"CZ.02.1.01/0.0/0.0/16_019/0000765"
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Recent research has already shown that circular RNAs (circRNAs) are functional in gene expression regulation and potentially related to diseases. Due to their stability, circRNAs can also be used as biomarkers for diagnosis. However, the function of most circRNAs remains unknown, and it is expensive and time-consuming to discover it through biological experiments. In this paper, we predict circRNA annotations from the knowledge of their interaction with miRNAs and subsequent miRNA-mRNA interactions. First, we construct an interaction network for a target circRNA and secondly spread the information from the network nodes with the known function to the root circRNA node. This idea itself is not new; our main contribution lies in proposing an efficient and exact deterministic procedure based on the principle of probability-generating functions to calculate the p-value of association test between a circRNA and an annotation term. We show that our publicly available algorithm is both more effective and efficient than the commonly used Monte-Carlo sampling approach that may suffer from difficult quantification of sampling convergence and subsequent sampling inefficiency. We experimentally demonstrate that the new approach is two orders of magnitude faster than the Monte-Carlo sampling, which makes summary annotation of large circRNA files feasible; this includes their reannotation after periodical interaction network updates, for example. We provide a summary annotation of a current circRNA database as one of our outputs. The proposed algorithm could be generalized towards other types of RNA in way that is straightforward.
BACKGROUND: Ubiquitin ligases (Ub-ligases) are essential intracellular enzymes responsible for the regulation of proteome homeostasis, signaling pathway crosstalk, cell differentiation and stress responses. Individual Ub-ligases exhibit their unique functions based on the nature of their substrates. They create a complex regulatory network with alternative and feedback pathways to maintain cell homeostasis, being thus important players in many physiological and pathological conditions. However, the functional classification of Ub-ligases needs to be revised and extended. METHODS: In the current study, we used a novel semantic biclustering technique for expression profiling of Ub-ligases and ubiquitination-related genes in the murine gastrointestinal tract (GIT). We accommodated a general framework of the algorithm for finding tissue-specific gene expression clusters in GIT. In order to test identified clusters in a biological system, we used a model of epithelial regeneration. For this purpose, a dextran sulfate sodium (DSS) mouse model, following with in situ hybridization, was used to expose genes with possible compensatory features. To determine cell-type specific distribution of Ub-ligases and ubiquitination-related genes, principal component analysis (PCA) and Uniform Manifold Approximation and Projection technique (UMAP) were used to analyze the Tabula Muris scRNA-seq data of murine colon followed by comparison with our clustering results. RESULTS: Our established clustering protocol, that incorporates the semantic biclustering algorithm, demonstrated the potential to reveal interesting expression patterns. In this manner, we statistically defined gene clusters consisting of the same genes involved in distinct regulatory pathways vs distinct genes playing roles in functionally similar signaling pathways. This allowed us to uncover the potentially redundant features of GIT-specific Ub-ligases and ubiquitination-related genes. Testing the statistically obtained results on the mouse model showed that genes clustered to the same ontology group simultaneously alter their expression pattern after induced epithelial damage, illustrating their complementary role during tissue regeneration. CONCLUSIONS: An optimized semantic clustering protocol demonstrates the potential to reveal a readable and unique pattern in the expression profiling of GIT-specific Ub-ligases, exposing ontologically relevant gene clusters with potentially redundant features. This extends our knowledge of ontological relationships among Ub-ligases and ubiquitination-related genes, providing an alternative and more functional gene classification. In a similar way, semantic cluster analysis could be used for studding of other enzyme families, tissues and systems.
