1111. International Conference Decade of Decadence: 1914–1924 : spaces, societies and belongings in the Adriatic borderland in historical comparison2024, druge monografije in druga zaključena dela Povzetek: Historians have long come to realize the importance of the World War I as the seminal event leading to a short 20th century. If traditional research has often conceptualized the war and post-war years as two distinct historical periods, new studies have emphasized entangle-ments and intertwinements between war- and post-war processes. This turn was influenced by a gradual geographical balance and the inclusion of Eastern and Central Europe in the re-search focus. Wars, collapse of Empires and long-existing State structures, and similar events brought about processes of redefinition of territories and its peoples. The focus on volatile, overlapping and, at times, competing centers of power (States, national, regional and local structures), will allow us to reconsider criteria and concepts of citizenship and belonging that have shaped European politics of governance. Our conference focuses on the Northern Adri-atic transnational borderland from the beginning of World War I in July 1914 to the Treaty of Rome in January 1924, when the Adriatic question was temporarily settled. This decade is of fundamental importance at the global level, while the Northern Adriatic represents a unique laboratory to study the transformations of Europe in the Twentieth Century. The focus is on the question of citizenship beyond nation-state frameworks and monothematic disciplines, in which the question of citizenship is linked to the migratory movement of people. Taking the Northern Adriatic as a case study, this conference aims at rethinking the questions of citizen-ships, national affiliations, territorial belongings and state sovereignty. This will enable us to contribute to a growing dialogue in international academia and to contemporary societal de-bates at a time, when citizenship and the rights linked to it are the subject of intense discus-sions. We aim at reconsidering rigid understandings of center and periphery and restoring a more composite history of twentieth century Europe. Objavljeno v DiRROS: 29.05.2024; Ogledov: 266; Prenosov: 258
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1112. Mechanism of action, potency and efficacy : considerations for cell therapiesCarl G. Simon Jr., Erich H. Bozenhardt, Christina M. Celluzzi, David Dobnik, Melanie L. Grant, Uma Lakshmipathy, Thiana Nebel, 2024, izvirni znanstveni članek Povzetek: One of the most challenging aspects of developing advanced cell therapy products (CTPs) is defining the mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented that is consistent with the existing regulatory guidelines, but also accommodates what has been learned from the 27 US FDA-approved CTPs. Available information regarding MOA, potency and efficacy for the 27 FDA-approved CTPs is reviewed to provide background and perspective. Potency process and efficacy process charts are introduced to clarify and illustrate the relationships between six key concepts: MOA, potency, potency test, efficacy, efficacy endpoint and efficacy endpoint test. Careful consideration of the meaning of these terms makes it easier to discuss the challenges of correlating potency test results with clinical outcomes and to understand how the relationships between the concepts can be misunderstood during development and clinical trials. Examples of how a product can be “potent but not efficacious” or “not potent but efficacious” are presented. Two example applications of the framework compare how MOA is assessed in cell cultures, animal models and human clinical trials and reveals the challenge of establishing MOA in humans. Lastly, important considerations for the development of potency tests for a CTP are discussed. These perspectives can help product developers set appropriate expectations for understanding a product’s MOA and potency, avoid unrealistic assumptions and improve communication among team members during the development of CTPs. Ključne besede: cell therapy product, efficacy endpoint test, mechanism of action, potency test, metrology Objavljeno v DiRROS: 27.05.2024; Ogledov: 275; Prenosov: 277
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1113. Mutual-visibility problems on graphs of diameter twoSerafino Cicerone, Gabriele Di Stefano, Sandi Klavžar, Ismael G. Yero, 2024, izvirni znanstveni članek Povzetek: The mutual-visibility problem in a graph $G$ asks for the cardinality of a largest set of vertices $S\subseteq V(G)$ so that for any two vertices $x,y \in S$ there is a shortest $x,y$-path $P$ so that all internal vertices of $P$ are not in $S$. This is also said as $x,y$ are visible with respect to $S$, or $S$-visible for short. Variations of this problem are known, based on the extension of the visibility property of vertices that are in and/or outside $S$. Such variations are called total, outer and dual mutual-visibility problems. This work is focused on studying the corresponding four visibility parameters in graphs of diameter two, throughout showing bounds and/or closed formulae for these parameters. The mutual-visibility problem in the Cartesian product of two complete graphs is equivalent to (an instance of) the celebrated Zarankiewicz's problem. Here we study the dual and outer mutual-visibility problem for the Cartesian product of two complete graphs and all the mutual-visibility problems for the direct product of such graphs as well. We also study all the mutual-visibility problems for the line graphs of complete and complete bipartite graphs. As a consequence of this study, we present several relationships between the mentioned problems and some instances of the classical Turán problem. Moreover, we study the visibility problems for cographs and several non-trivial diameter-two graphs of minimum size. Ključne besede: mutual-visibility set, mutual-visibility number, diameter-two graphs, line graphs, cographs Objavljeno v DiRROS: 27.05.2024; Ogledov: 307; Prenosov: 232
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1114. Health-related quality of life assessed by the EORTC QLQ-C30 questionnaire in the general Slovenian populationVaneja Velenik, Ajra Šečerov Ermenc, Jasna But-Hadžić, Vesna Zadnik, 2017, izvirni znanstveni članek Povzetek: The aim of our study was to obtain reference data of the EORTC QLQ-C30 quality of life dimensions for the general Slovenian population. We intend to provide the researchers and clinicians in our country with the expected mean health-related quality of life (HRQL) scores for distinctive socio-demographic population groups. Methods. The EORTC QLQ-C30 questionnaire supplemented by a socio-demographic inquiry was mailed or distributed to 1,685 randomly selected individuals in the Slovenian population aged 18 % 90. Answers from 1,231 subjects representing socio-demographic diversity of the Slovenian population were collected and transformed into EORTC dimensions and symptoms. The impact of socio-demographic features on HRQL scores was assessed by multiple linear regression models. Results. Gender, age and self-rated social class are the important confounders in the quality of life scores in our population. Men reported better quality of life on the majority of the specific scales and, at the same time, reported fewer symptoms. There was no gender-specific difference in cognitive functioning. The mean scores were consistently lower with age in both sexes. Conclusions. This is the first study to report the normative EORTC QLQ-C30 scores for one of the south-eastern European populations. The reported expected mean scores allow Slovenian oncologists to estimate what the quality of life in cancer patients would be, had they not been ill. As they are derived by common methodology, our results can easily be included in any further international comparisons or in the calculation of European summarized HRQL scores. Objavljeno v DiRROS: 24.05.2024; Ogledov: 285; Prenosov: 174
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1115. Treatment-related cardiovascular toxicity in long-term survivors of testicular cancerJasenka Gugić Kevo, Lorna Zadravec-Zaletel, Irena Oblak, 2017, pregledni znanstveni članek Povzetek: Testicular cancer is the most common malignancy in young men. Considering increasing incidence, exceptionally high cure rate, as well as long life expectancy, assessment of long term toxicity in testicular cancer survivors is of great importance. In the last decades a major effort has been made in order to reduce toxicity of treatment, while maintaining its high effectiveness. Conclusions Actual knowledge on treatment toxicity is based on outdated treatment modalities. Hopefully, modern treatment modalities could reduce toxicity, but, there is no firm confirmation for that at the moment, as data dealing with late sequelae of modern treatment of testicular cancer are not available yet due to the short period of observation. The life-threatening cardiovascular toxicity in testicular cancer survivors is major complication of platinum-based chemotherapy, mediastinal radiotherapy and even subdiaphragmatic radiotherapy. Ključne besede: testicular cancer, cardiovascular toxicity, long-term survivors Objavljeno v DiRROS: 24.05.2024; Ogledov: 370; Prenosov: 189
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1116. Genetic counselling, BRCA1/2 status and clinico-pathologic characteristics of patients with ovarian cancer before 50 years of ageMirjam Cvelbar, Marko Hočevar, Srdjan Novaković, Vida Stegel, Andraž Perhavec, Mateja Krajc, 2017, izvirni znanstveni članek Povzetek: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years. Patients and methods. All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities. Results. Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected. Conclusions. The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to all EOC patients younger than 50 years. Regarding clinical data, it is important to perform their re-interpretation in everyday clinical practice, because this may influence therapeutic possibilities to be offered. Ključne besede: ovarian cancer, BRCA 1/2, genetic counseling Objavljeno v DiRROS: 24.05.2024; Ogledov: 310; Prenosov: 190
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1117. Leiomyosarcoma of the renal vein : analysis of outcome and prognostic factors in the world case series of 67 patientsMarko Novak, Andraž Perhavec, Katherine E. Maturen, Snežana Pavlović Djokić, Simona Jereb, Darja Eržen, 2017, izvirni znanstveni članek Povzetek: Background Leiomyosarcoma is a rare malignant mesenchymal tumour. Some cases of leiomyosarcoma of the renal vein (LRV) have been reported in the literature, but no analysis of data and search for prognostic factors have been done so far. The aim of this review was to describe the LRV, to analyse overall survival (OS), local recurrence free survival (LRFS) and distant metastases free survival (DMFS) in LRV world case series and to identify significant predictors of OS, LRFS and DMFS. Methods Cases from the literature based on PubMed search and a case from our institution were included. Results Sixty-seven patients with a mean age of 56.6 years were identified; 76.1% were women. Mean tumour size was 8.9 cm; in 68.7% located on the left side. Tumour thrombus extended into the inferior vena cava lumen in 13.4%. All patients but one underwent surgery (98.5%). After a median follow up of 24 months, the OS was 79.5%. LRFS was 83.5% after a median follow up of 21.5 months and DMFS was 76.1% after a median follow up of 22 months. Factors predictive of OS in univariate analysis were surgical margins, while factors predictive of LRFS were inferior vena cava luminal extension and grade. No factors predictive of DMFS were identified. In multivariate analysis none of the factors were predictive of OS, LRFS and DMFS. Conclusions Based on the literature review and presented case some conclusions can be made. LRV is usually located in the hilum of the kidney. It should be considered in differential diagnosis of renal and retroperitoneal masses, particularly in women over the age 40, on the left side and in the absence of haematuria. Core needle biopsy should be performed. Patients should be managed by sarcoma multidisciplinary team. LRV should be surgically removed, with negative margins. Ključne besede: leiomysarcoma, renal vein, surgery, outcomes, prognostic factors Objavljeno v DiRROS: 24.05.2024; Ogledov: 316; Prenosov: 236
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1118. Cancer burden in Slovenia with the time trends analysisVesna Zadnik, Maja Primic-Žakelj, Katarina Lokar, Katja Jarm, Urška Ivanuš, Tina Žagar, 2017, izvirni znanstveni članek Povzetek: Background The aim of our study was to describe cancer burden and time trends of all cancers combined, the most frequent as well as the rare cancers in Slovenia. Patients and methods The principal data source was the population-based Cancer Registry of Republic of Slovenia. The cancer burden is presented by incidence and prevalence for the period 1950%2013 and by mortality for years 1985%2013. The time trends were characterized in terms of an average annual percent change estimated by the log-linear joinpoint regression. The Dyba-Hakulinen method was used for estimation of incidence in 2016 and the projections of cancer incidence for the year 2025 were calculated applying the Globocan projection software. Results In recent years, near 14,000 Slovenes were diagnosed with cancer per year and just over 6,000 died; more than 94,000 people who were ever diagnosed with cancer are currently living among us. The total burden of cancer is dominated by five most common cancer sites: skin (non-melanoma), colon and rectum, lung, breast and prostate, together representing almost 60% of all new cancer cases. On average the incidence of common cancers in Slovenia is increasing for 3.0% per year in last decade, but the incidence of rare cancers is stable. Conclusions Because cancer occurs more among the elderly, and additionally more numerous post-war generation is entering this age group, it is expected that the burden of this disease will be growing further, even if the level of risk factors remains the same as today. Ključne besede: cancer burden, cancer registry, incidence, prevalence Objavljeno v DiRROS: 24.05.2024; Ogledov: 312; Prenosov: 258
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1119. Electrotransfer of plasmid DNA radiosensitizes B16F10 tumors through activation of immune responseMonika Savarin, Urška Kamenšek, Maja Čemažar, Richard Heller, Gregor Serša, 2017, izvirni znanstveni članek Povzetek: Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors. Materials and methods. The murine melanoma B16F10 tumors, growing on the back of C57Bl/6 mice, were treated by triple gene electrotransfer and irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice. Furthermore, histological analysis of tumors (necrosis, apoptosis, proliferation, vascularization, presence of hypoxia and infiltration of immune cells,) was used to evaluate the therapeutic mechanisms. Results. Gene electrotransfer of plasmid silencing endoglin predominantly indicated vascular targeted effects of the therapy, since significant tumor growth delay and 44% of tumor free mice were obtained. In addition, irradiation had minor effects on radioresistant melanoma, with 11% of mice tumor free. The combined treatment resulted in excellent effectiveness with 88% of mice tumor free, with more than half resistant to secondary tumor challenge, which was observed also with the plasmid devoid of the therapeutic gene. Histological analysis of tumors in the combined treatment group, demonstrated similar mode of action of the gene electrotransfer of plasmid encoding shRNA for silencing endoglin and devoid of it, both through the induction of an immune response. Conclusions. The results of this study indicate that irradiation can in radioresistant melanoma tumors, by release of tumor associated antigens, serve as activator of the immune response, besides directly affecting tumor cells and vasculature. The primed antitumor immune response can be further boosted by gene electrotransfer of plasmid, regardless of presence of the therapeutic gene, which was confirmed by the high radiosensitization, resulting in prolonged tumor growth delay and 89% of tumor free mice that were up to 63% resistant to secondary challenge of tumor. In addition, gene electrotransfer of therapeutic plasmid for silencing endoglin has also a direct effect on tumor vasculature and tumors cells; however in combination with radiotherapy this effect was masked by pronounced immune response. Ključne besede: gene therapy, electrotransfer, plasmid, irradiation, immune response, melanoma Objavljeno v DiRROS: 24.05.2024; Ogledov: 333; Prenosov: 236
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1120. Poročilo o izvedbi naloge javnega naročila: »Monitoring ogljika v gozdnih tleh, mokriščih in urbanih tleh« - MEJNIK 4 : končno poročiloAleksander Marinšek, Daniel Žlindra, Mitja Ferlan, Erika Kozamernik, Boštjan Mali, Peter Horvat, Eva Zagorac, Nastja Mesarec, Janez Bergant, Borut Vrščaj, Primož Simončič, 2023, končno poročilo o rezultatih raziskav Ključne besede: monitoring, ogljik, gozdna tla, mokrišča, urbana tla Objavljeno v DiRROS: 24.05.2024; Ogledov: 342; Prenosov: 281
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