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Origanum compactum, Melaleuca alternifolia, and Cinnamomum camphora essential oils are recognized for their therapeutic potential, including their selective cytotoxicity against cancer cell lines. Our research focused on examining the cytotoxic effects of these essential oils on three human carcinoma cell lines: lung carcinoma (H460), cervical adenocarcinoma (HeLa), and colorectal carcinoma (HCT116). The MTT-based cell viability assay was used to assess the cytotoxicity of essential oils. The results demonstrated that all three essential oils exhibited dose-dependent cytotoxic potential, with varying levels of growth inhibition across the cell lines. Notably, the highest sensitivity was observed in H460 cells, and the lowest sensitivity was found in HCT116 cells. Origanum compactum demonstrated the strongest cytotoxicity across all cell lines (GI50 73 - 154 nL/mL), making it the most promising candidate for further investigation, particularly for lung and cervical cancer treatment.

Naim Salkić, Ana Budimir, Namik Trtak, Daniel Maleč, Eldad Kaljić, Safet Velić

Introduction: Sensory integration is the way in which the nervous system processes information from the senses. Irregularities or disturbances in brain function that make it difficult to integrate sensory input from stimuli lead to sensory disintegration. The proprioceptive sensory system provides information about joint and body movements, extent, strength, duration and direction of movement, position of the body or body parts in space, and muscle tone. The aim of this study is to investigate the prevalence of sensory integration disorders of the proprioceptive sensory system in children with intellectual disabilities and children without developmental disabilities and to determine whether the existing difference is statistically significant. Methods: The study was conducted on a sample of 60 respondents. The first subsample of respondents (n = 30) consisted of children with intellectual disabilities. The second subsample of respondents (n = 30) consisted of children without developmental disabilities of the same chronological age. The measuring instrument “Questionnaire for examining proprioceptive sensory sensitivity” was used. Data were collected by observing the respondents and interviewing the rehabilitator and the child’s parents. The frequencies and percentages of the respondents’ answers for all variables were calculated. To determine the statistical significance of differences, the Mann-Whitney U test and Wilcoxon W test were used at a statistical significance level of p < 0.05. Results: The results show that 81.4% of children with intellectual disabilities have difficulties with sensory integration of the sensations of the proprioceptive sensory system, manifested as hypersensitivity (37.6%), hyposensitivity (19.5%), and mixed sensory response (24.3%). Sensory integration difficulties are also experienced by 75.7% of children without developmental disabilities, manifested by hypersensitivity (17.62%), hyposensitivity (27.6%), and mixed sensory reactions (30.5%). There is a statistically significant difference in the variables: high-risk games, fine motor tasks, and activities requiring physical strength. For the other variables, the difference in sensory integration is not statistically significant. Conclusion: 81.4% of children with intellectual disabilities and 75.7% of children without developmental disabilities have difficulties in sensory integration of the proprioceptive sensory system. Children with intellectual disabilities show better integration of proprioceptive sensory input in activities requiring physical strength and in activities with eyes closed or covered. In all other activities, they show poorer sensory integration of proprioceptive sensations than children without developmental disabilities.

Hugang Feng, Daqi Deng, Rashmi Dahiya, Libin Wang, Jingkun Zeng, Benjy Jek Yang Tan, F. Byrne, Scott T C Shepherd et al.

Nela Kelam, Marin Ogorevc, Ivona Gotovac, I. Kuzmić Prusac, Katarina Vukojević, M. Saraga-Babic, S. Mardešić

