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Item A single-cell level comparison of human inner ear organoids with the human cochlea and vestibular organs(Cell Press, 2023) van der Valk, Wouter H.; van Beelen, Edward S. A.; Steinhart, Matthew R.; Nist-Lund, Carl; Osorio, Daniel; de Groot, John C. M. J.; Sun, Liang; van Benthem, Peter Paul G.; Koehler, Karl R.; Locher, Heiko; Otolaryngology -- Head and Neck Surgery, School of MedicineInner ear disorders are among the most common congenital abnormalities; however, current tissue culture models lack the cell type diversity to study these disorders and normal otic development. Here, we demonstrate the robustness of human pluripotent stem cell-derived inner ear organoids (IEOs) and evaluate cell type heterogeneity by single-cell transcriptomics. To validate our findings, we construct a single-cell atlas of human fetal and adult inner ear tissue. Our study identifies various cell types in the IEOs including periotic mesenchyme, type I and type II vestibular hair cells, and developing vestibular and cochlear epithelium. Many genes linked to congenital inner ear dysfunction are confirmed to be expressed in these cell types. Additional cell-cell communication analysis within IEOs and fetal tissue highlights the role of endothelial cells on the developing sensory epithelium. These findings provide insights into this organoid model and its potential applications in studying inner ear development and disorders.Item The Effectiveness of Robot-Assisted, Task-Specific Ankle Training in Improving Deficits Across the Three Domains of the ICF in Children with Cerebral Palsy (CP)(2018-11) Alotaibi, Madawi H.; Arnold, Brent; Altenburger, Peter; Munk, Niki; Dierks, TracyCerebral Palsy (CP) is considered to be the leading cause of motor disability among children. Children with CP present with multiple physical impairments including decreased strength and range of motion (ROM), increased spasticity, and poor balance and coordination. These impairments often lead to limitations in ankle motor control that impacts balance and gait function, which puts children at a higher risk for developing other problems. In recent studies, robotic devices have been developed to address poor motor control of the upper and lower extremities. Aim: The aim of this study is to investigate the extent to which the robot-assisted, taskspecific ankle trainer improve deficits across the three domains of the International Classification of Functioning, Disability and Health (ICF) in children with CP. Method: This is a quasi-experimental, single group, repeated measure design with four time-testing points through a set training session/protocol. A convenience sample of 5 children with CP were enrolled in the study. All children received 6-weeks of ankle robot training that included two 45-60 minute sessions per week, for a total of 12 sessions. Data from Tardieu Scale of spasticity, Boyd and Graham selective motor control, Pediatric Balance Scale, goniometer, hand held dynamometer, gait mat analysis, accelerometer, LIFE-H for children questionnaires, ultrasound, and robotic evaluation were collected at the different time points (1 week and 1 month pre training and 1 week and 1 month post training). Descriptive statistics and repeated measure (ANOVA) were used with SPSS software for data analysis. Results: All participants showed improvement in 1. Body Function and Structures (ROM, tone, strength, balance, ankle control and performance, and muscle architecture), 2. Activity (gait and activity counts) and 3. Participations over the course of the study. Conclusion: The results revealed the potential of robot-assisted, task-specific ankle training to improve motor performance and capacity at the body function, activity and participation level. Training appeared to have a lasting impact as most gains were maintained one month following training.Item Molecular, metabolic, and functional CD4 T cell paralysis in the lymph node impedes tumor control(Elsevier, 2023) Guo, Mengdi; Abd-Rabbo, Diala; Bertol, Bruna C.; Carew, Madeleine; Lukhele, Sabelo; Snell, Laura M.; Xu, Wenxi; Boukhaled, Giselle M.; Elsaesser, Heidi; Halaby, Marie Jo; Hirano, Naoto; McGaha, Tracy L.; Brooks, David G.; Microbiology and Immunology, School of MedicineCD4 T cells are central effectors of anti-cancer immunity and immunotherapy, yet the regulation of CD4 tumor-specific T (TTS) cells is unclear. We demonstrate that CD4 TTS cells are quickly primed and begin to divide following tumor initiation. However, unlike CD8 TTS cells or exhaustion programming, CD4 TTS cell proliferation is rapidly frozen in place by a functional interplay of regulatory T cells and CTLA4. Together these mechanisms paralyze CD4 TTS cell differentiation, redirecting metabolic circuits, and reducing their accumulation in the tumor. The paralyzed state is actively maintained throughout cancer progression and CD4 TTS cells rapidly resume proliferation and functional differentiation when the suppressive constraints are alleviated. Overcoming their paralysis established long-term tumor control, demonstrating the importance of rapidly crippling CD4 TTS cells for tumor progression and their potential restoration as therapeutic targets.