Despite patients with stage II melanoma being relatively high risk, contributing to 30% of melanoma-associated deaths, there remains a relatively low individual chance of melanoma recurrence. Therefore, strategies are required to better select those patients at highest risk of recurrence. We have developed assays using circulating tumour DNA (ctDNA) to detect minimal residual disease (MRD) or molecular recurrence of melanoma. Originally, the DETECTION trial was designed to perform ctDNA sampling in addition to clinical follow-up in patients with stage IIB/C melanoma. Those with ctDNA detected were randomized 1 : 1 in a double-blind fashion to continue routine follow-up with the investigators’ choice of treatment if they developed disease recurrence or were unblinded and treated with nivolumab. Since its opening, adjuvant therapy has been licensed, with trials showing approximately 6% absolute reduction in distant metastasis in stage IIB/C melanoma with 1 year of antiprogrammed cell death protein 1 therapy; however, grade 3 or 4 toxicity was observed in 16% of patients, with 25% experiencing lifelong endocrine disorders. Better enrichment of patients at high risk of recurrence, and avoiding treatment toxicity in those who do not require it, therefore remains highly relevant. As DETECTION had only started recruitment, there was opportunity to redesign it, which we present here. We have designed tumour-informed assays targeting BRAF (V600E/K/R), NRAS (G12D, Q61K/L/R) and the H-TERT promoter region (−124 and −146) mutations for ctDNA detection using droplet digital polymerase chain reaction. DETECTION has been redesigned as a phase III trial with the primary objectives of elucidating (i) whether MRD/molecular relapse following curative intent surgery can be identified earlier than clinical relapse and (ii) whether early treatment of molecular recurrence based on ctDNA detection is noninferior to adjuvant therapy in preventing distant metastasis. Patients (n = 1000) with stage IIB/C/III/IV resected BRAF/NRAS/TERT promoter mutant cutaneous melanoma, ECOG 0/1 and adequate organ function, with complete resection performed within 12 weeks and radiological/clinical disease-free status confirmed and no prior immune/targeted therapy will be included. Patients will be randomized 1 : 1 to either 1 year of adjuvant therapy (arm A) or longitudinal ctDNA monitoring (arm B) and treatment only if a local recurrence (surgery followed by 1 year of adjuvant therapy with ongoing ctDNA monitoring) or ctDNA detection (2 years of the investigators’ choice of therapy). The primary endpoint is distant metastasis-free survival. CtDNA is a useful tool to monitor for MRD/molecular relapse. The DETECTION trial will assess whether it can be used to safely monitor patients and systemically treat only those at highest risk of melanoma progression.

Background Research concerned with attitudes towards COVID-19 vaccination in upper middle-income countries such as Bosnia and Herzegovina (B&H) is scarce. Currently, B&H has the lowest number of fully vaccinated adults in Europe, and the highest cumulative number of COVID-19 deaths and SARS-CoV-2 infected individuals. The aim of our study was to examine the factors associated with COVID-19 vaccination status in B&H. Methods An online survey among 1304 B&H adults was conducted in October 2021 evaluating vaccine acceptance, together with socio-demographic variables, attitudes and beliefs related to COVID-19 vaccination. Results The results from a binary logistic regression indicate that those who believed that the COVID-19 vaccine was effective were 45 times more likely to be vaccinated compared to those who did not. We also show that those who had received childhood immunisations were 41 times more likely to be vaccinated against COVID-19 compared to those who had never been previously immunised. Other significant factors were related to respondents’ trust in government institutions and healthcare policymakers as well as trust in public healthcare workers. Conclusion We suggest that future vaccination campaigns should be aimed at educating the public regarding the importance and safety of vaccines, together with strengthening trust in the public health system.

Abstract This paper studies the extent individuals are willing to undertake energy efficiency measures, with evidence coming from a developing country (Bosnia and Herzegovina). The goal of this paper is to analyze energy-savings behaviors, aiming to understand what is typically meant under the term energy efficiency, who is more likely to know the meaning, and the extent individuals are willing to undertake some energy efficiency measures. The sample size used in this paper is a random stratified sample of 1,415 individuals coming from various backgrounds. Our logistic regression models found no statistically significant predictor across all ten measures used in the study. However, past experience, age, and being married are relatively common across these ten energy-saving behaviors. These results might be beneficial in defining policies in order to promote energy-saving behaviors.

