Breast cancer is one of the most prevalent diseases among women worldwide and is highly associated with cancer-related mortality. Of the four major molecular subtypes, HER2-positive and triple-negative breast cancer (TNBC) comprise more than 30% of all breast cancers. While the HER2-positive subtype lacks estrogen and progesterone receptors and overexpresses HER2, the TNBC subtype lacks estrogen, progesterone and HER2 receptors. Although advances in molecular biology and genetics have substantially ameliorated breast cancer disease management, targeted therapies for the treatment of estrogen-receptor negative breast cancer patients are still restricted, particularly for TNBC. On the other hand, it has been demonstrated that microRNAs, miRNAs or small non-coding RNAs that regulate gene expression are involved in diverse biological processes, including carcinogenesis. Moreover, circulating miRNAs in serum/plasma are among the most promising diagnostic/therapeutic tools as they are stable and relatively easy to quantify. Various circulating miRNAs have been identified in several human cancers including specific breast cancer subtypes. This review aims to discuss the role of circulating miRNAs as potential diagnostic and prognostic biomarkers as well as therapeutic targets for estrogen-receptor negative breast cancers, HER2+ and triple negative.

Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient’s biology and outcome. We found that WPS can induce the epithelial–mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan–Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients’ survival.

Introduction: The most common cause of myocardial ischemia is atherosclerotic epicardial coronary artery disease, present in 90% of patients. Risk factors positively correlate with the onset, development and subsequent complications of atherosclerotic disease. Aim: Determine the percentage frequency of classic risk factors for coronary disease in patients with non-ST segment elevation myocardial infarction (NSTEMI), with regard to gender. Methods: A retrospective study was conducted on 600 respondents, treated for NSTEMI at the Clinic for Internal Medicine of the University Clinical Center (UKC) Tuzla, in the period from June 2016 to December 2019. Results: Overall, smoking was the leading risk factor (65%), followed by hypertension (58%), hyperlipoproteinemia (39%), overweight (33%), positive family burden (30%) and diabetes mellitus (19%). In male patients, the leading risk factor was smoking, rating at 74%, while in female patients – it was hypertension at 67%. In younger groups of patients leading risk factors were smoking and a positive family burden. Conclusion: With adequate prevention and treatment measures, a significant reduction in the prevalence of the cardiovascular disease can be achieved, since the risk factors for its development have long been known. Quitting smoking is one of the most effective secondary prevention measure since it reduces the reinfarction risk rate by 50%. Knowledge of coronary risks, as well as success in reducing them, can greatly contribute to patients’ overall sense of contentment and significantly raise their self-confidence.

Abstract One of the biggest challenges facing the education system in Bosnia and Herzegovina is bridging the gap between the current state of higher education and the demand for research, innovation and a robust STEM (Science, Technology, Engineering, Mathematics) curriculum. Higher education instiutions (HEIs) face poor R&D infrastructure while companies struggle with limited resources and the lack of internal researchers, all of which affect their capabilities to utilize university knowledge and research that will lead to further collaborations and innovations in STEM. Universities are primarily seen as a source of future employees as well as as a source of knowledge and innovation. This study aims to provide an overview and systematic analysis of the current state of scientific and research infrastructure and human resources in public and private universities located in the Sarajevo Canton region. This is done by using primary data collected through semi-structured interviews and a self-reporting comprehensive questionnaire in order to identify areas where further reforms and investments are needed. An analysis of the secondary data sources, such as current strategic documents and the existing assessments of education, was conducted. Consequently, this study offers several practical implications, including policy recommendations in areas such as higher education, research infrastructure and academic excellence, cooperation with the private sector, and IT infrastructure improvements.

