bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Scleroderma Patient-centered Intervention Network (SPIN) Cohort: protocol for a cohort multiple randomised controlled trial (cmRCT) design to support trials of psychosocial and rehabilitation interventions in a rare disease context
Authors: Kwakkenbos Linda , Jewett Lisa R , Baron Murray , Bartlett Susan J , Furst Dan , Gottesman Karen , Khanna Dinesh , Malcarne Vanessa L , Mayes Maureen D , Mouthon Luc , Poiraudeau Serge , Sauve Maureen , Nielson Warren R , Poole Janet L , Assassi Shervin , Boutron Isabelle , Ells Carolyn , van den Ende Cornelia HM , Hudson Marie , Impens Ann , Körner Annett , Leite Catarina , Costa Maia Angela , Mendelson Cindy , Pope Janet , Steele Russell J , Suarez-Almazor Maria E , Ahmed Sara , Coronado-Montoya Stephanie , Delisle Vanessa C , Gholizadeh Shadi , Jang Yeona , Levis Brooke , Milette Katherine , Mills Sarah D , Razykov Ilya , Fox Rina S , Thombs Brett D 
Published: August 2013

IntroductionPsychosocial and rehabilitation interventions are increasingly used to attenuate disability and improve health-related quality of life (HRQL) in chronic diseases, but are typically not available for patients with rare diseases. Conducting rigorous, adequately powered trials of these interventions for patients with rare diseases is difficult. The Scleroderma Patient-centered Intervention Network (SPIN) is an international collaboration of patient organisations, clinicians and researchers. The aim of SPIN is to develop a research infrastructure to test accessible, low-cost self-guided online interventions to reduce disability and improve HRQL for people living with the rare disease systemic sclerosis (SSc or scleroderma). Once tested, effective interventions will be made accessible through patient organisations partnering with SPIN.Methods and analysisSPIN will employ the cohort multiple randomised controlled trial (cmRCT) design, in which patients consent to participate in a cohort for ongoing data collection. The aim is to recruit 1500–2000 patients from centres across the world within a period of 5 years (2013–2018). Eligible participants are persons ≥18 years of age with a diagnosis of SSc. In addition to baseline medical data, participants will complete patient-reported outcome measures every 3 months. Upon enrolment in the cohort, patients will consent to be contacted in the future to participate in intervention research and to allow their data to be used for comparison purposes for interventions tested with other cohort participants. Once interventions are developed, patients from the cohort will be randomly selected and offered interventions as part of pragmatic RCTs. Outcomes from patients offered interventions will be compared with outcomes from trial-eligible patients who are not offered the interventions.Ethics and disseminationThe use of the cmRCT design, the development of self-guided online interventions and partnerships with patient organisations will allow SPIN to develop, rigourously test and effectively disseminate psychosocial and rehabilitation interventions for people with SSc.
Caregivers’ confidence in performing child safety seat installations: what matters most?
Authors: Mirman Jessica H , Curry Allison E , Zonfrillo Mark R , Corregano Lauren M , Seifert Sara , Arbogast Kristy B 
Published: August 2013

BackgroundAlthough effective when used correctly, child restraint systems (CRS) are commonly misused. Caregivers must make accurate judgements about the quality of their CRS installations, but there is little research on the psychological, technological, or contextual factors that might influence these judgements.MethodsSeventy-five caregivers were observed installing a CRS into a vehicle and completed self-report surveys measuring risk appraisals, previous utilisation of CRS resources, task difficulty, and confidence that the CRS was installed correctly.ResultsApproximately 30% of caregivers installed the CRS inaccurately and insecurely, but reported that it was correctly installed. Predictors of confidence were ease of use (β=0.47) and exposure to CRS resources (β=−0.34). Installation errors and CRS security were unrelated to caregivers’ confidence.ConclusionsAn interdisciplinary approach is needed to understand factors influencing caregivers’ judgements about their installations, optimise channels to connect caregivers to CRS resources, and to design safety technologies in light of these findings.
Explaining the social patterning of lung function in adulthood at different ages: the roles of childhood precursors, health behaviours and environmental factors
Authors: Gray Linsay A , Leyland Alastair H , Benzeval Michaela , Watt Graham C M 
Published: August 2013

