bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical presentation, diagnostic findings and outcome in dogs diagnosed withpresumptive spinal‐only meningoen‐cephalomyelitis of unknown origin
Authors: Cornelis I. , Volk H. A. , Van Ham L. , De Decker S. 
Published: March 2017

ObjectivesTo summarise clinical presentation, diagnostic findings and long‐term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone.MethodsMedical records were reviewed for dogs diagnosed with presumptive spinal‐only meningoencephalomyelitis of unknown origin between 2006 and 2015.Results21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T3‐L3 myelopathy, and spinal hyperaesthesia was a common finding (71%). A spinal cord lesion was visible in 90% of cases on magnetic resonance imaging. Eighteen lesions (86%) showed parenchymal contrast enhancement and 17 lesions (81%) showed contrast enhancement of overlying meninges. All dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. At time of data capture, 10/21 dogs (48%) had died or been euthanased because of the condition. Overall median survival time was 669 days.Clinical SignificanceMeningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. Magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. Overall, long‐term survival is guarded, approximately 50% of dogs will die or be euthanased despite appropriate therapy.
Augmentation of hepatitis C virus‐specific immunity and sustained virologic response
Authors: Shrivastava S. , Wilson E. , Poonia B. , Tang L. , Osinusi A. , Kohli A. , Kottilil S. 
Published: March 2017

SummaryTreatment for chronic hepatitis C virus (HCV) infection has rapidly evolved into interferon‐free directly acting antiviral regimens (DAA) that result in high sustained virologic response. DAAs primarily work by suppressing HCV replication and rely less on the immune system than interferon‐based therapies. However, it is unclear whether the immune system recovers with suppression of HCV replication and contributes to HCV clearance with DAA therapy. We previously demonstrated HCV clearance is associated with increased HCV‐specific immunity in CHCV‐GT‐1‐infected patients during treatment with sofosbuvir (SOF)+ribavirin (RBV). Here, we aimed to analyse changes in HCV‐specific immunological responses associated with viral clearance with combination DAA therapy of SOF+ledipasvir (LDV) for 12 weeks in CHCV‐GT1 (N=14) patients who relapsed without augmentation of HCV‐specific immunity during treatment with SOF+RBV. Phenotypic and functional changes within the T‐cell compartment of PBMCs pre‐ and post‐treatment were analysed. Retreatment of relapsers with LDV/SOF resulted in all patients attaining SVR12. Suppression of HCV was associated with a decline in T‐cell exhaustion markers (CD57; Tim3; PD1) along with augmented of HCV‐specific T‐cell IFN‐gamma responses post‐treatment. Addition of LDV to SOF was associated with augmentation of HCV‐specific immunity and SVR in patients who previously failed SOF+RBV therapy without increased immunity. These findings demonstrate a novel effect of DAA in inducing host immune responses to aid HCV clearance and achieve SVR.
Comparative transcriptomic analysis of key genes involved in flavonoid biosynthetic pathway and identification of a flavonol synthase from Artemisia annua L.
Authors: Liu S. , Liu L. , Tang Y. , Xiong S. , Long J. , Liu Z. , Tian N. 
Published: March 2017

Abstract

The regulatory mechanism of flavonoids, which synergise anti‐malarial and anti‐cancer compounds in Artemisia annua, is still unclear.

In this study, an anthocyanidin‐accumulating mutant callus was induced from A. annua and comparative transcriptomic analysis of wild‐type and mutant calli performed, based on the next‐generation Illumina/Solexa sequencing platform and de novo assembly.

A total of 82,393 unigenes were obtained and 34,764 unigenes were annotated in the public database. Among these, 87 unigenes were assigned to 14 structural genes involved in the flavonoid biosynthetic pathway and 37 unigenes were assigned to 17 structural genes related to metabolism of flavonoids. More than 30 unigenes were assigned to regulatory genes, including R2R3‐MYB, bHLH and WD40, which might regulate flavonoid biosynthesis. A further 29 unigenes encoding flavonoid biosynthetic enzymes or transcription factors were up‐regulated in the mutant, while 19 unigenes were down‐regulated, compared with the wild type. Expression levels of nine genes involved in the flavonoid pathway were compared using semi‐quantitative RT‐PCR, and results were consistent with comparative transcriptomic analysis. Finally, a putative flavonol synthase gene (AaFLS1) was identified from enzyme assay in vitro and in vivo through heterogeneous expression, and confirmed comparative transcriptomic analysis of wild‐type and mutant callus.

