Coupage de tierra y vino.

[ES] Coupage es una palabra adoptada del francés que describe el arte de la mezcla de vinos para mejorar sus propiedades y cualidades. Eso es, en esencia, lo que se busca con este proyecto arquitectónico: una mezcla entre la gente, el pueblo, las tradiciones y la tierra. El proyecto, emplazado en Huércanos, un municipio de 800 habitantes de La Rioja Alta, trata de acercar la cultura del vino a los más jóvenes. Dado que la mayoría del pueblo se dedica al mundo del vino gracias a la bodega cooperativa, se busca generar un espacio conectado a ella tanto de enseñanza e investigación como de reunión en el que la gente del lugar pueda aprender e interesarse por el mundo vitivinícola. Es, por tanto, un centro donde conocer la viticultura, la enología y la cultura del vino. Esto se realizará mediante la creación de espacios comunes, espacios docentes, jardines interactivos para observar el desarrollo de la vid, espacios de cata e investigación, entre otros.[EN] Coupage is a French-adopted word that describes the art of mixing wines so as to enhance its properties and qualities. That is in essence, what is sought with this architectural project: a mixture between the people, the village, its traditions and the land. The project, located in Huércanos, a municipality of 800 inhabitants in La Rioja Alta, tries to bring the wine culture to the youngest. Thanks to the winemaking cooperative most of the people are dedicated to the world of wine. Therefore, it seeks to generate a space connected to it both teaching and research and gathering place in which locals can learn and take an interest in this world; hence it is a centre where one can learn about viniculture, oenology and wine culture. This will be done through the establishment of common spaces, schools, interactive gardens to observe vine development, tasting and research spaces among others.Loras Marca, A. (2021). Coupage de tierra y vino. Universitat Politècnica de València. http://hdl.handle.net/10251/173415TFG

Análisis constructivo de la arquitectura modular actual destinada a viviendas unifamiliares

[ES] El trabajo consiste en el estudio de la arquitectura modular, prefabricada, destinada a las viviendas unifamiliares. El trabajo tendrá una breve reseña histórica de este tipo de construcciones hasta llegar a analizar el estado actual de la arquitectura prefabricada en este ámbito. El análisis se realizará estudiando los distintos sistemas constructivos empleados, por ejemplo modulos tridimensionales o entramados ligeros prefanricados. El estudio del sistema constructivo se materializa mediante el dibujo de los detalles constructivos con identificación de todos los componentes.[EN] The work consists in the study of modular architecture, prefabricated, for single-family homes. The work will have a brief historical review of this type of constructions until analyzing the current state of prefabricated architecture in this area. The analysis will be carried out by studying the different construction systems used, for example three-dimensional modules or prefanricated light frames. The study of the construction system is materialized by drawing the construction details with identification of all components.[CA] El treball consisteix enl’estudi de l’arquitectura modular, prefabricada, destinada a les vivendes unifamiliars. El treball tindrà una breu ressenya històrica d’aquest tipus de construccions fins arribar a analitzar l’estat actual de l’arquitectura en aquest àmbit. L'anàlisi es realitzarà estudiant els diferents sistemes constructius empleats, per exemple, mòduls tridimensionals o entramats lleugers prefabricats. L'estudi del sistema constructiu es materialitza mitjançant el dibuix delsdetalls constructius amb identificació de tots els components.Loras Marca, A. (2020). Análisis constructivo de la arquitectura modular actual destinada a viviendas unifamiliares. Universitat Politècnica de València. http://hdl.handle.net/10251/162287TFG

