bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Expression Induced by Epstein-Barr Virus LMP1-CTAR1: Potential Role of bcl3
Authors: Edwards Rachel Hood , Marquitz Aron R. , Raab-Traub Nancy 
Published: April 2015

ABSTRACT
The Epstein-Barr virus protein latent membrane protein 1 (LMP1) has two NF-κB activating domains within its intracellular carboxy terminus (carboxy-terminal activating region 1 [CTAR1] and CTAR2). LMP1-CTAR1 is required for B-lymphocyte transformation, is capable of transforming rodent fibroblasts, and uniquely activates phosphoinositol (PI3) kinase, the noncanonical NF-κB pathway, and expression of the epidermal growth factor receptor (EGFR). In this study, the effects of LMP1-CTAR1 on cellular gene expression were determined by high-throughput sequencing. Additionally, the binding of bcl3 was determined using chromatin immunoprecipitation (ChIP) and sequencing. LMP1-CTAR1 induced few changes in transcription with more genes showing decreased expression. Ingenuity pathway analysis indicated significant enrichment for genes involved in cancer and cellular movement, survival, growth, and proliferation pathways. ChIP in combination with high-throughput sequencing (ChIP-Seq) identified bcl3 binding for more than 2,000 genes in LMP1-CTAR1-expressing cells with more than 90% of the peaks at genes detected within the probable promoter region. Only a small subset of the genes with significant changes in expression had corresponding peaks in the bcl3 ChIP. However, both NFKB2 and PI3 kinase were identified in the bcl3 ChIP. Additionally, many of the predicted upstream regulators for the changes in expression were identified in the bcl3 ChIP. Analysis of the proteins in the NF-κB pathway revealed many changes identified by the high-throughput RNA sequencing (RNA-Seq) and bcl3 ChIP that would likely activate noncanonical NF-κB signaling and possibly inhibit canonical NF-κB signaling. These findings suggest that the two LMP1 signaling domains modulate their combined activity and that the bcl3 transcription factor is likely responsible for some of the unique effects of CTAR1 on cellular expression.

IMPORTANCE
The Epstein-Barr virus protein latent membrane protein 1 (LMP1) has potent effects on cell growth. LMP1 has two regions, carboxy-terminal activating region 1 (CTAR1) and CTAR2, that distinctly activate NF-κB, a transcription factor complex involved in activation of important host genes. In this study, analysis of the effects on cellular gene expression revealed that CTAR1 significantly affected cellular expression in part through effects on a specific form of NF-κB. The data suggest that LMP1 can activate a distinct subset of host gene expression through its CTAR1 domain which in combination with other signaling effects induced by the CTAR2 domain likely affects cell movement, survival, and growth.
Prevalence, incidence and risk factors for overuse injuries of the wrist in young athletes: a systematic review
Authors: Kox Laura S , Kuijer P Paul F M , Kerkhoffs Gino M M J , Maas Mario , Frings-Dresen Monique H W 
Published: April 2015

BackgroundOveruse wrist injuries can cause long-term symptoms in young athletes performing wrist-loading sports. Information on the prevalence, incidence and associated risk factors is required.PurposeWe aimed to review the prevalence and incidence of overuse wrist injuries in young athletes and to identify associated risk factors. We focused on popular wrist-loading youth sports—gymnastics, tennis, field hockey, volleyball, judo and rowing.Study designSystematic review.MethodsWe conducted a literature search on athletes aged <18 years performing wrist-loading focus sports. Prevalence, incidence and/or risk factor ORs for overuse wrist injuries were extracted directly or calculated from reported data.ResultsThe search identified six studies on prevalence, five on incidence, and one on risk factors. Prevalence rates were 32–73% forwrist painand 10–28% foroveruse wrist injury. Incidence rates were 7–9% forwrist painand 0.02–26% foroveruse wrist injury.The three criteria associated with wrist pain were (with OR): age of 10–14 years (11.5), training intensity (1.2), and earlier onset of gymnastics training (1.97).ConclusionsPrevalence and incidence of overuse wrist injuries was high in multiple studies of gymnasts, and largely unknown in other wrist-loading focus sports. Three key risk factors for wrist pain in gymnasts were age between 10 and 14 years, earlier training commencement, and training intensity. Using ‘wrist pain’ in defining overuse, and further investigating risk factors can aid in identifying overuse wrist injuries in young athletes.
Fitness for purpose study of the Field Assessment Conditioning Tool (FACT): a research protocol
Authors: MacKinnon Ralph James , Kennedy Chris , Doherty Catherine , Shepherd Michael , Cole Joanne , Stenfors-Hayes Terese ,   on behalf of the INSPIRE Trauma Outreach Research Group (http://www.inspiresim.com)
Published: April 2015

