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Relevance. Food allergy (FA) is an important public health concern, particularly among children, with an increasing prevalence. It is associated with a significant decrease in the quality of life for patients and their families due to the need to avoid allergens and the risk of severe allergic reactions, such as anaphylaxis. Despite active research, the primary treatment remains elimination diets, which limit patients’ options and highlight the need for new therapeutic solutions.Aim of the review. This review aims to summarize the current treatment methods for food allergy, discuss the challenges in evaluating the effectiveness of interventions, and highlight the importance of standardizing outcomes in clinical trials to improve comparability and practical relevance.Content. The review discusses modern therapeutic approaches for food allergy, such as oral, epicutaneous, and sublingual immunotherapies, which have shown positive results in achieving tolerance to allergens. Special attention is given to safety concerns, particularly for children, emphasizing the need for further research. The potential use of biological agents, such as omalizumab, in food allergy treatment is also explored. The review addresses challenges in choosing and standardizing endpoints in clinical trials, where most focus on desensitization and immunological markers, while patient-centered outcomes, such as quality of life, remain under-researched. The implementation of “core outcome sets” is highlighted as an important step toward improving data comparability and forming a more objective basis for clinical recommendations.Conclusions. The review emphasizes significant progress in food allergy treatment but notes the need for further research to ensure the safety of new therapies, particularly for children. Standardizing outcomes in clinical trials plays a key role in improving the quality and comparability of research, which will, in turn, help develop more effective clinical guidelines and improve patients’ quality of life.

This study investigates the optimization of Laser Powder Bed Fusion (LPBF) process parameters to enhance the mechanical properties of the Russian Ni superalloy VZh159 (a close analogue of IN718) material that is commonly used in critical aerospace applications, and the corresponding studies of the grain structure within and near the melt pool formed by a single laser scan line. Through a factorial experimental approach, the influence of laser power and scanning speed on the tensile strength, yield strength, and ductility was determined. Metallurgically sound samples (based on hydrostatic weighing data and microscopy, with practically no pores detected) were obtained with nine combinations of power and scanning speed, showing significant variation in the tensile strength (in the 1,040–1,220 MPa range) and yield strength (in the 560–1,100 MPa range), which correlated with the cross-sectional area of the single scan line (for example, the depth of the melt pool varied in the range 410–530 µm), while the average grain size (deduced from Electron Backscatter Diffraction (EBSD) images) remained statistically unchanged. Key findings indicate that the optimal LPBF parameters are a laser power of 250 W, a scanning speed of 600 mm/s, and a hatch distance of 0.12 mm, which together yield the best combination of high tensile strength and ductility. This study provides new insights into the effects of LPBF parameters on the microstructure, particularly the formation of the γ′ strengthening phase and its correlation with mechanical performance. The research addresses a critical gap in understanding the relationship between LPBF processing conditions and the resulting microstructural and mechanical properties, offering potential improvements in manufacturing efficiency and material performance.

Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body's natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

ObjectiveDelayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1.MethodsA total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year.ResultsAt biopsy, 54 patients had UPCR

In this study, composites obtained through low-temperature carbonization of elastomeric matrix highly filled with graphite, carbon black and short carbon fibers were studied for the purpose of determining residual stresses at different scales using a combination of several complementary methods. The state-of-the-art techniques included X-ray stress analysis using the sin2⁡ψ method, the micro-ring-core technique via Focused Ion Beam milling and Digital Image Correlation (FIB-DIC), the contour method, the strain gauge method, and the hole drilling technique with digital laser speckle pattern interferometry (DLSPI). It was found that the contour method could not be used implemented for residual stress evaluation due to the low electrical conductivity of composite. Moreover, the DLSPI hole drilling method did not reveal any fringes indicating significant residual stress level exceeding a few MPa. The strain gauge method also revealed a narrow residual stress distribution with an average value of approximately zero. In contrast, the X-ray sin2⁡ψ method as well as FIB-DIC technique both returned values of about 150–250 MPa. A hierarchical model of the composite is proposed based on the Davidenkov Type I–II–III stress classification that provides an explanation of these observations.

Abstract Metal-organic frameworks (MOFs) have emerged as a versatile material platform for a wide range of applications. However, the development of practical devices is constrained by their inherently low mechanical stability. The synthesis of MOFs in a monolithic morphology represents a viable way for the transition of these materials from laboratory research to real-world applications. For the design of MOF-based devices, the mechanical characterization of such materials cannot be overlooked. In this regard, stress-strain relationships represent the most valuable tool for assessing the mechanical response of materials. Here, we use flat punch nanoindentation, micropillar compression and Raman microspectroscopy to investigate the stress-strain behaviour of MOF monoliths. A pseudo-plastic flow is observed under indentation, where the confining pressure prevents unstable crack propagation. Material flow is accommodated by grain boundary sliding, with occasional stepwise cracking to accommodate excessive stress building up. Micropillar compression reveals a brittle failure of ZIF-8, while plastic flow is observed for MIL-68.

The urgency of the problem of community-acquired pneumonia in children is due to the high incidence rate. In the etiological structure of bacterial pneumonia, Streptococcus pneumoniae and Mycoplasma pneumonia (Mp) prevail.Purpose: to identify clinical, laboratory and instrumental features of mycoplasmal pneumonia in children.Materials and methods. A retrospective, single-center cohort study of 266 case histories of children aged 4 months to 17 years who were in Children’s City Clinical Hospital No. 9 in 2019 with a referral diagnosis of pneumonia was carried out. To verify the diagnosis of pneumonia, the method of chest X-ray was used, for the etiological diagnosis, the method of PCR swabs from the nasopharynx, ELISA for the detection of antibodies of the IgM and IgG classes was used. Results. The diagnosis of pneumonia was confirmed in 190 children. The diagnosis of pneumonia caused by M. pneumoniae (MpP) was established in 76 (40%) children, they made up the 1st group. The remaining 114 (60%) children with community-acquired pneumonia of another etiology (CAP) made up the 2nd group – comparisons. The diagnosis of MpP was confirmed in 46 (60.5%) children by the detection of IgM, in 12 (15.8%) by the detection of Mp genetic material, and in 18 (23.7%) by positive both IgM and PCR. The median age of children in the group with MpP was 9.6 years, in the comparison group – 4 years (p

The determination of residual stresses by combining blind hole drilling and optical interferometric measurement of relief deformation is re-visited to evaluate its applicability to aerospace structures. The experimental methodology involves drilling a deep blind hole and evaluating the hole diameter increments in the principal strain directions using electronic speckle-pattern interferometry (ESPI). This is followed by the determination of the principal residual stress components via the solution of the inverse correlation problem. The study presents the pathway to overcoming one of the primary obstacles in residual stress determination, namely, the optimization of the measurement and interpretation procedures to obtain reliable results. It can be concluded from the analysis of the problem that the formulae connecting the raw experimental data and to the sought residual stress component values lead to a well-posed inverse problem. This makes it possible to obtain estimations of the measurement uncertainty. High density fringe patterns from ESPI provide a rapid and reliable method for residual stress determination, as illustrated using examples of approximately 160 MPa stresses in irregular zones of thick-walled structures.

Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.

In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis. 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines. 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved. Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Polycrystalline diffraction is a robust methodology employed to assess elastic strain within crystalline components. The Extended Caking (exCaking) method represents a progression of this methodology beyond the conventional azimuthal segmentation (Caking) method for the quantification of elastic strains using Debye–Scherrer 2D X-ray diffraction rings. The proposed method is based on the premise that each complete diffraction ring contains comprehensive information about the complete elastic strain variation in the plane normal to the incident beam, which allows for the introduction of a novel algorithm that analyses Debye–Scherrer rings with complete angular variation using ellipse geometry, ensuring accuracy even for small eccentricity values and offering greater accuracy overall. The console application of the exCaking method allows for the accurate analysis of polycrystalline X-ray diffraction data according to the up-to-date rules presented in the project repository. This study presents both numerical and empirical examinations and error analysis to substantiate the method’s reliability and accuracy. A specific validation case study is also presented to analyze the distribution of residual elastic strains in terms of force balance in a Ti-6Al-4V titanium alloy bar plastically deformed by four-point bending.

This paper details the utilization of the focused ion beam digital image correlation (FIB-DIC) technique for measuring in-plane displacements and the employment of the height digital image correlation (hDIC) technique as a two-step DIC method for determining displacements without an out-of-plane component within the region of interest. Consideration is given to the microscopy data’s measurement scale and resolution to confirm the capability of both techniques to conduct micro-scale correlations with nano-scale sensitivity, making them suitable for investigating the residual elastic strains formed due to processing. The sequential correlation procedure of the FIB-DIC technique has been optimized to balance accuracy and performance for correlating sequential scanning electron microscope (SEM) images. Conversely, the hDIC technique prioritizes the accurate correlation of SEM images directly with the reference state without a sequential procedure, offering optimal computational performance through advanced parallel computing tools, particularly suited for correlating profilometry data related to large-scale displacements. In this study, the algorithm of the hDIC technique is applied as a two-step DIC to evaluate the elastic strain relaxation on the surface of a ring core drilled using a focused ion beam. Both techniques are utilized to correlate the same SEM images collected during the monitoring of the ring drilling process. A comparison of the correlation results of both techniques is undertaken to quantify the near-surface residual elastic strains, with an analysis conducted to discern the accuracy of the hDIC algorithm. Furthermore, the distinctions between the two techniques are delineated and discussed.

Aim. To study the relationship between the structural and functional left ventricular (LV) parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with type 2 diabetes (T2D) without clinical manifestations of cardiovascular diseases, as well as to evaluate the possibility of their use for early diagnosis of subclinical LV dysfunction.Material and methods. Data from 120 patients of both sexes aged 45-75 years (57,11±7,9 years) were analyzed. They were divided into three following groups: 1st — with T2D (n=47), 2nd — with prediabetes (n=20), 3rd — control (n=53). All participants underwent transthoracic echocardiography with assessment of the linear and volumetric heart dimensions, systolic and diastolic LV function. Speckle tracking echocardiography was analyzed with calculation of LV global longitudinal strain (GLS). The blood levels of NT-proBNP and inflammatory markers were determined (high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6).Results. According to echocardiography, patients with carbohydrate metabolism disorders revealed significantly higher LV mass values, LV posterior wall thickness, and relative wall thickness in comparison with the control group. Transmitral flow parameters, as well as tissue Doppler sonography, in the T2D and prediabetes groups were significantly different from those in the control group. GLS in the groups of patients with carbohydrate metabolism disorders was lower than in the control group (p=0,001). The level of NT-proBNP was significantly higher in the T2D and prediabetes groups compared to the control group, while in all three groups it did not exceed normal values (p

Transient receptor potential (TRP) channels are a large and diverse family of transmembrane ion channels that are widely expressed, have important physiological roles, and are associated with many human diseases. These proteins are actively pursued as promising drug targets, benefitting greatly from advances in structural and mechanistic studies of TRP channels. At the same time, the complex, polymodal activation and regulation of TRP channels have presented formidable challenges. In this short review, we summarize recent progresses toward understanding the structural basis of TRP channel function, as well as potential ligand binding sites that could be targeted for therapeutics. A particular focus is on the current understanding of the molecular mechanisms of TRP channel activation and regulation, where many fundamental questions remain unanswered. We believe that a deeper understanding of the functional mechanisms of TRP channels will be critical and likely transformative toward developing successful therapeutic strategies targeting these exciting proteins. This endeavor will require concerted efforts from computation, structural biology, medicinal chemistry, electrophysiology, pharmacology, drug safety and clinical studies.