Identification of omic profiles for diagnosis and monitoring of bladder cancer

La presente Tesis titulada Identificación de perfiles ómicos para el diagnóstico y la monitorización del cáncer de vejiga se centra en la identificación de biomarcadores metabolómicos urinarios no invasivos para el diagnóstico y la monitorización del cáncer de vejiga (CaV). Con este fin, se han utilizado dos plataformas analíticas: la Resonancia Magnética Nuclear (Nuclear Magnetic Resonance, 1H NMR) y la Cromatografía Líquida de alta resolución acoplada a la Espectrometría de Masas (Ultraperformance Liquid Chromatography–Mass Spectrometry, UPLC-MS). Además, se han analizado tejidos vesicales mediante la técnica de Resonancia Magnética Nuclear de Alta Resolución con Giro de Ángulo Mágico (High-Resolution Magic Angle Spinning NMR, HRMAS NMR) para obtener más información sobre las vías metabólicas alteradas en el CaV y evaluar su relación con los perfiles metabólicos urinarios alterados. Por otro lado, se han realizado análisis transcriptómicos en tejidos vesicales para identificar genes metabólicos clave en el CaV. Finalmente, se han llevado a cabo estudios integradores con los datos metabolómicos y transcriptómicos para estudiar las conexiones entre genes y metabolitos y establecer su asociación con el metaboloma urinario. Inicialmente, en el capítulo cuarto se presenta un perfil metabólico capaz de distinguir los tejidos tumorales de los tejidos no tumorales con una sensibilidad y especificidad del 100%, independientemente del estadio y el grado del tumor. Además, se muestran los metabolitos que forman parte de este perfil, así como las vías metabólicas alteradas asociadas a la carcinogénesis vesical. Por otro lado, tras la realización de análisis transcriptómicos en esos mismos tejidos, se detalla como los genes metabólicos están siendo regulados a la baja en los tumores de vejiga mediante la acción de represores transcripcionales, marcas de histonas y procesos de splicing alternativo. Además, mediante un análisis integrativo entre los datos metabolómicos y transcriptómicos, se muestra la concordancia entre los resultados obtenidos a través de estas dos técnicas que representan diferentes niveles de regulación molecular. Finalmente, se muestra un perfil metabólico urinario identificado mediante 1H NMR capaz de distinguir orinas con CaV de orinas control (recogidas después de la cirugía) con una significativa sensibilidad (90,9%) y especificidad (76,9%). Como las muestras de orina y de tejido se recogieron de los mismos pacientes, al final del capítulo se describen las conexiones encontradas entre las rutas metabólicas alteradas en tejidos y orinas Los siguientes dos capítulos de la tesis se centran principalmente en la búsqueda de biomarcadores no invasivos de CaV en muestras de orina para el seguimiento de esta enfermedad a través de dos técnicas analíticas. Con el objetivo de validar el perfil urinario como biomarcador de monitorización de CaV, se llevó a cabo un estudio con muestras urinarias adicionales de pacientes con CaV no músculo-invasivo (CVNMI). Las muestras urinarias se recogieron mensualmente durante un período de seguimiento activo. El perfil metabolómico urinario detectado mediante 1H NMR presentó sensibilidades y especificidades alrededor del 85% en la clasificación de las orinas tumorales, e incluso detectó las recidivas tumorales en un estado temprano de su desarrollo, anticipándose en algunos casos a la visualización de éstas mediante cistoscopia. Este quinto capítulo también detalla los metabolitos discriminantes que forman parte de este perfil metabolómico y su relación con las rutas bioquímicas alteradas en el CaV. Finalmente, el sexto capítulo de la tesis muestra los resultados de un estudio clínico llevado a cabo con un gran número de muestras de orina recolectadas de pacientes con CVNMI antes y después de la cirugía, así como durante un periodo de seguimiento posterior. En este caso, las muestras urinarias se analizaron mediante UPLC-MS y se estudiaron las vías metabólicas perturbadas vinculadas al CaV. Algunas muestras de orina fueron comunes a las analizadas por 1H NMR, y en general, los datos de los dos estudios fueron concordantes. El análisis de las trayectorias longitudinales del biomarcador metabólico urinario capaz de discriminar las muestras tumorales de las controles permitió una evaluación preliminar de su utilidad como biomarcador de seguimiento para la detección de las recurrencias en pacientes con CVNMI. En general, los resultados presentados en esta tesis respaldan la hipótesis de la existencia de una huella metabólica urinaria vinculada a las alteraciones tumorales presentes en los tejidos vesicales, capaz de detectar y predecir las recurrencias durante el período de vigilancia en pacientes con CVNMI. Además, los buenos resultados obtenidos y la concordancia entre ambos estudios urinarios (1H NMR y UPLC-MS) posicionan la metabolómica al frente de las técnicas ómicas para la búsqueda de biomarcadores robustos y dinámicos que reflejen la biología del tumor.The present Thesis entitled Identification of omic profiles for diagnosis and monitoring of bladder cancer is focused on identifying non-invasive urinary metabolomic biomarkers of diagnosis and monitoring of bladder cancer (BC). In order to achieve this objective, two analytical strategies based on Nuclear Magnetic Resonance (1H NMR) and Ultraperformance Liquid Chromatography–Mass Spectrometry (UPLC-MS) have been used for the analysis of urine samples. Besides, bladder tissue samples have been analyzed by High-Resolution Magic Angle Spinning NMR (HRMAS NMR) technique to get further insight into altered metabolic pathways in BC and assess their link with altered urinary metabolomic profiles. On the other hand, transcriptomic analysis has been carried out in bladder tissues to identify key metabolic genes in BC. Additionally, integrative studies using metabolomic and transcriptomic data have been performed to study the gene-metabolite networks in BC and its association with the altered urinary metabolome. Initially, a metabolic profile able to distinguish BC tissues from non-tumor tissues with a sensitivity and specificity of 100%, independently of stage and grade of the tumor, is presented in chapter four. Moreover, the metabolites that take part of this profile are showed, as well as, the disturbed metabolic pathways linked to BC carcinogenesis. On the other hand, the transcriptomic analysis performed in these same tissues is described, indicating principally that metabolic genes are downregulated in bladder tumors and that transcriptional repressors, histone marks, and alternatively splicing processes may be regulating those genes. Additionally, an integrative analysis between metabolomic and transcriptomic data is detailed, showing concordance between the results obtained through these two techniques that represent different levels of molecular regulation. Finally, a 1H NMR-based urinary metabolic profile capable of distinguishing BC urines from control urines (collected after surgery) with significant sensitivity (90.9%) and specificity (76.9%) is shown. Urine and tissue samples were collected from the same patients, so at the end of chapter, the connections between the perturbed metabolic pathways in tissues and urines are described. The following two chapters of the thesis are focused principally on searching non-invasive biomarkers of BC in urine samples for monitoring this disease by means of two analytical techniques. In order to validate the urinary profile as a biomarker for monitoring, a study with additional urinary samples collected from patients with NMIBC was carried out. Urinary samples were collected monthly during a follow-up period. The urinary 1H NMR metabolic profile showed a sensitivity and specificity around 85% classifying BC urines. Moreover, tumor recurrences were detected by the metabolic profile in an early stage of disease, anticipating in some cases to the BC visualization by cystoscopy. The altered metabolic pathways in the urinary metabolome were also identified. Finally, the sixth chapter of the thesis exhibits the results of an investigative clinical study carried out in a large number or urinary samples collected from NMIBC patients before and after surgery, as well as during the subsequent surveillance. In this case, the urine samples were analyzed through UPLC-MS and perturbed metabolic pathways were assessed. Some urinary samples were common to those analyzed by 1H NMR, and data were in agreement. The analysis of the longitudinal trajectories of the metabolic biomarker discriminating between BC and control samples allowed a preliminary evaluation of its potential utility to monitor NMIBC relapse in patients undergoing surveillance for tumor recurrence. On the whole, the results presented in this thesis give support to the hypothesis of the existence of a urinary metabolic signature linked with tumor alterations in BC tissues able to detect and predict recurrences during the surveillance period of patients with NMIBC. Moreover, the good results obtained and the concordance between the urinary analyses by 1H NMR and UPLC–MS highlight the metabolomics as a competitive omic for searching biomarkers, since offers robust and dynamic information about the biology of the tumor

