bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic and combined endosonographic staging of lung cancer (SCORE study)
Authors: Crombag Laurence M.M. , Dooms Christophe , Stigt Jos A. , Tournoy Kurt G. , Schuurbiers Olga C.J. , Ninaber Maarten K. , Buikhuisen Wieneke A. , Hashemi Sayed M.S. , Bonta Peter I. , Korevaar Daniël A. , Annema Jouke T. 
Published: December 2018

Guidelines recommend endosonography for mediastinal nodal staging in patients with resectable nonsmall cell lung cancer (NSCLC). We hypothesise that a systematic endobronchial ultrasound (EBUS) evaluation combined with an oesophageal investigation using the same EBUS bronchoscope (EUS-B) improves mediastinal nodal stagingversusthe current practice of targeted positron emission tomography (PET)-computed tomography (CT)-guided EBUS staging alone.A prospective, multicentre, international study (NCT02014324) was conducted in consecutive patients with (suspected) resectable NSCLC. After PET-CT, patients underwent systematic EBUS and EUS-B. Node(s) suspicious on CT, PET, EBUS and/or EUS-B imaging and station 4R, 4L and 7 (short axis ≥8 mm) were sampled. For patients without N2/N3 disease determined on endosonography, surgical-pathological staging was the reference standard.229 patients were included in this study. The prevalence of N2/N3 disease was 103 out of 229 patients (45%). A PET-CT-guided targeted approach by EBUS identified 75 patients with N2/N3 disease (sensitivity 73%, 95% CI 63–81%; negative predictive value (NPV) 81%, 95% CI 74–87%). Four additional patients with N2/N3 disease were found by systematic EBUS (sensitivity 77%, 95% CI 67–84%; NPV 84%, 95% CI 76–89%) and five more by EUS-B (84 patients total; sensitivity 82%, 95% CI 72–88%; NPV 87%, 95% CI 80–91%). Additional clinical relevant staging information was obtained in 23 out of 229 patients (10%).Systematic EBUS followed by EUS-B increased sensitivity for the detection of N2/N3 disease by 9% compared to PET-CT-targeted EBUS alone.
Fibroblast growth factor 21 predicts outcome in community-acquired pneumonia: secondary analysis of two randomised controlled trials
Authors: Ebrahimi Fahim , Wolffenbuttel Carole , Blum Claudine A. , Baumgartner Christine , Mueller Beat , Schuetz Philipp , Meier Christian , Kraenzlin Marius , Christ-Crain Mirjam , Betz Matthias Johannes 
Published: December 2018

Acute systemic inflammatory conditions are accompanied by profound alterations of metabolism. However, the role of fibroblast growth factor 21 (FGF21), a recently identified central regulator of metabolism, is largely unknown in community-acquired pneumonia (CAP). This study aims to characterise the pattern of FGF21 in pneumonia and associations with disease severity and outcome.This is a secondary analysis of two independent multicentre randomised controlled trials in patients presenting to the emergency department with CAP. Primary and secondary efficacy parameters included 30-day mortality, length of hospital stay, time to clinical stability and duration of antibiotic treatment.A total of 509 patients were included in the analysis. FGF21 levels at admission strongly correlated with disease severity, as measured by the Pneumonia Severity Index. Increased levels of FGF21 were associated with prolonged time to clinical stability, antibiotic treatment and hospitalisation. FGF21 levels at admission were significantly higher in nonsurvivors than in survivors, yielding a 1.61-fold increased adjusted odds ratio of 30-day mortality (95% CI 1.21–2.14; p=0.001). Moreover, FGF21 was found to identify patients for 30-day mortality with superior discriminative power compared with routine diagnostic markers.Moderate-to-severe CAP patients with higher levels of FGF21 were at increased risk for clinical instability, prolonged hospitalisation and 30-day all-cause mortality.
Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases
Authors: Eyries Mélanie , Montani David , Nadaud Sophie , Girerd Barbara , Levy Marilyne , Bourdin Arnaud , Trésorier Romain , Chaouat Ari , Cottin Vincent , Sanfiorenzo Céline , Prevot Grégoire , Reynaud-Gaubert Martine , Dromer Claire , Houeijeh Ali , Nguyen Karine , Coulet Florence , Bonnet Damien , Humbert Marc , Soubrier Florent 
Published: December 2018

