COLAEVA: Visual Analytics and Data Mining Web-Based Tool for Virtual Coaching of Older Adult Populations

The global population is aging in an unprecedented manner and the challenges for improving the lives of older adults are currently both a strong priority in the political and healthcare arena. In this sense, preventive measures and telemedicine have the potential to play an important role in improving the number of healthy years older adults may experience and virtual coaching is a promising research area to support this process. This paper presents COLAEVA, an interactive web application for older adult population clustering and evolution analysis. Its objective is to support caregivers in the design, validation and refinement of coaching plans adapted to specific population groups. COLAEVA enables coaching caregivers to interactively group similar older adults based on preliminary assessment data, using AI features, and to evaluate the influence of coaching plans once the final assessment is carried out for a baseline comparison. To evaluate COLAEVA, a usability test was carried out with 9 test participants obtaining an average SUS score of 71.1. Moreover, COLAEVA is available online to use and explore.This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 769830

Pathogenic and low-frequency variants in children with central precocious puberty

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP. Methods: Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results: Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion: The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.Peer reviewe

Images of the United States in the literature of Octavio Paz, Carlos Fuentes, and Jose Emilio Pacheco

There is contact between the United States and Mexico unlike that of any other two countries in the world. This does not mean that we understand each other any better; on the contrary, misconceptions and erroneous images still abound. The United States, which represents a geographic proximity but a cultural and historical distance from its neighbors to the South, has often been placed under scrutiny by Mexican writers. This dissertation examines the many images of the United States that exist in Mexico and how these images are reflected in the literature of representative contemporary Mexican writers (Octavio Paz, Carlos Fuentes, and Jose Emilio Pacheco). Also discussed are the changes these images have undergone from one generation of authors to another, and how these changes may reflect societal and historical events as well as new trends in the Mexican novel. This dissertation draws from established criticism of the modern Mexican novel, as well as from recent historical studies of Mexican-United States relations. As a point of comparison, critical studies that examine Mexico in the works of American and British writers are also referred to. Selected essays of Paz and Fuentes are used to establish their philosophies of the other. The novels of Fuentes to be examined include La region mas transparente, Gringo viejo, and Cristobal Nonato, and the texts of Pacheco discussed are La fiesta brava and Batallas en el desierto. The dissertation concludes that although many of these texts rely on stereotypical images that both sides have of the other, these images are never maintained throughout, being either undermined or destroyed through closer contact and dialogue, the presentation of alternatives, sarcasm and irony, or through a process of disillusionment

Images of the United States in the literature of Octavio Paz, Carlos Fuentes, and Jose Emilio Pacheco

There is contact between the United States and Mexico unlike that of any other two countries in the world. This does not mean that we understand each other any better; on the contrary, misconceptions and erroneous images still abound. The United States, which represents a geographic proximity but a cultural and historical distance from its neighbors to the South, has often been placed under scrutiny by Mexican writers. This dissertation examines the many images of the United States that exist in Mexico and how these images are reflected in the literature of representative contemporary Mexican writers (Octavio Paz, Carlos Fuentes, and Jose Emilio Pacheco). Also discussed are the changes these images have undergone from one generation of authors to another, and how these changes may reflect societal and historical events as well as new trends in the Mexican novel. This dissertation draws from established criticism of the modern Mexican novel, as well as from recent historical studies of Mexican-United States relations. As a point of comparison, critical studies that examine Mexico in the works of American and British writers are also referred to. Selected essays of Paz and Fuentes are used to establish their philosophies of the other. The novels of Fuentes to be examined include La region mas transparente, Gringo viejo, and Cristobal Nonato, and the texts of Pacheco discussed are La fiesta brava and Batallas en el desierto. The dissertation concludes that although many of these texts rely on stereotypical images that both sides have of the other, these images are never maintained throughout, being either undermined or destroyed through closer contact and dialogue, the presentation of alternatives, sarcasm and irony, or through a process of disillusionment

A pulse of simulated root exudation alters the composition and temporal dynamics of microbial metabolites in its immediate vicinity

