SMAD4 is a tumour suppressor gene that is mutated in up to 60% of pancreatic ductal adenocarcinoma (PDAC) tumours. Activins are members of the TGF-b signalling superfamily which signal through SMAD4 and are generally associated with an oncogenic process, with differing effects on tumour and stromal cells, such as cancer associated fibroblasts (CAFs). We sought to further elucidate the role of activin within PDAC and perturb activin signalling in vitro and in vivo. Analysis was performed of publicly available human datasets alongside human and murine single-cell RNA-sequencing datasets to study the effect of activin expression on survival and tumourigenesis. We developed anti-activin monoclonal antibodies to perturb activin signalling in PDAC mice, with deep analysis of tumour composition including immune cells and CAFs via a multitude of basic science techniques. We demonstrated that circulating activin levels are higher in PDAC patients than in healthy volunteers, whilst activin overexpression is associated with reduced overall survival in PDAC patients. Activin was shown to be predominantly expressed by contractile (collagen-depositing) CAFs, as opposed to inflammatory CAFs. Activin expression co-localises with fibroblasts, and anti-activin antibodies can reduce the collagen content of dense PDAC tumours. Additionally, anti-activin antibodies led to a statistically significant increase in CD4 and CD8 T-cell infiltration into murine PDAC tumours. We have shown that activin is overexpressed in PDAC, and high expression is associated with a more aggressive disease process. Anti-activin antibodies can alter the composition of desmoplastic PDAC tumours and increase the immune infiltrate of these typically “immune cold” tumours.

Abstract Avian influenza, commonly known as bird flu, is a highly infectious viral disease that affects birds, including wild water birds and poultry. The emergence and spread of highly pathogenic avian influenza (HPAI) strains, such as H5N1, have raised concerns due to their potential to cause severe outbreaks and cross the species barrier, leading to human infections and global public health emergencies. In this study, we report the first case of HPAI H5N1 detection in Montenegro. Twenty-six carcasses of dalmatian pelicans were found in Skadar Lake, Montenegro, and the H5N1 subtype was confirmed through molecular testing in the samples from pelicans. The whole influenza genome was sequenced and belonging to clade 2.3.4.4b was determined.

: Variants of proportional navigation (PN) are perhaps mostly used guidance laws for tactical homing missiles. PN aims to generate commanding missile lateral acceleration proportional to line of sight (LOS) angular rate, so that missile velocity vector rotates in such a way to assure interception of a target. In order to generate commanding lateral accelerations, the guidance system needs measurements of LOS angular rate and the closing velocity between the missile and the target, or the missile velocity. A device which provides guidance information is referred to as the missile seeker. In the case of imaging based seekers (visible light (EO), infrared light (IIR)), LOS rate is estimated using imaging sensor, while closing or missile velocity is measured using appropriate sensors or guess estimated. In this paper, we present the design and simulation of a missile homing system which includes: true PN guidance law, linear multiloop acceleration autopilot, and gimbaled imaging based missile seeker. Target seeker uses advanced deep machine learning object detection YOLO (You only look once) model, for target detection and tracking as well as LOS rate estimation. Comprehensive simulation model, consisting of full 6DOF missile and controls dynamics, 3D world and camera model, is developed. Intensive simulation results show performances of the proposed missile homing system.

The sharpnose sevengill shark (Heptranchias perlo) is a rare and poorly understood deep‐sea species, with only a few records in the Adriatic Sea over the last two centuries and a significant gap in sightings. Throughout 2023, three new records are documented in the southernmost Adriatic Sea, found at depths ranging from 391 to 452 m off Vlorë. This study marks the first comprehensive health examination of a deep‐sea shark, investigating potential trauma and injuries resulting from trawling. It encompasses pathological and histopathological examinations, supplemented by magnetic resonance imaging (MRI). The research highlights alarming post‐capture mortality rates in this data deficient species, discusses further conservation implications, and proposes protective measures for the species. Beyond addressing critical knowledge gaps, this study advocates for collaborative efforts with local fishermen to establish long‐term monitoring and obtain data on the frequency and abundance of elusive species.

