1161. IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesisMarchien G. Dallinga, Yasmin I. Habani, Richelle P. Kayser, Cornelis J. F. van Noorden, Ingeborg Klaassen, Reinier O. Schlingemann, 2020, izvirni znanstveni članek Povzetek: Purpose
We have previously identified insulin-like growth factor 2 (IGF2) and insulin-like growth factor 1 receptor (IGF1R) as essential proteins for tip cell maintenance and sprouting angiogenesis. In this study, we aim to identify other IGF family members involved in endothelial sprouting angiogenesis.
Methods
Effects on sprouting were analyzed in human umbilical vein endothelial cells (HUVECs) using the spheroid-based sprouting model, and were quantified as mean number of sprouts per spheroid and average sprout length. RNA silencing technology was used to knockdown gene expression. Recombinant forms of the ligands (IGF1 and IGF2, insulin) and the IGF-binding proteins (IGFBP) 3 and 4 were used to induce excess effects. Effects on the tip cell phenotype were analyzed by measuring the fraction of CD34+ tip cells using flow cytometry and immunohistochemistry in a 3D angiogenesis model. Experiments were performed in the presence and absence of serum.
Results
Knockdown of IGF2 inhibited sprouting in HUVECs, in particular when cultured in the absence of serum, suggesting that components in serum influence the signaling of IGF2 in angiogenesis in vitro. We then determined the effects of IGFBP3 and IGFBP4, which are both present in serum, on IGF2-IGF1R signaling in sprouting angiogenesis in the absence of serum: knockdown of IGFBP3 significantly reduced sprouting angiogenesis, whereas knockdown of IGFBP4 resulted in increased sprouting angiogenesis in both flow cytometry analysis and immunohistochemical analysis of the 3D angiogenesis model. Other IGF family members except INSR did not affect IGF2-IGF1R signaling.
Conclusions
Serum components and IGF binding proteins regulate IGF2 effects on sprouting angiogenesis. Whereas IGFBP3 acts as co-factor for IGF2-IGF1R binding, IGFBP4 inhibits IGF2 signaling.
Ključne besede: Angiogenesis, tip cells, IGF2, IGF binding proteins, endothelial cells, cultured cells, endothelial growth factors
Objavljeno v DiRROS: 23.07.2024; Ogledov: 273; Prenosov: 208
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1162. Multiannual trend of micro-pollutants in sediments and benthic community response in a Mediterranean lagoon (Sacca di Goro, Italy)Valentina Pitacco, Michele Mistri, Carla Rita Ferrari, Adriano Sfriso, Andrea Augusto Sfriso, Cristina Munari, 2020, izvirni znanstveni članek Povzetek: Long-term variations of ecological status in a Mediterranean coastal lagoon (Sacca di Goro, Northern Adriatic) were investigated, combining data on the concentration of surface sediment contaminants and on the structure of the macrobenthic community. The aim was to assess any amount of chemical contamination and check the response of the macrobenthic community to sediment contamination. Over the studied period, the sediments of the lagoon showed contamination by trace metals and organochlorine pesticides, with most of them exceeding the thresholds indicated by the Italian legislation in many samples. Contamination by polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs) and polycyclic aromatic hydrocarbons (PAHs) instead never exceeded the threshold. The ecological status based on the macrobenthic community, evaluated through biotic indices (AMBI and M-AMBI), fell below the Good/Moderate threshold in most samples. The results indicate a possible influence of toxic compounds in sediment on benthic organisms, but most of the variability shown by the macrobenthic community is probably due to other factors. The difficulty in establishing a cause/effect relationship was due to the co-occurrence and variability of various stressors (both natural and anthropogenic) and their interactions. The methods currently used for monitoring transitional waters thus seem insufficient to disentangle the effect of pollutants and other environmental variables on the benthos. Integrated approaches (e.g., bioaccumulation and toxicity tests) are thus needed for a more precise identification of the risk posed by a high concentration of pollutants in such environments.
