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Оn March 27, 2023, а multidisciplinary Advisory Board meeting was held in Moscow with the participation of Е.V. Artamonova, Е.А. Busko, V.V. Didenko, А.D. Zikiryakhodzhaev, М.S. Karpova, G.Е. Kvetenadze, P.V. Krivorot’ko, М.L. Mazo, А.V. Petrovsky, О.S. Puchkova, S.V. Serebryakova under the chairmanship of I.Е. Tyurin and N.I. Rozhkova. The participants discussed different issues of early diagnostics and treatment planning of breast cancer. We present the conclusion made by the Advisory Board.

En las zonas altas del trópico de Colombia, el pasto kikuyo (Cenchrus clandestinus) es la opción forrajera predominante. Conocer su valor energético in vivo es fundamental para la formulación de raciones. Los objetivos de este trabajo fueron: (i) Determinar la densidad energética del pasto kikuyo en términos de energía digestible (ED), metabolizable (EM) y neta (EN) a partir de pruebas de balance en vacas lecheras de la raza Holstein; (ii) Evaluar el potencial del pasto kikuyo para sostener la producción de leche en animales alimentados mayoritariamente con pasto; (iii) Estimar la tasa de sustitución (TS) del pasto kikuyo, entendida como la reducción en el consumo de pasto cuando se incorpora un suplemento concentrado en la dieta. Se utilizó un diseño transeccional de naturaleza descriptiva, en el cual se emplearon cuatro vacas lactantes con 196 días en lactancia, que diariamente consumieron pasto kikuyo ad libitum (98.4% del consumo total) más 0.3 kg de suplemento/animal/día. Para realizar la partición energética, se cuantificaron las pérdidas energéticas a través de las heces, orina, emisión entérica de metano y producción de calor; además, se determinó la producción de leche con la dieta, basada mayoritariamente en pasto. Al restringir el suplemento concentrado, todos los animales perdieron peso (-2.4%), aumentaron el consumo de materia seca (MS) de pasto (+24.6%), disminuyeron el consumo de MS total (-17.2%) y la producción de leche corregida al 4% de grasa (LCG4, -18.3%). La densidad energética de la dieta en términos de ED y EM fue de 2.78±0.13 y 2.37±0.08 Mcal/kg MS, respectivamente, mientras su contenido de EN fue estimado en 1.39±0.26 Mcal/kg MS. La producción de leche con base en el consumo de pasto, estimada a partir del balance energético, fue 13.20±3.84, fluctuando entre 8.8 y 15.9 kg LCG4/animal/día. La TS fue 0.56±0.10 kg MS de pasto/kg MS de concentrado.

Abstract Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM). We enrolled 25 patients aged ≥18 years diagnosed with BCBM and rGBM to receive a single intravenous dose of SG at 10 mg/kg given one day before resection and continued on days 1 and 8 of 21-day cycles following recovery. The PFS was 8 months and 2 months for BCBM and rGBM cohorts, respectively. The OS was 35.2 months and 9.5 months, respectively. Grade≥3 AE included neutropenia (28%), hypokalemia (8%), seizure (8%), thromboembolic event (8%), urinary tract infection (8%) and muscle weakness of the lower limb (8%). In post-surgical tissue, the median total SN-38 was 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, thus fulfilling the primary endpoint. Biomarker analysis suggests delivery of payload by direct release at target site and that hypoxic changes do not drive indirect release. Secondary endpoint of OS was 35.2 months for the BCBM cohort and 9.5 months for rGBM. Non-planned exploratory endpoint of ORR was 38% for BCBM and 29%, respectively. Exploratory endpoint of Trop-2 expression was observed in 100% of BCBM and 78% of rGBM tumors. In conclusion, SG was found to be well tolerated with adequate penetration into intracranial tumors and promising preliminary activity within the CNS. Trial Registration: Trial (NCT03995706) enrolled at Clinical Trials.gov as Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0: https://clinicaltrials.gov/study/NCT03995706?cond=NCT03995706 .

Introduction. The article is devoted to the 100th anniversary of the birth of a major railway economist, Doctor of Economic Sciences, Professor Anatoliy Petrovich Abramov, who made a great contribution to the development of national economic science. The economists works reflect an extraordinary bright personality who left an indelible trace in the memory of those who worked with this outstanding person.Materials and methods. The article uses facts of Anatoliy Abramov biography, memories of his colleagues at the institute, and his achievements in the form of numerous scientific publications.Results. The article outlines the outstanding economist life journey, explores his contribution to the development of economic science in railway transport, reveals his multifaceted talent.Discussion and conclusion. This article is an opportunity to pay tribute to the memory of Anatoliy Abramov, famous railway economist, founder and head of a scientific school and remarkable person.

