bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual counselling for patients with cardiovascular disease: protocol for a pilot study of the CHARMS sexual counselling intervention
Authors: Murphy Patrick J , Mc Sharry Jenny , Casey Dympna , Doherty Sally , Gillespie Paddy , Jaarsma Tiny , Murphy Andrew W , Newell John , O'Donnell Martin , Steinke Elaine E , Toomey Elaine , Byrne Molly 
Published: June 2016

IntroductionSexual problems are common with cardiovascular disease, and can negatively impact quality of life. To address sexual problems, guidelines have identified the importance of sexual counselling during cardiac rehabilitation, yet this is rarely provided. The Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention aims to improve the provision of sexual counselling in cardiac rehabilitation in Ireland.Methods and analysisThis is a multicentre pilot study for the CHARMS intervention, a complex, multilevel intervention delivered within hospital-based cardiac rehabilitation programmes. The intervention includes (1) training in sexual counselling for staff, (2) a staff-led patient education and support intervention embedded within the cardiac rehabilitation programme, (3) a patient information booklet and (4) an awareness raising poster. The intervention will be delivered in two randomly selected cardiac rehabilitation centres. In each centre 30 patients will be recruited, and partners will also be invited to participate. Data will be collected from staff and patients/partners at T1 (study entry), T2 (3-month follow-up) and T3 (6-month follow-up). The primary outcome for patients/partners will be scores on the Sexual Self-Perception and Adjustment Questionnaire. Secondary outcomes for patients/partners will include relationship satisfaction; satisfaction with and barriers to sexual counselling in services; sexual activity, functioning and knowledge; physical and psychological well-being. Secondary outcomes for staff will include sexuality-related practice; barriers to sexual counselling; self-ratings of capability, opportunity and motivation; sexual attitudes and beliefs; knowledge of cardiovascular disease and sex. Fidelity of intervention delivery will be assessed using trainer self-reports, researcher-coded audio recordings and exit interviews. Longitudinal feasibility data will be gathered from patients/partners and staff via questionnaires and interviews.Ethics and disseminationThis study is approved by the Research Ethics Committee (REC) of the National University of Ireland, Galway. Findings will be disseminated to cardiac rehabilitation staff, patients/partners and relevant policymakers via appropriate publications and presentations.
β-Blockers in sepsis: protocol for a systematic review and meta-analysis of randomised control trials
Authors: Duan Erick H , Oczkowski Simon J W , Belley-Cote Emilie , Whitlock Richard , Lamontagne Francois , Devereaux Phillip J , Cook Deborah J 
Published: June 2016

IntroductionSepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of β-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of β-blockers in adults with sepsis using data from randomised control trials.Methods and analysisWe will identify randomised control trials comparing treatment with β-blockers, versus placebo or standard care in adults with sepsis. Data sources will include MEDLINE, EMBASE, CENTRAL, clinical trial registries and conference proceedings. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, risk of bias assessment and evaluation of the quality of the evidence using the GRADE approach.Ethics and disseminationOur systematic review will evaluate the effects of β-blockers in adults with sepsis, comprehensively summarising and appraising the available evidence from randomised control trials. The results of this systematic review will help clinicians treating patients with sepsis to understand the potential role of β-blockade, and inform future research on this topic. Our findings will be disseminated through conference presentation and publication in a peer-reviewed journal.Trial registration numberCRD42016036933.
Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study
Authors: Newton Julia L , Finkelmeyer Andreas , Petrides George , Frith James , Hodgson Tim , Maclachlan Laura , MacGowan Guy , Blamire Andrew M 
Published: June 2016

