BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. METHODOLOGY: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. RESULTS: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. CONCLUSIONS: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.

• Klíčová slova
• Bipolar disorder, Functional connectivity, Major depressive disorder, Multivariate pattern analysis, Resting state,
• MeSH
• bipolární porucha * patofyziologie   diagnostické zobrazování   MeSH
• depresivní porucha unipolární * patofyziologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• konektom metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mapování mozku metody   MeSH
• mozek patofyziologie   diagnostické zobrazování   MeSH
• multivariační analýza MeSH
• nervová síť diagnostické zobrazování   patofyziologie   MeSH
• nervové dráhy patofyziologie   diagnostické zobrazování   MeSH
• průřezové studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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

Based on X-ray measurements of the head of 187 adult men with cleft lip and/or palate, the authors compared, using the multivariate method, deviations in the craniofacial morphology between different types of clefts in the following seven groups: cleft lip alone, complete and incomplete isolated cleft palate, cleft of the soft palate only, unilateral complete and incomplete and bilateral complete cleft lip and palate. The X-ray films were evaluated according to Jarabak's method. A special position is held by cleft lip alone with minimal skeletal and dental effects. Isolated clefts of the palate display in skeletal analysis the same basic deviations as clefts of the lip and palate; in dental analysis the deviations are smaller (in particular there is no retroinclination of the upper incisors). The effect is much milder in isolated clefts of the soft palate. In cleft lip and palate there is, in contrast to isolated clefts of the palate, retrusion of the mandible; in bilateral clefts, in conjunction with persisting protrusion of the premaxilla the depth of the upper jaw is not reduced, the facial skeleton is not flattened and the sagittal intermaxillary relations are not impaired. In the basic developmental pattern there is, however, no difference between different types of clefts which affect the palate (probably in conjunction with postoperative sequelae). The variable which differentiates most types of clefts in the skeletal analysis is the depth of the maxilla; in the dental analysis it is the interincisal angle, which is, however, influenced by treatment. Jarabak's analysis can record the basic deviations of the configuration of the bony face with a cleft but does not detect some important characteristics such as the vertical proportionality of the face and the posteroposition of the maxilla. The assessment of the soft profile is, however, inadequate and unsuitable.

• MeSH
• analýza rozptylu MeSH
• dospělí MeSH
• kefalometrie * MeSH
• lidé MeSH
• mandibula patologie   MeSH
• maxila patologie   MeSH
• mezičelistní vztahy MeSH
• multivariační analýza MeSH
• obličej * MeSH
• obličejové kosti patologie   MeSH
• patro měkké abnormality   patologie   MeSH
• ret patologie   MeSH
• řezáky patologie   MeSH
• rozštěp patra klasifikace   patologie   chirurgie   MeSH
• rozštěp rtu klasifikace   patologie   chirurgie   MeSH
• zubní okluze MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Modulations of 11 prospective biochemical markers of impacts of aquatic pollutants in liver tissue of chub (Leuciscus cephalus), caught at several sampling sites of a river with various pollution types and rates, were matched against analytical data of concentrations of organochlorine compounds, polycyclic aromatic hydrocarbons (PAHs), and heavy metals. Multivariate principal component analysis (PCA) of the field data showed general patterns of biochemical responses to different types of pollutants and relationships among the biomarkers. Cytochrome P4501A-dependent 7-ethoxyresorufin O-deethylase (EROD) activity, inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin and structurally related planar compounds, was strongly enhanced in the more contaminated areas. Compared with polychlorinated aromatic hydrocarbons, PAHs did not contribute so significantly to EROD induction. Testosterone 6 beta- and 16 alpha-hydroxylase activities, as an expression of the cytochrome P4503A27, were slightly increased at several sites but were significantly decreased in samples from some heavily polluted areas. Recently, these activities have been suggested as potential biomarkers of exposure to contaminants that do not induce cytochrome P4501A. In this study, their inhibition or induction was not associated with a specific class of monitored contaminants, and selectivities of these modulations are still to be investigated. Similar modulations of the prospective biochemical indicators of oxidative stress, including microsomal glutathione S-transferase activity, cytosolic glutathione S-transferase with ethacrynic acid, and glutathione reductase, were demonstrated by PCA. The pattern of the modulations of the microsomal nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lipid peroxidation in vitro differed from the responses of the rest of oxidative stress parameters at some sampling sites. Further biochemical markers of oxidative stress under study, including in vivo lipid peroxidation, in vitro production of reactive oxygen species, and the concentration of metallothioneins did not correlate well with the concentrations of the contaminants. Principal component analysis demonstrated that the EROD activity, glutathione-dependent enzymes, and Fe(II)-enhanced lipid peroxidation formed a suitable battery of biomarkers of exposure.

• MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• chlorované uhlovodíky toxicita   MeSH
• Cyprinidae metabolismus   MeSH
• cytochrom P-450 CYP1A1 biosyntéza   metabolismus   MeSH
• enzymová indukce MeSH
• játra účinky léků   embryologie   MeSH
• multivariační analýza MeSH
• peroxidace lipidů účinky léků   MeSH
• polycyklické sloučeniny toxicita   MeSH
• steroid-16-alfa-hydroxylasa MeSH
• těžké kovy toxicita   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• chlorované uhlovodíky MeSH
• cytochrom P-450 CYP1A1 MeSH
• polycyklické sloučeniny MeSH
• steroid-16-alfa-hydroxylasa MeSH
• těžké kovy MeSH

Natural resistance to Mycobacterium bovis bacillus Calmette-Guérin (BCG) is determined by the Bcg gene (Nramp1), which is exclusively expressed by mature macrophages. The Nramp1 gene is a dominant autosomal gene that has two allelic forms; r confers resistance and s confers susceptibility to infection with intracellular pathogen. Although the wide range of pleiotropic immunological effects of the Nramp1 gene has been described, the exact mechanism of its action remains elusive. In this study we searched for differentially expressed proteins that might provide clues in the studies on Nramp1 gene function. We performed two-dimensional gel electrophoresis of cellular proteins prepared from a B10R macrophage line derived from mice carrying the r allele of the Nramp1 gene, B10S macrophages carrying the s allele, and B10R-Rb macrophages transfected with Nramp1-ribozyme. The classification of protein patterns and selection of distinct proteins characteristic of r or s allele-carrying macrophages was performed using the principal component analysis. We found differential expression of four proteins with the following isoelectric point/molecular weight (pI/Mr) in B10R macrophages compared to B10S and B10R-Rb macrophages: 6.6/25, 7.0/22, 9.1/31.5, and 5.3/8.5. The protein 7.0/22 has been identified as Mn-superoxide dismutase and the best candidate for protein p6.6/25 seems to be Bcl-2 according to the immunoblot analysis. When the splenic macrophages carrying the r or s allele were analyzed, the changes in relative abundance for proteins 6.6/25 and p7.0/22 were satisfactorily reproduced. Overall, the two identified proteins are important in the regulation of intracellular redox balance and the regulation of apoptosis in macrophages, respectively. Our findings may suggest their possible biological role in the innate immunity against intracellular pathogens.

• MeSH
• 2D gelová elektroforéza * MeSH
• buněčné linie MeSH
• makrofágy metabolismus   MeSH
• membránové proteiny genetika   MeSH
• multivariační analýza MeSH
• Mycobacterium bovis imunologie   MeSH
• myši MeSH
• přirozená imunita MeSH
• proteiny přenášející kationty * MeSH
• transportní proteiny genetika   MeSH
• tuberkulóza MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• membránové proteiny MeSH
• natural resistance-associated macrophage protein 1 MeSH Prohlížeč
• proteiny přenášející kationty * MeSH
• transportní proteiny MeSH

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.

• Klíčová slova
• MRI, bipolar disorder, body mass index, obesity, principal component analysis, psychiatry,
• MeSH
• analýza hlavních komponent * MeSH
• bipolární porucha * diagnostické zobrazování   farmakoterapie   patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• mozková kůra diagnostické zobrazování   patologie   MeSH
• obezita * diagnostické zobrazování   MeSH
• schizofrenie diagnostické zobrazování   patologie   farmakoterapie   patofyziologie   MeSH
• shluková analýza MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We examined how penalized linear discriminant analysis with resampling, which is a supervised, multivariate, whole-brain reduction technique, can help schizophrenia diagnostics and research. In an experiment with magnetic resonance brain images of 52 first-episode schizophrenia patients and 52 healthy controls, this method allowed us to select brain areas relevant to schizophrenia, such as the left prefrontal cortex, the anterior cingulum, the right anterior insula, the thalamus, and the hippocampus. Nevertheless, the classification performance based on such reduced data was not significantly better than the classification of data reduced by mass univariate selection using a t-test or unsupervised multivariate reduction using principal component analysis. Moreover, we found no important influence of the type of imaging features, namely local deformations or gray matter volumes, and the classification method, specifically linear discriminant analysis or linear support vector machines, on the classification results. However, we ascertained significant effect of a cross-validation setting on classification performance as classification results were overestimated even though the resampling was performed during the selection of brain imaging features. Therefore, it is critically important to perform cross-validation in all steps of the analysis (not only during classification) in case there is no external validation set to avoid optimistically biasing the results of classification studies.

• Klíčová slova
• classification, computational neuroanatomy, cross-validation, magnetic resonance imaging, pattern recognition, penalized linear discriminant analysis, schizophrenia, support vector machines,
• Publikační typ
• časopisecké články MeSH

This study attempts to develop a general aetiological concept of essential hypertension by multidimensional investigation of its various risk factors in childhood and adolescence. The investigation is based on married couples and their children (609 parents and their 639 children, a total of 1248 persons), all of them chosen under special aspects. Familial and environmental characteristics of children and young people with hypertension are compared with those of normotensive volunteers of the same age. The multi-dimensionally interacting factors found to be associated with hypertension in children are: hypertension, diabetes and early infarction in relatives of the first or second degree as well as overweight at birth, obesity, nutritional patterns in the earliest and later stages of life, social environment and physical activity of the children and adolescents. The familial factors most likely lead to a predisposition to hypertension while environmental factors may subsequently contribute to its manifestation.

• MeSH
• dítě MeSH
• dospělí MeSH
• hypertenze etiologie   genetika   MeSH
• infarkt myokardu etiologie   MeSH
• kojenec MeSH
• koronární nemoc etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• obezita komplikace   MeSH
• předškolní dítě MeSH
• riziko MeSH
• senioři MeSH
• tělesná námaha MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The Carpathian Basin represents the cradle of human agricultural development during the Neolithic period, when large parts were transformed into 'cultural landscapes' by first farmers from the Balkans. It is assumed that an Early Neolithic subsistence economy established along the hydrologic systems and on Chernozem soil patches, which developed from loess deposits. However, recent results from soil chemistry and geoarchaeological analyses raised the hypothesis that extensive Chernozem coverage developed from increased land-use activity and that Early Neolithic 'cultural' groups were not restricted to loess-covered surfaces but rather preferred hydromorphic soils that formed in the floodplains. This article performs multivariable statistics from large datasets of Neolithic sites in Hungary and allows tracing Early to Late Neolithic site preferences from digital environmental data. Quantitative analyses reveal a strong preference for hydromorphic soils, a significant avoidance of loess-covered areas, and no preference for Chernozem soils throughout the Early Neolithic followed by a strong transformation of site preferences during the Late Neolithic period. These results align with socio-cultural developments, large-scale mobility patterns, and land-use and surface transformation, which shaped the Carpathian Basin and paved the way for the agricultural revolution across Europe.

• MeSH
• algoritmy MeSH
• archeologie MeSH
• časové faktory MeSH
• geologické jevy MeSH
• hydrologie MeSH
• multivariační analýza MeSH
• půda MeSH
• teoretické modely * MeSH
• zemědělství * MeSH
• zeměpis MeSH
• životní prostředí * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Balkánský poloostrov MeSH
• Názvy látek
• půda MeSH

Industrial sites affected by anthropogenic contamination, both past and present-day, commonly have intricate pollutant patterns, and source discrimination can be thus highly challenging. To this goal, this paper presents a novel approach combining multivariate statistics and environmental forensic techniques. The efficiency of this methodology was exemplified in a severely polluted estuarine area (Avilés, Spain), where factor analysis and clustering were performed to identify sub-areas with distinct geochemical behaviour. Once six clusters were defined and a pollution index applied, forensic tools revealed that the As speciation, Pb isotopes, and PAHs molecular ratios were useful to categorise the cluster groups on the basis of distinct pollution sources: Zn-smelting, coaly particles and waste disposal. Overall, this methodology offers valuable insight into pollution sources identification, which can be extended to comparable scenarios of complexly polluted environmental compartments. The information gathered using this approach is also important for the planning of risk assessment procedures and potential remediation strategies.

• Klíčová slova
• Arsenic speciation, Lead isotopes, Pollution sources, Polycyclic aromatic hydrocarbons, Toxic elements,
• MeSH
• hodnocení rizik MeSH
• látky znečišťující půdu * analýza   MeSH
• monitorování životního prostředí MeSH
• polycyklické aromatické uhlovodíky * analýza   MeSH
• průmyslový odpad analýza   MeSH
• těžké kovy * analýza   MeSH
• znečištění životního prostředí MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• látky znečišťující půdu * MeSH
• polycyklické aromatické uhlovodíky * MeSH
• průmyslový odpad MeSH
• těžké kovy * MeSH