bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dexamethasone, melphalan, actinomycin‐D and cytarabine chemotherapy protocol as a rescue treatment for feline lymphoma
Authors: Elliott J. , Finotello R. 
Published: October 2017

Nineteen cats with relapsed high‐grade/large‐cell lymphoma were treated with dexamethasone, melphalan, actinomycin‐D and cytarabine (DMAC). All cats had received Cyclophosphamide, Vincristine, Prednisolone (COP) as first‐line chemotherapy and most cats had received at least 2 prior rescue agents with 14 of 19 having received both epirubicin and lomustine. Five cats (26%) exhibited a response (defined as an improvement or resolution of tumour‐associated clinical signs/tumour volume, or complete/partial response) to chemotherapy though no patients received more than 2 cycles of DMAC. Most cats tolerated the protocol well though 3 patients exhibited Veterinary Cooperative Oncology Group (VCOG) grade 4 neutropenia and 1 patient exhibited grade 4 thrombocytopenia. The median progression‐free survival and overall survival from starting DMAC were 14 and 17 days respectively. There is still an unmet need for successful rescue chemotherapy protocol for cats with relapsed lymphoma.[Correction added on 02 November 2017, after first online publication: The expansion for the term DMAC was previously incorrect and has been corrected in this current version.]
Reliability of muscle blood flow and oxygen consumption response from exercise using near‐infrared spectroscopy
Authors: Lucero Adam A. , Addae Gifty , Lawrence Wayne , Neway Beemnet , Credeur Daniel P. , Faulkner James , Rowlands David , Stoner Lee 
Published: October 2017

New Findings
What is the central question of this study?
Continuous‐wave near‐infrared spectroscopy, coupled with venous and arterial occlusions, offers an economical, non‐invasive alternative to measuring skeletal muscle blood flow and oxygen consumption, but its reliability during exercise has not been established.

What is the main finding and its importance?
Continuous‐wave near‐infrared spectroscopy devices can reliably assess local skeletal muscle blood flow and oxygen consumption from the vastus lateralis in healthy, physically active adults. The patterns of response exhibited during exercise of varying intensity agree with other published results using similar methodologies, meriting potential applications in clinical diagnosis and therapeutic assessment.

Near‐infrared spectroscopy (NIRS), coupled with rapid venous and arterial occlusions, can be used for the non‐invasive estimation of resting local skeletal muscle blood flow (mBF) and oxygen consumption (), respectively. However, the day‐to‐day reliability of mBF and responses to stressors such as incremental dynamic exercise has not been established. The aim of this study was to determine the reliability of NIRS‐derived mBF and responses from incremental dynamic exercise. Measurements of mBF and were collected in the vastus lateralis of 12 healthy, physically active adults [seven men and five women; 25 (SD 6) years old] during three non‐consecutive visits within 10 days. After 10 min rest, participants performed 3 min of rhythmic isotonic knee extension (one extension every 4 s) at 5, 10, 15, 20, 25 and 30% of maximal voluntary contraction (MVC), before four venous occlusions and then two arterial occlusions. The mBF and increased proportionally with intensity [from 0.55 to 7.68 ml min−1 (100 ml)−1 and from 0.05 to 1.86 ml O2 min−1 (100 g)−1, respectively] up to 25% MVC, where they began to plateau at 30% MVC. Moreover, an mBF/ muscle oxygen consumption ratio of ∼5 was consistent for all exercise stages. The intraclass correlation coefficient for mBF indicated high to very high reliability for 10–30% MVC (0.82–0.9). There was very high reliability for across all exercise stages (intraclass correlation coefficient 0.91–0.96). In conclusion, NIRS can reliably assess muscle blood flow and oxygen consumption responses to low‐ to moderate‐intensity exercise, meriting potential applications in clinical diagnosis and therapeutic assessment.
Pharmacokinetic Modeling of Voriconazole To Develop an Alternative Dosing Regimen in Children
Authors: Gastine Silke , Lehrnbecher Thomas , Müller Carsten , Farowski Fedja , Bader Peter , Ullmann-Moskovits Judith , Cornely Oliver A. , Groll Andreas H. , Hempel Georg 
Published: October 2017

