bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dilated cardiomyopathy mutations in δ-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability
Authors: Campbell Matthew D. , Witcher Marc , Gopal Anoop , Michele Daniel E. 
Published: March 2016

Delta-sarcoglycan is a component of the sarcoglycan subcomplex within the dystrophin-glycoprotein complex located at the plasma membrane of muscle cells. While recessive mutations in δ-sarcoglycan cause limb girdle muscular dystrophy 2F, dominant mutations in δ-sarcoglycan have been linked to inherited dilated cardiomyopathy (DCM). The purpose of this study was to investigate functional cellular defects present in adult cardiac myocytes expressing mutant δ-sarcoglycans harboring the dominant inherited DCM mutations R71T or R97Q. This study demonstrates that DCM mutant δ-sarcoglycans can be stably expressed in adult rat cardiac myocytes and traffic similarly to wild-type δ-sarcoglycan to the plasma membrane, without perturbing assembly of the dystrophin-glycoprotein complex. However, expression of DCM mutant δ-sarcoglycan in adult rat cardiac myocytes is sufficient to alter cardiac myocyte plasma membrane stability in the presence of mechanical strain. Upon cyclical cell stretching, cardiac myocytes expressing mutant δ-sarcoglycan R97Q or R71T have increased cell-impermeant dye uptake and undergo contractures at greater frequencies than myocytes expressing normal δ-sarcoglycan. Additionally, the R71T mutation creates an ectopic N-linked glycosylation site that results in aberrant glycosylation of the extracellular domain of δ-sarcoglycan. Therefore, appropriate glycosylation of δ-sarcoglycan may also be necessary for proper δ-sarcoglycan function and overall dystrophin-glycoprotein complex function. These studies demonstrate that DCM mutations in δ-sarcoglycan can exert a dominant negative effect on dystrophin-glycoprotein complex function leading to myocardial mechanical instability that may underlie the pathogenesis of δ-sarcoglycan-associated DCM.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/dilated-cardiomyopathy-delta-sarcoglycan-mutations-cause-cardiomyocyte-membrane-instability/ .
Nuclear Receptor Corepressor 1 Expression and Output Declines with Prostate Cancer Progression
Authors: Lopez Sandra M. , Agoulnik Alexander I. , Zhang Manqi , Peterson Leif E. , Suarez Egla , Gandarillas Gregory A. , Frolov Anna , Li Rile , Rajapakshe Kimal , Coarfa Christian , Ittmann Michael M. , Weigel Nancy L. , Agoulnik Irina U. 
Published: March 2016

Abstract
Purpose: Castration therapy in advanced prostate cancer eventually fails and leads to the development of castration-resistant prostate cancer (CRPC), which has no cure. Characteristic features of CRPC can be increased androgen receptor (AR) expression and altered transcriptional output. We investigated the expression of nuclear receptor corepressor 1 (NCOR1) in human prostate and prostate cancer and the role of NCOR1 in response to antiandrogens.
Experimental Design: NCOR1 protein levels were compared between matched normal prostate and prostate cancer in 409 patient samples. NCOR1 knockdown was used to investigate its effect on bicalutamide response in androgen-dependent prostate cancer cell lines and transcriptional changes associated with the loss of NCOR1. NCOR1 transcriptional signature was also examined in prostate cancer gene expression datasets.
Results: NCOR1 protein was detected in cytoplasm and nuclei of secretory epithelial cells in normal prostate. Both cytoplasmic and nuclear NCOR1 protein levels were lower in prostate cancer than in normal prostate. Prostate cancer metastases show significant decrease in NCOR1 transcriptional output. Inhibition of LNCaP cellular proliferation by bicalutamide requires NCOR1. NCOR1-regulated genes suppress cellular proliferation and mediate bicalutamide resistance. In the mouse, NCOR1 is required for bicalutamide-dependent regulation of a subset of the AR target genes.
Conclusions: In summary, we demonstrated that NCOR1 function declines with prostate cancer progression. Reduction in NCOR1 levels causes bicalutamide resistance in LNCaP cells and compromises response to bicalutamide in mouse prostate in vivo. Clin Cancer Res; 22(15); 3937–49. ©2016 AACR.
Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy
Authors: Alix-Panabières Catherine , Pantel Klaus 
Published: March 2016

