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Single-cell RNA sequencing is increasing our understanding of the behavior of complex tissues or organs, by providing unprecedented details on the complex cell type landscape at the level of individual cells. Cell type definition and functional annotation are key steps to understanding the molecular processes behind the underlying cellular communication machinery. However, the exponential growth of scRNA-seq data has made the task of manually annotating cells unfeasible, due not only to an unparalleled resolution of the technology but to an ever-increasing heterogeneity of the data. Many supervised and unsupervised methods have been proposed to automatically annotate cells. Supervised approaches for cell-type annotation outperform unsupervised methods except when new (unknown) cell types are present. Here, we introduce SigPrimedNet an artificial neural network approach that leverages (i) efficient training by means of a sparsity-inducing signaling circuits-informed layer, (ii) feature representation learning through supervised training, and (iii) unknown cell-type identification by fitting an anomaly detection method on the learned representation. We show that SigPrimedNet can efficiently annotate known cell types while keeping a low false-positive rate for unseen cells across a set of publicly available datasets. In addition, the learned representation acts as a proxy for signaling circuit activity measurements, which provide useful estimations of the cell functionalities.

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OBJECTIVE: To study the associated effect of a complete course of antenatal corticosteroids (ACSs) on mortality and morbidity rates among preterm infants in our population. STUDY DESIGN: Observational prospective study of infants born at less than 32 weeks' gestation and admitted to our Neonatal Care Unit between January 2012 and December 2018. We analyzed mortality at discharge and respiratory and neurological morbidity, both during hospitalization and at 24 months' postmenstrual age. RESULTS: The study included a total of 710 patients with a median gestational age of 28.5 weeks (IQR 26.4-30.5) and mean weight of 1.090 g (IQR 800-1.391). Of which, 62.4% received a complete course of antenatal steroids. Given the differences observed in the baseline characteristics of patients who either did or did not receive a full course of antenatal steroids, a propensity score covariate adjustment was performed for all estimations. The effect of ACS therapy differs depending on sex with a positive effect on acute respiratory morbidity and mortality in male patients of less than 29 weeks' gestation. In female infants, there is no significant beneficial association between ACS therapy and mortality or any of the morbidities studied. CONCLUSION: In our population of preterm infants, treatment with antenatal steroids is associated with a different effect depending on sex. Antenatal steroids therapy associated with a positive effect in male patients with a gestational age of less than 29 weeks.

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Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value of harmonized D-dimer levels upon admission for the prediction of in-hospital mortality in COVID-19 patients. All-cause in-hospital mortality was defined as endpoint. For harmonization of D-dimer levels, we designed a model based on the transformation of method-specific regression lines to a reference regression line. The ability of D-dimer for prediction of death was explored by receiver operating characteristic curves analysis and the association with the endpoint by Cox regression analysis. Study population included 2663 patients. In-hospital mortality rate was 14.3%. Harmonized D-dimer upon admission yielded an area under the curve of 0.66, with an optimal cut-off value of 0.945 mg/L FEU. Patients with harmonized D-dimer ≥ 0.945 mg/L FEU had a higher mortality rate (22.4% vs. 9.2%; p < 0.001). D-dimer was an independent predictor of in-hospital mortality, with an adjusted hazard ratio of 1.709. This is the first study in which a harmonization approach was performed to assure comparability of D-dimer levels measured by different assays. Elevated D-dimer levels upon admission were associated with a greater risk of in-hospital mortality among COVID-19 patients, but had limited performance as prognostic test.

