bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary benign metastasizing leiomyoma presented as acute respiratory distress
Authors: Pastré Jean , Juvin Karine , Grand Bertrand , Gibault Laure , Valcke Judith , Israël‐Biet Dominique
Published: January 2017

Benign metastasizing leiomyoma (BML) is a very rare condition and is characterized by the presence of benign smooth muscle tumours in organs distant from the uterus, most commonly the lung. It generally affects women of reproductive age and prognostic is usually excellent. However, the course of the disease is unpredictable. We report here the case of a 76‐year‐old woman with a previous medical history of uterine benign leiomyomas in whom BML was acutely revealed by a respiratory distress due to voluminous pulmonary and pleural leiomyomas requiring surgical extraction. Clinical evolution was remarkable by resistance to medical treatment and development of rare bone localization.

BML is a contradictory entity characterized by benign histological features but with metastatic potential. Pulmonologists as well as oncologists in charge of patients with multiple pulmonary nodules and a history of uterine leiomyoma should be aware of this potential diagnosis in order to implement appropriate diagnostic procedures for this benign tumour.
Semi‐automated detection of eagle nests: an application of very high‐resolution image data and advanced image analyses to wildlife surveys
Authors: Andrew Margaret E. , Shephard Jill M.
Published: January 2017

Very high‐resolution (VHR) image data, including from unmanned aerial vehicle (UAV) platforms, are increasingly acquired for wildlife surveys. Animals or structures they build (e.g. nests) can be photointerpreted from these images, however, automated detection is required for more efficient surveys. We developed semi‐automated analyses to map white‐bellied sea eagle (Haliaeetus leucogaster) nests in VHR aerial photographs of the Houtman Abrolhos Islands, Western Australia, an important breeding site for many seabird species. Nest detection is complicated by high environmental heterogeneity at the scale of nests (~1–2 m), the presence of many features that resemble nests and the variability of nest size, shape and context. Finally, the rarity of nests limits the availability of training data. These challenges are not unique to wildlife surveys and we show how they can be overcome by an innovative integration of object‐based image analyses (OBIA) and the powerful machine learning one‐class classifier Maxent. Maxent classifications using features characterizing object texture, geometry and neighborhood, along with limited object color information, successfully identified over 90% of high quality nests (most weathered and unusually shaped nests were also detected, but at a slightly lower rate) and labeled <2% of objects as candidate nests. Although this overestimates the occurrence of nests, the results can be visually screened to rule out all but the most likely nests in a process that is simpler and more efficient than manual photointerpretation of the full image. Our study shows that semi‐automated image analyses for wildlife surveys are achievable. Furthermore, the developed strategies have broad relevance to image processing applications that seek to detect rare features differing only subtly from a heterogeneous background, including remote sensing of archeological remains. We also highlight solutions to maximize the use of imperfect or uncalibrated image data, such as some UAV‐based imagery and the growing body of VHR imagery available in Google Earth and other virtual globes.
Imaging in gynecological disease (12): clinical and ultrasound features of invasive and non‐invasive malignant serous ovarian tumors
Authors: Moro F. , Baima Poma C. , Zannoni G. F. , Vidal Urbinati A. , Pasciuto T. , Ludovisi M. , Moruzzi M. C. , Carinelli S. , Franchi D. , Scambia G. , Testa A. C.
Published: January 2017

Objectives

To describe clinical and ultrasound features of different subclasses of malignant serous ovarian tumors according to the World Health Organization 2014 classification.

Methods

Patients with a histological diagnosis of borderline tumor (BOT), non‐invasive and invasive low‐grade serous carcinoma (LGSC) and high‐grade serous carcinoma (HGSC), who had undergone preoperative ultrasound examination, were retrospectively identified from two ultrasound centers. The masses were described using the terms of the International Ovarian Tumor Analysis Group.

Results

Sixty‐four (15.8%) women had a serous BOT, 11 (2.7%) a non‐invasive LGSC, 31 (7.6%) an invasive LGSC and 300 (73.9%) had a HGSC. The vast majority of BOTs (82.3%) and non‐invasive LGSCs (90.9%) were Stage I according to the International Federation of Gynecology and Obstetrics (FIGO) classification scheme, whereas most invasive LGSCs (74.2%) and HGSCs (74.0%) were FIGO Stage III. On ultrasound examination, most borderline lesions were described as unilocular‐solid (54.7%) or as multilocular‐solid (29.7%) cysts. Papillary projections were present in 52 (81.3%) BOTs. Most non‐invasive LGSCs (63.6%) were multilocular‐solid cysts and 81.8% had papillary projections. Invasive LGSCs were multilocular‐solid cysts in 54.8% of cases, and papillary projections were present in 32.3% of lesions. HGSCs were multilocular‐solid (32.7%) or solid (64.0%) masses, with papillary projections in only 7% of cases.

