Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology

Human phenotype ontology; Prenatal diagnosis; Prenatal phenotypingOntología del fenotipo humano; Diagnóstico prenatal; Fenotipado prenatalOntologia del fenotip humà; Diagnòstic prenatal; Fenotipat prenatalTechnological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care.European Commission; National Human Genome Research Institute; NIH Office of the Director; The European Union's EIT-Health Innovation Program bp2020-2022, Grant/Award Numbers: #211015, #20062; NIH Office of the Director (OD), the European Union's Horizon 2020 research and innovation program, Grant/Award Number: 779257; NHGRI, Grant/Award Numbers: 2R24OD011883-05A1, 1U24HG011449-01A

Estrategias transdisciplinarias en un proceso de formación universitaria

Due to the constant changes that we live, it is of the utmost importance that in the educational discipline, innovative actions are reflected, especially in the imparting of knowledge, skills, methodologies and transdisciplinary strategies that contribute in a way the resolution of complex situations and through the application of real cases, these approximations are achieved in educational practice, leaving students with real and experiential learning. A systematic review is presented whose objective is to analyze transdisciplinary strategies used at the higher level. In this article, 3 investigations that show strategies, competencies and teaching methodologies in a university intervention were analyzed. For this purpose, a search was made for articles published between 2009 and 2022, in the Redalyc, Scielo and Dialnet databases. The keywords used were strategies, transdisciplinarity and university education. The results show that the strategies applied with a transdisciplinary approach support the teaching methodology. The areas of medicine, education, pedagogy and administration were explored. In conclusion, the review of the studies allows us to specify what strategies exist, and to analyze them, since they contribute to the significant, experiential and real learning of the students, to their motivation and to collaborative work.Debido a los constantes cambios que vivimos es de suma importancia que, en la disciplina educativa se vean reflejadas acciones innovadoras sobre todo en los saberes, competencias, metodologías y estrategias transdiciplinarias que aporten soluciones a situaciones complejas y mediante la aplicación de casos reales se logren esas aproximaciones en la práctica educativa, dejando en los estudiantes aprendizajes significativos y vivenciales. Se presenta una revisión sistemática cuyo objetivo consiste en analizar estrategias transdisciplinarias utilizadas en el nivel superior. En este artículo se analizaron 7 investigaciones que muestran estrategias, competencias y metodologías de enseñanza en una intervención universitaria. Para tal fin, se realizó una búsqueda de artículos publicados entre el año 2009 hasta el 2022, en las bases de datos de Redalyc, Scielo y Dialnet. Las palabras claves utilizadas fueron; estrategias, transdisciplinariedad y formación universitaria. Los resultados muestran que las estrategias aplicadas con enfoque transdisciplinar, apoyan a la metodología docente. Se exploraron las áreas de medicina, educación, pedagogía y administración. En conclusión, la revisión de los estudios permite precisar que estrategias existen, y analizarlas contribuyen al aprendizaje significativo de los estudiantes, a su motivación y al trabajo colaborativo.Debido a los constantes cambios que vivimos es de suma importancia que, en la disciplina educativa se vean reflejadas acciones innovadoras sobre todo en los saberes, competencias, metodologías y estrategias transdiciplinarias que aporten soluciones a situaciones complejas y mediante la aplicación de casos reales se logren esas aproximaciones en la práctica educativa, dejando en los estudiantes aprendizajes significativos y vivenciales. Se presenta una revisión sistemática cuyo objetivo consiste en analizar estrategias transdisciplinarias utilizadas en el nivel superior. En este artículo se analizaron 7 investigaciones que muestran estrategias, competencias y metodologías de enseñanza en una intervención universitaria. Para tal fin, se realizó una búsqueda de artículos publicados entre el año 2009 hasta el 2022, en las bases de datos de Redalyc, Scielo y Dialnet. Las palabras claves utilizadas fueron; estrategias, transdisciplinariedad y formación universitaria. Los resultados muestran que las estrategias aplicadas con enfoque transdisciplinar, apoyan a la metodología docente. Se exploraron las áreas de medicina, educación, pedagogía y administración. En conclusión, la revisión de los estudios permite precisar que estrategias existen, y analizarlas contribuyen al aprendizaje significativo de los estudiantes, a su motivación y al trabajo colaborativo

Creatividad, innovación y emprendimiento una competencia holística en la educación universitaria: Revisión sistemática

Creativity, innovation and entrepreneurship are essential elements in the development of integrative projects for the area of physical culture. A systematic review is presented whose objective is to analyze the constitution of creativity, innovation and entrepreneurship competence in a holistic way in university education and the instruments that have been used to assess it. For this purpose, a search was carried out for articles published between 2017 and 2021, in the databases of Redalyc, Scielo, Dialnet, Eric, and academic Google. The keywords used were "creativity, innovation and entrepreneurship", "competition" and "university". The main results show that only 25% of the studies analyzed provide a comprehensive conceptualization of it. Regarding the area of knowledge, 50% of the documents reviewed come from engineering, be it computer science, industrial or aeronautics, and in a lower percentage from administration, investigation, health and pedagogy. 42% of the studies describe and provide innovative and creative tools, instruments or models for assessing the competence. It is concluded that the Creativity, Innovation and Entrepreneurship competence is the ability to generate new ideas of thought, extension and rupture of limits; for the genesis and resolution of problems in a novel way; knowing how to mobilize a set of sustainable ideas for the implementation of new processes, products and services.La creatividad, innovación y emprendimiento son elementos imprescindibles en el desarrollo de proyectos integradores para el área de la cultura física. Se presenta una revisión sistemática cuyo objetivo consiste en analizar la constitución de la competencia de creatividad, innovación y emprendimiento de manera holística en la educación universitaria y los instrumentos que se han utilizado para valorarla. Para tal fin, se realizó una búsqueda de artículos publicados entre el año 2017 hasta el 2021, en las bases de datos de Redalyc, Scielo, Dialnet, Eric y Google académico. Las palabras claves utilizadas fueron, “creatividad, innovación y emprendimiento”, “competencia” y “universidad”. Los principales resultados muestran que solo el 25% de los estudios analizados proporcionan una conceptualiación integral de la misma. Referente al área de conocimiento, un 50% de los documentos revisados provienen de la ingeniería, ya sea informática, industrial o aeronáutica y en un menor porcentaje de la administración, investigación, salud y pedagogía. Un 42% de los estudios describen y aportan herramientas, intrumentos o modelos innovadores y creativos para la valoración de la competencia. Se concluye, que la competencia Creatividad, innovación y emprendimiento es la capacidad para generar novedosas ideas de pensamiento, ampliación y ruptura de límites; para la génesis y resolución de los problemas de forma novedosa; al saber movilizar un conjunto de ideas sustentables para la implementación de nuevos procesos, productos y servicios

Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition

ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after γ-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM-kinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced γ-H2AX foci formation in response to γ-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced γ H2AX foci accumulation, in an ATM-dependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase

Lo glocal y el turismo. Nuevos paradigmas de interpretación.

El estudio del turismo se realiza desde múltiples escalas y enfoques, este libro aborda muchos temas que es necesario discutir desde diversas perspectivas; es el caso de la reflexión sobre la propia disciplina y sus conceptos, así como los asuntos específicos referidos al impacto territorial, los tipos de turismo, las cuestiones ambientales, el tema de la pobreza, la competitividad, las políticas públicas, el papel de las universidades, las áreas naturales protegidas, la sustentabilidad, la cultura, el desarrollo, la seguridad, todos temas centrales documentados y expuestos con originalidad y dominio del asunto. Lo multiescalar es básico para la comprensión del sistema turístico, sistema formado de procesos globales, regionales y locales. El eje de discusión del libro es lo glocal, esa interacción entre lo nacional y local con lo global

Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases

Altres ajuts: Generalitat de Catalunya, Departament de Salut; Generalitat de Catalunya, Departament d'Empresa i Coneixement i CERCA Program; Ministerio de Ciencia e Innovación; Instituto Nacional de Bioinformática; ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa; European Regional Development Fund (FEDER).Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%)

A Deep Insight into the Sialome of Rhodnius neglectus, a vector of chagas disease

Background Triatomines are hematophagous insects that act as vectors of Chagas disease. Rhodnius neglectus is one of these kissing bugs found, contributing to the transmission of this American trypanosomiasis. The saliva of hematophagous arthropods contains bioactive molecules responsible for counteracting host haemostatic, inflammatory, and immuneresponses. Methods/Principal Findings Next generation sequencing and mass spectrometry-based protein identification were performed to investigate the content of triatomine R. neglectus saliva.We deposited 4,230 coding DNA sequences (CDS) in GenBank. A set of 636 CDS of proteins of putative secretory nature was extracted from the assembled reads, 73 of them confirmed by proteomic analysis. The sialome of R. neglectus was characterized and serine protease transcripts detected. The presence of ubiquitous protein families was revealed, including lipocalins, serine protease inhibitors, and antigen-5. Metalloproteases, disintegrins, and odorant binding protein families were less abundant. Conclusions/Significance The data presented improve our understanding of hematophagous arthropod sialomes, and aid in understanding hematophagy and the complex interplay among vectors and their vertebrate hosts

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

&lt;p&gt;Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.&lt;/p&gt; &lt;p&gt;Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate &#60;60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.&lt;/p&gt; &lt;p&gt;Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.&lt;/p&gt