bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Ɣ-chain cytokine receptors as functional phenotype markers of PD-1and TIM-3-positive T cells in multiple myeloma
Authors: Batorov E. V. , Aristova V. A. , Ushakova G. Yu. , Sizikova S. A. , Denisova V. V. , Shevela E. Ya. , Ostanin A. A. , Chernykh E. R. 
Published: February 2023

T cells expressing checkpoint receptors PD-1, TIM-3 etc., are potential targets for monoclonal antibody immunotherapy in multiple myeloma (MM). However, checkpoint expressing T cell compartment includes different subsets, and their dysregulation following anti-checkpoint therapy can lead to the development of adverse events.The aim of this study was to evaluate activation markers – homeostatic cytokine receptors and transcription factors expressed by PD-1and TIM-3-positive T cells.Material and Methods. Relative counts of circulating PD-1and/or TIM-3-positive and negative T cells expressing common ɣ-chain cytokine receptors CD25, CD122, CD127, phosphorylated STAT5, and transcription factor EOMES associated with T cell exhaustion were studied using flow cytometry in 17 healthy donors, 22 MM patients with remission and 7 MM patients with progressive disease.Results. T cells expressing PD-1 and/or TIM-3 inhibitory checkpoint receptors in MM patients consisted of CD25+EOMESactivated cells, CD4+CD25+CD127-FOXP3+ regulatory T cells (Treg), CD4+CD25-EOMES+ dysfunctional cells. CD25+ T cells from healthy donors and MM patients, regardless of the expression of the studied checkpoint receptors, were EOMES-negative. No such association was found for CD122 and CD127 cytokine receptors. EOMES is a marker of T cell exhaustion for CD4+ T cells, but not for CD8+ T cells, in which it is more associated with activation. The proportion of CD4+ Tregs among circulating PD-1+ and TIM-3+ T cells was relatively low. A higher content of cytokine receptors in the population of TIM-3+ T cells may indicate the predominant involvement of TIM-3 in the control of homeostatic proliferation of mature T cells under lymphopenic conditions, while the expression of PD-1 may be more associated with the regulation of activation through T cell receptor. PD-1+ and/or TIM-3+ levels of activated, dysfunctional, and regulatory T cells can potentially be used to predict the safety and efficacy of targeted immunotherapy.
Feasibility of predicting the evolution of cerebral gliomas based on study of microRNA expression levels in blood plasma and saliva
Authors: Seliverstov R. Yu. , Zaraiskii M. I. , Gurchin A. F. , Kataeva G. V. , Tyurin R. V. , Naryshkin A. G. , Valerko V. G. 
Published: February 2023

The management of cerebral glioma (CG) remains challenging. Recently, methods based on the study of the expression levels of miRNAs in blood plasma have proven to be promising. The volume of tumor tissue is known to correlate with increased expression levels of microRNA-21 and -210. MicroRNA-15, -16, -34, -126 and -342 are involved in the regulation of tumor proliferative potential, and microRNA-128 is involved in the regulation of metabolic activity.The aim of the study was to evaluate the extended protocol for assessing the expression of microRNA-15, -16, -21, -34, -126, -128, -210, and -342 in the plasma and saliva of CG patients.Material and Methods. The study group consisted of 24 patients with supratentorial glioma (8 men and 16 women aged 41 to 71 years, mean age: 56 years). The control group consisted of 30 volunteers. MicroRNA expression was studied in plasma and saliva according to the StemLoop-RealTime protocol, using fluorescently labeled samples with small miRNA U6 as a reference gene. Statistical analysis was carried out using nonparametric methods.Results. The lack of CG stabilization and the most probable progression of the tumor with a poor prognosis was related to an increase in microRNA-21 and -210 expression levels and decrease in microRNA-128 expression and at least four of microRNA 15, -16, -34, -126, and -342. Stabilization of CG with a high probability of progression was associated with an increase in microRNA-21 or microRNA210 expression levels, decrease in no more than three of microRNA-15, -16, -34, -126, -342 expression levels as well as decrease in microRNA-128 expression. Stabilization of the tumor with a low probability of progression was associated with a decrease in the expression of microRNA-21 and -210 and in no more than one of miRNA-15, -16, -34, -126, -342 below the reference level, with a simultaneous increase in miRNA-128 expression.Conclusion. The determination of microRNA expression in blood plasma and saliva can be one of the important criteria for assessing the prognosis of CG.
LIMCH1 protein expression associated with lymph node metastasis in breast cancer
Authors: Alifanov V. V. , Tashireva L. A. , Zavyalova M. V. , Perelmuter V. M. 
Published: February 2023

