TTK

This system paper documents the technical foundations for the extension of the Topology ToolKit (TTK) to distributed-memory parallelism with the Message Passing Interface (MPI). While several recent papers introduced topology-based approaches for distributed-memory environments, these were reporting experiments obtained with tailored, mono-algorithm implementations. In contrast, we describe in this paper a versatile approach (supporting both triangulated domains and regular grids) for the support of topological analysis pipelines, i...

Metastatic colorectal cancer (CRC) is still in need of effective treatments. This study applies a holistic approach to propose new targets for treatment of primary and liver metastatic CRC and investigates their therapeutic potential in-vitro. An integrative analysis of primary and metastatic CRC samples was implemented for alternative target and treatment proposals. Integrated microarray samples were grouped based on a co-expression network analysis. Significant gene modules correlated with primary CRC and metastatic phenotypes were identified...

BACKGROUND: Given the intricate molecular complexities and heterogeneity inherent in T-cell immunotherapy of gastric cancer (GC), elucidative T-cell-related biomarkers were imperative needed for facilitating the prediction of GC patient prognosis and identify potential synergistic therapeutic targets. METHODS: We conducted COX regression analysis in TISIDB, TCGA-STAD, and GEO databases to identify 19 GC T-cell-mediated sensitivity tumor killing (TTK) genes (key GCTTKs)...

BACKGROUND: Lung cancer is a frequent malignancy with a poor prognosis. Extensive metabolic alterations are involved in carcinogenesis and could, therefore, serve as a reliable prognostic phenotype. AIMS: Our study aimed to develop a prognosis signature and explore the relationship between metabolic characteristic-related signature and immune infiltration in lung adenocarcinoma (LUAD). OBJECTIVE: TCGA-LUAD and GSE31210 datasets were used as a training set and a validation set, respectively...

Triclosan (TCS) is a wide-spectrum antibacterial agent that is found in various water environments. It has been reported to have estrogenic effects. However, the impact of TCS exposure on the reproductive system of zebrafish (Danio rerio) throughout their life cycle is not well understood. In this study, zebrafish fertilized eggs were exposed to 0, 10, and 50 μg/L TCS for 120 days. The study investigated the effects of TCS exposure on brain and testis coefficients, the expression of genes related to the hypothalamus-pituitary-gonadal (HPG) axis, hormone levels, vitellogenin (VTG) content, histopathological sections, and performed RNA sequencing of male zebrafish...

Primary hepatocellular carcinoma (HCC) affects people all over the world. Circular RNAs are involved in the growth and development of several malignancies and regulate a number of biological processes. However, the roles of has-circ-0009158 in HCC remain unknown. This study explored the expression and associated miRNA-mRNA network of has-circ-0009158 in HCC. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-circ-0009158 in the HCC tissues of 143 patients and four human HCC cell lines...

BACKGROUND: Despite the potential of immune checkpoint blockade (ICB) as a promising treatment for Pancreatic adenocarcinoma (PAAD), there is still a need to identify specific subgroups of PAAD patients who may benefit more from ICB. T cell-mediated tumor killing (TTK) is the primary concept behind ICB. We explored subtypes according to genes correlated with the sensitivity to TKK and unraveled their underlying associations for PAAD immunotherapies. METHODS: Genes that control the responsiveness of T cell-induced tumor destruction (GSTTK) were examined in PAAD, focusing on their varying expression levels and association with survival results...

BACKGROUND: Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor. METHODS: We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing...

Currently, cancer stem cells (CSCs) are regarded as the most promising target for cancer therapy due to their close association with tumor resistance, invasion, and recurrence. Thus, identifying CSCs-related genes and constructing a prognostic risk model associated with CSCs may be crucial for hepatocellular carcinoma (HCC) therapy. Xena Browser was used to download gene expression profiles and clinical data, while MSigDB was used to obtain genes associated with CSCs. Firstly, the non-negative matrix factorization (NMF) algorithm was used to cluster the HCC samples based on CSCs-related genes...

Background: Accumulating evidence indicates that non-coding RNAs (ncRNA), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), can function as competitive endogenous RNAs (ceRNAs) by binding to microRNAs (miRNAs) and regulating host gene expression at the transcriptional or post-transcriptional level. Dysregulation in ceRNA network regulation has been implicated in the occurrence and development of cancer. However, the lncRNA/circRNA-miRNA-mRNA regulatory network is still lacking in nasopharyngeal carcinoma (NPC)...

