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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Blood Biomarkers Discriminate Cerebral Amyloid Status and Cognitive Diagnosis when Collected with ACD-A Anticoagulant

Author(s): Zachary D. Green, Paul J. Kueck, Casey S. John, Jeffrey M. Burns and Jill K. Morris*

Volume 20, Issue 8, 2023

Published on: 01 December, 2023

Page: [557 - 566] Pages: 10

DOI: 10.2174/0115672050271523231111192725

open access plus

Abstract

Background: The development of biomarkers that are easy to collect, process, and store is a major goal of research on current Alzheimer’s Disease (AD) and underlies the growing interest in plasma biomarkers. Biomarkers with these qualities will improve diagnosis and allow for better monitoring of therapeutic interventions. However, blood collection strategies have historically differed between studies. We examined the ability of various ultrasensitive plasma biomarkers to predict cerebral amyloid status in cognitively unimpaired individuals when collected using acid citrate dextrose (ACD). We then examined the ability of these biomarkers to predict cognitive impairment independent of amyloid status.

Methods: Using a cross-sectional study design, we measured amyloid beta 42/40 ratio, pTau-181, neurofilament-light, and glial fibrillary acidic protein using the Quanterix Simoa® HD-X platform. To evaluate the discriminative accuracy of these biomarkers in determining cerebral amyloid status, we used both banked plasma and 18F-AV45 PET cerebral amyloid neuroimaging data from 140 cognitively unimpaired participants. We further examined their ability to discriminate cognitive status by leveraging data from 42 cognitively impaired older adults. This study is the first, as per our knowledge, to examine these specific tests using plasma collected using acid citrate dextrose (ACD), as well as the relationship with amyloid PET status.

Results: Plasma AB42/40 had the highest AUC (0.833, 95% C.I. 0.767-0.899) at a cut-point of 0.0706 for discriminating between the two cerebral amyloid groups (sensitivity 76%, specificity 78.5%). Plasma NFL at a cut-point of 20.58pg/mL had the highest AUC (0.908, 95% CI 0.851- 0.966) for discriminating cognitive impairment (sensitivity 84.8%, specificity 89.9%). The addition of age and apolipoprotein e4 status did not improve the discriminative accuracy of these biomarkers.

Conclusion: Our results suggest that the Aβ42/40 ratio is useful in discriminating clinician-rated elevated cerebral amyloid status and that NFL is useful for discriminating cognitive impairment status. These findings reinforce the growing body of evidence regarding the general utility of these biomarkers and extend their utility to plasma collected in a non-traditional anticoagulant.