ABSTRACT

The pharmacokinetic variability of voriconazole (VCZ) in immunocompromised children is high, and adequate exposure, particularly in the first days of therapy, is uncertain. A population pharmacokinetic model was developed to explore VCZ exposure in plasma after alternative dosing regimens. Concentration data were obtained from a pediatric phase II study. Nonlinear mixed effects modeling was used to develop the model. Monte Carlo simulations were performed to test an array of three-times-daily (TID) intravenous dosing regimens in children 2 to 12 years of age. A two-compartment model with first-order absorption, nonlinear Michaelis-Menten elimination, and allometric scaling best described the data (maximal kinetic velocity for nonlinear Michaelis-Menten clearance [
V
max
] = 51.5 mg/h/70 kg, central volume of distribution [
V
1
] = 228 liters/70 kg, intercompartmental clearance [
Q
] = 21.9 liters/h/70 kg, peripheral volume of distribution [
V
2
] = 1,430 liters/70 kg, bioavailability [
F
] = 59.4%,

K
m

= fixed value of 1.15 mg/liter, absorption rate constant = fixed value of 1.19 h
−1
). Interindividual variabilities for
V
max
,
V
1
,
Q
, and
F
were 63.6%, 45.4%, 67%, and 1.34% on a logit scale, respectively, and residual variability was 37.8% (proportional error) and 0.0049 mg/liter (additive error). Monte Carlo simulations of a regimen of 9 mg/kg of body weight TID simulated for 24, 48, and 72 h followed by 8 mg/kg two times daily (BID) resulted in improved early target attainment relative to that with the currently recommended BID dosing regimen but no increased rate of accumulation thereafter. Pharmacokinetic modeling suggests that intravenous TID dosing at 9 mg/kg per dose for up to 3 days may result in a substantially higher percentage of children 2 to 12 years of age with adequate exposure to VCZ early during treatment. Before implementation of this regimen in patients, however, validation of exposure, safety, and tolerability in a carefully designed clinical trial would be needed.
In Vivo
Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic Murine Thigh Infection Model
Authors: Zhou Yu-Feng , Tao Meng-Ting , He Yu-Zhang , Sun Jian , Liu Ya-Hong , Liao Xiao-Ping 
Published: October 2017

ABSTRACT

Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as
Escherichia coli
. This study monitored the
in vivo
efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against
E. coli
isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy (
R
2
= 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log
10
and 2-log
10
kill for each isolate were 38.7, 66.1, and 147.0 h, respectively.
In vivo
bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to
E. coli
.
Thrombocytopenia with Tedizolid and Linezolid
Authors: Lee Erica Yookyung , Caffrey Aisling R. 
Published: October 2017

ABSTRACT
Several studies have suggested the risk of thrombocytopenia with tedizolid, a second-in-class oxazolidinone antibiotic (approved June 2014), is less than that observed with linezolid (first-in-class oxazolidinone). Using data from the Food and Drug Administration adverse event reporting system (July 2014 through December 2016), we observed significantly increased risks of thrombocytopenia of similar magnitudes with both antibiotics: linezolid reporting odds ratio [ROR], 37.9 (95% confidence interval [CI], 20.78 to 69.17); tedizolid ROR, 34.0 (95% CI, 4.67 to 247.30).
A CTG Clade Candida Yeast Genetically Engineered for the Genotype-Phenotype Characterization of Azole Antifungal Resistance in Human-Pathogenic Yeasts
Authors: Accoceberry Isabelle , Rougeron Amandine , Biteau Nicolas , Chevrel Pauline , Fitton-Ouhabi Valérie , Noël Thierry 
Published: October 2017

ABSTRACT

A strain of the opportunistic pathogenic yeast
Candida lusitaniae
was genetically modified for use as a cellular model for assessing by allele replacement the impact of lanosterol C14α-demethylase
ERG11
mutations on azole resistance.
Candida lusitaniae
was chosen because it is susceptible to azole antifungals, it belongs to the CTG clade of yeast, which includes most of the
Candida
species pathogenic for humans, and it is haploid and easily amenable to genetic transformation and molecular modeling. In this work, allelic replacement is targeted at the
ERG11
locus by the reconstitution of a functional auxotrophic marker in the 3′ intergenic region of
ERG11
. Homologous and heterologous
ERG11
alleles are expressed from the resident
ERG11
promoter of
C. lusitaniae
, allowing accurate comparison of the phenotypic change in azole susceptibility. As a proof of concept, we successfully expressed in
C. lusitaniae
different
ERG11
alleles, either bearing or not bearing mutations retrieved from a clinical context, from two phylogenetically distant yeasts,
C. albicans
and
Kluyveromyces marxianus
.
Candida lusitaniae
constitutes a high-fidelity expression system, giving specific Erg11p-dependent fluconazole MICs very close to those observed with the
ERG11
donor strain. This work led us to characterize the phenotypic effect of two kinds of mutation: mutation conferring decreased fluconazole susceptibility in a species-specific manner and mutation conferring fluconazole resistance in several yeast species. In particular, a missense mutation affecting amino acid K143 of Erg11p in
Candida
species, and the equivalent position K151 in
K. marxianus
, plays a critical role in fluconazole resistance.
Potency of Meropenem-Vaborbactam in Lung Surfactant
Authors: Rubio-Aparicio Debora , Loutit Jeff , Dudley Michael , Lomovskaya Olga 
Published: October 2017

