bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metal artifact reduction in computed tomography using local models in an image block‐iterative scheme
Authors: Van Slambrouck Katrien , Nuyts Johan 
Published: November 2012

Purpose:In iterative reconstruction, metal artifacts can be reduced by applying more accurate reconstruction models that are usually also more computationally demanding. The hypothesis of this work is that these complex models only need to be applied in the vicinity of the metals and that a less complex model can be used for the remainder of the reconstruction volume.Methods:A method is described that automatically divides the reconstruction volume into metal and nonmetal regions. The different regions are called patches. A different energy and resolution model can be assigned to each of the patches. The patches containing metals are reconstructed with a fully polychromatic spectral model (IMPACT) and if necessary with an increased resolution model. The patch without metals is reconstructed with a simple polychromatic model (MLTRC) that only includes the spectral behavior of water attenuation. Comparing the computational complexity of IMPACT and MLTRC gives a ratio of 8:3. The different patches are updated sequentially as in a grouped coordinate algorithm. Two phantoms were simulated and measured: a circular phantom containing small metal cylinders and a body phantom representing a human pelvis with two femoral implants. As a first test, the sequential update of the patches was applied while using the same energy model for all patches. Second, the local model approach was applied using MLTRC for nonmetal regions and IMPACT for metal regions. The results of different iterative reconstruction schemes are compared to the results of projection completion, another important method for the reduction of metal artifacts.Results:Reconstruction schemes including the sequential update of the patches result in images with less streak artifacts compared to a regular reconstruction. The sequential update of each of the metal regions improves the relative convergence of the metals (edges and attenuation values) against the rest of the image, which leads to an improved artifact reduction. Using the combined IMPACT+MLTRC model results in a similar image quality as using IMPACT everywhere, while providing an important benefit regarding computational complexity. Some streak and shadow artifacts were still present, but all structures present in the phantom could be observed. Projection completion results in reconstructions with less obvious streak and shadow artifacts but tends to deform or erase structures lying close to or in between metallic structures.Conclusions:Metal artifact reduction with iterative reconstruction can be achieved by using complex models only locally without losing image quality. Separately updating metal regions leads to reduced streak artifacts. Structures lying close to or in between metals are often better reconstructed, compared to projection completion results, because all available information is used.
18β-Glycyrrhetinic Acid Inhibits Methicillin-Resistant Staphylococcus aureus Survival and Attenuates Virulence Gene Expression
Authors: Long Danyelle R. , Mead Julia , Hendricks Jay M. , Hardy Michele E. , Voyich Jovanka M. 
Published: November 2012

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance in
S. aureus
strains has created a need for alternative therapies to treat disease. A component of the licorice root
Glycyrrhiza
spp., 18β-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores the
in vitro
and
in vivo
effects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 μM. Upon exposure of
S. aureus
to sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, including
saeR
and
hla
. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression of
saeR
and
hla
genes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression in
S. aureus
both
in vitro
and
in vivo
.
Functional Analysis of Pneumococcal Drug Efflux Pumps Associates the MATE DinF Transporter with Quinolone Susceptibility
Authors: Tocci Nadia , Iannelli Francesco , Bidossi Alessandro , Ciusa Maria Laura , Decorosi Francesca , Viti Carlo , Pozzi Gianni , Ricci Susanna , Oggioni Marco Rinaldo 
Published: November 2012

