bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Canadian Assessment of Physical Literacy: Development of a Model of Children’s Capacity for a Healthy, Active Lifestyle Through a Delphi Process
Authors: Francis Claire E. , Longmuir Patricia E. , Boyer Charles , Andersen Lars Bo , Barnes Joel D. , Boiarskaia Elena , Cairney John , Faigenbaum Avery D. , Faulkner Guy , Hands Beth P. , Hay John A. , Janssen Ian , Katzmarzyk Peter T. , Kemper Han C. G. , Knudson Duane , Lloyd Meghann , McKenzie Thomas L. , Olds Tim S. , Sacheck Jennifer M. , Shephard Roy J. , Zhu Weimo , Tremblay Mark S. 
Published: June 2015

Background:The Canadian Assessment of Physical Literacy (CAPL) was conceptualized as a tool to monitor children’s physical literacy. The original model (fitness, activity behavior, knowledge, motor skill) required revision and relative weights for calculating/interpreting scores were required.Methods:Nineteen childhood physical activity/fitness experts completed a 3-round Delphi process. Round 1 was open-ended questions. Subsequent rounds rated statements using a 5-point Likert scale. Recommendations were sought regarding protocol inclusion, relative importance within composite scores and score interpretation.Results:Delphi participant consensus was achieved for 64% (47/73) of statement topics, including a revised conceptual model, specific assessment protocols, the importance of longitudinal tracking, and the relative importance of individual protocols and composite scores. Divergent opinions remained regarding the inclusion of sleep time, assessment/scoring of the obstacle course assessment of motor skill, and the need for an overall physical literacy classification.Conclusions:The revised CAPL model (overlapping domains of physical competence, motivation, and knowledge, encompassed by daily behavior) is appropriate for monitoring the physical literacy of children aged 8 to 12 years. Objectively measured domains (daily behavior, physical competence) have higher relative importance. The interpretation of CAPL results should be reevaluated as more data become available.
A Drug-Disease Model Describing the Effect of Oseltamivir Neuraminidase Inhibition on Influenza Virus Progression
Authors: Kamal Mohamed A. , Gieschke Ronald , Lemenuel-Diot Annabelle , Beauchemin Catherine A. A. , Smith Patrick F. , Rayner Craig R. 
Published: June 2015

ABSTRACT

A population drug-disease model was developed to describe the time course of influenza virus with and without oseltamivir treatment and to investigate opportunities for antiviral combination therapy. Data included viral titers from 208 subjects, across 4 studies, receiving placebo and oseltamivir at 20 to 200 mg twice daily for 5 days. A 3-compartment mathematical model, comprising target cells infected at rate β, free virus produced at rate
p
and cleared at rate
c
, and infected cells cleared at rate δ, was implemented in NONMEM with an inhibitory Hill function on virus production (
p
), accounting for the oseltamivir effect. In congruence with clinical data, the model predicts that the standard 75-mg regimen initiated 2 days after infection decreased viral shedding duration by 1.5 days versus placebo; the 150-mg regimen decreased shedding by an additional average 0.25 day. The model also predicts that initiation of oseltamivir sooner postinfection, specifically at day 0.5 or 1, results in proportionally greater decreases in viral shedding duration of 5 and 3.5 days, respectively. Furthermore, the model suggests that combining oseltamivir (acting to subdue virus production rate) with an antiviral whose activity decreases viral infectivity (β) results in a moderate additive effect dependent on therapy initiation time. In contrast, the combination of oseltamivir with an antiviral whose activity increases viral clearance (
c
) shows significant additive effects independent of therapy initiation time. The utility of the model for investigating the pharmacodynamic effects of novel antivirals alone or in combination on emergent influenza virus strains warrants further investigation.
Differences in Antibiotic-Induced Oxidative Stress Responses between Laboratory and Clinical Isolates of Streptococcus pneumoniae
Authors: Dridi Bédis , Lupien Andréanne , Bergeron Michel G. , Leprohon Philippe , Ouellette Marc 
Published: June 2015

