Los documentos de idoneidad técnica como potenciales incentivadotes de la industrialización de la construcción.

Los documentos de idoneidad técnica como potenciales incentivadotes de la industrialización de la construcción

Identification of cell surface targets for CAR-T cell therapies and antibody-drug conjugates in breast cancer

Background: Two promising therapeutic strategies in oncology are chimeric antigen receptor-T cell (CAR-T) therapies and antibody-drug conjugates (ADCs). To be effective and safe, these immunotherapies require surface antigens to be sufficiently expressed in tumors and less or not expressed in normal tissues. To identify new targets for ADCs and CAR-T specifically targeting breast cancer (BC) molecular and pathology-based subtypes, we propose a novel in silico strategy based on multiple publicly available datasets and provide a comprehensive explanation of the workflow for a further implementation. Methods: We carried out differential gene expression analyses on The Cancer Genome Atlas BC RNA-sequencing data to identify BC subtype-specific upregulated genes. To fully explain the proposed target-discovering methodology, as proof of concept, we selected the 200 most upregulated genes for each subtype and undertook a comprehensive analysis of their protein expression in BC and normal tissues through several publicly available databases to identify the potentially safest and viable targets. Results: We identified 36 potentially suitable and subtype-specific tumor surface antigens (TSAs), including fibroblast growth factor receptor-4 (FGFR4), carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), GDNF family receptor alpha 1 (GFRA1), integrin beta-6 (ITGB6) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). We also identified 63 potential TSA pairs that might be appropriate for co-targeting strategies. Finally, we validated subtype specificity in a cohort of our patients, multiple BC cell lines and the METABRIC database. Conclusions: Overall, our in silico analysis provides a framework to identify novel and specific TSAs for the development of new CAR-T and antibody-based therapies in BC

Ocean Circulation over North Atlantic underwater features in the path of the Mediterranean Outflow Water: Ormonde and Formigas seamounts, and the Gazul mud volcano

Seamounts constitute an obstacle to the ocean circulation, modifying it. As a result, a variety of hydrodynamical processes and phenomena may take place over seamounts, among others, flow intensification, current deflection, upwelling, Taylor caps, and internal waves. These oceanographic effects may turn seamounts into very productive ecosystems with high species diversity, and in some cases, are densely populated by benthic organisms, such corals, gorgonians, and sponges. In this study, we describe the oceanographic conditions over seamounts and other underwater features in the path of the Mediterranean Outflow Water (MOW), where populations of benthic suspensions feeders have been observed. Using CTD, LADPC and biochemical measurements carried out in the Ormonde and Formigas seamounts and the Gazul mud volcano (Northeast Atlantic), we show that Taylor caps were not observed in any of the sampled features. However, we point out that the relatively high values of the Brunt–Väisälä frequency in the MOW halocline, in conjunction with the slope of the seamount flanks, set up conditions for the breakout of internal waves and amplification of the currents. This may enhance the vertical mixing, resuspending the organic material deposited on the seafloor and, therefore, increasing the food availability for the communities dominated by benthic suspension feeders. Thus, we hypothesize that internal waves could be improving the conditions for benthic suspension feeders to grow on the slope of seamounts.En prens

Assessing the coastal hazard of Medicane Ianos through ensemble modelling

On 18 September 2020, Medicane Ianos hit the western coast of Greece, resulting in flooding and severe damage at several coastal locations. In this work, we aim at evaluating its impact on sea conditions and the associated uncertainty through the use of an ensemble of numerical simulations. We applied a coupled wave–current model to an unstructured mesh, representing the whole Mediterranean Sea, with a grid resolution increasing in the Ionian Sea along the cyclone path and the landfall area. To investigate the uncertainty in modelling sea levels and waves for such an intense event, we performed an ensemble of ocean simulations using several coarse (10 km) and high-resolution (2 km) meteorological forcings from different mesoscale models. The performance of the ocean and wave models was evaluated against observations retrieved from fixed monitoring stations and satellites. All model runs emphasized the occurrence of severe sea conditions along the cyclone path and at the coast. Due to the rugged and complex coastline, extreme sea levels are localized at specific coastal sites. However, numerical results show a large spread of the simulated sea conditions for both the sea level and waves, highlighting the large uncertainty in simulating this kind of extreme event. The multi-model and multi-physics approach allows us to assess how the uncertainty propagates from meteorological to ocean variables and the subsequent coastal impact. The ensemble mean and standard deviation were combined to prove the hazard scenarios of the potential impact of such an extreme event to be used in a flood risk management plan.</p

Impact of mediastinal, liver and lung 123I-metaiodobenzylguanidine (123I-MIBG) washout on calculated 123I-MIBG myocardial washout

PURPOSE: In planar (123)I-metaiodobenzylguanidine ((123)I-MIBG) myocardial imaging mediastinum (M) activity is often used as a background correction in calculating "washout" (WO). However, the most likely sources for counts that might produce errors in estimating myocardial (Myo) activity are lung (Lu) and liver (Li), which typically have higher counts/pixel (cpp) than M. The present study investigated the relationship between changes in Lu, Li and Myo activity between early and late planar (123)I-MIBG images, with comparison to M as the best estimator of non-specific background activity. METHODS: Studies on 98 subjects with both early (e) and late (l) planar (123)I-MIBG images were analysed. There were 68 subjects with chronic heart failure (CHF), 14 with hypertension (HTN) but no known heart disease and 16 controls (C). For each image, regions of interest (ROIs) were drawn: an irregular whole Myo, Lu, upper M and Li. For each ROI, WO was calculated as [(cpp(e)-cpp(l:decay corrected))/cpp(e)]x100%. RESULTS: Multivariable forward stepwise regression analysis showed that overall a significant proportion of the variation in Myo WO could be explained by a model containing M WO and Lu WO (37%, p < 0.001). Only in controls was M WO the sole variable explaining a significant proportion of the variation in Myo WO (27%, p = 0.023). CONCLUSION: Although increased Myo WO in CHF subjects reflects disease severity, part of the count differences measured on planar (123)I-MIBG myocardial images likely reflects changes in the adjacent and surrounding Lu tissue. The results for the controls suggest that this is the only group where a mediastinum correction alone may be appropriate for cardiac WO calculation

Influence of Psychological Factors on Pain and Disability in Anterior Knee Pain Patients

AKP patients express chronic pain but also disability. However, the correlation between pain and disability is not complete and linear. Some patients with a lot of pain show mild disability while others with much less pain also show great disability. The disability is profoundly influenced by other emotional and cognitive factors that are associated with the perception of pain. Therefore, the clinical efforts do not have to be focused only on treating the pain as a feeling but on identifying and modifying these factor

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses

Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem

Non-invasive imaging in the diagnosis of acute viral myocarditis

Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1–10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail