A test-statistic typically employed in the gene set enrichment analysis (GSEA) prevents this method from being genuinely multivariate. In particular, this statistic is insensitive to changes in the correlation structure of the gene sets of interest. The present paper considers the utility of an alternative test-statistic in designing the confirmatory component of the GSEA. This statistic is based on a pertinent distance between joint distributions of expression levels of genes included in the set of interest. The null distribution of the proposed test-statistic, known as the multivariate N-statistic, is obtained by permuting group labels. Our simulation studies and analysis of biological data confirm the conjecture that the N-statistic is a much better choice for multivariate significance testing within the framework of the GSEA. We also discuss some other aspects of the GSEA paradigm and suggest new avenues for future research.

• MeSH
• fenotyp MeSH
• modely genetické MeSH
• multivariační analýza MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů statistika a číselné údaje   MeSH
• stanovení celkové genové exprese statistika a číselné údaje   MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• analýza rozptylu metody   MeSH
• časové faktory MeSH
• Publikační typ
• časopisecké články MeSH

SUMMARY: The package MorphoTools2 is intended for multivariate analyses of morphological data. Commonly used tools are missing or scattered across several R packages. The new package, in order to make the workflow convenient and fast, wraps available statistical and graphical tools and provides a comprehensive framework for checking and manipulating input data, core statistical analyses and a wide palette of functions designed to visualize results. AVAILABILITY AND IMPLEMENTATION: Stable version is available from CRAN: https://cran.r-project.org/package=MorphoTools2. The development version is available from the following GitHub repository: https://github.com/MarekSlenker/MorphoTools2. The software is distributed under the GNU General Public Licence (v.3). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

• MeSH
• multivariační analýza MeSH
• průběh práce MeSH
• software * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The pharmaceutical industry has to tackle the explosion of high amounts of poorly soluble APIs. This phenomenon leads to numerous sophisticated solutions. These include the use of multifactorial data analysis identifying correlations between the components and dosage form properties, laboratory and production process parameters with respect to the API liberation Example of such API is bicalutamide. Improved liberation is achieved by particle size reduction. Laboratory batches, with different PSD of API, were filled into gelatinous capsules and consequently granulated for tablet compression. Comparative dissolution profiles with Casodex 150 mg (Astra Zeneca) were performed. The component analysis was used for the statistical evaluation of f1 and f2 factors and D(v,0.9) and D[4,3] parameters of PSD to identify optimal PSD values. Suitable PSD limits for API were statistically confirmed in laboratory and in commercial scale with respect to optimized tablet properties. The tablets were bioequivalent with originator (n = 20; 90% CI for ln AUC0-120: 99.8-111.9%; 90% CI for ln cmax: 101.1-112.9%). In conclusion, the micronisation of the API is still an efficient and inexpensive method improving the bioavailability, although there are more complicated and expensive methods available. Statistical multifactorial methods improved the safety and reproducibility of production.

• Klíčová slova
• Bicalutamide, bioequivalence, dissolution, multivariate statistics, particle size,
• MeSH
• anilidy chemická syntéza   metabolismus   MeSH
• biologická dostupnost MeSH
• chemie farmaceutická metody   MeSH
• multivariační analýza MeSH
• nitrily chemická syntéza   metabolismus   MeSH
• tablety MeSH
• terapeutická ekvivalence MeSH
• tosylové sloučeniny chemická syntéza   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anilidy MeSH
• bicalutamide MeSH Prohlížeč
• nitrily MeSH
• tablety MeSH
• tosylové sloučeniny MeSH

Automated head-space solid-phase microextraction (HS-SPME)-based sampling procedure, coupled to gas chromatography-time-of-flight mass spectrometry (GC-TOFMS), was developed and employed for obtaining of fingerprints (GC profiles) of beer volatiles. In total, 265 speciality beer samples were collected over a 1-year period with the aim to distinguish, based on analytical (profiling) data, (i) the beers labelled as Rochefort 8; (ii) a group consisting of Rochefort 6, 8, 10 beers; and (iii) Trappist beers. For the chemometric evaluation of the data, partial least squares discriminant analysis (PLS-DA), linear discriminant analysis (LDA), and artificial neural networks with multilayer perceptrons (ANN-MLP) were tested. The best prediction ability was obtained for the model that distinguished a group of Rochefort 6, 8, 10 beers from the rest of beers. In this case, all chemometric tools employed provided 100% correct classification. Slightly worse prediction abilities were achieved for the models "Trappist vs. non-Trappist beers" with the values of 93.9% (PLS-DA), 91.9% (LDA) and 97.0% (ANN-MLP) and "Rochefort 8 vs. the rest" with the values of 87.9% (PLS-DA) and 84.8% (LDA) and 93.9% (ANN-MLP). In addition to chromatographic profiling, also the potential of direct coupling of SPME (extraction/pre-concentration device) with high-resolution TOFMS employing a direct analysis in real time (DART) ion source has been demonstrated as a challenging profiling approach.

