High Diagnostic Potential Research Articles

Modern approaches to diagnosis and treatment of early-onset neonatal sepsis

Early-onset neonatal sepsis (EOS) remains the leading cause of morbidity and mortality, especially among premature babies. Therefore, accurate diagnosis, prompt monitoring of the course of the disease and an effective therapeutic strategy are a guarantee of improving the quality of medical care for newborns, as well as an important reserve for reducing perinatal losses. The aim of the work to summarize modern views on the diagnosis and treatment of early-onset neonatal sepsis in newborns with perinatal pathology. Results and their discussion. An analytical review of modern literature data on problematic issues of EOS diagnostics is carried out. The approaches are stated and the main directions of EOS management at the present stage are formulated. It was revealed that the lack of a consensus definition of neonatal sepsis, the nonspecificity of clinical data is a limiting factor in the timely accurate identification of the septic process. Insufficient diagnostic value of existing laboratory tests leads to defects in the registry and monitoring of this disease, the inability to conduct an objective assessment of the existing epidemiological and microbiological situation in the health care system and the subsequent effective implementation of preventive measures. Conclusions. In the conditions of modern scientific realities, none of the existing laboratory tests can sufficiently reliably confirm or deny the presence of EOS in a newborn child, which determines the search for new promising laboratory tests with high diagnostic and prognostic potential. The optimal treatment strategy for newborns with EOS is broad-spectrum antibiotics. However, today the global problem of excessive irrational prescribing of antibacterial drugs is associated with the formation of multidrug-resistant strains of bacteria, as well as the development of long-term adverse effects, which requires improved diagnostic and treatment algorithms for children who are in the risk group of the development of neonatal sepsis by implementing a comprehensive approach using modern accurate tests in the dynamics of the disease

Ultrasound of scrotal and penile emergency: how, why and when.

High-resolution ultrasound is the most common imaging technique used to supplement the physical examination of scrotum and penis with great accuracy in assisting the diagnosis of the various pathologies of male genital system, with the highest diagnostic potential in emergency conditions. Technical advancements in real-time high-resolution, color flow Doppler sonography and contrast enhanced ultrasonography (CEUS) have led to an increase in the clinical applications of scrotal and penile sonography. In this pictorial review we focus on common and uncommon male genitalia emergency with special emphasis on the role of ultrasound assessment and its specific findings to improve diagnostic accuracy.

Characterization of the monoclonal antibody specific to the ORF72 protein of koi herpesvirus and cellular distribution analysis of the viral protein.

Koi herpesvirus (KHV) is an emerging pathogen of koi and common carp that causes a severe disease and mass mortality of infected fish. The KHV ORF72 protein is an important capsid protein that has been suggested to be a candidate for the development of diagnostic reagents and KHV vaccines. The purpose of this study was to clone and express the KHV ORF72 gene for further preparation of a specific monoclonal antibody (mAb) and to analyse cellular distribution of the viral protein. The mAb 3E1 could specifically recognize the expressed ORF72 protein of transfected cells by indirect immunofluorescence, and the antigenic site recognized by the mAb 3E1 was mapped to the region of N-terminal 124 residues of KHV ORF72. This mAb was further demonstrated to specifically detect the KHV-infected fish tissue by immunohistochemistry, thereby suggesting its high diagnostic potential. In addition, the cellular distribution analysis of the KHV ORF72 protein revealed that the region of amino acid residues 125-247 was related to mitochondrial localization and proliferation. Furthermore, a putative nuclear export signal (NES) of ORF72 at the residues 201-212 was confirmed on the basis of its function associated with NES activity.

Nano Meets Micro-Translational Nanotechnology in Medicine: Nano-Based Applications for Early Tumor Detection and Therapy.