IntroductionAs part of a programme of research aiming to improve the outcomes of traumatically injured children, a multisource healthcare advocacy tool has been developed to allow trauma team members and hospital governance administrators to reflect and to act on complex trauma team-hospital systems interactions. We have termed this tool a Field Assessment Conditioning Tool (FACT). The FACT draws on quantitative data including clinical care points in addition to self-reflective qualitative data. The FACT is designed to provide feedback on this assessment data both horizontally across fellow potential team members and vertically to the hospital/organisation governance structure, enabling process gap identification and allowing an agenda of improvements to be realised. The aim of the study described in this paper is to explore the perceived fitness for purpose of the FACT to provide an opportunity for healthcare advocacy by healthcare professionals caring for traumatically injured children.Methods and analysisThe FACT will be implemented and studied in three district hospitals, each around a major trauma centre in the UK, USA and New Zealand. Using a qualitative approach with standardised semi-structured interviews and thematic analysis we will explore the following question: Is the FACT fit for purpose in terms of providing a framework to evaluate, reflect and act on the individual hospital's own performance (trauma team—hospital interactions) in terms of readiness to receive traumatically injured children?Ethics and disseminationEthics opinion was sought for each research host organisation participating and deemed not required. The results will be disseminated to participating sites, networks and published in high-impact journals.
Validity of self-reported diabetes among middle-aged and older Chinese adults: the China Health and Retirement Longitudinal Study
Authors: Yuan Xiaojing , Liu Tingting , Wu Lang , Zou Zhi-Yong , Li Changwei 
Published: April 2015

BackgroundSelf-reported diabetes has been found to be valid to evaluate people's diabetes status in the population of several countries. However, no such study has been conducted to assess the validity of self-reported diabetes in the Chinese population, the largest population with the highest rate of diabetes. The aim of our study is to evaluate the validity of self-reported diabetes among the middle-aged and older Chinese population.MethodsData from 11 601 participants, aged ≥45, of the China Health and Retirement Longitudinal Study (CHARLS) during 2011–2012, were analysed. Prevalent self-reported diabetes was compared with reference definition defined by fasting glucose, glycated haemoglobin and medication use. Sensitivity, specificity, positive predicted value, negative predicted value and κ value were calculated overall, by 5-year age groups, by education levels and by living areas.ResultsThe sensitivity of prevalent self-reported diabetes was 41.5%, and the specificity was 98.6%. The sensitivity of self-reported diabetes increased with education levels, and was much higher among urban residents than rural residents (58.2% vs 35.0%). The specificity was above 98% among all age groups, in different education levels, and in rural and urban areas. Self-reported diabetes had substantial agreement with reference definition among participants with above vocational school education or those living in urban areas (κ=0.658 and 0.646, respectively).ConclusionsAlthough the sensitivity of self-reported diabetes was poor among middle-aged and older Chinese adults, the specificity and positive predictive values were fairly good. Furthermore, self-reported diabetes performed well among those with more than vocational school educations or those living in urban areas.
001 PP: ONLINE CLINICAL MANAGEMENT PATHWAYS FOR CHLAMYDIA TREATMENT: ENRICHING FORMATIVE EVALUATION OF A COMPLEX E-HEALTH INTERVENTION
Authors: Aicken CRH , Estcourt CS , Gibbs J , Sonnenberg P , Mercer CH , Tickle L , Sutcliffe LJ , Sadiq ST , Shahmanesh M 
Published: April 2015

