Integration of RNA-Seq data with heterogeneous microarray data for breast cancer profiling

Background: Nowadays, many public repositories containing large microarray gene expression datasets are available. However, the problem lies in the fact that microarray technology are less powerful and accurate than more recent Next Generation Sequencing technologies, such as RNA-Seq. In any case, information from microarrays is truthful and robust, thus it can be exploited through the integration of microarray data with RNA-Seq data. Additionally, information extraction and acquisition of large number of samples in RNA-Seq still entails very high costs in terms of time and computational resources.This paper proposes a new model to find the gene signature of breast cancer cell lines through the integration of heterogeneous data from different breast cancer datasets, obtained from microarray and RNA-Seq technologies. Consequently, data integration is expected to provide a more robust statistical significance to the results obtained. Finally, a classification method is proposed in order to test the robustness of the Differentially Expressed Genes when unseen data is presented for diagnosis. Results: The proposed data integration allows analyzing gene expression samples coming from different technologies. The most significant genes of the whole integrated data were obtained through the intersection of the three gene sets, corresponding to the identified expressed genes within the microarray data itself, within the RNA-Seq data itself, and within the integrated data from both technologies. This intersection reveals 98 possible technology-independent biomarkers. Two different heterogeneous datasets were distinguished for the classification tasks: a training dataset for gene expression identification and classifier validation, and a test dataset with unseen data for testing the classifier. Both of them achieved great classification accuracies, therefore confirming the validity of the obtained set of genes as possible biomarkers for breast cancer. Through a feature selection process, a final small subset made up by six genes was considered for breast cancer diagnosis. Conclusions: This work proposes a novel data integration stage in the traditional gene expression analysis pipeline through the combination of heterogeneous data from microarrays and RNA-Seq technologies. Available samples have been successfully classified using a subset of six genes obtained by a feature selection method. Consequently, a new classification and diagnosis tool was built and its performance was validated using previously unseen samples.This work was supported by Project TIN2015-71873-R (Spanish Ministry of Economy and Competitiveness -MINECO- and the European Regional Development Fund -ERDF)

Innovación docente en Farmacología: relato de nuestra experiencia en el aprendizaje basado en artefactos (ABA)

En la cima del aprendizaje centrado en el alumnado, los profesores nos enfrentamos al desafío constante de incorporar estrategias en las que los estudiantes deben ser los protagonistas del proceso de enseñanza-aprendizaje y no unos meros receptores de información. En este sentido, los objetivos principales de la estrategia docente llevada a cabo durante los últimos años en una de nuestras asignaturas optativas son facilitar el aprendizaje de la Farmacología, favorecer el trabajo autónomo y propiciar el trabajo colaborativo entre nuestro alumnado. Con este propósito, esta propuesta de innovación docente consiste en utilizar una adaptación y mezcla del Aprendizaje basado en problemas (ABP) y el Aprendizaje basado en proyectos (ABPy), de manera que los alumnos trabajan, en cada tema, unos objetivos propuestos por ellos mismo en coordinación con el profesorado y luego los exponen mediante miniproyectos (artefactos). Debido a su carácter innovador y porque son menos comunes y menos conocidos en el ámbito académico, en este artículo profundizamos en la explicación de cómo implementamos las flashcards, la medicina narrativa y el Examen Clínico Estructurado Objetivo (ECOE) como ejemplos de artefactos obligatorios en nuestras clases. La ventaja de utilizar esta metodología, en comparación con un método tradicional centrado en la lección magistral, es que la implicación del alumnado es mayor a lo largo de todo el curso, asistiendo y trabajando en todas las clases, interactuando con los compañeros y el profesorado de manera continua y aprendiendo a buscar y gestionar información en fuentes bibliográficas fiables. Pioneering the approach of student-focused education, educators constantly grapple with the task of weaving in cutting-edge, interactive, fluid, and frequently artistic teaching techniques where students take center stage in the process of learning, instead of merely being passive receivers of knowledge. In this context, encouraging students to create their own learning resources can augment their educational experience, invigorating their engagement, diligence, and enthusiasm. The main objectives of the teaching strategy carried out in recent years in one of our elective subjects are to promote students’ autonomous work, facilitate the learning of Pharmacology, and encourage collaborative work among our students. For this purpose, this educational innovation proposal consists of using an adaptation and blend of Problem-Based Learning (PBL) and Project-Based Learning (PjBL), so that students work on objectives proposed by themselves in coordination with the teaching staff and then present them through a mini-project we have called artifacts. Due to their innovative nature and because they are less commonly used and less widely known in the academic field, in this article we delve into the explanation of how we implement flashcards, narrative medicine, and the Objective Structured Clinical Examination (OSCE) as examples of mandatory artifacts in our classes. The advantages of implementing this methodology, in contrast to a traditional approach reliant on conventional lectures, include heightened student engagement throughout the entirety of the course. Students attend and participate actively in all classes, continually interact with peers and faculty, and learn to critically seek out information from reliable bibliographic sources

