Supplementary Material for: Association of Dietary Patterns with Parkinson’s Disease: A Cross-Sectional Study Based on the United States National Health and Nutritional Examination Survey Database

Introduction: Although studies have explored some dietary patterns for Parkinson’s disease (PD), more other dietary patterns and food item under the dietary pattern are needed to investigate. This study aimed to identify more categories of dietary patterns for PD and further explore the association of single food item with PD. Methods: The 2015–2018 US National Health and Nutritional Examination Survey (NHANES) database was used for data extraction. The data on demographics and nutrient intake were collected. Dietary patterns were derived from food categories by factor analysis. The association between dietary patterns or single food item and PD was explored using logistic regression analysis in the overall and only in secure PD cases, and results were expressed as odds ratio (OR) with 95% confidence intervals (CIs). Sensitivity analysis was performed by excluding participants using unsecure PD medication. Results: Among 5,824 participants aged over 50 years, 91 were diagnosed as PD. Factor analysis identified 5 major dietary pattern factors. We observed that the increased adherence to Mediterranean diet (MeDi) was associated with the reduced odds of PD (OR = 0.78, 95% CI: 0.65–0.93). The higher adherence to Western pattern was associated with the increased odds of PD (OR = 2.19, 95% CI: 1.16–4.14). In addition, high intake of sweets under Western pattern was found to be associated with the higher odds of PD (OR = 2.01, 95% CI: 1.08–3.71). Conclusions: The odds of PD decreased by higher MeDi adherence and increased by higher Western pattern adherence, especially sweets intake in this pattern, suggesting population ≥50 years should adhere to MeDi pattern and decrease the adherence to Western pattern, reducing the intake of sweets

Supplementary Material for: Long Noncoding RNA Linc00152 Functions as a Tumor Propellant in Pan-Cancer

<b><i>Background/Aims:</i></b> The oncogenic role of linc00152 in pan-cancer is unclear. <b><i>Methods:</i></b> In this study, RNA-Seq of 33 breast specimens was performed, and the expression of linc00152 was validated by qPCR using 50 paired breast cancer tissues and adjacent normal tissues. This result combined with the expression of linc00152 in pan-cancer was revalidated by Gene Expression Omnibus and The Cancer Genome Atlas data. Next, the oncogenic roles of linc00152 in view of prognosis, chemoresistance, genomic and epigenetic regulation, including DNA methylation and histone modification, potential biological function enrichment, and basic molecular function in pan-cancer, were also evaluated <i>in vitro</i> and <i>in vivo</i>. <b><i>Results:</i></b> Linc00152 is upregulated in pan-cancer, especially in progressive cancer, and the high expression of linc00152 may lead to a worse prognosis and chemoresistance in pan-cancer patients. Amplification, DNA hypomethylation, promoter-like lncRNA characteristics and super-enhancer regulation are the drivers that lead to the upregulation of linc00152 in pan-cancer. Meanwhile, linc00152 was involved in cancer-related pathways, infection and immune response-associated pathways by enriched analysis using TCGA data. Finally, linc00152 was confirmed to promote the proliferation, migration and invasion in MDA-MB-231, SGC-7901 and 786-O. Moreover, RIP and RNA pull-down assays indicated that linc00152 can bind to EZH2 directly. <b><i>Conclusion:</i></b> All of the results indicated that linc00152 acted as an oncogenic propellant from various perspectives, and it may be an effective therapy target in pan-cancer

Supplementary Material for: Increased Expression of Nox1 in Neointimal Smooth Muscle Cells Promotes Activation of Matrix Metalloproteinase-9

<i>Objective:</i> Vascular injury causes neointimal hypertrophy, which is characterized by redox-mediated matrix degradation and smooth muscle cell (SMC) migration and proliferation. We hypothesized that, as compared to the adjacent medial SMCs, neointimal SMCs produce increased superoxide via NADPH oxidase, which induces redox-sensitive intracellular signaling to activate matrix metalloproteinase-9 (MMP-9). <i>Methods and Results:</i> Two weeks after balloon injury, rat aorta developed a prominent neointima, containing increased expression of NADPH oxidase and reactive oxygen species (ROS) as compared to the medial layer. Next, SMCs were isolated from either the neointima or the media and studied in culture. Neointimal-derived SMCs exhibited increased Nox1 expression and ROS levels as compared to medial SMCs. Neointimal SMCs had higher cell growth rates than medial SMCs. ROS-dependent ERK1/2 phosphorylation was greater in neointimal SMCs. MMP-9 activity, as detected by gel zymography, was greater in neointimal SMCs under resting and stimulated conditions and was prevented by expression of an antisense to Nox1 or treatment with an ERK1/2 inhibitor. <i>Conclusions:</i> Following vascular injury, the increased expression of Nox1 in SMCs within the neointima initiates redox-dependent phosphorylation of ERK1/2 and subsequent MMP-9 activation