BackgroundLung function successfully predicts subsequent health. Although lung function is known to decline over age, little is known about changes in association with socioeconomic status (SES) throughout life, and whether explanatory factors for association vary with age or patterns for non smokers.MethodsAnalyses were based on data on 24 500 participants aged ≥18 years from the 1995, 1998 and 2003 Scottish Health Surveys who were invited to provide 1 s forced expiratory volume (FEV1) and forced vital capacity (FVC) lung measurements. Sex-stratified multiple linear regression assessed lung function–SES (occupational social class) associations and attenuation by covariates in three age groups (2003 data (n=7928)).ResultsThe FEV1–SES patterns were clear (p<0.001) and constant over time. Relative to the least disadvantaged, FEV1in the most disadvantaged was lower by 0.28 L in men and 0.20 L in women under 40 years compared with differences of 0.51 L in men and 0.25 L in women over 64 years (pinteraction<0.001 men, pinteraction=0.004 women). The greatest attenuation of these results was seen by height, parental social class and smoking, especially among the under 65s. Second-hand smoke exposure and urban/rural residence had some impact among older groups. Adjusting for physical activity and weight had little effect generally. Similar patterns were seen for FVC and among never smokers.ConclusionsWe found cross-sectional evidence that SES disparity in lung function increases with age, especially for men. Our findings indicate that early-life factors may predict inequity during younger adulthood, with environmental factors becoming more important at older ages.
Economic analysis of the health impacts of housing improvement studies: a systematic review
Authors: Fenwick Elisabeth , Macdonald Catriona , Thomson Hilary 
Published: August 2013

BackgroundEconomic evaluation of public policies has been advocated but rarely performed. Studies from a systematic review of the health impacts of housing improvement included data on costs and some economic analysis. Examination of these data provides an opportunity to explore the difficulties and the potential for economic evaluation of housing.MethodsData were extracted from all studies included in the systematic review of housing improvement which had reported costs and economic analysis (n=29/45). The reported data were assessed for their suitability to economic evaluation. Where an economic analysis was reported the analysis was described according to pre-set definitions of various types of economic analysis used in the field of health economics.Results25 studies reported cost data on the intervention and/or benefits to the recipients. Of these, 11 studies reported data which was considered amenable to economic evaluation. A further four studies reported conducting an economic evaluation. Three of these studies presented a hybrid ‘balance sheet’ approach and indicated a net economic benefit associated with the intervention. One cost-effectiveness evaluation was identified but the data were unclearly reported; the cost-effectiveness plane suggested that the intervention was more costly and less effective than the status quo.ConclusionsFuture studies planning an economic evaluation need to (i) make best use of available data and (ii) ensure that all relevant data are collected. To facilitate this, economic evaluations should be planned alongside the intervention with input from health economists from the outset of the study. When undertaken appropriately, economic evaluation provides the potential to make significant contributions to housing policy.
Silent embolism after stent-assisted coiling of cerebral aneurysms: diffusion-weighted MRI study of 75 cases
Authors: Hahnemann M L , Ringelstein A , Sandalcioglu I E , Goericke S , Moenninghoff C , Wanke I , Forsting M , Sure U , Schlamann M 
Published: August 2013

PurposeNew ischemic brain lesions are common findings after cerebral diagnostic angiography and endovascular therapy. Diffusion-weighted MRI (DWI) can be used for detection of these lesions. The aim of the present study was to investigate the incidence of DWI lesions after stent-assisted coiling and the evaluation of possible risk factors.MethodsThe study included a total of 75 consecutive patients treated with stent-assisted coiling. Post-procedural DWI of the brain was performed to detect ischemic lesions. Demographic data, aneurysm characteristics and angiographic parameters were correlated with properties of DWI lesions.ResultsIn post-procedural DWI, 48 of the 75 patients (64%) had 163 DWI lesions in a pattern consistent with embolic events. The number of patients with DWI lesions was significantly increased in older patients (≥55 years) and longer intervention times (≥120 min). The ischemic brain volume was significantly increased in older patients (≥55 years) as well as in patients who were implanted with a shorter stent (<20 mm).ConclusionsThromboembolic events are common after stent-assisted coiling with an incidence comparable to DWI studies after coiling alone. Despite several devices and low operator experience, stent-assisted coiling for intracranial aneurysms has a very low risk of permanent neurologic disability. Further studies are necessary to improve the safety of stent-assisted coiling for patients in conditions with increased risk potential (age, procedure time, stent length).
Wall shear stress association with rupture status in volume matched sidewall aneurysms
Authors: Lauric Alexandra , Hippelheuser James , Cohen Alex D , Kadasi Laith M , Malek Adel M 
Published: August 2013