Background. Lymph node metastasis in breast cancer is not only a variant of cancer progression, but is also associated with the development of hematogenous metastases. The LIMCH1 protein is involved in the mesenchymal type of migration due to the activation of non-muscle myosin IIA.The objective of the study was to investigate the association of different LIMCH1 protein expression variants with lymph node metastasis.Material and Methods. The retrospective study included 53 patients with invasive breast carcinoma of no special type. The study group included all molecular genetic types (luminal A, luminal B, HER2-positive and triple negative). The median age of the patients was 55.4 ± 14 years. According to the TNM classification, patients had stage T1–3N0–3M0 breast cancer. The patients did not receive preoperative chemotherapy. The expression of the LIMCH1 protein in tumor cells was assessed using immunohistochemistry. Anti-LIMCH1Prestige (HPA004184, Sigma Aldrich, Germany) and anti-LIMCH1-C-term (SAB2700402, Sigma Aldrich, Germany) antibodies were used.Results. Lymph node metastases were more frequent in patients with LIMCH1 protein expression in tumor cells. This is true for cytoplasmic expression of the LIMCH1 protein detected by the CH domain, but not for submembrane expression or expression of the LIMCH1 protein detected by the LIM domain, regardless of localization in the cell. This phenomenon was not associated with the morphological heterogeneity of breast cancer. The most unfavorable factor for worse metastasis-free survival is the combination of the presence of lymph node metastases and cytoplasmic expression of the LIMCH1 protein detected by the CH domain.Conclusion. The development of synchronous lymph node metastases in breast cancer is associated with the presence of cytoplasmic expression of the LIMCH1 protein detected by the CH domain in the primary tumor tissue.
Development of in vitro laboratory models of the tumor immune microenvironment to evaluate quality parameters and specific efficacy of the dendritic cell vaccine
Authors: Nekhaeva T. L. , Danilova A. B. , Fedoros E. I. , Efremova N. A. , Emelyanova N. V. , Blokhina M. L. , Yurova M. N. , Tyndyk M. L. , Baldueva I. A. 
Published: February 2023

Purpose of the study:development ofin vitrolaboratory models to evaluate quality parameters and specific efficacy of dendritic cell vaccine (DCV).Material and Methods.Biological samples of malignant tumor patients treated with autologous dendritic cell vaccine (DC) were included into the study. Immature DCs (n=46) and mature DCs (n=56) were used to induce proliferation of antigen-specific T lymphocytes (n=227). Autologous tumor cells from skin melanoma (n=10) or sarcoma (n=8) patients in the xCELLigence® assay system were used to study thein vitroantitumor cytotoxic activity of generated CTLs (n=18). The secretion of cytokines and cytolytic proteins was studied by multiplex analysis. The subpopulation composition of effector T-lymphocytes was determined by flow cytometry.Results.We revealed that mature DCs (CD83+CD1a-) had a high expression of antigen presenting molecules (HLA-DR) and those providing migration of DCs into lymph nodes (CCR7) as well as costimulatory molecules CD80 and CD86 as compared to immature DCs (CD83-CD1a+). Induction of mature DCs was found to stimulate an increase in the relative content of proliferating T cells compared with stimulation of immature DCs (p<0.001) and specific PTA+ tumor lysate (p<0.001). When studying cytotoxic activity of effector T-lymphocytes, we developed 2Din vitromodels using xCELLigence® analytical system and revealed 2 types of interaction: 1)in vitromodel № 1 – decrease in cell index (CI) of autologous tumor cell culture in the presence of activated effector T lymphocytes; 2)in vitromodel № 2 – no change in CI of autologous tumor cell culture when co-cultured with activated effector T cells compared to control (72 h observation). The results demonstrated cytotoxic activity of antigen-specific T lymphocytes due to high content of terminally differentiated cytotoxic T lymphocytes (TEMRA), GrB-producing CTLs, and cytokine secretion profile.Conclusion.Requirements for the quality of personalized autologous DCs, including control of immunophenotypic characteristics were developed, and functional activity of Tlymphocytes during induction of mature vaccine DCs was evaluated. A laboratory procedure was developed for quantitative assessment of cytotoxic activity of antigen-specific T-lymphocytes against autologous tumor using the xCELLigence® analytical system, thus allowing for personalized monitoring and predicting the effectiveness of DСV treatment.
Increased activity of enzymes involved in purine metabolism as one of the factors of rectal cancer pathogenesis
Authors: Zuikov S. A. , Polunin G. E. 
Published: February 2023

