Background Parkinson disease (PD) is a common movement disorder. Patients with PD have multiple gait impairments that result in an increased risk of falls and diminished quality of life. Therefore, gait measurement is important for the management of PD. Objective We previously developed a smartphone-based dual-task gait assessment that was validated in healthy adults. The aim of this study was to test the validity of this gait assessment in people with PD, and to examine the association between app-derived gait metrics and the clinical and functional characteristics of PD. Methods Fifty-two participants with clinically diagnosed PD completed assessments of walking, Movement Disorder Society Unified Parkinson Disease Rating Scale III (UPDRS III), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety (HAM-A), and Hamilton Depression (HAM-D) rating scale tests. Participants followed multimedia instructions provided by the app to complete two 20-meter trials each of walking normally (single task) and walking while performing a serial subtraction dual task (dual task). Gait data were simultaneously collected with the app and gold-standard wearable motion sensors. Stride times and stride time variability were derived from the acceleration and angular velocity signal acquired from the internal motion sensor of the phone and from the wearable sensor system. Results High correlations were observed between the stride time and stride time variability derived from the app and from the gold-standard system (r=0.98-0.99, P<.001), revealing excellent validity of the app-based gait assessment in PD. Compared with those from the single-task condition, the stride time (F1,103=14.1, P<.001) and stride time variability (F1,103=6.8, P=.008) in the dual-task condition were significantly greater. Participants who walked with greater stride time variability exhibited a greater UPDRS III total score (single task: β=.39, P<.001; dual task: β=.37, P=.01), HAM-A (single-task: β=.49, P=.007; dual-task: β=.48, P=.009), and HAM-D (single task: β=.44, P=.01; dual task: β=.49, P=.009). Moreover, those with greater dual-task stride time variability (β=.48, P=.001) or dual-task cost of stride time variability (β=.44, P=.004) exhibited lower MoCA scores. Conclusions A smartphone-based gait assessment can be used to provide meaningful metrics of single- and dual-task gait that are associated with disease severity and functional outcomes in individuals with PD.

This study aims to investigate how the frequency settings of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) influence the motor symptoms of Parkinson’s disease (PD). Stimulation with frequencies less than 100 Hz (mostly 60 or 80 Hz) is considered low-frequency stimulation (LFS) and with frequencies greater than 100 Hz (mostly 130 or 150 Hz) is considered high-frequency stimulation (HFS). We conducted a comprehensive literature review and meta-analysis with a random-effect model. Ten studies with 132 patients were included in our analysis. The pooled results showed no significant difference in the total Unified Parkinson Disease Rating Scale part III (UPDRS-III) scores (mean effect, −1.50; p = 0.19) or the rigidity subscore between HFS and LFS. Compared to LFS, HFS induced greater reduction in the tremor subscore within the medication-off condition (mean effect, 1.01; p = 0.002), while no significance was shown within the medication-on condition (mean effect, 0.01; p = 0.92). LFS induced greater reduction in akinesia subscore (mean effect, −1.68, p = 0.003), the time to complete the stand-walk-sit (SWS) test (mean effect, −4.84; p < 0.00001), and the number of freezing of gait (FOG) (mean effect, −1.71; p = 0.03). These results suggest that two types of frequency settings may have different effects, that is, HFS induces better responses for tremor and LFS induces greater response for akinesia, gait, and FOG, respectively, which are worthwhile to be confirmed in future study, and will ultimately inform the clinical practice in the management of PD using STN-DBS.

Clear cell renal cell carcinoma (ccRCC) is one of the most common histological subtypes of renal cancer, with a poor prognosis. Our study aimed to identify a biomarker that is significantly associated with ccRCC prognosis and novel immunotherapeutic targets, as well as some novel molecular drugs for ccRCC. Based on the overlap of The Cancer Genome Atlas (TCGA)-Kidney Renal Clear Cell Carcinoma (KIRC) data and the ImmPort database, we obtained 1,292 immune-related genes (IRGs) and constructed a weighed co-expression network based on the IRGs. A total of 39 hub genes were screened out in three modules. CTLA4, which had the highest connectivity degree among the screened genes in a protein–protein interaction network (degree = 24), was selected. Internal validation based on the GEPIA database revealed that patients with a higher expression of CTLA4 had a significantly shorter overall survival time and disease-free survival time. Expression of CTLA4 was also closely correlated with local recurrence, pathologic stage, and immune infiltration level. External validation based on the Oncomine database and merged microarray-acquired dataset validated the mRNA expression level of hub genes. Gene-set enrichment analysis revealed that six KEGG signaling pathways, which were significantly associated with CTLA4, were enriched on immune-related pathways. Further analysis according to the TIMER database demonstrated that CTLA4 expression was positively related to dendritic cells (cor = 0.446, P = 1.32E-23) and negatively associated with tumor purity (cor = −0.267, P = 5.51E-09). Finally, we screened out 293 differentially expressed genes by integrating six datasets from the GEO database. The Connectivity Map (CMap) analysis revealed the strong potential of three small molecule drugs (monensin, quercetin, and fenbufen) for ccRCC treatment. In conclusion, CTLA4 was identified and validated in prognosis of ccRCC. CTLA4 may be a new prognostic biomarker and immunotherapeutic target for ccRCC. Monensin, quercetin, and fenbufen may be novel choices for ccRCC treatment.

Background Long non‐coding RNA taurine‐upregulated gene 1 (lncRNA TUG1) is reported to be involved in the progression and development of several malignancies; however, its role in Philadelphia chromosome‐negative acute lymphoblastic leukemia (Ph−ALL) is unknown. The present study aimed to explore the correlation of lncRNA TUG1 with disease risk, disease condition, and prognosis of adult Ph−ALL. Methods Total 101 adult Ph− ALL patients and 40 bone marrow (BM) donors were included, followed by detection of BM monocyte cell lncRNA TUG1 expression by reverse transcription‐quantitative polymerase chain reaction. According to the quantiles of lncRNA TUG1 expression in Ph− ALL patients, these patients were divided into four tiers: tier 1 (ranked in 0%~25%), tier 2 (ranked in 25%~50%), tier 3 (ranked in 50%~75%), and tier 4 (ranked in 75%~100%). Results LncRNA TUG1 was upregulated in Ph− ALL patients compared with healthy donors. Further analysis indicated that in Ph− ALL patients, higher lncRNA TUG1 tier was correlated with the presence of central nervous system leukemia, increased white blood cell level, and bone marrow blasts. Furthermore, higher lncRNA TUG1 tier was negatively associated with complete remission (CR) within 4 weeks, total CR, and allogeneic hematopoietic stem cell transplant achievement. In addition, higher lncRNA TUG1 tier was associated with decreased disease‐free survival and overall survival, which was further verified to be an independent factor by Cox's regression analysis. Conclusion lncRNA TUG1 presents potential to be a novel biomarker for disease risk assessment and survival surveillance in Ph− ALL management.