BackgroundHeritable forms of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH) diverge by lung histopathological lesions, clinical and para-clinical presentation, their responsible genes, and mode of transmission. Since the identification of theBMPR2gene in families affected by PAH, mutations in several other genes have been discovered for both forms. The mutation landscape in these new genes is not yet well known.MethodsWe set up a next-generation sequencing-based targeted sequencing gene panel allowing known genes for PAH and PVOD/PCH to be analysed simultaneously.Genetic analysis was prospectively performed on 263 PAH and PVOD/PCH patients (adult and paediatric cases).ResultsPathogenic mutations were identified in 19.5% of sporadic PAH patients (n=180), 54.5% of familial PAH patients and 13.3% of PVOD/PCH patients.BMPR2was the most frequently mutated gene, followed byTBX4in both paediatric and adult PAH.BMP9mutations were identified in 1.2% of adult PAH cases.EIF2AK4biallelic mutations were restricted to PVOD/PCH. A truncating mutation and a predicted loss-of-function variant were also identified inBMP10in two severely affected sporadic PAH female patients.ConclusionOur results confirm that mutations are found in genes beyondBMPR2in heritable PAH, emphasise the role ofTBX4andBMP9, and designateBMP10as a new PAH gene.
Still Fighting for Breath: a patient survey of the challenges and impact of severe asthma
Authors: Katsaounou Paraskevi , Odemyr Mikaela , Spranger Otto , Hyland Michael E. , Kroegel Claus , Conde Lorena Garcia , Gore Robin , Menzella Francesco , Domingo Ribas Christian , Morais-Almeida Mario , Gasser Matthias , Kasujee Ismail 
Published: December 2018

We conducted a large global survey, Still Fighting for Breath, in patients with severe persistent asthma, 10 years after the Fighting for Breath survey to assess the impact of disease on patients' lives and to determine if control and management have changed in recent years.Data were collected from 1333 adults (aged >18 years) and caregivers of children (aged 6–17 years) with severe persistent asthma from nine countries through an online survey conducted in 2016 by GfK.A decade after the first survey, our results showed that the impact of severe asthma has not changed significantly and a high proportion of patients with severe asthma remain inadequately controlled. A large discrepancy was observed between the proportion of patients who perceived their asthma to be well controlled (42%) and the proportion of patients who reported to be well controlled as per the Global Initiative for Asthma (GINA) assessment (6%). Although most patients perceived their asthma to be controlled, many experienced frequent symptoms that affected their daily lives.Thus, there is a need for improved management (support and strategies) of patients with severe persistent asthma and improved coordination of efforts that would enable these patients to achieve better disease control.
Retrospective validation of a new volumetric capnography parameter for the exclusion of pulmonary embolism at the emergency department
Authors: Fabius Timon M. , Eijsvogel Michiel M.M. , Brusse-Keizer Marjolein G.J. , Sanchez Olivier M. , Verschuren Franck , de Jongh Frans H.C. 
Published: December 2018

Volumetric capnography might be used to exclude pulmonary embolism (PE) without the need for computed tomography pulmonary angiography. In a pilot study, a new parameter (CapNoPE) combining the amount of carbon dioxide exhaled per breath (carbon dioxide production (VCO2)), the slope of phase 3 of the volumetric capnogram (slope 3) and respiratory rate (RR) showed promising diagnostic accuracy (where CapNoPE=(VCO2×slope 3)/RR).To retrospectively validate CapNoPE for the exclusion of PE, the volumetric capnograms of 205 subjects (68 with PE) were analysed, based on a large multicentre dataset of volumetric capnograms from subjects with suspected PE at the emergency department. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and diagnostic accuracy of the in-pilot established threshold (1.90 Pa·min) were calculated. CapNoPE was 1.56±0.97 Pa·min in subjects with PEversus2.51±1.67 Pa·min in those without PE (p<0.001). The AUC of the ROC curve was 0.714 (95% CI 0.64–0.79). For the cut-off of ≥1.90 Pa·min, sensitivity was 64.7%, specificity was 59.9%, the negative predictive value was 77.4% and the positive predictive value was 44.4%.The CapNoPE parameter is decreased in patients with PE but its diagnostic accuracy seems too low to use in clinical practice.
RETRACTED ARTICLE: Ras-ERK1/2 signaling contributes to the development of colorectal cancer via regulating H3K9ac
Authors: Tian Peng , Zhu Yanfei , Zhang Chao , Guo Xinyu , Zhang Peng , Xue Huanzhou 
Published: December 2018

Abstract
Backgrounds/aims
Ras is a control switch of ERK1/2 pathway, and hyperactivation of Ras-ERK1/2 signaling appears frequently in human cancers. However, the molecular regulation following by Ras-ERK1/2 activation is still unclear. This work aimed to reveal whether Ras-ERK1/2 promoted the development of colorectal cancer via regulating H3K9ac.