Ključne besede: coastal lagoon, macrobenthos, trace elements, organochlorine pesticides, PAHs, PCDD/Fs
Objavljeno v DiRROS: 23.07.2024; Ogledov: 279; Prenosov: 237
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1163. Poor perfusion of the microvasculature in peritoneal metastases of ovarian cancerArnoud W. Kastelein, Laura M.C. Vos, Juliette O. A. M. van Baal, Jasper J. Koning, Vashendriya V. V. Hira, Rienk Nieuwland, Willemien J. van Driel, Zühre Uz, Thomas M van Gulik, Jacco van Rheenen, Can Ince, Jan-Paul W.R. Roovers, Cornelis J. F. van Noorden, Christianne A. R. Lok, 2020, izvirni znanstveni članek Povzetek: Most women with epithelial ovarian cancer (EOC) suffer from peritoneal carcinomatosis upon first clinical presentation. Extensive peritoneal carcinomatosis has a poor prognosis and its pathophysiology is not well understood. Although treatment with systemic intravenous chemotherapy is often initially successful, peritoneal recurrences occur regularly. We hypothesized that insufficient or poorly-perfused microvasculature may impair the therapeutic efficacy of systemic intravenous chemotherapy but may also limit expansive and invasive growth characteristic of peritoneal EOC metastases. In 23 patients with advanced EOC or suspicion thereof, we determined the angioarchitecture and perfusion of the microvasculature in peritoneum and in peritoneal metastases using incident dark field (IDF) imaging. Additionally, we performed immunohistochemical analysis and 3-dimensional (3D) whole tumor imaging using light sheet fluorescence microscopy of IDF-imaged tissue sites. In all metastases, microvasculature was present but the angioarchitecture was chaotic and the vessel density and perfusion of vessels was significantly lower than in unaffected peritoneum. Immunohistochemical analysis showed expression of vascular endothelial growth factor and hypoxia inducible factor 1α, and 3D imaging demonstrated vascular continuity between metastases and the vascular network of the peritoneum beneath the elastic lamina of the peritoneum. We conclude that perfusion of the microvasculature within metastases is limited, which may cause hypoxia, affect the behavior of EOC metastases on the peritoneum and limit the response of EOC metastases to systemic treatment.
Ključne besede: microvasculature, microcirculation, EOC, peritoneal carcinomatosa, incident dark feld imaging
Objavljeno v DiRROS: 23.07.2024; Ogledov: 302; Prenosov: 226
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1164. New alien Mediterranean biodiversity records 2020Michel Bariche, Sara A. A. Al-Mabruk, Maria A. Ateş, Adnan Büyük, Fabio Crocetta, Michail Dritsas, Diala Edde, Ana Fortič, Lovrenc Lipej, 2020, izvirni znanstveni članek Povzetek: The current article presents 18 new records from seven Mediterranean countries. These records include one rhodophyte, four nudibranchs, two crustaceans, one stingray and 10 bony fishes. They are grouped by country as follows: Lebanon - first record of the Striped bass Morone saxatilis, the stingray Himantura leoparda, the Areolate grouper Epinephelus areolatus and the Spot-fin porcupinefish Diodon hystrix from various parts of the country; Turkey - first record of the invasive red alga Grateloupia turuturu from the sea of Marmara (region of Bandırma), the sea slug Goniobranchus obsoletus and the crab Arcania brevifrons from the Gulf of Antalya and the cladoceran Pleopis schmackeri from several locations along the Aegean Sea; Cyprus - first record of the alien sea slug Berthellina citrina from the region of Cape Greco and an observation of a butterflyfish Heniochus sp. from the northeastern side of the island; Greece - first record of the alien sea slug Anteaeolidiella lurana from the region of Heraklion in Crete and the record of the Atlantic spadefish Chaetodipterus faber and the Black surgeonfish Acanthurus cfr gahhm from Salamina Island; Slovenia - first record of the alien sea slug Thecacera pennigera from Izola; Italy - first record of the hybrid Striped bass (Morone saxatilis × Morone chrysops) from the northern Tyrrhenian Sea and a first record of the goldfish Carassius auratus from the region of Apulia; Libya - first record of the Red Sea goatfish Parupeneus forsskali and the African surgeonfish Acanthurus monroviae, respectively from the eastern (Al-Tamimi area) and the western shore (Al-Khums area).
Objavljeno v DiRROS: 23.07.2024; Ogledov: 521; Prenosov: 232
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1165. Genotype-environment interactions rule the response of a widespread butterfly to temperature variationFranziska Günter, Michaël Beaulieu, Kasimir F. Freiberg, Ines Welzel, Nia Toshkova, Anamarija Žagar, Tatjana Simčič, Klaus Fischer, 2020, izvirni znanstveni članek Povzetek: Understanding how organisms adapt to complex environments is a central goal of evolutionary biology and ecology. This issue is of special interest in the current era of rapidly changing climatic conditions. Here, we investigate clinal variation and plastic responses in life history, morphology and physiology in the butterfly Pieris napi along a pan‐European gradient by exposing butterflies raised in captivity to different temperatures. We found clinal variation in body size, growth rates and concomitant development time, wing aspect ratio, wing melanization and heat tolerance. Individuals from warmer environments were more heat‐tolerant and had less melanised wings and a shorter development, but still they were larger than individuals from cooler environments. These findings suggest selection for rapid growth in the warmth and for wing melanization in the cold, and thus fine‐tuned genetic adaptation to local climates. Irrespective of the origin of butterflies, the effects of higher developmental temperature were largely as expected, speeding up development; reducing body size, potential metabolic activity and wing melanization; while increasing heat tolerance. At least in part, these patterns likely reflect adaptive phenotypic plasticity. In summary, our study revealed pronounced plastic and genetic responses, which may indicate high adaptive capacities in our study organism. Whether this may help such species, though, to deal with current climate change needs further investigation, as clinal patterns have typically evolved over long periods.
Objavljeno v DiRROS: 23.07.2024; Ogledov: 273; Prenosov: 134
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1166. Plastics in cyanobacterial blooms - genotoxic effects of binary mixtures of cylindrospermopsin and bisphenols in HepG2 cellsKlara Hercog, Alja Štern, Sara Maisanaba Hernández, Metka Filipič, Bojana Žegura, 2020, izvirni znanstveni članek Povzetek: Ever-expanding environmental pollution is causing a rise in cyanobacterial blooms and the accumulation of plastics in water bodies. Consequently, exposure to mixtures of cyanotoxins and plastic-related contaminants such as bisphenols (BPs) is of increasing concern. The present study describes genotoxic effects induced by co-exposure to one of the emerging cyanotoxins—cylindrospermopsin (CYN)—(0.5 µg/mL) and BPs (bisphenol A (BPA), S (BPS), and F (BPF); (10 µg/mL)) in HepG2 cells after 24 and 72 h of exposure. The cytotoxicity was evaluated with an MTS assay and genotoxicity was assessed through the measurement of the induction of DNA double strand breaks (DSB) with the γH2AX assay. The deregulation of selected genes (xenobiotic metabolic enzyme genes, DNA damage, and oxidative response genes) was assessed using qPCR. The results showed a moderate reduction of cell viability and induction of DSBs after 72 h of exposure to the CYN/BPs mixtures and CYN alone. None of the BPs alone reduced cell viability or induced DSBs. No significant difference was observed between CYN and CYN/BPs exposed cells, except with CYN/BPA, where the antagonistic activity of BPA against CYN was indicated. The deregulation of some of the tested genes (CYP1A1, CDKN1A, GADD45A, and GCLC) was more pronounced after exposure to the CYN/BPs mixtures compared to single compounds, suggesting additive or synergistic action. The present study confirms the importance of co-exposure studies, as our results show pollutant mixtures to induce effects different from those confirmed for single compounds.
Ključne besede: cylindrospermopsin, CYN, bisphenols, BPA, BPS, BPF, BPAF, co-exposure, genotoxicity, cytotoxicity
Objavljeno v DiRROS: 23.07.2024; Ogledov: 312; Prenosov: 222
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1167. Protocol of the study for predicting empathy during VR sessions using sensor data and machine learningEmilija Kizhevska, Kristina Šparemblek, Mitja Luštrek, 2024, izvirni znanstveni članek Povzetek: Virtual reality (VR) technology is often referred to as the ‘ultimate empathy machine’ due to its capability to immerse users in alternate perspectives and environments beyond their immediate physical reality. In this study, participants will be immersed in 3-dimensional 360˚ VR videos where actors express different emotions (sadness, happiness, anger, and anxiousness). The primary objective is to investigate the potential relationship between participants’ empathy levels and the changes in their physiological attributes. The empathy levels will be self-reported with questionnaires, and physiological attributes will be measured using different sensors. The main outcome of the study will be a machine learning model to predict a person’s empathy level based on their physiological responses while watching VR videos. Despite the existence of established methodologies and metrics in research and clinical domains, our aim is to contribute to addressing the gap of a universally accepted “gold standard” for assessing empathy. Additionally, we expect to deepen our understanding of the relationship between different emotions and psychological attributes, gender differences in empathy, and the impact of narrative context on empathic responses.
