bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of real-time alerting on appropriate prescribing in kidney disease: a cluster randomized controlled trial
Authors: Awdishu Linda , Coates Carrie R , Lyddane Adam , Tran Kim , Daniels Charles E , Lee Joshua , El-Kareh Robert 
Published: November 2015

ABSTRACT

Background
Patients with kidney disease are at risk for adverse events due to improper medication prescribing. Few randomized controlled trials of clinical decision support (CDS) utilizing dynamic assessment of patients’ kidney function to improve prescribing for patients with kidney disease have been published.

Methods
We developed a CDS tool for 20 medications within a commercial electronic health record. Our system detected scenarios in which drug discontinuation or dosage adjustment was recommended for adult patients with impaired renal function in the ambulatory and acute settings – both at the time of the initial prescription (“prospective” alerts) and by monitoring changes in renal function for patients already receiving one of the study medications (“look-back” alerts). We performed a prospective, cluster randomized controlled trial of physicians receiving clinical decision support for renal dosage adjustments versus those performing their usual workflow. The primary endpoint was the proportion of study prescriptions that were appropriately adjusted for patients’ kidney function at the time that patients’ conditions warranted a change according to the alert logic. We employed multivariable logistic regression modeling to adjust for glomerular filtration rate, gender, age, hospitalized status, length of stay, type of alert, time from start of study, and clustering within the prescribing physician on the primary endpoint.

Results
A total of 4068 triggering conditions occurred in 1278 unique patients; 1579 of these triggering conditions generated alerts seen by physicians in the intervention arm and 2489 of these triggering conditions were captured but suppressed, so as not to generate alerts for physicians in the control arm. Prescribing orders were appropriate adjusted in 17% of the time vs 5.7% of the time in the intervention and control arms, respectively (odds ratio: 1.89, 95% confidence interval, 1.45-2.47, P &lt; .0001). Prospective alerts had a greater impact than look-back alerts (55.6% vs 10.3%, in the intervention arm).

Conclusions
The rate of appropriate drug prescribing in kidney impairment is low and remains a patient safety concern. Our results suggest that CDS improves drug prescribing, particularly when providing guidance on new prescriptions.
The role of deleterious substitutions in crop genomes
Authors: Kono Thomas J. Y. , Fu Fengli , Mohammadi Mohsen , Hoffman Paul J. , Liu Chaochih , Stupar Robert M. , Smith Kevin P. , Tiffin Peter , Fay Justin C. , Morrell Peter L. 
Published: November 2015

AbstractPopulations continually incur new mutations with fitness effects ranging from lethal to adaptive. While the distribution of fitness effects (DFE) of new mutations is not directly observable, many mutations likely have either no effect on organismal fitness or are deleterious. Historically, it has been hypothesized that a population may carry many mildly deleterious variants as segregating variation, which reduces the mean absolute fitness of the population. Recent advances in sequencing technology and sequence conservation-based metrics for inferring the functional effect of a variant permit examination of the persistence of deleterious variants in populations. The issue of segregating deleterious variation is particularly important for crop improvement, because the demographic history of domestication and breeding allows deleterious variants to persist and reach moderate frequency, potentially reducing crop productivity. In this study, we use exome resequencing of fifteen barley accessions and genome resequencing of eight soybean accessions to investigate the prevalence of deleterious SNPs in the protein-coding regions of the genomes of two crops. We conclude that individual cultivars carry hundreds of deleterious SNPs on average, and that nonsense variants make up a minority of deleterious SNPs. Our approach annotates known phenotype-altering variants as deleterious more frequently than the genome-wide average, suggesting that putatively deleterious variants are likely to affect phenotypic variation. We also report the implementation of a SNP annotation tool (BAD_Mutations) that makes use of a likelihood ratio test based on alignment of all currently publicly available Angiosperm genomes.
Genome-wide and single-base resolution DNA methylomes of the Sea Lamprey (Petromyzon marinus) Reveal Gradual Transition of the Genomic Methylation Pattern in Early Vertebrates
Authors: Zhang Zhao , Liu Gangbiao , Zhou Yangyun , Lloyd James P. B. , McCauley David W. , Li Weiming , Gu Xun , Su Zhixi 
Published: December 2015

