bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate Antimetastasis Drugs Suppress the Metastatic Capacity of Breast Cancer Cells by Reducing Membrane Fluidity
Authors: Zhao Weina , Prijic Sara , Urban Bettina C. , Tisza Michael J. , Zuo Yan , Li Lin , Tan Zhi , Chen Xiaoling , Mani Sendurai A. , Chang Jeffrey T. 
Published: January 2016

Abstract
Despite the high mortality from metastatic cancer, therapeutic targets to prevent metastasis are limited. Efforts to identify genetic aberrations that predispose tumors to metastasis have been mostly unsuccessful. To understand the nature of candidate targets for metastatic disease, we performed an in silico screen to identify drugs that can inhibit a gene expression signature associated with epithelial–mesenchymal transition (EMT). Compounds discovered through this method, including those previously identified, appeared to restrict metastatic capacity through a common mechanism, the ability to modulate the fluidity of cell membranes. Treatment of breast cancer cell lines with the putative antimetastasis agents reduced membrane fluidity, resulting in decreased cell motility, stem cell–like properties, and EMT in vitro, and the drugs also inhibited spontaneous metastasis in vivo. When fluidity was unchanged, the antimetastasis compounds could no longer restrict metastasis, indicating a causal association between fluidity and metastasis. We further demonstrate that fluidity can be regulated by cellular cholesterol flux, as the cholesterol efflux channel ABCA1 potentiated metastatic behaviors in vitro and in vivo. The requirement for fluidity was further supported by the finding in breast cancer patients that ABCA1 was overexpressed in 41% of metastatic tumors, reducing time to metastasis by 9 years. Collectively, our findings reveal increased membrane fluidity as a necessary cellular feature of metastatic potential that can be controlled by many currently available drugs, offering a viable therapeutic opportunity to prevent cancer metastasis. Cancer Res; 76(7); 2037–49. ©2016 AACR.
Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer
Authors: Regan Anderson Tarah M. , Ma Shi Hong , Raj Ganesh V. , Cidlowski John A. , Helle Taylor M. , Knutson Todd P. , Krutilina Raisa I. , Seagroves Tiffany N. , Lange Carol A. 
Published: January 2016

Abstract
Cancer cells use stress response pathways to sustain their pathogenic behavior. In breast cancer, stress response–associated phenotypes are mediated by the breast tumor kinase, Brk (PTK6), via the hypoxia-inducible factors HIF-1α and HIF-2α. Given that glucocorticoid receptor (GR) is highly expressed in triple-negative breast cancer (TNBC), we investigated cross-talk between stress hormone–driven GR signaling and HIF-regulated physiologic stress. Primary TNBC tumor explants or cell lines treated with the GR ligand dexamethasone exhibited robust induction of Brk mRNA and protein that was HIF1/2–dependent. HIF and GR coassembled on the BRK promoter in response to either hypoxia or dexamethasone, indicating that Brk is a direct GR/HIF target. Notably, HIF-2α, not HIF-1α, expression was induced by GR signaling, and the important steroid receptor coactivator PELP1 was also found to be induced in a HIF-dependent manner. Mechanistic investigations showed how PELP1 interacted with GR to activate Brk expression and demonstrated that physiologic cell stress, including hypoxia, promoted phosphorylation of GR serine 134, initiating a feed-forward signaling loop that contributed significantly to Brk upregulation. Collectively, our findings linked cellular stress (HIF) and stress hormone (cortisol) signaling in TNBC, identifying the phospho-GR/HIF/PELP1 complex as a potential therapeutic target to limit Brk-driven progression and metastasis in TNBC patients. Cancer Res; 76(6); 1653–63. ©2016 AACR.
Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization
Authors: Boussemart Lise , Girault Isabelle , Malka-Mahieu Hélène , Mateus Christine , Routier Emilie , Rubington Margot , Kamsu-Kom Nyam , Thomas Marina , Tomasic Gorana , Agoussi Sandrine , Breckler Marie , Laporte Mélanie , Lacroix Ludovic , Eggermont Alexander M. , Cavalcanti Andrea , Grange Florent , Adam Julien , Vagner Stéphan , Robert Caroline 
Published: January 2016

