Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (311)

ProteinN (25)

NSP5 (13)

ORF1ab (8)

ORF8 (5)


SARS-CoV-2 Proteins
    displaying 41 - 50 records in total 311
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    Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study

    Authors: Antonio Leidi; Flora Koegler; Roxane Dumont; Richard Dubos; Maria-Eugenia Zaballa; Giovanni Piumatti; Matteo Coen; Amandine Berner; Pauline Darbellay Farhoumand; Pauline Vetter; Nicolas Vuilleumier; Laurent Kaiser; Delphine Courvoisier; Andrew Azman; Idris Guessous; Silvia Stringhini

    doi:10.1101/2021.03.19.21253889 Date: 2021-03-20 Source: medRxiv

    Importance: Serological assays detecting specific IgG antibodies generated against the Spike protein PROTEIN following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection MESHD are being widely deployed in research studies and clinical practice. However, the duration and the effectiveness of the protection conferred by the immune response against future infection remains to be assessed in a large population. Objective: To estimate the incidence of newly acquired SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD in seropositiveindividuals from a population-based sample as compared to seronegative controls. Design: Retrospective longitudinal propensity-score matched cohort study. Setting: A seroprevalence survey including a population-based representative sample of the population from the canton of Geneva (Switzerland) was conducted between April and June 2020, immediately after the first pandemic wave. Each individual included in the seroprevalence survey was linked to a state centralized registry compiling virologically confirmed SARS-CoV-2 infections MESHD since the beginning of the pandemic. Participants: Participants aged twelve years old and over, who developed anti-spike IgG antibodies were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency MESHD, body mass index, smoking status and education level. Exposure: SARS-CoV-2 seropositivity. Main outcomes and measures: Our primary outcome was virologically confirmed SARS-CoV-2 infections MESHD which occurred from serological status assessment in April-June 2020 to the end of the second pandemic wave (January 2021). Additionally, incidence of infections, rate of testing and proportion of positive tests were analysed. Results: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (Standard Deviation, SD: 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of which 5 (1.0%) were considered as reinfections. By contrast, infection rate was significantly higher in seronegative individuals (15.5%, 154/996) during a similar mean follow-up of 34.7 (SD 3.2) weeks, corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositive subjects. Conclusions and relevance: Seroconversion after SARS-CoV-2 infection MESHD confers protection to successive viral contamination lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.

    Household transmission of SARS-CoV-2 R.1 lineage with spike E484K mutation in Japan

    Authors: Yosuke Hirotsu; Masao Omata

    doi:10.1101/2021.03.16.21253248 Date: 2021-03-20 Source: medRxiv

    We aimed to investigate SARS-CoV-2 emerging lineage harboring variants in receptor binding domain (RBD) of spike protein PROTEIN in Japan. Total nucleic acids were subjected to whole genome sequencing on samples from 133 patients with coronavirus disease MESHD ( COVID-19 MESHD). We obtained the SARS-CoV-2 genome sequence from these patients and examined variants in RBD. As a result, three patients were infected with SARS-CoV-2 harboring E484K mutation in January 2021. These three patients were relatives; one was in the 40s, and two were younger than 10 years old. They had no history of staying abroad and were living in Japan. This strains were classified into GR clade (GISAID), 20B clade (Nextstrain) and R.1 lineage (PANGO). As of March 5, 2021, the R.1 lineage have been identified in 305 samples and dominantly observed in the USA (44%, 135 / 305) and Japan (28%, 84 / 305) from the GISAID database. During the period between October 26, 2020 and February 23, 2021, the frequency of the R.1 lineage was 0.97% (84 / 8,629) of the total confirmed data in Japan and 0.15% (135 / 90,450) in the USA. Although SARS-CoV-2 R.1 lineage was not globally predominant as of March 2021, further analysis is needed to determine whether R.1 variant will disappear or expand in the future.

    Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike PROTEIN antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination

    Authors: Amihai Rottenstreich; Gila Zarbiv; Esther Oiknine-Djian; Roy Zigron; Dana G Wolf; Shay Porat

    doi:10.1101/2021.03.11.21253352 Date: 2021-03-12 Source: medRxiv

    BackgroundSevere acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) during pregnancy and early infancy can result in severe disease. Evaluating the serologic response after maternal vaccination during pregnancy and subsequent transplacental antibody transfer has important implications for maternal care and vaccination strategies. ObjectiveTo assess maternal and neonatal SARS-CoV-2 antibody levels after antenatal mRNA vaccination. Design, Setting, and ParticipantsThis study took place at Hadassah Medical Center in Jerusalem, Israel in February 2021. Maternal and cord blood sera were collected for antibody measurement from mother/newborn dyads following antenatal vaccination. ExposureSARS-CoV-2 BNT162b2 mRNA vaccination. Main outcome and measuresSpike protein (S PROTEIN) and receptor binding domain (RBD) - specific, IgG levels were evaluated in maternal and cord blood sera. ResultsThe study cohort consisted of 20 parturients, with a median maternal age of 32 y ears and a median gestational age of 393/7 weeks at the time of delivery. The median time lapsed from the first and second doses of vaccine administration until delivery was 33 [IQR 30-37] and 11 [IQR 9-15] days, respectively. Of the 20 dyads, all women an d infants were positive for anti S- and anti-RBD-specific IgG. Anti-S and anti-RBD-specific IgG levels in maternal sera were positively correlated to their respective concentrations in cord blood ({rho}s= 0.72; P<0.001 and {rho}s= 0.72; P <0.001, respectively). Anti-S and anti-RBD-specific IgG titers in cord blood were directly correlated with time lapsed since the administration of the first vaccine dose ({rho}s= 0.71; P =0.001 and {rho}s= 0.63; P=0.004, respectively). Conclusion and RelevanceIn this study, SARS-CoV-2 mRNA vaccine administered during pregnancy induced adequate maternal serologic response with subsequent efficient transplacental transfer. Our findings highlight that vaccination of pregnant women may provide maternal and neonatal protection from SARS-CoV-2 infection MESHD.

    Evaluation of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 MESHD patients in outbreak on a cruise ship

    Authors: Norihito Kaku; Fumitaka Nishimura; Yui Shigeishi; Rina Tachiki; Hironori Sakai; Daisuke Sasaki; Kenji Ota; Kei Sakamoto; Kosuke Kosai; Hiroo Hasegawa; Koichi Izumikawa; Koya Ariyoshi; Hiroshi Mukae; Jiro Yasuda; Kouichi Morita; Shigeru Konno; Katsunori Yanagihara

    doi:10.1101/2021.03.10.21253064 Date: 2021-03-12 Source: medRxiv

    Background A few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 MESHD ( COVID-19 MESHD) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 MESHD patients. Methods Blood samples were collected from 143 COVID-19 MESHD patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic MESHD were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins PROTEIN were measured using the enzyme-linked immunosorbent assay to compare false-negative- with positive-result samples. Results Sensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein PROTEIN, were significantly lower in blood samples with false-negative results than in those with positive results. Conclusions These findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 MESHD patients than required in the guidelines, and situations in which it is useful are limited.

    Chimeric spike mRNA vaccines protect against sarbecovirus challenge in mice

    Authors: David R. Martinez; Alexandra Schaefer; Sarah R. Leist; Gabriela De la Cruz; Ande West; Elena N. Atochina-Vasserman; Robert Parks; Maggie Barr; Dapeng Li; Boyd Yount; Drew Weissman; Barton Haynes; Stephanie A. Montgomery; Ralph S. Baric

