SNOMED2HL7: a tool to normalize and bind SNOMED CT concepts to the HL7 Reference Information Model

[Abstract] BACKGROUND: Current clinical research and practice requires interoperability among systems in a complex and highly dynamic domain. There has been a significant effort in recent years to develop integrative common data models and domain terminologies. Such efforts have not completely solved the challenges associated with clinical data that are distributed among different and heterogeneous institutions with different systems to encode the information. Currently, when providing homogeneous interfaces to exploit clinical data, certain transformations still involve manual and time-consuming processes that could be automated. OBJECTIVES: There is a lack of tools to support data experts adopting clinical standards. This absence is especially significant when links between data model and vocabulary are required. The objective of this work is to present SNOMED2HL7, a novel tool to automatically link biomedical concepts from widely used terminologies, and the corresponding clinical context, to the HL7 Reference Information Model (RIM). METHODS: Based on the recommendations of the International Health Terminology Standards Development Organisation (IHTSDO), the SNOMED Normal Form has been implemented within SNOMED2HL7 to decompose and provide a method to reduce the number of options to store the same information. The binding of clinical terminologies to HL7 RIM components is the core of SNOMED2HL7, where terminology concepts have been annotated with the corresponding options within the interoperability standard. A web-based tool has been developed to automatically provide information from the normalization mechanisms and the terminology binding. RESULTS: SNOMED2HL7 binding coverage includes the majority of the concepts used to annotate legacy systems. It follows HL7 recommendations to solve binding overlaps and provides the binding of the normalized version of the concepts. The first version of the tool, available at http://kandel.dia.fi.upm.es:8078, has been validated in EU funded projects to integrate real world data for clinical research with an 88.47% of accuracy. CONCLUSIONS: This paper presents the first initiative to automatically retrieve concept-centered information required to transform legacy data into widely adopted interoperability standards. Although additional functionality will extend capabilities to automate data transformations, SNOMED2HL7 already provides the functionality required for the clinical interoperability community.Instituto de Salud Carlos III; PI13/0202

Enzymatic upgrading of nanochitin using an ancient lytic polysaccharide monooxygenase

Numerous enzymes have the potential to upgrade biomass, converting it into high-tech materials for new applications. However, the features of natural enzymes often limit their use beyond chemical conversion of the substrate. The development of strategies for the enzymatic conversion of biomass into high-value materials may broaden the range of applications of enzymes and enzyme design techniques. A relevant case is lytic polysaccharide monooxygenase (LPMO), a class of enzymes that catalyzes the oxidative cleavage of glycosidic bonds. Here, we show that an ancestral LPMO can generate chitin nanocrystals. Physicochemical characterization of the chitin nanocrystals demonstrates modifications that make it superior compared to chitin obtained by chemical treatments. We show that the nanocrystals are suitable for controlled 2D and 3D cell cultures, as well as for engineering a biomatrix that combines with graphene oxide, forming a hybrid conductive bioink.This work has been supported by grants PID2019-109087RB-I00 to R.P.-J. from Spanish Ministry of Science and Innovation. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 964764 to R.P.-J. ‘Materials + Technologies’ Research Group also acknowledges UPV/EHU and the Basque Government in the frame of “Research Group” (GIU 18/216) and “Grupos Consolidados” (IT776-13), respectively. We also thank Gipuzkoako Foru Aldundia for financial Support. HEK293T cells were a kind gift from Dr. Maria Muñoz Caffarel (Biodonostia, San Sebastian, Spain)

Evaluation of an Artificial Intelligence web-based software to detect and classify dental structures and treatments in panoramic radiographs

Objectives: To evaluate the diagnostic reliability of a web-based Artificial Intelligence program on the detection and classification of dental structures and treatments present on panoramic radiographs. Methods: A total of 300 orthopantomographies (OPG) were randomly selected for this study. First, the images were visually evaluated by two calibrated operators with radiodiagnosis experience that, after consensus, established the “ground truth”. Operators’ findings on the radiographs were collected and classified as follows: metal restorations (MR), resin-based restorations (RR), endodontic treatment (ET), Crowns (C) and Implants (I). The orthopantomographies were then anonymously uploaded and automatically analyzed by the web-based software (Denti.Ai). Results were then stored, and a statistical analysis was performed by comparing them with the ground truth in terms of Sensitivity (S), Specificity (E), Positive Predictive Value (PPV) Negative Predictive Value (NPV) and its later representation in the area under (AUC) the Receiver Operating Characteristic (ROC) Curve. Results: Diagnostic metrics obtained for each study variable were as follows: (MR) S=85.48%, E=87.50%, PPV=82.8%, NPV=42.51%, AUC=0.869; (PR) S=41.11%, E=93.30%, PPV=90.24%, NPV=87.50%, AUC=0.672; (ET) S=91.9%, E=100%, PPV=100%, NPV=94.62%, AUC=0.960; (C) S=89.53%, E=95.79%, PPV=89.53%, NPV=95.79%, AUC=0.927; (I) S, E, PPV, NPV=100%, AUC=1.000. Conclusions: Findings suggest that the web-based Artificial intelligence software provides a good performance on the detection of implants, crowns, metal fillings and endodontic treatments, not being so accurate on the classification of dental structures or resin-based restorations. Clinical Significance: General diagnostic and treatment decisions using orthopantomographies can be improved by using web-based artificial intelligence tools, avoiding subjectivity and lapses from the clinician

Comorbidities in patients with Primary Sjögren's Syndrome and Systemic Lupus Erythematosus: A comparative registries-based study

OBJECTIVE: To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases. METHODS: This was a cross-sectional multicenter study where the prevalence of more relevant comorbidities in 2 cohorts was compared. Patients under followup from SJOGRENSER (Spanish Rheumatology Society Registry of Primary SS) and RELESSER (Spanish Rheumatology Society Registry of SLE), and who fulfilled the 2002 American-European Consensus Group and 1997 American College of Rheumatology classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex, and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when appropriate. RESULTS: A total of 437 primary SS patients (95% female) and 2,926 SLE patients (89% female) were included. The mean age was 58.6 years (interquartile range [IQR] 50.0-69.9 years) for primary SS patients and 45.1 years (IQR 36.4-56.3 years) for SLE patients (P?<?0.001), and disease duration was 10.4 years (IQR 6.0-16.7 years) and 13.0 years (IQR 7.45-19.76 years), respectively (P?<?0.001). Smoking, dyslipidemia, and arterial hypertension were associated less frequently with primary SS (odds ratio [OR] 0.36 [95% confidence interval (95% CI) 0.28-0.48], 0.74 [95% CI 0.58-0.94], and 0.50 [95% CI 0.38-0.66], respectively) as were life-threatening CV events (i.e., stroke or myocardial infarction; OR 0.57 [95% CI 0.35-0.92]). Conversely, lymphoma was associated more frequently with primary SS (OR 4.41 [95% CI 1.35-14.43]). The prevalence of severe infection was lower in primary SS than in SLE (10.1% versus 16.9%; OR 0.54 [95% CI 0.39-0.76]; P?<?0.001). CONCLUSION: Primary SS patients have a consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma is greater

Beneficial Effect of Ursodeoxycholic Acid in Patients with ACOX2 Deficiency-Associated Hypertransaminasemia

Background: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly trihydroxycholestanoic acid (THCA). Aims: To investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. Methods & results: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals, and 13 of their relatives, 7 individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by HPLC-MS/MS. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in 2 patients and 3 family members. Two additional non-related patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In ADAH patients, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized transaminases levels. Incubation of HuH-7 liver cells with THCA, which was efficiently taken up, but not through BA transporters, increased ROS production (flow cytometry), ER stress biomarkers (GRP78, CHOP and XBP1-S/XBP1-U ratio), and BAX¿ expression (RT-qPCR and immunoblot), whereas cell viability was decreased (MTT). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. Conclusion: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a non-invasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.This study was supported by the following grants: CIBERehd (EHD15PI05/2016); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819 and PI20/00189), co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”; “Junta de Castilla y León” (SA074P20); Fundació Marato TV3 (201916–31); AECC Scientific Foundation (2017/2020), Spain; and “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from grants PID2019-111669RBI- 100, PID2020-115055RB- I00 from Plan Nacional de I+D funded by the “Agencia Estatal de Investigación” (AEI) and the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH, as well as support from AGAUR of the “Generalitat de Catalunya” SGR-2017- 1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network. Marta Alonso-Peña was the recipient of a predoctoral fellowship from “Ministerio de Educación, Cultura y Deporte” (BOE-A- 2015- 9456; FPU-14/ 00214) and a Mobility Grant for Short Stays from “Ministerio de Ciencia, Innovación y Universidades” (EST17/00186). Ricardo Espinosa-Escudero is the recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). The funding sources were not involved in the research design or preparation of the articl

Informe del análisis documental y legislativo del proyecto de investigación: nuevas políticas educativas y su impacto en la equidad: gestión de las escuelas y desarrollo profesional docente (NUPE).

INFORME DEL ANÁLISIS DOCUMENTAL Y LEGISLATIVO DEL PROYECTO DE INVESTIGACIÓN: NUEVAS POLÍTICAS EDUCATIVAS Y SU IMPACTO EN LA EQUIDAD: GESTIÓN DE LAS ESCUELAS Y DESARROLLO PROFESIONAL DOCENTE (NUPE).Se han realizado nueve informes documentales: -Análisis documental de la normativa disponible en la legislación nacional y en la legislación de las diferentes Comunidades Autónomas (Andalucía, Canarias, Cataluña, Madrid y Valencia). Tenemos resultados de la investigación en materia de gestión, dirección, organización, currículo y desarrollo profesional docente. Se aprecia una voluntad de cambio con un corpus normativo que ha incorporado el lenguaje de la innovación, la investigación, la flexibilización, la participación, la inclusión, la igualdad, la diversidad, etc. No obstante su desarrollo y su concreción en el articulado no llegan a ser medidas que contribuyan a generar unas organizaciones educativas más inclusivas, unas direcciones de centros con autonomía de gestión para atender a las verdaderas demandas de los contextos particulares con un liderazgo más pedagógico y comunitario, una inspección que conecte con las problemáticas de los centros sin fiscalización y una formación del profesorado (inicial y permanente) que vayan más allá de las competencias a desarrollar para garantizar un rendimiento del alumnado como rendición de cuentas de la calidad de la escuela, y, a su vez, del sistema. También análisis de informes, artículos y documentos sobre la privatización en la educación. Se ha detectado un incremento de la privatización educativa. En particular Andalucía es una de las comunidades en que esta se desarrolla de una forma más impetuosa en los últimos 10 años. Desde 2011 a 2019 se ha producido el cierre de 7458 unidades de infantil, primaria y secundaria, perdiendo 4638 docentes de la enseñanza pública (82% 3en primaria). Se realiza una privatización por diseño, siguiendo el modelo de Madrid, que ya cuenta con un 45% de escuela privada, que amplían la segregación escolar desde 2013 en un 33%. También se va ampliando la privatización por defecto, donde crecen los centros privados en Formación Profesional y en Educación Infantil de 0-3 años.PROYECTOS DE I+D DE GENERACIÓN DE CONOCIMIENTO» DEL PROGRAMA ESTATAL DE GENERACIÓN DE CONOCIMIENTO Y FORTALECIMIENTO CIENTÍFICO Y TECNOLÓGICO DEL SISTEMA DE I+D+i. REFERENCIA PGC2018-095238-B-I00. MINISTERIO DE CIENCIA E INNOVACIÓ

Anti-IL-6 Receptor Tocilizumab in Refractory Graves? Orbitopathy: National Multicenter Observational Study of 48 Patients

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the e cacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age standard deviation 51 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 0.25 vs. 0.9 0.16; p = 0.0001), CAS (4.64 1.5 vs. 1.05 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 4.1 vs. 16.73 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 2.1 months, low disease activity (CAS 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or ine cacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Segmenting retinal vascular net from retinopathy of prematurity images using convolutional neural network

In this paper, we describe the experimentation with a convolutional neural network for segmenting retinal net from pathological fundus images of preterm born children. Segmenting retinal net from pathological fundus images is a fundamental task to aid computer diagnosis. We used U-net architecture for training and testing. Testing with ROPFI dataset, we obtained an area under the receiver operating curve equal to 0.9180; when average sensitivity is equal to 0.700, the average specificity is equal to 0.9710. This performance is higher than prior works using a similar dataset

Quantitative Measures for Medical Fundus and Mammography Images Enhancement

Enhancing the visibility of medical images is part of the initial or preprocessing phase within a computer vision system. This image preparation is essential for subsequent system tasks such as segmentation or classification. Therefore, quantitative validation of medical image preprocessing is crucial. In this work, four metrics are studied: Contrast Improvement Index (CII), Enhancement Measurement Estimation (EME), Entropy EME (EMEE), and Entropy. The objective is to find the best parameters for each metric. The study is performed on five medical image datasets, three retinal fundus sets (DRIVE, ROPFI, HRF-POORQ), and two mammography image sets (MIAS, DDSM). Metrics are calculated using a binary mask image to discard the background. Using the fundus and mask datasets, the best results were obtained with the EMEE and EMEE metrics, which achieved mean improvements of up to 186% and 75%, respectively. For mammography datasets and using masks of the region of interest, the two metrics with the highest percentage improvement were CII and EMEE, which obtained means of up to 396% and 129%, respectively. Based on the experimental results provided, we can conclude that EMEE, EME, and CII metrics can achieve better enhancement assessment in this type of medical imaging

genoDraw: A web tool for developing pedigree diagrams using the standardized human pedigree nomenclature integrated with biomedical vocabularies

The integration of genetic information in current clinical routine has raised a need for tools to exploit family genetic knowledge. On the clinical side, an application for managing and visualizing pedigree diagrams could provide genetics specialists with an integrated environment with potential positive impact on their current practice. This article presents a web tool (genoDraw) that provides clinical practitioners with the ability to create, maintain and visualize patients’ and their families’ information in the form of pedigree diagrams. genoDraw implements a graph-based three-step process for generating diagrams according to a de facto standard in the area and clinical terminologies. It also complies with five characteristics identified as indispensable for the next-generation of pedigree drawing software: comprehensiveness, data-drivenness, automation, interactivity and compatibility with biomedical vocabularies. The platform was implemented and tested, confirming its potential interest to clinical routine