Novel benzo[b]thienyl‐ and 2,2′‐bithienyl‐derived benzothiazoles and benzimidazoles were synthesized to study their antiproliferative and antitrypanosomal activities in vitro. Specifically, we assessed the impact that amidine group substitutions and the type of thiophene backbone have on biological activity. In general, the benzothiazole derivatives were more active than their benzimidazole analogs as both antiproliferative and antitrypanosomal agents. The 2,2′‐bithienyl‐substituted benzothiazoles with unsubstituted and 2‐imidazolinyl amidine showed the most potent antitrypanosomal activity, and the greatest selectivity was observed for the benzimidazole derivatives bearing isopropyl, unsubstituted and 2‐imidazolinyl amidine. The 2,2′‐bithiophene derivatives showed most selective antiproliferative activity. Whereas the all 2,2′‐bithienyl‐substituted benzothiazoles were selectively active against lung carcinoma, the benzimidazoles were selective against cervical carcinoma cells. The compounds with an unsubstituted amidine group also produced strong antiproliferative effects. The more pronounced antiproliferative activity of the benzothiazole derivatives was attributed to different cytotoxicity mechanisms. Cell cycle analysis, and DNA binding experiments provide evidence that the benzimidazoles target DNA, whereas the benzothiazoles have a different cellular target because they are localized in the cytoplasm and do not interact with DNA.

With the rapid deployment of quantum computers and quantum satellites, there is a pressing need to design and deploy quantum and hybrid classical-quantum networks capable of exchanging classical information. In this context, we conduct the foundational study on the impact of a mixture of classical and quantum noise on an arbitrary quantum channel carrying classical information. The rationale behind considering such mixed noise is that quantum noise can arise from different entanglement and discord in quantum transmission scenarios, like different memories and repeater technologies, while classical noise can arise from the coexistence with the classical signal. Towards this end, we derive the distribution of the mixed noise from a classical system’s perspective, and formulate the achievable channel capacity over an arbitrary distributed quantum channel in presence of the mixed noise. Numerical results demonstrate that capacity increases with the increase in the number of photons per usage.

Background The World Health Organization’s strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs. Objective We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform. Methods The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities. Results Seven European countries were selected, covering Europe’s geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence–based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors. Conclusions This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.

Bosnia and Herzegovina is ranked 73rd in the Global Gender Gap Index 2022. A questionable democratisation process, ethnonationalism, and changes in the political culture strongly affected gender equality, participation, and representation in Bosnia and Herzegovina. This article tackles the impact of preferential voting on the representation of women in the local councils following the last Local Elections in Bosnia and Herzegovina. The effect of gender quotas and placement mandates are examined across the following determinants: electoral unit magnitude, local community urbanisation rate, ethnic composition of municipalities, and ideological foundation of political parties. To test the main objectives and research questions, this paper examines the impact of preferential voting on gender political representation. A complete dataset for all candidates and municipalities of the 2020 Local Elections, officially released by the State Election Commission, was used. The descriptive analysis indicates that 19.86% of women candidates have been elected to the local councils. With regards to the residence, female candidates from rural areas have a lower tendency of being elected than candidates from highly urban municipalities. Regarding ethnicity, the number of seats won by female candidates was the largest for candidates with a Serb majority, followed by the Bosniak and the Croat ones. When considering political orientation, female candidates from parties with centrist political orientation have a higher tendency of being elected, closely followed by female candidates from parties with a leftist orientation.  Keywords: Gender Gap; Preferential Voting; Representation; Electoral Systems; 2020 Local Elections; Bosnia and Herzegovina

Mullite and mullite–alumina ceramics materials with dominance of the mullite phase are used in different areas of technology and materials science. Porous mullite ceramics materials can be used simultaneously as refractory heat insulators and also as materials for constructional elements. The purpose of this work was to investigate the WO3 nanoparticle influence on the evolution of the aluminum tungstate and zircon crystalline phases in mullite ceramics due to stabilization effects caused by different microsize ZrO2 and WO3. The use of nano-WO3 prevented the dissociation of zircon in the ceramic samples with magnesia-stabilized zirconia (MSZ), increased porosity by approximately 60 ± 1%, increased the intensity of the aluminum tungstate phase, decreased bulk density by approximately 1.32 ± 0.01 g/cm3, and increased thermal shock resistance by ensuring a loss of less than 5% of the elastic modulus after 10 cycles of thermal shock.

