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The rapid development of next-generation sequencing technologies and genomic data sharing initiatives during the post-Human Genome Project-era has catalyzed major advances in individualized medicine research. Genome-wide association studies (GWAS) have become a cornerstone of efforts towards understanding the genetic basis of complex diseases, leading to the development of polygenic scores (PGS). Despite their immense potential, the scarcity of standardized PGS development pipelines limits widespread adoption of PGS. Herein, we introduce PGSXplorer, a comprehensive Nextflow DSL2 pipeline that enables quality control of genomic data and automates the phasing, imputation, and construction of PGS models using reference GWAS data. PGSXplorer integrates various PGS development tools such as PLINK, PRSice-2, LD-Pred2, Lassosum2, MegaPRS, SBayesR-C, PRS-CSx and MUSSEL, improving the generalizability of PGS through multi-origin data integration. Tested with synthetic datasets, our fully Docker-encapsulated tool has demonstrated scalability and effectiveness for both single- and multi-population analyses. Continuously updated as an open-source tool, PGSXplorer is freely available with user tutorials at https://github.com/tutkuyaras/PGSXplorer, making it a valuable resource for advancing precision medicine in genetic research.

Numerous studies have examined classroom seating arrangements to enhance student safety and resource utilization during COVID-19. These studies typically aimed to maximize the minimum distance between students for a given number of students to be assigned. This paper distinguishes itself from the existing literature by not only assigning students as far apart as possible but also focusing on maximizing the average distance between students. We call this new problem the maximum diversity social-distancing problem (MDPs), a novel variant of the maximum diversity problem (MDP). This problem is a two-phased problem, where the first phase involves producing the maximum of minimum distance (max-min) between students, and once that is resolved, the max-min distance is used in the second phase for having the highest dispersion. The first phase is here solved by a new algorithm, which effectively determines max-min distance for each student allocation scenario. For the second phase, three exact and one greedy approximation MDPs models are proposed. In computational testing, we observe that the greedy approximation MDPs model mostly returns optimal solutions across all tested classrooms in less than a second. More importantly, utilizing the greedy one significantly improves student pair spacing, increasing the average distance by over 40 centimeters compared to the max-min distance approach of the literature. Later, this effective approach is integrated into the pandemic management platform, which proactively assists the university administration in preparing for and effectively managing future infection outbreaks.

Objective:In our study, we aimed to investigate the long-term effects of the acute phase parameters of C-reactive protein, procalcitonin, D-dimer, lymphocyte, thrombocyte and ferritin on the respiratory function parameters in patients hospitalized due to Coronavirus disease-2019 (COVID-19) pneumonia.Method:The present study was carried out with the retrospective evaluation of patients with COVID-19 pneumonia, who were hospitalized in Medipol University Hospital between March 2020 and June 2021, and who were 6 months to 1 year after discharge. The relationship between pulmonary function test results and acute period laboratory findings of 52 patients who applied for control purposes 6 months after discharge was examined.Results:Diffusing capacity for carbon monoxide (DLCO) (pred) value in 26 patients (50%), total lung capacity (TLC) value in 9 patients (17.3%), and residual volume (RV) (pred) value in 10 patients (19.2%) were below 80%. As a result of multiple linear regression analysis in our study, the maximum D-dimer level and maximum procalcitonin level were determined by DLCO (% pred) (adjusted R2 =0.645; p

This study aimed to compare the efficacy of percutaneous microwave ablation therapy (MWAT) and laparoscopic partial nephrectomy (LPN) in early-stage renal cell carcinoma (RCC) classified as T1a; a retrospective analysis was conducted on patients treated between January 2017 and November 2023. Oncological outcomes, radiological recurrence, length of stay (LOS), and costs were evaluated. The study included 110 patients, with no significant differences between the two groups regarding residual tumors, local tumor progression, and disease-free survival rates (p > 0.05). The LPN group showed significantly lower pre/postoperative serum urea and creatinine and higher estimated glomerular filtration rate values, whereas the MWA group experienced significantly lower mean costs, complication rates, LOS in the hospital, and procedure durations (p ≤ 0.05). However, post-procedure residual tumors and local tumor progression rates did not differ significantly between the LPN and MWAT groups (p > 0.05). MWAT is as effective as LPN for T1a RCC lesions. In addition, MWAT has lower costs than LPN and is a cost-effective treatment method. Therefore, MWAT minimizes hospital stay and complications and since the oncological results are similar to LPN, it might be considered as the first choice of treatment in young patients.

