The emergence of blockchain technologies, including smart contracts, enables the decentralization of applications that were previously controlled by a single entity. In many cases, however, smart contracts still need to distinguish between different user roles according to their assigned duties. To ensure security, smart contracts often apply a simple form of role-based access control (RBAC), where a dedicated administrator assigns users to roles that are authorized to invoke specific smart contract functions. As this solution contradicts the blockchain principles of decentralization and democratic decision making, smart contracts may also form decentralized autonomous organizations where governance decisions are based on voting by all participants. Many applications would benefit from a hybrid approach that involves roles with different permissions while still allowing for collaborative management. Therefore, we propose a novel mechanism for RBAC administration in smart contracts based on hierarchical roles and configurable administration rules for each role. Any change in the user-role relation requires joint approval by members of selected roles according to the associated rule. This enables decentralized organizational charts with flexible administration constraints, where each role corresponds to specific permissions in the decentralized application and any change is transparently and securely recorded on the blockchain. The practical feasibility of the approach is demonstrated by means of a prototypical implementation for the Ethereum blockchain. Several benchmarks are performed to analyze the potential overhead of different solution variants.

New resveratrol–thiophene and resveratrol–maltol hybrids were synthesized as cholinesterase inhibitors and antioxidants. As with photostability experiments, biological tests also found remarkable differences in the properties and behavior of thiophene and maltol hybrids. While resveratrol–thiophene hybrids have excellent inhibitory and antioxidant properties (similar to the activity of reference drug galantamine), maltols have been proven to be weaker inhibitors and antioxidants. The molecular docking of selected active ligands gave insight into the structures of docked enzymes. It enabled the identification of interactions between the ligand and the active site of both cholinesterases. The maltols that proved to be active cholinesterase inhibitors were able to coordinate Fe3+ ion, forming complexes of 1:1 composition. Their formation constants, determined by spectrophotometry, are very similar, lgK = 11.6–12.6, suggesting that Fe3+ binds to the common hydroxy-pyranone moiety and is hardly affected by the other aromatic part of the ligand. Accordingly, the characteristic bands in their individual absorption spectra are uniformly red-shifted relative to those of the free ligands. The crystal structures of two new resveratrol–maltol hybrids were recorded, giving additional information on the molecules’ intermolecular hydrogen bonds and packing. In this way, several functionalities of these new resveratrol hybrids were examined as a necessary approach to finding more effective drugs for complicated neurodegenerative diseases.

Aims: To evaluate the efficacy of metronidazole monotherapy and modified therapy with metronidazole + nifuroxazidefor the for treatment of a mild form of Clostridium difficile infection (CDI). Study Design: A prospective, randomized, controlled clinical trial. Place and Duration of Study: University of Applied Sciences Tuzla in the period from June 2018 to June 2019. Methodology: Sixty patients were included in the study, divided into two groups. One group received standard therapy (metronidazole) for the treatment of a mild form of CDI, while the other group was treated with modified therapy (metronidazole + nifuroxazide). Subjects with a developed clinical picture and a positive toxin test for Clostridium difficile were surveyed on the day of admission, then on the 4th, 10th, 14th and 30th days from the start of therapy. The goal of the research was to determine the impact of the modified therapy protocol on the number of stools and the presence of pain compared to standard therapy. Results: The modified therapy with metronidazole + nifuroxazide showed better pharmacological efficacy in the treatment of CDI compared to the standard therapy with metronidazole alone. The group of subjects who were treated with modified therapy reported a significantly lower number of stools (P=.001) and the absence of pain at the first and second check-ups. Conclusion: Nifuroxazide and metronidazole represent a combination of drugs that reduce the number of stools in the shortest possible time and result in the absence of abdominal pain in patients diagnosed with a mild form of CDI.

Smoking is a widely recognized risk factor in the emergence of cancers and other lung diseases. Studies of non-cancer lung diseases typically investigate the role that smoking has in chronic changes in lungs that might predispose patients to the diseases, whereas most cancer studies focus on the mutagenic properties of smoking. Large-scale cancer analysis efforts have collected expression data from both tumor and control lung tissues, and studies have used control samples to estimate the impact of smoking on gene expression. However, such analyses may be confounded by tumor-related micro-environments as well as patient-specific exposure to smoking. Thus, in this paper, we explore the utilization of mutational signatures to study environment-induced changes of gene expression in control lung tissues from lung adenocarcinoma samples. We show that a joint computational analysis of mutational signatures derived from sequenced tumor samples, and the gene expression obtained from control samples, can shed light on the combined impact that smoking and tumor-related micro-environments have on gene expression and cell-type composition in non-neoplastic (control) lung tissue. The results obtained through such analysis are both supported by experimental studies, including studies utilizing single-cell technology, and also suggest additional novel insights. We argue that the study provides a proof of principle of the utility of mutational signatures to be used as sensors of environmental exposures not only in the context of the mutational landscape of cancer, but also as a reference for changes in non-cancer lung tissues. It also provides an example of how a database collected with the purpose of understanding cancer can provide valuable information for studies not directly related to the disease.

Purpose Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. Materials and Methods The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. Results The PLK2 Crs15009-Crs963615 haplotype was under-represented in the GC group compared to that in the control group (Pcorr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM Trs228589-Ars189037-Grs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. Conclusions PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

The properties of semiconductor materials can be strongly affected by the addition of metallic nanoparticles. Here we investigate the properties of SiC+Au and Si3N4+Au thin films prepared by magnetron sputtering deposition followed by thermal annealing. The influence of gold addition on the optical and electrical properties is explored. We show the formation of self-assembled Au nanoparticles in SiC and Si3N4, with the size and arrangement properties determined by the deposition and annealing conditions. Both SiC- and Si3N4-based films show an increase in the overall absorption with increasing Au content, and its decrease with increasing annealing temperature. All films show the presence of surface plasmon resonance, whose peaks shift toward larger wavelengths with increasing Au nanoparticle size. The resistivity significantly drops with the Au content increase for both types of matrices, although the resistivity of Si3N4-based films is much higher. The incorporated quantity of Au in the host matrix was chosen in such a way to demonstrate that a huge range of optical and electrical characteristics is achievable. The materials are very interesting for application in opto-electronic devices.

Noise represents any unwanted sound that interferes with a person's work, psychological and health condition, and their rest time. Numerous studies indicate that noise affects changes in human behavior (aggression, social conflicts) and causes stress reactions associated with physiological reactions. It also affects the central and neurovegetative system, reduces attention and concentration ability, reduces work ability, and reduces work productivity. Noise pollution is a major environmental health problem in Europe, with the transport sector being its main cause. The noise level is mostly affected by the number of vehicles, traffic flow, relative share of passenger and freight vehicles, their speed, types and characteristics of the road, whether the traffic is one-way or two-way, intersections, weather conditions, etc. In order to adequately protect against the negative effects of traffic noise, it is necessary to take various measures to reduce it. This paper provides a comprehensive review of the literature with special measures for the protection, monitoring and reduction of the negative impact of traffic noise. Keywords: traffic, traffic noise, protection measures, noise barriers

Introduction: Energy drinks (EDs) are products in the form of a beverage or concentrated liquid designed to increase both mental and physical stimulations. Their popularity has grown tremendously, especially among children and adolescents, regardless of the growing number of undesirable health consequences associated with their consumption. This study aimed to evaluate the content of additives in EDs available in the Bosnian and Herzegovinian (B&H) markets. Methods: Twenty-two EDs from 15 brands were analyzed. The contents of quinine (QUIN), caffeine (CAF), benzoic acid (BZA), and sorbic acid (SA) were determined by high-performance liquid chromatography. Results: The median value of QUIN, CAF, SA, and BZA was 0.15 ppm, 309.05 ppm, 75.35 ppm, and 90.80 ppm, respectively. The highest CAF content variation was found in EDs of brand 4, and the lowest was in brand 6. A statistically significant difference was found between the obtained values in relation to the recommended daily intake of CAF for adolescents by the Centers for Disease Control and Prevention and the American Academy of Pediatrics (p < 0.001). Conclusion: The CAF content in EDs deviates by 10% from the content stated in the product declaration. All EDs on the B&H market should carry a clear warning: “High CAF content must not be mixed with alcohol and is not recommended for children, pregnant and/or lactating women, and CAF-sensitive individuals.” Given the behavioral trends associated with the potential risks of excessive CAF consumption, particularly among youth, national agencies in B&H should recognize areas of intervention such as responsible marketing and advertising, and education and awareness-raising. Further research and monitoring would be needed to determine the effectiveness of the various aspects of the proposed risk management approach.

Public health of people and individuals is the most important resource in the modern world. The sugar epidemic and cardiovascular diseases are linked to the obesity epidemic. As obesity appears at younger and younger ages, it is to be expected that the proportion of people who have been obese for the number of years will increase and that those practicing a "sedentary lifestyle" will move less and less. Diabetes mellitus type 2 (DMT2) and cardiovascular diseases (CD) are among the top ten causes of death in the world. It is observed that the association between DMT2 and CD risk is not the same for both sexes, with the cardiovascular risk associated with DMT2 being greater in women. Among the different strategies for the prevention and treatment of DMT2 and risk factors for CD, physical exercise has been largely recommended because of its positive effects on glycemic control, body mass, blood pressure, and lipid profile. A higher level of daily physical activity significantly reduces the risk of contracting numerous diseases such as: diabetes, diseases of the heart and blood vessels, certain forms of malignant diseases, obesity, asthma, osteoporosis and others.  Article visualizations:

Public health of people and individuals is the most important resource in the modern world. The sugar epidemic and cardiovascular diseases are linked to the obesity epidemic. As obesity appears at younger and younger ages, it is to be expected that the proportion of people who have been obese for the number of years will increase and that those practicing a "sedentary lifestyle" will move less and less. Diabetes mellitus type 2 (DMT2) and cardiovascular diseases (CD) are among the top ten causes of death in the world. It is observed that the association between DMT2 and CD risk is not the same for both sexes, with the cardiovascular risk associated with DMT2 being greater in women. Among the different strategies for the prevention and treatment of DMT2 and risk factors for CD, physical exercise has been largely recommended because of its positive effects on glycemic control, body mass, blood pressure, and lipid profile. A higher level of daily physical activity significantly reduces the risk of contracting numerous diseases such as: diabetes, diseases of the heart and blood vessels, certain forms of malignant diseases, obesity, asthma, osteoporosis and others.  Article visualizations:

Conflict of interest: COI declared see note COI notes: The authors declare no competing financial interests. MB is a consultant for Oxford Immunotech. AS is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. Preprint server: No; Author contributions and disclosures: LB, LH, AÖ, GB, MSC, HGL and MB contributed to conceptualization, funding acquisition and discussion of data. YG, KH and SM and DW performed experiments and analyzed data. LB, HMIS, CK, LH and AÖ recruited study participants, conducted management of participants during the study and analyzed data. AG and AS provided peptide pools to measure the spike-specific T cell responses. LB, DW, AÖ, LH, HGL and MB wrote the original draft of the manuscript. All authors reviewed and edited revisions of the manuscript and had final responsibility for the decision to submit for publication. Non-author contributions and disclosures: No; Agreement to Share Publication-Related Data and Data Sharing Statement: Emails to the corresponding author Clinical trial registration information (if any):

The classification of biological neuron types and networks poses challenges to the full understanding of the human brain’s organisation and functioning. In this paper, we develop a novel objective classification model of biological neuronal morphology and electrical types and their networks, based on the attributes of neuronal communication using supervised machine learning solutions. This presents advantages compared to the existing approaches in neuroinformatics since the data related to mutual information or delay between neurons obtained from spike trains are more abundant than conventional morphological data. We constructed two open-access computational platforms of various neuronal circuits from the Blue Brain Project realistic models, named Neurpy and Neurgen. Then, we investigated how we could perform network tomography with cortical neuronal circuits for the morphological, topological and electrical classification of neurons. We extracted the simulated data of 10,000 network topology combinations with five layers, 25 morphological type (m-type) cells, and 14 electrical type (e-type) cells. We applied the data to several different classifiers (including Support Vector Machine (SVM), Decision Trees, Random Forest, and Artificial Neural Networks). We achieved accuracies of up to 70%, and the inference of biological network structures using network tomography reached up to 65% of accuracy. Objective classification of biological networks can be achieved with cascaded machine learning methods using neuron communication data. SVM methods seem to perform better amongst used techniques. Our research not only contributes to existing classification efforts but sets the road-map for future usage of brain–machine interfaces towards an in vivo objective classification of neurons as a sensing mechanism of the brain’s structure.