bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a Unique Outer Membrane Protein Required for Oxidative Stress Resistance and Virulence of Francisella tularensis
Authors: Alqahtani Maha , Ma Zhuo , Ketkar Harshada , Suresh Ragavan Varadharajan , Malik Meenakshi , Bakshi Chandra Shekhar 
Published: January 2018

ABSTRACT

Francisella tularensis
, the causative agent of tularemia, lacks typical bacterial virulence factors and toxins but still exhibits extreme virulence. The bacterial multidrug efflux systems consist of an inner membrane, a transmembrane membrane fusion protein, and an outer membrane (OM) component that form a contiguous channel for the secretion of a multitude of bacterial products.
Francisella
contains three orthologs of the OM proteins; two of these, termed TolC and FtlC, are important for tularemia pathogenesis. The third OM protein, SilC, is homologous to the silver cation efflux protein of other bacterial pathogens. The
silC
gene (
FTL_0686
) is located on an operon encoding an Emr-type multidrug efflux pump of
F. tularensis
. The role of SilC in tularemia pathogenesis is not known. In this study, we investigated the role of SilC in secretion and virulence of
F. tularensis
by generating a
silC
gene deletion (Δ
silC
) mutant and its transcomplemented strain. Our results demonstrate that the Δ
silC
mutant exhibits increased sensitivity to antibiotics, oxidants, silver, diminished intramacrophage growth, and attenuated virulence in mice compared to wild-type
F. tularensis
. However, the secretion of antioxidant enzymes of
F. tularensis
is not impaired in the Δ
silC
mutant. The virulence of the Δ
silC
mutant is restored in NADPH oxidase-deficient mice, indicating that SilC resists oxidative stress
in vivo
. Collectively, this study demonstrates that the OM component SilC serves a specialized role in virulence of
F. tularensis
by conferring resistance against oxidative stress and silver.

IMPORTANCE
Francisella tularensis
, the causative agent of a fatal human disease known as tularemia, is a category A select agent and a potential bioterror agent. The virulence mechanisms of
Francisella
are not completely understood. This study investigated the role of a unique outer membrane protein, SilC, of a multidrug efflux pump in the virulence of
F. tularensis
. This is the first report demonstrating that the OM component SilC plays an important role in efflux of silver and contributes to the virulence of
F. tularensis
primarily by providing resistance against oxidative stress. Characterization of these unique virulence mechanisms will provide an understanding of the pathogenesis of tularemia and identification of potential targets for the development of effective therapeutics and prophylactics for protection from this lethal disease.
Dehydration of Prions on Environmentally Relevant Surfaces Protects Them from Inactivation by Freezing and Thawing
Authors: Yuan Qi , Telling Glenn , Bartelt-Hunt Shannon L. , Bartz Jason C. 
Published: January 2018

ABSTRACT

Chronic wasting disease (CWD) is an emerging prion disease in North America. Recent identification of CWD in wild cervids from Norway raises the concern of the spread of CWD in Europe. CWD infectivity can enter the environment through live animal excreta and carcasses where it can bind to soil. Well-characterized hamster prion strains and CWD field isolates in unadsorbed or soil-adsorbed forms that were either hydrated or dehydrated were subjected to repeated rounds of freezing and thawing. We found that 500 cycles of repeated freezing and thawing of hydrated samples significantly decreased the abundance of PrP
Sc
and reduced protein misfolding cyclic amplification (PMCA) seeding activity that could be rescued by binding to soil. Importantly, dehydration prior to freezing and thawing treatment largely protected PrP
Sc
from degradation, and the samples maintained PMCA seeding activity. We hypothesize that redistribution of water molecules during the freezing and thawing process alters the stability of PrP
Sc
aggregates. Overall, these results have significant implications for the assessment of prion persistence in the environment.