Nanomaterials have great potential for the prevention and treatment of cancer. Circulating tumor cells (CTCs) are cancer cells of solid tumor origin entering the peripheral blood after detachment from a primary tumor. The occurrence and circulation of CTCs are accepted as a prerequisite for the formation of metastases, which is the major cause of cancer-associated deaths. Due to their clinical significance CTCs are intensively discussed to be used as liquid biopsy for early diagnosis and prognosis of cancer. However, there are substantial challenges for the clinical use of CTCs based on their extreme rarity and heterogeneous biology. Therefore, methods for effective isolation and detection of CTCs are urgently needed. With the rapid development of nanotechnology and its wide applications in the biomedical field, researchers have designed various nano-sized systems with the capability of CTCs detection, isolation, and CTCs-targeted cancer therapy. In the present review, we summarize the underlying mechanisms of CTC-associated tumor metastasis, and give detailed information about the unique properties of CTCs that can be harnessed for their effective analytical detection and enrichment. Furthermore, we want to give an overview of representative nano-systems for CTC isolation, and highlight recent achievements in microfluidics and lab-on-a-chip technologies. We also emphasize the recent advances in nano-based CTCs-targeted cancer therapy. We conclude by critically discussing recent CTC-based nano-systems with high therapeutic and diagnostic potential as well as their biocompatibility as a practical example of applied nanotechnology.

GLAD-PCR Assay of R(5mC)GY Sites in the Regulatory Region of Tumor-Suppressor Genes Associated with Gastric Cancer.

At early stages of carcinogenesis, the regulatory regions of some tumor suppressor genes become aberrantly methylated at RCGY sites, which are substrates of DNA methyltransferase Dnmt3. Identification of aberrantly methylated sites in tumor DNA is considered to be the first step in the development of epigenetic PCR test systems for early diagnosis of cancer. Recently, we have developed a GLAD-PCR assay, a method for detecting the R(5mC)GY site in the genome position of interest even at significant excess of DNA molecules with a non-methylated RCGY site in this location. The aim of the present work is to use the GLAD-PCR assay to detect the aberrantly methylated R(5mC)GY sites in the regulatory regions of tumor suppressor genes (brinp1, bves, cacna2d3, cdh11, cpeb1, epha7, fgf2, galr1, gata4, hopx, hs3st2, irx1, lrrc3b, pcdh10, rprm, runx3, sfrp2, sox17, tcf21, tfpi2, wnt5a, zfp82, and znf331) in DNA samples obtained from gastric cancer (GC) tissues. The study of the DNA samples derived from 29 tumor and 25 normal gastric tissue samples demonstrated a high diagnostic potential of the selected RCGY sites in the regulatory regions of the irx1, cacna2d3, and epha7 genes; the total indices of sensitivity and specificity for GC detection being 96.6% and 100%, respectively.

Spectroscopic studies of the molecular composition of the dentinal and gingival fluids and their diagnostic potential for preventive screening of dentin caries

The aim of the work is a spectroscopic investigation and comparison of the molecular composition of dentine and gingival fluids as well as of their diagnostic potential for the preventive screening of dentin caries. Applying infrared spectroscopy including synchrotron radiation the samples of biological fluids taken from the oral cavity (dentine fluid, fluid from the gingival sulcus and blood) were studied for the patients with the progressive dentine caries. The part of this research was undertaken with the infrared microspectroscopy beamline at the Australian Synchrotron. Dentine and gingival fluids were shown to have no less complicated composition than the blood serum. Having all this in mind, in spite that these two fluids are derivatives of the blood serum, and a majority of the molecular groups observed in all of the three fluids can be detected in their IR-spectra, it follows that there is a number of signature modes that are in fact present in the IR spectra of only dentine and gingival fluids. This fact indicates at the molecular exchange between them under certain conditions. It means the high diagnostic potential in the study of the pathologic processes occurring in the oral fluid of a human. We have observed and fixed an increase of thiocyanates and esters in the samples of both dentine and gingival fluids under the development of dentin caries. Utilization of the gingival fluid for screening taking into account that its sampling is not such a complicated challenge as dentine fluid sampling will promote a transition to the personalized medicine, the development of high-technology healthcare and technology of the health preservation as a whole.