ObjectiveFlow induced tangential wall shear stress (WSS) is thought to be involved in aneurysm formation, growth, and rupture. Low WSS was previously associated with rupture, but definitive quantitative analyses remain scant as larger aneurysms are associated with lower WSS regardless of rupture status, and ruptured aneurysms are larger than unruptured aneurysms. Here, the intra-dome WSS was evaluated on 18 internal carotid artery aneurysms, volume matched as ruptured/unruptured pairs in order to remove the confounding effect of size dependence.MethodsComputational fluid dynamic simulations were performed and WSS was evaluated at peak systole, end diastole, and as time averaged over the cardiac cycle. WSS logarithmic scaling was applied to refine value discrimination at extrema. Ruptured/unruptured lesions were statistically evaluated using pairwise t test analysis. The effect of size on WSS was evaluated in parametric models.ResultsIn parametric data, there was a statistically significant negative correlation between volume and WSS values. In patient data, mean WSS was not statistically significant but low range WSS values were significantly lower for ruptured aneurysms, regardless of WSS evaluation (time averaged, peak systole, end diastole). Statistically, logarithmic WSS performed better than WSS, with minimum logarithmic WSS at end diastole being the best rupture status discriminator (p=0.001, area under the curve=0.98). Higher range and maximal WSS were not significantly significant.ConclusionsAneurysm size is a confounding factor to WSS rupture discrimination, and volume matched analysis is necessary for unbiased evaluation. While these results lend support to the hypothesis that lower WSS induces wall changes which may be associated with rupture, it raises questions regarding the extent of this association, which requires further exploration.
Thick-skin-dominated orogens; from initial inversion to full accretion: an introduction
Authors: Nemčok M. , Mora A. , Cosgrove J. 
Published: August 2013

Abstract
Fifty per cent of orogens have a thick-skin character, and have evolved from passive margin and intra-cratonic rift systems. One group of thick-skin provinces can be found at both pro- and retro-wedges of orogens associated with advancing subduction zones, that is, orogenic wedges whose advance vectors oppose the mantle flow. A second group can be found at pro-wedges of orogens associated with retreating subduction zones, that is, orogens whose advance vectors have the same direction as mantle flow. A third group is formed in intra-plate settings where mechanical strengthening is produced by internal shortening. Thick-skin province development is controlled by driving factors such as individual plate movement rates, overall convergence rates, orogen movement sense with respect to mantle flow, and pro-wedge v. retro-wedge location. These driving factors are themselves constrained by numerous internal and external factors. This introductory chapter focusses primarily on least-deformed case areas in order to understand the role of different factors in controlling the evolution of thick-skin tectonic provinces from the initial inversion stage to full accretion stage.
Potential and limits of combining studies of coarse- and fine-grained sediments for the coastal event history of a Caribbean carbonate environment
Authors: Scheffers Anja M. , Engel Max , May S. Matthias , Scheffers Sander R. , Joannes-Boyau Renaud , Hänssler Elke , Kennedy Katharina , Kelletat Dieter , Brückner Helmut , Vött Andreas , Schellmann Gerhard , Schäbitz Frank , Radtke Ulrich , Sommer Brigitte , Willershäuser Timo , Felis Thomas 
Published: August 2013

Abstract
The coastal deposits of Bonaire, Leeward Antilles, are among the most studied archives for extreme-wave events (EWEs) in the Caribbean. Here we present more than 400 electron spin resonance (ESR) and radiocarbon data on coarse-clast deposits from Bonaire’s eastern and western coasts. The chronological data are compared to the occurrence and age of fine-grained extreme-wave deposits detected in lagoons and floodplains. Both approaches are aimed at the identification of EWEs, the differentiation between extraordinary storms and tsunamis, improving reconstructions of the coastal evolution, and establishing a geochronological framework for the events. Although the combination of different methods and archives contributes to a better understanding of the interplay of coastal and archive-related processes, insufficient separation, superimposition or burying of coarse-clast deposits and restricted dating accuracy limit the use of both fine-grained and coarse-clast geoarchives to unravel decadal- to centennial-scale events. At several locations, distinct landforms are attributed to different coastal flooding events interpreted to be of tsunamigenic origin. Coastal landforms on the western coast have significantly been influenced by (sub)-recent hurricanes, indicating that formation of the coarse-clast deposits on the eastern coast is likely to be related to past events of higher energy.

Supplementary material:

The entire dataset of ESR and
14
C dating results used in this paper is available at
http://www.geolsoc.org.uk/SUP18637
.
Cyclin D1-Dependent Induction of Luminal Inflammatory Breast Tumors by Activated Notch3
Authors: Ling Hua , Sylvestre Jean-René , Jolicoeur Paul 
Published: August 2013

Abstract
Accumulating evidence suggests that Notch3 (N3) is involved in breast cancer development, but its precise contributions are not well understood. Here, we report that pregnant mice expressing an activated intracellular form of N3 (N3IC) exhibit a cyclin D1-dependent expansion of premalignant CD24+ CD29low luminal progenitors with enhanced differentiation potential in vitro and in vivo. Parous mice developed luminal mammary tumors in a cyclin D1-dependent manner. Notably, mice expressing higher levels of N3IC exhibited tumors resembling inflammatory breast cancer that frequently metastasized. N3IC-induced tumors contained a large percentage of tumor-initiating cells, but these were reduced significantly in tumors derived from N3IC transgenic mice that were heterozygous for cyclin D1. After transplantation in the presence of normal mammary cells, N3IC-expressing tumor cells became less malignant, differentiating into CK6+ CK18+ CK5− alveolar-like structures akin to expanded luminal progenitors from which they were likely derived. Taken together, our results argue that activated N3 signaling primarily affects luminal progenitors among mammary cell subsets, with more pronounced levels of activation influencing tumor type, and provide a novel model of inflammatory breast cancer. Cancer Res; 73(19); 5963–73. ©2013 AACR.
Menin Directly Represses Gli1 Expression Independent of Canonical Hedgehog Signaling
Authors: Gurung Buddha , Feng Zijie , Hua Xianxin 
Published: August 2013

Abstract
Multiple endocrine neoplasia type 1 (MEN-1), is a familial tumor syndrome resulting from mutations in the tumor suppressor gene menin (MEN1). Menin plays an essential role in both repressing and activating gene expression. However, it is not well understood how menin represses expression of multiple genes. Upon MEN1 excision, the transcription factor Gli1 and its target genes, including Ptch1 and c-Myc, were shown to be elevated in the absence of an apparent Hedgehog) pathway-activating ligand or when Smoothened (SMO), a key component of the pathway, is inhibited. Menin binds to the GLI1 promoter and recruits PRMT5, a histone arginine methyltransferase associated with transcriptional repression. Both PRMT5 binding and histone H4 arginine 3 methylation (H4R3m2s) are decreased at the GLI1 promoter in MEN1-excised cells. Moreover, MEN1 ablation resulted in increased binding of transcriptionally active Gli1 at the GLI1 promoter in a manner not influenced by the canonical Hedgehog signaling pathway. Inhibition of Gli1 by the small-molecule inhibitor GANT-61 led to decreased expression of Gli1 and its target genes in MEN1-depeleted cells. Furthermore, GANT-61 potently suppressed proliferation of MEN1-excised cells as compared with control cells. These findings uncover a novel epigenetic link whereby menin directly represses Gli1 expression, independent of the canonical Hedgehog signaling pathway, via PRMT5 and its repressive H4R3m2s mark.
Implications: Inhibition of GLI1 suppresses neuroendocrine tumors harboring mutations in the MEN1 gene. Mol Cancer Res; 11(10); 1215–22. ©2013 AACR.
Cancer Gene Discovery: Exploiting Insertional Mutagenesis
Authors: Ranzani Marco , Annunziato Stefano , Adams David J. , Montini Eugenio 
Published: August 2013

