Common Patterns of Prediction of Literacy Development in Different Alphabetic Orthographies

We are grateful to Brett Kessler for computing the consistency estimates in each of the four languages of this studyPrevious studies have shown that phoneme awareness, letter-sound knowledge, rapid automatized naming (RAN), and verbal memory span are reliable correlates of learning to read in English. However, the extent to which these different predictors have the same relative importance in different languages remains uncertain. In this article, we present the results from a 10-month longitudinal study that began just before or soon after the start of formal literacy instruction in four languages (English, Spanish, Slovak, and Czech). Longitudinal path analyses showed that phoneme awareness, letter-sound knowledge, and RAN (but not verbal memory span) measured at the onset of literacy instruction were reliable predictors, with similar relative importance, of later reading and spelling skills across the four languages. These data support the suggestion that in all alphabetic orthographies, phoneme awareness, letter-sound knowledge, and RAN may tap cognitive processes that are important for learning to read.Grant PITN-215961 – ELDEL from the Marie Curie, Seventh Framework Programm

Comparative analysis of IL-1β blood serum concentration, neutrophil-to-lymphocytes ratio in peripheral blood, and the levels of PD-L1 expression in malignant tissues of the patients with various solid tumors

The action of checkpoint inhibitors is based on activation of T cell antitumor immunity, and, therefore, the search for markers of lymphocyte functional activity before starting the therapy is highly relevant. Determination of the PD-L1 expression in tumor tissues reflects immunosuppressive activity of malignant cells, and it is used as a predictive marker in clinical practice. The ratio of neutrophils to lymphocytes in tumor tissue and in peripheral blood can also indicate the activity of adaptive immunity and correlates with the efficacy of therapy. It has been shown that a high level of interleukin 1 beta in the tumor microenvironment is associated with immunosuppression of lymphocytes and, possibly, reflects the activity of the tumor microenvironment. The aim of this work is to study the relationship between tumor expression of PD-L1, the concentration of serum interleukin-1 beta and the ratio of neutrophils and lymphocytes in peripheral blood.Before starting therapy with checkpoint inhibitors in patients with various solid tumors (n = 50), the serum level of interleukin-1 beta was determined by ELISA (ELISA-Best, Novosibirsk, Russia), expression of PD-L1 in the tumor by immunohistochemical method, complete blood count was performed using cytometry. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using the statistical methods of Fisher, Mann-Whitney, and Spearman.The average value of the index of the ratio of neutrophils and lymphocytes (NLR) in peripheral blood was 2.65± 0.21 (95% CI 2.22-3.07). The index value of more than 3.5 was found in 18% (9/50) of patients. The mean value of the PD-L1 expression level was 23.02±4.52% (95% CI 13.86-32.18). Expression of PD-L1 in tumor tissue was detected in 60.1% (25/40) of patients, among whom an increased expression of more than 50% was detected in 20.0% (5/25) of cases. A positive weak correlation was found between the concentration of interleukin 1 beta and the number of leukocytes (r = 0.34; p = 0.019) and index (r = 0.32; p = 0.029). The level of PD-L1 expression in tumor tissue also had a weak positive correlation with the serum interleukin 1 beta concentration (r = 0.33; p = 0.037) and the neutrophil-lymphocyte ratio (r = 0.33; p = 0.034). In the group of patients with PD-L1 expression > 5%, the mean value of the concentration of interleukin 1 beta was 1.65±0.62 pg/ml, and the mean value of the index was 4.26±0.94 х 10 9/l, which exceeds the values groups with undetectable PD-L1, but the differences were not statistically significant.The obtained result may indicate the influence of the immunosuppressive properties of the tumor on the state of the patient's immunity. Comprehensive determination of tumor PD-L1 expression, serum interleukin 1 beta concentration and the ratio of neutrophils and lymphocytes in peripheral blood can be used as an assessment of the patient's immune status before starting treatment with checkpoint inhibitors

