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61.
Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidence
Tjaša Oblak, Petra Škerl, Benjamin J. Narang, Rok Blagus, Mateja Krajc, Srdjan Novaković, Janez Žgajnar, 2023, original scientific article

Abstract: Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. Results: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. Conclusion: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.
Keywords: early breast cancer, polygenic risk score, risk prediction
Published in DiRROS: 21.03.2024; Views: 57; Downloads: 21
.pdf Full text (1,54 MB)

62.
Numerical modelling of macrosegregation in three-dimensional continuous casting of steel billets
Katarina Mramor, Robert Vertnik, Božidar Šarler, 2023, published scientific conference contribution

Abstract: Macrosegregation presents a considerable defect in the continuous casting of billets and can critically affect the final properties of the product. The numerical modelling can help to predict and better understand the segregation and flow patterns inside the mould. The process is modelled with a physical model described by a set of conservation equations describing the t heat transfer, turbulence, fluid flow, solidification and segregation. A two-equation low-Re k-epsilon model and Abe-Kondoh-Nagano closures are used to close governing equations in this incompressible fluid flow example. The Boussinesq approximation is applied to account for the thermo-solutal buoyancy effects, and the Darcy approximation is applied for the description of the flow through the porous mushy zone. On a microscale, a lever rule solidification model is used to couple liquid fraction, temperature and concentration. The three-dimensional model is solved with the method based on local collocation with multiquadric radial basis functions on seven-nodded subdomains. The aim of this contribution is to explore the three-dimensional macrosegregation patterns of 0.51 wt% carbon steel in the solidified shell of the steel in the mould.
Keywords: modeling, continuous casting of steel, CFD, turbulence modeling, LES, meshless methods, RANS
Published in DiRROS: 21.03.2024; Views: 57; Downloads: 41
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63.
The prognostic and predictive value of human gastrointestinal microbiome and exosomal mRNA expression of PD-L1 and IFNγ for immune checkpoint inhibitors response in metastatic melanoma patients : protocol trial
Ana Erman, Marija Ignjatović, Katja Leskovšek, Simona Miceska, Urša Lampreht Tratar, Maša Omerzel, Veronika Kloboves-Prevodnik, Maja Čemažar, Lidija Kandolf Sekulović, Gorazd Avguštin, Janja Ocvirk, Tanja Mesti, 2023, original scientific article

Abstract: Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study. Stool samples are submitted before the start of treatment, at the 12th (+/−2) week and 28th (+/−2) week, and at the occurrence of event (suspected disease progression/hyperprogression, immune-related adverse event (irAE), deterioration). Peripheral venous blood samples are taken additionally at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether the human gastrointestinal microbiome (bacterial and viral) and the exosomal mRNA expression of PD-L1 and IFNγ and its dynamics predicts the response to treatment with PD-1 and CTLA-4 inhibitors and its association with the occurrence of irAE. The response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclusions: This is the first study to combine and investigate multiple potential predictive and prognostic biomarkers and their dynamics in first line ICI in metastatic melanoma patients.
Keywords: gastrointestinal microbiome, mRNA expression of PD-L1 and IFNγ, immune checkpoint inhibitors, metastatic melanoma
Published in DiRROS: 21.03.2024; Views: 56; Downloads: 26
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64.
Meshless simulation of a macrosegregation benchmark considering the solid motion
Viktor Govže, Igor Vušanović, Božidar Šarler, 2023, published scientific conference contribution

Abstract: We have extended the existing two-dimensional rigid solid phase benchmark for binary substance with the solid phase motion in the present paper. Incompressible laminar Newtonian flow is assumed, and a standard mixture formulation is used for the mass, momentum, energy, and solute transport. A coherency solid motion model accounts for the free-floating grains, assuming that the solid velocity is proportional to the mixture velocity and the liquid fraction. The lever rule is used to describe the mass fractions of the phases. A two-dimensional benchmark is solved using the semi-implicit meshless diffuse approximate method with an adaptive subdomain upwinding strategy. The results of the meshless method are compared to the finite volume method results with a reasonable agreement. The new benchmark results show that the solid motion has an essential effect on the macrosegregation pattern.
Keywords: solidification, meshless methods, grain motion, benchmarks
Published in DiRROS: 21.03.2024; Views: 65; Downloads: 37
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Cetuximab in preoperative treatment of rectal cancer - term outcome of the XERT trial
Vaneja Velenik, Janja Ocvirk, Irena Oblak, Franc Anderluh, 2012, original scientific article

