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Background and aimsThere is an increased risk of lymphomas in inborn errors of immunity (IEI); however, germline genetic testing is rarely used in oncological patients, even in those with early onset of cancer. Our study focuses on a child with a recombination-activating gene 1 (RAG1) deficiency who was identified through a screening program for Slavic founder genetic variants among patients who died with malignancy at an early age in Belarus.ResultsWe identified one homozygous founder RAG1 variant out of 24 available DNA samples from 71 patients who developed lymphoma aged

Background. Among patients who have undergone coronary artery bypass surgery (CABG), the proportion of people with diabetes mellitus (DM) is about 40 %. To date, the problem of choosing the optimal method of surgical myocardial revascularization, which can provide the best result in this cohort, remains completely unresolved. The aim of the study. To assess the in-hospital and long-term results of bimammary and traditional bypass surgery in patients with type 2 diabetes mellitus. Methods. From September 2018 to December 2021, 176 CABG surgeries were performed in patients with coronary heart disease (CHD) and type 2 diabetes at the Federal Center for Cardiovascular Surgery (Krasnoyarsk). Group 1 (n = 45) included patients who underwent myocardial revascularization using two mammary arteries; group 2 (n = 131) included patients who underwent myocardial revascularization using traditional technique. After propensity score matching, 45 patients were selected into each group, comparable by basic preoperative characteristics. Results. In group 1, cardiopulmonary bypass surgeries were performed in 23 (51.1 %) patients (group 1CPB), off-pump surgeries – in 22 (58.2 %) (group 1OP); in group 2, all patients underwent cardiopulmonary bypass surgeries. Hospital mortality was recorded in group 2 in 1 (2.2 %) case. Deep sternal infection developed in 1 (4.5 %) patient in group 1OP. Long-term survival in group 2 was 85.3 %, in group 1CPB – 83.3 % (p = 0.689), in group 1OP – 84.2 % (p = 0.739). 84.2 % of patients in group 2 and 100 % in groups 1CPB and 1OP had no cardiovascular events (p = 0.144 and p = 0.145, respectively). Conclusion. Bimammary bypass surgery in patients with type 2 diabetes is a safe and effective method of surgical treatment of coronary artery disease in both shortand long-term period and may be the operation of choice in patients with multivessel disease. There were no differences in patient survival up to 45 months; bimammary revascularization was associated with 100 % absence of cardiac mortality.

Optimization methods, namely, gradient optimization methods, are a key part of neural network training. In this paper, we propose a new gradient optimization method using exponential decay and the adaptive learning rate using a discrete second-order derivative of gradients. The MAMGD optimizer uses an adaptive learning step, exponential smoothing and gradient accumulation, parameter correction, and some discrete analogies from classical mechanics. The experiments included minimization of multivariate real functions, function approximation using multilayer neural networks, and training neural networks on popular classification and regression datasets. The experimental results of the new optimization technology showed a high convergence speed, stability to fluctuations, and an accumulation of gradient accumulators. The research methodology is based on the quantitative performance analysis of the algorithm by conducting computational experiments on various optimization problems and comparing it with existing methods.

The Linum Insertion Sequence 1 (LIS-1) occurs in the genetically plastic flax genotypes in response to the lack or excess of mineral and water nutrition, but also naturally, and can be transmitted to the progeny. We have analyzed 21 ancient Belarusian varieties of flax Linum usitatissimum convar. elongatum Vav. et Ell. The LIS-1 presence or absence was checked for individual plants in at minimum two generations with primer-specific polymerase chain reaction (PCR) and agarose gel electrophoresis. The studied flax varieties formed four groups: non-responsive varieties (LIS-1 was not found, group NR); responsive, which formed and completely lost the insertion (group R0); responsive, which formed and retained LIS-1 (group R1); and responsive unstable (group R2). A statistically significant difference was found in ‘plant height’ (p < 0.05), ‘technical length of the stem’ (p < 0.05) between R0 and NR, and R2 and NR LIS-1 groups. The machine learning algorithm random forest classifier was used to predict the presence, absence or heterozygosity of LIS-1 in flax plants based on their growth and reproductive characteristics. As a result, the accuracy of the prediction was 98% on test data. In terms of sources for the selection of fibre flax varieties adaptive to environmental challenges, the most promising group consists of responsive varieties that have formed LIS-1 insertion (R0, R1 and R2 groups).