Conclusions

Papillary projections were the most typical ultrasound feature of non‐invasive (borderline and low‐grade) malignant serous tumors, while the presence of solid components but few, if any, papillations was the most representative feature of invasive (low‐grade and high‐grade) serous tumors. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Multiscale modeling methods in biomechanics
Authors: Bhattacharya Pinaki , Viceconti Marco
Published: January 2017

More and more frequently, computational biomechanics deals with problems where the portion of physical reality to be modeled spans over such a large range of spatial and temporal dimensions, that it is impossible to represent it as a single space–time continuum. We are forced to consider multiple space–time continua, each representing the phenomenon of interest at a characteristic space–time scale. Multiscale models describe a complex process across multiple scales, and account for how quantities transform as we move from one scale to another. This review offers a set of definitions for this emerging field, and provides a brief summary of the most recent developments on multiscale modeling in biomechanics. Of all possible perspectives, we chose that of the modeling intent, which vastly affect the nature and the structure of each research activity. To the purpose we organized all papers reviewed in three categories: ‘causal confirmation,’ where multiscale models are used as materializations of the causation theories; ‘predictive accuracy,’ where multiscale modeling is aimed to improve the predictive accuracy; and ‘determination of effect,’ where multiscale modeling is used to model how a change at one scale manifests in an effect at another radically different space–time scale. Consistent with how the volume of computational biomechanics research is distributed across application targets, we extensively reviewed papers targeting the musculoskeletal and the cardiovascular systems, and covered only a few exemplary papers targeting other organ systems. The review shows a research subdomain still in its infancy, where causal confirmation papers remain the most common. WIREs Syst Biol Med 2017, 9:e1375. doi: 10.1002/wsbm.1375

This article is categorized under:

Analytical and Computational Methods > Computational Methods

Models of Systems Properties and Processes > Mechanistic Models

Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Procedures and recommended times in the care process of the patient with pancreatic cancer: PAN-TIME consensus between scientific societies
Authors: Vera R. , Ferrández A. , Ferrer C. J. , Flores C. , Joaquín C. , López S. , Martín T. , Martín E. , Marzo M. , Sarrión A. , Vaquero E. , Zapatero A. , Aparicio J.
Published: January 2017

Purpose

Pancreatic cancer (PC) is a disease with bad prognosis. It is usually diagnosed at advanced stages and its treatment is complex. The aim of this consensus document was to provide recommendations by experts that would ameliorate PC diagnosis, reduce the time to treatment, and optimize PC management by interdisciplinary teams.

Methods

As a consensus method, we followed the modified Delphi methodology. A scientific committee of experts provided 40 statements that were submitted in two rounds to a panel of 87 specialists of 12 scientific societies.

Results

Agreement was reached for 39 of the 40 proposed statements (97.5%).

Conclusions

Although a screening of the asymptomatic population is not a feasible option, special attention to potential symptoms during primary care could ameliorate early diagnostic. It is especially important to decrease the period until diagnostic tests are performed. This consensus could improve survival in PC patients by decreasing the time to diagnose and time to treatment and by the implementation of multidisciplinary teams.
Introduction to Surface Engineering
Authors: Dearnley P. A.
Published: January 2017

This highly illustrated reference work covers the three principal types of surface technologies that best protect engineering devices and products: diffusion technologies, deposition technologies, and other less commonly acknowledged surface engineering (SE) techniques. Various applications are noted throughout the text and additionally whole chapters are devoted to specific SE applications across the automotive, gas turbine engine (GTE), metal machining, and biomedical implant sectors. Along with the benefits of SE, this volume also critically examines SE's limitations. Materials degradation pathways - those which can and those which cannot be mitigated by SE - are rigorously explained. Written from a scientific, materials engineering perspective, this concise text is supported by high-quality images and photo-micrographs which show how surfaces can be engineered to overcome the limits of conventionally produced materials, even in complex or hostile operating environments. This book is a useful resource for undergraduate and postgraduate students as well as professional engineers.
The Red Army and the Second World War
Authors: Hill Alexander
Published: January 2017

In a definitive new account of the Soviet Union at war, Alexander Hill charts the development, successes and failures of the Red Army from the industrialisation of the Soviet Union in the late 1920s through to the end of the Great Patriotic War in May 1945. Setting military strategy and operations within a broader context that includes national mobilisation on a staggering scale, the book presents a comprehensive account of the origins and course of the war from the perspective of this key Allied power. Drawing on the latest archival research and a wealth of eyewitness testimony, Hill portrays the Red Army at war from the perspective of senior leaders and men and women at the front line to reveal how the Red Army triumphed over the forces of Nazi Germany and her allies on the Eastern Front, and why it did so at such great cost.
The Political Bible in Early Modern England
Authors: Killeen Kevin
Published: January 2017