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INTRODUCCIÓN: La repercusión de la infección materna por SARS-CoV-2 y su riesgo de transmisión vertical es aún poco conocido. Las recomendaciones de las sociedades científicas buscan proporcionar seguridad para el recién nacido sin comprometer los beneficios del contacto precoz. El objetivo del estudio es describir las características y la evolución de recién nacidos de madres infectadas por SARS-CoV-2, así como las medidas implementadas siguiendo las recomendaciones de la Sociedad Española de Neonatología. MATERIAL Y MÉTODOS: Estudio observacional, prospectivo y unicentro de cohortes. Se diseñó un circuito específico para madres con infección por SARS-CoV-2 y sus hijos. Se recogieron datos epidemiológicos y clínicos de las madres y sus recién nacidos. Se realizó PCR al nacer y a los 14 días. RESULTADOS: Se incluyeron 73 madres y 75 neonatos. El 95,9% de infecciones maternas fueron diagnosticadas durante el tercer trimestre, el 43,8% fueron asintomáticas. La mediana de edad gestacional fue de 38 semanas (RIC: 37-40), el 25,9% de los neonatos requirió ingreso. En el 68% se realizó contacto piel con piel en paritorio y el 80% recibieron lactancia materna o donada exclusiva durante su estancia. No se objetivaron resultados positivos de PCR en la primera muestra obtenida nada más nacer, se objetivó un caso de PCR positiva en un neonato asintomático a los 14 días. CONCLUSIONES: El riesgo de transmisión de la infección por SARS-CoV-2 es bajo cumpliendo los protocolos de la Sociedad Española de Neonatología, permitiendo el alojamiento conjunto de madre e hijo, el contacto precoz y el establecimiento eficaz de la lactancia materna

INTRODUCTION: The impact of maternal SARS-CoV-2 infection and its risk of vertical transmission is still not well known. Recommendations from scientific societies seek to provide safety for newborns without compromising the benefits of early contact. The aim of the study is to describe characteristics and evolution of newborns born to mothers with SARS-CoV-2 infection, as well as the implemented measures following recommendations from the Sociedad Española de Neonatología. METHODS: Observational, prospective and single-center cohort study. A specific circuit was designed for mothers with SARS-CoV-2 infection and their newborns. Epidemiological and clinical data were collected. PCR were performed in newborns at delivery and at 14 days of age. RESULTS: 73 mothers and 75 newborns were included in the study. 95.9% of maternal infections were diagnosed during the third trimester of pregnancy, 43.8% were asymptomatic. Median gestational age was 38 weeks (IQR: 37-40), 25.9% of newborns required admission to Neonatology. Skin-to-skin mother care was performed in 68% of newborns, 80% received exclusive maternal or donated breast milk during hospital stay. No positive PCR results were observed in newborns at delivery, one case of positive PCR was observed in an asymptomatic neonate at 14 days of age. CONCLUSIONS: Risk of SARS-CoV-2 transmission is low when complying to the recommendations issued by Sociedad Española de Neonatología, allowing rooming-in and promoting breastfeeding

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BACKGROUND: Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I. METHODS: This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint. RESULTS: A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P < .001) in patients in whom troponin T was measured in comparison with troponin I. Sex-specific elevated troponin levels were significantly associated with 30-day mortality, with adjusted odds ratios (ORs) of 3.00 for total population, 3.20 for cardiac troponin T and 3.69 for cardiac troponin I. CONCLUSION: In this multicentre study, myocardial injury was a common finding in COVID-19 patients. Its prevalence increased when a sex-specific cut-off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30-day mortality, irrespective of cardiac troponin assay and cut-offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID-19.

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INTRODUCTION: The impact of maternal SARS-CoV-2 infection and its risk of vertical transmission is still not well known. Recommendations from scientific societies seek to provide safety for newborns without compromising the benefits of early contact. The aim of the study is to describe characteristics and evolution of newborns born to mothers with SARS-CoV-2 infection, as well as the implemented measures following recommendations from the Sociedad Española de Neonatología. METHODS: Observational, prospective and single-center cohort study. A specific circuit was designed for mothers with SARS-CoV-2 infection and their newborns. Epidemiological and clinical data were collected. PCR were performed in newborns at delivery and at 14 days of age. RESULTS: 73 mothers and 75 newborns were included in the study. 95.9% of maternal infections were diagnosed during the third trimester of pregnancy, 43.8% were asymptomatic. Median gestational age was 38 weeks (IQR: 37-40), 25.9% of newborns required admission to Neonatology. Skin-to-skin mother care was performed in 68% of newborns, 80% received exclusive maternal or donated breast milk during hospital stay. No positive PCR results were observed in newborns at delivery, one case of positive PCR was observed in an asymptomatic neonate at 14 days of age. CONCLUSIONS: Risk of SARS-CoV-2 transmission is low when complying to the recommendations issued by Sociedad Española de Neonatología, allowing rooming-in and promoting breastfeeding.

