bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of Children’s Physical Activity Levels in Physical Education, Recess, and Exergaming
Authors: Gao Zan , Chen Senlin , Stodden David F. 
Published: May 2014

Purpose:To compare young children’s different intensity physical activity (PA) levels in physical education, recess and exergaming programs.Methods:Participants were 140 first and second grade children (73 girls; Meanage= 7.88 years). Beyond the daily 20-minute recess, participants attended 75-minute weekly physical education classes and another 75-minute weekly exergaming classes. Children’s PA levels were assessed by ActiGraph GTX3 accelerometers for 3 sessions in the 3 programs. The outcome variables were percentages of time spent in sedentary, light PA and moderate-to-vigorous PA (MVPA).Results:There were significant main effects for program and grade, and an interaction effect for program by grade. Specifically, children’s MVPA in exergaming and recess was higher than in physical education. The 2nd-grade children demonstrated lower sedentary behavior and MVPA than the first-grade children during recess; less light PA in both recess and exergaming than first-grade children; and less sedentary behavior but higher MVPA in exergaming than first-grade children.Conclusions:Young children generated higher PA levels in recess and exergaming as compared with physical education. Hence, other school-based PA programs may serve as essential components of a comprehensive school PA program. Implications are provided for educators and health professionals.
In Vitro
Susceptibility of Equine-Obtained Isolates of Corynebacterium pseudotuberculosis to Gallium Maltolate and 20 Other Antimicrobial Agents
Authors: Norman T. E. , Batista M. , Lawhon S. D. , Zhang S. , Kuskie K. R. , Swinford A. K. , Bernstein L. R. , Cohen N. D. 
Published: May 2014

ABSTRACT

This study's objective was to determine the
in vitro
antimicrobial activities of gallium maltolate (GaM) and 20 other antimicrobial agents against clinical equine isolates of
Corynebacterium pseudotuberculosis
. The growth of cultured isolates was not inhibited by any concentration of GaM. MIC data revealed susceptibility to commonly used antimicrobials.
Influenza Viruses and mRNA Splicing: Doing More with Less
Authors: Dubois Julia , Terrier Olivier , Rosa-Calatrava Manuel 
Published: May 2014

ABSTRACTDuring their nuclear replication stage, influenza viruses hijack the host splicing machinery to process some of their RNA segments, the M and NS segments. In this review, we provide an overview of the current knowledge gathered on this interplay between influenza viruses and the cellular spliceosome, with a particular focus on influenza A viruses (IAV). These viruses have developed accurate regulation mechanisms to reassign the host spliceosome to alter host cellular expression and enable an optimal expression of specific spliced viral products throughout infection. Moreover, IAV segments undergoing splicing display high levels of similarity with human consensus splice sites and their viral transcripts show noteworthy secondary structures. Sequence alignments and consensus analyses, along with recently published studies, suggest both conservation and evolution of viral splice site sequences and structure for improved adaptation to the host. Altogether, these results emphasize the ability of IAV to be well adapted to the host’s splicing machinery, and further investigations may contribute to a better understanding of splicing regulation with regard to viral replication, host range, and pathogenesis.
Mechanisms of Linezolid Resistance among Coagulase-Negative Staphylococci Determined by Whole-Genome Sequencing
Authors: Tewhey Ryan , Gu Bing , Kelesidis Theodoros , Charlton Carmen , Bobenchik April , Hindler Janet , Schork Nicholas J. , Humphries Romney M. 
Published: May 2014

ABSTRACT

Linezolid resistance is uncommon among staphylococci, but approximately 2% of clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit resistance to linezolid (MIC, ≥8 µg/ml). We performed whole-genome sequencing (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28 linezolid-resistant CoNS (21
Staphylococcus epidermidis
isolates and 7
Staphylococcus haemolyticus
isolates) obtained from blood cultures at a large teaching health system in California between 2007 and 2012. The following well-characterized mutations associated with linezolid resistance were identified in the 23S rRNA: G2576U, G2447U, and U2504A, along with the mutation C2534U. Mutations in the L3 and L4 riboproteins, at sites previously associated with linezolid resistance, were also identified in 20 isolates. The majority of isolates harbored more than one mutation in the 23S rRNA and L3 and L4 genes. In addition, the
cfr
methylase gene was found in almost half (48%) of
S. epidermidis
isolates.
cfr
had been only rarely identified in staphylococci in the United States prior to this study. Isolates of the same sequence type were identified with unique mutations associated with linezolid resistance, suggesting independent acquisition of linezolid resistance in each isolate.

