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1.
J Infect ; 2022 Jul 03.
Article in English | MEDLINE | ID: covidwho-1914625

ABSTRACT

The ongoing global pandemic of Coronavirus disease 2019 (COVID-19) poses a serious threat to human health, with patients reportedly suffering from thrombus, vascular injury and coagulation in addition to acute and diffuse lung injury and respiratory diseases. Angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 entry, is also an important regulator of renin-angiotensin system (RAS) homeostasis, which plays an unsettled role in the pathogenesis of COVID-19. Here, we demonstrated that SARS-CoV-2 Spike protein activated intracellular signals to degrade ACE2 mRNA. The decrease of ACE2 and higher level of angiotensin (Ang) II were verified in COVID-19 patients. High dose of Ang II induced pulmonary artery endothelial cell death in vitro, which was also observed in the lung of COVID-19 patients. Our finding indicates that the downregulation of ACE2 potentially links COVID-19 to the imbalance of RAS.

2.
Disease Surveillance ; 37(1):17-21, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-1789478

ABSTRACT

Objective: To understand the infection status of major respiratory pathogens in pneumonia patients in the early phase of coronavirus disease 2019 (COVID-19) epidemic (January-March, 2020) in Tongzhou district of Beijing.

3.
Front Public Health ; 9: 666135, 2021.
Article in English | MEDLINE | ID: covidwho-1771101

ABSTRACT

BACKGROUND: The implementation of evidence-based approaches by general practitioners (GPs) is new in the primary care setting, and few quantitative studies have evaluated the impact of contextual factors on the attendance of these approaches. METHODS: In total, 892 GPs from 75 community healthcare centers (CHCs) in Shanghai completed our survey. We used logistic regression to analyze factors affecting the number of evidence-based chronic disease programs attended by GPs and whether they had held the lead position in such a program. RESULTS: A total of 346 (38.8%) of the practitioners had never participated in any evidence-based chronic disease prevention (EBCDP) program. The EBCDP interventions in which the GPs had participated were predominantly related to hypertension, diabetes, and cardiovascular disease. However, the proportion of GPs in the lead role was relatively low, between 0.8% (programs involving prevention and control of asthma) and 5.0% (diabetes). Organizational factors and areas were significantly associated with evidence-based practices (EBPs) of the GP, while monthly income and department were the most significantly related to GPs who have the lead role in a program. The results indicated that GPs who had taken the lead position had higher scores for policy and economic impeding factors. GPs who were men, had a higher income, and worked in prevention and healthcare departments and urban areas were more likely to take the lead position. CONCLUSION: Evidence-based programs for chronic diseases should be extended to different types of diseases. Personal, organizational, political, and economic factors and the factors of female sex, lower income, department type, and suburban area environment should be considered to facilitate the translation of evidence to practice.


Subject(s)
General Practitioners , China , Chronic Disease , Female , Humans , Male , Primary Health Care
4.
Mamm Genome ; 33(1): 143-156, 2022 03.
Article in English | MEDLINE | ID: covidwho-1767484

ABSTRACT

Mouse models are essential for dissecting disease mechanisms and defining potential drug targets. There are more than 18,500 mouse strains available for research communities in National Resource Center for Mutant Mice (NRCMM) of China, affiliated with Model Animal Research Center of Nanjing University and Gempharmatech Company. In 2019, Gempharmatech launched the Knockout All Project (KOAP) aiming to generate null mutants and gene floxed strains for all protein-coding genes in mouse genome within 5 years. So far, KOAP has generated 8,004 floxed strains and 9,769 KO (knockout) strains (updated to Oct, 2021). NRCMM also created hundreds of Cre transgenic lines, mutant knock-in models, immuno-deficient models, and humanized mouse models. As a member of the international mouse phenotyping consortium (IMPC), NRCMM provides comprehensive phenotyping services for mouse models. In summary, NRCMM will continue to support biomedical community with new mouse models as well as related services.


