Aristotle: stratified causal discovery for omics data

Background There has been a simultaneous increase in demand and accessibility across genomics, transcriptomics, proteomics and metabolomics data, known as omics data. This has encouraged widespread application of omics data in life sciences, from personalized medicine to the discovery of underlying pathophysiology of diseases. Causal analysis of omics data may provide important insight into the underlying biological mechanisms. Existing causal analysis methods yield promising results when identifying potential general causes of an observed outcome based on omics data. However, they may fail to discover the causes specific to a particular stratum of individuals and missing from others. Methods To fill this gap, we introduce the problem of stratified causal discovery and propose a method, Aristotle, for solving it. Aristotle addresses the two challenges intrinsic to omics data: high dimensionality and hidden stratification. It employs existing biological knowledge and a state-of-the-art patient stratification method to tackle the above challenges and applies a quasi-experimental design method to each stratum to find stratum-specific potential causes. Results Evaluation based on synthetic data shows better performance for Aristotle in discovering true causes under different conditions compared to existing causal discovery methods. Experiments on a real dataset on Anthracycline Cardiotoxicity indicate that Aristotle’s predictions are consistent with the existing literature. Moreover, Aristotle makes additional predictions that suggest further investigations.

Meta-analysis links dietary branched-chain amino acids to metabolic health in rodents

Background The role of dietary branched chain amino acids (BCAAs) and their effect on metabolic health is complex. How dietary BCAA levels and their interaction with background nutrition affect health is unclear. Here, we used meta-analysis and meta-regression, together with the nutritional modelling, to analyse the results of rodent studies that increased the level of dietary BCAAs and measured circulating levels, outcomes related to metabolic health, body mass and food intake. Results Across all studies, increasing dietary BCAAs resulted in increased levels of circulating BCAAs. These effects, however, were heavily moderated by background dietary levels whereby on high BCAA diets, further increases were not reflected in the blood. Impaired glucose tolerance was associated with elevated dietary BCAAs, with the greatest effect occurring with a simultaneous increase in total protein intake. Effects of dietary BCAAs on plasma glucose, insulin, or HOMA emerged only when dietary macronutrient background was considered. We found that elevated dietary BCAAs increases % body fat, with largest increases in adiposity occurring when BCAAs are increased on a high protein, low carbohydrate dietary background. Finally, we found that increased dietary BCAAs were associated with increased food intake when the background diet was low in BCAAs. Conclusion Our data highlights the interaction between BCAAs and background nutrition. We show that the effects of BCAAs on metabolic health cannot be studied in isolation but must be considered as part of complex mixture of dietary components.

Face Masks as a Factor in Eventuality of Changes in Driving Safety

During the COVID-19, pandemics or worsening virus situation, taxi and regular-route bus drivers are recommended to work in medical masks. However, the quantitative and qualitative influence of wearing protective face masks on safety of driving vehicles has not been previously studied. Therefore, this became the objective of preliminary studies to determine the specifics of the influence of a face protective mask on the change in psychophysiological qualities of a car driver as a factor in safety eventuality under urban traffic conditions.The method of an open-ended survey of 108 healthy adult drivers was used to obtain a quantitative subjective assessment of the effect of face masks on changing driving safety conditions and a comfortable emotional state while driving. A qualitative analysis of assessment of the level of psychophysiological qualities of drivers wearing and not wearing a face mask was carried out using Meleti hardware-software complex.A sharp decrease in neuropsychic functions with a simultaneous increase in quality of thinking and visual analysis of the traffic situation was revealed regarding the drivers wearing a face protective mask compared to those driving without a mask while the level of psychomotor reaction remains unchanged regardless of the gender of the driver.The subjective assessment of survey participants of the effect of a face mask on professionally important, psychophysiological characteristics of drivers revealed a significant (41,7 %) or insignificant (20,4 %) decrease in reaction, while 38 % of drivers did not notice significant changes in driving because of the effect of the mask.Based on these results, it is assumed that the face mask may serve as a predictor of a road pre-accident situation.To assess the effect of the face mask on the driver, a coefficient of eventuality of reducing road safety is proposed. It is recommended to use it as an additional factor in a situational pandemic environment when developing recommendations for the use of face masks for car and bus drivers, and when analysing the causes of road accidents.

