Limb loading enhances skill transfer between augmented and physical reality tasks during limb loss rehabilitation.

BACKGROUND: Virtual and augmented reality (AR) have become popular modalities for training myoelectric prosthesis control with upper-limb amputees. While some systems have shown moderate success, it is unclear how well the complex motor skills learned in an AR simulation transfer to completing the same tasks in physical reality. Limb loading is a possible dimension of motor skill execution that is absent in current AR solutions that may help to increase skill transfer between the virtual and physical domains. METHODS: We implemented an immersive AR environment where individuals could operate a myoelectric virtual prosthesis to accomplish a variety of object relocation manipulations. Intact limb participants were separated into three groups, the load control (CGLD; [Formula: see text]), the AR control (CGAR; [Formula: see text]), and the experimental group (EG; [Formula: see text]). Both the CGAR and EG completed a 5-session prosthesis training protocol in AR while the CGLD performed simple muscle training. The EG attempted manipulations in AR while undergoing limb loading. The CGAR attempted the same manipulations without loading. All participants performed the same manipulations in physical reality while operating a real prosthesis pre- and post-training. The main outcome measure was the change in the number of manipulations completed during the physical reality assessments (i.e. completion rate). Secondary outcomes included movement kinematics and visuomotor behavior. RESULTS: The EG experienced a greater increase in completion rate post-training than both the CGAR and CGLD. This performance increase was accompanied by a shorter motor learning phase, the EG's performance saturating in less sessions of AR training than the CGAR. CONCLUSION: The results demonstrated that limb loading plays an important role in transferring complex motor skills learned in virtual spaces to their physical reality analogs. While participants who did not receive limb loading were able to receive some functional benefit from AR training, participants who received the loading experienced a greater positive change in motor performance with their performance saturating in fewer training sessions.

Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 Possesses Prognostic Significance and Promotes Progression of Papillary Thyroid Cancer.

PURPOSE: Identification of novel biomarkers could benefit the clinical therapy and management of papillary thyroid carcinoma (PTC). Human endogenous retrovirus long terminal repeat-associating protein 2 (HHLA2) has been reported to play roles in the development of various cancers. The clinical significance and biological function of HHLA2 in PTC were investigated. PATIENTS AND METHODS: The expression level of HHLA2 was evaluated in PTC tissues (from 107 PTC patients) and cell lines (TPC-1, IHH-4, CGTH-W3, and MDA-T32 cells) by RT-qPCR. The clinical significance of HHLA2 was estimated with a series of statistical analyses. The biological function of HHLA2 was assessed with the CCK8 assay and transwell assay. RESULTS: HHLA2 was upregulated in PTC compared with the normal samples and was associated with the positive lymph node metastasis and advanced TNM stage of PTC patients. HHLA2 was an independent prognostic factor associated with the poor survival of PTC patients. Additionally, HHLA2 functioned as a tumor promoter that enhanced the progression of PTC cells. CONCLUSION: HHLA2 could serve as a prognostic biomarker and tumor promoter in PTC, providing a novel therapeutic target of PTC.

Downregulation of miR-140 is Correlated with Poor Prognosis and Progression of Thyroid Cancer.

BACKGROUND: The incidence of thyroid cancer is increasing rapidly and there is an urgent need to explore novel therapeutic targets for thyroid cancer. MiR-140 has been reported to affect the progression of various cancers, which makes it possible to play a role in thyroid cancer. This study aimed to investigate the expression and role of miR-140 in thyroid cancer. METHODS: The expression of miR-140 was investigated by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) in thyroid cancer tissues and cell lines. The prognostic value of miR- 140 in thyroid cancer was evaluated by Kaplan-Meier survival and Cox regression. Moreover, the effects of miR-140 on cell proliferation, migration, and invasion of thyroid cancer were investigated by CCK-8 and Transwell assay. RESULTS: MiR-140 was downregulated in thyroid cancer tissues and cells, which correlated with TNM stage and lymph node metastasis of patients. Patients with low miR-140 expression had a shorter survival time compared with that in patients with high miR-140 expression. Furthermore, miR-140 acts as an independent factor for the prognosis of thyroid cancer. Overexpression of miR-140 inhibited cell proliferation, migration, and invasion of thyroid cancer. CONCLUSION: MiR-140 can serve as a potential prognostic factor for patients with thyroid cancer and suppress the progression of thyroid cancer, which provides new insight for the therapeutic target for thyroid cancer.

Overexpression of miR-127 Predicts Poor Prognosis and Contributes to the Progression of Papillary Thyroid Cancer by Targeting REPIN1.

Papillary thyroid cancer (PTC) is a major kind of thyroid cancer with increasing recurrence and metastasis. MiR-127 has been demonstrated to play roles in many cancers with dysregulation. However, the function of miR-127 is still unknown. This study aimed to explore a novel biomarker for the progression and prognosis of PTC. A set of 118 patients with PTC were collected from the Affiliated Hospital of Qingdao University. qRT-PCR was used to detect the expression of miR-127 in PTC tissues and cells. The association between miR-127 expression and the clinicopathological features of patients were evaluated by the χ2 test, and the prognostic value of miR-127 was evaluated by Kaplan-Meier analysis and Cox regression analysis. The effect of miR-127 on cell proliferation, migration, and invasion of PTC was analyzed by CCK-8 and transwell assay. miR-127 was found to be upregulated in PTC tissues and cells correlated with the TNM stage and poor prognosis of PTC patients. MiR-127 and the TNM stage were considered as two independent prognostic indicators for PTC. Moreover, overexpression of miR-127 significantly enhanced cell proliferation, migration, and invasion of PTC by targeting REPIN1. miR-127 may be involved in the progression of PTC, which provides a new therapeutic strategy for PTC.

Upregulation of miR-421 predicts poor prognosis and promotes proliferation, migration, and invasion of papillary thyroid cancer cells.

BACKGROUND: Papillary thyroid carcinoma (PTC) represents the most frequent subtype of thyroid cancer (TC) with poor prognosis mainly due to the severe invasion and metastasis. As an oncogene, microRNA-421 (miR-421) is involved in the development of various cancers. This study was to investigate the clinical significance of miR-421 in PTC and its effects on the biological function of PTC cells. METHODS: The expression level of miR-421 in all tissues and PTC cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, the relationship between miR-421 expression and the clinicopathological feature was detected by chi-square analysis in 106 patients with PTC. In addition, Kaplan-Meier and multivariate Cox regression analysis were used to detect the survival time and the prognostic value of miR-421. Finally, the regulatory effect of miR-421 on the proliferation, migration, and invasion ability of PTC cells was detected by Cell Counting Kit (CCK-8) and Transwell assay. RESULTS: Compared with all control groups, the expression of miR-421 was significantly increased in 106 patients tissues and PTC cell lines (p < 0.001). In addition, patients with miR-421 upregulated in PTC showed more positive lymph node metastasis (p = 0.011), positive tumor infiltration (p = 0.031), and TNM stage III/IV (p = 0.019), and when miR-421 expression level was elevated, the survival rate of PTC patients was poor (log-rank test, p = 0.023). Furthermore, miR-421 might be an independent prognostic biomarker for PTC (hazard ratio [HR] = 3.172, 95% CI = 1.071-9.393, p = 0.037). Finally, increased levels of miR-421 can significantly promote cell proliferation, migration, and invasion (p < 0.01). CONCLUSION: miR-421 is a novel oncogene of PTC and is a valuable prognostic biomarker. Moreover, the upregulation of miR-421 enhances the proliferation, migration, and invasion of PTC cells.

Pri-Mir-34b/C and Tp-53 Polymorphisms are Associated With The Susceptibility of Papillary Thyroid Carcinoma: A Case-Control Study.

Tumor suppressor p53 directly regulated the abundance of the miR-34b/c. The interaction might contribute to certain cancer. We hypothesized that rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72Pro may be related to the risk of papillary thyroid carcinoma (PTC). A total of 784 patients with PTC and 1006 healthy controls were recruited to participate in this study. The variants were discriminated using a polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Additionally, the relative expression levels of miR-34b/c and TP-53 in 44 paired samples were revealed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A significantly increased risk of PTC was observed in the miR-34b/c rs4938723 CT, CC, and CT/CC genotypes compared with the TT genotype (CT vs TT: adjusted odds ratio [OR] = 1.51, 95%confidence interval [CI] = 1.23-1.85; CC vs TT: adjusted OR = 1.89, 95%CI = 1.39-2.63; CT/CC vs TT: adjusted OR = 1.59, 95%CI = 1.30-1.92, respectively). Significantly increased PTC susceptibility was also associated with the TP-53 Arg72Pro CC and CG/CC genotypes compared with the GG genotype (CC vs GG: adjusted OR = 2.04, 95%CI = 1.54-2.70; CG/CC vs GG: adjusted OR = 1.35, 95%CI = 1.11-1.67, respectively). Stratification analysis revealed that patients carrying the TP-53 Arg72Pro C allele and CC genotype had a significantly increased risk for developing N1 (C vs. G: OR = 1.27, 95%CI = 1.03-1.56; CC vs. GG: OR = 1.62, 95%CI = 1.07-2.46, respectively). Combined analysis showed that the genotypes of rs4938723 CT/CC + TP-53CG/CC increased the risk of PTC compared with rs4938723TT + TP-53GG (OR = 2.25, 95%CI = 1.67-3.03). Additionally, level of miR-34b was significantly upregulated in PTC patients.These findings indicate that the miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may contribute to the susceptibility of PTC.

Prediction of ipsilateral and contralateral central lymph node metastasis in unilateral papillary thyroid carcinoma: a retrospective study.

BACKGROUND: Prophylactic central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC) remains controversial and predictive factors for central lymph node (CLN) metastasis in unilateral PTC cases are not well defined. The aims of this study were to evaluate the rate of ipsilateral and contralateral CLN metastasis and to determine the clinicopathologic factors predictive for ipsilateral and contralateral CLN metastasis in unilateral PTC cases. METHODS: We retrospectively reviewed 218 PTC patients with clinically negative-node neck who have received total thyroidectomy with bilateral CLND. Pearson χ(2) test or Fisher exact test and multivariate analysis were used to evaluate relationships between CLN metastasis and demographic factors such as age, sex and the clinicopathologic factors. RESULTS: Ipsilateral and contralateral CLN metastasis were present in 47.7% (104/218) and 13.3% (29/218), respectively. Multivariate analysis showed that tumor size (>1 cm) (P=0.016; OR, 2.005) and age <45 years old (P=0.031; OR, 1.539) were the predictors of ipsilateral CLN metastasis, and prelaryngeal lymph node (LN) metastasis (P=0.028; OR, 2.970) and ipsilateral CLN metastasis (P<0.001; OR, 15.128) independently predicted contralateral CLN metastasis. CONCLUSIONS: CLN metastasis was common in PTC patients with clinically node-negative neck and the most common pattern of CLN metastasis was ipsilateral CLN metastasis. Prophylactic ipsilateral CLND may be an optional procedure and should be considered for patients with a tumor size >1 cm. Therapeutic bilateral CLND should be considered in patients with a tumor size >1 cm and especially, if there exists prelaryngeal LN or ipsilateral CLN metastasis on frozen section analysis.