INTRODUCCIÓN: La repercusión de la infección materna por SARS-Cov-2 y su riesgo de transmisión vertical es aún poco conocido. Las recomendaciones de las sociedades científicas buscan proporcionar seguridad para el recién nacido sin comprometer los beneficios del contacto precoz. El objetivo del estudio es describir las características y evolución de recién nacidos de madres infectadas por SARS-CoV2, así como las medidas implementadas siguiendo las recomendaciones de la Sociedad Española de Neonatología. MATERIAL Y MÉTODOS: Estudio observacional, prospectivo y unicentro de cohortes. Se diseñó un circuito específico para madres con infección por SARS-CoV2 y sus hijos. Se recogieron datos epidemiológicos y clínicos de las madres y sus recién nacidos. Se realizó PCR al nacer y a los 14 días. RESULTADOS: Se incluyeron 73 madres y 75 neonatos. El 95.9% de infecciones maternas fueron diagnosticadas durante el tercer trimestre, el 43.8% fueron asintomáticas. La mediana de edad gestacional fue 38 semanas (RIC:37­40), el 25.9% de los neonatos requirió ingreso. En el 68% se realizó contacto piel con piel en paritorio y el 80% recibieron lactancia materna o donada exclusiva durante su estancia. No se objetivaron resultados positivos de PCR en la primera muestra obtenida nada más nacer, se objetivó 1 caso de PCR positiva en un neonato asintomático a los 14 días. CONCLUSIONES: El riesgo de transmisión de la infección por SARS-CoV2 es bajo cumpliendo los protocolos de la Sociedad Española de Neonatología, permitiendo el alojamiento conjunto de madre e hijo, el contacto precoz y el establecimiento eficaz de la lactancia materna.

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Identification of predictors for severe disease progression is key for risk stratification in COVID-19 patients. We aimed to describe the main characteristics and identify the early predictors for severe outcomes among hospitalized patients with COVID-19 in Spain. This was an observational, retrospective cohort study (BIOCOVID-Spain study) including COVID-19 patients admitted to 32 Spanish hospitals. Demographics, comorbidities and laboratory tests were collected. Outcome was in-hospital mortality. For analysis, laboratory tests values were previously adjusted to assure the comparability of results among participants. Cox regression was performed to identify predictors. Study population included 2873 hospitalized COVID-19 patients. Nine variables were independent predictors for in-hospital mortality, including creatinine (Hazard ratio [HR]:1.327; 95% Confidence Interval [CI]: 1.040-1.695, p = .023), troponin (HR: 2.150; 95% CI: 1.155-4.001; p = .016), platelet count (HR: 0.994; 95% CI: 0.989-0.998; p = .004) and C-reactive protein (HR: 1.037; 95% CI: 1.006-1.068; p = .019). This is the first multicenter study in which an effort was carried out to adjust the results of laboratory tests measured with different methodologies to guarantee their comparability. We reported a comprehensive information about characteristics in a large cohort of hospitalized COVID-19 patients, focusing on the analytical features. Our findings may help to identify patients early at a higher risk for an adverse outcome.

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INTRODUCTION: The impact of maternal SARS-CoV-2 infection and its risk of vertical transmission is still not well known. Recommendations from scientific societies seek to provide safety for newborns without compromising the benefits of early contact. The aim of the study is to describe characteristics and evolution of newborns born to mothers with SARS-CoV-2 infection, as well as the implemented measures following recommendations from the Sociedad Española de Neonatología. METHODS: Observational, prospective and single-center cohort study. A specific circuit was designed for mothers with SARS-CoV-2 infection and their newborns. Epidemiological and clinical data were collected. PCR were performed in newborns at delivery and at 14 days of age. RESULTS: 73 mothers and 75 newborns were included in the study. 95.9% of maternal infections were diagnosed during the third trimester of pregnancy, 43.8% were asymptomatic. Median gestational age was 38 weeks (IQR: 37-40), 25.9% of newborns required admission to Neonatology. Skin-to-skin mother care was performed in 68% of newborns, 80% received exclusive maternal or donated breast milk during hospital stay. No positive PCR results were observed in newborns at delivery, one case of positive PCR was observed in an asymptomatic neonate at 14 days of age. CONCLUSIONS: Risk of SARS-CoV-2 transmission is low when complying to the recommendations issued by Sociedad Española de Neonatología, allowing rooming-in and promoting breastfeeding.

