Displaying publications 1 - 20 of 173 in total

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  1. Firdose A, Chong NHH, Ramli R, Aqma WS
    Lett Appl Microbiol, 2023 Feb 16;76(2).
    PMID: 36702549 DOI: 10.1093/lambio/ovad013
    The aim of this study was to test the antimicrobial, antiadhesive, and antibiofilm activities of a rhamnolipid extracted from Pseudomonas aeruginosa UKMP14T previously isolated from oil-contaminated soil in Malaysia against ESKAPE (i.e. multidrug resistant) pathogens. Zones of inhibition in an agar well diffusion assay were observed at 50 µg mL-1 concentrations of rhamnolipid for all the ESKAPE bacteria. The MIC and MBC values ranged between 7.81-62.5 µg mL-1 and 31.25-1000 µg mL-1, respectively. Percent killing was recorded to be >90% except for Klebsiella pneumoniae (86.84%). Furthermore, antiadhesion studies showed that there was 76% hindrance in attachment of Enterococcus faecium and 91% in Acinetobacter baumannii at 4 × MIC. The highest inhibition in adhesion was found at 4 × MIC, which was 46% for Ac. baumannii and 62% for Enterococcus faecium. Finally, the antibiofilm capability of the rhamnolipid was determined, which ranged between 25%-76% in Ac. baumannii and 35%-88% in Enterococcus faecium. To the best of our knowledge, this is the first study to include research on antimicrobial, antiadhesive and antibiofilm activities of rhamnolipid from the local isolate Ps. aeruginosa UKMP14T against ESKAPE bacteria. Obtained results suggest that this rhamnolipid can be exploited commercially for the production of novel antibiotics.
    Matched MeSH terms: Klebsiella pneumoniae
  2. Yeo CC
    Mol Microbiol, 2018 05;108(4):331-335.
    PMID: 29624768 DOI: 10.1111/mmi.13958
    GCN5-related N-acetyltransferase (GNAT) is a huge superfamily of proteins spanning the prokaryotic and eukaryotic domains of life. GNAT proteins usually transfer an acetyl group from acetyl-CoA to a wide variety of substrates ranging from aminoglycoside antibiotics to large macromolecules. Type II toxin-antitoxin (TA) modules are typically bicistronic and widespread in bacterial and archael genomes with diverse cellular functions. Recently, a novel family of type II TA toxins was described, which presents a GNAT-fold and functions by acetylating charged tRNA thereby precluding translation. These GNAT toxins are usually associated with a corresponding ribbon-helix-helix-fold (RHH) antitoxin. In this issue, Qian et al. describes a unique GNAT-RHH TA system, designated KacAT, from a multidrug resistant strain of the pathogen, Klebsiella pneumoniae. As most type II TA loci, kacAT is transcriptionally autoregulated with the KacAT complex binding to the operator site via the N-terminus region of KacA to repress kacAT transcription. The crystal structure of the KacT toxin is also presented giving a structural basis for KacT toxicity. These findings expand our knowledge on this newly discovered family of TA toxins and the potential role that they may play in antibiotic tolerance and persistence of bacterial pathogens.
    Matched MeSH terms: Klebsiella pneumoniae*
  3. Lukianova AA, Shneider MM, Evseev PV, Egorov MV, Kasimova AA, Shpirt AM, et al.
    Int J Mol Sci, 2023 Dec 09;24(24).
    PMID: 38139119 DOI: 10.3390/ijms242417288
    Klebsiella pneumoniae is a pathogen associated with various infection types, which often exhibits multiple antibiotic resistance. Phages, or bacterial viruses, have an ability to specifically target and destroy K. pneumoniae, offering a potential means of combatting multidrug-resistant infections. Phage enzymes are another promising therapeutic agent that can break down bacterial capsular polysaccharide, which shields K. pneumoniae from the immune response and external factors. In this study, Klebsiella phage K5 was isolated; this phage is active against Klebsiella pneumoniae with the capsular type K21. It was demonstrated that the phage can effectively lyse the host culture. The adsorption apparatus of the phage has revealed two receptor-binding proteins (RBPs) with predicted polysaccharide depolymerising activity. A recombinant form of both RBPs was obtained and experiments showed that one of them depolymerised the capsular polysaccharide K21. The structure of this polysaccharide and its degradation fragments were analysed. The second receptor-binding protein showed no activity on capsular polysaccharide of any of the 31 capsule types tested, so the substrate for this enzyme remains to be determined in the future. Klebsiella phage K5 may be considered a useful agent against Klebsiella infections.