    doi:10.1101/2021.03.11.434872 Date: 2021-03-12 Source: bioRxiv

    The emergence of SARS-CoV and SARS-CoV-2 MESHD in the 21st century highlights the need to develop universal vaccination strategies against the SARS-related Sarbecovirus subgenus. Using structure-guided chimeric spike designs and multiplexed immunizations, we demonstrate protection against SARS-CoV, SARS-CoV-2 MESHD, and bat CoV (BtCoV) RsSHC014 challenge in highly vulnerable aged mice. Chimeric spike mRNAs containing N-terminal domain (NTD), and receptor binding domains (RBD) induced high levels of broadly protective neutralizing antibodies against three high-risk sarbecoviruses: SARS-CoV MESHD, RsSHC014, and WIV-1. In contrast, SARS-CoV-2 mRNA vaccination not only showed a 10 to >500-fold reduction in neutralizing titers against heterologous sarbecovirus strains, but SARS-CoV MESHD challenge in mice resulted in breakthrough infection MESHD including measurable lung pathology. Importantly, chimeric spike mRNA vaccines efficiently neutralized both the D614G and the South African B.1.351 variants of concern despite some reduction in neutralization activity. Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections MESHD, while revealing the limited efficacy of SARS-CoV-2 spike PROTEIN vaccines against other sarbecoviruses.

    The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2

    Authors: Andrea L Cathcart; Colin Havenar-Daughton; Florian A Lempp; Daphne Ma; Michael Schmid; Maria L Agostini; Barbara Guarino; Julia Di iulio; Laura Rosen; Heather Tucker; Joshua Dillen; Sambhavi Subramanian; Barbara Sloan; Siro Bianchi; Jason Wojcechowskyj; Jiayi Zhou; Hannah Kaiser; Arthur Chase; Martin Montiel-Ruiz; Nadine Czudnochowski; Elisabetta Cameroni; Sarah Ledoux; Christophe Colas; Leah Soriaga; Amalio Telenti; Seungmin Hwang; Gyorgy Snell; Herbert W Virgin; Davide Corti; Christy M Hebner

    doi:10.1101/2021.03.09.434607 Date: 2021-03-10 Source: bioRxiv

    VIR-7831 and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein PROTEIN of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). VIR-7831 and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV MESHD) survivor. Both mAbs contain an LS mutation in the Fc region to prolong serum half-life and potentially enhance distribution to the respiratory mucosa. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection MESHD. VIR-7831 and VIR-7832 potently neutralize live wild-type SARS-CoV-2 in vitro as well as pseudotyped viruses encoding spike protein PROTEIN from the B.1.1.7, B.1.351 and P.1 variants. In addition, they retain activity against monoclonal antibody resistance mutations that confer reduced susceptibility to currently authorized mAbs. The VIR-7831/VIR-7832 epitope does not overlap with mutational sites in the current variants of concern and continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept concept wildtype SARS-CoV-2 infection MESHD model, animals treated with VIR-7831 had less weight loss MESHD, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that VIR-7831 and VIR-7832 are promising new agents in the fight against COVID-19 MESHD.

    Site-specific steric control of SARS-CoV-2 spike PROTEIN SARS-CoV-2 spike MESHD glycosylation

    Authors: Joel D Allen; Himanshi Chawla; Firdaus Samsudin; Lorena Zuzic; Aishwary Tukaram Shivgan; Yasunori Watanabe; Wan-Ting He; Sean Callaghan; Ge Song; Peter Yong; Philip J.M. Brouwer; Yutong Song; Helen M E Duyvesteyn; Tomas Malinauskas; Joeri Kint; Paco Pino; Maria J. Wurm; Martin Frank; David I Stuart; Rogier W. Sanders; Raiees Andrabi; Dennis R. Burton; Sai Li; Peter J Bond; Max Crispin

