A hybrid approach with agent-based simulation and clustering for sociograms

In the last years, some features of sociograms have proven to be strongly related to the performance of groups. However, the prediction of sociograms according to the features of individuals is still an open issue. In particular, the current approach presents a hybrid approach between agent-based simulation and clustering for simulating sociograms according to the psychological features of their members. This approach performs the clustering extracting certain types of individuals regarding their psychological characteristics, from training data. New people can then be associated with one of the types in order to run a sociogram simulation. This approach has been implemented with the tool called CLUS-SOCI (an agent-based and CLUStering tool for simulating SOCIograms). The current approach has been experienced with real data from four different secondary schools, with 38 real sociograms involving 714 students. Two thirds of these data were used for training the tool, while the remaining third was used for validating it. In the validation data, the resulting simulated sociograms were similar to the real ones in terms of cohesion, coherence of reciprocal relations and intensity, according to the binomial test with the correction of Bonferroni

Chickenpox outbreak in Herrera del Duque, Badajoz, Spain.

Introducción. La varicela es una enfermedad de distribución mundial con una elevada morbilidad y pocas complicaciones, aunque puede presentar cuadros clínicos graves en inmunodeprimidos y adultos sanos. El objeto de este estudio es identificar y describir las características y los costes de un brote epidémico en Extremadura, cuya tasa anual de casos declarados al sistema de Enfermedades de Declaración Obligatoria (EDO) oscila en alrededor de 5 por 1.000 habitantes. Métodos.Estudio descriptivo con búsqueda activa de casos entre los meses de noviembre del año 2000 y marzo de 2001, y de la susceptibilidad de la cohorte escolarizada del colegio de Herrera del Duque (Badajoz). Las definiciones de casos fueron recogidas de los protocolos de la Red de Vigilancia de la comunidad extremeña. La confirmación microbiológica se realizó por aislamiento del virus y por presencia de marcadores IgM e IgG en el suero del enfermo. Se analizaron los costes tangibles directos e indirectos y los no tangibles del brote. Resultados.De los 75 casos identificados, 71 (94,7%) eran niños de entre uno y 9 años, predominando el sexo masculino. La tasa de ataque fue de 18,5 casos por 1.000 habitantes, y del 68,2% en convivientes menores de 10 años. La evolución fue benigna, sin ingresos hospitalarios ni complicaciones. Se encontró un 71,6% de niños susceptibles en los de entre 3 y 8 años. Se analizó una posible agregación temporal de casos en el colegio, obteniéndose un riesgo relativo (RR) de 5,01 (p < 0,001). Se aisló el virus en las 4 muestras de vesículas estudiadas y la serología (IgM) fue positiva en los 9 sueros estudiados. El coste total de brote fue de 927,21 e, con una media de 12,53 e por caso, y 205 días de pérdida escolar. Conclusión. Se confirmó la existencia de un brote de varicela en el colegio de la localidad de Herrera del Duque, con transmisión persona a persona, que afectó a niños de entre uno y 9 años. La elevada susceptibilidad del alumnado, las características de la docencia y las reuniones previas a los carnavales tuvieron un papel determinante en la propagación de la epidemia. El coste estimado para este brote se corresponde con un gasto un 76% menor del producido por la vacunación con una dosis de los 75 casos de este brote.S

Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n = 39), sham-septic (n = 16), and healthy (n = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy

Evaluación del impacto de una intervención para mejorar las coberturas de vacunación frente a neumococo en pacientes con VIH

