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INTRODUCTION. In 2023, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published a new Guideline on Analytical Procedure Development (ICH Q14) and a revised version of the Guideline on Validation of Analytical Procedures (ICH Q2(R2)). Consequently, there is a need for a considerable revision of the approach to the development and validation of analytical procedures that is currently used in the Eurasian Economic Union (EAEU). A revision is also needed for the processes for evaluating and introducing variations to the analytical procedures described in medicinal product registration dossiers.AIM. This review aimed to analyse the significant changes made to international approaches to the development of analytical procedures, as well as to study the advantages and disadvantages of these approaches for pharmaceutical manufacturers and regulatory agencies in the EAEU.DISCUSSION. This review covers the key provisions and practical aspects of the enhanced approaches to the development of analytical procedures introduced by the ICH Q14 guideline. In particular, the review addresses the concepts of the analytical procedure life cycle (APLC) and the modified analytical quality-by-design (AQbD) approach; the development of the analytical target profile (ATP); analytical quality risk management; planning of the design of experiments (DoE) and the analytical procedure control strategy; and the validation, subsequent verification, transfer, and change management of analytical procedures. Additionally, the review describes the ICH Q2(R2) updates that accompany this new regulatory paradigm.CONCLUSIONS. The above guidelines fill the existing gap in recommendations for the development of analytical procedures. The use of the APLC and AQbD concepts provides both pharmaceutical companies and regulatory authorities with flexible approaches that are applicable to analytical procedures both during the development phase and once they have been implemented. Effective implementation of these international approaches in the Russian pharmaceutical industry and regulatory system requires a broad discussion between pharmaceutical industry professionals and regulatory agency experts, possibly, as part of a pilot project. After that, there will be a necessity to provide training for specialists involved in the development of analytical procedures and to amend the EAEU Rules for Marketing Authorisation and Expert Assessment of Medicinal Products for Human Use.

Quantification of pattern distortion in nanoimprint lithography (NIL) is required when applying it to specific applications, especially those with tight tolerances. We present a systematic study on full wafer NIL distortion using soft stamps made of different carrier foils and UV-curable polymer structure layers. These errors are evaluated by overlay patterning using NIL and optical lithography on 4-in. wafers over a distance of 80 mm. Potential causes for pattern distortion and possible correction methods are discussed in terms of stamp composition and environmental impact. Pattern distortion along axes causing dimensional change is stamp dependent, and stiffer stamps show less pattern dimensional change than the softer ones. In the best case, the minimum variation is 4 parts per million (ppm), and in the worst case, 252 ppm with a softer stamp. Stamp flatness and uniform contact during imprinting are important in reducing high-order pattern distortion. A maximum dimensional variation of 32 ppm in a batch run demonstrates good pattern repeatability. Long-term dimensional stability can be affected by relative humidity, with variations on the order of 100 ppm.

Introduction. Approaches to treatment of infertility have been progressively updated because the field of assisted reproductive technologies (ART) is a science-based symbiosis of the latest knowledge and advances in medicine, biology, and genetics. Today, a real-world clinical practice of a reproductive specialist needs to be assessed in the Russian Federation (RF) both in terms of a retrospectively analyzed development of RF in vitro fertilization (IVF) technologies and identifying promising approaches for infertility treatment in the future.Aim: analysis of current therapeutic tendencies and promising trends in real clinical practice of infertility in the Russian Federation.Materials and Methods. In 2022–2023 under the auspices of the Institute for Preventive and Social Medicine and the National Alliance for Public Health Advancement, a survey of reproductive doctors practicing at commercial and government ART centers was carried out. The questionnaire contained questions regarding describing a RF female patient’s portrait with an expected ovarian reserve and response to ovarian stimulation to propose a choice of ovarian stimulation protocol as well as basic and concomitant pharmacotherapy.Results. The opinion of 425 fertility doctors from 156 ART centers in 42 cities of the Russian Federation was assessed. A portrait of a female patient with infertility in the Russian Federation was determined in accordance with the ovarian reserve, expected response to gonadotropin-based stimulation (normal response – 40 %, hyporesponse – 40 %, hyperresponse – 20 % of patients). The basic pharmacotherapy in the stimulation protocol in the IVF program based on agonists and antagonists of gonadotropinreleasing hormone (GnRH), various gonadotropin-containing drugs in female patients with expected normal, hypo- and hyperresponse to ovarian stimulation was assessed. The dominant protocol consists of using GnRH antagonist most often observed in patients with hyper- (95 % of cases), normal (75 % of cases) and hypo-response (45.5 %). Preferences in the basic and concomitant pharmacotherapy in IVF programs were identified as well as current trends in embryo transfer in fresh and cryoprotocols (a tendency to freeze all obtained embryos - “freeze-all” strategy), preimplantation genetic testing methods (used in 30 % of protocols in normal responders, 60 % in hyporesponders and 10 % in hyperresponders) were described.Conclusion. Our study provides the most large-scale analysis of the real-world clinical practice of RF reproductive specialists. A portrait of a RF female patient with infertility, expected ovarian reserve and response to ovarian stimulation was described. Contemporary approaches to select stimulation protocol, basic and concomitant pharmacotherapy in real-world clinical practice were identified. The data obtained represent an important significant cross-section for current practical approaches in real-world practice of RF fertility doctors and can serve as the basis for assessing developing ART methods in the Russian Federation as well as be used to create an evidence base for analyzing future clinical and economic effectiveness of IVF programs in the Russian Federation.

This article presents the results of a detailed paleomagnetic study of five sections of the Permian-Triassic sedimentary rocks from the southeastern part of the Volga-Ural anteclise in the East European Platform (Orenburg region, Russia): Boevaya Gora, Vyazovka, Sambulak, Krasnogor, and Vozdvizhenka. The magnetic fabric determined by magnetic susceptibility anisotropy indicates that the rocks accumulated under the conditions of intense hydrodynamic activity. This makes it possible to reconstruct a predominantly submeridional transport of detrital material. The rocks of the Boevaya Gora section have a bipolar distribution of the characteristic component of their remanent magnetization, while other sections show a reversed polarity. In the Vyazovka section, the E/I method was used to calculate the inclination shallowing coefficient of the rocks (f = 0.79). The regional fold test yielded positive results, suggesting that the rocks of the studied sections were displaced after the deposition. For each section, paleomagnetic poles were calculated, with the poles of the Boevaya Gora and Vyazovka sections being the most reliable. The mean paleomagnetic pole coordinates of the studied sections, except the Sambulak section, are as follows: slat = 51.7°, slong = 55.8°, n = 4, plat = 48.5°, plong = 173.4°, α95 = 3.4°, paleolat = 23.4°.

IntroductionThe blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.MethodsInformation on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.ResultsThe median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab (n = 4) and sarilumab (n = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.ConclusionThe treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

A pair of nanostructured mirrors made of a diffraction grating inscribed in the top layer of a Bragg mirror are designed such that a phase shift near π and different reflected amplitudes exist between transverse electric (TE) and magnetic (TM) reflected polarization states at normal incidence. When a standing wave laser resonator is formed with two such mirrors and the two mirrors’ principal axes are twisted one with respect to the other, this phase shift condition suppresses multiple longitudinal mode emission arising from axial spatial hole burning. In addition, the different amplitudes of TE and TM reflected polarizations create polarization eigenstates with different round-trip losses, suppressing one polarization eigenstate. Laser experiments made with a Yb3+-doped Y3Al5O12 active material reveal enhanced purity of the emission spectrum compared to similar lasers using conventional laser mirrors. The proposed design enables a miniature single mode laser, replacing more complex designs usually needed to achieve that goal.

The relevance of the study is determined by the search for new solid fuels to expand the fuel and energy complex and improve resource-saving and environmentally friendly energy. The main aim: a comprehensive study of cardboard and coal combustion, including the determination of the main characteristics of the combustion of solid fuel mixtures, the determination of the main kinetic parameters and the establishment of the role of the components in the mixture combustion. Object: solid fuel mixture based on Kaa-Khem coal and cardboard. Methods. Thermal characteristics of fuels are determined according to: analytical moisture – SS R 33503-2015; ash content – SS R 55661-2013; yield of volatile components – SS R 55660-2013; calorific value – SS R 147-2013; content of carbon, hydrogen, nitrogen – SS R 32979-2014; oxygen – SS R 27313-2015; sulfur – SS 8606-2015. The fuel combustion was studied using an SDT Q600 differential thermal analyzer (TA Instruments-Waters LLC, USA). Ignition and burnout temperatures were determined using the curve crossing method. To determine the kinetic characteristics of individual fuels and fuel mixtures, a method based on the Coates–Redfern model was used. Results. The heat of combustion of Kaa-Khem coal is twice that of cardboard, while the volatile content of cardboard is 1,8 times higher than that of coal, which makes cardboard a promising additional fuel. An increase in the mass fraction of cardboard in the mixture does not affect the ignition temperature of the mixture and is about 300 °С. The addition of 25 % cardboard to coal has a positive effect on coal carbon residue combustion, increasing the maximum reaction rate by 30 % compared to the calculated data. The activation energy in this case is reduced by 3 9%, the combustion index is reduced by 2,5 times. The results of this study can be applied in the design of new heat and power equipment, or be taken into account when converting coal-burning boilers to burning solid fuel mixtures.

