bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal, qualitative and quantitative exploration of daily life and need for rehabilitation among patients with high-grade gliomas and their caregivers
Authors: Piil K , Jarden M , Jakobsen J , Christensen K Bang , Juhler M 
Published: July 2013

IntroductionHigh-grade gliomas (HGGs) are the most malignant type of brain tumours. The 5-year survival is 10% and a significant part of the ongoing research aims to increase survival through surgical and oncological treatments. Accordingly, there is an increasing need for investigating the HGG trajectory in order to recommend specific guidelines for rehabilitative and supportive interventions.Method and analysisThis study protocol (phase I) describes a longitudinal, qualitative, explorative and descriptive interview study of the life situation and need for rehabilitation among patients and their caregivers and a quantitative evaluation of health-related quality of life. Qualitative and quantitative data are collected in parallel, analysed separately and then merged. The finding of this study will, together with the existing literature, form the background for phase II, which is a feasibility study with a pre-experimental one-group design testing a rehabilitative and supportive intervention programme. The aim of this paper was to describe the design of an upcoming study. Interviews with 30 patients and 30 caregivers will provide information about how the life situation is experienced during the first year after being diagnosed with HGG. Quantitative measurements of quality of life, well-being and physical activity will provide additional information. More precisely, both qualitative and quantitative data will support the planning of the programme regarding the type of intervention(s), with or without supervision, the appropriate time along the trajectory, frequency, localisation, endpoint measurements and eligible patients and/or caregivers.Ethics and disseminationAccording to the Research Ethics Committee, approval is not needed for phase I as it is a non-intervention part of the study. Ethical approval of phase II will be sought at the time where the content of the intervention programme has been developed. Dissemination will occur through presentation and findings will be published in peer-reviewed journals.
Transjugular intrahepatic portosystemic shunt for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: study protocol for a randomised controlled trial
Authors: Qi Xingshun , He Chuangye , Yin Zhanxin , Wang Zhengyu , Zhang Hongbo , Yao Liping , Wang Jianhong , Xia Jielai , Cai Hongwei , Yang Zhiping , Bai Ming , Guo Wengang , Niu Jing , Wu Kaichun , Fan Daiming , Han Guohong 
Published: July 2013

IntroductionPortal vein thrombosis (PVT) increases the risk of variceal rebleeding in liver cirrhosis. However, the strategy for preventing variceal rebleeding in cirrhotic patients with PVT has not been explored. This study aims to evaluate whether the transjugular intrahepatic portosystemic shunt (TIPS) or conventional therapy is preferable for the prevention of variceal rebleeding in liver cirrhosis patients with PVT.Methods and analysisThis is a randomised controlled trial comparing the safety and efficacy of TIPS versus conventional therapy (ie, endoscopic therapy combined with non-selective β-blockers and anticoagulants) for the prevention of variceal rebleeding in cirrhotic patients with non-tumoral PVT. A total of 50 cirrhotic patients with PVT (thrombus >50% of portal vein lumen occupancy) and a history of variceal bleeding will be stratified according to the Child-Pugh class and degree of PVT, and randomised into the TIPS and conventional therapy groups. The primary objective was to compare the incidence of variceal rebleeding between the two groups. The secondary objectives were to compare the overall mortality, variceal rebleeding-related mortality, portal vein recanalisation and complications between the two groups, and to observe the progression of PVT in patients without portal vein recanalisation.Ethics and disseminationThis study was approved by the ethics committee of Xijing hospital (No. 20110224-5), and was registered at ClinicalTrials.gov (NCT01326949). All participants give written informed consent. The first patient was recruited into our study on 4 June 2011. A total of 29 patients were recruited through 5 March 2013 (14 and 15 patients assigned to the TIPS and conventional therapy groups, respectively). If TIPS is superior to conventional therapy for the prevention of variceal rebleeding in cirrhotic patients with PVT, TIPS might be recommended as the first-line therapy in such patients. But a small sample size potentially limits the generalisation of our conclusions.Trial registrationThis study was registered at ClinicalTrials.gov on 29 March 2011. The trial registration number isNCT01326949.Trial statusThe first patient was recruited into our study on 4 June 2011. A total of 29 patients were recruited through 5 March 2013 (14 and 15 patients assigned to the TIPS and conventional therapy groups, respectively).
Segmentation and growth of foothill thrust-belts adjacent to inverted grabens: the case of the Colombian Llanos foothills
Authors: Jimenez L. , Mora A. , Casallas W. , Silva A. , Tesón E. , Tamara J. , Namson J. , Higuera-Díaz I. C. , Lasso A. , Stockli D. 
Published: July 2013