Fundamentos: Las personas infectadas por el vi-rus de la inmunodeficiencia humana (VIH) presentan riesgo elevado de sufrir la enfermedad neumocócica invasiva, motivo por el que se recomienda su vacuna-ción frente al neumococo. El objetivo de este trabajo fue evaluar el impacto de implementar una consulta hospitalaria de vacunas en las coberturas de vacuna-ción de estos pacientes. Métodos: Se elaboró un estudio cuasiexperimental sin grupo control, de tipo antes/después, en el que se realizó un muestreo de casos consecutivos de pacientes con VIH remitidos a nuestra consulta entre el 1 noviembre de 2014 y el 30 junio de 2018. Las coberturas en el momento de la fecha de la cita para la valoración de su estado vacunal (en nuestra consulta) y después de ser atendido se compararon usando la prueba chi-cuadrado. Como referencia se utilizaron las del momento de la fecha de la primera cita. Resultados: Se analizaron 209 pacientes, en los que se obtuvieron mejoras estadísticamente signifi-cativas en sus coberturas vacunales: 2, 9% en el mo-mento de la fecha de la cita para la valoración en nuestra consulta y 88% después de ser atendidos en nuestra consulta (RR [IC95%]= 30, 7 [13, 92-67, 58]) para la vacuna antineumocócica conjugada 13-valen-te, y 16, 3% en el momento de la primera cita y 83, 7% después de ser atendidos en nuestra consulta (RR [IC95%]=5, 2 [3, 76-7, 04]) para la vacuna antineumo-cócica polisacárida 23-valente. Conclusiones: Implementar una consulta hospitalaria de vacunas representa una intervención efectiva para mejorar las coberturas de vacunación frente al neumococo en pacientes con VIH. Background: People affected by the human immunodeficiency virus (HIV) have a higher risk of invasive pneumococcal disease. Therefore, vaccination against streptococcus pneumoniae is recommended for that group. The objective of this study was to analyze the impact of implementing a hospital appointment to assess vaccination status as part of the vaccination schedule of HIV patients. Methods: We carried out a quasi-experimental uncontrolled before and after study with a sampling of consecutive cases of HIV patients referred to our department from November 1, 2014 to June 30, 2018. The study compared the vaccination coverage on the date of the appointment for an assessment of their vaccination status in our department and after the appointment. The analysis used the chi-squared test and the values on the date of the first appointment were taken as a reference. Results: 209 patients were analyzed, and a statistically significant improvement was observed regarding their vaccination coverage: 2.9% of the patients had been vaccinated on the date in which they made an appointment for assessment by our department, and 88.0% were vaccinated after they left (OR [95%CI]: 30.7 [13.92-67.58]) with the 13-valent pneumococcal conjugate vaccine; and 16.3% had been vaccinated on the date they made the first appointment vs. 83.7% after they came to the appointment (OR [95%CI]: 5.2 [3.76-7.04]) with the 23-valent polysaccharide pneumococcal vaccine. Conclusions: Implementing a hospital appointment for vaccination is an effective intervention to improve vaccination coverage against streptococcus pneumoniae in HIV patients

Infraestructura tecnológica de servicios semánticos para la Web Semántica

This project aims at creating a network of distributed interoperable semantic services for building more complex ones. These services will be available in semantic Web service libraries, so that they can be invoked by other systems (e.g., semantic portals, software agents, etc.). Thus, to accomplish this objective, the project proposes: a) To create specific technology for developing and composing Semantic Web Services. b) To migrate the WebODE ontology development workbench to this new distributed interoperable semantic service architecture. c) To develop new semantic services (ontology learning, ontology mappings, incremental ontology evaluation, and ontology evolution). d) To develop technological support that eases semantic portal interoperability, using Web services and Semantic Web Services. The project results will be open source, so as to improve their technological transfer. The quality of these results is ensured by a benchmarking process. Keywords: Ontologies and Semantic We

Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways

Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To “humanize” this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy. Keywords: alpha-synuclein; iPS cell; Parkinson’s disease; stem cell; mRNA translation; RNA-binding protein; LRRK2; VPS35; vesicle trafficking; yeas

Cohort study protocol: Bioresource in Adult Infectious Diseases (BioAID)

Introduction: Infectious diseases have a major impact on morbidity and mortality in hospital. Microbial diagnosis remains elusive for most cases of suspected infection which impacts on the use of antibiotics. Rapid advances in genomic technologies combined with high-quality phenotypic data have great potential to improve the diagnosis, management and clinical outcomes of infectious diseases.  The aim of the Bioresource in Adult Infectious Diseases (BioAID) is to provide a platform for biomarker discovery, trials and clinical service developments in the field of infectious diseases, by establishing a registry linking clinical phenotype to microbial and biological samples in adult patients who attend hospital with suspected infection. Methods and analysis: BioAID is a cohort study which employs deferred consent to obtain an additional 2.5mL RNA blood sample from patients who attend the Emergency Department (ED) with suspected infection when they undergo peripheral blood culture sampling.  Clinical data and additional biological samples including DNA, serum and microbial isolates are obtained from BioAID participants during hospital admission.  Participants are also asked to consent to be recalled for future studies. BioAID aims to recruit 10,000 patients from 5-8 sites across England.  Since February 2014 >4000 individuals have been recruited to the study.  The final cohort will be characterised using descriptive statistics including information on the number of cases that can be linked to biological and microbial samples to support future research studies. Ethical approval and section 251 exemption have been obtained for BioAID researchers to seek deferred consent from patients from whom a RNA specimen has been collected. Samples and meta-data obtained through BioAID will be made available to researchers worldwide following submission of an application form and research protocol.   Conclusions: BioAID will support a range of study designs spanning discovery science, biomarker validation, disease pathogenesis and epidemiological analyses of clinical infection syndromes

