Explore the vast range of titles available.

Objectives:Patients with rheumatoid arthritis (RA) have defective CD4+CD25+ regulatory T (Treg) cells and increased osteoclastogenesis. A similar situation has been described in collagen-induced arthritis (CIA). In this study, it was investigated whether a single transfer of polyclonally activated Treg cells inhibits CIA and osteoclastogenesis.Methods:Purified Treg cells were expanded in vitro with anti-CD3 and anti-CD28 antibody-coated beads and injected into DBA/1 mice. Mice were immunised with collagen type II (CII) in complete Freund adjuvant (CFA) and scores of arthritis were recorded. In vitro osteoclastogenesis assays were performed on splenocytes by stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)κB ligand (RANKL). Levels of anti-CII antibody and cytokines were determined in the supernatant using ELISA and Bio-Plex protein array system.Results:It was found that 106 activated Treg cells significantly counteracted the development of CIA, which was accompanied by decreased serum levels of TNFα and IL6, but not by inhibition of autoimmune antibody responses. The differentiation of osteoclasts in splenocyte cultures was significantly reduced in the presence of prestimulated Treg cells. Expression of cytokines that are described to inhibit osteoclastogenesis, including granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)γ, interleukin (IL)5 and IL10, were dramatically increased upon addition of Treg cells. Furthermore, splenocytes from mice that had been treated with Treg cells displayed an impaired capacity to develop into mature osteoclasts, suggesting that Treg cells abrogated osteoclastogenesis in vivo.Conclusions:Activated CD4+CD25+ Treg cells improve clinical symptoms of CIA, regulate cytokine production and inhibit osteoclastogenesis in vitro and in vivo.

Background Systemic juvenile idiopathic arthritis (sJIA) is one of the most severe pediatric systemic immune-inflammatory disorders, characterized by arthritis and systemic features including fever, rash, lymphadenopathy and leukocytosis. A frequent, potentially fatal complication of sJIA is macrophage activation syndrome (MAS). An excessive production of pro-inflammatory cytokines has been demonstrated in sJIA with or without MAS, yet the exact cause and pathogenesis are still unknown. Studies on gene expression profiles performed on freshly isolated peripheral blood mononuclear cells (PBMCs) from sJIA patients revealed a conspicuous absence of interferon-gamma (IFN-γ)-upregulated genes. This is a peculiar finding, given the highly inflammatory nature of sJIA and the concept that IFN-γ is a driver of MAS. Objectives In this study we explored whether PBMCs of sJIA patients have a defect in IFN-γ signaling by studying induced genes and proteins upon in vitro stimulation with IFN-γ. Methods 9 sJIA patients (7 under treatment and in remission, 1 with active disease despite treatment, 1 untreated) and 1 sJIA patient presenting with MAS were recruited from the University Hospital of Leuven after giving informed consent. PBMCs from patients and healthy controls were obtained by gradient centrifugation and were cultured for 24 hours in the presence or absence of IFN-γ. RNA was extracted from the harvested cells. cDNA was synthesized and qPCR was performed on different IFN-γ-induced genes. IFN-γ-induced proteins (interferon-induced protein (IP-10) and monocyte chemotactic factor-1 (MCP-1)) were analyzed in supernatant of cells, by ELISA. Results In PBMCs from healthy control patients, IFN-γ induced - as expected - upregulation of STAT 1 mRNA, an important IFN-γ-induced transcription factor, as well as other IFN-γ-induced genes such as indoleamine 2,3-dioxygenase (IDO) and IP-10. Some genes such as suppressor of cytokine signaling 3 (SOCS3), MCP-1 and interferon regulatory factor-1 (IRF-1) were not upregulated in healthy PBMCs. Most importantly, all of the IFN γ-associated genes that were significantly induced in healthy control PBMCs were at the least equally well induced in sJIA patients (in both treated, untreated and MAS conditions). Significant production of IP-10 protein was found in the supernatant of IFN-γ-stimulated PBMCs, and here again there was no difference between patients and controls. Conclusions We conclude that PBMCs from sJIA/MAS patients have no intrinsic defect in the IFN-γ machinery. Thus the absence of an IFN-γ signature in sJIA, as reported in gene expression studies, cannot be explained by decreased in vitro responsiveness of PBMCs to IFN-γ, and further research is required to explain this discrepancy. Disclosure of Interest None Declared

Background Systemic juvenile idiopathic arthritis (sJIA) is a disease characterized by arthritis and systemic features such as fever, rash, lymphadenopathy and leukocytosis. The underlying pathogenic mechanism of sJIA is not understood but prolonged stimulation of immune cells and excessive production of cytokines are considered to be important in the pathogenesis of the disease. Objectives The lack of a suitable animal model is a major drawback in the investigation of the pathogenesis of sJIA. We examined whether complete Freund’s adjuvant (CFA), a widely used reagent for chronic stimulation of the immune system, can elicit sJIA-like features in mice. Since interferon-gamma (IFN-γ) exerts key functions in activating and regulating innate and adaptive immune responses and given the disputable role of IFN-γ in sJIA patients, we examined our hypothesis in wild type as well as IFN-γ-deficient mice. Methods IFN-γ-deficient (IFN-γ KO) and wild type mice were injected s.c. with CFA. Body weight, clinical signs of arthritis, complete blood cell counts and peripheral blood biochemistry were monitored. Inflammatory cytokine levels were measured by qPCR and ELISA. Flow cytometry and histology were performed on spleen, liver, bone marrow and lymph nodes. Results Consistent with the immune stimulating properties of CFA, both IFN-γ KO and wild type mice showed splenomegaly and lymphadenopathy from 10 days after CFA challenge onward. Both substrains also developed weight loss; however, while this was transient in wild type animals, it was prolonged and more severe in IFN-γ KO mice. Furthermore, a proportion of the IFN-γ KO, but not wild type mice developed skin rashes as well as redness and swelling in the joints, histologically consistent with prominent synovitis. Complete blood counts demonstrated an increase in platelets and neutrophils in both substrains of mice, the increase being more pronounced in IFN-γ KO mice. IL-6 serum levels were significantly elevated in CFA-challenged IFN-γ KO mice only. Interestingly, between 11 to 40 days post CFA injection, approximately 30% of IFN-γ KO mice developed cytopenia and anemia, as evident from their significantly decreased lymphocyte and red blood cell counts, and decreases in hemoglobin and hematocrit levels. Intriguingly, in CFA-challenged IFN-γ KO mice, bone marrow, spleen, liver and blood showed a prominent infiltration of macrophages, including increased numbers of hemophagocytic macrophages. Conclusions Upon challenge with CFA, IFN-γ KO mice developed clinical, biological and pathological features similar to those seen in patients with sJIA. A proportion of these mice also developed severe inflammation with wasting, anemia and hemophagocytosis, features that are seen in a subset of sJIA patients, diagnosed with macrophage activation syndrome (MAS). To our knowledge, this is the first animal model of sJIA showing an association with MAS. Our data demonstrate that IFN-γ is not required for chronic anemia and hemophagocytosis and challenge the concept that IFN-γ is the critical driver of MAS. Disclosure of Interest None Declared

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that occurs in 0.5-1.0% of the population worldwide. The primary affected organ is the small diarthrodial joint, where the synovial membrane, cartilage and bone tissue will be damaged, ultimately leading to joint deformity and disability of the patient. In the pathogenesis of RA, the synovial membrane becomes hyperplastic and will be infiltrated with T cells, B cells, neutrophils and macrophages. A hallmark of RA is the progressive destruction of bone tissue caused by an elevated bone resorption by osteoclasts, multinuclear cells derived from the monocyte/macrophage lineage. Objectives Our goal was to provide a method to visualize and quantify joint inflammation by the use of an animal model of RA, namely collagen-induced arthritis (CIA). We focused on the macrophage mannose receptor (MMR), since this protein is a well described marker for macrophages, which are numerously present in inflamed tissues. Methods CIA was induced in DBA/1 mice by the injection of collagen type II in Complete Freund’s adjuvant. Flow cytometry and qPCR were used to study the expression of MMR in vitro in macrophages and osteoclasts and in vivo in CIA. SPECT/CT imaging with 99mTc-labeled nanobodies generated against MMR was performed to visualize and quantify MMR expression in the joints of mice. Results MMR expression was shown to be highly upregulated in cultures of bone marrow-derived macrophages and osteoclasts by qPCR and by flow cytometry using MMR-targeting nanobodies. Ex vivo, we identified MMR in lymph nodes, spleen and bone marrow of naïve and arthritic mice. Interestingly, we detected expression of MMR in the synovial fluid, and to a lesser extent in synovium, of mice with CIA. More specifically, MMR was present on CD11b+F4/80+ macrophages isolated from the synovial fluid of the inflamed joints. SPECT/CT imaging was used to detect MMR in vivo in mice with CIA. Therefore, nanobodies against MMR were radioactively labeled with 99mTc, while nanobodies targeting a bacterial enzyme were used as controls. We observed high signals of MMR in lymph nodes, spleen and liver in naïve conditions as well as after immunization. Importantly, the joints of arthritic mice displayed high retention of MMR nanobody. The signal from SPECT imaging was significantly higher in mice with arthritic symptoms compared to naïve animals or immunized mice without clinical symptoms. Conclusions The use of MMR nanobodies in SPECT/CT imaging generates the possibility to track and quantify inflammatory macrophages in vivo in arthritic joints. In vivo quantification of joint inflammation by non-invasive techniques would be a great help in diagnosis and monitoring of disease processes as well as testing the efficiency of (new) drugs. Disclosure of Interest None Declared

