Blood groups, erythrocyte antigens, and transfusion are fundamental areas of medicine and are related to many disciplines of science like hematology, immunology, surgery, and genetics. This book is a collection of information related to blood groups and transfusion, and a practical resource for all concerned physicians. The book is divided into two sections. The first section includes chapters on blood transfusion reactions and hemolytic disease of the fetus. The second section includes information for the future perspectives of blood group antigens. This book will be a stepping stone for scientists who are rapidly advancing their science journey.
This book examines how Russia, the world’s most complicated country, is governed. As it resumes its place at the centre of global affairs, the book explores Russia’s overarching strategies, and how it organizes itself (or not) in policy areas ranging from foreign policy and national security to health care, education, immigration, science, sport, agriculture, the environment and criminal justice. The book also discusses the structures and institutions on which Russia relies in order to deliver its goals in these areas of national life, as well as what’s to be done, in policy terms, to improve the country’s performance in its first post-Soviet century. Edited by Irvin Studin, the book includes contributions from a tremendous list of Russia’s leading thinkers and specialists, including Alexei Kudrin, Vladimir Mau, Alexander Auzan, Simon Kordonsky, Fyodor Lukyanov, Natalia Zubarevich and Andrey Melville.
The authors proposed and mathematically described model of a new type of the Fermi-Pasta-Ulam recurrence (the FPU auto recurrence) and hypothesized an adequate description of the heart's electrical dynamics within the observed phenomenon. The dynamics of the FPU auto recurrence making appropriate electrical dynamics of the normal functioning of the heart in the form of an electrocardiogram (ECG) was obtained by a computer model study. The model solutions in the form of the FPU auto recurrence – ECG Fourier spectrum were evaluated for resistance to external disturbances in the form of random effects, as well as periodic perturbation at a frequency close to the heart beating rate of about 1 Hz. In addition, in order to simulate the dynamics of myocardial infarction model, studied the effect of the surface area of the myocardium on the stability and shape of the auto recurrence – ECG spectrum. It has been found that the intense external disturbing periodic impacts at a frequency of about 1 Hz lead to a sharp disturbance spectrum shape FPU auto recurrence – ECG structure. In addition, the decrease in the surface of the myocardium by 50% in the model led to the destruction of structures of the auto recurrence – ECG, which corresponds to the state of atrial myocardium. Research models have revealed a hypothetical basis of coronary heart disease in the form of increasing the energy of high-frequency harmonics spectrum of the auto recurrence by reducing the energy of low-frequency harmonic spectrum of the auto recurrence, which ultimately leads to a sharp decrease in myocardial contractility. In order to test the hypothesis has been studied more than 20,000 ECGs both healthy people and patients with cardiovascular disease. As a result of these studies, it was found that the dynamics of the electrical activity of normal functioning of the heart can be interpreted by the display of the detected by authors the FPU auto recurrence, and coronary heart disease is a violation of the energy ratio between the low and high frequency harmonics of the FPU auto recurrence Fourier spectrum equal to the ECG spectrum. Thus, the hypothesis has been confirmed.
The materials of The International Scientific – Practical Conference is presented below. The Conference reflects the modern state of innovation in education, science, industry and social-economic sphere, from the standpoint of introducing new information technologies.
It is interesting for a wide range of researchers, teachers, graduate students and professionals in the field of innovation and information technologies.
Adequate assessment of individual functional motor potentials is important for developing appropriate rehabilitation strategies in ischemic stroke . Microstructural changes in corticospinal tract (CST) and corpus callosum (CC) were repeatedly correlated to post-stroke outcome [2, 3]. However, relationship between them and functional recovery remains unclear. Here we investigated relationship between integrity of CST and CC assessed with diffusion tensor imaging (DTI) and brain functional state assessed with navigated transcranial magnetic stimulation (nTMS) in chronic ischemic supratentorial stroke.
The present volume is the fourth issue of the Yearbook series entitled ‘Evolution’. The title of the present volume is ‘From Big Bang to Nanorobots’. In this way we demonstrate that all phases of evolution and Big History are covered in the articles of the present Yearbook. Several articles also present the forecasts about future development.
The main objective of our Yearbook as well as of the previous issues is the creation of a unified interdisciplinary field of research in which the scientists specializing in different disciplines could work within the framework of unified or similar paradigms, using the common terminology and searching for common rules, tendencies and regularities. At the same time for the formation of such an integrated field one should use all available opportunities: theories, laws and methods. In the present volume, a number of such approaches are used.
The volume consists of four sections: Universal Evolutionary Principles; Biosocial Evolution, Ecological Aspects, and Consciousness; Projects for the Future; In Memoriam.
This Yearbook will be useful both for those who study interdisciplinary macroproblems and for specialists working in focused directions, as well as for those who are interested in evolutionary issues of Cosmology, Biology, History, Anthropology, Economics and other areas of study. More than that, this edition will challenge and excite your vision of your own life and the new discoveries going on around us!
The book presents the most important aspects of safe digital image workflows, starting from the basic practical implications and gradually uncovering the underlying concepts and algorithms. With an easy-to-follow, down-to-earth presentation style, the text helps you to optimize your diagnostic imaging projects and connect the dots of medical informatics.
In the context of global efforts to move towards universal coverage in health systems, this report reviews health financing reforms in the Republic of Moldova and looks in particular at how the population´s access to health services has been affected. In 2004, as has been widely documented elsewhere, wholesale reforms were made to the way in which government funds were used to fund health services, shifting the system overnight from a highly fragmented and inflexible one, to one in which funds for the health sector were pooled nationally, allowing improved risk-sharing as a result of greater flexibility to allocate funds in line with health needs. A new source of funding in the form of a payroll tax for health was also introduced directly leading to a growth in total levels of government health spending. A second phase of reforms starting in 2009 addressed the issue of gaps in population coverage under mandatory health insurance, with legislative measures taken to ensure that all citizens of Moldova had access to primary health care, and to ensure that the poor receive subsidized health insurance. Fiscal constraints have limited the full implementation of these reforms however. Moldova has shown that it is prepared to tackle difficult policy issues head on and has articulated clear goals for the sector. In particular, the Roadmap “Accelerating Reforms: addressing the needs of the health area through investment policies” approved on 1 March 2012, lays a clear agenda for the next phase or priority reforms focusing on principally on service delivery reorganization but also on health financing. This is the correct focus given that progress on a number of priority indicators such as equity in access to services and financial protection has been limited in recent years. This report summarizes the main impact of health financing reforms to date and agrees with the Roadmap about the major challenges for the coming decade, in particular the need to address inefficiencies in service delivery, but also to ensure that the close link between guaranteed benefits and available funding is maintained in future policy decisions.
In humans, trophoblast hypoxia during placental development can be a cause of serious pregnancy complications, such as preeclampsia and fetal growth restriction. The pathogenesis of these conditions is not fully clear and may be associated with changed expression of some genes and regulatory molecules, including miRNA, in trophoblast cells. The aim of this study was to analyze miRNA profiles and measure the expression of their target genes in a model of trophoblast hypoxia. Human choriocarcinoma BeWo b30 cells were used as a trophoblast model. Hypoxia was induced by cobalt chloride (CoCl2) and an oxyquinoline derivative. MRNA and miRNA expression profiles were evaluated by means of next generation sequencing (NGS); the expression of individual genes was analyzed by PCR. We studied the secondary structure of mRNAs of target genes for those miRNAs whose expression had changed significantly and analyzed potential competition between these miRNAs for the binding site. The observed changes in the expression of the key genes involved in the response to hypoxia confirmed the feasibility of using CoCl2 and the oxyquinoline derivative as hypoxia inducers. The analysis revealed an increase in miR-374 levels following the activation of the hypoxia pathway in our trophoblast model. The changes were accompanied by a reduction in FOXM1 mRNA expression; this mRNA is a target for hsa-miR-374a-5p and hsa-miR374b-5p, which can compete with hsa-miR-21-5p for the binding sites on FOXM1 mRNA. The involvement of FOXM1 in the regulation of the invasive cell potential suggests the role of miR-374 and FOXM1 in the pathogenesis of disrupted trophoblast invasion during placental development as predisposing for fetal growth restriction and preeclampsia.
The Keap1-Nrf2 signaling axis is a validated and promising target for cellular defense and survival pathways. This minireview discusses the potential off-target effects and their impact on future drug development originating from Keap1-targeting small molecules that function as displacement activators of the redox-sensitive transcription factor Nrf2. We argue that small-molecule displacement activators, similarly to electrophiles, will release both Nrf2 and other Keap1 client proteins from the ubiquitin ligase complex. This non-specificity is likely unavoidable and may result in off-target effects during Nrf2 activation by targeting Keap1. The small molecule displacement activators may also target Kelch domains in proteins other than Keap1, causing additional off-target effects unless designed to ensure specificity for the Kelch domain only in Keap1. A potentially promising and alternative therapeutic approach to overcome this non-specificity emerging from targeting Keap1 is to inhibit the Nrf2 repressor Bach1 for constitutive activation of the Nrf2 pathway and bypass the Keap1-Nrf2 complex.
The spatial accuracy of transcranial magnetic stimulation (TMS) may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here, we investigate the within-limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid-based sulcus-informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5–10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI-based analysis, we studied normalized MNI MCRs. For the reliability assessment, we calculated intraclass correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within-limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We, thus, provide novel evidence that inter-muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions.
In many rare disease Phase II clinical trials, two objectives are of interest to an investigator: maximising the statistical power and maximising the number of patients responding to the treatment. These two objectives are competing, therefore, clinical trial designs offering a balance between them are needed. Recently, it was argued that response-adaptive designs such as families of multi-arm bandit (MAB) methods could provide the means for achieving this balance. Furthermore, response-adaptive designs based on a concept of context-dependent (weighted) information criteria were recently proposed with a focus on Shannon’s differential entropy. The information-theoretic designs based on the weighted Renyi, Tsallis and Fisher informations are also proposed. Due to built-in parameters of these novel designs, the balance between the statistical power and the number of patients that respond to the treatment can be tuned explicitly. The asymptotic properties of these measures are studied in order to construct intuitive criteria for arm selection. A comprehensive simulation study shows that using the exact criteria over asymptotic ones or using information measures with more parameters, namely Renyi and Tsallis entropies, brings no sufficient gain in terms of the power or proportion of patients allocated to superior treatments. The proposed designs based on information-theoretical criteria are compared to several alternative approaches. For example, via tuning of the built-in parameter, one can find designs with powercomparable to the fixed equal randomisation’s but a greater number of patients responded in the trials.
The review analyzes the potential advantages and problems associated with using HIF prolyl hydroxylase inhibitors as a treatment for COVID-19. HIF prolyl hydroxylase inhibitors are known to boost endogenous erythropoietin (Epo) and activate erythropoiesis by stabilizing and activating the hypoxia inducible factor (HIF). Recombinant Epo treatment has anti-inflammatory and healing properties, and thus, very likely, will be beneficial for moderate to severe cases of COVID-19. However, HIF PHD inhibition may have a significantly broader effect, in addition to stimulating the endogenous Epo production. The analysis of HIF target genes reveals that some HIF-targets, such as furin, could play a negative role with respect to viral entry. On the other hand, HIF prolyl hydroxylase inhibitors counteract ferroptosis, the process recently implicated in vessel damage during the later stages of COVID-19. Therefore, HIF prolyl hydroxylase inhibitors may serve as a promising treatment of COVID-19 complications, but they are unlikely to aid in the prevention of the initial stages of infection.
Background and Purpose Despite the continuing efforts in multimodal assessment of the motor system after stroke, conclusive findings on the complementarity of functional and structural metrics of the corticospinal tract (CST) integrity and the role of the contralesional hemisphere are still missing. The aim of this work was to find the best combination of the motor system parameters, allowing classification of patients into three predefined groups of upper limb motor recovery.
Methods 35 chronic ischemic stroke patients (47 [26–66] y.o., 29 [6–58] months post-stroke) with only supratentorial lesion and unilateral upper extremity weakness were enrolled. Patients were divided into three groups depending on the upper limb motor recovery. Non-parametric statistical tests and regression analysis were used to investigate the relationships among structural and functional motor system parameters, probed by diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS). In addition, stratification rules were tested, using a decision tree classifier to identify parameters explaining motor recovery.
Results Fractional anisotropy (FA) ratio in the internal capsule (IC) and absence/presence of motor evoked potentials (MEPs), were equally discriminative of the worst motor outcome group (96% accuracy). MEP presence diverged for two investigated hand muscles. Concurrently, for the three recovery groups’ classification, the best parameter combination was: IC FA ratio and Fréchet distance between the contralesional and ipsilesional CST FA profiles (91% accuracy). No other metrics had any additional value for patients’ classification.
Conclusions This study demonstrates that IC FA ratio and MEPs absence are equally important markers for poor recovery. Importantly, we found that MEPs should be controlled in more than one hand muscle. Finally, we show that better separation between different motor recovery groups may be achieved when considering the whole CST FA profile.