Subject(s)
Genome , Animals , China , Disease Models, Animal , Humans , Mice , Mice, Knockout , Phenotype
5.
Atmos Environ (1994) ; 278: 119076, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1763592

ABSTRACT

After the global outbreak of COVID-19, the Chinese government took many measures to control the spread of the virus. The measures led to a reduction in anthropogenic emissions nationwide. Data from a single particle aerosol mass spectrometer in an eastern Chinese megacity (Hangzhou) before, during, and after the COVID-19 lockdown (5 January to February 29, 2020) was used to understand the effect lockdown had on atmospheric particles. The collected single particle mass spectra were clustered into eight categories. Before the lockdown, the proportions of particles ranked in order of: EC (57.9%) < K-SN (13.6%) < Fe-rich (10.2%) < ECOC (6.7%) < K-Na (6.6%) < OC (3.4%) < K-Pb (1.0%) < K-Al (0.7%). During the lockdown period, the EC and Fe-rich particles decreased by 42.8% and 93.2% compared to before lockdown due to reduced vehicle exhaust and industrial activity. By contrast, the K-SN and K-Na particles containing biomass burning tracers increased by 155.2% and 45.2% during the same time, respectively. During the lockdown, the proportions of particles ranked in order of: K-SN (39.7%) < EC (38.1%) < K-Na (11.0%) < ECOC (7.7%) < OC (1.2%) < K-Pb (0.9%) < Fe-rich (0.8%) < K-Al (0.6%). Back trajectory analysis indicated that both inland (Anhui and Shandong provinces) and marine transported air masses may have contributed to the increase in K-SN and K-Na particles during the lockdown, and that increased number of fugitive combustion points (i.e., household fuel, biomass combustion) was a contributing factor. Therefore, the results imply that regional synergistic control measures on fugitive combustion emissions are needed to ensure good air quality.

6.
Infectious Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-1699253

ABSTRACT

Objective Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and has led to a global coronavirus disease 2019 (COVID-19) pandemic. Currently, incomplete understanding of how SARS-CoV-2 arrogates the host cell to establish its life cycle has led to slow progress in the development of effective drugs. Results In this study, we found that SARS-CoV-2 hijacks the host protein EWSR1 (Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1) to promote the activity of its helicase NSP13 to facilitate viral propagation. NSP13 is highly conserved among coronaviruses and is crucial for virus replication, providing chemical energy to unwind viral RNA replication intermediates. Treatment with different SARS-CoV-2 NSP13 inhibitors in multiple cell lines infected with SARS-CoV-2 effectively suppressed SARS-CoV-2 infection. Using affinity-purification mass spectrometry, the RNA binding protein EWSR1 was then identified as a potent host factor that physically associated with NSP13. Furthermore, silencing EWSR1 dramatically reduced virus replication at both viral RNA and protein levels. Mechanistically, EWSR1 was found to bind to the NTPase domain of NSP13 and potentially enhance its dsRNA unwinding ability. Conclusion In conclusion, our results pinpoint EWSR1 as a novel host factor for NSP13 that could potentially be used for drug repurposing as a therapeutic target for COVID-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310880

ABSTRACT

We examine corporate pandemic bonds whose proceeds are committed to COVID-19 containing activities. We find an average cumulative abnormal stock return of 1.33–1.71% during the five trading days surrounding their issuance announcement. Also, their yield spread is 8.9–18 basis points lower than that of otherwise similar non-pandemic bonds. Additional evidence suggests that these findings are due to the government’s supports for pandemic bond issuances rather than the prosocial clienteles of financial investors.

8.
Innovation in Aging ; 5(Supplement_1):244-244, 2021.
Article in English | PMC | ID: covidwho-1584706

ABSTRACT

The purpose of this symposium is to highlight the mental health needs and factors associated with mental health among informal caregivers of older adults in Asia. The symposium consists of five papers. The first paper explores the perceived role, needs, and rewards of informal caregiving among caregivers of residents in independent long-term care facilities in South India. The second paper presents a systematic review and meta-analysis on the association between long-term care service use and informal caregiver burden, depression, and health status. The third paper examines the association between caregivers’ characteristics and quality of life among informal caregivers of older adults with cognitive impairment in China. The fourth paper examines the association between coping strategies and caregiver burden and depression among Chinese caregivers of older adults with cognitive impairment. The last paper examines the association between cohort, meaning making, and depression among adult caregivers during the COVID-19 pandemic in Hong Kong. Taken together, these five papers underscore of the mental health needs and protective and risk factors of mental well-being among caregivers in Asia. Findings of those papers inform the development and adaptation of culturally sensitive interventions to improve mental health outcomes among informal caregivers in Asia. The disccuant will comment on the strengths and limitations of these papers in terms of their contributions to the theory, research, and practice on mental health among informal caregivers in Asia.

