Center for Clinical & Basic Research

This paper explores the transformation of waste eelgrass (Zostera marina), commonly found along European coastlines, into sustainable acoustic panels through circular business models (CBMs). The study adopts a qualitative, exploratory approach involving literature review, participatory stakeholder workshops to identify and assess the challenges and opportunities in this innovation ecosystem. Key insights are derived from the Power Bio project, which facilitated co-creation of business model prototypes with municipalities, producers, and biomass collectors. The research highlights significant environmental benefits such as carbon reduction and beach aesthetics improvement, alongside economic advantages including premium pricing and cost avoidance. However, it also uncovers barriers like supply chain instability, regulatory fragmentation, and low public awareness. Methodologically, the study draws on tools like the Triple Layered Business Model Canvas (TLBMC) and design thinking to integrate sustainability and stakeholder engagement. By aligning theoretical insights with empirical stakeholder input, the paper offers a grounded model for municipalities and entrepreneurs aiming to repurpose coastal biomass waste. It contributes both to the academic discourse on circular bioeconomy and provides actionable recommendations for sustainable building practices. The findings align with EU goals on climate neutrality and sustainable construction, offering a scalable pathway from coastal nuisance to green innovation. Keywords: Circular Economy; Bioeconomy; Biomass Waste; Circular Business Model; Acoustic Panels; Build Environment

The Upper and Lower Airways Northern European Consensus (ULANC) and the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized their first workshop in Copenhagen in January 2024. The aim of the “Primary care physicians and nurses with an interest in Global Airway Diseases 2024” was to bring the concept of the global airway to the front line of medical care. ULANC is a multidisciplinary European consortium, that aims to improve the management of comorbid ear, nose and throat (ENT) conditions, such as chronic rhinosinusitis with nasal polyposis (CRSwNP), in patients also suffering from asthma. EUFOREA is an international non-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic respiratory diseases through the implementation of optimal patient care via educational, research, and advocacy activities. The inclusive and multidisciplinary approach of ULANC and EUFOREA was reflected in the keynote lectures and workshop faculty coming from the allergology, pulmonology, ENT, and primary health care fields around the central theme of global airway diseases. The current report aims at providing a comprehensive overview of the key statements by the faculty of the “Primary care physicians and nurses with interest in Global Airway Diseases 2024”, allowing all stakeholders in the respiratory field to be up-dated and ready to join forces in Europe and beyond.

Abstract Immune checkpoint inhibitors targeting TIM3, a molecule frequently co-expressed with PD1 on exhausted T cells and myeloid cells, represent a promising approach in cancer immunotherapy. Inhibition of TIM3 in myeloid cells promotes their activation and has been shown to enhance anti-tumor responses in both monotherapy and combination with immunotherapy or chemotherapy in mouse models (PMID: 34108686). Sym023 (S095018) offers a novel strategy for targeting TIM3 with distinct properties. Beyond blocking the binding of galectin 9 and phosphatidylserine to TIM3, our preclinical studies demonstrate that Sym023 has a direct effect on dendritic cells, inducing their maturation and triggering downstream activation of T cells. In mouse models, the combination of Sym023 (S095018) with an anti-PD1 antibody significantly improved survival and tumor control. Based on these findings and existing literature, the safety and efficacy of the combination of Sym023 with anti-PD1 (sym021) was evaluated in a phase Ib/II expansion study (Sym021-02; NCT04641871) in biliary tract cancer (BTC) patients. An in-depth biomarker plan was implemented to analyze biopsies at screening and the end of cycle 1 (EOC1). On 19 tumor biopsies, 7-plex immunohistochemistry (IHC) and transcriptomic profiling (Nanostring) were performed to study the changes in immune infiltrates during the treatment course. The combination of Sym023 and Sym021 led to increased levels of IFNg and myeloid chemokines (e.g., CXCL9, CXCL10). Treatment resulted in a higher density of activated T cells within the tumor islets, along with the upregulation of cytotoxicity-related genes. Transcriptomic profiling further revealed an upregulation of antigen processing pathways, supporting the translatability of Sym023’s mechanism of action on both T cells and myeloid cells in patients. Drawing from preclinical and biomarker data from the Sym021-02 trial, a biomarker-driven analysis was conducted to identify patients most likely to respond to the Sym023 and anti-PD1 combination. Through this translational analysis, non-small cell lung cancer (NSCLC) was identified as having significant infiltration by myeloid cells and CD8+ T cells, along with high intra-tumoral TIM3 expression, positioning NSCLC as a relevant and promising indication for this combination therapy. A platform trial (NCT06162572) featuring an arm combining cemiplimab (anti-PD1) with Sym023 (S095018) was launched for first-line treatment of patients with advanced/metastatic NSCLC with high PDL1 expression. Citation Format: Julia Geronimi, Aditi Varthaman, Trine Lindsted, Franziska Uhlenbrock, Camilla Frölich, Vincent Lombardi, Christelle Cousin, Mathieu Boucher, Audrey Delmas, Pauline Darcel, Xenophon Ianopulos, Hélène Kaplon. Forging strong bidirectional preclinical and translational research for optimized drug development of Sym023 (S095018), a novel anti-TIM3 antibody [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B029.

ObjectiveThis study aimed to investigate the longitudinal bi-directional relationship between self-reported restrictive eating behaviours and sleep characteristics within a sample of UK adolescents from the Millennium Cohort Study (MCS).MethodUsing a Structural Equation Modelling approach, the present study investigated the prospective associations between individual sleep behaviours (e.g., sleep timing, sleep onset latency, social jetlag) at age 14 and restrictive eating behaviours at age 17. Moreover, the association between restrictive eating behaviours (age 14) and self-reported sleep quality (age 17) was tested. A mediation analysis was conducted to explore the role of depressive symptoms in these relationships. In total, N = 6,041 young people provided self-report data at both timepoints (sweep 6 & 7) and a subsample of N = 2,164 additionally provided diary data on their sleep behaviours over two separate 24 h periods.ResultsSleep indicators at age 14 did not significantly predict changes in restrictive eating behaviours across time. However, engagement in restrictive eating behaviours at age 14 significantly predicted poorer self-perceived sleep quality three years later (β = 0.06, SE = 0.01, p <.01). Depressive symptoms fully mediated this relationship (indirect effect: β = 0.05, SE = 0.04, p <.001).DiscussionThe present study provides evidence for a prospective positive association between restrictive eating behaviours and subsequent poorer sleep quality in a large, general population sample. Findings of the mediation analysis suggest mood as a potential target for tertiary prevention when addressing restrictive eating behaviours as an eating disorder risk factor in adolescents.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00787-025-02641-9.

Abstract Background: Adenosine signaling is a central immunosuppressive mechanism affecting a broad set of immune cell types. Adenosine is generated from extracellular ATP by a group of ectonucleotidases including CD39 and CD73. Suppressing the adenosine pathway via CD73 blockade may enhance the potential of checkpoint inhibitor therapies.S095024 (Sym024) is a fully human, effector-function attenuated antibody that binds to human and cynomolgus CD73 with sub-nM affinity. Methods: Preclinically, the stoichiometry and conformational structure of the binding interaction between CD73 and S095024 was assessed by SEC-MALS and cryo-EM and the ability of S095024 to inhibit CD73 activity was done in vitro covering 3-, 6- and 24-hour incubation periods. The clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of S095024 alone or in combination with Sym021, an anti-PD1 antibody, was investigated in a first-in-human study (NCT04672434) in patients with selected types of advanced solid tumors. Following assessment of single agent S095024 (100 to 1500 mg IV Q2W) in part I, the safety and tolerability of S095024 (300 to 1500 mg IV Q2W) was assessed in combination with Sym021 (200 mg IV Q2W) in part II. A part IIa was added: patients received 3000 mg IV Q2W of S095024 in Cycle 1, followed by 3000 mg S095024 + 200 mg Sym021 from Cycle 2 onwards. Results: Structural data indicate that S095024 binds to CD73 in a unique configuration by bridging the two monomers of the molecule, interacting in a 1:1 stoichiometry and effectively preventing the conformational state cycling required for catalysis. Functional data using a 20x cell line panel harboring a broad range of CD73 expression levels demonstrates that this interaction modus results in deep enzymatic inhibition. As of 12 Oct 2023, 43 patients have been treated with, S095024 in the FIH study. S095024, as a single agent (N=18) and in combination with PD-1 blockade (N=25) was well tolerated across all dose levels. The most frequent treatment emergent adverse events (≥15% patients) were fatigue, nausea, diarrhea, dyspnea, and vomiting. A dose proportional increase in drug exposure, both in monotherapy and combination, was observed starting at 900 mg. Target engagement assessed both peripherally (free soluble CD73) and intra-tumorally (enzymatic activity), showed a sustained decrease in free soluble CD73 in blood at dose levels ≥1500 mg and dose-dependent CD73 modulation, with &amp;gt;80% inhibition reached at ≥1500 mg in tumor biopsies. Conclusions: These findings reveal the potential of S095024 (Sym024) to prevent adenosine-mediated tumor evasion and support further clinical investigation. Citation Format: Anna Spreafico, Jordi R. Ahnert, David Sommerhalder, Maria Almena-Carrasco, Najah Harouki Crochemore, Xenophon Ianopulos, Janus S. Jakobsen, Emily Armbruster, Audrey Delmas, Amédée des Georges, Camilla Fröhlich, Julia Geronimi, Michael M. Grandal, Randi W. Hansen, Johan Lantto, Julie Legrand, Franck Levasseur, Matteo Riva, Christelle Rodrigues, Vanessa Seif, Vasileios Askoxylakis, Nehal Lakhani. Molecular and early clinical characterization of the anti-CD73 antibody S095024 (Sym024) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3737.

&lt;p&gt;See abstract and datasets [10.5281/zenodo.5849300]&lt;br&gt; &lt;br&gt; There exist a large number of methods that can be used for anomaly detection/fault detection in collaborative robots. However, studies on these methods tend to only focus on a single or a couple of such methods, which can make it challenging to gauge their relative merits in specific robot scenarios. In this paper, we conduct a comprehensive comparison of 15 methods for anomaly detection, including methods based on principle component analysis, local outlier factor, and autoencoders. The methods are assessed in a typical pick-and-place application with respect to their capacity to detect a broad range of exogenous anomalies. The results of the study show that several methods perform well, but that their performance profiles differ across the studied anomalies. The results also give an indication of the application characteristics that have the potential to make anomaly detection challenging.&lt;/p&gt;