bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sociodemographic Factors, Population Density, and Bicycling for Transportation in the United States
Authors: Nehme Eileen K. , Pérez Adriana , Ranjit Nalini , Amick Benjamin C. , Kohl Harold W. 
Published: April 2015

Background:Transportation bicycling is a behavior with demonstrated health benefits. Population-representative studies of transportation bicycling in United States are lacking. This study examined associations between sociodemographic factors, population density, and transportation bicycling and described transportation bicyclists by trip purposes, using a US-representative sample.Methods:This cross-sectional study used 2009 National Household Travel Survey datasets. Associations among study variables were assessed using weighted multivariable logistic regression.Results:On a typical day in 2009, 1% of Americans older than 5 years of age reported a transportation bicycling trip. Transportation cycling was inversely associated with age and directly with being male, with being white, and with population density (≥ 10,000 vs < 500 people/square mile: odd ratio, 2.78, 95% confidence interval, 1.54–5.05). Those whose highest level of education was a high school diploma or some college were least likely to bicycle for transportation. Twenty-one percent of transportation bicyclists reported trips to work, whereas 67% reported trips to social or other activities.Conclusions:Transportation bicycling in the United States is associated with sociodemographic characteristics and population density. Bicycles are used for a variety of trip purposes, which has implications for transportation bicycling research based on commuter data and for developing interventions to promote this behavior.
Antifungal Activities of SCY-078 (MK-3118) and Standard Antifungal Agents against Clinical Non-Aspergillus Mold Isolates
Authors: Lamoth Frédéric , Alexander Barbara D. 
Published: April 2015

ABSTRACT

The limited armamentarium of active and oral antifungal drugs against emerging non-
Aspergillus
molds is of particular concern. Current antifungal agents and the new orally available beta-1,3-
d
-glucan synthase inhibitor SCY-078 were tested
in vitro
against 135 clinical non-
Aspergillus
mold isolates. Akin to echinocandins, SCY-078 showed no or poor activity against
Mucoromycotina
and
Fusarium
spp. However, SCY-078 was highly active against
Paecilomyces variotii
and was the only compound displaying some activity against notoriously panresistant
Scedosporium prolificans
.
Comparison of the
In Vitro
Activities of Newer Triazoles and Established Antifungal Agents against Trichophyton rubrum
Authors: Deng Shuwen , Zhang Chao , Seyedmousavi Seyedmojtaba , Zhu Shuang , Tan Xin , Wen Yiyang , Huang Xin , Lei Wenzhi , Zhou Zhaojing , Fang Wenjie , Shen Shuaishuai , Deng Danqi , Pan Weihua , Liao Wanqing 
Published: April 2015

ABSTRACT

One hundred eleven clinical
Trichophyton rubrum
isolates were tested against 7 antifungal agents. The geometric mean MICs of all isolates were, in increasing order: terbinafine, 0.03 mg/liter; voriconazole, 0.05 mg/liter; posaconazole, 0.11 mg/liter; isavuconazole, 0.13 mg/liter; itraconazole, 0.26 mg/liter; griseofulvin, 1.65 mg/liter; and fluconazole, 2.12 mg/liter.
Epidemiology of Vancomycin-Resistant Enterococci in Canadian Hospitals (CANWARD Study, 2007 to 2013)
Authors: Simner P. J. , Adam H. , Baxter M. , McCracken M. , Golding G. , Karlowsky J. A. , Nichol K. , Lagacé-Wiens P. , Gilmour M. W. ,   Canadian Antimicrobial Resistance Alliance (CARA), Hoban D. J. , Zhanel G. G. 
Published: April 2015

ABSTRACT

Of 1,927
Enterococcus
species isolates collected across Canada from 2007 to 2013, 80 (4.2%) were identified as vancomycin-resistant enterococci (VRE). VRE infections during this time tripled in Canadian hospitals, from 1.8% to 6.0% (
P
= 0.03). All VRE were
Enterococcus faecium
, with 90% possessing
vanA
. The prevalence of
vanB
decreased from 37.5% in 2007 to 0% in 2013 (
P
< 0.05). The VRE were multidrug resistant, but 70.6%, 86.3%, and 100% were susceptible to doxycycline, linezolid, and daptomycin, respectively.
Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis
Authors: Gunawardana Manjula , Remedios-Chan Mariana , Miller Christine S. , Fanter Rob , Yang Flora , Marzinke Mark A. , Hendrix Craig W. , Beliveau Martin , Moss John A. , Smith Thomas J. , Baum Marc M. 
Published: April 2015

ABSTRACT

Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day
−1
in vitro
was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml
−1
; interquartile range [IQR], 0.60 to 1.50 ng ml
−1
) and tenofovir (TFV; median, 15.0 ng ml
−1
; IQR, 8.8 to 23.3 ng ml
−1
), the product of
in vivo
TAF hydrolysis. High concentrations (median, 512 fmol/10
6
cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations.
The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host
Authors: Bhullar Kirandeep , Zarepour Maryam , Yu Hongbing , Yang Hong , Croxen Matthew , Stahl Martin , Finlay B. Brett , Turvey Stuart E. , Vallance Bruce A. 
Published: April 2015

ABSTRACT

Bacterial pathogens produce a number of autotransporters that possess diverse functions. These include the family of serine protease autotransporters of
Enterobacteriaceae
(SPATEs) produced by enteric pathogens such as
Shigella flexneri
and enteroaggregative
Escherichia coli
. Of these SPATEs, one termed “protein involved in colonization,” or Pic, has been shown to possess mucinase activity
in vitro
, but to date, its role in
in vivo
enteric pathogenesis is unknown. Testing a
pic
null (Δ
picC
) mutant in
Citrobacter rodentium
, a natural mouse pathogen, found that the
C. rodentium
Δ
picC
strain was impaired in its ability to degrade mucin
in vitro
compared to the wild type. Upon infection of mice, the Δ
picC
mutant exhibited a hypervirulent phenotype with dramatically heavier pathogen burdens found in intestinal crypts. Δ
picC
mutant-infected mice suffered greater barrier disruption and more severe colitis and weight loss, necessitating their euthanization between 10 and 14 days postinfection. Notably, the virulence of the Δ
picC
mutant was normalized when the
picC
gene was restored; however, a PicC point mutant causing loss of mucinase activity did not replicate the Δ
picC
phenotype. Exploring other aspects of PicC function, the Δ
picC
mutant was found to aggregate to higher levels
in vivo
than wild-type
C. rodentium
. Moreover, unlike the wild type, the
C. rodentium
Δ
picC
mutant had a red, dry, and rough (RDAR) morphology
in vitro
and showed increased activation of the innate receptor Toll-like receptor 2 (TLR2). Interestingly, the
C. rodentium
Δ
picC
mutant caused a degree of pathology similar to that of wild-type
C. rodentium
when infecting TLR2-deficient mice, showing that despite its mucinase activity, PicC's major role
in vivo
may be to limit
C. rodentium
's stimulation of the host's innate immune system.
Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites
Authors: Stella Nicholas A. , Lahr Roni M. , Brothers Kimberly M. , Kalivoda Eric J. , Hunt Kristin M. , Kwak Daniel H. , Liu Xinyu , Shanks Robert M. Q. 
Published: April 2015

ABSTRACTSerratia marcescensgenerates secondary metabolites and secreted enzymes, and it causes hospital infections and community-acquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressedcrpmutant phenotypes. Evidence supports that the putative response regulatoreepRwas directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin- and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promotersin vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes.IMPORTANCEThis study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacteriumSerratia marcescensto produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allowS. marcescensto compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science.
Unraveling the Mechanism for the Viability Deficiency of Shewanella oneidensis oxyR Null Mutant
Authors: Shi Miaomiao , Wan Fen , Mao Yinting , Gao Haichun 
Published: April 2015

