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1.
FASEB J ; 35(9): e21870, 2021 09.
Article in English | MEDLINE | ID: covidwho-1373669

ABSTRACT

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium-induced intestinal inflammation in mice. It inhibited the production of pro-inflammatory cytokines IL-6 and TNFα, and promoted the expression of anti-inflammatory cytokine IL-10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS-stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half-life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down-regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal-specific KLHL5 deficiency, a CUL3-interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3-KLHL5 may function as an E3 for ATF2 degradation.


Subject(s)
Activating Transcription Factor 2/metabolism , Down-Regulation/drug effects , Drugs, Chinese Herbal/pharmacology , Flavanones/pharmacology , Glucosides/pharmacology , Inflammation/drug therapy , Proteolysis/drug effects , Ubiquitin Thiolesterase/deficiency , Animals , Cell Line , Colitis/chemically induced , Colitis/drug therapy , Cullin Proteins/metabolism , Cytokines/metabolism , Dextran Sulfate/pharmacology , Dextran Sulfate/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Flavanones/therapeutic use , Glucosides/therapeutic use , Inflammation/chemically induced , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Phosphorylation/drug effects , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Pyrroles/pharmacology , Pyrrolidines/pharmacology , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitination
2.
J Hazard Mater ; 421: 126799, 2022 01 05.
Article in English | MEDLINE | ID: covidwho-1336648

ABSTRACT

Stack aerosols are generated within vertical building drainage stacks during the discharge of wastewater containing feces and exhaled mucus from toilets and washbasins. Fifteen stack aerosol-related outbreaks of coronavirus disease 2019 (COVID-19) in high-rise buildings have been observed in Hong Kong and Guangzhou. Currently, we investigated two such outbreaks of COVID-19 in Hong Kong, identified the probable role of chimney effect-induced airflow in a building drainage system in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We injected tracer gas (SF6) into the drainage stacks via the water closet of the index case and monitored tracer gas concentrations in the bathrooms and along the facades of infected and non-infected flats and in roof vents. The air temperature, humidity, and pressure in vertical stacks were also monitored. The measured tracer gas distribution agreed with the observed distribution of the infected cases. Phylogenetic analysis of the SARS-CoV-2 genome sequences demonstrated clonal spread from a point source in cases along the same vertical column. The stack air pressure and temperature distributions suggested that stack aerosols can spread to indoors through pipe leaks which provide direct evidence for the long-range aerosol transmission of SARS-CoV-2 through drainage pipes via the chimney effect.


Subject(s)
Aerosols , Air Microbiology , COVID-19 , Housing , COVID-19/transmission , Hong Kong , Humans , Phylogeny , SARS-CoV-2
3.
BMJ Open ; 11(5): e050084, 2021 05 19.
Article in English | MEDLINE | ID: covidwho-1236465

ABSTRACT

OBJECTIVE: The outbreak of COVID-19 has major impacts on the psychological health of the public. This study aimed to investigate the anxiety and depression levels of the general population during the rapid progressing stage of COVID-19 pandemic in China and to explore the associated factors. DESIGN AND SETTING: A cross-sectional online survey. PARTICIPANTS: 2651 Chinese people. MEASURES: The Hospital Anxiety and Depression Scale was used to measure their psychological health. A structured questionnaire collected possible associated factors, including sociodemographic characteristics, health information, contact history-related information, experience and perceptions, knowledge and education and adopted precautions. Multiple linear regression was conducted to explore the factors associated with anxiety and depression. RESULTS: The mean score of anxiety and depression was 4.35 and 4.38, respectively. The rates of people with anxiety and depressive symptoms (with >7 score in the subscale) were 14.15% and 17.35%, respectively. Participants without political party membership, with contact history of COVID-19, going out or gathering, taking Chinese medicine herbs, being unsatisfied with current precautions, perceiving higher risks of infection, lower knowledge and poorer health presented higher anxiety and depression levels. Moreover, those who were females, married, lived alone and wore mask were more anxious; whereas people who were younger, experienced public health crisis, did not take precautions (regular work-rest, exercise) had higher depression level. CONCLUSIONS: During the rapid progressing stage of COVID-19 pandemic in China, one-seventh and one-sixth respondents presented anxiety and depression symptoms, respectively. The risk factors for anxiety and depression included the following: without political party membership, with contact history of COVID-19, going out or gathering, wearing masks, taking Chinese medicine herbs, being unsatisfied with current precautions, perceiving higher susceptibility, lower knowledge and poorer health status. Extensive information and psychological support should be provided to improve the mental health of the general population.