AbstractIn eukaryotes, cytosine methylation is a primary heritable epigenetic modification of the genome that regulates many cellular processes. While the whole-genome methylation pattern has been generally conserved in different eukaryotic groups, invertebrates and vertebrates exhibit two distinct patterns. Whereas almost all CpG sites are methylated in most vertebrates, with the exception of short unmethylated regions call CpG islands, the most frequent pattern in invertebrate animals is ‘mosaic methylation’, comprising domains of heavily methylated DNA interspersed with domains that are methylation free. The mechanism by which the genome methylation pattern transited from a mosaic to a global pattern and the role of the one or two-round whole-genome duplication in this transition remain largely elusive, partly owing to the lack of methylome data from early vertebrates. In this study, we used the whole-genome bisulfite-sequencing technology to investigate the genome-wide methylation in three tissues (heart, muscle, and sperm) from the sea lamprey, an extant Agarthan vertebrate. Analyses of methylation level and the extent of CpG dinucleotide depletion of geneencoding, intergenic and promoter regions revealed a gradual increase in the methylation level from invertebrates to vertebrates, with the sea lamprey exhibiting an intermediate position. In addition, the methylation level of the majority of CpGs was intermediate in each sea lamprey tissue, indicating a high level of heterogeneity of methylation status between individual cells. In this regard, we defined the genomic methylation pattern of sea lamprey as “global genomic DNA intermediate methylation”. The methylation features in different genomic regions, such as the transcription start site (TSS) region of the gene body, exon-intron boundaries, transposons, as well as genes grouping with different expression levels, supported the gradual methylation transition hypothesis. We further discussed that the copy number difference in DNA methylation transferases and the loss of the PWWP domain and/or DNTase domain in DNMT3 sub-family enzymes may have contributed to the methylation pattern transition in early vertebrates. These findings demonstrate an intermediate genomic methylation pattern between invertebrates and jawed vertebrates, providing evidence that supports the hypothesis that methylation patterns underwent a gradual transition from invertebrates (mosaic) to vertebrates (global).
Automated long-term recording and analysis of neural activity in behaving animals
Authors: Dhawale Ashesh K. , Poddar Rajesh , Kopelowitz Evi , Normand Valentin , Wolff Steffen B. E. , Ölveczky Bence P. 
Published: December 2015

SummaryAddressing how neural circuits underlie behavior is routinely done by measuring electrical activity from single neurons during experimental sessions. While such recordings yield snapshots of neural dynamics during specified tasks, they are ill-suited for tracking single-unit activity over longer timescales relevant for most developmental and learning processes, or for capturing neural dynamics across different behavioral states. Here we describe an automated platform for continuous long-term recordings of neural activity and behavior in freely moving animals. An unsupervised algorithm identifies and tracks the activity of single units over weeks of recording, dramatically simplifying the analysis of large datasets. Months-long recordings from motor cortex and striatum made and analyzed with our system revealed remarkable stability in basic neuronal properties, such as firing rates and inter-spike interval distributions. Interneuronal correlations and the representation of different movements and behaviors were similarly stable. This establishes the feasibility of high-throughput long-term extracellular recordings in behaving animals.HighlightsWe record neural activity and behavior in rodents continuously (24/7) over monthsAn automated spike-sorting method isolates and tracks single units over many weeksNeural dynamics and motor representations are highly stable over long timescalesNeurons cluster into functional groups based on their activity in different stateseTOC BlurbDhawale et al. describe experimental infrastructure for recording neural activity and behavior continuously over months in freely moving rodents. A fully automated spike-sorting algorithm allows single units to be tracked over weeks of recording. Recordings from motor cortex and striatum revealed a remarkable long-term stability in both single unit activity and network dynamics.
Segmental interpolation surface: a tool to dissect environmental effects on plant water-use efficiency in drought prone scenarios
Authors: Quero Gaston , Simondi Sebastian , Borsani Omar 
Published: December 2015

