Swiss School of Archaeology in Greece
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Targeting the extracellular matrix with Tenascin-C-specific CAR T cells extends survival in preclinical models of glioblastoma
No full textGlioblastoma (GBM) is an aggressive brain tumor associated with poor outcome and limited treatment options. Chimeric antigen receptor (CAR) T cells targeting cell surface antigens were shown to induce tumor regression in patients with GBM, although efficacy was transient. To broaden the range of tumor-restricted antigens, we developed CAR T cells targeting Tenascin-C (TNC), a secreted extracellular matrix protein that is overexpressed in GBM and plays a critical role in tumor progression.
Second-generation CAR T cells were engineered to target the alternatively spliced fibronectin type III (FNIII)-D domain of TNC using a single-chain variable fragment isolated from the R6N antibody and coupled to a CD28 costimulatory domain. TNC-CAR T cells were evaluated in vitro for antigen specificity, activation, and cell proliferation using TNC-expressing patient-derived GBM cell lines cultured as adherent cells or as neurospheres. Reactivity toward purified TNC protein, tumor supernatant, and ex vivo patient tumor samples was also assessed. Cytotoxic CAR T-cell activity was tested against TNC-positive and TNC-negative GBM cell lines, including bystander effects mediated by secreted TNC. In vivo efficacy and safety were determined in NOD scid gamma mice bearing patient-derived GBM tumors.
TNC-CAR T cells demonstrated activation when exposed to TNC-positive GBM cells, cell-derived supernatants, or purified TNC protein. They exhibited potent cytotoxicity against TNC-expressing, GBM-derived adherent cells and neurospheres, and induced bystander killing of TNC-negative cells in the presence of either TNC-secreting cells or purified TNC. In vivo, TNC-CAR T cells efficiently infiltrated tumors, triggered cancer cell apoptosis, and significantly extended survival of mice bearing patient-derived GBM, with no evidence of off-tumor toxicity. Notably, TNC-CAR T cells were activated exclusively in the presence of tumor samples and showed no reactivity toward patient-derived non-tumor tissues.
Targeting the alternatively spliced FNIII-D domain of TNC with CAR T cells offers a promising therapeutic approach for GBM. TNC-CAR T cells demonstrated specific tumor recognition, robust antitumor activity and the ability to induce bystander effects mediated by secreted TNC. Their efficacy in preclinical models, combined with a favorable safety profile, underscores their potential for clinical translation.
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group
Cross-Cultural Validation of the Sexual Desire Inventory (SDI-2) in 42 Countries and 26 Languages
No full textSexual desire is a complex construct with important implications for sexual functioning and well-being. In this research, we translated the Sexual Desire Inventory (SDI-2), a widely used scale for assessing sexual (desire), into 25 languages from English and used data from the International Sex Survey (ISS) to (a) investigate its psychometric properties (i.e. factorial structure, reliability, validity, and measurement invariance) and (b) explore the expression of sexual desire across different countries, genders, and sexual orientations. A total of 82,243 participants from 42 countries completed the SDI-2, along with other sexuality-related scales. Confirmatory factor analysis supported a three-factor solution for the SDI-2 (CFI = .980; RMSEA = .060), encompassing the domains of "Partner-related," "Attractive-person-related," and "Solitary" sexual desire. The reliability of the total score and subscales were excellent. Likewise, correlations with other sexuality-related variables were positive yet weak-to-moderate in effect size. Measurement invariance tests supported its use across countries, languages, genders, and sexual orientations. Analysis of SDI-2 scores according to these variables supported its ability to capture group-based differences in sexual desire. In sum, the SDI-2 constitutes a psychometrically robust measure for the assessment of sexual desire in non-clinical samples with utility in large-scale cross-cultural studies
Paul Bouffartigue, Caroline Lanciano-Morandat et Claude Paraponaris (dir.) (2023), Jean-Pierre Poitou. De la psychologie expérimentale à l’anthropologie des connaissances.
No full textThe Human Thyroid-Derived CI-huThyrEC Cell Line Expresses the Thyrotropin (TSH) Receptor and Thyroglobulin but Lacks Other Essential Characteristics of Thyroid Follicular Cells.
No full textBackground: Thyroid hormone synthesis requires the normal function of thyroid follicular cells and adequate nutritional intake of iodine. For in vitro studies on thyroid cell pathophysiology, the immortalized FRTL5 rat thyroid cell line and a derivative thereof, the PCCL3 cell line, are widely used. However, a permanent human thyroid cell line is currently lacking. A recent report described a cell line obtained from human thyroid cells designated as Cl-huThyrEC. Methods: Four clones of Cl-huThyrEC cells were obtained and cultured in the presence of thyroid stimulating hormone (TSH). The expression of key genes defining the thyroid follicular cell phenotype was determined by reverse-transcription PCR (RT-PCR) in FRTL5, PCCL3, and Cl-huThyrEC cells. The latter were cultured as monolayers and as organoids in Matrigel. Iodide uptake was measured and compared among the cell lines. Results: Gene expression analysis reveals that Cl-huThyrEC cells express the thyroid-restricted transcription factors (PAX8, NKX2.1, FOXE1), the TSH receptor (TSHR), and thyroglobulin (TG), but they do not express the sodium-iodide symporter (NIS), thyroid peroxidase (TPO), and pendrin (SLC26A4). In functional studies, Cl-huThyrEC cells are unable to concentrate iodide. Conclusions: Despite the expression of certain key genes that are limited or restricted to thyroid follicular cells, Cl-huThyrEC cells lack some of the essential characteristics of thyroid follicular cells, in particular, NIS. Hence, their utility as a model system for thyroid follicular cells is limited
Circulating tumor-associated and neoantigen-specific endogenous T cells in children treated for B-acute lymphoblastic leukemia.
No full textRethinking the routine: Are repeat blood cultures necessary after completion of infective endocarditis treatment?
No full textAmong 598 infective endocarditis (IE) episodes, follow-up blood cultures within 14 days of antimicrobial treatment completion were performed in 135 (23%) cases and detected only 2 (1.5%) recurrences. This strategy failed to identify 8 (6%) additional IE recurrences diagnosed between days 15 and 120, underscoring its limited utility.
© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America
EndoCompass Project: Research Roadmap for Reproductive and Developmental Endocrinology
No full textEndocrine science remains underrepresented in European Union research programs despite the fundamental role of hormone health in human well-being. Analysis of the CORDIS database reveals a persistent gap between the societal impact of endocrine disorders and their research prioritization. At national funding level, endocrine societies report limited or little attention of national research funding towards endocrinology. The EndoCompass project - a joint initiative between the European Society of Endocrinology and the European Society of Paediatric Endocrinology, aimed to identify and promote strategic research priorities in endocrine science to address critical hormone-related health challenges.
Research priorities were established through comprehensive analysis of the EU CORDIS database covering the Horizon 2020 framework period (2014-2020). Expert consultation was conducted to identify key research priorities, followed by broader stakeholder engagement including society members and patient advocacy groups.
Research priorities encompass variations in sex development, hypothalamic-pituitary-gonadal regulation, and female and male reproductive disorders. Key areas include improving diagnostic capacity through (epi)genetic analysis, optimizing hormonal treatments, developing fertility preservation strategies. Special emphasis is placed on establishing pan-European registries, developing novel reproductive technologies, and exploring environmental impacts on reproductive health.
This component of the EndoCompass project provides an evidence-based roadmap for strategic research investment. This framework identifies crucial investigation areas into reproductive and developmental endocrinology pathophysiology, prevention, and treatment strategies, ultimately aimed at reducing the burden of these disorders on individuals and society. The findings support the broader EndoCompass objective of aligning research funding with areas of the highest potential impact in endocrine health.
© 2025 The Author(s). Published by S. Karger AG, Basel
Developing a taxonomy framework for assessing human capital provision: A case study of Southern Italian municipalities
No full textThe decline of rural areas emerges as a central aspect of European and national policies. Decline manifests itself in distinct forms, resulting from the interaction among exogenous and local factors. Understanding the different socio-economic trends and tangible and intangible conditions of rural areas, defined as the intra-rural divide, is central to the definition of priorities of public policies. Within this framework, the proposed study focuses on the notion of Territorial Capital (TC) with a particular focus on Human Capital (HC) as a conceptual frame for investigating the intra-rural divide. Different unsupervised learning methods have been employed to identify clusters of similar administrative units in terms of HC provision using a set of 12 input indicators, enabling a deeper understanding of the intra-rural divide. The study area consists of six southern Italian regions, specifically chosen due to their pronounced disparities. The present work contributes to the discipline of regional and urban studies by developing a novel taxonomy framework specifically for assessing HC disparities at a detailed local level, thereby making the concept of the intra-rural divide measurable and analyzable and enabling the definition of targeted policies respondent to individual areas’ needs
AI detectors are poor western blot classifiers: a study of accuracy and predictive values.
No full textThe recent rise of generative artificial intelligence (AI) capable of creating scientific images presents a challenge in the fight against academic fraud. This study evaluates the efficacy of three free web-based AI detectors in identifying AI-generated images of western blots, which is a very common technique in biology. We tested these detectors on AI-generated western blot images (n = 48, created using ChatGPT 4) and on authentic western blots (n = 48, from articles published before the rise of generative AI). Each detector returned a very different sensitivity (Is It AI?: 0.9583; Hive Moderation: 0.1875; and Illuminarty: 0.7083) and specificity (Is It AI?: 0.5417; Hive Moderation: 0.8750; and Illuminarty: 0.4167), and the predicted positive predictive value (PPV) for each was low. This suggests significant challenges in confidently determining image authenticity based solely on the current free AI detectors. Reducing the size of western blots reduced the sensitivity, increased the specificity, and did not markedly affect the accuracy of the three detectors, and only slightly improved the PPV of one detector (Is It AI?). These findings highlight the risks of relying on generic, freely available detectors that lack sufficient reliability, and demonstrate the urgent need for more robust detectors that are specifically trained on scientific contents such as western blot images