Cross-national aspects of the transformation of organizational culture in a pandemic

The ever-decreasing danger of coronavirus infection is forcing scientists from various fields of science to unite to assess not only the medical and epidemiological consequences of the development of this strange disease, but also social and socio-cultural changes in society. In this regard, it becomes necessary to summarize and understand the resource capabilities of various scientific areas to identify both general and specific aspects of the transformation of organizational culture in the context of the COVID-19 pandemic. That is why the authors considered it relevant to analyze the emerging scientific approaches and methods for diagnosing the degree of influence of the pandemic on social processes. The most important manifestation of the cross-cultural aspects of transformation is their socio-psychological base, which reflects similar forms of behavior of individuals in situations of collective stress. The presented study reflects a multidisciplinary approach to intangible factors in the development of social processes under the pressure of global challenges associated with the development of an unknown disease — COVID-19. A special place is occupied by the case related to the change in the attitude of Russian society to culture and cinema in the context of a pandemic. The results of scientific research include identified trends in the impact of COVID-19 on social and economic processes in all countries affected by the pandemic. The authors identified the national characteristics of organizational cultures in a pandemic. The novelty of the study lies in the formalized concept of the cross-national aspects of the transformation of organizational culture in a pandemic. The conclusions and approaches of the authors can be used in the development of national programs to overcome the consequences of COVID-19, taking into account international experience in the economy, social sphere and culture

GPU-accelerated ray-casting for 3D fiber orientation analysis

Orientation analysis of fibers is widely applied in the fields of medical, material and life sciences. The orientation information allows predicting properties and behavior of materials to validate and guide a fabrication process of materials with controlled fiber orientation. Meanwhile, development of detector systems for high-resolution non-invasive 3D imaging techniques led to a significant increase in the amount of generated data per a sample up to dozens of gigabytes. Though plenty of 3D orientation estimation algorithms were developed in recent years, neither of them can process large datasets in a reasonable amount of time. This fact complicates the further analysis and makes impossible fast feedback to adjust fabrication parameters. In this work, we present a new method for quantifying the 3D orientation of fibers. The GPU implementation of the proposed method surpasses another popular method for 3D orientation analysis regarding accuracy and speed. The validation of both methods was performed on a synthetic dataset with varying parameters of fibers. Moreover, the proposed method was applied to perform orientation analysis of scaffolds with different fibrous micro-architecture studied with the synchrotron μCT imaging setup. Each acquired dataset of size 600x600x450 voxels was analyzed in less 2 minutes using standard PC equipped with a single GPU

ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation.

Pyroptosis is a lytic form of cell death that is induced by inflammatory caspases upon activation of the canonical or noncanonical inflammasome pathways. These caspases cleave gasdermin D (GSDMD) to generate an N-terminal GSDMD fragment, which executes pyroptosis by forming membrane pores. We found that calcium influx through GSDMD pores serves as a signal for cells to initiate membrane repair by recruiting the endosomal sorting complexes required for transport (ESCRT) machinery to damaged membrane areas, such as the plasma membrane. Inhibition of the ESCRT-III machinery strongly enhances pyroptosis and interleukin-1β release in both human and murine cells after canonical or noncanonical inflammasome activation. These results not only attribute an anti-inflammatory role to membrane repair by the ESCRT-III system but also provide insight into general cellular survival mechanisms during pyroptosis

A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion.

Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva's vertebrate ortholog, MFSD1, rescues the minerva mutant's migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis

Innovative potential of regional economic development: problems and prospects

Innovative potential in modern conditions is a significant factor in the development of the regional economy. The problems of research of innovative potential are of particular importance, since its effective use affects the competitiveness of the region, the level of its socio-economic development and has a significant impact on the economy of the country as a whole. The purpose of the study is to identify the main factors hindering the formation and effective use of the innovative potential of the region. The object of the study were the tools that determine the innovative potential of the region. The results of the study are the substantiation of promising areas of practical use of the scientific and technical and technological potential of the region. The author paid special attention to the study of promising directions for the development of innovative potential based on the use of innovative structures. The prospects for further research in this area are due to the fact that for a country that sets itself the goal of ensuring economic growth, the use of the existing innovative potential of the regions is of particular importance. The solution of this problem requires the activation of scientific research on issues related to improving the quality of the use of the innovative potential of the region

Experience of medical treatment of neonates with Ebstein anomaly in the intensive care unit

Background: Neonates with Ebstein anomaly may remain a  challenge for neonatal intensive care units due to continuously changing clinical manifestations. Maintaining an adequate cardiac output in the presence of cardiomegaly, severe cyanosis, high pulmonary vascular resistance, and rhythm disorders is a difficult task.Aim: To demonstrate the possibility of conservative management, as well as clinical and instrumental criteria of assessment of neonates with Ebstein anomaly and arterial hypoxemia and cardiomegaly.Materials and methods: Four neonates aged from 3 to 8 days of life were admitted to the neonate intensive care unit due to persistent arterial hypoxemia (SaO2 ≤ 90%) and O2-dependence. Their cardiothoracic ratios ranged from 55 to 75% and were higher in the neonate with initial severe tricuspidal insufficiency (stage 3–4). Great Ormond Street Echocardiography (GOSE) score > 1 was found in 2 neonates with clinical manifestation of severe heart failure, arterial hypoxemia and cardiomegaly.Results: During the following 3 to 4 days, two neonates (aged 5 and 6 days) were transferred to the 2nd stage of care due to the absence of clinical manifestations of heart failure and severe hypoxemia. In the other two cases, intensive management was necessary, with catecholamine support, oxygen therapy, infusion of prostaglandin E1, anti-arrhythmic agents, with no surgical intervention.Conclusion: The majority of symptomatic neonates with Ebstein anomaly can be stabilized in the settings of adequate conservative management. However, some of them would require transition from conservative treatment to surgical intervention. Such clinical and instrumental criteria, as SaO2, cardiothoracic ratio, and GOSE are the main benchmarks to choose between conservative and surgical strategy

Guanylate-Binding Protein-Dependent Noncanonical Inflammasome Activation Prevents Burkholderia thailandensis-Induced Multinucleated Giant Cell Formation.

Inflammasomes are cytosolic multiprotein signaling complexes that are activated upon pattern recognition receptor-mediated recognition of pathogen-derived ligands or endogenous danger signals. Their assembly activates the downstream inflammatory caspase-1 and caspase-4/5 (human) or caspase-11 (mouse), which induces cytokine release and pyroptotic cell death through the cleavage of the pore-forming effector gasdermin D. Pathogen detection by host cells also results in the production and release of interferons (IFNs), which fine-tune inflammasome-mediated responses. IFN-induced guanylate-binding proteins (GBPs) have been shown to control the activation of the noncanonical inflammasome by recruiting caspase-4 on the surface of cytosolic Gram-negative bacteria and promoting its interaction with lipopolysaccharide (LPS). The Gram-negative opportunistic bacterial pathogen Burkholderia thailandensis infects epithelial cells and macrophages and hijacks the host actin polymerization machinery to spread into neighboring cells. This process causes host cell fusion and the formation of so-called multinucleated giant cells (MNGCs). Caspase-1- and IFN-regulated caspase-11-mediated inflammasome pathways play an important protective role against B. thailandensis in mice, but little is known about the role of IFNs and inflammasomes during B. thailandensis infection of human cells, particularly epithelial cells. Here, we report that IFN-γ priming of human epithelial cells restricts B. thailandensis-induced MNGC formation in a GBP1-dependent manner. Mechanistically, GBP1 does not promote bacteriolysis or impair actin-based bacterial motility but acts by inducing caspase-4-dependent pyroptosis of the infected cell. In addition, we show that IFN-γ priming of human primary macrophages confers a more efficient antimicrobial effect through inflammasome activation, further confirming the important role that interferon signaling plays in restricting Burkholderia replication and spread. IMPORTANCE The Gram-negative bacteria of the Burkholderia species are associated with human diseases ranging from pneumonia to life-threatening melioidosis. Upon infection through inhalation, ingestion, or the percutaneous route, these bacteria can spread and establish granuloma-like lesions resulting from the fusion of host cells to form multinucleated giant cells (MNGCs). Burkholderia resistance to several antibiotics highlights the importance to better understand how the innate immune system controls infections. Here, we report that interferons protect human epithelial cells against Burkholderia-induced MNGC formation, specifically through the action of the interferon-induced GBP1 protein. Mechanistically, GBP1 acts by inducing caspase-4-dependent cell death through pyroptosis, allowing the infected cells to be quickly eliminated before bacterial spread and the formation of MNGCs. This study provides evidence that interferon-induced innate immune activation, through GBP1 and caspase-4, confers protection against Burkholderia infection, potentially opening new perspectives for therapeutic approaches

