Development Of Early Diagnosis Research Articles

Implication of exon 4 TP53 Gene mutations in colorectal cancers in Senegalese patients

Background: Colorectal cancer (CRC) is a major cause of death in men and women, comprising about 10% of cancer deaths after breast and lung cancer. The most significant risk factors currently implicated in the etiology of this cancer are genetic, likely due to several mutations. Methods: The study explored the involvement of genetic factors in these pathologies; specifically, exon 4 of the TP53 gene was studied in 15 CRC patients and compared with 10 healthy individuals as controls. The position of the marker mutations was determined with the Mutation Surveyor software version 5.1.2. DnaSP version 5.10, MEGA version 7.014, and the program Arlequin version 3.1 were used to highlight the parameters of variability, differentiation, and the demo-genetic evolution of our study populations. The pathogenicity of the mutations was determined through Polyphen2, TAMISER, and ClinVar. Results: Our results showed the presence of a recurrent mutation of the TP53 gene in both tumor and healthy tissue where proline was replaced with arginine at codon 72. This mutation was predicted to be benign. The presence of this mutation in healthy tissue can be considered a relatively late event in colorectal tumorigenesis. In addition, the P47L, D49A, W53S, and D48G mutations appeared to be suspicious because they were predicted to be potentially damaging. This finding suggests the genes’ involvement in the pathology of CRCs in our study population. The cancer tissue sequences contained an average of 2.59 nucleotide differences that resulted in amino acid changes. The Nei genetic distance confirms this variability between tumor tissues. Conclusion: These results suggest that variants in exon 4 of the TP53 gene may contribute to the development of CRCs. These mutations could constitute molecular markers in CRC and possibly help in the development of early diagnosis

Current Value of Perioperative Therapies for Resectable or Borderline Resectable Pancreatic Cancer.

Invasive pancreatic ductal carcinoma is a representative refractory malignant tumor, and even with the development of early diagnosis and treatment techniques, the treatment outcome has been remarkably poor. Surgical resection is the curative treatment for resectable pancreatic cancer and borderline resectable pancreatic cancer. However, the survival rate in patients with pancreatic cancer treated by resection alone is low because of the high postoperative recurrence rate. In this review article, we report recent studies on perioperative treatment for pancreatic cancer. Perioperative therapy is the addition of chemotherapy or radiation therapy before or after surgery to improve resectability and curative effects. Because it is difficult to cure redsecttable pancreatic cancer by surgery alone, multidisciplinary treatment combined with perioperative adjuvant chemotherapy is the current standard of care. Although perioperative chemotherapy and chemoradiotherapy have been investigated for borderline resectable pancreatic cancer, the effectiveness of preoperative treatment has not been sufficiently proven. Potentially curative pancreatic cancer is treated by surgery plus perioperative therapy; treatment cannot be either alone. We regard the successful completion of surgery and perioperative care as the key to improving treatment outcomes. Therefore, ongoing randomized controlled trials for the treatment of BR-pancreatic cancer are expected to induce further improvements survival outcomes of patients with BR-pancreatic cancer.

Nanomaterials-Mediated Therapeutics and Diagnosis Strategies for Myocardial Infarction.

The alarming mortality and morbidity rate of myocardial infarction (MI) is becoming an important impetus in the development of early diagnosis and appropriate therapeutic approaches, which are critical for saving patients’ lives and improving post-infarction prognosis. Despite several advances that have been made in the treatment of MI, current strategies are still far from satisfactory. Nanomaterials devote considerable contribution to tackling the drawbacks of conventional therapy of MI by improving the homeostasis in the cardiac microenvironment via targeting, immune modulation, and repairment. This review emphasizes the strategies of nanomaterials-based MI treatment, including cardiac targeting drug delivery, immune-modulation strategy, antioxidants and antiapoptosis strategy, nanomaterials-mediated stem cell therapy, and cardiac tissue engineering. Furthermore, nanomaterials-based diagnosis strategies for MI was presented in term of nanomaterials-based immunoassay and nano-enhanced cardiac imaging. Taken together, although nanomaterials-based strategies for the therapeutics and diagnosis of MI are both promising and challenging, such a strategy still explores the immense potential in the development of the next generation of MI treatment.

