PURPOSE The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1/2 mutations treated with talazoparib are reported. METHODS Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Patients with germline BRCA-mutated human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer were not eligible for this study. Primary end point was disease control (DC) determined by investigator assessment of objective response (OR) or stable disease (SD) of at least 16 weeks duration (SD16+). The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = 0.82; α = .10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety. RESULTS Twenty-eight patients (20 cancer types) with BRCA1/2 mutations were enrolled from December 2019 to September 2021 and collapsed into a single histology pooled cohort for analysis. All patients were evaluable for efficacy. One complete response, nine partial response, and six SD16+ were observed for DC and OR rates of 57% (one-sided 90% CI, 43 to 100) and 36% (95% CI, 19 to 56), respectively. The null hypothesis of a 15% DC rate was rejected (P < .001). Patients with OR had the following tumor types: breast (2), nonmelanoma skin, mesothelioma, stomach, uterus, non-small cell lung cancer, ovary, hepatocellular carcinoma, and pancreas. Thirteen patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to talazoparib. All were consistent with the drug label except bilirubin increase and hyponatremia (both grade 3 AEs). CONCLUSION Talazoparib demonstrated antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations, including cancer types for which poly ADP-ribose polymerase inhibitors are not yet US Food and Drug Administration-approved.

Introduction: Vaccines for protection against 10 infectious diseases are available in the Program of Regular Immunization in the Federation of Bosnia and Herzegovina. These vaccines save the lives of up to 3 million people worldwide every year. The latest report of the Institute of Public Health of the Federation of Bosnia and Herzegovina on regular immunization carried out during 2020 shows that the rate of vaccination of children during the 2019 coronavirus disease (COVID-19) pandemic with regular vaccines has decreased compared to previous years. Such a situation in the health system leads to a potential risk of outbreaks of infectious diseases that are prevented by vaccination.Objective: To examine the impact of the COVID-19 pandemic on the regular immunization of children in the Mostar Health Center.Materials and methods: A retrospective cross-sectional epidemiological study was conducted. Data on regular immunization of children from theMostar Health Center, Herzegovina-Neretva County in the Federation of Bosnia and Herzegovina from 2017, 2018, 2021 and 2022 were used.Results: A statistically significant difference was obtained in vaccination against measles, mumps and rubella during a period of four years. Vaccination with the mentioned vaccines was significantly higher in 2017 and 2018 than in 2021 and 2022.Conclusion: It was shown that the COVID-19 pandemic affected the regular immunization of children in the Mostar Health Center.Keywords: regular immunization of children, COVID 19 pandemic, MMR vaccine, Mostar

ntroduction: The thyroid hormone secretion disorders may be hyperthyroidism (reduced TSH levels and increased levels of FT3 and FT4) and subclinical hyperthyroidism (decreased concentration of TSH with normal FT3 and FT4).Aim: To investigate levels of thyroid hormones (TSH, FT3, and FT4) in patients with hyperthyroidism or subclinical hyperthyroidism treated at Tuzla Blue Clinic.Materials and methods:The study included 120 patients divided into three groups: a control group, groups with respondents who have hyperthyroidism, and a group of patients with subclinical hyperthyroidism. The concentrations of the hormones TSH, FT3, and FT4 were analyzed. The determination was carried out on the device IMMULITE 1 Siemens using the immunochemistry method. Results:TSH between our group investigated the existence of significant statistical differences between the control group and the group with hyperthyroidism (p<0.0001) and between the control group and the group withsubclinical hyperthyroidism (p=0.0001), and the parameter FT3 showed that a statistically significant difference exists between the control group and the group with hyperthyroidism (p<0.0001), and between patients with hyperthyroidism andsubclinical hyperthyroidism (p<0.0001). For FT4, we found a statistically significant difference between the control group and the group with hyperthyroidism (p<0.0001) and between groups with hyperthyroidism and subclinical hyperthyroidism (p <0.0001).Conclusions: The concentration of TSH is reduced in both hyperthyroidism and subclinical hyperthyroidism. The serum concentrations of FT3 and FT4 are elevated in hyperthyroidism, while in subclinical hyperthyroidism, the serum concentrations of FT3 and FT4 stand in the reference area.Keywords:Thyrotropin, thyroxine, TSH, FT3, FT4, hyperthyroidism

