bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive Oxygen Species Can Provide Atheroprotection via NOX4-Dependent Inhibition of Inflammation and Vascular Remodeling
Authors: Gray Stephen P. , Di Marco Elyse , Kennedy Kit , Chew Phyllis , Okabe Jun , El-Osta Assam , Calkin Anna C. , Biessen Erik A.L. , Touyz Rhian M. , Cooper Mark E. , Schmidt Harald H.H.W. , Jandeleit-Dahm Karin A.M. 
Published: December 2015

Objective—
Oxidative stress is considered a hallmark of atherosclerosis. In particular, the superoxide-generating type 1 NADPH oxidase (NOX1) has been shown to be induced and play a pivotal role in early phases of mouse models of atherosclerosis and in the context of diabetes mellitus. Here, we investigated the role of the most abundant type 4 isoform (NOX4) in human and mouse advanced atherosclerosis.

Approach and Results—

Plaques of patients with cardiovascular events or established diabetes mellitus showed a surprising reduction in expression of the most abundant but hydrogen peroxide (H
2
O
2
)-generating type 4 isoform (Nox4), whereas Nox1 mRNA was elevated, when compared with respective controls. As these data suggested that NOX4-derived reactive oxygen species may convey a surprisingly protective effect during plaque progression, we examined a mouse model of accelerated and advanced diabetic atherosclerosis, the streptozotocin-treated
ApoE
−/−
mouse, with (
NOX4
−/−
) and without genetic deletion of Nox4. Similar to the human data, advanced versus early plaques of wild-type mice showed reduced Nox4 mRNA expression. Consistent with a rather protective role of NOX4-derived reactive oxygen species,
NOX4
−/−
mice showed increased atherosclerosis when compared with wild-type mice. Deleting NOX4 was associated with reduced H
2
O
2
forming activity and attenuation of the proinflammatory markers, monocyte chemotratic protein-1, interleukin-1β, and tumor necrosis factor-α, as well as vascular macrophage accumulation. Furthermore, there was a greater accumulation of fibrillar collagen fibres within the vascular wall and plaque in diabetic
Nox4
−/−
ApoE
−/−
mice, indicative of plaque remodeling. These data could be replicated in human aortic endothelial cells in vitro, where Nox4 overexpression increased H
2
O
2
and reduced the expression of pro-oxidants and profibrotic markers. Interestingly, Nox4 levels inversely correlated with Nox2 gene and protein levels. Although NOX2 is not constitutively active unlike NOX4 and forms rather superoxide, this opens up the possibility that at least some effects of NOX4 deletion are mediated by NOX2 activation.

Conclusions—

Thus, the appearance of reactive oxygen species in atherosclerosis is apparently not always a nondesirable oxidative stress, but can also have protective effects. Both in humans and in mouse, the H
2
O
2
-forming NOX4, unlike the superoxide-forming NOX1, can act as a negative modulator of inflammation and remodeling and convey atheroprotection. These results have implications on how to judge reactive oxygen species formation in cardiovascular disease and need to be considered in the development of NOX inhibitory drugs.
Novel Pulse Oximetry Sonifications for Neonatal Oxygen Saturation Monitoring
Authors: Hinckfuss Kelly , Sanderson Penelope , Loeb Robert G. , Liley Helen G. , Liu David 
Published: December 2015

Objective We aimed to test whether the use of novel pulse oximetry sounds ( sonifications) better informs listeners when a neonate’s oxygen saturation (SpO2) deviates from the recommended range. Background Variable-pitch pulse oximeters do not accurately inform clinicians via sound alone when SpO2 is outside the target range of 90% to 95% for neonates on supplemental oxygen. Risk of blindness, organ damage, and death increase if SpO2 remains outside the target range. A more informative sonification may improve clinicians’ ability to maintain the target range. Method In two desktop experiments, nonclinicians’ ability to detect SpO2 range and direction of change was tested with novel versus conventional sonifications of simulated patient data. In Experiment 1, a “shoulder” sonification used larger pitch differences between adjacent saturation percentages for SpO2 values outside the target range. In Experiment 2, a “beacon” sonification used equal-appearing pitch differences, but when SpO2 was outside the target range, a fixed-pitch reference tone from the center of the target SpO2 range preceded every fourth pulse tone. Results The beacon sonification improved range identification accuracy over the control display (85% vs. 60%; p < .001), but the shoulder sonification did not (55% vs. 52%). Conclusion The beacon provided a distinct auditory alert and reference that significantly improved nonclinical participants’ ability to identify SpO2 range. Application Adding a beacon to the variable-pitch pulse oximeter sound may help clinicians identify when, and by how much, a neonate’s SpO2 deviates from the target range, particularly during patient transport situations when auditory information becomes essential.
Performance indicators and the new governmentality of water utilities in France
Authors: Renou Yvan 
Published: December 2015

