General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

Artificial intelligence for predicting mortality in hospitalized COVID-19 patients.

Background: The global demographic situation has been significantly impacted by the COVID-19 pandemic. The objective of this study was to develop a model that predicts the risk of COVID-associated mortality using clinical and laboratory data collected within 72 h of hospital admission.

Materials And Methods: A total of 3024 subjects with PCR-confirmed COVID-19 were admitted to Almazov National Research Medical Center between May 2020 and August 2021.

Vitamin D Metabolism Parameters and Cytokine Profile in COVID-19 Patients with Bolus Cholecalciferol Supplementation.

Unlabelled: Recent studies have demonstrated the relationship between vitamin D deficiency, infection severity and mortality from COVID-19. This study aimed to analyze the vitamin D metabolites and cytokine expression levels of COVID-19 patients who were hospitalized with bolus cholecalciferol supplementation.

Materials And Methods: This study represents the next stage of the open-label randomized pilot conducted by the Almazov National Medical Research Centre.

The Low-Waste Grafting Copolymerization Modification of Chitosan Is a Promising Approach to Obtaining Materials for Food Applications.

Chitosan takes second place of the most abundant polysaccharides naturally produced by living organisms. Due to its abundance and unique properties, such as its polycationic nature, ability to form strong elastic porous films, and antibacterial potential, it is widely used in the food industry and biomedicine. However, its low solubility in both water and organic solvents makes its application difficult.

Transcriptome-wide association study of the plasma proteome reveals cis and trans regulatory mechanisms underlying complex traits.

Regulation of transcription and translation are mechanisms through which genetic variants affect complex traits. Expression quantitative trait locus (eQTL) studies have been more successful at identifying cis-eQTL (within 1 Mb of the transcription start site) than trans-eQTL. Here, we tested the cis component of gene expression for association with observed plasma protein levels to identify cis- and trans-acting genes that regulate protein levels.

Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-differential effects via GAUDI.

Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments with shared ancestry in admixed genomes.

VITAMIN D STATUS IN CHILDREN WITH PARALITIC SYNDROMS.

Objective: The aim: Determination of serum 25(OH)D in the children with paralytic syndromes and its distribution depending on age, sex, taking anticonvulsant drugs, nutritional status for a period of one year (autumn-spring) of one center.

Patients And Methods: Materials and methods: There were recruited of 77 children with paralytic syndromes and 73 health children for the same period aged from 1 till 18 years. The study included a scrutiny of medical history and analysis of medical documents, assessment of motor dysfunction by GMFCS, and nutritional status.

Multivariate adaptive shrinkage improves cross-population transcriptome prediction and association studies in underrepresented populations.

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios.

Targeting hormone-resistant breast cancer cells with docetaxel: a look inside the resistance.

The study aims to analyze the effect of long-term incubation of ERα-positive MCF7 breast cancer cells with 4-hydroxytamoxifen (HT) on their sensitivity to tubulin polymerization inhibitor docetaxel. The analysis of cell viability was performed by the MTT method. The expression of signaling proteins was analyzed by immunoblotting and flow cytometry.

Multivariate adaptive shrinkage improves cross-population transcriptome prediction for transcriptome-wide association studies in underrepresented populations.

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized methods that leverage shared regulatory effects across different conditions, in this case, across different populations may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWAS) using different methods (Elastic Net, Joint-Tissue Imputation (JTI), Matrix eQTL, Multivariate Adaptive Shrinkage in R (MASHR), and Transcriptome-Integrated Genetic Association Resource (TIGAR)) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios.

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study.

Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients.

Protein prediction for trait mapping in diverse populations.

Genetically regulated gene expression has helped elucidate the biological mechanisms underlying complex traits. Improved high-throughput technology allows similar interrogation of the genetically regulated proteome for understanding complex trait mechanisms. Here, we used the Trans-omics for Precision Medicine (TOPMed) Multi-omics pilot study, which comprises data from Multi-Ethnic Study of Atherosclerosis (MESA), to optimize genetic predictors of the plasma proteome for genetically regulated proteome-wide association studies (PWAS) in diverse populations.

[Progressive supranuclear palsy].

Progressive supranuclear palsy (PSP) is a heterogeneous progressive neurodegenerative disease characterized by onset after 50 years old, Parkinson's syndrome, early development of postural instability, absence or transient reaction to levodopa drugs, neuropsychological disorders, dysphagia and dysarthria and eye movement disorders. The review provides an analysis of modern data on etiology, clinical presentation, differential diagnosis of the disease. The morphological picture and neuroimaging features, as well as modern ideas about treatment, are described.

On the cross-population generalizability of gene expression prediction models.

The genetic control of gene expression is a core component of human physiology. For the past several years, transcriptome-wide association studies have leveraged large datasets of linked genotype and RNA sequencing information to create a powerful gene-based test of association that has been used in dozens of studies. While numerous discoveries have been made, the populations in the training data are overwhelmingly of European descent, and little is known about the generalizability of these models to other populations.

Characterizing the mechanosensitive response of Paraburkholderia graminis membranes.

Bacterial mechanosensitive channels gate in response to membrane tension, driven by shifts in environmental osmolarity. The mechanosensitive channels of small conductance (MscS) and large conductance (MscL) from Escherichia coli (Ec) gate in response to mechanical force applied to the membrane. Ec-MscS is the foundational member of the MscS superfamily of ion channels, a diverse family with at least fifteen subfamilies identified by homology to the pore lining helix of Ec-MscS, as well as significant diversity on the N- and C-termini.

Macroeconomic dataset for comparative studies on coastal and inland regions in innovation space of Russia.

This article presents regional-level data that can be used for comparative territorial studies on innovation dynamics. The dataset covers a series of 50 indicators grouped into a matrix of 5 elements of regional innovation system (human resources - HR, infrastructure, research & development sector - R&D, innovative milieu, framework conditions) and 5 components of innovation security (economic, scientific and technological - S&T, social, political, geo-ecological). This complex set of interrelated data enables to grasp the catalyst and inhibitor factors that have a significant impact on the sustainable development of a particular regional innovation system.

Accuracy of Gene Expression Prediction From Genotype Data With PrediXcan Varies Across and Within Continental Populations.

Using genetic data to predict gene expression has garnered significant attention in recent years. PrediXcan has become one of the most widely used gene-based methods for testing associations between predicted gene expression values and a phenotype, which has facilitated novel insights into the relationship between complex traits and the component of gene expression that can be attributed to genetic variation. The gene expression prediction models for PrediXcan were developed using supervised machine learning methods and training data from the Depression Genes and Networks (DGN) study and the Genotype-Tissue Expression (GTEx) project, where the majority of subjects are of European descent.

Geospatial dataset for analyzing socio-economic regional divergence of European regions.

This data article presents macroeconomic data that can be used for comparative territorial studies. The data cover a sample of 413 regions (national administrative-territorial units corresponding to second level of a common classification of territorial units for statistics of the European Commission - NUTS 2 level region of the European Union, and comparable administrative-territorial units outside the EU) of 48 European countries, including Cyprus, Turkey, the European part of Russia, and two partially recognized states - the Republic of Kosovo and the Pridnestrovian Moldavian Republic. The statistical database covers a five-year period of 2010-2014.

Herpes Simplex Virus Type 1 Shedding in Tears and Nasal and Oral Mucosa of Healthy Adults.

Background: Herpes simplex virus type 1 (HSV-1) is prevalent worldwide and causes mucocutaneous infections of the oral area. We aimed to define the frequency and anatomic distribution of HSV-1 reactivation in the facial area in persons with a history of oral herpes.

Methods: Eight immunocompetent HSV-1 seropositive adults were evaluated for shedding of HSV-1 from 12 separate orofacial sites (8 from oral mucosa, 2 from nose, and 2 from conjunctiva) 5 days a week and from the oral cavity 7 days a week for approximately 5 consecutive weeks by a HSV DNA PCR assay.

Developing 'integrative' zebrafish models of behavioral and metabolic disorders.

Recently, the pathophysiological overlap between metabolic and mental disorders has received increased recognition. Zebrafish (Danio rerio) are rapidly becoming a popular model organism for translational biomedical research due to their genetic tractability, low cost, quick reproductive cycle, and ease of behavioral, pharmacological or genetic manipulation. High homology to mammalian physiology and the availability of well-developed assays also make the zebrafish an attractive organism for studying human disorders.

Perspectives on zebrafish models of hallucinogenic drugs and related psychotropic compounds.

Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs' action.

High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: quantitative imaging and correlation with iron.

We report R(2) and R(2) in human hippocampus from five unfixed post-mortem Alzheimer's disease (AD) and three age-matched control cases. Formalin-fixed tissues from opposing hemispheres in a matched AD and control were included for comparison. Imaging was performed in a 600MHz (14T) vertical bore magnet at MR microscopy resolution to obtain R(2) and R(2) (62 μm×62 μm in-plane, 80 μm slice thickness), and R(1) at 250 μm isotropic resolution.