Classification of kinematic and electromyographic signals associated with pathological tremor using machine and deep learning.

Peripheral Electrical Stimulation (PES) of afferent pathways has received increased interest as a solution to reduce pathological tremors with minimal side effects. Closed-loop PES systems might present some advantages in reducing tremors, but further developments are required in order to reliably detect pathological tremors to accurately enable the stimulation only if a tremor is present. This study explores different machine learning (K-Nearest Neighbors, Random Forest and Support Vector Machines) and deep learning (Long Short-Term Memory neural networks) models in order to provide a binary (Tremor; No Tremor) classification of kinematic (angle displacement) and electromyography (EMG) signals recorded from patients diagnosed with essential tremors and healthy subjects. Three types of signal sequences without any feature extraction were used as inputs for the classifiers: kinematics (wrist flexion-extension angle), raw EMG and EMG envelopes from wrist flexor and extensor muscles. All the models showed high classification scores (Tremor vs. No Tremor) for the different input data modalities, ranging from 0.8 to 0.99 for the f1 score. The LSTM models achieved 0.98 f1 scores for the classification of raw EMG signals, showing high potential to detect tremors without any processed features or preliminary information. These models may be explored in real-time closed-loop PES strategies to detect tremors and enable stimulation with minimal signal processing steps

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy.Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients.Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi.Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems.The Instituto de Salud Carlos III.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved

Genetic analysis for physical nut traits in almond

Peer ReviewedPublishe

Transcriptomal profiling of the cellular response to DNA damage mediated by Slug (Snai2)

Snai2-deficient cells are radiosensitive to DNA damage. The function of Snai2 in response to DNA damage seems to be critical for its function in normal development and cancer. Here, we applied a functional genomics approach that combined gene-expression profiling and computational molecular network analysis to obtain global dissection of the Snai2-dependent transcriptional response to DNA damage in primary mouse embryonic fibroblasts (MEFs), which undergo p53-dependent growth arrest in response to DNA damage. Although examination of the response showed that overall expression of p53 target gene expression patterns was similarly altered in both control and Snai2-deficient cells, we have identified and validated candidate Snai2 target genes linked to Snai2 gene function in response to DNA damage. This work defines for the first time the effect of Snai2 on p53 target genes in cells undergoing growth arrest, elucidates the Snai2-dependent molecular network induced by DNA damage, points to novel putative Snai2 targets, and suggest a mechanistic model, which has implications for cancer management

Response of Quercus ilex seedlings to Phytophthora spp. root infection in a soil infestation test