International audienceRoot exudation increases the concentration of readily available carbon (C) compounds in its immediate environment. This creates 'hotspots' of microbial activity characterized by accelerated soil organic matter turnover with direct implications for nutrient availability for plants. However, our knowledge of the microbial metabolic processes occurring in the immediate vicinity of roots during and after a root exudation event is still limited. Using reverse microdialysis, we simulated root exudation by releasing a 13 C-labelled mix of low-molecularweight organic C compounds at mm-sized locations in undisturbed soil. Combined with stable isotope tracing, we investigated the fine-scale temporal and spatial response of microbial metabolism, soil chemistry, and traced microbial respiration and uptake of exuded compounds. Our results show that a 9-h simulated root exudation pulse leads to i) a large local respiration event and ii) alteration of the temporal dynamics of soil metabolites over the following 12 day at the exudation spot. Notably, we observed a threefold increase in ammonium concentrations at 12 h and increased nitrate concentrations five days after the pulse. Moreover, various short-chain fatty acids (acetate, propionate, formate) increased over the following days, indicating altered microbial metabolic pathways and activity. Phospholipid and neutral lipid fatty acids (PLFAs, NLFAs) of all major microbial groups were significantly 13 C-enriched within a 5 mm radius around the microdialysis probes, but not beyond. The highest relative 13 C enrichment was observed in fungal NLFAs, indicating that a significant proportion of the exuded compounds had been incorporated into fungal storage compounds. Our findings indicate that the punctual release of low-molecular-weight organic C compounds into intact soil significantly changes microbial metabolism and activity in its immediate surroundings, enhancing mineralization of native organic nitrogen. This highlights the versatility of microbial metabolic pathways in response to rapidly changing C availability and their effectiveness in increasing nutrient availability near plant roots

Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples

Background BRCA1 and BRCA2 are the two principal tumour suppressor genes associated with inherited high risk of breast and ovarian cancer. Genetic testing of BRCA1/2 will often reveal one or more sequence variants of uncertain clinical significance, some of which may affect normal splicing patterns and thereby disrupt gene function. mRNA analyses are therefore among the tests used to interpret the clinical significance of some genetic variants. However, these could be confounded by the appearance of naturally occurring alternative transcripts unrelated to germline sequence variation or defects in gene function. To understand which novel splicing events are associated with splicing mutations and which are part of the normal BRCA2 splicing repertoire, a study was undertaken by members of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium to characterise the spectrum of naturally occurring BRCA2 mRNA alternate-splicing events. Methods mRNA was prepared from several blood and breast tissue-derived cells and cell lines by contributing ENIGMA laboratories. cDNA representing BRCA2 alternate splice sites was amplified and visualised using capillary or agarose gel electrophoresis, followed by sequencing. Results We demonstrate the existence of 24 different BRCA2 mRNA alternate-splicing events in lymphoblastoid cell lines and both breast cancer and non-cancerous breast cell lines. Conclusions These naturally occurring alternate-splicing events contribute to the array of cDNA fragments that may be seen in assays for mutation-associated splicing defects. Caution must be observed in assigning alternate-splicing events to potential splicing mutations

Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty

Background Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP Methods Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP

Anticoagulation Prior to COVID-19 Infection Has No Impact on 6 Months Mortality: A Propensity Score–Matched Cohort Study

The coronavirus disease 2019 (COVID-19) shows high incidence of thromboembolic events in humans. In the present study, we aimed to evaluate if anticoagulation prior to COVID-19 infection may impact clinical profile, as well as mortality rate among patients hospitalized with COVID-19. The study was based on retrospective analysis of medical records of patients with laboratory confirmed SARS-CoV-2 infection. After propensity score matching (PSM), a group of 236 patients receiving any anticoagulant treatment prior to COVID-19 infection (AT group) was compared to 236 patients without previous anticoagulation (no AT group). In 180 days, the observation we noted comparable mortality rate in AT and no AT groups (38.5% vs. 41.1%, p = 0.51). Similarly, we did not observe any statistically significant differences in admission in the intensive care unit (14.1% vs. 9.6%, p = 0.20), intubation and mechanical ventilation (15.0% vs. 11.6%, p = 0.38), catecholamines usage (14.3% vs. 13.8%, p = 0.86), and bleeding rate (6.3% vs. 8.9%, p = 0.37) in both groups. Our results suggest that antithrombotic treatment prior to COVID-19 infection is unlikely to be protective for morbidity and mortality in patients hospitalized with COVID-19