ABSTRACT

Oxidants were shown to contribute to the lethality of bactericidal antibiotics in different bacterial species, including the laboratory strain
Streptococcus pneumoniae
R6. Resistance to penicillin among
S. pneumoniae
R6 mutants was further shown to protect against the induction of oxidants upon exposure to unrelated bactericidal compounds. In the work described here, we expanded on these results by studying the accumulation of reactive oxygen species in the context of antibiotic sensitivity and resistance by including
S. pneumoniae
clinical isolates. In
S. pneumoniae
R6, penicillin, ciprofloxacin, and kanamycin but not the bacteriostatic linezolid, erythromycin, or tetracycline induced the accumulation of reactive oxygen species. For the three bactericidal compounds, resistance to a single molecule prevented the accumulation of oxidants upon exposure to unrelated bactericidal antibiotics, and this was accompanied by a reduced lethality. This phenomenon does not involve target site mutations but most likely implicates additional mutations occurring early during the selection of resistance to increase survival while more efficient resistance mechanisms are being selected or acquired. Bactericidal antibiotics also induced oxidants in sensitive
S. pneumoniae
clinical isolates. The importance of oxidants in the lethality of bactericidal antibiotics was less clear than for
S. pneumoniae
R6, however, since ciprofloxacin induced oxidants even in ciprofloxacin-resistant
S. pneumoniae
clinical isolates. Our results provide a clear example of the complex nature of the mode of action of antibiotics. The adaptive approach to oxidative stress of
S. pneumoniae
is peculiar, and a better understanding of the mechanism implicated in response to oxidative injury should also help clarify the role of oxidants induced by antibiotics.
Characterization of IncI1 Sequence Type 71 Epidemic Plasmid Lineage Responsible for the Recent Dissemination of CTX-M-65 Extended-Spectrum β-Lactamase in the Bolivian Chaco Region
Authors: Riccobono Eleonora , Di Pilato Vincenzo , Di Maggio Tiziana , Revollo Carmen , Bartoloni Alessandro , Pallecchi Lucia , Rossolini Gian Maria 
Published: June 2015

ABSTRACT

During the last decade, a significant diffusion of CTX-M-type extended-spectrum β-lactamases (ESBLs) was observed in commensal
Escherichia coli
from healthy children in the Bolivian Chaco region, with initial dissemination of CTX-M-2, which was then replaced by CTX-M-15 and CTX-M-65. In this work, we demonstrate that the widespread dissemination of CTX-M-65 observed in this context was related to the polyclonal spreading of an IncI1 sequence type 71 (ST71) epidemic plasmid lineage. The structure of the epidemic plasmid population was characterized by complete sequencing of four representatives and PCR mapping of the remainder (
n
= 16). Sequence analysis showed identical plasmid backbones (similar to that of the reference IncI1 plasmid, R64) and a multiresistance region (MRR), which underwent local microevolution. The MRR harbored genes responsible for resistance to β-lactams, aminoglycosides, florfenicol, and fosfomycin (with microevolution mainly consisting of deletion events of resistance modules). The
bla
CTX-M-65
module harbored by the IncI1 ST71 epidemic plasmid was apparently derived from IncN-type plasmids, likely via IS
26
-mediated mobilization. The plasmid could be transferred by conjugation to several different enterobacterial species (
Escherichia coli
,
Cronobacter sakazakii
,
Enterobacter cloacae
,
Klebsiella oxytoca
,
Klebsiella pneumoniae
, and
Salmonella enterica
) and was stably maintained without selective pressure in these species, with the exception of
K. oxytoca
and
S. enterica
. Fitness assays performed in
E. coli
recipients demonstrated that the presence of the epidemic plasmid was apparently not associated with a significant biological cost.
Resistance Analysis of Baseline and Treatment-Emergent Variants in Hepatitis C Virus Genotype 1 in the AVIATOR Study with Paritaprevir-Ritonavir, Ombitasvir, and Dasabuvir
Authors: Krishnan Preethi , Tripathi Rakesh , Schnell Gretja , Reisch Thomas , Beyer Jill , Irvin Michelle , Xie Wangang , Larsen Lois , Cohen Daniel , Podsadecki Thomas , Pilot-Matias Tami , Collins Christine 
Published: June 2015