Dysfunction of neutrophils in patients with cystic fibrosis (CF) is best characterized in bronchoalveolar lavage (BAL), whereas peripheral blood neutrophils are less examined, and the results are contradictory, especially in younger populations. Therefore, this work aimed to study functional and phenotypic changes in circulating neutrophils in children with CF. The study included 19 CF children (5–17 years) and 14 corresponding age-matched healthy children. Isolated neutrophils were cultured either alone or with different stimuli. Several functions were studied: apoptosis, NET-osis, phagocytosis, and production of reactive oxygen species (ROS), neutrophil elastase (NE), and 11 cytokines. In addition, the expression of 20 molecules involved in different functions of neutrophils was evaluated by using flow cytometry. CF neutrophils showed reduced apoptosis and lower production of NE and IL-18 compared to the healthy controls, whereas IL-8 was augmented. All of these functions were further potentiated after neutrophil stimulation, which included higher ROS production and the up-regulation of CD11b and IL-10 expression. NET-osis was higher only when neutrophils from moderate–severe CF were treated with Pseudomonas aeruginosa, and the process correlated with forced expiratory volume in the first second (FEV1). Phagocytosis was not significantly changed. In conclusion, circulating neutrophils from children with CF showed fewer impaired changes in phenotype than in function. Functional abnormalities, which were already present at the baseline levels in neutrophils, depended on the type of stimuli that mimicked different activation states of these cells at the site of infection.

Today, tourism represents a strong and important economic branch, whether it concerns economically developed and underdeveloped countries as well as developing countries. It can increase employment in almost all countries, regardless of their level of development. Today's moment is marked by pronounced global crises, which again have a strong negative impact on the economic and social aspects of society, both globally and locally. Tourism, due to its characteristics and the positive effects it achieves in the process of realizing all activities in its area, can greatly reduce the percentage of unemployment in local communities. This positive effect of reducing unemployment is reflected in the possibility of employment for all categories of the unemployed, and particularly vulnerable groups of the unemployed such as people with disabilities, women, young people, the long-term unemployed, etc. Encouraging tourism in states or certain regions can have a favourable positive effect on employment within the territory. the same. For countries and regions that have developed tourism and that do not have pronounced problems with unemployment, activities through tourism increase the country's balance of payments as additional income through exports. Underdeveloped regions and countries and developing countries, by increasing activities through tourism, in addition to being an important source of income, realize a particularly important positive effect through the reduction of unemployment rates in them. Many developed countries, among which Austria is the leader, as a highly developed tourist destination for a long time, institutionally, have realized and use the potential offered by tourism to increase employment and actively use it to reduce the unemployment rate. Unfortunately, in our country and its tourist regions, where tourism is often one of the most important economic branches, this has not been done and they still record high rates of unemployment. Tourism in Bosnia and Herzegovina and Sarajevo Canton is a sector that can make a significant contribution to faster economic development. In our country and its regions and cantons, there are great potentials for increasing tourism activities, which will generate a greater number of jobs in tourism as well as tourism-related economic branches. To successfully solve the problem of unemployment in Bosnia and Herzegovina, its regions and cantons, positive experiences of tourism development through selective forms of tourism can be used, also using models of successful experiences from the world and the countries of the European Union. Keywords: tourism, unemployment, selective forms of tourism, European Union unemployment, Sarajevo Canton unemployment.

Abstract Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a p-value < 3.3 × 10–5 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1) to be associated with the COPD risk and two with the LC risk (HLA-C, HLA-B), with statistical significance. We also identified two SNPs located in the IL2RA gene associated with LC (rs2386841; p = 1.86 × 10−4) and COPD (rs11256442; p = 9.79 × 10−3) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.

Characterizing the size distribution of airborne particles carrying SARS-CoV-2 virus is essential for understanding and predicting airborne transmission and spreading of COVID-19 disease in hospitals as well as public and home indoor settings. Nonetheless, few data are currently available on virus-laden particle size distribution. Thus, the aim of this study is reporting the total concentrations and size distributions of SARS-CoV-2- genetic material in airborne particles sampled in hospital and home environments. A nanoMOUDI R122 cascade impactor (TSI, USA) was used to collect size-segregated aerosol down to the sub-micron range in home and in three different hospital environments in presence of infected patients in order to provide the concentration of airborne SARS-CoV-2 genetic material for each particle size range at different sampling locations. Providing one of the largest datasets of detailed size-fractionated airborne SARS-CoV-2 RNA to date, we found that 45.2 % of the total sub- and super-micrometric fractions were positive for SARS-CoV-2 with its genetic material being present in 17.7 % of sub-micrometric (0.18–1 μm) and 81.9 % of super-micrometric (>1 μm) fractions. The highest concentration of SARS-CoV-2 genetic material in total suspended particles (5.6 ± 3.4 RNA copies m−3) was detected in the room occupied with patients with more severe COVID-19 symptoms collected during the patients' high flow nasal oxygen therapy. The highest concentration at certain particle size fraction strongly depends on the sampling environment. However, the contribution of SARS-CoV-2 genetic material was in favour of super-micrometric compared to sub-micrometric particle size range. The evaluation of the individual risk of infection was carried out on the basis of the obtained data considering a hypothetical exposure scenario. The obtained results indicate the necessity of the protective masks in presence of infected subjects, especially while staying for longer period of time in the hospital environments.

The primary goal of this research was to determine the differences in kinematic parameters between the first and second serves in tennis among the elite players of the German league. The sample of respondents in this research consisted of 30 elite male senior players of the German League who have "Leistungklasse" from 1 to 7. The kinematic parameters that were analyzed are: Height of ball impact (KPVUL), Racket speed (KPBRE), Ball speed (KPBLO), The angle at the elbow joint of the arm that hits the ball (KPULZ), Oscillation of the vertical projection of the center of gravity of the body (KPOVP), Jump height (KPVSK), Ball launch height (KPVIL), The point of contact between the ball and the racket "sweetspot" (KPMLR), Ball rotation "Top spin" (KPRLO). The video recording required for kinematic analysis was acquired with two Casio EX-F1 digital cameras at a frequency of 200 images per second. The camera was placed at an angle of 900 in relation to the recording plane, and they were at a distance of 10 m. Space calibration was performed with the help of a calibration frame (200 x 200 cm). We have installed Zepp Tennis Smart Sensor 2.0 in the handle of the Wilson Pro Staff RF97 Autograph racket, using the Zepp Tennis application software. "Kinovea" software was used for service analysis and obtaining kinematic parameters from video recordings. By analyzing the results of the T-test for independent samples, it can be seen that there are statistically significant differences in five of the nine analyzed kinematic parameters : KPBRE – kinematic parameter of racket speed (Sig.=.000), KPBLO – kinematic parameter of ball speed (Sig.=.000), KPULZ – kinematic parameter angle in the elbow joint (Sig.=.000), KPMLR – kinematic parameter point of contact between the ball and the racket (Sig.=.000), as well as a variable KPRLO – kinematic parameter of ball rotation (Sig.=.000). Larger numeric values in variables: KPVUL – kinematic parameter ball impact height, KPOVP – kinematic parameter of oscillation of the vertical projection of the center of gravity of the body, KPVSK – kinematic parameter jump height and KPVIL – kinematic parameter ball impact height, show a difference but it is not enough to be statistically different. Key words: tennis, kinematic analysis, racket speed, Zepp sensor

This article investigates the relationship between the dimensions of the Theory of Planned Behaviour (which includes attitude toward behavior, subjective norm, and perceived control behavior) and entrepreneurial intentions and intrapreneurial intentions, considering entrepreneurial orientation as a moderator. Using the snowball sampling method, cross-sectional data were collected from 437 respondents. After testing for reliability and validity using confirmatory factor analysis, hypotheses were tested using hierarchical regression. The results indicate that the attitudes toward entrepreneurship and perceived behavioral control positively relate to entrepreneurial intentions. In contrast, attitude toward intrapreneurship is the only dimension of the theory of planned behavior positively related to intrapreneurial intentions. The moderating role of entrepreneurial orientation is only significant for the relationship between attitude toward entrepreneurship and entrepreneurial intentions. Based on the results, several recommendations are made for businesses and policymakers to boost entrepreneurial activity among the current labor force.

Multi-criteria decision-making (MCDM) methods have gained increased attention in sustainable engineering, where complex decision-making problems require consideration of multiple criteria and stakeholder perspectives. This review paper provides a comprehensive overview of the different MCDM methods, their applications in sustainable engineering, and their strengths and weaknesses. The paper discusses the concept of sustainable engineering, its principles, and the different areas where MCDM methods have been applied, including energy, manufacturing, transportation, and environmental engineering. Case studies of real-world applications are presented and analyzed, highlighting the main findings and implications for engineering practice. Finally, the challenges and limitations of MCDM methods in sustainable engineering are discussed, and future research directions are proposed. This review contributes to the understanding of the role of MCDM methods in sustainable engineering and provides guidance for researchers and practitioners.

Introduction: The most important biochemical reactions of the human organism take place in the liver, and therefore it represents one of the most important organs for life. Parameters that play an important role in the diagnosis and monitoring of patients are the enzymes ALT, AST, GGT, ALP, and bilirubin. Objective: To evaluate the serum activity of enzymes and bilirubin in patients with liver cirrhosis and liver cancer. Materials and methods: The study included 120 patients aged over 50 years. Among them, 40 patients had liver cirrhosis, 40 had cancer and liver metastases, and 40 patients were apparently healthy (control group). The concentrations of AST, ALT, GGT, and ALP were determined on Abbott Architect i2000sr biochemical analyzer and Dimension analyzer. Results: The study showed that the mean values of the studied parameters were significantly higher in subjects with liver cirrhosis and cancer with liver metastases than in the control group. A statistically significant difference (p <0.05) was found in ALP and bilirubin concentrations between the studied groups. In addition, the study revealed a statistically significant difference (p <0.05) in ALT, AST, and GGT activity between subjects with cancer and the control group and subjects with cirrhosis and the control group. Conclusions: The results confirm that the activities of enzymes ALT, AST, GGT, ALP, and bilirubin were increased in subjects with cirrhosis and cancer compared to the control group.