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Objective: Coronavirus disease 2019 (COVID-19) cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to increase worldwide. Although some data from pediatric series are available, more evidence is required, especially in neonates, a group with specific characteristics that deserve special attention. This study aimed to describe general and clinical characteristics, management, and treatment of postnatal-acquired (community and nosocomial/hospital-acquired) COVID-19 neonatal cases in Spain. Methods: This was a national prospective epidemiological study that included cases from a National Registry supported by the Spanish Society of Neonatology. Neonates with postnatal SARS-CoV-2 infection were included in this study. General data and infection-related information (mode and source of transmission, age at diagnosis, clinical manifestations, need for hospitalization, admission unit, treatment administered, and complementary studies performed, hospital stay associated with the infection) were collected. Results: A total of 40 cases, 26 community-acquired and 14 nosocomial were registered. Ten were preterm newborns (2 community-acquired and 8 nosocomial COVID-19 cases). Mothers (in both groups) and healthcare workers (in nosocomial cases) were the main source of infection. Hospital admission was required in 22 community-acquired cases [18 admitted to the neonatal intermediate care unit (NIMCU) and 4 to the neonatal intensive care unit (NICU)]. Among nosocomial COVID-19 cases (n = 14), previously admitted for other reasons, 4 were admitted to the NIMCU and 10 to the NICU. Ten asymptomatic patients were registered (5 in each group). In the remaining cases, clinical manifestations were generally mild in both groups, including upper respiratory airways infection, febrile syndrome or acute gastroenteritis with good overall health. In both groups, most severe cases occurred in preterm neonates or neonates with concomitant pathologies. Most of the cases did not require respiratory support. Hydroxychloroquine was administered to 4 patients in the community-acquired group and to 2 patients in the nosocomial group. Follow-up after hospital discharge was performed in most patients. Conclusions: This is the largest series of COVID-19 neonatal cases in Spain published to date. Although clinical manifestations were generally mild, prevention, treatment, and management in this group are essential.

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The genus Trichoderma (Hypocreaceae, Ascomycota) consists of globally distributed fungi. In Algeria, few studies have explored the diversity of this genus, and in the majority of works identification is based on phenotypic characters. Here, nine Trichoderma strains were collected from Algeria in different locations, namely: seven in the south and two in the northwest. Also, we used 17 reference strains that were taken from the NCBI database for the phylogeny analysis. Our study is based on an integrated approach using micro and macro phenotypic characters and multiple DNA analysis (internal transcribed spacer (ITS): ITS1-4 region; translation elongation factor 1: tef1 gene). Our study reports, for the first time, three species of Trichoderma in Algeria, namely: T. atrobrunneum (south), T. longibrachiatum (south), and T. afroharzianum (northwest). It is noteworthy that T. atrobrunneum is a species previously described in European Mediterranean countries, and its presence in the soil of southern Algeria indicates that the diversity of the geographic environments and different climates of Algeria offers the possibility for the survival of diverse Trichoderma species. Knowledge on the diversity of these fungi may contribute to their future exploitation in biotechnological applications and to the biological control of plant diseases.