The plant Citrullus colocynthis, a member of the squash (Cucurbitaceae) family, has a long history in traditional medicine. Based on the ancient knowledge about the healing properties of herbal preparations, plant-derived small molecules, e.g., salicylic acid, or quinine, have been integral to modern drug discovery. Additionally, many plant families, such as Cucurbitaceae, are known as a rich source for cysteine-rich peptides, which are gaining importance as valuable pharmaceuticals. In this study, we characterized the C. colocynthis peptidome using chemical modification of cysteine residues, and mass shift analysis via matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. We identified the presence of at least 23 cysteine-rich peptides in this plant, and eight novel peptides, named citcol-1 to -8, with a molecular weight between ~3650 and 4160 Da, were purified using reversed-phase high performance liquid chromatography (HPLC), and their amino acid sequences were determined by de novo assignment of b- and y-ion series of proteolytic peptide fragments. In silico analysis of citcol peptides revealed a high sequence similarity to trypsin inhibitor peptides from Cucumis sativus, Momordica cochinchinensis, Momordica macrophylla and Momordica sphaeroidea. Using genome/transcriptome mining it was possible to identify precursor sequences of this peptide family in related Cucurbitaceae species that cluster into trypsin inhibitor and antimicrobial peptides. Based on our analysis, the presence or absence of a crucial Arg/Lys residue at the putative P1 position may be used to classify these common cysteine-rich peptides by functional properties. Despite sequence homology and the common classification into the inhibitor cysteine knot family, these peptides appear to have diverse and additional bioactivities yet to be revealed.

In medium-size, spiny striatal neurons of the direct pathway, dopamine D1- and adenosine A1-receptors are coexpressed and are mutually antagonistic. Recently, a mutation in the gene encoding the A1-receptor (A1R), A1R-G279S7.44, was identified in an Iranian family: two affected offspring suffered from early-onset l-DOPA–responsive Parkinson’s disease. The link between the mutation and the phenotype is unclear. Here, we explored the functional consequence of the G279S substitution on the activity of the A1-receptor after heterologous expression in HEK293 cells. The mutation did not affect surface expression and ligand binding but changed the susceptibility to heat denaturation: the thermodynamic stability of A1R-G279S7.44 was enhanced by about 2 and 8 K when compared with wild-type A1-receptor and A1R-Y288A7.53 (a folding-deficient variant used as a reference), respectively. In contrast, the kinetic stability was reduced, indicating a lower energy barrier for conformational transitions in A1R-G279S7.44 (73 ± 23 kJ/mol) than in wild-type A1R (135 ± 4 kJ/mol) or in A1R-Y288A7.53 (184 ± 24 kJ/mol). Consistent with this lower energy barrier, A1R-G279S7.44 was more effective in promoting guanine nucleotide exchange than wild-type A1R. We detected similar levels of complexes formed between D1-receptors and wild-type A1R or A1R-G279S7.44 by coimmunoprecipitation and bioluminescence resonance energy transfer. However, lower concentrations of agonist were required for half-maximum inhibition of dopamine-induced cAMP accumulation in cells coexpressing D1-receptor and A1R-G279S7.44 than in those coexpressing wild-type A1R. These observations predict enhanced inhibition of dopaminergic signaling by A1R-G279S7.44 in vivo, consistent with a pathogenic role in Parkinson’s disease. SIGNIFICANCE STATEMENT Parkinson’s disease is caused by a loss of dopaminergic input from the substantia nigra to the caudate nucleus and the putamen. Activation of the adenosine A1-receptor antagonizes responses elicited by dopamine D1-receptor. We show that this activity is more pronounced in a mutant version of the A1-receptor (A1R-G279S7.44), which was identified in individuals suffering from early-onset Parkinson’s disease.

Evidence on early achievements, challenges and opportunities would help low-income and middle-income countries (LMICs) accelerate implementation of health and health-related sustainable development goals (HHSDGs). A series of country-specific and multicountry consultative meetings were conducted during 2018–2019 that involved 15 countries across five regions to determine the status of implementation of HHSDGs. Almost 120 representatives from health and non-health sectors participated. The assessment relied on a multidomain analytical framework drawing on existing public health policy frameworks. During the first 5 years of the sustainable development goals (SDGs) era, participating LMICs from South and Central Asia, East Africa and Latin America demonstrated growing political commitment to HHSDGs, with augmentation of multisectoral institutional arrangements, strengthening of monitoring systems and engagement of development partners. On the other hand, there has been limited involvement of civic society representatives and academia, relatively few capacity development initiatives were in place, a well-crafted communication strategy was missing, and there is limited evidence of additional domestic financing for implementing HHSDGs. While the momentum towards universal health coverage is notable, explicit linkages with non-health SDGs and integrated multisectoral implementation strategies are lacking. The study offers messages to LMICs that would allow for a full decade of accelerated implementation of HHSDGs, and points to the need for more implementation research in each domain and for testing interventions that are likely to work before scale-up.