Abstract reasoning is associated with the ability to detect relations among objects, ideas, events. It underlies the understanding of other individuals’ thoughts and intentions. In natural settings, individuals have to infer relevant associations that have proven to be reliable or precise predictors. Salience theory suggests that the attribution of meaning to stimulus depends on their contingency, saliency, and relevance to adaptation. So far, subjective estimates of relevance have mostly been explored in motivation and implicit learning. Mechanisms underlying formation of associations in abstract thinking with regard to their subjective relevance, or salience, are not clear. Applying novel computational methods, we investigated relevance detection in categorization tasks in 17 healthy individuals. Two models of relevance detection were developed: a conventional one with nouns from the same semantic category, an aberrant one based on an insignificant common feature. Control condition introduced non-related words. The participants were to detect either a relevant principle or an insignificant feature to group presented words. In control condition they inferred that the stimuli were irrelevant to any grouping idea. Cross-frequency phase coupling analysis revealed statistically distinct patterns of synchronization representing search and decision in the models of normal and aberrant relevance detection. Significantly distinct frontotemporal functional networks with central and parietal components in the theta and alpha frequency bands may reflect differences in relevance detection.
Question:Paired pulse transcranial magnetic stimulation(ppTMS) is a common approach to probe cortical excitatory and inhi-bitory processes [a]. ppTMS paradigms can be classified by the inter-stimulus interval (ISI) to long and short interval ppTMS. It isassumed, that short interval ppTMS phenomena such as short-inter-val cortical inhibition phenomenon (SICI) are rather focal and arediscussed in terms of surround inhibition in the motor cortex [b].Longer interval ppTMS phenomena are believed to be based on morewidespread trans-synaptic mechanisms[c]. The topographic aspectsof these ppTMS phenomena are not fully understood yet. The associ-ation of the various ppTMS phenomena studied in different musclesof the same limb remains unexplored. The aim of this study was toassess the interaction of ppTMS phenomena, probed in differentupper limb muscles. We hypothesized that the correlation amongthe different hand muscles within the ppTMS phenomenon willdepend on the ppTMS ISI.Methods:19 healthy right-handed volunteers participated in thestudy (15 females, 18–30 y.o.). Four ppTMS phenomena (SICI/LICI –short-interval/long-interval intracortical inhibition, SICF – short nterval intracortical facilitation and ICF – intracortical facilitation)were probed using navigated TMS (MagPro X100, Localite TMSNavigator) applied at the APB hotspot of the left primary motor cor-tex. We registered motor evoked potentials (MEPs) from four rightupper limb muscles: abductor pollicis brevis (APB), extensor digito-rum communis (EDC), abductor digiti minimi (ADM) and biceps bra-chii (BB). Spearman’s rank correlation coefficient was calculated toevaluate an association of inter-muscle ppTMS phenomena.Multiple comparisons were controlled with the FDR. For the finalanalysis we considered only correlations between spatially sepa-rated muscles with sufficiently high amplitudes of MEPs during sin-gle pulse TMS.Results:SICI, ICF and LICI phenomena correlated significantlyamong all the considered muscles‘ pairs. SICI for APBEDC:r=0.793,p= 0.000; for ADMEDC:r= 0.905,p= 0.000. ICF for APBEDC:r= 0.639,p= 0.000; for ADMEDC:r= 0.639,p= 0.000.SICF for APBEDC:r= 0.423,p> 0.05; for ADMEDC:r= 0.779,p= 0.000. LICI for APBEDC:r= 0.575,p= 0.000; for ADMEDC:r= 0.704,p= 0.004.Conclusion:In agreement with the previous data, we did not finda clear association among different ppTMS phenomena. In contrastto our hypothesis, there is no link between ISI and the correlationof the same ppTMS phenomenon among muscles. The lack of thecorrelation between APB and EDC in SICF might be explained bySICF peculiar mechanism through the superposition of D-and I-waves [d]; and by a specialized functionality of the thenar, compar-ing to hypothenar muscles, – the idea which should be further ver-ified in the following experiments.
Epigenetic alterations represent promising therapeutic targets in cancer treatment. Recently it was revealed that small molecules have the potential to act as microRNA silencers. Capacity to bind the discrete stem-looped structure of pre-miR-21 and prevent its maturation opens opportunities to utilize such compounds for the prevention of initiation, progression, and chemoresistance of cancer. Molecular simulations performed earlier identified 3,3′-diindolylmethane (DIM) as a potent microRNA-21 antagonist. However, data on DIM and microRNA-21 interplay is controversial, which may be caused by the limitations of the cell lines.
In this study, we established a tumor organoid culture from metastatic breast cancer and tested the efficiency of DIM in combination with common chemotherapeutic drugs used in clinic. Organoids shared morphologic features with the primary tumor, captured tumor heterogeneity, and possessed unique genetic characteristics. Here, we report that DIM suppresses mir-21-5p expression and enhances susceptibility of patient-derived breast cancer organoid to cyclophosphamide and methotrexate treatment. Our data support the hypothesis that small molecules can be utilized as microRNA silencers to overcome cancer-related drug resistance and other pathologies.