Simple Summary This study explores hypoxia-inducible factors (HIFs) in glioblastoma development, progression, and treatment. Reviewing 104 relevant studies, it highlights diverse global contributions, with China leading at 23.1%. The most productive year was 2019, contributing 11.5% of the studies. Key factors studied included HIF1α, HIF2α, osteopontin, and cavolin-1, involving pathways such as GLUT1, GLUT3, VEGF, PI3K-Akt-mTOR, and ROS. HIF expression correlates with glioblastoma progression, survival, neovascularization, glucose metabolism, migration, and invasion. Overcoming treatment resistance and the lack of biomarkers is crucial for integrating HIF-related therapies into glioblastoma treatment to improve patient outcomes. Abstract Background: The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas. Methodology: The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction. Results: Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion. Conclusion: Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.

Introduction: Influenza is an acute, infectious disease of the human respiratory system, caused byinfluenza viruses. Since it is a vaccine-preventable disease, medical students as future health professionals should be involved in programs promoting the importance of flu vaccination.Aim: Compare knowledge, attitude and practice of vaccination against influenza among students of the firstand sixthyear of School of Medicine of University of Mostar.Subjects and methods: The study included a total of81 students of the School of Medicine of the University of Mostar. The data were collected using a questionnaire that consists from demographic data of the respondents andtwenty questions with the offered answers about the knowledge, attitude and practice of vaccination against influenza.Results: Sixth-year students showed greater knowledge about contraindications for vaccination. Both groups of students showed mainly positive attitudes about influenza vaccination. No surveyed student was vaccinated against influenza and many of them reasoned that influenza is not a serious illness.Conclusions: Despite good knowledge and mostly positive attitudes about influenza vaccination, no student who participated in the study was vaccinated against influenza. Therefore, it would be useful for medical students to provide additional information about the importance of illness prevention, because they represent an important part of the future workforce in the health system, that will affect the global attitudes of vaccination.Keywords: influenza, vaccination, knowledge, practice, students

Hereditary cardiomyopathies include a diverse spectrum of myocardial disorders characterized by mechanical and electrical abnormalities, among which hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are distinguished. This paper dives into the genetic foundations of these conditions, with a focus on mutations in genes encoding sarcomere proteins, thin filament proteins, and calcium homeostasis regulators. The familial aggregation of cardiomyopathies underscores the substantial genetic component, with autosomal dominant inheritance patterns predominant in some cases. Genetic testing and counseling emerge as pivotal tools for early diagnosis, risk assessment, and the formulation of personalized treatment strategies. The integration of genetic insights into clinical management holds promise for improving patient outcomes and reducing disease burden. Further analysis of the molecular mechanisms underlying hereditary cardiomyopathies is critical for identifying novel therapeutic targets and advancing precision medicine approaches. By comprehensively exploring the genetic underpinnings of cardiomyopathies, this paper contributes to our understanding of these complex diseases and highlights the potential for innovative interventions to enhance patient care in the field of cardiovascular medicine.

Atherosclerosis, one of the leading causes of death in developed countries is characterized by lumen reduction of blood vessels due to local thickening of internal blood vessels caused by plaque/atheroma. It begins in childhood, goes for a long time without manifesting symptoms, increasing with age it begins to seriously threaten health. The most important risk factors for the development of atherosclerotic disease are: hyperlipidemia, hypertension, smoking, diabetes, high fibrinogen, excessive weight, increased level of homocysteine, physical inactivity, heredity and immune response in some diseases. The primary intention of prevention is to preclude the occurrence of risk factors for atherosclerosis, and the secondary is to prevent the development or aggravation of the illness along with the reduction or control of existing risks. There is an increasing number of studies that show that children are overweight, which in adolescence is certainly a risk factor for the onset of many chronic diseases, namely: cardiovascular, type 2 diabetes, orthopedic, and psychological diseases. The obesity epidemic is one of the most serious health problems of today affecting individuals of all ages. Atherosclerosis demands action with the aim of early detection and treatment as well as the reduction of development of risk factors for coronary artery diseases. Finding the most effective preventive measures for obesity in each country requires precise epidemiological data on the number of obese children and youth, as well as on their eating and activity habits.