Leukemia multiclass assessment and classification from Microarray and RNA-seq technologies integration at gene expression level

In more recent years, a significant increase in the number of available biological experiments has taken place due to the widespread use of massive sequencing data. Furthermore, the continuous developments in the machine learning and in the high performance computing areas, are allowing a faster and more efficient analysis and processing of this type of data. However, biological information about a certain disease is normally widespread due to the use of different sequencing technologies and different manufacturers, in different experiments along the years around the world. Thus, nowadays it is of paramount importance to attain a correct integration of biologically-related data in order to achieve genuine benefits from them. For this purpose, this work presents an integration of multiple Microarray and RNA-seq platforms, which has led to the design of a multiclass study by collecting samples from the main four types of leukemia, quantified at gene expression. Subsequently, in order to find a set of differentially expressed genes with the highest discernment capability among different types of leukemia, an innovative parameter referred to as coverage is presented here. This parameter allows assessing the number of different pathologies that a certain gen is able to discern. It has been evaluated together with other widely known parameters under assessment of an ANOVA statistical test which corroborated its filtering power when the identified genes are subjected to a machine learning process at multiclass level. The optimal tuning of gene extraction evaluated parameters by means of this statistical test led to the selection of 42 highly relevant expressed genes. By the use of minimum- Redundancy Maximum-Relevance (mRMR) feature selection algorithm, these genes were reordered and assessed under the operation of four different classification techniques. Outstanding results were achieved by taking exclusively the first ten genes of the ranking into consideration. Finally, specific literature was consulted on this last subset of genes, revealing the occurrence of practically all of them with biological processes related to leukemia. At sight of these results, this study underlines the relevance of considering a new parameter which facilitates the identification of highly valid expressed genes for simultaneously discerning multiple types of leukemia.This work was supported by Project TIN2015-71873-R (Spanish Ministry of Economy and Competitiveness -MINECO- and the European Regional Development Fund -ERDF) and Junta de Andalucı´a (P12–TIC–2082)

Aglomeración acústica de partículas

PACS: 43.35, 43.25.-- Publicado en el Vol. XXXI, núm. 3-4, tercer y cuarto trimestre 2000 de la Revista de Acústica: Número especial dedicado al XXV Aniversario del Instituto de Acústica del C.S.I.C.[ES] En este trabajo se presenta una recopilación de las principales aportaciones llevadas a cabo en el campo de la aglomeración acústica de partículas desde 1972. A lo largo de este periodo de tiempo se ha consolidado esta línea de investigación. Se han estudiado y simulado numéricamente los mecanismos básicos del proceso de aglomeración. Paralelamente se han desarrollado y validado nuevos sistemas macrosónicos a escala de laboratorio y de planta piloto para la retención de partículas finas (0.1 - 2.5 μm) en efluentes industriales. Los principales logros científicos llevados a cabo en esta temática han dado lugar a más de setenta publicaciones internacionales.[EN] A summary of the most relevant R+D contributions since 1972 on the acoustic particle agglomeration is presented in this paper. Along this period the research topic has been well consolidated. The basic mechanisms involved in the agglomeration process have been studied and simulated numerically. In parallel, new macrosonic systems at laboratory and pilot plant scale have been developed and validated to reduce fine particle emissions (0.1 - 2.5 μm). The main scientific results obtained were published in more than seventy international papers.Peer reviewe

Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment

BackgroundObesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation.AimThis study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities.Patients and methodsEpidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed.ResultsSignificant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia.ConclusionThe beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS

Women and gambling disorder: Assessing dropouts and relapses in cognitive behavioral group therapy

Background: Gender-specific literature focused on gambling disorder (GD) is scarce, and women with GD have been understudied. Therefore, the aim of this study was to estimate the short-term effectiveness in women with GD (n = 214) of a group standardized cognitive-behavioral therapy (CBT) and to identify the most relevant predictors of the primary therapy outcomes (dropout and relapse). Methods: The manualized CBT consisted of 16 weekly outpatient group sessions. Women were provided with resources to obtain a better understanding of the GD, to improve self-control and to manage risk situations. Results: The dropout risk was higher for women with lower GD severity and higher psychopathological distress. Among other factors, lower education levels were a significant predictor of the relapse risk and and the frequency of relapses was higher for divorced women with a preference for non-strategic gambling and with substances consumption. Conclusions: Our findings evidence women-specific predictors of the primary therapy outcomes. The results highlight the need to design psychological interventions that address dropout and relapse risk factors in women

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe