bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide characterization of microRNA in foxtail millet (Setaria italica)
Authors: Yi Fei , Xie Shaojun , Liu Yuwei , Qi Xin , Yu Jingjuan 
Published: December 2013

Abstract

Background
MicroRNAs (miRNAs) are a class of short non-coding, endogenous RNAs that play key roles in many biological processes in both animals and plants. Although many miRNAs have been identified in a large number of organisms, the miRNAs in foxtail millet (Setaria italica) have, until now, been poorly understood.

Results
In this study, two replicate small RNA libraries from foxtail millet shoots were sequenced, and 40 million reads representing over 10 million unique sequences were generated. We identified 43 known miRNAs, 172 novel miRNAs and 2 mirtron precursor candidates in foxtail millet. Some miRNA*s of the known and novel miRNAs were detected as well. Further, eight novel miRNAs were validated by stem-loop RT-PCR. Potential targets of the foxtail millet miRNAs were predicted based on our strict criteria. Of the predicted target genes, 79% (351) had functional annotations in InterPro and GO analyses, indicating the targets of the miRNAs were involved in a wide range of regulatory functions and some specific biological processes. A total of 69 pairs of syntenic miRNA precursors that were conserved between foxtail millet and sorghum were found. Additionally, stem-loop RT-PCR was conducted to confirm the tissue-specific expression of some miRNAs in the four tissues identified by deep-sequencing.

Conclusions
We predicted, for the first time, 215 miRNAs and 447 miRNA targets in foxtail millet at a genome-wide level. The precursors, expression levels, miRNA* sequences, target functions, conservation, and evolution of miRNAs we identified were investigated. Some of the novel foxtail millet miRNAs and miRNA targets were validated experimentally.
The carotid plaque imaging in acute stroke (CAPIAS) study: protocol and initial baseline data
Authors: Bayer-Karpinska Anna , Schwarz Florian , Wollenweber Frank A , Poppert Holger , Boeckh-Behrens Tobias , Becker Alexander , Clevert Dirk A , Nikolaou Konstantin , Opherk Christian , Dichgans Martin , Saam Tobias 
Published: December 2013

Abstract

Background
In up to 30% of patients with ischemic stroke no definite etiology can be established. A significant proportion of cryptogenic stroke cases may be due to non-stenosing atherosclerotic plaques or low grade carotid artery stenosis not fulfilling common criteria for atherothrombotic stroke. The aim of the CAPIAS study is to determine the frequency, characteristics, clinical and radiological long-term consequences of ipsilateral complicated American Heart Association lesion type VI (AHA-LT VI) carotid artery plaques in patients with cryptogenic stroke.

Methods/Design
300 patients (age >49 years) with unilateral DWI-positive lesions in the anterior circulation and non- or moderately stenosing (<70% NASCET) internal carotid artery plaques will be enrolled in the prospective multicenter study CAPIAS. Carotid plaque characteristics will be determined by high-resolution black-blood carotid MRI at baseline and 12 month follow up. Primary outcome is the prevalence of complicated AHA-LT VI plaques in cryptogenic stroke patients ipsilateral to the ischemic stroke compared to the contralateral side and to patients with defined stroke etiology. Secondary outcomes include the association of AHA-LT VI plaques with the recurrence rates of ischemic events up to 36 months, rates of new ischemic lesions on cerebral MRI (including clinically silent lesions) after 12 months and the influence of specific AHA-LT VI plaque features on the progression of atherosclerotic disease burden, on specific infarct patterns, biomarkers and aortic arch plaques.

Discussion
CAPIAS will provide important insights into the role of non-stenosing carotid artery plaques in cryptogenic stroke. The results might have implications for our understanding of stroke mechanism, offer new diagnostic options and provide the basis for the planning of targeted interventional studies.

Trial Registration

NCT01284933
High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor
Authors: Auf Gregor , Jabouille Arnaud , Delugin Maylis , Guérit Sylvaine , Pineau Raphael , North Sophie , Platonova Natalia , Maitre Marlène , Favereaux Alexandre , Vajkoczy Peter , Seno Masaharu , Bikfalvi Andreas , Minchenko Dmitri , Minchenko Oleksandr , Moenner Michel 
Published: December 2013

Abstract

Background
Epidermal growth factor (EGF) receptors contribute to the development of malignant glioma. Here we considered the possible implication of the EGFR ligand epiregulin (EREG) in glioma development in relation to the activity of the unfolded protein response (UPR) sensor IRE1α. We also examined EREG status in several glioblastoma cell lines and in malignant glioma.

Methods
Expression and biological properties of EREG were analyzed in human glioma cells in vitro and in human tumor xenografts with regard to the presence of ErbB proteins and to the blockade of IRE1α. Inactivation of IRE1α was achieved by using either the dominant-negative strategy or siRNA-mediated knockdown.

Results
EREG was secreted in high amounts by U87 cells, which also expressed its cognate EGF receptor (ErbB1). A stimulatory autocrine loop mediated by EREG was evidenced by the decrease in cell proliferation using specific blocking antibodies directed against either ErbB1 (cetuximab) or EREG itself. In comparison, anti-ErbB2 antibodies (trastuzumab) had no significant effect. Inhibition of IRE1α dramatically reduced EREG expression both in cell culture and in human xenograft tumor models. The high-expression rate of EREG in U87 cells was therefore linked to IRE1α, although being modestly affected by chemical inducers of the endoplasmic reticulum stress. In addition, IRE1-mediated production of EREG did not depend on IRE1 RNase domain, as neither the selective dominant-negative invalidation of the RNase activity (IRE1 kinase active) nor the siRNA-mediated knockdown of XBP1 had significant effect on EREG expression. Finally, chemical inhibition of c-Jun N-terminal kinases (JNK) using the SP600125 compound reduced the ability of cells to express EREG, demonstrating a link between the growth factor production and JNK activation under the dependence of IRE1α.

Conclusion
EREG may contribute to glioma progression under the control of IRE1α, as exemplified here by the autocrine proliferation loop mediated in U87 cells by the growth factor through ErbB1.
Plasma levels of the MMP-9:TIMP-1 complex as prognostic biomarker in breast cancer: a retrospective study
Authors: Thorsen Stine B , Christensen Sarah LT , Würtz Sidse Ø , Lundberg Martin , Nielsen Birgitte S , Vinther Lena , Knowles Mick , Gee Nick , Fredriksson Simon , Møller Susanne , Brünner Nils , Schrohl Anne-Sofie , Stenvang Jan 
Published: December 2013

AbstractBackgroundWorldwide more than one million women are annually diagnosed with breast cancer. A considerable fraction of these women receive systemic adjuvant therapy; however, some are cured by primary surgery and radiotherapy alone. Prognostic biomarkers guide stratification of patients into different risk groups and hence improve management of breast cancer patients. Plasma levels of Matrix Metalloproteinase-9 (MMP-9) and its natural inhibitor Tissue inhibitor of metalloproteinase-1 (TIMP-1) have previously been associated with poor patient outcome and resistance to certain forms of chemotherapy. To pursue additional prognostic information from MMP-9 and TIMP-1, the level of the MMP-9 and TIMP-1 complex (MMP-9:TIMP-1) was investigated in plasma from breast cancer patients.MethodsDetection of protein:protein complexes in plasma was performed using a commercially available ELISA kit and, for the first time, the highly sensitive in-solution proximity ligation assay (PLA). We screened plasma from 465 patients with primary breast cancer for prognostic value of the MMP-9:TIMP-1 complex. Both assays were validated and applied for quantification of MMP-9:TIMP-1 concentration. In this retrospective study, we analyzed the association between the concentration of the MMP-9:TIMP-1 complex and clinicopathological data and disease free survival (DFS) in univariate and multivariate survival analyses.ResultsFollowing successful validation both assays were applied for MMP-9:TIMP-1 measurements. Of the clinicopathological parameters, only menopausal status demonstrated significant association with the MMP-9:TIMP-1 complex; P = 0.03 and P = 0.028 for the ELISA and PLA measurements, respectively. We found no correlation between the MMP-9:TIMP-1 protein complex and DFS neither in univariate nor in multivariate survival analyses.ConclusionsDespite earlier reports linking MMP-9 and TIMP-1 with prognosis in breast cancer patients, we here demonstrate that plasma levels of the MMP-9:TIMP-1 protein complex hold no prognostic information in primary breast cancer as a stand-alone marker. We demonstrate that the highly sensitive in-solution PLA can be employed for measurements of protein:protein complexes in plasma.
Depression and decision-making capacity for treatment or research: a systematic review
Authors: Hindmarch Thomas , Hotopf Matthew , Owen Gareth S 
Published: December 2013