ABSTRACT
AVIATOR, a phase 2 clinical trial, evaluated ritonavir-boosted paritaprevir (a protease inhibitor), ombitasvir (an NS5A inhibitor), and dasabuvir (a nonnucleoside polymerase inhibitor) (the three-drug [3D] regimen) with or without ribavirin (RBV) for 8, 12, or 24 weeks in 406 HCV genotype 1 (GT1)-infected patients. The rate of sustained virologic response 24 weeks after treatment ranged from 88% to 100% across the arms of the 3D regimen with or without RBV; 20 GT1a-infected patients and 1 GT1b-infected patient experienced virologic failure (5.2%). Baseline resistance-conferring variants in NS3 were rare. M28V in GT1a and Y93H in GT1b were the most prevalent preexisting variants in NS5A, and C316N in GT1b and S556G in both GT1a and GT1b were the most prevalent variants in NS5B. Interestingly, all the GT1a sequences encoding M28V in NS5A were from the United States, while GT1b sequences encoding C316N and S556G in NS5B were predominant in the European Union. Variants preexisting at baseline had no significant impact on treatment outcome. The most prevalent treatment-emergent resistance-associated variants (RAVs) in GT1a were R155K and D168V in NS3, M28T and Q30R in NS5A, and S556G in NS5B. The single GT1b-infected patient experiencing virologic failure had no RAVs in any target. A paritaprevir-ritonavir dose of 150/100 mg was more efficacious in suppressing R155K in NS3 than a 100/100-mg dose. In patients who failed after receiving 12 or more weeks of treatment, RAVs were selected in all 3 targets, while most patients who relapsed after 8 weeks of treatment did so without any detectable RAVs. Results from this study guided the selection of the optimal treatment regimen, treatment duration, and paritaprevir dose for further development of the 3D regimen. (This study has been registered at ClinicalTrials.gov under registration number NCT01464827.)
Toxicity and SidJ-Mediated Suppression of Toxicity Require Distinct Regions in the SidE Family of Legionella pneumophila Effectors
Authors: Havey James C. , Roy Craig R. 
Published: June 2015

ABSTRACT

Intracellular bacteria use a variety of strategies to evade degradation and create a replicative niche.
Legionella pneumophila
is an intravacuolar pathogen that establishes a replicative niche through the secretion of more than 300 effector proteins. The function of most effectors remains to be determined. Toxicity in yeast has been used to identify functional domains and elucidate the biochemical function of effectors. A library of
L. pneumophila
effectors was screened using an expression plasmid that produces low levels of each protein. This screen identified the effector SdeA as a protein that confers a strong toxic phenotype that inhibits yeast replication. The toxicity of SdeA was suppressed in cells producing the effector SidJ. The effector SdeA is a member of the SidE family of
L. pneumophila
effector proteins. All SidE orthologs encoded by the Philadelphia isolate of
Legionella pneumophila
were toxic to yeast, and SidJ suppressed the toxicity of each. We identified a conserved central region in the SidE proteins that was sufficient to mediate yeast toxicity. Surprisingly, SidJ did not suppress toxicity when this central region was produced in yeast. We determined that the amino-terminal region of SidE was essential for SidJ-mediated suppression of toxicity. Thus, there is a genetic interaction that links the activity of SidJ and the amino-terminal region of SidE, which is required to modulate the toxic activity displayed by the central region of the SidE protein. This suggests a complex mechanism by which the
L. pneumophila
effector SidJ modulates the function of the SidE proteins after translocation into host cells.
Interactions and Localization of Escherichia coli Error-Prone DNA Polymerase IV after DNA Damage
Authors: Mallik Sarita , Popodi Ellen M. , Hanson Andrew J. , Foster Patricia L. 
Published: June 2015

ABSTRACT

Escherichia coli
's DNA polymerase IV (Pol IV/DinB), a member of the Y family of error-prone polymerases, is induced during the SOS response to DNA damage and is responsible for translesion bypass and adaptive (stress-induced) mutation. In this study, the localization of Pol IV after DNA damage was followed using fluorescent fusions. After exposure of
E. coli
to DNA-damaging agents, fluorescently tagged Pol IV localized to the nucleoid as foci. Stepwise photobleaching indicated ∼60% of the foci consisted of three Pol IV molecules, while ∼40% consisted of six Pol IV molecules. Fluorescently tagged Rep, a replication accessory DNA helicase, was recruited to the Pol IV foci after DNA damage, suggesting that the
in vitro
interaction between Rep and Pol IV reported previously also occurs
in vivo
. Fluorescently tagged RecA also formed foci after DNA damage, and Pol IV localized to them. To investigate if Pol IV localizes to double-strand breaks (DSBs), an I-SceI endonuclease-mediated DSB was introduced close to a fluorescently labeled LacO array on the chromosome. After DSB induction, Pol IV localized to the DSB site in ∼70% of SOS-induced cells. RecA also formed foci at the DSB sites, and Pol IV localized to the RecA foci. These results suggest that Pol IV interacts with RecA
in vivo
and is recruited to sites of DSBs to aid in the restoration of DNA replication.

