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SARS-CoV-2 proteins

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    IL-6 HGNC and D-Dimer at Admission Predicts Cardiac Injury MESHD and Early Mortality during SARS-CoV-2 Infection MESHD

    Authors: Daoyuan Si; Beibei Du; Bo Yang; Lina Jin; Lujia Ni; Qian Zhang; Zhongfan Zhang; Mohammed Ali Azam; Patrick F.H Lai; Stephane Masse; Huan Sun; Xingtong Wang; Slava Epelman; Patrick R Lawler; Ping Yang; Kumaraswamy Nanthakumar

    doi:10.1101/2021.03.22.21254077 Date: 2021-03-29 Source: medRxiv

    BACKGROUND: We recently described mortality of cardiac injury MESHD in COVID-19 MESHD patients. Admission activation of immune, thrombotic MESHD biomarkers and their ability to predict cardiac injury MESHD and mortality patterns in COVID-19 MESHD is unknown. METHODS: This retrospective cohort study included 170 COVID-19 MESHD patients with cardiac injury MESHD at admission to Tongji Hospital in Wuhan from January 29-March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS: Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death MESHD were elevate levels of interleukin 6 HGNC ( IL-6 HGNC) (p<0.0001), Tumor Necrosis Factor-a HGNC Tumor Necrosis Factor-a MESHD ( TNF-a HGNC) (p=0.0025), and C-reactive protein HGNC ( CRP HGNC) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic MESHD pathway activation. Increasing cTnI HGNC levels were associated with those of increasing IL-6 HGNC (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS: In COVID-19 MESHD patients with cardiac injury MESHD, admission IL-6 HGNC and D-dimer predicted subsequent elevation of cTnI HGNC and early death MESHD, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury MESHD.

    Cerebrospinal fluid in COVID-19 MESHD neurological complications: no cytokine storm or neuroinflammation.

    Authors: Maria A. Garcia; Paula V. Barreras; Allie Lewis; Gabriel Pinilla; Lori J. Sokoll; Thomas Kickler; Heba Mostafa; Mario Caturegli; Abhay Moghekar; Kathryn C. Fitzgerald; - Hopkins Neuro-COVID-19 Group; Carlos A Pardo

    doi:10.1101/2021.01.10.20249014 Date: 2021-01-12 Source: medRxiv

    BACKGROUND. Neurological complications MESHD occur in COVID-19 MESHD. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 MESHD subjects with neurological complications MESHD and determine presence of neuroinflammatory changes implicated in pathogenesis. METHODS. Cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 MESHD subjects with neurological complications categorized by diagnosis ( stroke MESHD, encephalopathy MESHD, headache MESHD) and illness severity (critical, severe, moderate, mild). COVID-19 MESHD CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders MESHD and stroke MESHD controls (n=82). Cytokines ( IL-6 HGNC, TNF-alpha HGNC, IFN-gamma HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC), inflammation MESHD and coagulation markers (high-sensitivity- C Reactive Protein HGNC [hsCRP], ferritin, fibrinogen HGNC, D-dimer, Factor VIII) and neurofilament light chain ( NF-L HGNC), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA. RESULTS. CSF from COVID-19 MESHD subjects showed a paucity of neuroinflammatory changes, absence of pleocytosis MESHD or specific increases in pro-inflammatory markers or cytokines ( IL-6 HGNC, ferritin, or D-dimer). Anti-SARS-CoV2 antibodies in CSF of COVID-19 MESHD subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. A similar increase of pro-inflammatory cytokines ( IL-6 HGNC, TNF-alpha HGNC;, IL-12p70) and IL-10 HGNC in CSF of COVID-19 MESHD and non- COVID-19 MESHD stroke MESHD subjects was observed compared to controls. CSF-NF-L was elevated in subjects with stroke MESHD and critical COVID-19 MESHD. CSF-hsCRP was present almost exclusively in COVID-19 MESHD cases. CONCLUSION. The paucity of neuroinflammatory changes in CSF of COVID-19 MESHD subjects and lack of SARS-CoV2 RNA do not support the presumed neurovirulence of SARS-CoV2 or neuroinflammation MESHD in pathogenesis of neurological complications in COVID-19 MESHD. Elevated CSF-NF-L indicates neuroaxonal injury MESHD in COVID-19 MESHD cases. The role of CSF SARS-CoV2 IgG antibodies is still undetermined.

    Altered Transcript Levels of Cytokines in COVID-19 MESHD Patients

    Authors: Majid Samsami; Alireza Fatemi; Reza Jalili Khoshnoud; Karim Kohansal; Arezou Sayad; Shabnam Soghala; Shahram Arsang-Jang; Mohammad Taheri; Soudeh Ghafouri-Fard

    doi:10.21203/rs.3.rs-126215/v1 Date: 2020-12-10 Source: ResearchSquare

    The pandemic caused by severe acute respiratory syndrome coronavirus 2 MESHD and the related disorder i.e. “ coronavirus disease 2019 MESHD” ( COVID-19 MESHD) have encouraged researchers to unravel the molecular mechanism of disease severity. Several lines of evidence support the impact of "cytokine storm" in the pathogenesis of severe forms of the disorder MESHD. We aimed to assess the expression levels of nine cytokine coding in COVID-19 MESHD patients admitted in a hospital. Expression levels of IFN-G HGNC, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-17 HGNC, TGF-B HGNC, IL-8 HGNC and IL-1B HGNC were significantly higher in COVID-19 MESHD patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 HGNC whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Expression of TNF-A HGNC was not different between COVID-19 MESHD patients and healthy controls. Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 MESHD patients and controls. The area under curve (AUC) values range from 0.94 for IFN-G HGNC to 1.0 for IL-2 HGNC and IL-1B HGNC. After combining the transcript levels of all cytokines, AUC, sensitivity and specificity values reached 1.0, 1.0 and 0.99, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 HGNC with AUC value of 0.68, had the best diagnostic power among cytokine coding genes. Expression of none of cytokine coding genes was correlated with the assessed clinical/demographic data including age, gender, ICU admission, or CRP HGNC/ESR levels. Our study provides further evidence for contribution of “cytokine storm” in the pathobiology of moderate/severe forms of COVID-19 MESHD.

    Clinical and molecular characteristics of COVID-19 MESHD patients with persistent SARS-CoV-2 infection MESHD

    Authors: Chaoyang Sun; Junpeng Fan; Jia Huang; Ensong Guo; Yu Fu; Si Liu; Rourou Xiao; Chen Liu; Funian Lu; Tianyu Qin; Chao He; Zizhuo Wang; Xu Qin; Dianxing Hu; Lixin You; Xi Li; Tian Wang; Peng Wu; Gang Chen; Jianfeng Zhou; Kezhen Li

    doi:10.21203/rs.3.rs-86940/v1 Date: 2020-10-02 Source: ResearchSquare

    The clinical features, molecular characteristics, and immune responses of COVID-19 MESHD patients with persistent SARS-CoV-2 infection MESHD are not yet well described. In this study, we investigated the differences in clinical parameters, laboratory indexes, plasma cytokines, and peripheral blood mononuclear cell responses, which were assessed using single-cell RNA-sequencing in patients with non-critical COVID-19 MESHD with long durations (LDs) and short durations (SDs) of viral shedding. Our results revealed that clinical parameters and laboratory indexes, such as c-reactive protein (CRP) HGNC and D-dimer, were comparable between SDs and LDs. Most inflammatory cytokines/chemokines, such as IL-2 HGNC, IL2R HGNC, TNFα HGNC/β, IL1β HGNC, and CCL5 HGNC were present at low levels in LDs. Our single-cell RNA-sequencing revealed a reconfiguration of the peripheral immune cell phenotype in LDs, including decreases in natural killer (NK) cells and CD14+ monocytes and an increase in regulatory T cells (Tregs). Furthermore, most cell subsets in LDs consistently exhibited reduced expression of ribosomal protein (RP) genes, indicating dysfunctions in cytokine/chemokine synthesis, folding, modification, and assembly. Accordingly, the negative correlation between the RP levels and viral shedding duration was validated in an independent cohort of bulk-RNA-sequencing data from 103 non-critical patients, which may help guide clinical management and resource allocation. Moreover, peripheral T and NK cells and memory B cells in LDs likely failed to activate, which contributed to the persistence of viral shedding.