Methods
A vector for expression of K-Ras mutated at G12 V and T35S was transfected into SW48 cells, and the acetylation of H3K9 was measured by Western blot analysis. MTT assay, colony formation assay, transwell assay, chromatin immunoprecipitation and RT-qPCR were performed to detect whether H3K9ac was contributed to K-Ras-mediated cell growth and migration. Furthermore, whether HDAC2 and PCAF involved in modification of H3K9ac following Ras-ERK1/2 activation were studied.

Results
K-Ras mutated at G12 V and T35S induced a significant activation of ERK1/2 signaling and a significant down-regulation of H3K9ac. Recovering H3K9 acetylation by using a mimicked H3K9ac expression vector attenuated the promoting effects of Ras-ERK1/2 on tumor cells growth and migration. Besides, H3K9ac can be deacetylated by HDAC2 and MDM2-depedent degradation of PCAF.

Conclusion
H3K9ac was a specific target for Ras-ERK1/2 signaling pathway. H3K9 acetylation can be modulated by HDAC2 and MDM2-depedent degradation of PCAF. The revealed regulation provides a better understanding of Ras-ERK1/2 signaling in tumorigenesis.
Detection of Relapse by Tumor Markers Versus Imaging in Children and Adolescents With Nongerminomatous Malignant Germ Cell Tumors: A Report From the Children’s Oncology Group
Authors: Fonseca Adriana , Xia Caihong , Lorenzo Armando J. , Krailo Mark , Olson Thomas A. , Pashankar Farzana , Malogolowkin Marcio H. , Amatruda James F. , Billmire Deborah F. , Rodriguez-Galindo Carlos , Frazier A. Lindsay , Shaikh Furqan 
Published: December 2018

PURPOSE To investigate relapse detection methods among children and adolescents with nongerminomatous malignant germ cell tumors (MGCTs) and to determine whether tumor markers alone might be sufficient for surveillance. METHODS We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs. The method used to detect relapse was assessed based on case report forms, tumor markers, imaging, and pathology reports. Relapses were classified into one of two categories on the basis of whether they were (1) detectable by tumor marker elevation or (2) not detectable by tumor markers. RESULTS A total of 302 patients were enrolled, and 284 patients had complete data for review. Seven patients had normal tumor markers at initial diagnosis, and none experienced a relapse. At a median follow-up of 5.3 years, 48 patients (16.9%) had experienced a relapse. After central review, 47 of 48 relapses (98%) were detected by tumor marker elevation. Of the 47 patients, 16 (33.3%) had abnormal tumor markers with normal/unknown imaging, 31 patients (64.6%) had abnormal tumor markers with abnormal imaging, and one patient (2.1%) had abnormal imaging with unknown marker levels at relapse. CONCLUSION Tumor marker elevation is a highly sensitive method of relapse surveillance, at least among children and adolescents with tumor marker elevation at initial diagnosis. Eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCT.
Influence of substrate orientation on tadpoles feeding efficiency
Authors: Annibale Fabiane Santana , de Sousa Verônica Thiemi Tsutae , de Sousa Carlos Eduardo , Venesky Matthew D. , Rossa-Feres Denise de Cerqueira , Nomura Fausto , Wassersug Richard J. 
Published: December 2018

In nature, tadpoles encounter food on substrates oriented at different angles (e.g. vertically along stems, horizontally on the bottom). We manipulated the orientation of food-covered surfaces to test how different orientations of surfaces affect tadpoles’ feeding efficiency. We studied taxa that differed in the oral morphology of their larvae and position in the water column. We hypothesized that species would differ in their ability to graze upon surfaces at different orientations and that differences in the tadpoles’ feeding ability would result in different growth rates for the species.
The orientation of food-covered surfaces did not affect the growth rate of species with bottom-dwelling tadpoles (whose growth rate varied only between species). Among species with midwater tadpoles, some appear to have a generalist strategy and experienced a high relative growth rate on numerous substrate orientations whereas others achieved high growth rates only on flat substrates (i.e. at 0° and 180°).
We conclude that oral morphology constrains tadpoles’ ability to feed at different substrate orientations, and this could lead to niche partitioning in structurally complex aquatic environments. Because physical parameters of the environment can affect tadpoles’ growth rate, characterizing these features might help us better understanding how competition structures tadpole assemblages.
An amphipathic helix of vinexin α is necessary for a substrate stiffness-dependent conformational change in vinculin
Authors: Hino Naoya , Ichikawa Takafumi , Kimura Yasuhisa , Matsuda Michiyuki , Ueda Kazumitsu , Kioka Noriyuki 
Published: December 2018