IMPORTANCE
Linezolid is one of a limited number of antimicrobials available to treat drug-resistant Gram-positive bacteria, but resistance has begun to emerge. We evaluated the genomes of 28 linezolid-resistant staphylococci isolated from patients. Multiple mutations in the rRNA and associated proteins previously associated with linezolid resistance were found in the isolates investigated, underscoring the multifocal nature of resistance to linezolid in
Staphylococcus
. Importantly, almost half the
S. epidermidis
isolates studied harbored a plasmid-borne
cfr
RNA methylase gene, suggesting that the incidence of
cfr
may be higher in the United States than previously documented. This finding has important implications for infection control practices in the United States. Further,
cfr
is commonly detected in bacteria isolated from livestock, where the use of phenicols, lincosamides, and pleuromutilins in veterinary medicine may provide selective pressure and lead to maintenance of this gene in animal bacteria.
Pneumocystis jirovecii Can Be Productively Cultured in Differentiated CuFi-8 Airway Cells
Authors: Schildgen Verena , Mai Stephanie , Khalfaoui Soumaya , Lüsebrink Jessica , Pieper Monika , Tillmann Ramona L. , Brockmann Michael , Schildgen Oliver 
Published: May 2014

ABSTRACT

Although
Pneumocystis jirovecii
is a well-known and serious pathogen, all previous attempts to isolate, cultivate, and propagate this fungus have failed. This serious challenge in microbiology was addressed in the present study. We examined whether
P. jirovecii
could be cultured in a permanent three-dimensional air-liquid interface culture system formed by CuFi-8 cells, a differentiated pseudostratified airway epithelial cell line. Cultured pseudostratified cells were inoculated with bronchoalveolar fluid that had been confirmed to be positive for
P. jirovecii
using PCR. Five days later, the cells and basal medium were harvested and tested for
P. jirovecii
using quantitative PCR (qPCR), commercially available immunofluorescence detection assays, and Grocott staining of formalin-fixed, paraffin-embedded thin sections of infected-cell cultures. We successfully productively cultivated and propagated
P. jirovecii
from these
P. jirovecii
-positive bronchoalveolar lavage fluid (BALF) samples. Furthermore, we provide evidence that
P. jirovecii
induced cytopathic effects on lung epithelial cells and was even invasive in cell culture. To the best of our knowledge, the cell culture system developed herein represents the first methodology to enable molecular analyses of this pathogen’s life cycle and further
in vitro
studies of
P. jirovecii
, such as assessments of drug sensitivity and resistance as well as investigations of the pathogen’s stability against environmental factors and disinfectants.

IMPORTANCE
This is the first report of the successful productive cultivation and propagation of
Pneumocystis jirovecii
, a human-pathogenic fungus of major clinical significance. These findings are groundbreaking because they will influence the field of diagnostic microbiology, facilitate the testing of antibiotics against
P. jirovecii
, and enable stability studies of this pathogen when exposed to the environmental factors and chemicals that hospitals are required to use for disinfection. Because productively culturing
P. jirovecii
has been attempted unsuccessfully for several decades, this study represents a breakthrough in this field.
Responsiveness of motion sensors to detect change in sedentary and physical activity behaviour
Authors: Swartz Ann M , Rote Aubrianne E , Cho Young Ik , Welch Whitney A , Strath Scott J 
Published: May 2014