AbstractWater use efficiency (WUE), defined as the ratio of biomass (B) produced per unit of water transpired (E) by plants, is an important determinant of plant productivity. A mathematical approach was developed with the purpose explaining the WUE of two forage legumes (clover and birdsfoot trefoil). The approach applied involved an interpolation method by cubic spline which results in the smoothest curve that fits the set of data points obtained experimentally. The results obtained show the importance of recognizing the WUE as a function of two variables, one represents the supply (θ) and the other represents the demand (D). It is important to note that these surfaces generated by the model allowed the estimation of the WUE value for any value of θ and any value of D, showing it is able to dissect the effect of both environmental variables on WUE. From the surface generated by the model, a scalar field plot (SFP) was created. Analysis of these SFPs allowed decomposing the environmental effect on B and E parameters defining WUE. The SFPs allow identify, in one picture, what are the environmental conditions and what variable are explaining a high WUE in both species. Spline application for generating SFP could have a significant impact on the quantitative understanding of the WUE and our study represents a first step towards an analytical and integrated view of this parameters.Mathematics Subject Classification92B05 65D05 65D07 65D10
Soluble epoxide hydrolase: A potential target for metabolic diseases
Authors: He Jinlong , Wang Chunjiong , Zhu Yi , Ai Ding 
Published: December 2015

AbstractEpoxyeicosatrienoic acids (EETs), important lipid mediators derived from arachidonic acid, have many beneficial effects in metabolic diseases, including atherosclerosis, hypertension, cardiac hypertrophy, diabetes, non‐alcoholic fatty liver disease, and kidney disease. Epoxyeicosatrienoic acids can be further hydrolyzed to less active diols by the enzyme soluble epoxide hydrolase (sEH). Increasing evidence suggests that inhibition of sEH increases levels of EETs, which have anti‐inflammatory effects and can prevent the development of hypertension, atherosclerosis, heart failure, fatty liver, and multiple organ fibrosis. Arachidonic acid is the most abundant omega‐6 polyunsaturated fatty acid (PUFA) and shares the same set of enzymes with omega‐3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid. The omega‐3 PUFAs and metabolites, such as regioisomeric epoxyeicosatetraenoic acids and epoxydocosapentaenoic acids, have been reported to have strong vasodilatory and anti‐inflammatory effects. Therefore, sEH may be a potential therapeutic target for metabolic disorders. In this review, we focus on our and other recent studies of the functions of sEH, including the effects of its eicosanoid products from both omega‐3 and omega‐6 PUFAs, in various metabolic diseases. We also discuss the possible cellular and molecular mechanisms underlying the regulation of sEH.
Behavioural responses of Vespula germanica (Hymenoptera: Vespidae) wasps exposed to essential oils
Authors: Buteler Micaela , Lozada Mariana , D'Adamo Paola , Melo Romina Ayelen Luz , Stadler Teodoro 
Published: December 2015

AbstractSecondary plant metabolites such as those present in essential oils can be toxic to herbivorous insects and also repel attack, given they play a role in selection and acceptance of host plants. However, few studies have dealt with the use of plant‐based repellents to manage invasive wasps. The objective was to assess essential oils with potential as wasp repellents, and to gain further insight as to how they affect the learning capacities of these insects. Five essential oils were tested on Vespula germanica (Fabricius) wasps in field choice and no‐choice tests. When given a choice, foragers avoided the treated baits almost completely. Wind tunnel bioassays demonstrated that wasps recognise the repellent essential oils through olfactory cues, leading to a dose‐dependent decreased response to the food stimulus. The effect of the repellents on the cognitive ability of V. germanica workers was also studied in relation to food search efficiency. Naive workers landed on the treated baits, although it took them longer than to land on control baits. When workers were allowed to forage on a food bait twice before a repellent was added, an effect on relocation behaviour was observed. The returning workers arriving to a feeding site with essential oil were reticent to land on it, suggesting that there is indeed a repellent effect and not just masking of the food source. A push–pull system combining attractive baits with the use of plant‐based repellents is a promising management strategy in urban settings for this insect pest.
Spontaneous bilateral haemothorax as presentation of primary pleural epithelioid haemangioendothelioma
Authors: Ferreiro Lucía , San‐José Esther , Suárez‐Antelo Juan , Abdulkader Ihab , Martínez‐de‐Alegría Anxo , González‐Barcala Francisco‐Javier , Valdés Luis 
Published: December 2015