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OBJECTIVE: To investigate if the use of a visible respiratory function monitor (RFM) to use lower tidal volumes (Vts) during positive pressure ventilation (PPV) in the delivery room (DR) reduces the need of surfactant administration and invasive mechanical ventilation during the first 72 hours after birth of preterm infants <32 weeks' gestational age (GA). STUDY DESIGN: Infants <32 weeks' GA (n = 106) requiring noninvasive PPV were monitored with a RFM at birth and randomized to visible (n = 54) or masked (n = 52) display on RFM. Pulmonary data were recorded during the first 10 minutes after birth. Secondary analysis stratified patients by GA (<28, 28-29+6, or ≥30 weeks). RESULTS: Median expiratory Vts during inflations were greater in the masked group (7 mL/kg) than in the visible group (5.8 mL/kg; p = 0.001) same as peak inflation pressure (PIP) administered (21.5 vs. 19.7 cmH2O; p < 0.001). Consequently, minute volumes were greater in the masked group (256 vs. 214 mL/kg/min; p < 0.001), with no differences in respiratory rate. These differences were higher in those <30 weeks' GA. There was no difference in the need of surfactant administration or intubation during the first 72 hours of age. CONCLUSION: Using a RFM in the DR prevents the use of large Vt and PIP during respiratory support inflations, mostly in the more immature newborn infants, but with no other short-term benefits.

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The olive oil assessment involves the use of a standardized sensory analysis according to the "panel test" method. However, there is an important interest to design novel strategies based on the use of Gas Chromatography (GC) coupled to mass spectrometry (MS), or ion mobility spectrometry (IMS) together with a chemometric data treatment for olive oil classification. It is an essential task in an attempt to get the most robust model over time and, both to avoid fraud in the price and to know whether it is suitable for consumption or not. The aim of this paper is to combine chemical techniques and Deep Learning approaches to automatically classify olive oil samples from two different harvests in their three corresponding classes: extra virgin olive oil (EVOO), virgin olive oil (VOO), and lampante olive oil (LOO). Our Deep Learning model is built with 701 samples, which were obtained from two olive oil campaigns (2014-2015 and 2015-2016). The data from the two harvests are built from the selection of specific olive oil markers from the whole spectral fingerprint obtained with GC-IMS method. In order to obtain the best results we have configured the parameters of our model according to the nature of the data. The results obtained show that a deep learning approach applied to data obtained from chemical instrumental techniques is a good method when classifying oil samples in their corresponding categories, with higher success rates than those obtained in previous works.

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BACKGROUND: Biclustering algorithms search for groups of genes that share the same behavior under a subset of samples in gene expression data. Nowadays, the biological knowledge available in public repositories can be used to drive these algorithms to find biclusters composed of groups of genes functionally coherent. On the other hand, a distance among genes can be defined according to their information stored in Gene Ontology (GO). Gene pairwise GO semantic similarity measures report a value for each pair of genes which establishes their functional similarity. A scatter search-based algorithm that optimizes a merit function that integrates GO information is studied in this paper. This merit function uses a term that addresses the information through a GO measure. RESULTS: The effect of two possible different gene pairwise GO measures on the performance of the algorithm is analyzed. Firstly, three well known yeast datasets with approximately one thousand of genes are studied. Secondly, a group of human datasets related to clinical data of cancer is also explored by the algorithm. Most of these data are high-dimensional datasets composed of a huge number of genes. The resultant biclusters reveal groups of genes linked by a same functionality when the search procedure is driven by one of the proposed GO measures. Furthermore, a qualitative biological study of a group of biclusters show their relevance from a cancer disease perspective. CONCLUSIONS: It can be concluded that the integration of biological information improves the performance of the biclustering process. The two different GO measures studied show an improvement in the results obtained for the yeast dataset. However, if datasets are composed of a huge number of genes, only one of them really improves the algorithm performance. This second case constitutes a clear option to explore interesting datasets from a clinical point of view.

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OBJECTIVES: Analyze a set of data of hydrogen breath tests by use of data mining tools. Identify new patterns of H2 production. METHODS: Hydrogen breath tests data sets as well as k-means clustering as the data mining technique to a dataset of 2571 patients. RESULTS: Six different patterns have been extracted upon analysis of the hydrogen breath test data. We have also shown the relevance of each of the samples taken throughout the test. CONCLUSIONS: Analysis of the hydrogen breath test data sets using data mining techniques has identified new patterns of hydrogen generation upon lactose absorption. We can see the potential of application of data mining techniques to clinical data sets. These results offer promising data for future research on the relations between gut microbiota produced hydrogen and its link to clinical symptoms.