This illuminating new study considers the Bible as a political document in seventeenth-century England, revealing how the religious text provided a key language of political debate and played a critical role in shaping early modern political thinking. Kevin Killeen demonstrates how biblical kings were as important in the era's political thought as any classical model. The book mines the rich and neglected resources of early modern quasi-scriptural writings - treatise, sermon, commentary, annotation, poetry and political tract - to show how deeply embedded this political vocabulary remained, across the century, from top to bottom and across all religious positions. It shows how constitutional thought, in this most tumultuous era of civil war, regicide and republic, was forged on the Bible, and how writers ranging from King James, Joseph Hall or John Milton to Robert Filmer and Thomas Hobbes can be better understood in the context of such vigorous biblical discourse.
Criminal Law in Liberal and Fascist Italy
Authors: Garfinkel Paul
Published: January 2017

By extending the chronological parameters of existing scholarship, and by focusing on legal experts' overriding and enduring concern with 'dangerous' forms of common crime, this study offers a major reinterpretation of criminal-law reform and legal culture in Italy from the Liberal (1861–1922) to the Fascist era (1922–43). Garfinkel argues that scholars have long overstated the influence of positivist criminology on Italian legal culture and that the kingdom's penal-reform movement was driven not by the radical criminological theories of Cesare Lombroso, but instead by a growing body of statistics and legal researches that related rising rates of crime to the instability of the Italian state. Drawing on a vast array of archival, legal and official sources, the author explains the sustained and wide-ranging interest in penal-law reform that defined this era in Italian legal history while analyzing the philosophical underpinnings of that reform and its relationship to contemporary penal-reform movements abroad.
Dialogue, Argumentation and Education
Authors: Schwarz Baruch B. , Baker Michael J.
Published: January 2017

New pedagogical visions and technological developments have brought argumentation to the fore of educational practice. Whereas students previously 'learned to 'argue', they now 'argue to learn': collaborative argumentation-based learning has become a popular and valuable pedagogical technique, across a variety of tasks and disciplines. Researchers have explored the conditions under which arguing to learn is successful, have described some of its learning potentials (such as for conceptual change and reflexive learning) and have developed Internet-based tools to support such learning. However, the further advancement of this field presently faces several problems, which the present book addresses. Three dimensions of analysis - historical, theoretical and empirical - are integrated throughout the book. Given the nature of its object of study - dialogue, interaction, argumentation, learning and teaching - the book is resolutely multidisciplinary, drawing on research on learning in educational and psychological sciences, as well as on philosophical and linguistic theories of dialogue and argumentation.
Going Beyond Aid
Authors: Lin Justin Yifu , Wang Yan
Published: January 2017

Developing countries have for decades been trying to catch up with the industrialized high-income countries, but only a few have succeeded. Historically, structural transformation has been a powerful engine of growth and job creation. Traditional development aid is inadequate to address the bottlenecks for structural transformation, and is hence ineffective. In this book, Justin Yifu Lin and Yan Wang use the theoretical foundations of New Structural Economics to examine South-South development aid and cooperation from the angle of structural transformation. By studying the successful economic transformation of countries such as China and South Korea through 'multiple win' solutions based on comparative advantages and economy of scale, and by presenting new ideas and different perspectives from emerging market economies such as Brazil, India and other BRICS countries, they bring a new narrative to broaden the ongoing discussions of post-2015 development aid and cooperation as well as the definitions of aid and cooperation.
Saving the Market from Itself
Authors: Mitchell Christopher
Published: January 2017

The 2007–9 financial crisis threatened economic disaster on a scale not seen since the Great Depression, but rapid state action prevented the widely feared devastation. The German response was considerably more generous to banks than the American or British bailouts. Drawing on interviews and primary sources in government, private firms, and media, Mitchell explains how the structure of national financial systems and interbank relationships produced extensive private rescues and pressure on different states. Mitchell explores the different responses and results in Germany, the UK and the US using a combination of detailed case study analyses of the three countries' responses to the crisis and a quantitative analysis of patterns of state responses to financial crises. This book will be essential reading for scholars and advanced students of political economy, comparative politics, economic sociology, economics, and public policy.
After Rape
Authors: Porter Holly
Published: January 2017

Following the ICC intervention in 2005, northern Uganda has been at the heart of international justice debates. The emergent controversy, however, missed crucial aspects of Acholi realities: that the primary moral imperative in the wake of wrongdoing was not punishment but, instead, the restoration of social harmony. Drawing upon abundant fieldwork and in-depth interviews with almost 200 women, Holly Porter examines issues surrounding wrongdoing and justice, and sexual violence and rape, among the Acholi people in northern Uganda. This intricate exploration offers evidence of a more complicated and nuanced explanation of rape and its aftermath, suggesting a re-imagining of the meanings of post-atrocity justice, whilst acknowledging the role of sex, power and politics in all sexual experiences between coercion and consent. With its wide investigation of social life in northern Uganda, this provocative study offers vital analysis for those interested in sexual and gender violence, post-conflict reconstruction and human rights.
Forecasting long-lived Lagrangian vortices from their objective Eulerian footprints
Authors: Serra Mattia , Haller George
Published: January 2017

