bluuebunny/crossref_metadata_2025_split huggingface dataset:
A patient alignment solution for lung SBRT setups based on a deformable registration technique
Authors: Lu Bo , Mittauer Kathryn , Li Jonathan , Samant Sanjiv , Dagan Roi , Okunieff Paul , Kahler Darren , Liu Chihray 
Published: November 2012

Purpose:In this work, the authors propose a novel registration strategy for translation‐only correction scenarios of lung stereotactic body radiation therapy setups, which can achieve optimal dose coverage for tumors as well as preserve the consistency of registrations with minimal human interference.Methods:The proposed solution (centroid‐to‐centroidor CTC solution) uses the average four‐dimensional CT (A4DCT) as the reference CT. The cone‐beam CT (CBCT) is deformed to acquire a new centroid for the internal target volume (ITV) on the CBCT. The registration is then accomplished by simply aligning the centroids of the ITVs between the A4DCT and the CBCT. Sixty‐seven cases using 64 patients (each case is associated with separate isocenters) have been investigated with the CTC method and compared with the conventional gray‐value (G) mode and bone (B) mode registration methods. Dosimetric effects among the tree methods were demonstrated by 18 selected cases. The uncertainty of the CTC method has also been studied.Results:The registration results demonstrate the superiority of the CTC method over the other two methods. The differences in the D99 and D95 ITV dose coverage between the CTC method and the original plan is small (within 5%) for all of the selected cases except for one for which the tumor presented significant growth during the period between the CT scan and the treatment. Meanwhile, the dose coverage differences between the original plan and the registration results using either the B or G method are significant, as tumor positions varied dramatically, relative to the rib cage, from their positions on the original CT. The largest differences between the D99 and D95 dose coverage of the ITV using the B or G method versus the original plan are as high as 50%. The D20 differences between any of the methods versus the original plan are all less than 2%.Conclusions:The CTC method can generate optimal dose coverage to tumors with much better consistency compared with either the G or B method, and it is especially useful when the tumor position varies greatly from its position on the original CT, relative to the rib cage.
The effect of breathing irregularities on quantitative accuracy of respiratory gated PET/CT
Authors: Teo Boon‐Keng , Saboury Babak , Munbodh Reshma , Scheuermann Joshua , Torigian Drew A. , Zaidi Habib , Alavi Abass 
Published: November 2012

Purpose:4D positron emission tomography and computed tomography (PET/CT) can be used to reduce motion artifacts by correlating the raw PET data with the respiratory cycle. The accuracy of each PET phase is dependent on the reproducibility and consistency of the breathing cycle during acquisition. The objective of this study is to evaluate the impact of breathing amplitude and phase irregularities on the quantitative accuracy of 4D PET standardized uptake value (SUV) measurements. In addition, the magnitude of quantitative errors due to respiratory motion and partial volume error are compared.Methods:Phantom studies were performed using spheres filled with18F ranging from 9 to 47 mm in diameter with background activity. Motion was simulated using patient breathing data. The authors compared the accuracy of SUVs derived from gated PET (4 bins and 8 bins, phase‐based) for ideal, average, and highly irregular breathing patterns.Results:Under ideal conditions, gated PET produced SUVs that were within (−5.4 ± 5.3)% of the static phantom measurements averaged across all sphere sizes. With breathing irregularities, the quantitative accuracy of gated PET decreased. Gated PET SUVs (best of 4 bins) were (−9.6 ± 13.0)% of the actual value for an average breather and decreased to (−17.1 ± 10.8)% for a highly irregular breather. Without gating, the differences in the SUV from actual value were (−28.5 ± 18.2)%, (−25.9 ± 14.4)%, and (−27.9 ± 18.2)% for the ideal, average, and highly irregular breather, respectively.Conclusions:Breathing irregularities reduce the quantitative accuracy of gated PET/CT. Current gated PET techniques may underestimate the actual lesion SUV due to phase assignment errors. Evaluation of respiratory trace is necessary to assess accuracy of data binning and its effect on 4D PET SUVs.
Neisseria gonorrhoeae Strain with High-Level Resistance to Spectinomycin Due to a Novel Resistance Mechanism (Mutated Ribosomal Protein S5) Verified in Norway
Authors: Unemo Magnus , Golparian Daniel , Skogen Vegard , Olsen Anne Olaug , Moi Harald , Syversen Gaute , Hjelmevoll Stig Ove 
Published: November 2012

