ABSTRACT Flaviviruses such as the dengue (DENV) and the Zika virus (ZIKV) are important human pathogens causing around 100 million symptomatic infections each year. During infection, small subgenomic flavivirus RNAs (sfRNAs) are formed inside the infected host cell as a result of incomplete degradation of the viral RNA genome by cellular exoribonuclease XRN1. Although the full extent of sfRNA functions is to be revealed, these non-coding RNAs are key virulence factors and their detrimental effects on multiple cellular processes seem to consistently involve molecular interactions with RNA-binding proteins (RBPs). Discovery of such sfRNA-binding host-factors has followed established biochemical pull-down approaches skewed towards highly abundant proteins hampering proteome-wide coverage. Yeast three-hybrid (Y3H) systems represent an attractive alternative approach. To facilitate proteome-wide screens for RBP, we revisited and improved existing RNA-Y3H methodology by (1) implementing full-length ORF libraries in combination with (2) efficient yeast mating to increase screening depth and sensitivity, and (3) stringent negative controls to eliminate over-representation of non-specific RNA-binders. These improvements were validated employing the well-characterized interaction between DDX6 (DEAD-box helicase 6) and sfRNA of DENV as paradigm. Our advanced Y3H system was used to screen for human proteins binding to DENV and ZIKV sfRNA, resulting in a list of 69 putative sfRNA-binders, including several previously reported as well as numerous novel RBP host factors. Our methodology requiring no sophisticated infrastructure or analytic pipeline may be employed for the discovery of meaningful RNA–protein interactions at large scale in other fields.

This paper investigates the use of conceptual metaphor as discourse pheno­menon, especially its persuasive role in political discourse. This study aims to identify conceptual metaphors that are expressed by metaphorical expressions in text corpus, to classify these metaphors by finding their source domains, to examine their conceptual structure and discourse potential. The purpose of the discussion is to describe and interpret social relations expressed by dominant metaphorical concepts that conceptualize political realm in a complex political setting and times of crisis and uprisings. Furthermore, the paper gives an insight into purposes and effects of using conceptual metaphors in this distinct political context. Text corpus consists of political speeches delivered by presi­dents of Tunis, Egypt and Libya during Arab Spring.

Ustikolina market has been mentioned since 1394 for the business of the local population, which was especially engaged in the wax trade. In addition, Du­brovnik merchants were active in Ustikolina very early on. According to some of the leading historians of the medieval period, Ustikolina could not withstand the competition of the nearby, more advanced markets, Goražde and Foča. However, from the content of sources, it is evident that the Ottoman authorities have been recorded revenues from the market tax on the Ustikolina market since the first census of 1468/1469. That means that there were trade activities before that period. In order to improve trade, in the middle of the 16th century, the local judge sent to Porte a written petition to change the weekly market in Ustikolina. It was requested that the market be held on Fridays instead of Saturdays. Local authorities wanted to rationalize and facilitate the activities of the population of Ustikolina and its surroundings and make them able to do the most important weekly tasks on the same day and attend the obligatory Friday prayer. The paper pays special attention to the analysis of the document that Porte sent to the local judge in this regard. The content of the mentioned document reveals the way in which the Ottoman state solved certain problems that were important for the local community, and the holding of the weekly market was one of those. Also, from the document, it can be established that Ustikolina had a local Muslim community, a mosque where the central weekly prayer was performed, a market, and an established market day, which were the basic preconditions for declaring a place for an urban settlement. The paper mentions similar practices from the local area, but also from the main capital of Istanbul, which is one of the indicators to what extent it was centralized the Ottoman state in the 16th century. Based on the above, can be seen the efficiency of the governing apparatus whose administrative ar­rangement in the way of functioning of large and small places was not left to chance. In the concrete example, it can be seen that the issue of establishing and changing the weekly market was resolved officially, which was defined by the state protocol.