    Plasma Levels of Phospholipids in Patients With COVID-19 MESHD; A Promising Simple Biochemical Parameter to Evaluate the Disease Severity

    Authors: Mohammed Abdalla; Noor Eldin Mohamed Ismail; ahmed h mohamed; Rita M Borik; Ali a ali; Yasser O Mosaad

    doi:10.21203/rs.3.rs-57302/v1 Date: 2020-08-11 Source: ResearchSquare

    Background Cronavirus-19 ( COVID-19 MESHD) pandemic is a worldwide public health problem knowing in China recently from December 25, 2019. Phospholipids are structural components of mammalian cytoskeleton and cell membranes. Phospholipids is an anionic lipid found in mammalian membranes in low amounts (1–2%) of the total phospholipids. Also, it suppressed viral attachment to the plasma membrane and subsequent replication in lung cells.  Aim: The present study was carried out to explain the correlation between the plasma phospholipids as well as secretory phospholipase-A2α2 (sPLA2α2) and cytokine storm; tumor necrosis factor ( TNF)-α HGNC, interleukin--1β HGNC ( IL-1β HGNC), interleukin-6 (IL)-6 HGNC and interleukin-13 HGNC ( IL-13_ HGNC levels of patients with COVID-19 MESHD to assess the infection severity. Methods: Serum samples from enrolled 34 patients with mild, moderate, and acute COVID-19 MESHD infection. Complete blood picture (CBC), plasma d-dimer, ferritin, C-reactive protein HGNC ( CRP HGNC), lipid profile, phospholipids, sPLA2α2 and TNF-α HGNC, IL-1β HGNC, IL-6 HGNC and IL-13 HGNC as well as lung computed tomography (CT) imaging.Results: CBC showed that the presence of leukopenia, lymphopenia, eosinopenia in patient with mild, moderate, and acute COVID-19 MESHD infection. Also, significant increase in plasma d-dimer, CRP HGNC, ferritin, triacyclglycerols, TNF-α HGNC, IL-1β HGNC, IL-6 HGNC and IL-13 HGNC levels as well as sPLA2α2 activity when compared to normal persons. However, plasma levels of phospholipids, cholesterol, HDL-C and LDL-C were decreased significantly in patient with acute COVID-19 MESHD infection only, when compared to normal persons. In addition, lung computed tomography (CT) scan showed that the presence of ground glass opacity (GGO), bronchial wall thickening, crazy paving sign as well as right, left, upper and lower lung predominant in patient with mild, moderate and acute COVID-19 MESHD infection. The levels of blood leukopenia, lymphopenia and eosinopenia as well as plasma phospholipids d-dimer, CRP HGNC, ferritin, cytokine storm and sPLA2α2 were pronounced in group of patients with acute COVID-19 MESHD infection more the mild and moderate one.Conclusion: The present study was showed that there is a correlation between plasma phospholipids depletion as well as elevation sPLA2α2 and cytokines storm with the severity of COVID-19 MESHD infection. Also, the plasma phospholipids levels can used to estimate COVID-19 MESHD infection severity and help to identify patients into three classes: mild, moderate and severe one.

    Early initiation of Extracorporeal Blood Purification using the AN69ST (oXiris®) hemofilter as a treatment modality for COVID - 19 patients: a single-centre case series

    Authors: Petar Ugurov; Dijana Popevski; Tanja Gramosli; Dashurie Neziri; Dragica Vuckova; Emil Stoicovski; Lidija Veljanovska-Kiridjievska; Katerina Ignevska; Sanja Mehandziska; Elena Ambarkova; Rodney Alexander Rosalia; Zan Mitrev

