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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22269041

RESUMO

BackgroundSince identification, infections by new SARS-CoV-2 variant Omicron are rapidly increasing worldwide. There is huge gap of knowledge regarding virus behaviour in the population from low and middle income countries. Delhi being unique population with a high seropositivity and vaccination rate against COVID-19 infection. We aimed to study the epidemiological and clinical presentations of few early cases of community spread of Omicron infection in the state. MethodsThis is a prospective study where respiratory specimen from all RT-PCR confirmed positive cases between November 25th-December 23rd 2021 collected from five districts of Delhi were subjected to whole genome sequencing. Complete demographic and clinical details were recorded. We also analyzed the formation of local and familial clusters and eventual community transmission. FindingsOut of the 264 cases included during study period, 68.9% (n=182)were identified as Delta and its sub-lineages while 31.06% (n=82) were Omicron with BA.1 as the predominant sub-lineage (73.1%). Most of the Omicron cases were asymptomatic (n=50,61%) and not requiring any hospitalizations. A total of 72 (87.8%) cases were fully vaccinated. 39.1% (n=32) had a history of travel and/or contacts while 60.9 (n=50) showed a community transmission. A steep increase in the daily progression of Omicron cases with its preponderance in the community was observed from 1.8% to 54%. InterpretationThis study is among the first from India to provide the evidence of community transmission of Omicron with significantly increased breakthrough infections, decreased hospitalization rates, and lower rate of symptomatic infections among individuals with high seropositivity against SARS-CoV-2 infections.

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21268451

RESUMO

BackgroundWe conducted a repeat serosurvey in Delhi, India to estimate the seroprevalence of SARS-CoV-2 in the general population and compare the antibody prevalence in the vaccinated and non-vaccinated groups. MethodsThis cross-sectional study was conducted from September 24 to October 14 2021 in 280 wards of Delhi among 27811 participants selected through a multistage sampling technique with housing settlement based stratification. The SARS-CoV-2 immunoglobulin (IgG) antibodies were screened with the VITROS(R) (Ortho Clinical Diagnostics, Raritan, NJ, USA) assay (90% sensitivity, 100% specificity). ResultsA total of 24895 (89.5%) samples were seropositive. The crude seroprevalence was 87.99% (95% CI 89.1, 89.8), weighted for age and sex was 88% (95% CI 87.6, 88.4), and after adjustment of assay performance was estimated as 97.5% (95% CI 97.0, 98.0). The weighted seroprevalence in the 11 districts ranged from 84.9% (South-West district) to 90.8% (East district) Females in all the age-groups (<18, 18-49 and [≥]50) had significantly higher odds of seropositivity (p<0.001). On adjusted analysis, the odds of seroconversion in the participants vaccinated with at-least one dose of either Covid-19 vaccine (Covishield/Covaxin) was more than four times compared to the unvaccinated (aRR 4.2 (3.8, 4.6)). The seroprevalence was also comparable among the complete and partially vaccinated subgroups for both vaccines (Table 4). Most (86.8%) seropositive individuals had a SARS-CoV-2 signal/cut-off [≥]4.0 except in children O_TBL View this table: org.highwire.dtl.DTLVardef@1482d5forg.highwire.dtl.DTLVardef@19ab8a1org.highwire.dtl.DTLVardef@cf675dorg.highwire.dtl.DTLVardef@8b427aorg.highwire.dtl.DTLVardef@b96a54_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 4.C_FLOATNO O_TABLECAPTIONVaccination status and seroprevalence of antibodies to SARS-CoV-2, Delhi, September-October 2021* C_TABLECAPTION C_TBL ConclusionsWe observed IgG antibodies against SARS-CoV-2 in most of the general population of Delhi with likely higher antibody titres in the vaccinated compared to the unvaccinated groups.

3.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21268472

RESUMO

We conducted this study to estimate seroprevalence of neutralizing antibodies in the general population and to further correlate it with the IgG SARS-CoV-2 IgG levels. This present cross-sectional analysis was conducted as a sequel to a state level community-based seroepidemiological study in Delhi, India. A total of 2564 seropositive samples were selected from 25622 seropositive samples through simple random sampling. Neutralizing capacity was estimated by performing a surrogate virus neutralization test with the sVNT (GenScript) assay. Neutralizing antibody against the SARS-CoV-2 virus was operationally considered as detected when the signal inhibition was [≥]30%. A total of 2233 (87.1%, 95% C.I. 85.7, 88.3) of the 2564 SARS-CoV-2 seropositive samples had detectable neutralizing antibodies. On bi-variate analysis but not on adjusted analysis, Covid-19 vaccination showed a statistically significant association with the presence of neutralizing antibodies (p<0.001). The signal/ cut off (S/CO) of SARS-CoV-2 IgG ranged from 1.00 to 22.8 (median 11.40). In samples with S/CO [≥]4.00, the neutralizing antibodies ranged from 94.5 to 100%, while in samples with S/CO <4.00, it ranged from 52.0 to 79.2%. The neutralizing antibody seroprevalence strongly correlated with the S/CO range (r=0.62, p=0.002). In conclusion, in populations with high SARS-CoV-2 seroprevalence, neutralizing antibodies are generated in nearly 9 of 10 seropositive individuals.

4.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21267912

RESUMO

BackgroundThere is a prolonged RT-PCR positivity seen in COVID-19 infected patients up to 2-3 months. We aim to investigate the presence of viral particles inside Extracellular vesicles (EV) and its role in underlying liver disease patients. MethodsSARS CoV2 nasal RT-PCR positive n=78 {n=24(66.6%) chronic liver disease (CLD); n=52 (81.3%) non-liver disease} were studied. SARS CoV2 patients were also followed up for day (d) 7, 14 and 28. Extracellular vesicles were isolated using differential ultracentrifugation. SARS CoV2 RNA was measured using qRT-PCR by Altona Real Star kit. ResultsIn baseline RT-PCR positive patients, SARS-CoV2 RNA inside the EV was present in 64/74 (82%) patients with comparable viral load between VTM and EV (mean 1CT - 0.033{+/-}0.005 vs. 1CT - 0.029{+/-}0.014, p=ns). On follow-up at day 7, of the 24 patients negative for COVID19, 10 (41%) had persistence of virus in the EV (1CT - 0.028{+/-}0.004) and on day 14, 14 of 40 (35%) negative RT-PCR had EVs with SARS CoV2 RNA (1CT - 0.028{+/-}0.06). The mean viral load decreased at day7 and day14 in nasal swab from baseline (p=0.001) but not in EV. SARS-CoV2 RNA otherwise undetectable in plasma, was found to be positive in EV in 12.5% of COVID19 positive patients. Interestingly, significantly prolonged and high viral load was found in EV at day 14 in CLD-COVID19 patients compared to COVID19 alone (p=0.002). The high cellular injury was seen in CLD-COVID19 infected patients with significant high levels of EV associated with endothelial cells and hepatocytes than COVID19 alone (p=0.004; 0.001). ConclusionIdentification of SARS-CoV2 RNA in EV, in RT-PCR negative patients indicates persistence of infection for and likely recurrence of the infection. EV associated RNA may determine the clinical course of subjects with undetectable SARS-CoV2 virus and this may also have relevance in management of chronic liver disease patients.

5.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21263331

RESUMO

BackgroundWe report the findings of a large follow-up community-based serosurvey and correlating it with the COVID-19 test-positivity rate and the case load observed during the peak of the second wave of the Covid-19 pandemic in Delhi, India. MethodsIndividuals of age [≥]5 years were recruited from 274 wards of the state (population [~] 19.6 million) during January 11 to January 22 2021. A total of 100 participants each were included from all the wards for a net sample size of [~]28,000. A multi-stage sampling technique was applied for selection of participants for the household serosurvey. Anti SARS CoV-2 IgG antibodies were detected by using the VITROS assay (90% Sn, 100% Sp). ResultsAntibody positivity was observed in 14,298 (50.76%) of the 28,169 samples. The age, sex and district population weighted seroprevalence of the IgG SARS-CoV-2 was 50.52% (95% C.I. 49.94-51.10) and after adjustment for assay characteristics was 56.13% (95% C.I. 55.49-56.77). On adjusted analysis, participants aged [≥]50 years, of female gender, housewives, having ever lived in containment zones, urban slum dwellers, and diabetes or hypertensive patients had significantly higher odds of SARS-CoV-2 antibody positivity. The peak infection rate and the test positivity rate since October 2020 were initially observed in mid-November 2020 with a subsequent steep declining trend, followed by a period of persistently low case burden lasting until the first week of March 2021. This was followed by a steady increase followed by an exponential surge in infections from April 2021 onwards culminating in the second wave of the pandemic. ConclusionsThe presence of infection induced immunity from SARS-CoV-2 even in more than one in two people can be ineffective in protecting the population.

6.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21259546

RESUMO

BackgroundIndia saw a massive surge and emergence of SARS CoV2 variants. We elucidated clinical and humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19 vaccine in healthcare workers (HCWs). MethodsThe study was conducted on 1858 HCWs receiving two doses of ChAdOx1 nCoV-19 vaccine. Serial blood samples were collected to measure SARS CoV2 IgG and neutralizing antibodies. 46 RT-PCR positive samples from VBT infections were subjected to whole genome sequencing (WGS). ResultsInfection was confirmed in 219 (11.79%) HCWs of which 21.46% (47/219) were non-vaccinated, significantly more (p <0.001) than 9.52% (156/1639) vaccinated group. VBT infections were significantly higher in doctors and nurses compared to other hospital staff (p <0.001). Unvaccinated individuals had 1.57 times higher risk of infection compared to partially vaccinated (p 0.02) and 2.49 times than fully vaccinated (<0.001). Partially vaccinated were at higher risk of infection than fully vaccinated (RR 1.58,p 0.01). There were 3 (1.36%) severe cases and 1 death in unvaccinated group compared to none in the vaccinated. Non-response after 14 days of second dose was seen in 6.5% (3/46) and low antibody levels (1-4.62 S/CO) in 8.69% (4/46). Delta variant (B.1.617.2) was dominant (69.5%) and reinfection was documented in 4 (0.06%) HCWs. ConclusionsNearly one in ten vaccinated HCWs can get infected, more so with only single dose (13.65%) than two doses (8.62%). Fully vaccinated are better protected with higher humoral immune response. Genomic analysis revealed an alarming rise of Delta variant (B.1.617.2) in VBT infections.

7.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-423415

RESUMO

RationaleCOVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. MethodsrfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. Measurements and Main ResultsIn-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5M rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 M). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5M rfhSP-D. ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.

8.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20219337

RESUMO

BackgroundThe role of convalescent plasma (COPLA) for the treatment of severely ill Corona Virus Disease-2019 is under investigation. We compared the efficacy and safety of convalescent plasma with fresh frozen plasma (FFP) in severe COVID-19 patients. Methods and findingsThis was an open-label, single-centre phase II RCT on 29 patients with severe COVID-19 from India. One group received COPLA with standard medical care (SMC) (n=14), and another group received FFP with SMC (n=15). A total of 29 patients were randomized in the two treatment groups. Eleven out of 14 (78.5%) patients remained free of ventilation at day seven in the intervention arm while the proportion was 14 out of 15 (93.3 %) in the control arm (p= 0.258). The median reductions in RR per min at 48-hours in COPLA-group and FFP group were -6.5 and -3 respectively [p=0.004] and at day seven were -14.5 and -10 respectively (p=0.008). The median improvements in percentage O2 saturation at 48-hours were 6.5 and 2 respectively [p=0.001] and at day seven were 10 and 7.5 respectively (p=0.026). In the COPLA-group, the median improvement in PaO2/FiO2 was significantly superior to FFP at 48-hours [41.94 and 231.15, p=0.009], and also at day-7 [5.55 and 77.01 p<0.001]. We did not find significant differences in hospitalization duration between the groups (0.08). ConclusionCOPLA therapy resulted in rapid improvement in respiratory parameters and shortened time to clinical recovery, although no significant reduction in mortality was observed in this pilot trial. We need larger trials to draw conclusive evidence on the use of Convalescent plasma in COVID-19. This trial is registered with ClinicalTrial.gov (identifier: NCT04346446).

9.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20166330

RESUMO

BackgroundRespiratory viral infections are an important cause of acute respiratory tract infections. They are caused by both Influenza and non influenza viruses. Respiratory viral infections are known to be associated with severe clinical outcome especially in the critically ill. A constant surveillance is needed for early etiological identification which can help in timely and appropriate management and will further help in prevention of indiscriminate use of antibiotics in patients with viral etiology. MethodsIn this retrospective study, clinical records of all adult liver disease patients with clinically confirmed ARI, whose request for respiratory viral testing were received in the virology laboratory during September 2016 - March 2019 were reviewed. Respiratory viruses were identified by real time PCR on FilmArray 2.0 instrument (BioFire Diagnostics, Utah, USA) using Respiratory panel as per the manufacturers instructions. ResultsOf the 603 patients of liver disease with clinically confirmed influenza like illness, over all incidence of respiratory viral infection was 24.3% (n= 147). Infections by non-influenza viruses (87, 59.1%) were more than influenza group of viruses. Mortality was higher in non influenza group (43, 49.4%) as compared to influenza (24, 40%) [p=0.015] being maximum in Rhinovirus, 22 (32.8%). Two peaks were observed in both influenza and non influenza groups, first in the months of January and February and the other one in August and October. ConclusionWith the emergence of SARS-CoV-2 it has now become imperative for a constant surveillance of the non influenza viruses for early etiological identification of the respiratory viral infection for proper and timely management in the critically ill. HighlightsO_LIPatients with liver cirrhosis having Respiratory viral infections have a poor outcome in terms of morbidity and mortality. C_LIO_LIMortality associated with non influenza viruses (NIV) is more as compared to influenza virus infections. C_LIO_LICOVID-19 pandemic and higher mortality in NIVs warrants a constant monitoring of respiratory viral infections. C_LI

10.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20147082

RESUMO

Rapid diagnosis and precise prognostication of SARS-CoV-2 infection remains a major challenge. A multi-omic approach was adopted, and in the discovery phase, global proteome/metaproteome/metabolome were analysed in the respiratory specimens of SARS-CoV-2 positive [n=20], negative [n=20], and H1N1 positive [n=5] cases. We identified MX1 (MX Dynamin Like GTPase 1) and WARS (Tryptophan--tRNA ligase) as clues to viral diagnosis and validated in 200 SARS-CoV-2 suspects. MX1 >30pg/ml and WARS >25ng/ml segregated virus positives patients [(AUC=94%CI(0.91-0.97)]. Distinct increase in SARS-CoV-2 induced immune activation, metabolic reprograming and a decrease in oxygen transport, wound healing, fluid regulation, vitamin and steroid metabolism was seen (p<0.05). Multi-omics profiling correlated with viraemia and segregated asymptomatic COVID-19 patients. Additionally, the multiomics approach identified increased respiratory pathogens [Burkholderiales, Klebsiella pneumonia] and decreased lactobacillus salivarius (FDR<0.05, p<0.05) in COVID-19 specimens. ConclusionNovel proteins [MX1 and WARS] can rapidly and reliably diagnose SARS-CoV-2 infection and identify asymptomatic and mild disease.

11.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20128793

RESUMO

IntroductionTimely diagnosis is essential for the containment of the disease and breaks in the chain of transmission of SARS-CoV-2. The present situation demands countries to scale up their testing and design innovative strategies to conserve diagnostic kits and reagents. The pooling of samples saves time, manpower, and most importantly diagnostic kits and reagents. In the present study, we tried to define the pool size that could be applied with acceptable confidence for testing. Material and methodsWe used repeatedly tested positive clinical sample elutes having different levels of SARS CoV 2 RNA and negative sample elutes to prepare seven series of 11 pools each, having pool sizes ranging from 2 to 48 samples to estimate the optimal pool size. Each pool had one positive sample elute in different compositions. All the pools were tested by SARS CoV 2 RT-qPCR. ResultsOut of the 77 pools, only 53 (68.8%) were found positive. The sensitivity of pools of 2 to 48 samples was decreased from 100% (95% CL; 98.4-100) to 41.41% (95% CL; 34.9-48.1). The maximum size of the pool with acceptable sensitivity (>95%) was found to be of 6 samples. For the pool size of 6 samples, the sensitivity was 97.8% and the efficiency of pooling was 0.38. ConclusionThe pooling of samples is a practical way for scaling up testing and ultimately containing the further spread of the COVID-19 pandemic.

12.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20079095

RESUMO

BackgroundCorona virus disease 2019 (COVID-19) which initially started as a cluster of pneumonia cases in the Wuhan city of China has now become a full blown pandemic. Timely diagnosis of COVID-19 is the key in containing the pandemic and breaking the chain of transmission. In low and middle income countries availability of testing kits has become the major bottle neck in testing. Novel methods like pooling of samples are the need of the hour. MethodExtracted RNA samples were randomly placed in pools of 8 on a 96 well plate. Both individual RNA (ID) and pooled RNA RT-qPCR for the screening E gene were done in the same plate and the positivity for the E gene was seen. ResultsThe present study demonstrated that pool testing with 8 RNA samples can easily detect even up to a single positive sample with Ct value as high as 38. The present study also showed that the results of pool testing is not affected by number of positive samples in a pool. ConclusionPooling of 8 RNA samples can reduce the time and expense by one eighth, and can help expand diagnostic capabilities, especially during constrained supply of reagents and PCR kits for the diagnosis of SARS-CoV-2 infection.

13.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-039198

RESUMO

The recent Coronavirus Disease 2019 (COVID-19) causes an immense health crisis to global public health. The COVID-19 is the etiologic agent of a recently arose disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Presently, there is no vaccine available against this emerged viral disease. Therefore, it is indeed a need of the hour to develop an effectual and safe vaccine against this decidedly pandemic disease. In the current study, we collected SARS-CoV-2 genome which is prominent in India against human host, further more using reverse vaccinology here we claim effective vaccine candidates that can be mile stone in battle against COVID19. This novel study divulged one promising antigenic peptide GVYFASTEK from surface glycoprotein (protein accession no. - QIA98583.1) of SARS-CoV-2, which was predicated to be interacted with MHC alleles and showed up to 90% conservancy and high value of antigenicity. Subsequently, the molecular docking and simulation studies were verified molecular interaction of this prime antigenic peptide with the residues of HLA-A*11-01 allele for MHC Class I. After vigorous analysis, this peptide was predicted to be suitable epitope which is capable to induce the strong cell-mediated immune response against the SARS-CoV-2. Consequences from the current study could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable and virtuous platform to provide timely countermeasure of this dangerous pandemic disease, COVID-19.

14.
Artigo | WPRIM (Pacífico Ocidental) | ID: wpr-832220

RESUMO

Background/Aims@#Acute exacerbations of chronic hepatitis B (CHB-AEs) are common in endemic areas and are often presumed to be acute hepatitis B (AHB) due to their similarities in clinical and serological pictures, presenting a major diagnostic dilemma. This study aimed to identify laboratory markers for differentiating between the two groups, and to establish the cut-off value for significant markers. @*Methods@#A retrospective analysis of records was conducted for patients who presented with clinical features of acute hepatitis along with hepatitis B surface antigen (HBsAg) and IgM antibody to hepatitis B core antigen (IgM anti-HBc) positivity from May 2015 to May 2017. A total of 172 patients were enrolled and grouped as AHB (n=89) and CHB-AE (n=83) based on their history of hepatitis B virus infection and duration of HBsAg persistence. Virological and biochemical parameters were analyzed and compared. Cut-off values, sensitivity, and specificity of the variables were calculated. @*Results@#The median value of signal by cut-off (S/Co) ratio for IgM anti-HBc was significantly higher in AHB group (30.44) compared to CHB-AE group (8.63) with a sensitivity and specificity of 97% and 84%, respectively, at a cut-off of 20.5 (P<0.01). The mean international normalized ratio (INR) was significantly greater in CHB-AE (1.88±1.24) group compared to AHB group (1.62±0.17) with a sensitivity and specificity of 57.9% and 45.1%, respectively, at a cut-off value of 1.27. @*Conclusions@#A value of 20.5 S/Co of IgM anti-HBc and 1.27 INR could be helpful in differentiating between AHB and CHB-AE.

15.
J Family Med Prim Care ; 5(1): 108-13, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27453853

RESUMO

INTRODUCTION: Chronic noncommunicable diseases (NCDs) including cardiovascular diseases (CVDs) are the leading cause of death in the world, and their incidence is rising rapidly due to increasing rates of risk factors such as hypertension, dyslipidemia, diabetes, obesity, physical inactivity, and tobacco use. These risk factors track from childhood to adulthood, and their distribution varies among males and females; hence, there is a need to determine risk factor prevalence among adolescent age group so as to plan preventive strategies. OBJECTIVE: To determine the distribution of risk factors of CVDs amongst high school boys and girls of urban Dibrugarh, Assam. SUBJECTS AND METHODS: A cross-sectional study was conducted from October 2012 to June 2013 in the schools of urban Dibrugarh, Assam wherein data was collected from 1000 students of Class 8-10 using multistage random sampling and risk factors were assessed using WHO steps methodology. STATISTICAL ANALYSIS: Statistical analysis was done using SPSS 16 software and test of differences used were Chi-square test and t-test. RESULTS: The prevalence of ever tobacco use was 32.3% among boys and 6.6% among girls (P < 0.001) while ever alcohol use was reported by 11.9% boys and 1% girls (P < 0.001). Prevalence of overweight and hypertension was found to be higher among girls (11.7% and 24.1%) as compared to boys (6.8% and 18.1%). Prevalence of hypercholesterolemia was higher among boys while high triglycerides levels were more prevalent among girls. CONCLUSION: The study revealed a high prevalence of various risk factors among boys and girls. There is a need to reduce the risk factor prevalence of CVD among this group of the population to address the future epidemic of NCD. Different health promotional activities need to be implemented to target boys and girls as the risk factor distribution among these groups is different.

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