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1.
Diagnostic performance of p16/Ki-67 dual immunostaining at different number of positive cells in cervical smears in women referred for colposcopy
Uršula Salobir Gajšek, Andraž Dovnik, Iztok Takač, Urška Ivanuš, Tine Jerman, Simona Šramek Zatler, Alenka Repše-Fokter, 2021, original scientific article

Abstract: . The aim of the study was to evaluate the diagnostic accuracy of p16/Ki-67 dual immunostaining (p16/ Ki-67 DS) in cervical cytology and the number of positive p16/Ki-67 cells to diagnose high grade cervical intraepithelial neoplasia (CIN2+) in colposcopy population. Subjects and methods. We performed an analysis on a subset cohort of 174 women enrolled within a large-scale randomised controlled human papillomavirus (HPV) self-sampling project organised as part of the population-based Cervical Cancer Screening Programme ZORA in Slovenia. This subset cohort of patients was invited to the colposcopy clinic, underwent p16/Ki-67 DS cervical cytology and had the number of p16/Ki-67 positive cells determined. Results. Among analysed women, 42/174 (24.1%) had histologically confirmed CIN2+. The risk for CIN2+ was increasing with the number of positive cells (p < 0.001). The sensitivity of p16/Ki-67 DS for detection of CIN2+ was 88.1%, specificity was 65.2%, positive predictive value was 44.6% and negative predictive value was 94.5%. Conclusions. Dual p16/Ki-67 immunostaining for the detection of CIN2+ has shown high sensitivity and high negative predictive value in our study, which is comparable to available published data. The number of p16/Ki-67 positive cells was significantly associated with the probability of CIN2+ detection. We observed a statistically significant and clinically relevant increase in specificity if the cut-off for a positive test was shifted from one cell to three cells.
Keywords: cervical cytology, high-grade dysplasia, p16/Ki-67 immunostaining
Published in DiRROS: 22.07.2024; Views: 20; Downloads: 4
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2.
MitomiRs: their roles in mitochondria and importance in cancer cell metabolism
Andrej Renčelj, Nada Gvozdenović, Maja Čemažar, 2021, review article

Abstract: Background. MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in almost all biological path- ways. They regulate post-transcriptional gene expression by binding to the 3%untranslated region (3%UTR) of messenger RNAs (mRNAs). MitomiRs are miRNAs of nuclear or mitochondrial origin that are localized in mitochondria and have a crucial role in regulation of mitochondrial function and metabolism. In eukaryotes, mitochondria are the major sites of oxidative metabolism of sugars, lipids, amino acids, and other bio-macromolecules. They are also the main sites of adenosine triphosphate (ATP) production. Conclusions. In the review, we discuss the role of mitomiRs in mitochondria and introduce currently well studied mito- miRs, their target genes and functions. We also discuss their role in cancer initiation and progression through the regu- lation of mRNA expression in mitochondria. MitomiRs directly target key molecules such as transporters or enzymes in cell metabolism and regulate several oncogenic signaling pathways. They also play an important role in the Warburg effect, which is vital for cancer cells to maintain their proliferative potential. In addition, we discuss how they indirectly upregulate hexokinase 2 (HK2), an enzyme involved in glucose phosphorylation, and thus may affect energy metabo- lism in breast cancer cells. In tumor tissues such as breast cancer and head and neck tumors, the expression of one of the mitomiRs (miR-210) correlates with hypoxia gene signatures, suggesting a direct link between mitomiR expression and hypoxia in cancer. The miR-17/92 cluster has been shown to act as a key factor in metabolic reprogramming of tumors by regulating glycolytic and mitochondrial metabolism. This cluster is deregulated in B-cell lymphomas, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, and T-cell lymphomas, and is particularly overexpressed in several other cancers. Based on the current knowledge, we can conclude that there is a large number of miRNAs present in mitochondria, termed mitomiR, and that they are important regulators of mitochondrial function. Therefore, mitomiRs are important players in the metabolism of cancer cells, which need to be further investigated in order to develop a potential new therapies for cancer.
Keywords: microRNAs, mitomiR, mitochondria, cancer cell metabolism
Published in DiRROS: 22.07.2024; Views: 22; Downloads: 4
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3.
4.
Recycling of different incineration ashes in the construction sector : perspectives from Slovenia
Vesna Zalar Serjun, 2024, original scientific article