- MeSH
- gastrointestinální trakt metabolismus MeSH
- lidé MeSH
- myši MeSH
- sémantika * MeSH
- shluková analýza MeSH
- ubikvitin genetika metabolismus MeSH
- ubikvitinligasy * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Microwave ablation (MWA) is a clinically established modality for treatment of lung tumors. A challenge with existing application of MWA, however, is local tumor progression, potentially due to failure to establish an adequate treatment margin. This study presents a robust simulation-based treatment planning methodology to assist operators in comparatively assessing thermal profiles and likelihood of achieving a specified minimum margin as a function of candidate applied energy parameters. METHODS: We employed a biophysical simulation-based probabilistic treatment planning methodology to evaluate the likelihood of achieving a specified minimum margin for candidate treatment parameters (i.e., applied power and ablation duration for a given applicator position within a tumor). A set of simulations with varying tissue properties was evaluated for each considered combination of power and ablation duration, and for four different scenarios of contrast in tissue biophysical properties between tumor and normal lung. A treatment planning graph was then assembled, where distributions of achieved minimum ablation zone margins and collateral damage volumes can be assessed for candidate applied power and treatment duration combinations. For each chosen power and time combination, the operator can also visualize the histogram of ablation zone boundaries overlaid on the tumor and target volumes. We assembled treatment planning graphs for generic 1, 2, and 2.5 cm diameter spherically shaped tumors and also illustrated the impact of tissue heterogeneity on delivered treatment plans and resulting ablation histograms. Finally, we illustrated the treatment planning methodology on two example patient-specific cases of tumors with irregular shapes. RESULTS: The assembled treatment planning graphs indicate that 30 W, 6 min ablations achieve a 5-mm minimum margin across all simulated cases for 1-cm diameter spherical tumors, and 70 W, 10 min ablations achieve a 3-mm minimum margin across 90% of simulations for a 2.5-cm diameter spherical tumor. Different scenarios of tissue heterogeneity between tumor and lung tissue revealed 2 min overall difference in ablation duration, in order to reliably achieve a 4-mm minimum margin or larger each time for 2-cm diameter spherical tumor. CONCLUSIONS: An approach for simulation-based treatment planning for microwave ablation of lung tumors is illustrated to account for the impact of specific geometry of the treatment site, tissue property uncertainty, and heterogeneity between the tumor and normal lung.
OBJECTIVE: The accuracy of phase-contrast magnetic resonance imaging (PC-MRI) measurement is investigated using a computational fluid dynamics (CFD) model with the objective to determine the magnitude of the flow underestimation due to turbulence behind a narrowed valve in a phantom experiment. MATERIALS AND METHODS: An acrylic stationary flow phantom is used with three insertable plates mimicking aortic valvular stenoses of varying degrees. Positive and negative horizontal fluxes are measured at equidistant slices using standard PC-MRI sequences by 1.5T and 3T systems. The CFD model is based on the 3D lattice Boltzmann method (LBM). The experimental and simulated data are compared using the Bland-Altman-derived limits of agreement. Based on the LBM results, the turbulence is quantified and confronted with the level of flow underestimation. RESULTS: LBM gives comparable results to PC-MRI for valves up to moderate stenosis on both field strengths. The flow magnitude through a severely stenotic valve was underestimated due to signal void in the regions of turbulent flow behind the valve, consistently with the level of quantified turbulence intensity. DISCUSSION: Flow measured by PC-MRI is affected by noise and turbulence. LBM can simulate turbulent flow efficiently and accurately, it has therefore the potential to improve clinical interpretation of PC-MRI.
- MeSH
- aortální chlopeň * MeSH
- aortální stenóza * MeSH
- fantomy radiodiagnostické MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- rychlost toku krve MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an attractive alternative to bariatric surgery for obese diabetic patients. This article aims to study dynamical aspects of the glycaemic profile that may influence DJBL effects. METHODS: Thirty patients underwent DJBL implantation and were followed for 10 months. Continuous glucose monitoring (CGM) was performed before implantation and at month 10. Dynamical variables from CGM were measured: coefficient of variation of glycaemia, mean amplitude of glycaemic excursions (MAGE), detrended fluctuation analysis (DFA), % of time with glycaemia under 6.1 mmol/L (TU6.1), area over 7.8 mmol/L (AO7.8) and time in range. We analysed the correlation between changes in both anthropometric (body mass index, BMI and waist circumference) and metabolic (fasting blood glucose, FBG and HbA1c) variables and dynamical CGM-derived metrics and searched for variables in the basal CGM that could predict successful outcomes. RESULTS: There was a poor correlation between anthropometric and metabolic outcomes. There was a strong correlation between anthropometric changes and changes in glycaemic tonic control (∆BMI-∆TU6.1: rho = - 0.67, P < .01) and between metabolic outcomes and glycaemic phasic control (∆FBG-∆AO7.8: r = .60, P < .01). Basal AO7.8 was a powerful predictor of successful metabolic outcome (0.85 in patients with AO7.8 above the median vs 0.31 in patients with AO7.8 below the median: Chi-squared = 5.67, P = .02). CONCLUSIONS: In our population, anthropometric outcomes of DJBL correlate with improvement in tonic control of glycaemia, while metabolic outcomes correlate preferentially with improvement in phasic control. Assessment of basal phasic control may help in candidate profiling for DJBL implantation.
- MeSH
- biologické markery analýza MeSH
- diabetes mellitus 2. typu komplikace chirurgie MeSH
- dospělí MeSH
- duodenum chirurgie MeSH
- glykovaný hemoglobin analýza MeSH
- hmotnostní úbytek MeSH
- jejunum chirurgie MeSH
- krevní glukóza analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom etiologie prevence a kontrola MeSH
- morbidní obezita patofyziologie chirurgie MeSH
- následné studie MeSH
- prognóza MeSH
- senioři MeSH
- žaludeční bypass metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Although motor speech disorders represent an early and prominent clinical feature of multiple system atrophy (MSA), the potential usefulness of speech assessment as a diagnostic tool has not yet been explored. This cross-sectional study aimed to provide a comprehensive, objective description of motor speech function in the parkinsonian (MSA-P) and cerebellar (MSA-C) variants of MSA. Speech samples were acquired from 80 participants including 18 MSA-P, 22 MSA-C, 20 Parkinson's disease (PD), and 20 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on quantitative acoustic analysis of 14 speech dimensions. A mixed type of dysarthria involving hypokinetic, ataxic and spastic components was found in the majority of MSA patients independent of phenotype. MSA-P showed significantly greater speech impairment than PD, and predominantly exhibited harsh voice, imprecise consonants, articulatory decay, monopitch, excess pitch fluctuation and pitch breaks. MSA-C was dominated by prolonged phonemes, audible inspirations and voice stoppages. Inappropriate silences, irregular motion rates and overall slowness of speech were present in both MSA phenotypes. Speech features allowed discrimination between MSA-P and PD as well as between both MSA phenotypes with an area under curve up to 0.86. Hypokinetic, ataxic and spastic dysarthria components in MSA were correlated to the clinical evaluation of rigidity, cerebellar and bulbar/pseudobulbar manifestations, respectively. Distinctive speech alterations reflect underlying pathophysiology in MSA. Objective speech assessment may provide an inexpensive and widely applicable screening instrument for differentiation of MSA and PD from controls and among subtypes of MSA.
- MeSH
- akustika řeči MeSH
- dysartrie diagnóza etiologie patofyziologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- multisystémová atrofie komplikace patofyziologie MeSH
- nemoci mozečku komplikace patofyziologie MeSH
- parkinsonské poruchy komplikace patofyziologie MeSH
- průřezové studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Pallidal deep-brain stimulation of the internal globus pallidus (GPi-DBS) is an effective treatment for dystonia. However, GPi-DBS may cause important stimulation-induced side effects such as hypokinetic dysarthria, which is particularly manifested by articulation rate abnormalities. However, little data regarding the effect of the location of the electrode and stimulation parameters for pallidal stimulation on articulation rate in dystonia is available. Speech data were acquired from 18 dystonic patients with GPi-DBS and 18 matched healthy controls. Each of dystonic patients was tested twice within 1 day in both the GPi-DBS ON and GPi-DBS OFF stimulation conditions. Compared to healthy controls, the decreased diadochokinetic rate and slower articulation rate in dystonic patients were observed in both stimulation conditions. No significant differences in speech rate measures between stimulation conditions were detected with no relation to contact localization and stimulation intensity. Our findings do not support the use articulation rate as a surrogate marker of stimulation-induced changes to the speech apparatus in dystonia.
- MeSH
- dospělí MeSH
- dysartrie etiologie MeSH
- dystonické poruchy terapie MeSH
- globus pallidus * MeSH
- hluboká mozková stimulace škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