ABSTRACTOxidative stresses triggered by reactive oxygen species (ROS) that damage various cellular components are unavoidable for virtually all living organisms. In defense, microorganisms have evolved sophisticated mechanisms to sense, respond to, and battle against ROS.Shewanella oneidensis, an important research model for applied and environmental microbes, employs OxyR to mediate the response to H2O2by derepressing the production of the major H2O2scavenger KatB as a major means toward these goals. Surprisingly, despite enhanced H2O2degradation, theoxyRmutant carries a viability deficiency phenotype (plating defect), which can be suppressed by the addition of exogenous iron species. Experiments showed that the defect was not due to iron starvation. Rather, multiple lines of evidence suggested that H2O2generated abiotically in lysogeny broth (LB) is responsible for the defect by quickly killing mutant cells. We then showed that the iron species suppressed the plating defect by two distinct mechanisms, either as an H2O2scavenger without involving living cells or as an environmental cue to stimulate an OxyR-independent response to help cells cope with oxidative stress. Based on the suppression of the plating defect by overproduction of H2O2scavengersin vivo, we propose that cellular components that are vulnerable to H2O2and responsible for the defect may reside outside the cytoplasm.IMPORTANCEIn bacteria, OxyR is the major regulator controlling the cellular response to H2O2. The loss of OxyR results in reduced viability in many species, but the underlying mechanism is unknown. We showed inS. oneidensisthat this defect was due to H2O2generated abiotically in LB. We then showed that this defect could be corrected by the addition of Fe2+or catalase to the LB or increased intracellular production of catalase. Further analyses revealed that Fe2+was able not only to decompose H2O2directly but also to stimulate the activity of OxyR-independent H2O2-scavenging enzymes. Our data indicate that iron species play a previously underappreciated role in protecting cells from H2O2in environments.
The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP
Authors: Almblad Henrik , Harrison Joe J. , Rybtke Morten , Groizeleau Julie , Givskov Michael , Parsek Matthew R. , Tolker-Nielsen Tim 
Published: April 2015

ABSTRACTThe opportunistic human pathogenPseudomonas aeruginosaexpresses numerous acute virulence factors in the initial phase of infection, and during long-term colonization it undergoes adaptations that optimize survival in the human host. Adaptive changes that often occur during chronic infection give rise to rugose small colony variants (RSCVs), which are hyper-biofilm-forming mutants that commonly possess mutations that increase production of the biofilm-promoting secondary messenger cyclic di-GMP (c-di-GMP). We show that RSCVs display a decreased production of acute virulence factors as a direct result of elevated c-di-GMP content. Overproduction of c-di-GMP causes a decrease in the transcription of virulence factor genes that are regulated by the global virulence regulator Vfr. The low level of Vfr-dependent transcription is caused by a low level of its coactivator, cyclic AMP (cAMP), which is decreased in response to a high level of c-di-GMP. Mutations that cause reversion of the RSCV phenotype concomitantly reactivate Vfr-cAMP signaling. Attempts to uncover the mechanism underlying the observed c-di-GMP-mediated lowering of cAMP content provided evidence that it is not caused by inhibition of adenylate cyclase production or activity and that it is not caused by activation of cAMP phosphodiesterase activity. In addition to the studies of the RSCVs, we present evidence that the deeper layers of wild-typeP. aeruginosabiofilms have high c-di-GMP levels and low cAMP levels.IMPORTANCEOur work suggests that cross talk between c-di-GMP and cAMP signaling pathways results in downregulation of acute virulence factors inP. aeruginosabiofilm infections. Knowledge about this cross-regulation adds to our understanding of virulence traits and immune evasion byP. aeruginosain chronic infections and may provide new approaches to eradicate biofilm infections.
Diversity of Class 1 Integron Gene Cassette Rearrangements Selected under Antibiotic Pressure
Authors: Barraud Olivier , Ploy Marie-Cécile 
Published: April 2015

ABSTRACTIntegrons are bacterial genetic elements able to capture and express genes contained within mobile gene cassettes. Gene cassettes are expressed via a Pc promoter and can be excised from or integrated into the integron by integrase IntI. Although the mechanisms of gene cassette integration and excision are well known, the kinetics and modes of gene cassette shuffling leading to new gene cassette arrays remain puzzling. It has been proposed that under antibiotic selective pressure, IntI-mediated rearrangements can generate integron variants in which a weakly expressed gene cassette moves closer to Pc, thus leading to higher-level resistance. To test this hypothesis, we used an integron with four gene cassettes,intI1-aac(6′)-Ib-dfrA15-aadA1-catB9, and applied selective pressure with chloramphenicol, resistance to which is encoded bycatB9. Experiments were performed with three different Pc variants corresponding to three IntI1 variants. All three integrases, even when not overexpressed, were able to bringcatB9closer to Pc via excision of thedfrA15andaadA1gene cassettes, allowing their host bacteria to adapt to antibiotic pressure and to grow at high chloramphenicol concentrations. Integrase IntI1R32_H39, reported to have the highest recombination activity, was able, when overexpressed, to trigger multiple gene cassette rearrangements. Although we observed a wide variety of rearrangements withcatB9moving closer to Pc and leading to higher chloramphenicol resistance, “cut-and-paste” relocalization ofcatB9to the first position was not detected. Our results suggest that gene cassette rearrangements via excision are probably less cost-effective than excision and integration of a distal gene cassette closer to Pc.IMPORTANCEIntegrons are bacterial genetic elements able to capture and express gene cassettes. Gene cassettes are expressed via a Pc promoter; the closer they are to Pc, the more strongly they are expressed. Gene cassettes can be excised from or integrated into the integron by integrase IntI. The kinetics and modes of gene cassette shuffling, leading to new gene cassette arrays remain puzzling. We used an integron with 4 antibiotic resistance gene cassettes and applied selective pressure with the antibiotic for which resistance was encoded by cassette 4. All IntI variants were able to bring cassette 4 closer to Pc. Rearrangements occur via excision of the previous gene cassettes instead of cut-and-paste relocalization of the fourth gene cassette.
The effect of teamwork training on team performance and clinical outcome in elective orthopaedic surgery: a controlled interrupted time series study
Authors: Morgan Lauren , Hadi Mohammed , Pickering Sharon , Robertson Eleanor , Griffin Damian , Collins Gary , Rivero-Arias Oliver , Catchpole Ken , McCulloch Peter , New Steve 
Published: April 2015

ObjectivesTo evaluate the effectiveness of aviation-style teamwork training in improving operating theatre team performance and clinical outcomes.Setting3 operating theatres in a UK district general hospital, 1 acting as a control group and the other 2 as the intervention group.Participants72 operations (37 intervention, 35 control) were observed in full by 2 trained observers during two 3-month observation periods, before and after the intervention period.InterventionsA 1-day teamwork training course for all staff, followed by 6 weeks of weekly in-service coaching to embed learning.Primary and secondary outcome measuresWe measured team non-technical skills using Oxford NOTECHS II, (evaluating the whole team and the surgical, anaesthetic and nursing subteams, and evaluated technical performance using the Glitch count. We evaluated compliance with the WHO checklist by recording whether time-out (T/O) and sign-out (S/O) were attempted, and whether T/O was fully complied with. We recorded complications, re-admissions and duration of hospital stay using hospital administrative data. We compared the before–after change in the intervention and control groups using 2-way analysis of variance (ANOVA) and regression modelling.ResultsMean NOTECHS II score increased significantly from 71.6 to 75.4 in the active group but remained static in the control group (p=0.047). Among staff subgroups, the nursing score increased significantly (p=0.006), but the anaesthetic and surgical scores did not. The attempt rate for WHO T/O procedures increased significantly in both active and control groups, but full compliance with T/O improved only in the active group (p=0.003). Mean glitch rate was unchanged in the control group but increased significantly (7.2–10.2/h, p=0.002) in the active group.ConclusionsTeamwork training was associated with improved non-technical skills in theatre teams but also with a rise in operative glitches.
DEVELOPING A MODEL TO INVOLVE SERVICE USERS IN A MULTI-CENTRED TRIAL OF A COMPLEX INTERVENTION IN PRE-HOSPITAL EMERGENCY CARE
Authors: Koniotou M , Halter M , Evans B A , Porter A , Gaze S ,   on behalf of the Safer 2 Team
Published: April 2015