Background Classical ST‐T waveform changes on standard 12‐lead ECG have limited sensitivity in detecting acute coronary syndrome (ACS) in the emergency department. Numerous novel ECG features have been previously proposed to augment clinicians' decision during patient evaluation, yet their clinical utility remains unclear. Methods and Results This was an observational study of consecutive patients evaluated for suspected ACS (Cohort 1 n=745, age 59±17, 42% female, 15% ACS; Cohort 2 n=499, age 59±16, 49% female, 18% ACS). Out of 554 temporal‐spatial ECG waveform features, we used domain knowledge to select a subset of 65 physiology‐driven features that are mechanistically linked to myocardial ischemia and compared their performance to a subset of 229 data‐driven features selected by multiple machine learning algorithms. We then used random forest to select a final subset of 73 most important ECG features that had both data‐ and physiology‐driven basis to ACS prediction and compared their performance to clinical experts. On testing set, a regularized logistic regression classifier based on the 73 hybrid features yielded a stable model that outperformed clinical experts in predicting ACS, with 10% to 29% of cases reclassified correctly. Metrics of nondipolar electrical dispersion (ie, circumferential ischemia), ventricular activation time (ie, transmural conduction delays), QRS and T axes and angles (ie, global remodeling), and principal component analysis ratio of ECG waveforms (ie, regional heterogeneity) played an important role in the improved reclassification performance. Conclusions We identified a subset of novel ECG features predictive of ACS with a fully interpretable model highly adaptable to clinical decision support applications. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04237688.

Sustainable traffic system management under conditions of uncertainty and inappropriate road infrastructure is a responsible and complex task. In Bosnia and Herzegovina (BiH), there is a large number of level crossings which represent potentially risky places in traffic. The current state of level crossings in BiH is a problem of the greatest interest for the railway and a generator of accidents. Accordingly, it is necessary to identify the places that are currently a priority for the adoption of measures and traffic control in order to achieve sustainability of the whole system. In this paper, the Šamac–Doboj railway section and passive level crossings have been considered. Fifteen different criteria were formed and divided into three main groups: safety criteria, road exploitation characteristics, and railway exploitation characteristics. A novel integrated fuzzy FUCOM (full consistency method)—fuzzy PIPRECIA (pivot pairwise relative criteria importance assessment) model was formed to determine the significance of the criteria. When calculating the weight values of the main criteria, the fuzzy Heronian mean operator was used for their averaging. The evaluation of level crossings was performed using fuzzy MARCOS (measurement of alternatives and ranking according to compromise solution). An original integrated fuzzy FUCOM–Fuzzy PIPRECIA–Fuzzy MARCOS model was created as the main contribution of the paper. The results showed that level crossings 42 + 690 (LC4) and LC8 (82 + 291) are the safest considering all 15 criteria. The verification of the results was performed through four phases of sensitivity analysis: resizing of an initial fuzzy matrix, comparative analysis with other fuzzy approaches, simulations of criterion weight values, and calculation of Spearman’s correlation coefficient (SCC). Finally, measures for the sustainable performance of the railway system were proposed.

Este é um estudo prospectivo, transversal, descritivo com abordagem quantitativa, desenvolvido de 2017 a 2018, numa unidade municipal de saúde de Belém-PA; e que tem como objetivo avaliar o conhecimento de comunicantes de hanseníase antes e após uma ação educativa, acerca dos sinais e sintomas da doença, os riscos de adoecimento e as formas de prevenção. Fizeram parte da pesquisa 93 comunicantes, das quais 48% acreditava que a doença era transmitida por utensílios, assim como 54% afirmava ser uma patologia letal. Existiam lacunas significativas de conhecimento sobre a hanseníase por parte dos contatos intradomiciliares contatados. Identificou-se impacto positivo da ação educativa, com aumento do nível de conhecimento sobre a hanseníase entre os comunicantes. 

