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J. Panić, Arianna Defeudis, G. Balestra, V. Giannini, S. Rosati

Goal: Artificial intelligence applied to medical image analysis has been extensively used to develop non-invasive diagnostic and prognostic signatures. However, these imaging biomarkers should be largely validated on multi-center datasets to prove their robustness before they can be introduced into clinical practice. The main challenge is represented by the great and unavoidable image variability which is usually addressed using different pre-processing techniques including spatial, intensity and feature normalization. The purpose of this study is to systematically summarize normalization methods and to evaluate their correlation with the radiomics model performances through meta-analyses. This review is carried out according to the PRISMA statement: 4777 papers were collected, but only 74 were included. Two meta-analyses were carried out according to two clinical aims: characterization and prediction of response. Findings of this review demonstrated that there are some commonly used normalization approaches, but not a commonly agreed pipeline that can allow to improve performance and to bridge the gap between bench and bedside.

Milena Mlakić, Ema Đurčević, I. Odak, Danijela Barić, Ines Juričević, Ivana Šagud, F. Burčul, Z. Lasić et al.

Naphtho-triazoles and thienobenzo-triazoles have so far proven to be very potent inhibitors of the enzyme butyrylcholinesterase (BChE). Based on these results, in this work, new thienobenzo-thiazoles were designed and synthesized, and their potential inhibitory activity was tested and compared with their analogs, naphtho-oxazoles. The synthesis was carried out by photochemical cyclization of thieno-thiazolostilbenes obtained in the first reaction step. Several thienobenzo-thiazoles and naphtho-oxazoles have shown significant potential as BChE inhibitors, together with the phenolic thiazolostilbene being the most active of all tested compounds. These results are significant as BChE has been attracting growing attention due to its positive role in the treatment of Alzheimer’s disease. Computational examination based on the DFT approach enabled the characterization of the geometry and electronic structure of the studied molecules. Furthermore, the molecular docking study, accompanied by additional optimization of complexes ligand-active site, offered insight into the structure and stabilizing interactions in the complexes of studied molecules and BChE.

Uroš Stamenković, S. Ivanov, I. Marković, M. Gorgievski, Kristina Božinović, Avram Kovačević

The influence of the ageing temperature on the hardness, electrical conductivity, thermal diffusivity and thermal conductivity of the EN AW-7075 aluminium alloy was studied in this paper. After solution treating the alloy at 480 °C for 1 h and quenching it in ice water, the investigated alloy was characterized using Differential Thermal Analysis (DTA) in order to determine the optimal temperatures for the isochronal ageing treatments. Afterwards, isochronal ageing was conducted at the temperature range of 110 °C-250 °C for 30 min The hardness, electrical conductivity, thermal diffusivity, thermal conductivity and microstructural features were investigated during the ageing treatments. Hardness had a peak value after ageing at 150 °C, while other properties gradually increased with the ageing temperature. Microstructural investigation of the aged alloy by SEM-EDS revealed the existence of precipitated phases that appear homogenously distributed in the microstructure.

G. Minervini, R. Franco, M. Marrapodi, L. Fiorillo, A. Badnjević, G. Cervino, M. Cicciù

The inflammatory injury of the mucous membranes lining the digestive tract, from the mouth to the anus, is called mucositis. One of the intriguing and compelling new therapeutic modalities that has emerged in recent decades due to advances in our understanding of this condition’s pathophysiology is probiotics. The purpose of this meta-analysis is to evaluate the efficiency of probiotics in the treatment of chemotherapy-induced mucositis for head and neck malignancies; a literature search was performed on PubMed, Lilacs, and Web of Science, and articles published from 2000 to 31 January 2023 were considered, according to the keywords entered. The term “Probiotics” was combined with “oral mucositis” using the Boolean connector AND; at the end of the research, 189 studies were identified from the search on the three engines. Only three were used to draw up the present systematic study and metanalysis; this meta-analysis showed that the treatment of mucositis with probiotics is an effective method, and the analysis of the results of these studies showed that the use of probiotics promoted a decrease in the severity of mucositis symptoms.

At the end of 2018, Gazi Husrev-bey library in Sarajevo and the renowned institution for historical research in the Republic of Turkey, Türk Tarih Kurumu, signed a protocol on cooperation on the project of preparing and publishing the regesta of the voluminous manuscript Tārīẖ-i Enveri, History of Muhamed Enveri Kadić. For the next four years, both of these institutions, which kept the first copies of the History, undertook a series of activities in order to realize the signed project. On January 13, 2023, the Gazi Husrev-bey library marked its 486th anniversary by promoting the planned and completed part of the work. The fact that the name and work of this special archivist, copyist, poet, epigrapher and bibliophile was known in detail by a limited number of people outside the fields of Orientalism, Ottoman studies and history, imposes the need to present, in a concise form, his character, work and visions.