Abstract
“Liquid biopsy” focusing on the analysis of circulating tumor cells (CTC) and circulating cell-free tumor DNA (ctDNA) in the blood of patients with cancer has received enormous attention because of its obvious clinical implications for personalized medicine. Analyses of CTCs and ctDNA have paved new diagnostic avenues and are, to date, the cornerstones of liquid biopsy diagnostics. The present review focuses on key areas of clinical applications of CTCs and ctDNA, including detection of cancer, prediction of prognosis in patients with curable disease, monitoring systemic therapies, and stratification of patients based on the detection of therapeutic targets or resistance mechanisms.
Significance: The application of CTCs and ctDNA for the early detection of cancer is of high public interest, but it faces serious challenges regarding specificity and sensitivity of the current assays. Prediction of prognosis in patients with curable disease can already be achieved in several tumor entities, particularly in breast cancer. Monitoring the success or failure of systemic therapies (i.e., chemotherapy, hormonal therapy, or other targeted therapies) by sequential measurements of CTCs or ctDNA is also feasible. Interventional studies on treatment stratification based on the analysis of CTCs and ctDNA are needed to implement liquid biopsy into personalized medicine. Cancer Discov; 6(5); 479–91. ©2016 AACR.
Intraoperative Defibrillation Testing of Subcutaneous Implantable Cardioverter‐Defibrillator Systems—A Simple Issue?
Authors: Frommeyer Gerrit , Zumhagen Sven , Dechering Dirk G. , Larbig Robert , Bettin Markus , Löher Andreas , Köbe Julia , Reinke Florian , Eckardt Lars 
Published: March 2016

Background

The results of the recently published randomized
SIMPLE
trial question the role of routine intraoperative defibrillation testing. However, testing is still recommended during implantation of the entirely subcutaneous implantable cardioverter‐defibrillator (S‐
ICD
) system. To address the question of whether defibrillation testing in S‐
ICD
systems is still necessary, we analyzed the data of a large, standard‐of‐care prospective single‐center S‐
ICD
registry.

Methods and Results

In the present study, 102 consecutive patients received an S‐
ICD
for primary (n=50) or secondary prevention (n=52). Defibrillation testing was performed in all except 4 patients. In 74 (75%; 95%
CI
0.66–0.83) of 98 patients, ventricular fibrillation was effectively terminated by the first programmed internal shock. In 24 (25%; 95%
CI
0.22–0.44) of 98 patients, the first internal shock was ineffective and further internal or external shock deliveries were required. In these patients, programming to reversed shock polarity (n=14) or repositioning of the sensing lead (n=1) or the pulse generator (n=5) led to successful defibrillation. In 4 patients, a safety margin of <10 J was not attained. Nevertheless, in these 4 patients, ventricular arrhythmias were effectively terminated with an internal 80‐J shock.

Conclusions

Although it has been shown that defibrillation testing is not necessary in transvenous
ICD
systems, it seems particular important for S‐
ICD
systems, because in nearly 25% of the cases the primary intraoperative test was not successful. In most cases, a successful defibrillation could be achieved by changing shock polarity or by optimizing the shock vector caused by the pulse generator or lead repositioning.
DNA-assisted identification of Caulerpa (Caulerpaceae, Chlorophyta) reduces species richness estimates for the Eastern Tropical Pacific
Authors: FERNÁNDEZ-GARCÍA CINDY , WYSOR BRIAN , RIOSMENA-RODRÍGUEZ RAFAEL , PEÑA-SALAMANCA ENRIQUE , VERBRUGGEN HEROEN 
Published: March 2016

