A Sharp Turn toward the Market: Economic Reform in Russia (1992–1998) and Its Consequences

By analyzing and systematizing the literature accumulated over the past twenty years on the history of reforms, we can put in order the existing views on the processes that took place during these transformations and de ne a new vector in understanding the socio-economic development of Russia in the last decade of the 20th century and the rst decades of the 21st century. The rst step in this direction is the analysis of publications that re ect the preparation, progress and results of the contemporary economic reforms in the 1990s. The historiographic review includes the monographs written both by the advocates of the shock therapy, and their opponents and critics, rst of all, Members of the Russian Academy of Sciences. The study of this literature allows to reveal the spectrum of opinions on whether the shock therapy was the preferred version of transformations, on assessing the results of reforms by the end of the 1990s and the opportunities for alternative ways to make the transition from a planned to a market economy. In particular, the advocates of the «shock therapy» refer to the threat of famine and civil war to justify decisions that led to decline in output, hyperin ation and other negative trends. Their critics point out that the lack of public support caused the market reforms to fail. By acknowledging the obvious, i. e. a signi cant deterioration of economic indicators, the advocates see their success in establishing the system of market institutions, and, on this basis, insist there was no alternative to implemented version of reforms. In turn, their opponents believe that the alternatives to the «shock therapy» existed, and their distinctive feature would have been the gradual cultivation and not the forced administrative introduction of market economy institutions.This article has been prepared with the support in the form of a Grant No. 16–02–00016a from the Russian Foundation for Humanities

Historical Research at the Institute of Economics UB RAS: the Heritage of A. V. Bakunin and New Methodological Possibilities of Cliometrics and Synergetics

The most intensive historical research in the Institute of Economics of the Ural Scientific Center of the USSR Academy of Sciences (now the Ural Branch of the Russian Academy of Sciences) was carried out during the period when the Department of History was in its structure under the leadership of Doctor of Historical Sciences, Professor A.V. Bakunin in 1978-1988. However, this tradition was continued in the following decades. At the same time, the main attention was paid to the further development of the methodological and methodological foundations of historical and economic analysis. In particular, the analytical apparatus of cliometrics, including simulation modeling and retro-alternative forecasting, was used to verify the hypotheses substantiated by quantitative features. At present, work is underway to deepen the understanding of such an integral element of the cliometric interpretation of the historical process as the “bifurcation point”.Наиболее интенсивно исторические исследования в Институте экономики УНЦ АН СССР (ныне – УрО РАН) осуществлялись в период наличия в его структуре Отдела истории под руководством д-ра ист. наук, профессора А.В. Бакунина в 1978-1988 гг. Однако и в последующие десятилетия данная традиция была продолжена. При этом основное внимание уделялось дальнейшему развитию методологических и методических основ историко-экономического анализа. В частности, для верификации гипотез, обоснованием которых являются количественные признаки, использовался аналитический аппарат клиометрики, включая имитационное моделирование и ретроальтернативное прогнозирование. В настоящее время ведётся работа по углублению представлений о таком неотъемлемом элементе клиометрической трактовки исторического процесса, как «точка бифуркации»

Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery

During the pandemic of severe respiratory distress syndrome coronavirus 2 (SARS-CoV2), many novel therapeutic modalities to treat Coronavirus 2019 induced disease (COVID-19) were explored. This study summarizes 195 clinical trials of advanced cell therapies targeting COVID-19 that were registered over the two years between January 2020 to December 2021. In addition, this work also analyzed the cell manufacturing and clinical delivery experience of 26 trials that published their outcomes by July 2022. Our demographic analysis found the highest number of cell therapy trials for COVID-19 was in United States, China, and Iran (N=53, 43, and 19, respectively), with the highest number per capita in Israel, Spain, Iran, Australia, and Sweden (N=0.641, 0.232, 0,223, 0.194, and 0.192 trials per million inhabitants). The leading cell types were multipotent mesenchymal stromal/stem cells (MSCs), natural killer (NK) cells, and mononuclear cells (MNCs), accounting for 72%, 9%, and 6% of the studies, respectively. There were 24 published clinical trials that reported on infusions of MSCs. A pooled analysis of these MSC studies found that MSCs provide a relative risk reduction for all-cause COVID-19 mortality of RR=0.63 (95% CI 0.46 to 0.85). This result corroborates previously published smaller meta-analyses, which suggested that MSC therapy demonstrated a clinical benefit for COVID-19 patients. The sources of the MSCs used in these studies and their manufacturing and clinical delivery methods were remarkably heterogeneous, with some predominance of perinatal tissue-derived products. Our results highlight the important role that cell therapy products may play as an adjunct therapy in the management of COVID-19 and its related complications, as well as the importance of controlling key manufacturing parameters to ensure comparability between studies. Thus, we support ongoing calls for a global registry of clinical studies with MSC products that could better link cell product manufacturing and delivery methods to clinical outcomes. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the near future, preventing pathology through vaccination still remains the best protection to date. We conducted a systematic review and meta-analysis of advanced cell therapy clinical trials as potential novel treatment for COVID-19 (resulting from SARS-CoV-2 coronavirus infection), including analysis of the global clinical trial landscape, published safety/efficacy outcomes (RR/OR), and details on cell product manufacturing and clinical delivery. This study had a 2-year observation interval from start of January 2020 to end of December 2021, including a follow-up period until end of July to identify published outcomes, which covers the most vivid period of clinical trial activity, and is also the longest observation period studied until today. In total, we identified 195 registered advanced cell therapy studies for COVID-19, employing 204 individual cell products. Leading registered trial activity was attributed to the USA, China, and Iran. Through the end of July 2022, 26 clinical trials were published, with 24 out of 26 articles employing intravenous infusions (IV) of mesenchymal stromal/stem cell (MSC) products. Most of the published trials were attributed to China and Iran. The cumulative results from the 24 published studies employing infusions of MSCs indicated an improved survival (RR=0.63 with 95% Confidence Interval 0.46 to 0.85). Our study is the most comprehensive systematic review and meta-analysis on cell therapy trials for COVID-19 conducted to date, clearly identifying the USA, China, and Iran as leading advanced cell therapy trial countries for COVID-19, with further strong contributions from Israel, Spain, Australia and Sweden. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the future, preventing pathology through vaccination remains the best protection

Connexin-43 prevents hematopoietic stem cell senescence through transfer of reactive oxygen species to bone marrow stromal cells

Hematopoietic stem cell (HSC) aging has become a concern in chemotherapy of older patients. Humoral and paracrine signals from the bone marrow (BM) hematopoietic microenvironment (HM) control HSC activity during regenerative hematopoiesis. Connexin-43 (Cx43), a connexin constituent of gap junctions (GJs) is expressed in HSCs, down-regulated during differentiation, and postulated to be a self-renewal gene. Our studies, however, reveal that hematopoietic-specific Cx43 deficiency does not result in significant long-term competitive repopulation deficiency. Instead, hematopoietic Cx43 (H-Cx43) deficiency delays hematopoietic recovery after myeloablation with 5-fluorouracil (5-FU). 5-FU-treated H-Cx43-deficient HSC and progenitors (HSC/P) cells display decreased survival and fail to enter the cell cycle to proliferate. Cell cycle quiescence is associated with down-regulation of cyclin D1, up-regulation of the cyclin-dependent kinase inhibitors, p21cip1. and p16INK4a, and Forkhead transcriptional factor 1 (Foxo1), and activation of p38 mitogen-activated protein kinase (MAPK), indicating that H-Cx43-deficient HSCs are prone to senescence. The mechanism of increased senescence in H-Cx43-deficient HSC/P cells depends on their inability to transfer reactive oxygen species (ROS) to the HM, leading to accumulation of ROS within HSCs. In vivo antioxidant administration prevents the defective hematopoietic regeneration, as well as exogenous expression of Cx43 in HSC/P cells. Furthermore, ROS transfer from HSC/P cells to BM stromal cells is also rescued by reexpression of Cx43 in HSC/P. Finally, the deficiency of Cx43 in the HM phenocopies the hematopoietic defect in vivo. These results indicate that Cx43 exerts a protective role and regulates the HSC/P ROS content through ROS transfer to the HM, resulting in HSC protection during stress hematopoietic regeneration

