Ludwig Boltzmann Institute for Cancer Research

ABSTRACTExtracellular vesicles (EVs) have emerged as powerful mediators of intercellular communication with significant potential across biomedical, veterinary, cosmetic, agricultural and environmental applications. However, the translation of EV‐based discoveries into practical and commercially viable products remains constrained by scientific complexity, regulatory uncertainty and manufacturing challenges. To address these barriers, the International Society for Extracellular Vesicles (ISEV) established the Translation, Regulation and Advocacy Committee (ISEV‐TRA). ISEV‐TRA aims to catalyse the responsible advancement of EV technologies by fostering cross‐sector collaboration, harmonising quality and regulatory frameworks and providing strategic advocacy to enhance market readiness. Through targeted initiatives—such as workshops and the development of translational resources and guidance—ISEV‐TRA seeks to bridge the gap between research and real‐world implementation. By promoting dialogue amongst academia, industry, investors and policymakers, ISEV‐TRA positions itself as a central driver in shaping the global roadmap for EV translation and commercialisation.

While surgical skill is acquired during training, objectively evaluating training’s impact is challenging. However, new possibilities in measuring wrist tremor during surgical procedures have emerged due to novel wearable sensors. In this study, the effect of simulator-based neurosurgical resident training on wrist tremor was assessed using a smartwatch. A study involving nine neurosurgical residents performing simulator-based training on unruptured intracranial aneurysm clipping procedures was conducted. Residents performed four training sessions on two days (180 clippings in total). Three cohorts were formed receiving in between the two days either: no training, video-based training, or video-based training with augmented reality. Wrist acceleration was measured using a smartwatch. Wrist tremor was calculated using the acceleration data in time and frequency domains (peak power, total power, and peak frequency). Video-based training with augmented reality showed a statistically significant reduction in total power as well as in peak power, with reductions of 56% (p = 0.0186) and 69% (p = 0.0021), between day 0 and day 14, respectively. Wrist tremor assessment using a smartwatch confirmed the positive impact of video-based and augmented reality training on neurosurgical residents’ confidence in surgical training procedures by reducing wrist tremor, making it a valuable tool for skill assessment.

Investigation of the eccentric quasi-isometric (EQI) resistance exercise has started in recent years. However, the biomechanical characteristics and fatigue effects of EQI muscle actions in the ankle plantar flexors remain unexplored. This study aimed to compare the biomechanical characteristics of plantarflexion EQIs and post-EQI acute fatigue between two different loading intensities. Twenty regularly physically active participants (9 men, 11 women) completed 3 sets comprising of a single EQI muscle contraction at 75% and 90% (one intensity for each leg in a random order) of maximal voluntary isometric contraction (MVIC) on an isokinetic dynamometer. Outcome variables included total contraction time, torque impulse, angular velocities and range of motion during EQI muscle actions, as well as pre- and post-contraction MVIC measures. The analysis indicated no statistically significant effect of EQI muscle-action on MVIC torque (main effect of time: p = 0.636). There were also no statistically significant differences between EQI muscle actions performed at 75% and 90% MVIC regarding angular velocity (p = 0.244). However, executing EQI muscle contraction at 75% MVIC resulted in statistically significantly larger total contraction time, total torque impulse, and range of motion (p < 0.001) compared to EQI at 90% MVIC. These findings suggest that performing EQI contractions at 75% MVIC may be more effective for generating greater mechanical stimulus without inducing significant acute fatigue.

Abstract Polyploidization refers to the balanced increase in gene copy number and is a feature of specialized cells in different mammalian tissues, including the liver and the heart. During organogenesis, hepatocytes and cardiomyocytes undergo scheduled polyploidization events to increase their cellular or nuclear DNA content. This is thought to improve cellular output and enable for rapid genetic adaptation in response to stress. Yet, excessive increases in ploidy can also be disadvantageous and increase the risk of genome instability. Hence, a dedicated machinery, the PIDDosome multi-protein complex, has evolved to prevent exacerbated increases in DNA content. Using targeted mutagenesis in mice, we show that the PIDDosome controls hepatocyte ploidy in a cell-autonomous manner and that sequential and quantitative auto-processing of PIDD1 is key for accurate control of ploidy in postnatal development of liver and heart. Stoichiometric imbalances in bioactive PIDD1-fragments impair p53-dependent and independent cell cycle arrest responses during organogenesis, as well as caspase-2-dependent apoptosis caused by centrosome amplification. Strikingly, targeted mutagenesis of the caspase cleavage motif in the critical E3-ligase controlling p53 protein levels, Mdm2, impairs ploidy control in hepatocytes, but not in cardiomyocytes, indicative of the existence of alternative caspase-2 substrates that help to restrict ploidy in the heart.

Hemophilia is a rare X-linked bleeding disorder caused by mutations in the F8 or F9 gene (hemophilia A or B), leading to deficient factor VIII or IX proteins, respectively. Hemophilia-related complications caused by bleeding into the joints (the hallmark of hemophilia) and age-related comorbidities occur frequently and impact the functionality and quality of life of persons with hemophilia (PwH). Given the chronic nature of hemophilia, we hypothesized that hemophilia has an association with accelerated biological aging. Therefore, we investigated biological aging biomarkers, i.e., telomere length and mitochondrial DNA (mtDNA) copy number with a quantitative polymerase chain reaction-based assay in PwH (N=99) and age- and sex-matched healthy controls (N=61). The association of telomere length and mtDNA copy number with hemophilia severity was investigated using ordinary least-squares linear regression models allowing for interactions with chronological age. Telomere length (6.09 [interquartile range (IQR), 4.79-7.68] kb vs. 10.07 [IQR, 7.93-12.66] kb; P<0.001) and mtDNA copy number (243.17 [IQR, 206.54-293.79] vs. 495.52 [IQR, 399.60-615.06]; P<0.001) were significantly lower in PwH compared to healthy controls. Persons with severe hemophilia had longer telomere length than those with non-severe hemophilia (6.29 [IQR, 5.36-8.05] kb vs. 5.12 [IQR, 3.97-6.58] kb), while no difference in mtDNA copy number was observed. We observed accelerated biological aging, indicated by shorter telomere length and lower mtDNA copy number, in PwH compared to healthy controls. Interestingly, telomere length shortening was more pronounced in non-severe than in severe hemophilia, which needs further investigations. Further research is needed to understand the underlying mechanisms of biological aging in hemophilia.

Background/Objectives: Secure large-bore cannula insertion is critical for effective extracorporeal membrane oxygenation (ECMO), as inadequate fixation can lead to complications such as infection, dislodgment, and life-threatening events. With inconsistent guidelines for ECMO line management, this study compares the effectiveness of traditional suture fixation to an adhesive securement method in the prevention of ECMO cannula dislodgment using an in vitro model. Methods: Porcine skin and muscle tissue sections were prepared and mounted in a custom holder. A 21F venous ECMO cannula was inserted using a modified Seldinger technique. Three fixation methods were randomly compared: (1) three silk sutures, and (2a) one silk suture with a CathGrip adhesive anchoring device. In addition, a sub-analysis was performed using (2b) the Hollister adhesive anchoring device. A uniaxial testing machine simulated 50 mm cannula dislodgment, measuring tensile forces at 12.5, 25, and 50 mm dislodgment points. Results: A total of 26 ECMO cannula fixations using sutures, 26 with adhesive CathGrip, six with a Hollister device, and three controls were tested across six porcine samples. Sutures demonstrated greater variability in force at maximum dislocation, with 27% rupturing at 50 mm. In contrast, CathGrip provided greater flexibility without tearing. The adhesive exhibited higher stiffness (2.38 N/mm vs. 2.09 N/mm, p < 0.001) and dislodgment energy (0.034 J vs. 0.032 J, p = 0.002) in the 0-5 mm range, while sutures showed greater stiffness in the 5-50 mm range (1.42 N/mm vs. 1.18 N/mm, p < 0.001). At larger displacements (25 mm and 50 mm) and in total energy absorption, no statistically significant differences were observed (p = 0.57). In a sub-analysis, the six fixations using the Hollister device exhibited higher variability and significantly lower dislodgment forces at 25 mm (p = 0.033) and 50 mm (p = 0.004) compared to the CathGrip device. Conclusions: This study suggests that adhesive anchoring methods, such as CathGrip, may provide comparable or potentially superior fixation strength to sutures for ECMO cannula stabilization under controlled conditions. However, further research, including clinical trials, is necessary to confirm these findings, evaluate long-term performance, and explore the implications for dislodgment risk and infection prevention in clinical practice.