Fully-Automatic 3D Intuitive Visualization of Age-Related Macular Degeneration Fluid Accumulations in OCT Cubes

[Abstract]: Age-related macular degeneration is the leading cause of vision loss in developed countries, and wet-type AMD requires urgent treatment and rapid diagnosis because it causes rapid irreversible vision loss. Currently, AMD diagnosis is mainly carried out using images obtained by optical coherence tomography. This diagnostic process is performed by human clinicians, so human error may occur in some cases. Therefore, fully automatic methodologies are highly desirable adding a layer of robustness to the diagnosis. In this work, a novel computer-aided diagnosis and visualization methodology is proposed for the rapid identification and visualization of wet AMD. We adapted a convolutional neural network for segmentation of a similar domain of medical images to the problem of wet AMD segmentation, taking advantage of transfer learning, which allows us to work with and exploit a reduced number of samples. We generate a 3D intuitive visualization where the existence, position and severity of the fluid were represented in a clear and intuitive way to facilitate the analysis of the clinicians. The 3D visualization is robust and accurate, obtaining satisfactory 0.949 and 0.960 Dice coefficients in the different evaluated OCT cube configurations, allowing to quickly assess the presence and extension of the fluid associated to wet AMD.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding for open access charge: Universidade da Coruña/CISUG. The research was funded by Instituto de Salud Carlos III, Government of Spain through the PI17/00940 and DTS18/00136 research projects, Ministerio de Ciencia e Innovación y Universidades, Government of Spain, RTI2018-095894-B-I00 research project, Ayudas para la formación de profesorado universitario (FPU), grant ref. FPU18/02271; Ministerio de Ciencia e Innovación, Government of Spain through the research project with reference PID2019-108435RB-I00; Consellería de Cultura, Educación e Universidade, unta de Galicia, Grupos de Referencia Competitiva, grant ref. ED431C 2020/24; CITIC, as Research Center accredited by Galician University System, is funded by “Consellería de Cultura, Educación e Universidade from Xunta de Galicia”, supported in an 80% through ERDF Funds, ERDF Operational Programme Galicia 2014-2020, and the remaining 20% by “Secretaría Xeral de Universidades” (Grant ED431G 2019/01). Emilio López Varela acknowledges its support under FPI Grant Program through the PID2019-108435RB-I00 project.Financiado para publicación en acceso aberto: Universidade da Coruña/CISUGXunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0

Socio-Demographic Health Determinants Are Associated with Poor Prognosis in Spanish Patients Hospitalized with COVID-19

Introduction Social vulnerability is a known determinant of health in respiratory diseases. Our aim was to identify whether there are socio-demographic factors among COVID-19 patients hospitalized in Spain and their potential impact on health outcomes during the hospitalization. Methods A multicentric retrospective case series study based on administrative databases that included all COVID-19 cases admitted in 19 Spanish hospitals from 1 March to 15 April 2020. Socio-demographic data were collected. Outcomes were critical care admission and in-hospital mortality. Results We included 10,110 COVID-19 patients admitted to 18 Spanish hospitals (median age 68 (IQR 54–80) years old; 44.5% female; 14.8% were not born in Spain). Among these, 779 (7.7%) cases were admitted to critical care units and 1678 (16.6%) patients died during the hospitalization. Age, male gender, being immigrant, and low hospital saturation were independently associated with being admitted to an intensive care unit. Age, male gender, being immigrant, percentile of average per capita income, and hospital experience were independently associated with in-hospital mortality. Conclusions Social determinants such as residence in low-income areas and being born in Latin American countries were associated with increased odds of being admitted to an intensive care unit and of in-hospital mortality. There was considerable variation in outcomes between different Spanish centers.JPA is under contract within the Ramón y Cajal Program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). Investigators of Spanish Social-Environmental COVID-19 Register: Steering Committee: F. Javier Martín-Sánchez, Adrián Valls Carbó, Carmen Martínez Valero, Juan de D. Miranda, Juan Pedro Arrebola, Marta Esteban López, Annika Parviainen, Òscar Miró, Pere Llorens, Sònia Jiménez, Pascual Piñera, Guillermo Burillo, Alfonso Martín, Jorge García Lamberechts, Javier Jacob, Aitor Alquézar, Juan González del Castillo, Amanda López Picado and Iván Núñez. Participating centers: Oscar Miró y Sonia Jimenez. Hospital Clinic de Barcelona. José María Ferreras Amez. Hospital Clínico Universitario Lozano Blesa. Rafael Rubio Díaz. Complejo Hospitalario de Toledo. Julio Javier Gamazo del Rio. Hospital Universitario de Galdakao. Héctor Alonso. Hospital Universitario Miguel de Valdecilla. Pablo Herrero. Hospital Universitario Central de Asturias. Noemí Ruiz de Lobera. Hospital San Pedro de Logroño. Carlos Ibero. Complejo Hospitalario de Navarra. Plácido Mayan. Hospital Clínico Universitario de Santiago. Rosario Peinado. Complejo Hospitalario Universitario de Badajoz. Carmen Navarro Bustos. Hospital Universitario Virgen de la Macarena. Jesús Álvarez Manzanares. Hospital Universitario Rio Hortega. Francisco Román. Hospital Universitario General de Alicante. Pascual Piñera. Hospital Universitario Reina Sofia de Murcia. Guillermo Burillo. Hospital Universitario de Canarias de Tenerife. Javier Jacob. Hospital Universitario de Bellvitge. Carlos Bibiano. Hospital Universitario Infanta Leonor.Peer reviewe

CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative

13 páginas,1 figura, 3 tablas, 1 apéndice. Se extraen los autores pertenecientes a The CIBERER network que trabajan en Centros del CSIC del Appendix ACIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.This study has been funded by Instituto de Salud Carlos III (ISCIII) and Spanish Ministry of Science and InnovationPeer reviewe

Implications of non-coding RNA on biology and evolution: from first hominids to modern humans-Review

Massive genomic/transcriptomic sequencing has revealed a shocking paradox: pervasive or spurious transcription. Although such event is unwanted in principle, some of such transcripts may scape degradation, being further selected by evolution, with fascinating consequences on biology, including our brain development and what made us humans. Indeed, non-coding RNA are involved in many regulatory processes, across the central dogma of molecular biology, and even epigenetics events. Interestingly, that is partially accomplished regulating the expression and function of small RNA, like miRNA. More strikingly, non-coding RNA are involved in neuron physiology and brain neurogenesis, including outgrowth or neuron projections, synaptic functions and translation in synapses. Besides, non- coding RNA can be exported-imported between cells, through exosome vesicles. Surprisingly, some non-coding RNA are indeed translated into micropeptides, which may be involved in brain development. All that allows the remarkable cognitive power of the human brain. Unfortunately, this exquisite development, that made us humans, is specially prone to internal and external perturbations. They may generate neurodevelopmental, neurodegenerative and neuropsychiatric disorders, to which humans are more prone than other primates.La secuenciación genómica/transcriptómica masiva ha revelado una paradoja impactante: la transcripción generalizada o espuria. Aunque tal evento es no deseado en principio, algunos de tales transcritos pueden escapar de la degradación, siendo seleccionados por la evolución, con consecuencias fascinantes en biología, incluido el desarrollo de nuestro cerebro y lo que nos hizo humanos. De hecho, los ARN no codificantes están involucrados en muchos procesos reguladores, a través de todo el dogma central de la biología molecular, e incluso en eventos epigenéticos. Curiosamente, ello se logra parcialmente regulando la expresión y la función de ARN pequeños, como los miARN. Más sorprendentemente, los ARN no codificantes están involucrados en la fisiología de las neuronas y la neurogénesis cerebral, incluyendo las excrecencias o proyecciones neuronales, funciones sinápticas y traducción en sinapsis. Además, el ARN no codificante puede exportarse-importarse entre células, a través de vesículas de exosomas. Sorprendentemente, algunos ARN no codificantes se traducen en micropéptidos, que pueden estar involucrados en el desarrollo del cerebro. Todo eso permite el notable poder cognitivo del cerebro humano. Desafortunadamente, este desarrollo exquisito, que nos hizo humanos, es especialmente propenso a perturbaciones internas y externas. Así, pueden generarse trastornos del neurodesarrollo, neurodegenerativos y neuropsiquiátricos, a los cuales los humanos somos más propensos que otros primates