The present work has provided important target genes for the regulation of flavonoid biosynthesis in A. annua.
Shadow analysis via the C+K Visioline: A technical note
Authors: Houser T. , Zerweck C. , Grove G. , Wickett R. 
Published: March 2017

Background/purposeThis research investigated the ability of shadow analysis (via the Courage + Khazaka Visioline and Image Pro Premiere 9.0 software) to accurately assess the differences in skin topography associated with photo aging.MethodsAnalyses were performed on impressions collected from a microfinish comparator scale (GAR Electroforming) as well a series of impressions collected from the crow's feet region of 9 women who represent each point on the Zerweck Crow's Feet classification scale. Analyses were performed using a Courage + Khazaka Visioline VL 650 as well as Image Pro Premiere 9.0 software.ResultsShadow analysis showed an ability to accurately measure the groove depth when measuring impressions collected from grooves of known depth. Several shadow analysis parameters showed a correlation with the expert grader ratings of crow's feet when averaging measurements taken from the North and South directions. The Max Depth parameter in particular showed a strong correlation with the expert grader's ratings which improved when a more sophisticated analysis was performed using Image Pro Premiere.ConclusionWhen used properly, shadow analysis is effective at accurately measuring skin surface impressions for differences in skin topography. Shadow analysis is shown to accurately assess the differences across a range of crow's feet severity correlating to a 0‐8 grader scale. The Visioline VL 650 is a good tool for this measurement, with room for improvement in analysis which can be achieved through third party image analysis software.
Treatment of supraventricular tachycardia in a horse
Authors: Whelchel Dorothy D. , Tennent‐Brown Brett S. , Coleman Amanda E. , Rapoport Gregg S. , Blas‐Machado Uriel , Maisenbacher Herbert W. , Credille Brenton C. , Giguère Steeve 
Published: March 2017

AbstractObjectiveTo describe the treatment of persistent supraventricular tachycardia (SVT) in a young horse in endurance training.Case SummaryA 6‐year‐old Arab gelding in endurance training presented for a dysrhythmia and decreased performance. SVT was diagnosed and conversion to a normal sinus rhythm was achieved following administration of a constant rate infusion of amiodarone. However, reversion to SVT occurred shortly after initiation of ridden exercise. A second attempt to convert the dysrhythmia with amiodarone failed, but normal sinus rhythm was achieved with transvenous electrical cardioversion (TVEC). Postmortem examination of the heart revealed extensive fibrous replacement of most of the left atrial myocardium; these changes likely provided the structural substrate for the dysrhythmia. The underlying cause of the fibrosis was not identified.New or Unique Information ProvidedSVT is a form of supraventricular tachyarrhythmia rarely diagnosed in the horse. A recent report has described sudden death of a horse following attempted conversion of SVT with oral flecainide acetate. In the present report, we describe short‐term conversion of SVT in a horse using intravenous amiodarone with no significant adverse effects. When the dysrhythmia recurred, the animal was donated for teaching purposes and conversion was achieved with TVEC. Normal sinus rhythm persisted for 2 weeks until the horse was euthanized for postmortem evaluation of the heart. Intravenous amiodarone or TVEC could be considered as treatments for supraventricular tachyarrhyhmias other than atrial fibrillation in the horse.
Effectiveness of an Online Educational Module in Improving Evidence‐Based Practice Skills of Practicing Registered Nurses
Authors: Moore Lora 
Published: March 2017

ABSTRACTBackgroundImplementation of evidence‐based practice (EBP) at the bedside has been difficult to achieve. Significant gaps between current research and actual practice have been identified and must be addressed in effort to increase utilization of EBP.AimsThe purpose of this study was to evaluate the efficacy of an online EBP educational intervention and to examine the relationship between educational preparation and years of nursing experience on nurses’ practice, attitudes, and knowledge and skills of EBP.MethodsAn experimental pretest‐posttest design study with three randomized groups utilizing the EBPQ instrument was conducted.ResultsNo significant differences were noted in EBPQ subscale scores of practice, attitude, or knowledge and skills from pre‐ to posttest. In addition, no statistical difference in EBPQ subscale scores regarding educational preparation or years of experience were noted.Linking Evidence to PracticeWhile nurses report positive attitudes toward EBP, their perceptions of practice and knowledge and skills score much lower. Educational interventions are needed for practicing nurses to overcome this knowledge deficit to successfully implement EBP. However, the use of online, independent, computer‐based learning modules, while cost‐efficient and offer several benefits when educating nurses, may not necessarily be the most effective method for teaching EBP knowledge and skills to practicing nurses.
Factors influencing utilization of hospital services by adult sickle cell disease patients: a systematic review
Authors: Benenson Irina , Jadotte Yuri , Echevarria Mercedes 
Published: March 2017

EXECUTIVE SUMMARY

Background
Painful vaso-occlusive crisis is a hallmark of sickle cell disease (SCD) that commonly results in utilization of hospital services. Recurrent use of hospital services by SCD patients is associated with high healthcare costs and adverse clinical outcomes. Understanding the factors influencing the pattern of utilization is a first step in improving medical care of this patient population while reducing healthcare expenditures.

Objectives
The primary objective of this systematic review was to determine what modifiable and non-modifiable factors influence utilization of hospital services by adult SCD patients.

Inclusion criteria Types of participants
Adult SCD patients of both sexes who utilized hospital services for acute or emergency care.

Types of factors/exposure
Non-modifiable and modifiable factors influencing utilization of hospital services.

Types of studies
Prospective and retrospective cohort studies, case-control and analytical cross-sectional studies.

Outcomes
The primary outcome of interest was high utilization of hospital services by adult SCD patients based on non-modifiable and modifiable factors measured as an odds ratio (analytical outcome). The secondary outcome was the prevalence of non-modifiable and modifiable factors among SCD patients who utilized hospital services measured as an event rate (descriptive outcome).

Search strategy
A comprehensive multi-step search was undertaken to find both published and unpublished studies. Only studies published in the English language were included. The search was not limited by year of publication.

Methodological quality
Retrieved papers were assessed for methodological quality using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument.

Data extraction
Data were extracted using a researcher-developed tool.

Data synthesis
Included studies were combined in a statistical meta-analysis. The meta-analysis was based on a random effect model. For studies that did not allow statistical pooling, the findings have been presented in a narrative form.

Results
Fourteen studies were included in this review. The analysis demonstrated that male patients accounted for 40.8% (95% confidence interval [CI] 0.370–0.447) of all utilizing patients. Sickle cell disease patients who were publically insured accounted for 76.5% (95% CI 0.632–0.861) of all patients who had hospital encounters. Patients aged 25–35 years had the highest rate of utilization, and the rate of utilization declined in patients older than 50 years. High utilizing patients had more diagnoses of acute chest syndrome and sepsis than patients who were moderate or low utilizers.

Conclusion
The majority of SCD patients who utilized hospital services were women, young people and publically insured individuals. Patients with particularly high level of utilization had more frequent diagnoses of acute chest syndrome and sepsis.
Robust Topology Design of Complex Infrastructure
Systems
Authors: Piacenza Joseph R. , Proper Scott , Bozorgirad Mir Abbas , Hoyle Christopher , Tumer Irem Y. 
Published: March 2017

