Onto-CC: a web server for identifying Gene Ontology conceptual clusters

The Gene Ontology (GO) vocabulary has been extensively explored to analyze the functions of coexpressed genes. However, despite its extended use in Biology and Medical Sciences, there are still high levels of uncertainty about which ontology (i.e. Molecular Process, Cellular Component or Molecular Function) should be used, and at which level of specificity. Moreover, the GO database can contain incomplete information resulting from human annotations, or highly influenced by the available knowledge about a specific branch in an ontology. In spite of these drawbacks, there is a trend to ignore these problems and even use GO terms to conduct searches of gene expression profiles (i.e. expression + GO) instead of more cautious approaches that just consider them as an independent source of validation (i.e. expression versus GO). Consequently, propagating the uncertainty and producing biased analysis of the required gene grouping hypotheses. We proposed a web tool, Onto-CC, as an automatic method specially suited for independent explanation/validation of gene grouping hypotheses (e.g. coexpressed genes) based on GO clusters (i.e. expression versus GO). Onto-CC approach reduces the uncertainty of the queries by identifying optimal conceptual clusters that combine terms from different ontologies simultaneously, as well as terms defined at different levels of specificity in the GO hierarchy. To do so, we implemented the EMO-CC methodology to find clusters in structural databases [GO Directed acyclic Graph (DAG) tree], inspired on Conceptual Clustering algorithms. This approach allows the management of optimal cluster sets as potential parallel hypotheses, guided by multiobjective/multimodal optimization techniques. Therefore, we can generate alternative and, still, optimal explanations of queries that can provide new insights for a given problem. Onto-CC has been successfully used to test different medical and biological hypotheses including the explanation and prediction of gene expression profiles resulting from the host response to injuries in the inflammatory problem. Onto-CC provides two versions: Ready2GO, a precalculated EMO-CC for several genomes and an Advanced Onto-CC for custom annotation files (http://gps-tools2.wustl.edu/onto-cc/index.html)

A Configurable Sensor Network Applied to Ambient Assisted Living

The rising older people population has increased the interest in Ambient Assisted Living systems. This article presents a system for monitoring the disabled or older persons developed from an existing surveillance system. The modularity and adaptability characteristics of the system allow an easy adaptation for a different purpose. The proposed system uses a network of sensors capable of motion detection that includes fall warning, identification of persons and a configurable control system which allows its use in different scenarios

Performance Evaluation of a Biometric System Based on Acoustic Images

An acoustic electronic scanning array for acquiring images from a person using a biometric application is developed. Based on pulse-echo techniques, multifrequency acoustic images are obtained for a set of positions of a person (front, front with arms outstretched, back and side). Two Uniform Linear Arrays (ULA) with 15 λ/2-equispaced sensors have been employed, using different spatial apertures in order to reduce sidelobe levels. Working frequencies have been designed on the basis of the main lobe width, the grating lobe levels and the frequency responses of people and sensors. For a case-study with 10 people, the acoustic profiles, formed by all images acquired, are evaluated and compared in a mean square error sense. Finally, system performance, using False Match Rate (FMR)/False Non-Match Rate (FNMR) parameters and the Receiver Operating Characteristic (ROC) curve, is evaluated. On the basis of the obtained results, this system could be used for biometric applications

Evolution of genetic networks for human creativity

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more protein-coding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.Peer reviewe

Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease

Background: The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Aim: To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Methods: A review of data in SpRGD from patients'' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (=1994, cohort A; =1995, cohort B). Results: A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed = 1994 and 53 = 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p < 0.001) and different between the subtypes, GD1: 8.2 (0.2-16.5) years and GD3: 2.8 (0.17-10.2) years (p < 0.001). There were more severe patients in the group diagnosed before 1994 (p = 0.045) carrying L444P (2), D409H (2), G377S (1), G195W (1) or the recombinant mutation. The patients'' diagnosed =1994 showed worse cytopenias, higher chance of bone vascular complications at diagnosis and previous spleen removal. The patients started ERT at a median time after diagnosis of 5.2 years [cohort A] and 1.6 years [cohort B] (p < 0.001). Conclusions: The early diagnosis of Gaucher disease in the era of ERT availability has permitted to reduce the incidence of severe and irreversible initial complication in pediatric patients, and this has permitted better development of these patients. This is the largest pediatric cohort from a national registry

Subjects With Diabetes Mellitus Are at Increased Risk for Developing Tuberculosis : A Cohort Study in an Inner-City District of Barcelona (Spain)