This paper explores the possibility of using recycled seashells from marine coasts of the Mali Ston Bay in Dubrovnik-Neretva County, Croatia, to create a novel bio material derived from waste seashells. In this research, two types of waste seashells, mussel (Mytilus galloprovincialis) and oyster (Ostrea edulis), combined with natural, non-toxic binders (bone glue) were investigated experimentally. The goal is to develop a sustainable material, suitable for the production of furniture and decorative objects. The parameters studied, included physical and mechanical properties of this material. The results showed that this bio composite material, derived from recycled seashells, is hygroscopic and has low compression strength. It should be used for making furniture components that don't bear heavy loads and it is suitable only for interior applications. This study presents an eco-friendly and sustainable material option, while optimizing the recycling of food waste materials.

Bosnia and Herzegovina (BiH) accumulates challenges in the areas of research and innovation (R&I), agricultural water management (AWM) and their intersection. In the decade 2012–2022, the BiH gross domestic product per capita in current US$ increased by 6.2% annually. However, improvements are slowly arriving in R&I and AWM. In this period, relevant challenges to AWM have materialized, such as climate change effects or the need to implement an interconnected vision of ecosystem services. In the R&I arena, the societal demand for knowledge goods remains low, while the reforms of higher education and R&I funding systems have become urgent. This paper set out to elaborate a realistic and feasible policy roadmap to consolidate R&I in AWM in BiH. The methodology included an assessment of policies and sector performance, the analysis of stakeholder perceptions, the development of strategic directions and the design of a strategy. Desk research and stakeholder consultations (33 interviews, six workshops, 179 persons in total) were used to take stock of the current situation and expectations for the future. Stakeholders were divided into knowledge supply and knowledge demand, with five and six subcategories, respectively. Relations were established among the key enabling factors, the needs and the capacities of the involved stakeholders. The TOWS (Threats, Opportunities, Weaknesses and Strengths) matrix permitted to identify policy strategies. A Weaknesses – Opportunities, conservative or mini-maxi strategy was selected, owing to the relevance of system weaknesses (such as low investments, poor return of R&I to society or low R&I for AWM adaptation) and opportunities (such as the Green Agenda for the Western Balkans, Smart Specialization or regional partnerships). The policy roadmap was structured along three policy goals: strengthen R&I, strengthen AWM and identify / fund local R&I priorities for AWM. Policy goals included policy instruments promoting eco-efficient use of resources and sustainable development of rural areas.

Background. Oxidative stress and inflammation are closely related pathophysiological processes, both occurring in type 2 diabetes mellitus (T2DM). In addition to the standard treatment of T2DM, a potential strategy has been focused on the use of bile acids (BAs) as an additional treatment. Ursodeoxycholic acid (UDCA), as the first BA used in humans, improves glucose and lipid metabolism and attenuates oxidative stress. The aim of this study was to evaluate the potential metabolic, anti-inflammatory, and antioxidative effects of UDCA in patients with T2DM. Methods. This prospective, double-blind, placebo-controlled clinical study included 60 patients with T2DM, randomly allocated to receive UDCA or placebo. Subjects were treated with 500 mg tablets of UDCA or placebo administered three times per day (total dose of 1500 mg/day) for eight weeks. Two study visits, at the beginning (F0) and at the end (F1) of the study, included the interview, anthropometric and clinical measurements, and biochemical analyses. Results. UDCA treatment showed a significant reduction in body mass index (p=0.024) and in diastolic blood pressure (p=0.033), compared to placebo. In addition, there was a statistically significant difference in waist circumference in the UDCA group before and after treatment (p<0.05). Although no statistical significance was observed at the two-month follow-up assessment, an average decrease in glucose levels in the UDCA group was observed. After two months of the intervention period, a significant decrease in the activity of liver enzymes was noticed. Furthermore, a significant reduction in prooxidative parameters (TBARS, NO2-, H2O2) and significant elevation in antioxidative parameters such as SOD and GSH were found (p<0.001). Conclusions. The eight-week UDCA administration showed beneficial effects on metabolic and oxidative stress parameters in patients with T2DM. Thus, UDCA could attenuate the progression and complications of diabetes and should be considered as an adjuvant to other diabetes treatment modalities. This trial is registered with NCT05416580.

Background: The recognition of comorbidities is relevant for asthma management, especially if these conditions/diseases are treatable traits such as anxiety. This study aimed to explore the associations between asthma severity and child and parent asthma-related anxiety and to recognize the most common specific fears. Methods: This cross-sectional study consisted of 150 parents and their children diagnosed with asthma, and was conducted at the Pediatric Clinic of the University Hospital Center Split in Croatia. All children, from ages 3 to 17 years, underwent a thorough clinical examination. A total of 150 parents and 108 children filled out an asthma-related anxiety questionnaire in paper form. Results: Parents of children with moderate and severe asthma had higher asthma-related anxiety due to restrictions related to asthma symptoms (p = 0.032), and children diagnosed with moderate and severe asthma had greater anxiety due to restrictions related to asthma symptoms than children diagnosed with mild asthma (p = 0.004). Children’s anxiety was the highest when they experienced an asthmatic attack during physical activity (PA), and they fear that they will not be successful in sports or dancing due to asthma. Parents commonly reported the fear of an asthma attack without warning signs (p < 0.001), fear of drug side effects (p < 0.001), fear of absence from school (p = 0.006), and fear of an asthma attack during PA (p < 0.001). Conclusions: The current study reports findings of increased parental levels of anxiety when compared to their children, related to fear of an asthma attack occurring without warning signs, fear of side effects and fear of absence from school, as well as the fear of an asthma attack occurring during sports activities. When assessing individual items on anxiety associated with asthma, children most commonly reported concern related to physical activity.

The purpose of this study was to evaluate the effects of Dab1 gene silencing on the immunoexpression of light chain 3 beta (Lc3b), glucose regulating protein 78 (Grp78), heat shock cognate 71 (Hsc70), mammalian target of rapamycin (mTOR) and lysosomal-associated membrane protein 2A (Lamp2a) in the lung tissue of developing yotari (Dab1−/−) and wild-type (wt) mice. The lung epithelium and mesenchyme of the embryos at gestational days E13.5 and E15.5 were examined using immunofluorescence and semi-quantitative methods. In the pulmonary mesenchyme and epithelium, Grp78 and Lc3b of moderate fluorescence reactivity was demonstrated in wt mice for both evaluated time points, while yotari mice exhibited only epithelial reactivity for the same markers. Mild punctate expression of Hsc70 was observed for both genotypes. A significant difference was present when analyzing mTOR expression, where wt mice showed strong perinuclear staining in the epithelium. According to our data, Dab1 gene silencing may result in autophagy abnormalities, which could then cause respiratory system pathologies via defective lung cell degradation by lysosome-dependent cell elimination.

The progression of telecommunications, starting from the inception of 1G networks in 1979 to the advent of 5G technology in 2019, represents a significant journey of advancement for humanity. As we approach the era of 5G, characterized by heightened machine-to-machine connectivity and transformative applications in AI, IoT, and cloud computing, it becomes imperative to acknowledge and address concerns regarding its potential impacts on health and the environment. Utilizing machine learning algorithms, particularly implemented in Python for this research, provides a potent approach to analyzing intricate datasets concerning 5G signals and their potential correlations with healthcare outcomes. After carefully cleaning and preparing the data and conducting linear regression analysis, uncovered evidence backing the notion that 5G antennas emit greater levels of radiation compared to 4G antennas emerged - a fact often concealed by corporations. Despite relying on a restricted dataset, the results emphasize the necessity for more accurate data to improve model precision. Ongoing research endeavors are vital to alleviate public anxieties regarding 5G technology, thereby fostering trust and bolstering awareness on a wider front.

