IRF: Institutional Repository FHNW
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Development of a mechanistic understanding and novel therapeutic strategies for TFE3-rearranged renal cell carcinoma
(American Association for Cancer Research, 2026) Basu, Debleena; Bolck, Hella; Rutishauser, Dorothea; Leary, Peter; Charraga Garcia, Daniela; Kahraman, Abdullah; Rupp, Niels; Pauli, Chantal; Moch, Holger
TFE3 rearranged renal cell carcinoma (TFE3-tRCC) is a rare subtype of renal cell carcinoma (RCC) harboring gene fusions that trigger oncogenic activation of TFE3 transcription factor. The frequency of this rare tumor is surprisingly high in children and young adults (20% to 75% of childhood RCCs) compared to older adults (ranges between 1% and 5%). Importantly, TFE3-tRCC can show aggressive behavior with rapid progression and little to no response to drugs commonly used for renal cancer treatment. In this project we aim to define gene expression programs of distinct TFE3 fusions to uncover molecular events driven by chimeric TFE3 and delineate their consequences for important cancer phenotypes. By identifying fusion-specific pathway alterations, we seek to propose novel therapeutic strategies tailored to the patients with these fusions. Using a cohort of 31 patients with suspected diagnosis of TFE3-tRCC, we have employed a novel customized RNA-based targeted Next generation Sequencing (NGS) panel to determine putative fusion partners of TFE3. Next, high throughput technologies like short read and long read RNA sequencing and ChIP sequencing were used to characterize the molecular landscape downstream of different fusion events. Finally, to explore the influence of the transcriptional diversity on therapeutic decisions, we aim to perform molecularly informed drug screening in our in vitro models followed by in vivo validation. With our newly developed targeted NGS panel, we have characterized our patient cohort and identified 7 distinct TFE3 fusion partners in 25 cases out of 31. The putative partners are ASPSCR1, LUC7L3, MED15, NonO, PRCC, RBM10, and SFPQ. Certain partners confer unique tumor morphologies, e.g., MED15::TFE3 fusion associates with cystic features. Our transcriptomic analysis shows tumors with same fusion tend to cluster together, driven by shared pathway upregulation (OXPHOS, lysosomal pathway, autophagy, proteasome etc.). Differential upregulation of pathways such as immune response, metabolic pathways, mitophagy, RNA splicing etc. highlight fusion specific identity, informing fusion driven molecular characteristics. Preliminary in vitro chromatin accessibility data suggests the potential involvement of the chimeric TFE3 protein in alternative splicing regulation, which is further consistent with splicing enrichment observed in our transcriptomic analysis. Different fusion partners for TFE3 likely impact the dysregulation of the chimeric protein and drives tumorigenesis. However, our limited understanding of the molecular landscape and clinical consequences of the different TFE3 fusions presents as the major obstacle towards development of targeted therapeutic strategies for this disease. In this scenario of unmet clinical needs, we seek to define the molecular features of TFE3-tRCC, thereby uncovering specific vulnerabilities of tumor cells that prompt the development of new targeted therapeutic strategies.
01A - Beitrag in wissenschaftlicher Zeitschrift
Negotiating HIV protection in the era of online dating and Pre-Exposure-Prophylaxis (PrEP). Insights into how men having sex with men (MSM) living in Switzerland negotiate their HIV protection with non-steady partners
(Springer, 2026) Gredig, Daniel; Bigoni, Daniele; Bogdanovic, Jasmina; Weber, Patrick
HIV protection depends on the consent and cooperation of sexual partners, which requires negotiation. Early HIV-related research identified condom negotiation strategies. However, strategies used specifically among men having sex with men (MSM) remained underexamined. This project explored how HIV-negative MSM negotiate their protection from HIV when having sex with non-steady partners, considering current risk reduction practices, the availability of several effective biomedical prevention options, the strong presence of STIs and prevailing online dating. We conducted in-person interviews with a maximum variation sample of 29 MSM, aged 21–80, combining narrative interviewing with a virtual-reality serious game and a series of standardized questions. We analyzed the interview data using content analysis, combining deductive and inductive approaches. We identified three categories of negotiation strategies used in chats, during in-person dates or when having sex: (i) subject-centered strategies anchored in the will and determination of MSM; (ii) strategies centered on sexual arousal, asserting MSM’s preferred protection strategy; (iii) strategies centered on risk communication. Further, we identified actions that interrupt negotiations and directly enforce protection or bypass negotiations. Participants combined several strategies during negotiations. The strategies also demonstrated versatility: most were used for various aims and were not systematically related to a specific personal protection strategy. This study posits an elaborate range of HIV-protection negotiation strategies used by MSM, including strategies not previously described. It contributes to a more nuanced understanding of negotiation strategies and encourages prevention professionals to reflect on the attention given to negotiation strategies in prevention offers.