Development of anti-chloro 192 tyrosine HDL apoA-I antibodies for the immunodiagnosis of cardiovascular diseases

High density lipoproteins (HDL) are considered cardio protective. Apolipoprotein A-I (apoA-I), a major component of HDL helps in reverse cholesterol transport, whose function is greatly affected during atherosclerosis due to oxidation by myeloperoxidase. Amino acid tyrosine residue of apoA-I at position 192 and 166 are sensitive to oxidation by myeloperoxidase resulting in the generation of chlorinated and nitrated apoA-I and they are believed to be present in atherosclerotic plaques and in circulation. These oxidized apoA-I have been suggested as potential indicator(s) of CVD risks in humans. To detect the levels of oxidized apoA-I there is a need for developing monoclonal antibodies (mAbs) with high specificity and sensitivity that could be utilized routinely in clinical immune based assays for blood plasma or for in vivo imaging. In this study, chemically chlorinated apoA-I (chlorinated 192tyrosine- apoA-I) and a short synthetic peptide, containing the corresponding chlorinated tyrosine residue, conjugated to keyhole limpet hemocyanin (KLH) carrier protein were used for immunization. Stable hybridoma clones F7D5 and G11E3 were found to be highly sensitive and reactive towards chlorinated 192tyrosine- apoA-I. Interestingly, these mAbs also displayed positive reaction with atherosclerotic plaques obtained from mouse and human biopsies. In vitro or in vivo diagnostic tests could be developed either by detecting oxidized apoA-I in human plasma or by directly imaging atheroma plaques as both mAbs were shown to stain human atheroma. The anti-chlorinated 192tyrosine- apoA-I mAbs described in this study may have a high diagnostic potential in predicting CVD risks.

Abstract 837: Circulating cell-free DNA methylation assay: Towards early detection of multiple cancer types

Abstract Background: Alterations in DNA methylation play a key role in tumor initiation, and methylation markers are well established for detecting various cancer types. Cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is a non-invasive method to obtain representative epigenetic information from solid tumors. In the present study, we identified and validated cancer-specific methylation markers for diagnosis of liver, breast and colorectal cancers with high sensitivity and specificity. Methods: Three blinded validation studies were performed in order to evaluate individual panels of DNA methylation markers developed for the detection of liver, breast or colorectal cancers. For the liver cancer panel study, samples drawn from 154 subjects were analyzed, including healthy donors (30) and subjects diagnosed with benign liver disease (10), liver cancer stage I-IV (60), or another cancer type (30). For the breast cancer panel study, samples drawn from 151 subjects were analyzed, including healthy donors (39) and subjects diagnosed with benign breast disease (15), breast cancer stage I-IV (65), or another cancer type (32). For the colorectal cancer panel study, samples drawn from 154 subjects were analyzed, including healthy donors (42) and subjects diagnosed with benign colorectal disease (14), colorectal cancer stage I-IV (68), or another cancer type (30). Cell-free DNA was extracted from all samples, bisulfite converted, and DNA methylation was quantified at target sites by using the IvyGene Platform for each of the three cancer-specific marker panel. Results: By quantifying DNA methylation at the target sites, the cancer-specific markers were able to differentiate subjects diagnosed with cancer from both healthy donors and subjects with benign diseases. The liver cancer cfDNA methylation panel showed an overall sensitivity of 95% and specificity of 97.5%. Whereas, the breast cancer cfDNA methylation panel correctly identified the breast cancer samples for an overall calculated sensitivity of 89% and specificity of 96%. The colorectal cancer cfDNA methylation panel also showed high overall sensitivity of 93% and specificity of 100%. Conclusions: These results demonstrate the high diagnostic potential of cfDNA methylation markers isolated from blood for the detection of multiple cancers at various stages with high sensitivity and specificity. In addition, a quantitative analysis of cfDNA methylation signature provides an opportunity for monitoring of disease. The benefits of a sensitive and specific assay to identify and monitor cancer is anticipated to aid disease management and ultimately, improve patient outcomes. Citation Format: Dhruvajyoti Roy, David Taggart, Lianghong Zheng, Dan Liu, Gen Li, Mingzhen Li, Kang Zhang, Richard A. Van Etten. Circulating cell-free DNA methylation assay: Towards early detection of multiple cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 837.