This research focused on the determination of potentially toxic elements (PTEs) distribution in different agricultural soils and Ambrosia atremisiifolia L. (ragweed) at seven, different locations in the northern part of Bosnia and Herzegovina (BiH). Quantification of PTEs was done using atomic absorption spectrophotometry provided after acid digestion of the air-dried samples of soil and plant material. Determined content of elements in the soils increased as follows: Cd<Pb<Cu<Zn<Cr<Ni<Mn<Fe and were under the allowed maximum for unpolluted soils, except for Ni and Cr. However, transfer of Ni and Cr from the soil to the ragweed as well as their bioaccumulation was not intensive. Established metal contents ratio from plant tissues (root and shoot) to soil for both elements, represented their bioaccumulation factors (BAF), which were extremely low in the roots, as well as in the shoots, both in average less than 0.2. On the other hand, Zn showed a tendency to accumulate in ragweed shoots (BAF=2.07). The study showed that uptake and accumulation of PTEs in the ragweed was mainly influenced by their content in the soil, as well as specific characteristics and biological role of each element. Hence, content of PTEs in the ragweed tissue could be used as the soil contamination degree indicator.

In the validation of microclimate simulation software, the comparison of simulation results with on-site measurements is a common practice. To ensure reliable validation, it is crucial to utilize high-quality temperature sensors with a deviation smaller than the average absolute error of the simulation software. However, previous validation campaigns have identified significant absolute errors, particularly during periods of high solar radiation, possibly attributed to the use of non-ventilated radiation shields. This study addresses the issue by introducing a ventilated radiation shield created through 3D printing, aiming to enhance the accuracy of measurements on cloudless summer days with intense solar radiation. The investigation employs two pairs of sensors, each comprising one sensor with a ventilated and one with a non-ventilated radiation shield, placed on a south-oriented facade with two distinct albedos. Results from the measurement campaign indicate that the air temperature measured by the non-ventilated sensor is elevated by up to 2.8 °C at high albedo and up to 1.9 °C at a low albedo facade, compared to measurements with the ventilated radiation shield. An in-depth analysis of means, standard deviations, and 95% fractiles highlights the strong dependency of the non-ventilated sensor error on wind velocity. This research underscores the importance of employing ventilated radiation shields for accurate microclimate measurements, particularly in scenarios involving high solar radiation, contributing valuable insights for researchers and practitioners engaged in microclimate simulation validation processes.

This paper reports the impact of screen-printed PEDOT:PSS conductive ink on the optical properties of polyester fabric and colourimetric properties of yellow screen printing ink printed in a different number of layers. Yellow was chosen as one of four process colours which should theoretically suffer the most prominent changes from PEDOT:PSS overprinting. The study found that PEDOT:PSS ink significantly impacts the optical properties of the fabric and yellow ink, especially regarding the lightness and b-coordinate of the yellow ink. The acid treatment of samples, to increase PEDOT:PSS conductivity, also affected the optical characteristics through partial neutralization of the changes in the b-coordinate, especially when the sample was printed with a larger number of layers of the yellow ink and a smaller number of layers of PEDOT:PSS ink. Samples with two layers of yellow and one layer of PEDOT:PSS ink showed good conductivity results even without acid treatment, while the base colour appeared slightly darker. This change in the lightness can be compensated to some extent, proving that the aforementioned combination of PEDOT:PSS and base ink layers are the best when aspects, such as optical characteristics, conductivity, the complexity of production, production time, and limitations of the use of substrate materials are taken into account. This study provides useful insights for optimizing the printing process of PEDOT:PSS conductive inks over screen printed fabrics for various applications, including wearable electronics and smart textiles.