Abstract
BRAF inhibitors (BRAFi) elicit therapeutic responses in metastatic melanoma, but alarmingly, also induce the formation of secondary benign and malignant skin tumors. Here, we report the emergence and molecular characterization of 73 skin and extracutaneous tumors in 31 patients who underwent BRAFi therapy. The majority of patients presented with classic epidermal tumors such as verrucous papillomas, keratoacanthomas, and squamous cell carcinomas (SCC). However, 15 patients exhibited new or rapidly progressing tumors distinct from these classic subtypes, such as lymph node metastasis, new melanomas, and genital and oral mucosal SCCs. Genotyping of the tumors revealed that oncogenic RAS mutations were found in 58% of the evaluable tumor samples (38/66) and 49% of the control tumors from patients not treated with BRAFi (30/62). Notably, proximity ligation assays demonstrated that BRAF–CRAF heterodimerization was increased in fixed tumor samples from BRAFi-treated patients compared with untreated patients. Our findings reveal that BRAF–CRAF complex formation is significantly associated with BRAFi treatment, and may therefore serve as a useful biomarker of BRAFi-induced cutaneous and extracutaneous tumor formation. Cancer Res; 76(6); 1476–84. ©2016 AACR.
Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia/Reperfusion
Authors: Santos-Gallego Carlos G. , Vahl Torsten P. , Goliasch Georg , Picatoste Belen , Arias Teresa , Ishikawa Kiyotake , Njerve Ida U. , Sanz Javier , Narula Jagat , Sengupta Partho P. , Hajjar Roger J. , Fuster Valentin , Badimon Juan J. 
Published: January 2016

Background—
Fingolimod, a sphingosine-1-phosphate receptor agonist, is used for the treatment of multiple sclerosis and exerts antiapoptotic properties. We hypothesized that sphingosine-1-phosphate receptor activation with fingolimod during acute myocardial infarction (MI) inhibits apoptosis, leading to increased myocardial salvage, reduced infarct size, and mitigated left ventricular (LV) remodeling in a porcine model of ischemia/reperfusion.

Methods and Results—
Ischemia/reperfusion was induced in pigs by balloon occlusion of the left anterior descending artery, followed by reperfusion. Animals randomly received fingolimod or saline (control). In short-term experiments, fingolimod treatment activated the cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways in the infarct border zone 24 hours after MI, leading to decreased cardiomyocyte apoptosis and reduced myocardial oxidative stress. These effects were abolished by specific inhibitors of both pathways, demonstrating that fingolimod-induced cardioprotection was mediated by reperfusion injury salvage kinase and survivor activating factor enhancement pathways. In long-term experiments, fingolimod significantly improved myocardial salvage, reduced infarct size, and improved systolic LV function measured by cardiac magnetic resonance 1 week and 1 month after MI. Importantly, fingolimod mitigated the development of adverse post-MI LV remodeling 1 month after MI. Specifically, fingolimod treatment led to a significant reduction in LV mass, LV dilatation, and neurohormonal activation, and it preserved LV geometry. Furthermore, fingolimod decreased interstitial fibrosis, cardiomyocyte hypertrophy, and chronic activation of Akt and extracellular receptor kinase 1/2 in the remote noninfarcted myocardium.

Conclusions—
Sphingosine-1-phosphate receptor activation with fingolimod during acute MI reduced infarct size via the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, improved systolic LV function, and mitigated post-MI LV remodeling. Our data strongly support a cardioprotective role for sphingosine-1-phosphate receptor activation during MI.
Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Delcroix Marion , Lang Irene , Pepke-Zaba Joanna , Jansa Pavel , D’Armini Andrea M. , Snijder Repke , Bresser Paul , Torbicki Adam , Mellemkjaer Sören , Lewczuk Jerzy , Simkova Iveta , Barberà Joan A. , de Perrot Marc , Hoeper Marius M. , Gaine Sean , Speich Rudolf , Gomez-Sanchez Miguel A. , Kovacs Gabor , Jaïs Xavier , Ambroz David , Treacy Carmen , Morsolini Marco , Jenkins David , Lindner Jaroslav , Dartevelle Philippe , Mayer Eckhard , Simonneau Gérald 
Published: January 2016

Background—
Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension.