ABSTRACT

The pneumococcal chromosome encodes about 140 transporters, many of which are predicted to be involved in efflux. In order to critically evaluate pneumococcal efflux, a series of transporter mutants were constructed, and their phenotypes were assayed by disk diffusion, microdilution drug susceptibility testing (MIC testing), growth of cultures at sub-MIC concentrations, and phenotype microarray analysis. Mutants with mutations in seven ATP binding cassette (ABC) transporters, three multiantimicrobial extrusion (MATE) family efflux pumps, and one major facilitator superfamily (MFS) transporter were obtained in
Streptococcus pneumoniae
strain DP1004. The susceptibility of these 11 mutants to over 250 different substances was compared to that of the parent strain. Of the tested transporters, only the ABC transporter PatAB (SP2073-5) presented a clear multidrug resistance (MDR) profile, as the mutant showed significantly increased susceptibility to ethidium bromide, acriflavine, and berberine. Among the other transporters analyzed, the mutants devoid of the MATE efflux pump SP2065 exhibited reduced susceptibility to novobiocin, and those with mutations of the MATE family DinF transport system (SP1939) exhibited increased susceptibility to moxifloxacin, ciprofloxacin, and levofloxacin. This change in quinolone MIC was found to be independent from the competence-mediated effect of quinolones on the
cinA-recA-dinF
operon. Furthermore, the
dinF
mutant, in contrast to the parental strain, allowed selection for quinolone-resistant mutants when exposed to moxifloxacin. These data confirm the clear MDR profile of the PatAB ABC transporter and suggest for the MATE DinF a phenotype associated with quinolone susceptibility, particularly for moxifloxacin.
Pharmacokinetics and Pharmacodynamics of Anidulafungin for Experimental Candida Endophthalmitis: Insights into the Utility of Echinocandins for Treatment of a Potentially Sight-Threatening Infection
Authors: Livermore J. L. , Felton T. W. , Abbott J. , Sharp A. , Goodwin J. , Gregson L. , Warn P. A. , Howard S. J. , Hope W. W. 
Published: November 2012

ABSTRACTCandidachorioretinitis and endophthalmitis are relatively common manifestations of disseminated candidiasis. Anidulafungin is increasingly used for the treatment of disseminated candidiasis, but its efficacy forCandidaendophthalmitis is not known. A nonneutropenic model of hematogenousCandidaendophthalmitis was used. Anidulafungin at 5, 10, and 20 mg/kg was initiated at 48 h postinoculation. The fungal densities in the kidney and vitreous humor were determined. Anidulafungin concentrations in the plasma and vitreous humor were measured using high-performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic model was used to link anidulafungin concentrations with the observed antifungal effect. The area under the concentration-time curve (AUC) associated with stasis was determined in the both the kidney and the vitreous humor. The results were bridged to humans to identify likely dosages that are associated with significant antifungal activity within the eye. Inoculation ofCandida albicansresulted in logarithmic growth in both the vitreous humor and the kidney. The pharmacokinetics of anidulafungin were linear. There was dose-dependent penetration of the anidulafungin into the vitreous humor. The exposure-response relationships in the kidney and vitreous were completely discordant. AUCs of 270 and 100 were required for stasis in the eye and kidney, respectively. The currently licensed regimen results in an AUC for an average patient that is associated with stasis in the kidney but minimal antifungal activity in the eye. We conclude that anidulafungin penetrates the eye in a dose-dependent manner and that dosages higher than those currently licensed are required to achieve significant antifungal activity in the eye.
Interaction of Platelets and Anidulafungin against Aspergillus fumigatus
Authors: Perkhofer Susanne , Striessnig Barbara , Sartori Bettina , Hausott Barbara , Ott Helmut W. , Lass-Flörl Cornelia 
Published: November 2012

ABSTRACT

The combination of platelets and anidulafungin at 0.03 μg/ml significantly (
P
< 0.05) reduced the germination rate and hyphal elongation in
Aspergillus fumigatus
compared to those with either anidulafungin only or an untreated control. Platelets decreased the expression of the
fks
gene, which plays an important role in cell wall synthesis. Our results suggest that human platelets plus anidulafungin might contribute to defense against
A. fumigatus
.
Rapid Isolation and Susceptibility Testing of Leptospira spp. Using a New Solid Medium, LVW Agar
Authors: Wuthiekanun Vanaporn , Amornchai Premjit , Paris Daniel H. , Langla Sayan , Thaipadunpanit Janjira , Chierakul Wirongrong , Smythe Lee D. , White Nicholas J. , Day Nicholas P. J. , Limmathurotsakul Direk , Peacock Sharon J. 
Published: November 2012