Aim. To evaluate the long-term results of complete bilateral internal thoracic artery (BITA) grafting and traditional coronary bypass grafting (CABG) in patients with multivessel CAD.Material and methods. From June 2018 to December 2021, 646 CABG operations were performed in patients with multivessel CAD at the Federal Center for Cardiovascular Surgery (Krasnoyarsk). There were 178 patients receiving BITA grafting and 468 — traditional revascularization technique. After propensity score matching, 356 patients were selected, of which 99 had on-pump BITA (group 1), 178 — on-pump traditional revascularization (group 2), and 79 — off-pump BITA (group 3). There were more males (p=0,143 and p=0,547). The groups were comparable in age (p=0,343 and p=0,104), body mass index (p=0,532 and p=0,759), diabetes (p= 0,705 and p=0,667), the number of hemodynamically significant coronary stenoses (p=0,370 and p=0,595).Results. The follow-up period lasted 32,8±8,52 months. Long-term patient survival was 83,9% in group 2,93% in group 1 (p=0,041) and 94% in group 3 (p=0,039). Freedom from cardiovascular mortality was 100% in both groups of BITA grafting and 92,5% in group 2 (p=0,001 and p=0,039), freedom from major cardiovascular events was 94,2% in group 1, 85,1% in group 2 and 98,5% in group 3 (p=0,032 and p=0,03).Conclusion. BITA grafting is a modern effective and safe method of surgical myocardial revascularization both on- and off-pump. Up to 33 months. BITA grafting was associated with significantly better patient survival, complete freedom from cardiovascular mortality and a lower incidence of major cardiovascular events.

AIOLOS, also known as IKZF3, is a transcription factor that is highly expressed in the lymphoid lineage and is critical for lymphocyte differentiation and development. Here, we report on 9 individuals from 3 unrelated families carrying AIOLOS variants Q402* or E82K, which led to AIOLOS haploinsufficiency through different mechanisms of action. Nonsense mutant Q402* displayed abnormal DNA binding, pericentromeric targeting, posttranscriptional modification, and transcriptome regulation. Structurally, the mutant lacked the AIOLOS zinc finger (ZF) 5-6 dimerization domain, but was still able to homodimerize with WT AIOLOS and negatively regulate DNA binding through ZF1, a previously unrecognized function for this domain. Missense mutant E82K showed overall normal AIOLOS functions; however, by affecting a redefined AIOLOS protein stability domain, it also led to haploinsufficiency. Patients with AIOLOS haploinsufficiency showed hypogammaglobulinemia, recurrent infections, autoimmunity, and allergy, but with incomplete clinical penetrance. Altogether, these data redefine the AIOLOS structure-function relationship and expand the spectrum of AIOLOS- associated diseases., Introduction The IKAROS family members consist of 5 zinc-finger (ZF) transcription factors encoded by IKZF1 to IKZF5. IKAROS (IKZF1), HELIOS (IKZF2), and AIOLOS (IKZF3) are highly expressed in the lymphoid [...]

Aim. To identify predictors of heart failure in patients with dilated cardiomyopathy (DCM) and ischemic myocardial dilatation (IMD).Material and methods. In total, we examined 221 patients with cardiomyopathies: DCM and IMD. The mean age of the patients was 55,30±9,69 years (minimum — 20 years, maximum — 77 years). From the total number of patients, a group of patients with DCM (idiopathic origin) (group 1) was identified in the amount of 111 people, of which 99 were men (89,2%) and 12 women (10,8%). The mean age of patients with DCM was 51,73±9,74 years, for men — 51,00±8,96 years, for women — 57,75±3,71 years. The median age in DCM patients was 53,00 [48,00; 58,00], for men — 53,00 [46,00; 57,00], in women — 59,50 [49,00; 68,75]. Patients with IMD (ischemic origin) consisted of 110 people (group 2), of which 100 were men (91,5%) and 10 women (8,5%). The mean age of patients with IMD was 58,68±8,38 years, for men — 58,29±8,46 years, for women — 62,90±6,29 years. The median age in patients with IMD was 58,00 [53,50; 63,50], in men — 58,00 [52,00; 63,00], in women — 61,50 [59,25; 66,00]. Biological material (venous blood) was taken from all patients for molecular genetic analysis. To isolate the DNA structure, the phenol-chloroform extraction was used. Using the polymerase chain reaction, genotyping of gene polymorphisms was carried out, followed by analysis of restriction fragment length polymorphisms.Results. To assess the left ventricular systolic function, the ejection fraction was assessed. Heart failure and its severity are most often associated with a decrease in left ventricular (LV) systolic function. In our study, in the group of patients with DCM, the mean LV ejection fraction (EF) was 25,105±6,76, while in IMD group — 20,255±4,49 (p=0,0001). This confirms that these two groups have severe heart failure associated with impaired LV systolic function — a decrease in EF