Taxonomy and species richness estimates for the genus Caulerpa have proven challenging due to the difficulty of assessing morphological species limits. In the present study we evaluate the taxonomy of the genus and assess species distributions in the Eastern Tropical Pacific (ETP), based on morphology and tufA sequence data. Molecular analyses revealed six species-level clades: C. verticillata, C. sertularioides, C. cupressoides, C. serrulata, C. racemosa and C. chemnitzia (part of C. racemosa-peltata complex). Our results reduce species richness estimates throughout the ETP by over 54% (from 13 to 6). In accordance with recent studies, our morphological and DNA results warrant the recognition of C. chemnitzia to comprise the morphological entities C. laetevirens, C. peltata and C. vanbossea complex. We continue the use of ecads as a practical identification tool for morphological diversity below the species level present in the ETP. In addition we formally recognize the synonymy of C. racemosa var. macrophysa with the lineage of C. racemosa proposed in recent studies. The six species of Caulerpa found in this study are of pantropical in distribution. Within the ETP region, four species have restricted distributions (C. verticillata, C. cupressoides, C. serrulata, C. racemosa), while two show a wide latitudinal distribution (C. chemnitzia and C. sertularioides).
Tumor Biomarkers in Spindle Cell Variant Squamous Cell Carcinoma of the Head and Neck
Authors: Rosko Andrew J. , Birkeland Andrew C. , Wilson Kevin F. , Muenz Daniel G. , Bellile Emily , Bradford Carol R. , McHugh Jonathan B. , Spector Matthew E. 
Published: March 2016

ObjectiveTo determine biomarkers of recurrence and survival in patients with spindle cell variant squamous cell carcinoma (SpSCC) of the head and neck.Study DesignRetrospective case control study.SettingTertiary academic center.Subjects and MethodsThirty‐two SpSCC patients (mean age, 68.8) between 1987 and 2009 were identified and reviewed. A tissue microarray (TMA) was constructed from tumor specimens. Tumor biomarkers under study included p16, epidermal growth factor receptor (EGFR), p53, EZH2, cyclin D1, CD104, HGFa, p21, and cMET. An additional TMA was constructed from patients with non‐SpSCC oral cavity squamous cell carcinoma for comparative purposes. The main outcomes were overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS).ResultsIn the SpSCC cohort, tumors positive for cMet had worse OS (P <. 001). Patients positive for cMet (P =. 007), cyclin D1 (P =. 019), and p16 (P =. 004) had worse DSS. Recurrence‐free survival was also worse in patients with tumors positive for cMet (P =. 037), cyclin D1 (P =. 012), and p16 (P <. 001). Compared with the oral cavity cohort, there was a significantly larger proportion of patients in the SpSCC group with tumors staining positive for cMet and a lower proportion of tumors positive for cyclin D1.ConclusioncMet, cyclin D1, and p16 are predictive tumor biomarkers for risk of recurrence and worse DSS in patients with SpSCC.
Defining post-sternotomy mediastinitis for clinical evidence-based studies
Authors: van Wingerden Jan J , de Mol Bas AJM , van der Horst Chantal MAM 
Published: March 2016

Background Considerable advances have already been made in the treatment of deep thoracic wound infections following a median sternotomy for cardiac surgery. Further improvement in diagnosis, treatment, and outcome will require a targeted approach by multidisciplinary teams. Clear communication and synergy between the various clinical and supportive disciplines would assist in removing the last barriers to standardized evidence-based studies and the development of improved evidence-based guidelines. Methods An extensive literature search without language restrictions was carried out on PubMed (Medline), EMBASE, and Web of Science, covering the period 1988 to week 16, 2014, and a manual search of the reference lists was performed regarding all possible definitions and classifications of post-sternotomy mediastinitis. Two hundred and eighteen papers describing post-sternotomy infections in a multitude of terms were identified, and the strengths and weaknesses of the most popular definitions and terms relating specifically to post-sternotomy infections were examined. Results This study revealed that clinicians use a multitude of terms to describe post-sternotomy infections without defining the condition under treatment. Occasionally, older epidemiological (surveillance) definitions were used. It also shows that supportive disciplines have their own definitions, or interpretations of existing definitions, to describe these infections. Conclusion The outcome of this study is that clinicians have adopted no single definition, which is essential for further improvement for evidence-based studies. We suggest that it is possible to adopt a single term for thoracic infection after a sternotomy (and only sternotomy), and propose a clinical definition for this purpose.
Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura
Authors: McIlvried Lisa A , Cruz J Agustin , Borghesi Lisa A , Gold Michael S 
Published: March 2016

