Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. Here we report four new patients carrying biallelic DNASE1L3 pathogenic variations, including two previously unreported mutations. Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission. Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesis with C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.

The application of electronic findings to biology and medicine has significantly impacted health and wellbeing [...]

Background: Pandemic caused by the COVID-19 virus brought tremendous changes in the lifestyle of adolescents, about which numerous studies have been published. Due to extended restrictions, long term impact should be investigated.Methods: This cross-sectional study enrolled 953 voluntary participants aged 14 to 21, from different regions of B&H. Participants were asked to complete an online 37-item survey, regarding socio-demographics, geographic, social characteristics, dietary and lifestyle habits, physical activity, including their consumption of dietary, vitamin and mineral supplements. They also needed to provide information about their weight, height and weight change during the entire period of the COVID-19 pandemic from March 2020 until the end of November when the study was completed. For data entry and analysis, SPSS (version 25) and Microsoft Excel were used.Results: At the time of completing the survey, a slightly lower BMI of participants was noticed compared to the time before the pandemic. A statistically significant difference was determined between males and females BMI, boys BMI was slightly higher. Females gained and men lost BW. Increased intake of unhealthy types of food was associated with weight change. Increased mental stress during the pandemic was associated with dietary changes, respectively with decreased as also increased food amount. High percent of participants (40.4%) who increased their physical activity did not alter their eating in the form of the food amount. This study reported use of some dietary supplements which have not been used before the pandemic by 63.5% participants.Conclusions: This paper presents a unique insight into the changing lifestyle and eating habits of adolescents in B&H during lockdown and post-lockdown period of research. Considering that pandemic is still ongoing, data from study like this may be useful to create further steps in battling the pandemic.

Advances in single-cell RNA sequencing (scRNAseq) technologies uncovered an unexpected complexity in tumors, underlining the relevance of intratumor heterogeneity to cancer progression and therapeutic resistance. Heterogeneity in the mutational composition of cancer cells is a result of distinct (sub)clonal expansions, each with a distinct metastatic potential and resistance to specific treatments. Unfortunately, due to their low read coverage per cell, scRNAseq datasets are too sparse and noisy to be used for detecting expressed mutations in single cells. Additionally, the large number of cells and mutations present in typical scRNAseq datasets are too large for available computational tools to, e.g., infer distinct subclones, lineages or trajectories in a tumor. Finally, there are no principled methods to assess distinct subclones inferred through single-cell sequencing data and the genomic alterations that seed and potentially cause them. Here we present Trisicell, a computational toolkit for scalable mutational intratumor heterogeneity inference and assessment from scRNAseq as well as single-cell genome or exome sequencing data. Trisicell allows reliable identification of distinct clonal lineages of a tumor, offering the ability to focus on the most important subclones and the genomic alterations that are associated with tumor proliferation. We comprehensively assessed Trisicell on a melanoma model by comparing distinct lineages and subclones it identifies on scRNAseq data, to those inferred using matching bulk whole exome (bWES) and transcriptome (bWTS) sequencing data from clonal sublines derived from single cells. Our results demonstrate that distinct lineages and subclones of a tumor can be reliably inferred and evaluated based on mutation calls from scRNAseq data through the use of Trisicell. Additionally, they reveal a strong correlation between aggressiveness and mutational composition, both across the inferred subclones, and among human melanomas. We also applied Trisicell to infer and evaluate distinct subclonal expansion patterns of the same mouse melanoma model after treatment with immune checkpoint blockade (ICB). After integratively analyzing our cell-specific mutation calls with their expression profiles, we observed that each subclone with a distinct set of novel somatic mutations is strongly associated with a specific developmental status. Moreover, each subclone had developed a unique ICB-resistance mechanism. These results demonstrate that Trisicell can robustly utilize scRNAseq data to delineate intratumor heterogeneity and help understand biological mechanisms underlying tumor progression and resistance to therapy.

This paper presents a new method of steganography based on a combination of Catalan objects and Voronoi–Delaunay triangulation. Two segments are described within the proposed method. The first segment describes the process of embedding data and generating a complex stego key. The second segment explains the extraction of a hidden message. The main goal of this paper is to transfer a message via the Internet (or some other medium) using an image so that the image remains absolutely unchanged. In this way, we prevented the potential attacker from noticing some secret message hidden in that picture. Additionally, the complex stego key consists of three completely different parts (the image, the encrypted Delaunay triangulation, and the array Rk in Base64 code), which are very difficult to relate with each other. Finally, a few security analyses of the proposed method are conducted, as well as the corresponding steganalysis.

OBJECTIVES To define metastatic categories based on their prognostic significance. We hypothesized that oligometastasis in patients with head and neck squamous cell carcinoma (HNSCC) is associated with better post-distant metastasis disease specific survival (post-DM DSS) compared to patients with polymetastasis. Furthermore, the impact on survival of synchronous versus metachronous distant metastasis (DM) occurrence was assessed. MATERIALS AND METHODS Retrospective cohort study in which patients with DM were stratified into three groups: oligometastasis (maximum of 3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site) and explosive-disseminating metastasis (spread to ≥3 anatomic sites or >3 metastatic foci in 2 anatomic sites). In addition, patients were divided into synchronous versus metachronous DM. RESULTS Between January 1, 2006 and December 31, 2013, a total of 2687 patients with HNSCC were identified, of which 324 patients developed DM. In this group, 115 (35.5%) patients had oligometastasis, 64 (19.8%) patients had explosive metastasis and 145 (44.8%) patients had explosive-disseminating metastasis. Their median post-DM DSS were 4.7 months, 4.1 months and 1.7 months respectively (p < .001). Synchronous DM was associated with more favorable survival rates in univariable and multivariable analyses than metachronous DM with recurrence of the index tumor (6-month post-DM DSS probability of 0.51 vs 0.17, p < .001). CONCLUSION Oligometastasis in HNSCC signifies a better prognosis than a polymetastatic pattern. Metachronous DM occurrence with recurrence of the primary index tumor is associated with an unfavorable prognosis.