Abstract The chemical composition, structural and plastometric properties of different-ranked coals from Mongolia deposits were studied. The non-isothermal iso-conversion Ozawa–Flynn–Wall and Friedman model-free methods were used to assess kinetic parameters and to differentiate decomposition steps. Key peculiarities of the pyrolysis kinetics of brown and bituminous coals were revealed and discussed in terms of the composition and plastometric properties. Brown coal was shown to undergo three decomposition steps with ever increasing activation energy as temperature increased because of the decomposition of thermally more and more stable molecular fragments. The pyrolysis of bituminous coals occurred in four steps, the activation energy having extreme mode of temperature dependence. An important new finding was that the temperature range of the second, major pyrolysis step well corresponded to that between the softening and re-solidification temperatures according to Gieseler plastometry. The yield and composition of the pyrolysis products obtained under isothermal conditions were also characterized depending on coal rank and temperature, and the ways for qualified utilizations were offered.

Proteins synthesized by cells of various tissues may have common functions, but at the same time have a heterologous structure. Previously, it was experimentally confirmed that lung suffractant proteins can be synthesized by chondrocytes of articular cartilage. Articular cartilage proteoglycans, such as lubricin (PRG4) and aggrecan (ACAN), have partially similar functions to surfactant proteins (SP-A, SP-B, SP-C, and SP-D). The main goal of the work was to evaluate of structural homology between these proteins. The Ugene program was the source of the of multiple and paired alignment results using the ClustalW and Smith–Waterman algorithm, and the MEGA11 program provided phylogenetic analysis. A common domain of the Lectin C-type family with a high degree of similarity to the domains of EGF-like proteoglycans (ACAN) and SMB 1 (PRG4) was found in ALAN, SP and SP-D proteins. The Sasposin domains of the SP-B protein had the greatest similarity with the PRG4 and ACAN domains over 57%. The BRICHOS domain of the SP-C protein had similarities with the SMB1, SMB2 (PRG4) and EGF-like (ACAN) domains. The mucin domain in the PRG4 structure was not detected. The phylogenetic analysis revealed about stidied proteins to have low level of evolution homology, as evidenced by bootstrap support.

The advent of the COVID-19, specialists are increasingly encountering previously unknown pathological conditions in their practice. For some time, we have believed that COVID-19 in children is most often mild and asymptomatic. However, with the passage of time and the accumulation of the experience, it became obvious that the new infectious disease it will be quite severe in children. Differential diagnosis of multiple organ disorders in children during the COVID-19 pandemic should be primary carried out with the Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C), as well as Long-COVID-19. According to published data, the manifestations of these conditions are due to frequent lesions of the gastrointestinal tract (60–100 %), cardiovascular (80 %), nervous (29–58 %) and respiratory (21–65 %) systems. At present, there is no exact idea of these pathological conditions, the criteria for their diagnosis and the tactics of managing children, not only at the stage of diagnosis, but also at the stage of observation. The authors present a diagnostically complex clinical case describing the development of multiple organ damage in a 7-year-old child after contact with a mother who was sick with COVID-19. The data on the course features, the results of the examination and the difficulties of differential diagnosis of this case with other diseases with a similar clinic are summarized.

The article is devoted to the peculiarities of the perception of blacksmiths and blacksmithing by the folklore consciousness of the indigenous ethnic groups of the southern part of the Russian Far East — the Nanais, Orochs, Ulchis, Negidals, Udeges, Oroks (Uilta) of Sakhalin, who are considered to be distant descendants of the Mohe and Jurchens. The novelty of the study lies in the fact that for the first time from the general array of the narrative folklore of the Tungus-speaking peoples, texts were singled out, where the central character is an anthropomorphic character, in the guise of which the main tools of blacksmithing are presented: a head-hammer, a chest — blacksmith furs, legs-skewers, hands ticks. The study showed that in the oral work of the Far Eastern aborigines, iron and craft attributes often received a negative assessment; the magical properties attributed to the blacksmith were transferred to iron products and tools of his labor, represented by images of cannibalistic monsters. At the same time, the masters themselves could remain positive heroes, endowed with the features of a demiurge. At the same time, the masters themselves could remain positive heroes, endowed with the features of a demiurge. It is concluded that the anthropomorphization of blacksmith tools is a representative element of the plot, widespread among the Far Eastern Tungus-Manchus, but unknown to the Nivkhs.

IntroductionThe present study aimed to describe the phenotypic features and genetic spectrum of arrhythmogenic cardiomyopathy (ACM) presented in childhood and test the validity of different diagnostic approaches using Task Force Criteria 2010 (TFC) and recently proposed Padua criteria.Patients and methodsThirteen patients (mean age at diagnosis 13.6 ± 3.7 years) were enrolled using “definite” or “borderline” diagnostic criteria of ACM according to the TFC 2010 and the Padua criteria in patients

This paper presents the results of a systematic analysis of the design of inheritance by contract, which is quite new for Russian legislation and its place in the system of agricultural land turnover. This novel was introduced in 2019 and, of course, received some critical assessment from both legal scholars and law enforcement officials. The paper raises a number of issues related to some unequal characteristics of the rights and obligations of the testator and the heir, possible difficulties in applying within the framework of inheritance of agricultural land. In fact, the parties to the inheritance agreement, based on the right regulation of their status, have unequal opportunities to protect their interests, the testator is endowed with greater will and freedom when making and implementing this transaction. Nevertheless, the formation of new norms in legislation, especially in the civil law sphere, has a direct significant impact on the sustainable development of the agro-industrial complex in particular and, in general, on the self-determination of Russian statehood and its integration into the world system. The author analyzes the results of the legal regulation of this institution in foreign legislation, as well as examines historical experience. A study of the inheritance system in other states, as well as a comparative legal analysis of the legislations of various countries, has been conducted. In the course of the study, the author comes to the conclusion that there is a need for more detailed regulation and legislative regulation of this institution, working out clear criteria for distinguishing an inheritance contract from inheritance by will, as well as eliminating practical difficulties for using it in the agro-industrial complex, including when inheriting agricultural land.

The paper considers the construction of a very low-level waste disposal facility (VLLW) at the Rostov NPP with a volume of 11,000 m3. Information about formation and management of VLLW at Rostov NPP is given. Characteristics of 11,000 m3 VLLW disposal facility is presented. The design documentation provides for construction of the VLLW disposal facility intended for disposal of very low-level waste of hazard classes IV and V formed as a result of Rostov NPP production activities and meeting the criteria of disposal acceptability.

Background: Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography either by invasive catheterization (ICA) or computed tomography (CTA). Prior studies employed single-molecule, amplification-independent RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD. The present studies employed Illumina RNAseq and network co-expression analysis to identify systematic changes underlying CAD. Methods: Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by Illumina total RNA sequencing (RNAseq) to identify transcripts associated with CAD in 177 patients presenting for elective invasive coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs) and to identify patterns of changes through whole genome co-expression network analysis (WGCNA). Results: The correlation between Illumina amplified RNAseq and the prior SeqLL unamplified RNAseq was quite strong (r = 0.87), but there was only 9 % overlap in the DEGs identified. Consistent with the prior RNAseq, the majority (93 %) of DEGs were down-regulated ∼1.7-fold in patients with moderate to severe CAD (>20 % stenosis). DEGs were predominantly related to T cells, consistent with known reductions in Tregs in CAD. Network analysis did not identify pre-existing modules with a strong association with CAD, but patterns of T cell dysregulation were evident. DEGs were enriched for transcripts associated with ciliary and synaptic transcripts, consistent with changes in the immune synapse of developing T cells. Conclusions: These studies confirm and extend a novel mRNA signature of a Treg-like defect in CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.

The work determines the characteristics of the processes of thermal decomposition and combustion when heating coal, cedar needles, and their mixtures with different fuel particle sizes. Based on the results of thermal analysis, the following characteristics were determined: the temperature at which the coke residue ignition occurs, the temperature at which the combustion process is completed, and the combustion index. An analysis was carried out of the interaction between the fuel mixture components on the characteristics of their combustion for compositions (50% coal and 50% biomass) with a particle size of 100–200 μm and 300–400 μm. The combustion kinetic parameters of individual solid fuels and their mixtures containing 50% coal and 50% biomass are compared. The activation energy for coal combustion was 60.3 kJ mol−1, for biomass 24.6 kJ mol−1, and for mixture 42.5 kJ mol−1. The co-combustion of coal and biomass has a positive effect on the main combustion characteristics of solid fuels. Fuels with particle sizes of 100–200, 200–300, and 300–400 μm were studied at temperatures of 500–800 °C under heating conditions in a heated airflow. Using a hardware-software complex for high-speed video recording of fast processes, the ignition delay times were determined, the values of which for the considered fuels vary in the range from 0.01 to 0.20 s. Adding 50 wt% biomass with particle sizes of 100–200, 200–300, and 300–400 μm to coal reduces the ignition delay times of mixtures by 55, 41, and 27%, respectively. The results obtained can become the basis for the conversion and design of modern power plants operating on solid fuel mixtures to co-combust coal with biomass.