Abstract
Optimizing the topology of complex infrastructure systems can minimize the impact of cascading failures due to an initiating failure event. This paper presents a model-based design approach for the concept-stage robust design of complex infrastructure systems, as an alternative to modern network analysis methods. This approach focuses on system performance after cascading has occurred and examines design tradeoffs of the resultant (or degraded) system state. In this research, robustness is classically defined as the invariability of system performance due to uncertain failure events, implying that a robust network has the ability to meet minimum performance requirements despite the impact of cascading failures. This research is motivated by catastrophic complex infrastructure system failures such as the August 13th Blackout of 2003, highlighting the vulnerability of systems such as the North American power grid (NAPG). A mathematical model was developed using an adjacency matrix, where removing network connections simulates uncertain failure events. Performance degradation is iteratively calculated as failures cascade throughout the system, and robustness is measured by the lack of performance variability over multiple cascading failure scenarios. Two case studies are provided: an extrapolated IEEE 14 test bus and the Oregon State University (OSU) campus power network. The overarching goal of this research is to understand key system design tradeoffs between robustness, performance objectives, and cost, and explore the benefits of optimizing network topologies during the concept-stage design of these systems (e.g., microgrids).
A Risk Score for Fluconazole Failure among Patients with Candidemia
Authors: Ostrosky-Zeichner Luis , Harrington Rachel , Azie Nkechi , Yang Hongbo , Li Nanxin , Zhao Jing , Koo Valerie , Wu Eric Q. 
Published: March 2017

ABSTRACT

This study aimed to develop a prediction model to identify patients with candidemia who were at high risk of failing fluconazole treatment. Adult patients in the United States with candidemia who received fluconazole during hospitalization were selected from the Cerner Health Facts Hospital Database (04/2004 to 03/2013). Fluconazole failure was defined as switching/adding another antifungal, positive
Candida
culture ≥10 days after fluconazole initiation, or death during hospitalization. Patients were randomized into modeling and validation samples. Using the modeling sample, a regression analysis of least absolute shrinkage and selection operator was used to select risk predictors of fluconazole failure (demographics,
Candida
species, initiation of fluconazole before positive culture and after admission, and comorbidities, procedures, and treatments during the 6 months before admission and fluconazole initiation). The prediction model was evaluated using the validation sample. We found that of 987 identified patients (average age of 61 years, 51% male, 72% Caucasian), 49% failed and 51% did not fail fluconazole treatment. Of those who failed, 70% switched or added another antifungal, 21% had a second positive
Candida
test, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission,
Candida glabrata
or
Candida krusei
infection, hematological malignancy, venous thromboembolism (VTE), enteral nutrition, use of nonoperative intubation/irrigation, and other antifungal use. All but VTE were associated with a higher risk of failure. The model's c-statistic was 0.65, with a Hosmer-Lemeshow test
P
value of 0.23. In summary, this prediction model identified patients with a high risk of fluconazole failure, illustrating the potential value and feasibility of personalizing candidemia treatment.
MCR-1.6, a New MCR Variant Carried by an IncP Plasmid in a Colistin-Resistant Salmonella enterica Serovar Typhimurium Isolate from a Healthy Individual
Authors: Lu Xin , Hu Yongfei , Luo Ming , Zhou Haijian , Wang Xiaoxun , Du Yu , Li Zhenpeng , Xu Jialiang , Zhu Baoli , Xu Xuebin , Kan Biao 
Published: March 2017

ABSTRACT

In this study, we report a novel
mcr-1
gene variant, named
mcr-1.6
, carried by an IncP plasmid in a colistin-resistant
Salmonella enterica
serovar Typhimurium isolate from a healthy person. Compared with
mcr-1
, the
mcr-1.6
gene contains two single-nucleotide polymorphisms, one of which results in an arginine to histidine variation (Arg536→His). The plasmid carrying the
mcr-1.6
gene was designated pMCR1.6_P053 and is similar to a recently discovered
mcr-1
-bearing plasmid found in
Klebsiella pneumoniae
.
Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model
Authors: Bergen Phillip J. , Bulitta Jürgen B. , Kirkpatrick Carl M. J. , Rogers Kate E. , McGregor Megan J. , Wallis Steven C. , Paterson David L. , Nation Roger L. , Lipman Jeffrey , Roberts Jason A. , Landersdorfer Cornelia B. 
Published: March 2017

