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The most important task of modern production development is to provide the mineral and raw materials sector of the economy with resources included in the list of strategic raw materials, including flake graphite. In addition to natural raw materials, the source of its obtaining can be metallurgical production wastes not involved in processing. Development of metallurgical dust beneficiation technology will solve the problem of obtaining high-purity flake graphite with a crystal structure close to ideal and in demand in the production of high-tech materials. It will allow creating a renewable raw material base of graphite and utilising metallurgical production wastes. The research included the study of dust beneficiation by coarseness, magnetic and flotation methods, the influence of dust disintegration processes on beneficiation indicators. Based on the established technological properties of the components of dusts, magnetic, flotation and gravity beneficiation methods can be applied for their separation in different sequence. It is shown that dusts from different sites have different enrichability by these methods, and it should be taken into account when developing a complex technology of their processing. The degree of beneficiation increases in a row of dusts from the blast furnace shop (BF) – electric steel smelting shop (ESS) – oxygen-converter shop (OCS). The method of grinding has a significant influence on the separation indicators – at dry grinding in a centrifugal-impact mill with subsequent pneumatic classification the quality of graphite concentrates increases by 22.7 % of carbon for BF dust and by 13.48 % of carbon for ESS dust. OCS dust beneficiation indicators are high at coarse grinding with steel medium – mass fraction of carbon 96.1 %.

Congenital viral infections are one of the pressing issues in modern neonatology. Due to the fact that viremia is a common stage in the infection process, the fetus is at high risk of intrauterine hematogenic infection, which can harm various organs and systems. The most frequently observed manifestations of congential viral infections are: intrauterine growth restriction (IUGR), micro- and macrocephaly, fetal hydrocephalus, hepatosplenomegaly, pneumonia, bone lesions, rash and haematological abnormalities. Even though these clinical manifestations are not specific, identifying the etiological factor is often a necessary step to determine the future management of the newborn. The aim of this paper is to collect and summarize literary data on lymphocytic choriomeningitis virus (LCMV) and Zika virus. Results: congenital infections caused by LCMV and Zika virus share similar clinical features. Laboratory and instrumental diagnostic methods facilitate carrying out the differential diagnosis and establishing prognosis and the best clinical approach to the patient.

Duchenne muscular dystrophy is a severe genetic disease caused by mutations in the dystrophin gene (DMD), which lead to a significant decrease or complete absence of the protein of the same name in muscle fibers. The disease manifests itself in boys from the age of 2–5 years in the form of progressive muscular weakness, cardiomyopathy and respiratory failure. As a result of progression, patients lose the ability to move by adolescence and die in the third decade from cardiopulmonary complications. However, timely pathogenetic therapy for Duchenne muscular dystrophy can prolong the life of patients and improve its quality. In this regard, early diagnosis of the disease and early initiation of pathogenetic therapy are very important.The article describes two clinical cases of the disease in siblings with onset at 2 years of age and different ages of diagnosis. Pathogenetic therapy in the first case made it possible to prolong the patient’s outpatient stay and improve the quality of life, and early diagnosis and initiation of pathogenetic therapy in the second case avoided disease progression and contributed to the development of new motor skills. The presented clinical case demonstrates the need for early diagnosis of the disease even before the onset of clinical manifestations.

This review presents an analysis of the literature data for the last 10 years (2012–2022) investigating the effect of eating disorders on the health of adolescent girl, its diagnosis, and possible tactics of gynecologist. The most common predictor of restoring menstrual function in girls with this pathology is body mass index change, however normalization of weight does not lead to remission in all cases. Thus, estimation of fat percentage, insulin-like growth factor, and leptin is more effective. We suggest directing further research on the study of more effective methods of reproductive disorders correction and the development of multidisciplinary clinical guidelines for the effective diagnosis and management of eating disorders and any gynecological complications.