Abstract
Insertional mutagenesis has been used as a functional forward genetics screen for the identification of novel genes involved in the pathogenesis of human cancers. Different insertional mutagens have been successfully used to reveal new cancer genes. For example, retroviruses are integrating viruses with the capacity to induce the deregulation of genes in the neighborhood of the insertion site. Retroviruses have been used for more than 30 years to identify cancer genes in the hematopoietic system and mammary gland. Similarly, another tool that has revolutionized cancer gene discovery is the cut-and-paste transposons. These DNA elements have been engineered to contain strong promoters and stop cassettes that may function to perturb gene expression upon integration proximal to genes. In addition, complex mouse models characterized by tissue-restricted activity of transposons have been developed to identify oncogenes and tumor suppressor genes that control the development of a wide range of solid tumor types, extending beyond those tissues accessible using retrovirus-based approaches. Most recently, lentiviral vectors have appeared on the scene for use in cancer gene screens. Lentiviral vectors are replication-defective integrating vectors that have the advantage of being able to infect nondividing cells, in a wide range of cell types and tissues. In this review, we describe the various insertional mutagens focusing on their advantages/limitations, and we discuss the new and promising tools that will improve the insertional mutagenesis screens of the future.
Visual Overview: http://mcr.aacrjournals.org/content/11/10/1141/F1.large.jpg.
Mol Cancer Res; 11(10); 1141–58. ©2013 AACR.
The Small Cell Lung Cancer-Specific Isoform of RE1-Silencing Transcription Factor (REST) Is Regulated By Neural-Specific Ser/Arg Repeat-Related Protein of 100 kDa (nSR100)
Authors: Shimojo Masahito , Shudo Yoshie , Ikeda Masatoshi , Kobashi Tomoyo , Ito Seiji 
Published: August 2013

Abstract
Small cell lung cancer (SCLC) is a highly malignant form of cancer, which originates from primitive neuroendocrine cells in the lung. SCLC cells express several autocrine neurotransmitters/neuropeptides and their respective receptors. Expression of these neuronal markers is frequently regulated by RE1-silencing transcription factor (REST). In SCLC cells, an SCLC-specific isoform of REST (sREST) is highly expressed, whereas REST expression is undetectable, suggesting that the expression of sREST correlates with the pathogenesis of SCLC. Expression of sREST, which is derived through alternative splicing of REST, is abnormally regulated in SCLC cells, but the mechanism is unknown. Most recently, nSR100 (SRRM4) was described as an activator of REST alternative splicing. We now show that nSR100 is highly expressed in SCLC cells correlating with high sREST and low REST expression. Adhesion to the extracellular matrix (ECM) is thought to enhance tumorigenicity and confer resistance to apoptosis. Interestingly, nSR100 expression is enhanced in cells grown with ECM. Overexpression of REST caused repression of sREST and nSR100, the latter containing RE1 element controlled by REST. Culturing the SCLC cell line NCI-N417 cells with ECM also upregulated RE1-containing gene, the voltage-gated calcium channel subunit. Inhibition of the PI3K/Akt/mTOR pathway by LY294002 induced nSR100 expression, whereas the specific MEK/ERK inhibitor U0126 inhibited nSR100 expression. Repressing nSR100 by siRNA effectively repressed sREST, and conversely increased REST in NCI-N417 cells. Taken together, this report clarifies the ECM-dependent signaling pathway that impacts nSR100 expression and its regulation of alternative splicing in SCLC.
Implications: The splicing factor nSR100 may be novel SCLC-specific biomarker, as well as a therapeutic target. Mol Cancer Res; 11(10); 1258–68. ©2013 AACR.