Analysis on Investment of Small and Medium Entrepreneurship

The article presents the results of the author's analysis and evaluation of investments in small and medium entrepreneurship, the empirical testing of hypotheses about the presence of the differentiation value of investment and the possibility of describing the existing regularities with the use of economic and mathematical models. During models` constructing we used official statistical indicators characterizing the set of small enterprises, medium enterprises and individual entrepreneurs in all regions of the Russian Federation. There are two classes of models describing the volumes of investments accounted, respectively, to one entrepreneurial structure and one employee. Logical and statistical analysis showed that all developed models are approximate well  the original data over the entire range of their changes. It is proved that the volume of investment, both in terms of entrepreneurial structure and one of its employees differs significantly depending on the number of employees of entrepreneurial structures, regions, and economic activities, which specialize in entrepreneurial structures. The developed model and the resulting patterns can be used to solve a wide range of tasks while monitoring business activities, development design and forecasting in this sector of the economy at the federal, regional and municipal levels of management. Keywords: Small and medium enterprises; individual entrepreneurs; investment; economic and mathematical models; regions of the country. JEL Classifications: L26; O1

Comparative Evaluation of Pyrolysis and Hydrothermal Liquefaction for Obtaining Biofuel from a Sustainable Consortium of Microalgae Arthrospira platensis with Heterotrophic Bacteria

This article presents a comparative evaluation of pyrolysis and hydrothermal liquefaction (HTL) for obtaining biofuel from microalgal biomass (MAB). The research was carried out using biomass of a stable microalgae-bacteria consortium based on Arthrospira platensis. A. platensis was chosen because of its simple cultivation and harvesting. Pyrolysis was carried out at temperatures of 300, 400, 500, and 600 °C with a constant rate of temperature change of 10 °C/min; HTL was carried out at temperatures of 270, 300, and 330 °C. The bio-oil yield obtained by HTL (38.8–45.7%) was significantly higher than that of pyrolysis (up to 21.9%). At the same time, the bio-coal yields using both technologies were almost the same—about 27%. Biochar (bio-coal) can be considered as an alternative strategy for CO2 absorption and subsequent storage since it is 90% geologically stabilized carbon

Нарушение формирования пола 45,Х/46,XY: клинико-лабораторная характеристика пациентов

Aim. To study the clinical and laboratory characteristics of patients with disorders of sex development (DSD) 45,Х/46,ХY.Materials and methods. The study included 248 patients with genital malformations from early neonatal period to 18 years. The group of patients with DSD 45,Х/46,ХY was formed according to the results of cytogenetic and molecular cytogenetic examination. Anthropometric data, external and internal genitalia, hormonal parameters in mini-pubertal, neutral and pubertal periods were assessed; histological examination of the gonads and screening of development malformations were performed.Results. DSD of 46,ХY karyotype was revealed in 48% (120/248) cases, 46,ХХ DSD – 38% (93/248), DSD with sex chromosome pathology – 14% (35/248) patients. Chromosome DSD was represented by Klinefelter syndrome, Shereshevsky – Ulrich – Turner syndrome, chimeric DSD, and ovotesticular DSD, but the majority of patients had mosaicism 45,Х/46,ХY (65%). In the group of patients with NFP 45,X/46,XY, the median degree of masculinization of the external genitalia by the scale of the external masculinization score (EMS) was 3 [1; 5,5]. Among the defects of external genitalia in most cases (82%, 18/22) there was a combination of cryptorchidism with hypospadias. Derivatives of the Mueller ducts were detected in 91% (20/22) of patients. Most patients (77%) adapt the male passport field. There were no statistically significant differences in the structure of the external and internal genitalia between the groups of patients adapted in the male and female passport fields.The analysis of hormonal indexes revealed a positive correlation between the content of basal testosteron in the mini-pubertal period and the index of masculinization of the external genitalia by the EMS scale (p = 0,002; r = 0,9). In the period of mini-puberty an increase in the level of gonadotropic hormones was detected in 89% (8/9) of children, a combined increase of luteinizing and follicle-stimulating hormones (FSH) being observed in 33% (3/9), an isolated increase of FSH – in 56% (5/9) of cases. In the pubertal period hypergonadotropic hypogonadism was revealed in 75% (3/4) of patients.The results of the histological study of the gonads were heterogenous. Gonads are represented by a different degree of dysgenesis of testicular tissue: from a mild, histologically-like gonad in cryptorchidism to streak and ovotestis.Among the extragonadal manifestations of the disease, inguinal hernia (86%), heart defects (77%) and kidney defects (36%) are prominent. Pathological growth retardation was diagnosed in 23% of children.Conclusion. In the structure of the disease chromosomal DSD accounts for 14% of observations. A group of patients with DSD 45,X/46,XY is heterogenous in the degree of gonadal dysgenesis, the structure of the external and internal genitalia.Цель исследования. Изучить клинико-лабораторную характеристику пациентов с нарушением формирования пола (НФП) 45,Х/46,ХY.Материал и методы. В исследование включены 248 пациентов с неправильным строением наружных гениталий от раннего неонатального периода до 18 лет. По результатам цитогенетического и молекулярно-цитогенетического обследований сформирована группа пациентов с НФП, обусловленного мозаицизмом 45,Х/46,ХY. Проведена оценка антропометрических показателей, наружных и внутренних гениталий, гормональных показателей в мини-пубертате, нейтральном и пубертатном периодах, гистологическое исследование гонад, скрининг пороков развития.Результаты. НФП с кариотипом 46,ХY выявлено в 48% (120/248) случаев, с кариотипом 46,ХХ – в 38% (93/248), НФП с патологией половых хромосом – в 14% (35/248) наблюдений. Хромосомное НФП представлено следующими вариантами: синдромы Кляйнфельтера, Шерешевского – Ульриха – Тернера, химеризм, овотестикулярное, но большую часть составили пациенты с мозаицизмом 45,Х/46,ХY (65%). В группе пациентов с НФП 45,Х/46,ХY медиана cтепени маскулинизации наружных гениталий по шкале External Masculinization Score (EMS) составила 3 [1; 5,5]. Среди пороков развития наружных гениталий в большинстве случаев (82%, 18/22) имело место сочетание крипторхизма с гипоспадией. Дериваты Мюллеровых протоков выявлены у 91% (20/22) пациентов. Большая часть пациентов (77%) адаптируется в мужском паспортном поле. Не выявлено статистически значимых различий в строении наружных и внутренних гениталий между группами пациентов, адаптируемых в мужском и женском паспортном поле.При анализе гормональных показателей выявлена положительная корреляционная взаимосвязь между содержанием базального тестостерона в период мини-пубертата и индексом маскулинизации наружных гениталий по шкале EMS (р = 0,002; r = 0,9). В период мини-пубертата повышение уровня гонадотропных гормонов выявлено у 89% (8/9) детей, из которых сочетанное повышение лютеинизирующего гормона и фолликулостимулирующего гормона (ФСГ) отмечено в 33% (3/9), изолированное повышение ФСГ в 56% (5/9) случаев. В пубертатном периоде у 75% (3/4) пациентов выявлен гипергонадотропный гипогонадизм.По результатам гистологического исследования гонад отмечена гетерогенная картина. Гонады представлены различной степенью дисгенезии тестикулярной ткани: от легкой, близкой к гистологическому строению гонад при крипторхизме, до streak и овотестис.Среди внегонадных проявлений заболевания лидируют паховые грыжи (86%), пороки сердца (77%) и почек (36%). Патологическая задержка роста диагностирована у 23% детей.Выводы. В структуре заболевания на хромосомное НФП приходится 14% наблюдений. Группа пациентов с НФП 45,Х/46,ХY гетерогенна по степени дисгенезии гонад, строению наружных и внутренних половых органов

Monitoring of breast cancer progression via aptamer-based detection of circulating tumor cells in clinical blood samples

Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX.Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients’ blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses.Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression.Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes

Genetic landscape in Russian patients with familial left ventricular noncompaction

BackgroundLeft ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).MethodsAll index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.ResultsA total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants −8 of 54 (14.8%) −have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 −7.37; p <0.001) per variant after adjustment for sex, age, and family.ConclusionOverall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients

Исходы оперативного лечения патологии щитовидной железы у детей

Background. In recent years there has been a tendency of increase in the proportion of nodular goiter and Graves’ disease in thyroid pathology in children, which necessitates a choice of rational tactics for treatment of these diseases. At present there is no optimal method of treatment for thyroid gland pathology, but one of the methods is surgery. Thyroid surgery due to the determination of the indications and choice of the optimal volume of the surgical intervention continues to be under debate as postoperative complications of surgical treatment of thyroid diseases in children are possible.Aim: to study the outcomes of surgical treatment for thyroid pathology in children, depending on the volume of operation.Materials and methods. This article presents the results of a survey of 77 children operated on in the period of 2002–2016 for Graves’ disease, single-node goiter, and multinodular goiter. The examination included the determination of the levels of ionized calcium and TSH, FT4, FT3 in the blood serum, the evaluation of the functional state of the pituitary-thyroid system, thyroid ultrasound examination, and examination by an otolaryngologist.Results. The incidence of adverse outcomes of surgical treatment in children with nodular goiter was 27%. Adverse outcomes were observed equally often after organ-preserving operations and after thyroidectomy, but they were of different structure. The frequency of postoperative complications after thyroidectomy performed on the nodular goiter was 27%. Complications presented as postsurgical hypoparathyroidism and vocal cord paresis. In children with nodular goiter, after thyroidectomy hypoparathyroidism occurred more frequently than paresis of the vocal folds. Symptomatic hypocalcemia was observed more frequently than the asymptomatic variant, and in most cases hypoparathyrodism was transient. Among children with a single-node goiter who underwent organ-preserving surgery on the thyroid gland postoperative complications such as hypoparathyroidism and paresis of the vocal folds were not identified. Adverse outcomes (disease recurrence, postoperative hypothyroidism) were observed equally often after hemithyrodectomy and node enucleation. But the risk of recurrence of nodular goiter was significantly more common in children after node enucleation than after hemithyroidectomy and postsurgical hypothyroidism was more common in children with nodular goiter after hemithyrodectomy than after node enucleation. The frequency of adverse outcomes of surgical treatment of Graves’ disease in children was 14%. Complications were presented by post-surgical hypoparathyroidism and vocal cord paresis. All complications occurred only after thyroidectomy. When compared adverse outcomes of thyroidectomy were equally common in both nodular goiter and Graves ‘disease, but persistent dysfunction in the form of permanent hypoparathyroidism and permanent vocal cord paresis were more common in Graves’ disease than in nodular goiter.Conclusion. The results obtained demonstrate the heterogeneity of surgical treatment outcomes structure which depends on the surgical intervention volume.Введение. В последние годы отмечается тенденция к росту доли узлового зоба и болезни Грейвса в структуре патологии щитовидной железы у детей, что определяет необходимость выбора рациональной тактики лечения этих заболеваний. Оптимального способа лечения данной патологии щитовидной железы на сегодняшний день не существует, но одним из методов лечения является хирургический. Остается дискуссионным вопрос хирургии щитовидной железы в связи с определением показаний и выбора оптимального объема оперативного вмешательства у детей, так как возможны послеоперационные осложнения.Цель исследования. Изучить исходы оперативного лечения патологии щитовидной железы у детей в зависимости от объема операции.Материал и методы. В статье приводятся сведения о результатах обследования 77 детей, оперированных в период 2002–2016 гг. по поводу болезни Грейвса, одноузлового и многоузлового зоба.Обследование включало определение значения ионизированного кальция в сыворотке крови, оценку функционального состояния гипофизарно-тиреоидной системы: исследовался сывороточный уровень тиреотропного гормона, свободного (св.) тироксина, св. трийодтиронина, проводились ультразвуковое исследование щитовидной железы, осмотр оториноларинголога.Результаты. Установлено, что частота неблагоприятных исходов оперативного лечения среди детей с узловым зобом составила 27%. Осложнения одинаково часто встречались как после органосохраняющих операций, так и после тиреоидэктомии, но отличались по своей структуре. Частота послеоперационных осложнений (послеоперационный гипопаратиреоз, парез голосовых складок) после тиреоидэктомии, выполненной по поводу узлового зоба, составила 27%. У детей с узловым зобом после тиреоидэктомии гипопаратиреоз возникал чаще, чем парез голосовых складок. Симптоматическая гипокальциемия отмечалась чаще, чем бессимптомная, и в абсолютном большинстве случаев гипопаратиреоз носил транзиторный характер.Среди детей с одноузловым зобом, которым проведена органосохраняющая операция на щитовидной железе таких послеоперационных осложнений, как гипопаратиреоз, парез голосовых складок, не выявлено. Неблагоприятные исходы (рецидив заболевания, послеоперационный гипотиреоз) одинаково часто встречались как после гемитиреоидэктомии, так и после энуклеации узла. Но риск развития рецидива узлового зоба достоверно чаще возникал у детей после проведенной энуклеации узла, чем после гемитиреоидэктомии, а послеоперационный гипотиреоз чаще возникал у детей с узловым зобом после гемитиреоидэктомии, чем после энуклеации узла.Частота неблагоприятных исходов оперативного лечения болезни Грейвса (послеоперационный гипопаратиреоз и парез голосовых складок) у детей составила 14%. Все осложнения возникли только после тиреоидэктомии.При сравнении неблагоприятных исходов тиреоидэктомии осложнения одинаково часто встречались как при узловом зобе, так и при болезни Грейвса. Но стойкие нарушения функции в виде перманентного гипопаратиреоза и перманентного пареза голосовых складок чаще встречались при болезни Грейвса, чем при узловом зобе. Полученные результаты позволяют сделать вывод о гетерогенности структуры исходов оперативного лечения, которая зависит от объема оперативного лечения

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

Liver cancer is the third leading cause of cancer death worldwide. Representing such a dramatic impact on our lives, liver cancer is a significant public health concern. Sustainable and reliable methods for preventing and treating liver cancer require fundamental research on its molecular mechanisms. Cell lines are treated as in vitro equivalents of tumor tissues, making them a must-have for basic research on the nature of cancer. According to recent discoveries, certified cell lines retain most genetic properties of the original tumor and mimic its microenvironment. On the other hand, modern technologies allowing the deepest level of detail in omics landscapes have shown significant differences even between samples of the same cell line due to cross- and mycoplasma infection. This and other observations suggest that, in some cases, cell cultures are not suitable as cancer models, with limited predictive value for the effectiveness of new treatments. HepG2 is a popular hepatic cell line. It is used in a wide range of studies, from the oncogenesis to the cytotoxicity of substances on the liver. In this regard, we set out to collect up-to-date information on the HepG2 cell line to assess whether the level of heterogeneity of the cell line allows in vitro biomedical studies as a model with guaranteed production and quality