ABSTRACT

Pathogenic
Leptospira
spp., the causative agents of leptospirosis, are slow-growing Gram-negative spirochetes. Isolation of
Leptospira
from clinical samples and testing of antimicrobial susceptibility are difficult and time-consuming. Here, we describe the development of a new solid medium that facilitates more-rapid growth of
Leptospira
spp. and the use of this medium to evaluate the Etest's performance in determining antimicrobial MICs to drugs in common use for leptospirosis. The medium was developed by evaluating the effects of numerous factors on the growth rate of
Leptospira interrogans
strain NR-20157. These included the type of base agar, the concentration of rabbit serum (RS), and the concentration and duration of CO
2
incubation during the initial period of culture. The highest growth rate of NR-20157 was achieved using a Noble agar base supplemented with 10% RS (named LVW agar), with an initial incubation at 30°C in 5% CO
2
for 2 days prior to continuous culture in air at 30°C. These conditions were used to develop the Etest for three species,
L. interrogans
(NR-20161),
L. kirschnerii
(NR-20327), and
L. borgpetersenii
(NR-20151). The MICs were read on day 7 for all samples. The Etest was then performed on 109 isolates of pathogenic
Leptospira
spp. The MIC
90
values for penicillin G, doxycycline, cefotaxime, ceftriaxone, and chloramphenicol were 0.64 units/ml and 0.19, 0.047, 0.5, and 2 μg/ml, respectively. The use of LVW agar, which enables rapid growth, isolation of single colonies, and simple antimicrobial susceptibility testing for
Leptospira
spp., provides an opportunity for new areas of fundamental and applied research.
Tigecycline Displays
In Vivo
Bactericidal Activity against Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae after 72-Hour Exposure Period
Authors: Tessier Pamela R. , Nicolau David P. 
Published: November 2012

ABSTRACT

Progressively enhanced activity of a humanized tigecycline (TGC) regimen was noted over 3 days against an extended-spectrum-β-lactamase (ESBL)-producing
Escherichia coli
isolate and an ESBL-producing
Klebsiella pneumoniae
isolate. Bacterial density reduction approximated 3 log
10
approaching bactericidal activity at 72 h. This level of activity has not been previously noted for compounds such as tetracyclines, normally considered bacteriostatic antimicrobials. Extended regimen studies
in vivo
may aid in better delineation of antimicrobial effects, producing improved correlation with clinical outcomes.
FIM-1, a New Acquired Metallo-β-Lactamase from a Pseudomonas aeruginosa Clinical Isolate from Italy
Authors: Pollini Simona , Maradei Simona , Pecile Patrizia , Olivo Giuseppe , Luzzaro Francesco , Docquier Jean-Denis , Rossolini Gian Maria 
Published: November 2012

ABSTRACT

Acquired metallo-β-lactamases (MBLs) are resistance determinants of increasing clinical importance in Gram-negative bacterial pathogens, which confer a broad-spectrum β-lactam resistance, including carbapenems. Several such enzymes have been described since the 1990s. In the present study, a novel acquired MBL, named FIM-1, was identified and characterized. The
bla
FIM-1
gene was cloned from a multidrug-resistant
Pseudomonas aeruginosa
clinical isolate (FI-14/157) cultured from a patient with a vascular graft infection in Florence, Italy. The isolate belonged in the sequence type 235 epidemic clonal lineage. The FIM-1 enzyme is a member of subclass B1 and, among acquired MBLs, exhibited the highest similarity (ca. 40% amino acid identity) with NDM-type enzymes. In
P. aeruginosa
FI-14/157, the
bla
FIM-1
gene was apparently inserted into the chromosome and associated with IS
CR19
-like elements that were likely involved in the capture and mobilization of this MBL gene. Transfer experiments of the
bla
FIM-1
gene to an
Escherichia coli
strain or another
P. aeruginosa
strain by conjugation or electrotransformation were not successful. The FIM-1 protein was produced in
E. coli
and purified by two chromatography steps. Analysis of the kinetic parameters, carried out with the purified enzyme, revealed that FIM-1 has a broad substrate specificity, with a preference for penicillins (except the 6α-methoxy derivative temocillin) and carbapenems. Aztreonam was not hydrolyzed. Detection of this novel type of acquired MBL in a
P. aeruginosa
clinical isolate underscores the increasing diversity of such enzymes that can be encountered in the clinical setting.
The Target of Daptomycin Is Absent from Escherichia coli and Other Gram-Negative Pathogens
Authors: Randall Christopher P. , Mariner Katherine R. , Chopra Ian , O'Neill Alex J. 
Published: November 2012