Abstract
The geometry, kinematics and evolution of thick- and thin-skinned fold and thrust-belts have been characterized for many tectonic provinces. However, the impact of prior extension in the structural evolution of fold and thrust-belts remains under-appreciated. We use a series of balanced cross sections across areas of thin- and thick-skinned tectonics superimposed over former extensional structures in order to characterize the style of deformation, segmentation and displacement magnitude. We detect the style of fault linkage in foothill settings adjacent to inversion belts. The most relevant aspect is the presence of inherited ‘soft linkages’ generating zones of displacement deficit, which in contraction interact laterally with en-echelon inverted segments via ‘detachment linkages’. We document the temporal development and interaction between inverted faults and fault splays branching from them where both are coeval but where the frontal fault tips propagate more slowly during Oligocene and Early Miocene times. Later, during the Neogene, the frontal fault splays slip faster than the main inversion fault. The structural style of thrust-belt development displays along-strike variations, which reflect the changes in sedimentation rates and mechanical conditions of deformation. However, the timing and magnitude of shortening remain uniform along-strike.
Volcano monitoring applications of the Ozone Monitoring Instrument
Authors: McCormick Brendan T. , Edmonds Marie , Mather Tamsin A. , Campion Robin , Hayer Catherine S. L. , Thomas Helen E. , Carn Simon A. 
Published: July 2013

Abstract

The Ozone Monitoring Instrument (OMI) is a satellite-based ultraviolet (UV) spectrometer with unprecedented sensitivity to atmospheric sulphur dioxide (SO
2
) concentrations. Since late 2004, OMI has provided a high-quality SO
2
dataset with near-continuous daily global coverage. In this review, we discuss the principal applications of this dataset to volcano monitoring: (1) the detection and tracking of large eruption clouds, primarily for aviation hazard mitigation; and (2) the use of OMI data for long-term monitoring of volcanic degassing. This latter application is relatively novel, and despite showing some promise, requires further study into a number of key uncertainties. We discuss these uncertainties, and illustrate their potential impact on volcano monitoring with OMI through four new case studies. We also discuss potential future avenues of research using OMI data, with a particular emphasis on the need for greater integration between various monitoring strategies, instruments and datasets.
Measuring global volcanic degassing with the Ozone Monitoring Instrument (OMI)
Authors: Carn S. A. , Krotkov N. A. , Yang K. , Krueger A. J. 
Published: July 2013

Abstract

The ultraviolet (UV) Ozone Monitoring Instrument (OMI), launched on NASA's Aura satellite in July 2004, was the first space-based sensor to provide operational sulphur dioxide (SO
2
) measurements (OMSO2) for use by the scientific community. Herein, we discuss the application of OMSO2 data for the monitoring of global volcanic SO
2
emissions, with an emphasis on lower tropospheric volcanic plumes. We review the algorithms used to produce OMSO2 data and highlight some key measurement sensitivity issues. The data processing scheme used to generate web-based OMSO2 data subsets for volcanic regions and estimate SO
2
burdens in volcanic plumes is outlined. We describe three techniques to derive SO
2
emission rates from the OMSO2 measurements, and employ one method (using single OMI pixels to estimate SO
2
fluxes) to elucidate SO
2
flux detection thresholds on a global scale. Applications of OMSO2 data to volcanic degassing studies are demonstrated using four case studies. These examples show how OMSO2 measurements correlate with changes in eruptive activity at Kilauea volcano (Hawaii), constrain small, potentially significant SO
2
releases from reawakening, historically inactive volcanoes, track long-term changes in SO
2
degassing from Nyiragongo volcano (D.R. Congo), and detect SO
2
emissions from the remote Lastarria Volcano (Chile), in the actively deforming Lazufre region.
microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2
Authors: Liao Wen-Ting , Li Ting-Ting , Wang Zheng-Gen , Wang Shu-Yang , He Mei-Rong , Ye Ya-Ping , Qi Lu , Cui Yan-Mei , Wu Ping , Jiao Hong-Li , Zhang Chi , Xie Yi-Jun , Wang Jun-Xian , Ding Yan-Qing 
Published: July 2013