ABSTRACT

Gonorrhea may become untreatable, and new treatment options are essential. Verified resistance to spectinomycin is exceedingly rare. However, we describe a high-level spectinomycin-resistant (MIC, >1,024 μg/ml)
Neisseria gonorrhoeae
strain from Norway with a novel resistance mechanism. The resistance determinant was a deletion of codon 27 (valine) and a K28E alteration in the ribosomal protein 5S. The traditional spectinomycin resistance gene (16S rRNA) was wild type. Despite this exceedingly rare finding, spectinomycin available for treatment of ceftriaxone-resistant urogenital gonorrhea would be very valuable.
Raltegravir Pharmacokinetics in Treatment-Naive Patients Is Not Influenced by Race: Results from the Raltegravir Early Therapy in African-Americans Living with HIV (REAL) Study
Authors: Wohl David A. , Dumond Julie B. , Blevins Suzanne , Pittard Donna , Ragan David , Wang Ruili , Massengale Kelley , Walsh Kendall , Floris-Moore Michelle , Eron Joseph J. , Richardson Amy , Hudgens Michael G. , Kashuba Angela D. M. 
Published: November 2012

ABSTRACT

Racial differences in antiretroviral treatment responses remain incompletely explained and may be a consequence of differential pharmacokinetics (PK) associated with race. Raltegravir, an inhibitor of HIV-1 integrase, is commonly used in the treatment of HIV-infected patients, many of whom are African-American. However, there are few data regarding the PK of raltegravir in African-Americans. HIV-infected men and women, self-described as African-American and naive to antiretroviral therapy were treated with raltegravir (RAL) at 400 mg twice a day, plus a fixed dose of tenofovir-emtricitabine (TDF/FTC) at 300 mg/200 mg once daily. Intensive PK sampling was conducted over 24 h at week 4. Drug concentrations at two trough values of 12 and 24 h after dosing (
C
12
and
C
24
), area under the concentration-curve values (AUC), maximum drug concentration (
C
max
), and the time at which this concentration occurred (
T
max
) in plasma were estimated with noncompartmental pharmacokinetic methods and compared to data from a subset of white subjects randomized to the RAL twice a day (plus TDF/FTC) arm of the QDMRK study, a phase III study of the safety and efficacy of once daily versus twice daily RAL in treatment naive patients. A total of 38 African-American participants were enrolled (90% male) into the REAL cohort with the following median baseline characteristics: age of 36 years, body mass index (BMI) of 23 kg/m
2
, and a CD4 cell count of 339/ml. Plasma HIV RNA levels were below 200 copies/ml in 95% of participants at week 4. The characteristics of the 16 white QDMRK study participants were similar, although fewer (69%) were male, the median age was higher (45 years), and BMI was lower (19 kg/m
2
). There was considerable interindividual variability in RAL concentrations in both cohorts. Median
C
12
in REAL was 91 ng/ml (range, 10 to 1,386) and in QDMRK participants was 128 ng/ml (range, 15 to 1,074). The
C
max
median concentration was 1,042 ng/ml (range, 196 to 10,092) for REAL and 1,360 ng/ml (range, 218 to 9,701) for QDMRK. There were no significant differences in any RAL PK parameter between these cohorts of African-American and white individuals. Based on plasma PK, and with similar adherence rates, the performance of RAL among HIV-infected African-Americans should be no different than that of infected patients who are white.
Preclinical Characterization of GS-9669, a Thumb Site II Inhibitor of the Hepatitis C Virus NS5B Polymerase
Authors: Fenaux Martijn , Eng Stacey , Leavitt Stephanie A. , Lee Yu-Jen , Mabery Eric M. , Tian Yang , Byun Daniel , Canales Eda , Clarke Michael O. , Doerffler Edward , Lazerwith Scott E. , Lew Willard , Liu Qi , Mertzman Michael , Morganelli Philip , Xu Lianhong , Ye Hong , Zhang Jennifer , Matles Mike , Murray Bernard P. , Mwangi Judy , Zhang Jingyu , Hashash Ahmad , Krawczyk Steve H. , Bidgood Alison M. , Appleby Todd C. , Watkins William J. 
Published: November 2012

ABSTRACT

GS-9669 is a highly optimized thumb site II nonnucleoside inhibitor of the hepatitis C virus (HCV) RNA polymerase, with a binding affinity of 1.35 nM for the genotype (GT) 1b protein. It is a selective inhibitor of HCV RNA replication, with a mean 50% effective concentration (EC
50
) of ≤11 nM in genotype 1 and 5 replicon assays, but lacks useful activity against genotypes 2 to 4. The M423T mutation is readily generated clinically upon monotherapy with the thumb site II inhibitors filibuvir and lomibuvir, and it is notable that GS-9669 exhibited only a 3-fold loss in potency against this variant in the genotype 1b replicon. Rather than M423T, resistance predominantly tracks to residues R422K and L419M and residue I482L in GT 1b and 1a replicons, respectively. GS-9669 exhibited at least additive activity in combination with agents encompassing four other direct modes of action (NS3 protease, NS5A, NS5B via an alternative allosteric binding site, and NS5B nucleotide) as well as with alpha interferon or ribavirin in replicon assays. It exhibited high metabolic stability in
in vitro
human liver microsomal assays, which, in combination with its pharmacokinetic profiles in rat, dog, and two monkey species, is predictive of good human pharmacokinetics. GS-9669 is well suited for combination with other orally active, direct-acting antiviral agents in the treatment of genotype 1 chronic HCV infection. (This study has been registered at ClinicalTrials.gov under registration number NCT01431898.)
Pegylated Interferon Fractal Pharmacokinetics: Individualized Dosing for Hepatitis C Virus Infection
Authors: Jain Mamta K. , Pasipanodya Jotam G. , Alder Lara , Lee William M. , Gumbo Tawanda 
Published: November 2012

ABSTRACT
Despite recent advances in hepatitis C virus (HCV) therapeutics, the combination of pegylated interferon and ribavirin (PEGIFN/RBV) remains the cornerstone of treatment. Optimization and individualization of PEGIFN dosing could improve outcomes. Week one PEGIFN serum concentrations in 42 HCV genotype 1-infected patients treated with conventional PEGIFN/RBV were analyzed using multicompartmental pharmacokinetic models. For each patient, pharmacokinetic parameter estimates, weight, age, interleukin-28B (IL-28B) single-nucleotide polymorphism, CD4 count, baseline HCV RNA, gender, race, and HIV status were examined using classification and regression tree analysis to identify factors predictive of sustained viral response (SVR). Survival analysis was performed to compare the time to undetectable viral load in patients with and without the highest scoring predictor. PEGIFN concentrations varied at least 87-fold. Pharmacokinetics were best described by a two-compartment model with an 8.4-h absorption lag. Patient weight correlated with PEGIFN systemic clearance based on fractal geometry relationships. SVR was achieved in 36% of patients; a PEGIFN cumulative 1-week area under the curve (AUC) of ≤0.79 mg · h/liter scored highest in predicting poor response, followed by a weight of ≥93.7 kg. Patients with a PEGIFN AUC of >0.79 mg · h/liter achieved undetectable viral load more rapidly than those with a lower AUC (hazard ratio, 1.63; 95% confidence interval, 1.21 to 2.04). PEGIFN exhibits wide pharmacokinetic variability, mainly driven by patient weight, so that the standard dose may not reach levels needed to achieve SVR. Optimizing dose to patient weight and PEGIFN AUC in the first week offers a solution to improve SVR and to potentially shorten duration of therapy.
Recruitment and Rearrangement of Three Different Genetic Determinants into a Conjugative Plasmid Increase Copper Resistance in Pseudomonas syringae
Authors: Gutiérrez-Barranquero José A. , de Vicente Antonio , Carrión Víctor J. , Sundin George W. , Cazorla Francisco M. 
Published: November 2012