The aim of the study was to analyze dynamic changes in the motivational and psychoemotional features of patients with drug addiction disorders at different stages of the treatment and rehabilitation process (TRP). The study involved 226 patients (163 men and 63 women) with narcological disorders. The following scales were used: Socrates, DASS-21 and GSE. Using the Socrates scale, results were obtained indicating: 1) significantly higher scores on the Ambivalence subscale at the early and recovery stages of the TRP in patients diagnosed with alcohol dependence (p≤0.05); 2) significantly higher scores on the total score (p≤0.001), the Ambivalence subscale (p≤0.05), and the Action subscale (p≤0.05) (p≤0.05) at the restorative and stabilizing stages of LRP, typical for women. Evaluation of the features of the DASS-21 revealed: 1) the presence of signs of moderate depression in patients with drug dependence (p≤0.01) and mild stress (p≤0.01) at the early stage of TRP were determined; 2) at the restorative stage of TRP, a higher level of depression (p≤0.01), anxiety (p≤0.05) and stress (p≤0.001) was detected in the group of patients with drug dependence. The analysis of the results obtained will make it possible to provide targeted assistance to patients with drug use disorders and increase the effectiveness of psychological and psychotherapeutic interventions in clinical practice.

Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells. Here, we introduce a preconditioning strategy targeting CD45 on hematopoietic cells with CAR45 T cells. To avoid fratricide of CD45 CAR T cells, genomic disruption of the CD45 gene was performed on human CD45 CAR T cells in combination with the signaling kinase inhibitor dasatinib. CD45Δ CAR45 T cells showed high cytotoxicity in vitro and depletion of tumor cells in vivo. These cells were effective in elimination of human hematopoietic cells engrafted in humanized immunodeficient mice by transfusion with human blood-derived hematopoietic stem cells (HSCs). Similarly, CD45Δ CAR45 natural killer (NK) cells exhibited potent cytotoxicity toward tumor cell lines and human hematopoietic cells in vitro. Thus, we provide the proof of concept for the generation and preclinical efficacy of fratricide-resistant CAR45 T and NK cells directed against CD45-expressing tumors and hematopoietic cells.

Background: Sasanlimab (PF-06801591), a humanized immunoglobulin G4 monoclonal antibody, binds to programmed cell death protein-1 (PD-1), preventing ligand (PD-L1) interaction. Objectives: To evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of two subcutaneous sasanlimab dosing regimens. Design: An open-label study consisting of phases Ib and II. Phase Ib: non-randomized, dose escalation, and expansion study in Asian participants with advanced malignancies. Phase II: conducted globally in participants with non-small-cell lung cancer with PD-L1 positive or PD-L1 status unknown tumors; participants were randomized 1:2 to receive subcutaneous sasanlimab 300 mg once every 4 weeks (300 mg-Q4W) or 600 mg once every 6 weeks (600 mg-Q6W). Methods: Primary endpoint in phase Ib: dose-limiting toxicity (DLT) occurring in first treatment cycle; in phase II: C trough and AUC. Results: A total of 155 participants (phase Ib, n = 34; phase II, n = 121) received sasanlimab. Phase Ib: no DLT reported. Phase II: ratio of adjusted geometric mean for AUC tau was 231.2 (90% CI, 190.1–281.2) and C trough was 111.5 (90% CI, 86.3–144.0) following 600 mg-Q6W (test) versus 300 mg-Q4W (reference). Phase Ib: grade 3 treatment-related adverse events (TRAEs) occurred in 1/4 (25%) and 3/12 (25%) participants treated in 300 mg-Q4W dose escalation and expansion cohorts, respectively. Phase II: grade 3 TRAEs occurred in 3/41 (7.3%) and 3/80 (3.8%) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively; no grade 4/5 TRAEs. Phase II: confirmed objective response was observed in 11/41 (26.8% (95% CI, 14.2–42.9)) and 12/80 (15.0% (95% CI, 8.0–24.7)) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively. Conclusions: Phase Ib regimens were considered safe with no DLTs reported. In phase II, 600 mg-Q6W regimen criteria were met for AUC tau and C trough metrics to support PK-based extrapolation of efficacy of alternative regimen. Regimens were well tolerated, showing anti-tumor activity in participants with advanced solid tumors. Administration of sasanlimab at a dose of 600 mg-Q6W subcutaneously may serve as a convenient alternative to 300 mg-Q4W administration. Trial registration: NCT04181788 (ClinicalTrials.gov); 2019-003818-14 (EudraCT).