This article aims to examine the potential transformation of practices triggered by the introduction of performance indicators in the water utilities in France in the late 2000s. We show that the transformative dynamic that, on the face of it, is brought about by this new governance tool is put into question by the multitude of brakes (political, economic, social and environmental) impeding its deployment. The article analyses the limits of the system by applying Foucault’s governmentality approach, defined by the analytical framework of the management tools as reformulated by Lascoumes and Le Galès. Points for practitioners In particular, following the adoption of the Water Framework Directive in 2000, European states have had to streamline their drinking water and sanitation utilities. New methods of regulation, borrowing more markedly than in the past from market logics, have thus gradually taken hold. In this article, we examine the controversial performance indicators of the water and sanitation utilities, whose effectiveness and legitimacy are regularly questioned. We seek to clarify the structuring of the current debate and identify possible ways to improve their functioning on the basis of the French case.
The ‘local turn’ in historical perspective: two city case studies in Britain and Germany
Authors: Hackett Sarah E. 
Published: December 2015

This article addresses the ‘local turn’ of migration and integration policies in historical perspective in Newcastle upon Tyne and Bremen. It draws upon a wide range of government documentation and offers a comparative assessment of both cities’ policies from the 1960s onwards. It discusses the vertical dimension of policymaking though an exploration of the local governance of migrant integration in relation to the national level. Although Britain and Germany's post-war immigration histories and political structures have often been perceived as contrasting, this article reveals a convergence in these cities’ governments’ approaches to their own local diverse societies. These case studies question the long-term impact of overarching national constitutional structures on city-level migration policies. Findings are framed within the local governance and multi-level governance MLG debates. Points for practitioners European cities are increasingly being recognized for the role they play in devising and implementing their own migration and integration policies. Yet very little is known about the relationship between this ‘local turn’ and multi-level governance (MLG). Practitioners can learn more about cities’ policymaking processes and the extent to which these have been influenced by national agendas, as well as about how research of a historical and cross-country and cross-city nature can inform the on-going policy debate.
Detecting Residual/Recurrent Head Neck Squamous Cell Carcinomas Using PET or PET/CT
Authors: Cheung Phylannie K. F. , Chin Ronald Y. , Eslick Guy D. 
Published: December 2015

ObjectiveTo evaluate the diagnostic accuracy of positron emission tomography (PET) and PET/computed tomography (CT) for detecting residual and/or recurrent local and regional disease and distant metastases in patients with head and neck squamous cell carcinomas (HNSCCs) following radiotherapy with or without chemotherapy.Data SourcesA systematic review with no language restrictions was conducted using PREMEDLINE, MEDLINE, EMBASE, and Google Scholar.Review MethodsOnly prospective studies with histopathological and/or clinical follow‐up that assessed the diagnostic accuracy of PET and PET/CT in detecting residual and/or recurrent disease following radiotherapy with or without chemotherapy in patients with HNSCCs were included.ResultsTwenty‐seven studies were identified. The pooled sensitivity and specificity of PET and PET/CT for detecting residual or recurrent disease at the primary site was 86.2% and 82.3%, respectively. For residual and recurrent neck disease, the sensitivity and specificity were 72.3% and 88.3%, while for distant metastases, the values were 84.6% and 94.9%.ConclusionsPET and PET/CT are highly accurate in detecting residual and/or recurrent HNSCC. PET/CT is more specific than PET alone. Specificity is also greater for scans performed more than 12 weeks after radiotherapy with or without chemotherapy. The authors support the use of PET/CT after 12 weeks posttreatment for the assessment of residual or recurrent disease.
The impact of an end-of-life healthcare ethics educational intervention
Authors: Molloy Claire , McCarthy Joan , Tyrrell Mark 
Published: December 2015

Background The impact of healthcare ethics educational interventions on participants’ ethical development is rarely reported on and assessed; even less attention is paid to educational interventions that focus on end-of-life ethical issues. Aim To evaluate the impact of the Ethical Framework for End-of-Life Care Study Sessions Programme ( EOLCSS) on the moral development of healthcare staff who are delivering end-of-life care. Methods The EOLCSS was delivered to 20 multi-disciplinary health care staff in Ireland in May 2013. Effect on moral reasoning was measured pre and post education using the Defining Issues Test 2 (DIT2). Inferential statistics were used to examine the relationships between change in DIT2 scores and demographic variables. Results Participants experienced moral reasoning development following receipt of EOLCSS. Age and previous ethics education contributed to the observed changes in moral reasoning. Conclusions Receipt of the EOLCSS may contribute to moral reasoning development in practicing healthcare professionals.
Cardiac ACE2/angiotensin 1–7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy
Authors: Diniz Gabriela P. , Senger Nathalia , Carneiro-Ramos Marcela S. , Santos Robson A. S. , Barreto-Chaves Maria Luiza M. 
Published: December 2015