    doi:10.1101/2021.03.08.433764 Date: 2021-03-09 Source: bioRxiv

    A central tenet in the design of recombinant vaccines is the display of native-like antigens in the elicitation of protective immunity. However, the diversity of global vaccine strategies against Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) poses challenges to benchmark antigens across global vaccine programs. Here, we investigate the glycosylation of a variety of recombinant SARS-CoV-2 spike PROTEIN proteins from five different laboratories and compare them against the glycan shield of an infectious virus. The site-specific stalling of glycan maturation is a highly sensitive reporter of local protein structure and we find there is remarkable conservation of this feature across all samples. Analysis of molecular dynamics simulations of a fully glycosylated spike supports a model of steric restrictions that shape enzymatic processing of the glycans. Furthermore, we show that there is a conserved glycosylation pattern across the monomeric receptor binding domain (RBD) protein and the complete trimeric spike (S) protein PROTEIN. This is in contrast to RBD glycosylation in Middle East respiratory syndrome coronavirus (MERS-CoV MESHD) where quaternary architecture limits glycan processing when in the context of full-length MERS-CoV S protein PROTEIN. These results suggest that spike-based immunogen glycosylation reproducibly recapitulates viral glycosylation.

    SARS-CoV-2 mRNA vaccines induce a robust germinal centre reaction in humans

    Authors: Ali Ellebedy; Jackson Turner; Jane O'Halloran; Elizaveta Kalaidina; Wooseob Kim; Aaron Schmitz; Tingting Lei; Mahima Thapa; Rita Chen; James Case; Fatima Amanat; Adriana Rauseo; Alem Haile; Michael Klebert; Teresa Suessen; William Middleton; Florian Krammer; Sharlene Teefey; Michael Diamond; Rachel Presti; Xuping Xie; Pei-Yong Shi

    doi:10.21203/ Date: 2021-03-08 Source: ResearchSquare

    Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) messenger RNA (mRNA)-based vaccines are ~95% effective in preventing coronavirus disease 2019 MESHD. However, the dynamics of antibody secreting plasmablasts (PBs) and germinal centre (GC) B cells induced by these vaccines in SARS-CoV-2 naïve and antigen-experienced humans remains unclear. Here we examined peripheral blood and/or lymph node (LN) antigen-specific B cell responses in 32 individuals who received two doses of BNT162b2, an mRNA-based vaccine encoding the full-length SARS-CoV-2 spike PROTEIN (S) gene. Circulating IgG- and IgA-secreting PBs targeting the S protein PROTEIN peaked one week after the second immunization then declined and were undetectable three weeks later. PB responses coincided with maximal levels of serum anti-S binding and neutralizing antibodies to a historical strain as well as emerging variants, especially in individuals previously infected with SARS-CoV-2, who produced the most robust serological responses. Fine needle aspirates of draining axillary LNs identified GC B HGNC cells that bind S protein PROTEIN in all participants sampled after primary immunization. GC responses increased after boosting and were detectable in two distinct LNs in several participants. Remarkably, high frequencies of S-binding GC B HGNC cells and PBs were maintained in draining LNs for up to seven weeks after first immunization, with a substantial fraction of the PB pool class-switched to IgA. GC B HGNC cell-derived monoclonal antibodies predominantly targeted the RBD, with fewer clones binding to the N-terminal domain or shared epitopes within the S proteins PROTEIN of human betacoronaviruses OC43 and HKU1. Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a robust and persistent GC B HGNC cell response that engages pre-existing as well as new B cell clones, which enables generation of high-affinity, broad, and durable humoral immunity.

    Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike PROTEIN specific IgG antibodies with virus neutralization functions following virus infection MESHD

    Authors: Mary K Foley; Samuel D Searle; Ali Toloue; Ryan Booth; Alec Falkenham; Darryl Falzarano; Salvatore Rubino; Magen Francis; Mara McNeil; Christopher Richardson; Jason J LeBlanc; Sharon Oldford; Volker Gerdts; Melissa K Andrew; Shelly McNeil; Barry Clarke; Kenneth Rockwood; David J Kelvin; Alyson A Kelvin

    doi:10.1101/2021.03.05.21252707 Date: 2021-03-08 Source: medRxiv

    BackgroundThe SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2 MESHD) has led to more than 114 million COVID-19 MESHD cases and >2.5 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 MESHD increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19 MESHD, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection MESHD. Here we investigated the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. MethodsExtreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection MESHD. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike PROTEIN protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. FindingsFifteen long-term care residents were investigated for SARS-CoV-2 infection MESHD. All individuals had a Clinical Frailty scale score [≥]5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis. InterpretationExtreme older frail individuals and centenarians were able to elicit robust IgG and IgA antibodies directed toward SARS-CoV-2 spike PROTEIN protein. The antibodies were able to neutralize the virus. Humoral responses were still detectable after 60 days from initial diagnosis. Together, these data suggest that recovered participants who are of extreme old age would be protected if re-exposed to the same SARS-CoV-2 viral variant. Considering the threat of SARS-CoV-2 and COVID-19 MESHD to older age groups and long-term care facilities, the humoral responses to SARS-CoV-2 in older age groups is of public health importance and has implications to vaccine responses. FundingCanadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan.

    Serological reconstruction of COVID-19 MESHD epidemics through analysis of antibody kinetics to SARS-CoV-2 proteins MESHD

    Authors: Stephane Pelleau; Tom Woudenberg; Jason Rosado; Francoise Donnadieu; Laura Garcia; Thomas Obadia; Soazic Gardais; Yasmine Elgharbawy; Aurelie Velay; Maria Gonzalez; Jacques-Yves Nizou; Nizar Khelil; Konstantinos Zannis; Charlotte Cockram; Sarah Merkling; Annalisa Meola; Solen Kerneis; Benjamin Terrier; Jerome de Seze; Delphine Planas; Olivier Schwartz; Francois Dejardin; Stephane Petres; Cassandre von Platen; Laurence Arowas; Louise Perrin de Facci; Darragh Duffy; Cliona Ni Cheallaigh; Niall Conlon; Liam Townsend; Heidi Auerswald; Marija Backovic; Bruno Hoen; Arnaud Fontanet; Ivo Mueller; Samira Fafi-Kremer; Timothee Bruel; Michael T White

    doi:10.1101/2021.03.04.21252532 Date: 2021-03-08 Source: medRxiv

    Infection with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. Waning antibody levels lead to reduced sensitivity of serological diagnostic tests over time. This undermines the utility of serological surveillance as the SARS-CoV-2 pandemic progresses into its second year. Here we develop a multiplex serological test for measuring antibodies of three isotypes (IgG, IgM, IgA) to five SARS-CoV-2 antigens (Spike (S), receptor binding domain (RBD), Nucleocapsid (N PROTEIN), Spike subunit 2, Membrane-Envelope fusion) and the Spike proteins PROTEIN of four seasonal coronaviruses. We measure antibody responses in several cohorts of French and Irish hospitalized patients and healthcare workers followed for up to eleven months after symptom onset. The data are analysed with a mathematical model of antibody kinetics to quantify the duration of antibody responses accounting for inter-individual variation. One year after symptoms, we estimate that 36% (95% range: 11%, 94%) of anti-S IgG remains, 31% (9%, 89%) anti-RBD IgG remains, and 7% (1%, 31%) anti-N IgG remains. Antibodies of the IgM isotype waned more rapidly, with 9% (2%, 32%) anti-RBD IgM remaining after one year. Antibodies of the IgA isotype also waned rapidly, with 10% (3%, 38%) anti-RBD IgA remaining after one year. Quantitative measurements of antibody responses were used to train machine learning algorithms for classification of previous infection and estimation of time since infection. The resulting diagnostic test classified previous infections with 99% specificity and 98% (95% confidence interval: 94%, 99%) sensitivity, with no evidence for declining sensitivity over the time scale considered. The diagnostic test also provided accurate classification of time since infection into intervals of 0 - 3 months, 3 - 6 months, and 6 - 12 months. Finally, we present a computational method for serological reconstruction of past SARS-CoV-2 transmission using the data from this test when applied to samples from a single cross-sectional sero-prevalence survey.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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