Pulmonary embolism (PE) is an important cause of sudden death and is difficult to diagnose. Therefore unnecessary radiological investigations are often resorted to. Although some inflammatory parameters in the hemogram have been found to play a role in the diagnosis of PE, many parameters have not been adequately investigated. We aimed to evaluate potential inflammatory parameters in hemogram in the diagnosis of PE and to determine the parameters with the highest diagnostic value. This single-center, retrospective study was performed by evaluating 114 cases with suspected PE admitted to the emergency department between January 2017 and June 2022. Among 114 cases, 62 cases with a definitive diagnosis of PE by pulmonary computed tomography angiography served as the PE group and 52 cases without PE served as the control group. Admission hemogram parameters of both groups were recorded. Potential chronic diseases and acute conditions affecting hemogram were excluded from the study . In the multivariate model; immature granulocyte (IG), neutrophil/lymphocyte ratio (NLR), monocyte % and platelet large cell ratio (P-LCR) were found to be significantly and independently effective in differentiating cases with and without PE ( P ˂.05). Our findings suggest that high IG, high NLR, high monocyte %, and low P-LCR values have diagnostic value in cases with suspected PE. However the usability of IGs in the diagnosis of PE is a new finding. Hemogram is cheap, easily accessible, and potential inflammatory biomarkers in hemograms may increase physicians’ awareness in the diagnosis of PE.

The transcription factors FRA1 and FLI1 regulate cell migration and cell junction organization genes in muscle-invasive bladder cancer, and loss of these factors reduces cancer cell invasion, pointing toward a therapeutic avenue.

BackgroundTNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known.MethodsPrimary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes in vitro. The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients.ResultsTRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells in vitro. Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content.ConclusionsTRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization.

Existing memristors cannot be reconfigured to meet the diverse switching requirements of various computing frameworks, limiting their universality. Here, the authors present a nanocrystal memristor that can be reconfigured on-demand to address these limitations

Low-grade gliomas (LGG) are central nervous system Grade I tumors, and as they progress they are becoming one of the deadliest brain tumors. There is still great need for timely and accurate diagnosis and prognosis of LGG. Herein, we aimed to identify diagnostic and prognostic biomarkers associated with LGG, by employing diverse computational approaches. For this purpose, differential gene expression analysis on high-throughput transcriptomics data of LGG versus corresponding healthy brain tissue, derived from TCGA and GTEx, respectively, was performed. Weighted gene co-expression network analysis of the detected differentially expressed genes was carried out in order to identify modules of co-expressed genes significantly correlated with LGG clinical traits. The genes comprising these modules were further used to construct gene co-expression and protein-protein interaction networks. Based on the network analyses, we derived a consensus of eighteen hub genes, namely, CD74, CD86, CDC25A, CYBB, HLA-DMA, ITGB2, KIF11, KIFC1, LAPTM5, LMNB1, MKI67, NCKAP1L, NUSAP1, SLC7A7, TBXAS1, TOP2A, TYROBP, and WDFY4. All detected hub genes were up-regulated in LGG, and were also associated with unfavorable prognosis in LGG patients. The findings of this study could be applicable in the clinical setting for diagnosing and monitoring LGG.

Keratins (KRTs) are the intermediate filament-forming proteins of epithelial cells, classified, according to their physicochemical properties, into “soft” and “hard” keratins. They have a key role in several aspects of cancer pathophysiology, including cancer cell invasion and metastasis, and several members of the KRT family serve as diagnostic or prognostic markers. The human genome contains both, functional KRT genes and non-functional KRT pseudogenes, arranged in two uninterrupted clusters on chromosomes 12 and 17. This characteristic renders KRTs ideal for evolutionary studies. Herein, comprehensive phylogenetic analyses of KRT homologous proteins in the genomes of major taxonomic divisions were performed, so as to fill a gap in knowledge regarding the functional implications of keratins in cancer biology among tumor-bearing species. The differential expression profiles of KRTs in diverse types of cancers were investigated by analyzing high-throughput data, as well. Several KRT genes, including the phylogenetically conserved ones, were found to be deregulated across several cancer types and to participate in a common protein-protein interaction network. This indicates that, at least in cancer-bearing species, these genes might have been under similar evolutionary pressure, perhaps to support the same important function(s). In addition, semantic relations between KRTs and cancer were detected through extensive text mining. Therefore, by applying an integrative in silico pipeline, the evolutionary history of KRTs was reconstructed in the context of cancer, and the potential of using non-mammalian species as model organisms in functional studies on human cancer-associated KRT genes was uncovered.