BackgroundResearch collaborations with patient and professional groups can ensure health research funders are aware of what matters to patients, carers and clinicians. Increasing service user involvement in research improves research quality, accountability and provision of patient-centred services. There is little evidence about involving service users in trials or pre-hospital emergency care research. Most research involving service users concerns a condition or treatment rather than service delivery or point of entry to the healthcare system.The SAFER 2 trial evaluates a complex intervention enabling paramedics to assess older people who fall and call 999 and, where appropriate, refer them to a community care pathway.ObjectiveTo describe a model for involving service users in a multi-centred trial in emergency care.MethodA Standard Operating Procedure (SOP) for including service users was developed by the clinical trials unit West Wales Organisation for Rigorous Trials in Health (WWORTH). This recommends involvement processes and supportive working practices, based on evidence and good practice.We adapted this SOP to develop a model to involve service users in our trial of a complex intervention in pre-hospital care.ResultsWe included service users at three different decision levels of involvement:Strategic level: Data Monitoring and Ethics Committee, Trial Steering Committee, Trial Management Group and Trial Development Group. These are the standard bodies that manage and oversee the trial.Local level: management committees. These take decisions about running the trial in each study site.Service user reference groups: these groups of patients and carers meet with the site researcher to discuss issues affecting patients likely to be recruited into the study.ConclusionThe principles and processes of the SOP provided a model that could be replicated across each trial site. We found it necessary to tailor and adapt.
Clinically Relevant Molecular Subtypes in Leiomyosarcoma
Authors: Guo Xiangqian , Jo Vickie Y. , Mills Anne M. , Zhu Shirley X. , Lee Cheng-Han , Espinosa Inigo , Nucci Marisa R. , Varma Sushama , Forgó Erna , Hastie Trevor , Anderson Sharon , Ganjoo Kristen , Beck Andrew H. , West Robert B. , Fletcher Christopher D. , van de Rijn Matt 
Published: April 2015

Abstract
Purpose: Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts.
Experimental Design: Ninety-nine cases of leiomyosarcoma were expression profiled with 3′end RNA-Sequencing (3SEQ). Consensus clustering was conducted to determine the optimal number of subtypes.
Results: We identified 3 leiomyosarcoma molecular subtypes and confirmed this finding by analyzing publically available data on 82 leiomyosarcoma from The Cancer Genome Atlas (TCGA). We identified two new formalin-fixed, paraffin-embedded tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I leiomyosarcoma and ARL4C for subtype II leiomyosarcoma. A leiomyosarcoma tissue microarray with known clinical outcome was used to show that subtype I leiomyosarcoma is associated with good outcome in extrauterine leiomyosarcoma while subtype II leiomyosarcoma is associated with poor prognosis in both uterine and extrauterine leiomyosarcoma. The leiomyosarcoma subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that leiomyosarcoma subtypes may respond differentially to these targeted therapies.
Conclusions: We confirm the existence of 3 molecular subtypes in leiomyosarcoma using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating leiomyosarcoma in a subtype-specific targeted approach. Clin Cancer Res; 21(15); 3501–11. ©2015 AACR.