Abstract Seven spider mite species were recorded for the first time in Serbia: Bryobia macedonica Hatzinikolis & Panou, 1996 and Bryobia querci Hatzinikolis & Panou, 1997 from Bryobiinae, and Eutetranychus orientalis Klein, 1936; Oligonychus bicolor Banks, 1894; Oligonychus platani McGregor, 1950 Tetranychus canadensis McGregor, 1950 and Tetranychus ludeni Zacher, 1913 from Tetranychinae. Together with previously reported data, these findings raise the number of known tetranychid species in Serbia to 44, the second highest number of spider mite species recorded in the Balkan countries. The records of O. bicolor and T. canadensis are also the first ones on the Balkan Peninsula. The most frequent species were T. ludeni and E. orientalis, found in 24 and 13 out of 57 sampling locations. Spider mites were recorded on host plants in four basic habitat types, but predominantly in cultivated habitats and woodlands. A total of 27 plant species from nine families were recorded as hosts for newly recorded spider mites, including 12 plant species as new hosts for four tetranychids, and three plant species as new hosts for the family Tetranychidae. Plant family Rosaceae had the highest number of new hosts (7) and harbored the highest number of spider mite species (5). Tetranychus ludeni had the highest number of host plants (11) with two plant species as its new hosts. Oligonychus bicolor was found on eight host plants including five new hosts for this species and one new host for the family Tetranychidae. The other two new hosts for the family Tetranychidae harbored O. platani and B. querci, respectively. Symptoms of heavy infestations by E. orientalis and T. ludeni were recorded on host plants in several locations.

Six blood groups (Rh, MN, Duffy, Kidd, Kell, and Lutheran) were investigated among three major ethnic groups (Bosniaks, Bosnian Croats, and Bosnian Serbs), as well as 10 regional subpopulations across Bosnia and Herzegovina (B&H): Krajina; Posavina; northeastern, eastern, middle, and central Bosnia; Sarajevo region; eastern, central, and western Herzegovina. This is the first study that introduces the molecular genetic typing of five blood groups within the B&H population, with the exception of the RhD blood group. The sample consisted of 450 buccal swabs from unrelated individuals. Five blood group systems (RhD, RhC, RhE, Kidd, MN) were genotyped by PCR with sequence specific primers, while three blood group systems (Kell, Duffy, Lutheran) were genotyped by the PCR-restriction-fragment-length polymorphism method. Minor variation of genetic diversity was observed within the three major B&H ethnic groups, as well as within the 10 subpopulations stratified according to geographical criteria. No genetic differentiation among ethnic groups was noticed. These results are in agreement with the results of previous studies based on different molecular genetics markers, which indicate that the three B&H ethnic groups belong to the same gene pool. A similar level of genetic variance was observed within regional subpopulations, with no significant genetic differentiation among them. Comparison of intrapopulation genetic diversity of the B&H population with other European and non-European populations, based on three loci (RHD, MN, and KEL), clearly show that the level of genetic diversity of the B&H population is within the European range.

BACKGROUND Aim of our study is to provide an insight into the genetic expression landscape of GREB1L, ITGA10 and CRELD2 which are important in human genitourinary tract development which might help elucidate the critical stages for the onset of kidney anomalies. METHODS Morphological parameters were analyzed using immunohistochemistry on human foetal (13-38 w) and postnatal (1.5 and 7.5y) human kidney samples. RESULTS GREB1L marker had a strong intensity and the highest rate in proximal tubules (PTC) of 1.5 years' kidney (90.25%). In the distal tubules (DCT) there were statistically significant differences in 13 w, 15 w, 16 w, 21 w, 38 w and 7.5y regarding 1.5y (Kruskal-Wallis test, p < 0.001). There was significantly more GREB1L in the glomeruli at 21 w and 38 w in regard to all other stages (Kruskal-Wallis test, p < 0.01). ITGA10 staining intensity was strongest in PCT with the highest rate in 13 w (92.75%), while the lowest rate was found in glomeruli and DCT (Kruskal-Wallis test, p < 0.001). CRELD2 had the strongest staining intensity in PCT with the highest rate in 13 w and 1.5y (92.25%) and lowest in the glomeruli of 7.5 years (24.3 %). In DCT there were statistically significant differences in CRELD2 positive cells in 13 w, 15 w, 16 w, 21 w, 38 w and 7.5y regarding 1.5y (Kruskal-Wallis test, p < 0.01). ITGA10 and CRELD2 co-localised in the postnatal period in DCT. CONCLUSION High kidney expressions of GREB1L, ITGA10 and CRELD2 even in the postnatal period implicate their importance not only for the onset of CAKUT in the case of their mutation but also for maintenance of kidney homeostasis.