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants. Longitudinal analysis showed persistent T cell lymphopenia during infancy, often associated with nail dystrophy. Adult individuals with heterozygous FOXN1 variants had in most cases normal CD4+ but lower than normal CD8+ cell counts. We hypothesized a FOXN1 gene dosage effect on the function of thymic epithelial cells (TECs) and thymopoiesis and postulated that these effects would be more prominent early in life. To test this hypothesis, we analyzed TEC subset frequency and phenotype, early thymic progenitor (ETP) cell count, and expression of FOXN1 target genes (Ccl25, Cxcl12, Dll4, Scf, Psmb11, Prss16, and Cd83) in Foxn1nu/+ (nu/+) mice and age-matched wild-type (+/+) littermate controls. Both the frequency and the absolute count of ETP were significantly reduced in nu/+ mice up to 3 weeks of age. Analysis of the TEC compartment showed reduced expression of FOXN1 target genes and delayed maturation of the medullary TEC compartment in nu/+ mice. These observations establish a FOXN1 gene dosage effect on thymic function and identify FOXN1 haploinsufficiency as an important genetic determinant of T cell lymphopenia at birth.

The choice of an optimal, most safe and physiological place in the heart for the electrode implantation is an issue to be solved by a specialist in surgery of heart arrhythmias. According to the literature, the techniques to stimulate both cardiac apex and other alternative areas are imperfect. At present, stimulation of the heart conduction system, namely, the His bundle is considered a promising area in arrhythmology. This type of stimulation is a physiological one, while it involves the His-Purkinje system. We present a successful clinical case of the electrode implantation with a two-chamber pacemaker to the heart conduction system in a 67-year-old patient with permanent atrial fibrillation. The surgical intervention made it possible to reduce the QRS length from 180 to 110 ms. This clinical case shows that the heart conduction system pacing allows for implementation of the principles of physiological stimulation in patients with impaired atrioventricular conduction. The technique with a two-chamber pacemaker is feasible in clinical practice.

Key Clinical Message Partial leukocyte adhesion deficiency type 1 (LAD‐1) deficiency is extremely rare condition with milder infectious manifestation and immune system imbalance leads to increased risks of autoinflammatory complications, such as pyoderma gangrenosum, that can be triggered by trauma or pregnancy. In patients with spice‐site ITGB2 variants, partial expression can occur due to different β2 integrin isophorms expression. Abstract LAD‐1, OMIM ID #116920 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene that encodes the CD18 β2 integrin subunit. According to the CD18 expression, LAD‐1 is categorized as severe (30%). Here, we describe a 22‐year‐old female, who presented with inflammatory skin disease and oral cavity, as well as respiratory tract infections during the first year of life. LAD‐1 was diagnosed at the age of 2 years by low expression of CD18 (1%). Whole‐exome sequencing identified homozygous c. 59‐10C>A variant in the ITGB2 gene. Despite severe phenotype, the patient survived to adulthood without hematopoietic stem cell transplantation and became pregnant at the age of 20 years, with pregnancy complicated by a pyoderma gangrenosum‐like lesion. During her life, CD18 expression increased from 1% to 9%; at 22 years of age, 5% of neutrophils and 9% of lymphocytes were CD18+. All CD18+‐lymphocytes were predominantly memory/effector cytotoxic T cells. However, revertant mosaicism was not being established suggesting that CD18 expression variability may be mediated by other mechanisms such as different β2 integrin isophorms expression.