BackgroundThe purpose of this study was to determine the responsiveness of two motion sensors to detect change in sedentary behaviour (SB) and physical activity (PA) during an occupational intervention to reduce sitting time.MethodsSB and PA were assessed using a hip-worn Actigraph GTX3 (AG) and a thigh-worn activPAL (AP) during three consecutive workdays throughout baseline and intervention periods. Mean scores at baseline and intervention were estimated by hierarchical linear models (HLM) with robust SEs, adjusting for random variance of average scores between participants. Change scores (mean baseline minus mean intervention) were calculated for each device. Response to change was assessed for each device using the standardised response mean.Results67 adults (45±11 years; 29.3±7.7 kg/m2) wore the acceleration-based motion sensors for 8.3 (SD=1.2) and 8.3 (SD=1.1) h during the baseline and intervention periods, respectively. HLM showed that AP sitting/lying time (−16.5 min, −5%), AP stepping (+7.5 min, 19%), AP steps/day (+838 steps/day, +22%), AP sit-to-stand transitions (+3, +10%), AG SB (−14.6 min, −4%), AG lifestyle moderate-intensity PA (LMPA, +4 min, +15%) and AG MPA (+3 min, 23%) changed significantly between the baseline and the intervention period. Standardised response means for AP sitting/lying time, stepping, steps/day, sit-to-stand transitions and AG SB, LMPA and MPA were above 0.3, indicating a small but similar responsiveness to change.ConclusionsResponsiveness to change in SB and PA was similar and comparable for the AP and AG, indicating agreement across both measurement devices.
The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer
Authors: Treasure Tom , Monson Kathryn , Fiorentino Francesca , Russell Christopher 
Published: May 2014

ObjectiveIn patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit?DesignA randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative.Setting58 hospitals in the UK.ParticipantsFrom 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms.Interventions‘Second-look’ surgery with intention to remove any recurrence discovered.Primary outcome measureSurvival.ResultsBy February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival.ConclusionsThe trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years.Trial registration numberISRCTN76694943.
Impact of anaemia on clinical outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry
Authors: Puurunen Marja , Kiviniemi Tuomas , Nammas Wail , Schlitt Axel , Rubboli Andrea , Nyman Kai , Karjalainen Pasi , Kirchhof Paulus , Lip Gregory Y H , Airaksinen Juhani K E 
Published: May 2014

ObjectivesAnaemia has an adverse impact on the outcome in the general patient population undergoing percutaneous coronary intervention (PCI). The aim of this study was to analyse the impact of anaemia on the 12-month clinical outcome of patients with atrial fibrillation (AF) undergoing PCI and therefore requiring intense antithrombotic treatment. We hypothesised that anaemia might be associated with a worse outcome and more bleeding in these anticoagulated patients.SettingData were collected from 17 secondary care centres in Europe.ParticipantsConsecutive patients with AF undergoing PCI were enrolled in the prospective, multicenter AFCAS (Atrial Fibrillation undergoing Coronary Artery Stenting) registry. Altogether, 929 patients participated in the study. Preprocedural haemoglobin concentration was available for 861 (92.7%; 30% women). The only exclusion criteria were inability or unwillingness to give informed consent. Anaemia was defined as a haemoglobin concentration of <12 g/dL for women and <13 g/dL for men.Outcome measuresThe primary endpoint was occurrence of major adverse cardiac and cerebrovascular events (MACCE) or bleeding events.Results258/861 (30%) patients had anaemia. Anaemic patients were older, more often had diabetes, higher CHA2DS2-VASc scores, prior history of heart failure, chronic renal impairment and acute coronary syndrome. Anaemic patients had more MACCE than non-anaemic (29.1% vs 19.4%, respectively, p=0.002), and minor bleeding events (7.0% vs 3.3%, respectively, p=0.028), with a trend towards more total bleeding events (25.2% vs 21.7%, respectively, p=0.059). No difference was observed in antithrombotic regimens at discharge. In multivariate analysis, anaemia was an independent predictor of all-cause mortality at 12-month follow-up (hazard ratio 1.62, 95% CI 1.05 to 2.51, p=0.029).ConclusionsAnaemia was a frequent finding in patients with AF referred for PCI. Anaemic patients had a higher all-cause mortality, more thrombotic events and minor bleeding events. Anaemia seems to be an identification of patients at risk for cardiovascular events and death.Trial registrationClinicalTrials.gov numberNCT00596570.
Geochemical record of fluid flow and dolomitization of carbonate platforms: ascending freshwater–mesohaline mixing, Miocene of Spain
Authors: Li Zhaoqi , Goldstein Robert H. , Franseen Evan K. 
Published: May 2014