The m ain objective of this paper is to explore the potential of the qualitative research paradigm in addressing complex topics related to identity formation and development. There has been a shift in conceptualizations of education’s purpose, with scholars arguing that the paradigm of identity formation (rather than the paradigm of preparation) should be promoted in educational contexts. This implies that education should aim to enhance personhood and facilitate the formation of personal identities in young individuals. Traditional quantitative studies, relying on statistical analyses of numerical data, are becoming less effective in providing insights into the increasingly diverse pathways of human development and the dynamic environments in which they take place. Quantification of human experience and development is encountering a growing pushback in the postmodernity. Conversely, the qualitative research paradigm offers a fresh and authentic perspective by delving into real-life biographies and encompassing the entirety of human experience. However, it is important to note that the qualitative paradigm has specific epistemological characteristics that define the scope of inquiry it generates.

The objective of this paper was to create an economical and abecedarian 3D printing method for the production of solid microneedles, as a more efficient transdermal drug delivery method, for day-to-day use in companion animals. The process of 3D printing was conducted using two types of 3D printers, utilizing the FDM and SLA printing techniques. Modulus of Elasticity was calculated for the determination of mechanical properties of the material, wherethe printed specimen was subjected to axial loading, and deformations were measured using an optical scanner. Post-processing was conducted by washing microneedles in isopropyl alcohol, followed by UV curing. The procedure of testing penetration capabilities was conducted at two sites of cat skin: Auris externa and the lateral part of the abdomen. The SLA printing method was more precise, resulting in higher quality microneedles for animal use compared to the FDM printing technique. Modulus of Elasticity was calculated and the value E=0.9 GPa can be used. Testing proved that the printed model was able to penetrate the skin at the tested sites. The use of microneedles is simple and economical, and therefore has wide applications in small animal practice. Veterinarians can access microneedle design repositories and print them for more effective transdermal drug delivery. The multifunctionality and transferability of the design in the present study ensure that it can be further modified to provide personalized therapy.

The purpose of this study was to preliminary analyze the financial literacy in Bosnia and Herzegovina by considering three main dimensions: interest, inflation, and diversification. The target population was working-age individuals (18–65 years old). By using a cross-sectional questionnaire-based survey, 638 useful responses were collected. The data was presented through a series of descriptive statistics and frequencies. The results present the extent of financial literacy by considering several demographic factors, such as gender, age category, education, and an individual monthly income, as well as a comparative assessment with previous studies. The findings provide evidence of moderate financial literacy in Bosnia and Herzegovina as every third (fourth) respondent was able to answer correctly all three questions addressing financial literacy application (definitions). Similarly, to previous studies, financial literacy depends on the income, education, and age of respondents as well. The study is a pioneer one and extends the literature by examining this important construct within Bosnia and Herzegovina.

Patulin synthase (PatE) from Penicillium expansum is a flavin‐dependent enzyme that catalyses the last step in the biosynthesis of the mycotoxin patulin. This secondary metabolite is often present in fruit and fruit‐derived products, causing postharvest losses. The patE gene was expressed in Aspergillus niger allowing purification and characterization of PatE. This confirmed that PatE is active not only on the proposed patulin precursor ascladiol but also on several aromatic alcohols including 5‐hydroxymethylfurfural. By elucidating its crystal structure, details on its catalytic mechanism were revealed. Several aspects of the active site architecture are reminiscent of that of fungal aryl‐alcohol oxidases. Yet, PatE is most efficient with ascladiol as substrate confirming its dedicated role in biosynthesis of patulin.

The aim of this study was to compare the dissolution properties of ibuprofen solid oral dosage forms commercially available in Bosnia and Herzegovina and to estimate the influence of dissolution medium composition on the drug release. Eight products (A-H) were subjected to in vitro dissolution test using experimental conditions described in USP42–NF37. Dissolution properties of one selected product were examined in the presence of alcohol (22.2% v/v) and fruit juice (22.2% v/v). Products marked B-H complied with the pharmacopeial criteria. Dissolution profile of product B was similar with dissolution profiles of products D, E, F and G and similarity was also found between products A-D, C-G, D-G and E-F. Drug release from most of the examined preparations fitted best to the Weibull kinetic model. In the presence of alcohol in the medium, higher amount of ibuprofen was dissolved. Contrary, ibuprofen dissolved in the presence of fruit juice was significantly lower. Differences in the dissolution profiles of investigated preparations suggest that their interchangeability should be additionally considered and demonstrated with in vivo bioequivalence studies. Presence of different substances in the medium can affect dissolution properties of ibuprofen, emphasizing the importance of the patient’s compliance.