Zvonimir Jažo, Mateo Glumac, Vlatka Paštar, Sanida Bektić, Mila Radan, Ivana Carev

In our study, we investigated the chemical composition and cytotoxic activity of essential oils isolated from Dalmatian sage (Salvia officinalis L.) collected along the Adriatic coast of Croatia. Scanning electron microscopy (SEM) was used to examine the morphology of the stem and leaf surfaces. Essential oil excretory glands were detected on both the leaves and stem surfaces. The essential oils were isolated by hydrodistillation, and their chemical composition was determined by gas chromatography and mass spectrometry (GC-MS). Sage essential oils were mixtures of terpene compounds, among which the most common were: α- and β-thujone, camphor, and 1,8-cineol. Cytotoxic activity was tested using MTS assay on multiple cell lines: normal and immortalized fibroblasts (HF77FA and HDF-Tert), immortalized lung line (BEAS-2B), and breast adenocarcinoma (MDA-MB-231). The growth of treated cells was determined relative to control conditions without treatment. The immortalized lung line was the least resistant to the activity of the essential oils, whereas immortalized fibroblasts were the most resistant. Statistical analysis has connected the cytotoxic effect and chemical composition of the studied essential oils. To the best of our knowledge, this work is the first testing of the cytotoxic activity of S. officinalis EO’s on the BEAS-2B, HF77FA, and HDF-Tert cell lines. The presented data on essential oil chemical composition and cytotoxic effect on 4 types of human cells supports pharmacotherapeutic potential this plant is known to have.

Dženana Klepo, S. Maleskic Kapo, M. Mačkić-Đurović, I. Aganović-Mušinović, L. Burnazović-Ristić

Background: Thiomersal is used as a preservative of some vaccines or as a trace from the pathogen inactivation process in vaccine production. Prophylactic use of paracetamol upon vaccination is still common, even though paracetamol decreases immune response on some vaccines. Considering the cytotoxic and genotoxic potential of thiomersal and paracetamol and possible interaction in vivo, in vitro study was performed. Methods: The genotoxic and cytotoxic effects of thiomersal and paracetamol combination were examined on human lymphocyte cultures by using two methods: analysis of chromosomal aberrations and cytokinesis-block micronucleus cytome assay. Blood samples of three healthy donors were analyzed with the following concentrations of tested substances: thiomersal 1 µg/ml and 0.5 µg/ml, paracetamol 20 µg/ml, thiomersal 0.5 µg/ml with paracetamol 20 µg/ml and thiomersal 1.0 µg/ml with paracetamol 20 µg/ml. Results: The analysis of structural chromosomal aberrations was significantly increased in all treated cultures. In cells treated with the combination of thiomersal 1 µg/ml and 20 µg/ml of paracetamol, the number of aberrations was significantly decreased. Cytokinesis-block micronucleus cytome assay analyses showed significantly increased micronucleus frequency in lymphocytes cultivated with thiomersal 1 µg/ml compared to lymphocytes cultures exposed to thiomersal 0.5 µg/ml. Conclusions: Induction of structural chromosome aberrations and micronucleus is shown as a sign of genotoxicity for the examined concentrations of thiomersal and paracetamol. The suppressing effect of paracetamol on thiomersal genotoxicity in lymphocytes culture treated with thiomersal was shown to be indicative of further examination of paracetamol use in the prevention of genotoxicity.

A. Frkatović-Hodžić, Anika Mijakovac, Karlo Miškec, Arina V. Nostaeva, S. Sharapov, A. Landini, T. Haller, E. B. van den Akker et al.

Glycans are an essential structural component of Immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation). We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Up- and downregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.

Nina Šimunić-Briški, R. Zekić, Vedran Dukarić, Mateja Očić, A. Frkatović-Hodžić, Helena Deriš, G. Lauc, Damir Knjaz

Regular exercise improves health, modulating the immune system and impacting inflammatory status. Immunoglobulin G (IgG) N-glycosylation reflects changes in inflammatory status; thus, we investigated the impact of regular exercise on overall inflammatory status by monitoring IgG N-glycosylation in a previously inactive, middle-aged, overweight and obese population (50.30 ± 9.23 years, BMI 30.57 ± 4.81). Study participants (N = 397) underwent one of three different exercise programs lasting three months with blood samples collected at baseline and at the end of intervention. After chromatographically profiling IgG N-glycans, linear mixed models with age and sex adjustment were used to investigate exercise effects on IgG glycosylation. Exercise intervention induced significant changes in IgG N-glycome composition. We observed an increase in agalactosylated, monogalctosylated, asialylated and core-fucosylated N-glycans (padj = 1.00 × 10−4, 2.41 × 10−25, 1.51 × 10−21 and 3.38 × 10−30, respectively) and a decrease in digalactosylated, mono- and di-sialylated N-glycans (padj = 4.93 × 10−12, 7.61 × 10−9 and 1.09 × 10−28, respectively). We also observed a significant increase in GP9 (glycan structure FA2[3]G1, β = 0.126, padj = 2.05 × 10−16), previously reported to have a protective cardiovascular role in women, highlighting the importance of regular exercise for cardiovascular health. Other alterations in IgG N-glycosylation reflect an increased pro-inflammatory IgG potential, expected in a previously inactive and overweight population, where metabolic remodeling is in the early stages due to exercise introduction.