ABSTRACT

Critically ill patients frequently have substantially altered pharmacokinetics compared to non-critically ill patients. We investigated the impact of pharmacokinetic alterations on bacterial killing and resistance for commonly used meropenem dosing regimens. A
Pseudomonas aeruginosa
isolate (MIC
meropenem
0.25 mg/liter) was studied in the hollow-fiber infection model (inoculum ∼10
7.5
CFU/ml; 10 days). Pharmacokinetic profiles representing critically ill patients with augmented renal clearance (ARC), normal, or impaired renal function (creatinine clearances of 285, 120, or ∼10 ml/min, respectively) were generated for three meropenem regimens (2, 1, and 0.5 g administered as 8-hourly 30-min infusions), plus 1 g given 12 hourly with impaired renal function. The time course of total and less-susceptible populations and MICs were determined. Mechanism-based modeling (MBM) was performed using S-ADAPT. All dosing regimens across all renal functions produced similar initial bacterial killing (≤∼2.5 log
10
). For all regimens subjected to ARC, regrowth occurred after 7 h. For normal and impaired renal function, bacterial killing continued until 23 to 47 h; regrowth then occurred with 0.5- and 1-g regimens with normal renal function (
fT
>5×MIC
= 56 and 69%,
fC
min
/MIC < 2); the emergence of less-susceptible populations (≥32-fold increases in MIC) accompanied all regrowth. Bacterial counts remained suppressed across 10 days with normal (2-g 8-hourly regimen) and impaired (all regimens) renal function (
fT
>5×MIC
≥ 82%,
fC
min
/MIC ≥ 2). The MBM successfully described bacterial killing and regrowth for all renal functions and regimens simultaneously. Optimized dosing regimens, including extended infusions and/or combinations, supported by MBM and Monte Carlo simulations, should be evaluated in the context of ARC to maximize bacterial killing and suppress resistance emergence.
In Vivo
Pharmacokinetic and Pharmacodynamic Profiles of Antofloxacin against Klebsiella pneumoniae in a Neutropenic Murine Lung Infection Model
Authors: Zhou Yu-Feng , Tao Meng-Ting , Huo Wei , Liao Xiao-Ping , Sun Jian , Liu Ya-Hong 
Published: March 2017

ABSTRACT

Antofloxacin is a novel broad-spectrum fluoroquinolone under development for the treatment of infections caused by a diverse group of bacterial species. We explored the pharmacodynamic (PD) profile and targets of antofloxacin against seven
Klebsiella pneumoniae
isolates by using a neutropenic murine lung infection model. Plasma and bronchopulmonary pharmacokinetic (PK) studies were conducted at single subcutaneous doses of 2.5, 10, 40, and 160 mg/kg of body weight. Mice were infected intratracheally with
K. pneumoniae
and treated using 2-fold-increasing total doses of antofloxacin ranging from 2.5 to 160 mg/kg/24 h administered in 1, 2, 3, or 4 doses. The
E
max
Hill equation was used to model the dose-response data. Antofloxacin could penetrate the lung epithelial lining fluid (ELF) with pharmacokinetics similar to those in plasma with linear elimination half-lives over the dose range. All study strains showed a 3-log
10
or greater reduction in bacterial burden and prolonged postantibiotic effects (PAEs) ranging from 3.2 to 5.3 h. Dose fractionation response curves were steep, and the free-drug area under the concentration-time curve over 24 h (AUC
0–24
)/MIC ratio was the PD index most closely linked to efficacy (
R
2
= 0.96). The mean free-drug AUC
0–24
/MIC ratios required to achieve net bacterial stasis, a 1-log
10
kill, and a 2-log
10
kill for each isolate were 52.6, 89.9, and 164.9, respectively. When integrated with human PK data, these PD targets could provide a framework for further optimization of dosing regimens. This could make antofloxacin an attractive option for the treatment of respiratory tract infections involving
K. pneumoniae
.