MicroRNAs represent major regulatory components of the disease epigenome and they constitute powerful biomarkers for the accurate diagnosis and prognosis of various diseases, including cancers. The advent of high-throughput technologies facilitated the generation of a vast amount of miRNA-cancer association data. Computational approaches have been utilized widely to effectively analyze and interpret these data towards the identification of miRNA signatures for diverse types of cancers. Herein, a novel computational workflow was applied to discover core sets of miRNA interactions for the major groups of neoplastic diseases by employing network-based methods. To this end, miRNA-cancer association data from four comprehensive publicly available resources were utilized for constructing miRNA-centered networks for each major group of neoplasms. The corresponding miRNA-miRNA interactions were inferred based on shared functionally related target genes. The topological attributes of the generated networks were investigated in order to detect clusters of highly interconnected miRNAs that form core modules in each network. Those modules that exhibited the highest degree of mutual exclusivity were selected from each graph. In this way, neoplasm-specific miRNA modules were identified that could represent potential signatures for the corresponding diseases.

Intestinal ischemia reperfusion injury (IRI) is a challenging problem and it adversely affects the healing of colonic anastomosis. Our experimental study aimed to investigate the role of mesenchymal stem cells (MSC) administration in the healing of colonic anastomosis. A total of 33 rats were grouped as Control, IRI and MSC treatment groups. Three rats were reserved for obtaining MSCs. Colonic resection and anastomosis procedure was performed in all groups. Anastomotic line was wrapped with MSCs impregnated spongostan after colonic anastomosis in the rats of the MSC treatment group. All rats were sacrificed and anastomotic line were sampled for examination on the post operative seventh day. Tissue hydroxyproline (HP) levels and anastomotic bursting pressures were statistically compared. Anastomotic bursting pressures were found to be significantly high in MSC treatment group rats. The lowest anastomotic bursting pressure was detected in IRI group rats. Hydroxyproline content of the anastomotic sites were also found to be significantly higher in the rats of the MSC treatment group when compared with the IRI group rats. Our study showed that the detrimental effects of IRI on the healing process of colonic anastomosis in an experimental model may be alleviated with the treatment of MSCs.

Background: Limited data is available on the use of cold-scalpel and electrocautery blades in Cesarean delivery (CD) operations. This randomized controlled trial aimed to compare their use for subcutaneous incisions in terms of blood loss and postoperative pain in women undergoing repeat CD. Methods: A total of 149 women scheduled for elective CD underwent spinal anesthesia, Pfannenstiel transverse skin incision with a cold-scalpel blade, and subsequent subcutaneous incisions until the peritoneum with a cold-scalpel or electrocautery blade. Perioperative blood loss and postoperative pain were evaluated. Results: The groups were similar in terms of maternal age, physical characteristics, and gestational age. The electrocautery group recorded significantly less blood loss and pain at the postoperative 6th and 12th hours. No significant correlation was found between blood loss or pain and women’s physical characteristics or gestational age. Discussion: Perioperative and postoperative pain associated with CD is one of the predominant causes of anxiety in mothers. This study demonstrated that the use of electrocautery for subcutaneous incisions was associated with lower blood loss and lower postoperative pain compared to the cold-scalpel incisions in pregnant women undergoing repeat C-sections with Pfannenstiel incision. The study supports the recently shifting trend regarding the use of electrocautery instead of the scalpel.

In this study, we retrospectively evaluated patients with upper gastrointestinal bleeding (UGB) who were followed up at our center over a 3 year period and aimed to determine the factors affecting mean platelet volume (MPV) in patients with UGB, temporal changes in MPV during UGB, and the relationship between MPV values and the severity of UGB. Patients and methods: A total of 170 patients who were hospitalized between January 2010 and December 2013 with a diagnosis of UGB, completed a 72-hour follow up, and had a baseline blood count performed within 6 months were evaluated retrospectively. Demographic, clinical, and laboratory data, along with MPV values at baseline, on admission, and at 4 hours, 1 day, 2 days, 3 days, and discharge, were evaluated. Number Cruncher Statistical System (NCSS) 2007 was used for statistical analyses. Results: Women and patients with comorbid diseases had higher baseline MPV values; this effect disappeared after admission for UGB and reappeared at discharge. MPV values were lowest at the start of the bleeding and significantly increased during the course of UGB. Baseline MPV and MPV at discharge values were similar. There was no statistically significant relationship between any MPV measurement and transfusion amount. Conclusion: The effects of gender and comorbid diseases were negated by the presence of UGB and returned after UGB was controlled. MPV levels exhibited temporal changes during the course of UGB, indicating that MPV can be used as a marker; however, no statistical relationship was found between temporal MPV values and transfusion amount, a marker for UGB severity. [Med-Science 2020; 9(4.000): 1036-40]