IMPORTANCE
DNA polymerase IV (Pol IV/DinB) is an error-prone DNA polymerase capable of bypassing DNA lesions and aiding in the restart of stalled replication forks. In this work, we demonstrate
in vivo
localization of fluorescently tagged Pol IV to the nucleoid after DNA damage and to DNA double-strand breaks. We show colocalization of Pol IV with two proteins: Rep DNA helicase, which participates in replication, and RecA, which catalyzes recombinational repair of stalled replication forks. Time course experiments suggest that Pol IV recruits Rep and that RecA recruits Pol IV. These findings provide
in vivo
evidence that Pol IV aids in maintaining genomic stability not only by bypassing DNA lesions but also by participating in the restoration of stalled replication forks.
Cyclic Di-GMP-Regulated Periplasmic Proteolysis of a Pseudomonas aeruginosa Type Vb Secretion System Substrate
Authors: Cooley Richard B. , Smith T. Jarrod , Leung Wilfred , Tierney Valerie , Borlee Bradley R. , O'Toole George A. , Sondermann Holger 
Published: June 2015

ABSTRACT

We previously identified a second-messenger-regulated signaling system in the environmental bacterium
Pseudomonas fluorescens
which controls biofilm formation in response to levels of environmental inorganic phosphate. This system contains the transmembrane cyclic di-GMP (c-di-GMP) receptor LapD and the periplasmic protease LapG. LapD regulates LapG and controls the ability of this protease to process a large cell surface adhesin protein, LapA. While LapDG orthologs can be identified in diverse bacteria, predictions of LapG substrates are sparse. Notably, the opportunistic pathogen
Pseudomonas aeruginosa
harbors LapDG orthologs, but neither the substrate of LapG nor any associated secretion machinery has been identified to date. Here, we identified
P. aeruginosa
CdrA, a protein known to mediate cell-cell aggregation and biofilm maturation, as a substrate of LapG. We also demonstrated LapDG to be a minimal system sufficient to control CdrA localization in response to changes in the intracellular concentration of c-di-GMP. Our work establishes this biofilm signaling node as a regulator of a type Vb secretion system substrate in a clinically important pathogen.

IMPORTANCE
Here, the biological relevance of a conserved yet orphan signaling system in the opportunistic pathogen
Pseudomonas aeruginosa
is revealed. In particular, we identified the adhesin CdrA, the cargo of a two-partner secretion system, as a substrate of a periplasmic protease whose activity is controlled by intracellular c-di-GMP levels and a corresponding transmembrane receptor via an inside-out signaling mechanism. The data indicate a posttranslational control mechanism of CdrA via c-di-GMP, in addition to its established transcriptional regulation via the same second messenger.
Cost-effectiveness of the New Zealand diabetes in pregnancy guideline screening recommendations
Authors: Coop Catherine , Edlin Richard , Brown Julie , Farquhar Cindy 
Published: June 2015

ObjectiveTo compare the cost-effectiveness of 2 possible screening strategies for gestational diabetes mellitus (GDM) from the perspective of the New Zealand health system, developed as part of a gestational diabetes guideline.DesignA decision analytic model was built comparing 2-step screening (glycated haemoglobin (HbA1c) test at first booking and a 2 h 75 g oral glucose tolerance test (OGTT) as a single test at 24–28 weeks) with 3-step screening (HbA1c test at first booking and a 1 h glucose challenge test (GCT) followed by a 2 h 75 g OGTT when indicated from 24–28 weeks) using a 9-month time horizon.SettingA hypothetical cohort of 62 000 pregnant women in New Zealand.MethodsProbabilities, costs and benefits were derived from the literature, and supplementary data was obtained from National Women's Annual Clinical Reports. Main outcome measures, screening and treatment costs (NZ$2013) and effect on health outcomes (incidence of complications).ResultsThe total cost for both strategies under baseline assumptions shows that the 2-step screening strategy would cost NZ$1.38 m more than the 3-step screening strategy overall. The additional cost per case detected was NZ$12 460 per case. The model found that the 2-step screening strategy identifies 12 more women with diabetes and 111 more women with GDM when compared against the 3-step screening strategy. We assessed the effect of changing the sensitivity and specificity of the OGTT. The baseline model assumed that the 2 h 75 g OGTT has a sensitivity and specificity of 95%. The 2-step strategy becomes more cost-effective when the diagnostic accuracy measures are improved.ConclusionsAdopting a 2-step strategy would moderately increase the number of GDM cases detected at the same time as moderately increasing the number of women with false negatives at a significant cost to the health system. Further evidence on the benefits of the 2 different approaches would be welcome.
Association between environmental tobacco smoke and depression among Korean women
Authors: Kim Na Hyun , Kim Hyeon Chang , Lee Joo Young , Lee Ju-Mi , Suh Il 
Published: June 2015

