Circulating microRNAs as potential diagnostic biomarkers for osteoporosis

Osteoporosis is the most common age-related bone disease worldwide and is usually clinically asymptomatic until the first fracture happens. MicroRNAs are critical molecular regulators in bone remodelling processes and are stabilised in the blood. The aim of this project was to identify circulatory microRNAs associated with osteoporosis using advanced PCR arrays initially and the identified differentially-expressed microRNAs were validated in clinical samples using RT-qPCR. A total of 161participants were recruited and 139 participants were included in this study with local ethical approvals prior to recruitment. RNAs were extracted, purified, quantified and analysed from all serum and plasma samples. Differentially-expressed miRNAs were identified using miRNA PCR arrays initially and validated in 139 serum and 134 plasma clinical samples using RT-qPCR. Following validation of identified miRNAs in individual clinical samples using RT-qPCR, circulating miRNAs, hsa-miR-122-5p and hsa-miR-4516 were statistically significantly differentially-expressed between non-osteoporotic controls, osteopaenia and osteoporosis patients. Further analysis showed that the levels of these microRNAs were associated with fragility fracture and correlated with the low bone mineral density in osteoporosis patients. The results show that circulating hsa-miR-122-5p and hsa-miR-4516 could be potential diagnostic biomarkers for osteoporosis in the future

Mapping Study about Usability Requirements Elicitation

[EN] The HCI community has developed guidelines and recommendations for improving the usability system that are usually applied at the last stages of the software development process. On the other hand, the SE community has developed sound methods to elicit functional requirements in the early stages, but usability has been relegated to the last stages together with other nonfunctional requirements. Therefore, there are no methods of usability requirements elicitation to develop software within both communities. An example of this problem arises if we focus on the Model-Driven Development paradigm, where the methods and tools that are used to develop software do not support usability requirements elicitation. In order to study the existing publications that deal with usability requirements from the first steps of the software development process, this work presents a mapping study. Our aim is to compare usability requirements methods and to identify the strong points of each oneThis work has been developed with the support of MICINN (PROS-Req TIN2010-19130-C02-02), UV (UV-INV-PRECOMP12-80627), GVA (ORCA PROMETEO/2009/015), and co-financed with ERDF. We acknowledge the support of the ITEA2 Call 3 UsiXML (20080026) and funding by the MITYC (TSI-020400-2011-20)Ormeño Ayala, YI.; Panach Navarrete, JI. (2013). Mapping Study about Usability Requirements Elicitation. Springer. 672-687. https://doi.org/10.1007/978-3-642-38709-8_43S672687Publish or Perish, http://www.harzing.comAcerbis, R., Bongio, A., Brambilla, M., Butti, S.: WebRatio 5: An Eclipse-Based CASE Tool for Engineering Web Applications. In: Baresi, L., Fraternali, P., Houben, G.-J. (eds.) ICWE 2007. LNCS, vol. 4607, pp. 501–505. Springer, Heidelberg (2007)Akoumianakis, D., Katsis, A., Vidakis, N.: Non-functional User Interface Requirements Notation (NfRn) for Modeling the Global Execution Context of Tasks. In: Coninx, K., Luyten, K., Schneider, K.A. (eds.) TAMODIA 2006. LNCS, vol. 4385, pp. 259–274. Springer, Heidelberg (2007)Ameller, D., Franch, X., Cabot, J.: Dealing with Non-Functional Requirements in Model-Driven Development. In: 18th IEEE International Conference on Requirements Engineering (RE), Sydney, NSW, pp. 189–198 (2010)Bass, L., John, B.: Linking Usability to Software Architecture Patterns through General Scenarios. Journal of Systems and Software 66(3), 