Supplementary Material for: High Prevalence of Mild Cognitive Impairment in the Elderly: A Community-Based Study in Four Cities of the Hebei Province, China

<b><i>Background:</i></b> Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia. This study was designed to determine the prevalence of MCI in the elderly in the Hebei province, China, and explore its related factors. <b><i>Methods:</i></b> Participants included 2,601 community-dwelling people aged 60 years or older who resided in the four major cities of the Hebei province. In stage 1 of the study, the Mini-Mental State Examination and the Montreal Cognitive Assessment were administered for screening purposes. In stage 2, the subjects who screened positive were further examined by neurologists. The diagnosis of MCI was made according to Petersen's criteria. <b><i>Results: </i></b>The estimated prevalence of MCI was 21.3%. MCI was more prevalent at age 65-69 (28.3%), and its overall rates among men (24.1%) were higher than those of women (19.9%). The higher prevalence of MCI was associated with very old age (≥80 years old; OR = 2.457, 95% CI = 1.471-4.104), male gender (OR = 1.363, 95% CI = 1.097-1.694), low education level (OR = 2.439, 95% CI = 1.623-3.663), and poor economic status (OR = 2.882, 95% CI = 1.949-4.255). <b><i>Conclusions:</i></b> Our findings show a high prevalence of MCI in the elderly urban population in the Hebei province. Gender, education level, and economic status may have an important role in the etiology of MCI

Supplementary Material for: Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

<b><i>Background/Aims:</i></b> Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. <b><i>Methods:</i></b> We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity. <b><i>Results:</i></b> We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (<i>P</i>=0.031), tumour node metastasis stage (<i>P</i>=0.01), histological grade (<i>P</i>=0.037), and shorter overall survival (<i>P</i>=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (<i>P</i><0.0001). TPM2 knockdown significantly reduced cell sensitivity to paclitaxel. <b><i>Conclusion:</i></b> TPM2 is a potential novel tumour suppressor gene in breast cancer. TPM2 is associated with poor survival and chemoresistance to paclitaxel in breast cancer, and TPM2 may represent a promising therapeutic gene target for breast cancer patients with chemoresistance

Supplementary Material for: A Novel Method for Tracking Neck Motions Using a Skin-Conformable Wireless Accelerometer: A Pilot Study

Introduction: Cervical spine disease is a leading cause of pain and disability. Degenerative conditions of the spine can result in neurologic compression of the cervical spinal cord or nerve roots and may be surgically treated with an anterior cervical discectomy and fusion (ACDF) in up to 137,000 people per year in the United States. A common sequelae of ACDF is reduced cervical range of motion (CROM) with patient-based complaints of stiffness and neck pain. Currently, tools for assessment of CROM are manual, subjective, and only intermittently utilized during doctor or physical therapy visits. We propose a skin-mountable acousto-mechanic sensor (ADvanced Acousto-Mechanic sensor; ADAM) as a tool for continuous neck motion monitoring in postoperative ACDF patients. We have developed and validated a machine learning neck motion classification algorithm to differentiate between eight neck motions (right/left rotation, right/left lateral bending, flexion, extension, retraction, protraction) in healthy normal subjects and patients. Methods: Sensor data from 12 healthy normal subjects and 5 patients were used to develop and validate a Convolutional Neural Network (CNN). Results: An average algorithm accuracy of 80.0 ± 3.8% was obtained for healthy normal subjects (94% for right rotation, 98% for left rotation, 65% for right lateral bending, 87% for left lateral bending, 89% for flexion, 77% for extension, 50% for retraction, 84% for protraction). An average accuracy of 67.5 ± 5.8% was obtained for patients. Discussion: ADAM, with our algorithm, may serve as a rehabilitation tool for neck motion monitoring in postoperative ACDF patients. Sensor-captured vital signs and other events (extubation, vocalization, physical therapy, walking) are potential metrics to be incorporated into our algorithm to offer more holistic monitoring of patients after cervical spine surgery