IMPORTANCE
Prions excreted into the environment by infected animals, such as elk and deer infected with chronic wasting disease, persist for years and thus facilitate horizontal transmission of the disease. Understanding the fate of prions in the environment is essential to control prion disease transmission. The significance of our study is that it provides information on the possibility of prion degradation and inactivation under natural weathering processes. This information is significant for remediation of prion-contaminated environments and development of prion disease control strategies.
Physical activity at age 11 years and chronic disabling fatigue at ages 13 and 16 years in a UK birth cohort
Authors: Collin Simon M , Norris Tom , Deere Kevin C , Jago Russell , Ness Andy R , Crawley Esther 
Published: January 2018

ObjectiveTo investigate associations of physical activity at age 11 years with chronic disabling fatigue (CDF) at ages 13 and 16 years.DesignLongitudinal birth cohort.SettingSouth-West England.ParticipantsAdolescents enrolled in the Avon Longitudinal Study of Parents and Children.Outcomes and exposuresWe identified adolescents who had disabling fatigue of >6 months' duration without a known cause at ages 13 and 16 years. Total and moderate-to-vigorous physical activity and sedentary time at age 11 years were measured by accelerometry over a 7-day period.ResultsA total physical activity level 100 counts/min higher at age 11 years was associated with 25% lower odds of CDF at age 13 years (OR=0.75 (95% CI 0.59 to 0.95)), a 1% increase in the proportion of monitored time spent in moderate-to-vigorous activity was associated with 16% lower odds of CDF (OR=0.84 (95% CI 0.69 to 1.01)) and a 1-hour increase in sedentary time was associated with 35% higher odds of CDF (OR=1.35 (95% CI 1.02 to 1.79)). Disabling fatigue of only 3–5 months’ duration at age 13 years had weaker associations with physical activity, and CDF at age 16 years was not associated with physical activity at age 11 years.ConclusionsChildren who had chronic disabling fatigue at age 13 years had lower levels of total and moderate-to-vigorous physical activity and more sedentary time 2 years previously, but this association could be explained by reverse causation.
Time in therapeutic range and stability over time for warfarin users in clinical practice: a retrospective cohort study using linked routinely collected health data in Alberta, Canada
Authors: McAlister Finlay A , Wiebe Natasha , Hemmelgarn Brenda R 
Published: January 2018

ObjectivesWhether warfarin-treated patients with non-valvular atrial fibrillation (NVAF) who exhibit good control will experience deterioration in control over time is uncertain. We designed this study to examine the time in therapeutic range (TTR) in a population-based cohort of patients with NVAF recently initiated on warfarin.DesignRetrospective cohort study using routinely collected health data from 2008 to 2015.SettingThe Canadian province of Alberta.ParticipantsAll adults with NVAF who were taking warfarin for >1 month.Main outcome measuresFrequency of international normalised ratio (INR) monitoring and the Rosendaal TTR with time zero set at 31 days after the first warfarin dispensation.ResultsOf 57 669 patients with NVAF dispensed warfarin for >1 month, 17 099 (29.7%) had <3 INRs measured in months 1–6. Of the 40 570 who went for regular INR monitoring in months 1–6 (median number of INRs 11, IQR 7–16), 16 639 (41.0%) met the definition of good control (TTR>65%); good control continued to be exhibited by 8177 (57.1% of those who remained on warfarin) during months 7–12 and 6804 (56.8% of continuing warfarin users) in months 13–18. Good control in the first 6 months predicted good control over the subsequent year: adjusted OR (aOR) 4.0(95%CI 3.8 to 4.2), c index 0.685(95%CI 0.679 to 0.691) for months 7–12 and aOR 3.2(95%CI 3.1 to 3.3), c index 0.665(95%CI 0.659 to 0.671) for months 13–18.ConclusionsNearly one-third of warfarin-treated patients had insufficient INR monitoring—this could influence the initial choice of anticoagulant and identifies a target for future quality improvement efforts. Of those warfarin-treated patients who went for regular INR monitoring, 41% exhibited levels of control similar to that in randomised trials and this deteriorated by half over time. However, in patients who have already exhibited adherence with regular monitoring and good TTR, warfarin may still be a reliable anticoagulation option.
Study protocol for a randomised, controlled platform trial estimating the effect of autobiographical Memory Flexibility training (MemFlex) on relapse of recurrent major depressive disorder
Authors: Hitchcock Caitlin , Gormley Siobhan , O’Leary Cliodhna , Rodrigues Evangeline , Wright Isobel , Griffiths Kirsty , Gillard Julia , Watson Peter , Hammond Emily , Werner-Seidler Aliza , Dalgleish Tim 
Published: January 2018

IntroductionMajor depressive disorder (MDD) is a chronic condition. Although current treatment approaches are effective in reducing acute depressive symptoms, rates of relapse are high. Chronic and inflexible retrieval of autobiographical memories, and in particular a bias towards negative and overgeneral memories, is a reliable predictor of relapse. This randomised controlled single-blind trial will determine whether a therapist-guided self-help intervention to ameliorate autobiographical memory biases using Memory Flexibility training (MemFlex) will increase the experience of depression-free days, relative to a psychoeducation control condition, in the 12 months following intervention.Methods and analysisIndividuals (aged 18 and above) with a diagnosis of recurrent MDD will be recruited when remitted from a major depressive episode. Participants will be randomly allocated to complete 4 weeks of a workbook providing either MemFlex training, or psychoeducation on factors that increase risk of relapse. Assessment of diagnostic status, self-report depressive symptoms, depression-free days and cognitive risk factors for depression will be completed post-intervention, and at 6 and 12 months follow-up. The cognitive target of MemFlex will be change in memory flexibility on the Autobiographical Memory Test- Alternating Instructions. The primary clinical endpoints will be the number of depression-free days in the 12 months following workbook completion, and time to depressive relapse.Ethics and disseminationEthics approval has been granted by the NHS National Research Ethics Committee (East of England, 11/H0305/1). Results from this study will provide a point-estimate of the effect of MemFlex on depressive relapse, which will be used to inform a fully powered trial evaluating the potential of MemFlex as an effective, low-cost and low-intensity option for reducing relapse of MDD.Trial registrationnumberNCT02614326.
Patient engagement in hospital health service planning and improvement: a scoping review
Authors: Liang Laurel , Cako Albina , Urquhart Robin , Straus Sharon E , Wodchis Walter P , Baker G. Ross , Gagliardi Anna R 
Published: January 2018

ObjectivesPatient engagement (PE) improves patient, organisation and health system outcomes, but most research is based on primary care. The primary purpose of this study was to describe the characteristics of published empirical research that evaluated PE in hospital health service improvement.DesignScoping review.MethodsFive databases were searched from 2006 to September 2016. English language studies that evaluated patient or provider beliefs, participation in PE, influencing factors or impact were eligible. Screening and data extraction were done in triplicate. PE characteristics, influencing factors and impact were extracted and summarised.ResultsFrom a total of 3939 search results, 227 studies emerged as potentially relevant; of these, 217 were not eligible, and 10 studies were included in the review. None evaluated behavioural interventions to promote or support PE. While most studies examined involvement in standing committees or projects, patient input and influence on decisions were minimal. Lack of skill and negative beliefs among providers were PE barriers. PE facilitators included careful selection and joint training of patients and providers, formalising patient roles, informal interaction to build trust, involving patients early in projects, small team size, frequent meetings, active solicitation of patient input in meetings and debriefing after meetings. Asking patients to provide insight into problems rather than solutions and deploying provider champions may enhance patient influence on hospital services.ConclusionsGiven the important role of PE in improving hospital services and the paucity of research on this topic, future research should develop and evaluate behavioural interventions for PE directed at patients and providers informed by the PE barriers and facilitators identified here. Future studies should also assess the impact on various individual and organisational outcomes.
Fatty liver index, albuminuria and the association with chronic kidney disease: a population-based study in China
Authors: Sun Kan , Lin Diaozhu , Li Feng , Qi Yiqin , Feng Wanting , Yan Li , Chen Chaogang , Ren Meng , Liu Dan 
Published: January 2018

ObjectivesThe effects of lipid metabolism disorder on renal damage have drawn much attention. Using the fatty liver index (FLI) as a validated indicator of hepatic steatosis, this study aims to provide insight about the possible links between fatty liver and the development of chronic kidney disease (CKD).SettingHospital.ParticipantsWe performed a population-based study on 9436 subjects aged 40 years or older.Primary and secondary outcome measuresFLI is calculated using an algorithm based on body mass index, waist circumference, triglycerides and γ-glutamyltransferase. Increased urinary albumin excretion was defined according to the urinary albumin to creatinine ratio ranges ≥30 mg/g. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or presence of albuminuria.ResultsThere were 620 (6.6%) subjects categorised to have increased urinary albumin excretion and 753 (8.0%) subjects categorised to have CKD. Participants with higher FLI had increased age, blood pressure, low-density lipoprotein cholesterol, fasting plasma glucose, fasting insulin and decreased eGFR level. Prevalence of increased urinary albumin excretion and CKD tended to increase with the elevated FLI quartiles. In logistic regression analysis, compared with subjects in the lowest quartile of FLI, the adjusted ORs in the highest quartile were 2.30 (95% CI 1.36 to 3.90) for increased urinary albumin excretion and 1.93 (95% CI 1.18 to 3.15) for CKD.ConclusionHepatic steatosis evaluated by FLI is independently associated with increased urinary albumin excretion and prevalence of CKD in middle-aged and elderly Chinese.
Evaluating the role of prereduction hip traction in the management of infants and children with developmental dysplasia of the hip (DDH): protocol for a systematic review and planned meta-analysis
Authors: Walton Sarah , Schaeffer Emily , Mulpuri Kishore , Cundy Peter , Williams Nicole 
Published: January 2018

IntroductionDevelopmental dysplasia of the hip (DDH) affects 4–6 per 1000 live births in developed countries. Effective treatment to realign the hip is necessary to avoid long-term morbidities and maximise functional outcome. Treatment options depend on patient age but typically involve hip bracing and/or reduction under general anaesthetic. Some centres also employ prereduction hip traction. Historical papers suggest traction reduces risk of avascular necrosis (AVN) femoral head and reduces requirement for open reduction. However, several studies including a large retrospective cohort study, dispute this. We propose to perform the first systematic review and meta-analysis to clarify the value of prereduction hip traction in the management of DDH in children under the age of 3 years by identifying whether it impacts on the rate of successful closed reduction (CR) and risk of AVN.Methods and analysisWe will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify potentially relevant studies. Studies reporting on incidence of successful CR, AVN femoral head and complications associated with prereduction hip traction in children of less than 3 years with DDH will be eligible for inclusion. Only randomised controlled trials, prospective and retrospective case–control and comparative cohort studies will be included in quantitative review. There will be no study design restrictions for inclusion in qualitative review. Following study selection, full-text paper retrieval, data extraction and synthesis, studies will be assessed for risk of bias and heterogeneity. If the included studies are sufficiently homogeneous, then we will perform meta-analysis. A narrative synthesis of the systematic review’s results will also be presented.Ethics and disseminationFormal ethical approval is not required as primary patient data will not be collected. The systematic review’s results will be disseminated through a peer-reviewed publication.Trial registration numberCRD42017064254; Pre-results.
Differences in talking-to-the-room behaviour between novice and expert teams during simulated paediatric resuscitation: a quasi-experimental study
Authors: Burtscher Michael J , Jordi Ritz Eva-Maria , Kolbe Michaela 
Published: January 2018

BackgroundTeam coordination represents an important factor for clinical performance. Research in this area suggests that not only behaviour frequencies but also patterns of team coordination constitute a central aspect of teamwork. However, little is known about potential differences in coordination patterns between novice teams (ie, teams of inexperienced members) and expert teams (ie, teams of experienced members). The current study addresses this gap by investigating the use of talking-to-the-room—an important implicit coordination behaviour—in novice teams versus expert teams.AimTo illustrate differences in coordination behaviour between novice and expert teams. This will provide important knowledge for simulation-based training.MethodsThe study was conducted in the context of two resuscitation training courses (introductory course and refresher course) for staff members at a children’s hospital. Volunteers from both courses participated in the study. They were randomly assigned to 16 teams each consisting of one physician and two nurses. The study used a quasi-experimental design with two conditions (novice vs expert). Participants of the introductory course were assigned to the novice condition (eight teams), and participants of the refresher course were assigned to the expert condition (eight teams). All teams completed the same standardised paediatric resuscitation scenario. They were videotaped during the simulation, and team coordination behaviour was coded using Co-ACT.ResultsLag-sequential analysis of 1902 distinct coordination acts revealed that novice teams and expert teams differed significantly in their coordination behaviour. Expert teams were characterised by patterns in which implicit coordination behaviour (ie, talking to the room) was followed by further implicit coordination behaviour and not followed by explicit coordination behaviour (ie, instructions), whereas the reverse was found for novice teams.ConclusionThe current study highlights role of coordination patterns for understanding teamwork in healthcare and provides important insights for team training.
Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes
Authors: Williams David S , Mouradov Dmitri , Jorissen Robert N , Newman Marsali R , Amini Elham , Nickless David K , Teague Julie A , Fang Catherine G , Palmieri Michelle , Parsons Marie J , Sakthianandeswaren Anuratha , Li Shan , Ward Robyn L , Hawkins Nicholas J , Faragher Ian , Jones Ian T , Gibbs Peter , Sieber Oliver M 
Published: January 2018

ObjectiveTumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear.DesignA prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and BRAF/KRAS mutations. Consensus molecular subtype (CMS) status was determined for 142 cases. Associations with 5-year disease-free survival (DFS) were evaluated and validated in an independent cohort of 602 patients.ResultsTumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; Pmultivariate<0.001) and TIL-low/pMMR tumours (HR=2.67; 95% CI=1.47 to 4.84; Pmultivariate=0.001) showed poor DFS. Outcomes of patients with TIL-low/dMMR and TIL-low/pMMR tumours were similar. TIL-high/pMMR tumours showed intermediate survival rates. These findings were validated in an independent cohort. TIL/MMR status was a more significant predictor of prognosis than National Comprehensive Cancer Network high-risk features and was a superior predictor of prognosis compared with genomic (dMMR, pMMR/BRAFwt/KRASwt, pMMR/BRAFmut/KRASwt, pMMR/BRAFwt/KRASmut) and transcriptomic (CMS 1-4) subtypes.ConclusionTIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes.
Strongly Connected Spanning Subgraph for Almost Symmetric Networks
Authors: Abu-Affash A. Karim , Carmi Paz , Tzur Anat Parush 
Published: January 2018

In the strongly connected spanning subgraph ([Formula: see text]) problem, the goal is to find a minimum weight spanning subgraph of a strongly connected directed graph that maintains the strong connectivity. In this paper, we consider the [Formula: see text] problem for two families of geometric directed graphs; [Formula: see text]-spanners and symmetric disk graphs. Given a constant [Formula: see text], a directed graph [Formula: see text] is a [Formula: see text]-spanner of a set of points [Formula: see text] if, for every two points [Formula: see text] and [Formula: see text] in [Formula: see text], there exists a directed path from [Formula: see text] to [Formula: see text] in [Formula: see text] of length at most [Formula: see text], where [Formula: see text] is the Euclidean distance between [Formula: see text] and [Formula: see text]. Given a set [Formula: see text] of points in the plane such that each point [Formula: see text] has a radius [Formula: see text], the symmetric disk graph of [Formula: see text] is a directed graph [Formula: see text], such that [Formula: see text]. Thus, if there exists a directed edge [Formula: see text], then [Formula: see text] exists as well. We present [Formula: see text] and [Formula: see text] approximation algorithms for the [Formula: see text] problem for [Formula: see text]-spanners and for symmetric disk graphs, respectively. Actually, our approach achieves a [Formula: see text]-approximation algorithm for all directed graphs satisfying the property that, for every two nodes [Formula: see text] and [Formula: see text], the ratio between the shortest paths, from [Formula: see text] to [Formula: see text] and from [Formula: see text] to [Formula: see text] in the graph, is at most [Formula: see text].