Displaying publications 1 - 20 of 33 in total

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  1. An Y, Cipollo JF
    Anal Biochem, 2011 Aug 1;415(1):67-80.
    PMID: 21545787 DOI: 10.1016/j.ab.2011.04.018
    Here a mass spectrometry-based platform for the analysis of glycoproteins is presented. Glycopeptides and released glycans are analyzed, the former by quadrupole orthogonal time-of-flight liquid chromatography/mass spectrometry (QoTOF LC/MS) and the latter by permethylation analysis using matrix-assisted laser desorption/ionization (MALDI)-TOF MS. QoTOF LC/MS analysis reveals the stochastic distribution of glycoforms at occupied sequons, and the latter provides a semiquantitative assessment of overall protein glycosylation. Hydrophilic interaction chromatography (HILIC) was used for unbiased enrichment of glycopeptides and was validated using five model N-glycoproteins bearing a wide array of glycans, including high-mannose, complex, and hybrid subtypes such as sulfo and sialyl forms. Sialyl and especially sulfated glycans are difficult to analyze because these substitutions are labile. The conditions used here allow detection of these compounds quantitatively, intact, and in the context of overall glycosylation. As a test case, we analyzed influenza B/Malaysia/2506/2004 hemagglutinin, a component of the 2006-2007 influenza vaccine. It bears 11 glycosylation sites. Approximately 90% of its glycans are high mannose, and 10% are present as complex and hybrid types, including those with sulfate. The stochastic distribution of glycoforms at glycosylation sites is revealed. This platform should have wide applications to glycoproteins in basic sciences and industry because no apparent bias for any glycoforms is observed.
  2. Dang L, An Y, Okajima S, Mound LA
    Zookeys, 2023;1185:241-253.
    PMID: 38074906 DOI: 10.3897/zookeys.1185.113895
    Species of the Oriental subtropical and tropical genus Phylladothrips of fungus-feeding thrips exhibit some diagnostic character states, usually with abdominal tergite VIII bearing two pairs of wing-retaining setae and male tergite IX setae S2 about as long as S1. These species are quite small, and the maxillary stylets unusually broad for Phlaeothripinae. Phylladothripstrisetaesp. nov. from Xizang, China and P.selangorsp. nov. from Selangor, Malaysia are described, and P.fasciae is newly recorded from China. All 11 species in this genus are revised with an illustrated key.
  3. Cui Z, Cui S, Qin L, An Y, Zhang X, Guan J, et al.
    Asian J Pharm Sci, 2023 Sep;18(5):100848.
    PMID: 37881796 DOI: 10.1016/j.ajps.2023.100848
    Virus-capsid mimicking mucus-permeable nanoparticles are promising oral insulin carriers which surmount intestinal mucus barrier. However, the impact of different virus-capsid mimicking structure remains unexplored. In this study, utilizing biotin grafted chitosan as the main skeleton, virus-mimicking nanoparticles endowed with biologic-shell (streptavidin coverage) and polymeric-shell (hyaluronic acid/alginate coating) were designed with insulin as a model drug by self-assembly processes. It was demonstrated that biologic-shell mimicking nanoparticles exhibited a higher intestinal trans-mucus (>80%, 10 min) and transmucosal penetration efficiency (1.6-2.2-fold improvement) than polymeric-shell counterparts. Uptake mechanism studies revealed caveolae-mediated endocytosis was responsible for the absorption of biologic-shell mimicking nanoparticles whereas polymeric-shell mimicking nanoparticles were characterized by clathrin-mediated pathway with anticipated lysosomal insulin digestion. Further, in vivo hypoglycemic study indicated that the improved effect of regulating blood sugar levels was virus-capsid structure dependent out of which biologic-shell mimicking nanoparticles presented the best performance (5.1%). Although the findings of this study are encouraging, much more work is required to meet the standards of clinical translation. Taken together, we highlight the external structural dependence of virus-capsid mimicking nanoparticles on the muco-penetrating and uptake mechanism of enterocytes that in turn affecting their in vivo absorption, which should be pondered when engineering virus-mimicking nanoparticles for oral insulin delivery.
  4. Golder V, Kandane-Rathnayake R, Hoi AY, Huq M, Louthrenoo W, An Y, et al.
    Arthritis Res Ther, 2017 03 20;19(1):62.
    PMID: 28320433 DOI: 10.1186/s13075-017-1256-6
    BACKGROUND: Systemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). Recently, meeting a definition of a lupus low disease activity state (LLDAS), analogous to low disease activity in rheumatoid arthritis, was preliminarily validated as associated with protection from damage accrual. The LLDAS definition has not been previously evaluated for association with patient-reported outcomes. The objective of this study was to determine whether LLDAS is associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of patients with SLE.
    METHODS: HR-QoL was measured using the Medical Outcomes Study 36-item short form health survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using the SLE disease activity index (SLEDAI-2 K), physician global assessment (PGA) and LLDAS.
    RESULTS: Significant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level and damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p 
  5. Golder V, Kandane-Rathnayake R, Hoi AY, Huq M, Louthrenoo W, An Y, et al.
    Arthritis Res Ther, 2016 11 09;18(1):260.
    PMID: 27829463 DOI: 10.1186/s13075-016-1163-2
    BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic heterogeneous disease with considerable burden from disease activity and damage. A novel clinical treatment target in the form of the lupus low disease activity state (LLDAS) has been recently reported, with retrospective validation showing that time spent in LLDAS translates to reduced damage accrual. The objectives of this study were to describe the frequency and identify the predictors of attaining LLDAS in a large multinational cohort of patients with SLE.
    METHODS: Data were collected at the recruitment visit in patients with SLE enrolled in a longitudinal study in nine countries. Data were analysed cross-sectionally against the recently published definition of LLDAS, and the frequency and characteristics associated with presence of LLDAS were determined. Stepwise multivariable logistic regression was used to determine predictors of LLDAS.
    RESULTS: Of the 1846 patients assessed, criteria for LLDAS were met by 44 %. Patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95 % CI 0.19-0.49, p 
  6. Kandane-Rathnayake R, Golder V, Louthrenoo W, Luo SF, Jan Wu YJ, Li Z, et al.
    Int J Rheum Dis, 2019 Mar;22(3):425-433.
    PMID: 30398013 DOI: 10.1111/1756-185X.13431
    AIM: The aim of this manuscript is to describe the development of the Asia Pacific Lupus Collaboration (APLC) cohort.

    METHOD: The APLC cohort is an ongoing, prospective longitudinal cohort. Adult patients who meet either the American College of Rheumatology (ACR) Modified Classification Criteria for systemic lupus erythematosus (SLE), or the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria, and provide informed consent are recruited into the cohort. Patients are routinely followed up at 3- to 6-monthly intervals. Information on demographics, clinical manifestations, treatment, pathology results, outcomes, and patient-reported quality of life (Short-form 36 version 2) are collected using a standardized case report form. Each site is responsible for obtaining local ethics and governance approval, patient recruitment, data collection, and data transfer into a centralized APLC database.

    RESULTS: The latest APLC cohort comprises 2160 patients with >12 000 visits from Australia, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. The APLC has proposed the Lupus Low Disease Activity State (LLDAS) as a treat-to-target (T2T) endpoint, and reported several retrospective and cross-sectional analyses consistent with the validity of LLDAS. Longitudinal validation of LLDAS as a T2T endpoint is currently underway.

    CONCLUSION: The APLC cohort is one of the largest contemporary SLE patient cohorts in the world. It is the only cohort with substantial representation of Asian patients. This cohort represents a unique resource for future clinical research including evaluation of other endpoints and quality of care.

  7. Kandane-Rathnayake R, Louthrenoo W, Luo SF, Wu YJ, Chen YH, Golder V, et al.
    Arthritis Care Res (Hoboken), 2022 Dec;74(12):2033-2041.
    PMID: 34197023 DOI: 10.1002/acr.24740
    OBJECTIVE: Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort.

    METHODS: Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) and medication details, captured at every visit from 2013-2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time-to-discontinuation of medications, stratified by SLE disease activity.

    RESULTS: Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment; GC, AM, or IS only; GC plus AM; GC plus IS; AM plus IS; and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits, and biologics in only 3%. Time-to-discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time-adjusted mean SLEDAI-2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS.

    CONCLUSION: Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.

  8. Kandane-Rathnayake R, Louthrenoo W, Golder V, Luo SF, Wu YJ, Lateef A, et al.
    Rheumatology (Oxford), 2021 Nov 03;60(11):5185-5193.
    PMID: 33693676 DOI: 10.1093/rheumatology/keab217
    OBJECTIVE: The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort.

    METHODS: Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses.

    RESULTS: Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia.

    CONCLUSION: Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.

  9. Connelly K, Kandane-Rathnayake R, Hoi A, Louthrenoo W, Hamijoyo L, Luo SF, et al.
    Arthritis Rheumatol, 2023 Mar;75(3):401-410.
    PMID: 36122172 DOI: 10.1002/art.42350
    OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up.

    METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied.

    RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P 

  10. Yeo AL, Kandane-Rathnayake R, Koelmeyer R, Golder V, Louthrenoo W, Chen YH, et al.
    Rheumatology (Oxford), 2024 Feb 01;63(2):525-533.
    PMID: 37208196 DOI: 10.1093/rheumatology/kead231
    OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive.

    METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare.

    RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P 3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009).

    CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

  11. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(11):970.
    PMID: 34793584 DOI: 10.1140/epjc/s10052-021-09721-5
    A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 Te at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325 Ge for a massless neutralino, and a neutralino mass up to 700 Ge for a top squark mass of 1150 Ge . Top squarks with masses from 145 to 295 Ge , for neutralino masses from 0 to 100 Ge , with a mass difference between the top squark and the neutralino in a window of 30 Ge around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 Ge .
  12. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Dragicevic M, et al.
    Phys Rev Lett, 2021 Dec 24;127(26):261804.
    PMID: 35029469 DOI: 10.1103/PhysRevLett.127.261804
    A search for long-lived particles (LLPs) produced in decays of standard model (SM) Higgs bosons is presented. The data sample consists of 137  fb^{-1} of proton-proton collisions at sqrt[s]=13  TeV, recorded at the LHC in 2016-2018. A novel technique is employed to reconstruct decays of LLPs in the end cap muon detectors. The search is sensitive to a broad range of LLP decay modes and to masses as low as a few GeV. No excess of events above the SM background is observed. The most stringent limits to date on the branching fraction of the Higgs boson to LLPs subsequently decaying to quarks and τ^{+}τ^{-} are found for proper decay lengths greater than 6, 20, and 40 m, for LLP masses of 7, 15, and 40 GeV, respectively.
  13. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Sep 22;131(12):121901.
    PMID: 37802954 DOI: 10.1103/PhysRevLett.131.121901
    The dependence of the ratio between the B_{s}^{0} and B^{+} hadron production fractions, f_{s}/f_{u}, on the transverse momentum (p_{T}) and rapidity of the B mesons is studied using the decay channels B_{s}^{0}→J/ψϕ and B^{+}→J/ψK^{+}. The analysis uses a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 61.6  fb^{-1}. The f_{s}/f_{u} ratio is observed to depend on the B p_{T} and to be consistent with becoming asymptotically constant at large p_{T}. No rapidity dependence is observed. The ratio of the B^{0} to B^{+} meson production fractions, f_{d}/f_{u}, is also measured, for the first time in proton-proton collisions, using the B^{0}→J/ψK^{*0} decay channel. The result is found to be within 1 standard deviation of unity and independent of p_{T} and rapidity, as expected from isospin invariance.
  14. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Oct 13;131(15):151803.
    PMID: 37897747 DOI: 10.1103/PhysRevLett.131.151803
    We present an observation of photon-photon production of τ lepton pairs in ultraperipheral lead-lead collisions. The measurement is based on a data sample with an integrated luminosity of 404  μb^{-1} collected by the CMS experiment at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02  TeV. The γγ→τ^{+}τ^{-} process is observed for τ^{+}τ^{-} events with a muon and three charged hadrons in the final state. The measured fiducial cross section is σ(γγ→τ^{+}τ^{-})=4.8±0.6(stat)±0.5(syst)  μb, where the second (third) term corresponds to the statistical (systematic) uncertainty in σ(γγ→τ^{+}τ^{-}) in agreement with leading-order QED predictions. Using σ(γγ→τ^{+}τ^{-}), we estimate a model-dependent value of the anomalous magnetic moment of the τ lepton of a_{τ}=0.001_{-0.089}^{+0.055}.
  15. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 07;131(1):011803.
    PMID: 37478454 DOI: 10.1103/PhysRevLett.131.011803
    The first search exploiting the vector boson fusion process to probe heavy Majorana neutrinos and the Weinberg operator at the LHC is presented. The search is performed in the same-sign dimuon final state using a proton-proton collision dataset recorded at sqrt[s]=13  TeV, collected with the CMS detector and corresponding to a total integrated luminosity of 138  fb^{-1}. The results are found to agree with the predictions of the standard model. For heavy Majorana neutrinos, constraints on the squared mixing element between the muon and the heavy neutrino are derived in the heavy neutrino mass range 50 GeV-25 TeV; for masses above 650 GeV these are the most stringent constraints from searches at the LHC to date. A first test of the Weinberg operator at colliders provides an observed upper limit at 95% confidence level on the effective μμ Majorana neutrino mass of 10.8 GeV.
  16. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Aug 11;131(6):061801.
    PMID: 37625071 DOI: 10.1103/PhysRevLett.131.061801
    A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, H→cc[over ¯], produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at sqrt[s]=13  TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138  fb^{-1}. Novel charm jet identification and analysis methods using machine learning techniques are employed. The analysis is validated by searching for Z→cc[over ¯] in VZ events, leading to its first observation at a hadron collider with a significance of 5.7 standard deviations. The observed (expected) upper limit on σ(VH)B(H→cc[over ¯]) is 0.94 (0.50_{-0.15}^{+0.22})pb at 95% confidence level (C.L.), corresponding to 14 (7.6_{-2.3}^{+3.4}) times the standard model prediction. For the Higgs-charm Yukawa coupling modifier, κ_{c}, the observed (expected) 95% C.L. interval is 1.1
  17. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 28;131(4):041803.
    PMID: 37566864 DOI: 10.1103/PhysRevLett.131.041803
    A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138  fb^{-1} collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ_{2V}, excluding κ_{2V}=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.
  18. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Jul 28;131(4):041801.
    PMID: 37566854 DOI: 10.1103/PhysRevLett.131.041801
    A search for the standard model (SM) Higgs boson (H) produced with transverse momentum (p_{T}) greater than 450 GeV and decaying to a charm quark-antiquark (cc[over ¯]) pair is presented. The search is performed using proton-proton collision data collected at sqrt[s]=13  TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138  fb^{-1}. Boosted H→cc[over ¯] decay products are reconstructed as a single large-radius jet and identified using a deep neural network charm tagging technique. The method is validated by measuring the Z→cc[over ¯] decay process, which is observed in association with jets at high p_{T} for the first time with a signal strength of 1.00_{-0.14}^{+0.17}(syst)±0.08(theo)±0.06(stat), defined as the ratio of the observed process rate to the SM expectation. The observed (expected) upper limit on σ(H)B(H→cc[over ¯]) is set at 47 (39) times the SM prediction at 95% confidence level.
  19. Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, Damanakis K, et al.
    Phys Rev Lett, 2023 Sep 08;131(10):101801.
    PMID: 37739361 DOI: 10.1103/PhysRevLett.131.101801
    We present the first direct search for exotic Higgs boson decays H→AA, A→γγ in events with two photonlike objects. The hypothetical particle A is a low-mass spin-0 particle decaying promptly to a merged diphoton reconstructed as a single photonlike object. We analyze the data collected by the CMS experiment at sqrt[s]=13  TeV corresponding to an integrated luminosity of 136  fb^{-1}. No excess above the estimated background is found. We set upper limits on the branching fraction B(H→AA→4γ) of (0.9-3.3)×10^{-3} at 95% confidence level for masses of A in the range 0.1-1.2 GeV.
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