Abstract Clinopodium alpinum subsp. orontium (K.Malý) Govaerts and Thymus bracteosus Vis. ex Benth. are endemic Lamiaceae species in Bosnia and Herzegovina with rather limited data about their cytotoxic and genotoxic effects. This study aimed to analyse phenolic compounds composition of C. alpinum subsp. orontium and T. bracteosus aqueous and dimethyl sulphoxide (DMSO) extracts and their cytotoxic and genotoxic potential in human peripheral blood lymphocyte cultures. Among 33 analytes, 17 were identified and quantified in the examined extracts with the rosmarinic and chlorogenic acids as main constituents. Genotoxic effects of extracts from both species are proven at the highest applied dose. T. bracteosus extracts and DMSO as a solvent exhibited stronger genotoxic potential that should be further investigated in tumour cell lines. Nevertheless, non-endemic species with similar phenolic composition and bioactivity should be the first choice for medicinal purposes. Graphical Abstract

The present study was designed to determine the efficacy of a novel multicomponent mycotoxin detoxifying agent (MMDA) containing modified zeolite (Clinoptilolite), Bacillus subtilis, B. licheniformis, Saccharomyces cerevisiae cell walls and silymarin against the deleterious effects of Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) in broiler chicks. A total of 160 one-day-old Ross 308® broiler chicks were randomly allocated in four treatment groups, with four replicates, according to the following experimental design for 42 days. Group A received a basal diet; Group B received a basal diet contaminated with AFB1 and OTA at 0.1 mg/kg and 1 mg/kg, respectively; Group C received a basal diet contaminated with AFB1 and OTA and MMDA at 1 g/kg feed, and Group D received a basal diet contaminated with AFB1 and OTA and MMDA at 3 g/kg feed. Results showed that ingested mycotoxins led to significant (p ≤ 0.05) reduction in body weight and feed conversion from 25 days of age, induced histopathological changes, increased the pH of the intestinal content, and altered the biochemical profile of birds with significantly (p ≤ 0.05) increased aspartate aminotransferase (AST) values (p ≤ 0.05). On the other hand, the supplementation of MMDA significantly (p ≤ 0.05) improved the feed conversion ratio (FCR) during the second part of the study, diminished biochemical alterations, reduced pH in jejunal and ileal content, and E. coli counts in the caeca of birds (p ≤ 0.05). It may be concluded that the dietary supplementation of the MMDA partially ameliorated the adverse effects of AFB1 and OTA in broilers and could be an efficient tool in a mycotoxin control program.

In the first phases of study and design documentation of rural roads, one of the key parameters to determine in the analyses is the Design Hourly Volume (DHV). The required level of service and the feasibility of the project depend to a large extent on a properly established DHV. Essentially, the problem is to determine the value of the K-factor for a certain nth highest hour of the year. This paper points to the need for additional analysis of existing databases of long-term automatic traffic counting, from which the necessary guidance for planners and designers can be derived, enabling them to understand and apply the K-factors in a clearer and more detailed way. Using specific data examples, characteristic sections of rural roads with different functions and types (seasonal variations) of traffic demand were selected to show significant differences in the values of the K-factors for the same selected nth highest hour of the year. Several guidelines (BiH, Slovenia, Croatia, Italy, Serbia) were analysed beforehand to get a better understanding of how the K-factor or DHV is explained and used in different countries. The main objective of the article is to show that, on the basis of the existing databases of continuous automatic counting in these countries, with additional analyses presented in this paper or in a similar form, significant regularities in determining the DHV can be achieved, eliminating difficulties of application in engineering practice. As all guidelines practically recommend the use of HCM in capacity analyses, specific examples are selected to show the difference between the definition of HCM for a route with dominant recreational traffic and our route with dominant tourist traffic (recreational versus tourist).

When reconstructing existing or constructing completely new intersections, the main problem is determining the type of future intersection. Capacity is one of the key indicators that influence the choice of traffic control type. In this paper, using different scenarios of theoretical traffic flow distributions and traffic volume scenarios, the authors have determined the applicability area of two-lane roundabouts. The results obtained were used to improve the existing applicability diagrams of the various intersection types presented in several issues of US Highway Capacity Manuals (US HCM). Capacity in each scenario is determined using HCM 2010 and Hagring methods with practically obtained values of the time gap acceptance parameters.

Building Information Modelling (BIM) is a relatively new technology. The industry, especially when it comes to infrastructure projects, is just beginning to realize the potential benefits of it. Large capital projects are being done today using BIM technology and standards, while in Bosnia and Herzegovina today, we do not have a project implemented by it. BIM is still exhibiting varying states of maturity among its participants. The research was carried out in B&H to realize perceptions of BIM in the infrastructures projects from the perspective of different participants (investor, consultant, designer, supervising engineer, contractor, supplier). The following aims are to demonstrate perception about BIM, the willingness to apply it, and different varying states of maturity among its participants and the current degree of application in practice