Pancreatic adenocarcinoma is one of the most aggressive and lethal forms of cancer. Chemotherapy is the primary treatment for pancreatic cancer, but resistance to the drugs used remains a major challenge. A genome-wide CRISPR interference and knockout screen in the PANC-1 cell line with the drug nab-paclitaxel has identified a group of spindle assembly checkpoint (SAC) genes that enhance survival in nab-paclitaxel. Knockdown of these SAC genes (BUB1B, BUB3, and TTK) attenuates paclitaxel-induced cell death...

Mechanical prosthetic valve dysfunction can be structural or non-structural. Structural valve dysfunction includes disc dislodgement, disc fracture, and strut fracture. These events in an implanted valve are rare but could pose a risk to life. TTK Chitra heart valve prosthesis (CHVP), an Indian-made single tilting disc valve, has been implanted since 1990 as reported by Vayalappil and Bhuvaneswar (2005). There is limited literature on the structural valve dysfunction of CHVP. We hereby submit images of the dysfunctional valve from our patient, a case of acute severe mitral paravalvular regurgitation 16 years after implantation of CHVP...

BACKGROUND: Rheumatic fever and rheumatic heart disease is endemic in India. Mitral valve replacement with mechanical valve is the commonest surgical procedure performed in rheumatic heart disease (RHD). However, there are no studies reporting the long-term outcomes of mechanical mitral valve replacement in rheumatic heart disease from India. OBJECTIVE: The primary objective of the study was to look at the long-term survival following mechanical mitral valve replacement in RHD...

As the largest peripheral lymphoid organ in poultry, the spleen plays an essential role in regulating the body's immune capacity. However, compared with chickens and ducks, information about the age- and breed-related changes in the goose spleen remains scarce. In this study, we systematically analyzed and compared the age-dependent changes in the morphological, histological, and transcriptomic characteristics between Landes goose (LG; Anser anser ) and Sichuan White goose (SWG; Anser cygnoides ). The results showed a gradual increase in the splenic weights for both LG and SWG until week 10, while their splenic organ indexes reached the peak at week 6...

BACKGROUND: Adipose-derived stem cells (ADSCs) are closely associated with the survival rate of transplanted fat in breast reconstruction after breast cancer surgery. Nevertheless, the intrinsic mechanisms regulating ADSCs adipogenic differentiation remain ambiguous. The aim of our study was to explore the relevant genes and pathways to elucidate the potential mechanisms of adipogenic differentiation in ADSCs. METHODS: The Gene Expression Omnibus (GEO) dataset GSE61302 was downloaded and analyzed to identify differentially expressed genes (DEGs)...

Breast cancer arises from a series of molecular alterations that disrupt cell cycle checkpoints, leading to aberrant cell proliferation and genomic instability. Targeted pharmacological inhibition of cell cycle regulators has long been considered a promising anti-cancer strategy. Initial attempts to drug critical cell cycle drivers were hampered by poor selectivity, modest efficacy and haematological toxicity. Advances in our understanding of the molecular basis of cell cycle disruption and the mechanisms of resistance to CDK4/6 inhibitors have reignited interest in blocking specific components of the cell cycle machinery, such as CDK2, CDK4, CDK7, PLK4, WEE1, PKMYT1, AURKA and TTK...

BACKGROUND: Threonine and tyrosine kinase (TTK) is associated with invasion and metastasis in various tumors. However, the prognostic importance of TTK and its correlation with immune infiltration in endometrial cancer (EC) remain unclear. METHODS: The expression profile of TTK was analyzed using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteome Cancer Analysis Consortium (CPTAC). TTK protein and mRNA levels were verified in EC cell lines. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TTK to distinguish between normal and EC tissues...

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment...

Threonine tyrosine kinase (TTK) is a critical component of the spindle assembly checkpoint and plays a pivotal role in mitosis. TTK has been identified as a potential therapeutic target for human cancers. Here, we describe our design, synthesis and evaluation of a class of covalent TTK inhibitors, exemplified by 16 (SYL1073). Compound 16 potently inhibits TTK kinase with an IC50 of 0.016 μM and displays improved selectivity in a panel of kinases. Mass spectrometry analysis reveals that 16 covalently binds to the C604 cysteine residue in the hinge region of the TTK kinase domain...

Despite progress in the application of checkpoint immunotherapy against various tumors, attempts to utilize immune checkpoint blockade (ICB) agents in triple negative breast cancer (TNBC) have yielded limited clinical benefits. The low overall response rate of checkpoint immunotherapy in TNBC may be attributed to the immunosuppressive tumor microenvironment (TME). In this study, we investigated the role of mitogen-associated kinase TTK in reprogramming immune microenvironment in TNBC. Notably, TTK inhibition by BAY-1217389 induced DNA damage and the formation of micronuclei containing dsDNA in the cytosol, resulting in elicition of STING signal pathway and promoted antitumor immunity via the infiltration and activation of CD8+ T cells...