ІНФОРМАЦІЙНІ ТЕХНОЛОГІЇ І СИСТЕМИ ДЛЯ РАННЬОЇ ДІАГНОСТИКИ ОНКОЛОГІЧНИХ ЗАХВОРЮВАНЬ ЗА РІВНЕМ ЦИРКУЛЮЮЧИХ ПУХЛИННИХ КЛІТИН

Most modern systems and technologies of the automated analysis of medical microscopic images and early diagnostics of oncological diseases are analyzed in the article. The methods and algorithms used for image processing, segmentation, determination of parameters of the object, which are determined manually and require additional knowledge, make it significantly complicated for their practical application in clinical medicine due to insufficient knowledge of medical staff.В статье проанализировано большинство современных систем и технологий автоматизированного анализа медицинских микроскопических изображений и ранней диагностики онкологических заболеваний. Методы и алгоритмы, применяемые для обработки изображений, сегментации, определения параметров объекта, определяются в ручном режиме и требуют дополнительных знаний, это существенно затрудняет их практическое применение в клинической медицине вследствие недостаточного количества знаний у медицинского персонала.Проаналізовано більшість сучасних систем і технологій автоматизованого аналізу медичних мікроскопічних зображень та ранньої діагностики онкологічних захворювань. Методи та алгоритми, що застосовуються для оброблення зображень, сегментації, визначення параметрів об'єкта, визначаються в ручному режимі та потребують додаткових знань, це суттєво ускладнює їх практичне застосування в клінічній медицині внаслідок недостатньої кількості знань у медичного персонал

Multiplicative slices, relativistic Toda and shifted quantum affine algebras

We introduce the shifted quantum affine algebras. They map homomorphically into the quantized $K$-theoretic Coulomb branches of $3d\ {\mathcal N}=4$ SUSY quiver gauge theories. In type $A$, they are endowed with a coproduct, and they act on the equivariant $K$-theory of parabolic Laumon spaces. In type $A_1$, they are closely related to the open relativistic quantum Toda lattice of type $A$.Comment: 125 pages. v2: references updated; in section 11 the third local Lax matrix is introduced. v3: references updated. v4=v5: 131 pages, minor corrections, table of contents added, Conjecture 10.25 is now replaced by Theorem 10.25 (whose proof is based on the shuffle approach and is presented in a new Appendix). v6: Final version as published, references updated, footnote 4 adde

Normative resistance to responsibility to protect in times of emerging multipolarity: the cases of Brazil and Russia

This article assesses the normative resistance to Responsibility to Protect adopted by Brazil and Russia against the backdrop of their international identities and self-assigned roles in a changing global order. Drawing upon the framework of Bloomsfield's norm dynamics role spectrum, it argues that while the ambiguous Russian role regarding this principle represents an example of 'norm antipreneurship', particularities of Brazil's resistance are better grasped by a new category left unaccounted for by this model, which this study portrays as 'contesting entrepreneur'.- (undefined

Интерлейкин IL-1β стимулирует ревитализацию хрящевого матрикса назальными хондроцитами человека in vitro

Revitalization of decellularized or devitalized matrix scaffolds in tracheal tissue engineering typically involves seeding the autologous recipient cells or allogeneic cells under long-term cultivation. Objective: to study the capability of human nasal chondrocytes for colonization of devitalized scaffolds based on native human tracheal cartilage, with proinflammatory stimulation (cytokine) by adding Interleukin-1-beta (IL-1β) to the culture medium. Materials and methods. Scaffolds for tracheal tissue engineering were obtained from native human tracheal cartilage through devitalization and laser etching. The scaffold was revitalized by seeding the human nasal chondrocytes. Histological examination was performed after staining with hematoxylin and safranin-O, with further microscopy using a Nikon Eclipse L200 light microscope. X-ray microtomography was performed on a Phoenix nanotom m apparatus. Electron microscopy was performed on a Nova NanoSEM 230 setup. Results. There was statistically significant increase in the intensity of colonization (p = 0.0008) with nasal chondrocytes and stimulation of their migration activity (p < 0.0001) in the presence of IL-1β compared with the control groups. Conclusion. Addition of proinflammatory cytokine IL-1β (1 μg/ml) to the culture medium enhances volumetric seeding of devitalized cartilage scaffold with human nasal chondrocytes, allowing to create highly revitalized materials for tracheal tissue engineering.Ревитализация децеллюляризированных или девитализированных матриксов для тканевой инженерии трахеи, как правило, предполагает заселение матрикса-носителя на основе донорской хрящевой ткани аутологичными клетками реципиента или аллогенными клетками в условиях длительного культивирования. Цель работы – изучить эффективность колонизации девитализированных матриксов на основе естественной хрящевой ткани трахеи человека назальными хондроцитами человека при добавлении к питательной среде провоспалительного цитокина Интерлейкин-1-бета (IL-1β). Материалы и методы. Матриксы-носители для тканевой инженерии трахеи получали на основе естественной хрящевой ткани трахеи человека методом девитализации и лазерного травления. Ревитализацию матриксов проводили путем заселения назальных хондроцитов человека. Гистологическое исследование проводили после окрашивания гематоксилином и сафранином-О с дальнейшей микроскопией на световом микроскопе Nikon Eclipse L200. Рентгеновская микротомография выполнялась на аппарате Phoenix nanotom m. Электронная микроскопия проводилась на установке Nova NanoSEM 230. Результаты. Выявлено статистически значимое увеличение интенсивности колонизации назальными хондроцитами (p = 0,0008) и стимулирование их миграционной активности (p < 0,0001) в присутствии IL-1β по сравнению с контрольными группами. Выводы. Добавление провоспалительного цитокина IL-1β в концентрации 1 мкг/мл к питательной среде способствует объемному заселению девитализированного хрящевого матрикса назальными хондроцитами человека, позволяя создавать высокоревитализированные материалы для тканевой инженерии трахеи