Methods and Results—

A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90–95), 91% (95% CI, 87–93), and 89% (95% CI, 86–92) in operated patients (n=404), and only 88% (95% CI, 83–91), 79% (95% CI, 74–83), and 70% (95% CI, 64–76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension–targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49–11.62;
P
=0.0065 and HR, 4.76; 95% CI, 1.76–12.88;
P
=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95–1.90;
P
=0.0992 and HR, 1.50; 95% CI, 1.20–1.88;
P
=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36–6.69;
P
=0.0065 and HR, 2.15; 95% CI, 1.18–3.94;
P
=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension–targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients.

Conclusions—
The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients.
Development of real-time PCR primers for the quantification of Meloidogyne graminicola, Hirschmanniella oryzae and Heterodera cajani, pests of the major crops in Myanmar
Authors: Katsuta Akane , Toyota Koki , Min Yu Yu , Maung The Thiri 
Published: January 2016

The rice root-knot nematode,Meloidogyne graminicola, and the rice root nematode,Hirschmanniella oryzae, are soil-borne pests causing damage to rice, and the pigeon pea cyst nematode,Heterodera cajani, is a pest to beans and sesame. Real-time PCR primers were designed for quantification. Relationships between the threshold cycle (Ct:y) values and number (no.) of nematodes inoculated () were:M. graminicola: ;H. oryzae: ; andH. cajani: .Meloidogyne graminicolaandH. oryzaewere detected in 25 and 38 out of 50 soils, collected from different fields in the lowland and central area of Myanmar, and their densities ranged from 1.0 to 4779 and from 0.4 to 787 (20 g soil)−1, respectively, whileH. cajaniwas detected only in two fields (3 and 268 (20 g soil)−1). The DNA-based method enables rapid and reliable quantification of the nematodes in soil.
The Development and Evaluation of Countermeasures to Tactile Change Blindness
Authors: Riggs Sara Lu , Sarter Nadine 
Published: January 2016

Objective: The goal of the present study was to develop and empirically evaluate three countermeasures to tactile change blindness (where a tactile signal is missed in the presence of a tactile transient). Each of these countermeasures relates to a different cognitive step involved in successful change detection. Background: To date, change blindness has been studied primarily in vision, but there is limited empirical evidence that the tactile modality may also be subject to this phenomenon. Change blindness raises concerns regarding the robustness of tactile and multimodal interfaces. Method: Three countermeasures to tactile change blindness were evaluated in the context of a highly demanding monitoring task. One countermeasure was proactive (alerting the participant to a possible change before it occurred) whereas the other two were adaptive (triggered after the change upon an observed miss). Performance and subjective data were collected. Results: Compared to the baseline condition, all countermeasures improved intramodal tactile change detection. Adaptive measures resulted in the highest detection rates, specifically when signal gradation was employed (i.e., when the intensity of the tactile signal was increased after a miss was observed). Conclusion: Adaptive displays can be used to counter the effects of change blindness and ensure that tactile information is reliably detected. Increasing the tactile intensity after a missed change appears most promising and was the preferred countermeasure. Application: The findings from this study can inform the design of interfaces employing the tactile modality to support monitoring and attention management in data-rich domains.
Sensemaking and the political–administrative interface: the challenges of strategically steering and managing a local public service
Authors: Audette-Chapdelaine Marianne 
Published: January 2016

Our study focuses on the relationship between elected officials and managers in the context of local services management. We analyse the political–administrative interface using Weick’s theory of sensemaking. Our research, based on the case of water services management in Montreal, shows that the loss of expertise in the public sector, coupled with a lack of political vision, leads to a mismatch between the actions envisaged by the managers and the resources available. The organizational purpose needs to be politically defined in order to achieve a reciprocal influence in policy making. This collaboration, or complementarity of politics and administration, allows shared sensemaking that is essential both to a management diagnosis in line with the organizational mission and to strategic decision-making which takes into account the civil servants’ recommendations. Points for practitioners Some urban infrastructures, such as water infrastructure, are neither easily visible nor accessible. Thus, there is sometimes a wide gap between managers’ interpretation of the situation and that of the citizens and elected officials. This is a challenge for the development of common sensemaking. Elected officials must be able to count on a competent civil service that provides them with reliable information, enabling them to make trade-offs with all the relevant facts at hand. It is also in the public interest that elected officials maintain strategic control of the water activity in order for public action to efficiently contribute to the political vision.
Development and validation of parallel short forms PaSA-cardio for the assessment of general anxiety in cardiovascular rehabilitation patients using Rasch analysis
Authors: Abberger Birgit , Haschke Anne , Tully Phillip J , Forkmann Thomas , Berger Janna , Wirtz Markus , Bengel Juergen , Baumeister Harald 
Published: January 2016

Objective: To develop and validate parallel short forms for the assessment of general anxiety in cardiovascular rehabilitation patients, that facilitate repeated measurement over time without contamination from residual practice effect variance. Design: Development of the parallel short forms using Rasch analysis. Validation study. Setting: Cardiac rehabilitation centres in Germany. Subjects: Cardiovascular rehabilitation patients. Interventions: Not applicable. Main measures: Parallel short forms PaSA-cardio, Hospital Anxiety and Depression Scale, Short Form Health Survey SF-12 and Structured Clinical Interview for DSM-IV Axis I Disorders. Results: Each version of the parallel short forms (PaSA-cardio-I and PaSA-cardio-II) comprises ten items. The two forms fitted to the Rasch model with a non-significant item–trait interaction (PaSA-cardio-I: chi-square = 39.49, degrees of freedom = 30, probability = 0.12; PaSA-cardio-II: chi-square = 26.56, degrees of freedom = 30, probability = 0.65). Person-separation reliability was 0.75/0.76. Unidimensionality could be verified. Correlation between the two models was 0.94 and 0.95, and correlations with the underlying item bank were 0.95 and 0.93. Validity could be confirmed. The area under the curve was between 0.88 and 0.97 for PaSA-cardio-I and between 0.92 and 0.95 for PaSA-cardio-II. Conclusions: Assessment of general anxiety in cardiovascular rehabilitation patients with the PaSA-cardio was valid, economical and accurate. The two forms of the PaSA-cardio are equivalent and allow retest without contamination from residual practice effect variance.
Dynamics of a haemodynamic headache: A case report and literature review of headache secondary to flow inversion of the internal jugular vein
Authors: Pereira Liliana , Campos Costa Elisa , Nunes Teresa , Saraiva Paulo , Ferreira Joel , Cruz Pedro , Rodrigues Miguel 
Published: January 2016

Background Haemodialysis arteriovenous fistulas have common local and regional complications, but are rarely associated with neurological symptoms. Case report A 43-year-old woman presented with short acute episodes of unilateral, non-throbbing, severe headache, vertigo and left lateropulsion. She had undergone renal transplantation and had a still-functioning left brachial arteriovenous fistula. No abnormality was detected on neurological examination or on brain parenchymal imaging. Colour Doppler ultrasonography showed a subclavian steal syndrome of the left vertebral artery and reversed flow in the left internal jugular vein. Ligation of the arteriovenous fistula had to be delayed as a result of renal graft dysfunction. Six months later she developed a headache attributed to intracranial hypertension. All symptoms subsided after ligation of the arteriovenous fistula. Literature review We identified 16 case reports of central neurological complications attributed to haemodialysis brachial fistulas. Headache descriptions were scarce and were not fully detailed. Conclusions The case of our patient suggests that unilateral, episodic, non-throbbing, non-postural headache with transient neurological symptoms can be caused by combined arterial and venous flow abnormalities secondary to a high-flow arteriovenous brachial fistula. In this setting, this pattern of headache may precede overt signs of intracranial hypertension and may be used as a warning sign of cerebral venous congestion.
Human rights conflicts experienced by nurses migrating between developed countries
Authors: Palese Alvisa , Dobrowolska Beata , Squin Anna , Lupieri Giulia , Bulfone Giampiera , Vecchiato Sara 
Published: January 2016