Hearing impairment alters the sound input received by the human auditory system, reducing speech comprehension in noisy multi-talker auditory scenes. Despite such challenges, attentional modulation on the envelope tracking in multi-talker scenarios is comparable between normal hearing (NH) and hearing impaired (HI) participants, with previous research suggesting an over-representation of the speech envelopes in HI individuals (see, e.g., Fuglsang et al. 2020 and Presacco et al. 2019), even though HI participants reported difficulties in performing the task. This result raises an important question: What speech-processing stage could reflect the difficulty in attentional selection, if not envelope tracking? Here, we use scalp electroencephalography (EEG) to test the hypothesis that such difficulties are underpinned by an over-representation of phonological-level information of the ignored speech sounds. To do so, we carried out a re-analysis of an EEG dataset where EEG signals were recorded as HI participants fitted with hearing aids attended to one speaker (target) while ignoring a competing speaker (masker) and spatialised multi-talker background noise. Multivariate temporal response function analyses revealed that EEG signals reflect stronger phonetic-feature encoding for target than masker speech streams. Interestingly, robust EEG encoding of phoneme onsets emerged for both target and masker streams, in contrast with previous work on NH participants and in line with our hypothesis of an over-representation of the masker. Stronger phoneme-onset encoding emerged for the masker, pointing to a possible neural basis for the higher distractibility experienced by HI individuals. Significance Statement This study investigated the neural underpinnings of attentional selection in multi-talker scenarios in hearing-impaired participants. The impact of attentional selection on phonological encoding was assessed with electroencephalography (EEG) in an immersive multi-talker scenario. EEG signals encoded the phonetic features of the target (attended) speech more strongly than those of the masker (ignored) speech; but interestingly, they encoded the phoneme onsets of both target and masker speech. This suggests that the cortex of hearing-impaired individuals may over-represent higher-level features of ignored speech sounds, which could contribute to their higher distractibility in noisy environments. These findings provide insight into the neural mechanisms underlying speech comprehension in hearing-impaired individuals and could inform the development of novel approaches to improve speech perception in noisy environments.

BACKGROUND DEPendency of association on the number of Top Hits (DEPTH) is an approach to identify candidate susceptibility regions by considering the risk signals from overlapping groups of sequential variants across the genome. METHODS We conducted a DEPTH analysis using a sliding window of 200 SNPs to colorectal cancer (CRC) data from the Colon Cancer Family Registry (CCFR) (5,735 cases and 3,688 controls), and GECCO (8,865 cases and 10,285 controls) studies. A DEPTH score >1 was used to identify candidate susceptibility regions common to both studies. We compared DEPTH results against those from conventional GWAS analyses of these two studies as well as against 132 published susceptibility regions. RESULTS Initial DEPTH analysis revealed 2,622 (CCFR) and 3,686 (GECCO) candidate susceptibility regions, of which 569 were common to both studies. Bootstrapping revealed 40 and 49 candidate susceptibility regions in the CCFR and GECCO data sets, respectively. Notably, DEPTH identified at least 82 regions that would not be detected using conventional GWAS methods, nor had they been identified by previous CRC GWASs. We found four reproducible candidate susceptibility regions (2q22.2, 2q33.1, 6p21.32, 13q14.3). The highest DEPTH scores were in the HLA locus at 6p21 where the strongest associated SNPs were rs762216297, rs149490268, rs114741460, and rs199707618 for the CCFR data, and rs9270761 for the GECCO data. CONCLUSIONS DEPTH can identify candidate susceptibility regions for CRC not identified using conventional analyses of larger datasets. IMPACT DEPTH has potential as a powerful complementary tool to conventional GWAS analyses for discovering susceptibility regions within the genome.

Fiber links have proven to be the most robust tools for ultra-stable frequency dissemination over various distance ranges, thanks to an active compensation of the fiber propagation noise [1]. Here, we present our setup for local ultra-stable frequency distribution within an institute, fully based on digital electronics. We use a Red Pitaya SDRlab122 - 16 (RP16) platform to perform a Doppler cancellation scheme, based on a heterodyne Michelson interferometer using a single acousto-optic modulator (AOM) at 110 MHz, in order to cancel the phase noise arising from a 90 m-long fiber link at 1542 nm. The experimental setup is shown in Fig. 1.