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management

Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium

Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7–8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new ‘Dynamic International Prognostic Scoring System (DIPSS)-plus' prognostic model for primary myelofibrosis (PMF) and the clinical relevance of distinguishing essential thrombocythemia from prefibrotic PMF are discussed

ARAP3 Functions in Hematopoietic Stem Cells

ARAP3 is a GTPase-activating protein (GAP) that inactivates Arf6 and RhoA small GTPases. ARAP3 deficiency in mice causes a sprouting angiogenic defect resulting in embryonic lethality by E11. Mice with an ARAP3 R302,303A mutation (Arap3KI/KI) that prevents activation by phosphoinositide-3-kinase (PI3K) have a similar angiogenic phenotype, although some animals survive to adulthood. Here, we report that hematopoietic stem cells (HSCs) from rare adult Arap3KI/KI bone marrow are compromised in their ability to reconstitute recipient mice and to self-renew. To elucidate the potential cell-autonomous and non-cell-autonomous roles of ARAP3 in hematopoiesis, we conditionally deleted Arap3 in hematopoietic cells and in several cell types within the HSC niche. Excision of Arap3 in hematopoietic cells using Vav1-Cre does not alter the ability of ARAP3-deficient progenitor cells to proliferate and differentiate in vitro or ARAP3-deficient HSCs to provide multi-lineage reconstitution and to undergo self-renewal in vivo. Thus, our data suggest that ARAP3 does not play a cell-autonomous role in HSPCs. Deletion of Arap3 in osteoblasts and mesenchymal stromal cells using Prx1-Cre resulted in no discernable phenotypes in hematopoietic development or HSC homeostasis in adult mice. In contrast, deletion of Arap3 using vascular endothelial cadherin (VEC or Cdh5)-driven Cre resulted in embryonic lethality, however HSCs from surviving adult mice were largely normal. Reverse transplantations into VEC-driven Arap3 conditional knockout mice revealed no discernable difference in HSC frequencies or function in comparison to control mice. Taken together, our investigation suggests that despite a critical role for ARAP3 in embryonic vascular development, its loss in endothelial cells minimally impacts HSCs in adult bone marrow

THE EXPERIENCE OF RETROALTERNATIVE PROGNOSING OF SOCIO-ECONOMIC SYSTEMS DEVELOPMENT (ON THE EXAMPLE OF AGRICULTUREAL COMPLEX OF SVERDLOVSKAYA AREA IN 1990 YEARS)

This article demonstrates the heuristic opportunities for analysing regional social-economic systems by using the methods of retro-alternativistics. The article also substantiates the methodological aspects of using cliometrics for modelling economic processes which never took place in the past. On the basis of retro-alternative forecasting method the counterfact imitation modelling of agricultural development in the Middle Urals in 1995 − 1998 has been accomplished

Dayly profile microalternations of ECG-signals according to dispersion mapping

This report presents preliminary results of the analysis of the circadian monitoring factors of dispersion mapping (DM). Analyzed daily ECG monitoring in healthy individuals in a free life activity (I group), the data obtained during the research program "Mars-500" in 6 healthy men (2 group), in patients with hypertension (3 group) and IHD with episode of ventricular arrhythmia I-II class on Launu (4 group). For analysis areas by duration in 15-20 minutes from each hour «were cut". Study of the circadian factors of ECG-signal microalternations is a new diagnostic approach to the analysis of electrophisiological status and diagnostic test of the revealing of the myocardium lesions. DM method can be used to obtain new data on electrophysiological features of the myocardium during the day and the diagnosis of myocardium electrical heterogenicity