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Purpose: A virtual reality (VR) system, where surgeons can practice procedures on virtual anatomies, is a scalable and cost-effective alternative to cadaveric training. The fully digitized virtual surgeries can also be used to assess the surgeon's skills using measurements that are otherwise hard to collect in reality. Thus, we present the Fully Immersive Virtual Reality System (FIVRS) for skull-base surgery, which combines surgical simulation software with a high-fidelity hardware setup., Methods: FIVRS allows surgeons to follow normal clinical workflows inside the VR environment. FIVRS uses advanced rendering designs and drilling algorithms for realistic bone ablation. A head-mounted display with ergonomics similar to that of surgical microscopes is used to improve immersiveness. Extensive multi-modal data are recorded for post-analysis, including eye gaze, motion, force, and video of the surgery. A user-friendly interface is also designed to ease the learning curve of using FIVRS., Results: We present results from a user study involving surgeons with various levels of expertise. The preliminary data recorded by FIVRS differentiate between participants with different levels of expertise, promising future research on automatic skill assessment. Furthermore, informal feedback from the study participants about the system's intuitiveness and immersiveness was positive., Conclusion: We present FIVRS, a fully immersive VR system for skull-base surgery. FIVRS features a realistic software simulation coupled with modern hardware for improved realism. The system is completely open source and provides feature-rich data in an industry-standard format., (© 2023. CARS.)

Chemokine CXCL12 promotes growth and metastasis of more than 20 different human cancers, as well as pathogenesis of other common diseases. CXCL12 binds two different receptors, CXCR4 and CXCR7, both of which recruit and signal through the cytosolic adapter protein β-arrestin 2. Differences in CXCL12-dependent recruitment of β-arrestin 2 in cells expressing one or both receptors remain poorly defined. To quantitatively investigate parameters controlling association of β-arrestin 2 with CXCR4 or CXCR7 in cells co-expressing both receptors, we used a systems biology approach combining real-time, multi-spectral luciferase complementation imaging with computational modeling. Cells expressing only CXCR4 maintain low basal association with β-arrestin 2, and CXCL12 induces a rapid, transient increase in this interaction. In contrast, cells expressing only CXCR7 have higher basal association with β-arrestin 2 and exhibit more gradual, prolonged recruitment of β-arrestin 2 in response to CXCL12. We developed and fit a data-driven computational model for association of either CXCR4 or CXCR7 with β-arrestin 2 in cells expressing only one type of receptor. We then experimentally validated model predictions that co-expression of CXCR4 and CXCR7 on the same cell substantially decreases both the magnitude and duration of CXCL12-regulated recruitment of β-arrestin 2 to CXCR4. Co-expression of both receptors on the same cell only minimally alters recruitment of β-arrestin 2 to CXCR7. In silico experiments also identified β-arrestin 2 as a limiting factor in cells expressing both receptors, establishing that CXCR7 wins the "competition" with CXCR4 for CXCL12 and recruitment of β-arrestin 2. These results reveal how competition for β-arrestin 2 controls integrated responses to CXCL12 in cells expressing both CXCR4 and CXCR7. These results advance understanding of normal and pathologic functions of CXCL12, which is critical for developing effective strategies to target these pathways therapeutically.