We derive a non-dimensional metric to quantify the expected Lagrangian persistence of objectively defined Eulerian vortices in two-dimensional unsteady flows. This persistence metric is the averaged deviation of the vorticity from its spatial mean over the Eulerian vortex, normalized by the instantaneous material leakage from the Eulerian vortex. The metric offers a model- and frame-independent tool for uncovering the instantaneous Eulerian signature of long-lived Lagrangian vortices. Using satellite-derived ocean velocity data, we show that Lagrangian vortex-persistence predictions by our metric significantly outperform those inferred from other customary Eulerian diagnostics, such as the potential vorticity gradient and the Okubo–Weiss criterion.
Development and validation of an instrument for assessing collective psychological ownership in organizational field settings
Authors: Pierce Jon L , Jussila Iiro , Li Dahui
Published: January 2017

Recently, there emerged a theory of collective psychological ownership – an intersubjective sense of possession for different objects within the work and organizational context (e.g., work space). This shared mind-set has been cast as having the potential to explain a variety of collective, work-related attitudes, and actions. Preventing scientific inquiry into this phenomenon is the absence of an instrument for the measurement of this construct. The purpose of this work was the development and validation of such an instrument. To this end, work with a panel of judges and three sequentially conducted field studies was undertaken. Construct validation evidence (e.g., content, discriminant, nomological, and incremental validity) for an instrument for the assessment of collective psychological ownership is provided.
A Simple and Practical Algorithm for Accurate Gravitational Magnification Maps
Authors: Walters S. J. , Forbes L. K.
Published: January 2017

In this brief communication, a new method is outlined for modelling magnification patterns on an observer’s plane using a first-order approximation to the null geodesic path equations for a point mass lens. For each ray emitted from a source, an explicit calculation is made for the change in position on the observer’s plane due to each lens mass. By counting the number of points in each small area of the observer’s plane, the magnification at that point can be determined. This allows for a very simple and transparent algorithm. A short Matlab code sample for creating simple magnification maps due to multiple point lenses is included in an appendix.
Can probiotics modulate human disease by impacting intestinal barrier function?
Authors: Bron Peter A. , Kleerebezem Michiel , Brummer Robert-Jan , Cani Patrice D. , Mercenier Annick , MacDonald Thomas T. , Garcia-Ródenas Clara L. , Wells Jerry M.
Published: January 2017

Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chemical and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is one of the major aetiological factors associated with several gastrointestinal diseases, including infection by pathogens, obesity and diabetes, necrotising enterocolitis, irritable bowel syndrome and inflammatory bowel disease. The notion that specific probiotic bacterial strains can affect barrier integrity fuelled research in whichin vitrocell lines, animal models and clinical trials are used to assess whether probiotics can revert the diseased state back to homeostasis and health. This review catalogues and categorises the lines of evidence available in literature for the role of probiotics in epithelial integrity and, consequently, their beneficial effect for the reduction of gastrointestinal disease symptoms.
On the Presence of an Anticoagulin in the Salivary Glands and Intestines of Argas persicus
Authors: Nuttal George H. F. , Strickland Cyril
Published: January 2017

In the literature relating to the Ixodoidea there are a number of cases recorded of injurious effects following the bites of ticks. We do not refer to diseases like piroplasmosis and spirochaetosis which are known to be tick-transmitted, nor to other infective processes which may start at the seat of tick's bite. The effects we refer to follow almost immediately upon the infliction of the bite and are distinctly toxic in character. These effects appear to have been more frequently observed following upon bites inflicted by species of Argas and Ornithodoros.
Do People Favour Policies that Protect Future Generations? Evidence from a British Survey of Adults
Authors: GRAHAM HILARY , BLAND J. MARTIN , COOKSON RICHARD , KANAAN MONA , WHITE PIRAN C. L.
Published: January 2017

Long-range temporal choices are built into contemporary policy-making, with policy decisions having consequences that play out across generations. Decisions are made on behalf of the public who are assumed to give much greater weight to their welfare than to the welfare of future generations. The paper investigates this assumption. It briefly discusses evidence from sociological and economic studies before reporting the findings of a British survey of people's intergenerational time preferences based on a representative sample of nearly 10,000 respondents. Questions focused on two sets of policies: (i) health policies to save lives and (ii) environmental policies to protect against floods that would severely damage homes, businesses and other infrastructure. For both sets of policies, participants were offered a choice of three policy options, each bringing greater or lesser benefits to their, their children's and their grandchildren's generations. For both saving lives and protecting against floods, only a minority selected the policy that most benefited their generation; the majority selected policies bringing equal or greater benefits to future generations. Our study raises questions about a core assumption of standard economic evaluation, pointing instead to concern for future generations as a value that many people hold in common.
Horace,Odes4.1: a Contradiction Removed
Authors: Kovacs David
Published: January 2017

Odes4.1 is difficult to understand on a literal level. At its beginning Horace is complaining that Venus, after leaving him alone for many years, is attacking him, that is, he is feeling a reawakening of sexual desire. But after suggesting that the goddess go off to visit Paullus Fabius Maximus and describing the rewards the young man will give her, he returns to himself. Now, he says, he is delighted by neither woman nor boy nor by the prospect of mutuality in love, that is, he isnotin the grip oferos. Additionally, the use ofiuuare, ‘delight’, with a person as subject seems to be without any parallel. These problems disappear if in l. 29 we readmiforme: ‘I no longerhaveeither woman or boy (as lover) nor do Ihavethe hope of mutual affection.’ Horace's having no lover and no hope of one is compatible with his feeling a generalized desire for sex or a desire for someone unattainable. The tone of the last two quatrains is affected as well as the contribution of the poem to the fourth book of odes.
Why do we remember? The communicative function of episodic memory
Authors: Mahr Johannes B. , Csibra Gergely
Published: January 2017

Episodic memory has been analyzed in a number of different ways in both philosophy and psychology, and most controversy has centered on its self-referential,autonoeticcharacter. Here, we offer a comprehensive characterization of episodic memory in representational terms and propose a novel functional account on this basis. We argue that episodic memory should be understood as a distinctive epistemic attitude taken toward an event simulation. In this view, episodic memory has a metarepresentational format and should not be equated with beliefs about the past. Instead, empirical findings suggest that the contents of human episodic memory are often constructed in the service of the explicit justification of such beliefs. Existing accounts of episodic memory function that have focused on explaining its constructive character through its role in future-oriented mental time travel do justice neither to its capacity to ground veridical beliefs about the past nor to its representational format. We provide an account of the metarepresentational structure of episodic memory in terms of its role in communicative interaction. The generative nature of recollection allows us to represent and communicate the reasons why we hold certain beliefs about the past. In this process, autonoesis corresponds to the capacity to determine when and how to assert epistemic authority in making claims about the past. A domain where such claims are indispensable are human social engagements. Such engagements commonly require the justification of entitlements and obligations, which is often possible only by explicit reference to specific past events.
Grounding world society: Spatiality, cultural heritage, and our world as shared geographies
Authors: Weinert Matthew S.
Published: January 2017

The concept of world society has elicited sharp criticism for being too diffuse and amorphous owing to its synonymy with all transborder social relations, equability with humankind, or conflation with solidarist international society. To overcome these shortcomings, this article reconfigures world society by attaching otherwise unmoored social activity to an understanding of the world as comprised of shared social spaces. This spatialised reading foregrounds constellations of relations that have emerged in conjunction with discrete geographies – natural, economic, cyberspatial, cultural, anthropic – within which humans interact, and demonstrates that the world has become an actionable, political concept generative of activities peculiar to the space itself. A review of English School literature extracts four theses – purposive, plural, spatial, and stewardship – that invite conceptual reconstruction of world society. The article then addresses the discursive construction of cultural heritage as a worldly space populated with distinctive institutions and cognitive and normative commitments, and is followed by reflections on the added value of such an approach and directions for future research.
WHEN DOES A PERSON BEGIN?
Authors: Baker Lynne Rudder
Published: January 2017

According to the Constitution View of persons, a human person is
wholly constituted by (but not identical to) a human organism. This view
does justice both to our similarities to other animals and to our
uniqueness. As a proponent of the Constitution View, I defend the thesis
that the coming-into-existence of a human person is not simply a matter of
the coming-into-existence of an organism, even if that organism ultimately
comes to constitute a person. Marshalling some support from developmental
psychology, I give a broadly materialistic account of the
coming-into-existence of a human person. I argue for the metaphysical
superiority of the Constitution View to Biological Animalism, Thomistic
Animalism, and other forms of Substance Dualism. I conclude by discussing
the single implication of the Constitution View for thinking about
abortion.
INVESTMENT AND FORWARD-LOOKING MONETARY POLICY: A WICKSELLIAN SOLUTION TO THE PROBLEM OF INDETERMINACY
Authors: McKnight Stephen
Published: January 2017

Recent research has shown that forward-looking Taylor rules are subject to indeterminacy in New Keynesian models with capital and investment spending. This paper shows that adopting a forward-looking Wicksellian rule that responds to the price level, rather than to inflation, is one potential remedy for the indeterminacy problem. This result is shown to be robust to variations in both the labor supply elasticity and the degree of price stickiness, the inclusion of capital adjustments costs, and if output also enters into the interest-rate feedback rule. Finally, it is shown that the superiority of Wicksellian rules over Taylor rules is not only confined to forward-looking policy, but also extends to both backward-looking and contemporaneous-looking specifications of the monetary policy rule.
The Role of Participant Responsiveness on a Socio-Emotional Learning Program
Authors: Pereira Nádia Salgado , Marques-Pinto Alexandra
Published: January 2017

