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Background: Some molluscan hemocyanins (Hcs) have significant immunological and antitumor potential, enabling their application in oncology. The antitumor activity of Hcs from marine snails Rapana venosa (RvH), giant keyhole limpet Megathura crenulata (KLH) and garden snails Helix lucorum (HlH), as well as their different derivatives, were studied in vitro on a permanent T24 cell line of bladder cancer and normal urothelial cell line HL 10/29 compared to doxorubicin. Methods: The antiproliferative activity of the tested Hcs was determined using WST-1 assay and BrdU ELISA assay. Morphological changes in both urothelial cell lines were confirmed by fluorescence microscopy. The proteomic analysis of a cell line of bladder cancer before and after treatment with functional unit (FU) βc-HlH-h using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry revealed differences in the expression of some proteins. Results: Studies prove that the T24 tumor cell line is dose- and time-dependent, sensitive to the action of the tested isoforms and the glycosylated FU of these hemocyanins. Selective inhibition of T24 cell growth was observed after incubation with structural subunits (βc-HlH, RvHI and RvHII) and FUs (βc-HlH-h and RvHII-e). Fluorescent microphotographs did not show apoptotic or necrotic alterations in the normal urothelial cell line HL 10/29. The FU βc-HlH-h demonstrated the highest antiproliferative effect (similarly to doxorubicin), in which predominantly apoptotic and less late apoptotic or necrotic changes in the tumor cells were observed. Several down- and up-regulated proteins identified by proteome analysis may be associated with the apoptosis pathway. Conclusions: The present study illustrated the selectivity of the cytotoxic effect of Hcs against the Т24 cancer cell line. This is the first report of protein expression in T24 human bladder cancer cells under the influence of FU βc-HlH-h. That is probably due to the specific oligosaccharide structures rich in methylated hexoses exposed on the surface of βc-HlH-h.

We applied a genomic in situ hybridization (GISH) to analyze the genomic constitution of and meiotic pairing in interspecific somatic hybrids, and in a wide subset of backcrossing derivatives (BC1–BC5), from three interspecific combinations involving the cultivated potato, Solanum tuberosum (AAAA genome), and three diploid (1 EBN) wild Mexican potato species (genome BB)—S. tarnii, S. pinnatisectum, and S. bulbocastanum. The theoretically expected genomic composition was detected in the somatic hybrids (AAAABB) and in the BC1 progeny (AAAAB), whereas in the subsequent BC2–BC4 generations, the partial loss of alien chromosomes was observed and almost all the BC5 genotypes showed a complete chromosome elimination of wild species. GISH revealed a homoeologous pairing between the chromosomes of the A- and the B-genomes in each of the hybrid progenies. Using GISH, we selected introgression lines with a single chromosome of the wild species in a potato genome background, as well as introgression lines with intergenomic recombinant chromosomes. Moreover, via molecular screening, BC hybrids with diagnostic markers for the R-genes conferring resistance to late blight disease and to the quarantine pest of the potato–Columbia root-knot nematode—were selected. The potential application of the results obtained for the planning of introgressive schemes directed to the breeding of advanced lines with multiple disease and pest resistance is discussed.

The most crucial step in deep anterior lamellar keratoplasty (DALK) is to achieve a bare Descemet's membrane. We aimed to assess a new femtosecond laser software that allows for a precise intrastromal tunnel creation for big bubble (BB) air injection using a real-time microscope-integrated optical coherence tomography.A retrospective review of 61 eyes of 61 patients with keratoconus. Before introducing the new software update, DALK was performed using a partial-assisted femtosecond laser (partial-thickness circular cut followed by a lamellar cut) with manual intrastromal tunnel creation (partial FS-DALK group). After the software update, the femtosecond laser created the intrastromal tunnel (full FS-DALK group).In the full FS-DALK group, the BB's formation was significantly higher (64.3% vs. 36.4%, p = 0.04), and surgery time was shorter (21.8 ± 5.1 vs. 25.6 ± 6.8 min, p = 0.025) than in the partial FS-DALK. Penetrating keratoplasty conversion rate (7.1% vs. 15.1%, p = 0.432) was similar between the groups. Both groups showed statistically significant improvement in uncorrected and corrected distance visual acuity, central corneal thickness, surface asymmetry, and regularity indices. Endothelial cell density loss at 12 and 18 months was lower in the full compared with the partial FS-DALK group (12 months:10.0% vs. 16; 18 months: 10.7 vs. 16.5%, p 0.001 for both comparisons).Creating the intrastromal guiding tunnel using FS laser for air injection resulted in a higher rate of BB formation, reduced long-term endothelial cell loss, and operating room time.

The article investigates theoretical foundations of public management in the socio-humanitarian sphere of metropolises based on the smart city concept. It defines the essence of the concept of "public management in the socio-humanitarian sphere" in a metropolis, which should be considered as a multi-branch and inter-sectoral complex formed with the involvement of local authorities, business partners, the public, and citizens, and aims to create, maintain, and develop a favorable safe environment as a unified system of life and livelihood of the city based on the balanced development of the main sectors of the economy and socio-humanitarian sphere. The abstract also defines criteria for the efficiency of public management in the socio-humanitarian sphere within a modern metropolis, which include integrity, sustainability, and security of the subjects in obtaining a positive effect of solving socio-humanitarian issues within a metropolis. The main mechanism of public administration in a metropolis is establishment of interaction in the triad "power - business - community" and coordination of their interests (business - "here and now", community - "the welfare of our children", the state - "the welfare of citizens"). It is confirmed that the digitalization of public administration contributes to strengthening control over the use of all types of resources for the optimal development of the socio-humanitarian sphere of Ukrainian cities.

The article proposes a study on one of the concepts of the circular economy – the sharing economy. To achieve the goals of sustainable development and reduce environmental threats, the world community has adopted the concept of a circular economy, a closed-loop economy. One of the entrepreneurial models of the circular economy is the sharing economy. The purpose of the study is to develop theoretical provisions on increasing the influence of the sharing economy on improving the quality of life of the population. The sharing economy in our study is considered as a model using which projects aimed at improving the quality of life of the population can be implemented. It is presented that social entrepreneurs play a significant role in implementing of such projects, who strive to achieve the social effect in the field of improving the quality of life of the population. Within the frameworks of the sharing economy social entrepreneurs implement their projects by applying investment resources: impact investing and crowdfunding. Using these investment resources in practices is hindered due to the fact that the entrepreneurs do not have enough knowledge about those and their investment opportunities in a sharing economy. In the theoretical aspect, we believe, there is not enough research on the impact of the sharing economy on improving the quality of life of the population. In this work, an attempt is made to expand the theoretical understanding of the sharing economy aimed at improving the quality of life of the population. As the methodological basis of the study, the author used the basic provisions of economic theory, circular economy, sharing economy, digital economy, the concept of social entrepreneurship, and theoretical and methodological aspects of the quality of life of the population. The information base of the study was the expert and statistical data of the “Our Future” Foundation for Regional Social Programs (https://nb-fund.ru/), HSE University, and other data on the development of the social entrepreneurship sector in Russia. The theoretical result of the study is the definition of some interdisciplinary provisions related to the concept of the quality of life of the population based on the use of investment resources for the implementation of projects of the sharing economy by social entrepreneurs with a view to their further application in research. The practical area of application of the results and provisions will be the use of crowdfunding and impact investing to increase the effectiveness of implementation of projects of social entrepreneurs in order to improve the quality of life of the population.

The topological cues of fibrous scaffolds (in particular extracellular matrix (ECM)-mimetic nanofibers) have already proven to be a powerful tool for influencing neuronal morphology and behavior. Remote photothermal optical treatment provides additional opportunities for neuronal activity regulation. A combination of these approaches can provide “smart” 3D scaffolds for efficient axon guidance and neurite growth. In this study we propose two alternative approaches for obtaining biocompatible photothermal scaffolds: surface coating of nylon nanofibers with light-to-heat converting nanoparticles and nanoparticle incorporation inside the fibers. We have determined photoconversion efficiency of fibrous nanomaterials under near infrared (NIR) irradiation, as well as biocompatible photothermal treatment parameters. We also measured photo-induced intracellular heating upon contact of cells with a plasmonic surface. In the absence of NIR stimulation, our fibrous scaffolds with a fiber diameter of 100 nm induced an increase in the proportion of β3-tubulin positive cells, while thermal stimulation of neuroblastoma cells on nanoparticles-decorated scaffolds enhanced neurite outgrowth and promoted neuronal maturation. We demonstrate that contact guidance decorated fibers can stimulate directional growth of processes of differentiated neural cells. We studied the impact of nanoparticles on the surface of ECM-mimetic scaffolds on neurite elongation and axonal branching of rat hippocampal neurons, both as topographic cues and as local heat sources. We show that decorating the surface of nanofibers with nanoparticles does not affect the orientation of neurites, but leads to strong branching, an increase in the number of neurites per cell, and neurite elongation, which is independent of NIR stimulation. The effect of photothermal stimulation is most pronounced when cultivating neurons on nanofibers with incorporated nanoparticles, as compared to nanoparticle-coated fibers. The resulting light-to-heat converting 3D materials can be used as tools for controlled photothermal neuromodulation and as “smart” materials for reconstructive neurosurgery.

Background. Despite the fact that COVID-19 usually manifests with severe pneumonia, there is a growing body of evidence that life-threatening multiorgan damage is caused by vascular and hemostatic abnormalities. Since there is no established therapy, assessing antithrombotics is indeed important. Sulodexide, a compound derived from porcine intestinal mucosa is a mixture of fast-moving heparin fraction (80%)and dermatan sulfate (20%), is approved in Europe and currently in trials for COVID-19 indication. Methods. This single-center, prospective, observational study included 28 patients with mild COVID-19 hospitalized in the Central Clinical Hospital of the Presidential Administration of the Russian Federation. Patients in the control group (n = 14) were treated using routine therapy according to current guidelines, while patients in the experimental group (n = 14) had the routine treatment supplemented with daily intravenous injections of sulodexide in 600-unit doses. Scanning electron microscopy was utilized to examine the blood specimens derived from the cubital vein at admission and at 10 days after hospitalization, which was approximately the average duration of patients’ treatment in the hospital (11.6 ± 0.4 days). Results. Sulodexide significantly (by 40%) diminished the score of circulating endothelial cells, potentially indicating its antiviral endothelium-protective properties. It also prevented the extra activation of the platelets and the formation of erythrocytic sludges. Among patients in the control group, the share of activated platelets rose from 37 ± 5% to 45 ± 6% (p = 0.04) over the course of the study period, whereas among patients in the experimental group, the share of activated platelets remained practically unchanged (43 ± 6% vs. 38 ± 4%, p = 0.22). The score of erythrocytic sludges in the control group remained practically the same (4.8 ± 1.1 at admission vs. 3.9 ± 0.9 after 10 days, p = 0.67), whereas in the experimental group, it significantly decreased (from 5.7 ± 1.7 to 2.4 ± 0.9, p = 0.03). Conclusions. Sulodexide is able to defend endothelium, normalize blood, and, seemingly, prevent thrombosis. Therefore, it may be considered as a promising and effective agent for the treatment of patients with mild COVID-19. Broader randomized trials are needed to assess whether the observed findings will transform into sustained long-term clinical benefit.

The purpose of this report is to comment the results from long-term growth hormone (GH) treatment of Bulgarian patients suffering from rare genetic disease-Prader-Willi syndrome (PWS) with reference to the age, body composition, complications and genetic etiology. Statistical analysis was performed by ANOVA with post hoc Kruskal-Wallis test and Dunn's multiple comparison tests. In 90% of the patients maternal uniparental disomy (mUPD) was found to be the cause of the disease. No cases due to imprinting defects are found. The BMI data shows no statistically significant difference between BMI at diagnosis (21.850), at the beginning of the GH therapy (21.852) and current BMI (24.09) - measured under the GH background. Early GH treatment allows to overcome arising obstacles in time and to improve the quality of life for PWS children and their families. During the fourteen years study period only ten patients were diagnosed with the disease. Ninety percent (n=9) of the children were found to be with maternal UPD (mUPD) and only one case was due to deletion in 15q11-13. These results are in agreement with other studies in the field which shows the need for reassessment and new robust statistical analysis of the frequency of genetic mechanisms for PWS.

Several variants of hybrid polyelectrolyte microcapsules (hPEMC) were designed and produced by modifying in situ gelation methods and layer-by-layer (LbL) techniques. All of the hPEMC designs tested in the study demonstrated high efficiency of the model hydrophilic compound loading into the carrier cavity. In addition, the microcarriers were characterized by high efficiency of incorporating the model hydrophobic compound rhodamine B isothiocyanate (RBITC) into the hydrophobic layer consisting of poly-(d,l)-lactide-co-glycolide (PLGA), oligo-(l)-lactide (OLL), oligo-(d)-lactide (OLD) and chitosan/gelatin/poly-l-lactide copolymer (CGP). The obtained microcapsules exhibited high storage stability regardless of the composition and thickness of the polyelectrolyte shell. Study of the impact of hybrid polyelectrolyte microcapsules on viability of the adhesive L929 and suspension HL-60 cell lines revealed no apparent toxic effects of hPEMC of different architecture on live cells. Interaction of hPEMC with peritoneal macrophages for the course of 48 h resulted in partial deformation and degradation of microcapsules accompanied by release of the content of their hydrophilic (BSA–fluorescein isothiocyanate conjugate (BSA-FITC)) and hydrophobic (RBITC) layer. Our results demonstrate the functional efficiency of novel hybrid microcarriers and their potential for joint delivery of drugs with different physico-chemical properties in complex therapy.

The article is devoted to the peculiarities of autonomous sensory meridional response technologies application in marketing and advertising communication. In the context of the modern information oversaturation of a person, it is a promising technology of advertising due to its anti-stress orientation and indirect influence on the subconscious of recipients, which helps to create a favourable perception of an advertised product by the audience.

The long history of potato breeding includes the numerous introgressions of resistance genes from many wild species of South and Central America as well as from cultivated species into the breeding genepool. Most R genes belong to the NLR family with nucleotide-binding site–leucine-rich repeat. The aim of this research concerns an evaluation of NLR genes expression in transcriptomes of three potato cultivars (Evraziya, Siverskij, Sudarynya), which combine genetic material from wild and cultivated potato species, and each bears intragenic markers of RB/Rpi-blb1/Rpi-sto1 genes conferring broad-range resistance to late blight. The transcriptomes of the cultivars were compared before and 24 h after the Phytophthora infestans inoculation. The induction of RB/Rpi-blb1/Rpi-sto1 transcript after 24 h of inoculation was detected in the resistant cultivars Siverskij and Sudarynya but not in susceptible cv. Evraziya. This demonstrates the importance of transcriptomic assay for understanding the results of marker-assisted selection and phenotyping. Interestingly, assembling the transcriptomes de novo and analysis with NLR-parser tool revealed significant fractions of novel NLR genes with no homology to the reference genome from 103 (cv. Siverskij) to 160 (S. stoloniferum, 30514/15). Comparison of novel NLRs demonstrated a relatively small intersection between the genotypes that coincided with their complex pedigrees with several interspecific hybridization events. These novel NLRs may facilitate the discovery of new efficient R genes.

Potato is one of the most important food crops in the world and also in the Russian Federation. Among harmful organisms reducing potato yield potential, the potato cyst nematodes (PCN) are considered to be ones of the most damaging pests. Information on PCN resistant cultivars is important for potato breeding and production. Russian potato cultivars are characterized in the state-bio-test program for resistance to only one PCN species Globodera rostochiensis and one pathotype Ro1 which is reported to be present in the country. This study aimed to find domestic cultivars with multiple resistances to different PCN species and different pathotypes using phenotyping coupled with molecular marker analysis due to the risk of the occasional introduction of new pests. The phenotypic response was determined by the inoculation of plants with pathotypes Ro5 of G. rostochiensis and Pa3 of G. pallida. The obtained results were supplemented by the state-bio-test data on resistance to Ro1 of G. rostochiensis. Nine of 26 Russian cultivars were resistant both to Ro5 and Ro1 pathotypes and two cultivars possess multiple resistances to both PCN species. Most tested molecular markers associated with the Gpa2, GpaVvrn, GpaVsspl, Grp1 loci showed discrepancies with phenotyping. However, a predictive haplotype and epistatic effect were detected.

Nowadays, the diagnosis of Alzheimer’s disease is a complex process that involves several clinical tests. Cerebrospinal fluid contains common Alzheimer-related biomarkers that include amyloid beta 1-42 (Aβ1-42) and tau proteins. In this work, we propose vibrational spectroscopy techniques supported by machine learning for the detection of biomarkers in cerebrospinal fluid that are related with Alzheimer’s by prediction models. Vibrational spectroscopy provides the entire biochemical composition of the body fluid, and thus, small but typical physiological changes related with the pathology can be ascertained. Within a machine learning framework, Raman and FTIR spectra were analyzed, which were taken from samples of healthy volunteers in comparison with samples from patients clinically diagnosed with Alzheimer’s. We find that a logistic regression model can discriminate between healthy control and Alzheimer’s patients with a precision of 98%, when the input for the model combines data from both vibrational spectroscopy methods. Our approach shows high discriminative capabilities and constitutes a proof of concept for an alternative and accurate tool for the diagnosis of Alzheimer’s disease.

Cerebrospinal fluid contains specific biomarkers of Alzheimer’s disease that include amyloid beta peptides and tau proteins. In this work, we present for the first time possible evidence that the formation of the constituents of cerebrospinal fluid during drying is related with Alzheimer’s. We use machine learning to examine optical microscope images of dried cerebrospinal fluid patterns from patients with Alzheimer’s and healthy controls to create a diagnostic model. To analyze the images, the histogram of oriented gradients is used as a feature descriptor. Each image is mapped into the corresponding feature space, and principal component analysis is applied for dimensionality reduction. A machine-learning prediction model with a sensitivity of 82% was built. These promising preliminary results show great potential for new rapid and low-cost diagnostic pathways in the detection of Alzheimer’s disease.

One of the best documented Indo-European civilizations that inhabited Bulgaria is the Thracians, who lasted for more than five millennia and whose origin and relationships with other past and present-day populations are debated among researchers. Here we report 25 new complete mitochondrial genomes of ancient individuals coming from three necropolises located in different regions of Bulgaria – Shekerdja mogila, Gabrova mogila and Bereketska mogila – dated to II-III millennium BC. The identified mtDNA haplogroup composition reflects the mitochondrial variability of Western Eurasia. In particular, within the ancient Eurasian genetic landscape, Thracians locate in an intermediate position between Early Neolithic farmers and Late Neolithic-Bronze Age steppe pastoralists, supporting the scenario that the Balkan region has been a link between Eastern Europe and the Mediterranean since the prehistoric time. Spatial Principal Component Analysis (sPCA) performed on Thracian and modern mtDNA sequences, confirms the pattern highlighted on ancient populations, overall indicating that the maternal gene pool of Thracians reflects their central geographical position at the gateway of Europe.

Coronary heart disease (CHD) is a major cause of mortality and morbidity in Europe. CHD is usually caused by atherosclerosis. Despite extensive studies that have identified a large number of genetic variants, strong evidence of association with CHD are not easily replicable in different populations. Two DNA pools were constructed: one with 32 Bulgarian centenarians and one with 61 young healthy Bulgarian individuals. The pools were whole-exome sequenced and variants were annotated and quality filtered (89,810 filtered variants). Allele frequencies were estimated and Fisher’s exact test was used to evaluate the significance of allele frequency differences between the two pools. Two publicly available databases, Ensembl and DisGeNET, were used as a source of 2025 CHD-associated variants (CHD-AVs). These single nucleotide polymorphisms were screened in our data and 158 variants in 133 genes were found. ToppGene pathways analysis of genes called in both pools discovered participation of 37 genes in 9 significantly over-represented pathways. Eight variants in these 37 genes have significantly higher frequency in young individuals, and are nominated for CHD association. Variants called only in the young individuals pool (13 variants) are also nominated for association with CHD. Based on sufficiently unambiguous literature data, from the nominated variants, we prioritize five as associated with CHD in the studied Bulgarian sample. Centenarian genomes can be used to provide additional information regarding the clinical relevance of genetic variants reported as associated with CHD.

The article discusses the problems of the innovative activity of managers in Russian enterprises as one of the conditions for the development of the labour potential of a region. The paper shows the main reasons for the low innovative activity of Russian enterprises. The systems of labour relations that have developed, as a rule, generate labour and innovative passivity as well as the opportunistic behaviour of managers. Most Russian enterprises lack incentive schemes for managers’ innovative activity. We propose a systematic approach to stimulating the innovative activity of managers, relying on the authors’ experience of researching the innovative activity of managers in a number of enterprises. The authors’ system «Innovation», which is a Russian version of the Japanese lean manufacturing system, stimulates the innovative activity of personnel. Implementing this system in the enterprises of the Ural Federal District has convincingly shown that in modern conditions, a radical increase in the innovative activity of business managers is possible. It, therefore, stimulates the development of regional labour potential. Our hypothesis is that a high innovative activity of managers in Russian enterprises is possible by developing and implementing a two-sided incentive system for stimulating managers’ innovative activity. Such a system should provide not only incentives for innovative activity but also managers’ responsibility for their innovative passivity. We suggest a system of concepts of the innovative activity of personnel, which is necessary when organizing work to stimulate the innovative activity of enterprise managers. For the first time in the theory of incentives for staff and practical activities of enterprises, we propose to introduce a semi-annual assessment of the innovative activity of managers. The assessment of managers’ innovative activity is an instrument for incentives for an enterprise. Moreover, for managers, it becomes one of the motivational factors for the manifestation of innovation activity. The research results were applied in the development of the System of Innovative Activity of Managers in OAO Uralelectromed and OAO Shadrinsky Auto Aggregate Plant. The results of the research can be applied in industrial enterprises of different legal status and forms of ownership.

It is unknown whether transient transgenerational epigenetic responses to environmental challenges affect the process of evolution, which typically unfolds over many generations. Here, we show that in C. elegans, inherited small RNAs control genetic variation by regulating the crucial decision of whether to self-fertilize or outcross. We found that under stressful temperatures, younger hermaphrodites secrete a male-attracting pheromone. Attractiveness transmits transgenerationally to unstressed progeny via heritable small RNAs and the Argonaute Heritable RNAi Deficient-1 (HRDE-1). We identified an endogenous small interfering RNA pathway, enriched in endo-siRNAs that target sperm genes, that transgenerationally regulates sexual attraction, male prevalence, and outcrossing rates. Multigenerational mating competition experiments and mathematical simulations revealed that over generations, animals that inherit attractiveness mate more and their alleles spread in the population. We propose that the sperm serves as a "stress-sensor" that, via small RNA inheritance, promotes outcrossing in challenging environments when increasing genetic variation is advantageous.

Reversible and irreversible heavy loaded thrust bearings of a hydrogenerator are investigated. The problem of oil wedge microgeometry profiling for load capacity optimization is considered. The analysis is based on optimization methods using variational calculus. The results of oil wedge microgeometry optimization for reversible and irreversible thrust bearings are presented.

Background Globodera rostochiensis belongs to major potato pathogens with a sophisticated mechanism of interaction with roots of the host plants. Resistance of commercial varieties is commonly based on specific R genes introgressed from natural populations of related wild species and from native potato varieties grown in the Andean highlands. Investigation of molecular resistance mechanisms and screening the natural populations for novel R genes are important for both fundamental knowledge on plant pathogen interactions and breeding for durable resistance. Here we exploited the Solanum phureja accessions collected in South America with contrasting resistance to G. rostochiensis. Results The infestation of S. phureja with G. rostochiensis juveniles resulted in wounding stress followed by activation of cell division and tissue regeneration processes. Unlike the susceptible S. phureja genotype, the resistant accession reacted by rapid induction of variety of stress response related genes. This chain of molecular events accompanies the hypersensitive response at the juveniles’ invasion sites and provides high-level resistance. Transcriptomic analysis also revealed considerable differences between the analyzed S. phureja genotypes and the reference genome. Conclusion The molecular processes in plant roots associated with changes in gene expression patterns in response to G. rostochiensis infestation and establishment of either resistant or susceptible phenotypes are discussed. De novo transcriptome assembling is considered as an important tool for discovery of novel resistance traits in S. phureja accessions.

Objectives: The aim of the present study was to evaluate the clinical relevance of mutations in tumor suppressor genes using whole-exome sequencing data from centenarians and young healthy individuals. Methods: Two pools, one of centenarians and one of young individuals, were constructed and whole-exome sequencing was performed. We examined the whole-exome sequencing data of Bulgarian individuals for carriership of tumor suppressor gene variants. Results: Of all variants annotated in both pools, 5080 (0.06%) are variants in tumor suppressor genes but only 46 show significant difference in allele frequencies between the two studied groups. Four variants (0.004%) are pathogenic/risk factors according to single nucleotide polymorphism database: rs1566734 in PTPRJ, rs861539 in XRCC3, rs203462 in AKAP10, and rs486907 in RNASEL. Discussion: Based on their high minor allele frequencies and presence in the centenarian group, we could reclassify them from pathogenic/risk factors to benign. Our study shows that centenarian exomes can be used for re-evaluating the clinically uncertain variants.

The aim of the present study was to detect copy number variations (CNVs) related to tumour progression and metastasis of urothelial carcinoma through whole-genome scanning. A total of 30 bladder cancer samples staged from pTa to pT4 were included in the study. DNA was extracted from freshly frozen tissue via standard phenol-chloroform extraction and CNV analysis was performed on two alternative platforms (CytoChip Oligo aCGH, 4x44K and Infinium OncoArray-500K BeadChip; Illumina, Inc.). Data were analysed with BlueFuse Multi software and Karyostudio, respectively. The results highlight the role of genomic imbalances in regions containing genes with metastatic and proliferative potential for tumour invasion. A high level of genomic instability in uroepithelial tumours was observed and a total of 524 aberrations, including 175 losses and 349 gains, were identified. The most prevalent genetic imbalances affected the following regions: 1p, 1q, 2q, 4p, 4q, 5p, 5q, 6p, 6q, 7q, 8q, 9p, 9q, 10p, 10q, 11q, 13q and 17q. High-grade tumours more frequently harboured genomic imbalances (n=227) than low-grade tumours (n=103). A total of 36 CNVs in high-grade bladder tumours were detected in chromosomes 1-5, 8-11, 14, 17, 19 and 20. Furthermore, five loss of heterozygosity variants containing 176 genes were observed in high-grade bladder cancer and may be used as potential targets for precision therapy. Revealing specific chromosomal regions related to the metastatic potential of uroepithelial tumours may lay a foundation for implementing molecular CNV profiling of bladder tumours as part of a routine progression risk estimation strategy, thus expanding the personalized therapeutic approach.

Mutations in the receptor of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are used as biomarkers for predicting the response of treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs). Non-small cell lung cancer patients usually have activating EGFR mutations that leads to a very good response when they are treated with EGFR TKIs. Our tumor samples were examined for the presence of sensitive mutations in the EGFR gene, resistant mutations or the absence of mutations. To identify the types of the mutation, we used a real-time polymerase chain reaction (RT-PCR) method. Additionally, we evaluated the frequency of EGFR mutations and their association with smoking status, gender and histology. The tumor samples (n = 551) were tested for 29 somatic mutations in the EGFR gene. Sensitive mutations in the EGFR genes were found in 55 NSCLC samples (10.0%). The prevalence of EGFR mutations was much higher for females than for males (27.1 vs. 3.9%, p EGFR mutations was greater in subjects who had never smoked than in smokers (15.0 vs. 6.08%, p EGFR mutations was higher in adenocarcinomas than in other histological types (14.9 vs. 5.1%; p EGFR gene are more frequent in females than in males, in adenocarcinoma than other histological types and in non smokers than smokers.