Personalized diagnosis in suspected myocardial infarction

Background: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hscTn)- based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays. Methods: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability ( ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients. Results: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline- recommended strategy. Conclusion We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care

Ṭshensṭokhoṿ : arṭiḳlen un bilder fun alṭe un naye tsayṭn : Di anṭṿiḳlung fun yishev /

Digital imag

qtlXplorer: an online systems genetics browser in the Eucalyptus Genome Integrative Explorer (EucGenIE)

Background: Affordable high-throughput DNA and RNA sequencing technologies are allowing genomic analysis of plant and animal populations and as a result empowering new systems genetics approaches to study complex traits. The availability of intuitive tools to browse and analyze the resulting large-scale genetic and genomic datasets remain a significant challenge. Furthermore, these integrative genomics approaches require innovative methods to dissect the flow and interconnectedness of biological information underlying complex trait variation. The Plant Genome Integrative Explorer (PlantGenIE.org ) is a multi-species database and domain that houses online tools for model and woody plant species including Eucalyptus. Since the Eucalyptus Genome Integrative Explorer (EucGenIE) is integrated within PlantGenIE, it shares genome and expression analysis tools previously implemented within the various subdomains (ConGenIE, PopGenIE and AtGenIE). Despite the success in setting up integrative genomics databases, online tools for systems genetics modelling and high-resolution dissection of complex trait variation in plant populations have been lacking.Results: We have developed qtlXplorer (https://eucgenie.org/QTLXplorer) for visualizing and exploring systems genetics data from genome-wide association studies including quantitative trait loci (QTLs) and expression-based QTL (eQTL) associations. This module allows users to, for example, find co-located QTLs and eQTLs using an interactive version of Circos, or explore underlying genes using JBrowse. It provides users with a means to build systems genetics models and generate hypotheses from large-scale population genomics data. We also substantially upgraded the EucGenIE resource and show how it enables users to combine genomics and systems genetics approaches to discover candidate genes involved in biotic stress responses and wood formation by focusing on two multigene families, laccases and peroxidases.Conclusions: qtlXplorer adds a new dimension, population genomics, to the EucGenIE and PlantGenIE environment. The resource will be of interest to researchers and molecular breeders working in Eucalyptus and other woody plant species. It provides an example of how systems genetics data can be integrated with functional genetics data to provide biological insight and formulate hypotheses. Importantly, integration within PlantGenIE enables novel comparative genomics analyses to be performed from population-scale data

Thioredoxin from the Indianmeal moth Plodia interpunctella: cloning and test of the allergenic potential in mice.

BACKGROUND/OBJECTIVE: The Indianmeal moth Plodia interpunctella is a highly prevalent food pest in human dwellings, and has been shown to contain a number of allergens. So far, only one of these, the arginine kinase (Plo i 1) has been identified. OBJECTIVE: The aim of this study was to identify further allergens and characterise these in comparison to Plo i 1. METHOD: A cDNA library from whole adult P. interpunctella was screened with the serum of a patient with indoor allergy and IgE to moths, and thioredoxin was identified as an IgE-binding protein. Recombinant thioredoxin was generated in E. coli, and tested together with Plo i 1 and whole moth extracts in IgE immunoblots against a large panel of indoor allergic patients' sera. BALB/c mice were immunised with recombinant thioredoxin and Plo i 1, and antibody production, mediator release from RBL cells, T-cell proliferation and cytokine production were measured. RESULT: For the first time a thioredoxin from an animal species was identified as allergen. About 8% of the sera from patients with IgE against moth extracts reacted with recombinant P. interpunctella thioredoxin, compared to 25% reacting with recombinant Plo i 1. In immunised BALB/c mice, the recombinant allergens both induced classical Th2-biased immune responses such as induction IgE and IgG1 antibodies, upregulation of IL-5 and IL-4 and basophil degranulation. CONCLUSION: Thioredoxin from moths like Plo i 1 acts like a classical Type I allergen as do the thioredoxins from wheat or corn. This clearly supports the pan-allergen nature of thioredoxin. The designation Plo i 2 is suggested for the new P. interpunctella allergen

Cellular immune responses.

<p>IL-5, IL-4 and IFN-γ levels in supernatants of restimulated spleen cell cultures of mice, treated with 1 µg (black bars), 5 µg (grey bars) or 25 µg (striped bars) of (A), thioredoxin or (B), arginine kinase, or sham-treated (white bars). Groups were compared to sham-treated controls. *p<0.05, **p<0.01.</p

Immunoblot inhibition experiment.

<p>Extracts from <i>E. kuehniella</i> were separated by polyacrylamide electrophoresis, blotted onto nitrocellulose, and strips were probed with serum samples preincubated with or without 10 µg of recombinant allergen overnight. Lane 1, thioredoxin (Plo i 2) positive serum; lane 2, same serum preincubated with recombinant <i>P. interpunctella</i> thioredoxin; lane 3, arginine kinase (Plo i 1) positive serum; lane 4, same serum preincubated with recombinant Plo i 1; lane 5, nonallergic control serum, lane 6, same serum preincubated with Plo i 2; lane 7, same serum preincubated with Plo i 1; lane 8, buffer control. Molecular weights [kDa] are indicated at the left side, the positions of thioredoxin (TRX) and arginine kinase (AK) at the right side.</p

IgE immunoblots with patients' sera.

<p>Top panels: extracts from whole mediterranean flour moths (<i>E. kuehniella</i>) were separated by polyacrylamide electrophoresis, blotted onto nitrocellulose, and probed with the sera from various groups of patients with indoor allergy or seafood allergy as well as from control individuals. The indoor allergic patient groups were: M, housedust mite allergic patients (n = 69), M+D, patients allergic to mites and animal dander (n = 43), D−M, patients with allergy to animal dander but not to mites (n = 20). Patients SF, seafood allergic patients (n = 22), NC, nonallergic control individuals (n = 2), BC, buffer control without serum, only secondary anti-IgE antibody. Molecular weights [kDa] are indicated at the left side. Bottom panels, the recombinant <i>P. interpunctella</i> 40 kDa arginine kinase (AK) and 12 kDa thioredoxin (TRX) were probed with those patients' sera containing IgE to <i>E. kuehniella</i>, and only the parts of the strips containing the two recombinant allergens are shown.</p