ABSTRACT

Antistaphylococcal agents commonly lack activity against Gram-negative bacteria like
Escherichia coli
owing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against Gram negatives. Here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent from
E. coli
and other Gram-negative pathogens.
Measurement of Anti-Erythropoiesis-Stimulating Agent IgG4 Antibody as an Indicator of Antibody-Mediated Pure Red Cell Aplasia
Authors: Weeraratne Dohan K. , Kuck Andrew J. , Chirmule Narendra , Mytych Daniel T. 
Published: November 2012

ABSTRACTPatients treated with erythropoietin-based erythropoiesis-stimulating agents (ESAs) can develop a rare but life-threatening condition called antibody-mediated pure red cell aplasia (amPRCA). The antibody characteristics in a nephrology patient with amPRCA include high antibody concentrations with neutralizing activity and a mixed IgG subclass including anti-ESA IgG4 antibodies. In contrast, anti-ESA IgG4 antibody is generally not detected in baseline samples and antibody-positive non-PRCA patients. Therefore, we validated a highly sensitive immunoassay on the ImmunoCAP 100 instrument to quantitate anti-ESA IgG4 antibodies using a human recombinant anti-epoetin alfa (EPO) IgG4 antibody as a calibrator. The biotinylated ESA was applied to a streptavidin ImmunoCAP, and bound anti-ESA IgG4 antibodies were detected using a β-galactosidase-conjugated mouse anti-human IgG4 antibody. The validated assay was used to detect anti-ESA IgG4 in amPRCA and non-PRCA patients. The immunoassay detected 15 ng/ml of human anti-EPO IgG4 antibody in the presence of a 200 M excess of human anti-ESA IgG1, IgG2, or IgM antibody and tolerated 2 μg/ml of soluble erythropoietin. All patient samples with confirmed amPRCA had measurable anti-ESA IgG4 antibodies. In addition, 94% (17/18) of non-PRCA patient samples were antibody negative or had below 15 ng/ml of anti-ESA IgG4 antibodies. This novel immunoassay can measure low-nanogram quantities of human anti-ESA IgG4 antibodies in the presence of other anti-ESA antibodies. An increased concentration of anti-ESA IgG4 antibody is associated with the development of amPRCA. We propose that the measurement of anti-ESA specific IgG4 antibodies may facilitate early detection of amPRCA in patients receiving all ESAs structurally related to human erythropoietin.
Sublethal Staphylococcal Enterotoxin B Challenge Model in Pigs To Evaluate Protection following Immunization with a Soybean-Derived Vaccine
Authors: Hudson Laura C. , Seabolt Brynn S. , Odle Jack , Bost Kenneth L. , Stahl Chad H. , Piller Kenneth J. 
Published: November 2012