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The Regression Network plugin for Cytoscape (RegNetC) implements the RegNet algorithm for the inference of transcriptional association network from gene expression profiles. This algorithm is a model tree-based method to detect the relationship between each gene and the remaining genes simultaneously instead of analyzing individually each pair of genes as correlation-based methods do. Model trees are a very useful technique to estimate the gene expression value by regression models and favours localized similarities over more global similarity, which is one of the major drawbacks of correlation-based methods. Here, we present an integrated software suite, named RegNetC, as a Cytoscape plugin that can operate on its own as well. RegNetC facilitates, according to user-defined parameters, the resulted transcriptional gene association network in .sif format for visualization, analysis and interoperates with other Cytoscape plugins, which can be exported for publication figures. In addition to the network, the RegNetC plugin also provides the quantitative relationships between genes expression values of those genes involved in the inferred network, i.e., those defined by the regression models.

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Gene expression data analysis is based on the assumption that co-expressed genes imply co-regulated genes. This assumption is being reformulated because the co-expression of a group of genes may be the result of an independent activation with respect to the same experimental condition and not due to the same regulatory regime. For this reason, traditional techniques are recently being improved with the use of prior biological knowledge from open-access repositories together with gene expression data. Biclustering is an unsupervised machine learning technique that searches patterns in gene expression data matrices. A scatter search-based biclustering algorithm that integrates biological information is proposed in this paper. In addition to the gene expression data matrix, the input of the algorithm is only a direct annotation file that relates each gene to a set of terms from a biological repository where genes are annotated. Two different biological measures, FracGO and SimNTO, are proposed to integrate this information by means of its addition to-be-optimized fitness function in the scatter search scheme. The measure FracGO is based on the biological enrichment and SimNTO is based on the overlapping among GO annotations of pairs of genes. Experimental results evaluate the proposed algorithm for two datasets and show the algorithm performs better when biological knowledge is integrated. Moreover, the analysis and comparison between the two different biological measures is presented and it is concluded that the differences depend on both the data source and how the annotation file has been built in the case GO is used. It is also shown that the proposed algorithm obtains a greater number of enriched biclusters than other classical biclustering algorithms typically used as benchmark and an analysis of the overlapping among biclusters reveals that the biclusters obtained present a low overlapping. The proposed methodology is a general-purpose algorithm which allows the integration of biological information from several sources and can be extended to other biclustering algorithms based on the optimization of a merit function.

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BACKGROUND: Zebrafish is a clinically-relevant model of heart regeneration. Unlike mammals, it has a remarkable heart repair capacity after injury, and promises novel translational applications. Amputation and cryoinjury models are key research tools for understanding injury response and regeneration in vivo. An understanding of the transcriptional responses following injury is needed to identify key players of heart tissue repair, as well as potential targets for boosting this property in humans. RESULTS: We investigated amputation and cryoinjury in vivo models of heart damage in the zebrafish through unbiased, integrative analyses of independent molecular datasets. To detect genes with potential biological roles, we derived computational prediction models with microarray data from heart amputation experiments. We focused on a top-ranked set of genes highly activated in the early post-injury stage, whose activity was further verified in independent microarray datasets. Next, we performed independent validations of expression responses with qPCR in a cryoinjury model. Across in vivo models, the top candidates showed highly concordant responses at 1 and 3 days post-injury, which highlights the predictive power of our analysis strategies and the possible biological relevance of these genes. Top candidates are significantly involved in cell fate specification and differentiation, and include heart failure markers such as periostin, as well as potential new targets for heart regeneration. For example, ptgis and ca2 were overexpressed, while usp2a, a regulator of the p53 pathway, was down-regulated in our in vivo models. Interestingly, a high activity of ptgis and ca2 has been previously observed in failing hearts from rats and humans. CONCLUSIONS: We identified genes with potential critical roles in the response to cardiac damage in the zebrafish. Their transcriptional activities are reproducible in different in vivo models of cardiac injury.

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