10 research outputs found
An automated nD model creation on BIM models
The construction technology (CONTEC) method
was originally developed for automated CONTEC planning
and project management based on the data in the form of
a budget or bill of quantities. This article outlines a new
approach in an automated creation of the discrete nD building information modeling (BIM) models by using data from
the BIM model and their processing by existing CONTEC
method through the CONTEC software. This article outlines
the discrete modeling approach on BIM models as one of the
applicable approaches for nD modeling. It also defines the
methodology of interlinking BIM model data and CONTEC
software through the classification of items. The interlink
enables automation in the production of discrete nD BIM
model data, such as schedule (4D) including work distribution end resource planning, budget (5D)âbased on integrated pricing system, but also nD data such as health and
safety risks (6D) plans (H&S Risk register), quality plans,
and quality assurance checklists (7D) including their monitoring and environmental plans (8D). The methodology of
the direct application of the selected classification system,
as well as means of data transfer and conditions of data
transferability, is described. The method was tested on the
case study of an office building project, and acquired data
were compared to actual construction time and costs. The
case study proves the application of the CONTEC method
as a usable method in the BIM model environment, enabling the creation of not only 4D, 5D models but also nD
discrete models up to 8D models in the perception of the
construction management process. In comparison with
the existing BIM classification systems, further development of the method will enable full automated discrete nD
model creation in the BIM model environment
Short article : Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy
Background NLRC5 is an interferon Îł-inducible protein, which plays a role in immune surveillance with a potential influence on cancer survival. Objective We aimed to evaluate the effect of potential regulatory variants in NLRC5 on overall survival and survival after 5-fluorouracil (5-FU)-based therapy of colorectal cancer (CRC) patients. Patients and methods We carried out a case-only study in a Czech population of 589 cases; 232 received 5-FU-based therapy. Eleven variants within NLRC5 were selected using in-silico tools. Associations between polymorphisms and survival were assessed by Cox regression analysis adjusting for age at diagnosis, sex, and TNM stage. Survival curves were derived using the Kaplan-Meier method. Results Two variants showed a significant association with survival. All patients and metastasis-free patients at the time of diagnosis (pM0) who were homozygous carriers of the minor allele of rs27194 had a decreased overall survival (OS all and OS pM0) and event-free survival (EFS pM0) under a recessive model (OS all P=0.003, OS pM0 P=0.005, EFS pM0 P=0.01, respectively). OS was also decreased for all patients and for pM0 patients who carried at least one minor allele of rs289747 (OS all P=0.03 and OS pM0 P=0.003, respectively). Among CRC patients, who underwent a 5-FU-based adjuvant regimen, rs12445252 was associated with OS all, OS pM0 and EFS pM0, according to the dosage of the minor allele T (OS all P=0.0004, OS pM0 P=0.0001, EFS pM0 P=0.008, respectively). Conclusion Our results showed that polymorphisms in NLRC5 may be used as prognostic markers of survival of CRC patients, as well as for survival in response to 5-FU treatment
Epistatic effect of TLR3 and cGASâSTINGâIKKΔâTBK1âIFN signaling variants on colorectal cancer risk
Abstract Objective The TLR3/cGASâSTINGâIFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Methods The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools. Results Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11â2.53, Pâvalue = .01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07â3.84, Pâvalue = .03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03â2.27, Pâvalue = .03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5â6 risk alleles compared to those with 0â2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pairâwise interactions within and between the CGAS, TMEM173, IKBKE, and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis. Conclusions Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management
Epistatic effect of TLR3 and cGAS-STING-IKKΔ-TBK1-IFN signaling variants on colorectal cancer risk
Objective: The TLR3/cGAS-STING-IFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Methods: The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools. Results: Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11-2.53, P-value =.01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07-3.84, P-value =.03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03-2.27, P-value =.03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5-6 risk alleles compared to those with 0-2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pair-wise interactions within and between the CGAS, TMEM173, IKBKE, and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis. Conclusions: Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management
A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study
Background & aims: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for non-invasive CRC diagnosis. Methods: A total of 1,273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRC, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumor/adenoma paired with adjacent mucosa, 210 plasma extracellular vesicles samples, and 185 fecal immunochemical tests (FIT) leftover samples. Results: Twenty-five miRNAs showed altered levels in stool of CRC patients in both cohorts (adj. P<.05). A five-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from controls (AUC=0.86, 95% CI=0.79-0.94) and was validated in an independent cohort (AUC=0.96, 95% CI=0.92-1.00). The signature classified controls from low-/high-stage tumors, and advanced adenomas (AUC=0.82, 95% CI=0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, while fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in FIT leftover samples showed good correlation with those of stool collected in preservative buffer and their alterations can be detected in adenoma or CRC patients. Conclusions: Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving a non-invasive diagnosis and screening strategies
Investigation of single and synergic effects of <i>NLRC5</i> and <i>PD-L1</i> variants on the risk of colorectal cancer
<div><p>Constitutive activation of interferon signaling pathways has been reported in colorectal cancer (CRC), leading to a strong CD8<sup>+</sup> T cell response through stimulation of <i>NLRC5</i> expression. Primed CD8<sup>+</sup> T cell expansion, however, may be negatively regulated by <i>PD-L1</i> expression. Additionally, aberrant <i>PD-L1</i> expression enables cancer cells to escape the immune attack. Our study aimed to select potential regulatory variants in the <i>NLRC5</i> and <i>PD-L1</i> genes by using several online <i>in silico</i> tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, microRNA and transcription factor binding site prediction tools and to investigate their influence on CRC risk in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Logistic regression analysis adjusted for age and gender reported a moderate association between rectal cancer risk and two <i>NLRC5</i> SNPs, rs1684575 T>G (OR: 1.60, 95% CI: 1.13â2.27, recessive model) and rs3751710 (OR: 0.70, 95% CI: 0.51â0.96, dominant model). Given that a combination of genetic variants, rather than a single polymorphism, may explain better the genetic etiology of CRC, we studied the interplay between the variants within <i>NLRC5</i>, <i>PD-L1</i> and the previously genotyped <i>IFNGR1</i> and <i>IFNGR2</i> variants, to evaluate their involvement in the risk of CRC development. Overall we obtained 18 pair-wise interactions within and between the <i>NLRC5</i> ad <i>PD-L1</i> genes and 6 more when <i>IFNGR</i> variants were added. Thirteen out of the 24 interactions were below the threshold for the FDR calculated and controlled at an arbitrary level q*<0.10. Furthermore, the interaction <i>IFNGR2</i> rs1059293 C>Tâ<i>NLRC5</i> rs289747 G>A (P<0.0001) remained statistically significant even after Bonferroni correction. Our data suggest that not only a single genetic variant but also an interaction between two or more variants within genes involved in immune regulation may play important roles in the onset of CRC, providing therefore novel biological information, which could eventually improve CRC risk management but also PD-1-based immunotherapy in CRC.</p></div
<i>NLRC5-PD-L1</i> pair-wise interactions with cases and controls.
<p>Only the best genetic model of each SNP pair is shown.</p
Characteristics of the colorectal cancer patients.
<p>Characteristics of the colorectal cancer patients.</p
<i>NLRC5-PD-L1-IFNGR1/2</i> pair-wise interactions.
<p> The color indicates the SNPsâ location displayed by UCSC Genome Browser on lymphoblastoid cell lines (GM12878).</p