ABSTRACT

We describe the genetic organization of a copper-resistant plasmid containing
copG
and
cusCBA
genes in the plant pathogen
Pseudomonas syringae
. Chromosomal variants of
czcCBA
and a plasmid variant of
cusCBA
were present in different
P. syringae
pathovar strains. Transformation of the copper-sensitive
Pseudomonas syringae
pv. syringae FF5 strain with
copG
or
cusCBA
conferred copper resistance, and quantitative real-time PCR (qRT-PCR) experiments confirmed their induction by copper.
Combinatorial Design of a Highly Efficient Xylose-Utilizing Pathway in Saccharomyces cerevisiae for the Production of Cellulosic Biofuels
Authors: Kim Byoungjin , Du Jing , Eriksen Dawn T. , Zhao Huimin 
Published: November 2012

ABSTRACT

Balancing the flux of a heterologous metabolic pathway by tuning the expression and properties of the pathway enzymes is difficult, but it is critical to realizing the full potential of microbial biotechnology. One prominent example is the metabolic engineering of a
Saccharomyces cerevisiae
strain harboring a heterologous xylose-utilizing pathway for cellulosic-biofuel production, which remains a challenge even after decades of research. Here, we developed a combinatorial pathway-engineering approach to rapidly create a highly efficient xylose-utilizing pathway for ethanol production by exploring various combinations of enzyme homologues with different properties. A library of more than 8,000 xylose utilization pathways was generated using DNA assembler, followed by multitiered screening, which led to the identification of a number of strain-specific combinations of the enzymes for efficient conversion of xylose to ethanol. The balancing of metabolic flux through the xylose utilization pathway was demonstrated by a complete reversal of the major product from xylitol to ethanol with a similar yield and total by-product formation as low as 0.06 g/g xylose without compromising cell growth. The results also suggested that an optimal enzyme combination depends on not only the genotype/phenotype of the host strain, but also the sugar composition of the fermentation medium. This combinatorial approach should be applicable to any heterologous pathway and will be instrumental in the optimization of industrial production of value-added products.
Examination of the Genome-Wide Transcriptional Response of Escherichia coli O157:H7 to Cinnamaldehyde Exposure
Authors: Visvalingam Jeyachchandran , Hernandez-Doria Juan David , Holley Richard A. 
Published: November 2012

ABSTRACT

Cinnamaldehyde is a natural antimicrobial that has been found to be effective against many food-borne pathogens, including
Escherichia coli
O157:H7. Although its antimicrobial effects have been well investigated, limited information is available on its effects at the molecular level. Sublethal treatment at 200 mg/liter cinnamaldehyde inhibited growth of
E. coli
O157:H7 at 37°C and for ≤2 h caused cell elongation, but from 2 to 4 h growth resumed and cells reverted to normal length. To understand this transient behavior, genome-wide transcriptional analysis of
E. coli
O157:H7 was performed at 2 and 4 h of exposure to cinnamaldehyde in conjunction with reverse-phase high-performance liquid chromatography (RP-HPLC) analysis for cinnamaldehyde and other cinnamic compounds. Drastically different gene expression profiles were obtained at 2 and 4 h. RP-HPLC analysis showed that cinnamaldehyde was structurally stable for at least 2 h. At 2 h of exposure, cinnamaldehyde induced expression of many oxidative stress-related genes and repressed expression of DNA, protein, O-antigen, and fimbrial synthetic genes. At 4 h, many cinnamaldehyde-induced repressive effects on
E. coli
O157:H7 gene expression were reversed, and cells became more motile and grew at a slightly higher rate. Data indicated that by 4 h,
E. coli
O157:H7 was able to convert cinnamaldehyde into the less toxic cinnamic alcohol using dehydrogenase/reductase enzymes (YqhD and DkgA). This is the first study to characterize the ability of
E. coli
O157:H7 to convert cinnamaldehyde into cinnamic alcohol which, in turn, showed that the antimicrobial activity of cinnamaldehyde is mainly attributable to its carbonyl aldehyde group.
Wide Distribution and Genetic Diversity of “Candidatus Neoehrlichia mikurensis” in Rodents from China
Authors: Li Hao , Jiang Jiafu , Tang Fang , Sun Yi , Li Zengde , Zhang Weilong , Gong Zhengda , Liu Kun , Yang Hong , Liu Wei , Cao Wuchun 
Published: November 2012