Background/Objectives: The human kallikrein-related peptidase 6 (KLK6), a serine protease with trypsin-like properties, belongs to the 15-member kallikrein (KLK) gene family and is predominantly recognized for its role in oncogenesis, neurodegenerative disorders, and skin conditions. Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across cell membranes. AQP1 is constitutively active in the kidneys and plays a crucial role in reabsorbing filtered water, while AQP2 is regulated by vasopressin and is essential for maintaining body fluid homeostasis. The primary objective of the present study is to investigate the spatio-temporal expression patterns of KLK6, AQP1, and AQP2 throughout normal human nephrogenesis and congenital kidney and urinary tract (CAKUT) abnormalities: duplex kidneys, horseshoe kidneys, and dysplastic kidneys. Methods: An immunofluorescence analysis of KLK6, AQP1, and AQP2 was performed on 37 paraffin-embedded fetal kidney samples. The area percentage of KLK6 in the kidney cortex was calculated in normal developing samples during developmental phases 2, 3, and 4 and compared with CAKUT samples. Results: KLK6 exhibits distinct spatiotemporal expression patterns during human kidney development, with consistent localization in proximal tubules. Its subcellular positioning shifts from the basolateral cytoplasm in early phases to the apical cytoplasm in later stages, which may be strategically positioned to act on its substrate in either the peritubular space or the tubular fluid. KLK6 expression followed a quadratic trajectory, peaking at Ph4. This marked increase in the final developmental phase aligns with its strong expression in mature kidneys, suggesting a potential role in proximal tubule differentiation and functional maturation through facilitating extracellular matrix remodeling and activating proteinase-activated receptors, modulating the signaling pathways that are essential for tubular development. In duplex kidneys, structural abnormalities such as ureteral obstruction and hydronephrosis may upregulate KLK6 as part of a reparative response, while its downregulation could impair epithelial remodeling and cytoskeletal integrity, exacerbating dysplastic phenotypes. Conclusions: These findings highlight the potential of KLK6 involvement in normal kidney development and the pathology of CAKUT.

M. Benedikt, F. Zimmermann, B. Auchmann, W. Bartmann, J. Burnet, C. Carli, A. Chanc'e, P. Craievich et al.

In response to the 2020 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) Feasibility Study was launched as an international collaboration hosted by CERN. This report describes the FCC integrated programme, which consists of two stages: an electron-positron collider (FCC-ee) in the first phase, serving as a high-luminosity Higgs, top, and electroweak factory; followed by a proton-proton collider (FCC-hh) at the energy frontier in the second phase. FCC-ee is designed to operate at four key centre-of-mass energies: the Z pole, the WW production threshold, the ZH production peak, and the top/anti-top production threshold - delivering the highest possible luminosities to four experiments. Over 15 years of operation, FCC-ee will produce more than 6 trillion Z bosons, 200 million WW pairs, nearly 3 million Higgs bosons, and 2 million top anti-top pairs. Precise energy calibration at the Z pole and WW threshold will be achieved through frequent resonant depolarisation of pilot bunches. The sequence of operation modes remains flexible. FCC-hh will operate at a centre-of-mass energy of approximately 85 TeV - nearly an order of magnitude higher than the LHC - and is designed to deliver 5 to 10 times the integrated luminosity of the HL-LHC. Its mass reach for direct discovery extends to several tens of TeV. In addition to proton-proton collisions, FCC-hh is capable of supporting ion-ion, ion-proton, and lepton-hadron collision modes. This second volume of the Feasibility Study Report presents the complete design of the FCC-ee collider, its operation and staging strategy, the full-energy booster and injector complex, required accelerator technologies, safety concepts, and technical infrastructure. It also includes the design of the FCC-hh hadron collider, development of high-field magnets, hadron injector options, and key technical systems for FCC-hh.

M. Benedikt, F. Zimmermann, B. Auchmann, W. Bartmann, J. Burnet, C. Carli, A. Chanc'e, P. Craievich et al.

Volume 1 of the FCC Feasibility Report presents an overview of the physics case, experimental programme, and detector concepts for the Future Circular Collider (FCC). This volume outlines how FCC would address some of the most profound open questions in particle physics, from precision studies of the Higgs and EW bosons and of the top quark, to the exploration of physics beyond the Standard Model. The report reviews the experimental opportunities offered by the staged implementation of FCC, beginning with an electron-positron collider (FCC-ee), operating at several centre-of-mass energies, followed by a hadron collider (FCC-hh). Benchmark examples are given of the expected physics performance, in terms of precision and sensitivity to new phenomena, of each collider stage. Detector requirements and conceptual designs for FCC-ee experiments are discussed, as are the specific demands that the physics programme imposes on the accelerator in the domains of the calibration of the collision energy, and the interface region between the accelerator and the detector. The report also highlights advances in detector, software and computing technologies, as well as the theoretical tools /reconstruction techniques that will enable the precision measurements and discovery potential of the FCC experimental programme. This volume reflects the outcome of a global collaborative effort involving hundreds of scientists and institutions, aided by a dedicated community-building coordination, and provides a targeted assessment of the scientific opportunities and experimental foundations of the FCC programme.