01A - Beitrag in wissenschaftlicher Zeitschrift
A matrix approach to developing a digital internal communication strategy
(SAGE, 2026) Wuersch, Lucia; Neher, Alain; Peter, Marc K.; Maley, Jane; Wong, Alfred
Digital transformation (DT) has reshaped organisations, evolving internal communication (IC) into digital internal communication (DIC). Despite growing interest, there is still a lack of comprehensive frameworks to guide organisations in developing DIC strategies triggered by DT. This study addresses this gap by expanding existing DIC conceptualisations, integrating new elements, such as applied Artificial Intelligence (AI), and incorporating a planned–organic dimension. Using a conceptual approach, the research presents a multidimensional view of DIC as a strategic management function that helps achieve organisational goals. The proposed DIC matrix combines technical elements (digital channels and platforms, policies, applied AI, and informal apps) with social aspects (digital leadership, capability development, culture, and collaboration) along the social–technical and planned–organic axes. This novel approach enriches strategic communication literature and fosters organisational competencies and digital trust, essential for sustainable success. The emerging DIC maturity model provides actionable guidance and a ready-to-use rubric, allowing leaders and communication professionals to design tailored DIC strategies, fully leverage digital tools, and align communication practices with strategic goals.
01A - Beitrag in wissenschaftlicher Zeitschrift
Resilience by design. emergency architecture, testing and the ecology of aid (1970–1980)
(Routledge, 2026) Messell, Tania
Since the late 2000s, the humanitarian sector has witnessed what scholars have described as an ‘innovation turn’ in response to what humanitarian innovators conceive as the field’s inefficient, backwards-looking and top-down inner workings. In this context, aid actors have increasingly embraced design methodologies in pursuing creative, participatory and human-centred responses to humanitarian crises. However, this turn overshadows a longer history of intersections between design and humanitarian governance. This article contributes to filling this gap by tracing how design and innovation met in the field of post-disaster shelters in the 1970s. Echoing today’s ‘innovation turn’, the period witnessed widespread efforts to innovate cross-border disaster relief interventions amongst international aid actors. Examining the development, implementation and aftermath of the A-frame shelter, a post-disaster housing solution developed by Carnegie Mellon University and the consultancy Intertect between 1974 and 1977, the article argues that the project announced a new understanding of the role of design responses to disasters, that of a practice that through participative and iterative problem-solving methods aimed to produce mobile protocols capable of rendering local populations more resilient to environmental catastrophes. The article thereby exposes and critically examines the longstanding intersections between humanitarian aid, design and early resilience thinking.
01A - Beitrag in wissenschaftlicher Zeitschrift
Towards robust probabilistic maps in Deep Brain Stimulation. exploring the impact of patient number, stimulation counts, and statistical approaches
(Frontiers Research Foundation, 2026) Bucciarelli, Vittoria; Vogel, Dorian; Wårdell, Karin; Coste, Jérôme; Blomstedt, Patric; Lemaire, Jean-Jacques; Guzman, Raphael; Hemm-Ode, Simone; Nordin, Teresa
Introduction Probabilistic Stimulation Maps (PSMs) are increasingly employed to identify brain regions associated with optimal therapeutic outcomes in Deep Brain Stimulation (DBS). However, their reliability and generalizability are challenged by the limited size of most patient cohorts and the inherent variability introduced by different statistical methods and input data configurations. This study aimed to investigate the geometrical variability of Probabilistic Sweet Spots (PSS) as a function of both the number of patients (nPat) and the number of stimulations per patient (nStim), and to model a stability boundary defining the minimum data requirements for obtaining geometrically stable PSS. Methods Three statistical approaches–Bayesian t -test, Wilcoxon test with False Discovery Rate (FDR) correction, and Wilcoxon test with nonparametric permutation correction–were applied to two patient cohorts: a primary cohort of 36 patients undergoing DBS for Parkinson’s Disease (PD), and a secondary cohort of 61 patients treated for Essential Tremor (ET), used to assess generalizability. Stimulation test data was collected intra-operatively for the first cohort and post-operatively for the second one. Geometric stability was evaluated based on variability in PSS volume extent and centroid location. Results The analysis revealed a non-linear trade-off between nPat and nStim to yield stable PSS. A stability boundary was defined, representing the minimum combinations of nPat–nStim required for anatomically robust PSS. Among the tested methods, the Bayesian t -test achieved stability with smaller sample sizes (∼15 patients) and demonstrated a consistent performance across both cohorts. In contrast, the Wilcoxon-based methods showed variable behavior between cohorts, which differed in symptom type and testing phase (intra-operative testing vs. post-operative screening). Discussion The proposed PSS stability boundary provides a practical reference for designing DBS studies and stimulation screening protocols aimed at probabilistic mapping. The Bayesian t -test emerged as a reliable method across both cohorts, supporting its potential in studies with limited sample sizes and scenarios where the method needs to be readily generalized to varying symptoms. These findings underscore the importance of considering both cohort size and stimulation count in probabilistic DBS mapping and call for further investigation into method-specific sensitivities to clinical and procedural factors.
01A - Beitrag in wissenschaftlicher Zeitschrift