Aim To investigate how immigrants from the Balkan region experienced their current life situation after living in Sweden for 30 years or more. Materials The study was designed as a qualitative study using data from interviews with informants from five Balkan countries. The inclusion criteria were informants who were immigrants to Sweden and had lived in Sweden for more than 30 years. Five groups comprising sixteen informants were invited to participate in the study, and they all agreed. Results The analysis of the interviews resulted in three main categories: "from someone to no one", "labour market", and "discrimination". All the informants reported that having an education and life experience was worth-less, having a life but having to start over, re-educating, applying for many jobs but often not being answered, and finally getting a job for which every in-formant was educated but being humiliated every day and treated separately as well as being discriminated against. Conclusion Coming to Sweden with all their problems, having an education and work experience that was equal to zero in Sweden, studying Swedish and re-reading/repeating all their education, looking for a job and not receiving answers to applications, and finally getting a job but being treated differently and discriminated against on a daily basis was experienced by all the in-formants as terrible. Even though there are enough similar studies in Sweden, it is always good to write more to help prospective immigrants and prospective employers in Sweden.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, characterized by an increased concentration of catecholamines, free radicals, and inflammatory cytokines, endothelial dysfunction, and increased apoptotic activity. High doses of isoprenaline are used in animal models to induce Takotsubo (TT)-like myocardial injury. The aim of the study was to investigate the antiapoptotic effects of liraglutide in experimental TTS and its role in the NF-κB pathway. Wistar rats were pretreated with liraglutide for 10 days, and on days 9 and 10, TT-like myocardial injury was induced with isoprenaline. After the sacrifice on day 11, hearts were isolated for histopathological and immunohistochemical analysis. Liraglutide reduced isoprenaline-induced cardiomyocyte apoptosis by decreasing cleaved caspase-3 (CC3), BCL-2-associated X protein (BAX), and NF-κB and increasing B-cell lymphoma/leukemia-2 (BCL-2). An increase in NF-κB in isoprenaline-treated rats was in positive correlation with proapoptotic markers (BAX and CC3) and in negative correlation with antiapoptotic marker BCL-2. Liraglutide increased BCL-2 and decreased NF-κB, BAX, and CC3, preserving the same correlations of NF-κB to apoptotic markers. It is concluded that liraglutide protects cardiomyocytes against isoprenaline-induced apoptosis in experimental TT-like myocardial injury through downregulation of the NF-κB pathway.

Simple Summary A total laryngectomy and/or pharyngectomy is an important therapy modality for advanced primary and recurrent laryngeal and hypopharyngeal squamous cell carcinoma. The surgical margins are an important prognostic factor. Resection margins for head and neck cancer surgery are clear >5 mm, close 1–5 mm and positive <1 mm. However, the anatomy of the larynx and hypopharynx is complex and resections are constrained by the anatomical relationship with the surrounding structures. The aim of this study is to investigate if a margin >5 mm is feasible. Clear resection margins are not always feasible in some resection surfaces in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for the maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery. Abstract Background: Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin >5 mm is advised by the Royal College of Pathologists. However, this cannot always be achieved during laryngeal and hypopharyngeal surgery. The aim of this study is to identify the resection surfaces and measure the maximum feasible margins per subsite. The clinical relevance of these maximum feasible resection margins were analyzed in this descriptive anatomical study. Methods: head and neck surgeons and a pathologist from the Erasmus MC performed a total laryngectomy and laryngopharyngectomy on a head and neck specimen specifically available for research. Results: For a total laryngectomy, resection margins >5 mm were not feasible for the ventral and dorsal resection surface. For a total laryngopharyngectomy, resection margins >5 mm were not feasible for the ventral, dorsal and lateral resection surface. Conclusion: Clear resection margins, defined as a margin >5 mm, are not always feasible in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery.

