Improving FPGA Based Impedance Spectroscopy Measurement Equipment by Means of HLS Described Neural Networks to Apply Edge AI

[EN] The artificial intelligence (AI) application in instruments such as impedance spectroscopy highlights the difficulty to choose an electronic technology that correctly solves the basic performance problems, adaptation to the context, flexibility, precision, autonomy, and speed of design. Present work demonstrates that FPGAs, in conjunction with an optimized high-level synthesis (HLS), allow us to have an efficient connection between the signals sensed by the instrument and the artificial neural network-based AI computing block that will analyze them. State-of-the-art comparisons and experimental results also demonstrate that our designed and developed architectures offer the best compromise between performance, efficiency, and system costs in terms of artificial neural networks implementation. In the present work, computational efficiency above 21 Mps/DSP and power efficiency below 1.24 mW/Mps are achieved. It is important to remark that these results are more relevant because the system can be implemented on a low-cost FPGA.This work was supported in part by the Spanish MCIU under Project PID2020-116816RB-I00 (MCIU/FEDER) and in part by GVA under Project INNEST/2020/248.Fe, J.; Gadea Gironés, R.; Monzó Ferrer, JM.; Tébar Ruiz, Á.; Colom Palero, RJ. (2022). Improving FPGA Based Impedance Spectroscopy Measurement Equipment by Means of HLS Described Neural Networks to Apply Edge AI. Electronics. 11(13):1-14. https://doi.org/10.3390/electronics11132064114111

A Single Argonaute Gene Participates in Exogenous and Endogenous RNAi and Controls Cellular Functions in the Basal Fungus Mucor circinelloides

The mechanism of RNAi is well described in metazoans where it plays a role in diverse cellular functions. However, although different classes of endogenous small RNAs (esRNAs) have been identified in fungi, their biological roles are poorly described due, in part, to the lack of phenotype of mutants affected in the biogenesis of these esRNAs. Argonaute proteins are one of the key components of the RNAi pathways, in which different members of this protein family participate in the biogenesis of a wide repertoire of esRNAs molecules. Here we identified three argonaute genes of the fungus Mucor circinelloides and investigated their participation in exogenous and endogenous RNAi. We found that only one of the ago genes, ago-1, is involved in RNAi during vegetative growth and is required for both transgene-induced RNA silencing and the accumulation of distinct classes of esRNAs derived from exons (ex-siRNAs). Classes I and II ex-siRNAs bind to Ago-1 to control mRNA accumulation of the target protein coding genes. Class III ex-siRNAs do not specifically bind to Ago-1, but requires this protein for their production, revealing the complexity of the biogenesis pathways of ex-siRNAs. We also show that ago-1 is involved in the response to environmental signals, since vegetative development and autolysis induced by nutritional stress are affected in ago-1(-) M. circinelloides mutants. Our results demonstrate that a single Ago protein participates in the production of different classes of esRNAs that are generated through different pathways. They also highlight the role of ex-siRNAs in the regulation of endogenous genes in fungi and expand the range of biological functions modulated by RNAi

Accuracy of urea breath test performed immediately after emergency endoscopy in peptic ulcer bleeding

Producción CientíficaThe aim of this work is to investigate the accuracy of the urea breath test (UBT) performed immediately after emergency endoscopy in peptic ulcer bleeding (PUB). METHODS: Urea breath test was carried out right after emergency endoscopy in patients with PUB. The accuracy of this early UBT was compared to a delayed one after hospital discharge that was considered the gold standard. Clinical and epidemiological factors were analyzed in order to study their influence on the accuracy of the early UBT. RESULTS: Early UBT was collected without any complication and good acceptance from all the 74 patients included. In 53 of the patients (71.6%), a delayed UBT was obtained. Comparing concordance between the two tests we have calculated an accuracy of 83% for the early UBT. Sensibility and specificity were 86.36 and 66%, respectively, with a positive predictive value of 92.68% and negative predictive value of 50% (Kappa index = 0.468; p = 0.0005; CI: 95%). We found no influence of epidemiological factors, clinical presentation, drugs, times to gastroscopy, Forrest classification, endoscopic therapy, hemoglobin, and urea levels over the accuracy of early UBT. CONCLUSIONS: Urea breath test carried out right after emergency endoscopy in PUB is an effective, safe, and easy-to-perform procedure. The accuracy of the test is not modified by clinical or epidemiological factors, ulcer stage, or by the type of therapy applied. However, we have found a low negative predictive value for early UBT, so a delayed test is mandatory for all negative cases

Gender Biases and Diagnostic Delay in Inflammatory Bowel Disease: Multicenter Observational Study

Background: Female gender could be a cause of diagnostic delay in inflammatory bowel disease (IBD). The aim of this study was to investigate the diagnostic delay in women vs men and potential causes. Methods: This multicenter cohort study included 190 patients with recent diagnosis of IBD (disease duration <7 months). Reconstruction of the clinical presentation and diagnostic process was carried out in conjunction with the semistructured patient interview, review, and electronic medical records. Results: The median time from symptom onset to IBD diagnosis was longer in women than in men: 12.6 (interquartile range, 3.7-31) vs 4.5 (2.2-9.8) months for Crohn’s disease (CD; P = .008) and 6.1 (3-11.2) vs 2.7 (1.5-5.6) months for ulcerative colitis (UC; P = .008). Sex was an independent variable related to the time to IBD diagnosis in Cox regression analysis. The clinical presentation of IBD was similar in both sexes. Women had a higher percentage of misdiagnosis than men (CD, odds ratio [OR], 3.9; 95% confidence [CI], 1.5-9.9; UC, OR 3.0; 95% CI, 1.2-7.4). Gender inequities in misdiagnosis were found at all levels of the health system (emergency department, OR 2.4; 95% CI, 1.1-5.1; primary care, OR 2.5; 95% CI, 1.3-4.7; gastroenterology secondary care, OR 3.2; 95% CI, 1.2-8.4; and hospital admission, OR 4.3; 95% CI, 1.1-16.9). Conclusions: There is a longer diagnostic delay in women than in men for both CD and UC due to a drawn-out evaluation of women, with a higher number of misdiagnoses at all levels of the health care system.This study was supported by Instituto de Salud Carlos III (PI 18/01547), GETECCU (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa, Grant 2017) and SVPD (Sociedad Valenciana de Patología Digestiva, Grant 2017)

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies

A non-canonical RNA silencing pathway promotes mRNA degradation in basal fungi

The increasing knowledge on the functional relevance of endogenous small RNAs (esRNAs) as riboregulators has stimulated the identification and characterization of these molecules in numerous eukaryotes. In the basal fungus Mucor circinelloides, an emerging opportunistic human pathogen, esRNAs that regulate the expression of many protein coding genes have been described. These esRNAs share common machinery for their biogenesis consisting of an RNase III endonuclease Dicer, a single Argonaute protein and two RNA-dependent RNA polymerases. We show in this study that, besides participating in this canonical dicer-dependent RNA interference (RNAi) pathway, the rdrp genes are involved in a novel dicer-independent degradation process of endogenous mRNAs. The analysis of esRNAs accumulated in wild type and silencing mutants demonstrates that this new rdrp-dependent dicer-independent regulatory pathway, which does not produce sRNA molecules of discrete sizes, controls the expression of target genes promoting the specific degradation of mRNAs by a previously unknown RNase. This pathway mainly regulates conserved genes involved in metabolism and cellular processes and signaling, such as those required for heme biosynthesis, and controls responses to specific environmental signals. Searching the Mucor genome for candidate RNases to participate in this pathway, and functional analysis of the corresponding knockout mutants, identified a new protein, R3B2. This RNase III-like protein presents unique domain architecture, it is specifically found in basal fungi and, besides its relevant role in the rdrp-dependent dicer-independent pathway, it is also involved in the canonical dicer-dependent RNAi pathway, highlighting its crucial role in the biogenesis and function of regulatory esRNAs. The involvement of RdRPs in RNA degradation could represent the first evolutionary step towards the development of an RNAi mechanism and constitutes a genetic link between mRNA degradation and post-transcriptional gene silencing