Amaç: Şiddetli akut pankreatit (SAP) yüksek morbidite ve mortalite riski taşır. SAP'nin proenflamatuar yanıt fazı kontrol edilemezse, çoklu organ yetmezliği (ÇOY) ile sonuçlanabilir. Nükleer faktör-kappa B (NF-κB) aktivasyonu ÇOY'un gelişiminde önemli bir rol oynar. Bu çalışmada, bir anti-enflamatuar ve immünsüpresif ajan olan triptolidin SAP'lı sıçanlarda iyileştirici etkilerinin araştırılması amaçlanmıştır.Gereç ve Yöntemler: Toplam 20 Wistar-Albino sıçanı SAP ve triptolide tedavi (TT) grubu olmak üzere iki gruba ayrıldı. SAP her iki grupta da intraperitoneal cerulein (50 mg/kg) enjeksiyonu ile indüklendi. TT grubuna, SAP indüksiyonundan 24 saat sonra tek bir doz (0.2 mg/kg) triptolid uygulandı. Serum ALT, AST, GGT, Lipaz, Glikoz, ALP ve amilaz düzeyleri ve pankreatik doku örnekleri incelendi.Bulgular: Serum glukoz ve amilaz düzeyleri TT grubunda anlamlı olarak daha düşük bulundu (sırasıyla p=0.011 ve p=0.035). Diğer biyokimyasal parametreler açısından gruplar arasında anlamlı bir fark yoktu. Pankreas ödemi, asiner hücre dejenerasyonu, yağ nekrozu, intrapankreatik&perivasküler inflamasyon ve peripankreatik yağ dokusunda inflamasyon her iki grupta da sık görülen histopatolojik bulgulardı. Gruplar arasında histopatolojik değişiklikler açısından anlamlı bir fark yoktu.Sonuç: Cerulein kaynaklı pankreatit, deneysel SAP için başarılı bir yöntemdir. Tek doz triptolid tedavisinin iyileştirici etkileri SAP'nin erken evresinde belirgin değildir. Pankreatik doku histopatolojik ve biyokimyasal parametreler açısından incelendiğinde, triptolidin enflamatuar ve oksidatif stres üzerindeki terapötik etkileri yeterli düzeyde değildi.

This study investigates the motion characteristics of soft alginate microrobots in complex fluidic environments utilizing wireless magnetic fields for actuation. The aim is to explore the diverse motion modes that arise due to shear forces in viscoelastic fluids by employing snowman-shaped microrobots. Polyacrylamide (PAA), a water-soluble polymer, is used to create a dynamic environment with non-Newtonian fluid properties. Microrobots are fabricated via an extrusion-based microcentrifugal droplet method, successfully demonstrating the feasibility of both wiggling and tumbling motions. Specifically, the wiggling motion primarily results from the interplay between the viscoelastic fluid environment and the microrobots’ non-uniform magnetization. Furthermore, it is discovered that the viscoelasticity properties of the fluid influence the motion behavior of the microrobots, leading to non-uniform behavior in complex environments for microrobot swarms. Through velocity analysis, valuable insights into the relationship between applied magnetic fields and motion characteristics are obtained, facilitating a more realistic understanding of surface locomotion for targeted drug delivery purposes while accounting for swarm dynamics and non-uniform behavior.

Epigenetic deregulation is a critical theme which needs further investigation in bladder cancer research. One of the most highly mutated genes in bladder cancer is KDM6A, which functions as an H3K27 demethylase and is one of the MLL3/4 complexes. To decipher the role of KDM6A in normal versus tumor settings, we identified the genomic landscape of KDM6A in normal, immortalized, and cancerous bladder cells. Our results showed differential KDM6A occupancy in the genes involved in cell differentiation, chromatin organization, and Notch signaling depending on the cell type and the mutation status of KDM6A. Transcription factor motif analysis revealed HES1 to be enriched at KDM6A peaks identified in the T24 bladder cancer cell line; moreover, it has a truncating mutation in KDM6A and lacks a demethylase domain. Our co-immunoprecipitation experiments revealed TLE co-repressors and HES1 as potential truncated and wild-type KDM6A interactors. With the aid of structural modeling, we explored how truncated KDM6A could interact with TLE and HES1, as well as RUNX and HHEX transcription factors. These structures provide a solid means of studying the functions of KDM6A independently of its demethylase activity. Collectively, our work provides important contributions to the understanding of KDM6A malfunction in bladder cancer.

Objectives: Fetal megacystis is very rare; however this problem may be associated with other structural or chromosomal abnormalities leading to morbidity and mortality. Due to renal injury and pulmonary hypoplasia, prognosis is poor especially in fetuses with early onset oligohydramnios. In this study, we evaluated the management strategies and outcomes of fetal megacystis in our hospital. Study Design: The data of cases who were prenatally diagnosed with megacystis between 1 January 2017 and 31 December 2019 were analyzed. Ultrasonography findings and antennal interventions were withdrawn from computerized database. Information about postpartum status was also received. The data were analyzed in terms of diagnostic methods, fetal interventions (vesicosynthesis (VS), vesicoamniotic shunt (VAS)), potential prognostic markers and short/long-term prognostic results. Results: A total of 15 megacystis patients were detected. One of the fetuses was female and the remaining cases were male. Six of the patients were isolated. Ten patients underwent invasive procedures for prenatal aneuploidy diagnosis and one of them diagnosed with trisomy 18. Totally, 4 patients underwent VS; however no VAS was recorded. Four fetuses were terminated and intrauterine fetal demise occurred in 2 fetuses. Four patients were lost during follow up. Survival rate was 33.3%. Conclusion: Fetal megacystis is an important ultrasonographic finding which may be a component of chromosomal / genetic anomalies. This problem may also be isolated in some cases. Because of the poor outcome, parents should be well informed and all interventions should be offered to families.

The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all differentiated adult cell morphologies without requiring embryonic stem cells is one of the most important discoveries in molecular biology. Among the uses of iPSCs is the generation of neuron cells and organoids to study the biological cues underlying neuronal and brain development, in addition to neurological diseases. These iPSC-derived neuronal differentiation models allow us to examine the gene regulatory factors involved in such processes. Among these regulatory factors are long non-coding RNAs (lncRNAs), genes that are transcribed from the genome and have key biological functions in establishing phenotypes, but are frequently not included in studies focusing on protein coding genes. Here, we provide a comprehensive analysis and overview of the coding and non-coding transcriptome during multiple stages of the iPSC-derived neuronal differentiation process using RNA-seq. We identify previously unannotated lncRNAs via genome-guided de novo transcriptome assembly, and the distinct characteristics of the transcriptome during each stage, including differentially expressed and stage specific genes. We further identify key genes of the human neuronal differentiation network, representing novel candidates likely to have critical roles in neurogenesis using coexpression network analysis. Our findings provide a valuable resource for future studies on neuronal differentiation.

Objective:The magnification of the operative microscope or loop used in microsurgical varicocelectomy facilitates defining the anatomical structures. Even if the microsurgical approach is chosen, still, there is a 1% chance of iatrogenic testicular artery ligation and this may lead to the testicular atrophy. In this study, our aim was to present the efficacy and safety of the micro-Doppler ultrasound (USG) used during microsurgical varicocelectomy for the first time in Turkiye.Materials and Methods:A total of 46 patients with clinical varicocele underwent microsurgical varicocelectomy from May 2018 to July 2019. The da Vinci surgical system (CordaMed, İstanbul) was used in 5 patients and a standard operating microscope was used in 41 patients. Once the spermatic cord was brought up during the surgery, the velocity time integral microvascular Doppler system (Deltamed, Ankara) was used to identify the testicular vessels. The micro-Doppler USG probe allowed differentiation of the vessel by hearing the arterial pulsation audio.Results:Microsurgical varicocelectomy was performed in 46 patients and 48 spermatic cord units. The mean number of spermatic veins that were ligated in each spermatic cord unit was 3.05 (2-5) and each spermatic cord unit had mean 1.4 (1-3) spermatic arteries that were preserved. The mean follow-up duration was 9 months and none of the patients developed testicular atrophy after the procedure.Conclusion:The use of micro-Doppler USG in micro-surgical varicocelectomy seems to be an effective and safe method that facilitates the identification of testicular vessels. With the aid of micro-Doppler USG, even very small size arteries could be easily identified and iatrogenic damage could be avoided.