Altres ajuts: Spanish Ministry of Economy and the Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (Catalan Health Institute, PREDOC_ECO-19/2).Background: Tuberculosis is the leading cause of mortality from lung infectious disease worldwide in recent years, and its incidence has re-emerged in large cities in low-incidence countries due to migration and socioeconomic deprivation causes. Diabetes mellitus and tuberculosis are syndemic diseases, with diabetes being considered a risk factor for developing tuberculosis. Objective: To investigate whether diabetic patients were at increased risk of tuberculosis living in an inner-district of a large city of northeastern Spain. Methods: Observational matched retrospective cohort study based on clinical records from the population of the lowest socioeconomic status in Barcelona (Ciutat Vella district). A cohort including patients with type 1 and type 2 diabetes mellitus in 2007 and new cases until 2016 (8004 subjects), matched 1:1 by sex and age with a non-diabetic cohort. Follow-up period was until December 31st 2018. We evaluated the risk of developing tuberculosis in diabetic patients compared to non-diabetic patients during the follow up period. We used time-to-event analysis to estimate the incidence of tuberculosis, and competing risks regression by clusters and conditional Cox regression models to calculate the hazard ratio (HR) and its 95% confidence intervals (CI). Results: Among the 16,008 included subjects, the median follow-up was 8.7 years. The mean age was 57.7 years; 61.2% men and 38.8% women in both groups. The incidence of tuberculosis was 69.9 per 100,000 person-years in diabetic patients, and 40.9 per 100,000 person-years in non-diabetic patients (HR = 1.90; CI: 1.18-3.07). After adjustment for the country of origin, chronic kidney disease, number of medical appointments, BMI, alcoholism and smoking, the risk remained higher in diabetic patients (1.66: CI 0.99-2.77). Additionally, subjects from Hindustan or with a history of alcohol abuse also showed a higher risk of developing tuberculosis (HR = 3.51; CI:1.87-6.57, and HR = 2.73; CI:1.22-6.12 respectively). Conclusion: People with diabetes mellitus were at higher risk of developing tuberculosis in a large cohort recruited in an inner-city district with a high incidence for this outcome, and low socioeconomic conditions and high proportion of migrants. This risk was higher among Hindustan born and alcohol abusers

Mastectomía ahorradora de piel y pezón en carcinoma ductal in situ. Seguridad oncológica a 10 años

Objetivo El objetivo es evaluar la seguridad oncológica a 10 años de la mastectomía ahorradora de piel y pezón (MAP) en pacientes con carcinoma ductal in situ (CDIS). Método Análisis observacional retrospectivo. Se realizaron 35 MAP en pacientes con CDIS durante 2005-2018. Evaluamos resultados histológicos, oncológicos y de morbilidad. Resultados Las indicaciones más frecuentes fueron márgenes afectos tras tumorectomía (31, 5%), multifocalidad/multicéntricidad (22, 8%), tumor >3 cm (8, 6%) correlación desfavorable tamaño tumoral/mama (8, 6%) y decisión de la paciente (8, 6%). La técnica más usada fue incisión lateral externa en 11 pacientes, seguida de técnica de Spira en nueve casos. La presencia de CDIS se confirmó en 22 pacientes y en 11 no se encontró tumor en la pieza de mastectomía. La tasa de complicaciones fue 22, 8%. Tras una mediana de seguimiento de 104 meses (DE 69, 9) no se observó necrosis del pezón. Un 20% de pacientes precisó reintervención a largo plazo. Once pacientes (31, 4%) recibieron tratamiento adyuvante (QT y/o RT). Solamente una paciente presentó recurrencia local (2, 8%) 28 meses tras la intervención. Una paciente presentó metástasis tras 78 meses de SLE. Las tasas de SLE y SG fueron 94, 3% y 97, 22%. El análisis univariante mostró dos factores de riesgo de recurrencia: edad <40 [OR (IC95) 2, 529 (1, 230 - 5, 199)] y márgenes afectos [OR (IC95) 5, 242 (2, 041 - 13, 464)]. Conclusión La MAP es factible y segura en pacientes con CDIS no candidatas a cirugía conservadora. Objective: The aim of this study was to assess the oncological safety of nipple-sparing mastectomy (NSM) in patients with ductal in situ carcinoma (DCIS) over a 10-year period. Method: Retrospective observational analysis. A total of 35 NSM were performed in patients with DCIS from 2005 - 2018. We assessed the histological, oncological and morbidity results. Results: The most frequent indications were margin involvement after lumpectomy (31.5%), multifocality / multicentricity (22.8%), tumour size >3 cm (8.6%) unfavourable tumour / breast size correlation (8.6%) and patient choice (8.6%). The most commonly used technique was external lateral incision in 11 patients, followed by the Spira technique in 9 patients. DCIS was confirmed in 22 patients and no tumour was found in mastectomy specimen in 11 patients. The complication rate was 22.8%. After a median follow-up of 104 months (SD 69.9) there was no nipple necrosis. In all, 20% of the patients required long-term reintervention. Eleven patients (31.4%) underwent adjuvant treatment (chemotherapy and / or radiotherapy). Only one patient showed local recurrence (2.8%) 28 months after the intervention. One patient developed metastases after 78 months of disease-free survival (DFS). DFS and overall survival rates were 94.3% and 97.22%. Univariate analysis showed two risk factors for recurrence: age <40 years [OR (95% CI) 2.529 (1.230-5.199)] and margin involvement [OR (95% CI) 5.242 (2.041 - 13.464)]. Conclusion: NSM is safe and feasible in patients with DCIS who are not candidates for conservative surgery