M. Benedikt, F. Zimmermann, B. Auchmann, W. Bartmann, J. Burnet, C. Carli, A. Chanc'e, P. Craievich et al.

Volume 3 of the FCC Feasibility Report presents studies related to civil engineering, the development of a project implementation scenario, and environmental and sustainability aspects. The report details the iterative improvements made to the civil engineering concepts since 2018, taking into account subsurface conditions, accelerator and experiment requirements, and territorial considerations. It outlines a technically feasible and economically viable civil engineering configuration that serves as the baseline for detailed subsurface investigations, construction design, cost estimation, and project implementation planning. Additionally, the report highlights ongoing subsurface investigations in key areas to support the development of an improved 3D subsurface model of the region. The report describes development of the project scenario based on the 'avoid-reduce-compensate' iterative optimisation approach. The reference scenario balances optimal physics performance with territorial compatibility, implementation risks, and costs. Environmental field investigations covering almost 600 hectares of terrain - including numerous urban, economic, social, and technical aspects - confirmed the project's technical feasibility and contributed to the preparation of essential input documents for the formal project authorisation phase. The summary also highlights the initiation of public dialogue as part of the authorisation process. The results of a comprehensive socio-economic impact assessment, which included significant environmental effects, are presented. Even under the most conservative and stringent conditions, a positive benefit-cost ratio for the FCC-ee is obtained. Finally, the report provides a concise summary of the studies conducted to document the current state of the environment.

Darijo Raca, Gregory Provan, Ahmed Zahran

Accurate Throughput Prediction (TP) represents a real challenge for reliable adaptive streaming in challenging mediums, such as cellular networks. State-of-the-art solutions adopt Deep Learning (DL) models to improve TP accuracy for various multimedia systems. This paper illustrates that designing blackbox TP engines that depend solely on the model’s capacity and power of learning does not achieve consistent accuracy across all throughput ranges. Additionally, we propose MATURE, a novel multi-stage DL-based TP model designed to capture network operating context to improve prediction accuracy. MATURE’s prediction involves characterising the operating context before estimating the network throughput. We show that MATURE delivers consistent, accurate prediction for all throughput ranges in both 4G and 5G networks. We also show that light-weight mature models that use quantized parameters maintain their accuracy while featuring up to 100x faster inference, thus making them suitable for mobile implementation. Our real video streaming experiments further show that MATURE improves the average user Quality of Experience (QoE) by up to 20% when compared to other throughput prediction methods.

S. Salinger, Aleksandra Kozic, B. Džudović, B. Subotic, J. Matijašević, M. Benic, V. Miloradović, Ema Jevtic et al.

Newly or already diagnosed cancer might significantly influence the clinical presentation, outcome, and therapy of acute pulmonary embolism (PE).

The current state of research on the anti-SARS-CoV-2 potential of artemisinin-related compounds has identified arteannuin B as a potent inhibitor of the nCoV-2019BetaCov/Wuhan/WiV04/2019 and BetaCov/Italy/CDG1/2020 strains of the virus. The aim of this work was to fractionate the targeted sesquiterpenoid compounds, arteannuin B and artemisinin, from the complex matrix of the crude ethanolic leaf extract of Artemisia annua L. using high-speed countercurrent chromatography (HSCCC) and to test the simplified or purified fractions against the genomically characterized Alpha SARS-CoV-2 variant in vitro. This is the first detailed in vitro anti-SARS-CoV-2 study using an analytically characterized supercritical fluid extract of A. annua L. The preparative HSCCC method enabled the isolation of purified arteannuin B in a single chromatographic step, which was confirmed by LC-ESI-QTOF-MS/MS. The MS data confirmed the selectivity of the HSCCC method for the targeted fractionation of artemisinin from the complex matrix, as it was successfully separated from the EtOH crude extract without co-elution with arteannuin B. Antiviral activity determined by quantitative real-time PCR (qRT-PCR) yielded half-maximal effective concentrations (EC50) of 93.7 µg/mL (SC-CO2 extract), 173.5 µg/mL (EtOH extract), 187.3 µg/mL (artemisinin knockout fraction), 38.1 µg/mL (arteannuin B fraction), and >100 µg/mL (artemisinin). The arteannuin B fraction was highly active at 50 µg/mL (p < 0.0001) and 100 µg/mL (p < 0.0001), and inhibited the amplification of the SARS-CoV-2 N and RdRp genes by 84% and 100%, respectively. An important contribution of this study is the demonstration of the antiviral activity of arteannuin B against the Alpha variant of SARS-CoV-2, which is known to have increased infectivity and transmissibility.