ABSTRACT

“
Candidatus
Neoehrlichia mikurensis” was detected by PCR in 4.0% (34/841) of the rodents tested in this study. The 34 rodents represented nine species from seven regions of China. Phylogenetic analyses based on the partial
groEL
and nearly entire 16S rRNA gene sequences of the agent revealed genetic diversity, which was correlated with its geographic origins.
Gene Identification and Substrate Regulation Provide Insights into Sulfur Accumulation during Bioleaching with the Psychrotolerant Acidophile Acidithiobacillus ferrivorans
Authors: Liljeqvist Maria , Rzhepishevska Olena I. , Dopson Mark 
Published: November 2012

ABSTRACT

The psychrotolerant acidophile
Acidithiobacillus ferrivorans
has been identified from cold environments and has been shown to use ferrous iron and inorganic sulfur compounds as its energy sources. A bioinformatic evaluation presented in this study suggested that
Acidithiobacillus ferrivorans
utilized a ferrous iron oxidation pathway similar to that of the related species
Acidithiobacillus ferrooxidans
. However, the inorganic sulfur oxidation pathway was less clear, since the
Acidithiobacillus ferrivorans
genome contained genes from both
Acidithiobacillus ferrooxidans
and
Acidithiobacillus caldus
encoding enzymes whose assigned functions are redundant. Transcriptional analysis revealed that the
petA1
and
petB1
genes (implicated in ferrous iron oxidation) were downregulated upon growth on the inorganic sulfur compound tetrathionate but were on average 10.5-fold upregulated in the presence of ferrous iron. In contrast, expression of
cyoB1
(involved in inorganic sulfur compound oxidation) was decreased 6.6-fold upon growth on ferrous iron alone. Competition assays between ferrous iron and tetrathionate with
Acidithiobacillus ferrivorans
SS3 precultured on chalcopyrite mineral showed a preference for ferrous iron oxidation over tetrathionate oxidation. Also, pure and mixed cultures of psychrotolerant acidophiles were utilized for the bioleaching of metal sulfide minerals in stirred tank reactors at 5 and 25°C in order to investigate the fate of ferrous iron and inorganic sulfur compounds. Solid sulfur accumulated in bioleaching cultures growing on a chalcopyrite concentrate. Sulfur accumulation halted mineral solubilization, but sulfur was oxidized after metal release had ceased. The data indicated that ferrous iron was preferentially oxidized during growth on chalcopyrite, a finding with important implications for biomining in cold environments.
Detection of Putatively Thermophilic Anaerobic Methanotrophs in Diffuse Hydrothermal Vent Fluids
Authors: Merkel Alexander Y. , Huber Julie A. , Chernyh Nikolay A. , Bonch-Osmolovskaya Elizaveta A. , Lebedinsky Alexander V. 
Published: November 2012