Abstract There is a growing body of research in the field of interaction between automated vehicles and other road users in their vicinity. To facilitate such interactions, researchers and designers have explored designs, and this line of work has yielded several concepts of external Human-Machine Interfaces (eHMI) for vehicles. Literature and media review reveals that the description of interfaces is often lacking in fidelity or details of their functionalities in specific situations, which makes it challenging to understand the originating concepts. There is also a lack of a universal understanding of the various dimensions of a communication interface, which has impeded a consistent and coherent addressal of the different aspects of the functionalities of such interface concepts. In this paper, we present a unified taxonomy that allows a systematic comparison of the eHMI across 18 dimensions, covering their physical characteristics and communication aspects from the perspective of human factors and human-machine interaction. We analyzed and coded 70 eHMI concepts according to this taxonomy to portray the state of the art and highlight the relative maturity of different contributions. The results point to a number of unexplored research areas that could inspire future work. Additionally, we believe that our proposed taxonomy can serve as a checklist for user interface designers and researchers when developing their interfaces.

: Culture is shared assumptions, beliefs, attitudes, or beliefs that helps individuals or groups to respond various actions or events that they face in daily life. Besides, leadership is art of influencing others to achieve desired objectives in organizations. On one hand, the growing body of the literature argues the effectiveness of the transformational leadership. On the other hand, cultural background has different impacts on this leadership style. In this respect, current paper aims to point out some consequences of transformational leadership in various cultures. As a result, it has been observed that because of its charismatic and simulative characteristics, these leaders are more effective on developed countries and innovative characteristics rather than group oriented and depressed cultures.

Background: Cancer patients are particularly vulnerable to COVID-19, partially owing to their compromised immune systems and curbed or cut cancer healthcare services caused by the pandemic. As a result, cancer caregivers may have to shoulder triple crises: the COVID-19 pandemic, pronounced healthcare needs from the patient, and elevated need for care from within. While technology-based health interventions have the potential to address unique challenges cancer caregivers face amid COVID-19, limited insights are available. Thus, to bridge this gap, we aim to identify technology-based interventions designed for cancer caregivers and report the characteristics and effects of these interventions concerning cancer caregivers’ distinctive challenges amid COVID-19. Methods: A systematic search of the literature will be conducted in PubMed, PsycINFO, CINAHL, and Scopus from the database inception to the end of March, 2021. Articles that center on technology-based interventions for cancer caregivers will be included in the review. The search strategy will be developed in consultation with an academic librarian who is experienced in systematic review studies. Titles, abstracts, and full-text articles will be screened against eligibility criteria developed a priori. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedures will be followed for the reporting process. Conclusions: COVID-19 has upended cancer care as we know it. Findings of this study can shed light on evidence-based and practical solutions cancer caregivers can utilize to mitigate the unique challenges they face amid COVID-19. Furthermore, results of this study will also offer valuable insights for researchers who aim to develop interventions for cancer caregivers in the context of COVID-19. In addition, we also expect to be able to identify areas for improvement that need to be addressed in order for health experts to more adequately help cancer caregivers weather the storm of global health crises like COVID-19 and beyond. Study Protocol Registration: PROSPERO CRD42020196301

Parental and familial factors influence numerous aspects of adolescents’ lives, including their physical activity level (PAL). The purpose of this study was to evaluate the changes in PAL which occurred during the COVID-19 pandemic, and to evaluate influence of sociodemographic and parental/familial factors on PAL levels before and during pandemic in adolescents from Bosnia and Herzegovina. The sample included 688 adolescents (15–18 years of age; 322 females) who were tested on two occasions: in January 2020 (baseline; before the COVID-19 pandemic) and in April 2020 (follow-up; during the COVID-19 pandemic lockdown). Variables included PAL (measured by the Physical Activity Questionnaire for Adolescents–PAQ-A) as well as sociodemographic-, parental-, and familial factors. A significant decline in PALs was recorded between baseline and follow-up (t-test: 11.88, p < 0.001). Approximately 50% of adolescents underwent sufficient PAL at baseline, while only 24% of them were achieving sufficient PAL at the time of follow-up measurement. Paternal education was positively correlated (OR (95%CI): baseline: 6.63 (4.58–9.96), follow-up: 3.33 (1.19–7.01)), while familial conflict was negatively correlated (baseline: 0.72 (0.57–0.90), follow-up: 0.77 (0.60–0.99)) with PALs before and during the pandemic. This study highlights the importance of the parent–child relationship and parental/familiar support in promoting physical activity both during regular life and during crises and health challenging situations like the COVID-19 pandemic.