ABSTRACT
Extracellular matrix (ECM) stiffness regulates various cell behaviors, including cell differentiation, proliferation and migration. Vinculin and vinexin α (an isoform encoded by the SORBS3 gene), both of which localize to focal adhesions, cooperatively function as mechanosensors of ECM stiffness. On a rigid ECM, vinexin α interacts with vinculin and induces a conformational change in vinculin to give an ‘open’ form, which promotes nuclear localization of Yes-associated protein (YAP, also known as YAP1) and transcriptional coactivator with a PDZ-binding motif (TAZ, also known as WWTR1) (hereafter YAP/TAZ). However, the detailed mechanism by which vinexin α induces the conformational change in vinculin has not been revealed. Here, we identify an amphipathic helix named H2 as a novel vinculin-binding site in vinexin α. The H2 helix interacts with the vinculin D1b subdomain and promotes the formation of a talin–vinculin–vinexin α ternary complex. Mutations in the H2 region not only impair the ability of vinexin α to induce the ECM stiffness-dependent conformational change in vinculin but also to promote nuclear localization of YAP/TAZ on rigid ECM. Taken together, these results demonstrate that the H2 helix in vinexin α plays a critical role in ECM stiffness-dependent regulation of vinculin and cell behaviors.
Curvature-dependent constraints drive remodeling of epithelia
Authors: Maechler Florian A. , Allier Cédric , Roux Aurélien , Tomba Caterina 
Published: December 2018

ABSTRACT
Epithelial tissues function as barriers that separate the organism from the environment. They usually have highly curved shapes, such as tubules or cysts. However, the processes by which the geometry of the environment and the cell's mechanical properties set the epithelium shape are not yet known. In this study, we encapsulated two epithelial cell lines, MDCK and J3B1A, into hollow alginate tubes and grew them under cylindrical confinement forming a complete monolayer. MDCK monolayers detached from the alginate shell at a constant rate, whereas J3B1A monolayers detached at a low rate unless the tube radius was reduced. We showed that this detachment is driven by contractile stresses in the epithelium and can be enhanced by local curvature. This allows us to conclude that J3B1A cells exhibit smaller contractility than MDCK cells. Monolayers inside curved tubes detach at a higher rate on the outside of a curve, confirming that detachment is driven by contraction.
The depolymerase activity of MCAK shows a graded response to Aurora B kinase phosphorylation through allosteric regulation
Authors: McHugh Toni , Zou Juan , Volkov Vladimir A. , Bertin Aurélie , Talapatra Sandeep K. , Rappsilber Juri , Dogterom Marileen , Welburn Julie P. I. 
Published: December 2018

ABSTRACT
Kinesin-13 motors regulate precise microtubule dynamics and limit microtubule length throughout metazoans by depolymerizing microtubule ends. Recently, the kinesin-13 motor family member MCAK (also known Kif2C) has been proposed to undergo large conformational changes during its catalytic cycle, as it switches from being in solution to being bound to microtubules. Here, we reveal that MCAK has a compact conformation in solution through crosslinking and electron microscopy experiments. When MCAK is bound to the microtubule ends, it adopts an extended conformation with the N-terminus and neck region of MCAK interacting with the microtubule. Interestingly, the region of MCAK that interacts with the microtubule is the region phosphorylated by Aurora B and contains an end binding (EB) protein-binding motif. The level of phosphorylation of the N-terminus results in a graded microtubule depolymerase activity. Here, we show that the N-terminus of MCAK forms a platform to integrate Aurora B kinase downstream signals and in response fine-tunes its depolymerase activity during mitosis. We propose that this allosteric control mechanism allows decoupling of the N-terminus from the motor domain of MCAK to allow MCAK depolymerase activity at kinetochores.
Interdisciplinarity master programs in Greek universities: Οrganization and cognitive conditions
Authors: Stamelos Georgios , Aggelopoulos Georgios 
Published: December 2018