Subject(s)
COVID-19 , Pandemics , Anxiety/epidemiology , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Disease Outbreaks , Female , Humans , Male , SARS-CoV-2 , Surveys and Questionnaires
4.
Front Pharmacol ; 12: 644718, 2021.
Article in English | MEDLINE | ID: covidwho-1167359

ABSTRACT

RNA interference (RNAi), also known as gene silencing, is a biological process that prevents gene expression in certain diseases such as cancer. It can be used to improve the accuracy, efficiency, and stability of treatments, particularly genetic therapies. However, challenges such as delivery of oligonucleotide drug to less accessible parts of the body and the high incidence of toxic side effects are encountered. It is therefore imperative to improve their delivery to target sites and reduce their harmful effects on noncancerous cells to harness their full potential. In this study, the role of RNAi in the treatment of COVID-19, the novel coronavirus disease plaguing many countries, has been discussed. This review aims to ascertain the mechanism and application of RNAi and explore the current challenges of RNAi therapy by identifying some of the cancer delivery systems and providing drug information for their improvement. It is worth mentioning that delivery systems such as lipid-based delivery systems and exosomes have revolutionized RNAi therapy by reducing their immunogenicity and improving their cellular affinity. A deeper understanding of the mechanism and challenges associated with RNAi in cancer therapy can provide new insights into RNAi drug development.

5.
Seizure ; 88: 102-108, 2021 May.
Article in English | MEDLINE | ID: covidwho-1164463

ABSTRACT

OBJECTIVES: To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis. METHODS: This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening. RESULTS: A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P < 0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P < 0.05) were independently related to seizure increase during the pandemic. CONCLUSIONS: During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.


Subject(s)
COVID-19/psychology , Epilepsy/epidemiology , Quality of Life/psychology , Seizures/epidemiology , Adult , COVID-19/epidemiology , China/epidemiology , Disease Outbreaks , Female , Humans , Male , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
6.
Cancer Sci ; 112(6): 2522-2532, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1138103

ABSTRACT

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.


Subject(s)
COVID-19/mortality , Neoplasms/virology , Nomograms , Aged , Area Under Curve , China , Decision Support Techniques , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Precision Medicine , Retrospective Studies , Risk Factors , Survival Analysis
7.
Cancer ; 127(3): 437-448, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1023277

ABSTRACT

BACKGROUND: To the authors' knowledge, little is known regarding the association between recent oncologic treatment and mortality in patients with cancer who are infected with coronavirus disease 2019 (COVID-19). The objective of the current study was to determine whether recent oncologic treatment is associated with a higher risk of death among patients with carcinoma who are hospitalized with COVID-19. METHODS: Data regarding 248 consecutive patients with carcinoma who were hospitalized with COVID-19 were collected retrospectively from 33 hospitals in Hubei Province, China, from January 1, 2020, to March 25, 2020. The follow-up cutoff date was July 22, 2020. Univariable and multivariable logistic regression analyses were performed to identify variables associated with a higher risk of death. RESULTS: Of the 248 patients enrolled, the median age was 63 years and 128 patients (52%) were male. On admission, 147 patients (59%) did not undergo recent oncologic treatment, whereas 32 patients (13%), 25 patients (10%), 12 patients (5%), and 10 patients (4%), respectively, underwent chemotherapy, surgery, targeted therapy, and radiotherapy. At the time of last follow-up, 51 patients (21%) were critically ill during hospitalization, 40 of whom had died. Compared with patients without receipt of recent oncologic treatment, the mortality rate of patients who recently received oncologic treatment was significantly higher (24.8% vs 10.2%; hazard ratio, 2.010 [95% CI, 1.079-3.747; P = .027]). After controlling for confounders, recent receipt of chemotherapy (odds ratio [OR], 7.495; 95% CI, 1.398-34.187 [P = .015]), surgery (OR, 8.239; 95% CI, 1.637-41.955 [P = .012]), and radiotherapy (OR, 15.213; 95% CI, 2.091-110.691 [P = .007]) were identified as independently associated with a higher risk of death. CONCLUSIONS: The results of the current study demonstrated a possible association between recent receipt of oncologic treatment and a higher risk of death among patients with carcinoma who are hospitalized with COVID-19.


Subject(s)
COVID-19/mortality , Carcinoma/therapy , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma/mortality , China/epidemiology , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 603-608, 2020 Oct 25.
Article in Chinese | MEDLINE | ID: covidwho-934531

ABSTRACT

OBJECTIVE: To establish reuse process of positive pressure powered air-filter protective hoods during coronavirus disease 2019 (COVID-19) epidemic. METHODS: The procedure of pretreatment, storage, recovery, cleaning, disinfection and sterilization process of positive pressure powered air-filter protective hoods, which were used in the treatment of COVID-19 infection patients was established in Central Sterile Supply Department of the hospital. The cleaning and disinfection effects of the protective hoods after treatment were examined by magnifying glass method, residual protein detection method, real-time PCR, and agar pour plate method. RESULTS: Twenty five used protective hoods underwent totally 135 times of washing, disinfecting and sterilizing procedures. After washing, all the protein residue tests and COVID-19 nucleic acid tests showed negative results. After sterilizing, all the protective hoods met sterility requirement. All the tested protective hoods were undamaged after reprocessing. CONCLUSIONS: The established reuse procedures for used positive pressure powered air-filter protective hoods are safe.


Subject(s)
Air Filters , Coronavirus Infections , Disinfection , Equipment Reuse , Pandemics , Pneumonia, Viral , Sterilization , Air Filters/standards , Air Filters/virology , Betacoronavirus , COVID-19 , Coronavirus Infections/prevention & control , Disinfection/standards , Equipment Reuse/standards , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Sterilization/standards
9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 609-613, 2020 Oct 25.
Article in Chinese | MEDLINE | ID: covidwho-932374

ABSTRACT

OBJECTIVE: To compare three sterilizing methods for reusable medical goggles. METHODS: A total of 180 medical goggles of the same brand and same model were randomly divided into three groups. In group A the goggles were first soaked with 2000 mg/L chlorine-containing disinfectant and then cleaned manually; goggles in other two groups were sterilized using pre-programmed automatic spray cleaning and disinfection machine, the disinfection program was set to 90 ℃ for 5 min in group B and 70 ℃ for 30 min in group C. The quality of the sterilization was monitored by visual inspection with luminous magnifying glass and residual protein detection assay. User satisfaction on cleanliness of medical goggles, clarity of mirror surface and suitability of elastic bands was investigated with questionnaire survey. RESULTS: The qualification rates verified by visual inspection were 82.4%, 84.6%and 98.3%in group A, B and C, respectively, the qualification rate in group C was significantly higher than those in group B and group C (all P<0.05). The qualification rates verified by residual protein detection assay were 96.7%, 100.0%and 100.0%in group A, B and C, respectively (P>0.05). A total of 54 questionnaires were submitted for the survey. The satisfaction rates were 100.0%, 90.7%and 94.4% for cleanliness of medical goggles, clarity of mirror surface and suitability of elastic bands, respectively. CONCLUSIONS: Machinery sterilization set 70 ℃ for 30 min has better cleaning and sterilizing effects for reusable medical goggles.


Subject(s)
Eye Protective Devices , Sterilization , Eye Protective Devices/standards , Sterilization/methods , Surveys and Questionnaires
11.
J Immunother Cancer ; 8(2)2020 09.
Article in English | MEDLINE | ID: covidwho-748814

ABSTRACT

BACKGROUND: Individualized prediction of mortality risk can inform the treatment strategy for patients with COVID-19 and solid tumors and potentially improve patient outcomes. We aimed to develop a nomogram for predicting in-hospital mortality of patients with COVID-19 with solid tumors. METHODS: We enrolled patients with COVID-19 with solid tumors admitted to 32 hospitals in China between December 17, 2020, and March 18, 2020. A multivariate logistic regression model was constructed via stepwise regression analysis, and a nomogram was subsequently developed based on the fitted multivariate logistic regression model. Discrimination and calibration of the nomogram were evaluated by estimating the area under the receiver operator characteristic curve (AUC) for the model and by bootstrap resampling, a Hosmer-Lemeshow test, and visual inspection of the calibration curve. RESULTS: There were 216 patients with COVID-19 with solid tumors included in the present study, of whom 37 (17%) died and the other 179 all recovered from COVID-19 and were discharged. The median age of the enrolled patients was 63.0 years and 113 (52.3%) were men. Multivariate logistic regression revealed that increasing age (OR=1.08, 95% CI 1.00 to 1.16), receipt of antitumor treatment within 3 months before COVID-19 (OR=28.65, 95% CI 3.54 to 231.97), peripheral white blood cell (WBC) count ≥6.93 ×109/L (OR=14.52, 95% CI 2.45 to 86.14), derived neutrophil-to-lymphocyte ratio (dNLR; neutrophil count/(WBC count minus neutrophil count)) ≥4.19 (OR=18.99, 95% CI 3.58 to 100.65), and dyspnea on admission (OR=20.38, 95% CI 3.55 to 117.02) were associated with elevated mortality risk. The performance of the established nomogram was satisfactory, with an AUC of 0.953 (95% CI 0.908 to 0.997) for the model, non-significant findings on the Hosmer-Lemeshow test, and rough agreement between predicted and observed probabilities as suggested in calibration curves. The sensitivity and specificity of the model were 86.4% and 92.5%. CONCLUSION: Increasing age, receipt of antitumor treatment within 3 months before COVID-19 diagnosis, elevated WBC count and dNLR, and having dyspnea on admission were independent risk factors for mortality among patients with COVID-19 and solid tumors. The nomogram based on these factors accurately predicted mortality risk for individual patients.


Subject(s)
Coronavirus Infections/mortality , Hospital Mortality , Neoplasms/therapy , Nomograms , Pneumonia, Viral/mortality , Age Factors , Aged , Area Under Curve , Betacoronavirus , COVID-19 , China/epidemiology , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Dyspnea/physiopathology , Fatigue/physiopathology , Female , Heart Rate , Humans , Leukocyte Count , Logistic Models , Lung Neoplasms/complications , Lung Neoplasms/therapy , Lymphocyte Count , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Neoplasms/complications , Neoplasms/pathology , Neutrophils , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Pulmonary Disease, Chronic Obstructive/complications , ROC Curve , Retrospective Studies , Risk Assessment , SARS-CoV-2
12.
Cancer ; 126(17): 4023-4031, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-612086

ABSTRACT

BACKGROUND: Patients with cancer have a higher risk of coronavirus disease 2019 (COVID-19) than noncancer patients. The authors conducted a multicenter retrospective study to investigate the clinical manifestations and outcomes of patients with cancer who are diagnosed with COVID-19. METHODS: The authors reviewed the medical records of hospitalized patients who were treated at 5 hospitals in Wuhan City, China, between January 5 and March 18, 2020. Clinical parameters relating to cancer history (type and treatment) and COVID-19 were collected. The primary outcome was overall survival (OS). Secondary analyses were the association between clinical factors and severe COVID-19 and OS. RESULTS: A total of 107 patients with cancer were diagnosed with COVID-19, with a median age of 66 years (range, 37-98 years). Lung (21 patients; 19.6%), gastrointestinal (20 patients; 18.7%), and genitourinary (20 patients; 18.7%) cancers were the most common cancer diagnoses. A total of 37 patients (34.6%) were receiving active anticancer treatment when diagnosed with COVID-19, whereas 70 patients (65.4%) were on follow-up. Overall, 52.3% of patients (56 patients) developed severe COVID-19; this rate was found to be higher among patients receiving anticancer treatment than those on follow-up (64.9% vs 45.7%), which corresponded to an inferior OS in the former subgroup of patients (hazard ratio, 3.365; 95% CI, 1.455-7.782 [P = .005]). The detrimental effect of anticancer treatment on OS was found to be independent of exposure to systemic therapy (case fatality rate of 33.3% [systemic therapy] vs 43.8% [nonsystemic therapy]). CONCLUSIONS: The results of the current study demonstrated that >50.0% of infected patients with cancer are susceptible to severe COVID-19. This risk is aggravated by simultaneous anticancer treatment and portends for a worse survival, despite treatment for COVID-19.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Neoplasms/epidemiology , Neoplasms/mortality , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , China/epidemiology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Incidence , Male , Middle Aged , Neoplasms/drug therapy , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Retrospective Studies , Risk , SARS-CoV-2 , Severity of Illness Index , Steroids/therapeutic use , Survival Rate , Treatment Outcome
14.
J Adv Nurs ; 2020 May 24.
Article in English | MEDLINE | ID: covidwho-361360

ABSTRACT

AIMS: To investigate the willingness of Chinese nurses to practice in Hubei combating the coronavirus disease 2019 and to explore the associated factors. DESIGN: A cross-sectional survey. METHODS: Clinical nurses were conveniently recruited by an online link in three provinces out of Hubei, including Hunan (Central south), Chongqing (Southwest) and Xinjiang (Northwest) during 4-10 February 2020. A structured questionnaire was distributed by an online investigation system. Information on sociodemographic characteristics, willingness, possible influencing factors (previous experience, health status, training conditions, perceptions on volunteering to practice in Hubei, family attitude, and insurance) was collected. Binary logistic regression was conducted to explore the association of different factors with the willingness decision of nurses. RESULTS: A total of 11,183 nurses participated in this survey and a high proportion of them were willing to volunteer to practice in Hubei combating the epidemic. Nurses who were likely to volunteer had the following characteristics: younger, unmarried, members of the Communist Party of China, with senior professional qualification, working in critical care departments, with support from their families, with adequate training and learning, with good health status and low levels of anxiety. The regression model could explain 31.1% of the variances of the willingness decision of nurses. CONCLUSIONS: A high proportion of nurses in China were willing to practice in Hubei during the coronavirus disease 2019 epidemic. Adequate training and psychological support would facilitate nurses to volunteer during the outbreak of an infectious disease. IMPACT: The study identified a high proportion of nurses in China were willing to practice in Hubei combating the coronavirus disease 2019 epidemic. The findings will provide valuable references for nurses and decision makers to formulate better plans for increasing nursing workforce during such kind of public health crisis.

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