Objectives: Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin–angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1–7 (Ang 1–7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1–7, ACE2 and Mas receptor levels. Methods: Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days. Results: Although plasma Ang 1–7 levels were unchanged by hyperthyroidism, cardiac Ang 1–7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1–7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1–7 levels were accompanied by increased Mas receptor protein levels. Conclusion: The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH.
Bony Versus Soft Tissue Reconstruction for Anterior Shoulder Instability
Authors: McLaughlin Richard James , Miniaci Anthony , Jones Morgan H. 
Published: December 2015

Background: One complication of anteroinferior glenohumeral shoulder dislocation is a critical bone defect that requires surgical repair to prevent recurrent instability. However, controversy exists regarding the surgical management because both open and arthroscopic surgeries have respective advantages and disadvantages. Moreover, it is difficult to determine the patient’s preferred treatment, as factors that influence treatment choice include recurrence rates, morbidity of the procedures, and patient preferences. Hypothesis: Patients who have a higher probability of recurrent instability after arthroscopic surgery will select open surgery whereas patients with a lower probability of recurrent instability after arthroscopic surgery will favor arthroscopy. Study Design: Economic and decision analysis; Level of evidence, 2. Methods: A decision tree was constructed to model each hypothetical outcome after open or arthroscopic surgery for glenohumeral instability in patients with bone defects. A literature review was performed to determine the probability of occurrence for each node while utility values for each outcome were obtained via patient-administered surveys given to 50 patients without prior history of shoulder injury or dislocation. Fold-back analysis was then performed to show the optimal treatment strategy. Finally, sensitivity analysis established the thresholds at which open treatment becomes the optimal treatment. Results: The ultimate expected value—the objective evaluation of all potential outcomes after choosing either open or arthroscopic surgery—was found to be greater for arthroscopic surgery than for open surgery (87.17 vs 81.64), indicating it to be the preferred treatment. Results of sensitivity analysis indicated that open surgery becomes the preferred treatment when probability of recurrence after arthroscopic treatment is ≥23.8%, although varying the utility, defined as an aggregate patient preference for a particular outcome, has no effect on the model. When the rate of no complication after open surgery is 97.6%, open surgery becomes the patient’s preferred treatment. Conclusion: Arthroscopic surgery is an acceptable treatment if recurrent instability occurs consistently at ≤23.8%. This has important implications given the technical difficulty of successfully performing arthroscopic fixation to resolve recurrent anteroinferior glenohumeral dislocations associated with critical osseous defects. However, due to a lack of clinical outcomes studies, more research is needed to better predict the optimal operative treatment.
Inhibitory effects of metformin at low concentration on epithelial–mesenchymal transition of CD44+CD117+ ovarian cancer stem cells
Authors: Zhang Rongrong , Zhang Ping , Wang Hong , Hou Dongming , Li Wentao , Xiao Guishan , Li Chenwei 
Published: December 2015

AbstractBackgroundAlthough metformin, a first-line drug for treating diabetes, may play an important role in inhibition of epithelial ovarian cancer cell growth and cancer stem cells (CSCs), metformin at low dose showed less effect on the proliferation of ovarian cancer cells. In this study, we evaluated the effect of metformin at low dose on ovarian CSCs in order to understand the molecular mechanisms underlying.MethodsThe inhibitory effects of metformin at los dose on proliferation and population of ovarian cancer cells including SKOV3 and A2780 were assessed by cell proliferation assay and flow cytometry. Quantitative real-time PCR assay on expression of Bcl-2, Survivin and Bax was performed to determine the effect of metformin at low dose on epithelial-mesenchymal transition (EMT) of cancer cells and CSCs. Tumor sphere formation assay was also performed to evaluate the effect of metformin on spheres forming ability of CSCs. The therapeutic efficacy and the anti-CSC effects of metformin at low dose were investigated by using both SKOV3 cells and primary tumor xenografts. In addition, the CSC frequency and EMT in tumor xenograft models were also assessed by flow cytometry and quantitative real-time PCR.ResultsMetformin at low dose did not affect the proliferation of ovarian cancer cells. However, it inhibited population of CD44+CD117+selectively, neither CD133+nor ALDH+cells. It suppressed expression of snail2, twist and vimentin significantly in cancer cells and CD44+CD117+CSCsin vitro. Low dose of metformin reduced survivin expression in CSCs. Low concentrations of metformin inhibited the secondary and the tertiary tumor sphere formation, decreased SKOV3 and primary ovarian tumor xenograft growth, enhanced the anticancer effect of cisplatin, and lowered the proportion of CD44+CD117+CSCs in the xenograft tissue. Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44+CD117+ovarian CSCsin vivo.ConclusionsOur results implicate that metformin at low dose inhibits selectively CD44+CD117+ovarian CSCs through inhibition of EMT and potentiates the effect of cisplatin.
CyAnimator: Simple Animations of Cytoscape Networks
Authors: Morris John H. , Vijay Dhameliya , Federowicz Steven , Pico Alexander R. , Ferrin Thomas E. 
Published: December 2015