Aim: to study changes in the activities of purine nucleotide degradation enzymes – adenosine deaminase (ADA) and xanthine oxidase (XO) in patients with rectum cancer (RC).Material and Methods. The activity of purine nucleotide degradation enzymes was studied in blood plasma and tissue homogenates: tumor tissue and normal rectal mucosa in 70 patients with stage I–IV RC. The histological type of RC was adenocarcinoma. The levels of ADA and XO activities were measured using spectrophotometry.Results. The activity of ADA and XO in blood serum of RC patients was significantly higher than that of healthy people. A significant increase in the activity of ADA and XO in tumor tissue compared to normal tissue was also found. The relationship between the activities of the enzymes of purine catabolism in blood plasma and tissues were revealed. An increase in purine catabolism depending on the stage of RC was found.Conclusion. The increased ADA and XO activities indicated the enhanced purine catabolism not only in malignant transformation, but also in tumor progression.
Современное материнство в сельской местности Азербайджана: карьера, семья и ценности воспитания
Authors: Алмазова Ольга В. , Азимзаде Айдан А. , Гаврилова Маргарита В. , Бабаев Мурад А. 
Published: February 2023

Введение. Характерными чертами современного материнства являются желание женщин совмещать профессиональную карьеру с воспитанием детей, стремление форсировать развитие ребенка при осведомленности о нормативных этапах развития. Эти черты по-разному проявляются в разных социокультурных условиях. Была поставлена задача проследить, как современные тенденции отражаются на представлениях о воспитании детей у мам, проживающих в сельской местности Азербайджана, что является неизученной проблематикой. Методы. Выборка – 411 мам дошкольников, проживающих в сельской местности Азербайджана. Диагностический материал: опросник родительских убеждений о воспитании (E. Hembacher, M. C. Frank) и авторская анкета, направленная на получение дополнительных сведений об отношении к материнству и ожидания от ребенка. Результаты. Установлено, что азербайджанские женщины в большей степени ориентированы на то, чтобы быть женами и мамами, а не заниматься профессиональной деятельностью. В вопросах воспитания детей мамы доверяют старшим членам семьи и специалистам и не доверяют интернет-ресурсам. Наиболее предпочитаемыми качествами для своих детей называют патриотизм, уважение старших и стремление повышать образование и культурный уровень. Разделяемыми большинством азербайджанских мам, проживающих в сельской местности, утверждениями в вопросах воспитания детей являются следующие: «важно научить ребенка слушаться и уважать старших»; «важно дать детям возможность исследовать мир»; «надо читать ребенку и говорить с ним, даже пока он сам не может говорить»; «родители должны утешать детей, когда они напуганы или расстроены» и «родители должны знать, что любит и что не любит их ребенок» и др. Обсуждение результатов. Азербайджанские мамы детей 3–7 лет, проживающие в сельской местности, не стремятся форсировать развитие ребенка, нацелены на реализацию себя в семейных ролях и имеют основные, но не всегда полные, знания об особенностях развития детей дошкольного возраста.
Осознанное восприятие: дискретность vs непрерывность
Authors: Костина Дарья И. , Филиппова Маргарита Г. , Аллахвердов Михаил В. , Аллахвердов Виктор М. 
Published: February 2023

