NLRP12-related autoinflammatory disease (NLRP12-AID) is an exceptionally rare autosomal dominant disorder caused by germline mutations in NLRP12 gene. Very few patients with NLRP12-AD have been ...identified worldwide; therefore, there is a scarcity of data on phenotypic presentation of this syndrome. Here we provide evidence that NLRP12-AID may have clinical manifestations characteristic for primary immune deficiencies (PID). 246 children with periodic fever (PF) of unknown origin were subjects to the next generation sequencing (NGS) analysis; 213 of these patients had signs of primary immunodeficiency (PID) manifested by recurrent infections, while 33 kids had isolated PF. The NGS panel was composed of 302 genes implicated in PID and/or AID. 15 patients (9 girls and 6 boys) with NLRP12-AID were identified. Median age of first AID-related fever episode was 12 months, ranging from 2 months to 13 years. Main clinical features of NLRP12-related AID were periodic fever (100%), abdominal pain and diarrhea (47%), arthralgia (20%), headache (20%) and failure to thrive (33%). Nine patients demonstrated increased susceptibility to infection and two children suffered from Crohn’s disease. Administration of short courses of NSAID or corticosteroids resulted in resolution of the disease flare. In one severe case, canakinumab (anti-interleukin-1β antibody) was successfully used. Significant number of patients with genetically assigned diagnosis of NLPR12-AID has clinical features which close resemble primary immune deficiency. This phenotypic overlap may result in underdiagnosis of NLPR12-AID among patients with PID.
Primary immune deficiencies are usually attributed to genetic defects and, therefore, frequently referred to as inborn errors of immunity (IEI). We subjected the genomic DNA of 333 patients with ...clinical signs of IEI to next generation sequencing (NGS) analysis of 344 immunity‐related genes and, in some instances, additional genetic techniques. Genetic causes of the disease were identified in 69/333 (21%) of subjects, including 11/18 (61%) of children with syndrome‐associated IEIs, 45/202 (22%) of nonsyndromic patients with Jeffrey Modell Foundation (JMF) warning signs, 9/56 (16%) of subjects with periodic fever, 3/30 (10%) of cases of autoimmune cytopenia, 1/21 (5%) of patients with unusually severe infections and 0/6 (0%) of individuals with isolated elevation of IgE level. There were unusual clinical observations: twins with severe immunodeficiency carried a de novo CHARGE syndrome‐associated SEMA3E c.2108C>T (p.S703L) allele; however, they lacked clinical features of CHARGE syndrome. Additionally, there were genetically proven instances of Netherton syndrome, Х‐linked agammaglobulinemia, severe combined immune deficiency (SCID), IPEX and APECED syndromes, among others. Some patients carried recurrent pathogenic alleles, such as AIRE c.769C>T (p.R257*), NBN c.657del5, DCLRE1C c.103C>G (p.H35D), NLRP12 c.1054C>T (p.R352C) and c.910C>T (p.H304Y). NGS is a powerful tool for high‐throughput examination of patients with malfunction of immunity.
Vaccination is critical to preventing the spread of diseases. It stimulates the immune system to produce antibodies that fight specific diseases, eradicating and reducing their incidence. However, ...despite the proven benefits, there is hesitation and skepticism in some areas due to side effects and lack of knowledge. Developing a data collection and processing system to analyze vaccination is critical in today’s world. Vaccines are necessary to minimize morbidity and mortality, but success depends on analyzing data on vaccine use and efficacy. This system can identify potential side effects and adverse reactions, ensuring vaccine safety and building public confidence. This research focuses on IT support for analyzing vaccination side effects. The aim of this work is to develop an architecture model of the system to collect and process data on the health status of vaccinated patients. The research methodology consists of analyzing sources on the consequences and side effects of vaccination. On the basis of this knowledge, the key attributes (stakeholders, sources of information, input data, data analysis processes) of the data collection and analysis system were analyzed using an enterprise architecture approach. As a result, a general model of the architecture of the data collection and analysis system was proposed.
The novel class of gallium catalysts based on cationic gallium phthalocyanines (RPcGa+) with SbF6 – and Sb2F11 – weakly coordinating anions was developed in order to using in the catalytic version ...for gallium-specific chemistry. Two cycloaddition/annulation processes of styrylmalonates with aromatic aldehydes and styrene were implemented in the catalytic version using this approach. The synthetic strategy to gallium phthalocyanines and their structural features were studied in details, including the use of specially adapted 71Ga NMR spectroscopy in combination with 19F and 121Sb ones, as well as the mechanistic aspects.
The rearrangement of cyclopropylketone arylhydrazones generated in situ from arylhydrazine hydrochlorides and ketones leads to formation of tryptamine derivatives. The use of ...(2-arylcyclopropyl)ethanones in the reactions with model 4-bromophenylhydrazine hydrochloride gives branched tryptamines with aryl groups in the α-position to the amino group, while (2-methylcyclopropyl)ethanone gives a mixture of α- and β-substituted products in a ratio of 1:3. The method was found effective in the synthesis of enantiomerically pure tryptamine. Thus, (R,R)-(2-phenylcyclopropyl)ethanone gives the (S)-α-phenyltryptamine derivative with an enantiomeric excess over 99%.
Information technologies (IT) architecture and infrastructure is a significant cost item, especially for enterprises with complex production infrastructure and equipment that require automated and ...digital devices to collect and process primary data on technological and production processes. Most investment models for enterprise-wide development projects usually do not take into account the automation's costs, including the design and implementation of information systems. The Enterprise Architecture (EA) paradigm has been proposed to bridge the gap between the business and the IT sector. The study aims to develop investment models for projects for the implementation and development of EA solutions, including IT architectures that eliminate the shortcomings of existing approaches. The research methodology is based on the analysis of published approaches to investment models for projects creating and developing EA, IT architectures with the identification of their advantages and limitations, and on the analysis of IT investment assessment practices in Russian infrastructure-intensive companies. As a result, investment and appraisal models are proposed that have advantages associated with the ability to calculate the effect of an integrated approach to the implementation of IT solutions, a more accurate calculation of an investment project cost by taking into account the IT system's cost, a reduction in the investment cycle of development and implementation of architectural solutions, including physical and IT component.
The COVID-19 pandemic has severely tested humanity, revealing the need to develop and improve the medical, economic, managerial, and IT components of vaccine management systems. The vaccine lifecycle ...includes vaccine research and development, production, distribution, and vaccination of the population. To manage this cycle effectively the proper organizational and IT support model of the interaction of vaccine lifecycle management stakeholders is needed - which are an innovation ecosystem and an appropriate virtual platform. A literature review has revealed the lack of methodological basis for the vaccine innovation ecosystem and virtual platform. This article is devoted to the development of a complex approach for the development of an innovation ecosystem based on vaccine lifecycle management and a virtual platform which provides the data exchange environment and IT support for the ecosystem stakeholders. The methodological foundation of the solution, developed in the article, is an enterprise architecture approach, CALS technologies, supply chain management and an open innovation philosophy. The results, presented in the article, are supposed to be a reference set of models for the creation of a vaccine innovation ecosystem, both during pandemics and periods of stable viral load.
The reaction of di(methoxycarbonyl)tetrazine with substituted cycloprop‐2‐ene‐1‐carboxylates gives a series of 3,4‐diazanorcaradienes and 1,2‐diazepines. The influence of the nature of cyclopropenes ...and the reaction conditions on its selectivity was investigated. The addition of nucleophiles to norcaradienes was studied and a rare example of the “walk” rearrangement in this class of compounds was revealed.
Methyl cyclopropenecarboxylates and dimethoxycarbonyltetrazine undergo cascade cycloaddition and retro‐cycloaddition reactions. Depending on substituents in cyclopropenes the reaction either leads to diazanorcaradienes or is accompanied with an electrocyclic ring‐opening and a proton migration or a “walk” rearrangement.
The purpose of this paper is to describe how government could support the green initiatives using various policies. In this report was considered the example of Estonia and how this European country ...implies a feed-in tariff model. The subsidy solicitation was described and compared to the real project of solar panel construction. Current paper could be beneficial for those who would like to gain more theoretical understanding how countries increase the interest in renewable energy investing among local citizens.
As Russian economy is still largely oriented on commodities production, there are a lot of cities where mining and commodity-oriented enterprises are the backbone of city economy. The mentioned ...enterprises mostly define the life quality of citizens in such cities, thus there are high requirements for engineering of city-forming enterprises. The paper describes the enterprise architecture approach for management system engineering of the mining enterprises. The paper contains the model of the mining enterprise architecture, the approach to the development and implementation of an integrated management system based on the concept of enterprise architecture and the structure of information systems and information technology infrastructure of the mining enterprise.
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