Reconstruction of one-dimensional chaotic maps from sequences of probability density functions

In many practical situations, it is impossible to measure the individual trajectories generated by an unknown chaotic system, but we can observe the evolution of probability density functions generated by such a system. The paper proposes for the first time a matrix-based approach to solve the generalized inverse Frobenius–Perron problem, that is, to reconstruct an unknown one-dimensional chaotic transformation, based on a temporal sequence of probability density functions generated by the transformation. Numerical examples are used to demonstrate the applicability of the proposed approach and evaluate its robustness with respect to constantly applied stochastic perturbations

Экспериментальная ортотопическая имплантация тканеинженерной конструкции трахеи, созданной на основе заселенного мезенхимальными и эпителиальными клетками девитализированного матрикса

Objective: to study the viability of a tissue-engineered graft (TEG) based on a devitalized tracheal scaffold (DTS) seeded with mesenchymal stromal and epithelial cells in an experiment on rabbits with assessment of cytocompatibility and biocompatibility in vivo. Materials and methods. Syngeneic mesenchymal stromal bone marrow cells (MSBMCs) and syngeneic lung epithelial cells of rabbit were obtained. The morphology and phenotype of the MSBMC culture were confirmed via immunofluorescence staining for CD90 and CD271 markers. Pulmonary epithelial cells obtained by enzymatic treatment of minced rabbit lung tissue were stained with CKPan, CK8/18 and CK14 markers characteristic of epithelial cells. The donor trachea was devitalized in three successive freezethawing cycles. Double-layer cell seeding of DTS was performed under static and dynamic culturing. Orthotopic implantation of TEGs was performed at the site of the anterolateral wall defect in the rabbit that was formed as a result of tracheal resection over four rings. Results were evaluated by computed tomography, histological and immunohistochemical analyzes. Results. A TEG implant, based on DTS, with bilayer colonization by cell cultures of rabbit MSBMC and epithelial cells was obtained. Three months after implantation, TEG engraftment was noted, no tracheal wall stenosis was observed. However, slight narrowing of the lumen in the implantation site was noted. Six months after implantation, viability of TEG was confirmed by histological method. Epithelialization and vascularization of the tracheal wall, absence of signs of purulent inflammation and aseptic necrosis were shown. The small narrowing of the lumen of trachea was found to have been caused by chronic inflammation due to irritation of the mucous membrane with suture material. Conclusion. A new model for assessing the viability of a tissue engineering implant when closing a critical airway defect was created. The developed TEG – based on DTS seeded (bilayer) by lung epithelial cells and BMSCs – was successfully used to replace non-extended tracheal defects in an in vivo experiment. The use of tracheal tissue-engineered graft for orthotopic implantation showed biocompatibility with minimal tissue response.Цель. Изучить жизнеспособность тканеинженерной конструкции (ТИК) на основе девитализированного трахеального матрикса (ДТМ), заселенного мезенхимальными стромальными и эпителиальными клетками, на модели оценки жизнеспособности тканеинженерного имплантата при закрытии критического дефекта дыхательных путей у кроликов. Оценить потенциал ТИК к поддержанию стабильного просвета трахеи в области имплантации. Материалы и методы. Получены сингенные мезенхимальные стромальные клетки костного мозга (МСК КМ) и сингенные эпителиоциты легкого кролика. Морфологию и фенотип культуры МСК КМ подтверждали иммунофлюоресцентным окрашиванием на маркеры CD90 и CD271. Клетки легочного эпителия, полученные методом энзиматической обработки измельченной ткани легкого кролика, были окрашены на характерные для эпителиальных клеток маркеры CKPan, CK8/18 и CK14. Девитализация донорской трахеи проведена тремя последовательными циклами замораживания–оттаивания. Двухслойное заселение ДТМ клетками выполнено в условиях статичного и динамического культивирования. Проведена ортотопическая имплантация ТИК на место дефекта переднебоковой стенки трахеи кролика, сформированного в результате резекции трахеи на протяжении четырех колец. Оценка результатов выполнена методами компьютерной томографии, гистологического и иммуногистохимического анализов. Результаты. Получен имплантат ТИК на основе ДТМ с двухслойным заселением клеточными культурами МСК КМ и эпителиоцитов кролика. Через 3 мес. после имплантации отмечалось приживление ТИК, стенозирования стенки трахеи не наблюдалось, однако отмечалось незначительное сужение просвета в области имплантации. На 6-й мес. после имплантации жизнеспособность тканеинженерной конструкции подтверждалась гистологическим методом. Показана эпителизация и васкуляризация стенки трахеи, отсутствие признаков гнойного воспаления и асептического некроза. Определена причина небольшого сужения просвета трахеи хроническое воспаление, вызванное раздражением слизистой шовным материалом. Заключение. Получена модель для оценки жизнеспособности тканеинженерного имплантата при закрытии критического дефекта дыхательных путей. Разработанная ТИК на основе ДТМ, двухслойно заселенного эпителиоцитами легкого и МСК КМ, была успешно применена для замещения непротяженных дефектов трахеи в эксперименте in vivo. Минимальная тканевая реакция на ТИК трахеи была обусловлена биосовместимостью имплантата

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Small Intestinal Bacterial Overgrowth in Various Specialties of Medical Practice (Literature Review and Expert Council Resolution)

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

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants