147 research outputs found

    PROPERTIES OF TWO U.S. INFLATION MEASURES (1985-2005)

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    Analyses are presented of 84 quarterly observations 1/85-4/05 on two U.S. index numbers of nominal prices often employed to measure inflation. Analyses are designed to answer two key questions of interest to macroeconomists. Is inflation stationary (I(0)) or stochastically non-stationary (I(1))? If it is I(1), is it scalar or multivariate? Both measures of inflation are found clearly to be I(1) and, for these measures, inflation is found clearly to be scalar. The paper also illustrates univariate analysis procedures (and report standards) considered to be more effective and convincing than those found in the existing literature on inflation measures.

    In silico Approach for Validating and Unveiling New Applications for Prognostic Biomarkers of Endometrial Cancer

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    Bioinformática; Cáncer de endometrio; Biomarcador pronósticoBioinformàtica; Càncer d'endometri; Biomarcador pronòsticBioinformatics; Endometrial cancer; Prognostic biomarkerEndometrial cancer (EC) mortality is directly associated with the presence of prognostic factors. Current stratification systems are not accurate enough to predict the outcome of patients. Therefore, identifying more accurate prognostic EC biomarkers is crucial. We aimed to validate 255 prognostic biomarkers identified in multiple studies and explore their prognostic application by analyzing them in TCGA and CPTAC datasets. We analyzed the mRNA and proteomic expression data to assess the statistical prognostic performance of the 255 proteins. Significant biomarkers related to overall survival (OS) and recurrence-free survival (RFS) were combined and signatures generated. A total of 30 biomarkers were associated either to one or more of the following prognostic factors: histological type (n = 15), histological grade (n = 6), FIGO stage (n = 1), molecular classification (n = 16), or they were associated to OS (n = 11), and RFS (n = 5). A prognostic signature composed of 11 proteins increased the accuracy to predict OS (AUC = 0.827). The study validates and identifies new potential applications of 30 proteins as prognostic biomarkers and suggests to further study under-studied biomarkers such as TPX2, and confirms already used biomarkers such as MSH6, MSH2, or L1CAM. These results are expected to advance the quest for biomarkers to accurately assess the risk of EC patients.This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) grant number PI17/02155, PI20/00644, and the IFI19/00029 to E.C.-d.l.R., the Ministerio de ciencia, Innovación y Universidades through a RETOS Colaboración (RTC-2017-6261-1), both co-financed by the European Regional Development Fund (FEDER); from Fundación Científica Asociación Española Contra el Cáncer (AECC) grant number GCTRA1804MATI and CIBERONC network grant number CB16/12/00328; and Grups Consolidats de la Generalitat de Catalunya (2017SGR1661). E.C. is supported by an Investigator Grant from AECC (INVES20051COLA). E.M.-G. was supported by Televie grant F5/20/5-TLV/DD

    TweetMT : a parallel microblog corpus

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    We introduce TweetMT, a parallel corpus of tweets in four language pairs that combine five languages (Spanish from/to Basque, Catalan, Galician and Portuguese), all of which have an official status in the Iberian Peninsula. The corpus has been created by combining automatic collection and crowdsourcing approaches, and it is publicly available. It is intended for the development and testing of microtext machine translation systems. In this paper we describe the methodology followed to build the corpus, and present the results of the shared task in which it was tested

    BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

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    Glycolysis; Melanomas; Targeted therapyGlucólisis; Melanomas; Terapia dirigidaGlucòlisi; Melanomes; Teràpia dirigidaNRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRASQ61-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRASQ61-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib.This work was funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “A way to make Europe”/“Investing in your future”) PI14/0375-Fondos FEDER J.A.R., PI17/00043-Fondos FEDER; J.A.R., PI20/0384-Fondos FEDER; J.A.R., Euronanomed2-ISCIII (AC16/00019)-Fondos FEDER; J.A.R., Asociación Española Contra el Cancer (AECC-GCB15152978SOEN) (supported P.G.M., K.M.); J.A.R., Ramón Areces Foundation (supported K.M. and research); J.A.R. (PI17/00412)-Fondos FEDER; R.B., A.M., A.N.S. We thank A. Zorzano’s laboratory for technical assistance and performance of Seahorse technology

    Mixed Th2 and non-Th2 inflammatory pattern in the asthma-COPD overlap : a network approach

