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M. Barakovic, Matthias Weigel, A. Cagol, S. Schaedelin, R. Galbusera, Po-Jui Lu, Xin-Jie Chen, L. Melie-García et al.

Pathological data showed focal inflammation and regions of diffuse neuronal loss in the cortex of people with multiple sclerosis (MS). In this work, we applied a novel model (“soma and neurite density imaging (SANDI)”) to multishell diffusion-weighted MRI data acquired in healthy subjects and people with multiple sclerosis (pwMS), in order to investigate inflammation and degeneration-related changes in the cortical tissue of pwMS. We aimed to (i) establish whether SANDI is applicable in vivo clinical data; (ii) investigate inflammatory and degenerative changes using SANDI soma fraction (fsoma)—a marker of cellularity—in both cortical lesions and in the normal-appearing-cortex and (iii) correlate SANDI fsoma with clinical and biological measures in pwMS. We applied a simplified version of SANDI to a clinical scanners. We then provided evidence that pwMS exhibited an overall decrease in cortical SANDI fsoma compared to healthy subjects, suggesting global degenerative processes compatible with neuronal loss. On the other hand, we have found that progressive pwMS showed a higher SANDI fsoma in the outer part of the cortex compared to relapsing–remitting pwMS, possibly supporting current pathological knowledge of increased innate inflammatory cells in these regions. A similar finding was obtained in subpial lesions in relapsing–remitting patients, reflecting existing pathological data in these lesion types. A significant correlation was found between SANDI fsoma and serum neurofilament light chain—a biomarker of inflammatory axonal damage—suggesting a relationship between SANDI soma fraction and inflammatory processes in pwMS again. Overall, our data show that SANDI fsoma is a promising biomarker to monitor changes in cellularity compatible with neurodegeneration and neuroinflammation in the cortex of MS patients.

Nina Kudumija, Jelka Pleadin, Tina Lešić, Darija Vratarić, Danijel Petrovič, Ana Vulić

Thyrostats are a group of forbidden substances in food producing animals that increase water absorption in muscle tissue and the gastrointestinal tract of animals. These substances can be abused as illegal growth promoters as oral drugs on farms before slaughtering. The consequences of their illegal use on farm animals include higher yield though inferior meat quality, while these substances also pose a potential risk to human health, and so their application is banned in European Union Member States. Thiouracil (2-thiouracil) (TU) is the representative, and belongs to the group of thyrostats but also can be naturally present in the urine of farm animals fed with feed containing Brassicaceae species. The aim of this study was to monitor TU concentrations in pig and bovine urine in the period from 2015 to 2023. For this purpose, 391 urine samples were collected as a part of the National Residue Control Plan (NRCP) and TU concentrations were determined by liquid chromatography tandem mass spectrometry. TU was detected in 89 of 391 samples, or 22.76%. TU concentration ranged from 1.66 to 28.30 μg/L, and a statistically significant difference (P < 0.05) was determined in urine TU concentrations between pigs and bovines. Mean concentrations of TU varied by year, and ranged from 1.66 to 8.06 μg/L in pig urine and from 5.92 to 13.68 μg/L in bovine urine. None of the analysed urine samples contained TU concentration in excess of 30 μg/L, which is the cut-off value to distinguish potentially natural origin resulting from a cruciferous diet (Brassicaceae species). The results exclude the possibility of abuse of this substances in the livestock industry in the Republic of Croatia.