Lifestyle Evolution And Peroxidase Diversity In Agaricales As Revealed By Comparative Genomics

Descripción de 1 páginas de la comunicación oral presentada en Oxizymes2022 10th edition of the international “Oxizymes” meeting. Siena, Italy, July 5-8, 2022Basidiomycetes of the class Agaricomycetes have developed complex enzymatic machineries that allow them to decompose plant polymers, including lignin. Within this group, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles in comparison with fungi from other orders. With the aim of shedding light on the evolution of lignocellulose-decaying lifestyles in Agaricales we conducted a comparative analysis of 52 Agaricomycetes genomes [1]. This study revealed that Agaricales possess a large diversity of hydrolytic and oxidative enzymes. Surprisingly, computer-assisted gene-family evolution analysis of these enzymes revealed that a few oxidoreductase families showed significantly higher evolutionary rates. Based on these gene families we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. According to this, we determined that changes in the oxidative enzymatic toolkit of ancestral Agaricales correlate with the evolution of their ability to grow not only on wood, but also on leaf and grass litter and decayed wood. In this context, the aboye families were analyzed and special attention was paid to peroxidases as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes responsible for lignin degradation. We identified a widespread presence of new ligninolytic peroxidase types in Agaricales, some of them not previously identified in this order, and others also not found in woodrottingPolyporales and other orders of Agaricomycetes. Peroxidase evolution was analyzed in Agaricomycetes by ancestral sequence reconstruction and several major evolutionary pathways were unveiled. The study of the newly identified peroxidases will provide insight into their role in the lignin degradation process. In fact, these studies have already been initiated with the expression and characterization of the first lignin peroxidase identified in Agaricales. [1] Ruiz-Dueñas FJ, Barrasa JM, Sánchez-García M, Camarero S, Miyauchi S, Serrano A, et al., 2021, Mol Biol Evol, 38, 1428-1446.Projects/contracts BI02017-86559-R, BI02015-7369-JIN, AGL2014-55971-R, NSFgrant-1457721 , CEFOX-031 B0831 S, PIE-201620E081 , ANR-11-LABX-0002-01 , US-DOE-DE-AC02-05CH11231N

Resistance to butyrate impairs bile acid-induced apoptosis in human colon adenocarcinoma cells via up-regulation of Bcl-2 and inactivation of Bax

AbstractA critical risk factor in colorectal carcinogenesis and tumor therapy is the resistance to the apoptotic effects of different compounds from the intestinal lumen, among them butyrate (main regulator of colonic epithelium homeostasis). Insensitivity to butyrate-induced apoptosis yields resistance to other agents, as bile acids or chemotherapy drugs, allowing the selective growth of malignant cell subpopulations. Here we analyze bile acid-induced apoptosis in a butyrate-resistant human colon adenocarcinoma cell line (BCS-TC2.BR2) to determine the mechanisms that underlay the resistance to these agents in comparison with their parental butyrate-sensitive BCS-TC2 cells. This study demonstrates that DCA and CDCA still induce apoptosis in butyrate-resistant cells through increased ROS production by activation of membrane-associated enzymes and subsequent triggering of the intrinsic mitochondrial apoptotic pathway. Although this mechanism is similar to that described in butyrate-sensitive cells, cell viability is significantly higher in resistant cells. Moreover, butyrate-resistant cells show higher Bcl‐2 levels that confer resistance to bile acid-induced apoptosis sequestering Bax and avoiding Bax-dependent pore formation in the mitochondria. We have confirmed that this resistance is reverted using the Bcl-2 inhibitor ABT-263, thus demonstrating that the lower sensitivity of butyrate-resistant cells to the apoptotic effects of bile acids is mainly due to increased Bcl-2 levels