Aim of investigation Due to compelling evidence in support of links between sex, stress, sympathetic post-ganglionic innervation, dural immune cells, and migraine, our aim was to characterize the impacts of these factors on the type and proportion of immune cells in the dura. Methods Dural immune cells were obtained from naïve or stressed adult male and female Sprague Dawley rats for flow cytometry. Rats with surgical denervation of sympathetic post-ganglionic neurons of the dura were also studied. Results Immune cells comprise ∼17% of all cells in the dura. These included: macrophages/granulocytes (“Macs”; 63.2% of immune cells), dendritic cells (0.88%), T-cells (4.51%), natural killer T-cells (0.51%), natural killer cells (3.08%), and B-cells (20.0%). There were significantly more Macs and fewer B- and natural killer T-cells in the dura of females compared with males. Macs and dendritic cells were significantly increased by stress in males, but not females. In contrast, T-cells were significantly increased in females with a 24-hour delay following stress. Lastly, Macs, dendritic cells, and T-cells were significantly higher in sympathectomized-naïve males, but not females. Conclusions It may not only be possible, but necessary to use different strategies for the most effective treatment of migraine in men and women.
Changes in bioactive compounds and oxidative enzymes of fresh-cut pomegranate arils during storage as affected by deficit irrigation and postharvest vapor heat treatments
Authors: Peña-Estévez María E , Gómez Perla A , Artés Francisco , Aguayo Encarna , Martínez-Hernández Ginés Benito , Galindo Alejandro , Torecillas Arturo , Artés-Hernández Francisco 
Published: March 2016

The effect of postharvest vapor heat treatments at 95℃ (4, 7, and 10 s) regarding a conventional sanitizing treatment with 100 mg NaClO l−1 on enzyme activities (phenylalanine ammonia lyase, polyphenol oxidase, and peroxidase), phenolic content, and total antioxidant capacity of fresh-cut pomegranates arils throughout 18 days at 5℃ was studied. Furthermore, the effect of two sustained deficit irrigation (SDI) strategies, compared to a standardly irrigated control (CTRL), was also studied on such quality parameters throughout storage. Arils from CTRL-irrigated fruit registered phenylalanine ammonia lyase, peroxidase, and polyphenol oxidase initial activities of 60.6, 382, and 14.4 U g-1 fw, respectively. Arils from sustained deficit irrigation fruit registered 46–58% lower phenylalanine ammonia lyase values while polyphenol oxidase and peroxidase activities did not register great variants (<9%) among both sustained deficit irrigation treatments. Postharvest vapor heat treatments enhanced phenylalanine ammonia lyase activity in those samples from sustained deficit irrigation fruit although no great peroxidase and polyphenol oxidase (<2–5%) increases were observed. Arils from SDI1 fruit registered higher phenolic content than those values reported for CTRL samples. However, phenolic compounds decreased during storage, in a greater extent for sustained deficit irrigation samples, although 7 s arils achieved better phenolic compounds retention in sustained deficit irrigation samples. Vapor heat treatments reduced up to twofold the total antioxidant capacity losses observed in samples sanitized by conventional NaOCl treatment during shelf life. Conclusively, postharvest vapor heat treatment for 7 and 10 s used to extend the shelf life of pomegranate arils up to 18 days at 5℃ reduced the losses of health-promoting compounds during storage compared to conventional NaOCl sanitizing treatment.
Unpacking knowledge translation in participatory research: a micro-level study
Authors: Lillehagen Ida , Heggen Kristin , Engebretsen Eivind 
Published: March 2016

Objectives Funding bodies, policy makers, researchers and clinicians are seeking strategies to increase the translation of knowledge between research and practice. Participatory research encompasses a range of approaches for clinicians’ involvement in research in the hope of increasing the relevance and usability of research. Our aim was to explore how knowledge is translated and integrated in participants’ presentations and negotiations about knowledge. Methods Twelve collaboration meetings were observed, and discussions between researchers and clinicians were recorded. The material was examined using the following analytical terms: knowledge object, knowledge form, knowledge position and knowledge tasks. Results We identified a recurring rhetorical pattern in translational processes that we call ‘relevance testing’: a strategy by which the participants attempt to create coherence and identify relevance across different contexts. The limitation of this translational strategy was a tendency to reinforce a ‘two-communities’ logic: re-establishing the separated worlds and rationales between clinicians and researchers. The ‘translational work’ that unfolds during discussions remains implicit. It may be that participants are unable to explicitly address and identify the knowledge translation processes because they lack necessary conceptual tools. Conclusions Our results contribute to increased awareness about translational processes and provide a language through which barriers to translation can be addressed.
The childcatchers: An exploration of the representations and discourses of social work in UK film and television drama from the 1960s to the present day
Authors: Edmondson David , King Martin 
Published: March 2016

Summary This article reports on research undertaken to critically examine portrayals, representations and discourses of social work and social workers in UK film and television drama from the 1960s to the present day. The research analysed four film and television dramas where social work and social workers were featured: Cathy Come Home (1966), Ladybird Ladybird (1994), Happy Go Lucky (2008) and Oranges and Sunshine (2010). The research aimed to examine portrayals and representations of social work and social workers in UK film and television drama; inform and develop an understanding of contemporary narratives and discourses about social work and contribute to debates about the purpose and future of social work. Findings Portrayals and representations of social work in UK film and television drama often encourage and reinforce an overly simplistic, hostile and negative impression of the profession, work which is presented as predominantly focused on child protection and the removal of children from families. Social workers are typically characterised as incompetent, bureaucratic, well-meaning but misguided. This potentially endorses neo-liberal ideologies and discourses about welfare, welfare recipients, welfare provision and social service. Applications This approach to the topic offers an accessible and interesting platform for research, teaching and policy development, which has the potential to critically inform debates about the future and purpose of social work and welfare in the United Kingdom.
The place of service-user expertise in evidence-based practice
Authors: Davies Kate , Gray Mel 
Published: March 2016

Summary This article considers the place of service-user knowledge and expertise within an evidence-based practice perspective. It makes a strong argument that client involvement is a core principle of Sackett et al.'s foundational approach in evidence-based medicine. In so doing, it draws on research on service-users' perceptions and experiences of evidence-based practice. Findings For service users, evidence-based practice lacks relevance and trustworthiness unless it explicitly factors in the expertise of service users themselves. Evidence-based practice is seen to have merit as a tool for enhancing accountability, but service users see a role for themselves at individual and representative levels in the process of evidence-based practice. They place a high value on the expertise derived from lived experience, and recognise that fluctuations in capacity and changes in circumstances of many service users require a flexible approach to their participation in decision making. A pragmatic approach to the conceptualisation of evidence is recommended, which not only maintains scientific rigour inherent in evidence-based practice but also more strongly emphasises the process of analysing evidence appropriate to a particular individual's preferences and circumstances. Applications For human service practitioners, this study emphasises the need to develop professional skills in assessing the capacities, circumstances and preferences of clients and analysing and applying evidence for practice in ways that conform to a client-centred approach. It also indicates a need for researchers and practitioners to recognise and value service-user expertise.
Looking into care: The reliability and feasibility of a Taxonomy of Care for Youth
Authors: Evenboer KE , Huyghen AMN , Tuinstra J , Reijneveld SA , Knorth EJ 
Published: March 2016

Summary Classifying the care provided to children with emotional and behavioural problems can provide empirical insights into the relationship between child characteristics, the care offered and outcomes after leaving care. The Taxonomy of Care for Youth (TOCFY) has recently been shown to validly classify this care in six domains covering all aspects of care. The aim of this study was to assess the inter-rater reliability and feasibility of TOCFY. Two raters independently classified the care provided to 200 children (50 per organisation) from organisations in primary health care, child and youth care, and mental health care (two organisations), based on their care records. We assessed inter-rater reliability and the degree to which TOCFY categories could be applied anyhow, that is its feasibility. Findings Mean agreement was 89.8% between raters; excluding the cases scored as ‘unknown’, the mean agreement was 82.2%. TOCFY-categories could be applied for over 90% regarding each of the six domains. Applications TOCFY is a valid, reliable and feasible instrument to classify care within different types of care organisations. Give these promising findings, application and further evaluation of TOCFY is recommended.