BackgroundNovel online clinical management pathways for chlamydia (eSexualHealthClinic) are being developed, enabling people to receive treatment remotely from clinical settings, with minimal contact with healthcare-professionals. Development follows Medical Research Council complex interventions guidance, and is iteratively informed by qualitative research.In a mixed-methods pilot study, the eSexualHealthClinic is being explored for acceptability and preliminary evidence of effectiveness, among people who tested positive for chlamydia through conventional services. They receive test-results by text-message, and are offered online care. After completing an automated consultation, they can collect antibiotics from community pharmacies. If they prefer, or if medically appropriate, they are managed in clinic.ObjectiveTo describe how the pilot study's qualitative component will deepen our understanding of its quantitative findings, further informing intervention development.MethodsOngoing semi-structured follow-up telephone-interviews with people who used the eSexualHealthClinic, exploring views and experiences. Interviews are informed by the Theory of Planned Behaviour, also considering expectations and previous experiences of healthcare, emotional and contextual factors, themes from our previous qualitative research, and allowing emergent themes. Since prevention of transmission is paramount for infection control, reasons for delayed treatment are explored.Contribution of qualitative researchInteractions with the eSexualHealthClinic are time-logged, and participants are surveyed after completing care. These detailed quantitative data provide limited information on reasons for delays, (dis)satisfaction, and unmet needs. Qualitative research enables in-depth, contextualised exploration of these issues, including influences on care-seeking unanticipated by researchers, which cannot be examined quantitatively.Integration of qualitative and quantitative findings will enable participants' care-seeking behaviour to be more fully understood, informing care-pathway refinement, for maximum clinical and public health benefit.DiscussionOnline healthcare is expanding. During development of novel web-based care-pathways, navigated with minimal supervision, understanding care-seeking behaviour through qualitative research is vital. This understanding is enhanced by mixed-methods design, where qualitative and quantitative research are mutually-enriching.
004 OP: ENACTING PPI IN QUALITATIVE MENTAL HEALTH RESEARCH: PEER RESEARCHER INVOLVEMENT IN DATA ANALYSIS IN THE ‘CORE’ STUDY
Authors: Morant N , Lloyd-Evans B ,   CORE project team led by S. Johnson
Published: April 2015

Patient and public involvement (PPI) is now an expected component of UK publicly-funded health research. Compatibilities with PPI aims and values mean that qualitative research is often a vehicle for enacting PPI. This presentation focuses on the involvement of “peer researchers” (service users and carers) in qualitative data analysis, and offers critical reflections of the practicalities of this process in the context of mental health research and an academic-led project.“CORE” (Crisis resolution team Optimisation and RElapse prevention) is a large NIHR-funded research project that aims to optimise the functioning of crisis resolution teams (CRTs). CRTs provide intensive home-based treatment for people experiencing an acute mental health crisis, as an alternative to hospital admission. They exist in all NHS Mental Health Trusts in England, but their performance and effectiveness is variable. The CORE project adopts a collaborative model of service user and carer involvement within an academic-led project. A large service user and carer working group contributes to a range of project activities including a qualitative study of stakeholders' views on current and best CRT practice, in which peer researchers have conducted interviews and been involved in data analysis.Faced with a large data set of more than 100 pieces of data, and little existing guidance on peer researcher involvement in qualitative data analysis, we attempted to develop an approach that enabled genuine involvement and maximised the methodological benefits of collaboration. Additional aims were to build research skills and capacity, and to obtain feedback from participants about their experiences of this. Peer researcher involvement began in the early stages of thematic analysis, in order to maximise contributions to the development of thematic codes at the point when these were most fluid and open. This was part of a staged process that meshed the work and perspectives of peer researchers with those of the academic researcher team. The presentation will describe this process and the rationale behind it, and discuss critical issues such as whether academic-led collaborations perpetuate or have the capacity to challenge existing power inequalities that are greater in mental health than other healthcare contexts.
006 OP: METHODOLOGICAL LIMITATIONS AND ADVANCES IN STUDYING CULTURE AND MENTAL HEALTH: SIGNIFICANCE OF QUALITATIVE APPROACHES
Authors: Patel R 
Published: April 2015

Social Epidemiology has had a long standing position in health research and covers distribution and determinants of health-related states in defined populations. The domain investigates patterns and causality, revealing health inequalities which aim to prevent and control health related issues. Understandably this field of research has advanced biological fields in exploring the relevance of social, cultural, environmental and economic factors that also play a fundamental role in ill health which is crucially ignored in biological standpoints. However, the dynamic of current societies is continuously changing and for example some areas in the UK are distinctively culturally diverse. By using my study of exploring reasons behind low reported rates of mental illness within the Gujarati community in Leicester I will argue that Social Epidemiology is limiting as method of studying in particular ethnic groups and mental health.This presentation will firstly, address the current problems with epidemiological studies in this area such as ecological fallacy, cultural stereotypes and validity of official statistics. Secondly, I will argue that qualitative research and sociological approaches are progressive for studying mental health. With reference to interview data I will outline a few current cultural complexities such as religion, language and changing traditions faced by both first and second generation migrants.Finally, I will conclude by proposing to progress mental health provision for ethnic groups there is much to be learnt about the intrinsic relationship culture has on mental health. Both qualitative methods and sociological approaches accommodate this required necessity. Having recognised the significance qualitative research has in health, we are faced with the problem of incorporating this in the universal province of the medical model of health which indeed is tricky and perhaps not one that is welcomed by all.
LLPi: Liverpool Lung Project Risk Prediction Model for Lung Cancer Incidence
Authors: Marcus Michael W. , Chen Ying , Raji Olaide Y. , Duffy Stephen W. , Field John K. 
Published: April 2015

Abstract
Identification of high-risk individuals will facilitate early diagnosis, reduce overall costs, and also improve the current poor survival from lung cancer. The Liverpool Lung Project prospective cohort of 8,760 participants ages 45 to 79 years, recruited between 1998 and 2008, was followed annually through the hospital episode statistics until January 31, 2013. Cox proportional hazards models were used to identify risk predictors of lung cancer incidence. C-statistic was used to assess the discriminatory accuracy of the models. Models were internally validated using the bootstrap method. During mean follow-up of 8.7 years, 237 participants developed lung cancer. Age [hazard ratio (HR), 1.04; 95% confidence interval (CI), 1.02–1.06], male gender (HR, 1.48; 95% CI, 1.10–1.98), smoking duration (HR, 1.04; 95% CI, 1.03–1.05), chronic obstructive pulmonary disease (HR, 2.43; 95% CI, 1.79–3.30), prior diagnosis of malignant tumor (HR, 2.84; 95% CI, 2.08–3.89), and early onset of family history of lung cancer (HR, 1.68; 95% CI, 1.04–2.72) were associated with the incidence of lung cancer. The LLPi risk model had a good calibration (goodness-of-fit χ2 7.58, P = 0.371). The apparent C-statistic was 0.852 (95% CI, 0.831–0.873) and the optimism-corrected bootstrap resampling C-statistic was 0.849 (95% CI, 0.829–0.873). The LLPi risk model may assist in identifying individuals at high risk of developing lung cancer in population-based screening programs. Cancer Prev Res; 8(6); 570–5. ©2015 AACR.
Catheter Ablation of Ventricular Tachycardia and Mortality in Patients With Nonischemic Dilated Cardiomyopathy
Authors: Dinov Borislav , Arya Arash , Schratter Alexandra , Schirripa Valentina , Fiedler Lukas , Sommer Philipp , Bollmann Andreas , Rolf Sascha , Piorkowski Christopher , Hindricks Gerhard 
Published: April 2015

Background—
Data on outcomes after catheter ablation of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy (NIDCM) are insufficient. We aimed to investigate the effects of successful catheter ablation of VT on cardiac mortality in patients with NIDCM.

Methods and Results—

One hundred two patients with NIDCM (86 men; mean age, 58.8±15.2 years; mean ejection fraction, 33.3±11.9%) underwent VT ablation. After catheter ablation, a programmed ventricular stimulation to test for success was performed. Complete VT noninducibility was achieved in 62 (61%) patients and partial success or failure in 32 (31%) patients. During 2 years of follow-up, VT recurrence was observed in 33 patients (53%) without inducible VTs and in 24 patients (75%) with inducible VT inducible (
P
=0.041). VT inducibility was associated with higher VT recurrence (adjusted hazard ratio, 1.84; 95% confidence interval, 1.08–3.13;
P
=0.025). The primary end point of all-cause mortality was reached in 9 patients (15%) with noninducible VTs versus 11 patients (34%) with inducible sustained VTs (
P
=0.026). VT inducibility was associated with all-cause mortality (adjusted hazard ratio, 2.73; 95% confidence interval, 1.003–7.43;
P
=0.049).