The Level of Histone Deacetylase 4 is Associated with Aging Cartilage Degeneration and Chondrocyte Hypertrophy.

PurposeTo determine the role of histone deacetylase 4 (HDAC4)-controlled chondrocyte hypertrophy in the onset and development of age-related osteoarthritis (OA).MethodsMorphological analysis of human knee cartilages was performed to observe structural changes during cartilage degeneration. HDAC4 expression was deleted in adult aggrecan (Acan)-CreERT2; HDAC4fl/fl transgenic mice. The onset and development of age-related OA were investigated in transgenic and control mice using hematoxylin and eosin (H&E) and Safranin O staining. Furthermore, the progression of ACLT-induced OA following adenovirus-mediated HDAC4 overexpression was explored in rats. The expression levels of genes related to hypertrophy, cartilage matrix and its digestion, and chondrocyte proliferation were investigated using qPCR. Immunohistochemistry (IHC) was used to explore the mechanisms underlying HDAC4-controlled age-related changes in OA progression.ResultsIn human cartilage, we performed morphological analysis and IHC, the results showed that hypertrophy-related structural changes are related to HDAC4 expression. Age-related OA was detected early (OARSI scores 2.7 at 8-month-old) following HDAC4 deletion in 2-month-old mice. Furthermore, qPCR and IHC results showed changes in hypertrophy-related genes Col10a1, Runx2 and Sox9 in chondrocytes, particularly in the expression of Runt-related transcription factor 2 (Runx2, 13.29±0.99 fold). The expression of the main cartilage matrix-related genes Col2a1 and Acan decreased, that of cartilage matrix digestion-related gene MMP-13 increased, while that of chondrocyte proliferation-related genes PTHrP, Ihh and Gli1 changed. In contrast, rat cartilage’s qPCR and IHC results showed opposite outcomes after HDAC4 overexpression.ConclusionBased on the results above, we concluded that HDAC4 expression regulates the onset and development of age-related OA by controlling chondrocyte hypertrophy. These results may help in the development of early diagnosis and treatment of age-related OA.

A new hybrid ensemble machine-learning model for severity risk assessment and post-COVID prediction system.

Starting from December 2019, the COVID-19 pandemic has globally strained medical resources and caused significant mortality. It is commonly recognized that the severity of SARS-CoV-2 disease depends on both the comorbidity and the state of the patient's immune system, which is reflected in several biomarkers. The development of early diagnosis and disease severity prediction methods can reduce the burden on the health care system and increase the effectiveness of treatment and rehabilitation of patients with severe cases. This study aims to develop and validate an ensemble machine-learning model based on clinical and immunological features for severity risk assessment and post-COVID rehabilitation duration for SARS-CoV-2 patients. The dataset consisting of 35 features and 122 instances was collected from Lviv regional rehabilitation center. The dataset contains age, gender, weight, height, BMI, CAT, 6-minute walking test, pulse, external respiration function, oxygen saturation, and 15 immunological markers used to predict the relationship between disease duration and biomarkers using the machine learning approach. The predictions are assessed through an area under the receiver-operating curve, classification accuracy, precision, recall, and F1 score performance metrics. A new hybrid ensemble feature selection model for a post-COVID prediction system is proposed as an automatic feature cut-off rank identifier. A three-layer high accuracy stacking ensemble classification model for intelligent analysis of short medical datasets is presented. Together with weak predictors, the associative rules allowed improving the classification quality. The proposed ensemble allows using a random forest model as an aggregator for weak repressors' results generalization. The performance of the three-layer stacking ensemble classification model (AUC 0.978; CA 0.920; F1 score 0.921; precision 0.924; recall 0.920) was higher than five machine learning models, viz. tree algorithm with forward pruning; Naïve Bayes classifier; support vector machine with RBF kernel; logistic regression, and a calibrated learner with sigmoid function and decision threshold optimization. Aging-related biomarkers, viz. CD3+, CD4+, CD8+, CD22+ were examined to predict post-COVID rehabilitation duration. The best accuracy was reached in the case of the support vector machine with the linear kernel (MAPE = 0.0787) and random forest classifier (RMSE = 1.822). The proposed three-layer stacking ensemble classification model predicted SARS-CoV-2 disease severity based on the cytokines and physiological biomarkers. The results point out that changes in studied biomarkers associated with the severity of the disease can be used to monitor the severity and forecast the rehabilitation duration.

Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma.

Esophageal cancer (EC) is a common malignant disease in eastern countries. However, a study of the metabolomic characteristics associated with other biological factors in esophageal squamous cell carcinoma (ESCC) is limited. Interleukin enhancer binding factor 2 (ILF2) and ILF3, double-stranded RNA-binding proteins, have been reported to contribute to the occurrence and development of various types of malignancy. Nevertheless, the underlying functions of ILF2 and ILF3 in ESCC metabolic reprogramming have never been reported. This study aimed to contribute to the metabolic characterization of ESCC and to investigate the metabolomic alterations associated with ILF2 and ILF3 in ESCC tissues. Here, we identified 112 differential metabolites, which were mainly enriched in phosphatidylcholine biosynthesis, fatty acid metabolism, and amino acid metabolism pathways, based on liquid chromatography–mass spectrometry and capillary electrophoresis–mass spectrometry approaches using ESCC tissues and paired para-cancer tissues from twenty-eight ESCC patients. In addition, ILF2 and ILF3 expression were significantly elevated in EC tissues compared to the histologically normal samples, and closely associated with PI3K/AKT and MAPK signaling pathways in ESCC. Moreover, in ESCC tissues with a high ILF2 expression, several short-chain acyl-carnitines (C3:0, C4:0, and C5:0) related to the BCAA metabolic pathway and long-chain acyl-carnitines (C14:0, C16:0, C16:0-OH, and C18:0) involved in the oxidation of fatty acids were obviously upregulated. Additionally, a series of intermediate metabolites involved in the glycolysis pathway, including G6P/F6P, F1,6BP, DHAP, G3P, and 2,3BPG, were remarkably downregulated in highly ILF3-expressed ESCC tissues compared with the corresponding para-cancer tissues. Overall, these findings may provide evidence for the roles of ILF2 and ILF3 during the process of ESCC metabolic alterations, and new insights into the development of early diagnosis and treatment for ESCC. Further investigation is needed to clarify the underlying mechanism of ILF2 and ILF3 on acyl-carnitines and the glycolysis pathway, respectively.

Frequency of arterial hypertension, diabetes and dyslipidemia in children after kidney transplants.

Pediatric kidney transplant patients have an increased risk of developing arterial hypertension, dyslipidemia, carbohydrate intolerance and diabetes mellitus, risk factors associated with increased cardiovascular morbidity and mortality. This study evaluates the frequency of arterial hypertension, dyslipidemia and alteration in carbohydrate metabolism in a cohort of pediatric kidney transplant patients during 2006-2016 at the Pablo Tobon Uribe Hospital, in Colombia. Retrospective descriptive study in which descriptive statistics were used. Additionally, a bivariate analysis was performed to compare patients according to the outcome of arterial hypertension, dyslipidemia and alteration in carbohydrate metabolism. From a total of 48 pediatric kidney transplants in the period studied, complete information was obtained from 43 patients at one year of follow-up. There was a post-transplant frequency of hypertension of 86%, dyslipidemia 48%, carbohydrate intolerance 14% and diabetes of 2%. In the evaluated cohort a high frequency of arterial hypertension and dyslipidemia was found after kidney transplantation. The development of early diagnosis and treatment guidelines is suggested to reduce the impact of these diseases associated with cardiovascular risk in adult life.