[EN] Phytophthora species are the main agents associated with oak (Quercus spp.) decline, together with the changing environmental conditions and the intensive land use. The aim of this study was to evaluate the susceptibility of Quercus ilex to the inoculation with eight Phytophthora species. Seven to eight month old Q. ilex seedlings grown from acorns, obtained from two Spanish origins, were inoculated with P. cinnamomi, P. cryptogea, P. gonapodyides, P. megasperma, P. nicotianae, P. plurivora, P. psychrophila and P. quercina. All Phytophthora inoculated seedlings showed decline and symptoms including small dark necrotic root lesions, root cankers, and loss of fine roots and tap root. The most aggressive species were P. cinnamomi, P. cryptogea, P. gonapodyides, P. plurivora and P. psychrophila followed by P. megasperma., while Phytophthora quercina and P. nicotianae were the less aggressive species. Results obtained confirm that these Phytophthora species could constituted a threat to Q. ilex ecosystems and the implications are further discussed.The authors are grateful to A. Solla and his team from the Centro Universitario de Plasencia-Universidad de Extremadura (Spain) for helping in the acorns collection and to the CIEF (Centro para la Investigación y Experimentación Forestal, Generalitat Valenciana, Valencia, Spain) for providing the acorns. This research was supported by funding from the project AGL2011- 30438-C02-01 (Ministerio de Economía y Competitividad, Spain).Mora-Sala, B.; Abad Campos, P.; Berbegal Martinez, M. (2018). Response of Quercus ilex seedlings to Phytophthora spp. root infection in a soil infestation test. European Journal of Plant Pathology. https://doi.org/10.1007/s10658-018-01650-6SÁlvarez, L. A., Pérez-Sierra, A., Armengol, J., & García-Jiménez, J. (2007). 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Three new species of Phytophthora from European oak forests. Mycological Research, 106, 397–411.Jung, T., Orlikowski, L., Henricot, B., Abad-Campos, P., Aday, A. G., Aguín Casal, O., Bakonyi, J., Cacciola, S. O., Cech, T., Chavarriaga, D., Corcobado, T., Cravador, A., Decourcelle, T., Denton, G., Diamandis, S., Dogmus-Lehtijärvi, H. T., Franceschini, A., Ginetti, B., Glavendekic, M., Hantula, J., Hartmann, G., Herrero, M., Ivic, D., Horta Jung, M., Lilja, A., Keca, N., Kramarets, V., Lyubenova, A., Machado, H., Magnano di San Lio, G., Mansilla Vázquez, P. J., Marçais, B., Matsiakh, I., Milenkovic, I., Moricca, S., Nagy, Z. Á., Nechwatal, J., Olsson, C., Oszako, T., Pane, A., Paplomatas, E. J., Pintos Varela, C., Prospero, S., Rial Martínez, C., Rigling, D., Robin, C., Rytkönen, A., Sánchez, M. E., Scanu, B., Schlenzig, A., Schumacher, J., Slavov, S., Solla, A., Sousa, E., Stenlid, J., Talgø, V., Tomic, Z., Tsopelas, P., Vannini, A., Vettraino, A. M., Wenneker, M., Woodward, S., & Peréz-Sierra, A. (2016). Widespread Phytophthora infestations in European nurseries put forest, semi-natural and horticultural ecosystems at high risk of Phytophthora diseases. Forest Pathology, 46, 134–163.Kroon, L. P., Brouwer, H., de Cock, A. W., & Govers, F. (2012). The genus Phytophthora anno 2012. Phytopathology, 102, 348–364.Linaldeddu, B. T., Scanu, B., Maddau, L., & Franceschini, A. (2014). Diplodia corticola and Phytophthora cinnamomi: the main pathogens involved in holm oak decline on Caprera Island (Italy). Forest Pathology, 44, 191–200.Luque, J., Parladé, J., & Pera, J. (2000). Pathogenicity of fungi isolated from Quercus suber in Catalonia (NE Spain). Forest Pathology, 30, 247–263.Luque, J., Parladé, J., & Pera, J. (2002). Seasonal changes in susceptibility of Quercus suber to Botryosphaeria stevensii and Phytophthora cinnamomi. Plant Pathology, 51, 338–345.MAGRAMA. (2014). Diagnóstico del Sector Forestal Español. Análisis y Prospectiva - Serie Agrinfo/Medioambiente n° 8. Ed. Ministerio de Agricultura, Alimentación y Medio Ambiente. In NIPO: 280-14-081-9.Martín-García, J., Solla, A., Corcobado, T., Siasou, E., & Woodward, S. (2015). Influence of temperature on germination of Quercus ilex in Phytophthora cinnamomi, P. gonapodyides, P. quercina and P. psychrophila infested soils. Forest Pathology, 45, 215–223.Maurel, M., Robin, C., Capron, G., & Desprez-Loustau, M. L. (2001). Effects of root damage associated with Phytophthora cinnamomi on water elations, biomass accumulation, mineral nutrition and vulnerability to water deficit of five oak and chestnut species. Forest Pathology, 31, 353–369.McKinney, H. H. (1923). Influence of soil temperature and moisture on infection of wheat seedlings by Helminthosporium sativum. Journal of Agricultural Research, 26, 195–217.Moralejo, E., Pérez-Sierra, A., Álvarez, L. A., Belbahri, L., Lefort, F., & Descals, E. (2009). Multiple alien Phytophthora taxa discovered on diseased ornamental plants in Spain. Plant Pathology, 58, 100–110.Mora-Sala, B., Berbegal, M., & Abad-Campos, P. (2018). The use of qPCR reveals a high frequency of Phytophthora quercina in two Spanish holm oak areas. Forests, 9(11):697. https://doi.org/10.3390/f9110697 .Moreira, A. C., & Martins, J. M. S. (2005). Influence of site factors on the impact of Phytophthora cinnamomi in cork oak stands in Portugal. Forest Pathology, 35, 145–162.Mrázková, M., Černý, K., Tomosovsky, M., Strnadová, V., Gregorová, B., Holub, V., Panek, M., Havrdová, L., & Hejná, M. (2013). Occurrence of Phytophthora multivora and Phytophthora plurivora in the Czech Republic. Plant Protection Science, 49, 155–164.Navarro, R. M., Gallo, L., Sánchez, M. E., Fernández, P., & Trapero, A. (2004). Efecto de distintas fertilizaciones de fósforo en la resistencia de brinzales de