BackgroundProlgolimab is the first Russian PD-1 inhibitor approved for the first-line treatment of unresectable or metastatic melanoma and advanced non-small cell lung cancer. It was approved in two weight-based regimens of 1 mg/kg Q2W and 3 mg/kg Q3W, but because of re-evaluation of weight-based dosing paradigm, studying of a fixed-dose regimen was considered perspective.MethodsWe conducted a multicenter, single-arm, open-label efficacy, pharmacokinetics, and safety study to obtain data that would allow the approval of the new flat dosing regimen of prolgolimab in patients with previously untreated unresectable or metastatic melanoma (BCD-100-8/FLAT, NCT05783882). The primary objective was to prove the non-inferiority of prolgolimab 250 mg Q3W versus prolgolimab 1 mg/kg Q2W for the treatment of patients with unresectable or metastatic melanoma in terms of ORR according to RECIST 1.1. Patients from the MIRACULUM study (BCD-100-2/MIRACULUM, NCT03269565) comprised a historical control group.ResultsOne hundred fourteen patients received prolgolimab 250 mg Q3W, and 61 patients received prolgolimab (Prolgo) 1 mg/kg Q2W (historical control). Objective response was achieved by 33.3% [95% confidence interval (CI): 24.8, 42.8] of patients in the Prolgo 250 mg group compared with 32.8% (95% CI: 21.3, 46.0) of patients in the Prolgo 1 mg/kg group. Risk difference was 0.00, 95% CI (−0.12; NA), p = 0.0082. Both regimens were well tolerated, and safety profiles were comparable. The pharmacokinetic analysis (PK) showed that the regimen with the fixed dose of 250 mg Q3W was characterized by higher PK parameters. The immunogenicity study did not detect binding antibodies to prolgolimab in any of the subjects.ConclusionThe obtained results showed that the selected fixed dosing regimen of prolgolimab 250 mg Q3W is characterized by efficacy and safety parameters comparable to that observed for the 1 mg/kg Q2W regimen.

Aim: to discuss current views on the clinical significance, diagnostic opportunities, and therapeutic approaches in the treatment of small intestinal bacterial overgrowth (SIBO) as an important component in the gut microbiota function assessment, to assess the awareness of physicians and the opportunities in the diagnosis and treatment of this disease in patients in the Federal districts of the Russian Federation, as well as to present the proceedings of the Expert Council held on December 16, 2023 in Moscow.Key points. SIBO is a common syndrome often associated with irritable bowel syndrome, liver cirrhosis, asthma, and congestive heart failure, being also a predictor of early death in the elderly. Today, in many regions of the Russian Federation, there are limitations for instrumental diagnosis of this disease — lack of awareness among doctors, unavailability of gas analyzers for diagnosing SIBO, lack of information about the need to diagnose SIBO in the standards of compulsory health insurance. Rifaximin is the first-line treatment due to the highest therapeutic efficacy. One of the ways to increase the efficacy of SIBO treatment is to include strain-specific probiotics in the treatment regimen. Saccharomyces boulardii CNCM I-745 is thought to be the most studied, promising probiotic. The review also presents statistical data on the issues in the diagnosis and treatment of SIBO in the regions of the Russian Federation.Conclusion. Optimization of approaches to the diagnosis and treatment of SIBO, the development of domestic gas analyzers, increasing the awareness of physicians in all regions of the Russian Federation, as well as the development and optimization of clinical recommendations appear to be necessary measures to increase the effectiveness of medical care, the duration and quality of life of the Russian population. These goals can be achieved within the framework of Federal programs under the supervision of specialized reference centers of the Ministry of Health of the Russian Federation.