This paper focuses on the development of interdisciplinarityin the Master’s programs in Greek universities. For our analysis, we searched for tools from the Sociology of Organisations (Mayntz) and the Sociology of Science (Whitley). We argue that the University and its keyactors have adopted interdisciplinarity, firstly, as a means to increase institutional funding, and secondly, with care so as not to disturb theinternal institutional structure and the power relations between the key actors in the University. Indeed, on the one hand, universities, responding to the public calls for interdisciplinary programs, took advantage of the European support program for Greece in order to enrich their infrastructures. On the other hand, the new structures and functions (interdisciplinary Master’s programs) remain loose and weak. So the central role of the Department and laboratories remains intact. As a consequence, the internal relations of the institutional actors are protected. Thus, interdisciplinarity seems to be a low priority issue. However, it is interesting to consider that more than 10 years after theend of European funding, the majority of these programs remains active.
Recommendations for an EU-IRQ energy centre from stakeholders and experts network studies: The research component
Authors: Karim U. F. A. 
Published: December 2018

Abstract
Results from stakeholders mapping and analysis are used to prepare for an EU-IRQ energy centre (EUIEC). The centre consists of research, training, business, policy and dialogue components. This article focuses on setting up the research centre. EUIEC could be built on good examples taking advantage of EU-IRQ bilateral agreements and ongoing intense developments in Iraq’s energy sector involving top international companies and their large networks. The author advocates actively and mutually facilitating the process particularly in the kick-off and start-up phase (two to five) years. A multi-disciplinary experts’ network setting is recommended that fits best when integrated with the other EUIEC components and services. Recommendations are made to cluster mono-disciplinary research programmes and projects (RP) into multi-disciplinary themes and research areas (RA). The final EUIEC organization, RP and facilities integrating all its components will require further efforts from the consultants, lead stakeholders and experts building up on preliminary results from this study.
Systems of seeing: Virtual gaze interaction
Authors: Ambrose Jeremiah 
Published: December 2018

Abstract
Augmenting Berger’s Ways of Seeing (1972), this article seeks to define and contextualize the most dominant form of perceptual interaction in virtual reality. Combining my own practice with an art-historical overview, I explore a creative application of interactive 360° film, whilst also addressing the need to critically engage with this new medium. I propose that given the rate at which metadata became one of the most valuable commodities of the twenty-first century, our ocular interactions will no doubt become subsumed into these systems. As the discourse of digital artistic practice shifts from digital to post-digital a central concern of virtual reality is the disembodiment it generates, but the irony here is that the first-person body is in fact a virtual camera. More in line with Vertov’s (1896–1954) prescient cybernetic concepts surrounding the kino-eye, virtual gaze interaction offers utopian real-time interaction in the same breath as it exemplifies an Orwellian nightmare. Beyond this cinematographic perspective of the virtual body is the more pertinent need to explore the implications and potential applications of this new type of interaction. The gaze has been a site of theoretical discussion for many theorists, including; Sartre, Foucault and Virilio. However, the interactive gaze is still a site in need of a discourse. Discussed in this article is a site-specific installation, which physically and virtually demonstrates an application of virtual gaze interaction applied to Magritte’s La Clef Des Songes (The Key to Dreams). Extending from Berger’s choice in cover art, it uses different forms of reproduction towards a focus not on what is lost, but what is gained through these new processes of visual interaction. In addition to establishing a historiography and associated praxis for virtual gaze interaction, I present a framework for digital futures pertaining to ocular interactions in media art and beyond. Embedded in this discussion are considerations on the politics of vision and the potential impact this will have on how we perceive and the perception of media art.
O QUE É POSITIVISMO, AFINAL? E QUAL POSITIVISMO?
Authors: Streck Lenio Luiz 
Published: December 2018

Eros Roberto Grau publicou contundente artigo no jornal O Estado de São Paulo, em maio de 2018, “em defesa do positivismo jurídico”. O ponto é que positivismo não é “aplicar a letra ‘fria’ [sic] da lei”. Talvez já tenha sido quando, na França, a Escola da Exegese, baseada em Montesquieu dizia que o juiz era a bouche de la loi. Desde então, o juiz mudou, a lei mudou, a França mudou, o Brasil mudou, o mundo mudou. Logo, mudou o positivismo também. Positivismo é muito mais do que aquilo que foi a sua formulação original: o legalismo. O professor e ex-ministro Eros Roberto Grau acerta no início, quando liga ao positivismo uma ideia de separação entre concepções — talvez, para os positivistas, conceitos —, sejam elas(es) meramente pessoais, subjetivas(os), ou não, de justiça e direito positivo. Essa ideia pode ser vista na clássica formulação de John Austin, pai da jurisprudência analítica.