M. Salibašić, S. Pušina, Edin Hodžić, E. Bičakčić, Emsad Halilović, Sara Ganić

Abstract: Surgical correction of inguinal hernias is the most commonly used surgical procedure in the world. Currently only three surgical techniques have been validated, that is the Shouldice technique, the Lichtenstein technique, and laparoscopic techniques such as transabdominal preperitoneal (TAPP) hernioplasty and totally extraperitoneal endoscopic hernioplasty (TEP).The aim of the study: The aim of this study is to show the results in terms of postoperative recovery, complications, length of hospitalization after inguinal hernia surgery in patients who underwent the Lichtenstein and the laparoscopic (TAPP) methods.Material and methods: This is a monocentric, retrospective cohort study, conducted in the period from 2019 to 2023. The research period covered 70 patients who underwent surgery at the Clinic for General and Abdominal Surgery with Glandular Surgery, of the University Clinical Center, Sarajevo. The patients were divided into two groups: Group 1: 20 patients who underwent the TAPP method and Group 2: 50 patients who underwent the Lichtenstein method. All patients underwent surgery performed by two doctors.Results: One woman (1.4%) and 69 men (98.6%) participated in the research. Of the total number, 50 patients (72.5%) were treated with the Lichtenstein technique, and 19 (27.5%) were treated with the TAPP technique (p=0.539). The statistical results did not show a significant difference in the average age between patients who underwent the Lichtenstein and the TAPP technique (T=0.759; p=0.450).Discussion: There was no significant difference in relation to age and type of surgery (T=0.759; p=0.450). There was no statistical difference in the choice of surgical approach in relation to the laterality of the hernia (P<0.001), nor any statistically significant difference between the TAPP and Lichtenstein surgical procedures in relation to BMI T=0.613; p=0.542. Our analyses showed that patients treated with the TAPP technique had a statisticallysignificantly higher probability of shorter postoperative hospitalization compared to those treated with the Lichtenstein technique (B=0.245; p=0.019). Two patients in the study had complications within 30 days (Clavien-Dindo Grade I and Grade IIIB).Conclusion: Using an individual approach for each patient, surgical treatment of hernia using laparoscopic TAPP can be the first choice in patients without comorbidities, without previous pelvic surgery, bilaterality or recurrence of previous surgery (anterior approach). Patients treated with the laparoscopic technique (TAPP) have a shorter hospitalization time, which ultimately affects the economic aspect.

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), necessitates effective management strategies. This study aims to evaluate the real-world efficacy of vedolizumab, a newer biological therapy, in treating IBD in Bosnia and Herzegovina. A retrospective observational study was conducted across six medical centers, involving 139 IBD patients, 76 with UC and 63 with CD. Patients were assessed for clinical remission and other outcomes at the 26-week mark post vedolizumab treatment initiation. At 26 weeks, clinical remission was achieved in 82.9% of UC patients and 85.7% of CD patients. Mucosal healing was observed in 38.1% of CD patients. The efficacy of vedolizumab did not significantly differ based on prior anti-tumor necrosis factor (anti-TNF) exposure. Notably, the clinical scoring tools for predicting vedolizumab response showed limited applicability in this cohort. Vedolizumab demonstrated high efficacy in treating both UC and CD in real-world settings in Bosnia and Herzegovina, underscoring its potential as a significant therapeutic option in IBD management.

C. Zimmermann, Adrian Michelmann, Yannick Daniel, Markus D. Enderle, N. Salkić, W. Linzenbold

Simple Summary The manual measurement of ablation zones (AZs) in radiofrequency ablation (RFA) therapy is prone to inaccuracies, highlighting the need for automated methods. Our study investigated the effectiveness of an Artificial Intelligence (AI) model, Mask2Former, in automating AZ measurements from ultrasound images, comparing its performance against manual techniques. Conducted on chicken breast and liver samples, the study found the AI model to achieve high accuracy, particularly in chicken breast tissue, with no significant difference in measurements between AI and manual methods. These results suggest that the Mask2Former model can significantly reduce variability in manual measurements, marking a step forward in the automation of AZ measurement in RFA therapy research and potentially improving the precision of treatment assessments. Abstract Background: The accurate delineation of ablation zones (AZs) is crucial for assessing radiofrequency ablation (RFA) therapy’s efficacy. Manual measurement, the current standard, is subject to variability and potential inaccuracies. Aim: This study aims to assess the effectiveness of Artificial Intelligence (AI) in automating AZ measurements in ultrasound images and compare its accuracy with manual measurements in ultrasound images. Methods: An in vitro study was conducted using chicken breast and liver samples subjected to bipolar RFA. Ultrasound images were captured every 15 s, with the AI model Mask2Former trained for AZ segmentation. The measurements were compared across all methods, focusing on short-axis (SA) metrics. Results: We performed 308 RFA procedures, generating 7275 ultrasound images across liver and chicken breast tissues. Manual and AI measurement comparisons for ablation zone diameters revealed no significant differences, with correlation coefficients exceeding 0.96 in both tissues (p < 0.001). Bland–Altman plots and a Deming regression analysis demonstrated a very close alignment between AI predictions and manual measurements, with the average difference between the two methods being −0.259 and −0.243 mm, for bovine liver and chicken breast tissue, respectively. Conclusion: The study validates the Mask2Former model as a promising tool for automating AZ measurement in RFA research, offering a significant step towards reducing manual measurement variability.

