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Background Francis Crick’s central dogma provides a residue-by-residue mechanistic explanation of the flow of genetic information in living systems. However, this principle may not be sufficient for explaining how random mutations cause continuous variation of quantitative highly polygenic complex traits. Chargaff’s second parity rule (CSPR), also referred to as intrastrand DNA symmetry, defined as near-exact equalities G ≈ C and A ≈ T within a single DNA strand, is a statistical property of cellular genomes. The phenomenon of intrastrand DNA symmetry was discovered more than 50 years ago; at present, it remains unclear what its biological role is, what the mechanisms are that force cellular genomes to comply strictly with CSPR, and why genomes of certain noncellular organisms have broken intrastrand DNA symmetry. The present work is aimed at studying a possible link between intrastrand DNA symmetry and the origin of genetic interactions in quantitative traits. Methods Computational analysis of single-nucleotide polymorphisms in human and mouse populations and of nucleotide composition biases at different codon positions in bacterial and human proteomes. Results The analysis of mutation spectra inferred from single-nucleotide polymorphisms observed in murine and human populations revealed near-exact equalities of numbers of reverse complementary mutations, indicating that random genetic variations obey CSPR. Furthermore, nucleotide compositions of coding sequences proved to be statistically interwoven via CSPR because pyrimidine bias at the 3rd codon position compensates purine bias at the 1st and 2nd positions. Conclusions According to Fisher’s infinitesimal model, we propose that accumulation of reverse complementary mutations results in a continuous phenotypic variation due to small additive effects of statistically interwoven genetic variations. Therefore, additive genetic interactions can be inferred as a statistical entanglement of nucleotide compositions of separate genetic loci. CSPR challenges the neutral theory of molecular evolution—because all random mutations participate in variation of a trait—and provides an alternative solution to Haldane’s dilemma by making a gene function diffuse. We propose that CSPR is symmetry of Fisher’s infinitesimal model and that genetic information can be transferred in an implicit contactless manner.

Abstract Background Approaches to the evaluation of pulmonary arterial hypertension (PAH) in premature calves by using lung‐specific epithelial and endothelial biomarkers are needed. Objective To investigate the evaluation of PAH in premature calves with and without respiratory distress syndrome (RDS) by using lung‐specific epithelial and endothelial biomarkers and determine the prognostic value of these markers in premature calves. Animals Fifty premature calves with RDS, 20 non‐RDS premature calves, and 10 healthy term calves. Methods Hypoxia, hypercapnia, and tachypnea were considered criteria for RDS. Arterial blood gases (PaO2, PaCO2, oxygen saturation [SO2], base excess [BE], and serum lactate concentration) were measured to assess hypoxia. Serum concentrations of lung‐specific growth differentiation factor‐15 (GDF‐15), asymmetric dimethylarginine (ADMA), endothelin‐1 (ET‐1), vascular endothelial growth factor (VEGF), and surfactant protein D (SP‐D) were measured to assess PAH. Results Arterial blood pH, PaO2, SO2, and BE of premature calves with RDS were significantly lower and PaCO2 and lactate concentrations higher compared to non‐RDS premature and healthy calves. The ADMA and SP‐D concentrations of premature calves with RDS were lower and serum ET‐1 concentrations higher than those of non‐RDS premature and healthy calves. No statistical differences for GDF‐15 and VEGF were found among groups. Conclusions and Clinical Importance Significant increases in serum ET‐1 concentrations and decreases in ADMA and SP‐D concentrations highlight the utility of these markers in the diagnosis of PAH in premature calves with RDS. Also, we found that ET‐1 was a reliable diagnostic and prognostic biomarker for PAH and predicting mortality in premature calves.

Objectives: to evaluate the advantage of preserving the subvalvular structures of the mitral valve from both leaflets compared with the preservation of the subvalvular structures only from the posterior valve during mitral valve replacement surgery (MVR). Methods: A retrospective analysis of case histories of 41 patients with isolated rheumatic lesions of the mitral valve who underwent MVR, which were divided into 2 groups: with complete preservation of subvalvular structures (n = 24) and preservation of only the posterior leaflet (n = 17), was performed. Results: In the group with complete preservation of the chordal-papillary apparatus, there was a significant decrease in the end-systolic volume (p

Background. Acute intestinal infections (AII) caused by Shiga-like toxin-producing Escherichia coli and accompanied by hemolytic uremic syndrome (HUS) development are characterized by rapid progression and poor prognosis. Bloody diarrhea (hemorrhagic colitis) requires timely medical treatment both at young age and at adolescence. The severe course of HUS affected by AII caused by enterohaemorrhagic Escherichia coli requires additional medical attention and timely renal replacement therapy (hemodialysis).Clinical Case Description. The description and analysis of the severe course of HUS affected by AII in 14 years old adolescent girl is presented. There were some difficulties during diagnostics and thus the pathogenetic therapy onset was delayed. Differential diagnosis between typical and atypical HUS was performed. The disease was characterized by rapid progression of acute kidney injury, cerebrovascular disease and ischemia, multiple organ dysfunction syndrome and disseminated intravascular coagulation resulting in fatal case.Conclusion. Atypical HUS is the most frequent cause of multiple organ dysfunction syndrome alongside with acute kidney injury. The challenges of early diagnostics of atypical GUS in childhood are not fully solved nowadays and require additional attention of pediatricians. The clinical case of atypical GUS complicated by intestinal infection caused by enterohaemorrhagic Escherichia coli is described in this article. The severity of the disease course was due to the early manifestation of extrarenal symptoms and multiple organ failure.

Relevance of the discussed issue is caused by the need to describe and predict gas/oil ratio growth on highly watered oil fields at late stages of exploration. The aim of the research is to justify the phenomenon of trade gas-oil ratio increase during exploration of fields at late stages on the basis of studying oil gas dissolution effect in passing extracted water and the analysis of separation conditions on oil preparation facilities. Methods. For modeling easy hydrocarbonic components of oil dissolution in water the authors have used the modified Soave-Redliсh-Kwong equation of state taking into account water mineralization and the program complex Aspen HYSYS for assessing ablation of easy oil components in gas phase during separation at booster pump stations and the central oil gathering station depending on the termobaric conditions of separation. Results. On the basis of simulation it is shown that the growth of trade gas-oil ratio occurs at increase of water content of oil wells at the oilfields, which are operated by maintaining the reservoir pressure by water injection at pressures higher than the saturation pressure of oil. This growth is induced on the one hand by extraction of light hydrocarbon fractions from the passing extracted water, on the other hand by increase of oil separation temperature at the surface objects (booster pump stations, preliminary water discharge installations, central collection points). The contribution of gas dissolved in the passing extracted water is the main reason: at water content over 90-95 % the trade gas-oil ratio can multiply grow in comparison with gas content of reservoir oil. The increase of temperature of oil separation by 5-10 °C results in padding increase of gas-oil ratio by 5-10 % because of transition of a part of fluid hydrocarbons to gas-eous state.

Background: The share of healthcare-related expenditure in the Gross Domestic Product of Kazakhstan is relatively small, and it is strategically important to restructure budgetary expenses in favor of healthcare with simultaneous redistribution of resources in accordance with changing demands and prioritization of high-quality medical care. The aim of this study was to analyze resource provision to healthcare organizations in Kazakhstan and its structure and level assessment. Materials and Methods: The study is based on a comparative assessment of technical and technological equipment of medical institutions in Almaty, Kazakhstan. We analyzed the scope and structure of the financial component of the resource base in Almaty. We carried out information processing and analysis methods, content analysis, mathematical treatment, as well as conducted case studies. Also, we held opinion poll among medical staff (specialists, managerial staff ) (n = 300) P for trend < 0.001 and patients (n = 210) P for trend < 0.001. Results: About 18.8% of patients do not receive medical care because of defects of the equipment, whereas 19.9% of patients claim that the reason of refusal of the provision of medical services is an equipment overload. Conclusion: Most of the respondents referred to on poor technical equipment, mismatch with the world standards of performance and competitiveness. Lack of advanced medical technology, inadequate financing, insufficient supply of domestic medical equipment, and inadequate procurement by tender were also noted. The obtained data point to the need for optimization and upgrading medical equipment at various levels of healthcare.

Human apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme in the base excision repair (BER) and nucleotide incision repair (NIR) pathways. We recently analyzed the conformational dynamics and kinetic mechanism of wild-type (wt) protein, in a stopped-flow fluorescence study. In this study, we investigated the mutant enzyme APE1K98A using the same approach. Lys98 was known to hydrogen bond to the carboxyl group of Asp70, a residue implicated in binding the divalent metal ion. Our data suggested that the conformational selection and induced fit occur during the enzyme action. We expanded upon the evidence that APE1 can pre-exist in two conformations. The isomerization of an enzyme-product complex in the BER process and the additional isomerization stage of enzyme-substrate complex in the NIR process were established for APE1K98A. These stages had not been registered for the wtAPE1. We found that the K98A substitution resulted in a 12-fold reduction of catalytic constant of 5'-phosphodiester bond hydrolysis in (3-hydroxytetrahydrofuran-2-yl)methyl phosphate (F, tetrahydrofuran) containing substrate, and in 200-fold reduction in 5,6-dihydrouridine (DHU) containing substrate. Thus, the K98A substitution influenced NIR more than BER. We demonstrated that the K98A mutation influenced the formation of primary unspecific enzyme-substrate complex in a complicated manner, depending on the Mg(2+) concentration and pH. This mutation obstructed the induced fit of enzyme in the complex with undamaged DNA and F-containing DNA and appreciably decreased the stability of primary complex upon interaction of enzyme with DNA, containing the natural apurinic/apyrimidinic (AP) site. Furthermore, it significantly delayed the activation of the less active form of enzyme during NIR and slowed down the conformational conversion of the complex of enzyme with the cleavage product of DHU-substrate. Our data revealed that APE1 uses the same active site to catalyze the cleavage of DHU- and AP-substrates.

We address the prediction of the number of new cases and deaths for the coronavirus disease 2019 (COVID-19) over a future horizon from historical data (forecasting). We use a model-based approach based on a stochastic Susceptible-Infections-Removed (SIR) model with time-varying parameters, which captures the evolution of the disease dynamics in response to changes in social behavior, non-pharmaceutical interventions, and testing rates. We show that, in the presence of asymptomatic cases, such model includes internal parameters and states that cannot be uniquely identified solely on the basis of measurements of new cases and deaths, but this does not preclude the construction of reliable forecasts for future values of these measurements. Such forecasts and associated confidence intervals can be computed using an iterative algorithm based on nonlinear optimization solvers, without the need for Monte Carlo sampling. Our results have been validated on an extensive COVID-19 dataset covering the period from March through December 2020 on 144 regions around the globe.

Human thymine-DNA glycosylase (TDG) excises T mispaired with G in a CpG context to initiate the base excision repair (BER) pathway. TDG is also involved in epigenetic regulation of gene expression by participating in active DNA demethylation. Here we demonstrate that under extended incubation time the full-length TDG (TDGFL), but neither its isolated catalytic domain (TDGcat) nor methyl-CpG binding domain-containing protein 4 (MBD4) DNA glycosylase, exhibits significant excision activity towards T and C in regular non-damaged DNA duplex in TpG/CpA and CpG/CpG contexts. Time course of the cleavage product accumulation under single-turnover conditions shows that the apparent rate constant for TDGFL-catalysed excision of T from T•A base pairs (0.0014–0.0069 min−1) is 85–330-fold lower than for the excision of T from T•G mispairs (0.47–0.61 min−1). Unexpectedly, TDGFL, but not TDGcat, exhibits prolonged enzyme survival at 37°C when incubated in the presence of equimolar concentrations of a non-specific DNA duplex, suggesting that the disordered N- and C-terminal domains of TDG can interact with DNA and stabilize the overall conformation of the protein. Notably, TDGFL was able to excise 5-hydroxymethylcytosine (5hmC), but not 5-methylcytosine residues from duplex DNA with the efficiency that could be physiologically relevant in post-mitotic cells. Our findings demonstrate that, under the experimental conditions used, TDG catalyses sequence context-dependent removal of T, C and 5hmC residues from regular DNA duplexes. We propose that in vivo the TDG-initiated futile DNA BER may lead to formation of persistent single-strand breaks in non-methylated or hydroxymethylated chromatin regions. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this study is to examine the sense of school belonging and sportspersonship behaviors of students who participate in traditional children's games. The research was designed using a quasi-experimental model with a pre-test and post-test control group and was conducted over a period of 16 weeks. The study group consisted of a total of 1871 students, including 1379 middle school and 492 high school students, continuing their education in Eskil, Aksaray during the 2023–2024 academic year. The experimental group students participated in the games and inter-school tournaments within the scope of the “2nd I Live My Values with Traditional Games Project” No intervention was applied to the control group after the introduction of the games. The “School Belongingness Scale” and the “Physical Education Course Sportspersonship Behavior Scale” were used as data collection tools. For data analysis, MANOVA, paired samples t-test, and regression analysis were employed. The findings of the study indicated that both the experimental and control groups showed positive scores in pre-test and post-test measures of school belongingness and sportspersonship behaviors. However, the experimental group demonstrated significant improvements in their sense of school belonging and sportspersonship behaviors in favor of the post-test. While no significant change was observed in the control group's sense of school belonging, a decline was noted in their sportspersonship behaviors. The experimental group exhibited greater development in school belongingness and sportspersonship behaviors compared to the control group. Although middle school students showed improvements in their sense of school belonging, high school students experienced a more substantial emotional development. No significant differences were found in school belongingness and sportspersonship behaviors based on the students' gender. Sportspersonship behavior predicted school belongingness by 11%, suggesting that positive sportspersonship behaviors increased school attachment among children. In conclusion, it was determined that students participating in traditional children's games developed a more positive sense of school belonging and sportspersonship behaviors over time. Based on the positive outcomes of student participation in traditional games, it is recommended to promote these games, incorporate them into physical education classes, and increase participation in tournaments.

Background: Gonarthrosis (GA) is a chronic degenerative disease. This study aimed to determine the frailty level of patients with GA aged 65 and over and to investigate the effect of pain on frailty. Methods: The population of this cross-sectional study consisted of patients and their relatives who applied to the orthopedics and traumatology outpatient clinic of a university hospital for examination, follow-up and treatment from October 1, 2021, to January 31, 2022. The study was completed with 160 elderly people aged 65 years and over. Data were collected using Personal Information Form, Tilburg Frailty Indicator (TFI), Get Up and Go Test (GGT), and Geriatric Pain Scale (GPS). Simple descriptive statistics, as well as correlation and multiple linear regression analysis, were used to analyze the data using SSPS 20. The significance level was set at p

Amaç: Bu çalışma, SARS-CoV-2 (COVID-19) pandemisinin sağlık sistemlerinin etkinliği üzerindeki etkisini araştırmayı amaçlamıştır.Yöntem: Çalışmada, aylak tabanlı model, panel veri analizi, Malmquist Toplam Faktör Verimlilik Endeksi ve istatistiksel fark testi kullanılmıştır. Çalışmanın girdi değişkenleri olarak; 1.000 kişiye düşen hekim sayısı, satın alma gücü paritesine göre Amerikan doları olarak kişi başına düşen sağlık harcaması, 1.000.000 kişiye düşen bilgisayarlı tomografi cihazı sayısı; çıktı değişkenleri olarak ise, erkeklerde ve kadınlarda doğumda beklenen yaşam süresi kullanılmıştır.Bulgular: COVID-19 pandemisi aylak tabanlı model ve Malmquist Toplam Faktör Verimlilik Endeksi skorlarını anlamlı bir şekilde azaltmıştır (p

Abstract Background Mitochondrial biogenesis (MB) induction has recently emerged as potential therapeutic approaches in kidney pathology and the mitochondria-targeted therapies should be investigated to improve treatment of animals with kidney diseases. This study aimed to investigate the effects of MB induction with sildenafil citrate on the cGMP/NO pathway, glomerular filtration, and reduction of kidney damage and fibrosis (TGF-β/SMAD pathway) in cats with acute on chronic kidney disease (ACKD). Thirty-three cats were divided into the non-azotemic (healthy) group (n:8) and the ACKD group (n:25), comprising different breeds, sexes, and ages. Sildenafil citrate was administered to the non-azotemic and ACKD groups (2.5 mg/kg, PO, q12 hours) for 30 days. Serum and urine NO, MDA, NGAL, KIM-1, TGF-β1, IL-18, FGF 23, PGC-1α and cGMP concentrations were measured. Results Serum cGMP concentrations increased (P

Abstract Digitalization is a key concept that transformed the various industries through technologies like Internet of Things (IoT), Artificial Intelligence (AI), and Digital Twin (DT). Although innovations provided by the advancement of digitalization have paved the way for more efficient operations and products for transportation, the rail transportation sector struggles to keep up with the rest of the transportation industry, since trains are designed to last for decades, and the insufficient infrastructure investment leads to multiple railroad derailments across the globe. Therefore, the primary aim is to transform current railway systems into human-centric, adaptable, sustainable and future-proof networks, aligning with Industry 5.0 (I5.0) and Circular Economy (CE) model supported by the restorative and long-lasting design of the trains. This transformation necessitates leveraging digitalization and emerging technologies to address the needs of passengers, operators, and maintenance personnel. This article provides a comprehensive review focusing on the application of IoT, AI, CE principles, and digital twin trains to existing railway infrastructure and assets. The analysis delves into developing system architecture for proposed solutions and their impact on operation, maintenance, sustainability, and passenger comfort, supported by track record analysis. The integration of these technologies and concepts, particularly AI-powered services, is anticipated to yield immediate advancements in the digitalization of railway transportation, enhancing efficiency and safety measures.

Abstract Purpose Oncology is the primary field in medicine with a high rate of artificial intelligence (AI) use. Thus, this study aimed to investigate the trends of AI in oncology, evaluating the bibliographic characteristics of articles. We evaluated the related research on the knowledge framework of Artificial Intelligence (AI) applications in Oncology through bibliometrics analysis and explored the research hotspots and current status from 1992 to 2022. Methods The research employed a scientometric methodology and leveraged scientific visualization tools such as Bibliometrix R Package Software, VOSviewer, and Litmaps for comprehensive data analysis. Scientific AI-related publications in oncology were retrieved from the Web of Science (WoS) and InCites from 1992 to 2022. Results A total of 7,815 articles authored by 35,098 authors and published in 1,492 journals were included in the final analysis. The most prolific authors were Esteva A (citaition = 5,821) and Gillies RJ (citaition = 4288). The most active institutions were the Chinese Academy of Science and Harward University. The leading journals were Frontiers ın Oncology and Scientific Reports. The most Frequent Author Keywords are "machine learning", "deep learning," "radiomics", "breast cancer", “melanoma” and "artificial intelligence," which are the research hotspots in this field. A total of 10,866 Authors' keywords were investigated. The average number of citations per document is 23. After 2015, the number of publications proliferated. Conclusion The investigation of Artificial Intelligence (AI) applications in the field of Oncology is still in its early phases especially for genomics, proteomics, and clinicomics, with extensive studies focused on biology, diagnosis, treatment, and cancer risk assessment. This bibliometric analysis offered valuable perspectives into AI's role in Oncology research, shedding light on emerging research paths. Notably, a significant portion of these publications originated from developed nations. These findings could prove beneficial for both researchers and policymakers seeking to navigate this field.

Objective: Breast cancer (BC) is highly heterogeneous and one of the most common cancers. Luminal A (LUM A) is a subtype of BC with a better prognosis than other BC subtypes. The molecular mechanisms underlying the initiation and progression of the LUM A subtype are still unclear. Big data generated from microarray and sequencing systems can be re-analyzed, especially with the help of various in silico tools developed in recent years, and made applicable for in vitro and in vivo research. This work aimed to identify genes that may play a role in the progression of LUM A subtype of BC using both computational and laboratory-based methods. Materials and Methods: Overlapping genes associated with BC were identified from the The Cancer Genome Atlas database, GSE233242, GSE100925 geodata sets, and the geneshot tool. The network functional analysis between overlapping genes was determined with STRING 12.0. Expression levels of overlapping genes in BC were investigated with the TNMplot (https://tnmplot.com/analysis/) in silico tool. The effect of overlapping genes on the overall survival of LUM A cancer patients was defined using the Kaplan-Meier plotter tool. Expressions of genes identified using bioinformatics data were investigated via quantitative real-time -polymerase chain reaction (qRT-PCR) in LUM A tumor and adjacent tissue samples. The data were evaluated using the t-test. Both the sensitivity and specificity of selected genes have been determined using the receiver operating characteristic curve. Results: In silico investigation showed that eleven genes were possibly associated with BC. Among them CDC25A, AURKB, and TOP2A were considerably increased in LUM A samples according to qRT-PCR results. An overall survival analysis also showed that overexpression of these three genes could reduce the overall survival of LUM A patients. Conclusion: The genes CDC25A, AURKB, and TOP2A may play crucial functions in LUM A pathogenesis. Therapeutic strategies that diminish the expression of these connected genes may enhance the prognosis of LUM A patients.