Abstract
Purpose: To investigate the clinicopathologic significance, role, and mechanism of action of microRNA-224 (miR-224) in colorectal cancer.
Experimental Design: Real-time PCR was used to quantify miR-224 expression. The association of miR-224 with the clinicopathologic features and survival was evaluated in 110 colorectal cancer patients. The role of miR-224 in colorectal cancer was investigated using in vitro and in vivo assays. Luciferase reporter assays were conducted to confirm target gene associations.
Results: miR-224 was overexpressed in colorectal cancer. High-level expression of miR-224 was significantly associated with an aggressive phenotype and poor prognosis. Overexpression of miR-224 promoted colorectal cancer cell proliferation in vitro and tumor growth in vivo. Specifically, miR-224 accelerated the G1–S phase transition through activation of AKT/FOXO3a signaling, downregulation of p21Cip1 and p27Kip1, and upregulation of cyclin D1. Moreover, both PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, antagonists of PI3K/AKT signaling, were confirmed as bona fide targets of miR-224. miR-224 directly targeted the 3′-untranslated regions of the PHLPP1 and PHLPP2 mRNAs and repressed their expression.
Conclusion: This study reveals functional and mechanistic links between miRNA-224 and the tumor suppressors PHLPP1 and PHLPP2 in the pathogenesis of colorectal cancer. miR-224 not only plays important roles in the regulation of cell proliferation and tumor growth in colorectal cancer, but also has potential as a prognostic marker or therapeutic target for colorectal cancer. Clin Cancer Res; 19(17); 4662–72. ©2013 AACR.
The perioperative management of new direct oral anticoagulants: a question without answers
Authors: Castillo Jordi , Andrés José de , Gomar Carmen , Gómez-Luque Aurelio , Hidalgo Francisco , Llau Juan V. , Sierra Pilar , Torres Luis M. , Ferrandis Raquel 
Published: July 2013

SummaryNew direct oral anticoagulant agents (DOAC) are currently licensed for thromboprophylaxis after hip and knee arthroplasty and for longterm prevention of thromboembolic events in non-valvular atrial fibrillation as well as treatment and secondary prophylaxis of venous thromboembolism. Some other medical indications are emerging. Thus, anaesthesiologists are increasingly likely to encounter patients on these drugs who need elective or emergency surgery. Due to the lack of experience and data, the management of DOAC in the perioperative period is controversial. In this article, we review available information and recommendations regarding the periprocedural management of the currently most clinically developed DOAC, apixaban, dabigatran, and rivaroxaban. We discuss two trends of managing patients on DOAC for elective surgery. The first is stopping the DOAC 1–5 days before surgery (depending on the drug, patient and bleeding risk) without bridging. The second is stopping the DOAC 5 days preoperatively and bridging with low-molecular-weight heparin. The management of patients on DOAC needing emergency surgery is also reviewed. As no data exist for the use of haemostatic products for the reversal of the anticoagulant effect in these cases, rescue treatment recommendations are proposed.
Structural analysis of protein Z gene variants in patients with foetal losses
Authors: Caliandro Rocco , Nico Giovanni , Tiscia Giovanni , Favuzzi Giovanni , De Stefano Valerio , Rossi Elena , Margaglione Maurizio , Grandone Elvira 
Published: July 2013

SummaryThe role of protein Z (PZ) in the etiology of human disorders is unclear. A number of PZ gene variants, sporadic or polymorphic and found exclusively in the serine protease domain, have been observed. Crystal structures of PZ in complex with the PZ-dependent inhibitor (PZI) have been recently obtained. The aim of this study was a structural investigation of the serine protease PZ domain, aiming at finding common traits across disease-linked mutations. We performed 10–20 ns molecular dynamics for each of the observed PZ mutants to investigate their structure in aqueous solution. Simulation data were processed by novel tools to analyse the residue-by-residue backbone flexibility. Results showed that sporadic mutations are associated with anomalous flexibility of residues belonging to specific regions. Among them, the most important is a loop region which is in contact with the longest helix of PZI. Other regions have been identified, which hold anomalous flexibility associated with potentially protective gene variants. In conclusion, a possible interpretation of effects associated with observed gene variants is provided. The exploration of PZ/PZI interactions seems essential in explaining these effects.
Platelets are a previously unrecognised source of MIF
Authors: Wirtz Theresa , Bucala Richard , Hundelshausen Philipp von , Strüßmann Tim , Tillmann Sabine , Bernhagen Jürgen 
Published: July 2013

SummaryMacrophage migration inhibitory factor (MIF) is an inflammatory cytokine with chemokine-like functions and a role in atherogenesis. MIF is secreted by various cells including endothelial cells and macrophages. Platelets are another prominent cell type with a role in atherogenesis and are a rich source of atherogenic chemokines. We asked whether platelets express and secrete MIF. In comparison, CXCL12 release was determined. We examined the subcellular localisation of MIF in platelets/ megakaryocytes, studied its co-localisation with other plateletderived mediators and asked whether platelets contain MIF mRNA. Moreover, we probed the functional role of platelet-derived MIF in inflammatory cell recruitment. Using Western blot and ELISA, we demonstrated and quantitated MIF protein in human and mouse platelets. Applying confocal-microscopy, MIF was found to localise in granularlike structures, but did not co-localise with known platelet cytokines. qPCR indicated that platelets contain low levels of MIF mRNA. ELISA measurements from human platelet supernatants showed that, whereas thrombin and collagen triggered the release of MIF and CXCL12, ADP and oxidised LDL promoted CXCL12 but not MIF secretion. Using Transwell assays, we demonstrated that platelet supernatants promoted monocyte chemotaxis and that this was blocked by neutralising MIF antibodies. This is the first report demonstrating MIF secretion from activated platelets, suggesting that platelets are a previously unrecognised source of MIF in inflammatory processes. There are distinct activating stimuli for MIF and CXCL12 secretion. A substantial portion of the chemotactic capacity of stimulated platelet supernatants is contributed by MIF, suggesting a role for platelet-derived MIF in atherogenic cell recruitment.
Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism
Authors: Alfonso Ana , Jiménez David , Capitán Carmen Fernández , Prandoni Paolo , Wells Philip S. , Vidal Gemma , Barillari Giovanni , Monreal Manuel , Lecumberri Ramón ,   and the RIETE Investigators
Published: July 2013

SummaryIn patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a ‘real life’ population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 ± 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% CI, 10.2–14.2) for recurrent VTE, and 19.7% (95% CI, 17.4–22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% CI, 13.6–18.9), compared to 2.0% (95% CI, 0–4.2) beyond this period. The CFR of bleeding was 20.2% (95% CI, 17.5–23.1) during the first three months, compared to 18.2% (95% CI, 14.0–23.2) beyond this period. The CFR of recurrent VTE was higher in patients initially presenting with PE (18.5%; 95% CI, 15.3–22.1) than in those with DVT (6.3%; 95% CI, 4.5–8.6), and in patients with provoked VTE (16.3%; 95% CI, 13.6–19.4) than in those with unprovoked VTE (5.5%; 95% CI, 3.5–8.0). In conclusion, the CFR of recurrent VTE decreased over time during anticoagulation, while the CFR of major bleeding remained stable. The CFR of recurrent VTE was higher in patients initially presenting with PE and in those with provoked VTE.
Hepatic Remnant Lipoprotein Clearance by Heparan Sulfate Proteoglycans and Low-Density Lipoprotein Receptors Depend on Dietary Conditions in Mice
Authors: Foley Erin M. , Gordts Philip L.S.M. , Stanford Kristin I. , Gonzales Jon C. , Lawrence Roger , Stoddard Nicole , Esko Jeffrey D. 
Published: July 2013

Objective—
Chylomicron and very low-density lipoprotein remnants are cleared from the circulation in the liver by heparan sulfate proteoglycan (HSPG) receptors (syndecan-1), the low-density lipoprotein receptor (LDLR), and LDLR-related protein-1 (LRP1), but the relative contribution of each class of receptors under different dietary conditions remains unclear.

Approach and Results—

Triglyceride-rich lipoprotein clearance was measured in
AlbCre
+
Ndst1
f/f
,
Ldlr
−/−
, and
AlbCre
+
Lrp1
f/f
mice and mice containing combinations of these mutations. Triglyceride measurements in single and double mutant mice showed that HSPGs and LDLR dominate clearance under fasting conditions and postprandial conditions, but LRP1 contributes significantly when LDLR is absent. Mice lacking hepatic expression of all 3 receptors (
AlbCre
+
Ndst1
f/f
Lrp1
f/f
Ldlr
−/−
) displayed dramatic hyperlipidemia (870±270 mg triglyceride/dL; 1300±350 mg of total cholesterol/dL) and exhibited persistent elevated postprandial triglyceride levels because of reduced hepatic clearance. Analysis of the particles accumulating in mutants showed that HSPGs preferentially clear a subset of small triglyceride-rich lipoproteins (≈20–40 nm diameter), whereas LDLR and LRP1 clear larger particles (≈40–60 nm diameter). Finally, we show that HSPGs play a major role in clearance of triglyceride-rich lipoproteins in mice fed normal chow or under postprandial conditions but seem to play a less significant role on a high-fat diet.

Conclusions—
These data show that HSPGs, LDLR, and LRP1 clear distinct subsets of particles, that HSPGs work independently of LDLR and LRP1, and that HSPGs, LDLR, and LRP1 are the 3 major hepatic triglyceride-rich lipoprotein clearance receptors in mice.
Cyclophilin A Is Required for Angiotensin II–Induced p47phox Translocation to Caveolae in Vascular Smooth Muscle Cells
Authors: Soe Nwe Nwe , Sowden Mark , Baskaran Padmamalini , Smolock Elaine M. , Kim Yeonghwan , Nigro Patrizia , Berk Bradford C. 
Published: July 2013

Objective—

Angiotensin II (AngII) signal transduction in vascular smooth muscle cells (VSMC) is mediated by reactive oxygen species (ROS). Cyclophilin A (CyPA) is a ubiquitously expressed cytosolic protein that possesses peptidyl-prolyl
cis-trans
isomerase activity, scaffold function, and significantly enhances AngII-induced ROS production in VSMC. We hypothesized that CyPA regulates AngII-induced ROS generation by promoting translocation of NADPH oxidase cytosolic subunit p47phox to caveolae of the plasma membrane.

Approach and Results—

Overexpression of CyPA in CyPA-deficient VSMC (CyPA
−/−
VSMC) significantly increased AngII-stimulated ROS production. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors (VAS2870 or diphenylene iodonium) significantly attenuated AngII-induced ROS production in CyPA and p47phox-overexpressing CyPA
−/−
VSMC. Cell fractionation and sucrose gradient analyses showed that AngII-induced p47phox plasma membrane translocation, specifically to the caveolae, was reduced in CyPA
−/−
VSMC compared with wild-type–VSMC. Immunofluorescence studies demonstrated that AngII increased p47phox and CyPA colocalization and translocation to the plasma membrane. In addition, immunoprecipitation of CyPA followed by immunoblotting of p47phox and actin showed that AngII increased CyPA and p47phox interaction. AngII-induced p47phox and actin cell cytoskeleton association was attenuated in CyPA
−/−
VSMC. Mechanistically, inhibition of p47phox phosphorylation and phox homology domain deletion attenuated CyPA and p47phox interaction. Finally, cyclosporine A and CyPA-peptidyl-prolyl
cis-trans
isomerase mutant, R55A, inhibited AngII-stimulated CyPA and p47phox association in VSMC, suggesting that peptidyl-prolyl
cis-trans
isomerase activity was required for their interaction.

Conclusions—
These findings provide the mechanism by which CyPA is an important regulator for AngII-induced ROS generation in VSMC through interaction with p47phox and cell cytoskeleton, which enhances the translocation of p47phox to caveolae.
Le juge et la coutume internationale : perspective de l’Union européenne et de la Cour de justice
Authors: Malenovský Jiří 
Published: July 2013

Abstract
Jiří Malenovský presents the perspective of the European Union (EU) and of the Court of Justice of the European Union (CJEU) with regard to the issue of the judge and international custom. His presentation focuses notably on (I) the EU’s contribution to the formation of customary rules and on (II) the various approaches taken by the CJEU over time as to the binding force of international custom in the EU’s legal order. Furthermore, Jiří Malenovský illustrates (III) the various degrees of openness towards international custom in the case-law of the CJEU. He also presents (IV) the criteria used by the CJEU in its cautious attempts to identify both the existence and the content of the rules of international customary law. Finally, he provides information with regard to (V) the CJEU’s evaluation of the direct effect/applicability and enforceability of customary international rules.