P. Kovačević, V. Djajic, R. Škrbić, N. Milivojevic, M. Jereb, P. Gradisek, V. Gorjup

BACKGROUND: Critical care medicine is a young branch of medicine, of which the development was much faster in High Income Countries (HICs) than in Low Resources Settings (LRS). Slovenia, as one of the successor states of former Yugoslavia, passed the process of transition and joined the European Union successfully. On the contrary, Bosnia and Herzegovina (B&H) went through the extremely difficult process of transition (four years of civil war), which left a deep scar to the healthcare system, including critical care medicine. OBJECTIVE: To examine the impact of HICs on the development of critical care in LRS. METHOD: This review examined the process of growing up the first modern Medical Intensive Care Unit (MICU) in the Republic of Srpska. RESULTS: The five-year process of transferring critical care knowledge from Slovenia to the health care system of Republic of Srpska has contributed to the existence of modern and state of the art MICU with tremendous social effects. CONCLUSION: The model of using the impact of HICs for improving critical care in LRS can be extrapolated to other similar settings.

K. Aleksić, Ivana Stojković Simatović, A. Stanković, Ljiljana Veselinović, S. Stojadinović, V. Rac, Nadežda Radmilović, V. Rajić et al.

Catalytic materials are the greatest challenge for the commercial application of water electrolysis (WEs) and fuel cells (FCs) as clean energy technologies. There is a need to find an alternative to expensive and unavailable platinum group metal (PGM) catalysts. This study aimed to reduce the cost of PGM materials by replacing Ru with RuO2 and lowering the amount of RuO2 by adding abundant and multifunctional ZnO. A ZnO@RuO2 composite in a 10:1 molar ratio was synthesized by microwave processing of a precipitate as a green, low-cost, and fast method, and then annealed at 300°C and 600°C to improve the catalytic properties. The physicochemical properties of the ZnO@RuO2 composites were investigated by X-ray powder diffraction (XRD), Raman and Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), UV-Vis diffuse reflectance spectroscopy (DRS), and photoluminescence (PL) spectroscopy. The electrochemical activity of the samples was investigated by linear sweep voltammetry in acidic and alkaline electrolytes. We observed good bifunctional catalytic activity of the ZnO@RuO2 composites toward HER and OER in both electrolytes. The improved bifunctional catalytic activity of the ZnO@RuO2 composite by annealing was discussed and attributed to the reduced number of bulk oxygen vacancies and the increased number of established heterojunctions.

Vedad Hulusic, Linda Gusia, N. Luci, Michael Smith

Museums are traditionally considered learning environments and are ordinarily used for non-formal education. Physical museums, while being irreplaceable, are limited to a physical space, requiring mobility and physical presence. In addition, traditional exhibitions are not designed for interaction and physical exploration of artefacts. With the focus being shifted from museum exhibits to visitors’ experience, utilization of emerging technologies and co-creation of virtual museums not only helps in preservation of cultural heritage, but enhances the dissemination, engagement, and experience, while addressing the mobility and the plurality of voices and perspectives represented. In this work, we designed and developed the School House Virtual Museum with tangible user interfaces based on participatory, interdisciplinary, and co-creative methods with students and a larger community of researchers, artists, and practitioners working on heritage and memory. In a user study with 62 participants, usability and user experience were explored and the potential contribution of such virtual museums to learning, based on critical, cross-disciplinary, and participatory dialogue, both in cultural and educational institutions/programs has been investigated. The results have confirmed that the system has been well designed and developed, and the user experience was largely positive. The responses from educators and students confirmed that the application holds potential as a learning and education tool in either museums, schools, or when used independently.

Artur Hermann, Michael Wolf, Nataša Trkulja, I. B. Jemaa, Anis Bkakria, F. Kargl

Smart traffic lights systems (STLSs) are a promising approach to improve traffic efficiency at intersections. They rely on the information sent by vehicles via C2X communication (like in cooperative awareness messages (CAMs)) at the managed intersection. While there exists a large body of work on privacy-enhancing technologies (PETs) for cooperative Intelligent Transport Systems (cITS) in general, such PETs like changing pseudonyms often impact the performance of cITS applications. This paper analyzes the extent to which different PETs affect the performance of two types of STLSs, a phase-based and a reservation-based STLS. These are implemented in SUMO and combined with four different PETs. Through extensive simulations we then investigate the impact of those PETs on STLS performance metrics like time loss, waiting time, fuel consumption, and average velocity. Our analysis shows that the impact of PETs on performance varies greatly depending on the type of STLS. Finally, we propose a hybrid STLS which is a combination of the two STLS types as a potential solution for limiting the negative impact of PETs on performance.

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