Abstract

This paper constrains fluid flow and chemistry in Miocene dolomites of Spain, where dolomitization has been ascribed to ascending freshwater–mesohaline mixing. End-Miocene dolomite formed as replacement and cement with the same widespread cathodoluminescence. Fluid inclusion final melting temperatures of ice (
T
m ice
: −0.2 to −2.3 °C) indicate mixing of freshwater and evaporated seawater. δ
18
O and δ
13
C data mostly show positive covariation, and only some have variable δ
13
C and invariant δ
18
O, arguing that mixing was more important than sulphate reduction. Data range from +0.9 to +6.0‰ for δ
18
O and from −4.5 to +3.0‰ for δ
13
C (VPDB (Vienna Pee Dee Belemnite)). Lower stratigraphic units are more depleted isotopically than upper units, suggesting upwards flow of freshwater.
87
Sr/
86
Sr values (0.70866–0.70904) range from less than to greater than late Miocene seawater. δ
18
O, δ
13
C and Sr analyses show that freshwater interacted with basement, confirming injection of freshwater from below. Upwards flow of freshwater, driven by low density and hydraulic head, created fluid mixing and CO
2
degassing. Comparison of La Molata dolomite to other dolomites of the western Mediterranean suggests that ascending freshwater–mesohaline mixing may be widespread, and that local composition of basement is not the primary driver of dolomitization. The model is broadly applicable to carbonates adjacent to highs, where freshwater discharged into slightly evaporated seawater.
VDR Activity Is Differentially Affected by Hic-5 in Prostate Cancer and Stromal Cells
Authors: Solomon Joshua D. , Heitzer Marjet D. , Liu Teresa T. , Beumer Jan H. , Parise Robert A. , Normolle Daniel P. , Leach Damien A. , Buchanan Grant , DeFranco Donald B. 
Published: May 2014

Abstract
Patients with prostate cancer treated with androgen deprivation therapy (ADT) eventually develop castrate-resistant prostate cancer (CRPC). 1,25-Dihydroxyvitamin D3 (1,25D3/calcitriol) is a potential adjuvant therapy that confers antiproliferative and pro-differentiation effects in vitro, but has had mixed results in clinical trials. The impact of the tumor microenvironment on 1,25D3 therapy in patients with CRPC has not been assessed. Transforming growth factor β (TGFβ), which is associated with the development of tumorigenic “reactive stroma” in prostate cancer, induced vitamin D3 receptor (VDR) expression in the human WPMY-1 prostate stromal cell line. Similarly, TGFβ enhanced 1,25D3-induced upregulation of CYP24A1, which metabolizes 1,25D3 and thereby limits VDR activity. Ablation of Hic-5, a TGFβ-inducible nuclear receptor coregulator, inhibited basal VDR expression, 1,25D3-induced CYP24A1 expression and metabolism of 1,25D3 and TGFβ-enhanced CYP24A1 expression. A Hic-5–responsive sequence was identified upstream (392–451 bp) of the CYP24A1 transcription start site that is occupied by VDR only in the presence of Hic-5. Ectopic expression of Hic-5 sensitized LNCaP prostate tumor cells to growth-inhibitory effects of 1,25D3 independent of CYP24A1. The sensitivity of Hic-5–expressing LNCaP cells to 1,25D3-induced growth inhibition was accentuated in coculture with Hic-5–ablated WPMY-1 cells. Therefore, these findings indicate that the search for mechanisms to sensitize prostate cancer cells to the antiproliferative effects of VDR ligands needs to account for the impact of VDR activity in the tumor microenvironment.
Implications: Hic-5 acts as a coregulator with distinct effects on VDR transactivation, in prostate cancer and stromal cells, and may exert diverse effects on adjuvant therapy designed to exploit VDR activity in prostate cancer. Mol Cancer Res; 12(8); 1166–80. ©2014 AACR.
Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure
Authors: Gupte Anisha A. , Hamilton Dale J. , Cordero-Reyes Andrea M. , Youker Keith A. , Yin Zheng , Estep Jerry D. , Stevens Robert D. , Wenner Brett , Ilkayeva Olga , Loebe Matthias , Peterson Leif E. , Lyon Christopher J. , Wong Stephen T.C. , Newgard Christopher B. , Torre-Amione Guillermo , Taegtmeyer Heinrich , Hsueh Willa A. 
Published: May 2014

Background—
Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood.