ABSTRACT

The anaerobic oxidation of methane (AOM) is carried out by a globally distributed group of uncultivated
Euryarchaeota
, the anaerobic methanotrophic arachaea (ANME). In this work, we used G+C analysis of 16S rRNA genes to identify a putatively thermophilic ANME group and applied newly designed primers to study its distribution in low-temperature diffuse vent fluids from deep-sea hydrothermal vents. We found that the G+C content of the 16S rRNA genes (
P
GC
) is significantly higher in the ANME-1GBa group than in other ANME groups. Based on the positive correlation between the
P
GC
and optimal growth temperatures (
T
opt
) of archaea, we hypothesize that the ANME-1GBa group is adapted to thrive at high temperatures. We designed specific 16S rRNA gene-targeted primers for the ANME-1 cluster to detect all phylogenetic groups within this cluster, including the deeply branching ANME-1GBa group. The primers were successfully tested both
in silico
and in experiments with sediment samples where ANME-1 phylotypes had previously been detected. The primers were further used to screen for the ANME-1 microorganisms in diffuse vent fluid samples from deep-sea hydrothermal vents in the Pacific Ocean, and sequences belonging to the ANME-1 cluster were detected in four individual vents. Phylotypes belonging to the ANME-1GBa group dominated in clone libraries from three of these vents. Our findings provide evidence of existence of a putatively extremely thermophilic group of methanotrophic archaea that occur in geographically and geologically distinct marine hydrothermal habitats.
Inhibition of Staphylococcus aureus Invasion into Bovine Mammary Epithelial Cells by Contact with Live Lactobacillus casei
Authors: Bouchard Damien S. , Rault Lucie , Berkova Nadia , Le Loir Yves , Even Sergine 
Published: November 2012

ABSTRACT

Staphylococcus aureus
is a major pathogen that is responsible for mastitis in dairy herds.
S. aureus
mastitis is difficult to treat and prone to recurrence despite antibiotic treatment. The ability of
S. aureus
to invade bovine mammary epithelial cells (bMEC) is evoked to explain this chronicity. One sustainable alternative to treat or prevent mastitis is the use of lactic acid bacteria (LAB) as mammary probiotics. In this study, we tested the ability of
Lactobacillus casei
strains to prevent invasion of bMEC by two
S. aureus
bovine strains, RF122 and Newbould305, which reproducibly induce acute and moderate mastitis, respectively.
L. casei
strains affected adhesion and/or internalization of
S. aureus
in a strain-dependent manner. Interestingly,
L. casei
CIRM-BIA 667 reduced
S. aureus
Newbould305 and RF122 internalization by 60 to 80%, and this inhibition was confirmed for two other
L. casei
strains, including one isolated from bovine teat canal. The protective effect occurred without affecting bMEC morphology and viability. Once internalized, the fate of
S. aureus
was not affected by
L. casei
. It should be noted that
L. casei
was internalized at a low rate but survived in bMEC cells with a better efficiency than that of
S. aureus
RF122. Inhibition of
S. aureus
adhesion was maintained with heat-killed
L. casei
, whereas contact between live
L. casei
and
S. aureus
or bMEC was required to prevent
S. aureus
internalization. This first study of the antagonism of LAB toward
S. aureus
in a mammary context opens avenues for the development of novel control strategies against this major pathogen.
Biofilm as an Environment for Dissemination of
stx
Genes by Transduction
Authors: Solheim H. T. , Sekse C. , Urdahl A. M. , Wasteson Y. , Nesse L. L. 
Published: November 2012

ABSTRACT

Dissemination of Shiga toxin (Stx)-encoding bacteriophages is the most likely mechanism for the spread of Stx-encoding genes and the emergence of new Stx-producing
Escherichia coli
(STEC). Biofilm has been reported to be a place where horizontal gene transfer by plasmid conjugation and DNA transformation may occur, and in this study, horizontal gene transfer by transduction has been demonstrated. Transfer of Stx-encoding bacteriophages to potentially pathogenic
E. coli
in biofilm was observed at both 20°C and 37°C. The infection rates were higher at 37°C than at 20°C. To our knowledge, this study is the first to show lateral gene transfer in biofilm mediated by a temperate bacteriophage. The study shows that the biofilm environment can be suitable for transduction events and can thereby be an environment for the emergence of new pathogenic
E. coli
.