Abstract: Preoperative capecitabine-based chemoradiotherapy (CRT) is feasible for the treatment of resectable locally advanced rectal cancer (LARC). To try to improve efficacy, we conducted a phase II studz in which the epidermal growth factor receptor-targeting monoclonal antibody cetuximab was added to capecitabine-based CRT. The results for long-term survival and for an analysis investigating the relationship between survival and patient and disease characteristics, including tumour KRAS mutation status, and surgery type, are presented. Patients with resectable LARC received capecitabine (1250mg/m2 twice daily, orally) for 2 weeks followed by cetuximab alone (400 mg/m2 for 1 week) and then with CRT (250 mg/m2/week) comprising capecitabine (825 mg/m2 twice daily) and radiotherapy to the small pelvis (45 Gz in 25 1.8-Gz fractions), five dazs a week for five weeks. Surgery was conducted six weeks following CRT, with post-operative chemotherapy with capecitabine (1250 mg/m2 twice daily for 14 days every 21 days) three weeks later. Forty-seven patients were enrolled and 37 underwent treatment. Twenty-eight of the patients (75.7%) had T3N+ disease. Thirty-six patients were evaluable for efficacy. The median follow-up time was 39.0 months (range 5.0-87.0). The three-year local control, disease-free survival, relapse-free survival and overall survival rates were 96.9% (95% CI 90.0-100), 72.2% (57.5-86.9), 74.3% (95% CI 59.8-88.8) and 68.1% (95% CI 36.7-99.4), respectively. There was no significant association between survival and gender, age, tumour location in the rectum, type of surgery, pathological T or N status, tumour regression grade or tumour KRAS mutation status, although sample sizes were small. Preoperative cetuximab plus capecitabine-based CRT was feasible in patients with resectable LARC and was associated with an impressive three-year local control rate. The use of tumour KRAS mutation status as a biomarker for the efficacy of cetuximab-based regimens in this setting requires further investigation.
Published in DiRROS: 21.03.2024; Views: 53; Downloads: 24
.pdf Full text (332,74 KB)

68.
Inguinal or inguino-iliac/obturator lymph node dissection after positive inguinal sentinel lymph node in patients with cutaneous melanoma
Nebojša Glumac, Marko Hočevar, Vesna Zadnik, Marko Snoj, 2012, original scientific article

Abstract: The aim of the study was to determine whether the presence of inguinal sentinel lymph node (SLN) metastases smaller than 2 mm (micrometastases) subdivided according to the number of micrometastases predicts additional, non-sentinel inguinal, iliac or obturator lymph node involvement in completion lymph node dissection (CLND). Positive inguinal SLN was detected in 58 patients (32 female, 26 male, median age 55 years) from 743 consecutive and prospectively enrolled patients with primary cutaneous melanoma stage I and II who were treated with SLN biopsy between 2001 and 2007. Micrometastases in inguinal SLN were detected in 32 patients, 14 were single, 2 were double, and 16 were multiple. Twenty-six patients had macrometastases. No patient with any micrometastases or a single SLN macrometastasis in the inguinal region had any iliac/obturator non-sentinel metastases after CLND in our series. Furthermore, no patient with single SLN micrometastasis in the inguinal region had any non-sentinel metastases at all after CLND in our series. In these cases respective CLND might be omitted.
Published in DiRROS: 21.03.2024; Views: 48; Downloads: 20
.pdf Full text (307,79 KB)

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Application of a meshless space-time adaptive approach to phase-field modelling of polycrystalline solidification
Tadej Dobravec, Boštjan Mavrič, Božidar Šarler, 2023, published scientific conference contribution

Abstract: We have developed a 2-D numerical meshless adaptive approach for phase-field modelling of dendritic solidification. The quadtree-based approach decomposes the computational domain into quadtree sub-domains of different sizes. The algorithm generates uniformly-distributed computational nodes in each quadtree sub-domain. We apply the meshless radial basis function generated finite difference method and the forward Euler scheme to discretise governing equations in each computational node. The fixed ratio between the characteristic size and the node spacing of a quadtree sub-domain ensures space adaptivity. The adaptive time-stepping accelerates the calculations further. In the framework of previous research studies, we used the approach to solve quantitative phase-field models for single dendrite growth in pure melts and dilute binary alloys. In the present study, we upgrade the solution procedure for the modelling growth of multiple differently oriented dendrites. Along with the space-time adaptive approach, we apply non-linear preconditioning of the phase-field equation to increase computational efficiency. We investigate a novel numerical approach's accuracy and computational efficiency by simulating the equiaxed dendrite growth from a dilute binary alloy.
Keywords: dendritic growth, phase-field method, meshless methods, polycrystalline solidification
Published in DiRROS: 21.03.2024; Views: 59; Downloads: 40
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