Аннотация: Введение. Является ли восприятие дискретным или непрерывным? Этот вопрос имеет давнюю историю, но в свете полученных в последние годы экспериментальных данных снова обретает актуальность. Имеющиеся модели опираются на разное понимание дискретности, и в них выделяются разные единицы дискретного восприятия. Теоретическое обоснование. В статье рассматривается развитие дискретных моделей восприятия и разбираются различные теоретические обоснования дискретности. Результаты и их обсуждение. Приводится обзор экспериментальных исследований, поддерживающих дискретные модели, обсуждаются основные направления их критики. Результаты новых исследований поддерживают идею о том, что дискретно именно осознаваемое восприятие, тогда как неосознаваемая обработка информации может быть непрерывной или осуществляться с бо́льшим временны́м разрешением. Сравниваются два популярных современных подхода к дискретному восприятию. В рамках одного из них предполагается, что дискретная единица восприятия относительно невелика и связана с временны́м разрешением, при этом она не является универсальной – дискретизация может осуществляться с разной частотой, например, для разных модальностей. В рамках второго подхода дискретизация связывается с необходимостью вычисления наилучшей осмысленной интерпретации поступающих данных. Дискретная единица в этом подходе (временно́е окно неосознаваемой обработки) является универсальной, но ее длительность не фиксирована и зависит от характера поступающих данных. Также предлагается альтернативный подход, опирающийся на положения концепции негативного выбора В. М. Аллахвердова, из которой также следует существование окна неосознаваемой обработки, длительность которого не является постоянной. Новизна данного подхода в том, что длительность окна связывается со сложностью операций контроля, задачей которого является отбор информации для поступления в сознание. Обсуждается возможность использования этого подхода для объяснения временно́й динамики эффектов прайминга и мигания внимания, за непостоянством временны́х границ которой мы видим проявление общей логики дискретизации.
A Review and Meta-analysis on Trastuzumab Resistance in Patients with
HER2+ Breast Cancer
Authors: Júnior Alexandre Holzbach , Cima Bernardo Perin , Staffen Mari Dalva , Lindenau Juliana Dal-Ri , Netto Muniz Yara Costa 
Published: February 2023

Background:
Trastuzumab is a monoclonal antibody that revolutionized the treatment of
HER2+ breast cancer. However, about 30% of patients demonstrate resistance to this drug

Objective:
The purpose of this study is to identify the mechanisms involved in resistance to treatment
with trastuzumab in women undergoing HER2+ breast cancer treatment.

Methods:
A wide review and meta-analysis were performed in the PubMed and Scielo databases up to
January 2022. All articles that analyzed the efficacy of the drug in HER2+ human patients treated with
trastuzumab were selected, except reviews, meta-analyses, and reports. Egger’s test was applied to
verify publication bias. Forest plot and PRISMA flowchart were employed.

Results:
60 articles were selected for the review and 15 included in the meta-analysis. A total of 102 resistance
mechanisms were identified, 73 of which are different from each other. The mechanisms have been
classified into 5 different categories. The main resistance mechanisms found are in the PI3K/Akt/mTOR
pathway or related to low HER2, often resulting from failure to assess HER2 status. Both groups presented
statistical significance. The two groups were not significantly different from each other.

Conclusion:
Drug resistance is the main challenge of trastuzumab-based treatment. To overcome this
challenge, it is important to continue efforts to understand the mechanisms of cancer drug resistance,
identify therapies that can treat refractory cancer to current therapies, and possibly create a panel of
genes that predict resistance, avoiding symptomatic and economic costs. The main limitation of this
study was the selection and population bias.

PROSPERO Registration Number:
This study is registered in PROSPERO (CRD42020169304).
Research Advances of Clinical Application of Oncolytic Viruses in Treatment
of Gynecologic Cancers
Authors: Deng Mingjing , Wang Qi 
Published: February 2023

Abstract:
Oncolytic viruses (OVs) have become one of the main strategies of cancer biotherapy. They
are genetically engineered or naturally occurring viruses that selectively replicate and kill tumor cells
without harming normal tissues. Gynecologic cancers have become a major health problem for women.
OVs therapy plays an increasingly important role in the treatment of gynecological tumors with promising
clinical effects. A variety of OVs is used in the treatment of gynecological tumors, either as single
oncolytic virus therapy or in combination with other therapies. Some oncolytic virus therapies have
entered early clinical trials and have shown favorable safety, clinical activity, and immune activation.
The present study summarized the anti-tumor mechanism of OVs and their modifications. The study
reviewed the latest clinical progress on the application of the OVs in the treatment of gynecologic cancers.
The unique challenges in the development of the viruses as a novel drug for the treatment of gynecologic
oncology were also discussed and their future prospects were elucidated.
A Framework of Nutrient Analyser Model for Comparing Food Nutrients
Authors: Ng Set Foong , Tukiman Norbaiti , Ismail Azianti , Khalid Ahmad Khudzairi , Yunos Nurhazirah Mohamad , Norizan Nurul Aznyda 
Published: February 2023

Background:
Consumers’ lack of nutritional awareness causes them to have little interest
in reading and analysing nutritional information on food labels. Rigorous and scientific
comparisons of the nutrient contents of commercial buns are rarely conducted in Malaysia.