187–197 (2003)Creissac Campos, J., Harrison, M.D.: Systematic Analysis of Control Panel Interfaces Using Formal Tools. In: Graham, T.C.N. (ed.) DSV-IS 2008. LNCS, vol. 5136, pp. 72–85. Springer, Heidelberg (2008)Carrizo, D., Dieste, O., Juristo, N.: Study of Elicitation Techniques Adequacy. In: 11th Workshop on Requirements Engineering, Spain, Barcelona, pp. 104–114 (2008)Cronholm, S., Bruno, V.: Do you Need General Principles or Concrete Heuristics?: A Model for Categorizing Usability Criteria. In: 20th Australasian Conference on Computer-Human Interaction: Designing for Habitus and Habitat. ACM, Cairns (2008)Cysneiros, L.M., Leite, J.C.S.P.: Nonfunctional Requirements: from Elicitation to Conceptual Models. IEEE Trans. on Softw. Eng. 30(5), 328–350 (2004)Cysneiros, L.M., Werneck, V.M., Kushniruk, A.: Reusable Knowledge for Satisficing Usability Requirements. In: 13th IEEE International Conference on Requirement Engineering, pp. 463–464. IEEE Computer Society, Washington, DC (2005)Chung, L., do Prado Leite, J.C.S.: On Non-Functional Requirements in Software Engineering. In: Borgida, A.T., Chaudhri, V.K., Giorgini, P., Yu, E.S. (eds.) Conceptual Modeling: Foundations and Applications. LNCS, vol. 5600, pp. 363–379. Springer, Heidelberg (2009)Daniel, S., Rita de Almeida, P., Isbela, M.: OOHDM-Web: An Environment for Implementation of Hypermedia Applications in the WWW. SIGWEB Newsl. 8(2), 18–34 (1999)Dieste, O., Lopez, M., Ramos, F.: Updating a Systematic Review about Selection of Software Requirements Elicitation Techniques. In: 11th Workshop in Requirements Engineering, Barcelona, Spain (2008)Doerr, J., Kerkow, D., Koenig, T., Olsson, T., Suzuki, T.: Non-functional Requirements in Industry - Three Case Studies Adopting an Experience-based NFR Method. In: 13th IEEE International Conference on Requirements Engineering, Washington, DC, USA, pp. 373–384 (2005)Escalona, M.J., Arag, G.: NDT. A Model-Driven Approach for Web Requirements. IEEE Trans. Softw. Eng. 34(3), 377–390 (2008)Escalona, M.J., Koch, N., Filipe, J., Cordeiro, J., Pedrosa, V.: Metamodeling the Requirements of Web Systems Web Information Systems and Technologies, vol. 1, pp. 267–280. Springer, Heidelberg (2007)Fatwanto, A., Boughton, C.: Analysis, Specification and Modeling of Non-Functional Requirements for Translative Model-Driven Development. In: International Conference on Computational Intelligence and Security, Washington, DC, USA, pp. 405–410 (2008)Fernandez, A., Insfran, E., Abrahão, S.: Usability Evaluation Methods for the Web: A Systematic Mapping Study. Information and Software Technology 53(8), 789–817 (2011)Fleiss, J.L.: Statistical Methods for Rates and Proportions. John Wiley & Sons, New York (1981)Folmer, E., Bosch, J.: Architecting for usability: A Survey. Journal of Systems and Software 70(1), 61–78 (2004)Grosse-Wentrup, D., Stier, A., Hoelscher, U., Dössel, O., Schlegel, W.C.: Supporting Tool for Usability Specifications. In: World Congress on Medical Physic and Biomedical Engineering, Munich, Germany, pp. 845–847. Springer (2009)Henninger, S.: A Methodology and Tools for Applying Context-specific Usability Guidelines to Interface Design. Journal Interacting with Computers 12(3), 225–243 (2000)Journal Citation Reports, http://ip-science.thomsonreuters.comJokela, T., Koivumaa, J., Pirkola, J., Salminen, P., Kantola, N.: Methods for Quantitative Usability Requirements: A Case Study on the Development of the User Interface of a Mobile Phone. Personal Ubiquitous Comput. 