Objavljeno v DiRROS: 23.07.2024; Ogledov: 264; Prenosov: 115
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1168. A ǂFramework for applying data-driven AI/ML models in reliabilityRok Hribar, Margarita Antoniou, Gregor Papa, 2024, samostojni znanstveni sestavek ali poglavje v monografski publikaciji Povzetek: In this chapter, we present a framework for applying artificial intelligence (AI)/machine learning (ML) in reliability, in the context of the iRel40 project. Data-driven models are becoming an increasingly fruitful tool for detecting patterns in complex data and identifying the circumstances in which they occur. Using only data, gathered along the value chain, data-driven methods are now being used to detect indications of potential early failures, signs of wear out or degradation, and other unwanted events within the development, fabrication, or service phases of the electronic components and systems. We present general considerations that were found to be important during the iRel40 project, when designing pipelines that combine data processing with the AI/ML models for predicting or detecting reliability issues. This chapter serves as an introduction to the definitions and concepts used within the specific use cases that rely on the AI/ML methodology within the iRel40 project.
Ključne besede: machine learning, artificial intelligence, data-driven models
Objavljeno v DiRROS: 23.07.2024; Ogledov: 213; Prenosov: 89
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1169. Reliability improvements for in-wheel motorGašper Petelin, Rok Hribar, Stane Ciglarič, Jernej Herman, Anton Biasizzo, Peter Korošec, Gregor Papa, 2024, samostojni znanstveni sestavek ali poglavje v monografski publikaciji Povzetek: Setting up a reliable electric propulsion system in the automotive sector requires an intelligent condition monitoring device capable of reliably assessing the state and the health of the electric motor. To allow for a massive integration of such monitoring devices, they must be inexpensive and small. These requirements limit their accuracy. However, we show in this chapter that these limitations can be significantly reduced by appropriate processing of the sensor data. We have used machine learning models (random forest and XGBoost) to transform very noisy motor winding insulation resistance measurements made by a low-cost device into a much more reliable value that can compete with measurements made by a high-priced state-of-the-art measurement system. The proposed method is an important building block for a future smart condition monitoring system and enables a cost-effective and accurate assessment of the condition of electric motor health in connection with the condition of their winding insulation.
Ključne besede: machine learning models, low-cost device, electric motor
Objavljeno v DiRROS: 23.07.2024; Ogledov: 262; Prenosov: 117
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1170. Disease control with prior platinum-based chemotherapy is prognostic for survival in patients with metastatic urothelial cancer treated with atezolizumab in real-world practiceMarina Mencinger, Dushan Mangaroski, Urška Bokal, 2021, izvirni znanstveni članek Povzetek: Background. Atezolizumab, a programmed-death ligand-1 (PD-L1) inhibitor, is a novel treatment option for patients with metastatic urothelial cancer (mUC). Clinical prognostic factors, survival outcomes, and the safety of patients with mUC treated with atezolizumab, in a real-world setting, were investigated.Patients and methods. 62 patients with mUC, treated at the Institute of Oncology Ljubljana between May 8th 2018 and Dec 31st 2019, were included. Response rates and immune-related adverse events (irAE) were collected. Progression-free survival and overall survival times were assessed using the Kaplan-Meier method. The Cox propor-tional hazards model was applied to identify the factors affecting survival. Results. Of 62 patients, five (8.1%) have not yet been evaluated and 20 (32%) died prior to the first radiographic evaluation. We observed clinical benefit in 19 (33%), objective response in 12 (21%), and complete response in five (9%) patients. Median overall survival for the whole population was 6.8 (95% CI, 2.6–11.0), for platinum-naïve 8.7 (95% CI: 0.8–16.5), and for the platinum-treated group 6.8 (95% CI, 3.7–10) months. At the 5.8 (0.3–23.1) month median follow-up, the median duration of the response was not reached. IrAE occurred in 20 (32%) patients and seven (11%) of them discontinued the treatment. Multivariate analysis in platinum-treated patients showed that a treatment-free interval of more than six months was prognostic for overall survival (OS). Conclusions. Responses to atezolizumab led to long disease remission in a subset of our patients. The median OS in our real-world population was compromised by a large percentage of patients with poor ECOG performance status (PS). A treatment-free interval from chemotherapy was associated with the longer survival of platinum-treated pa-tients with mUC receiving further atezolizumab.
Ključne besede: PD-L1 inhibitor, urothelial cancer, bladder, atezolizumab
Objavljeno v DiRROS: 23.07.2024; Ogledov: 281; Prenosov: 156
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