BACKGROUND: Several studies involving various suicidal phenotypes based on the strategy of the search of genome-wide associations with single nucleotide polymorphisms have been performed recently. These studies need to be generalized. AIM: To systematize the findings of a number of genome-wide association studies (GWAS) for suicidal phenotypes, annotate the identified markers, analyze their functionality, and possibly substantiate the hypothesis holding that these phenotypes reflect a nonspecific set of gene variants that are relevant as relates to stress-vulnerability as a key endophenotype of suicidal behavior (SB). METHODS: A search on the PubMed and related resources using the combinations “suicide AND GWAS” and “suicidal behavior AND GWAS” was performed. It yielded a total of 34 independent studies and meta-analyses. RESULTS: For the 10 years since such studies emerged, they have undergone significant progress. Estimates of the SNP heritability of SB in some cases are comparable with estimates of heritability based on the twin method. Many studies show a high genetic correlation with the genomic markers of the most common mental disorders (depression, bipolar disorder, schizophrenia, post-traumatic stress disorder). At the same time, a genomic architecture specific to SB is also encountered. Studies utilizing the GWAS strategy have not revealed any associations of SB with candidate genes that had been previously studied in detail (different neurotransmitters, stress response system, polyamines, etc.). Frequently reported findings from various studies belong in three main groups: 1) genes involved in cell interactions, neurogenesis, the development of brain structures, inflammation, and the immune responses; 2) genes encoding receptors for neurotrophins and various components of the intracellular signaling systems involved in synaptic plasticity, embryonic development, and carcinogenesis; and 3) genes encoding various neuro-specific proteins and regulators. CONCLUSION: In general, GWAS in the field of suicidology mainly serve the purpose of a deeper understanding of the pathophysiology of suicidal behavior. However, they also demonstrate growing capability in terms of predicting and preventing suicide, especially when calculating the polygenic risk score among certain populations (psychiatric patients) and in combination with tests of different modalities. From our point of view, there exists a set of markers revealed by the GWAS strategy that seems to point to a leading role played by stress vulnerability, an endophenotype that is formed during early development and which subsequently comes to play the role of key pathogenetic mechanism in SB.

BACKGROUND: Anhedonia is characterized by a reduced ability to anticipate, experience, and/or learn about pleasure. This phenomenon has a transdiagnostic nature and is one of the key symptoms of mood disorders, schizophrenia, addictions, and somatic conditions. AIM: To evaluate the genetic architecture of anhedonia and its overlap with other mental disorders and somatic conditions. METHODS: We performed a genome-wide association study of anhedonia on a sample of 4,520 individuals from a Russian non-clinical population. Using the available summary statistics, we calculated polygenic risk scores (PRS) to investigate the genetic relationship between anhedonia and other psychiatric or somatic phenotypes. RESULTS: No variants with a genome-wide significant association were identified. PRS for major depression, bipolar disorder, and schizophrenia were significantly associated with anhedonia. Conversely, no significant associations were found between PRS for anxiety and anhedonia, which aligns well with existing clinical evidence. None of the PRS for somatic phenotypes attained a significance level after correction for multiple comparisons. A nominal significance for the anhedonia association was determined for omega-3 fatty acids, type 2 diabetes mellitus, and Crohn’s disease. CONCLUSION: Anhedonia has a complex polygenic architecture, and its presence in somatic diseases or normal conditions may be due to a genetic predisposition to mood disorders or schizophrenia.