    Matched MeSH terms: Klebsiella pneumoniae/metabolism
  4. Ngeow YF, Cheng HJ, Chen JW, Yin WF, Chan KG
    Sensors (Basel), 2013;13(11):15242-51.
    PMID: 24284772 DOI: 10.3390/s131115242
    Klebsiella pneumoniae is one of the most common Gram-negative bacterial pathogens in clinical practice. It is associated with a wide range of disorders, ranging from superficial skin and soft tissue infections to potentially fatal sepsis in the lungs and blood stream. Quorum sensing, or bacterial cell-cell communication, refers to population density-dependent gene expression modulation. Quorum sensing in Proteobacteria relies on the production and sensing of signaling molecules which are mostly N-acylhomoserine lactones. Here, we report the identification of a multidrug resistant clinical isolate, K. pneumoniae strain CSG20, using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We further confirmed quorum sensing activity in this strain with the use of high resolution tandem liquid chromatography quadrupole mass spectrometry and provided evidence K. pneumoniae strain CSG20 produced N-hexanoyl-homoserine lactone (C6-HSL). To the best of our knowledge, this is the first report on the production of N-hexanoylhomoserine lactone (C6-HSL) in clinical isolate K. pneumoniae.
    Matched MeSH terms: Klebsiella pneumoniae/drug effects; Klebsiella pneumoniae/metabolism*
  5. Hanafin PO, Abdul Rahim N, Sharma R, Cess CG, Finley SD, Bergen PJ, et al.
    CPT Pharmacometrics Syst Pharmacol, 2023 Mar;12(3):387-400.
    PMID: 36661181 DOI: 10.1002/psp4.12923
    Carbapenemase-resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time-kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h. A mechanism-based model (MBM) was developed using time-kill data in S-ADAPT describing PMB-CHL PD activity against each isolate. Previously published results of PMB (1 mg/L continuous infusion) and CHL (Cmax : 8 mg/L; bolus q6h) mono and combination regimens were evaluated using an in vitro one-compartment dynamic infection model against a KP clinical isolate (108 CFU/ml inoculum) over 24 h to obtain bacterial samples for multi-omics analyses. The differentially expressed genes and metabolites in these bacterial samples served as input to develop a partial least squares regression (PLSR) in R that links PD responses with the multi-omics responses via a multi-omics pathway analysis. PMB efficacy was increased when combined with CHL, and the MBM described the observed PD well for all strains. The PLSR consisted of 29 omics inputs and predicted MBM PD response (R2  = 0.946). Our analysis found that CHL downregulated metabolites and genes pertinent to lipid A, hence limiting the emergence of PMB resistance. Our workflow linked insights from analysis of multi-omics data with MBM to identify biological mechanisms explaining observed PD activity in combination therapy.
    Matched MeSH terms: Klebsiella pneumoniae/genetics; Klebsiella pneumoniae/metabolism
  6. Hassoun-Kheir N, Guedes M, Arieti F, Pezzani MD, Gladstone BP, Robotham JV, et al.
    Euro Surveill, 2024 Nov;29(47).
    PMID: 39574390 DOI: 10.2807/1560-7917.ES.2024.29.47.2400212
    To reduce antimicrobial resistance (AMR), pathogen-specific AMR burden data are crucial to guide target selection for research and development of vaccines and monoclonal antibodies (mAbs). We identified knowledge gaps through previously conducted systematic reviews, which informed a Delphi expert consultation on future AMR research priorities and harmonisation strategies to support data-driven decision-making. Consensus (≥80% agreement) on importance and feasibility of research topics was achieved in two rounds, involving 24 of 39 and 19 of 24 invited experts, respectively. Priority pathogens and resistance profiles for future research were identified: third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli, for bloodstream and urinary tract infections, respectively, and meticillin-resistant Staphylococcus aureus for surgical-site infections. Prioritised high-risk populations included surgical, haemato-oncological and transplant patients. Mortality and resource use were prioritised as health-economic outcomes. The importance of age-stratified data and inclusion of a non-infected comparator group were highlighted. This agenda provides guidance for future research to fill knowledge gaps and support data-driven selection of target pathogens and populations for new preventive and treatment strategies, specifically vaccines and mAbs, to effectively address the AMR burden in Europe. These research priorities are also relevant to improve the evidence base for future AMR burden estimates.
    Matched MeSH terms: Klebsiella pneumoniae/drug effects; Klebsiella pneumoniae/immunology
  7. Lau MY, Ponnampalavanar S, Lee WS, Jabar KA, Chua KH, Idris N, et al.
    J Infect Chemother, 2020 Oct;26(10):1058-1061.
    PMID: 32546330 DOI: 10.1016/j.jiac.2020.05.009
    The emergence of carbapenemase-producing Enterobacteriaceae has become a major global concern. OXA-48-like carbapenemase gene and its variants have been increasingly reported worldwide. This study reported the first OXA-181-producing Klebsiella quasipneumoniae isolate in Malaysia. This bacterium was isolated from blood specimen of a three-year-old boy with Alagille syndrome who had liver biopsy on October 2016. He had undergone liver transplant in India ten months previously. The genotypic and phenotypic characteristics of the strain were elucidated in this study. To our best knowledge, this is the first report of OXA-181-producing K. quasipneumoniae in Malaysia.
    Matched MeSH terms: Klebsiella pneumoniae/genetics
  8. Dulyayangkul P, Wan Nur Ismah WAK, Douglas EJA, Avison MB
    Antimicrob Agents Chemother, 2020 06 23;64(7).
    PMID: 32312773 DOI: 10.1128/AAC.02208-19
    Meropenem-vaborbactam resistance in Klebsiella pneumoniae isolates is associated with loss-of-function mutations in the OmpK35 and OmpK36 porins. We identify two previously unknown loss-of-function mutations that confer cefuroxime resistance in K. pneumoniae isolates. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor that controls capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem-vaborbactam in a KPC-3-producing K. pneumoniae isolate.
    Matched MeSH terms: Klebsiella pneumoniae
  9. Baqer AA, Nor NSM, Alagely HS, Musa M, Adnan NA
    Pol Merkur Lekarski, 2023;51(1):35-41.
    PMID: 36960898 DOI: 10.36740/Merkur202301105
    OBJECTIVE: Aim: Klebsiella pneumonia has emerged as an increasingly important cause of community-acquired nosocomial infections and many of these strains are highly virulent and exhibit a strong propensity to spread. Infections cause by K. pneumonia produces carbapen¬emase (KPC) enzyme and can be difficult to treat since only a few antibiotics are effective against them. Bacteriophage targeting this strain can be an alternative treatment. Characterisation of bacteriophage is utmost important in assisting the application of bacteriophage in phage therapy.

    PATIENTS AND METHODS: Materials and methods: In the present study, the lytic bacteriophage, k3w7, isolated by the host Klebsiella pneumoniae kP2 was characterised using transmission electron microscope (TEM), plaque assay, and restriction digestive enzyme to investigate mor¬phology, host spectrum, bacteriophage life cycle and stability accordingly.

    RESULTS: Results and conclusions: As shown by TEM, k3w7 was observed to have the characteristic of icosahedral heads 100 nm and contractile sheaths 120 nm suggesting it belongs to the family of myoviridae.The Investigation has done on the phage growth cycle showed a short latent period of 20 min and a burst size of approximately 220 plaque forming units per infected cell. Stability test showed the phage was stable over a wide range of pH and temperatures. According to restriction analysis, k3w7 had 50 -kb double-stranded DNA genome as well as the heterogeneous nature of genetic material. These findings suggest that K3W7 has a potential use in therapy against infections caused by K. pneumonia produces carbapenemase.

    Matched MeSH terms: Klebsiella pneumoniae
  10. Mahdi Yahya Mohsen S, Hamzah HA, Muhammad Imad Al-Deen M, Baharudin R
    Malays J Med Sci, 2016 Mar;23(2):14-20.
    PMID: 27547110 MyJurnal
    To assess antimicrobial susceptibility of extended-spectrum β-lactamase- (ESBL-) producing Klebsiella pneumoniae and Escherichia coli isolates from Hospital Tengku Ampuan Afzan (HTAA), as well as to identify ESBL genes.
    Matched MeSH terms: Klebsiella pneumoniae
  11. Al-Marzooq F, Yusof MY, Tay ST
    Jpn J Infect Dis, 2013;66(6):555-7.
    PMID: 24270152
    Matched MeSH terms: Klebsiella pneumoniae/classification*; Klebsiella pneumoniae/drug effects; Klebsiella pneumoniae/enzymology; Klebsiella pneumoniae/genetics
  12. Raju SV, Sarkar P, Pasupuleti M, Saraswathi NT, Arasu MV, Al-Dhabi NA, et al.
    PMID: 33465517 DOI: 10.1016/j.cbpc.2021.108974
    Development of antimicrobial drugs against multidrug-resistant (MDR) bacteria is a great focus in recent years. TG12, a short peptide molecule used in this study was screened from tachykinin (Tac) protein of an established teleost Channa striatus (Cs) transcriptome. Tachykinin cDNA has 345 coding sequence, that denotes a protein contained 115 amino acids; in which a short peptide (TG12) was identified at 83-94. Tachykinin mRNA upregulated in C. striatus treated with Aeromonas hydrophila and Escherichia coli lipopolysaccharide (LPS). The mRNA up-regulation was studied using real-time PCR. The up-regulation tachykinin mRNA pattern confirmed the immune involvement of tachykinin in C. striatus during infection. Further, the identified peptide, TG12 was synthesized and its toxicity was demonstrated in hemolytic and cytotoxic assays using human erythrocytes and human dermal fibroblast cells, respectively. The toxicity study exhibited that the toxicity of TG12 was similar to negative control, phosphate buffer saline (PBS). Moreover, the antibiogram of TG12 was active against Klebsiella pneumonia ATCC 27736, a major MDR bacterial pathogen. Further, the antimicrobial activity of TG12 against pathogenic bacteria was screened using minimum inhibitory concentration (MIC) and anti-biofilm assays, altogether TG12 showed potential activity against K. pneumonia. Fluorescence assisted cell sorter flow cytometer analysis (FACS) and field emission scanning electron microscopy (FESEM) was carried on TG12 with K. pneumonia; the results showed that TG12 significantly reduced K. pneumonia viability as well as TG12 disrupt its membrane. In conclusion, TG12 of CsTac is potentially involved in the antibacterial immune mechanisms, which has a prospectus efficiency in pharma industry against MDR strains, especially K. pneumonia.
    Matched MeSH terms: Klebsiella pneumoniae/drug effects*
  13. Al-Khdhairawi A, Sanuri D, Akbar R, Lam SD, Sugumar S, Ibrahim N, et al.
    Comput Biol Chem, 2023 Feb;102:107800.
    PMID: 36516617 DOI: 10.1016/j.compbiolchem.2022.107800
    Antimicrobial peptides (AMPs) are short peptides with a broad spectrum of antimicrobial activity. They play a key role in the host innate immunity of many organisms. The growing threat of microorganisms resistant to antimicrobial agents and the lack of new commercially available antibiotics have made in silico discovery of AMPs increasingly important. Machine learning (ML) has improved the speed and efficiency of AMP discovery while reducing the cost of experimental approaches. Despite various ML platforms developed, there is still a lack of integrative use of ML platforms for AMP discovery from publicly available protein databases. Therefore, our study aims to screen potential AMPs with antibiofilm properties from databases using ML platforms, followed by protein-peptide molecular docking analysis and molecular dynamics (MD) simulations. A total of 5850 peptides classified as non-AMP were screened from UniProtKB and analyzed using various online ML platforms (e.g., CAMPr3, DBAASP, dPABBs, Hemopred, and ToxinPred). Eight potential AMP peptides against Klebsiella pneumoniae with antibiofilm, non-toxic and non-hemolytic properties were then docked to MrkH, a transcriptional regulator of type 3 fimbriae involved in biofilm formation. Five of eight peptides bound more strongly than the native MrkH ligand when analyzed using HADDOCK and HPEPDOCK. Following the docking studies, our MD simulated that a Neuropeptide B (Peptide 3) bind strongly to the MrkH active sites. The discovery of putative AMPs that exceed the binding energies of the native ligand underscores the utility of the combined ML and molecular simulation strategies for discovering novel AMPs with antibiofilm properties.
    Matched MeSH terms: Klebsiella pneumoniae*
  14. Zulkifli MH, Teh LK, Lee LS, Zakaria ZA, Salleh MZ
    Genome Announc, 2013;1(4).
    PMID: 23950113 DOI: 10.1128/genomeA.00418-13
    Klebsiella pneumoniae PR04 was isolated from a patient hospitalized in Malaysia. The draft genome sequence of K. pneumoniae PR04 shows differences compared to the reference sequences of K. pneumoniae strains MGH 78578 and NTUH-K2044 in terms of their genomic structures.
    Matched MeSH terms: Klebsiella pneumoniae
  15. Yin WF, Purmal K, Chin S, Chan XY, Koh CL, Sam CK, et al.
    Sensors (Basel), 2012;12(3):3472-83.
    PMID: 22737019 DOI: 10.3390/s120303472
    Bacteria communicate by producing quorum sensing molecules called autoinducers, which include autoinducer-1, an N-hexanoyl homoserine lactone (AHL), and autoinducer-2. Bacteria present in the human oral cavity have been shown to produce autoinducer-2, but not AHL. Here, we report the isolation of two AHL-producing Klebsiella pneumoniae strains from the posterior dorsal surface of the tongue of a healthy individual. Spent culture supernatant extracts from K. pneumoniae activated the biosensors Agrobacterium tumefaciens NTL4(pZLR4) and Escherichia coli [pSB401], suggesting the presence of both long and short chain AHLs. High resolution mass spectrometry analyses of these extracts confirmed that both K. pneumoniae isolates produced N-octanoylhomoserine lactone and N-3-dodecanoyl-L-homoserine lactone. To the best of our knowledge, this is the first report of the isolation of K. pneumoniae from the posterior dorsal surface of the human tongue and the production of these AHLs by this bacterium.
    Matched MeSH terms: Klebsiella pneumoniae/classification; Klebsiella pneumoniae/isolation & purification*; Klebsiella pneumoniae/metabolism
  16. Jiménez-Castellanos JC, Wan Nur Ismah WAK, Takebayashi Y, Findlay J, Schneiders T, Heesom KJ, et al.
    J Antimicrob Chemother, 2018 Jan 01;73(1):88-94.
    PMID: 29029194 DOI: 10.1093/jac/dkx345
    Objectives: In Klebsiella pneumoniae, overproduction of RamA results in reduced envelope permeability and reduced antimicrobial susceptibility but clinically relevant resistance is rarely observed. Here we have tested whether RamA overproduction can enhance acquired β-lactam resistance mechanisms in K. pneumoniae and have defined the envelope protein abundance changes upon RamA overproduction during growth in low and high osmolarity media.

    Methods: Envelope permeability was estimated using a fluorescent dye accumulation assay. β-Lactam susceptibility was measured using disc testing. Total envelope protein production was quantified using LC-MS/MS proteomics and transcript levels were quantified using real-time RT-PCR.

    Results: RamA overproduction enhanced β-lactamase-mediated β-lactam resistance, in some cases dramatically, without altering β-lactamase production. It increased production of efflux pumps and decreased OmpK35 porin production, though micF overexpression showed that OmpK35 reduction has little impact on envelope permeability. A survey of K. pneumoniae bloodstream isolates revealed ramA hyperexpression in 3 of 4 carbapenemase producers, 1 of 21 CTX-M producers and 2 of 19 strains not carrying CTX-M or carbapenemases.

    Conclusions: Whilst RamA is not a key mediator of antibiotic resistance in K. pneumoniae on its own, it is potentially important for enhancing the spectrum of acquired β-lactamase-mediated β-lactam resistance. LC-MS/MS proteomics analysis has revealed that this enhancement is achieved predominantly through activation of efflux pump production.

    Matched MeSH terms: Klebsiella pneumoniae/drug effects*; Klebsiella pneumoniae/genetics; Klebsiella pneumoniae/metabolism*
  17. Al-Marzooq F, Ngeow YF, Tay ST
    Int J Antimicrob Agents, 2015 Apr;45(4):445-6.
    PMID: 25631676 DOI: 10.1016/j.ijantimicag.2014.12.013
    Matched MeSH terms: Klebsiella pneumoniae/enzymology*; Klebsiella pneumoniae/genetics; Klebsiella pneumoniae/isolation & purification
  18. Mohamed Paid, Y., Muhammad Amir, K., Mustafa Bakri, A., Low, S.H.
    MyJurnal
    An outbreak of pneumonia occurred among 1,491 recruits undergoing training at the Army Recruit Training Center, Port Dickson, Negeri Sembihxn, between july to August 2000. They had reported for training 2 weeks before and were placed in new modern concrete 4 floors buiMing with well ventilated dorm. A total of 70 recruits were ajjfected and one died. The attack rate was 4.7% and the case fatality rate was 1.4%. The outbreak ajfected recruits from all the jive companies; J (21/299,
    30.0%) , G (19/298, 27.1 %), I (14/298, 20.0%), H (13/298, 18.6%) and F (3/298, 4.3%) . The main presenting symptoms were fever (68/70, 97.1%), cough (62/70, 88.6%), and chest pain (35/70, 50 .0%) . This was a common site outbreak with the mode of spread from person to person through infected droplet. The outbreak has three peaks, which was at lst, 4th and 6th week respectively and lasted for eight weeks. The organisms isobted through blood culture were Streptococcal pneumoniae and Klebsiella pneumoniae. All the cases were managed and treated as in-patients at four dijjferent hospitals depending on the severity of the illness. The main control activities carried out were separation of ill recruits from the healthy, reducing the number of recruits in the dormitories and encourage recruits to drink a lot of water while in training.
    Matched MeSH terms: Klebsiella pneumoniae
  19. Kong ZX, Karunakaran R, Abdul Jabar K, Ponnampalavanar S, Chong CW, Teh CSJ
    Microb Drug Resist, 2021 Oct;27(10):1319-1327.
    PMID: 33877888 DOI: 10.1089/mdr.2020.0096
    Background: Hypermucoviscous carbapenem-resistant Klebsiella pneumoniae (hmCRKp) is emerging globally and approaching the worst-case scenario in health care system. Aims: The main objective in this study was to determine the hypermucoviscous characteristics among the carbapenem-resistant K. pneumoniae (CRKp) isolated from a teaching hospital in Malaysia. The association of hypermucoviscous phenotype with the virulence traits and clinical presentations were also investigated. Methods: A retrospective study was conducted in University Malaya Medical Centre (UMMC). The presence of hypermucoviscous K. pneumoniae was identified among a collection of CRKp clinical isolates (first isolate per patient) from 2014 to 2015 using string test. Correlation between clinical and microbial characteristics of the hmCRKp was investigated. Results: A total of nine (7.5%) hmCRKp were detected among 120 CRKp isolates. Majority of the isolates were hospital acquired or health care-associated infections. None of the patients had typical pyogenic liver abscess. All of the hmCRKp isolates harbored carbapenemase genes and were multidrug resistant. K1/K serotype, peg-344, allS, and magA were not identified among hmCRKp isolates, whereas aerobactin siderophore receptor gene (iutA), iroB, rmpA, and rmpA2 were detected. Only three hmCRKp isolates were resistant to serum bactericidal. Conclusions: All the isolates presented inconclusive evidence for the interpretation of hypervirulence. Therefore, more study should be performed in the future to have a better understanding of the virulence mechanisms in correlation with the clinical and microbial determinants.
    Matched MeSH terms: Klebsiella pneumoniae/drug effects*; Klebsiella pneumoniae/genetics*; Klebsiella pneumoniae/isolation & purification
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