Triage of stroke patients in the chain of acute stroke care

By advancing existing stroke triage systems, diagnosis and timely access of stroke patients to specialized care can be improved, which in turn can have a tremendous impact on current clinical practice. The overall aim of this thesis was to assess various ways to improve stroke triage in the chain of acute stroke. To begin with patient triage by assessing the patient’s entrance into the chain of acute stroke care (Part I). To improve patient triage, the focus should be to directly involve the ambulance once stroke is suspected. In Part II, prehospital triage tools to improve patient selection in the ambulance are identified en validated. Prehospital triage tools that can help identify patients who are more likely to have large anterior vessel occlusion or can differentiate between patients with acute ischemic stroke and intracerebral hemorrhage, will improve patient selection in the ambulance and thereby result in earlier initiation of endovascular treatment, thereby improving patient outcomes. In the last part (Part III), in-hospital factors are investigated that are known to have an adverse effect on patient outcome in the final part of the chain of acute stroke care, as continued efforts need to be made to further reduce in-hospital delays.The Dutch Heart FoundationLUMC / Geneeskund

Genomic and exoproteomic diversity in plant biomass degradation approaches among Aspergilli

We classified the genes encoding carbohydrate-active enzymes (CAZymes) in 17 sequenced genomes representing 16 evolutionarily diverse Aspergillus species. We performed a phylogenetic analysis of the encoding enzymes, along with experimentally characterized CAZymes, to assign molecular function to the Aspergilli CAZyme families and subfamilies. Genome content analysis revealed that the numbers of CAZy genes per CAZy family related to plant biomass degradation follow closely the taxonomic distance between the species. On the other hand, growth analysis showed almost no correlation between the number of CAZyme genes and the efficiency in polysaccharide utilization. The exception is A. clavatus where a reduced number of pectinolytic enzymes can be correlated with poor growth on pectin. To gain detailed information on the enzymes used by Aspergilli to breakdown complex biomass, we conducted exoproteome analysis by mass spectrometry. These results showed that Aspergilli produce many different enzymes mixtures in the presence of sugar beet pulp and wheat bran. Despite the diverse enzyme mixtures produced, species of section Nigri, A. aculeatus, A. nidulans and A. terreus, produce mixtures of enzymes with activities that are capable of digesting all the major polysaccharides in the available substrates, suggesting that they are capable of degrading all the polysaccharides present simultaneously. For the other Aspergilli, typically the enzymes produced are targeted to a subset of polysaccharides present, suggesting that they can digest only a subset of polysaccharides at a given time.Peer reviewe

Circulating tRNA fragments as a novel biomarker class to distinguish acute stroke subtypes

Early blood biomarkers to diagnose acute stroke could drastically reduce treatment delays. We investigated whether circulating small non-coding RNAs can serve as biomarkers to distinguish between acute ischemic stroke (IS), intracerebral hemorrhage (ICH) and stroke mimics (SM). In an ongoing observational cohort study, we performed small RNA-sequencing in plasma obtained from a discovery cohort of 26 patients (9 IS, 8 ICH and 9 SM) presented to the emergency department within 6 h of symptom onset. We validated our results in an independent dataset of 20 IS patients and 20 healthy controls. ICH plasma had the highest abundance of ribosomal and tRNA-derived fragments, while microRNAs were most abundant in plasma of IS patients. Combinations of four to five tRNAs yielded diagnostic accuracies (areas under the receiver operating characteristics curve) up to 0.986 (ICH vs. IS and SM) in the discovery cohort. Validation of the IS and SM models in the independent dataset yielded diagnostic accuracies of 0.870 and 0.885 to distinguish IS from healthy controls. Thus, we identified tRNA-derived fragments as a promising novel class of biomarkers to distinguish between acute IS, ICH and SM, as well as healthy controls.Development and application of statistical models for medical scientific researc

A Reduction in Time with Electronic Monitoring In Stroke (ARTEMIS): study TA protocol for a randomised multicentre trial

Neuro Imaging Researc

The gold-standard genome of <i>Aspergillus niger</i> NRRL 3 enables a detailed view of the diversity of sugar catabolism in fungi

The fungal kingdom is too large to be discovered exclusively by classical genetics. The access to omics data opens a new opportunity to study the diversity within the fungal kingdom and how adaptation to new environments shapes fungal metabolism. Genomes are the foundation of modern science but their quality is crucial when analysing omics data. In this study, we demonstrate how one gold-standard genome can improve functional prediction across closely related species to be able to identify key enzymes, reactions and pathways with the focus on primary carbon metabolism.Based on this approach we identified alternative genes encoding various steps of the different sugar catabolic pathways, and as such provided leads for functional studies into this topic. We also revealed significant diversity with respect to genome content, although this did not always correlate to the ability of the species to use the corresponding sugar as a carbon source. Key words: Aspergillus, Genomic diversity, Gold standard genome, Sugar catabolis

Prognostic value of deep learning-mediated treatment monitoring in lung cancer patients receiving immunotherapy

BackgroundCheckpoint inhibitors provided sustained clinical benefit to metastatic lung cancer patients. Nonetheless, prognostic markers in metastatic settings are still under research. Imaging offers distinctive advantages, providing whole-body information non-invasively, while routinely available in most clinics. We hypothesized that more prognostic information can be extracted by employing artificial intelligence (AI) for treatment monitoring, superior to 2D tumor growth criteria.MethodsA cohort of 152 stage-IV non-small-cell lung cancer patients (NSCLC) (73 discovery, 79 test, 903CTs), who received nivolumab were retrospectively collected. We trained a neural network to identify morphological changes on chest CT acquired during patients' follow-ups. A classifier was employed to link imaging features learned by the network with overall survival.ResultsOur results showed significant performance in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.69 (p < 0.01), up to AUC 0.75 (p < 0.01) in the first 3 to 5 months of treatment, and 0.67 AUC (p = 0.01) for durable clinical benefit (6 months progression-free survival). We found the AI-derived survival score to be independent of clinical, radiological, PDL1, and histopathological factors. Visual analysis of AI-generated prognostic heatmaps revealed relative prognostic importance of morphological nodal changes in the mediastinum, supraclavicular, and hilar regions, lung and bone metastases, as well as pleural effusions, atelectasis, and consolidations.ConclusionsOur results demonstrate that deep learning can quantify tumor- and non-tumor-related morphological changes important for prognostication on serial imaging. Further investigation should focus on the implementation of this technique beyond thoracic imaging.Pathogenesis and treatment of chronic pulmonary disease

Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndromic Intellectual Disability and Deficient Histone Acetylation

Genetics of disease, diagnosis and treatmen

Systems biology approaches to unravel the molecular mechanisms of human ciliopathies

Contains fulltext : 230657.pdf (publisher's version ) (Open Access)Radboud University, 26 maart 2021Promotor : Roepman, R.313 p

Requests and politeness in vietnamese as a native language

Pragmatics234685-71