AbstractBackgroundPsychiatric disorders can pose problems in the assessment of decision-making capacity (DMC). This is so particularly where psychopathology is seen as the extreme end of a dimension that includes normality. Depression is an example of such a psychiatric disorder. Four abilities (understanding,appreciating,reasoningand ability toexpress a choice) are commonly assessed when determining DMC in psychiatry and uncertainty exists about the extent to which depression impacts capacity to make treatment or research participation decisions.MethodsA systematic review of the medical ethical and empirical literature concerning depression and DMC was conducted. Medline, EMBASE and PsycInfo databases were searched for studies of depression and consent and DMC. Empirical studies and papers containing ethical analysis were extracted and analysed.Results17 publications were identified. The clinical ethics studies highlightedappreciationof information as the ability that can be impaired in depression, indicating that emotional factors can impact on DMC. The empirical studies reporting decision-making ability scores also highlighted impairment ofappreciationbut without evidence of strong impact. Measurement problems, however, looked likely. The frequency of clinical judgements of lack of DMC in people with depression varied greatly according to acuity of illness and whether judgements are structured or unstructured.ConclusionsDepression can impair DMC especially if severe. Most evidence indicatesappreciationas the ability primarily impaired by depressive illness. Understanding and measuring theappreciationability in depression remains a problem in need of further research.
In triple negative breast tumor cells, PLC-β2 promotes the conversion of CD133high to CD133low phenotype and reduces the CD133-related invasiveness
Authors: Brugnoli Federica , Grassilli Silvia , Piazzi Manuela , Palomba Maria , Nika Ervin , Bavelloni Alberto , Capitani Silvano , Bertagnolo Valeria 
Published: December 2013

AbstractBackgroundBeyond its possible correlation with stemness of tumor cells, CD133/prominin1 is considered an important marker in breast cancer, since it correlates with tumor size, metastasis and clinical stage of triple-negative breast cancers (TNBC), to date the highest risk breast neoplasia.MethodsTo study the correlation between the levels of CD133 expression and the biology of breast-derived cells, CD133lowand CD133highcell subpopulations isolated from triple negative MDA-MB-231 cells were compared in terms of malignant properties and protein expression.ResultsHigh expression of CD133 characterizes cells with larger adhesion area, lower proliferation rate and reduced migration speed, indicative of a less undifferentiated phenotype. Conversely, when compared with CD133lowcells, CD133highcells show higher invasive capability and increased expression of proteins involved in metastasis and drug-resistance of breast tumors. Among the signalling proteins examined, PLC-β2 expression inversely correlates with the levels of CD133 and has a role in inducing the CD133highcells to CD133lowcells conversion, suggesting that, in TNBC cells, the de-regulation of this PLC isoform is responsible of the switch from an early to a mature tumoral phenotype also by reducing the expression of CD133.ConclusionsSince CD133 plays a role in determining the invasiveness of CD133highcells, it may constitute an attractive target to reduce the metastatic potential of TNBC. In addition, our data showing that the forced up-regulation of PLC-β2 counteracts the invasiveness of CD133-positive MDA-MB-231 cells might contribute to identify unexplored key steps responsible for the TNBC high malignancy, to be considered for potential therapeutic strategies.
Resveratrol promotes myogenesis and hypertrophy in murine myoblasts
Authors: Montesano Anna , Luzi Livio , Senesi Pamela , Mazzocchi Nausicaa , Terruzzi Ileana 
Published: December 2013

Abstract

Background
Nutrigenomics elucidate the ability of bioactive food components to influence gene expression, protein synthesis, degradation and post-translational modifications.
Resveratrol (RSV), natural polyphenol found in grapes and in other fruits, has a plethora of health benefits in a variety of human diseases: cardio- and neuroprotection, immune regulation, cancer chemoprevention, DNA repair, prevention of mitochondrial disorder, avoidance of obesity-related diseases. In skeletal muscle, RSV acts on protein catabolism and muscle function, conferring resistance against oxidative stress, injury and cell death, but its action mechanisms and protein targets in myogenesis process are not completely known. Myogenesis is a dynamic multistep process regulated by Myogenic Regulator Factors (MRFs), responsible of the commitment of myogenic cell into skeletal muscle: mononucleated undifferentiated myoblasts break free from cell cycle, elongate and fuse to form multinucleated myotubes. Skeletal muscle hypertrophy can be defined as a result of an increase in the size of pre-existing skeletal muscle fibers accompanied by increased protein synthesis, mainly regulated by Insulin Like Growth Factor 1 (IGF-1), PI3-K/AKT signaling pathways.
Aim of this work was the study of RSV effects on proliferation, differentiation process and hypertrophy in C2C12 murine cells.

Methods
To study proliferative phase, cells were incubated in growth medium with/without RSV (0.1 or 25 μM) until reaching sub confluence condition (24, 48, 72 h). To examine differentiation, at 70% confluence, cells were transferred in differentiation medium both with/without RSV (0.1 or 25 μM) for 24, 48, 72, 96 hours. After 72 hours of differentiation, the genesis of hypertrophy in neo-formed myotubes was analyzed.

Results
Data showed that RSV regulates cell cycle exit and induces C2C12 muscle differentiation. Furthermore, RSV might control MRFs and muscle-specific proteins synthesis. In late differentiation, RSV has positive effects on hypertrophy: RSV stimulates IGF-1 signaling pathway, in particular AKT and ERK 1/2 protein activation, AMPK protein level and induces hypertrophic morphological changes in neo-formed myotubes modulating cytoskeletal proteins expression.

Conclusions
RSV might control cell cycle promoting myogenesis and hypertrophy in vitro, opening a novel field of application of RSV in clinical conditions characterized by chronic functional and morphological muscle impairment.
Fixed points of mappings with a contractive iterate at a point in partial metric spaces
Authors: Ilić Dejan , Pavlović Vladimir , Rakočević Vladimir 
Published: December 2013

Abstract
In 1994, Matthews introduced and studied the concept of partial metric space and obtained a Banach-type fixed point theorem on complete partial metric spaces. In this paper we study fixed point results of new mappings with a contractive iterate at a point in partial metric spaces. Our results generalize and unify some results of Sehgal, Guseman and Ćirić for mappings with a generalized contractive iterate at a point to partial metric spaces. We give some generalized versions of the fixed point theorem of Matthews. The theory is illustrated by some examples.
Log-binomial models: exploring failed convergence
Authors: Williamson Tyler , Eliasziw Misha , Fick Gordon Hilton 
Published: December 2013

Abstract
Background
Relative risk is a summary metric that is commonly used in epidemiological investigations. Increasingly, epidemiologists are using log-binomial models to study the impact of a set of predictor variables on a single binary outcome, as they naturally offer relative risks. However, standard statistical software may report failed convergence when attempting to fit log-binomial models in certain settings. The methods that have been proposed in the literature for dealing with failed convergence use approximate solutions to avoid the issue. This research looks directly at the log-likelihood function for the simplest log-binomial model where failed convergence has been observed, a model with a single linear predictor with three levels. The possible causes of failed convergence are explored and potential solutions are presented for some cases.