Implicaciones del ARN no codificante en biología y evolución: desde los primeros homínidos hasta los humanos modernos - Revisión

Massive genomic/transcriptomic sequencing has revealed a shocking paradox: pervasive or spurious transcription. Although such event is unwanted in principle, some of such transcripts may scape degradation, being further selected by evolution, with fascinating consequences on biology, including our brain development and what made us humans. Indeed, non-coding RNA are involved in many regulatory processes, across the central dogma of molecular biology, and even epigenetics events. Interestingly, that is partially accomplished regulating the expression and function of small RNA, like miRNA. More strikingly, non-coding RNA are involved in neuron physiology and brain neurogenesis, including outgrowth or neuron projections, synaptic functions and translation in synapses. Besides, non-coding RNA can be exported-imported between cells, through exosome vesicles. Surprisingly, some non-coding RNA are indeed translated into micropeptides, which may be involved in brain development. All that allows the remarkable cognitive power of the human brain. Unfortunately, this exquisite development, that made us humans, is specially prone to internal and external perturbations. They may generate neurodevelopmental, neurodegenerative and neuropsychiatric disorders, to which humans are more prone than other primates.La secuenciación genómica/transcriptómica masiva ha revelado una paradoja impactante: la transcripción generalizada o espuria. Aunque tal evento es no deseado en principio, algunos de tales transcritos pueden escapar de la degradación, siendo seleccionados por la evolución, con consecuencias fascinantes en biología, incluido el desarrollo de nuestro cerebro y lo que nos hizo humanos. De hecho, el ARN no codificante está involucrado en muchos procesos reguladores, a través de todo el dogma central de la biología molecular, e incluso en eventos epigenéticos. Curiosamente, ello se logra parcialmente regulando la expresión y la función de ARN pequeños, como los miARN. Más sorprendentemente, el ARN no codificante está involucrado en la fisiología de las neuronas y la neurogénesis cerebral, incluyendo las excrecencias o proyecciones neuronales, funciones sinápticas y traducción en sinapsis. Además, el ARN no codificante puede exportarse-importarse entre células, a través de vesículas de exosomas. Sorprendentemente, algunos ARN no codificantes se traducen en micropéptidos, que pueden estar involucrados en el desarrollo del cerebro. Todo eso permite el notable poder cognitivo del cerebro humano. Desafortunadamente, este desarrollo exquisito, que nos hizo humanos, es especialmente propenso a perturbaciones internas y externas. Así, pueden generarse trastornos del neurodesarrollo, neurodegenerativos y neuropsiquiátricos, a los cuales los humanos somos más propensos que otros primates

Implications of non-coding RNA on biology and evolution: from first hominids to modern humans