Circulating neutrophil counts and mortality in septic shock

Producción CientíficaPolynuclear neutrophils can play dual roles in sepsis: on the one hand they mediate major antimicrobial activities and on the other hand they can contribute to the development of multiple organ failure [1]. Nonetheless, in spite of the importance of these cells in sepsis, the influence of the circulating neutrophil count (CNC) on the prognosis of septic patients with this pathology has not been properly evaluated. We analyzed the association between CNC and outcome in two cohorts of patients with diagnostic criteria of septic shock (SS) [2]: the first was recruited in the context of a single center study (EXPRESS study, discovery cohort, n = 195; Table 1), and the second in the context of a multi-centric study (GRECIA study, validation cohort, n = 194; Table 2). Written informed consent was obtained from each patient or their legal representative. The two studies were approved by the Research Ethics Committee of the Hospital Clínico Universitario, Valladolid, Spain (for the EXPRESS study) and Hospital Universitario Río Hortega, Valladolid, Spain (coordinating center for the GRECIA study).Instituto de Salud Carlos III (grant PI 10/01362)Junta de Castilla y León (grant BOCYL-D-26072010

The RNAi machinery controls distinct responses to environmental signals in the basal fungus Mucor circinelloides

BACKGROUND: RNA interference (RNAi) is a conserved mechanism of genome defence that can also have a role in the regulation of endogenous functions through endogenous small RNAs (esRNAs). In fungi, knowledge of the functions regulated by esRNAs has been hampered by lack of clear phenotypes in most mutants affected in the RNAi machinery. Mutants of Mucor circinelloides affected in RNAi genes show defects in physiological and developmental processes, thus making Mucor an outstanding fungal model for studying endogenous functions regulated by RNAi. Some classes of Mucor esRNAs map to exons (ex-siRNAs) and regulate expression of the genes from which they derive. To have a broad picture of genes regulated by the silencing machinery during vegetative growth, we have sequenced and compared the mRNA profiles of mutants in the main RNAi genes by using RNA-seq. In addition, we have achieved a more complete phenotypic characterization of silencing mutants.  RESULTS: Deletion of any main RNAi gene provoked a deep impact in mRNA accumulation at exponential and stationary growth. Genes showing increased mRNA levels, as expected for direct ex-siRNAs targets, but also genes with decreased expression were detected, suggesting that, most probably, the initial ex-siRNA targets regulate the expression of other genes, which can be up- or down-regulated. Expression of 50% of the genes was dependent on more than one RNAi gene in agreement with the existence of several classes of ex-siRNAs produced by different combinations of RNAi proteins. These combinations of proteins have also been involved in the regulation of different cellular processes. Besides genes regulated by the canonical RNAi pathway, this analysis identified processes, such as growth at low pH and sexual interaction that are regulated by a dicer-independent non-canonical RNAi pathway.  CONCLUSION: This work shows that the RNAi pathways play a relevant role in the regulation of a significant number of endogenous genes in M. circinelloides during exponential and stationary growth phases and opens up an important avenue for in-depth study of genes involved in the regulation of physiological and developmental processes in this fungal model

Environmental valuation by the local population and visitors for zoning a protected area

Protected natural areas have traditionally played an important role in tourist destinations. There are over one hundred thousand of these areas throughout the world and to date, their landscapes and biodiversity have constituted the main factor attracting visitors. Although these components have not lost their power to attract, many tourist destinations now highlight the relationship between nature and traditional culture. On one hand, the planning and management of natural areas have fundamentally been based on biophysical aspects; hence, their name. But, on the other, the socioeconomic perspective is of great importance and should be incorporated further into this management. The professional field of the sciences of ‘nature’, which so far has played a major role in these areas, along with the disciplines of social sciences and humanities, faces the challenge of integrating their analysis methods, which can be directly applied to an understanding of the dynamics of present-day tourism. This integration could consider protected areas and territories beyond their physical boundaries. Our team, with experience in the development of environmental analysis models applied to the zoning and subsequent declaration of these areas, has proposed a new procedure for evaluating carrying capacities and tourism potentialities, integrating environmental (landscape), anthropological (local society and visitors) and socioeconomic (living standard and quality of life of local population) perspectives. The research relates this kind of components through multivariate analyses, geo-referenced databases and questionnaires. The pathway of the model is landscape functioning (ecosystem) and its function for society (ecosystem services)

Modelling entomological-climatic interactions of Plasmodium falciparum malaria transmission in two Colombian endemic-regions: contributions to a National Malaria Early Warning System

BACKGROUND: Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model. METHODS: The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process. RESULTS: Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897–0.668 (P > 0.95) and 0.0002–0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission. CONCLUSION: The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System