Results
Among the principal causes is a failure of the fitting algorithm to converge despite the log-likelihood function having a single finite maximum. Despite these limitations, log-binomial models are a viable option for epidemiologists wishing to describe the relationship between a set of predictors and a binary outcome where relative risk is the desired summary measure.

Conclusions
Epidemiologists are encouraged to continue to use log-binomial models and advocate for improvements to the fitting algorithms to promote the widespread use of log-binomial models.
Network based elucidation of drug response: from modulators to targets
Authors: Iorio Francesco , Saez-Rodriguez Julio , Bernardo Diego di 
Published: December 2013

Abstract
Network-based drug discovery aims at harnessing the power of networks to investigate the mechanism of action of existing drugs, or new molecules, in order to identify innovative therapeutic treatments. In this review, we describe some of the most recent advances in the field of network pharmacology, starting with approaches relying on computational models of transcriptional networks, then moving to protein and signaling network models and concluding with “drug networks”. These networks are derived from different sources of experimental data, or literature-based analysis, and provide a complementary view of drug mode of action. Molecular and drug networks are powerful integrated computational and experimental approaches that will likely speed up and improve the drug discovery process, once fully integrated into the academic and industrial drug discovery pipeline.
A Suzuki type unique common fixed point theorem for hybrid pairs of maps under a new condition in partial metric spaces
Authors: Rao KPR , Rao KPK , Aydi Hassen 
Published: December 2013

Abstract
In this paper, we introduce a new condition namely, the (W.C.C) condition and give some Suzuki-type, unique, common fixed-point theorems for pairs of hybrid mappings in partial metric spaces using a partial Hausdorff metric. These results generalize and extend the several comparable results in this literature in metric and partial metric spaces.
Influence of acute kidney injury on short- and long-term outcomes in patients undergoing cardiac surgery: risk factors and prognostic value of a modified RIFLE classification
Authors: Lopez-Delgado Juan C , Esteve Francisco , Torrado Herminia , Rodríguez-Castro David , Carrio Maria L , Farrero Elisabet , Javierre Casimiro , Ventura Josep L , Manez Rafael 
Published: December 2013

Abstract
Introduction
The development of acute kidney injury (AKI) is associated with poor outcome. The modified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for AKI, which classifies patients with renal replacement therapy needs according to RIFLE failure class, improves the predictive value of AKI in patients undergoing cardiac surgery. Our aim was to assess risk factors for post-operative AKI and the impact of renal function on short- and long-term survival among all AKI subgroups using the modified RIFLE classification.

Methods
We prospectively studied 2,940 consecutive cardiosurgical patients between January 2004 and July 2009. AKI was defined according to the modified RIFLE system. Pre-operative, operative and post-operative variables usually measured on and during admission, which included main outcomes, were recorded together with cardiac surgery scores and ICU scores. These data were evaluated for association with AKI and staging in the different RIFLE groups by means of multivariable analyses. Survival was analyzed via Kaplan-Meier and a risk-adjusted Cox proportional hazards regression model. A complete follow-up (mean 6.9 ± 4.3 years) was performed in 2,840 patients up to April 2013.

Results
Of those patients studied, 14% (n = 409) were diagnosed with AKI. We identified one intra-operative (higher cardiopulmonary bypass time) and two post-operative (a longer need for vasoactive drugs and higher arterial lactate 24 hours after admission) predictors of AKI. The worst outcomes, including in-hospital mortality, were associated with the worst RIFLE class. Kaplan-Meier analysis showed survival of 74.9% in the RIFLE risk group, 42.9% in the RIFLE injury group and 22.3% in the RIFLE failure group (P <0.001). Classification at RIFLE injury (Hazard ratio (HR) = 2.347, 95% confidence interval (CI) 1.122 to 4.907, P = 0.023) and RIFLE failure (HR = 3.093, 95% CI 1.460 to 6.550, P = 0.003) were independent predictors for long-term patient mortality.

Conclusions
AKI development after cardiac surgery is associated mainly with post-operative variables, which ultimately could lead to a worst RIFLE class. Staging at the RIFLE injury and RIFLE failure class is associated with higher short- and long-term mortality in our population.