encina y alcornoque a Phytophthora cinnamomi Rands. Investigación Agraria. Sistemas y Recursos Forestales, 13, 550–558.Panabières, F., Ali, G., Allagui, M., Dalio, R., Gudmestad, N., Kuhn, M., Guha Roy, S., Schena, L., & Zampounis, A. (2016). Phytophthora nicotianae diseases worldwide: new knowledge of a long-recognised pathogen. Phytopathologia Mediterranea, 55, 20–40.Pérez-Sierra, A., & Jung, T. (2013). Phytophthora in woody ornamental nurseries. In: Phytophthora: A global perspective (pp. 166-177). Ed. by Lamour, K. Wallingford: CABI.Pérez-Sierra, A., Mora-Sala, B., León, M., García-Jiménez, J., & Abad-Campos, P. (2012). Enfermedades causadas por Phytophthora en viveros de plantas ornamentales. Boletín de Sanidad Vegetal-Plagas, 38, 143–156.Pérez-Sierra, A., López-García, C., León, M., García-Jiménez, J., Abad-Campos, P., & Jung, T. (2013). Previously unrecorded low-temperature Phytophthora species associated with Quercus decline in a Mediterranean forest in eastern Spain. Forest Pathology, 43, 331–339.Redondo, M. A., Pérez-Sierra, A., & Abad-Campos, P. (2015). Histology of Quercus ilex roots during infection by Phytophthora cinnamomi. Trees - Structure and Function, 29, 1943–5197.Ríos, P., Obregón, S., de Haro, A., Fernández-Rebollo, P., Serrano, M. S., & Sánchez, M. E. (2016). Effect of Brassica Biofumigant Amendments on Different Stages of the Life Cycle of Phytophthora cinnamomi. Journal of Phytopathology, 164, 582–594.Rizzo, D. M., Garbelotto, M., Davidson, J. M., Slaughter, G. W., & Koike, S. T. (2002). Phytophthora ramorum as the cause of extensive mortality of Quercus spp. and Lithocarpus densiflorus in California. Plant Disease, 86, 205–214.Robin, C., Desprez-Loustau, M. L., Capron, G., & Delatour, C. (1998). First record of Phytophthora cinnamomi on cork and holm oaks in France and evidence of pathogenicity. Annales Des Sciences Forestieres, 55, 869–883.Robin, C., Capron, G., & Desprez-Loustau, M. L. (2001). Root infection by Phytophthora cinnamomi in seedlings of three oak species. Plant Pathology, 50, 708–716.Rodríguez-Molina, M. C., Torres-Vila, L. M., Blanco-Santos, A., Núñez, E. J. P., & Torres-Álvarez, E. (2002). Viability of holm and cork oak seedlings from acorns sown in soils naturally infected with Phytophthora cinnamomi. Forest Pathology, 32, 365–372.Romero, M. A., Sánchez, J. E., Jiménez, J. J., Belbahri, L., Trapero, A., Lefort, F., & Sánchez, M. E. (2007). New Pythium taxa causing root rot in Mediterranean Quercus species in southwest Spain and Portugal. Journal of Phytopathology, 115, 289–295.Sánchez de Lorenzo-Cáceres J. M. (2001). Guía de las plantas ornamentales. S.A. Mundi-Prensa Libros. ISBN 9788471149374. 688 pp.Sánchez, M. E., Caetano, P., Ferraz, J., & Trapero, A. (2002). Phytophtora disease of Quercus ilex in south-western Spain. Forest Pathology, 32, 5–18.Sánchez, M. E., Sánchez, J. E., Navarro, R. M., Fernández, P., & Trapero, A. (2003). Incidencia de la podredumbre radical causada por Phytophthora cinnamomi en masas de Quercus en Andalucía. Boletín de Sanidad Vegetal-Plagas, 29, 87–108.Sánchez, M. E., Andicoberry, S., & Trapero, A. (2005). Pathogenicity of three Phytophthora spp. causing late seedling rot of Quercus ilex ssp. ballota. Forest Pathology, 35, 115–125.Sánchez, M. E., Caetano, P., Romero, M. A., Navarro, R. M., & Trapero, A. (2006). Phytophthora root rot as the main factor of oak decline in southern Spain. In: Progress in Research on Phytophthora Diseases of Forest Trees. Proceedings of the Third International IUFRO Working Party S07.02.09. Meeting at Freising. Germany 11-18 September 2004. Brasier C. M., Jung T., Oßwald W. (Eds). Forest Research. Farnham, UK. pp. 149-154.Scanu, B., Linaldeddu, B. T., Deidda, A., & Jung, T. (2015). Diversity of Phytophthora species from declining Mediterranean maquis vegetation, including two new species, Phytophthora crassamura and P. ornamentata sp. nov. PLoS ONE, 10. https://doi.org/10.1371/journal.pone.0143234 .Schmitthenner, A. F., & Canaday, C. H. (1983). Role of chemical factors in the development of Phytophthora diseases. In: Phytophthora. Its biology, taxonomy, ecology, and pathology (pp.189-196). Ed. by Erwin D. C., Bartnicki-Garcia S., Tsao P. H. St. Paul, : The American Phytopathological Society.Scibetta, S., Schena, L., Chimento, A., Cacciola, S. A., & Cooke, D. E. L. (2012). A molecular method to assess Phytophthora diversity in environmental samples. Journal of Microbiological Methods, 88, 356–368.Sena, K., Crocker, E., Vincelli, P., & Barton, C. (2018). Phytophthora cinnamomi as a driver of forest change: Implications for conservation and management. Forest Ecology and Management, 409, 799–807.Thines, M. (2013). Taxonomy and phylogeny of Phytophthora and related oomycetes In: Phytophthora: A global perspective (pp. 11-18). Ed. by Lamour, K. Wallingford: CABI.Tsao, P. H. (1990). Why many Phytophthora root rots and crown rots of tree and horticultural crops remain undetected. EPPO Bulletin, 20, 11–17.Tuset, J. J., Hinarejos, C., Mira, J. L., & Cobos, M. (1996). Implicación de Phytophthora cinnamomi Rands en la enfermedad de la seca de encinas y alcornoques. Boletín de Sanidad Vegetal-Plagas, 22, 491–499.Vettraino, A. M., Barzanti, G. P., Bianco, M. C., Ragazzi, A., Capretti, P., Paoletti, E., & Vannini, A. (2002). Occurrence of Phytophthora species in oak stands in Italy and their association with declining oak trees. Forest Pathology, 32, 19–28.Xia, K., Hill, L. M., Li, D. Z., & Walters, C. (2014). Factors affecting stress tolerance in recalcitrant embryonic axes from seeds of four Quercus (Fagaceae) species native to the USA or China. Annals of Botany, 114, 1747–1759

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises

La castidad de la doncella: erotismo y poesía en Cervantes

The question of eroticism on Cervantes’ poetry is a tricky point, which has to be analyzed in the light of the editorial works of the author, its poetical bet in a series of key parliaments, and the revision of some spicy elements in his poems, as well as a brief confrontation to contemporary poetry. To sum up, Cervantes’ eroticism (esthetic, moral, and sexual) is a question of genre which has no space on his poetry, so that its discard and its reflections about the subject are significant.La cuestión del erotismo en la poesía de Cervantes es un asunto peliagudo, que se tiene que examinar a la luz de las labores editoriales del ingenio, su apuesta poética en una serie de parlamentos clave y la revisión de los elementos picantes de sus poemas, así como en un rápido careo con la poesía de su tiempo. En breve, el erotismo cervantino (estético, moral y sexual) es una cuestión de género que no tenía entrada en la poesía, de modo que tanto su descarte como sus reflexiones al respecto son significativas de su idea poética

Negative responses of highland pines to anthropogenic activities in inland Spain: a palaeoecological perspective

Palaeoecological evidence indicates that highland pines were dominant in extensive areas of the mountains of Central and Northern Iberia during the first half of the Holocene. However, following several millennia of anthropogenic pressure, their natural ranges are now severely reduced. Although pines have been frequently viewed as first-stage successional species responding positively to human disturbance, some recent palaeobotanical work has proposed fire disturbance and human deforestation as the main drivers of this vegetation turnover. To assess the strength of the evidence for this hypothesis and to identify other possible explanations for this scenario, we review the available information on past vegetation change in the mountains of northern inland Iberia. We have chosen data from several sites that offer good chronological control, including palynological records with microscopic charcoal data and sites with plant macro- and megafossil occurrence. We conclude that although the available long-term data are still fragmentary and that new methods are needed for a better understanding of the ecological history of Iberia, fire events and human activities (probably modulated by climate) have triggered the pine demise at different locations and different temporal scales. In addition, all palaeoxylological, palynological and charcoal results obtained so far are fully compatible with a rapid human-induced ecological change that could have caused a range contraction of highland pines in western Iberia

High Quality Long-Term CD4+ and CD8+ Effector Memory Populations Stimulated by DNA-LACK/MVA-LACK Regimen in Leishmania major BALB/c Model of Infection

Heterologous vaccination based on priming with a plasmid DNA vector and boosting with an attenuated vaccinia virus MVA recombinant, with both vectors expressing the Leishmania infantum LACK antigen (DNA-LACK and MVA-LACK), has shown efficacy conferring protection in murine and canine models against cutaneus and visceral leishmaniasis, but the immune parameters of protection remain ill defined. Here we performed by flow cytometry an in depth analysis of the T cell populations induced in BALB/c mice during the vaccination protocol DNA-LACK/MVA-LACK, as well as after challenge with L. major parasites. In the adaptive response, there is a polyfunctional CD4+ and CD8+ T cell activation against LACK antigen. At the memory phase the heterologous vaccination induces high quality LACK-specific long-term CD4+ and CD8+ effector memory cells. After parasite challenge, there is a moderate boosting of LACK-specific CD4+ and CD8+ T cells. Anti-vector responses were largely CD8+-mediated. The immune parameters induced against LACK and triggered by the combined vaccination DNA/MVA protocol, like polyfunctionality of CD4+ and CD8+ T cells with an effector phenotype, could be relevant in protection against leishmaniasis