ObjectivesTo explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements.MethodsCardiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47) and matched case-by-case controls. Total volume (TV), red cell volume (RCV) and plasma volume (PV) measurements were performed (41 CFS and 10 controls) using the indicator dilution technique using simultaneous 51-chromium labelling of red blood cells and 125-iodine labelling of serum albumin.ResultsThe CFS group length of history (mean±SD) was 14±10 years. Patients with CFS had significantly reduced end-systolic and end-diastolic volumes together with reduced end-diastolic wall masses (all p<0.0001). Mean±SD RCV was 1565±443 mL with 26/41 (63%) having values below 95% of expected. PV was 2659±529 mL with 13/41 (32%) <95% expected. There were strong positive correlations between TV, RCV and PV and cardiac end-diastolic wall mass (all p<0.0001; r2=0.5). Increasing fatigue severity correlated negatively with lower PV (p=0.04; r2=0.2). There were no relationships between any MR or volume measurements and length of history, suggesting that deconditioning was unlikely to be the cause of these abnormalities.ConclusionsThis study confirms an association between reduced cardiac volumes and blood volume in CFS. Lack of relationship between length of disease, cardiac and plasma volumes suggests findings are not secondary to deconditioning. The relationship between plasma volume and severity of fatigue symptoms suggests a potential therapeutic target in CFS.
Staged re-evaluation of non-culprit lesions in ST segment elevation myocardial infarction: a retrospective study
Authors: Thim Troels , Egholm Gro , Olesen Kevin Kris Warnakula , Kaltoft Anne , Terkelsen Christian Juhl , Krusell Lars Romer , Kristensen Steen Dalby , Bøtker Hans Erik , Christiansen Evald Høj , Maeng Michael 
Published: June 2016

ObjectiveIt remains unknown whether complete revascularisation is optimally performed in patients with ST segment elevation myocardial infarction (STEMI) during the index or at staged procedures. The aims of this study were to quantify the number of primary percutaneous coronary intervention (PCI) procedures in which non-culprit lesions needed further evaluation, to determine the consequence of the re-evaluation and to quantify adverse cardiac events during the waiting time for re-evaluation and intervention.MethodsThe study was observational and retrospective and included all patients with STEMI treated with primary PCI during 1 year at our centre.ResultsAmong the 507 patients with STEMI, 374 were considered sufficiently treated with culprit lesion PCI only. Complete primary multivessel revascularisation was performed in 11 patients. Non-culprit lesion re-evaluation was planned for 122 patients (24%). Of these 122 patients, 3 patients died during their index admission. Follow-up data were not available for 3 patients. Among the 116 patients, 187 non-culprit lesions were re-evaluated and 77 patients (66.4%) underwent revascularisation with treatment of 119 lesions (63.3%). Re-evaluation was performed after a median of 30 days (25th centile: 9 days, 75th centile: 35 days). During the waiting time for re-evaluation, two patients underwent a new primary PCI due to stent thrombosis of the index culprit lesion.ConclusionsStaged re-evaluation of non-culprit lesions observed in patients with STEMI was required in 24% of a primary PCI cohort. Intervention was performed in 66.4% of patients scheduled for re-evaluation. We observed no adverse events related to the non-culprit lesions during the waiting time for a staged re-evaluation or intervention.
Chemical erosion of the bentonite buffer: do we observe it in nature?
Authors: Reijonen Heini M. , Marcos Nuria 
Published: June 2016

Abstract
It is planned to use bentonites as buffer materials in various types of geological repositories designed to host radioactive waste. For the bentonite materials, the hydrological and hydrogeochemical conditions are two of the main environmental factors affecting their evolution, assessed for a period of up to 1 Ma. Since it has been observed in laboratory tests that smectite, in particular montmorillonite, forms colloids and disperses in very dilute conditions, a scenario for chemical erosion has been discussed at length, especially in relation to geological repositories located in future glaciated terrains and locations otherwise potentially hosting dilute groundwaters. General understanding, based on laboratory experiments, is that bentonite erosion does not occur when the total charge equivalent of cations in groundwater is higher than 4 mM. However, based on current knowledge, it seems that chemical erosion is not observed in repository-relevant natural systems where groundwater conditions are below the given limit. Further investigation is therefore suggested to provide a better scientific understanding of the mechanisms involved in stabilizing smectites in these natural systems.
An improved model for through-diffusion experiments: application to strontium and tritiated water (HTO) diffusion in Boom Clay and compacted illite
Authors: Aertsens M. , Van Laer L. , Maes N. , Govaerts J. 
Published: June 2016