At the beginning of the 21st century in St. Petersburg, the number of species of trees and shrubs that have entered a reproductive state has noticeably increased. A number of them produced seed offspring for the first time over a long period of introduction. In such conditions, when the levels of adaptation change so noticeably and the biological characteristics of different plant species manifest themselves differently, the role and importance of conducting and processing long-term series of continuous phenological observations undoubtedly increases. During the period of continuous phenological monitoring (1980–2022) in the Botanical Garden of Peter the Great Komarov Botanical Institute Russian Academy of Sciences established that against the backdrop of climate warming in St. Petersburg, which began in the late 1980s, biological cyclicity, according to N. E. Bulygin, manifests itself in the alternation of early warm periods (1989, 1990, 1992, 1995, 2007, 2008, 2014, 2015, 2016, 2019, 2020, 2022) and late cold years (1980, 1982, 1985, 1987, 1996, 1998, 2003, 2004, 2006, 2011, 2012, 2013), which is reflected on the reproductive activity of woody plants and their ability to survive winter conditions. For the period 2001–2022 238 species entered the reproductive state, many of which had previously been in a vegetative state for decades. The improvement in the reproductive sphere of plants is especially noticeable after the abnormally warm winter of 2006/07; it intensified in 2015. This year and 2020 became the warmest during the period of instrumental meteorological observations in St. Petersburg. 50.8 % of cases of the first flowering and fruiting occur in early warm years; and only 16.4 % of cases – in late cold years. When summing up the results of introduction and assessing the prospects for breeding woody plants for urban floristics, it is necessary to take into account the cyclical climate of the region, the seasonal rhythm of plant development and their rhythm-adaptive connections.

The article deals with the lithology and geochemistry of organic matter of Upper Devonian-Lower Carboniferous deposits (Carbonate Devonian) of the eastern part of the South Tatar arch. Rocks of this age have a high generative potential due to increased concentrations of organic matter (OM) and its phytogenic and zoophytogenic composition. They refer to non-traditional sources of hydrocarbons. The generative potential depends on the facial environment and the transformation of OM. The highest potential have carbonate-siliceous and siliceous-carbonate rhythmites domannic horizon.

Berezovsky depression, located on the northeast of the Pre-Patom foredeep, is a promising target for hydrocarbon prospecting, as evidenced by oil and gas shows established while drilling, the presence of structures and natural reservoirs. However, this area has not yet been adequately explored due to the low drilling density. Geochemical study of organic matter (OM) of the Riphean, Vendian and Lower Cambrian sediments showed that the main oil and gas source rock is represented by terrigenous-carbonate Vendian deposits. Rocks of the Seralakh Formation possess highest initial and residual potential, as well as interlayers of rocks with heightened content of algal OM in the Vendian and Lower Cambrian sections. The oxidation of OM during sedimentation and the presence of bottom algae could have a negative impact on the generation potential of these deposits, which led to a decrease in OM concentrations and deterioration of kerogen; most likely, these factors determine the smaller resources of the Berezovsky depression. Probably, the study of the Riphean complex deserves attention, because there are oil-source rocks highly enriched in OM in the Middle and Upper Riphean of the south-west of the Baikal-Patom fold zone, the transformation of which is corresponded to peak of «oil window» – «gas window».

Unconventional oil and gas resource development and exploration is the one of the most prospective concept in petroleum geology. High carbon Khadum facies are investigated as unconventional resources in the Precaucas basin and contain gas, gas condensate and oil accumulations. Oligocene and Lower Miocene structure, prospectivity and fields distribution are the one of the most relevant subjects nowadays.This study is focused on the main stages Late Eocene and Early Oligocene deposits formation and the paleogeography of the Khadum formation in the Precaucas oil and gas basin. The new prospective zones are developed in Khadum formation based on the complex analysis of seismic, paleogeography and lithofacies analysis.

The paper considers palaeoincisions in the Turnean limestones of the Volga-Ural basin, made by alluvial-deluvial sediments of the Visean age and containing interlayers of coals. Processes occurring in these sediments (catagenic reduction of thickness of coal beds and coal-bearing mudstones, aggressive influence of products of defluidization of coal organic matter on the host rocks, etc.) strengthen the fluid dynamic heterogeneity of intracrustal deposits and contribute to emigration of hydrocarbons (HC). The main oil-and-gas-generating strata in the Carboniferous section include rocks of the Tournaisian stage and the Bobrikovsky horizon of the Viseian stage. Palaeoincisions, along with the area distribution of Viseian coals, can be considered as centers of fluid generation, including liquid and gas HC.

To get properties and characteristics of oil and gas source rocks and for other geological aims, geologists analyzes core samples from wells and outcrop samples. But we should probably somehow correct geochemical source rock properties data we get on outcrop samples, because organic matter could change significantly due to oxidizing and weathering. This problem is very important but poorly developed in modern publications, so it attracted our interest and led to this investigation. Published information on the organic matter weathering which change it’s content and quality in sedimentary rocks is collected and summarized in this article. The changes of the kerogen (isolated from the mineral matrix) elemental composition during its long-term storage are presented.We compared the results we get in laboratory and results of other authors who dealt with natural changes of organic matter in outcrops. An attempt to interpret the results obtained from the point of view of hypergene changes in OM was made. Uncertainties that require further study and development are indicated. This work is the first step to better understanding of weathering effect on organic matter content and properties – question of great importance for making adequate oil and gas prospects estimations.This study continues the work of our foregoers and Teachers – geochemists of the Petroleum Geology Department of Lomonosov Moscow State University: N.B. Vassoevich, Yu.I. Korchagina, O.A. Radchenko, V.A. Uspensky, I.E. Leifman, A.N. Guseva, O.K. Bazhenova, T.A. Kiryukhina.

Background. The use of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in combination with endocrine therapy is a key initial treatment for advanced luminal HER2-negative (HR+/HER2-) breast cancer. The approval studies MONALEESA-2 and 7 demonstrated the efficacy and safety of ribociclib in combination with aromatase inhibitors as a first-line treatment in post- and premenopausal patients. In the Phase lllb CompLEEment-1 study, the same treatment regimen was evaluated in an extended patient population in terms of both safety and efficacy. The article presents an analysis of data from a subgroup of patients from Russia. Materials and methods. The study included 129 patients from Russia who met the inclusion criteria for the CompLEEment-1 study. The primary endpoint was the incidence of adverse events (AEs) at a median follow-up of 25.4 months. Secondary endpoints were median progression-free survival, objective response rate, and disease control. Results. The efficacy and safety results of the therapy in the subgroup of patients from Russia were consistent with the general population of patients included in CompLEEment-1. The incidence of AEs requiring dose adjustment or treatment interruption was 58.1%, and the permanent discontinuation rate was 15.5%. The most frequently reported treatment-related AEs grade 3 or higher were neutropenia and transaminase increased. Conclusion Data obtained in a subgroup of patients from the Russian Federation confirm the safety and tolerability of ribociclib in an extended population of patients with HR+/HER2- breast cancer in settings close to the real world.

Objective: To construct an indicator for assessing the complexity of UK veterans’ needs. Study design: Cross-sectional, secondary analysis. Methods: The study applied principal component (PCA) analysis as the method to determine the weights of different needs based on their interactions with each other, the effectiveness of the model was evaluated using bootstrapping. The dataset on UK veterans’ support provided by the “Soldiers, Sailors, Airmen and Families Associations” (SSAFA) (N = 35,208) was considered. The grant applications for different categories of support were used as indicators of different needs. The dimensions of breadth (number of different needs) and depth (number of grant applications to address the need) were incorporated in the assessment of complexity. Results: The complex needs indicator for the current sample was validated. The majority of cases had a complexity score of 1 or less. Conclusions: The research suggested and tested an assessment method for the complexity of veterans’ needs, that may be positively associated with higher risk of adverse health outcomes. This indicator can be used by decision-makers for risk stratification of the veteran population, thus supporting the allocation of resources in a more effective way.