Urinary metabolic signatures detect recurrences in non-muscle invasive bladder cancer

Patients with non-muscle invasive bladder cancer (NMIBC) undergo lifelong monitoring based on repeated cystoscopy and urinary cytology due to the high recurrence rate of this tumor. Nevertheless, these techniques have some drawbacks, namely, low accuracy in detection of low-grade tumors, omission of pre-neoplastic lesions and carcinomas in situ (CIS), invasiveness, and high costs. This work aims to identify a urinary metabolomic signature of recurrence by proton Nuclear Magnetic Resonance (1H NMR) spectroscopy for the follow-up of NMIBC patients. To do this, changes in the urinary metabolome before and after transurethral resection (TUR) of tumors are analyzed and a Partial Least Square Discriminant Analysis (PLS-DA) model is developed. The usefulness of this discriminant model for the detection of tumor recurrences is assessed using a cohort of patients undergoing monitoring. The trajectories of the metabolomic profile in the follow-up period provide a negative predictive value of 92.7% in the sample classification. Pathway analyses show taurine, alanine, aspartate, glutamate, and phenylalanine perturbed metabolism associated with NMIBC. These results highlight the potential of 1H NMR metabolomics to detect bladder cancer (BC) recurrences through a non-invasive approach

Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer

[EN] Metabolism reprogramming is considered a hallmark of cancer. The study of bladder cancer (BC) metabolism could be the key to developing new strategies for diagnosis and therapy. This work aimed to identify tissue and urinary metabolic signatures as biomarkers of BC and get further insight into BC tumor biology through the study of gene-metabolite networks and the integration of metabolomics and transcriptomics data. BC and control tissue samples (n = 44) from the same patients were analyzed by High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance and microarrays techniques. Besides, urinary profiling study (n = 35) was performed in the same patients to identify a metabolomic profile, linked with BC tissue hallmarks, as a potential non-invasive approach for BC diagnosis. The metabolic profile allowed for the classification of BC tissue samples with a sensitivity and specificity of 100%. The most discriminant metabolites for BC tissue samples reflected alterations in amino acids, glutathione, and taurine metabolic pathways. Transcriptomic data supported metabolomic results and revealed a predominant downregulation of metabolic genes belonging to phosphorylative oxidation, tricarboxylic acid cycle, and amino acid metabolism. The urinary profiling study showed a relation with taurine and other amino acids perturbed pathways observed in BC tissue samples, and classified BC from non-tumor urine samples with good sensitivities (91%) and specificities (77%). This urinary profile could be used as a non-invasive tool for BC diagnosis and follow-up.This research was funded by FEDER cofounded MINECO grant SAF2015-66015-R, MAT2015-64139-C4-1-R, MAT2015-64139-C4-3-R, ISCIII-RETICRD12/0036/0009, PIE 15/00076, CB/16/00228, CTQ2016-79561-P; and the PROMETEO II/2014/047 and PROMETEO 2018/24 projects.Loras, A.; Suárez-Cabrera, C.; Martínez-Bisbal, M.; Quintás, G.; Paramio, JM.; Martínez-Máñez, R.; Gil Grau, S.... (2019). Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer. Cancers. 11(5):1-19. https://doi.org/10.3390/cancers1105068611911

Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

Background: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. Methods/design: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. Discussion: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD

Detection of prostate cancer using a voltammetric electronic tongue

[EN] A simple method based on the multivariate analysis of data from urine using an electronic voltammetric tongue is used to detect patients with prostate cancer. A sensitivity of 91% and a specificity of 73% were obtained to distinguish the urine from cancer patients and the urine from non-cancer patients.The authors gratefully acknowledge the Ministerio de Economia y Competitividad and FEDER (project MAT2015-64139-C4-1-R (MINECO/FEDER)), the Generalitat Valenciana (project PROMETEOII/2014/047) and CIBER-BBN (NANOP-ROBE project) for their financial support. A. L. is grateful to the Generalitat Valenciana for her grant (Vali+d ACIF: 2015/115).Pascual, L.; Campos Sánchez, I.; Vivancos, J.; Quintás, G.; Loras Monfort, A.; Martínez-Bisbal, M.; Martínez-Máñez, R.... (2016). Detection of prostate cancer using a voltammetric electronic tongue. Analyst. 141(15):4562-4567. https://doi.org/10.1039/C6AN01044JS456245671411

UV-Induced Somatic Mutations Driving Clonal Evolution in Healthy Skin, Nevus, and Cutaneous Melanoma

Introduction: Due to its aggressiveness, cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. The origin of CM is closely linked to the appearance of UV-induced somatic mutations in melanocytes present in normal skin or in CM precursor lesions (nevi or dysplastic nevi). In recent years, new NGS studies performed on CM tissue have increased the understanding of the genetic somatic changes underlying melanomagenesis and CM tumor progression. Methods: We reviewed the literature using all important scientific databases. All articles related to genomic mutations in CM as well as normal skin and nevi were included, in particular those related to somatic mutations produced by UV radiation. Conclusions: CM development and progression are strongly associated with exposure to UV radiation, although each melanoma subtype has different characteristic genetic alterations and evolutionary trajectories. While BRAF and NRAS mutations are common in the early stages of tumor development for most CM subtypes, changes in CDKN2A, TP53 and PTEN, together with TERT promoter mutations, are especially common in advanced stages. Additionally, large genome duplications, loss of heterozygosity, and copy number variations are hallmarks of metastatic disease. Finally, the mutations driving melanoma targetedtherapy drug resistance are also summarized. The complete sequential stages of clonal evolution leading to CM onset from normal skin or nevi are still unknown, so further studies are needed in this field to shed light on the molecular pathways involved in CM malignant transformation and in melanoma acquired drug resistance

UV-Induced Somatic Mutations Driving Clonal Evolution in Healthy Skin, Nevus, and Cutaneous Melanoma

Introduction: Due to its aggressiveness, cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. The origin of CM is closely linked to the appearance of UV-induced somatic mutations in melanocytes present in normal skin or in CM precursor lesions (nevi or dysplastic nevi). In recent years, new NGS studies performed on CM tissue have increased the understanding of the genetic somatic changes underlying melanomagenesis and CM tumor progression. Methods: We reviewed the literature using all important scientific databases. All articles related to genomic mutations in CM as well as normal skin and nevi were included, in particular those related to somatic mutations produced by UV radiation. Conclusions: CM development and progression are strongly associated with exposure to UV radiation, although each melanoma subtype has different characteristic genetic alterations and evolutionary trajectories. While BRAF and NRAS mutations are common in the early stages of tumor development for most CM subtypes, changes in CDKN2A, TP53 and PTEN, together with TERT promoter mutations, are especially common in advanced stages. Additionally, large genome duplications, loss of heterozygosity, and copy number variations are hallmarks of metastatic disease. Finally, the mutations driving melanoma targeted-therapy drug resistance are also summarized. The complete sequential stages of clonal evolution leading to CM onset from normal skin or nevi are still unknown, so further studies are needed in this field to shed light on the molecular pathways involved in CM malignant transformation and in melanoma acquired drug resistance

Neural Stem Cells as Potential Glioblastoma Cells of Origin

Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults and it remains incurable. These tumors are very heterogeneous, resistant to cytotoxic therapies, and they show high rates of invasiveness. Therefore, patients face poor prognosis, and the survival rates remain very low. Previous research states that GBM contains a cell population with stem cell characteristics called glioma stem cells (GSCs). These cells are able to self-renew and regenerate the tumor and, therefore, they are partly responsible for the observed resistance to therapies and tumor recurrence. Recent data indicate that neural stem cells (NSCs) in the subventricular zone (SVZ) are the cells of origin of GBM, that is, the cell type acquiring the initial tumorigenic mutation. The involvement of SVZ-NSCs is also associated with GBM progression and recurrence. Identifying the cellular origin of GBM is important for the development of early detection techniques and the discovery of early disease markers. In this review, we analyze the SVZ-NSC population as a potential GBM cell of origin, and its potential role for GBM therapies