This study considers the inverse problems inherent in interpreting temperature logging data from an isolated segment of the injection well in order to ascertain its operating period and the thermophysical properties of the oil reservoir.The forward problem of thermal conductivity was reduced to a one-dimensional axisymmetric formulation within the oil reservoir layer, disregarding the vertical thermal exchange with neighboring layers.The inverse problem of determining the well operating period was solved by reformulating the forward problem with regard to the temperature field derivative, which enabled the use of first-order optimization methods. Thus, Nesterov’s method was applied. An algorithm to automatically scale one of the method’s parameters (step length) was developed, and the optimal value of the second parameter (inertial step) was calculated. This increased the efficiency of the method by 10 – 15 % in solving the problem under consideration.The algorithm’s stability against perturbations in the initial data on temperature and thermophysical properties was demonstrated. The sensitivity analysis revealed that a 1 % error in the temperature measurements results in a standard deviation of the solution, which is about 2 % from the true value of the well operating period. A similar level of error was seen when the thermal diffusivity was overor underestimated by approximately 15 %. The solution was little sensitive to variations in the heat transfer coefficient between the oil reservoir and the well at characteristic magnitudes; even with a twofold distortion, the error in the determination of the well operating period did not exceed 1.5 %. To mitigate the error in thermometry interpretation to 1 %, temperature measurements must have an error margin of no more than 0.25 %, alongside precisely specified thermophysical properties of the oil reservoir, or, alternatively, when temperature is measured accurately, the rock thermal diffusivity must be set within an error margin of less than 3 %, but it is nearly impossible under real conditions.Increasing the number of temperature measurements diminishes the sensitivity to measurement errors, with the optimal efficacy achieved at 10 measurements, rendering further increments impractical.Therefore, the algorithm’s stability and the solution’s sensitivity of the inverse problem of determining the reservoir thermal diffusivity for a given operating period of the well relative to temperature measurement errors were found. The results show that a 1 % error in temperature measurements leads to a standard deviation of about 6 % from the true value.

O movimento olímpico da modernidade e o processo de industrialização emergem praticamente no mesmo momento, quando o esporte é vislumbrado como um instrumento benéfico para manter o corpo produtivo e controlado. Nessa direção, as máquinas e as aspirações de ruptura com as representações culturais identificadas com o antigo fazem-se necessárias à conformação de outro imaginário social. O hipismo é uma das práticas esportivas que pode exemplificar a construção de descontinuidades e continuidades de representações na dinâmica entre o antigo e o moderno. O objetivo da pesquisa é investigar que representações culturais da modalidade do salto do hipismo foram estabelecidas por meio de fotografias veiculadas em reportagens sobre a participação brasileira nos Jogos Olímpicos entre os anos de 1948 e 1996. O recorte temporal da pesquisa situa-se entre o ano de 1948, quando, pela primeira vez, atletas brasileiros da modalidade Salto do Hipismo representaram o país em Jogos Olímpicos, e estende-se até o ano de 1996, o qual baliza a conquista da primeira medalha olímpica brasileira na referida modalidade hípica. De tal modo, atrelamos dois artefatos de modernidade e sua relação com o movimento olímpico, ao aplicarmos, como metodologia, a análise de imagens veiculadas pelas reportagens sobre as delegações brasileiras no cenário olímpico. Além disto, foram submetidos, à análise documental, jornais, revistas e demais periódicos que continham a temática disponível na Hemeroteca Digital (BNDigital) da Fundação Biblioteca Nacional. Ademais, foram acessadas imagens disponíveis em centros de memória do esporte, sites da Confederação Brasileira de Hipismo (CBH), de federações estaduais e da Federação Equestre Internacional (FEI). Diante da problemática da imagem como operador da memória esportiva e artefato de modernidade, a interpretação dos indícios está amparada no campo da Nova História Cultural, a fim de compreender como sucedeu o registro e quais as suas funções na composição de um artefato ou lugar de memória. Do mesmo modo, buscamos interpenetrar os registros que se conservam e aqueles que não permanecem, ao empenharmo-nos em cruzar aqueles que estão disponíveis nos centros de memória e nos sites oficiais com os demais encontrados na imprensa do período.

The purpose of this research is to contextualize the behavior of publications on complex thinking in education. A total of 428 documents compiled in Scopus from 1937 to 2022 were analyzed with a bibliometric study considering criteria such as "complex thinking", "complex thought", and "reasoning for complexity", all combined with education. The results show 153, 47, and 5 publications for each criterion with their related disciplines, citations, types of documents, universities, prominent authors, researching countries, and the general diachronic evolution of the subject, this allows to establish an idea about the implications of the present study according to one of the most important databases in the world. It is concluded that complex thinking and its relationship with education awakens a greater interest in the academy, not only because of its incidence in diverse fields that are nourished by it for the generation of new multidisciplinary knowledge but also because of the published research that demonstrates its transcendence.

Esta investigación aborda la identificación y el diagnóstico general de los materiales y/o colecciones patrimoniales bibliográficas y documentales (no archivísticas) bajo la custodia de instituciones, organizaciones o particulares, con asiento en las cabeceras de los municipios que conforman la subregión del Oriente antioqueño (Colombia). Se reconocieron acciones de organización, conservación, acceso y difusión que sobre ellos se han realizado o están realizándose, con el propósito de aportar insumos para la puesta en marcha del Plan Nacional de Patrimonio Bibliográfico y Documental, así como efectuar recomendaciones para la protección de estos materiales y/o colecciones y la inserción de su gestión en los planes nacionales, departamentales, locales o institucionales. Es un estudio cualitativo con enfoque comparativo, con ejercicios de aplicación de encuestas, entrevistas y observación directa, con visitas a los sitios y a las personas que potencialmente ejercen la función de custodia, esto previa revisión de bases de datos de cada tipo de institución, identificación desde la estructura municipal y personas naturales referidas por distintos medios. Se evidencia la existencia de una riqueza en colecciones en una amplia variedad de formatos con predominio de lo impreso. Se destacan las fotografías, prensa, monografías y la existencia, principalmente, de colecciones locales en un buen estado de conservación, en términos generales. Si bien puede decirse que se implementan acciones para la gestión del patrimonio, aún se carece de los medios y recursos necesarios y de procesos de formación para los custodios. Es fundamental que las autoridades locales y departamentales inviertan más en la conservación preventiva, organización y, especialmente, en difusión de las colecciones patrimoniales.

Introdução: A COVID-19 impactou negativamente a vida dos idosos, considerados como grupo de risco para o vírus. Objetivo: Este estudo longitudinal prospectivo teve como objetivo verificar as alterações na aptidão física de idosos durante o período da pandemia COVID-19, levando em consideração o sexo e a faixa etária. Métodos: Participaram do estudo 76 idosos (72,6 ± 6,47 anos), que faziam parte de um programa de extensão universitário. A aptidão física foi avaliada por meio da bateria de testes Senior Fitness Test (SFT). Os pesquisadores, devidamente treinados, aplicaram a SFT antes da pandemia (novembro de 2019) e durante a pandemia (abril de 2022). Resultados: Os resultados indicaram uma piora significativa na aptidão física dos idosos em todos os testes, exceto no teste de flexão de cotovelo. A maior redução na aptidão física foi observada no teste de caminhada de 6 minutos. Em relação ao sexo, tanto homens quanto mulheres apresentaram maiores reduções na resistência aeróbia e na força dos membros inferiores. Quanto à faixa etária, os idosos com 80 anos ou mais foram os mais afetados, apresentando as maiores reduções, especialmente na resistência aeróbia e na força dos membros inferiores. Conclusão: O estudo conclui que o período da pandemia de COVID-19 teve um impacto negativo significativo na aptidão física dos idosos, especialmente nas mulheres e nos idosos com 80 anos ou mais. Portanto, recomenda-se a implementação de atividades físicas para essas populações, com o objetivo de minimizar ou até reverter os impactos negativos causados pela COVID-19 na aptidão física dos idosos.

Glyoxalase I (GLO1) is the primary enzyme for detoxification of the reactive dicarbonyl methylglyoxal (MG). Loss of GLO1 promotes accumulation of MG resulting in a recapitulation of diabetic phenotypes. We previously demonstrated attenuated GLO1 protein in skeletal muscle from individuals with type 2 diabetes (T2D). However, whether GLO1 attenuation occurs prior to T2D and the mechanisms regulating GLO1 abundance in skeletal muscle are unknown. GLO1 expression and activity were determined in skeletal muscle tissue biopsies from 15 lean healthy individuals (LH, BMI: 22.4 ± 0.7) and 5 individuals with obesity (OB, BMI: 32.4 ± 1.3). GLO1 protein was attenuated by 26 ± 0.3 % in OB compared to LH skeletal muscle (p = 0.019). Similar reductions for GLO1 activity were observed (p = 0.102). NRF2 and Keap1 expression were equivocal between groups despite a 2-fold elevation in GLO1 transcripts in OB skeletal muscle (p = 0.008). GLO1 knock-down (KD) in human immortalized myotubes promoted downregulation of muscle contraction and organization proteins indicating the importance of GLO1 expression for skeletal muscle function. SIRT1 KD had no effect on GLO1 protein or activity whereas, SIRT2 KD attenuated GLO1 protein by 28 ± 0.29 % (p