground motion. Such shots however are hard to capture even for professionals, especially when the foreground motion is complex (e.g., non-linear motion trajectories).
In this work we propose a system to generate realistic, 3D-aware tracking shots from consumer videos. We show how computer vision techniques such as segmentation and structure-from-motion can be used to lower the barrier and help novice users create high quality tracking shots that are physically plausible. We also introduce a pseudo 3D approach for relative depth estimation to avoid expensive 3D reconstruction for improved robustness and a wider application range. We validate our system through extensive quantitative and qualitative evaluations.