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    Altres ajuts: The authors are grateful to all the patients who participated in the study. A number of investigators contributed to the study logistics and they are listed in the Supplementary materials. The project was endorsed by the COPD and Asthma Research Board (PII de EPOC y asma) of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR).The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO. We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO. This is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity 10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis. In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61-3.57] vs 1.11 [0.12-2.42] pg/mL, respectively; p =0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61-13.12] vs 7.03 [4.69-10.44] pg/mL, respectively; p <0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions. Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions

    Red de investigación en docencia universitaria de la UA: “Universidad, Docencia, Género e Igualdad” (II)

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    La Red de investigación en docencia universitaria “Universidad, docencia, genero e igualdad” persigue avanzar en la calidad e innovación de las enseñanzas universitarias a partir de la inclusión de la perspectiva de género. Se busca dar cumplimiento a las directrices generales de los nuevos planes de estudio respecto del principio de igualdad de oportunidades entre hombres y mujeres en la formación universitaria (Real Decreto 1393/2007. BOE nº 260, 30 de octubre de 2007). En la tercera edición de la Red, y dada su composición multidisciplinar, se desarrollaron dos líneas de investigación: por un lado, se continuó trabajando en el mantenimiento del “Portal web con recursos docentes con perspectiva de género”, proyecto financiado por el Instituto de la Mujer (PACUI, 2012) e iniciado en el curso 2012-2013, incrementándose en un 36% la colección de recursos; y, por otro, se inició una nueva línea de investigación con la que se busca desarrollar una herramienta informática de ayuda para la redacción de textos con lenguaje inclusivo

    Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease

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    T. Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged &lt;18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value &lt; 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.This work was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2), The study was cofunded by ERDF Funds (FEDER) from the European Commission, “A way of making Europe

    Effect of a Nutritional and Behavioral Intervention on Energy-Reduced Mediterranean Diet Adherence Among Patients With Metabolic Syndrome: Interim Analysis of the PREDIMED-Plus Randomized Clinical Trial

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    Key PointsQuestionWhat is the effect of a nutritional and behavioral intervention focused on encouraging an energy-reduced Mediterranean diet and physical activity on the dietary pattern of participants after 12 months? FindingsIn this preliminary analysis of an ongoing randomized clinical trial involving 6874 participants, an intervention focused on encouraging an energy-reduced Mediterranean diet and promoting physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significant increase in a measure of diet adherence, the 17-item energy-reduced Mediterranean diet score, at 12 months (4.7 points vs 2.5 points; score range, 0-17; minimal clinically important difference, 1 point). MeaningA nutritional and behavioral intervention focused on encouraging an energy-reduced Mediterranean diet and physical activity led to a significant improvement in a measure of diet adherence at 12 months. Further evaluation of the effects on long-term cardiovascular and other health outcomes is needed. ImportanceHigh-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary changes. ObjectiveTo assess the effect of a nutritional and physical activity education program on dietary quality. Design, Setting, and ParticipantsPreliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019. InterventionsParticipants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n=3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n=3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free. Main Outcomes and MeasuresThe primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point). ResultsAmong 6874 randomized participants (mean [SD] age, 65.0 [4.9] years; 3406 [52%] men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 [95% CI, 4.6-4.8]) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 [95% CI, 2.3-2.6]) (between-group difference, 2.2 [95% CI, 2.1-2.4]; P<.001). Conclusions and RelevanceIn this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed. Trial Registrationisrctn.com Identifier: ISRCTN89898870 This preliminary exploratory analysis of the ongoing PREDIMED-Plus randomized trial reports dietary adherence among Spanish community-dwelling participants with metabolic syndrome randomized to an energy-reduced Mediterranean diet, physical activity, and behavioral support vs an energy-unrestricted Mediterranean diet alone

    Longitudinal association of dietary acid load with kidney function decline in an older adult population with metabolic syndrome

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    Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR (n = 5,874) or UACR (n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase. Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, β: -0.64 ml/min/1.73 m2; 95% CI: -1.21 to -0.08 and NEAP, β: -0.56 ml/min/1.73 m2; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load. Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome. Keywords: albuminuria; chronic kidney disease (CKD); dietary acid load; glomerular filtration rate (GFR); kidney function; net endogenous acid production (NEAP); potential renal acid load (PRAL); renal nutrition
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