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Background and purpose: The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN. Methods: A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat‐primed PCR and GC‐rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno‐associated virus (AAV)‐mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection. Results: Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p‐value = 0.29). Skin biopsy showed P62‐positive intranuclear NOTCH2NLC‐polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa‐NOTCH2NLC‐(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN. Conclusions: Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons. [ABSTRACT FROM AUTHOR]

Background: There is a lack of large multicenter Parkinson's disease (PD) cohort studies and limited data on the natural history of PD in China. Objectives: The objective of this study was to launch the Chinese Parkinson's Disease Registry (CPDR) and to report its protocol, cross‐sectional baseline data, and prospects for a comprehensive observational, longitudinal, multicenter study. Methods: The CPDR recruited PD patients from 19 clinical sites across China between January 2018 and December 2020. Clinical data were collected prospectively using at least 17 core assessment scales. Patients were followed up for clinical outcomes through face‐to‐face interviews biennially. Results: We launched the CPDR in China based on the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network (PD‐MDCNC). A total of 3148 PD patients were enrolled comprising 1623 men (51.6%) and 1525 women (48.4%). The proportions of early‐onset PD (EOPD, age at onset ≤50 years) and late‐onset PD (LOPD) were 897 (28.5%) and 2251 (71.5%), respectively. Stratification by age at onset showed that EOPD manifested milder motor and nonmotor phenotypes and was related to increased probability of dyskinesia. Comparison across genders suggested a slightly older average age at PD onset, milder motor symptoms, and a higher rate of developing levodopa‐induced dyskinesias in women. Conclusions: The CPDR is one of the largest multicenter, observational, longitudinal, and natural history studies of PD in China. It offers an opportunity to expand the understanding of clinical features, genetic, imaging, and biological markers of PD progression. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Freeway accidents cause grave fatalities and economic losses. Further losses of life and property can be caused by secondary accidents or rear-end chain accidents. Therefore, a quick and accurate incident detection technique is vital to improve the road safety and traffic management system performance. Based on the set theory and data collected by smartphones, a low-cost incident detection algorithm is proposed, called set theory-based freeway incident detection algorithm (SFID). If a vehicle is involved in a traffic incident, the capacity of the road segment in one direction declines significantly, whereas there are no changes in the opposite direction. SFID uses this phenomenon to infer if an incident has occurred or not. To evaluate the performance of SFID, simulations are conducted under different conditions. The results show a high detection rate, low average detection time, and low false alarm rate. Furthermore, the proposed scheme is evaluated using real Wi-Fi data. The results are in concordance with those of simulations. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence, evolution, clinical characteristics, correlates and predictors of fatigue as well as to investigate the influence of comorbid fatigue on the longitudinal changes in motor and non-motor symptoms over a 2-year longitudinal follow-up period in a large cohort of patients with Parkinson's disease (PD)., Materials and Methods: A total of 2,100 PD patients were enrolled from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC), and their motor and non-motor symptoms were assessed biennially using comprehensive scales, including the 16-item Parkinson Fatigue Scale (PFS-16). Each PD patient was categorized as PD with or without fatigue on the basis of a cut-off mean PFS-16 score of 3.3., Results: The prevalence of fatigue in our cohort was 36.8%. Compared to PD patients without fatigue, PD patients with fatigue were more likely to be older, have a longer disease duration, and higher baseline levodopa equivalent daily dose (all p  < 0.05). Moreover, PD patients with fatigue showed more severe motor and non-motor phenotypes than those without fatigue. Overall, high total Unified Parkinson's Disease Rating Scale (UPDRS) score (odds ratio [OR] = 1.016, 95% confidence interval [CI]: 1.009-1.024), Non-Motor Symptoms Scale score (OR = 1.022, 95% CI: 1.015-1.029), postural instability and gait difficulty (PIGD) subtype (OR = 1.586, 95% CI: 1.211-2.079), presence of excessive daytime sleepiness (EDS; OR = 1.343, 95% CI: 1.083-1.666), and wearing-off (OR = 1.282, 95% CI: 1.023-1.607) were significantly associated with fatigue in PD patients (all p  < 0.05). High total UPDRS score at baseline (OR = 1.014, 95% CI: 1.002-1.027, p  = 0.028) increased the risk of developing fatigue during follow-up. Although significant, the odds ratios were low and confidence intervals were narrow. Analysis of disease progression showed significant group differences in motor and non-motor symptoms. In comparison with the never-fatigue group, the persistent-fatigue group showed significantly greater progression in motor, autonomic dysfunction, sleep, depression and cognitive symptoms (all p  < 0.05)., Conclusion: Increased disease severity, presence of the PIGD subtype, EDS, and wearing-off were associated with fatigue in PD patients. Significant subgroup-level differences were observed in the progression of motor and non-motor symptoms across different fatigue subgroups of PD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Xiang, Song, Zhao, Pan, Xu, Chen, Sun, Wu, Yan, Guo, Tang, Lei, Liu, for Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC).)