Epigenetic Changes in the Pathogenesis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects about 1% of the world’s population. The etiology of RA remains unknown. It is considered to occur in the presence of genetic and environmental factors. An increasing body of evidence pinpoints that epigenetic modifications play an important role in the regulation of RA pathogenesis. Epigenetics causes heritable phenotype changes that are not determined by changes in the DNA sequence. The major epigenetic mechanisms include DNA methylation, histone proteins modifications and changes in gene expression caused by microRNAs and other non-coding RNAs. These modifications are reversible and could be modulated by diet, drugs, and other environmental factors. Specific changes in DNA methylation, histone modifications and abnormal expression of non-coding RNAs associated with RA have already been identified. This review focuses on the role of these multiple epigenetic factors in the pathogenesis and progression of the disease, not only in synovial fibroblasts, immune cells, but also in the peripheral blood of patients with RA, which clearly shows their high diagnostic potential and promising targets for therapy in the future.

(R)-[18F]NEBIFQUINIDE: A promising new PET tracer for TSPO imaging

Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO), has a high diagnostic potential in neurodegenerative disorders and cancer. However, TSPO is considered a challenge for molecular imaging due to the poor availability of suitable radiotracers with adequate pharmacokinetic properties. Here, we describe the development of a radiofluorinated pyridinyl isoquinoline analogue of the established TSPO PET tracer (R)-[11C]PK11195 with improved binding properties in all known human TSPO phenotypes. We conducted a complete preclinical evaluation using in vitro, in vivo and ex vivo methods to assess the performance of this novel radiotracer and observed high specific binding of the radiotracer to TSPO, as well as high metabolic stability. Therefore, we propose this radiolabeled compound for further evaluation in animal models as well as in clinical trials.

Methodology of Teaching Graphic Methods for Solving Problems with Parameters as a Means to Achieve High Mathematics Learning Outcomes at School

The introduction of new standards of mathematical education requires to stop understanding of the learning process as the transfer of ready-made knowledge and experience. Educational activity built on the principle of self-construction of knowledge by schoolchildren is highly demanded in new environment. Tasks with parameters have high learning, development, research and diagnostic potential. It allows to identify and in the process of teaching mathematics to prepare students who possess subject knowledge at the highest level, corresponding to the trends of the time. The urgency of the problem under study is determined by the need for students to form the ability to solve problems with parameters in order to achieve high results in mathematical, intellectual and personal development. The aim of the research is to develop a methodology for teaching students how to solve problems with parameters as an effective means of high-quality mathematical studies. The authors have identified main methods for solving problems with parameters and approaches to their study, and proved the theoretical basis for the application of these methods in the learning process. Therefore, they have shown the role of the propaedeutic stage of teaching graphic methods for solving problems with parameters, its goals, objectives and content. The authors suggest a methodology for designing a system of tasks that contributes to achieving high learning outcomes, which has passed multi-stage approbation. Moreover, they prove the need to use the Live Mathematics software as an effective visualization tool for studying graphic methods for solving problems with parameters. The methodology described in the article can be used by teachers at school and extracurricular mathematics classes, by the authors of textbooks for students and teachers, and it can also be the basis for a special course for students of pedagogical universities.

Disturbed energy and amino acid metabolism with their diagnostic potential in mitral valve disease revealed by untargeted plasma metabolic profiling.

Mitral valve disease (MVD), including mitral valve regurgitation (MR) and mitral valve stenosis (MS), is a chronic and progressive cardiac malady. However, the metabolic alterations in MVD is not well-understood till now. The current gold standard diagnostic test, transthoracic echocardiography, has limitations on high-throughput measurement and lacks molecular information for early diagnosis of the disease. The present study aimed to investigate the biochemical alterations and to explore their diagnostic potential for MVD. Plasma metabolic profile derangements and their diagnostic potential were non-invasively explored in 34 MR and 20 MS patients against their corresponding controls, using high-throughput NMR-based untargeted metabolomics. Eighteen differential metabolites were identified for MR and MS patients respectively, on the basis of multivariate and univariate data analysis, which were mainly involved in energy metabolism, amino acid metabolism, calcium metabolism and inflammation. These differential metabolites, notably the significantly down-regulated formate and lactate, showed high diagnostic potential for MVD by using Spearman's rank-order correlation analysis and ROC analysis. To the best of our knowledge, the present study is the first one that explores the metabolic derangements and their diagnostic values in MVD patients using metabolomics. The findings indicated that metabolic disturbance occurred in MVD patients, with plasma formate and lactate emerged as important candidate biomarkers for MVD.