Abstract
Through-diffusion experiments are conventional experiments to measure the transport parameters of radionuclides in clays. Typically, a regular replacement of the outlet volume by a tracer-free volume is performed. In the classical approach, this type of through-diffusion experiment is modelled by assuming a zero concentration in the outlet volume. Nonetheless, this assumption is not always correct, usually because the outlet volume is insufficiently large or the time between two consecutive replacements of the outlet volume is too long. Therefore, a model was developed disregarding this assumption and, instead, considers the tracer concentration in the outlet volume to evolve, as in the experiments: the flux into the outlet volume increases the tracer concentration and, at each replacement, the tracer concentration in the outlet volume is set to zero. The model was used to reproduce the diffusion of strontium (Sr) and tritiated water (HTO) in illite and Boom Clay. Model results yielded good matches with the tracer evolution in the inlet and the outlet, and the tracer profile in the core at the end of the experiment.
Idelalisib Impacts Cell Growth through Inhibiting Translation-Regulatory Mechanisms in Mantle Cell Lymphoma
Authors: Yang Qingshan , Chen Lisa S. , Ha Min Jin , Do Kim-Anh , Neelapu Sattva S. , Gandhi Varsha 
Published: June 2016

Abstract
Purpose: PI3K is a critical node in the B-cell receptor pathway, which is responsible for survival and proliferation of B-cell malignancies. Idelalisib, a PI3Kδ-isoform–specific inhibitor, has been approved to treat B-cell malignancies. Although biological activity of the drug has been evaluated, molecular mechanisms and signaling pathway disruption leading to the biological effects of idelalisib are not yet well defined. Prior laboratory reports have identified transcription and translation as the primary events for attenuation of PI3Kα isoform. We hypothesized that PI3Kδ-isoform inhibition by idelalisib should also affect gene transcription and protein translation.
Experimental Design: Using three mantle cell lymphoma cell lines and primary cells from patients, biological consequences such as apoptosis/cell-cycle analysis, as well as RNA/protein synthesis were evaluated. Proteomics analyses (RPPA and immunoblot assays) defined molecular events downstream of PI3K/AKT cassette.
Results: Idelalisib treatment resulted in inhibition of protein synthesis, which correlated with reduction in cell size and cell growth. A moderate loss of viability without any change in cell-cycle profile was observed. Idelalisib treatment inhibited AKT activation, an immediate downstream PI3K effector, and also reduced phosphorylation levels of downstream AKT/mTOR pathway proteins such as PRAS40. In addition, idelalisib treatment impeded activation of the MAPK pathway, and MEK, ERK and p90RSK phosphorylation levels were reduced. Reduction in AKT, PDK1, and MEK phosphorylation correlated with protein synthesis inhibition.
Conclusions: Collectively, these results clarify the molecular mechanisms of actions and may provide biomarkers and targets for combination with idelalisib in B-cell malignancies. Clin Cancer Res; 23(1); 181–92. ©2016 AACR.
mTOR Inhibition Mitigates Enhanced mRNA Translation Associated with the Metastatic Phenotype of Osteosarcoma Cells In Vivo
Authors: Morrow James J. , Mendoza Arnulfo , Koyen Allyson , Lizardo Michael M. , Ren Ling , Waybright Timothy J. , Hansen Ryan J. , Gustafson Daniel L. , Zhou Ming , Fan Timothy M. , Scacheri Peter C. , Khanna Chand 
Published: June 2016

