Análisis del artículo de investigación de marketing: Características propias

Los investigadores del área de marketing de las universidades españolas tienen una especial preferencia por la publicación de sus artículos en revistas internacionales. La lengua utilizada en la mayoría de estas revistas es el inglés, lo que frecuentemente supone una dificultad añadida para estos investigadores puesto que no es sólo lacalidad de la investigación lo que van a valorar los evaluadores de las revistas, sino también la adecuada utilización de la lengua inglesa. Por esta razón, el análisis del inglés académico utilizado en los artículos de investigación se ha convertido en un campo de investigación tanto para el área de marketing e investigación de mercados, como para la de filología inglesa. El objetivo de este artículo es identificar los rasgos específicos y diferenciadores de los artículos de marketing, en una investigación conjunta de profesores de las dos áreas mencionadas

Point process methods in epidemiology: application to the analysis of human immunodeficiency virus/acquired immunodeficiency syndrome mortality in urban areas

The analysis of spatio-temporal patterns of disease or death in urban areas has been developed mainly from the ecological studies approach. These designs may have some limitations like the ecological fallacy and instability with few cases. The objective of this study was to apply the point process methodology, as a complement to that of aggregated data, to study HIV/AIDS mortality in men in the city of Alicante (Spain). A case-control study in residents in the city during the period 2004-2011 was designed. Cases were men who died from HIV/AIDS and controls represented the general population, matched by age to cases. The risk surfaces of death over the city were estimated using the log-risk function of intensities, and we contrasted their temporal variations over the two periods. High risk significant areas of death by HIV/AIDS, which coincide with the most deprived areas in the city, were detected. Significant spatial change of the areas at risk between the periods studied was not detected. The point process methodology is a useful tool to analyse the patterns of death by HIV/AIDS in urban areas

Evaluation of phototoxicity induced by the anticancer drug rucaparib

[EN] Rucaparib (RCP) is a potent selective inhibitor of both PARP-1 and PARP-2 enzymes that induces synthetic lethality in cancer cells. It is used for the treatment of breast and ovarian tumors harboring deleterious germline or somatic cancer susceptibility genes mutations. Although RCP has an indole chromophore in its structure, it displays a bathochromic shift of the absorption band towards the UVA region of sunlight, thus extending the active fraction of solar light able to produce photosensitivity reactions. In this context, it is highly interesting to study the photo(geno)toxicity disorders associated with this drug, bearing in mind that, for dermatologists it is crucial to understand the toxicity mechanism to improve clinical management. In the present work, RCP has shown to be potentially phototoxic, as observed in the neutral red uptake phototoxicity test. Moreover, this significant phototoxicity is attributed to both proteins and genomic DNA, as revealed in the protein photooxidation and comet assays. The results obtained are highly relevant concerning RCP photosafety and become clinically important in the context of identification of the cutaneous adverse events that can be associated with the targeted therapies. Interestingly, this is the first example of a PARP inhibitor able to induce photosensitized damage to biomolecules.The present work was supported by: the Spanish Government (PID2019-105391GB-C22, PID2020-115010RB-100 and BEAGAL 18/00211) and Generalitat Valenciana (ACIF/2018/153 fellowship for A. M-P). We would also like to thank IIS La Fe Microscopy Unit for technical assistance.Mateos-Pujante, A.; Jiménez Molero, MC.; Andreu, I. (2022). Evaluation of phototoxicity induced by the anticancer drug rucaparib. Scientific Reports. 12(1):1-10. https://doi.org/10.1038/s41598-022-07319-911012

L’externalització dels serveis esportius municipals. Estudi de cas a Bizkaia

En l’estudi que hem efectuat a Bizkaia, les entitats esportives municipals han incorporat l’externalització de serveis com una tècnica fonamental en la seva administració i gestió. En aquest cas, la subcontractació s’utilitza no només per a processos auxiliars a la producció i prestació del servei, sinó també i el que és més rellevant, en els processos clau de l’organització que són l’eix vertebral a partir del qual es conforma la missió o raó de ser de les entitats esportives municipals. La justificació de l’ús de l’externalització d’aquests serveis se centra bàsicament a buscar tècnics especialistes que assegurin més bona qualitat al servei ofert, a reduir costos i adequar-se a una demanda cada vegada més diversificada i exigent. En aquest sentit i sobretot per dur a terme la gestió de les escoles esportives municipals, són els clubs i les associacions esportives existents al municipi les entitats que adquireixen un protagonisme especial. L’ús d’aquesta tècnica d’externalització de serveis requereix ser inclosa dins de la pròpia estratègia de l’entitat, i cal formalitzar-ne el procés d’avaluació i control per poder conèixer l’impacte i l’efecte que, el també anomenat outsourcing, pugui tenir en els processos clau de les entitats esportives municipals

Photosensitivity to triflusal: formation of a photoadduct with ubiquitin demonstrated by photophysical and proteomic techniques

8 p.-7 fig.1 tab.Triflusal is a platelet aggregation inhibitor chemically related to acetylsalicylic acid, which is used for the prevention and/or treatment of vascular thromboembolisms, which acts as a prodrug. Actually, after oral administration it is absorbed primarily in the small intestine, binds to plasma proteins (99%) and is rapidly biotransformed in the liver into its deacetylated active metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). In healthy humans, the half-life of triflusal is ca. 0.5 h, whereas for HTB it is ca. 35 h. From a pharmacological point of view, it is interesting to note that HTB is itself highly active as a platelet anti-aggregant agent. Indeed, studies on the clinical profile of both drug and metabolite have shown no significant differences between them. It has been evidenced that HTB displays ability to induce photoallergy in humans. This phenomenon involves a cell-mediated immune response, which is initiated by covalent binding of a light-activated photosensitizer (or a species derived therefrom) to a protein. In this context, small proteins like ubiquitin could be appropriate models for investigating covalent binding by means of MS/MS and peptide fingerprint analysis. In previous work, it was shown that HTB forms covalent photoadducts with isolated lysine. Interestingly, ubiquitin contains seven lysine residues that could be modified by a similar reaction.With this background, the aim of the present work is to explore adduct formation between the triflusal metabolite and ubiquitin as model protein upon sunlight irradiation, combining proteomic and photophysical (fluorescence and laser flash photolysis) techniques. Photophysical and proteomic analysis demonstrates monoadduct formation as the major outcome of the reaction. Interestingly, addition can take place at any of the +-amino groups of the lysine residues of the protein and involves replacement of the trifluoromethyl moiety with a new amide function. This process can in principle occur with other trifluoroaromatic compounds and may be responsible for the appearance of undesired photoallergic side effects.Financial supportfromtheGeneralitatValenciana(Prometeo Program), the Spanish Government (MINECOCTQ2015-70164- P toVL-Vand SAF2012-36519 to DP-S) and the Carlos III Institute of Health(Grant RIRAAF,RETIC Sprogram, RD12/0013/0009 to MM and RD12/0013/0008 to DP-S,and Miguel Servet Contract CP11/00154forIA) is gratefully acknowledged.Peer reviewe

Coupling of sensors and machine learning algorithms in the qualitative analysis of wine

This article belongs to the Proceedings of The 8th International Symposium on Sensor ScienceThis work attempts the identification of the production year, the cultivar's region and the aging method used in the elaboration of different Spanish red wines, all from the "tempranillo" grape variety. The identification of such characteristics relies on the use of a voltammetric electronic tongue (ET) system formed by modified graphite-epoxy electrodes (GEC) and metallic electrodes to collect a set of six voltammograms per sample, and different chemometric tools to accomplish the final identifications. A large sample set that included 199 different wine samples from commercial and own elaboration origin were analysed with the electronic tongue system, using the cyclic voltammetry technique and without any sample pre-treatment. To process the extremely complex and high-dimensionality generated data, a compression strategy was used for the acquired voltammograms, using discrete wavelet transform (DWT). This treatment reduced the information to ca. 10%, preserving significant features from the voltammetric signals. Compressed data was evaluated firstly by unsupervised methods, i.e., principal component analysis (PCA), without much success as it was found that such methods were unable to unravel the patterns contained within such complex data samples. Finally, the processed electrochemical information was evaluated by supervised methods to accomplish the proper identification; among those methods were linear discriminant analysis (LDA), supported vector machines (SVM) or artificial neural networks (ANN). The best results were obtained using artificial neural networks (ANNs), achieving 96.1% of correct classification for bottled year, 86.8% for elaboration region (protected designation of origin) and 98.6% for maturation type with or without use of wood barrel

Materiales inéditos de Setefilla (Lora del Río, Sevilla)

Estudio de un conjunto cerámico de amplia tipología, recogido en La Mesa de Setefilla, que ofrece una cronología que abarca desde el siglo VIII al VI a. C.A study of pottery collection of varied typology, collected in La Mesa de Setefilla, chronologi- cally dated from the 8th century to the 6th century B.C

Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS

[EN] The human genome is constantly attacked by endogenous and exogenous agents (ultraviolet light, xenobiotics, reactive oxygen species), which can induce chemical transformations leading to DNA lesions. To combat DNA damage, cells have developed several repair mechanisms; however, if the repair is defective, DNA lesions lead to permanent mutations. Single-cell gel electrophoresis (COMET assay) is a sensitive and well-established technique for quantifying DNA damage in individual cells. Nevertheless, this tool lacks relationship with mutagenesis. Therefore, to identify errors that give rise to mutations it would be convenient to test an alternative known procedure, such as next generation sequencing (NGS). Thus, the present work aims to evaluate the photomutagenicity of neuroleptic drug chlorpromazine (CPZ), and its N-demethylated metabolites using COMET assay and to test NGS as an alternative method to assess photomutagenesis. In this context, upon exposure to UVA radiation, COMET assay reveals CPZ-photosensitized DNA damage partially repaired by cells. Conversely with this result, metabolites demethylchlorpromazine (DMCPZ) and didemethylchlorpromazine (DDMCPZ) promote extensive DNA-photodamage, hardly repaired under the same conditions. Parallel assessment of mutagenesis by NGS is consistent with these results with minor discrepancies for DDMCPZ. To our knowledge, this is the first example demonstrating the utility of NGS for evaluating drug-induced photomutagenicity.This study was funded by the Carlos III Institute (ISCIII) of Health (Grants: PI15/00303, PI18/00540, PI16/01877, CPII16/00052, the Thematic Networks and Co-operative Research Centres: ARADyAL RD16/0006/0004 and RD16/0006/0030), IB16170, GR18145 from Junta de Extremadura, Spain, co-funded by European Regional Development Fund and Generalitat Valenciana Prometeo/2017/075. We would also like to thank M. Dolores Coloma for technical assistance in the preliminary experiments.Agúndez, JA.; García-Martín, E.; Garcia-Lainez, G.; Miranda Alonso, MÁ.; Andreu Ros, MI. (2020). Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS. Scientific Reports. 10(1):1-6. https://doi.org/10.1038/s41598-020-63651-yS16101Bjelland, S. & Seeberg, E. Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat. Res. 531, 37–80 (2003).Friedberg, E. C. A brief history of the DNA repair field. Cell Res. 18, 3–7 (2008).Cadet, J. & Wagner, J. R. DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harb. Perspect. Biol. 5, (2013).Bauer, N. C., Corbett, A. H. & Doetsch, P. W. The current state of eukaryotic DNA base damage and repair. Nucleic Acids Res. 43, 10083–10101 (2015).Cadet, J. & Davies, K. J. A. Oxidative DNA damage & repair: An introduction. Free Radic. Biol. Med. 107, 2–12 (2017).Sancar, A., Lindsey-Boltz, L. A., Unsal-Kaçmaz, K. & Linn, S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73, 39–85 (2004).Roos, W. P., Thomas, A. D. & Kaina, B. DNA damage and the balance between survival and death in cancer biology. Nat. Rev. Cancer 16, 20–33 (2016).Møller, P. Assessment of reference values for DNA damage detected by the comet assay in human blood cell DNA. Mutat. Res. 612, 84–104 (2006).Azqueta, A. & Collins, A. R. The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch. Toxicol. 87, 949–968 (2013).Collins, A. R. et al. Controlling variation in the comet assay. Front. Genet. 5, 359 (2014).Møller, P. The comet assay: ready for 30 more years. Mutagenesis 33, 1–7 (2018).Shendure, J. & Ji, H. Next-generation DNA sequencing. Nat. Biotechnol. 26, 1135–1145 (2008).Metzker, M. L. Sequencing technologies—the next generation. Nat. Rev. Genet. 11, 31 (2010).Gawad, C., Koh, W. & Quake, S. R. Single-cell genome sequencing: current state of the science. Nat. Rev. Genet. 17, 175–188 (2016).Schwarz, U. I., Gulilat, M. & Kim, R. B. The Role of Next-Generation Sequencing in Pharmacogenetics and Pharmacogenomics. Cold Spring Harb. Perspect. Med. 9, (2019).Epstein, J. H., Brunsting, L. A., Petersen, M. C. & Schwarz, B. E. A study of photosensitivity occurring with chlorpromazine therapy. J. Invest. Dermatol. 28, 329–338 (1957).Kochevar, I. E., Chung, F. L. & Jeffrey, A. M. Photoaddition of chlorpromazine to DNA. Chem. Biol. Interact. 51, 273–284 (1984).Palumbo, F. et al. Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites. Toxicol. Appl. Pharmacol. 313, 131–137 (2016).Miki, Y. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).Wooster, R. et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789–792 (1995)

In vitro assessment of the photo(geno)toxicity associated with Lapatinib, a Tyrosine Kinase inhibitor

[EN] The epidermal growth factor receptors EGFR and HER2 are the main targets for tyrosine kinase inhibitors (TKIs). The quinazoline derivative lapatinib (LAP) is used since 2007 as dual TKI in the treatment of metastatic breast cancer and currently, it is used as an oral anticancer drug for the treatment of solid tumors such as breast and lung cancer. Although hepatotoxicity is its main side effect, it makes sense to investigate the ability of LAP to induce photosensitivity reactions bearing in mind that BRAF (serine/threonine-protein kinase B-Raf) inhibitors display a considerable phototoxic potential and that afloqualone, a quinazoline-marketed drug, causes photodermatosis. Metabolic bioactivation of LAP by CYP3A4 and CYP3A5 leads to chemically reactiveN-dealkylated (N-LAP) andO-dealkylated (O-LAP) derivatives. In this context, the aim of the present work is to explore whether LAP and itsN- andO-dealkylated metabolites can induce photosensitivity disorders by evaluating their photo(geno)toxicity through in vitro studies, including cell viability as well as photosensitized protein and DNA damage. As a matter of fact, our work has demonstrated that not only LAP, but also its metaboliteN-LAP have a clear photosensitizing potential. They are both phototoxic and photogenotoxic to cells, as revealed by the 3T3 NRU assay and the comet assay, respectively. By contrast, theO-LAP does not display relevant photobiological properties. Remarkably, the parent drug LAP shows the highest activity in membrane phototoxicity and protein oxidation, whereasN-LAP is associated with the highest photogenotoxicity, through oxidation of purine bases, as revealed by detection of 8-Oxo-dG.This study was funded by the Carlos III Institute (ISCIII) of Health (Grants: PI16/01877, CPII16/00052, ARADyAL RD16/0006/0030) co-funded by European Regional Development Fund, the Spanish Government (RYC-2015-17737, CTQ2017-89416-R,) and Generalitat Valenciana (Prometeo/2017/075). We would also like to thank IIS La Fe Microscopy Unit for technical assistance.García-Laínez, G.; Vayá Pérez, I.; Marín, MP.; Miranda Alonso, MÁ.; Andreu Ros, MI. (2021). In vitro assessment of the photo(geno)toxicity associated with Lapatinib, a Tyrosine Kinase inhibitor. Archives of Toxicology. 95(1):169-178. https://doi.org/10.1007/s00204-020-02880-6S16917895

Singlet oxygen and radical-mediated mechanisms in the oxidative cellular damage photosensitized by the protease inhibitor simeprevir

[EN] Hepatitis C, a liver inflammation caused by the hepatitis C virus (HCV), is treated with antiviral drugs. In this context, simeprevir (SIM) is an NS3/4A protease inhibitor used in HCV genotypes 1 and 4. It is orally admin-istered and achieves high virological cure rates. Among adverse reactions associated with SIM treatment, photosensitivity reactions have been reported. In the present work, it is clearly shown that SIM is markedly phototoxic, according to the in vitro NRU assay using BALB/c 3T3 mouse fibroblast. This result sheds light on the nature of the photosensitivity reactions induced by SIM in HCV patients, suggesting that porphyrin elevation in patients treated with SIM may not be the only mechanism responsible for SIM-associated photosensitivity. Moreover, lipid photoperoxidation and protein photooxidation assays, using human skin fibroblasts (FSK) and human serum albumin (HSA), respectively, reveal the capability of this drug to promote photodamage to cellular membranes. Also, DNA photo lesions induced by SIM are noticed through comet assay in FSK cells. Photo-chemical and photobiological studies on the mechanism of SIM-mediated photodamage to biomolecules indicate that the key transient species generated upon SIM irradiation is the triplet excited state. This species is efficiently quenched by oxygen giving rise to singlet oxygen, which is responsible for the oxidation of lipids and DNA (Type II mechanism). In the presence of HSA, the photobehavior is dominated by binding to site 3 of the protein, to give a stable SIM@HSA complex. Inside the complex, quenching of the triplet excited state is less efficient, which results in a longer triplet lifetime and in a decreased singlet oxygen formation. Hence, SIM-mediated photoox-idation of the protein is better explained through a radical (Type I) mechanism.Financial support from the Spanish Ministry of Science and Innovation [PID2020-115010RB-I00/AEI/10.13039/501100011033 (I.A), PID2019-105512RB-I00/AEI/10.13039/501100011033 (CG-B) and FPU predoctoral fellowship for M. El O.], Axencia Galega de Innovacion (2020-PG067, CG-B), the Xunta de Galicia [ED431C 2021/29 and the Centro singular de investigacion de Galicia accreditation 2019-2022 (ED431G 2019/03),], and the European Regional Development Fund (ERDF) is gratefully acknowledged. All authors are grateful to the Centro de Supercomputacion de Galicia (CESGA) for use of the Finis Terrae computer.García-Laínez, G.; El Ouardi, M.; Moreno, A.; Lence, E.; González-Bello, C.; Miranda, MÁ.; Andreu, I. (2023). Singlet oxygen and radical-mediated mechanisms in the oxidative cellular damage photosensitized by the protease inhibitor simeprevir. Free Radical Biology and Medicine. 194:42-51. https://doi.org/10.1016/j.freeradbiomed.2022.11.006425119