Purpose – This paper will explore the importance of material cultural heritage as a factor of an area’s tourism development. Zenica-Doboj Canton is located in the central part of Bosnia and Herzegovina. Canton's development of its tourist offer could be based on its material cultural and historical heritage and tourism in that area could take place throughout the year if other offers of services and products enabled it. This paper has a theoretical and an empirical value since both quantitative and qualitative methods will be used. Methodology – In addition to this, desk research of the existing literature will be carried out and the secondary data will be used to analyze the current state of tourism. Furthermore, authors will conduct an empirical research using qualitative methods of analysis. The empirical research is based on a structured questionnaire. More precisely, the local population of the Zenica-Doboj Canton will be questioned by using a sampling method in order to determine their role and importance in the product of cultural tourism. Based on the conducted survey through the SWOT analysis, the advantages and disadvantages of cultural tourism will be determined. Findings – The positive conclusion of the survey is that residents see cultural tourism as the most representative form of tourism in the Zenica-Doboj Canton whose development could significantly improve the economic situation of this particular area. A model for a product development will be presented in this paper on the basis of the obtained results. Contribution – It is concluded that the population's interest opens up the possibility of adapting the offer to tourists. Therefore, it is necessary to include the local population in the product formation because they are part of the product.

Purpose – The purpose of this paper is to determine the key factors that influence the probability of tourists’ return intention to the Opatija Riviera. Methodology – A structured questionnaire with a 5 point Likert scale was used within this research. The authors used the descriptive statistics to determine the satisfaction with the destination attributes, and attitudes regarding the novelty of offer and possibility of future revisit. With the use of T-test a statistically significant difference was determined for the score for the accommodation capacities, natural resources and novelty. Correlation analysis was used to determine the association between accommodation, natural resources, cultural resources, novelty, and return intention. Logistic regression model was used to get a better understanding of the factors that may influence probability of tourists’ return intention. Findings – Results indicate high level of satisfaction of tourists with the accommodation offer and natural resources, while the results for cultural tourist resources were not up to expectations. The results for novelty are moderate and consistent with the results expressed about possible return intention to Opatija Riviera in the future, which indicates the need for significant improvements within the offer. The results of a logistic regression model determined that the best predictors for repeat visit of tourists are primarily accommodation services, followed by natural resources and finally novelty. Contribution – Based on the findings acquired within this paper the authors proposed the guidelines for tourist offer improvement with a goal of increasing the satisfaction of tourists and stimulating them to revisit Opatija Riviera in the future.

Supplemental Digital Content is available in the text. The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells’ expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non–small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.

This paper presents a semi-automated approach for detecting conflicts and inconsistencies between architecture solutions. Inconsistencies occur when two or more architecture solutions rely on each other but cannot be satisfied, and conflicts when there are contradictions within one single decision specification, such as contradictory variable range and value. The proposed approach comprises a set of checks followed by transformations of architecture solutions specified according to a domain-specific-language, also created in the context of this work, into state machines. The semi-automated approach is implemented as a plugin for the MagicDraw modeling tool, and was evaluated in a project from the automotive domain.

Low back pain related to intervertebral disk (IVD) degeneration has a major socioeconomic impact on our aging society. Therefore, stem cell therapy to activate self-repair of the IVD remains an exciting treatment strategy. In this respect, tissue-specific progenitors may play a crucial role in IVD regeneration, as these cells are perfectly adapted to this niche. Such a rare progenitor cell population residing in the nucleus pulposus (NP) (NP progenitor cells [NPPCs]) was found positive for the angiopoietin-1 receptor (Tie2+), and was demonstrated to possess self-renewal capacity and in vitro multipotency. Here, we compared three sorting protocols; that is, fluorescence-activated cell sorting (FACS), magnetic-activated cell sorting (MACS), and a mesh-based label-free cell sorting system (pluriSelect), with respect to cell yield, potential to form colonies (colony-forming units), and in vitro functional differentiation assays for tripotency. The aim of this study was to demonstrate the efficiency of three widespread cell sorting methods for picking rare cells (<5%) and how these isolated cells then behave in downstream functional differentiation in adipogenesis, osteogenesis, and chondrogenesis. The cell yields among the isolation methods differed widely, with FACS presenting the highest yield (5.0% ± 4.0%), followed by MACS (1.6% ± 2.9%) and pluriSelect (1.1% ± 1.0%). The number of colonies formed was not significantly different between Tie2+ and Tie2− NPPCs. Only FACS was able to separate into two functionally different populations that showed trilineage multipotency, while MACS and pluriSelect failed to maintain a clear separation between Tie2+ and Tie2− populations in differentiation assays. To conclude, the isolation of NPPCs was possible with all three sorting methods, while FACS was the preferred technique for separation of functional Tie2+ cells. Impact Statement Tissue-specific progenitor cells such as nucleus pulposus progenitor cells of the IVD could become an ultimate cell source for tissue engineering strategies as these cells are presumably best adapted to the tissue's microenvironment. Fluorescence-activated cell sorting seemed to outcompete magnetic-activated cell sorting and pluriSelect concerning selecting a rare cell population from IVD tissue as could be demonstrated by improved cell yield and functional differentiation assays.

Introduction Acute appendicitis (AA) is the most common surgical condition of the abdomen in children. The aim of this study was to analyse the possible use of the neutrophil-to-lymphocyte ratio (NLR) in the diagnosis and prediction of AA complications in children. Material and methods We included 170 AA patients under 15 years of age, who were divided into the following groups: Group 1 – non-operated patients with AA, and Group 2 – patients who underwent appendectomy. Based on pathologic grades of AA, Group 2 was subdivided into: Group A – phlegmonous, Group B – gangrenous, and Group C – perforated AA. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Results In Group 2 NLR was significantly higher than in Group 1 (5.5 (1.9–9.9) vs. 2.3 (1.2–3.7); p < 0.001). A significant difference in NLR was found between Group C and Group A (p < 0.001), and as well as between Group B and Group A (p = 0.001). The determined optimal cut-off value of NLR in differentiating Group 1 vs. Group 2 was ≥ 3.48 (p < 0.001). In differentiating Group A from Group C the optimal cut-off value of NLR was ≥ 5.61 (p < 0.001). Furthermore, optimal cut-off value of NLR in differentiating Group A from Group B was ≥ 5.45 (p = 0.001). Conclusions The obtained results suggest that NLR could be used as a simple and reliable test in the diagnosis and prediction of AA complications in children. However, to draw definite conclusions on the predictive power of NLR as a marker of AA large multicentric studies are required.