CyAnimator (http://apps.cytoscape.org/apps/cyanimator) is a Cytoscape app that provides a tool for simple animations of Cytoscape networks. The tool allows you to take a series of snapshots (CyAnimator calls them frames) of Cytoscape networks. For example, the first frame might be of a network shown from a ”zoomed out” viewpoint and the second frame might focus on a specific group of nodes. Once these two frames are captured by the tool, it can animate between them by interpolating the changes in location, zoom, node color, node size, edge thickness, presence or absence of annotations, etc. The animations may be saved as a series of individual frames, animated GIFs, or H.264/MP4 movies.CyAnimator is available from within the Cytoscape App Manager or from the Cytoscape app store.
Computational identification of signaling pathways in protein interaction networks
Authors: Makolo Angela U. , Olagunju Temitayo A. 
Published: December 2015

The knowledge of signaling pathways is central to understanding the biological mechanisms of organisms since it has been identified that in eukaryotic organisms, the number of signaling pathways determines the number of ways the organism will react to external stimuli. Signaling pathways are studied using protein interaction networks constructed from protein-protein interaction data obtained from high-throughput experiments. However, these high-throughput methods are known to produce very high rates of false positive and negative interactions. To construct a useful protein interaction network from this noisy data, computational methods are applied to validate the protein-protein interactions. In this study, a computational technique to identify signaling pathways from a protein interaction network constructed using validated protein-protein interaction data was designed.A weighted interaction graph of Saccharomyces Cerevisiae was constructed. The weights were obtained using a Bayesian probabilistic network to estimate the posterior probability of interaction between two proteins given the gene expression measurement as biological evidence. Only interactions above a threshold were accepted for the network model.We were able to identify some pathway segments, one of which is a segment of the pathway that signals the start of the process of meiosis in S. Cerevisiae.
Stand by Me—Experiments on Help and Commitment in Coordination Games
Authors: Brandts Jordi , Cooper David J. , Fatas Enrique , Qi Shi 
Published: December 2015

We present experiments studying how high-ability individuals use help to foster efficient coordination. After an initial phase that traps groups in a low-productivity equilibrium, incentives to coordinate are increased, making it possible to escape this performance trap. The design varies whether high-ability individuals can offer help and, if so, whether they must commit to help for an extended period. If help is chosen on a round-by-round basis, the probability of escaping the performance trap is slightly reduced by allowing for help. The likelihood of success significantly improves if high-ability individuals must commit to help for an extended time. We develop and estimate a structural model of sophisticated learning that provides an explanation for why commitment is necessary. The key insight is that potential leaders who are overly optimistic about their ability to teach their followers are too fast to eliminate help in the absence of commitment. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2015.2269 . This paper was accepted by Teck-Hua Ho, behavioral economics.
Bias and the Commitment to Disclosure
Authors: Heinle Mirko S. , Verrecchia Robert E. 
Published: December 2015

This paper studies the propensity of firms to commit to disclose information that is subsequently biased, in the presence of other firms also issuing potentially biased information. An important aspect of such an analysis is the fact that firms can choose whether to disclose or withhold information. We show that allowing the number of disclosed reports to be endogenous introduces a countervailing force to some of the empirical predictions from the prior literature. For example, we find that as more firms issue reports or as the correlation across firms’ cash flows increases, the firm biases its report less. However, when we treat firms’ disclosure choices as endogenous, we show that the number of firms that commit to disclose decreases as the correlation across these cash flows increases, and this, in turn, offsets the direct effect of the correlation on bias. This paper was accepted by Mary Barth, accounting.
Do Brokers of Insiders Tip Other Clients?
Authors: McNally William J. , Shkilko Andriy , Smith Brian F. 
Published: December 2015

We examine trading activity around insider transactions on the Toronto Stock Exchange and find evidence that some traders mimic insider positions. Our unique data set allows us to establish a direct connection between insiders, their brokerages, and the brokerages’ other clients. The findings are consistent with the possibility that some brokerages tip their clients about insider trades. Insiders in our sample have good timing; returns are usually positive (negative) after insider purchases (sales). Insiders’ good timing translates to the mimicking transactions, which appear to be profitable net of trading costs. Evidence consistent with tipping is observed mainly for smaller independent brokerages. This paper was accepted by Brad Barber, finance.