In parallel with the developments in the world, the rate of change of culture is increasing. In the process of change, some traditions are changing, and some traditions are coming to the stage of extinction. “Peçiç” is one of the games that has not been able to keep up with the changes and updates in question and has entered the process of being forgotten. The stage that the digital game industry has reached and the demand it sees together with peçiç is the reason why many traditional games played together without any adult-child distinction have entered this process. Peçic is a game of chance, competition and strategy, played in two people or two teams, using sea shells on a plus-shaped floor divided into squares. The indispensable game of long winter nights, Ramadan days and bath entertainments, the dispatcher started to disappear after the environments in which it was played have lost its current status. Based on the data obtained from the written sources, this game, which has been played for more than a century, must be recorded without being destroyed. The game, which has been mentioned in historical sources, novels, letters, deserves a detailed examination in this age, where cultural differences are of great importance due to uniformization. In order to revive the game, it is seen that various organizations have been trying to raise awareness by organizing award winning tournament tournaments in recent years. This awareness support aim for a long time in various regions of Turkey regardless of the origin of the game work, which is known for and is played, local singing and differences in gameplay format thus gains local nature and has reached the conclusion that a part of the position of Turkish culture.

Abstract Background The last decade witnessed a number of genome-wide studies on human pre-implantation, which mostly focused on genes and provided only limited information on repeats, excluding the satellites. Considering the fact that repeats constitute a large portion of our genome with reported links to human physiology and disease, a thorough understanding of their spatiotemporal regulation during human embryogenesis will give invaluable clues on chromatin dynamics across time and space. Therefore, we performed a detailed expression analysis of all repetitive DNA elements including the satellites across stages of human pre-implantation and embryonic stem cells. Results We uncovered stage-specific expressions of more than a thousand repeat elements whose expressions fluctuated with a mild global decrease at the blastocyst stage. Most satellites were highly expressed at the 4-cell level and expressions of ACRO1 and D20S16 specifically peaked at this point. Whereas all members of the SVA elements were highly upregulated at 8-cell and morula stages, other transposons and small RNA repeats exhibited a high level of variation among their specific subtypes. Our repeat enrichment analysis in gene promoters coupled with expression correlations highlighted potential links between repeat expressions and nearby genes, emphasising mostly 8-cell and morula specific genes together with SVA_D, LTR5_Hs and LTR70 transposons. The DNA methylation analysis further complemented the understanding on the mechanistic aspects of the repeatome’s regulation per se and revealed critical stages where DNA methylation levels are negatively correlating with repeat expression. Conclusions Taken together, our study shows that specific expression patterns are not exclusive to genes and long non-coding RNAs but the repeatome also exhibits an intriguingly dynamic pattern at the global scale. Repeats identified in this study; particularly satellites, which were historically associated with heterochromatin, and those with potential links to nearby gene expression provide valuable insights into the understanding of key events in genomic regulation and warrant further research in epigenetics, genomics and developmental biology.

The COVID-19 pandemic has persisted for almost three years. However, the mechanisms linked to the SARS-CoV-2 effect on tissues and disease severity have not been fully elucidated. Since the onset of the pandemic, a plethora of high-throughput data related to the host transcriptional response to SARS-CoV-2 infections has been generated. To this end, the aim of this study was to assess the effect of SARS-CoV-2 infections on circulating and organ tissue immune responses. We profited from the publicly accessible gene expression data of the blood and soft tissues by employing an integrated computational methodology, including bioinformatics, machine learning, and natural language processing in the relevant transcriptomics data. COVID-19 pathophysiology and severity have mainly been associated with macrophage-elicited responses and a characteristic “cytokine storm”. Our counterintuitive findings suggested that the COVID-19 pathogenesis could also be mediated through neutrophil abundance and an exacerbated suppression of the immune system, leading eventually to uncontrolled viral dissemination and host cytotoxicity. The findings of this study elucidated new physiological functions of neutrophils, as well as tentative pathways to be explored in asymptomatic-, ethnicity- and locality-, or staging-associated studies.

Eradication of cancer cells through exposure to high doses of ionizing radiation (IR) is a widely used therapeutic strategy in the clinical setting. However, in many cases, cancer cells can develop remarkable resistance to radiation. Radioresistance represents a prominent obstacle in the effective treatment of cancer. Therefore, elucidation of the molecular mechanisms and pathways related to radioresistance in cancer cells is of paramount importance. In the present study, an integrative bioinformatics approach was applied to three publicly available RNA sequencing and microarray transcriptome datasets of human cancer cells of different tissue origins treated with ionizing radiation. These data were investigated in order to identify genes with a significantly altered expression between radioresistant and corresponding radiosensitive cancer cells. Through rigorous statistical and biological analyses, 36 genes were identified as potential biomarkers of radioresistance. These genes, which are primarily implicated in DNA damage repair, oxidative stress, cell pro-survival, and apoptotic pathways, could serve as potential diagnostic/prognostic markers cancer cell resistance to radiation treatment, as well as for therapy outcome and cancer patient survival. In addition, our findings could be potentially utilized in the laboratory and clinical setting for enhancing cancer cell susceptibility to radiation therapy protocols.