• MeSH
• multivariační analýza MeSH
• pivo analýza   MeSH
• řízení kvality MeSH
• těkavé organické sloučeniny analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• těkavé organické sloučeniny MeSH

INTRODUCTION: It is often questioned whether to perform replantation or revision amputation for amputation injuries in elderly patients and smokers. According to the current indication criteria, neither old age nor smoking in the absence of other risk factors are considered to be risk factors for replantation failure. However, many microsurgeons still may make the decision not to perform digital replantation based solely on these factors. MATERIAL AND METHODS: In order to evaluate the influence of both factors, we provided univariate and multivariate analyses of patients who underwent replantation at our centre during a 10-year period. We divided patients in two groups according to age (< and ≥ 60 years) and smoking status. RESULTS: In the univariate analysis, there were no differences in immediate results between the two age groups. In the multivariate analysis, no statistical difference was found in neither long-term nor short-term results between the two age groups and between smokers and non-smokers. CONCLUSION: Smoking and age should not be considered the only risk factors when deciding whether to perform digital replantation.

• MeSH
• amputace MeSH
• kouření tabáku * MeSH
• kouření * škodlivé účinky   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• replantace MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

CONTEXT: Mucoadhesive oral films, with their prolonged residence time at the site of application, offer a promising approach for protection of the oral lesion surface. The addition of sodium hyaluronate of different molecular weights as a second mucoadhesive polymer into the film matrix could positively influence the physico-mechanical and mucoadhesive properties of films. OBJECTIVE: The aim of this study was to investigate the formulation of a monolayered film matrix containing varying amounts of sodium hyaluronate and to test the properties of such matrices by applying different characterization methods. MATERIALS AND METHODS: Film matrix was composed of two mucoadhesive polymers, carmellose sodium and sodium hyaluronate, plasticized with glycerol. Resulting films were characterized with regard to their viscosity and physico-mechanical properties. RESULTS AND DISCUSSION: Multivariate data analysis was employed to evaluate the influence of varying amounts of mucoadhesive polymers on the main mucoadhesive oral films' properties. The lower content of sodium hyaluronate caused improvements in mechanical properties and residence time on the artificial oral mucosa, both of which are the main characteristics that determine the quality of the final product. CONCLUSIONS: The best results were obtained by samples containing carmellose sodium with a small amount of sodium hyaluronate (about 0.5% in casting dispersion).

• Klíčová slova
• Carmellose sodium, mucoadhesive oral films, multivariate data analysis, physico-mechanical properties, sodium hyaluronate, solvent casting method,
• MeSH
• adheziva chemie   metabolismus   MeSH
• adhezivita MeSH
• glycerol chemie   metabolismus   MeSH
• kyselina hyaluronová chemie   metabolismus   MeSH
• lidé MeSH
• multivariační analýza MeSH
• orální absorpce MeSH
• pevnost v tahu MeSH
• polymery MeSH
• sodná sůl karboxymethylcelulosy chemie   metabolismus   MeSH
• systémy cílené aplikace léků metody   MeSH
• ústní sliznice metabolismus   MeSH
• uvolňování léčiv MeSH
• viskozita MeSH
• zvláčňovadla chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adheziva MeSH
• glycerol MeSH
• kyselina hyaluronová MeSH
• polymery MeSH
• sodná sůl karboxymethylcelulosy MeSH
• zvláčňovadla MeSH

OBJECTIVES: A growing body of evidence highlights the persistent activation of the innate immune system and type I interferon (IFN) signature in the pathogenesis of rheumatoid arthritis (RA) and its association with disease activity. Since the recent study revealed heterogeneity in the IFN signature in RA, we investigated for the first time the heterogeneity in innate signature in RA. METHODS: The innate gene expression signature (10 TLRs, 7 IL1/IL1R family members, and CXCL8/IL8) was assessed in peripheral blood mononuclear cells from RA patients (n=67), both with active (DAS28≥3.2, n=32) and inactive disease (DAS28<3.2, n=35), and in healthy control subjects (n=55). RESULTS: Of the 13 deregulated innate genes (TLR2, TLR3, TLR4, TLR5, TLR8, TLR10, IL1B, IL1RN, IL18, IL18R1, IL1RAP, and SIGIRR/IL1R8) associated with RA, TLR10 and IL1RAP are being reported for the first time. Multivariate analysis based on utilising patient similarity networks revealed the existence of four patient's subsets (clusters) based on different TLR8 and IL1RN expression profiles, two in active and two in inactive RA. Moreover, neural network analysis identified two main gene sets describing active RA within an activity-related innate signature (TLR1, TLR2, TLR3, TLR7, TLR8, CXCL8/IL8, IL1RN, IL18R1). When comparing active and inactive RA, upregulated TLR2, TLR4, TLR6, and TLR8 and downregulated TLR10 (P<0.04) expression was associated with the disease activity. CONCLUSIONS: Our study on the comprehensive innate gene profiling together with multivariate analysis revealed a certain heterogeneity in innate signature within RA patients. Whether the heterogeneity of RA elucidated from diversity in innate signatures may impact the disease course and treatment response deserves future investigations.

• MeSH
• interferon typ I * imunologie   MeSH
• leukocyty mononukleární MeSH
• lidé MeSH
• multivariační analýza MeSH
• revmatoidní artritida * genetika   imunologie   metabolismus   MeSH
• toll-like receptory * genetika   imunologie   metabolismus   MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interferon typ I * MeSH
• toll-like receptory * MeSH

Differences among lipidomic profiles of healthy volunteers, obese people and three groups of cardiovascular disease (CVD) patients are investigated with the goal to differentiate individual groups based on the multivariate data analysis (MDA) of lipidomic data from plasma, erythrocytes and lipoprotein fractions of more than 50 subjects. Hydrophilic interaction liquid chromatography on ultrahigh-performance liquid chromatography (HILIC-UHPLC) column coupled with electrospray ionization mass spectrometry (ESI-MS) is used for the quantitation of four classes of polar lipids (phosphatidylethanolamines, phosphatidylcholines, sphingomyelins and lysophosphatidylcholines), normal-phase UHPLC-atmospheric pressure chemical ionization MS (NP-UHPLC/APCI-MS) is applied for the quantitation of five classes of nonpolar lipids (cholesteryl esters, triacylglycerols, sterols, 1,3-diacylglycerols and 1,2-diacylglycerols) and the potential of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is tested for the fast screening of all lipids without a chromatographic separation. Obtained results are processed by unsupervised (principal component analysis) and supervised (orthogonal partial least squares) MDA approaches to highlight the largest differences among individual groups and to identify lipid molecules with the highest impact on the group differentiation.

• Klíčová slova
• Cardiovascular diseases, Lipidomics, Lipids, Lipoprotein fractions, Multivariate data analysis, UHPLC/MS,
• MeSH
• dospělí MeSH
• kardiovaskulární nemoci krev   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   chemie   klasifikace   MeSH
• lipoproteiny krev   chemie   klasifikace   MeSH
• metoda nejmenších čtverců MeSH
• multivariační analýza MeSH
• obezita MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   MeSH
• výpočetní biologie MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lipidy MeSH
• lipoproteiny MeSH

Multivariate tail coefficients are an important tool when investigating dependencies between extreme events for different components of a random vector. Although bivariate tail coefficients are well-studied, this is, to a lesser extent, the case for multivariate tail coefficients. This paper contributes to this research area by (i) providing a thorough study of properties of existing multivariate tail coefficients in the light of a set of desirable properties; (ii) proposing some new multivariate tail measurements; (iii) dealing with estimation of the discussed coefficients and establishing asymptotic consistency; and, (iv) studying the behavior of tail measurements with increasing dimension of the random vector. A set of illustrative examples is given, and practical use of the tail measurements is demonstrated in a data analysis with a focus on dependencies between stocks that are part of the EURO STOXX 50 market index.

• Klíčová slova
• archimedean copula, consistency, estimation, extreme-value copula, multivariate analysis, tail dependency,
• Publikační typ
• časopisecké články MeSH