[EN] Massive genomic/transcriptomic sequencing has revealed a shocking paradox: pervasive or spurious transcription. Although such event is unwanted in principle, some of such transcripts may scape degradation, being further selected by evolution, with fascinating consequences on biology, including our brain development and what made us humans. Indeed, non-coding RNA are involved in many regulatory processes, across the central dogma of molecular biology, and even epigenetics events. Interestingly, that is partially accomplished regulating the expression and function of small RNA, like miRNA. More strikingly, non-coding RNA are involved in neuron physiology and brain neurogenesis, including outgrowth or neuron projections, synaptic functions and translation in synapses. Besides, non- coding RNA can be exported-imported between cells, through exosome vesicles. Surprisingly, some non-coding RNA are indeed translated into micropeptides, which may be involved in brain development. All that allows the remarkable cognitive power of the human brain. Unfortunately, this exquisite development, that made us humans, is specially prone to internal and external perturbations. They may generate neurodevelopmental, neurodegenerative and neuropsychiatric disorders, to which humans are more prone than other primates.[ES] La secuenciación genómica/transcriptómica masiva ha revelado una paradoja impactante: la transcripción generalizada o espuria. Aunque tal evento es no deseado en principio, algunos de tales transcritos pueden escapar de la degradación, siendo seleccionados por la evolución, con consecuencias fascinantes en biología, incluido el desarrollo de nuestro cerebro y lo que nos hizo humanos. De hecho, los ARN no codificantes están involucrados en muchos procesos reguladores, a través de todo el dogma central de la biología molecular, e incluso en eventos epigenéticos. Curiosamente, ello se logra parcialmente regulando la expresión y la función de ARN pequeños, como los miARN. Más sorprendentemente, los ARN no codificantes están involucrados en la fisiología de las neuronas y la neurogénesis cerebral, incluyendo las excrecencias o proyecciones neuronales, funciones sinápticas y traducción en sinapsis. Además, el ARN no codificante puede exportarse-importarse entre células, a través de vesículas de exosomas. Sorprendentemente, algunos ARN no codificantes se traducen en micropéptidos, que pueden estar involucrados en el desarrollo del cerebro. Todo eso permite el notable poder cognitivo del cerebro humano. Desafortunadamente, este desarrollo exquisito, que nos hizo humanos, es especialmente propenso a perturbaciones internas y externas. Así, pueden generarse trastornos del neurodesarrollo, neurodegenerativos y neuropsiquiátricos, a los cuales los humanos somos más propensos que otros primates.Supported by “Ministerio de Economía y Competitividad” (MINECO grant BIO2015-64737-R) and “Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria” (MINECO and INIA RF2012-00002-C02-02); “Consejería de Agricultura y Pesca” (041/C/2007, 75/C/2009 and 56/C/2010), “Consejería de Economía, Innovación y Ciencia” (P11-AGR-7322 and P12-AGR-0482) and “Grupo PAI” (AGR-248) of “Junta de Andalucía”; and “Universidad de Córdoba” (“Ayuda a Grupos”), Spain

Second-generation nucleic-acid sequencing and bioarchaeology - Review

The nucleic-acid revolution started 31 years ago. The development of the second-generation sequencing (SGS) has allowed a higher throughput and lower price per sequenced base, opening the possibility to sequence ancient genomes, including epigenetics. The main SGS platforms are described in this review: i) Roche 454 Life Sciences, based on emulsion PCR (emPCR) and further pyrosequencing; ii) Illumina (bridge-amplification and subsequent reversible-terminator sequencing); iii) Life Technologies SOLiD (emPCR coupled with oligonucleotide ligation to interrogate DNA); and iv) Life Technologies Ion-Torrent-chip (emPCR, further using microchip pH-meters). Different ancient genomes (including viruses, microorganisms, plants and animals) have been sequenced. This has allowed to study the evolution of pathogens, domestication of microorganisms, plants and animals, paleodiets and paleoenvironments, including climate changes. Some hurdles and challenges must yet be overcome, but the steady technological advances in nucleic-acid isolation, sequencing and bioinformatics (together with higher computing power) promise a bright future for bioarchaeology in general, and paleogenomics in particular, allowing to analyze not just single genomes, but also to address ancient population genomics and evolution.Supported by “Ministerio de Economía y Competitividad” (MINECO grants AGL2010-17316 and BIO2011-15237-E) and “Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria” (MINECO and INIA RF2012-00002-C02-02); “Consejería de Agricultura y Pesca” (041/C/2007, 75/C/2009 and 56/C/2010), “Consejería de Economía, Innovación y Ciencia” (P11-AGR-7322 and P12-AGR-0482) and “Grupo PAI” (AGR-248) of “Junta de Andalucía”; and “Universidad de Córdoba” (“Ayuda a Grupos”), Spain.Peer reviewe

Overexpression of CYB5R3 and NQO1, two NAD+-producing enzymes, mimics aspects of caloric restriction

© 2018 The Authors.Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH-dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD+/sirtuin pathway. The results highlight the importance of these NAD+ producers for the promotion of health and extended lifespan.This research was supported by the Intramural Research Program of the NIA, NIH, and the Instituto de Salud Carlos III FIS PI14-01962 (grant to P.N.). JMV was supported by the Spanish Ministerio de Economía y Competitividad grant BFU2015-64630-R. M.C.R and A.S.P. were supported by a fellowship from the Spanish “Ministerio de Educación, Cultura y Deporte,” award FPU14/06308 and FPU 14/00098 respectively