Identification of immune-infiltrating cell-related biomarkers in hepatocellular carcinoma based on gene co-expression network analysis

BackgroundHepatocellular carcinoma (HCC) is often caused by chronic liver infection or inflammation. Searching for potential immunotherapy targets will aid the early diagnosis and treatment of HCC.MethodsFirstly, detailed HCC data were downloaded from The Cancer Genome Atlas database. GDCRNATools was used for the comprehensive analysis of RNA sequencing data. Subsequently, the CIBERSORT package was used to estimate infiltration scores of 22 types of immune cells in complex samples. Furthermore, hub genes were identified via weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis. In addition, multiple databases were used to validate the expression of hub gene in the tumor tissue. Finally, prognostic, diagnostic and immunohistochemical analysis of key hub genes was performed.ResultsIn the present study, 9 hub genes were identified using WGCNA and PPI network analysis. Furthermore, the expression levels of 9 genes were positively correlated with the infiltration levels of CD8-positive T (CD8+ T) cells. In multiple dataset validations, the expression levels of CCL5, CXCR6, CD3E, and LCK were decreased in cancer tissues. In addition, survival analysis revealed that patients with LCK low expression had a poor survival prognosis (P < 0.05). Immunohistochemistry results demonstrated that CCL5, CD3E and LCK were expressed at low levels in HCC cancer tissues.ConclusionThe identification of CCL5, CXCR6, CD3E and LCK may be helpful in the development of early diagnosis and therapy of HCC. LCK may be a potential prognostic biomarker for immunotherapy for HCC.

Artificial Intelligence-Based Prediction of Covid-19 Severity on the Results of Protein Profiling

BackgroundCOVID-19 progresses slowly and negatively affects many people. However, mild to moderate symptoms develop in most infected people, who recover without hospitalization. Therefore, the development of early diagnosis and treatment strategies is essential. One of these methods is proteomic technology based on the blood protein profiling technique. This study aims to classify three COVID-19 positive patient groups (mild, severe, and critical) and a control group based on the blood protein profiling using deep learning (DL), random forest (RF), and gradient boosted trees (GBTs). MethodsThe dataset consists of 93 samples (60 COVID-19 patients, 33 control), and 370 variables obtained from an open-source website. The current dataset contains age, gender, and 368 protein, used to predict the relationship between disease severity and proteins using DL and machine learning approaches (RF, GBTs). An evolutionary algorithm tunes hyperparameters of the models and the predictions are assessed through accuracy, sensitivity, specificity, precision, F1 score, classification error, and kappa performance metrics. ResultsThe accuracy of RF (96.21%) was higher as compared to DL (94.73%). However, the ensemble classifier GBTs produced the highest accuracy (96.98%). TGB1BP2 in the cardiovascular II panel and MILR1 in the inflammation panel were the two most important proteins associated with disease severity. ConclusionsThe proposed model (GBTs) achieved the best prediction of disease severity based on the proteins compared to the other algorithms. The results point out that changes in blood proteins associated with the severity of COVID-19 may be used in monitoring and early diagnosis/treatment of the disease.

China Multi-Center Preschool Autism Project (CMPAP): Design and Methodologies to Identify Clinical Symptom Features and Biomarkers of Autism Spectrum Disorders.

Background: The etiology of autism spectrum disorder (ASD) has not yet been fully identified, but it seems to be triggered by complex genetic and environmental risk factors. Moreover, the tremendous etiological and clinical differences among individuals with ASD has had a major negative impact on early diagnosis and individualized treatment. Earlier diagnosis of precise clinical subtypes of ASD could lead to individualized treatment and a better prognosis. However, few large-scale epidemiological studies have explored precise clinical subtypes and clinically meaningful biomarkers, especially in China.Methods and Design: The China Multi-center Preschool Autism Project (CMPAP) includes nearly 3,000 children−1,469 individuals with ASD and 1,499 typically-developing (TD) controls—from 13 cities in China. Using a case-control design, each participant was comprehensively characterized in terms of feeding and disease history, maternal history, family history, clinical core symptoms, comorbidities, biochemical markers, genomics, urine/fecal metabonomics, and intestinal flora. In addition, data on environmental risk factors were obtained using interviews and electronic medical records.Conclusion: The study was designed to: (1) investigate age at diagnosis and treatment and family and social support for preschool children with ASD in China, (2) develop a more accurate clinical subtype and intervention system for the ICD-11, and (3) find the specific genes and environmental markers of different subtypes, which will help in the development of early diagnosis and individual intervention programs for preschool children with ASD. This study will provide the basis for improving national health policies for ASD in China.

Correlation of Single Nucleotide Gene Polymorphisms and Gastric Cancer Based on Magnetic Nanoparticles.

Gastric cancer (GC) is a serious threat to the health and lives of people around the world. In China, the incidence and mortality of gastric cancer are much higher than the world average, coupled with its low early diagnosis rate, low survival rate, poor prognosis, and complex etiology, especially the serious lack of effective early warning methods, which has become the main constraint on the diagnosis and treatment of gastric cancer factor. Therefore, finding reliable, effective, and specific markers that can be applied to early warning and diagnosis of gastric cancer has been a hot issue in gastric cancer research. Magnetic nanoparticles are an ideal molecular carrier for gene separation because they have many advantages such as easy operation, fast, high efficiency, and non-destructive non-recognition biological entities. Changes in gene levels can detect the development of early diagnosis and treatment of prognosis in patients with gastric cancer by affecting susceptibility, clinical phenotype, and drug response. PcG protein can modify chromatin and affect tumorigenesis. The experimental results show that the introduction of magnetic nanoparticles can improve the sensing signal, detection sensitivity and gene differentiation. Combined with the latest magnetic nanoparticle technology to analyze the relationship between SNPs of some genes in the pathways involved in gastric cancer treatment and DNA specificity, screening and identifying specific SNP markers are helpful to the mechanism of gastric cancer development. Understand to achieve the purpose of individualized treatment. By introducing the RAS-BRAF gene on the surface of magnetic nanoparticles, the surface of the magnetic particles was biologically functionalized and used for the separation and detection of proteins and pathogens, respectively. The results show that the system has excellent detection sensitivity and separation selectivity. At present, the research results of susceptible genes screened by coding gene association studies are inconsistent. In this study, PLCE1 gene was found to be used as a DNA gene identification method through high expression of cells to analyze that polymorphisms are closely related to the incidence of gastric cancer. In addition, the study suggests that PLCE1 gene may be a susceptible gene for tumor cells. The signaling pathways involved in the regulation play an important role in tumorigenesis, development, migration, and apoptosis, and are closely related to disease prognosis. Therefore, at the gene level More analysis of the role of these genes in gastric cancer is needed.

Biophoton Imaging Evaluation of the Process of Rheumatoid Arthritis in Rats

Rheumatoid arthritis (RA) is a common form of chronic inflammatory arthritis, and it mainly causes the destruction of small joints. The development of this disease is a relatively secret and repeated process, and therefore early diagnosis and evaluation of the disease is usually difficult. In this study, an arthritis model was successfully induced by injecting complete Freund’s adjuvant (CFA) into the toes of lower limbs of Wistar rats. Seven days after injection of CFA, obvious redness and swelling appeared at the toe joints of lower limbs accompanied by more sensitivity to thermal stimulation. Using the ultraweak bio-photon imaging system (UBIS) established by us, the toe joint area of the lower limbs of rats was imaged 7 days after injection of CFA. It was found that the volar part of lower limbs of arthritis rats showed significantly higher biophoton emissions compared with the control group. The results of this study may provide a basis for further research and devel-opment of early diagnosis and assessment of lesion progression of rheumatoid arthritis.

Abstract 6186: Protein panel for predicting the efficacy of neoadjuvant therapy for rectal cancer based on proteomics

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and more than 1/3 of all cases are rectal cancer.With the development of early diagnosis and precise treatment, the 5-year survival rate of rectal cancer has been greatly improved. Neoadjuvant radiotherapy and chemotherapy, as the standard treatment for locally advanced rectal cancer, have been included in the NCCN guidelines. However, due to tumor heterogeneity,the response rate to neoadjuvant radiotherapy and chemotherapy varies, and there is no effective method to predict the efficacy of neoadjuvant therapy for rectal cancer. The recent advance of pressure cycling technology (PCT) and data-independent acquisition mass spectrometry (DIA-MS) allows high-throughput and reproducible proteomic quantification for formalin-fixed paraffin-embedded (FFPE) biopsy-level tissue proteome. Methods: We collected 33 patients with rectal cancer who were treated with long-term radiotherapy and capecitabine chemotherapy in our center as the training cohort. Among them, a total of 23 cases with both pre-treatment endoscopic biopsy specimens and surgical pathological sections available were procured and reassessed the Tumor Regression Grade (TRG) after treatment as mentioned above. FFPE tissue samples from each individual were collected with two biological replicates. We further collected other 31 patients from another two independent hospitals as the validation cohort. All the samples were processed by PCT-DIA for proteomic profiling. Candidate proteins were selected from training cohort and confirmed in the validation cohort, as well as Immunohistochemistry (IHC). Results: A total of 5055 SwissProt proteins are quantified with high confidence and a high degree of reproducibility (R2=0.983) from 46 samples in the training cohort. Patients in training cohort were divided into two groups according to responsiveness to radiotherapy (TRG1+2: no significant benefit from radiotherapy; TRG3+4: significant benefit from radiotherapy) to explore differentially expressed proteins (adjusted p value &amp;lt; 0.05, fold change &amp;gt; 2). 35 up-regulated proteins and 114 down-regulated proteins were detected in the responded group. The suppressed proteins were mainly involved in immune response and cell activation, while the elevated proteins mostly participate metabolic processes. Six differentially expressed proteins were further confirmed in the validation cohort using DIA-MS and IHC. More details will be presented. Conclusion: We developed a predictive model composed of 6 proteins which exhibited promising roles for the responsiveness to neoadjuvant therapy in rectal patients. Citation Format: Kailun Xu, Biting Zhou, Xi Zheng, Yingkuan Shao, Jian Wang, Tiannan Guo, Shu Zheng. Protein panel for predicting the efficacy of neoadjuvant therapy for rectal cancer based on proteomics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6186.

DNAzyme-Powered Three-Dimensional DNA Walker Nanoprobe for Detection Amyloid β-Peptide Oligomer in Living Cells and in Vivo.

Amyloid β-peptide oligomer (AβO) is widely acknowledged as the promising biomarker for the diagnosis of Alzheimer's disease (AD). In this work, we designed a three-dimensional (3D) DNA walker nanoprobe for AβO detection and real-time imaging in living cells and in vivo. The presence of AβO triggered the DNAzyme walking strand to cleave the fluorophore (TAMRA)-labeled substrate strand modified on the gold nanoparticle (AuNP) surface and release TAMRA-labeled DNA fragment, resulting in the recovery of fluorescent signal. The entire process was autonomous and continuous, without external fuel strands or protease, and finally produced plenty of TAMRA fluorescence, achieving signal amplification effect. The nanoprobe enabled the quantitative detection of AβO in vitro, and the limit of detection was 22.3 pM. Given the good biocompatibility of 3D DNA walker nanoprobe, we extended this enzyme-free signal amplification method to real-time imaging of AβO. Under the microscope, nanoprobe accurately located and visualized the distribution of AβO in living cells. Moreover, in vivo imaging results showed that our nanoprobe could be used to effectively distinguish the AD mice from the wild-type mice. This nanoprobe with the advantages of great sensitivity, high specificity, and convenience, provides an outstanding prospect for AD's early diagnosis development.

THE TESTOSTERONE-CORTISOL MODEL AS A WAY TO UNDERSTAND THE MECHANISM OF ALCOHOL DEPENDENCE WHICH STARTED IN PUBERTY

The aim: Is to analyze the role of testosterone and cortisol in the mechanism of alcohol use disorders formation for further development of early diagnosis and prevention methods. Materials and methods: 155 adolescents at the preclinical stages of alcohol use disorders formation and 87 young patients with diagnosed alcohol dependence were studied by enzyme-linked immunoassay techniques. Results: The analysis of the obtained materials shows that the onset of search behaviors on alcohol consumption, frequency and alcohol abuse in adolescents occur with the participation of age-related processes of somatic puberty and the related syndromes of hormonal tension. The phasing of development and course of alcoholic disease includes pubertal age and alcohol-induced changes in the internal environment of the body. There is an increase in the concentration of testosterone and cortisol that initiates interest in alcohol first, and then under the influence of its toxic effect, the level of these hormones decreases. It should be borne in mind that significant differences in hormone concentrations were observed within the regulatory framework. Conclusions: An increase of testosterone and cortisol levels in puberty, combined with regular consumption of alcohol, may indicate a risk of addiction early. Further decrease of the levels of these hormones along with an increase of the frequency of alcohol consumption may be an early diagnostic feature of the alcohol use disorders.

MODERN APPROACHES TO EARLY RADIOLOGICAL DIAGNOSIS OF BONE AND CEREBRAL METASTASES OF PERIPHERAL NON-SMALL CELL LUNG CANCER

Objective:сonstructive principles development of early diagnosis of bone and cerebral metastases of peripheral non-small cell lung cancer (PNSCLC), is based on the targeted preventive and personalized application of radiological and nuclear diagnostic methods.Materials and methods.There was performed the retrospective analysis of medical cards of 1473 patients with peripheral non-small cell lung cancer for the evaluation of the characteristics and frequency of bones and brain metastases. The frequency and features of bone and brain metastases depending on clinical and morphological features of the primary lung tumor were studied. 118 patients with PNSCLC with bone and brain metastases, regardless of clinical symptoms, were examined using a wide range of modern radiological and nuclear methods.Conclusion:the original algorithm has been developed on the study of the diagnostic significance of medical imaging methods. The application of this algorithm will significantly improve the early diagnosis of bone and cerebral metastases and improve the staging of PNSCLC.

Development of Early Diagnosis and Therapeutic Agent for CTEPH Focused on a Novel Pathogenic Protein TAFI

Development of Early Diagnosis and Therapeutic Agent for CTEPH Focused on a Novel Pathogenic Protein TAFI

Volumetric optoacoustic tomography enables non-invasive in vivo characterization of impaired heart function in hypoxic conditions

Exposure to chronic hypoxia results in pulmonary hypertension characterized by increased vascular resistance and pulmonary vascular remodeling, changes in functional parameters of the pulmonary vasculature, and right ventricular hypertrophy, which can eventually lead to right heart failure. The underlying mechanisms of hypoxia-induced pulmonary hypertension have still not been fully elucidated while no curative treatment is currently available. Commonly employed pre-clinical analytic methods are largely limited to invasive studies interfering with cardiac tissue or otherwise ex vivo functional studies and histopathology. In this work, we suggest volumetric optoacoustic tomography (VOT) for non-invasive assessment of heart function in response to chronic hypoxia. Mice exposed for 3 consecutive weeks to normoxia or chronic hypoxia were imaged in vivo with heart perfusion tracked by VOT using indocyanide green contrast agent at high temporal (100 Hz) and spatial (200 µm) resolutions in 3D. Unequivocal difference in the pulmonary transit time was revealed between the hypoxic and normoxic conditions concomitant with the presence of pulmonary vascular remodeling within hypoxic models. Furthermore, a beat-to-beat analysis of the volumetric image data enabled identifying and characterizing arrhythmic events in mice exposed to chronic hypoxia. The newly introduced non-invasive methodology for analysis of impaired pulmonary vasculature and heart function under chronic hypoxic exposure provides important inputs into development of early diagnosis and treatment strategies in pulmonary hypertension.

Situation analysis of problems and prospects of the pediatric hematology-oncology in the CIS countries: the experience of a joint working group

Relevance. Continuous work in the field of optimization of approaches to the diagnosis and treatment of malignant neoplasms (MNP) in children has contributed to increase in overall survival (OS) to 80 % and higher in developed countries. Whereas in resource-limited countries there are some difficulties in access to the medical care leading to significantly lower OS. The key parameters in the improvement of the OS are improving the accessibility of diagnosis and treatment, application of advanced protocols of therapy, early diagnosis and other aspects. All these issues can be solved within the working group with the assistance of the leadership of the countries. The article reflects the results of the work of the expert group on children's oncology for the first half of 2018 on the analysis of the situation in the field of pediatric hematology and oncology of the Commonwealth of Independent countries (CIS). The view to analyzing has been the identification of the problems of the pediatric hematology-oncology in the CIS countries. Materials and methods . It was a two steps analysis: 1. There has been an online meeting in February–April, 2018. 2. There has been a master class in Moscow at the venue of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology on April, 23–25, 2018. The initiators of the formation of the working group were World Health Organization, Children’s research hospital of St. Jude, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and National Society of Pediatric Hematologists and Oncologists. The analysis has been carried out with the use of SWOT technology (S – strengths, W – weaknesses, O – opportunities and T – threats) by which have been identified strengths and weaknesses, potential threats and development prospects for each of the participating countries of the analysis and for the CIS in general. What is more, data on the incidence of MNP in children among the member States were received and outlined the promising avenues for the development. On the master class in Moscow there have been formed 4 working groups in the following areas: scientific work, health organization, developing of the educational technologies and introducing technologies aimed at improving the practical support for the patients. Results. Situation analyses of 11 CIS countries have been reviewed and it showed a different level of the development of pediatric hematology-oncology related to differences in the organization of the children’s health care system. Nevertheless, the key ways of the development of the service of pediatric hematology and oncology in the region have been determined: the development of early diagnosis and formation of oncological alertness, the development of uniform approaches to diagnosis and treatment based on the multicentre protocols, elaboration of the unified approaches to registering and recording children with MNP, creation of the unified educational programs for secondary and medical personnel, further elaboration of steps to optimize the children’s health care system. Conclusion. It has been shown that despite the difference in the organization of the pediatric hematology-oncology service the joint working group had succeed in determining the common problems and development prospects. There have been set out the specific proposals reflected in the master class resolution and have been identified subsequent stages of the work for the joint working group.

Patient Representation and Advocacy for Alzheimer Disease in Germany and Israel

This paper analyses self-declared aims and representation of dementia patient organizations and advocacy groups (POs) in relation to two recent upheavals: the critique of social stigmatization and biomedical research focusing on prediction. Based on twenty-six semi-structured interviews conducted in 2016–2017 with members, service recipients, and board representatives of POs in Germany and Israel, a comparative analysis was conducted, based on a grounded theory approach, to detect emerging topics within and across the POs and across national contexts. We identified a heterogeneous landscape, with the only Israeli PO focusing strongly on caretakers, whereas in Germany several POs claim to represent this patient collective. Shared aims of all POs were fighting social stigma, balancing the loss of patients’ individual autonomy, and the well-being of caretakers. By highlighting the emergence of new groups of dementia self-advocacy against the more traditional advocacy by others, this study highlights how advocacy and representation in the context of AD are embedded in the discursive context of stigmatization and revised disease conception. Future developments in early diagnosis and prediction of dementia, with more affected people likely to conduct dementia self-advocacy, might challenge existing representation structures even more.