bluuebunny/crossref_metadata_2025_split huggingface dataset:
Players’ and coaches’ knowledge and awareness of the BokSmartSafe Sixinjury prevention programme: an ecological cross-sectional questionnaire study
Authors: Sewry Nicola , Verhagen Evert , Lambert Mike , van Mechelen Willem , Brown James 
Published: November 2017

ObjectivesRugby has a high injury incidence and therefore BokSmart introduced theSafe Sixinjury prevention programme in 2014 in an attempt to decrease this incidence. In 2015, BokSmart used a ‘targeted marketing approach’ to increase the awareness and knowledge of theSafe Six. Therefore, the aim of this study was to determine the change in the knowledge of coaches and players of theSafe Sixprogramme, compared with the launch year, following a ‘targeted marketing approach’.DesignEcological cross-sectional questionnaire studySettingThe 2014–2016 South African rugby union youth week tournaments.ParticipantsQuestionnaires were completed by 4502 players and coaches who attended any of the four youth week tournaments during 2014–2016.Outcome measuresLogistic regression (adjusted OR, 95% CI) was performed in comparison to year prior to targeted marketing, separately for coaches and players, for changes in awareness and knowledge.ResultsThe awareness of theSafe Sixincreased significantly for players in 2015 (1.74 times (95% CI 1.49 to 2.04)) and in 2016 (1.54 times (95% CI 1.29 to 1.84)). Similarly for coaches, there was a 3.55 times (95% CI 1.23 to 9.99) increase in 2015 and a 10.11 times (95% CI 2.43 to 42.08) increase in 2016 compared with 2014. Furthermore, a player was significantly more likely to be aware of theSafe Sixif his coach was aware of the programme (p<0.05).ConclusionsThe knowledge and awareness of the BokSmartSafe Sixof both players and coaches increased in 2015 and 2016 (compared with 2014) since the launch of the programme. Coaches, the Unions/the South African Rugby Union and social media were the largest contributors to knowledge in coaches and players. While the ‘targeted marketing approach’ was associated with an increase in awareness, future studies should determine if this translates into behavioural change.
Laser scanning in vivo confocal microscopy (IVCM) for evaluating human corneal sub-basal nerve plexus parameters: protocol for a systematic review
Authors: De Silva Manikkuwadura Eranda Harshan , Zhang Alexis Ceecee , Karahalios Amalia , Chinnery Holly Rose , Downie Laura Elizabeth 
Published: November 2017

IntroductionLaser scanning in vivo confocal microscopy (IVCM) enables non-invasive, high-resolution imaging of the cornea. In recent years, there has been a vast increase in researchers using laser scanning IVCM to image and quantify corneal nerve parameters. However, a range of methodological approaches have been adopted. The primary aim of this systematic review is to critically appraise the reported method(s) of primary research studies that have used laser scanning IVCM to quantify corneal sub-basal nerve plexus (SBNP) parameters in humans, and to examine corneal nerve parameters in healthy individuals.Methods and analysisA systematic review of primary studies that have used laser scanning IVCM to quantify SBNP parameters in humans will be conducted. Comprehensive electronic searches will be performed in Ovid MedLine, Embase and the Cochrane Library. Two reviewers will independently assess titles and abstracts, and exclude studies not meeting the inclusion criteria. For studies judged eligible or potentially eligible, full texts will be independently assessed by two reviewers to determine eligibility. A third reviewer will resolve any discrepancies in judgement. Risk of bias will be assessed using a custom tool, covering five methodological domains: participant selection, method of image capture, method of image analysis, data reporting and other sources of bias. A systematic narrative synthesis of findings will be provided. A multilevel random-effects meta-analysis will be performed for corneal nerve parameters derived from healthy participants. This review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Ethics and disseminationAs this review considers published data, ethical approval is not required. We foresee that this synthesis will serve as a reference for future studies, and can be used to inform best practice standards for using IVCM in clinical research. A manuscript reporting the results of the review will be published and may also be presented at scientific conferences.
Long-Term Conditions Questionnaire (LTCQ): initial validation survey among primary care patients and social care recipients in England
Authors: Potter Caroline M , Batchelder Laurie , A’Court Christine , Geneen Louise , Kelly Laura , Fox Diane , Baker Matthew , Bostock Jennifer , Coulter Angela , Fitzpatrick Ray , Forder Julien E , Gibbons Elizabeth , Jenkinson Crispin , Jones Karen , Peters Michele 
Published: November 2017