Objective:
The first objective of this study is to classify nutrient contents in commercial buns into
beneficial and non-beneficial nutrients. The second objective is to develop a nutrient analyser
model framework to compare the nutrient contents for different types of commercial buns.

Methods:
The nutrient analyser model was developed based on the mathematical theory Technique
for Order of Preference by Similarity to the Ideal Solution (TOPSIS) and Shannon’s Entropy
Model. The framework of the nutrient analyser model using the two theories was developed.
Nutritional data taken from several commercial buns in Malaysia was applied to the model.

Results:
The results show that the model was able to identify the type of bun having the most beneficial
nutrient contents and the least non-beneficial nutrient contents.

Conclusion:
The framework of the nutrient analyser model could serve as a reference for other researchers.
The findings benefit the community and researchers as the results indirectly improve
consumer awareness of food nutrients prioritizing good health.
Glycation-induced Amyloid Formation in Proteins: An Emerging
Perspective to Explore Diabetes Associated Onset of Neurodegenerative
Symptoms
Authors: Prosad Banik Samudra 
Published: February 2023

Abstract:
Non-enzymatic protein glycation occurs spontaneously via the formation of sugarprotein
Schiff adducts. The end products of this pathway are terminally misfolded proteins popularly
known as Advanced Glycation End (AGE) Products. Glycated proteins account for a diverse
spectrum of physiological maladies including arteriosclerosis, renal failure, diabetic complications,
obesity, and neurological disorders. AGEs not only jeopardise the functionality of
modified proteins but also induce the formation of Covalent protein cross-links. Glycation has
the potential to induce the unfolding and refolding of globular proteins into cross-β structures
thus resembling many amyloid deposits like amyloid beta, tau protein, and prions. However,
glycation-induced amyloid formation is not a generic property of proteins; instead, it is guided by
the nature and conformation of the protein, the type of glycation agent as well as the solution
conditions governing the glycation reaction. The half-lives of AGE adducts are prolonged by
their impaired proteasomal clearance since glycation modifies the lysine residues and renders
them unavailable for ubiquitination. AGEs are cleared via sequestration with specific cell surface
receptors (RAGE); subsequently, downstream signalling events involving MAPK and NF-κB
result in the activation of inflammatory response or the apoptotic pathway. This perspective article
discusses the current developments in understanding the various facets of glycationassociated
protein aggregation and the corresponding development of amyloid-like entities.
A Cross-Validation of the Revised Moral Virtue Scale for Thai Nursing Students: Confirmatory Factor Analysis and Multiple-Group Approach
Authors: Orathai Pisamai , Chaimo Kesinee , Chuengkriangkrai Benchaporn 
Published: February 2023

Background
The preparation of ethics in the nursing profession must be an incubator when becoming a nursing student to raise awareness of the importance and the need for professional development. In evaluating nursing students’ moral behavior, it is essential to have a well-developed instrument that reflects the actual moral behavior of nursing students.

Objectives
To correct the limitations of the preliminary Moral Virtue Scale for Thai Nursing Students by developing and evaluating the construct validity and reliability of the revised scale.

Methods
An extensive literature review and the preliminary scale were used to synthesize and develop the moral virtue definition, domains, items, and hypothesized model. The revised scale was tested on 1,000 nursing students from two nursing education institutes. The sample was split into a calibration sample (n = 489) and a validation sample (n = 511) to examine the construct validity and reliability using confirmatory factor analysis and multiple-group analysis.

Results
Confirmatory factor analysis and a multiple-group approach provided evidence of construct validity and construct reliability. Both calibration and validation groups supported a consistent factor structure. The calibration group satisfied the Cronbach’s alpha coefficients of ten domains from .75 to .87. A full scale was .97. In the validation group, the Cronbach’s coefficient values ranged from .78 to .92, and a full scale was .98.

Conclusion
Providing a valid and reliable instrument in this study may benefit the nurse educators. The revised scale can potentially measure and monitor Thai nursing students' moral behavior.