The present study set out to evaluate participant responsiveness, one of the main dimensions of implementation quality, in a Socio-Emotional Learning after-school program using Educational Dance activities,Experiencing Emotions, and also to understand its influence on program outcomes. The sample involved 98 middle-school Portuguese pupils, 53 of whom participated in the program and 45 in after-school control sessions. Outcome measures included pre-test and post-test questionnaires of pupils’ socio-emotional skills, well-being and school engagement. A self-report item measured pupils’ satisfaction at the end of the program, and a checklist measuring attendance and homework completion was filled in by the facilitator at each session of the program and control condition. Results revealed (1) high levels of pupils’ satisfaction and attendance, and a medium-high level of homework completion towards the program; (2) that pupils’ higher attendance rate in the program predicted higher results in the self-management (p= .04,d= .57;p= .003,d= .87) and social awareness (p= .04,d= .59) SEL domains, emotional (p= .02,d= .67) and psychological (p= .009,d= .76) well-being and school engagement (p= .04,d= .56); (3) that pupils’ higher rate of homework completion in the program predicted higher results in the relationship skills SEL area (p= .04,d= .59) and in school engagement (p= .005,d= 1.50); (4) that pupils’ from the control condition higher rates of homework completion also predicted better school engagement (p= .006,d= .88). Implications for research and practice are discussed.
The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue
Authors: Elmi Giovanna , Di Pasquale Giuseppe , Pesavento Raffaele
Published: January 2017

Abstract. As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.
Autophagy dysregulation in Danon disease
Authors: Nascimbeni Anna Chiara , Fanin Marina , Angelini Corrado , Sandri Marco
Published: January 2017

The autophagy–lysosome system is critical for muscle homeostasis and defects in lysosomal function result in a number of inherited muscle diseases, generally referred to as autophagic vacuolar myopathies (AVMs). Among them, Danon Disease (DD) and glycogen storage disease type II (GSDII) are due to primary lysosomal protein defects. DD is characterized by mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. The DD mouse model suggests that inefficient lysosome biogenesis/maturation and impairment of autophagosome-lysosome fusion contribute to the pathogenesis of muscle wasting. To define the role of autophagy in human disease, we analyzed the muscle biopsies of DD patients and monitored autophagy and several autophagy regulators like transcription factor EB (TFEB), a master player in lysosomal biogenesis, and vacuolar protein sorting 15 (VPS15), a critical factor for autophagosome and endosome biogenesis and trafficking. Furthermore, to clarify whether the mechanisms involved are shared by other AVMs, we extended our mechanistic study to a group of adult GSDII patients. Our data show that, similar to GSDII, DD patients display an autophagy block that correlates with the severity of the disease. Both DD and GSDII show accumulation and altered localization of VPS15 in autophagy-incompetent fibers. However, TFEB displays a different pattern between these two lysosomal storage diseases. Although in DD TFEB and downstream targets are activated, in GSDII patients TFEB is inhibited. These findings suggest that these regulatory factors may have an active role in the pathogenesis of these diseases. Therapeutic approaches targeted to normalize these factors and restore the autophagic flux in these patients should therefore be considered.
MicroRNA-101 inhibits invasion and angiogenesis through targeting ITGA3 and its systemic delivery inhibits lung metastasis in nasopharyngeal carcinoma
Authors: Tang Xin-Ran , Wen Xin , He Qing-Mei , Li Ying-Qin , Ren Xian-Yue , Yang Xiao-Jing , Zhang Jian , Wang Ya-Qin , Ma Jun , Liu Na
Published: January 2017

Clinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC), and the treatment outcome of metastatic NPC remains disappointing, so there is a pressing need to identify novel therapeutic strategies. In accordance with our previous microarray data, we found that miR-101 was downregulated in NPC clinical specimens and cell lines. Ectopic expression of miR-101 significantly suppressed NPC cell migration, invasion and angiogenesis in vitro and inhibited angiogenesis and metastasis in vivo using the chicken chorioallantoic membrane model. Furthermore, ITGA3 was identified and validated as a novel target of miR-101, and the restoration of ITGA3 expression potently rescued the suppressive effects of miR-101. In addition, NPC patients with high ITGA3 expression had poorer overall survival and distant metastasis-free survival than patients with low ITGA3 expression, and ITGA3 overexpression was an independent poor prognostic factor in NPC. More importantly, we demonstrated that the systemic delivery of lentivirus-mediated miR-101 abrogated the lung metastatic colonization formation of NPC cells without obvious toxicity. Our study elucidates the molecular mechanisms of miR-101/ITGA3 pathway in regulating NPC metastasis and angiogenesis, and the systemic delivery of miR-101 provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for NPC patients.
Cancer-associated fibroblasts enact field cancerization by promoting extratumoral oxidative stress
Authors: Chan Jeremy Soon Kiat , Tan Ming Jie , Sng Ming Keat , Teo Ziqiang , Phua Terri , Choo Chee Chong , LI Liang , Zhu Pengcheng , Tan Nguan Soon
Published: January 2017

Histological inspection of visually normal tissue adjacent to neoplastic lesions often reveals multiple foci of cellular abnormalities. This suggests the presence of a regional carcinogenic signal that spreads oncogenic transformation and field cancerization. We observed an abundance of mutagenic reactive oxygen species in the stroma of cryosectioned patient tumor biopsies, indicative of extratumoral oxidative stress. Diffusible hydrogen peroxide (H2O2) was elevated in the conditioned medium of cultured skin epithelia at various stages of oncogenic transformation, and H2O2 production increased with greater tumor-forming and metastatic capacity of the studied cell lines. Explanted cancer-associated fibroblasts (CAFs) also had higher levels of H2O2 secretion compared with normal fibroblasts (FIBs). These results suggest that extracellular H2O2 acts as a field effect carcinogen. Indeed, H2O2-treated keratinocytes displayed decreased phosphatase and tensin homolog (PTEN) and increased Src activities because of oxidative modification. Furthermore, treating FIBs with CAF-conditioned medium or exogenous H2O2 resulted in the acquisition of an oxidative, CAF-like state. In vivo, the proliferative potential and invasiveness of composite tumor xenografts comprising cancerous or non-tumor-forming epithelia with CAFs and FIBs could be attenuated by the presence of catalase. Importantly, we showed that oxidatively transformed FIBs isolated from composite tumor xenografts retained their ability to promote tumor growth and aggressiveness when adoptively transferred into new xenografts. Higher H2O2 production by CAFs was contingent on impaired TGFβ signaling leading to the suppression of the antioxidant enzyme glutathione peroxidase 1 (GPX1). Finally, we detected a reduction in Smad3, TAK1 and TGFβRII expression in a cohort of 197 clinical squamous cell carcinoma (SCC) CAFs, suggesting that impaired stromal TGFβ signaling may be a clinical feature of SCC. Our study indicated that CAFs and cancer cells engage redox signaling circuitries and mitogenic signaling to reinforce their reciprocal relationship, suggesting that future anticancer approaches should simultaneously target ligand receptor and redox-mediated pathways.
Hepatitis B virus X protein promotes the stem-like properties of OV6+ cancer cells in hepatocellular carcinoma
Authors: Wang Chao , Wang Ming-da , Cheng Peng , Huang Hai , Dong Wei , Zhang Wei-wei , Li Peng-peng , Lin Chuan , Pan Ze-ya , Wu Meng-chao , Zhou Wei-ping
Published: January 2017

Hepatitis B virus X protein (HBx) and cancer stem-like cells (CSCs) have both been implicated in the occurrence and development of HBV-related hepatocellular carcinoma (HCC). However, whether HBx contributes to the stem-like properties of OV6+ CSCs in HCC remains elusive. In this study, we showed that the concomitant expression of HBx and OV6 was closely associated with the clinical outcomes and prognosis of patients with HBV-related HCC. HBx was required for the stem-like properties of OV6+ liver CSCs, including self-renewal, stem cell-associated gene expression, tumorigenicity and chemoresistance. Mechanistically, HBx enhanced expression of MDM2 by directly binding with MDM2 and inhibiting its ubiquitin-directed self-degradation. MDM2 translocation into the nucleus was also upregulated by HBx and resulted in enhanced transcriptional activity and expression of CXCL12 and CXCR4 independent of p53. This change in expression activated the Wnt/β-catenin pathway and promoted the stem-like properties of OV6+ liver CSCs. Furthermore, we observed that the expression of any two indicators from the HBx/MDM2/CXCR4/OV6 axis in HCC biopsies could predict the prognosis of patients with HBV-related HCC. Taken together, our findings indicate the functional role of HBx in regulating the stem-like properties of OV6+ CSCs in HCC through the MDM2/CXCL12/CXCR4/β-catenin signaling axis, and identify HBx, MDM2, CXCR4 and OV6 as a novel prognostic pathway and potential therapeutic targets for patients with HBV-related HCC patients.
Gα13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3β-NFATc1 signalling pathway
Authors: Wu Mengrui , Chen Wei , Lu Yun , Zhu Guochun , Hao Liang , Li Yi-Ping
Published: January 2017

Many positive signalling pathways of osteoclastogenesis have been characterized, but negative signalling pathways are less well studied. Here we show by microarray and RNAi that guanine nucleotide-binding protein subunit α13 (Gα13) is a negative regulator of osteoclastogenesis. Osteoclast-lineage-specific Gna13 conditional knockout mice have a severe osteoporosis phenotype. Gna13-deficiency triggers a drastic increase in both osteoclast number and activity (hyper-activation), mechanistically through decreased RhoA activity and enhanced Akt/GSK3β/NFATc1 signalling. Consistently, Akt inhibition or RhoA activation rescues hyper-activation of Gna13-deficient osteoclasts, and RhoA inhibition mimics the osteoclast hyperactivation resulting from Gna13-deficiency. Notably, Gα13 gain-of-function inhibits Akt activation and osteoclastogenesis, and protects mice from pathological bone loss in disease models. Collectively, we reveal that Gα13 is a master endogenous negative switch for osteoclastogenesis through regulation of the RhoA/Akt/GSK3β/NFATc1 signalling pathway, and that manipulating Gα13 activity might be a therapeutic strategy for bone diseases.
Consistent negative response of US crops to high temperatures in observations and crop models
Authors: Schauberger Bernhard , Archontoulis Sotirios , Arneth Almut , Balkovic Juraj , Ciais Philippe , Deryng Delphine , Elliott Joshua , Folberth Christian , Khabarov Nikolay , Müller Christoph , Pugh Thomas A. M. , Rolinski Susanne , Schaphoff Sibyll , Schmid Erwin , Wang Xuhui , Schlenker Wolfram , Frieler Katja
Published: January 2017

High temperatures are detrimental to crop yields and could lead to global warming-driven reductions in agricultural productivity. To assess future threats, the majority of studies used process-based crop models, but their ability to represent effects of high temperature has been questioned. Here we show that an ensemble of nine crop models reproduces the observed average temperature responses of US maize, soybean and wheat yields. Each day >30 °C diminishes maize and soybean yields by up to 6% under rainfed conditions. Declines observed in irrigated areas, or simulated assuming full irrigation, are weak. This supports the hypothesis that water stress induced by high temperatures causes the decline. For wheat a negative response to high temperature is neither observed nor simulated under historical conditions, since critical temperatures are rarely exceeded during the growing season. In the future, yields are modelled to decline for all three crops at temperatures >30 °C. Elevated CO2can only weakly reduce these yield losses, in contrast to irrigation.
Storing single photons emitted by a quantum memory on a highly excited Rydberg state
Authors: Distante Emanuele , Farrera Pau , Padrón-Brito Auxiliadora , Paredes-Barato David , Heinze Georg , de Riedmatten Hugues
Published: January 2017

Strong interaction between two single photons is a long standing and important goal in quantum photonics. This would enable a new regime of nonlinear optics and unlock several applications in quantum information science, including photonic quantum gates and deterministic Bell-state measurements. In the context of quantum networks, it would be important to achieve interactions between single photons from independent photon pairs storable in quantum memories. So far, most experiments showing nonlinearities at the single-photon level have used weak classical input light. Here we demonstrate the storage and retrieval of a paired single photon emitted by an ensemble quantum memory in a strongly nonlinear medium based on highly excited Rydberg atoms. We show that nonclassical correlations between the two photons persist after retrieval from the Rydberg ensemble. Our result is an important step towards deterministic photon–photon interactions, and may enable deterministic Bell-state measurements with multimode quantum memories.
Direct PIP2 binding mediates stable oligomer formation of the serotonin transporter
Authors: Anderluh Andreas , Hofmaier Tina , Klotzsch Enrico , Kudlacek Oliver , Stockner Thomas , Sitte Harald H. , Schütz Gerhard J.
Published: January 2017

The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization. After trafficking to the plasma membrane, however, the SERT stoichiometry is fixed. Stabilization of the oligomeric SERT complexes is mediated by the direct binding to phosphoinositide phosphatidylinositol-4,5-biphosphate (PIP2). The observed spatial decoupling of oligomer formation from the site of oligomer operation provides cells with the ability to define protein quaternary structures independent of protein density at the cell surface.
Drosophila FIT is a protein-specific satiety hormone essential for feeding control
Authors: Sun Jinghan , Liu Chang , Bai Xiaobing , Li Xiaoting , Li Jingyun , Zhang Zhiping , Zhang Yunpeng , Guo Jing , Li Yan
Published: January 2017

Protein homeostasis is critical for health and lifespan of animals. However, the mechanisms for controlling protein feeding remain poorly understood. Here we report that in Drosophila, protein intake-induced feeding inhibition (PIFI) is specific to protein-containing food, and this effect is mediated by a fat body (FB) peptide named female-specific independent of transformer (FIT). Upon consumption of protein food, FIT expression is greatly elevated. Secreted FIT peptide in the fly haemolymph conveys this metabolic message to the brain, thereby promoting the release of Drosophila insulin-like peptide 2 (DILP2) and suppressing further protein intake. Interestingly, Fit is a sexually dimorphic gene, and consequently protein consumption-induced insulin release, as well as protein feeding behaviour, are also dimorphic between sexes. Thus, our findings reveal a protein-specific satiety hormone, providing important insights into the complex regulation of feeding decision, as well as the sexual dimorphism in feeding behaviour.