bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.1375This 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

Abstract

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.
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

AbstractRecently, 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

AbstractIn 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

AbstractIntestinal 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.
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

AbstractLong-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

AbstractOdes4.1 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

AbstractEpisodic 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

AbstractThe 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.
The Role of Participant Responsiveness on a Socio-Emotional Learning Program
Authors: Pereira Nádia Salgado , Marques-Pinto Alexandra 
Published: January 2017

AbstractThe 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.
Autophagy dysregulation in Danon disease
Authors: Nascimbeni Anna Chiara , Fanin Marina , Angelini Corrado , Sandri Marco 
Published: January 2017

AbstractThe 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

AbstractClinically, 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

AbstractHistological 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

AbstractHepatitis 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

AbstractMany 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.