This study offers a detailed analysis of building information modelling (BIM) policy and implementation across Europe, significantly contributing to the sector’s digital transformation. By collating data from governmental, academic, and industry sources, it identifies key trends and evaluates the effectiveness of BIM policies in advancing technology within construction. A systematic literature review and text mining across major databases revealed an increasing focus on sustainability, particularly “life cycle assessment” and “energy efficiency”, aligning with the Industry 5.0 initiative. The research shows that 35% of European countries have or plan to introduce BIM mandates, highlighting BIM’s crucial role in enhancing construction practices and influencing policy frameworks. Insights from this study are valuable for researchers, practitioners, and policymakers, guiding the adoption and operationalization of BIM and emphasizing the need for thorough market preparation, including funding, training, and standardization. Additionally, the study suggests a correlation between a country’s economic development and its propensity to enforce BIM mandates. Future research could explore regional policy variations and delve into the theoretical aspects of policy adoption and innovation diffusion to further understand BIM uptake dynamics.

The construction industry continues to face significant challenges related to waste on construction sites, significantly impacting cost, timelines, and the quality of project outcomes. This study aims to identify contemporary sources of construction waste, assess their variability over time using data from 2016, 2021, and 2024, and evaluate strategies for their reduction. A mixed-methods approach was adopted, combining a literature review with a survey among Polish construction contractors. A total of 34 waste factors were assessed in terms of frequency and significance. Building Information Modelling (BIM) is recommended—based on both survey results and studies in the literature—as an effective strategy to optimise construction efficiency by reducing waste and supporting sustainability objectives. The analysis also shows increasing awareness and application of Lean Principles and BIM among contractors. By 2024, BIM use increased from 8% in 2016 to 63%, indicating broader recognition, although this recognition was still insufficient given the severity of reported waste. The findings revealed design errors as the most critical source of waste, alongside execution delays, quality defects, damages to completed works, and excessive workloads. Respondents also identified additional factors, including erroneous bid assumptions, unclear investor expectations, unrealistic deadlines, equipment failures, and overdesign. These underscore the need for strategic, technology-driven waste mitigation.

This study addresses the challenge of automating the creation of Exchange Information Requirements (EIRs) for construction projects using Building Information Modelling (BIM) and Digital Twins, as specified in the ISO 19650 standard. This paper focuses on automating the classification of EIR paragraphs according to the ISO 19650 standard’s categories, aiming to improve information management in construction projects. It addresses a gap in applying AI to enhance BIM project management, where barriers often include technological limitations, a shortage of specialists, and limited understanding of the methodology. The proposed method uses Word2Vec for text vectorisation and Support Vector Machines (SVMs) with an RBF kernel for text classification, and it attempts to apply Word2Vec with cosine similarity for text generation. The model achieved an average F1 score of 0.7, with predicted categories for provided sentences and similar matches for selected phrases. While the text classification results were promising, further refinement is required for the text generation component. This study concludes that integrating AI tools such as Word2Vec and SVM offers a feasible solution for enhancing EIR creation. However, further development of text generation, particularly using advanced techniques such as GPT, is recommended. These findings contribute to improving managing complex construction projects and advancing digitalization in the AECO sector.

Case studies available in the literature clearly point to the numerous benefits of BIM (Building Information Modeling), in addition to the barriers that participants of such projects may face. This paper is a case study of Employer’s Information Requirements (EIR) for preparing and managing BIM models in the design and construction of selected large public construction projects: the Cogiteon Lesser Poland Science Center (LPSC Cogiteon), the Krakow Music Center (KMC) and the Copernican Revolution Studio (CRS). The paper presents the main aspects included in EIRs. It discusses the technical (e.g., requirements for the Common Data Environment platform—CDE), management (including the scopes of responsibility of staff in charge of BIM) and strategic sections (primary expectations concerning Data Drops) of the EIR. Projects executed using BIM by public institutions allow for the application of insight gained as a result of their completion and the creation of a knowledge base or checklist for future projects. The projects discussed here, carried out using advanced BIM solutions, could potentially be developed further by the proposed content extension concerning levels of detail (this paper cites potential guidelines that can be applied), component elements concerning price and qualifications, so as to easily generate bills of costs, and information used in facility management which can also encourage facility manager cooperation. Examples of EIR provisions are presented based on an analysis of three completed construction projects carried out using advanced BIM solutions. BIM is still a new form of management and this paper expands the range of available EIR standards, in addition to presenting guidelines for their practical application in the construction industry.