The rise of grasslands is linked to atmospheric CO2 decline in the late Palaeogene

Grasslands are predicted to experience a major biodiversity change by the year 2100. A better understanding of how grasslands have responded to past environmental changes will help predict the outcome of current and future environmental changes. Here, we explore the relationship between past atmospheric CO2 and temperature fluctuations and the shifts in diversification rate of Poaceae (grasses) and Asteraceae (daisies), two exceptionally species-rich grassland families (~11,000 and ~23,000 species, respectively). To this end, we develop a Bayesian approach that simultaneously estimates diversification rates through time from time-calibrated phylogenies and correlations between environmental variables and diversification rates. Additionally, we present a statistical approach that incorporates the information of the distribution of missing species in the phylogeny. We find strong evidence supporting a simultaneous increase in diversification rates for grasses and daisies after the most significant reduction of atmospheric CO2 in the Cenozoic (~34 Mya). The fluctuations of paleo-temperatures, however, appear not to have had a significant relationship with the diversification of these grassland families. Overall, our results shed new light on our understanding of the origin of grasslands in the context of past environmental changes.

Dynamics of spike-and nucleocapsid specific immunity during long-term follow-up and vaccination of SARS-CoV-2 convalescents

Anti-viral immunity continuously declines over time after SARS-CoV-2 infection. Here, we characterize the dynamics of anti-viral immunity during long-term follow-up and after BNT162b2 mRNA-vaccination in convalescents after asymptomatic or mild SARS-CoV-2 infection. Virus-specific and virus-neutralizing antibody titers rapidly declined in convalescents over 9 months after infection, whereas virus-specific cytokine-producing polyfunctional T cells persisted, among which IL-2-producing T cells correlated with virus-neutralizing antibody titers. Among convalescents, 5% of individuals failed to mount long-lasting immunity after infection and showed a delayed response to vaccination compared to 1% of naïve vaccinees, but successfully responded to prime/boost vaccination. During the follow-up period, 8% of convalescents showed a selective increase in virus-neutralizing antibody titers without accompanying increased frequencies of circulating SARS-CoV-2-specific T cells. The same convalescents, however, responded to vaccination with simultaneous increase in antibody and T cell immunity revealing the strength of mRNA-vaccination to increase virus-specific immunity in convalescents.

Development, Implementation and Testing of Algorithm to Detect Ionopause-Like Structure Using Parallel Processing in the Martian Atmosphere

This study assesses the Martian ionopause using MAVEN datasets between periapsis and 150-600 km. Ionopause is an abrupt reduction of the electron density with increasing altitude. It is also required to verify the simultaneous increase of the electron temperature and variability below 400 km. To address this issue, we have adopted a computational approach in determining the ionopause-like density structure of the ionospheric profile. From computing thermal & magnetic pressures, radial magnetic field components, ionopause-like density gradient are detected and stored. The ionopause (theoretically) is formed where the total ionospheric pressure equals solar wind dynamic pressure. The present algorithm consists of a comprehensive set of conditions to be performed on the dataset sequentially. These include datasets from various instruments simultaneously observed. The primary objective of the present study is to describe the implementation and testing of this algorithm for big datasets of the Martian ionosphere and extract ionopause-like density gradient using automation. Keywords: Ionopause, Mars, Remote sensing, MAVEN dataset, Parallel-processing

Principles of care for adolescent girls with eating disorders and body disturbances disorders: lessons from the COVID-19 pandemic

The pandemic of the new coronavirus infection (COVID-19) has contributed to an increase in problems related to eating behavior and body image in the population. Various risk factors that have become relevant due to changes in the usual lifestyle have significantly affected the frequency of eating disorders in the adolescent population. This necessitated the adapting of new strategies for providing medical care in conditions of limited personal contact.The aim of the work is the methodological substantiation and systematization of modern approaches to the prevention and treatment of eating disorders, body image disorders and risk factors associated with them in adolescents in the conditions of the COVID-19 pandemic.Materials and methods. The methodological basis of the work is a comprehensive analysis of modern medical and social approaches and recommendations on the organization of assistance to adolescents with eating disorders and body image disorders, with a description of personal experience of using various interventions on an outpatient basis during the pandemic.Results: Prevention and treatment of eating disorders and body image disorders in adolescents during the pandemic should be aimed at specific risk factors those have proved to be the most relevant in connection with restrictive measures: involvement in body image-related social media content and active use of the media; reduction of physical activity with simultaneous increase in access to food; social isolation and reduction of social support; restriction of access to qualified care. The most reasonable approaches during the pandemic are the approaches focused on the family of a teenager using, if possible, remote forms of assistance.Conclusions: Currently, there are no norms and standards in the organization of assistance to adolescents with eating disorders and body image disorders in the pandemic context. However, the analysis of the implemented approaches aimed at various risk factors of these disorders will allow the use of the most effective preventive and therapeutic practices in the future.

RATIO OF TOTAL SLOW AND SUPER SLOW CEREBRAL BIOELECTRICAL ACTIVITY IN CHILDREN WITH HYPOXIA

The aim of the study is to identify changes in the total slow and super slow bioelectric activity of the cerebral hemispheres in 8–11-year-old children under reduced oxygen partial pressure in the inhaled air and in norm. Materials and Methods. The authors examined 82 8–11-year-old children. EEG registration was carried out on a complex Russian device "Telepat-103" with computer processing of the results. Slow potentials were recorded using a special computer complex for studying constant potential level (CPL) and cerebral energy consumption "Neuroenergon". Hypoxia was created by a special medical device "Hypoxicator" (Trade Medical). The choice of the oxygen content in the test hypoxic mixture (14 % O2) was based on the results of a three-stage hypoxic test carried out before the complex examination. Results. Hypoxia increases the index and amplitude of delta oscillations and decreases the number of alpha waves in 8–11-year-old children. The results obtained indicate that it is more important to provide the brain with a sufficient amount of oxygen corresponding to its needs than simply to increase the brain blood supply during hypoxia. The study also indicates the contribution of the body's sensitivity to hypoxic response. Under hypoxia, an increase in the constant potential level in the studied brain areas is observed in 8–11-year-old children. An increase in electrical activity during normobaric hypoxia is noted at low baseline values of constant potential level. An increase in the slow electrical brain activity occurs due to the change of brain energy supply according to the biochemical indicators of energy metabolism. Short-term hypoxia is accompanied by a simultaneous increase in slow-wave activity due to delta activity and CPL in 8–11-year-old children. Conclusion. Thus, we can say that a picture of functional brain activity with simultaneous inhibitory phenomena in the cortex is formed. It may reflect the development of a special state of the central nervous system. Key words: constant potential level, electroencephalography, hypoxia, adaptation to hypoxia. Цель работы – выявление изменений суммарной медленной и сверхмедленной биоэлектрической активности полушарий головного мозга у детей в возрасте от 8 до 11 лет в условиях нормального и сниженного парциального давления кислорода во вдыхаемом воздухе. Материалы и методы. Обследовано 82 ребенка 8–11-летнего возраста. Регистрация ЭЭГ осуществлялась на комплексной отечественной установке «Телепат-103» с компьютерной обработкой результатов. Медленные потенциалы фиксировались с помощью специального компьютерного комплекса для исследования уровня постоянных потенциалов (УПП) и энергозатрат головного мозга «Нейроэнергон». Гипоксические условия создавались аппаратом «Гипоксикатор» фирмы Trade Medical. Выбор содержания кислорода в тестирующей гипоксической смеси (14 % О2) основывался на результатах проведенного до комплексного обследования трехступенчатого гипоксического теста. Результаты. У детей от 8 до 11 лет действие гипоксии на головной мозг приводит к возрастанию индекса и амплитуды дельта-колебаний и убыванию числа альфа-волн. Полученные результаты говорят о том, что большое значение имеет не столько усиление кровоснабжения головного мозга при гипоксии, сколько обеспечение мозга достаточным, соответствующим его потребностям, количеством кислорода, а также о роли чувствительности организма к гипоксии. При воздействии гипоксии у детей этого возраста наблюдается возрастание уровня постоянных потенциалов в исследуемых областях головного мозга. При низких фоновых значениях уровня постоянных потенциалов отмечается возрастание электрической активности при нормобарической гипоксии. Возрастание медленной электрической активности головного мозга происходит из-за того, что изменяется энергообеспечение головного мозга по биохимическим показателям энергетического обмена. Действие кратковременной гипоксии сопровождается одновременным возрастанием медленноволновой активности за счет дельта-активности и УПП у детей от 8 до 11 лет. Выводы. Таким образом, можно говорить о том, что формируется своеобразная картина функциональной активности с одновременными тормозными явлениями в коре, что может являться отражением развития особого состояния центральной нервной системы. Ключевые слова: уровень постоянных потенциалов, электроэнцефалография, гипоксия, адаптация к гипоксии.