Conclusions—
In patients with NIDCM and recurrent sustained VTs, a complete ablation of all inducible VTs may be achieved in 60% of the cases. The complete noninducibility may be a preferable end point of ablation because it was associated with better long-term success. Importantly, if possible to achieve through ablation, a complete VT noninducibility was associated with reduction of the likelihood for all-cause mortality in patients with NIDCM.
Alcohol and Incident Heart Failure Among Middle-Aged and Elderly Men
Authors: Dorans Kirsten S. , Mostofsky Elizabeth , Levitan Emily B. , Håkansson Niclas , Wolk Alicja , Mittleman Murray A. 
Published: April 2015

Background—
Compared with no alcohol consumption, heavy alcohol intake is associated with a higher rate of heart failure (HF) whereas light-to-moderate intake may be associated with a lower rate. However, several prior studies did not exclude former drinkers, who may have changed alcohol consumption in response to diagnosis. This study aimed to investigate the association between alcohol intake and incident HF.

Methods and Results—

We conducted a prospective cohort study of 33 760 men aged 45 to 79 years with no HF, diabetes mellitus, or myocardial infarction at baseline participating in the Cohort of Swedish Men Study. We excluded former drinkers. At baseline, participants completed a food frequency questionnaire and reported other characteristics. HF was defined as hospitalization for or death from HF, ascertained by Swedish inpatient and cause-of-death records from January 1, 1998, through December 31, 2011. We constructed Cox proportional hazards models to estimate multivariable-adjusted incidence rate ratios. During follow-up, 2916 men were hospitalized for (n=2139) or died (n=777) of incident HF. There was a U-shaped relationship between total alcohol intake and incident HF (
P
=0.0004). There was a nadir at light-to-moderate alcohol intake: consuming 7 to <14 standard drinks per week was associated with a 19% lower multivariable-adjusted rate of HF compared with never drinking (incidence rate ratio, 0.81; 95% confidence interval, 0.69–0.96).

Conclusions—
In this cohort of Swedish men, there was a U-shaped relationship between alcohol consumption and HF incidence, with a nadir at light-to-moderate intake. Heavy intake did not seem protective.
Monitoring Vascular Permeability and Remodeling After Endothelial Injury in a Murine Model Using a Magnetic Resonance Albumin-Binding Contrast Agent
Authors: Lavin Begoña , Phinikaridou Alkystis , Lorrio Silvia , Zaragoza Carlos , Botnar René M. 
Published: April 2015

Background—

Despite the beneficial effects of vascular interventions, these procedures may damage the endothelium leading to increased vascular permeability and remodeling. Re-endothelialization of the vessel wall, with functionally and structurally intact cells, is controlled by endothelial nitric oxide synthase (NOS3) and is crucial for attenuating adverse effects after injury. We investigated the applicability of the albumin-binding MR contrast agent, gadofosveset, to noninvasively monitor focal changes in vascular permeability and remodeling, after injury, in NOS3-knockout (NOS3
−/−
) and wild-type (WT) mice in vivo.

Methods and Results—

WT and NOS3
−/−
mice were imaged at 7, 15, and 30 days after aortic denudation or sham-surgery. T
1
mapping (R
1
=1/T
1
, s
−1
) and delayed-enhanced MRI were used as measurements of vascular permeability (R
1
) and remodeling (vessel wall enhancement, mm
2
) after gadofosveset injection, respectively. Denudation resulted in higher vascular permeability and vessel wall enhancement 7 days after injury in both strains compared with sham-operated animals. However, impaired re-endothelialization and increased neovascularization in NOS3
−/−
mice resulted in significantly higher R
1
at 15 and 30 days post injury compared with WT mice that showed re-endothelialization and lack of neovascularization (R
1
[s
−1
]=15 days:

NOS3

−/−
4.02 [interquartile range, IQR, 3.77–4.41] versus

WT

2.39 [IQR, 2.35–2.92]; 30 days:

NOS3

−/−
4.23 [IQR, 3.94–4.68] versus

WT

2.64 [IQR, 2.33–2.80]). Similarly, vessel wall enhancement was higher in NOS3
−/−
but recovered in WT mice (area [mm
2
]=15 days:

NOS3

−/−
5.20 [IQR, 4.68–6.80] versus

WT

2.13 [IQR, 0.97–3.31]; 30 days:

NOS3

−/−
7.35 [IQR, 5.66–8.61] versus

WT

1.60 [IQR, 1.40–3.18]). Ex vivo histological studies corroborated the MRI findings.

Conclusions—
We demonstrate that increased vascular permeability and remodeling, after injury, can be assessed noninvasively using an albumin-binding MR contrast agent and may be used as surrogate markers for evaluating the healing response of the vessel wall after injury.