Rationale and design of the open-label, prospective, randomized study of the efficacy of intravenous versus oral iron deficiency therapy in improving left ventricular systolic function in patients with myocardial infarction (OPERA-MI)

Aim. Iron has a protective effect on cardiomyocytes during hypoxia, while iron deficiency (ID) directly affects its function, disrupting mitochondrial respiration, reducing their contractility and relaxation. Some studies have shown that ID is a predictor of adverse outcomes  in patients with acute coronary syndrome (ACS).  However, the impact of ID and its treatment, quality of life and prognosis of patients with ID and myocardial infarction (MI) has not been fully established. The study aim is to determine the effectiveness of intravenous ferric carboxymaltose  (FCM) compared  with oral iron (ferrous sulfate) in relation to left ventricular (LV) systolic function, assessed by echocardiography.Material and methods. This open-label, prospective, randomized study includes 360 patients  with or without ID who were  hospitalized  with acute  myocardial infarction (MI).  Patients with ID will be randomized (1:1) to intravenous FCM and oral ferrous sulfate therapy. Treatment in groups will be started at the time of hospitalization. Patients without ID will form the control group.  The follow-up period for patients will be 1 year. The primary endpoint was a reduction  in LV wall motion score  index (WMSI) in the FCM group compared  to the ferrous sulfate group. The key secondary endpoint is a composite endpoint of cardiovascular death, non-fatal MI and stroke, and hospitalization for decompensated heart failure.Conclusion. The OPERA-MI study will determine the effect  of ID treatment with intravenous FCM compared  with oral ferrous sulfate on WMSI, which reflects LV systolic function

Key differences between anti-PD-1/PD-L1 inhibitors

Indications  to immunotherapy in cancer treatment continue to expand, thus there are more and more questions about clinical aspects of using different checkpoint inhibitors. Despite similar mechanism of action between widely used antibodies to PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (durvalumab, avelumab, atezolizumab), inhibitors are different due to features of monoclonal antibodies structure they are based on. For instance, toxicity leading to discontinuation of treatment occurs more frequently with anti-PD-L1 drugs than PD-1 inhibitors. On the contrary, the average incidence of any grade IRAEs was higher in patients treated with anti-PD-1 drugs. The revealed differences in the toxicity of the analyzed groups of drugs could be associated with the type of action of the drug. The feature of the PD-L1 inhibitors is more frequent occurrence of antibody-dependent cellular cytotoxicity reactions. However, PD-1 inhibitors  showed a statistically significant survival benefit, according to a meta-analysis comparing anti-PD-1 and anti-PD-L1 groups. Besides data on differences in the efficacy and toxicity profiles of these agents, in this article we also analyze different issues in the structure of drug molecules, in particular, the role of LALA mutation in anti-PD-1 inhibitors. Understanding the key distinctive points of check-point inhibitors  (CPI) in the future may allow  to solve the problem of rechallenge  and reintroduction after management of severe IRAEs

Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry

Most patients with glioblastoma (GBM) die within 2 years. A major therapeutic goal is to target GBM stem cells (GSCs), a subpopulation of cells that contribute to treatment resistance and recurrence. Since their discovery in 2003, GSCs have been isolated using single-surface markers, such as CD15, CD44, CD133, and α6 integrin. It remains unknown how these single-surface marker-defined GSC populations compare with each other in terms of signaling and function and whether expression of different combinations of these markers is associated with different functional capacity. Using mass cytometry and fresh operating room specimens, we found 15 distinct GSC subpopulations in patients, and they differed in their MEK/ERK, WNT, and AKT pathway activation status. Once in culture, some subpopulations were lost and previously undetectable ones materialized. GSCs that highly expressed all 4 surface markers had the greatest self-renewal capacity, WNT inhibitor sensitivity, and in vivo tumorigenicity. This work highlights the potential signaling and phenotypic diversity of GSCs. Larger patient sample sizes and antibody panels are required to confirm these findings

Development of DNA-Biochip for Identification of Influenza A Virus Subtypes

Developed was the DNA-biochip to identify subtypes of influenza A virus, pathogenic for humans. Microchip was capable of detecting H1, H3, H5-subtypes of hemagglutinin (including H1-subtype of pandemic A/H1N1(2009) influenza virus ) and neuraminidase subtypes N1,N2 of influenza virus. This microchip was successfully tested on the strains of A/H5N1 highly pathogenic avian influenza virus, A/H1N1(2009) pandemic influenza virus, A/H1N1 and A/H3N2 seasonal influenza viruses

Defining and Detecting Crossover-Interference Mutants in Yeast

The analysis of crossover interference in many creatures is complicated by the presence of two kinds of crossovers, interfering and noninterfering. In such creatures, the values of the traditional indicators of interference are subject not only to the strength of interference but also to the relative frequencies of crossing over contributed by the two kinds. We formalize the relationship among these variables and illustrate the possibilities and limitations of classical interference analysis with meiotic tetrad data from wild-type Saccharomyces cerevisiae and from mlh1 and ndj1 mutants

Topological Photonics

Topology is revolutionizing photonics, bringing with it new theoretical discoveries and a wealth of potential applications. This field was inspired by the discovery of topological insulators, in which interfacial electrons transport without dissipation even in the presence of impurities. Similarly, new optical mirrors of different wave-vector space topologies have been constructed to support new states of light propagating at their interfaces. These novel waveguides allow light to flow around large imperfections without back-reflection. The present review explains the underlying principles and highlights the major findings in photonic crystals, coupled resonators, metamaterials and quasicrystals.Comment: progress and review of an emerging field, 12 pages, 6 figures and 1 tabl

CHARACTERISTICS OF AUTOIMMUNE INFLAMMATION IN THE PATIENTS WITH LUNG TUBERCULOSIS

Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis, being characterized by the development of caseous granulomas in various organs, mainly in lungs. M. tuberculosis is known to be a trigger for autoimmune inflammation, due to the possible mimicry of bacterial proteins as autoantigens. Recently, a significance of mesenchymal vimentin as an autoantigen in mycobacterial infections has been actively discussed. The aim of the present study was to determine autoantibodies for various vimentin modifications in the patients with tuberculosis.The study was performed in 2014-2017 and included 28 patients with pulmonary tuberculosis (group I), 30 patients with nonspecific lung diseases (group II): 15 with granulomatous polyangiitis, and 15 with different alveolites. Control group consisted of healthy subjects (n = 40). Concentration of antibodies to mutated citrullinated vimentin (anti-MCV) was measured using ELISA (ORGENTEC, Germany). The patients with elevated anti-MCV levels were tested for antibodies to cyclic citrullinated peptide (anti-CCP) using ELISA technique (EUROIMMUN, Germany). Statistical analysis was carried out using GraphPad Prism 6 (GraphPad Software, USA), Statistica 10 (Statsoft, USA) using nonparametric analysis of samples with Mann-Whitney and Chi-square criteria, and Spearman method for correlation analysis. The differences were considered statistically significant at p < 0.05.The anti-MCV concentrations were significantly higher in patients with tuberculosis (group I, 60.7% of cases, 17/28) than in group II, and control group (23.6 and 25.0% of cases, respectively). No statistically significant differences were revealed between the results of anti-MVC and anti-CCP levels in comparison group with the control group (p = 0.18).High levels of anti-MCV antibodies in the patients with pulmonary tuberculosis reflect an opportunity of developing autoimmune process in the disease pathogenesis. Measurement of plasma anti-MCV antibody concentrations may be important for correction of the therapy, especially upon administration of immunosuppressive and hormonal corticosteroid drugs. It has been shown that anti-CCP are not characteristic to the lung diseases