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.

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.

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.

We analyzed 53 patients with multiple myeloma coexistent with light chain amyloidosis to evaluate the influence on survival. Of them, 22 patients were treated with a bortezomib-based regimen, and the response rate was more effective than the other. The median overall survival for the total cohort was 12 months. Cardiac involvement significantly adversely affected survival (6 vs. 40 months), as did systolic blood pressure (< 90 mmHg, 3 vs. 8.5 months). Cardiovascular dysfunction caused by light chain amyloidosis is a major determinant of shortening survival for the total cohort. Background: We identified 53 patients with multiple myeloma (MM) who had biopsy evidence of light chain amyloidosis (AL), and studied their cardiac involvement and outcomes. Patients and Methods: Our cohort consisted of 53 patients in whom MM and AL were initially diagnosed from July 1, 2006 to June 30, 2016.The diagnosis of MM required > 10% of clonal plasma cells in bone marrow and 1 of the CRAB symptoms, meanwhile, the diagnosis of AL must meet pathologic diagnostic criteria and monoclonal immunoglobulin light chain. Echocardiograms and cardiac biomarker such as N terminal pro B-type natriuretic peptide was used for evaluation of cardiac damage on the baseline and before every cycle of the regimen. Results: There were 36 men and 17 women with a median age of 59 years; their main organ involvement was kidney (72%) and heart (62%). Of these, 22 patients were treated with a bortezomibbased regimen, and the response rate was more effective than the other 21 patients who received nonbortezomib-based regimens (64% vs. 29%). The median overall survival (OS) for the total cohort was 12 months (P < .05). The median OS of the MM cohort with International Staging System stage I and II together was 34 months, which was longer than that of patients with stage III of 8 months. The median OS in Mayo stages I, II, and III was 38, 8, and 1 months, respectively (P < .05). Cardiac involvement significantly adversely affected survival (6 vs. 40 months), as did systolic blood pressure (< 90 mmHg, 3 vs. 8.5 months). Conclusions: Patients coexistent with MM and AL is rare; AL has a negative impact on survival for the total cohort. Especially, cardiovascular dysfunction caused by AL maybe a major determinant of shortening survival.

Background/Objectives: Distinguishing between Parkinson's disease (PD) and multiple system atrophy (MSA) is challenging in the clinic because patients with these two conditions present with similar symptoms in motor dysfunction. Here, we aimed to determine whether tremor characteristics can serve as novel markers for distinguishing the two conditions. Methods: Ninety-one subjects with clinically diagnosed PD and 93 subjects with MSA were included. Tremor of the limbs was measured in different conditions (such as resting, postural, and weight-holding) using electromyography (EMG) surface electrodes and accelerometers. The dominant frequency, tremor occurrence rate, and harmonic occurrence rate (HOR) of the tremor were then calculated. Results: Our results demonstrated that the tremor dominant frequency in the upper limbs of the MSA group was significantly higher than that in the PD group across all resting ( F = 5.717, p = 0.023), postural ( F = 13.409, p < 0.001), and weight-holding conditions ( F = 9.491, p < 0.001) and that it was not dependent on the patient's age or disease course. The tremor occurrence rate (75.6 vs. 14.9%, χ 2 = 68.487, p < 0.001) and HOR (75.0 vs. 4.5%, χ 2 = 46.619, p < 0.001) in the resting condition were significantly lower in the MSA group than in the PD group. The sensitivity of the harmonic for PD diagnosis was 75.0% and the specificity was relatively high, in some cases up to 95.5%. The PPV and NPV were 95.2 and 75.9%, respectively. Conclusion: Our study confirmed that several tremor characteristics, including the dominant tremor frequency and the occurrence rate in different conditions, help detect PD and MSA. The presence of harmonics may serve as a novel marker to help distinguish PD from MSA with high sensitivity and specificity.

BACKGROUND Multiple myeloma (MM) complicated with extramedullary disease (EMD) has a poor prognosis and is a limiting factor in the treatment of MM, and no standard treatment is recommended in international guidelines. Few studies have reported MM with periorbital EMD. CASE SUMMARY In this paper, the clinical characteristics and survival of seven patients with multiple myeloma and orbital are described and analyzed. The common ocular symptoms were blurred vision, proptosis and/or eye movement disorders, IgG type MM may be a risk factor for orbital involvement. Of them, six patients were treated with bortezomib-based regimens. The median overall survival (OS) and progression free survival for the entire cohort were 48 and 33 mo, respectively, which was much worse than the OS reported for MM patients without orbital EMD . CONCLUSION Orbital MM may have significantly shortened survival for the entire cohort, so multidisciplinary collaboration is emphasized and recommended in the diagnosis and treatment of these difficult cases.

BACKGROUND Parkinson’s disease (PD) is common movement disorder and patients with PD had multiple gait impairments, leading to increased risk of falls, and diminished quality of life. The gait measurement in patients with Parkinson’s disease (PD) is thus important for the management of PD. OBJECTIVE We have developed and validated a smartphone-based assessment of gait, allowing the remote gait assessment in healthy cohorts. We here aimed to test the validity of this App-based gait measurement in people with PD and explore the association between the gait metrics measured by App and the clinical and functional characteristics in PD. METHODS Fifty-two participants with clinically-diagnosed PD completed assessments of walking, MDS-Unified Parkinson's Disease Rating Scale III (UPDRS III), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety (HAM-A) and Depression (HAM-D) rating scale tests. Participants followed multi-media 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). The locomotion data were simultaneously collected with the App and a gold-standard system. The gait stride times (ST) and stride time variability (STV) 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 between the ST and STV derived from the App and those from gold-standard system were observed (r=0.98~0.99, p<.0001), revealing excellent validity of the App-based gait assessment in PD. Compared to single-task, the ST (F=13.1, p=.0005) and STV (F=6.3, p=.01) in dual-task condition were significantly greater. Participants with greater STV in both conditions had greater total score of UPDRS III (r=0.37~0.39, p=.0007~.01), HAM-A (single-task: r=0.49, p=.007; dual-task: r=0.48, p=.009) and HAM-D (single-task: r=0.44, p=.01; dual-task: r=0.49, p=.009); and those with greater dual-task STV (r=0.48, p=.001) and/or dual-task cost to STV (r=0.44, p=.004) had lower MoCA score. CONCLUSIONS These results demonstrated that this ease-of-its-use smartphone-based gait measurement is validated and provides meaningful metrics that are associated with clinical and functional characteristics in PD.