ABSTRACT

This study investigated whether pulmonary surfactant has an effect on the
in vitro
antibacterial activity of either meropenem alone or meropenem in combination with vaborbactam at a fixed concentration of 8 μg/ml against several
Klebsiella pneumoniae
carbapenemase (KPC)-producing strains of Gram-negative bacteria. Results showed that the potency of meropenem alone and that of meropenem-vaborbactam were not affected when tested with pulmonary surfactant.
A Systematic Review and Meta-analyses of the Clinical Epidemiology of Carbapenem-Resistant Enterobacteriaceae
Authors: van Loon Karlijn , Voor in ‘t holt Anne F. , Vos Margreet C. 
Published: October 2017

ABSTRACTCarbapenem-resistantEnterobacteriaceae(CRE) are major health care-associated pathogens and responsible for hospital outbreaks worldwide. To prevent a further increase in CRE infections and to improve infection prevention strategies, it is important to summarize the current knowledge about CRE infection prevention in hospital settings. This systematic review aimed to identify risk factors for CRE acquisition among hospitalized patients. In addition, we summarized the environmental sources/reservoirs and the most successful infection prevention strategies related to CRE. A total of 3,983 potentially relevant articles were identified and screened. Finally, we included 162 studies in the systematic review, of which 69 studies regarding risk factors for CRE acquisition were included in the random-effects meta-analysis studies. The meta-analyses regarding risk factors for CRE acquisition showed that the use of medical devices generated the highest pooled estimate (odds ratio [OR] = 5.09; 95% confidence interval [CI] = 3.38 to 7.67), followed by carbapenem use (OR = 4.71; 95% CI = 3.54 to 6.26). To control hospital outbreaks, bundled interventions, including the use of barrier/contact precautions for patients colonized or infected with CRE, are needed. In addition, it is necessary to optimize the therapeutic approach, which is an important message to infectious disease specialists, who need to be actively involved in a timely manner in the treatment of patients with known CRE infections or suspected carriers of CRE.
Urinary Tract Conditions Affect Fosfomycin Activity against Escherichia coli Strains Harboring Chromosomal Mutations Involved in Fosfomycin Uptake
Authors: Martín-Gutiérrez G. , Docobo-Pérez F. , Rodriguez-Beltrán J. , Rodríguez-Martínez J. M. , Aznar J. , Pascual A. , Blázquez J. 
Published: October 2017

ABSTRACT

The steps by which
Escherichia coli
strains harboring mutations related to fosfomycin (FOS) resistance arise and spread during urinary tract infections (UTIs) are far from being understood. The aim of this study was to evaluate the effects of urine, pH, and anaerobiosis on FOS activity against a set of isogenic strains carrying the most prevalent chromosomal mutations conferring FOS resistance (Δ
uhpT
, Δ
glpT
, Δ
cyaA
, and Δ
ptsI
), either singly or in combination. We also studied fosfomycin-resistant
E. coli
clinical isolates from patients with UTI. Our results demonstrate that urinary tract physiological conditions might have a profound impact on FOS activity against strains with chromosomal FOS resistance mutations. Specifically, acidic pH values and anaerobiosis convert most of the strains categorized as resistant to fosfomycin according to the international guidelines to a susceptible status. Therefore, urinary pH values may have practical interest in the management of UTIs. Finally, our results, together with the high fitness cost associated with FOS resistance mutations, might explain the low prevalence of fosfomycin-resistant
E. coli
variants in UTIs.
Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females
Authors: Lennard Katie , Dabee Smritee , Barnabas Shaun L. , Havyarimana Enock , Blakney Anna , Jaumdally Shameem Z. , Botha Gerrit , Mkhize Nonhlanhla N. , Bekker Linda-Gail , Lewis David A. , Gray Glenda , Mulder Nicola , Passmore Jo-Ann S. , Jaspan Heather B. 
Published: October 2017