Denis Čaušević, C. Alexe, Nedim Čović, E. Panaet, Ensar Abazović, Raul Marian Todor, B. Rani, Gabriel-Stănică Lupu et al.

This study aimed to examine the habits, attitudes, and consumption patterns of food supplements (FS) among gym users in Sarajevo, Bosnia and Herzegovina, with respect to gender, age, and training experience. Understanding these behaviors is essential given the rising global trend in FS use, often without professional guidance, which can have implications for individual health and public awareness. By investigating local patterns, this study seeks to provide valuable insights into the motivations and risks associated with supplement consumption, contributing to evidence-based recommendations and policy-making in the field of fitness and nutrition. Methods: Cross-sectional data were collected from various fitness centers using an online questionnaire composed of 21 questions divided into three segments. A total of 614 participants (mean ± SD: 32.77 ± 9.82 years), including both male (67.8%) and female (32.2%) gym users, took part in the study. Results: Participants predominantly belonged to the 36–45 age group, with 70.0% (p < 0.001) reporting more than one year of regular gym attendance, and 40.4% indicating regular FS consumption (p < 0.05). Supplements were mainly used to support faster recovery (29.1%, p < 0.05) and muscle growth (25%, p < 0.05). Magnesium was the most commonly used supplement, equally favored across genders and age groups. Creatine, fish oil capsules, and multivitamins were also frequently consumed (p < 0.05). Self-prescription emerged as the predominant method of FS use (40.3%, p < 0.05), followed by advice from gym coaches (21.8%), with only 5.6% of participants receiving guidance from a nutritionist. Conclusions: The findings highlight a societal trend toward self-directed FS use, often influenced by informal sources, underscoring the importance of further research and the development of targeted, evidence-based educational strategies. Males reported higher FS consumption, with younger users more focused on muscle gain and older individuals prioritizing health maintenance. The reliance on non-expert recommendations raises concerns about the safety and effectiveness of FS usage in the fitness community.

Sihem Bakri, I. Dey, H. Šiljak, Marco Ruffini, Nicola Marchetti

O-RAN (Open-Radio Access Network) offers a flexible, open architecture for next-generation wireless networks. Network slicing within O-RAN allows network operators to create customized virtual networks, each tailored to meet the specific needs of a particular application or service. Efficiently managing these slices is crucial for future 6G networks. O-RAN introduces specialized software applications called xApps that manage different network functions. In network slicing, an xApp can be responsible for managing a separate network slice. To optimize resource allocation across numerous network slices, these xApps must coordinate. Traditional methods where all xApps communicate freely can lead to excessive overhead, hindering network performance. In this paper, we address the issue of xApp conflict mitigation by proposing an innovative Zero-Touch Management (ZTM) solution for radio resource management in O-RAN. Our approach leverages Multi-Agent Reinforcement Learning (MARL) to enable xApps to learn and optimize resource allocation without the need for constant manual intervention. We introduce a Graph Convolutional Network (GCN)-based attention mechanism to streamline communication among xApps, reducing overhead and improving overall system efficiency. Our results compare traditional MARL, where all xApps communicate, against our MARL GCN-based attention method. The findings demonstrate the superiority of our approach, especially as the number of xApps increases, ultimately providing a scalable and efficient solution for optimal network slicing management in O-RAN.

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