ObjectiveTo evaluate the association between environmental tobacco smoke (ETS) exposure and depression among Korean women.MethodsBetween 2008 and 2011, we examined 731 men and 1249 women (aged 39–85 years) for the Korean Genome and Epidemiology Study (KoGES)-Kangwha. Among 1208 never-smoking women, we excluded two women taking antidepressants and five women who did not complete the Beck Depression Inventory (BDI). Therefore, we performed a cross-sectional analysis on 1201 women. ETS exposure was assessed using a self-reported questionnaire, and was classified into three groups: no exposure, occasional exposure and regular exposure. Depression was assessed using the BDI score, which ranged from 0 to 63, and the presence of depression was defined as a BDI score ≥10.ResultsWomen exposed to ETS were more likely to have depression than those without ETS exposure (p=0.019). When BDI was analysed as a continuous variable, women exposed to ETS had significantly higher BDI scores after full adjustment (overall exposure: β=1.36, p=0.013; occasional exposure: β=1.15, p=0.063; regular exposure: β=1.90, p=0.039). ETS exposure was significantly associated with depression in a dose–response manner even after adjusting for age, body mass index, menopause, socioeconomic status, lifestyle and prevalent chronic diseases. The adjusted OR for depression (95% CI) was 1.72 (1.25 to 2.37) for overall ETS exposure, 1.56 (1.09 to 2.24) for occasional exposure and 2.19 (1.30 to 3.69) for regular exposure, when compared to no exposure.ConclusionsExposure to ETS was associated with depression among middle aged and elderly Korean women.
Validity and reliability of chronic tic disorder and obsessive-compulsive disorder diagnoses in the Swedish National Patient Register
Authors: Rück Christian , Larsson K Johan , Lind Kristina , Perez-Vigil Ana , Isomura Kayoko , Sariaslan Amir , Lichtenstein Paul , Mataix-Cols David 
Published: June 2015

ObjectivesThe usefulness of cases diagnosed in administrative registers for research purposes is dependent on diagnostic validity. This study aimed to investigate the validity and inter-rater reliability of recorded diagnoses of tic disorders and obsessive-compulsive disorder (OCD) in the Swedish National Patient Register (NPR).DesignChart review of randomly selected register cases and controls.Method100 tic disorder cases and 100 OCD cases were randomly selected from the NPR based on codes from the International Classification of Diseases (ICD) 8th, 9th and 10th editions, together with 50 epilepsy and 50 depression control cases. The obtained psychiatric records were blindly assessed by 2 senior psychiatrists according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and ICD-10.Primary outcome measurementPositive predictive value (PPV; cases diagnosed correctly divided by the sum of true positives and false positives).ResultsBetween 1969 and 2009, the NPR included 7286 tic disorder and 24 757 OCD cases. The vast majority (91.3% of tic cases and 80.1% of OCD cases) are coded with the most recent ICD version (ICD-10). For tic disorders, the PPV was high across all ICD versions (PPV=89% in ICD-8, 86% in ICD-9 and 97% in ICD-10). For OCD, only ICD-10 codes had high validity (PPV=91–96%). None of the epilepsy or depression control cases were wrongly diagnosed as having tic disorders or OCD, respectively. Inter-rater reliability was outstanding for both tic disorders (κ=1) and OCD (κ=0.98).ConclusionsThe validity and reliability of ICD codes for tic disorders and OCD in the Swedish NPR is generally high. We propose simple algorithms to further increase the confidence in the validity of these codes for epidemiological research.