ABSTRACTYoung African females are at an increased risk of HIV acquisition, and genital inflammation or the vaginal microbiome may contribute to this risk. We studied these factors in 168 HIV-negative South African adolescent females aged 16 to 22 years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters (subtypes), one of which was strongly associated with genital inflammation. In a multivariate model, the microbiome compositional subtype and hormonal contraception were significantly associated with genital inflammation. We identified 40 taxa significantly associated with inflammation, including those reported previously (Prevotella,Sneathia,Aerococcus,Fusobacterium, andGemella) as well as several novel taxa (including increased frequencies of bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3,Prevotella amnii,Prevotella pallens,Parvimonas micra,Megasphaera,Gardnerella vaginalis, andAtopobium vaginaeand decreased frequencies ofLactobacillus reuteri,Lactobacillus crispatus,Lactobacillus jensenii, andLactobacillus iners). Women with inflammation-associated microbiomes had significantly higher body mass indices and lower levels of endogenous estradiol and luteinizing hormone. Community functional profiling revealed three distinct vaginal microbiome subtypes, one of which was characterized by extreme genital inflammation and persistent bacterial vaginosis (BV); this subtype could be predicted with high specificity and sensitivity based on the Nugent score (≥9) or BVAB1 abundance. We propose that women with this BVAB1-dominated subtype may have chronic genital inflammation due to persistent BV, which may place them at a particularly high risk for HIV infection.
Lactobacillus rhamnosus L34 Attenuates Gut Translocation-Induced Bacterial Sepsis in Murine Models of Leaky Gut
Authors: Panpetch Wimonrat , Chancharoenthana Wiwat , Bootdee Kanthika , Nilgate Sumanee , Finkelman Malcolm , Tumwasorn Somying , Leelahavanichkul Asada 
Published: October 2017

ABSTRACT

Gastrointestinal (GI) bacterial translocation in sepsis is well known, but the role of
Lactobacillus
species probiotics is still controversial. We evaluated the therapeutic effects of
Lactobacillus rhamnosus
L34 in a new sepsis model of oral administration of pathogenic bacteria with GI leakage induced by either an antibiotic cocktail (ATB) and/or dextran sulfate sodium (DSS). GI leakage with ATB, DSS, and DSS plus ATB (DSS+ATB) was demonstrated by fluorescein isothiocyanate (FITC)-dextran translocation to the circulation. The administration of pathogenic bacteria, either
Klebsiella pneumoniae
or
Salmonella enterica
serovar Typhimurium, enhanced translocation. Bacteremia was demonstrated within 24 h in 50 to 88% of mice with GI leakage plus the administration of pathogenic bacteria but not with GI leakage induction alone or bacterial gavage alone.
Salmonella
bacteremia was found in only 16 to 29% and 0% of mice with
Salmonella
and
Klebsiella
administrations, respectively.
Klebsiella
bacteremia was demonstrated in 25 to 33% and 10 to 16% of mice with
Klebsiella
and
Salmonella
administrations, respectively.
Lactobacillus rhamnosus
L34 attenuated GI leakage in these models, as shown by the reductions of FITC-dextran gut translocation, serum interleukin-6 (IL-6) levels, bacteremia, and sepsis mortality. The reduction in the amount of fecal
Salmonella
bacteria with
Lactobacillus
treatment was demonstrated. In addition, an anti-inflammatory effect of the conditioned medium from
Lactobacillus rhamnosus
L34 was also demonstrated by the attenuation of cytokine production in colonic epithelial cells
in vitro
. In conclusion,
Lactobacillus rhamnosus
L34 attenuated the severity of symptoms in a murine sepsis model induced by GI leakage and the administration of pathogenic bacteria.
Novel Gene Encoding 5-Aminosalicylate 1,2-Dioxygenase from Comamonas sp. Strain QT12 and Catalytic Properties of the Purified Enzyme
Authors: Yu Hao , Zhao Shuxue , Guo Lizhong 
Published: October 2017

