Based on different immune responses under the glucose metabolizing type of papillary thyroid cancer and the response to anti-PD-1 therapy.

Glucose metabolism-related genes play an important role in the development and immunotherapy of many tumours, but their role in thyroid cancer is ambiguous. To investigate the role of glucose metabolism-related genes in the development of papillary thyroid cancer (PTC) and their correlation with the clinical outcome of PTC, we collected transcriptomic data from 501 PTC patients in the Cancer Genome Atlas (TCGA). We performed nonnegative matrix decomposition clustering of 2752 glucose metabolism-related genes from transcriptome data and classified PTC patients into three subgroups (C1 for high activation of glucose metabolism, C2 for low activation of glucose metabolism and C3 for moderate activation of glucose metabolism) based on the activation of different glucose metabolism-related genes in 10 glucose metabolism-related pathways. We found a positive correlation between the activation level of glucose metabolism and the tumour mutation burden (TMB), neoantigen number, mRNA stemness index (mRNAsi), age, and tumour stage in PTC patients. Next, we constructed a prognostic prediction model for PTC using six glucose metabolism-related genes (PGBD5, TPO, IGFBPL1, TMEM171, SOD3, TDRD9) and constructed a nomogram based on the risk score and clinical parameters of PTC patients. Both the prognostic risk prediction model and nomogram had high stability and accuracy for predicting the progression-free interval (PFI) in PTC patients. Patients were then divided into high-risk and low-risk groups by risk score. The high-risk group was sensitive to paclitaxel and anti-PD-1 treatment, and the low-risk group was sensitive to sorafenib treatment. We found that the high-risk group was enriched in inflammatory response pathways and associated with high level of immune cell infiltration. To verify the accuracy of the prognostic prediction model, we knocked down PGBD5 in PTC cells and found that the proliferation ability of PTC cells was significantly reduced. This suggests that PGBD5 may be a relatively important oncogene in PTC. Our study constructed a prognostic prediction model and classification of PTC by glucose metabolism-related genes, which provides a new perspective on the role of glucose metabolism in the development and immune microenvironment of PTC and in guiding chemotherapy, targeted therapy and immune checkpoint blockade therapy of PTC.

Results and Guidelines From a Repeated-Measures Design Experiment Comparing Standing and Seated Full-Body Gesture-Based Immersive Virtual Reality Exergames: Within-Subjects Evaluation.

BACKGROUND: Although full-body seated exercises have been studied in a wide range of settings (ie, homes, hospitals, and daycare centers), they have rarely been converted to seated exergames. In addition, there is an increasing number of studies on immersive virtual reality (iVR) full-body gesture-based standing exergames, but the suitability and usefulness of seated exergames remain largely unexplored. OBJECTIVE: This study aimed to evaluate the difference between playing a full-body gesture-based iVR standing exergame and seated exergame in terms of gameplay performance, intrinsic motivation, and motion sickness. METHODS: A total of 52 participants completed the experiment. The order of the game mode (standing and sitting) was counterbalanced. Gameplay performance was evaluated by action or gesture completion time and the number of missed gestures. Exertion was measured by the average heart rate (HR) percentage (AvgHR%), increased HR%, calories burned, and the Borg 6-20 questionnaire. Intrinsic motivation was assessed with the Intrinsic Motivation Inventory (IMI), whereas motion sickness was assessed via the Motion Sickness Assessment Questionnaire (MSAQ). In addition, we measured the fear of falling using a 10-point Likert scale questionnaire. RESULTS: Players missed more gestures in the seated exergame than in the standing exergame, but the overall miss rate was low (2.3/120, 1.9%). The analysis yielded significantly higher AvgHR%, increased HR%, calories burned, and Borg 6-20 rating of perceived exertion values for the seated exergame (all P<.001). The seated exergame was rated significantly higher on peripheral sickness (P=.02) and sopite-related sickness (MSAQ) (P=.004) than the standing exergame. The score of the subscale "value/usefulness" from IMI was reported to be higher for the seated exergame than the standing exergame. There was no significant difference between the seated exergame and standing exergame in terms of intrinsic motivation (interest/enjoyment, P=.96; perceived competence, P=.26; pressure/tension, P=.42) and the fear of falling (P=.25). CONCLUSIONS: Seated iVR full-body gesture-based exergames can be valuable complements to standing exergames. Seated exergames have the potential to lead to higher exertion, provide higher value to players, and be more applicable in small spaces compared with standing exergames. However, gestures for seated exergames need to be designed carefully to minimize motion sickness, and more time should be given to users to perform gestures in seated exergames compared with standing exergames.