ObjectiveThe aim of this study was to validate a new generic patient-reported outcome measure, the Long-Term Conditions Questionnaire (LTCQ), among a diverse sample of health and social care users in England.DesignCross-sectional validation survey. Data were collected through postal surveys (February 2016–January 2017). The sample included a healthcare cohort of patients recruited through primary care practices, and a social care cohort recruited through local government bodies that provide social care services.Participants1211 participants (24% confirmed social care recipients) took part in the study. Healthcare participants were recruited on the basis of having one of 11 specified long-term conditions (LTCs), and social care participants were recruited on the basis of receiving social care support for at least one LTC. The sample exhibited high multimorbidity, with 93% reporting two or more LTCs and 43% reporting a mental health condition.Outcome measuresThe LTCQ’s construct validity was tested with reference to the EQ-5D (5-level version), the Self-Efficacy for Managing Chronic Disease scale, an Activities of Daily Living scale and the Bayliss burden of morbidity scale.ResultsLow levels of missing data for each item indicate acceptability of the LTCQ across the sample. The LTCQ exhibits high internal consistency (Cronbach’s α=0.95) across the scale’s 20 items and excellent test–retest reliability (intraclass correlation coefficient=0.94, 95% CI 0.93 to 0.95). Associations between the LTCQ and all reference measures were moderate to strong and in the expected directions, indicating convergent construct validity.ConclusionsThis study provides evidence for the reliability and validity of the LTCQ, which has potential for use in both health and social care settings. The LTCQ could meet a need for holistic outcome measurement that goes beyond symptoms and physical function, complementing existing measures to capture fully what it means to live well with LTCs.
Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test
Authors: Zorzi Manuel , Hassan Cesare , Capodaglio Giulia , Fedato Chiara , Montaguti Adriana , Turrin Anna , Rosano Alberto , Monetti Daniele , Stocco Carmen , Baracco Susanna , Russo Francesca , Repici Alessandro , Rugge Massimo 
Published: November 2017

BackgroundThe long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear.MethodsIn a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (1) the FIT positivity rate, the CRC and advanced adenoma detection rate and the FIT’s positive predictive value (PPV) for advanced neoplasia, at each round of screening and (2) the cumulative CRC and advanced adenoma detection rate after five rounds of FIT.ResultsOver 12 years (2002–2014), 123 347 individuals were administered the FIT up to six times, and 781 CRCs and 4713 advanced adenomas were diagnosed. The CRC and advanced adenoma detection rates declined substantially from the first to the third (rate ratio (RR) 0.25, 95% CI 0.20 to 0.32) and second (RR 0.51, 95% CI 0.47 to 0.56) rounds, respectively, and then remained stable. The PPV for advanced neoplasia dropped by 18% in the second round (RR 0.82, 95% CI 0.77 to 0.89), with no further reduction thereafter due to a concomitant decline in the FIT positivity rate (RR first to sixth rounds: 0.56, 95% CI 0.53 to 0.60).The cumulative CRC and advanced adenoma detection rates over five consecutive rounds were 8.5‰ (95% CI 7.8 to 9.2), and 58.9‰ (95% CI 56.9 to 61.0), respectively.ConclusionsRepeated FIT significantly reduces the burden of colorectal disease while facilitating an efficient use of colonoscopy resources. The cumulative detection rate after five rounds of FIT is similar to primary screening with colonoscopy, supporting the need to account for the cumulative sensitivity of repeated FITs when evaluating the test’s efficacy.
Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD
Authors: Dicker Alison J , Crichton Megan L , Cassidy Andrew J , Brady Gill , Hapca Adrian , Tavendale Roger , Einarsson Gisli G , Furrie Elizabeth , Elborn J Stuart , Schembri Stuart , Marshall Sara E , Palmer Colin N A , Chalmers James D 
Published: November 2017

BackgroundIn cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear. Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae, a key COPD pathogen. We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD.MethodsPatients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality. A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota, through 16S rRNA PCR and sequencing, or airway inflammation during stable and exacerbated COPD.FindingsPatients with MBL deficiency with COPD were significantly less likely to have severe exacerbations (incidence rate ratio (IRR) 0.66, 95% CI 0.48 to 0.90, p=0.009), or to have moderate or severe exacerbations (IRR 0.77, 95% CI 0.60 to 0.99, p=0.047). MBL deficiency did not affect rate of FEV1 decline or mortality. In the subcohort, patients with MBL deficiency had a more diverse lung microbiota (p=0.008), and were less likely to be colonised with Haemophilus spp. There were lower levels of airway inflammation in patients with MBL deficiency.InterpretationPatients with MBL deficient genotype with COPD have a lower risk of exacerbations and a more diverse lung microbiota. This is the first study to identify a genetic association with the lung microbiota in COPD.
Pancreatic Ductal Adenocarcinoma Subtyping Using the Biomarkers Hepatocyte Nuclear Factor-1A and Cytokeratin-81 Correlates with Outcome and Treatment Response
Authors: Muckenhuber Alexander , Berger Anne Katrin , Schlitter Anna Melissa , Steiger Katja , Konukiewitz Björn , Trumpp Andreas , Eils Roland , Werner Jens , Friess Helmut , Esposito Irene , Klöppel Günter , Ceyhan Güralp O. , Jesinghaus Moritz , Denkert Carsten , Bahra Marcus , Stenzinger Albrecht , Sprick Martin R. , Jäger Dirk , Springfeld Christoph , Weichert Wilko 
Published: November 2017

Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis and poor therapeutic response to current chemotherapy regimens in unselected patient populations. Recently, it has been shown that PDAC may be stratified into functionally and therapeutically relevant molecular subgroups and that some of these subtypes can be recapitulated by IHC for KRT81 [quasi-mesenchymal (QM)/squamous/basal-like] and HNF1A (non-QM, overlap with exocrine/ADEX subtype).
Experimental Design: We validated the different outcome of the HNF1A/KRT81 PDAC subtypes in two independent cohorts of surgically treated patients and examined the treatment response to chemotherapy in a third cohort of unresectable patients. The first two cohorts included 262 and 130 patients, respectively, and the third independent cohort comprised advanced-stage PDAC patients who were treated with either FOLFIRINOX (64 patients) or gemcitabine (61 patients).
Results: In both cohorts with resected PDAC, the HNF1A-positive subtype showed the best, the KRT81-positive subtype the worst, and the double-negative subtype an intermediate survival (P &lt; 0.013 and P &lt; 0.009, respectively). In the chemotherapy cohort, the survival difference between the double-negative and the HNF1A-positive subtype was lost, whereas the dismal prognosis of KRT81-positive PDAC patients was retained (P &lt; 0.021). Patients with a KRT81-positive subtype did not benefit from FOLFIRINOX therapy, whereas those with HNF1A-positive tumors responded better compared with gemcitabine-based treatment (P &lt; 0.038).
Conclusions: IHC stratification recapitulating molecular subtypes of PDAC using HNF1A and KRT81 is associated with significantly different outcomes and responses to chemotherapy. These results may pave the way toward future pretherapeutic biomarker-based stratification of PDAC patients. Clin Cancer Res; 24(2); 351–9. ©2017 AACR.
Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers
Authors: Feola Iolanda , Volkers Linda , Majumder Rupamanjari , Teplenin Alexander , Schalij Martin J. , Panfilov Alexander V. , de Vries Antoine A.F. , Pijnappels Daniël A. 
Published: November 2017

Background:
Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers.

Methods and Results:

Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca
2+
-translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting).

Conclusions:
Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation.
Efficacy and Safety of the Use of Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Concomitant Aspirin Therapy
Authors: Bennaghmouch Naoual , de Veer Anne J.W.M. , Bode Kerstin , Mahmoodi Bakhtawar K. , Dewilde Willem J.M. , Lip Gregory Y.H. , Brueckmann Martina , Kleine Eva , ten Berg Jurriën M. 
Published: November 2017

Background:
Current guidelines recommend non–vitamin K antagonist oral anticoagulants (NOACs) as the first-choice therapy in patients with nonvalvular atrial fibrillation because these drugs have several benefits over the vitamin K antagonists (VKAs). It is unknown whether these benefits remain when NOACs have to be combined with aspirin therapy. To assess the efficacy and safety of NOACs compared with VKAs in patients with atrial fibrillation and concomitant aspirin therapy, we conducted a systematic review and study–based meta-analysis of published randomized controlled trials.

Methods:
A systematic electronic literature search was done in MEDLINE, EMBASE, and Cochrane CENTRAL Register of Controlled Trials for studies including published data of patients ≥18 years of age with nonvalvular atrial fibrillation, randomized to either VKAs or NOACs, or receiving aspirin therapy at any time during the study that report all-cause stroke or systemic embolism, vascular death, myocardial infarction, major bleeding, or intracranial hemorrhage as an outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome were extracted from the individual studies and pooled with random-effects meta-analysis.

Results:
This study-based meta-analysis was restricted to the subgroups of patients on aspirin therapy (n=21 722) from 4 randomized controlled trials comparing VKAs and NOACs (n=71 681) in nonvalvular atrial fibrillation. In this meta-analysis including patients on mainly low-dose aspirin, NOACs were found to be more effective (outcome of stroke or systemic embolism: HR, 0.78; 95% CI, 0.67–0.91; vascular death: HR, 0.85; 95% CI, 0.76–0.93) and as safe as VKAs with respect to major bleeding (HR, 0.83; 95% CI, 0.69–1.01). NOACs were safer with respect to the reduction of intracranial hemorrhage (HR, 0.38; 95% CI, 0.26–0.56).

Conclusions:
This study-based meta-analysis shows that it may be both safer and more effective to use NOACs compared with VKAs to treat patients with nonvalvular atrial fibrillation and concomitant aspirin therapy.
Increased Cardiac Arrhythmogenesis Associated With Gap Junction Remodeling With Upregulation of RNA-Binding Protein FXR1
Authors: Chu Miensheng , Novak Stefanie Mares , Cover Cathleen , Wang Anne A. , Chinyere Ikeotunye Royal , Juneman Elizabeth B. , Zarnescu Daniela C. , Wong Pak Kin , Gregorio Carol C. 
Published: November 2017

Background:
Gap junction remodeling is well established as a consistent feature of human heart disease involving spontaneous ventricular arrhythmia. The mechanisms responsible for gap junction remodeling that include alterations in the distribution of, and protein expression within, gap junctions are still debated. Studies reveal that multiple transcriptional and posttranscriptional regulatory pathways are triggered in response to cardiac disease, such as those involving RNA-binding proteins. The expression levels of FXR1 (fragile X mental retardation autosomal homolog 1), an RNA-binding protein, are critical to maintain proper cardiac muscle function; however, the connection between FXR1 and disease is not clear.

Methods:
To identify the mechanisms regulating gap junction remodeling in cardiac disease, we sought to identify the functional properties of FXR1 expression, direct targets of FXR1 in human left ventricle dilated cardiomyopathy (DCM) biopsy samples and mouse models of DCM through BioID proximity assay and RNA immunoprecipitation, how FXR1 regulates its targets through RNA stability and luciferase assays, and functional consequences of altering the levels of this important RNA-binding protein through the analysis of cardiac-specific FXR1 knockout mice and mice injected with 3xMyc-FXR1 adeno-associated virus.

Results:
FXR1 expression is significantly increased in tissue samples from human and mouse models of DCM via Western blot analysis. FXR1 associates with intercalated discs, and integral gap junction proteins Cx43 (connexin 43), Cx45 (connexin 45), and ZO-1 (zonula occludens-1) were identified as novel mRNA targets of FXR1 by using a BioID proximity assay and RNA immunoprecipitation. Our findings show that FXR1 is a multifunctional protein involved in translational regulation and stabilization of its mRNA targets in heart muscle. In addition, introduction of 3xMyc-FXR1 via adeno-associated virus into mice leads to the redistribution of gap junctions and promotes ventricular tachycardia, showing the functional significance of FXR1 upregulation observed in DCM.

Conclusions:
In DCM, increased FXR1 expression appears to play an important role in disease progression by regulating gap junction remodeling. Together this study provides a novel function of FXR1, namely, that it directly regulates major gap junction components, contributing to proper cell-cell communication in the heart.
Cholesterol Control Among Uninsured Adults Did Not Improve From 2001‐2004 to 2009‐2012 as Disparities With Both Publicly and Privately Insured Adults Doubled
Authors: Egan Brent M. , Li Jiexiang , Sarasua Sara M. , Davis Robert A. , Fiscella Kevin A. , Tobin Jonathan N. , Jones Daniel W. , Sinopoli Angelo 
Published: November 2017

Background
Low‐density lipoprotein cholesterol (LDL‐C) control is higher among insured than uninsured adults, but data on time trends and contributing factors are incomplete and important for improving health equity.

Methods and Results

Awareness, treatment, and control of elevated LDL‐C were compared among insured versus uninsured and publicly versus privately insured adults, aged 21 to 64 years, in National Health and Nutrition Examination Surveys from 2001 to 2004, 2005 to 2008, and 2009 to 2012 using Adult Treatment Panel‐3 criteria. Compared with insured adults, uninsured adults were younger; were more often minority; reported lower incomes, less education, and fewer healthcare encounters; and had lower awareness and treatment of elevated LDL‐C (
P
<0.0001). LDL‐C control was higher among insured than uninsured adults in 2001 to 2004 (mean±SEM, 21.4±1.6% versus 10.5±2.6%;
P
<0.01), and the gap widened by 2009 to 2012 (35.1±1.9% versus 11.3±2.2%;
P
<0.0001). Despite more minorities (
P
<0.01), greater poverty, and less education (
P
<0.001), publicly insured adults had more healthcare visits/year than privately insured adults (
P
<0.001) and similar awareness, treatment, and control of LDL‐C from 2001 to 2012. In multivariable logistic regression, significant positive predictors of cholesterol awareness, treatment, and control included more frequent health care (strongest), increasing age, private healthcare insurance versus uninsured, and hypertension. Public insurance (versus uninsured) was a significant positive predictor of LDL‐C control, whereas income <200% versus ≥200% of federal poverty was a significant negative predictor.

Conclusions
LDL‐C control improved similarly over time in publicly and privately insured adults but was stagnant among the uninsured. Healthcare insurance largely addresses socioeconomic barriers to effective LDL‐C management, yet poverty retains an independent adverse effect.