AbstractPleural epithelioid haemangioendothelioma (EHE) is a rare tumour that originates in the vascular endothelium with an intermediate degree of malignancy between haemangioma and angiosarcoma. Smoking and asbestos exposure are unproven risk factors and diagnosis is usually confirmed by thoracoscopy, since pleural fluid (PF) cytology is often not conclusive. Immunohistochemistry can also help to confirm the diagnosis. We report an 85‐year‐old patient with bilateral pleural EHE diagnosed by thoracoscopy, who debuted with a spontaneous bilateral haemothorax, the second described so far, and we conducted a thorough review of the literature to describe the clinical, radiological and prognostic features, as well as the PF, of this rare tumour.
Popularity and Social Preference in Chinese Adolescents: Associations with Social and Behavioral Adjustment
Authors: Niu Li , Jin Shenghua , Li Ling , French Doran C. 
Published: December 2015

AbstractThis study examined the characteristics associated with popularity and social preference in 769 14‐year‐old adolescents (54 percent boys) from mainland China. Consistent with findings from other countries, popularity and social preference were moderately correlated and overt aggression was positively correlated with popularity but negatively correlated with social preference. Prosocial behavior, athletic skill, dating, academic achievement, and mutual friends were positively associated with both popularity and social preference, with the effects for prosocial behavior, athletic skill, and dating greater for popularity than for social preference. The strong correlations between popularity and prosocial behavior are consistent with Confucian ideas of moral leadership and the obligations of high status individuals toward others. Cultural values are also reflected in the association of popularity with academic achievement. The inconsistent findings from China regarding the relation between aggression and popularity may stem from multiple factors including the absence of a suitable Chinese translation for popularity.
How computer simulations of the human heart can improve anti‐arrhythmia therapy
Authors: Trayanova Natalia A. , Chang Kelly C. 
Published: December 2015

AbstractOver the last decade, the state‐of‐the‐art in cardiac computational modelling has progressed rapidly. The electrophysiological function of the heart can now be simulated with a high degree of detail and accuracy, opening the doors for simulation‐guided approaches to anti‐arrhythmic drug development and patient‐specific therapeutic interventions. In this review, we outline the basic methodology for cardiac modelling, which has been developed and validated over decades of research. In addition, we present several recent examples of how computational models of the human heart have been used to address current clinical problems in cardiac electrophysiology. We will explore the use of simulations to improve anti‐arrhythmic pacing and defibrillation interventions; to predict optimal sites for clinical ablation procedures; and to aid in the understanding and selection of arrhythmia risk markers. Together, these studies illustrate how the tremendous advances in cardiac modelling are poised to revolutionize medical treatment and prevention of arrhythmia.
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Characterization of a Carbapenem-Hydrolyzing Enzyme, PoxB, in Pseudomonas aeruginosa PAO1
Authors: Zincke Diansy , Balasubramanian Deepak , Silver Lynn L. , Mathee Kalai 
Published: December 2015

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic pathogen often associated with severe and life-threatening infections that are highly impervious to treatment. This microbe readily exhibits intrinsic and acquired resistance to varied antimicrobial drugs. Resistance to penicillin-like compounds is commonplace and provided by the chromosomal AmpC β-lactamase. A second, chromosomally encoded β-lactamase, PoxB, has previously been reported in
P. aeruginosa
. In the present work, the contribution of this class D enzyme was investigated using a series of clean in-frame
ampC
,
poxB
, and
oprD
deletions, as well as complementation by expression under the control of an inducible promoter. While
poxB
deletions failed to alter β-lactam sensitivities, expression of
poxB
in
ampC
-deficient backgrounds decreased susceptibility to both meropenem and doripenem but had no effect on imipenem, penicillin, and cephalosporin MICs. However, when expressed in an
ampCpoxB
-deficient background, that additionally lacked the outer membrane porin-encoding gene
oprD
, PoxB significantly increased the imipenem as well as the meropenem and doripenem MICs. Like other class D carbapenem-hydrolyzing β-lactamases, PoxB was only poorly inhibited by class A enzyme inhibitors, but a novel non-β-lactam compound, avibactam, was a slightly better inhibitor of PoxB activity.
In vitro
susceptibility testing with a clinical concentration of avibactam, however, failed to reduce PoxB activity against the carbapenems. In addition,
poxB
was found to be cotranscribed with an upstream open reading frame,
poxA
, which itself was shown to encode a 32-kDa protein of yet unknown function.
Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration
Authors: Zimmermann Estevan Sonego , Laureano João Victor , dos Santos Camila Neris , Schmidt Stephan , Lagishetty Chakradhar V. , de Castro Whocely Victor , Dalla Costa Teresa 
Published: December 2015