Xylotrophic fungi are well known by their ability to excrete enzymes into environment. These fungi have important biotechnological potential and some of them produce industrial enzymes. Besides, xylotrophic fungal species have recently attracted a lot of attention among researchers as a source of antibacterial drugs. Aim. To analyze the effect of the carbon source in the culture medium, as well as the conditions of deep cultivation on the mycelium yield, proteolytic, cellulolytic and antimicrobial activity of the culture liquid of Trichoderma atroviride. Methods. Deep culture methods were used, partial purification was carried out with salting and subsequent dialysis, the cellulolytic activity was determined spectrophotometrically, antimicrobial activity was determined using the disc diffusion technique. Statistical analysis was performed using STATISTICA 6.0 software. Results. The highest cellulolytic activity (0.50±0.03 units/ml), mycelium yield and the smallest colony diameter were detected when cellulose was used as a carbon source. However, the highest proteolytic activity of the culture liquid was observed with glucose as a carbon source. The optimal temperature range for hydrolase activity was shown to be in the range of 25-30 °C. In comparison with Pleurotus ostreatus, the culture liquid of T. atroviride not only has more pronounced antimicrobial activity, but also inhibits the growth of Candida albicans. Conclusions. The culture liquid of isolated strain T. atroviride is a promising source of hydrolytic enzymes that can be used in organic farming and industry. The purified preparation obtained from the culture liquid of T. atroviride showed significant antimicrobial activity and can be successfully used for drug development in the future.

The article describes the peculiarities of drug provision for patients with psoriatic arthritis (PsA) in the Republic of Karelia. We present a clinical case of effective treatment with interleukin 17 inhibitor ixekizumab (IXE) in a randomized clinical trial and real clinical practice in a patient with PsA. The distinctive feature of this case is the severity of PsA course that was not controlled by standard methods of therapy. IXE treatment was characterized by a rapid clinical improvement of both articular and skin symptoms and subsequent achievement of remission, which lasted for 3 years (on the therapy). The forced interruption of the treatment led to the relapse of the disease in a short amount of time. In 2 years IXE therapy was resumed; after 6 months of continuing treatment a stable remission of PsA was achieved. The patient is still in clinical remission (on therapy).

Both annual (cotton, flax, hemp, etc.) and perennial (trees and grasses) plants can serve as a source of cellulose for fiber production. In recent years, the perennial herbaceous plant miscanthus has attracted particular interest as a popular industrial plant with enormous potential. This industrial crop, which contains up to 57% cellulose, serves as a raw material in the chemical and biotechnology sectors. This study proposes for the first time the utilization of miscanthus, namely Miscanthus Giganteus "KAMIS", to generate spinning solutions in N-methylmorpholine-N-oxide. Miscanthus cellulose's properties were identified using standard methods for determining the constituent composition, including also IR and atomic emission spectroscopy. The dry-jet wet method was used to make fibers from cellulose solutions with an appropriate viscosity/elasticity ratio. The structural characteristics of the fibers were studied using IR and scanning electron microscopy, as well as via X-ray structural analysis. The mechanical and thermal properties of the novel type of hydrated cellulose fibers demonstrated the possibility of producing high-quality fibers from miscanthus. [ABSTRACT FROM AUTHOR]

Optimization methods, namely, gradient optimization methods, are a key part of neural network training. In this paper, we propose a new gradient optimization method using exponential decay and the adaptive learning rate using a discrete second-order derivative of gradients. The MAMGD optimizer uses an adaptive learning step, exponential smoothing and gradient accumulation, parameter correction, and some discrete analogies from classical mechanics. The experiments included minimization of multivariate real functions, function approximation using multilayer neural networks, and training neural networks on popular classification and regression datasets. The experimental results of the new optimization technology showed a high convergence speed, stability to fluctuations, and an accumulation of gradient accumulators. The research methodology is based on the quantitative performance analysis of the algorithm by conducting computational experiments on various optimization problems and comparing it with existing methods. [ABSTRACT FROM AUTHOR]