Ye Zhang, A. Win, E. Makalic, D. Buchanan, R. Pai, A. Phipps, C. Rosty, Alex Boussioutas et al.

Survivors of colorectal cancer (CRC) are at risk of developing another primary colorectal cancer ‐ metachronous CRC. Understanding which pathological features of the first tumour are associated with risk of metachronous CRC might help tailor existing surveillance guidelines. Population‐based CRC cases were recruited from the United States, Canada and Australia between 1997 and 2012 and followed prospectively until 2022 by the Colon Cancer Family Registry. Metachronous CRC was defined as a new primary CRC diagnosed at least 1 year after the initial CRC. Those with the genetic cancer predisposition Lynch syndrome or MUTYH mutation carriers were excluded. Cox regression models were fitted to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the associations. Of 6085 CRC cases, 138 (2.3%) were diagnosed with a metachronous CRC over a median follow‐up time of 12 years (incidence: 2.0 per 1000 person‐years). CRC cases with a synchronous CRC were 3.4‐fold more likely to develop a metachronous CRC (adjusted HR: 3.36, 95% CI: 1.89–5.98) than those without a synchronous tumour. CRC cases with MMR‐deficient tumours had a 72% increased risk of metachronous CRC (adjusted HR: 1.72, 95% CI: 1.11–2.64) compared to those with MMR‐proficient tumours. Compared to cases who had an adenocarcinoma histologic type, those with an undifferentiated histologic type were 77% less likely to develop a metachronous CRC (adjusted HR: 0.23, 95% CI: 0.06–0.94). Existing surveillance guidelines for CRC survivors could be updated to include increased surveillance for those whose first CRC was diagnosed with a synchronous CRC or was MMR‐deficient.

Maja Drobnič-Radobuljac, U. Grošelj, R. Kaltiala, R. Vermeiren, D. Anagnostopoulos, Füsun Çuhadaroglu Çetin, Sofie Crommen, Stephan Eliez et al.

T. Tal, Oddvar Myhre, Ellen Fritsche, Joëlle Rüegg, K. Craenen, K. Aiello-Holden, Caroline Agrillo, Patrick J. Babin et al.

In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.

Luka Laura, Maja Arapović, Sanja Duvnjak, Jurica Arapović

Martina Arapović, Leona Puljić, Nikolina Kajić, B. Kartalović, Kristina Habschied, Krešimir Mastanjević

The hectic pace of modern life often leads to quick solutions, both in lifestyle and the choice of food we consume. The importance of the gut microbiome and its balance is being increasingly researched, with the prebiotic concept itself becoming a topic of scientific investigation. The aim of this paper is to analyze scientific studies on the understanding of prebiotics conducted between 2019 and 2024 in order to see what new knowledge, new sources, new ways of use, and newly established effects on certain disease states have been discovered during this period. The question that the authors are trying to answer is how specific prebiotics affect the growth and activity of selected probiotic strains in the human gut (have impact on gut microbiome) and what the implications of these interactions are. Four databases were searched: Pubmed/MEDLINE, Springerlink, Google Scholar, and Scopus. The keywords used were prebiotics, functional food, probiotics, gut microbiome, and trends. A systematic review of 30 scientific studies on the topic of prebiotics revealed significant advances in understanding and application. Research particularly indicates how prebiotics stimulate the growth of beneficial probiotic strains, such as Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, and Bifidobacterium. In addition, innovative approaches in food production, including pasta rich in prebiotic fibers, chocolate with inulin and stevia, and the use of fruit by-products, show promising results in creating “healthier” food options. Although the papers had differing objectives and research methodologies, certain similarities were found. All papers emphasized the importance of using prebiotics, although it depended on the type they come from and their impact on the gut microbiome, i.e., the stimulation of probiotic action within the gut microbiome, which consequently has benefits on health. This review serves as a springboard for further research in this exciting field, with the ultimate goal of harnessing the power of prebiotics to improve health outcomes.

This study explores the impact of digit(al)isation and convergence on television in Bosnia and Herzegovina, considering the fact that the digital revolution, sparked by the proliferation of advanced digital technologies, has brought significant changes to the media sphere. One of the key phenomena in contemporary media is media convergence, a multi-meaning concept influencing various stakeholders in the media landscape – media owners, management, journalists, editors, advertisers, and audiences. Qualitative research was conducted in this study, through semi-structured in-depth interviews (N=27) with management, journalists, and editors from Bosnian Herzegovinian TV stations (N=15). The aim of the study is to understand how media professionals navigate digital/convergent circumstances and which advantages and challenges they identify. Based on this research, it can be concluded that media professionals recognise the significance of quality content in the media (irrespective of technological changes), as well as the importance of collaborative effort that underscores shared responsibility to uphold standards and excellence within the dynamic digital media landscape.

S. Vranić, Z. Gatalica

Oncologic treatment has recently undergone substantial therapeutic paradigm shifts, from classical tumor-specific and biomarker-agnostic approaches to more molecular, biomarker-specific, and tumor-agnostic. Tumor-type (histology) agnostic drugs work across cancer types and present a novel shift in precision oncology. Compared with traditional cancer therapies, this novel approach implies molecularly informed treatment strategies and enables targeted treatment regardless of tumor histology (type). Such drugs are usually utilized in small clinical cohorts with diverse tumor types sharing a common genomic event (molecular biomarker). One of the key elements of this approach is the presence of a common biomarker across many tumor types. Biomarker predicts response to the targeted drugs, as well as deciphers potential resistance mechanisms. Read more in the PDF.

J. Kaesmacher, K. Treurniet, M. Kappelhof, T. Dobrocky, J. Ospel, A. Mujanović, J. Fiehler, B. Yan et al.

The expanded Thrombolysis in Cerebral Infarction (eTICI) scale is the default method to measure reperfusion success of endovascular treatment for acute ischemic stroke. It is an estimate of the percentage of the vascular territory affected by the initial occlusion, or target downstream territory (TDT), that is reperfused after the intervention. Traditionally, the size of the TDT is determined on the preinterventional catheter angiography images by delineating the antegrade capillary deficit caused by the catheter angiography target occlusion. As such, the current definition of eTICI grading is only suitable to estimate the efficacy of reperfusion strategies occurring after the baseline catheter angiogram. However, reperfusion therapy for acute ischemic stroke due to large vessel occlusion often encompasses intravenous thrombolysis therapy started prior to endovascular treatment but after cross‐sectional vascular imaging (computed tomography or magnetic resonance imaging) used to determine eligibility for endovascular treatment. The inherent shortcomings of the current eTICI scale to quantify preinterventional perfusion changes are discussed. We then argue that depending on the timing of the studied intervention – either between cross‐sectional imaging and endovascular treatment or after first intracranial catheter angiography – the TDT used to determine the eTICI grade should be based on the occlusion as seen on admission cross‐sectional vascular imaging or prethrombectomy catheter angiography, respectively. We propose a new conceptual framework to grade reperfusion based on the TDT derived from the occlusion seen on cross‐sectional vascular imaging: the cross‐sectional eTICI. Last, we discuss how this definition of the TDT more reliably measures preinterventional reperfusion and establishes homogenous definitions of embolization and infarctions in new territories.

G. Aad, E. Aakvaag, B. Abbott, S. Abdelhameed, K. Abeling, N. J. Abicht, S. H. Abidi, M. Aboelela et al.

This paper reports a summary of searches for a fermionic dark matter candidate in the context of theoretical models characterised by a mediator particle exchange in the s-channel. The data sample considered consists of pp collisions delivered by the Large Hadron Collider during its Run 2 at a centre-of-mass energy of s=13TeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s} = 13\,\textrm{TeV}$$\end{document} and recorded by the ATLAS detector, corresponding to up to 140 fb-1\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}. The interpretations of the results are based on simplified models where the new mediator particles can be spin-0, with scalar or pseudo-scalar couplings to fermions, or spin-1, with vector or axial-vector couplings to fermions. Exclusion limits are obtained from various searches characterised by final states with resonant production of Standard Model particles, or production of Standard Model particles in association with large missing transverse momentum.

Falak Bharadwaj, Arti Saxena, Rajender Kumar, Raman Kumar, Sandeep Kumar, Željko Stević

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