9.
J Immunol ; 207(7): 1848-1856, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1377034

ABSTRACT

Immune cell responses are strikingly altered in patients with severe coronavirus disease 2019 (COVID-19), but the immunoregulatory process in these individuals is not fully understood. In this study, 23 patients with mild and 22 patients with severe COVID-19 and 6 asymptomatic carriers of COVID-19 were enrolled, along with 44 healthy controls (HC). Peripheral immune cells in HC and patients with COVID-19 were comprehensively profiled using mass cytometry. We found that in patients with severe COVID-19, the number of HLA-DRlow/- monocytes was significantly increased, but that of mucosal-associated invariant T (MAIT) cells was greatly reduced. MAIT cells were highly activated but functionally impaired in response to Escherichia coli and IL-12/IL-18 stimulation in patients with severe COVID-19, especially those with microbial coinfection. Single-cell transcriptome analysis revealed that IFN-stimulated genes were significantly upregulated in peripheral MAIT cells and monocytes from patients with severe COVID-19. IFN-α pretreatment suppressed MAIT cells' response to E. coli by triggering high levels of IL-10 production by HLA-DRlow/--suppressive monocytes. Blocking IFN-α or IL-10 receptors rescued MAIT cell function in patients with severe COVID-19. Moreover, plasma from patients with severe COVID-19 inhibited HLA-DR expression by monocytes through IL-10. These data indicate a unique pattern of immune dysregulation in severe COVID-19, which is characterized by enrichment of suppressive HLA-DRlow/- monocytes associated with functional impairment of MAIT cells through the IFN/IL-10 pathway.


Subject(s)
COVID-19/immunology , Escherichia coli Infections/immunology , Escherichia coli/physiology , Interleukin-10/metabolism , Monocytes/immunology , Mucosal-Associated Invariant T Cells/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Asymptomatic Diseases , Cells, Cultured , Child , Coinfection , Disease Progression , Female , Humans , Immune Tolerance , Lymphocyte Activation , Male , Middle Aged , Severity of Illness Index , Young Adult
10.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1367846

ABSTRACT

Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/prevention & control , Peptidyl-Dipeptidase A/metabolism , Peptoids/pharmacology , SARS-CoV-2/drug effects , Virus Internalization/drug effects , COVID-19/drug therapy , COVID-19/virology , Humans , MCF-7 Cells , Peptoids/metabolism , Protein Binding/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism
11.
Journal of Intensive Medicine ; 2021.
Article in English | ScienceDirect | ID: covidwho-1157521

ABSTRACT

Coagulopathy, characterized by a high D-dimer level, is a common pathological occurrence in coronavirus disease 2019 (COVID-19) and is associated with poor prognosis. Severe cases with COVID-19 is associated with a significantly higher risk of deep vein thrombosis and acute pulmonary embolism. Pulmonary intravascular coagulopathy is the characteristic coagulopathy in COVID-19. Unlike sepsis-induced coagulopathy and disseminated intravascular coagulation, which are manifestations of systemic coagulopathy, pulmonary intravascular coagulopathy is a manifestation of a local coagulation disorder in the lung. The progression from pulmonary intravascular coagulopathy to sepsis-induced coagulopathy or disseminated intravascular coagulation in the context of COVID-19 may indicate that the patient's coagulation dysfunction has progressed from local to systemic. Exploring the associated coagulation disease will aid in the understanding of the pathophysiological mechanisms underlying severe COVID-19.

12.
JAMIA Open ; 3(4): 628-631, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1096540

ABSTRACT

A common research task in COVID-19 studies often involves the prevalence estimation of certain medical outcomes. Although point estimates with confidence intervals are typically obtained, a better approach is to estimate the entire posterior probability distribution of the prevalence, which can be easily accomplished with a standard Bayesian approach using binomial likelihood and its conjugate beta prior distribution. Using two recently published COVID-19 data sets, we performed Bayesian analysis to estimate the prevalence of infection fatality in Iceland and asymptomatic children in the United States.

