sj-docx-1-dhj-10.1177_20552076231207206 - Supplemental material for A mobile-based airway clearance care system using deep learning-based vision technology to support personalized home-based pulmonary rehabilitation for COAD patients: Development and usability testing

Supplemental material, sj-docx-1-dhj-10.1177_20552076231207206 for A mobile-based airway clearance care system using deep learning-based vision technology to support personalized home-based pulmonary rehabilitation for COAD patients: Development and usability testing by Jun-Ming Su, Kuan-Yuan Chen, Sheng-Ming Wu, Kang-Yun Lee and Shu-Chuan Ho in DIGITAL HEALTH</p

Thyroid hormone suppresses hepatocarcinogenesis via DAPK2 and SQSTM1-dependent selective autophagy

<p>Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showed that disruption of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy-related 7) via adeno-associated virus (AAV) vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase), which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from DEN-induced hepatotoxicity or carcinogenesis.</p

Data_Sheet_1_Associations between risk of Alzheimer's disease and obstructive sleep apnea, intermittent hypoxia, and arousal responses: A pilot study.docx

ObjectivesObstructive sleep apnea (OSA) may increase the risk of Alzheimer's disease (AD). However, potential associations among sleep-disordered breathing, hypoxia, and OSA-induced arousal responses should be investigated. This study determined differences in sleep parameters and investigated the relationship between such parameters and the risk of AD.MethodsPatients with suspected OSA were recruited and underwent in-lab polysomnography (PSG). Subsequently, blood samples were collected from participants. Patients' plasma levels of total tau (T-Tau) and amyloid beta-peptide 42 (Aβ42) were measured using an ultrasensitive immunomagnetic reduction assay. Next, the participants were categorized into low- and high-risk groups on the basis of the computed product (Aβ42 × T-Tau, the cutoff for AD risk). PSG parameters were analyzed and compared.ResultsWe included 36 patients in this study, of whom 18 and 18 were assigned to the low- and high-risk groups, respectively. The average apnea–hypopnea index (AHI), apnea, hypopnea index [during rapid eye movement (REM) and non-REM (NREM) sleep], and oxygen desaturation index (≥3%, ODI-3%) values of the high-risk group were significantly higher than those of the low-risk group. Similarly, the mean arousal index and respiratory arousal index (R-ArI) of the high-risk group were significantly higher than those of the low-risk group. Sleep-disordered breathing indices, oxygen desaturation, and arousal responses were significantly associated with an increased risk of AD. Positive associations were observed among the AHI, ODI-3%, R-ArI, and computed product.ConclusionsRecurrent sleep-disordered breathing, intermittent hypoxia, and arousal responses, including those occurring during the NREM stage, were associated with AD risk. However, a longitudinal study should be conducted to investigate the causal relationships among these factors.</p

Scatter plots of IHC scores of GLO1 and various clinicopathological features.

<p>(A) Scatter plot according to depth of wall invasion (<i>P</i> = 0.001, T1/T2 vs. T3/T4). (B) Scatter plot according to lymph node metastasis (<i>P</i><0.001, N0 versus N1–3). (C) Scatter plot according to pathological stage (<i>P</i><0.001, stages I/II versus stages III/IV). (D) Kaplan-Meir survival curves of two groups of gastric cancer patients defined by a GLO1 expression level cutoff value of 90, established on the basis of IHC scoring. The 5-year survival rate of the lower expression groups (n = 24) was significantly better than that of the higher expression groups (n = 90; 69.6% vs. 43.3%; log rank <i>P</i> = 0.0373).</p

Effects of GLO1 over-expression in SC-M1 cells.

<p>Two SC-M1-GLO1 over-expression clones (OG1 and OG2), and two control cell lines (C1, C2) were established. (A) Expression of GLO1 was determined using western blot analysis. β-actin was used as an internal control. (B) Cell proliferation, (C) Migration, and (D) Invasion abilities were assayed as described in “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034352#s2" target="_blank">Materials and Methods</a>”. Data were presented as folds from at least three independent experiments performed in duplicated. The fold changes (B–D), and differences examined using Mann-Whitney U method to compare values with vector control. ** <i>P</i><0.05.</p

Downstream target genes of GLO1 and their clinical correlations.