ABSTRACT

In an effort to develop a sustainable platform for manufacturing protein-based vaccine candidates, we expressed a triple mutant of staphylococcal enterotoxin B carrying the L45R, Y89A, and Y94A modifications in transgenic soybean seeds (soy-mSEB). Soy-mSEB possessed no detectable superantigen activity
in vitro
. We found that this soybean-derived, nontoxic mutant of SEB could be stably expressed, stored in seeds for extended periods at room temperature without degradation, and easily purified from contaminating soy proteins. Vaccination of pigs with purified soy-mSEB, or the identical triple mutant expressed in
Escherichia coli
(
E. coli
-mSEB), resulted in high antibody titers against the native toxin in immunized animals. In fact, titers were indistinguishable regardless of the immunogen used, demonstrating the equivalence of soy-mSEB and
E. coli
-mSEB vaccinations. Antisera from either immunized group were able to block native SEB superantigen activity in an
in vitro
neutralization assay. Similar results were obtained when immunized animals were challenged with a sublethal dose of native toxin. Significant reductions in toxin-induced serum cytokine levels were observed in soy-mSEB- and
E. coli
-mSEB-immunized pigs compared to control animals. The reductions in SEB-induced cytokine responses were similar regardless of the immunogen used for vaccination. Surprisingly, however, some clinical symptoms, such as prostration, lethargy, emesis, and/or diarrhea, were still observed in all immunized animals. These studies demonstrate the potential for soybean-derived proteins as a platform technology for sustainable vaccine manufacturing and the usefulness of a sublethal challenge model in pigs for evaluating the efficacy of potential SEB vaccine candidates.
Immunization of Mice with Formalin-Inactivated Spores from Avirulent Bacillus cereus Strains Provides Significant Protection from Challenge with Bacillus anthracis Ames
Authors: Vergis James M. , Cote Christopher K. , Bozue Joel , Alem Farhang , Ventura Christy L. , Welkos Susan L. , O'Brien Alison D. 
Published: November 2012

ABSTRACT

Bacillus anthracis
spores are the infectious form of the organism for humans and animals. However, the approved human vaccine in the United States is derived from a vegetative culture filtrate of a toxigenic, nonencapsulated
B. anthracis
strain that primarily contains protective antigen (PA). Immunization of mice with purified spore proteins and formalin-inactivated spores (FIS) from a nonencapsulated, nontoxigenic
B. anthracis
strain confers protection against
B. anthracis
challenge when PA is also administered. To investigate the capacity of the spore particle to act as a vaccine without PA, we immunized mice subcutaneously with FIS from nontoxigenic, nonencapsulated
B. cereus
strain G9241 pBCXO1
−
/pBC210
−
(dcG9241), dcG9241 Δ
bclA
, or 569-UM20 or with exosporium isolated from dcG9241. FIS vaccination provided significant protection of mice from intraperitoneal or intranasal challenge with spores of the virulent
B. anthracis
Ames or Ames Δ
bclA
strain. Immunization with dcG9241 Δ
bclA
FIS, which are devoid of the immunodominant spore protein BclA, provided greater protection from challenge with either Ames strain than did immunization with FIS from BclA-producing strains. In addition, we used prechallenge immune antisera to probe a panel of recombinant
B. anthracis
Sterne spore proteins to identify novel immunogenic vaccine candidates. The antisera were variably reactive with BclA and with 10 other proteins, four of which were previously tested as vaccine candidates. Overall our data show that immunization with FIS from nontoxigenic, nonencapsulated
B. cereus
strains provides moderate to high levels of protection of mice from
B. anthracis
Ames challenge and that neither PA nor BclA is required for this protection.
Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life
Authors: Reikie Brian A. , Naidoo Shalena , Ruck Candice E. , Slogrove Amy L. , de Beer Corena , la Grange Heleen , Adams Rozanne C. M. , Ho Kevin , Smolen Kinga , Speert David P. , Cotton Mark F. , Preiser Wolfgang , Esser Monika , Kollmann Tobias R. 
Published: November 2012

ABSTRACT

HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from infection. The possibility exists that altered response to vaccination contributes to the higher rate of infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following the WHO extended program on immunization (EPI). Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total IgG and antibodies specific for
Bordetella pertussis
,
Haemophilus influenzae
type b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine antibodies (maternal antibodies passively acquired) specific for tetanus were lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and HepB vaccination. HEU demonstrated stronger pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life.