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1.
Children ; 10(1):159, 2023.
Article in English | MDPI | ID: covidwho-2199829

ABSTRACT

During the coronavirus disease 2019 (COVID-19) outbreak, the prevalence of obesity increased globally;this may be associated with hypertension incidence. However, investigations on the changes in the prevalence of hypertension among children and adolescents are limited. This cross-sectional study investigated the prevalence of hypertension among 1428 youths aged 10-18 years using data from the Korea National Health and Nutrition Examination Survey 2018-2020. We assessed the prevalence of hypertension according to sex, age, body mass index (BMI), and residential district. The prevalence of hypertension increased from 7.1% to 12.5% in all participants. In the sex-specific analysis, the prevalence was found to be increased in boys. In the age-specific analysis, the prevalence was found to be increased in youths aged 13-15 years. In the BMI-specific analysis, an increase in the prevalence was prominent in the normal BMI group. In the residential district-specific analysis, the prevalence of hypertension among youth increased in urban areas. Our results show that the prevalence of hypertension increased among Korean children and adolescents during the COVID-19 outbreak. These findings suggest the importance of close monitoring of hypertension among youth during the COVID-19 pandemic.

2.
eBioMedicine ; 87:104401, 2023.
Article in English | ScienceDirect | ID: covidwho-2149637

ABSTRACT

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, contains a unique, four amino acid (aa) “PRRA” insertion in the spike (S) protein that creates a transmembrane protease serine 2 (TMPRSS2)/furin cleavage site and enhances viral infectivity. More research into immunogenic epitopes and protective antibodies against this SARS-CoV-2 furin cleavage site is needed. Methods Combining computational and experimental methods, we identified and characterized an immunogenic epitope overlapping the furin cleavage site that detects antibodies in COVID-19 patients and elicits strong antibody responses in immunized mice. We also identified a high-affinity monoclonal antibody from COVID-19 patient peripheral blood mononuclear cells;the antibody directly binds the furin cleavage site and protects against SARS-CoV-2 infection in a mouse model. Findings The presence of “PRRA” amino acids in the S protein of SARS-CoV-2 not only creates a furin cleavage site but also generates an immunogenic epitope that elicits an antibody response in COVID-19 patients. An antibody against this epitope protected against SARS-CoV-2 infection in mice. Interpretation The immunogenic epitope and protective antibody we have identified may augment our strategy in handling COVID-19 epidemic. Funding The National Natural Science Foundation of China (82102371, 91542201, 81925025, 82073181, and 81802870), the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2021-I2M-1-047 and 2022-I2M-2-004), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2020-PT310-006, 2019XK310002, and 2018TX31001), the National Key Research and Development Project of China (2020YFC0841700), US National Institute of Health (NIH) funds grant AI158154, University of California Los Angeles (UCLA) AI and Charity Treks, and UCLA DGSOM BSCRC COVID-19 Award Program. H.Y. is supported by Natural Science Foundation of Jiangsu Province (BK20211554 and BE2022728).

3.
Infection, Disease & Health ; 2022.
Article in English | ScienceDirect | ID: covidwho-2061245

ABSTRACT

Background Increased transmissibility of severe-acute-respiratory-syndrome-coronavirus-2(SARS-CoV-2) variants, such as the Omicron-variant, presents an infection-control challenge. We contrasted nosocomial transmission amongst hospitalized inpatients across successive pandemic waves attributed to the Delta- and Omicron variants, over a 9-month period in which enhanced-infection-prevention-measures were constantly maintained. Methods Enhanced-infection-prevention-measures in-place at a large tertiary hospital included universal N95-usage, routine-rostered-testing (RRT) for all inpatient/healthcare-workers (HCWs), rapid-antigen-testing (RAT) for visitors, and outbreak-investigation coupled with enhanced-surveillance (daily-testing) of exposed patients. The study-period lasted from 21st June 2021-21st March 2022. Chi-square test and multivariate-logistic-regression was utilized to identify factors associated with onward transmission and 28d-mortality amongst inpatient cases of hospital-onset COVID-19. Results During the Delta-wave, hospital-onset cases formed 2.7% (47/1727) of all COVID-19 cases requiring hospitalisation;in contrast, hospital onset-cases formed a greater proportion (17.7%, 265/1483;odds-ratio, OR=7.78, 95%CI=5.65-10.70) during the Omicron-wave, despite universal N95-usage and other enhanced infection-prevention measures that remained unchanged. The odds of 28d-mortality were higher during the Delta-wave compared to the Omicron-wave (27.7%, 13/47, vs. 10.6%, 28/265, adjusted-odds-ratio, aOR=2.78, 95%CI=1.02-7.69). Onward-transmission occurred in 21.2% (66/312) of hospital-onset cases;being on enhanced-surveillance (daily-testing) was independently associated with lower odds of onward-transmission (aOR=0.18, 95%CI=0.09-0.38) Conclusion A surge of hospital-onset COVID-19 cases was encountered during the Omicron-wave, despite continuation of enhanced infection-prevention measures;mortality amongst hospital-onset cases was reduced. The Omicron variant poses an infection-control challenge in contrast to Delta;surveillance is important especially in settings where infrastructural limitations make room-sharing unavoidable, despite the high risk of transmission.

4.
Current Psychology ; 41(8):5631-5639, 2022.
Article in English | ProQuest Central | ID: covidwho-1982338

ABSTRACT

To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the pandemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Among the 1493 questionnaires completed, 827 (55.39%) of these were men, and 422 (28.27%) of these were medical personnel. The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

5.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.07.29.502029

ABSTRACT

Continued evolution of the SARS-CoV-2 spike poses a challenge to immune interventions. To develop antibodies that protect against evolving SARS-CoV-2 viruses, we combined antibodies that recognize different RBD sites to generate a trivalent antibody that potently neutralized all major variants, including the most recent Omicron lineages. Negative stain electron microscopy suggests that this multispecific achieves synergistic neutralization by engaging different epitopes in specific orientations that facilitate inter-spike binding. These interactions resulted in not only improved potency but also importantly prevented virus escape, a feature not seen with parental antibody cocktails or the most potent clinical mAb. Such multispecific antibodies simplify treatment, maximize coverage, decrease the likelihood of SARS-CoV-2 escape, and provide the basis for building universal SARS-CoV-2 antibody therapies that are more likely to maintain broad reactivity for future variants.

6.
Trop Med Infect Dis ; 7(5)2022 May 07.
Article in English | MEDLINE | ID: covidwho-1862900

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, distinguishing dengue from COVID-19 in endemic areas can be difficult, as both may present as undifferentiated febrile illness. COVID-19 cases may also present with false-positive dengue serology. Hospitalisation protocols for managing undifferentiated febrile illness are essential in mitigating the risk from both COVID-19 and dengue. METHODS: At a tertiary hospital contending with COVID-19 during a dengue epidemic, a triage strategy of routine COVID-19 testing for febrile patients with viral prodromes was used. All febrile patients with viral prodromes and no epidemiologic risk for COVID-19 were first admitted to a designated ward for COVID-19 testing, from January 2020 to December 2021. RESULTS: A total of 6103 cases of COVID-19 and 1251 cases of dengue were managed at our institution, comprising a total of 3.9% (6103/155,452) and 0.8% (1251/155,452) of admissions, respectively. A surge in dengue hospitalisations in mid-2020 corresponded closely with the imposition of a community-wide lockdown. A total of 23 cases of PCR-proven COVID-19 infection with positive dengue serology were identified, of whom only two were true co-infections; both had been appropriately isolated upon admission. Average length-of-stay for dengue cases initially admitted to isolation during the pandemic was 8.35 days (S.D. = 6.53), compared with 6.91 days (S.D. = 8.61) for cases admitted outside isolation (1.44 days, 95%CI = 0.58-2.30, p = 0.001). Pre-pandemic, only 1.6% (9/580) of dengue cases were admitted initially to isolation-areas; in contrast, during the pandemic period, 66.6% (833/1251) of dengue cases were initially admitted to isolation-areas while awaiting the results of SARS-CoV-2 testing. CONCLUSIONS: During successive COVID-19 pandemic waves in a dengue-endemic country, coinfection with dengue and COVID-19 was uncommon. Routine COVID-19 testing for febrile patients with viral prodromes mitigated the potential infection-prevention risk from COVID-19 cases, albeit with an increased length-of-stay for dengue hospitalizations admitted initially to isolation.

7.
Infect Control Hosp Epidemiol ; : 1-5, 2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1815396

ABSTRACT

Sporadic clusters of healthcare-associated coronavirus disease 2019 (COVID-19) occurred despite intense rostered routine surveillance and a highly vaccinated healthcare worker (HCW) population, during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 δ (delta) variant. Genomic analysis facilitated timely cluster detection and uncovered additional linkages via HCWs moving between clinical areas and among HCWs sharing a common lunch area, enabling early intervention.

8.
Am J Infect Control ; 50(4): 465-468, 2022 04.
Article in English | MEDLINE | ID: covidwho-1653966

ABSTRACT

Sporadic clusters of health care-associated COVID-19 infection occurred in a highly vaccinated health care-workers and patient population, over a 3-month period during ongoing community transmission of the B.1.617.2 variant. Enhanced infection-prevention measures and robust surveillance systems, including routine-rostered-testing of all inpatients and staff and usage of N95-respirators in all clinical areas, were insufficient in achieving zero health care-associated transmission. The unvaccinated and immunocompromised remain at-risk and should be prioritized for enhanced surveillance.


Subject(s)
COVID-19 , COVID-19/prevention & control , Delivery of Health Care , Disease Outbreaks , Humans , Inpatients , SARS-CoV-2
10.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.06.02.446698

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current SARS-CoV-2 vaccines are based on spike (S) protein, S1 subunit, or receptor-binding domain (RBD) of prototype strain. Emergence of several novel SARS-CoV-2 variants has raised concern about potential immune escape. In this study, we performed an immunogenicity comparison of ancestral RBD, S1, and S ectodomain trimer (S-trimer) antigens and tested the efficacy of these prototype vaccines against the circulating variants, especially B.1.617 that has been linked to India's current COVID-19 surge. We found that RBD and S-trimer proteins could induce significantly higher neutralizing antibody titers than S1 protein. For the three vaccines, the neutralizing titers decreased over time, but still remained high for at least five months after immunization. Importantly, the three prototype vaccines were still effective in neutralizing the variants of concern, although B.1.351 and B.1.617.1 lineages showed varying degrees of reduction in neutralization by the immune sera. The vaccines-induced sera were shown to block receptor binding and inhibit S protein-mediated membrane fusion. In addition, the immune sera did not promote antibody-dependent enhancement (ADE) in vitro. Our work provides valuable information for development of SARS-CoV-2 subunit vaccines and also supports the continued use of ancestral RBD or S-based vaccines to fight the COVID-19 epidemic.


Subject(s)
31543 , 59585
11.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3783087

ABSTRACT

Background: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Methods: We generated a mouse-adapted strain SARS-CoV-2 by serial passages in the lung of BALB/c mice. Complete genome deep sequencing of different generations of viruses was performed to characterize the dynamics of the adaptive mutations in SARS-CoV-2. Indirect immunofluorescence analysis and Biolayer interferometry experiments demonstrated that two mutations in RBD significantly increased its binding affinity towards mouse ACE2. Significantly, TLR7/8 agonist Resiquimod block SARS-CoV-2 in vitro and in vivo. Findings: We adapted a wild-type SARS-CoV-2 by serial passages in the lung of BALB/c mice. The mouse-adapted strain WBP-1 showed increased infectivity in BALB/c mice and led to severe interstitial pneumonia. We characterized the dynamics of the adaptive mutations in SARS-CoV-2 and demonstrated that Q493K and Q498H in RBD significantly increased its binding affinity towards mouse ACE2. Additionally, The TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge, demonstrating this mouse-adapted strain is a useful tool to investigate COVID-19 and develop new therapies. Interpretation: We found for the first time that the Q493K and Q498H mutations in the RBD of WBP-1 enhanced its interactive affinities with mACE2. The mouse-adapted SARS-CoV-2 provides a valuable tool for the evaluation of novel antiviral and vaccine strategies, especially in determining the immunopathological consequences of any intervention. This study also verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo.Funding Statement: This research was funded by Emergency Science and Technology Project of Hubei Province(2020FCA046)and Independent Science and Technology Innovation Fund of Huazhong Agricultural University in 2020 (2662020PY002).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The animal experiments were approved by the Research Ethics Committee, Huazhong Agricultural University, Hubei, China (HZAUMO-2020-0007). All the animal experiments were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals from the Research Ethics Committee, Huazhong Agricultural University, Hubei, China.


Subject(s)
59585 , 31333 , 8348
12.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-23247.v3

ABSTRACT

Background: The clinical characteristics and outcomes of the 2019 novel coronavirus (COVID-19) pneumonia are different in Hubei compared to other regions in China. But there are few comparative studies on the differences between imported and local patients which may provide information of the different courses of the virus after transmission. Methods: : We investigated 169 cases of COVID-19 pneumonia in two centers in Hunan Province, and divided them into two groups according to epidemiological history, "imported patients" refers to patient with a clear history of travel in Wuhan within 14 days before onset, and " local patients” refers to local resident without a recent history of travel in Wuhan, aiming to analyze the difference in clinical characteristics and outcomes between the two groups. All the epidemiological, clinical, imaging, and laboratory data were analyzed and contrasted. Results: : The incidence of fever on admission in imported patients was significantly higher than local patients. There was a significantly higher proportion of abnormal pulmonary signs, hypokalemia, hyponatremia, prolonged PT, elevated D-dimer and elevated blood glucose in imported patients. Compared with local patients, the proportion using antibiotics, glucocorticoids and gamma globulin were significantly higher in imported patients. The moderate type was more common in local patients, and the severe type were more frequent in imported patients. In addition, the median duration of viral clearance was longer in imported patients. Conclusions: : In summary, we found that imported cases were more likely to develop into severe cases, compared with local patients and required more powerful treatments. Trial registration: Registered 21 st March 2020, and this study has been approved by the Medical Ethics Committee (Approved Number. 2020017).


Subject(s)
7186 , 59585 , 5444 , 7189
13.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-78282.v1

ABSTRACT

Objective To investigate the epidemiological characteristics, clinical features, treatment and short-term prognosis of SARS-CoV-2 infection in children.Methods A retrospective analysis was conducted in children with SARS-CoV-2 admitted to twelve hospitals in eight cities in Hunan province, China, from January 26, 2020 to June 30, 2020.Results A total of 48 children were enrolled in this study. 11 cases (23%) were asymptomatic, 15 cases (31%) were mild, 20 cases (42%) were moderate, and 2 cases (4%) were severe. No children were critical requiring intensive care. The most common symptom was fever (42%), cough (40%), fatigue (17%) and diarrhea (10%). The total peripheral blood leukocytes count decreased in two case (4%), Lymphocytopenia was present in 5 cases (10%). There were abnormal chest CT changes in 22 children (46%), including 15 (68%) with patchy ground glass opacity. In addition to supportive treatment, 41 children (85%) received antiviral therapy, 11 patients and (23%) were treated with antibiotics, 2 children (4%) were treated with methylprednisolone and IVIG. There was no death occurred.Conclusions Most children with SARS CoV-2 infection in Hunan province were asymptomatic, mild or moderate. Severe cases are rare. Close family contact was the main route of infection. The younger the age, the less obvious symptoms for children might be. Epidemiological history, nucleic acid test and chest imaging were important tools for the diagnosis in children.


Subject(s)
8402 , 3994 , 5444 , 37050 , 5325
14.
Int. j. health policy manag ; 2020.
Article in English | MEDLINE | ID: covidwho-690466

ABSTRACT

The control and prevention of public health emergencies can face severe challenges, especially financial and material challenges during the coronavirus disease 2019 (COVID-19). Enabling and ensuring smooth financial and material flows across levels, within the country, and across countries are essentially important to preparedness for global health emergencies, which cannot easily be achieved without being facilitated by preferential tax policies. China's preferential tax policy practice developed at early stages of the COVID-19 pandemic could be useful experiences which can be adapted to unique contexts of other countries, so different stakeholders including citizens could be effectively motivated and involved in the fight against the COVID-19 pandemic. However, we should see that these policies are temporary and issued as an afterthought. There is still much to learn about how epidemic responders and policy-makers can make the most of each other's expertise to fit into the wider information architecture of epidemic response.

15.
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.06.30.177097

ABSTRACT

The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.Competing Interest StatementThe authors have declared no competing interest.View Full Text

16.
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.05.21.107565

ABSTRACT

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Currently, there is no vaccine available for preventing SARS-CoV-2 infection. Like closely related severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 also uses its receptor-binding domain (RBD) on the spike (S) protein to engage the host receptor, human angiotensin-converting enzyme 2 (ACE2), facilitating subsequent viral entry. Here we report the immunogenicity and vaccine potential of SARS-CoV-2 RBD (SARS2-RBD)-based recombinant proteins. Immunization with SARS2-RBD recombinant proteins potently induced a multi-functional antibody response in mice. The resulting antisera could efficiently block the interaction between SARS2-RBD and ACE2, inhibit S-mediated cell-cell fusion, and neutralize both SARS-CoV-2 pseudovirus entry and authentic SARS-CoV-2 infection. In addition, the anti-RBD sera also exhibited cross binding, ACE2-blockade, and neutralization effects towards SARS-CoV. More importantly, we found that the anti-RBD sera did not promote antibody-dependent enhancement of either SARS-CoV-2 pseudovirus entry or authentic virus infection of Fc receptor-bearing cells. These findings provide a solid foundation for developing RBD-based subunit vaccines for SARS-CoV2.


Subject(s)
59585
17.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.04.28.20083246

ABSTRACT

Background: Cancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients. Design, Setting, and Participants: Data of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses. Results: A total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death. Conclusions: This is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic.


Subject(s)
30170 , 59585 , 9562 , 21079 , 3660
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