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The primary objective of transdisciplinary research (TDR) is to contribute to the solution of complex 'real-world' problems by integrating heterogeneous knowledge and achieving societal effects. However, establishing a continuous impact orientation during TDR processes remains a challenge, as the necessary tools are not yet sufficiently available. We developed and tested a half-day workshop format for strengthening the impact-oriented project management and research activities of seven TDR projects. Our findings indicate that the reflective impact workshops supported participants in pursuing societal effects systematically. Applying the methodological approach also fosters TDR process qualities such as knowledge integration. Conducted at different project stages, the results can serve as a basis for monitoring and adapting the project design. The reflective approachâ¢includes scientific and non-scientific TDR project team members,â¢draws on Theory of Change as a conceptual framework and motivates participants to reflect on plausible impact pathways and make implicit assumptions about interlinkages between different forms of societal effects explicit, andâ¢provides results which enable project partners to adjust their project design for greater societal effectiveness.
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Purpose: Bibliometric and scientometric analyses provide a structured approach to large amounts of data, enabling the prediction of research theme trends over time, the detection of shifts in the boundaries of disciplines, and the identification of the most productive countries, institutions and scholars. In the context of prostate-specific membrane antigen (PSMA)-targeted radiotheranostics, no bibliometric or scientometric analysis has been published thus far. Therefore, this study was conducted to identify key contributors to the literature, assess the global scientific production of related research, and possibly predict future development patterns. Methods: Scientometrics and bibliometrics were utilized to analyze the current body of knowledge while tracking its evolution to support scientific decision-making comprehensively and systematically. Science mapping techniques were employed to visualize research activities. Two different tools, Tableau and VOSviewer, were utilized, with VOSviewer being deemed the most suitable for the research objectives. The Web of Science (WoS) was used as the principal database for the searches. Results: Through the search process over a period of 30 years (January 1993-January 2023), 694 original studies in the English language were subjected to comprehensive analysis. By employing bibliometric and scientometric methods, multiple networks were created that mapped various concepts, such as publication trends, leading countries, cocitations, coauthorship among researchers and scientists, as well as coauthorship among organizations and funding agencies. This study revealed the evolutionary patterns, trends, outliers, and key players in the PSMA field, which enabled a more nuanced understanding of the research landscape. Conclusion: This research contributes to the enrichment of knowledge on PSMA-targeted radiotheranostics through detailed global bibliometric and scientometric analyses. It stresses the necessity for the development of communication platforms, the establishment of supportive infrastructures, and the implementation of proactive solutions to address emerging challenges. This study offers a significant resource for delineating effective strategies and identifying prominent funding bodies essential for continuous advancements in the field of PSMA-based diagnosis and therapy for prostate cancer. It is vital to sustain this momentum to ensure further progress in this pioneering area.
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In 1853, the perception of prostate cancer (PCa) as a rare ailment prevailed, was described by the eminent Londoner surgeon John Adams. Rapidly forward to 2018, the landscape dramatically altered. Currently, men face a one-in-nine lifetime risk of PCa, accentuated by improved diagnostic methods and an ageing population. With more than three million men in the United States alone grappling with this disease, the overall risk of succumbing to stands at one in 39. The intricate clinical and biological diversity of PCa poses serious challenges in terms of imaging, ongoing monitoring, and disease management. In the field of theranostics, diagnostic and therapeutic approaches that harmoniously merge targeted imaging with treatments are integrated. A pivotal player in this arena is radiotheranostics, employing radionuclides for both imaging and therapy, with prostate-specific membrane antigen (PSMA) at the forefront. Clinical milestones have been reached, including FDA- and/or EMA-approved PSMA-targeted radiodiagnostic agents, such as [18F]DCFPyL (PYLARIFY®, Lantheus Holdings), [18F]rhPSMA-7.3 (POSLUMA®, Blue Earth Diagnostics) and [68Ga]Ga-PSMA-11 (Locametz®, Novartis/ ILLUCCIX®, Telix Pharmaceuticals), as well as PSMA-targeted radiotherapeutic agents, such as [177Lu]Lu-PSMA-617 (Pluvicto®, Novartis). Concurrently, ligand-drug and immune therapies designed to target PSMA are being advanced through rigorous preclinical research and clinical trials. This review delves into the annals of PSMA-targeted radiotheranostics, exploring its historical evolution as a signature molecule in PCa management. We scrutinise its clinical ramifications, acknowledge its limitations, and peer into the avenues that need further exploration. In the crucible of scientific inquiry, we aim to illuminate the path toward a future where the enigma of PCa is deciphered and where its menace is met with precise and effective countermeasures. In the following sections, we discuss the intriguing terrain of PCa radiotheranostics through the lens of PSMA, with the fervent hope of advancing our understanding and enhancing clinical practice.
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Antígenos de Superfície , Glutamato Carboxipeptidase II , Neoplasias da Próstata , Compostos Radiofarmacêuticos , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Glutamato Carboxipeptidase II/metabolismo , Masculino , Antígenos de Superfície/metabolismo , Compostos Radiofarmacêuticos/uso terapêutico , Medicina Nuclear/métodos , Medicina Nuclear/história , Nanomedicina Teranóstica/métodos , Radioisótopos/uso terapêutico , História do Século XXI , História do Século XXRESUMO
[177Lu]Lu-PSMA-617 has recently been successfully approved by the FDA, the MHRA, Health Canada and the EMA as Pluvicto®. However, salivary gland (SG) and kidney toxicities account for its main dose-limiting side-effects, while its corresponding uptake and retention mechanisms still remain elusive. Recently, the presence of different ATP-binding cassette (ABC) transporters, such as human breast cancer resistance proteins (BCRP), multidrug resistance proteins (MDR1), multidrug-resistance-related proteins (MRP1, MRP4) and solute cassette (SLC) transporters, such as multidrug and toxin extrusion proteins (MATE1, MATE2-K), organic anion transporters (OAT1, OAT2v1, OAT3, OAT4) and peptide transporters (PEPT2), has been verified at different abundances in human SGs and kidneys. Therefore, our aim was to assess whether [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are substrates of these ABC and SLC transporters. For in vitro studies, the novel isotopologue ([α,ß-3H]Nal)Lu-PSMA-617 was used in cell lines or vesicles expressing the aforementioned human ABC and SLC transporters for inhibition and uptake studies, respectively. The corresponding probe substrates and reference inhibitors were used as controls. Our results indicate that [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are neither inhibitors nor substrates of the examined transporters. Therefore, our results show that human ABC and SLC transporters play no central role in the uptake and retention of [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 in the SGs and kidneys nor in the observed toxicities.
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Interest in catering for public sector schools is increasing due to its potential role in addressing the prevailing problems of malnutrition, food insecurity and non-sustainable food habits. Based on the case of secondary schools in Berlin, this study aims to explore this potential by focusing on the process of transformation towards healthy, inclusive and sustainable school catering. It employs a multi-perspective analysis based on the two concepts of food environment and social cohesion. Results are based on quantitative and qualitative data collected via an online survey of pupils from 25 secondary schools in Berlin as well as field notes from six stakeholder events. The survey findings were analyzed by descriptive means and provide explanations for the fact that most of the pupils (66.7%) never eat lunch at school. Based on the qualitative analysis of the stakeholder events, key tensions between actors from the federal state, municipal, school and private levels could be identified. Major areas of conflict arise due to (1) a lack of public funding and catering standards, (2) incompatible demands and preferences, (3) a lack of resources and opportunities for complementary education and participation, and (4) peer and parental influence. Transforming school food environments requires integrative strategies with interventions introduced by multiple actors operating on different levels.
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Serviços de Alimentação , Instituições Acadêmicas , Comportamento Alimentar , Almoço , Emprego , Insegurança AlimentarRESUMO
The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress. A particular area of research is the use of alpha-emitting radionuclides, which have unique physical properties associated with outstanding advantages, e.g., for single tumor cell targeting. Here, recent results and open questions regarding the production of alpha-emitting isotopes as well as their chemical combination with carrier molecules and clinical experience from compassionate use reports and clinical trials are discussed.
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Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate inflammatory processes. Here, we describe the discovery of two clinical candidate IRAK4 inhibitors, BAY1834845 (zabedosertib) and BAY1830839, starting from a high-throughput screening hit derived from Bayer's compound library. By exploiting binding site features distinct to IRAK4 using an in-house docking model, liabilities of the original hit could surprisingly be overcome to confer both candidates with a unique combination of good potency and selectivity. Favorable DMPK profiles and activity in animal inflammation models led to the selection of these two compounds for clinical development in patients.