University of Applied Sciences Mainz

Cells interpret mechanical cues from their microenvironment with spatiotemporal precision to guide adaptive behaviors. However, engineering synthetic mechanosensing systems with both cell-specificity and programmability remains challenging, especially when targeting ubiquitous classical mechanoreceptors. Here, we introduce an all-DNA mechanosensing platform based on aptamers that transmit force through noncanonical surface receptors. Aptamer–receptor recognition acts as a molecular gate for force transduction, enabling the design of mechanoprobes with cell-type selectivity. These probes interpret diverse mechanical inputs via distinct mechanisms, including actomyosin-driven contractility and membrane ruffling during macropinocytosis. By integrating aptamer mechanoprobes with upstream DNA reaction networks, we achieve reversible and temporally programmable mechanoresponses. This modular, all-nucleic-acid system offers a general framework for constructing tunable mechanotransduction circuits. It expands the design space for synthetic mechanobiology and provides opportunities for autonomous, multi-layered mechanical–biochemical regulation in tissue engineering, morphogenesis, and dynamic cell programming.

ABSTRACT A group of researchers from the humanities, economics, social sciences, natural and life science developed a definition of the topics complexity and emergence that can be applied across disciplines. Here, concepts of complexity and emergence in chemistry and biochemistry are discussed, to promote a discourse between the natural and life sciences and philosophy. Although chemical research often employs reductionist strategies, the properties of molecules and their linked functions exhibit emergent properties that cannot be inferred solely from their atomic constituents. Assembly theory and the work of Manfred Eigen offer ways to quantify and predict emergence in chemistry, particularly in relation to the origins and evolution of life. This review emphasizes the chemical prerequisites for life, such as the formation of natural products, the emergence of nucleic acids that carry information, and the functional roles of proteins. From a philosophical standpoint, modern ontology provides a means of understanding reality that is both process‐based and subject‐independent. By integrating chemistry, biology and philosophy, the synopsis of this review addresses the predictive, post facto and historically unique aspects of complex systems, offering a conceptual framework for comprehending the emergence of molecular function and the evolution of living systems.

Abstract Background: Current data support that metastatic hormone receptor-positive (HR+) and HER2-positive (HER2+) breast cancer offers distinct treatment options targeting both the hormone receptor and the HER2-pathway. This might lead to increased treatment efficacy with the potential of omitting chemotherapy in these patients. The aim of the randomized multicenter phase III DETECT V trial was to analyze the efficacy of chemotherapy free and CDK4/6 inhibitor containing treatment strategies compared to current standard treatment. Methods: Between 09/2015 and 11/2022, 271 patients with HER2+ and HR+ MBC in the 1st-3rd line setting were randomized 1:1 to receive trastuzumab and pertuzumab combined with either endocrine therapy or chemotherapy followed by maintenance therapy with dual HER2 targeted and endocrine therapy. Chemotherapy and the endocrine agents could be chosen from a variety of available regimens according to physicians’ choice. In January 2019, the protocol was amended with the addition of the CDK4/6 inhibitor ribociclib to both treatment arms. The primary objective of DETECT V was to compare tolerability between the treatment arms, and secondary objectives comprised the comparison of overall survival (OS), progression-free survival (PFS) and safety, as well as the evaluation of the effect of adding ribociclib to both treatment arms. Here we report results of the final efficacy analyses as based on the modified ITT set of 262 patients (9 patients did not receive any study treatment and were excluded). Of these, 120 patients were recruited before the addition of ribociclib (59 and 61 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively), and 142 patients were recruited after the addition of ribociclib (73 and 69 patients in the chemotherapy-free and chemotherapy-containing treatment arm, respectively). Results: Median patient age was 60 years, 202 (77.1%) of patients were in the first line setting and 137 (52.3%) patients had a metastasis-free interval (from primary diagnosis) exceeding 12 months. The overall comparison between all patients receiving chemotherapy-free and chemotherapy-containing treatment showed no significant difference with regard to OS and PFS (median OS not reached vs 46.1 months, HR 0.98, 95% CI 0.60 - 1.59, p = 0.93; median PFS 19.5 vs 23.0 months, HR 1.15, 95% CI 0.82 - 1.62, p = 0.42). However, both OS and PFS were significantly improved by the (non-randomized) addition of ribociclib (OS: median OS not reached vs 46.1 months, HR 0.43, 95% CI 0.26 - 0.72, p = 0.001; PFS: median PFS 29.7 vs 15.6 months, HR 0.48, 95% CI 0.34 - 0.67, p < 0.001). A separate analysis for the two treatment arms showed that the addition of ribociclib to chemotherapy-containing treatment significantly improved both OS (median OS not reached vs 38.7 months, HR 0.30, 95% CI 0.14 - 0.64, p = 0.002) and PFS (median PFS 33.1 vs 15.4 months, HR 0.35, 95% CI 0.21 - 0.59, p < 0.001), while the addition of ribociclib to chemotherapy-free treatment significantly improved PFS (median PFS 27.2 vs 15.6 months, HR 0.61, 95% CI 0.38 - 0.98, p = 0.040) but not OS (median OS not reached in both groups, HR 0.60, 95% CI 0.30 - 1.23, p = 0.163). An exploratory cross-cohort comparison revealed significantly improved outcome for patients receiving chemotherapy-free treatment plus ribociclib vs chemotherapy-containing treatment without ribociclib (OS: median OS not reached vs 38.7 months, HR 0.48, 95% CI 0.24 - 0.94, p = 0.033; PFS: median PFS 27.2 vs 15.4 months, HR 0.53, 95% CI 0.33 - 0.85, p = 0.008). Conclusion: Our results suggest that chemotherapy-free treatment for patients with HER2+ and HR+ MBC may be a valuable and effective treatment alternative, and may improve survival with the addition of ribociclib. Citation Format: W. Janni, T. Fehm, V. Müller, J. Blohmer, A. De Gregorio, T. Decker, A. Hartkopf, N. Ditsch, M. Schmidt, P. Wimberger, T. Engler, M. Banys-Paluchowski, P. A. Fasching, B. Rack, A. Schneeweiss, K. Pantel, T. W. Friedl, F. Schochter, J. Huober. Efficacy Analysis of the Randomized Phase III DETECT V trial: Treatment De-escalation by Omission of Chemotherapy and the Effect of Adding Ribociclib in HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF4-02.

Due to communication problems, people with primary progressive aphasia (PwPPA) are often affected in their self-image and experience a reduced quality of life (QoL). Biographic-narrative therapy is an effective approach to improve QoL in post-stroke aphasia. This study describes how PwPPA experienced their participation in the biographic-narrative intervention called Cope PPA. The intervention comprised a combination of five individual and seven group therapy sessions as well as the use of music and art therapy elements. Inclusion criteria were a capacity to give consent and sufficient visual/auditory abilities of PwPPA. Exclusion criteria were the presence of severe depression (MADRS > 35) or severe cognitive deficits (MMST < 10). After the therapy, PwPPA and their family members took part in half-hour semi-structured interviews. Interviews were analysed according to the reflexive thematic analysis by Braun and Clarke. The qualitative analysis was based on a data set of 34 interviews. A total of six themes were identified: (1) Participation required adherence; (2) Materials were considered remarkable; (3) Storytelling was conducted in an aphasia-free area; (4) Group participation created a sense of belonging; (5) Experiences encouraged self-reflection and (6) Coping is lengthy and ongoing. The findings of our reflexive thematic analysis suggest that PwPPA experienced the intervention as meaningful. Some PwPPA described the effects of our intervention on their self-image. Others emphasised that coping with their condition was an ongoing process requiring continuous support.

A bioinspired multilayer coating is developed for the protection of built cultural heritage, emulating the hierarchical architecture of natural nacre. The system is fabricated through the alternating deposition of mineralized calcium carbonate (CaCO3) and organic layers composed of chitosan and cellulose nanofibrils (CNFs), with poly-(acrylic acid) (PAA) acting as a mineralization-directing agent. A CO2-controlled environment promotes the formation of continuous crystalline CaCO3 layers with strong interfacial adhesion to marble substrates. The resulting composite multilayers exhibit stratified organization and mechanical properties comparable to those of the biogenic minerals. Nanoindentation and stiffness mapping reveal hardness and modulus values in the range of natural nacre, along with enhanced reinforcement with increasing numbers of multilayers. Mechanical durability under acidic conditions confirms the preservation of both structural integrity and aesthetic compatibility, with color changes remaining below perceptual thresholds (ΔEab < 5). The observed crack resistance, cohesive strength, and mechanical compatibility with the substrate highlight the effectiveness of the layered architecture for dissipating stress and inhibiting damage propagation. These results contribute to the development of an emerging class of bioinspired protective coatings that integrate mechanical resilience, chemical stability, and visual compatibility by establishing a groundwork for advanced materials tailored to the complex demands of cultural heritage conservation.

Gait deficits present an unresolved therapeutic challenge in Parkinson’s disease. At the behavioral level, symptoms exhibit heterogeneity, including bradykinesia and hypokinesia during cyclical limb movements, and sudden, involuntary interruptions in the gait sequence, known as freezing of gait. The neural activities driving these various deficits remain largely unknown. Here, we investigated the neural correlates of gait sequence interruptions with a deep phenotyping approach. For this, we transformed kinematic trajectories and cortical oscillations into continuous time series of neurobehavioral features. Next, we combined low-dimensional embedding with supervised classification to identify cortical oscillation features that drive gait deficits. In a rodent Parkinson’s disease model, our approach revealed that gait, akinesia, and stationary movements occupy distinct regions in the low-dimensional embedding space. Among the predominant features separating the states, Hjorth complexity and mobility modulated at akinesia onset. Additionally, we validated our findings in two Parkinson’s patients with freezing of gait, where neural features in STN recordings partially reflected the results in rodents. The presented neurobehavioral phenotyping approach is translational and can easily be generalized to the analysis of other complex movement disorders. Together, our results highlight specific neural features as potential biomarkers that may support the development of adaptive closed-loop algorithms for gait therapy in PD.

The study investigated the relationship between external and internal training load measures in 25 male elite youth soccer players (age: 16.6 ± 0.9 years, VO2max: 59 ± 4 ml/min/kg) over 3 months. External load (i.e., total distance, high metabolic power distance, high-speed running) was quantified using a local positioning system and related to subjective (RPE, sleep quality, drive (energy level)), biochemical (creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive protein (CRP), urea, cortisol, transferrin), and neuromuscular (CMJ) markers. Single day workload (1DL), exponential 7-day workload (7DL), and the acute: chronic workload ratio (ACWR) were calculated. 1DL parameters were correlated (Spearman’s rho) with RPE (range r = 0.24 to 0.43, p < 0.01) and 1DL distance was negatively related to drive (r = − 0.28, p < 0.001). LDH correlated positively with training load across all calculation methods (up to r = 0.27, p < 0.01). CK exhibited positive correlations to ACWR training load (r = 0.23 to 0.27, p < 0.05), while transferrin (ACWR) and CRP (1DL) showed negative associations to training load (r = − 0.21 to − 0.28, p < 0.05). CMJ eccentric mean force was negatively correlated with all ACWR training load variables (r = − 0.22 to − 0.25, p < 0.01). In summary, subjective measures showed stronger and more consistent associations with training load than biomarkers or neuromuscular testing. Practitioners may confidently use well-structured questionnaires for load monitoring in elite youth soccer.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-31487-z.

Multiple studies have investigated how serious games can foster learning in the context of education. However, findings on the impact of developing such serious games as an instructional approach are still limited, especially in education for sustainable development. Thus, this paper presents the Serious Game Development as an Instructional Approach (SGDIA) framework based on the ADDIE concept. Subsequently, a proof-of-concept study is applied to evaluate the impact of the course concept on learning. In an experimental pre-post study design at two German universities (n = 48), the effects on socio-emotional (values, self-efficacy) and cognitive (understanding, critical reflection) learning objectives relevant to education for sustainable development have been tested. The findings show that self-efficacy and pro-environmental values increased significantly after students participated in the serious game design course over three months. Additionally, in 23 out of the 48 participants, students who sought understanding during the three months of the teaching setting were more likely to critically reflect. As low-level methods of creating game content, such as simple game engines using visual programming, are becoming more widespread, the paper demonstrates how creating serious games can be a valid instructional method. Based on the findings, the potential of developing serious games as an instructional approach in higher education is discussed.