Successful surgery for a right ventricle rhabdomyoma in a neonate

Primary cardiac tumors are very rare in children. Rhabdomyoma is the most common benign tumor in fetuses and neonates. Most cases do not require any surgical intervention due to absence of clinical symptoms and a high rate of spontaneous regression within the first year of life. However, some neonates can have significant abnormalities of intracardial hemodynamics related to the obstruction of the left and right ventricle outflows; this is an indication to emergency surgery. As a rule, complete or partial resection of the tumor mass provides uneventful postoperative course and is not associated with a relapse of rhabdomyoma in the long-term.We present a clinical case of a 15-days old neonate who underwent an emergency surgery due to advanced tumor obstruction of the blood flow in the right ventricle outflow tract (RVOT). At preoperative echocardiography, there was a pulmonary artery systolic pressure gradient of 90 mm Hg. Moderate hypoxemia (SaO2 90%), breathing rate of up to 55 per minute, together with echocardiographic results, indicated the impaired pulmonary blood flow and the need for the tumor resection. The tumor was completely resected through the right ventricle access with cardiopulmonary bypass and cardioplegia, with subsequent autologous pericardium patching of the right ventricle. The postoperative period was uneventful; the patient was extubated at day 2 and discharged at day 11 after surgery. The diagnosis of rhabdomyoma was confirmed histologically. At one month after surgery, no additional tumor masses were found in the heart chambers and septum.Rhabdomyoma causing severe obstruction of the RVOT in a newborn is a rare life-threatening complication of the natural course of benign heart tumors in children. The presence of dyspnea at rest, moderate desaturation, and echocardiographic data determined the rejection of the conservative management commonly adopted in most cases of cardiac rhabdomyomas, and were indications for an emergency surgery. In the long-term postoperative period, magnetic resonance imaging should be done to exclude tuberous sclerosis

Optogenetic activators of apoptosis, necroptosis, and pyroptosis.

Targeted and specific induction of cell death in an individual or groups of cells hold the potential for new insights into the response of tissues or organisms to different forms of death. Here, we report the development of optogenetically controlled cell death effectors (optoCDEs), a novel class of optogenetic tools that enables light-mediated induction of three types of programmed cell death (PCD)-apoptosis, pyroptosis, and necroptosis-using Arabidopsis thaliana photosensitive protein Cryptochrome-2. OptoCDEs enable a rapid and highly specific induction of PCD in human, mouse, and zebrafish cells and are suitable for a wide range of applications, such as sub-lethal cell death induction or precise elimination of single cells or cell populations in vitro and in vivo. As the proof-of-concept, we utilize optoCDEs to assess the differences in neighboring cell responses to apoptotic or necrotic PCD, revealing a new role for shingosine-1-phosphate signaling in regulating the efferocytosis of the apoptotic cell by epithelia

The role of pulse oximetry in neonatal screening for critical and complex congenital heart defects

Background: Timely diagnosis of complex and critical congenital heart defects in neonates can help to avoid fatal complications of their natural history and to establish correct treatment strategies. Therefore, easily available and inexpensive screening methods for their routine diagnostics are important.Aim: To demonstrate the role of pulse oximetry in the diagnosis of complex and critical congenital heart defects.Materials and methods: Forty six neonates aged from 1 to 27 days with congenital heart defects, diagnosed after birth, were included into the study. Their diagnoses were verified by expert echocardiography performed after positive pulse oximetry test or due to unexplainable oxygen dependency and/or clinical manifestation of severe heart failure. The pulse oximetry test was considered positive with SaO2 < 95% in any extremity and the difference between the right hand and foot of above 3%.Results: The pulse oximetry test was positive in all neonates with transposition of the great arteries (n = 5), hypoplastic left heart syndrome (n = 6), total anomalous pulmonary venous collection (n = 2), common arterial trunk (n = 3), pulmonary artery atresia with ventricular septum defect (n = 1). The pulse oximetry test was non-informative in those with obstructive abnormalities of the left heart, such as aortic valve stenosis and aortic coarctation.Conclusion: The pulse oximetry test can be used for routine screening for complex and critical congenital heart defects in neonates