Abstract: The EU prioritizes transitioning to a circular economy, aiming to boost sustainable resource management through policies promoting recycling and reuse, benefiting both the environment and the economy. Many successful case studies demonstrate using various incineration waste by-products (ashes) as substitutes for natural materials, yielding environmental advantages and showcasing sustainable resource management practices. While extensive literature covers ash characterization and applications, the direct links between the properties of the main components, the amorphous phase, and research findings remain elusive. Analysis predominantly centers on microstructural phase development, influencing mechanical, physical, and chemical properties and guiding research interpretations. Existing standards for ash use primarily address coal-derived fly ash, with SIST EN 13282-2 allowing alternative sources like circulating fluidized bed and paper sludge incineration residues. Yet, beyond this standard, no regulations mandate using different ash types. Nonetheless, the applicability of ashes for the geotechnical composite materials has already been confirmed in the field since numerous geotechnical projects have been carried out in Slovenia. Such composites have been recognized as beneficial practices, and the majority of them also possess legal permission for usage according to the Slovenian Technical Approvals. Given the varying value and complexity of ashes, detailed characterization before use is crucial. Assessing the recycling potential of different ashes requires a precise definition of basic properties such as microstructure, minerals, and chemical composition. Emphasis should be placed on characterizing the hydraulic properties and gaining detailed insights into the amorphous phase, ensuring informed decision-making regarding their recycling processes.
Keywords: waste by-products from incineration processes, ashes, recycling, amorphous phase, (latent) hydraulic properties, hydration
Published in DiRROS: 22.07.2024; Views: 14; Downloads: 6
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5.
Simvastatin is effective in killing the radioresistant breast carcinoma cells
Bertram Aschenbrenner, Giulia Negro, Dragana Savic, Maxim Sorokin, Anton A. Buzdin, Ute Maria Ganswindt, Maja Čemažar, Gregor Serša, Sergej Skvortsov, Ira Skvortsova, 2021, original scientific article

Abstract: Background. Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. Materials and methods. Simvastatin, one of the most widely prescribed lipophilic statins was utilized to investigate potential radiosensitizing effects and an impact on cell survival and migration in radioresistant breast cancer cell lines. Results. Compared to parental cell counterparts, radioresistant MDA-MB-231-RR, T47D-RR andAu565-RR cells were characterized by upregulation of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR) expression accom-panied by epithelial-to-mesenchymal transition (EMT) activation. Radioresistant breast cancer cells can be killed by simvastatin via mobilizing of a variety of pathways involved in apoptosis and autophagy. In the presence of simvasta-tin migratory abilities and vimentin expression is diminished while E-cadherin expression is increased. Conclusions. The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes.
Keywords: radiotherapy, breast cancer, radioresistant cells
Published in DiRROS: 22.07.2024; Views: 14; Downloads: 8
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6.
Lastnosti lesa iz rudnika Sitarjevec
Miha Humar, Boštjan Lesar, Davor Kržišnik, Andreja Pondelak, Andrijana Sever Škapin, Angela Balzano, José Gonçalves, 2024, original scientific article