    doi:10.21203/rs.3.rs-44717/v1 Date: 2020-07-17 Source: ResearchSquare

    Introduction: Our understanding of the COVID-19 MESHD disease has been steadily evolving since the original outbreak in December 2019. Advanced disease is characterised by a hyperinflammatory state, systemic coagulopathies MESHD and multiorgan involvement, in particular respiratory distress. We here describe our initial experience with treating of COVID-19 MESHD patients based on early initiation of extracorporeal blood purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease severity following admission to our dedicated COVID-19 MESHD intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6 HGNC, IL-8 HGNC, TNF-α HGNC, C-Reactive Protein HGNC ( CRP HGNC), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen HGNC, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 - 4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability MESHD (= elevated Fibrinogen HGNC or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease MESHD (= dyspnoea MESHD, hypoxia MESHD, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure MESHD). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome MESHD. 8 Patients have been discharged - average ICU length-of-stay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood cells, stable levels of IL-6 HGNC (< 50 ng/mL) and a decrease of CRP HGNC and Fibrinogen HGNC. Conclusion: Means to monitor COVID-19 MESHD disease severity during hospitalisation are crucial to control disease progression and prevent hyperinflammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging. The combination of systemic heparin anticoagulation regimens and blood purification may prevent hyperinflammation, thromboembolism MESHD during hospitalisation and thus support clinical recovery. 

    Infliximab Attenuates Paediatric Inflammatory Multisystem Syndrome in SARS-CoV-2 (PIMS-TS)

    Authors: Joseph Meredith; Cher-Antonia Khedim; Paul Henderson; David C. Wilson; Richard K. Russell

    id:10.20944/preprints202006.0118.v1 Date: 2020-06-09 Source: Preprints.org

    Paediatric inflammatory multisystem syndrome MESHD temporally associated with SARS-CoV-2 (PIMS-TS) is a newly described condition. It has a spectrum of presentations related to hyperinflammation and cytokine storm. We report the first case of PIMS-TS in a child on established anti- Tumor Necrosis Factor-alpha HGNC (anti- TNF-α HGNC) therapy; a 10 year-old girl with ulcerative colitis MESHD treated with infliximab. The patient had 6-weeks of daily fever MESHD with mucocutaneous, gastrointestinal, renal and hematologic involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia (up to 691 µ/L; normal 15-80 µg/L), C-reactive protein (CRP) HGNC (>100mg/L for >10 days, normal 0-5 mg/L), erythrocyte sedimentation rate (ESR) consistently >100mm/hr (normal 0-15 mm/hr), raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase (LDH), anaemia MESHD and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin (PUO) were negative. The condition was refractory to treatment with intravenous immunoglobulin (IVIG) but improved within 24hrs of high dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow up. Polymerase chain reaction (PCR) and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock or organ failure MESHD. It is postulated that prior anti- TNF-α HGNC therapy attenuated the disease course. Infliximab therapy may interfere with serology testing and produce false negative results. This case supports the need for investigation into infliximab as primary therapy for PIMS-TS.

    Systemic Inflammation and Clinical Outcomes in COVID-19 MESHD: a retrospective study

    Authors: Meijia Wang; Zhenli Huang; Kun Tang; Pengfei Gao; Yanjiao Lu; Shanshan Wang; Tao Wang; Jungang Xie; Jianping Zhao

    doi:10.21203/rs.3.rs-27267/v1 Date: 2020-05-06 Source: ResearchSquare

    Background: COVID-19 MESHD causes epidemics and pandemics worldwide, but the role of pathophysiological parameters particularly systemic inflammation MESHD in COVID-19 MESHD has not been understood. We aimed to investigate clinical outcomes in view of systemic inflammation MESHD in COVID-19 MESHD.Methods:In this retrospective study, the demographic and clinical data of 225 confirmed COVID-19 MESHD cases on admission at Tongji Hospital from January 28 to February 15, 2020, were extracted and analyzed. These patients were categorized by inflammation MESHD state on the basis of the expression of inflammatory factors or classified as severe and non-severe according to 2019 American Thoracic Society / Infectious Disease Society of America guidelines.Results: Among 225 patients with confirmed COVID-19 MESHD, 155 patients (68.9%) categorized into hyperinflammation group and 70 (31.1%) were non- hyperinflammation group. Compared to non-hyperinflammation group, hyperinflammation group more frequently had chest tightness/dyspnea and lymphopenia MESHD, aberrant multiple indexes of organ function including the heart, liver, kidney, and coagulation, with higher level of C-reactive protein HGNC (hsCRP) as well as interleukin (IL)-6, IL-8 HGNC, tumour necrosis MESHD factor α ( TNF-α HGNC), etc. Hyperinflammation group were more likely to admit to intensive care unit (ICU) (52.3% vs 5.7%), receive ventilation (84.5% vs 10.0%) and be with higher mortality (44.5% vs 5.7%) than non-hyperinflammation group. The mortality of severe patients with hyperinflammation (60/99, 60.6%) was significantly higher than without hyperinflammation (2/20, 10.0%). Non-severe patients with hyperinflammation even tended to have higher mortality (9/56, 16.1%) than those in severe cases without hyperinflammation (2/20, 10%).Conclusion: Excessive systemic inflammation MESHD was correlated highly with poor clinical outcomes in COVID-19 MESHD, particularly in severe cases. Non-severe patients with hyperinflammation even tended to have higher mortality than those in severe cases without hyperinflammation.Trial registration: This is a retrospective observational study without a trial registration number.