Aim To investigate an association between eye injury and later academic and social performance. Materials A retrospective longitudinal study of taking measurements multiple times was conducted including all severe eye injuries admitted during 2011-2017 at the main regional clinic to investigate changes in academic success and social inclusion before and after an injury. Parents/caregivers were surveyed asking questions on academic performance, and community/social involvement. In 2023 data on employment status were obtained. Kappa (ĸ) and non-parametric Wilcox-on signed-rank test for multiple comparisons were used. For association of employment status and post-injury visual acuity Fisher score was tested. Results The total sample for assessing social inclusion and academic success was 36 and 25 children, respectively. In the following academic year ĸ agreements decreased from 0.88 (p<0.001) comparing pre-injury with a one-year post to 0.5106 (p<.0001) in the second year and 0.4750 (p=0.003) in the third, suggesting a deteriorating trend. A comparison of academic success before injury to two and three years after injury showed the trend significantly worsening with time (p=0.005, and 0.003, respectively). No association between an eye injury and social inclusion, as well as between employment and final visual acuity was noticed. Conclusion Our findings suggest no association between social inclusion, employment, and eye trauma, while in later years academic success may be more impacted by the eye injury. Due to eye injury unpredictability in childhood age, both an informed and supportive climate environment at home and school is essential to minimize deleterious responses to eye trauma.

Aim To investigate prognostic significance of preoperative levels of the Carbohydrate anti-gen 19-9 (CA 19-9) in patients with stage III rectal adenocarcinoma who underwent a treatment at the Clinical Centre of the University of Sarajevo. Materials A retrospective cohort study included 84 patients who underwent radical anterior rectal resection due to grade III rectal adenocarcinoma, followed by adjuvant chemotherapy according to the FOLFOX protocol (Oxaliplatin, Leucovorin, 5-Fluorouracil (5-FU)). The patients were divided into two groups according to CA 19-9 values (≥27 U/mL and <27 U/mL, respectively). Results High pre-operative CA 19-9 values predicted an increased probability of postoperative metastases, especially liver, lung and abdominopelvic metastases, as well as three-year disease-free survival (3Y-DFS) and three-year overall survival (3Y-OS). The 3Y-DFS rate for patients with high CA 19-9 was 64.5%, while for those with low CA 19-9 it was 87.2%. The 3Y-OS rate for patients with high CA 19-9 was 89.8%, while for those with low CA 19-9 it was 65.7%. Univariate and multivariate regression analysis confirmed that a high level of CA 19-9 is an independent predictor for DFS and OS shorter than three years. Conclusion Pre-operatively elevated values of CA 19-9 in rectal adenocarcinoma have a significant role in predicting the outcome in patients with stage III rectal adenocarcinoma.

This paper presents a system that is able to detect physical intrusion in a specific space based on temperature and humidity change. This specific space was housing hardware components important for information security management infrastructure. Presented system is able to predict that two spaces are connected and that there is a physical breach in protected space. The presented prediction approach involves identifying patterns in historical data, where the subsequent outcomes are already known in advance, and validating these patterns using more recent data. System is implemented using k-Nearest Neighbours, Random Forest, and Support Vector Machine algorithms in Python programming language on Raspberry Pi. Real observed data to predict if specific temperature and humidity indicates intrusion were used. This approach can be used to detect intrusions in the room or in other closed space. More specifically thermal equilibrium phenomenon between two spaces after barrier between them are opened was monitored. Through process of supervised learning using labelled data, system was able to detect intrusion by using k-nearest neighbours, random forest, and support vector machine with different accuracy. Presented model shows better results using k-nearest neighbours and support vector machine with accuracy of 100% compared to random forest with accuracy of 95%. The system is low cost because of cheap Raspberry Pi controller and sensors.