ABSTRACT

The 1,125-bp
mabB
gene encoding 5-aminosalicylate (5ASA) 1,2-dioxygenase, a nonheme iron dioxygenase in the bicupin family that catalyzes the cleavage of the 5ASA aromatic ring to form
cis
-4-amino-6-carboxy-2-oxohexa-3,5-dienoate in the biodegradation of 3-aminobenzoate, was cloned from
Comamonas
sp. strain QT12 and characterized. The deduced amino acid sequence of the enzyme has low sequence identity with that of other reported ring-cleaving dioxygenases. MabB was heterologously expressed in
Escherichia coli
cells and purified as a His-tagged enzyme. The optimum pH and temperature for MabB are 8.0 and 10°C, respectively. Fe
II
is required for the catalytic activity of the purified enzyme. The apparent

K
m

and
V
max
values of MabB for 5ASA are 52.0 ± 5.6 μM and 850 ± 33.2 U/mg, respectively. The two oxygen atoms incorporated into the product of the MabB-catalyzed reaction are both from the dioxygen molecule. Both 5ASA and gentisate could be converted by MabB; however, the catalytic efficiency of MabB for 5ASA was much higher (∼70-fold) than that for gentisate. The
mabB
-disrupted mutant lost the ability to grow on 3-aminobenzoate, and
mabB
expression was higher when strain QT12 was cultivated in the presence of 3-aminobenzoate. Thus, 5ASA is the physiological substrate of MabB.

IMPORTANCE
For several decades, 5-aminosalicylate (5ASA) has been advocated as the drug mesalazine to treat human inflammatory bowel disease and considered the key intermediate in the xenobiotic degradation of many aromatic organic pollutants. 5ASA biotransformation research will help us elucidate the microbial degradation of these pollutants. Most studies have reported that gentisate 1,2-dioxygenases (GDOs) can convert 5ASA with significantly high activity; however, the catalytic efficiency of these enzymes for gentisate is much higher than that for 5ASA. This study showed that MabB can convert 5ASA to
cis
-4-amino-6-carboxy-2-oxohexa-3,5-dienoate, incorporating two oxygen atoms from the dioxygen molecule into the product. Unlike GDOs, MabB uses 5ASA instead of gentisate as the primary substrate.
mabB
is the first reported 5-aminosalicylate 1,2-dioxygenase gene.
Characterization of Copy Number Control of Two Haloferax volcanii Replication Origins Using Deletion Mutants and Haloarchaeal Artificial Chromosomes
Authors: Maurer Sandy , Ludt Katharina , Soppa Jörg 
Published: October 2017

ABSTRACT

Haloferax volcanii
is polyploid and contains about 20 genome copies under optimal conditions. However, the chromosome copy number is highly regulated and ranges from two during phosphate starvation to more than 40 under conditions of phosphate surplus. The aim of this study was the characterization of the influence of two replication origins on the genome copy number. The origin repeats and the genes encoding
o
rigin
r
ecognition
c
omplex (ORC) proteins were deleted. The core origin oriC1-
orc1
(ori1) deletion mutant had a lower genome copy number and a higher level of fitness than the wild type, in stark contrast to the oriC2-
orc5
(ori2) deletion mutant. The genes adjacent to ori1 could not be deleted, and thus, at least two of them are probably essential, while deletion of the genes adjacent to ori2 was possible. Various fragments of and around the origins were cloned into a suicide plasmid to generate
h
aloarchaeal
a
rtificial
c
hromosomes (HACs). The copy number of the oriC1-
orc1
HAC was much higher than that of the oriC2-
orc5
HAC. The addition of adjacent genes influenced both the HAC copy number and the chromosome copy number. The results indicate that the origins of
H. volcanii
are not independent but that the copy number is regulated via a network of genes around the origins.

IMPORTANCE
Several species of archaea have more than one origin of replication on their major chromosome and are thus the only known prokaryotic species that allow the analysis of the evolution of multiorigin replication. The widely studied
Haloferax volcanii
H26 strain has a major chromosome with four origins of replication. Two origins, ori1 and ori2, were chosen for an in-depth analysis using deletion mutants and haloarchaeal artificial chromosomes. The analysis was not restricted to the core origin regions; origin-adjacent genes were also included. Because
H. volcanii
is polyploid, the effects on the chromosome copy number were of specific importance. The results revealed extreme differences between the two origins.