Abstract
Purpose: To successfully metastasize, tumor cells must respond appropriately to biological stressors encountered during metastatic progression. We sought to test the hypothesis that enhanced efficiency of mRNA translation during periods of metastatic stress is required for metastatic competence of osteosarcoma and that this metastasis-specific adaptation is amenable to therapeutic intervention.
Experimental Design: We employ novel reporter and proteomic systems that enable tracking of mRNA translation efficiency and output in metastatic osteosarcoma cells as they colonize the lungs. We test the potential to target mRNA translation as an antimetastatic therapeutic strategy through pharmacokinetic studies and preclinical assessment of the prototypic mTOR inhibitor, rapamycin, across multiple models of metastasis.
Results: Metastatic osteosarcoma cells translate mRNA more efficiently than nonmetastatic cells during critical stressful periods of metastatic colonization of the lung. Rapamycin inhibits translational output during periods of metastatic stress, mitigates lung colonization, and prolongs survival. mTOR-inhibiting exposures of rapamycin are achievable in mice using treatment schedules that correspond to human doses well below the MTDs defined in human patients, and as such are very likely to be tolerated over long exposures alone and in combination with other agents.
Conclusions: Metastatic competence of osteosarcoma cells is dependent on efficient mRNA translation during stressful periods of metastatic progression, and the mTOR inhibitor, rapamycin, can mitigate this translation and inhibit metastasis in vivo. Our data suggest that mTOR pathway inhibitors should be reconsidered in the clinic using rationally designed dosing schedules and clinical metrics related to metastatic progression. Clin Cancer Res; 22(24); 6129–41. ©2016 AACR.
Cholesterol Sulfonation Enzyme, SULT2B1b, Modulates AR and Cell Growth Properties in Prostate Cancer
Authors: Vickman Renee E. , Crist Scott A. , Kerian Kevin , Eberlin Livia , Cooks R. Graham , Burcham Grant N. , Buhman Kimberly K. , Hu Chang-Deng , Mesecar Andrew D. , Cheng Liang , Ratliff Timothy L. 
Published: June 2016

Abstract
Cholesterol accumulates in prostate lesions and has been linked to prostate cancer incidence and progression. However, how accumulated cholesterol contributes to prostate cancer development and progression is not completely understood. Cholesterol sulfate (CS), the primary sulfonation product of cholesterol sulfotransferase (SULT2B1b), accumulates in human prostate adenocarcinoma and precancerous prostatic intraepithelial neoplasia (PIN) lesions compared with normal regions of the same tissue sample. Given the enhanced accumulation of CS in these lesions, it was hypothesized that SULT2B1b-mediated production of CS provides a growth advantage to these cells. To address this, prostate cancer cells with RNAi-mediated knockdown (KD) of SULT2B1b were used to assess the impact on cell growth and survival. SULT2B1b is expressed and functional in a variety of prostate cells, and the data demonstrate that SULT2B1b KD, in LNCaP and other androgen-responsive (VCaP and C4-2) cells, results in decreased cell growth/viability and induces cell death. SULT2B1b KD also decreases androgen receptor (AR) activity and expression at mRNA and protein levels. While AR overexpression has no impact on SULT2B1b KD-mediated cell death, the addition of exogenous androgen is able to partially rescue the growth inhibition induced by SULT2B1b KD in LNCaP cells. These results suggest that SULT2B1b positively regulates the AR either through alterations in ligand availability or by interaction with critical coregulators that influence AR activity.
Implications: These findings provide evidence that SULT2B1b is a novel regulator of AR activity and cell growth in prostate cancer and should be further investigated for therapeutic potential. Mol Cancer Res; 14(9); 776–86. ©2016 AACR.
Polyphosphate is a novel cofactor for regulation of complement by a serpin, C1 inhibitor
Authors: Wijeyewickrema Lakshmi C. , Lameignere Emilie , Hor Lilian , Duncan Renee C. , Shiba Toshikazu , Travers Richard J. , Kapopara Piyushkumar R. , Lei Victor , Smith Stephanie A. , Kim Hugh , Morrissey James H. , Pike Robert N. , Conway Edward M. 
Published: June 2016

Key PointsPolyP, like heparin, is a physiologic cofactor for the C1-INH:C1s interaction, and thus a key negative regulator of complement. Colocalization of polyP with C1-INH in activated platelets suggests that its cofactor function is physiologically relevant.
Reduced epithelial suppressor of cytokine signalling 1 in severe eosinophilic asthma
Authors: Doran Emma , Choy David F. , Shikotra Aarti , Butler Claire A. , O'Rourke Declan M. , Johnston James A. , Kissenpfennig Adrien , Bradding Peter , Arron Joseph R. , Heaney Liam G. 
Published: June 2016

Severe asthma represents a major unmet clinical need. Eosinophilic inflammation persists in the airways of many patients with uncontrolled asthma, despite high-dose inhaled corticosteroid therapy. Suppressors of cytokine signalling (SOCS) are a family of molecules involved in the regulation of cytokine signallingviainhibition of the Janus kinase–signal transducers and activators of transcription pathway. We examined SOCS expression in the airways of asthma patients and investigated whether this is associated with persistent eosinophilia.Healthy controls, mild/moderate asthmatics and severe asthmatics were studied. Whole genome expression profiling, quantitative PCR and immunohistochemical analysis were used to examine expression of SOCS1, SOCS2 and SOCS3 in bronchial biopsies. Bronchial epithelial cells were utilised to examine the role of SOCS1 in regulating interleukin (IL)-13 signallingin vitro.SOCS1 gene expression was significantly lower in the airways of severe asthmatics compared with mild/moderate asthmatics, and was inversely associated with airway eosinophilia and other measures of T-helper type 2 (Th2) inflammation. Immunohistochemistry demonstrated SOCS1 was predominantly localised to the bronchial epithelium. SOCS1 overexpression inhibited IL-13-mediated chemokine ligand (CCL) 26 (eotaxin-3) mRNA expression in bronchial epithelial cells.Severe asthma patients with persistent airway eosinophilia and Th2 inflammation have reduced airway epithelial SOCS1 expression. SOCS1 inhibits epithelial IL-13 signalling, supporting its key role in regulating Th2-driven eosinophilia in severe asthma.
Exposure to ultrafine particles and respiratory hospitalisations in five European cities
Authors: Samoli Evangelia , Andersen Zorana Jovanovic , Katsouyanni Klea , Hennig Frauke , Kuhlbusch Thomas A.J. , Bellander Tom , Cattani Giorgio , Cyrys Josef , Forastiere Francesco , Jacquemin Bénédicte , Kulmala Markku , Lanki Timo , Loft Steffen , Massling Andreas , Tobias Aurelio , Stafoggia Massimo 
Published: June 2016

Epidemiological evidence on the associations between exposure to ultrafine particles (UFP), with aerodynamic electrical mobility diameters <100 nm, and health is limited. We gathered data on UFP from five European cities within 2001–2011 to investigate associations between short-term changes in concentrations and respiratory hospitalisations.We applied city-specific Poisson regression models and combined city-specific estimates to obtain pooled estimates. We evaluated the sensitivity of our findings to co-pollutant adjustment and investigated effect modification patterns by period of the year, age at admission and specific diagnoses.Our results for the whole time period do not support an association between UFP and respiratory hospitalisations, although we found suggestive associations among those 0–14 years old. We nevertheless report consistent adverse effect estimates during the warm period of the year, statistically significant after lag 2 when an increase by 10 000 particles per cm3was associated with a 4.27% (95% CI 1.68–6.92%) increase in hospitalisations. These effect estimates were robust to particles' mass or gaseous pollutants adjustment.Considering that our findings during the warm period may reflect better exposure assessment and that the main source of non-soluble UFP in urban areas is traffic, our results call for improved regulation of traffic emissions.
Consistency of biological networks inferred from microarray and sequencing data
Authors: Vinciotti Veronica , Wit Ernst C. , Jansen Rick , de Geus Eco J. C. N. , Penninx Brenda W. J. H. , Boomsma Dorret I. , ’t Hoen Peter A. C. 
Published: June 2016

AbstractBackgroundSparse Gaussian graphical models are popular for inferring biological networks, such as gene regulatory networks. In this paper, we investigate the consistency of these models across different data platforms, such as microarray and next generation sequencing, on the basis of a rich dataset containing samples that are profiled under both techniques as well as a large set of independent samples.ResultsOur analysis shows that individual node variances can have a remarkable effect on the connectivity of the resulting network. Their inconsistency across platforms and the fact that the variability level of a node may not be linked to its regulatory role mean that, failing to scale the data prior to the network analysis, leads to networks that are not reproducible across different platforms and that may be misleading. Moreover, we show how the reproducibility of networks across different platforms is significantly higher if networks are summarised in terms of enrichment amongst functional groups of interest, such as pathways, rather than at the level of individual edges.ConclusionsCareful pre-processing of transcriptional data and summaries of networks beyond individual edges can improve the consistency of network inference across platforms. However, caution is needed at this stage in the (over)interpretation of gene regulatory networks inferred from biological data.