    Potential of natural astaxanthin in alleviating the risk of cytokine storm and improve health in COVID-19 MESHD: A scoping review

    Authors: Jayanta Talukdar; Bhaskar Bhadra; Santanu Dasgupta; Vinod Nagle

    doi:10.21203/rs.3.rs-26458/v1 Date: 2020-05-02 Source: ResearchSquare

    Background: Natural astaxanthin as a potent anti-oxidant and broad-spectrum anti-inflammatory bioactive molecule plays important role in modulating the immune response, speculated to be a potential supplement to alleviate cytokine release storm in COVID-19 MESHD. Objective: Review of published literature to summarize the rationale for possible benefits of natural astaxanthin to support COVID-19 MESHD patients. Methods: Retrieved relevant literature from electronic databases including Google scholar, PubMed, Scopus, etc. and reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We adapted the article as scoping review. Results: Cytokine release syndrome (CRS) is reported as a common feature in COVID-19 MESHD, which can lead to potentially fatal, hyper-inflammatory acute respiratory distress condition MESHD, diagnosed with elevated serum level of pro-inflammatory cytokines like IL-6 HGNC, CRP HGNC, etc. that positively correlated with disease severity. Anti-inflammatory drug, like tocilizumab, etc. are under clinical trials as anti-CRS therapy. Astaxanthin can potentially alleviate CRS by regulating inflammatory cytokines by inhibiting the activities of NF-kB, TNF-α HGNC, JAK/ STAT-3 HGNC, etc. Available pre-clinical and clinical trials data support its excellent safety, and potential therapeutic and health benefits. Conclusions: Natural astaxanthin has tremendous potential as co-adjunctive supplement, desiring necessary clinical supports on its efficacy and beneficial against COVID-19 MESHD.

    Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 MESHD Pneumonia

    Authors: Jing Gong; Hui Dong; Song Qing Xia; Yi Zhao Huang; Dingkun Wang; Yan Zhao; Wenhua Liu; Shenghao Tu; Mingmin Zhang; Qi Wang; Fuer Lu

    doi:10.1101/2020.02.25.20025643 Date: 2020-02-27 Source: medRxiv

    Aim: The new coronavirus pneumonia MESHD ( COVID-19 MESHD) outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters MESHD on disease progression. This study analyzed blood inflammation MESHD indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation MESHD-related indicators with disease criticality was analyzed. Cut-off values for critically ill MESHD patients were speculated through the ROC curve. ResultsSignificantly, disease severity were associated with age (R=-0.564, P<0.001), interleukin-2 receptor ( IL2R HGNC) (R=-0.534, P<0.001), interleukin-6 HGNC ( IL-6 HGNC) (R=-0.535, P<0.001), interleukin-8 HGNC ( IL-8 HGNC) (R=-0.308, P<0.001), interleukin-10 HGNC ( IL-10 HGNC) (R=-0.422, P<0.001), tumor MESHD tumor HGNC necrosis MESHD factor ( TNF HGNC) (R=-0.322, P<0.001), C-reactive protein HGNC ( CRP HGNC) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=-0.56, P<0.001), neutrophil count (NC) (R=-0.585, P<0.001) and eosinophil counts (EC) (R=-0.299, P=0.01). ConclusionWith following parameters such as age >67.5 years, IL2R HGNC >793.5U/mL, CRP HGNC >30.7ng/mL, ferroprotein >2252g/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 MESHD to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19 MESHD, and IL-6 HGNC, TNF HGNC and IL-8 HGNC might be promising therapeutic targets.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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