ABSTRACT

Levofloxacin (LEV) is a broad-spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis, and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work, LEV free lung and prostate interstitial space fluid (ISF) concentrations were evaluated by microdialysis in Wistar rats after intravenous (i.v.) and intratracheal (i.t.) administration (7 mg/kg of body weight) with and without coadministration of the P-gp inhibitor tariquidar (TAR; 15 mg/kg administered i.v.). Plasma and tissue concentration/time profiles were evaluated by noncompartmental analysis (NCA) and population pharmacokinetics (popPK) analysis. The NCA showed significant differences in bioavailability (
F
) for the control group (0.4) and the TAR group (0.86) after i.t. administration. A four-compartment model simultaneously characterized total plasma and free lung (compartment 2) and prostate (compartment 3) ISF concentrations. Statistically significant differences in lung and prostate average ISF concentrations and levels of kidney active secretion in the TAR group from those measured for the control group (LEV alone) were observed. The estimated population means were as follows: volume of the central compartment (
V
1
), 0.321 liters; total plasma clearance (CL), 0.220 liters/h; TAR plasma clearance (CL
TAR
), 0.180 liters/h. The intercompartmental distribution rate constants (
K
values) were as follows:
K
12
, 8.826 h
−1
;
K
21
, 7.271 h
−1
;
K
13
, 0.047 h
−1
;
K
31
, 7.738 h
−1
;
K
14
, 0.908 h
−1
;
K
41
, 0.409 h
−1
;
K
21
lung TAR (
K
21LTAR
), 8.883 h
−1
;
K
31
prostate TAR (
K
31PTAR
), 4.377 h
−1
. The presence of P-gp considerably impacted the active renal secretion of LEV but had only a minor impact on the efflux from the lung following intratracheal dosing. Our results strongly support the idea of a role of efflux transporters other than P-gp contributing to LEV's tissue penetration into the prostrate.
σ Factor and Anti-σ Factor That Control Swarming Motility and Biofilm Formation in Pseudomonas aeruginosa
Authors: McGuffie Bryan A. , Vallet-Gely Isabelle , Dove Simon L. 
Published: December 2015

ABSTRACT

Pseudomonas aeruginosa
is capable of causing a variety of acute and chronic infections. Here, we provide evidence that
sbrR
(PA2895), a gene previously identified as required during chronic
P. aeruginosa
respiratory infection, encodes an anti-σ factor that inhibits the activity of its cognate extracytoplasmic-function σ factor, SbrI (PA2896). Bacterial two-hybrid analysis identified an N-terminal region of SbrR that interacts directly with SbrI and that was sufficient for inhibition of SbrI-dependent gene expression. We show that SbrI associates with RNA polymerase
in vivo
and identify the SbrIR regulon. In cells lacking SbrR, the SbrI-dependent expression of
muiA
was found to inhibit swarming motility and promote biofilm formation. Our findings reveal SbrR and SbrI as a novel set of regulators of swarming motility and biofilm formation in
P. aeruginosa
that mediate their effects through
muiA
, a gene not previously known to influence surface-associated behaviors in this organism.

IMPORTANCE
This study characterizes a σ factor/anti-σ factor system that reciprocally regulates the surface-associated behaviors of swarming motility and biofilm formation in the opportunistic pathogen
Pseudomonas aeruginosa
. We present evidence that SbrR is an anti-σ factor specific for its cognate σ factor, SbrI, and identify the SbrIR regulon in
P. aeruginosa
. We find that cells lacking SbrR are severely defective in swarming motility and exhibit enhanced biofilm formation. Moreover, we identify
muiA
(PA1494) as the SbrI-dependent gene responsible for mediating these effects. SbrIR have been implicated in virulence and in responding to antimicrobial and cell envelope stress. SbrIR may therefore represent a stress response system that influences the surface behaviors of
P. aeruginosa
during infection.