The application of medical images in pharmacy

Introduction: The development of medical imaging methods offers nowadays essential tools not only for early diagnosis of diseases, as well as in supporting the therapy, in concrete with regard to planning and monitoring. The techniques considered include the areas of Radiology (CT, MRI and fMRI) and Nuclear Medicine (PET), with a view to understand, mainly, its relationship to the Pharmacy area. CT (Computer Tomography) allows the creation of high-definition bi and three-dimensional anatomical images as a result of submitting the human body to x-rays that cross the tissues in multiple directions. This technique can involve the use of pharmaceutical drugs as contrast agents. MRI (Magnetic Ressonance Imaging) subjects individuals to magnetic fields and radio frequency pulses and allows to get precise information about the anatomical structure. fMRI (functional Magnetic Ressonance Imaging) makes it possible to obtain information about brain function from the study of changes in blood flow and oxygenation. Nuclear Medicine techniques use radiopharmaceuticals (composed of a radionuclide and a drug) that are mainly used for medical diagnosis, but also, in some cases, for therapy. Using the technique of PET (Positron Emission Tomography) is possible, for example, to study the metabolism of glucose, associating the radionuclide Fluor to glucose, and thus assess the evolution of tumors. Materials and methods: A research paper work was conducted in order to identify and evaluate the relationship between the field of Pharmacy and the application and operation of various medical imaging techniques. Application examples are given and it is explored, in particular, the integration of information from different techniques (hybrid or multimodal imaging). Results: Duff and collaborators [1] show how reliable associations between drug-related activity modulations and drug efficacy can be identified using fMRI, in particular concerning analgesics (pain medication). Domingos Vieira and colleagues [2] show the hybrid PET-MRI system high potential in the diagnosis of neurodegenerative diseases, especially in case of Alzheimer’s disease in which are used radiopharmaceuticals marked with 18F, in order to identify the amyloid plaques formed and to evaluate the use of glucose by the brain. Sawicki and collaborators [3] show the high diagnostic potential of 18F-FDG PET-MRI system in patients with breast cancer, in comparison with 18F-FDG PET-CT system, MRI, and CT techniques. Discussion and conclusions: Imaging techniques are powerful with regard to early diagnosis of various diseases, as well as in the therapy assessment and have a close relationship with the area of the Pharmacy. The use of hybrid systems presents typically advantage over the use of separate techniques.

Genetic heterogenety of tumour-like lesions of bones in maxillofacial area

Benign tumors and tumor-like lesions of the bones are rare. At present, their diagnosis is based on radiation and pathological methods. However, the genetic etiology of this group of diseases is being actively studied in order to search for molecular markers with high diagnostic and prognostic potential.

Epigenetic biomarkers for noninvasive detection of colorectal cancer.

45 Background: Aberrant DNA hypermethylation is known to be a major mechanism for inactivation of cancer-associated genes, including tumor suppressor genes, in colorectal cancer (CRC) and in other human cancers. Cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is a non-invasive method to obtain representative epigenetic information from solid tumors. In the present study, we identified and validated colorectal cancer-specific methylation markers for diagnosis of the disease with high sensitivity and specificity. We also compared the relative amount of DNA methylation at these target sites in relation to colorectal cancer stage. Methods: For marker validation, a total of 154 samples drawn from 68 subjects diagnosed with colorectal cancer (Stage I to IV), 42 healthy donors, 14 subjects with benign colorectal diseases, and 30 subjects diagnosed with other cancer types (breast, liver and lung cancer: 10 cases each) were obtained for a randomized, blinded study. Cell-free DNA was then extracted from the samples, bisulfite converted, and DNA methylation was quantified by using the IvyGene Platform. Results: By quantifying DNA methylation at the target sites, colorectal cancer samples were differentiated from samples drawn from healthy subjects or subjects with benign disease with an overall sensitivity of 93% (95% CI: 86-99) and specificity of 100% (95% CI: 85-100). All stages (I to IV) of colorectal cancer were identified with sensitivities ranging from 67% to 100%. None of the 30 samples drawn from subjects diagnosed with breast, liver or lung cancers were incorrectly identified as a colorectal cancer by the assay, for a calculated analytical specificity of 100%. Conclusions: These results demonstrate the high diagnostic potential of cfDNA methylation markers isolated from blood for the detection of colorectal cancer. Taken together, these findings establish the utility of methylation biomarkers for the detection of colorectal cancers as early as Stage I. In addition, a quantitative analysis of cfDNA provides an opportunity for non-invasive detection and monitoring of disease.

Abstract P4-01-25: Blood-based DNA methylation as epigenetic biomarkers for non-invasive detection of breast cancer

Abstract Background: DNA methylation significantly contributes to all hallmarks of cancer. In particular, promoter hypermethylation has been identified as a potential marker for early detection of cancer, therapy monitoring, assessment of prognosis or prediction of therapy response. Here, we identified and validated breast cancer-specific methylation markers for diagnosis of the disease with high sensitivity and specificity. Methods: 151 bio-banked samples were obtained for a randomized blind study; 65 subjects diagnosed with breast cancer (Stage I to IV), 15 subjects with benign breast disease, 32 subjects diagnosed with other cancer types (11 colorectal, 9 liver and 12 lung cancer), and 39 healthy donor samples. Cell-free DNA was then extracted from the samples, bisulfite converted, and DNA methylation was quantified by using the IvyGene Platform. Finally, the raw data were collected and analyzed to evaluate the test performance. Results: A total of 53 of the 65 breast cancer samples were correctly identified for an overall calculated sensitivity of 89% with little difference between the sensitivity of detecting Stage I to Stage IV breast cancer (range 88% to 94%). The breast cancer subjects were correctly identified with 96% specificity. Additionally, 28 of 32 samples drawn from healthy donor subjects (specificity 95%) and all 15 samples drawn from subjects diagnosed with benign breast disease (specificity 100%) were also correctly identified. Of the samples drawn from subjects with cancer other than breast cancer, over 96% of lung cancer, colorectal cancer and liver cancer samples were correctly identified as not breast cancer. Conclusion: The results demonstrate the high diagnostic potential of ctDNA methylation markers in the blood for the detection of breast cancer. In addition, a quantitative analysis of ctDNA provides an opportunity for non-invasive detection of cancer and it's benefits can be anticipated to improve patient management and healthcare quality.

Confocal laser endomicroscopy for upper tract urothelial carcinoma: validation of the proposed criteria and proposal of a scoring system for real-time tumor grading

PurposeConfocal laser endomicroscopy (CLE) is a fluorescence-based fiber-optic imaging technique with the potential for intraoperative grading of upper tract urothelial carcinoma (UTUC). This study aims to (1) investigate the prevalence of the previously proposed CLE criteria for bladder cancer in papillary UTUC, (2) estimate the diagnostic value of CLE for UTUC grading and (3) propose a scoring system for a more quantifiable approach of CLE-based grading of UTUC.Materials and methodsUreteroscopic CLE was performed in patients with UTUC. Following CLE imaging, co-localized biopsies were taken for histopathologic comparison. Postoperatively, two blinded raters assessed the CLE images.ResultsFifty-three papillary UTUCs (34 low grade and 19 high grade) were imaged with CLE in 36 patients. All the previously described CLE criteria were identifiable in varying proportions. After excluding 10 non-diagnostic recordings (5 low grade and 5 high grade) due to insufficient image quality, the histopathologic grade was correctly identified with CLE in 26 low-grade UTUCs (90%) and in 12 high-grade UTUCs (86%). The most prevalent CLE criteria with the highest diagnostic potential were cellular organization, morphology and cohesiveness of cells. A scoring system was proposed with these criteria, which yielded similar diagnostic accuracies.ConclusionsBased on the previously proposed criteria, CLE enables accurate grading of papillary UTUC at a non-diagnostic rate of 19%. The most prevalent CLE criteria with the highest diagnostic potential for grading of papillary UTUC are cellular organization, morphology and cohesiveness of cells. The proposed scoring system may simplify the assessment of CLE images for UTUC grading but external validation is required.

КРЕОЛІЗОВАНІ ТЕКСТИ (КОМІКСИ) ЯК ЗАСІБ АКТИВІЗАЦІЇ НАЦІОНАЛЬНОЇ ТА ГРОМАДЯНСЬКОЇ САМОІДЕНТИФІКАЦІЇ МОЛОДІ

The article is devoted to the problem of activation of national and civic identity. The authors determined the indicators of national and civic identity for qualitative content analysis of verbal and non-verbal components of multimodal texts (comics). The authors considered the peculiarities of usage of comics in training practice for: actualization of national and civic self-identification barriers of youth in different subsystems of social interaction; increasing the youth’s resistance to propaganda’s influence; fixation of positive change during the training. The authors established, that comics creation as a method has high diagnostic and developmental potential for activation of youth’s national and civic self-identification processes. It was shown, that usage of comics: 1) facilitates the interaction between verbal and non-verbal components of the comics and also has ample opportunities of its usage as a projective technique; 2) provides the procedure’s relevance for the target audience, since creative tasks, that involve comics creation are familiar to youth; 3) matches the basic ways of communication practices change (articulation, reconfiguration, borrowing); 4) enables the realization of clarification, prognostic modeling and construction (reconstruction) of the identification discourse. The authors revealed three basic intentions, that arised among the training participants during the comics’ remake: increase of the comics’ characters activity in defending their own national and civic identity, increase of characters’ assertiveness level (the ability to defend their own standpoint without the violation of anther individual’s moral rights) and willing to search for ways to constructively solve conflict situations. The existence of those intentions can be considered as evidence of participants’ positive change and general effectiveness of the training.

Dynamic metrics-based biomarkers to predict responders to anti-PD-1 immunotherapy

BackgroundAnti-PD-1 immunotherapies have shown clinical benefit in multiple cancers, but response was only observed in a subset of patients. Predicting which patients will respond is an urgent clinical need, but current companion diagnosis based on PD-L1 IHC staining shows limited predictability.MethodsA dynamic, metrics-based biomarker was developed to discriminate responders from non-responders for anti-PD-1 immunotherapy in B16F10 melanoma-bearing mice.ResultsSimilar to patients, there was considerable heterogeneity in response to anti-PD-1 immunotherapy in mice. Compared with the control group, 45% of anti-PD-1 antibody-treated mice displayed improved survival (defined as responders) and the remainder only gained little, if any, survival benefit from PD-1 blockade (non-responders). Interestingly, the dynamics of IFN-γ secretion by peripheral lymphocytes was associated with faster secretion onset (shorter lag time), stronger exponential phase, shorter time to half magnitude, and higher magnitude of secretion in responders at day 10 after tumour inoculation. To sufficiently predict responders from non-responders, IFN-γ secretion descriptors as well as phenotypic markers were subjected to multivariate analysis using orthogonal partial least-squares discriminant analysis (OPLS-DA).ConclusionsBy integrating phenotypic markers, IFN-γ secretion descriptors sufficiently predict response to anti-PD-1 immunotherapy. Such a dynamic, metrics-based biomarker holds high diagnostic potential for anti-PD-1 checkpoint immunotherapy.

Optische Kohärenztomographie-Angiographie: Stellenwert in der Glaukomdiagnostik

Optical coherence tomography angiography (OCTA) is anovel noninvasive method which enables aquantitative evaluation of retinal and optic nerve head (ONH) perfusion. In this article, we discuss the principles of the application of OCTA and give a summary of the knowledge gained by using this method in glaucoma patients. This article is based on aselective literature search and the analysis of own data. Quantitative OCTA parameters have agood reproducibility in glaucoma patients. Glaucoma patients show areduced flow density (FD) in the ONH and in the area of the macula compared with ahealthy control group. The FD parameters show agood diagnostic discriminatory power but are not superior to the structural parameters used in routine diagnostics. The reduced FD measured using OCTA correlates with the extent of functional and structural glaucoma damage. The OCTA is noninvasive, fast and reproducible. Initial results from studies on glaucoma patients show the high diagnostic potential of this method. The OCTA could become apart of clinical glaucoma management in the future.