Abstract: Rudarska tradicija v Litiji, segajoča v staro železno dobo, je vključevala intenzivno uporabo lesa v rudnikih, še posebej za podporo in zaščito rovov. Rudnik Sitarjevec je bil znova odprt za turizem leta 2017, in v letu 2021 so odprli glavni rov. Les ostaja ključen material v rudnikih, čeprav so ga v preteklosti nadomeščali z drugimi materiali. Uporabljeni les je izpostavljen razkroju zaradi visoke vlažnosti in gliv, kot je bela hišna goba. Ta gliva lahko povzroči razgradnjo lesa in je pogosta v vlažnih okoljih rudnikov. Obstoj gliv je pomemben, saj lahko vplivajo na obiskovalce rudnika. Visoka relativna zračna vlažnost (96,6 %) in stalna temperatura (10,1 °C) v rudniku ustvarjata razmere, ki so ugodne za rast gliv, vendar pa relativno nizka temperatura ni omejujoč dejavnik za razgradnjo lesa. Koncentracija glivnih spor v rudniku je visoka in je razložena z razširjenostjo gliv v samem rudniku. Poleg tega smo opazili, da je v lesu veliko anorganskih onesnaževal ter veliko kristalov.
Keywords: razkroj, bela hišna goba, težke kovine, kristali, spore
Published in DiRROS: 22.07.2024; Views: 14; Downloads: 2
.pdf Full text (4,45 MB)

7.
A protocol for accurate radiochromic film dosimetry using Radiochromic.com
Ignasi Méndez Carot, Juan José Rovira-Escutia, Božidar Casar, 2021, original scientific article

Abstract: Radiochromic films have many applications in radiology and radiation therapy. Generally, the dosim-etry system for radiochromic film dosimetry is composed of radiochromic films, flatbed scanner, and film analysis soft-ware. The purpose of this work is to present the effectiveness of a protocol for accurate radiochromic film dosimetry using Radiochromic.com as software for film analysis.Materials and methods. Procedures for image acquisition, lot calibration, and dose calculation are explained and analyzed. Radiochromic.com enables state-of-the-art models and corrections for radiochromic film dosimetry, such as the Multigaussian model for multichannel film dosimetry, and lateral, inter-scan, and re-calibration corrections of the response.Results. The protocol presented here provides accurate dose results by mitigating the sources of uncertainty that affect radiochromic film dosimetry. Conclusions. Appropriate procedures for film and scanner handling in combination with Radiochromic.com as software for film analysis make easy and accurate radiochromic film dosimetry feasible.
Keywords: radiochromic film, dosimetry, protocol
Published in DiRROS: 22.07.2024; Views: 13; Downloads: 4
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8.
Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolation
Tanja Jesenko, Živa Pišljar, Cvetka Grašič-Kuhar, Maja Čemažar, Urška Matkovič, Simona Miceska, Jerneja Varl, Anamarija Kuhar, Veronika Kloboves-Prevodnik, 2021, original scientific article

Abstract: Background. Circulating tumor cells (CTCs) have become an important biomarker in breast cancer. Different iso-lation tech-niques based on their biological or physical features were established. Currently, the most widely used methods for visualization after their separation are based on immunofluorescent staining, which does not provide the information on the morphology.Materials and methods. The aim of this study was to evaluate how two different separation techniques affect cell morphology and to analyse cell morphology with techniques used in routine cytopathological laboratory. A direct side-by-side comparison of physical (Parsortix%) and biological (MACS%) separation technique was performed.Results. In the preclinical setting, both isolation techniques retained the viability and antigenic characteristics of MCF7 breast cancer cells. Some signs of degeneration such as cell swelling, cytoplasmic blebs, villous projections and vacuolization were observed. In metastatic breast cancer patient cohort, morphological features of isolated CTCs were dependent on the separation technique. After physical separation, CTCs with preserved cell morphology were detected. After biological separation the majority of the isolated CTCs were so degenerated that their identity was difficult to confirm.Conclusions. Taken together, physical separation is a suitable technique for detection of CTCs with preserved cell morphology for the use in a routine cytopathological laboratory.
Keywords: circulating tumor cells, breast cancer, morphology
Published in DiRROS: 22.07.2024; Views: 13; Downloads: 5
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9.
Large ring test for evaluation of restrained shrinkage cracking : calibration and experimental trial
Zhongyu Xu, Lucija Hanžič, Harry Asche, Jurij Karlovšek, 2024, original scientific article

Abstract: The durability of shotcrete tunnel linings is significantly affected by restrained shrinkage cracking. Given the unique characteristics of shotcrete applied in tunnel linings, especially when dealing with accelerated shotcrete containing reinforcement fibres, it is necessary to upscale the ring test commonly used. This paper presents a comprehensive experiment using large ring tests with cast concrete to investigate the impact of upscaling ring test geometry. The two ring specimens demonstrated comparable cracking age (22 days) and strain measured in the steel ring, suggesting that consistent results can be obtained through the proposed instrumentation, calibration, and correction methods. Moreover, the estimated induced tensile stresses of the concrete rings (2.8 and 2.7 MPa) are slightly lower than the predicted tensile strength (3.3 MPa) at the age of cracking, which indicates that some driving forces contributing to restrained shrinkage cracking were not indicated in the strain gauge readings. Furthermore, the study identified multi-crack formation and additional potential causes for crack initiation, which include self-restraint due to the moisture gradient in the vertical direction, deflection of the concrete ring caused by its self-weight, and friction on the contact surface of the support. Therefore, optimising the geometry of the ring specimens and the apparatus is imperative to minimise additional driving forces and unmeasurable restraints for crack initiation, especially when employing the stress rate method to assess cracking potential.
Keywords: concrete, restrained shrinkage, tunnel lining, large ring test
Published in DiRROS: 22.07.2024; Views: 14; Downloads: 3
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10.
Can dynamic imaging, using 18F-FDG PET/CT and CT perfusion differentiate between benign and malignant pulmonary nodules?
Aleksander Marin, John T. Murchison, Kristopher M. Skwarski, Adriana A.S. Tavares, Alison Fletcher, William A. Wallace, Vladka Salapura, Edwin J.R. Van Beek, Saeed Mirsadraee, 2021, original scientific article

Abstract: Background. The aim of the study was to derive and compare metabolic parameters relating to benign and ma- lignant pulmonary nodules using dynamic 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) PET/CT, and nodule perfu- sion parameters derived through perfusion computed tomography (CT). Patients and methods. Twenty patients with 21 pulmonary nodules incidentally detected on CT underwent a dynamic 18F-FDG PET/CT and a perfusion CT. The maximum standardized uptake value (SUVmax) was measured on conventional 18F-FDG PET/CT images. The influx constant (Ki) was calculated from the dynamic 18F-FDG PET/CT data using Patlak model. Arterial flow (AF) using the maximum slope model and blood volume (BV) using the Patlak plot method for each nodule were calculated from the perfusion CT data. All nodules were characterized as malignant or benign based on histopathology or 2 year follow up CT. All parameters were statistically compared between the two groups using the nonparametric Mann-Whitney test. Results. Twelve malignant and 9 benign lung nodules were analysed (median size 20.1 mm, 9-29 mm) in 21 patients (male/female = 11/9; mean age +- SD: 65.3 +- 7.4; age range: 50-76 years). The average SUVmax values +- SD of the benign and malignant nodules were 2.2 +- 1.7 vs. 7.0 +- 4.5, respectively (p = 0.0148). Average Ki values in benign and malig- nant nodules were 0.0057 +- 0.0071 and 0.0230 +- 0.0155 min-1, respectively (p = 0.0311). Average BV for the benign and malignant nodules were 11.6857 +- 6.7347 and 28.3400 +- 15.9672 ml/100 ml, respectively (p = 0.0250). Average AF for the benign and malignant nodules were 74.4571 +- 89.0321 and 89.200 +- 49.8883 ml/100g/min, respectively (p = 0.1613). Conclusions. Dynamic 18F-FDG PET/CT and perfusion CT derived blood volume had similar capability to differentiate benign from malignant lung nodules.
Keywords: CT perfusion, malignant pulmonary nodules, benign pulmonary nodules
Published in DiRROS: 22.07.2024; Views: 13; Downloads: 3
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