Background: Some developed countries have recently changed their role in the context of international recruitment, becoming donors due to socio-economical and political factors such as recessions. This is also the case in Italy, where there has been a flow of immigrant nurses out of the country that has been documented over the past several years. In a short time, it has become a donor country to other developed European countries, such as the United Kingdom. Aims: To advance knowledge in the context of human rights conflicts and ethical implications of the decision-making process of nurses who migrate between developed countries, such as from Italy to the United Kingdom, during times of recession. Research design: A case study based on the descriptive phenomenological approach was undertaken in 2014. Participants and research context: A total of 26 Italian newly graduated nurses finding a job in the United Kingdom were interviewed via Skype and telephone. Ethical considerations: The Internal Review Board of the University approved the project. Findings: In accordance with the descriptive phenomenological approach undertaken, three main themes emerged: (1) escaping from the feeling of being refused/rejected in order to be desired, (2) perceiving themselves respected, as a person and as a nurse, in a growth project and (3) returning if the country changes its strategy regarding nurses. Discussion: Ethical implications in the context of human rights, such as autonomy of the decision, social justice and reciprocal obligation, non-maleficence and double effect, have been discussed. Conclusion: The call for investing in nurses and nurses’ care in developed countries facing recession is urgent. Investing in nurses means respecting individuals and citizens who are at risk of developing health problems during the recession.
Deprivileging the public sector workforce: Austerity, fragmentation and service withdrawal in Britain
Authors: Bach Stephen 
Published: January 2016

AbstractThe impact of the financial crisis has reignited debate about the scope and scale of public sector restructuring and its consequences for the workforce in Britain. The economic crisis precipitated austerity measures concentrated on expenditure reductions with the intention of reducing the public deficit. Because the public sector pay bill comprises over half of current public spending, achieving deficit reduction has major consequences for the total pay bill and the workforce. This article assesses the restructuring of the public sector and public sector employment relations in Britain and identifies underlying continuities in public sector restructuring over recent decades. Drawing on and repositioning New Labour’s legacy, the Coalition government used the economic crisis to establish a pro-austerity frame that has legitimated deep cuts in public sector employment and involved measures to refashion public sector employment relations. The article considers the consequences of this agenda and responses by trade unions and indicates some of the limits and uncertain prospects for public sector restructuring under conditions of austerity.
Parachordal fistula – a case report and a short review
Authors: Augusto Luís , Figueiredo Rita , Parreira Tiago , Silva Maria Luís , Pérez-Higueras Antonio 
Published: January 2016

Arteriovenous shunts of the neck and facial region rarely involve the external carotid artery and its branches. Most cases are considered to be iatrogenic or related to trauma but congenital shunts are rare. Parachordal arteriovenous fistulae are a group of embryologically derived arteriovenous shunts caused by defects involving the notochord, giving rise to cranial and paraspinal shunts. In the cranial regions, these shunts involve exclusively the metameric arteries – maxillary, ascending pharyngeal, occipital and vertebral. Signs and symptoms are variable, depending on the feeding vessel but also on the characteristics of the draining pathway. We report the case of a 17-year-old male patient with a shunt between the right internal maxillary artery and right external jugular vein detected at the age of 6, not associated with trauma, which we decided to treat because of an enlargement of the right cardiac atrium detected on routine examination. Digital subtraction angiography was performed to characterize the shunt followed by partial embolization with ballooning, coiling and Onyx injection. Echographic control 6 months after the procedure was compatible with complete occlusion of the shunt. We also perform a short review on this extremely rare entity.