SARS-CoV-2 is a betacoronavirus responsible for COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load without selective pressure and across the genome, compared to nsp7, nsp8 and nsp12, which form the core polymerase complex. We propose nsp14 as a priority research target for understanding genomic variance rate in SARS-CoV-2 isolates and nsp14 mutations as potential predictors for high mutability strains.

Numerous ground-based observatories are using small sized ground telescopes for scientific research purposes. The telescopes that are available on the market have three main problems. These issues can be listed as: positioning repeatability, tuning requirement according to different wind speeds for different seasons, and the mass changing via different scientific equipments added to the telescope. This study is aimed at resolving these issues for ground based small alt-azimuth telescopes. Establishing of a set and forget system is performed by designing an adaptive controller. Motor dynamics are taken into consideration for a realistic mathematical model. The Wind-Gust model that consists of a sum of sinusoidal disturbances with unknown phase, amplitude and frequency is used for the wind model. The purposed controller cancels the disturbance effects on the plant while operational positioning and also the makes the plant insensitive to mass changes. The Lyapunov approach is utilised when proving the asymptotic stability. The proposed controller’s success is illustrated with thorough numerical evaluation.

Since its emergence in Wuhan, China in late 2019, the origin and evolution of SARS-CoV-2 have been among the most debated issues related to COVID-19. Throughout its spread around the world, the viral genome continued acquiring new mutations and some of them became widespread. Among them, 14408 C>T and 23403 A>G mutations in RdRp and S, respectively, became dominant in Europe and the US, which led to debates regarding their effects on the mutability and transmissibility of the virus. In this study, we aimed to investigate possible differences between time-dependent variation of mutation densities (MDe) of viral strains that carry these two mutations and those that do not. Our analyses at the genome and gene level led to two important findings: First, time-dependent changes in the average MDe of circulating SARS-CoV-2 genomes showed different characteristics before and after the beginning of April, when daily new case numbers started levelling off. Second, this pattern was much delayed or even non-existent for the “mutant” (MT) strain that harbored both 14408 C>T and 23403 A>G mutations. Although these differences were not limited to a few hotspots, it is intriguing that the MDe increase is most evident in two critical genes, S and Orf1ab, which are also the genes that harbor the defining mutations of the MT genotype. The nature of these unexpected relationships warrants further research.

COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of the viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the dominance of its co-mutations in Europe and elsewhere.

Amaç: Bu çalışmada Streptokok enfeksiyonları ile ilişkili pediyatrik otoimmün nöropsikiyatrik bozukluklar (PANDAS) ve İnsan Lökosit Antijen (HLA) allelleri arasındaki ilişkinin incelenmesi amaçlanmıştır.Gereç ve Yöntem: Ani başlangıçlı obsesif kompulsif bozukluğu (OKB) olan 41 çocuk hastanın ve 88 sağlıklı çocuğun HLA alelleri PCR kullanılarak analiz edildi. Sonuçlar univariate ve multivariate lojistik regresyon analizi kullanılarak değerlendirildi.Bulgular: A1, B18 ve B35 allellerinin hastalık riskini azaltırken, DRB8, DRB5.2 ve DQ5 allellerinin hastalık riskini artırdığı saptanmıştır.Sonuç: Bu çalışmanın bulguları, araştırmacıların PANDAS'taki ilgili genleri ve gen ürünlerinin hastalığın gelişimine olan etkilerini incelemelerine yardımcı olacaktır. HLA sınıf II lokusları tarafından T-yardımcı hücrelere ekzojenik antijenlerin tanıtımı farklı otoimmün hastalıklarda belirlenmiştir. Bu bulguların PANDAS etiyolojisi ile benzerliği ve bu çalışmada bulunan hastalık riskini artıran allellerin, HLA sınıf II’de bulunması dikkat çekicidir.

Retroperitoneal and horseshoe abscesses are particularly important because of the anatomic characteristics and the clinical differences between treatment approaches. There are several challenges in treating perirectal and retroperitoneal abscess, the most important of which are partial recovery, high recurrence rates, and continence problems. A 65-yearold male patient underwent laparotomy at an external center with a diagnosis of ileus. Although no intraoperative pathology was detected, ileus persisted postoperatively, and the patient was referred to our clinic where he was diagnosed with a complicated horseshoe abscess, 9 cm in diameter and displaying retroperitoneal extension. Perirectal abscess drainage was performed, and the patient was discharged on the 5th day after the treatment. To the best of our knowledge, there have not been any previously reported cases of ileus caused by retroperitoneal abscess as a complication of horseshoe abscess. The case presented in this paper represents a rare complication, thereby contributing to the literature which remains to be explored.

This paper demonstrates a manipulation of snowman-shaped soft microrobots under a uniform rotating magnetic field. Each microsnowman robot consists of two biocompatible alginate microspheres with embedded magnetic nanoparticles. The soft microsnowmen were fabricated using a microfluidic device by following a centrifuge-based microfluidic droplet method. Under a uniform rotating magnetic field, the microsnowmen were rolled on the substrate surface, and the velocity response for increasing magnetic field frequencies was analyzed. Then, a microsnowman was rolled to follow different paths, which demonstrated directional controllability of the microrobot. Moreover, swarms of microsnowmen and single alginate microrobots were manipulated under the rotating magnetic field, and their velocity responses were analyzed for comparison.

Bu çalışmada, aktif süspansiyon sistemleri için yoldan gelen bozucu etkinin bilinmediği kabulü yapılarak, uyarlamalı kontrolcü tasarlanmıştır. Yol düzgünsüzlüğünden kaynaklanan bozucu, frekans, genlik ve faz değerleri bilinmeyen farklı sinüzoidal dalgaların toplamı olarak modellenmiş ve gözlemci tasarımı yapılmıştır. Böylece bozucu parametrize edilmiş ve geri adımlama yöntemi kullanılarak uyarlamalı kontrolcü tasarımı yapılmıştır. Kapalı çevrim sistemin kararlılığı kanıtlanmış ve yol bozucusu etkisi altında taşıt gövde ivmesinin bastırıldığı gösterilmiştir. Kontrolcünün performansı benzetim ile test edilmiştir.

Bu çalışmada, aktif süspansiyon sistemleri için yoldan gelen bozucu etkinin bilinmediği kabulü yapılarak, uyarlamalı kontrolcü tasarlanmıştır. Yol düzgünsüzlüğünden kaynaklanan bozucu, frekans, genlik ve faz değerleri bilinmeyen farklı sinüzoidal dalgaların toplamı olarak modellenmiş ve gözlemci tasarımı yapılmıştır. Böylece bozucu parametrize edilmiş ve geri adımlama yöntemi kullanılarak uyarlamalı kontrolcü tasarımı yapılmıştır. Kapalı çevrim sistemin kararlılığı kanıtlanmış ve yol bozucusu etkisi altında taşıt gövde ivmesinin bastırıldığı gösterilmiştir. Kontrolcünün performansı benzetim ile test edilmiştir.

Objective: This study aimed to present middle-term functional and radiological outcomes of the transfer of the lesser tuberosity in the management of reverse Hill-Sachs lesions following posterior dislocations of the shoulder. Patients and methods: With a diagnosis of neglected posterior shoulder dislocation (8 locked, 5 recurrent), 13 male patients (age range: 28–72; mean age: 39.3 years) who underwent the transfer of the lesser tuberosity due to reverse Hill-Sachs lesions, were retrospectively reviewed based on functional and radiological data. The etiologies were: epilepsy in 9 patients, a traffic accident in 2 patients, and fall in 2 patients. To assess the patients' functional level, American Shoulder and Elbow Surgeons (ASES) and Constant Scores were used, and the patients' range of motion at the last follow-up was measured. To evaluate the development of arthrosis, the final follow-up control plain radiographs were examined. The average size of the defects calculated from the axial computed tomography sets was 27% (range: 20%–40%). Results: The average length of follow-up was 30 months (range: 12–67 months). At the last follow-up visit, the main ASES and Constant Scores were 78 and 85, respectively, and the average degrees of flexion, abduction, and external rotation were 163°, 151°, and 70° respectively. The concentric reduction was observed postoperatively. Conclusion: McLaughlin procedure appears to be a safe and effective method in the treatment of neglected posterior shoulder dislocations with reverse Hill-Sachs lesion. Level of Evidence: Level IV, Therapeutic study. Keywords: Posterior shoulder dislocation, Reverse Hill-Sachs lesion, McLaughlin procedure, Transfer of the lesser tuberosity