<p>(A) HIF-1α, NF-kB, VEGF, CXCL8, CXCL1, and CXCR2 protein levels in TSGH cells transfected with GLO1 shRNA (KG1 and KG2) and control shRNA (C1 and C2). The gel was stained with Coomassie blue (CB), which was used as a loading control of conditional media. β-actin was used as an internal control for total cell lysates, and lamin A/C for nuclear proteins. (B) Knockdown of GLO1 suppressed activation of MMP2 and MMP9. Conditional media from C1, C2, KG1 and KG2 cells were collected and subjected to gelatin zymography. (C) Sections of formalin-fixed and paraffin-embedded tissues from three human gastric tumor tissues were immunostained with anti-GLO1 (a and b), anti-CXCL1 (c and d) or anti-CXCR2 antibodies (e and f). Coexpression of GLO1, CXCL1, and CXCR2 proteins detected in human gastric cancer tissues (b, d, and f). Noncancerous gastric mucosa with negative or lower expression of GLO1, CXCL1 and CXCR2 proteins (a, c, and e). Scale bar represents 200 µm.</p

Knockdown of GLO1 expression suppresses TSGH or AGS cell migration and invasion.

<p>Two TSGH-GLO1-silenced clones (KG1 and KG2), two AGS-GLO1-silenced clones (KS1 and KS2) sublines and control cell lines (TSGH-C1 and -C2; AGS-C1 and -C2) were established. (A, B) Expression of GLO1 was determined using western blot analysis. β-actin was used as an internal control. Cell migration (C, E) and invasion (D, F) abilities were assayed as described in “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034352#s2" target="_blank">Materials and Methods</a>”. Data were presented as folds from at least three independent experiments performed in duplicated. The fold changes (C–F), and differences examined using Mann-Whitney U method to compare values with vector control. ** <i>P</i><0.05.</p

Data_Sheet_1_Associations of the distance-saturation product and low-attenuation area percentage in pulmonary computed tomography with acute exacerbation in patients with chronic obstructive pulmonary disease.docx

BackgroundChronic obstructive pulmonary disease (COPD) has high global health concerns, and previous research proposed various indicators to predict mortality, such as the distance-saturation product (DSP), derived from the 6-min walk test (6MWT), and the low-attenuation area percentage (LAA%) in pulmonary computed tomographic images. However, the feasibility of using these indicators to evaluate the stability of COPD still remains to be investigated. Associations of the DSP and LAA% with other COPD-related clinical parameters are also unknown. This study, thus, aimed to explore these associations.MethodsThis retrospective study enrolled 111 patients with COPD from northern Taiwan. Individuals’ data we collected included results of a pulmonary function test (PFT), 6MWT, life quality survey [i.e., the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT)], history of acute exacerbation of COPD (AECOPD), and LAA%. Next, the DSP was derived by the distance walked and the lowest oxygen saturation recorded during the 6MWT. In addition, the DSP and clinical phenotype grouping based on clinically significant outcomes by previous study approaches were employed for further investigation (i.e., DSP of 290 m%, LAA% of 20%, and AECOPD frequency of ≥1). Mean comparisons and linear and logistic regression models were utilized to explore associations among the assessed variables.ResultsThe low-DSP group (ConclusionA lower value of the DSP was related to a greater worsening of symptoms, more-frequent exacerbations, poorer pulmonary function, and more-severe emphysema (higher LAA%). These readily determined parameters, including the DSP and LAA%, can serve as indicators for assessing the COPD clinical course and may can serve as a guide to corresponding treatments.</p

Clinicopathological Correlations of GLO1 expression (Q-RT-PCR) in 89 Gastric Cancer Patients.

1<p>Folds: measured by real time Q-RT-PCR in tumor tissues compared to adjacent non-tumor tissues; in mean±standard deviation.</p>2<p>Mann-Whitney U test (for 2 groups) or Kruskal Wallis test (for >2 groups).</p

Clinicopathological Correlations of GLO1 expression and 5-year Survival Rate in 114 Gastric Cancer Patients.

1<p>IHC scores of GLO1; in mean±standard deviation.</p>2<p>Mann-Whitney U test (for 2 groups) or Kruskal Wallis test (for >2groups).</p>3<p>5-year survival rate.</p>4<p>Log rank test.</p