10(6), 345–355 (2006)Jokela, T., Seffah, A., Gulliksen, J., Desmarais, M.C.: 8 Guiding Designers to the World of Usability: Determining Usability Requirements Through Teamwork, vol. 8, pp. 127–145. Springer, Netherlands (2005)Juristo, N.: Impact of Usability on Software Requirements and Design, pp. 55–77. Springer (2009)Juristo, N., Moreno, A.M., Sánchez, M.I.: Guidelines for Eliciting Usability Functionalities. IEEE Trans. Softw. Eng. 33(11), 744–758 (2007)Kitchenham, B.: Procedures for Performing Systematic Reviews. Technical Report TR/SE-0401 (2004)Kitchenham, B.A., Charters, S.: Guidelines for performing Systematic Literature Reviews in Software Engineering. EBSE Technica Report (2007)Lauesen, S., Younessi, H.: Six styles for usability requirements. In: REFSQ 1998 (1998)MacLean, A., Young, R.M., Bellotti, V.M.E., Moran, T.P.: Questions, Options, and Criteria: Elements of Design Space Analysis. Human-Computer Interaction 6(3), 201–250 (1996)Martinie, C., Palanque, P., Winckler, M., Conversy, S.: DREAMER: A Design Rationale Environment for Argumentation, Modeling and Engineering Requirements. In: 28th International Conference on Design of Communication, Säo Paulo, Brazil (2010)Mehwish, R., Emilia, M., Ewan, T.: A Systematic Review of Software Maintainability Prediction and Metrics, pp. 367–377. IEEE Computer Society, Washington, DC (2009)Mellado, D., Blanco, C., Sánchez, L.E., Fernandez, E.: A Systematic Review of Security Requirements Engineering. Comput. Stand. Interfaces 32(4), 153–165 (2010)Nguyen, Q.L.: Non-Functional Requirements Analysis Modeling for Software Product Lines. In: ICSE Workshop on Modeling in Software Engineering, Washington, DC, USA, pp. 56–61 (2009)Nielsen, J.: Usability Engineering. Morgan Kaufmann (1993)Panach, J.I., España, S., Moreno, A.M., Pastor, Ó.: Dealing with Usability in Model Transformation Technologies. In: Li, Q., Spaccapietra, S., Yu, E., Olivé, A. (eds.) ER 2008. LNCS, vol. 5231, pp. 498–511. Springer, Heidelberg (2008)Panach, J.I., España, S., Pederiva, I., Pastor, O.: Capturing Interaction Requirements in a Model Transformation Technology Based on MDA. Journal of Universal Computer Science (JUCS) 14(9), 1480–1495 (2007)Pastor, O., Molina, J.: Model-Driven Architecture in Practice. Springer (2007)Paterno, F.: Model-based Tools for Pervasive Usability. Interacting with Computers 17(3), 291–315 (2004)Refworks, http://www.refworks.com/Röder, H.: Using Interaction Requirements to Operationalize Usability. In: ACM Symposium on Applied Computing, Sierre, Switzerland (2010)Sajedi, A., Mahdavi, M., Pourshirmohammadi, A., Nejad, M.M.: Fundamental Usability Guidelines for User Interface Design. In: International Conference on Computational Sciences and Its Applications, ICCSA, Washington, DC, USA, pp. 106–113 (2008)Shehata, M., Eberlein, A., Fapojuwo, A.O.: A Taxonomy for Identifying Requirement Interactions in Software Systems. Comput. Netw. 51(2), 398–425 (2007)Sindhgatta, R., Thonse, S.: Functional and Non-functional Requirements Specification for Enterprise Applications. In: Bomarius, F., Komi-Sirviö, S. (eds.) PROFES 2005. LNCS, vol. 3547, pp. 189–201. Springer, Heidelberg (2005)Soares, M.S., Vrancken, J.L.M.: Model-Driven User Requirements Specification using SysML. Journal of Software 3(6), 57–68 (2008)Sutcliffe, A.G., Kurniawan, S., Jae-Eun, S.: A Method and Advisor Tool for Multimedia User Interface Design. Int. J. Hum.-Comput. Stud. 64(4), 375–392 (2006)Sutcliffe Alistair, G., Michele, R.: Experience with SCRAM, a SCenario Requirements Analysis Method. In: 3rd International Conference on Requirements Engineering: Putting Requirements Engineering to Practice, pp. 164–171. IEEE Computer Society (1998)Svensson, B., Gorschek, T., Regnell, B., Torkar, R., Shahrokni, A., Feldt, R.: Quality Requirements in Industrial Practice - An Extended Interview Study at Eleven Companies. IEEE Trans. Softw. Eng. 38(4), 923–935 (2012)Svensson, R.B., Höst, M., Regnell, B.: Managing Quality Requirements: A Systematic Review. In: 36th EUROMICRO Conference on Software Engineering and Advanced Applications (SEAA), pp. 261–268 (2010)Yi, L., Zhiyi, M., Weizhong, S.: Integrating Non-functional Requirement Modeling into Model Driven Development Method. In: 17th Asia Pacific Software Engineering Conference, Beijing, China (2010

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorder