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  1. Article: Automated Hierarchy Evaluation System of Large Vessel Occlusion in Acute Ischemia Stroke.

    You, Jia / Tsang, Anderson C O / Yu, Philip L H / Tsui, Eva L H / Woo, Pauline P S / Lui, Carrie S M / Leung, Gilberto K K

    Frontiers in neuroinformatics

    2020  Volume 14, Page(s) 13

    Abstract: Background: The detection of large vessel occlusion (LVO) plays a critical role in the diagnosis and treatment of acute ischemic stroke (AIS). Identifying LVO in the pre-hospital setting or early stage of hospitalization would increase the patients' ... ...

    Abstract Background: The detection of large vessel occlusion (LVO) plays a critical role in the diagnosis and treatment of acute ischemic stroke (AIS). Identifying LVO in the pre-hospital setting or early stage of hospitalization would increase the patients' chance of receiving appropriate reperfusion therapy and thereby improve neurological recovery.
    Methods: To enable rapid identification of LVO, we established an automated evaluation system based on all recorded AIS patients in Hong Kong Hospital Authority's hospitals in 2016. The 300 study samples were randomly selected based on a disproportionate sampling plan within the integrated electronic health record system, and then separated into a group of 200 patients for model training, and another group of 100 patients for model performance evaluation. The evaluation system contained three hierarchical models based on patients' demographic data, clinical data and non-contrast CT (NCCT) scans. The first two levels of modeling utilized structured demographic and clinical data, while the third level involved additional NCCT imaging features obtained from deep learning model. All three levels' modeling adopted multiple machine learning techniques, including logistic regression, random forest, support vector machine (SVM), and eXtreme Gradient Boosting (XGboost). The optimal cut-off for the likelihood of LVO was determined by the maximal Youden index based on 10-fold cross-validation. Comparisons of performance on the testing group were made between these techniques.
    Results: Among the 300 patients, there were 160 women and 140 men aged from 27 to 104 years (mean 76.0 with standard deviation 13.4). LVO was present in 130 (43.3%) patients. Together with clinical and imaging features, the XGBoost model at the third level of evaluation achieved the best model performance on testing group. The Youden index, accuracy, sensitivity, specificity, F1 score, and area under the curve (AUC) were 0.638, 0.800, 0.953, 0.684, 0.804, and 0.847, respectively.
    Conclusion: To the best of our knowledge, this is the first study combining both structured clinical data with non-structured NCCT imaging data for the diagnosis of LVO in the acute setting, with superior performance compared to previously reported approaches. Our system is capable of automatically providing preliminary evaluations at different pre-hospital stages for potential AIS patients.
    Language English
    Publishing date 2020-03-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452979-5
    ISSN 1662-5196
    ISSN 1662-5196
    DOI 10.3389/fninf.2020.00013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: 3D dissimilar-siamese-u-net for hyperdense Middle cerebral artery sign segmentation.

    You, Jia / Yu, Philip L H / Tsang, Anderson C O / Tsui, Eva L H / Woo, Pauline P S / Lui, Carrie S M / Leung, Gilberto K K / Mahboobani, Neeraj / Chu, Chi-Yeung / Chong, Wing-Ho / Poon, Wai-Lun

    Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society

    2021  Volume 90, Page(s) 101898

    Abstract: The hyperdense middle cerebral artery sign (HMCAS) representing a thromboembolus has been declared as a vital CT finding for intravascular thrombus in the diagnosis of acute ischemia stroke. Early recognition of HMCAS can assist in patient triage and ... ...

    Abstract The hyperdense middle cerebral artery sign (HMCAS) representing a thromboembolus has been declared as a vital CT finding for intravascular thrombus in the diagnosis of acute ischemia stroke. Early recognition of HMCAS can assist in patient triage and subsequent thrombolysis or thrombectomy treatment. A total of 624 annotated head non-contrast-enhanced CT (NCCT) image scans were retrospectively collected from multiple public hospitals in Hong Kong. In this study, we present a deep Dissimilar-Siamese-U-Net (DSU-Net) that is able to precisely segment the lesions by integrating Siamese and U-Net architectures. The proposed framework consists of twin sub-networks that allow inputs of left and right hemispheres in head NCCT images separately. The proposed Dissimilar block fully explores the feature representation of the differences between the bilateral hemispheres. Ablation studies were carried out to validate the performance of various components of the proposed DSU-Net. Our findings reveal that the proposed DSU-Net provides a novel approach for HMCAS automatic segmentation and it outperforms the baseline U-Net and many state-of-the-art models for clinical practice.
    MeSH term(s) Humans ; Middle Cerebral Artery ; Retrospective Studies ; Stroke/diagnostic imaging ; Tomography, X-Ray Computed ; Triage
    Language English
    Publishing date 2021-03-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639451-6
    ISSN 1879-0771 ; 0895-6111
    ISSN (online) 1879-0771
    ISSN 0895-6111
    DOI 10.1016/j.compmedimag.2021.101898
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong: a population-based cohort study.

    Tsui, Eva L H / Lui, Carrie S M / Woo, Pauline P S / Cheung, Alan T L / Lam, Peggo K W / Tang, Van T W / Yiu, C F / Wan, C H / Lee, Libby H Y

    BMC medical informatics and decision making

    2020  Volume 20, Issue 1, Page(s) 323

    Abstract: Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to ... ...

    Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients' clinical outcome on day 1 and day 5 of hospital admission.
    Methods: We did a retrospective analysis of a complete cohort of 1037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers' readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5.
    Results: The 1037 patients had a mean age of 37.8 (SD ± 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients' disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model's accuracy rate, macro-/micro-averaged sensitivity and specificity were 91.3%, 84.9%/91.3% and 96.0%/95.7% respectively, as compared to 94.2%, 95.9%/94.2% and 97.8%/97.1% under Day-5 model.
    Conclusions: Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients' outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care.
    MeSH term(s) Adult ; COVID-19 ; Female ; Hong Kong ; Humans ; Male ; Middle Aged ; Pandemics ; Retrospective Studies ; Triage/organization & administration
    Language English
    Publishing date 2020-12-07
    Publishing country England
    Document type Journal Article
    ISSN 1472-6947
    ISSN (online) 1472-6947
    DOI 10.1186/s12911-020-01338-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong

    Eva L. H. Tsui / Carrie S. M. Lui / Pauline P. S. Woo / Alan T. L. Cheung / Peggo K. W. Lam / Van T. W. Tang / C. F. Yiu / C. H. Wan / Libby H. Y. Lee

    BMC Medical Informatics and Decision Making, Vol 20, Iss 1, Pp 1-

    a population-based cohort study

    2020  Volume 19

    Abstract: Abstract Background This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims ...

    Abstract Abstract Background This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients’ clinical outcome on day 1 and day 5 of hospital admission. Methods We did a retrospective analysis of a complete cohort of 1037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers’ readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5. Results The 1037 patients had a mean age of 37.8 (SD ± 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients’ disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model’s accuracy rate, macro-/micro-averaged sensitivity and specificity were 91.3%, 84.9%/91.3% and 96.0%/95.7% respectively, as compared to 94.2%, 95.9%/94.2% and 97.8%/97.1% under Day-5 model. Conclusions Both Day-1 and Day-5 models can accurately predict the disease severity. ...
    Keywords COVID-19 ; Prognostic ; Prediction ; Clinical outcome ; Disease severity ; Triage ; Computer applications to medicine. Medical informatics ; R858-859.7
    Subject code 610
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Therapeutic efficacy of AAV-mediated restoration of PKP2 in arrhythmogenic cardiomyopathy.

    Kyriakopoulou, Eirini / Versteeg, Danielle / de Ruiter, Hesther / Perini, Ilaria / Seibertz, Fitzwilliam / Döring, Yannic / Zentilin, Lorena / Tsui, Hoyee / van Kampen, Sebastiaan J / Tiburcy, Malte / Meyer, Tim / Voigt, Niels / Tintelen, van J Peter / Zimmermann, Wolfram H / Giacca, Mauro / van Rooij, Eva

    Nature cardiovascular research

    2023  Volume 2, Issue 12, Page(s) 1262–1276

    Abstract: Arrhythmogenic cardiomyopathy is a severe cardiac disorder characterized by lethal arrhythmias and sudden cardiac death, with currently no effective treatment. Plakophilin 2 ( ...

    Abstract Arrhythmogenic cardiomyopathy is a severe cardiac disorder characterized by lethal arrhythmias and sudden cardiac death, with currently no effective treatment. Plakophilin 2 (
    Language English
    Publishing date 2023-12-07
    Publishing country England
    Document type Journal Article
    ISSN 2731-0590
    ISSN (online) 2731-0590
    DOI 10.1038/s44161-023-00378-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Burden of large vessel occlusion stroke and the service gap of thrombectomy: A population-based study using a territory-wide public hospital system registry.

    Tsang, Anderson C O / You, Jia / Li, Lai Fung / Tsang, Frederick C P / Woo, Pauline P S / Tsui, Eva L H / Yu, Philip / Leung, Gilberto K K

    International journal of stroke : official journal of the International Stroke Society

    2019  Volume 15, Issue 1, Page(s) 69–74

    Abstract: Background: Ischemic stroke due to large vessel occlusion can be effectively treated with thrombectomy but access to this treatment is limited in many parts of the world. Local incidence of large vessel occlusion is critical in determining the ... ...

    Abstract Background: Ischemic stroke due to large vessel occlusion can be effectively treated with thrombectomy but access to this treatment is limited in many parts of the world. Local incidence of large vessel occlusion is critical in determining the development of thrombectomy service, but reliable data from Asian countries are lacking.
    Aims: We performed a population-based study to estimate the burden of large vessel occlusion and the service gap for thrombectomy in Hong Kong.
    Methods: All acute ischemic stroke patients admitted in 2016 to the public healthcare system, which provided 90% of the emergency healthcare in the city, was identified from the Hong Kong Hospital Authority's central electronic database. The diagnosis of large vessel occlusion was retrospectively verified by two independent cerebrovascular specialists in a randomly sampled cohort based on clinical and neuroimaging data. The incidence of large vessel occlusion in the population was estimated through weighting the sample results and compared with the thrombectomy data in the same period.
    Results: There were 6859 acute ischemic stroke patients treated in the public health system in 2016. Amongst the 300 patients randomly sampled according to diagnosis coding, 130 suffered from anterior circulation large vessel occlusion. This translated to 918 patients (95% CI 653-1180) and 13.3% of all ischemic stroke patients. The estimated incidence of anterior circulation large vessel occlusion was 12.5 per 100,000 persons per year (95% CI 11.7-13.4). Large vessel occlusion stroke patients were more commonly female than male (67.4% vs. 31.6%, p = 0.003), and were older than non-large vessel occlusion stroke patients (mean of 80.5 years vs. 71.4 years, p = < 0.001). They also had higher 30-day mortality rate (31.1% vs. 4.6%, p = < 0.001), and longer hospital stay (mean 38.6 vs. 21.1 days, p = 0.003) than non-large vessel occlusion stroke. In the same period, 83 thrombectomies for large vessel occlusion were performed, representing 9.1% of the estimated large vessel occlusion incidence.
    Conclusion: The estimated incidence of anterior circulation large vessel occlusion in the Hong Kong Chinese population is lower than that in the West. There is however a substantial service gap for endovascular thrombectomy with less than 10% of large vessel occlusion patients receiving thrombectomy.
    MeSH term(s) Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Female ; Health Services Accessibility/statistics & numerical data ; Hong Kong/epidemiology ; Humans ; Ischemic Stroke/epidemiology ; Ischemic Stroke/mortality ; Length of Stay/statistics & numerical data ; Male ; Middle Aged ; Registries/statistics & numerical data ; Sex Factors ; Thrombectomy/statistics & numerical data ; Young Adult
    Language English
    Publishing date 2019-02-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2303728-3
    ISSN 1747-4949 ; 1747-4930
    ISSN (online) 1747-4949
    ISSN 1747-4930
    DOI 10.1177/1747493019830585
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: S100A10 promotes HCC development and progression via transfer in extracellular vesicles and regulating their protein cargos.

    Wang, Xia / Huang, Hongyang / Sze, Karen Man-Fong / Wang, Jin / Tian, Lu / Lu, Jingyi / Tsui, Yu-Man / Ma, Hoi Tang / Lee, Eva / Chen, Ao / Lee, Joyce / Wang, Ying / Yam, Judy Wai Ping / Cheung, Tan-To / Guan, Xinyuan / Ng, Irene Oi-Lin

    Gut

    2023  Volume 72, Issue 7, Page(s) 1370–1384

    Abstract: Objective: Growing evidence indicates that tumour cells exhibit characteristics similar to their lineage progenitor cells. We found that S100 calcium binding protein A10 (S100A10) exhibited an expression pattern similar to that of liver progenitor genes. ...

    Abstract Objective: Growing evidence indicates that tumour cells exhibit characteristics similar to their lineage progenitor cells. We found that S100 calcium binding protein A10 (S100A10) exhibited an expression pattern similar to that of liver progenitor genes. However, the role of S100A10 in hepatocellular carcinoma (HCC) progression is unclear. Furthermore, extracellular vesicles (EVs) are critical mediators of tumourigenesis and metastasis, but the extracellular functions of S100A10, particularly those related to EVs (EV-S100A10), are unknown.
    Design: The functions and mechanisms of S100A10 and EV-S100A10 in HCC progression were investigated in vitro and in vivo. Neutralising antibody (NA) to S100A10 was used to evaluate the significance of EV-S100A10.
    Results: Functionally, S100A10 promoted HCC initiation, self-renewal, chemoresistance and metastasis in vitro and in vivo. Of significance, we found that S100A10 was secreted by HCC cells into EVs both in vitro and in the plasma of patients with HCC. S100A10-enriched EVs enhanced the stemness and metastatic ability of HCC cells, upregulated epidermal growth factor receptor (EGFR), AKT and ERK signalling, and promoted epithelial-mesenchymal transition. EV-S100A10 also functioned as a chemoattractant in HCC cell motility. Of significance, S100A10 governed the protein cargos in EVs and mediated the binding of MMP2, fibronectin and EGF to EV membranes through physical binding with integrin αⅤ. Importantly, blockage of EV-S100A10 with S100A10-NA significantly abrogated these enhancing effects.
    Conclusion: Altogether, our results uncovered that S100A10 promotes HCC progression significantly via its transfer in EVs and regulating the protein cargoes of EVs. EV-S100A10 may be a potential therapeutic target and biomarker for HCC progression.
    MeSH term(s) Humans ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/pathology ; Cell Line, Tumor ; Extracellular Vesicles/metabolism ; Cell Communication
    Language English
    Publishing date 2023-01-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80128-8
    ISSN 1468-3288 ; 0017-5749
    ISSN (online) 1468-3288
    ISSN 0017-5749
    DOI 10.1136/gutjnl-2022-327998
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  8. Article ; Online: Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong: A population based cohort study

    TSUI, Eva L.H. / Lui, Carrie / Woo, Pauline P.S. / CHEUNG, Alan T.L. / Lam, Peggo K.W. / Tang, T.W. / YIU, C.F. / Wan, C.H. / Lee, Libby H.Y.

    medRxiv

    Abstract: Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study ... ...

    Abstract Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients9 clinical outcome on day 1 and day 5 of hospital admission. Methods: We did a retrospective analysis of a complete cohort of 1,037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers9 readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5. Results: The 1,037 patients had a mean age of 37.8 (SD ± 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients9 disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model9s accuracy rate, macro- and micro-averaged sensitivity and specificity were 91.3%, 84.9%-91.3% and 96.0%-95.7% respectively, as compared to 94.2%, 95.9%-94.2% and 97.8%-97.1% under Day-5 model. as compared to 94.2%, 95.0%-97.1% and 98.3%-98.6% under Day-5 model. Conclusions: Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients9 outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care. Keywords: COVID-19, prognostic, prediction, clinical outcome, disease severity, triage, step-down care
    Keywords covid19
    Language English
    Publishing date 2020-07-14
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.07.13.20152348
    Database COVID19

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  9. Article ; Online: Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong: A population based cohort study

    TSUI, Eva L.H. / Lui, Carrie / Woo, Pauline P.S. / CHEUNG, Alan T.L. / Lam, Peggo K.W. / Tang, T. W. / YIU, C. F. / Wan, C. H. / Lee, Libby H.Y.

    Abstract: Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study ... ...

    Abstract Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients' clinical outcome on day 1 and day 5 of hospital admission. Methods: We did a retrospective analysis of a complete cohort of 1,037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers' readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5. Results: The 1,037 patients had a mean age of 37.8 (SD {+/-} 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients' disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model's accuracy rate, macro- and micro-averaged sensitivity and specificity were 91.3%, 84.9%-91.3% and 96.0%-95.7% respectively, as compared to 94.2%, 95.9%-94.2% and 97.8%-97.1% under Day-5 model. Conclusions: Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients' outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care. Keywords: COVID-19, prognostic, prediction, clinical outcome, disease severity, triage, step-down care
    Keywords covid19
    Publisher MedRxiv; WHO
    Document type Article ; Online
    Note WHO #Covidence: #20152348
    DOI 10.1101/2020.07.13.20152348
    Database COVID19

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  10. Article: Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1.

    Zhang, Vanilla Xin / Sze, Karen Man-Fong / Chan, Lo-Kong / Ho, Daniel Wai-Hung / Tsui, Yu-Man / Chiu, Yung-Tuen / Lee, Eva / Husain, Abdullah / Huang, Hongyang / Tian, Lu / Wong, Carmen Chak-Lui / Ng, Irene Oi-Lin

    Cell & bioscience

    2021  Volume 11, Issue 1, Page(s) 217

    Abstract: Background: Controversy over the benefits of antioxidants supplements in cancers persists for long. Using hepatocellular carcinoma (HCC) as a model, we investigated the effects of exogenous antioxidants N-acetylcysteine (NAC) and glutathione (GSH) on ... ...

    Abstract Background: Controversy over the benefits of antioxidants supplements in cancers persists for long. Using hepatocellular carcinoma (HCC) as a model, we investigated the effects of exogenous antioxidants N-acetylcysteine (NAC) and glutathione (GSH) on tumor formation and growth.
    Methods: Multiple mouse models, including diethylnitrosamine (DEN)-induced and Trp53KO/C-MycOE-induced HCC models, mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection were used. In vitro assays including ROS assay, colony formation, sphere formation, proliferation, migration and invasion, apoptosis, cell cycle assays were conducted. Western blot was performed for protein expression and RNA-sequencing to identify potential gene targets.
    Results: In these multiple different mouse and cell line models, we observed that NAC and GSH promoted HCC tumor formation and growth, accompanied with significant reduction of intracellular reactive oxygen species (ROS) levels. Moreover, NAC and GSH promoted cancer stemness, and abrogated the tumor-suppressive effects of Sorafenib both in vitro and in vivo. Exogenous supplementation of NAC or GSH reduced the expression of NRF2 and GCLC, suggesting the NRF2/GCLC-related antioxidant production pathway might be desensitized. Using transcriptomic analysis to identify potential gene targets, we found that TMBIM1 was significantly upregulated upon NAC and GSH treatment. Both TCGA and in-house RNA-sequence databases showed that TMBIM1 was overexpressed in HCC tumors. Stable knockdown of TMBIM1 increased the intracellular ROS; it also abolished the promoting effects of the antioxidants in HCC cells. On the other hand, BSO and SSA, inhibitors targeting NAC and GSH metabolism respectively, partially abrogated the pro-oncogenic effects induced by NAC and GSH in vitro and in vivo.
    Conclusions: Our data implicate that exogenous antioxidants NAC and GSH, by reducing the intracellular ROS levels and inducing TMBIM expression, promoted HCC formation and tumor growth, and counteracted the therapeutic effect of Sorafenib. Our study provides scientific insight regarding the use of exogenous antioxidant supplements in cancers.
    Language English
    Publishing date 2021-12-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2593367-X
    ISSN 2045-3701
    ISSN 2045-3701
    DOI 10.1186/s13578-021-00731-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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