Learning Spatiotemporal Brain Dynamics in Adolescents via Multimodal MEG and fMRI Data Fusion Using Joint Tensor/Matrix Decomposition.

OBJECTIVE: Brain function is understood to be regulated by complex spatiotemporal dynamics, and can be characterized by a combination of observed brain response patterns in time and space. Magnetoencephalography (MEG), with its high temporal resolution, and functional magnetic resonance imaging (fMRI), with its high spatial resolution, are complementary imaging techniques with great potential to reveal information about spatiotemporal brain dynamics. Hence, the complementary nature of these imaging techniques holds much promise to study brain function in time and space, especially when the two data types are allowed to fully interact. METHODS: We employed coupled tensor/matrix factorization (CMTF) to extract joint latent components in the form of unique spatiotemporal brain patterns that can be used to study brain development and function on a millisecond scale. RESULTS: Using the CMTF model, we extracted distinct brain patterns that revealed fine-grained spatiotemporal brain dynamics and typical sensory processing pathways informative of high-level cognitive functions in healthy adolescents. The components extracted from multimodal tensor fusion possessed better discriminative ability between high- and low-performance subjects than single-modality data-driven models. CONCLUSION: Multimodal tensor fusion successfully identified spatiotemporal brain dynamics of brain function and produced unique components with high discriminatory power. SIGNIFICANCE: The CMTF model is a promising tool for high-order, multimodal data fusion that exploits the functional resolution of MEG and fMRI, and provides a comprehensive picture of the developing brain in time and space.

Multi-Subject Analysis for Brain Developmental Patterns Discovery via Tensor Decomposition of MEG Data.

Identification of informative signatures from electrophysiological signals is important for understanding brain developmental patterns, where techniques such as magnetoencephalography (MEG) are particularly useful. However, less attention has been given to fully utilizing the multidimensional nature of MEG data for extracting components that describe these patterns. Tensor factorizations of MEG yield components that encapsulate the data's multidimensional nature, providing parsimonious models identifying latent brain patterns for meaningful summarization of neural processes. To address the need for meaningful MEG signatures for studies of pediatric cohorts, we propose a tensor-based approach for extracting developmental signatures of multi-subject MEG data. We employ the canonical polyadic (CP) decomposition for estimating latent spatiotemporal components of the data, and use these components for group level statistical inference. Using CP decomposition along with hierarchical clustering, we were able to extract typical early and late latency event-related field (ERF) components that were discriminative of high and low performance groups ([Formula: see text]) and significantly correlated with major cognitive domains such as attention, episodic memory, executive function, and language comprehension. We demonstrate that tensor-based group level statistical inference of MEG can produce signatures descriptive of the multidimensional MEG data. Furthermore, these features can be used to study group differences in brain patterns and cognitive function of healthy children. We provide an effective tool that may be useful for assessing child developmental status and brain function directly from electrophysiological measurements and facilitate the prospective assessment of cognitive processes.

Correction: Belyaeva et al. Tuberculosis and Autoimmunity. Pathophysiology 2022, 29, 298-318.

The authors would like to make the following correction to the published paper [...].

Tuberculosis and Autoimmunity.

Tuberculosis remains a common and dangerous chronic bacterial infection worldwide. It is long-established that pathogenesis of many autoimmune diseases is mainly promoted by inadequate immune responses to bacterial agents, among them Mycobacterium tuberculosis. Tuberculosis is a multifaceted process having many different outcomes and complications. Autoimmunity is one of the processes characteristic of tuberculosis; the presence of autoantibodies was documented by a large amount of evidence. The role of autoantibodies in pathogenesis of tuberculosis is not quite clear and widely disputed. They are regarded as: (1) a result of imbalanced immune response being reactive in nature, (2) a critical part of TB pathogenicity, (3) a beginning of autoimmune disease, (4) a protective mechanism helping to eliminate microbes and infected cells, and (5) playing dual role, pathogenic and protective. There is no single autoimmunity-mechanism development in tuberculosis; different pathways may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages and dendritic cells, environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mycobacterium tuberculosis and host.

Taking the 4D Nature of fMRI Data Into Account Promises Significant Gains in Data Completion.

Functional magnetic resonance imaging (fMRI) is a powerful, noninvasive tool that has significantly contributed to the understanding of the human brain. FMRI data provide a sequence of whole-brain volumes over time and hence are inherently four dimensional (4D). Missing data in fMRI experiments arise from image acquisition limits, susceptibility and motion artifacts or during confounding noise removal. Hence, significant brain regions may be excluded from the data, which can seriously undermine the quality of subsequent analyses due to the significant number of missing voxels. We take advantage of the four dimensional (4D) nature of fMRI data through a tensor representation and introduce an effective algorithm to estimate missing samples in fMRI data. The proposed Riemannian nonlinear spectral conjugate gradient (RSCG) optimization method uses tensor train (TT) decomposition, which enables compact representations and provides efficient linear algebra operations. Exploiting the Riemannian structure boosts algorithm performance significantly, as evidenced by the comparison of RSCG-TT with state-of-the-art stochastic gradient methods, which are developed in the Euclidean space. We thus provide an effective method for estimating missing brain voxels and, more importantly, clearly show that taking the full 4D structure of fMRI data into account provides important gains when compared with three-dimensional (3D) and the most commonly used two-dimensional (2D) representations of fMRI data.

Pharmacogenetics in Primary Headache Disorders.

Primary headache disorders, such as migraine, tension-type headache (TTH), and cluster headache, belong to the most common neurological disorders affecting a high percentage of people worldwide. Headache induces a high burden for the affected individuals on the personal level, with a strong impact on life quality, daily life management, and causes immense costs for the healthcare systems. Although a relatively broad spectrum of different pharmacological classes for the treatment of headache disorders are available, treatment effectiveness is often limited by high variances in therapy responses. Genetic variants can influence the individual treatment success by influencing pharmacokinetics or pharmacodynamics of the therapeutic as investigated in the research field of pharmacogenetics. This review summarizes the current knowledge on important primary headache disorders, including migraine, TTH, and cluster headache. We also summarize current acute and preventive treatment options for the three headache disorders based on drug classes and compounds taking important therapy guidelines into consideration. Importantly, the work summarizes and discusses the role of genetic polymorphisms regarding their impact on metabolism safety and the effect of therapeutics that are used to treat migraine, cluster headache, and TTH exploring drug classes such as nonsteroidal anti-inflammatory drugs, triptans, antidepressants, anticonvulsants, calcium channel blockers, drugs with effect on the renin-angiotensin system, and novel headache therapeutics such as ditans, anti-calcitonin-gene-related peptide antibodies, and gepants. Genetic variants in important phase I-, II-, and III-associated genes such as cytochrome P450 genes, UGT genes, and different transporter genes are scrutinized as well as variants in genes important for pharmacodynamics and several functions outside the pharmacokinetic and pharmacodynamic spectrum. Finally, the article evaluates the potential and limitations of pharmacogenetic approaches for individual therapy adjustments in headache disorders.

Diagnostics, taxonomy, nomenclature and distribution of perennial Sesuvium (Aizoaceae) in Africa.

The taxonomy of perennial Sesuvium species in Africa has been poorly investigated until now. Previously five perennial species of Sesuvium were recognised in Africa (S. congense, S. crithmoides, S. mesembryanthemoides, S. portulacastrum, and S. sesuvioides). Based on the differing number of stamens, S. ayresii is accepted here as being distinct from S. portulacastrum. Field observations in Angola also led the authors to conclude that S. crystallinum and S. mesembryanthemoides are conspecific with S. crithmoides. A new subspecies, Sesuvium portulacastrum subsp. persoonii, is described from West Africa (Cape Verde, Gambia, Guinea-Bissau, Mauritania, Senegal). The molecular phylogeny indicates the position of S. portulacastrum subsp. persoonii within the "American lineage" as a part of the Sesuvium portulacastrum complex which needs further studies. A diagnostic key and taxonomic notes are provided for the six perennial species of Sesuvium found in Africa and recognised by the authors (S. ayresii, S. congense, S. crithmoides, S. portulacastrum subsp. portulacastrum, S. portulacastrum subsp. persoonii, S. verrucosum and the facultatively short-lived S. sesuvioides). The distribution of S. crithmoides, previously considered to be endemic to Angola, is now confirmed for the seashores of Republic of Congo and DR Congo. The American species S. verrucosum is reported for the first time for Africa (the Macaronesian islands: Cape Verde and the Canaries). It is locally naturalised in Gran Canaria, being a potentially invasive species. These findings as well as new records of S. verrucosum from Asia and the Pacific Islands confirm its proneness to transcontinental introduction. Lectotypes of S. brevifolium, S. crithmoides, S. crystallinum and S. mesembryanthemoides are selected. The seed micromorphology and anatomy of the perennial African species is studied. Compared to the seeds of some annual African Sesuvium investigated earlier, those of perennial species are smooth or slightly alveolate. The aril is one-layered and parenchymatous in all species and usually tightly covers the seed. The aril detachments from the seed coat that form a white stripe near the cotyledon area easily distinguish S. verrucosum from other species under study.

Vitamin D, Cathelicidin, Prolactin, Autoantibodies, and Cytokines in Different Forms of Pulmonary Tuberculosis versus Sarcoidosis.

BACKGROUND: Vitamin D insufficiency is associated with autoimmune and chronic inflammatory diseases such as tuberculosis and sarcoidosis. OBJECTIVES: To evaluate the vitamin D-dependent mechanisms of immunity and autoimmunity in different forms of pulmonary tuberculosis and sarcoidosis. METHODS: We measured the serum levels of 25(OH)D and 1,25(OH)2D, individual autoimmune profiles, plasma concentrations of cathelicidin, several hormones, and production of nine cytokines in patients with short- and long-duration tuberculosis and sarcoidosis. RESULTS: The level of 25(OH)D was significantly decreased in all patients. Concentration of 1,25(OH)2D was elevated only in sarcoidosis, prolactin content was augmented only in tuberculosis. We saw no expected increase of cathelicidin levels in tuberculosis and sarcoidosis. The individual mean immune reactivity levels of autoantibodies to 24 antigens were significantly lower in tuberculosis and sarcoidosis patients compared to healthy controls. Pronounced deviations from individual mean immune reactivity levels were found for several autoantigens in all patients. The induced production of interferon gamma-γ, interleukin (IL) 2, 17, and 8 by peripheral blood mononuclear cells was significantly increased in patients of both tuberculosis groups, but spontaneous production of tumor necrosis factor-α, IL-2, and IL-6 was lower in the tuberculosis patients than in healthy controls. We registered marked differences in the groups of tuberculosis patients. CONCLUSIONS: We demonstrated the role of vitamin D deficiency in poor cathelicidin response in  tuberculosis and sarcoidosis. Both diseases are accompanied by significant changes in the autoimmune profile, probably related to the status of vitamin D and cytokine regulation.

ThaleMine: A Warehouse for Arabidopsis Data Integration and Discovery.

ThaleMine (https://apps.araport.org/thalemine/) is a comprehensive data warehouse that integrates a wide array of genomic information of the model plant Arabidopsis thaliana. The data collection currently includes the latest structural and functional annotation from the Araport11 update, the Col-0 genome sequence, RNA-seq and array expression, co-expression, protein interactions, homologs, pathways, publications, alleles, germplasm and phenotypes. The data are collected from a wide variety of public resources. Users can browse gene-specific data through Gene Report pages, identify and create gene lists based on experiments or indexed keywords, and run GO enrichment analysis to investigate the biological significance of selected gene sets. Developed by the Arabidopsis Information Portal project (Araport, https://www.araport.org/), ThaleMine uses the InterMine software framework, which builds well-structured data, and provides powerful data query and analysis functionality. The warehoused data can be accessed by users via graphical interfaces, as well as programmatically via web-services. Here we describe recent developments in ThaleMine including new features and extensions, and discuss future improvements. InterMine has been broadly adopted by the model organism research community including nematode, rat, mouse, zebrafish, budding yeast, the modENCODE project, as well as being used for human data. ThaleMine is the first InterMine developed for a plant model. As additional new plant InterMines are developed by the legume and other plant research communities, the potential of cross-organism integrative data analysis will be further enabled.

Salix transect of Europe: latitudinal patterns in willow diversity from Greece to arctic Norway.

BACKGROUND: Willows (Salix spp.) are ecosystem "foundation species" that are hosts to large numbers of associated insects. Determining their patterns of distribution across Europe is therefore of interest for understanding the spatial distribution of associated fauna. The aim of this study was to record species composition at multiple sites on a long latitudinal gradient (megatransect) across Europe as a baseline for the future detailed analysis of insect fauna at these sites. In this way we used willow stands as comparable mesocosms in which to study floristic and faunistic changes with latitude across Europe. NEW INFORMATION: To determine spatial patterning of  an ecologically important group on a latitudinal gradient across Europe, we sampled willows at the stand level in 42 sites, approximately 100 km apart, from the Aegean (38.8°N) to the Arctic Ocean (70.6°N), but at a similar longitude (21.2 to 26.1°E). The sites were predominantly lowland (elevations 1 to 556 metres amsl, median = 95 m) and wet (associated with rivers, lakes, drainage ditches or wet meadows). The median number of willow taxa (species and hybrids) per stand was four, and varied from one to nine. There is a progressive increase in willow diversity from south to north with the median number of taxa per stand in southern Europe being three, and in northern Europe six. A total of 20 willow species were recorded, along with 12 hybrids. The most widespread willow in the transect was Salix alba L. (occurring in 20 sites out of 42) followed by S. triandra L. (15 sites), S. caprea L., S. phylicifolia L. (14 sites) and S. myrsinifolia Salisb., Salix ×fragilis L. (13 sites). Voucher specimens from this study are deposited in the herbaria of the Natural History Museum (BM) and the Royal Botanic Gardens Kew (K). These samples provide a "snapshot" of willow diversity along a latitudinal gradient and an indication of the geographically changing taxonomic diversity that is presented to willow-feeding herbivores across Europe. It is anticipated that further papers will examine the insect fauna collected from these sites as part of this study.

Porous composite prosthetic pylon for integration with skin and bone.

This article presents results of the further development and testing of the "skin and bone integrated pylon" (SBIP-1) for percutaneous (through skin) connection of the residual bone with an external limb prosthesis. We investigated a composite structure (called the SBIP-2) made of titanium particles and fine wires using mathematical modeling and mechanical testing. Results showed that the strength of the pylon was comparable with that of anatomical bone. In vitro and in vivo animal studies on 30 rats showed that the reinforcement of the composite pylon did not compromise its previously shown capacity for inviting skin and bone cell ingrowth through the device. These findings provide evidence for the safe and reliable long-term percutaneous transfer of vital and therapeutic substances, signals, and necessary forces and moments from a prosthetic device to the body.

Skin and bone integrated prosthetic pylon: a pilot animal study.

Direct skeletal attachment of limb prostheses is a viable alternative to traditional techniques that are based on a socket-residuum interface. Direct skeletal attachment may be a better or even the only method for patients with a very short residuum and high soft-tissue volume. The problem of integrating the prosthetic pylon with residual skin during direct skeletal attachment of a limb prosthesis has not been solved, and the use of a completely porous prosthetic pylon has not been the subject of focused, systematic research. In this in vivo study, we investigated cell (osteocyte, fibroblast, and keratinocyte) adhesion and penetration into the pores of a titanium pylon implanted in Wistar rats. The porous titanium pylon was implanted in the bone of the thigh residua of four rats. Electronic scanning and morphological analysis demonstrated integration of the pylon with the surrounding skin. These findings support the possibility of developing a natural barrier against the infection associated with direct skeletal attachment of limb prostheses.

Serum time course of two brain-specific proteins, alpha(1) brain globulin and neuron-specific enolase, in tick-born encephalitis and Lyme disease.

METHODS: Time courses of the serum concentrations of two brain-specific proteins (BSP), alpha(1) brain globulin (alpha(1)BG, an astroglial marker) and neuron-specific enolase (NSE), were studied in patients with severe tick-born encephalitis (TBE) and Lyme disease (LD; neuroborreliosis). The concentrations were determined on the second day of the acute phase and then on the 7th, 12th, 18th, and 23rd days. Apparent rate constants for the elimination of the BSP from blood (k(e)) were calculated with the non-linear regression. RESULTS: In patients with TBE, the highest serum concentrations of alpha(1)BG and NSE, observed on the second day, were followed by their monotonic decrease to the normal levels reached by the 23rd day. The mean k(e) values for alpha(1)BG and NSE were found to be significantly different (0.086+/-0.003 vs. 0.057+/-0.006 day(-1), respectively; p<0.05). Higher serum levels of both BSP were observed in the more severe clinical cases and in the cases with unfavorable outcomes. Similar profiles were also observed for the serum alpha(1)BG and NSE in LD. CONCLUSIONS: These results suggest that, in the patients examined, the blood-brain barrier was partially impaired; the quantitative parameters of the serum BSP time courses can be indicative of the extents of the neuronal and/or glial lesions.