Methods and Results—

We compared metabolomic, gene transcript, and protein data from 6 paired samples of failing human left ventricular tissue obtained during left ventricular assist device insertion (heart failure samples) and at heart transplant (post-left ventricular assist device samples). Nonfailing left ventricular wall samples procured from explanted hearts of patients with right heart failure served as novel comparison samples. Metabolomic analyses uncovered a distinct pattern in heart failure tissue: 2.6-fold increased pyruvate concentrations coupled with reduced Krebs cycle intermediates and short-chain acylcarnitines, suggesting a global reduction in substrate oxidation. These findings were associated with decreased transcript levels for enzymes that catalyze fatty acid oxidation and pyruvate metabolism and for key transcriptional regulators of mitochondrial metabolism and biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (
PGC1A
, 1.3-fold) and estrogen-related receptor α (
ERRA
, 1.2-fold) and γ (
ERRG
, 2.2-fold). Thus, parallel decreases in key transcription factors and their target metabolic enzyme genes can explain the decreases in associated metabolic intermediates. Mechanical support with left ventricular assist device improved all of these metabolic and transcriptional defects.

Conclusions—
These observations underscore an important pathophysiologic role for severely defective metabolism in heart failure, while the reversibility of these defects by left ventricular assist device suggests metabolic resilience of the human heart.
A Point Mutation in
Myh10
Causes Major Defects in Heart Development and Body Wall Closure
Authors: Ma Xuefei , Adelstein Robert S. 
Published: May 2014

Background—
The 3 isoforms of nonmuscle myosin (NM) II (NMII-A, NMII-B, and NMII-C) play various roles during mouse embryonic development. Previous work, using knockout and hypomorphic mice, showed that Myh10 encoding myosin heavy chain II-B is critical for cardiac and brain development. Ablating or decreasing NMII-B by 80% results in cardiac (ventricular septal defect, double outlet of the right ventricle) and brain defects but not midline fusion defects. Neither NMII-A nor II-C seems to play roles in early myocardial development.

Methods and Results—
We had previously generated point mutant knock-in mice and now report novel findings as a result of expressing motor-deficient NMII-B at wild-type levels. Homozygous mice die at embryonic day 14.5 in cardiac failure, exhibiting abnormalities not seen in NMII-B null and hypomorphic mice: a failure in midline fusion resulting in a cleft palate, ectopia cordis, and a large omphalocele. Fusion of the sternum and endocardial cushions is impaired in the mutant mice associated with a failure in apoptosis of the mesenchymal cells. Failure to disassemble myocyte cell–cell adhesions during cardiac outflow tract development contributes to impaired outflow tract myocardialization and displacement of the aorta to the right ventricle.

Conclusions—
Expression of motor-impaired NMII-B disrupts normal ventral body wall closure because of a dominant-negative effect. This is not because of the loss of NMII-B function but rather a gain-of-function resulting from prolonged cross-linking of NMII-B to actin filaments, thereby interfering with the dynamics of actomyosin cytoskeletal structure. Furthermore, impaired NMII-B motor activity inhibits outflow tract myocardialization, leading to mislocalization of the aorta.
Cross-Sectional Survey of Workload and Burnout Among Japanese Physicians Working in Stroke Care
Authors: Nishimura Kunihiro , Nakamura Fumiaki , Takegami Misa , Fukuhara Schunichi , Nakagawara Jyoji , Ogasawara Kuniaki , Ono Junichi , Shiokawa Yoshiaki , Miyachi Shigeru , Nagata Izumi , Toyoda Kazunori , Matsuda Shinya , Kataoka Hiroharu , Miyamoto Yoshihiro , Kitaoka Kazuyo , Kada Akiko , Iihara Koji 
Published: May 2014

Background—
Burnout is common among physicians and affects the quality of care. We aimed to determine the prevalence of burnout among Japanese physicians working in stroke care and evaluate personal and professional characteristics associated with burnout.

Methods and Results—
A cross-sectional design was used to develop and distribute a survey to 11 211 physicians. Physician burnout was assessed using the Maslach Burnout Inventory General Survey. The predictors of burnout and the relationships among them were identified by multivariable logistic regression analysis. A total of 2724 (25.3%) physicians returned the surveys. After excluding those who were not working in stroke care or did not complete the survey appropriately, 2564 surveys were analyzed. Analysis of the participants’ scores revealed that 41.1% were burned out. Multivariable analysis indicated that number of hours worked per week is positively associated with burnout. Hours slept per night, day-offs per week, years of experience, as well as income, are inversely associated with burnout. Short Form 36 mental health subscale was also inversely associated with burnout.

Conclusions—
The primary risk factors for burnout are heavy workload, short sleep duration, relatively little experience, and low mental quality of life. Prospective research is required to confirm these findings and develop programs for preventing burnout.