13.
East Asian Economic Review ; 24(4):441-468, 2020.
Article in English | ProQuest Central | ID: covidwho-1032684

ABSTRACT

Capital inflows have a strong presence that influences destination countries' development of institutions, which can in turn help resuscitate a stopped economy and re-attract capital that was lost during crises such as the recent public health crisis. While the previous literature emphasizes the mechanism that foreign investors press or even threaten the local government for change, this paper explores empirically whether institutional improvement can be achieved through the channel that host countries voluntarily reform institutions in anticipation of potential investments predicted by the exogenous geographical and cultural characteristics of the recipient countries. Given that countries with better institutional quality can accumulate larger FDI stocks, we still find that the need for more FDI, in contrast to FPI and debt, gives higher incentives to host countries to strategically improve their institutions before seeking capital overseas. Moreover, the predicted FDI exerts more prominent impacts on institutions on constraining elite than those involved in launching a business, enforcing contracts, and protecting properties. The results imply that a long-run plan for upgrading elite constraint institutions is crucial for a post-pandemic FDI reboot.

14.
Front Immunol ; 11: 596684, 2020.
Article in English | MEDLINE | ID: covidwho-1000092

ABSTRACT

Background: The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an unprecedented health crisis. The most common chronic illness among patients infected with SARS-CoV-2 is hypertension. Immune dysregulation plays an important role in SARS-CoV-2 infection and in the development of hypertension; however, the dynamic immunological characteristics of COVID-19 patients with hypertension remain largely unclear. Methods: In total, 258 hypertensive patients infected with SARS-CoV-2 were included in this study. CD38+HLA-DR+ and CD38+PD-1+ CD8+ T cells, IFNγ+CD4+ and IFNγ+CD8+ T cells, the titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and SARS-CoV-2 throat viral loads were measured weekly over 4 weeks after the onset of symptoms. Clinical outcomes were also monitored. Findings: CD4+ T lymphopenia was observed in 100% of the severe and critical cases. Compared with the surviving patients, the patients with fatal outcomes exhibited high and prolonged expression of CD38+HLA-DR+ and CD38+PD-1+ on CD8+ T cells, low expression of SARS-CoV-2-specific IFNγ+CD4+ and IFNγ+CD8+ T cells, low titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and high SARS-CoV-2 viral load during the illness. In the surviving patients, the viral load was significantly inversely correlated with SARS-CoV-2-specific IFNγ+CD8+and IFNγ+CD4+ T cells, IgG, IgM, and IgA. Interpretation: T lymphopenia is common in critical or severe COVID-19 cases with hypertension. Prolonged activation and exhaustion of CD8+ T cells were associated with severe disease. The delayed SARS-CoV-2-specific antibody responses may be insufficient for overcoming severe SARS-CoV-2 infection in the absence of SARS-CoV-2-specific cellular responses.


Subject(s)
Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Hypertension/pathology , SARS-CoV-2/immunology , COVID-19/pathology , Critical Illness , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Interferon-gamma/blood , Lymphopenia/blood , Retrospective Studies , Spike Glycoprotein, Coronavirus/immunology , Viral Load
16.
JAMIA Open ; 3(4): 496-499, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-894604

ABSTRACT

Accurate estimations of the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus 2 need to properly consider the specificity and sensitivity of the antibody tests. In addition, prior knowledge of the extent of viral infection in a population may also be important for adjusting the estimation of seroprevalence. For this purpose, we have developed a Bayesian approach that can incorporate the variabilities of specificity and sensitivity of the antibody tests, as well as the prior probability distribution of seroprevalence. We have demonstrated the utility of our approach by applying it to a recently published large-scale dataset from the US CDC, with our results providing entire probability distributions of seroprevalence instead of single-point estimates. Our Bayesian code is freely available at https://github.com/qunfengdong/AntibodyTest.

17.
Engineering (Beijing) ; 6(10): 1178-1184, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-832008

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease. Similar to H7N9 infection, pneumonia and cytokine storm are typical clinical manifestations of COVID-19. Our previous studies found that H7N9 patients had intestinal dysbiosis. However, the relationship between the gut microbiome and COVID-19 has not been determined. This study recruited a cohort of 57 patients with either general (n = 20), severe (n = 19), or critical (n = 18) disease. The objective of this study was to investigate changes in the abundance of ten predominant intestinal bacterial groups in COVID-19 patients using quantitative polymerase chain reaction (q-PCR), and to establish a correlation between these bacterial groups and clinical indicators of pneumonia in these patients. The results indicated that dysbiosis occurred in COVID-19 patients and changes in the gut microbial community were associated with disease severity and hematological parameters. The abundance of butyrate-producing bacteria, such as Faecalibacterium prausnitzii, Clostridium butyricum, Clostridium leptum, and Eubacterium rectale, decreased significantly, and this shift in bacterial community may help discriminate critical patients from general and severe patients. Moreover, the number of common opportunistic pathogens Enterococcus (Ec) and Enterobacteriaceae (E) increased, especially in critically ill patients with poor prognosis. The results suggest that these bacterial groups can serve as diagnostic biomarkers for COVID-19, and that the Ec/E ratio can be used to predict death in critically ill patients.

18.
J Am Med Inform Assoc ; 28(3): 472-476, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-799253

ABSTRACT

OBJECTIVE: Estimating the hospitalization risk for people with comorbidities infected by the SARS-CoV-2 virus is important for developing public health policies and guidance. Traditional biostatistical methods for risk estimations require: (i) the number of infected people who were not hospitalized, which may be severely undercounted since many infected people were not tested; (ii) comorbidity information for people not hospitalized, which may not always be readily available. We aim to overcome these limitations by developing a Bayesian approach to estimate the risk ratio of hospitalization for COVID-19 patients with comorbidities. MATERIALS AND METHODS: We derived a Bayesian approach to estimate the posterior distribution of the risk ratio using the observed frequency of comorbidities in COVID-19 patients in hospitals and the prevalence of comorbidities in the general population. We applied our approach to 2 large-scale datasets in the United States: 2491 patients in the COVID-NET, and 5700 patients in New York hospitals. RESULTS: Our results consistently indicated that cardiovascular diseases carried the highest hospitalization risk for COVID-19 patients, followed by diabetes, chronic respiratory disease, hypertension, and obesity, respectively. DISCUSSION: Our approach only needs (i) the number of hospitalized COVID-19 patients and their comorbidity information, which can be reliably obtained using hospital records, and (ii) the prevalence of the comorbidity of interest in the general population, which is regularly documented by public health agencies for common medical conditions. CONCLUSION: We developed a novel Bayesian approach to estimate the hospitalization risk for people with comorbidities infected with the SARS-CoV-2 virus.


Subject(s)
Bayes Theorem , COVID-19/complications , Hospitalization/statistics & numerical data , Comorbidity , Humans , Odds Ratio , SARS-CoV-2
19.
Cell ; 183(4): 1013-1023.e13, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-756810

ABSTRACT

Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Animals , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/chemistry , Antibodies, Viral/therapeutic use , Antigen-Antibody Reactions , Binding Sites , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cricetinae , Cryoelectron Microscopy , Disease Models, Animal , Epitopes/chemistry , Epitopes/immunology , Female , Lung/pathology , Male , Molecular Dynamics Simulation , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Protein Structure, Quaternary , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
20.
Front Genet ; 11: 783, 2020.
Article in English | MEDLINE | ID: covidwho-698302

ABSTRACT

The furin cleavage site in the spike glycoprotein of the SARS-CoV-2 coronavirus is considered important for the virus to enter the host cells. By analyzing 45828 SARS-CoV-2 genome sequences, we identified 103 strains of SARS-CoV-2 with various DNA mutations including 18 unique non-synonymous point mutations, one deletion, and six gains of premature stop codon that may affect the furin cleavage site. Our results revealed that the furin cleavage site might not be required for SARS-CoV-2 to enter human cells in vivo. The identified mutants may represent a new subgroup of SARS-CoV-2 coronavirus with reduced tropism and transmissibility as potential live-attenuated vaccine candidates.

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