[1]
Knopman DS, Haeberlein SB, Carrillo MC, et al. The national institute on aging and the alzheimer’s association research framework for alzheimer’s disease: Perspectives from the research roundtable. Alzheimers Dement 2018; 14(4): 563-75.
[http://dx.doi.org/10.1016/j.jalz.2018.03.002] [PMID: 29653607]
[2]
Clark CM, Pontecorvo MJ, Beach TG, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: A prospective cohort study. Lancet Neurol 2012; 11(8): 669-78.
[http://dx.doi.org/10.1016/S1474-4422(12)70142-4] [PMID: 22749065]
[3]
Blennow K, Zetterberg H. Biomarkers for Alzheimer’s disease: Current status and prospects for the future. J Intern Med 2018; 284(6): 643-63.
[http://dx.doi.org/10.1111/joim.12816] [PMID: 30051512]
[4]
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010; 6(3): 131-44.
[http://dx.doi.org/10.1038/nrneurol.2010.4] [PMID: 20157306]
[5]
Doecke JD, Pérez-Grijalba V, Fandos N, et al. Total Aβ 42 /Aβ 40 ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis. Neurology 2020; 94(15): e1580-91.
[http://dx.doi.org/10.1212/WNL.0000000000009240] [PMID: 32179698]
[6]
Nakamura A, Kaneko N, Villemagne VL, et al. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature 2018; 554(7691): 249-54.
[http://dx.doi.org/10.1038/nature25456] [PMID: 29420472]
[7]
Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology 2019; 93(17): e1647-59.
[http://dx.doi.org/10.1212/WNL.0000000000008081] [PMID: 31371569]
[8]
Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma phospho-tau217 for alzheimer disease vs other neurodegenerative disorders. JAMA 2020; 324(8): 772-81.
[http://dx.doi.org/10.1001/jama.2020.12134] [PMID: 32722745]
[9]
Janelidze S, Teunissen CE, Zetterberg H, et al. Head-to-head comparison of 8 plasma amyloid-β 42/40 assays in alzheimer disease. JAMA Neurol 2021; 78(11): 1375-82.
[http://dx.doi.org/10.1001/jamaneurol.2021.3180] [PMID: 34542571]
[10]
Thijssen EH, Verberk IMW, Vanbrabant J, et al. Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease. Sci Rep 2021; 11(1): 9736.
[http://dx.doi.org/10.1038/s41598-021-89004-x] [PMID: 33958661]
[11]
Vergallo A, Mégret L, Lista S, et al. Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer’s disease. Alzheimers Dement 2019; 15(6): 764-75.
[http://dx.doi.org/10.1016/j.jalz.2019.03.009] [PMID: 31113759]
[12]
Li WW, Shen YY, Tian DY, et al. Brain amyloid-β deposition and blood biomarkers in patients with clinically diagnosed alzheimer’s disease. J Alzheimers Dis 2019; 69(1): 169-78.
[http://dx.doi.org/10.3233/JAD-190056] [PMID: 30958377]
[13]
De Meyer S, Schaeverbeke JM, Verberk IMW, et al. Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis. Alzheimers Res Ther 2020; 12(1): 162.
[http://dx.doi.org/10.1186/s13195-020-00728-w] [PMID: 33278904]
[14]
Janelidze S, Stomrud E, Palmqvist S, et al. Plasma β-amyloid in Alzheimer’s disease and vascular disease. Sci Rep 2016; 6(1): 26801.
[http://dx.doi.org/10.1038/srep26801] [PMID: 27241045]
[15]
Rózga M, Bittner T, Batrla R, Karl J. Preanalytical sample handling recommendations for Alzheimer’s disease plasma biomarkers. Alzheimers Dement 2019; 11(1): 291-300.
[http://dx.doi.org/10.1016/j.dadm.2019.02.002] [PMID: 30984815]
[16]
Jonaitis EM, Zetterberg H, Koscik RL, et al. Crosswalk study on blood collection‐tube types for Alzheimer’s disease biomarkers. Alzheimers Dement 2022; 14(1): e12266.
[http://dx.doi.org/10.1002/dad2.12266] [PMID: 35155728]
[17]
György B, Pálóczi K, Kovács A, et al. Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube. Thromb Res 2014; 133(2): 285-92.
[http://dx.doi.org/10.1016/j.thromres.2013.11.010] [PMID: 24360116]
[18]
Bettin B, Gasecka A, Li B, et al. Removal of platelets from blood plasma to improve the quality of extracellular vesicle research. J Thromb Haemost 2022; 20(11): 2679-85.
[http://dx.doi.org/10.1111/jth.15867] [PMID: 36043239]
[19]
Ozawa T, Ijichi T, Shiraishi M. Measurement of canine blood microparticles by flow cytometry: Effect of anticoagulants and staining reagents. J Vet Med Sci 2021; 83(11): 1786-9.
[http://dx.doi.org/10.1292/jvms.21-0448] [PMID: 34615844]
[20]
Marx RE. Platelet-rich plasma (PRP): What is PRP and what is not PRP? Implant Dent 2001; 10(4): 225-8.
[http://dx.doi.org/10.1097/00008505-200110000-00002] [PMID: 11813662]
[21]
Aizawa H, Kawabata H, Sato A, et al. A comparative study of the effects of anticoagulants on pure platelet-rich plasma quality and potency. Biomedicines 2020; 8(3): 42.
[http://dx.doi.org/10.3390/biomedicines8030042] [PMID: 32106422]
[22]
Pignatelli P, Pulcinelli FM, Ciatti F, et al. Acid citrate dextrose (acd) formula a as a new anticoagulant in the measurement of in vitro platelet aggregation. J Clin Lab Anal 1995; 9(2): 138-40.
[http://dx.doi.org/10.1002/jcla.1860090211] [PMID: 7714666]
[23]
Swerdlow RH, Parks JK, Cassarino DS, et al. Cybrids in Alzheimer’s disease: A cellular model of the disease? Neurology 1997; 49(4): 918-25.
[http://dx.doi.org/10.1212/WNL.49.4.918] [PMID: 9339668]
[24]
Swerdlow RH, Parks JK, Miller SW, et al. Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann Neurol 1996; 40(4): 663-71.
[http://dx.doi.org/10.1002/ana.410400417] [PMID: 8871587]
[25]
Weintraub S, Salmon D, Mercaldo N, et al. The alzheimer’s disease centers’ uniform data set (UDS). Alzheimer Dis Assoc Disord 2009; 23(2): 91-101.
[http://dx.doi.org/10.1097/WAD.0b013e318191c7dd] [PMID: 19474567]
[26]
Morris JC. The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology 1993; 43(11): 2412.2--a.
[http://dx.doi.org/10.1212/WNL.43.11.2412-a] [PMID: 8232972]
[27]
Andreasson U, Perret-Liaudet A, van Waalwijk van Doorn LJC, et al. A practical guide to immunoassay method validation. Front Neurol 2015; 6: 179.
[http://dx.doi.org/10.3389/fneur.2015.00179] [PMID: 26347708]
[28]
Mattsson N, Zetterberg H, Janelidze S, et al. Plasma tau in Alzheimer disease. Neurology 2016; 87(17): 1827-35.
[http://dx.doi.org/10.1212/WNL.0000000000003246] [PMID: 27694257]
[29]
Gonzalez-Ortiz F, Turton M, Kac PR, et al. Brain-derived tau: A novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration. Brain 2023; 146(3): 1152-65.
[http://dx.doi.org/10.1093/brain/awac407] [PMID: 36572122]
[30]
Harn NR, Hunt SL, Hill J, Vidoni E, Perry M, Burns JM. Augmenting amyloid PET interpretations with quantitative information improves consistency of early amyloid detection. Clin Nucl Med 2017; 42(8): 577-81.
[http://dx.doi.org/10.1097/RLU.0000000000001693] [PMID: 28574875]
[31]
Taylor MK, Sullivan DK, Swerdlow RH, et al. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr 2017; 106(6): 1463-70.
[http://dx.doi.org/10.3945/ajcn.117.162263] [PMID: 29070566]
[32]
Joshi AD, Pontecorvo MJ, Clark CM, et al. Performance characteristics of amyloid PET with florbetapir F 18 in patients with alzheimer’s disease and cognitively normal subjects. J Nucl Med 2012; 53(3): 378-84.
[http://dx.doi.org/10.2967/jnumed.111.090340] [PMID: 22331215]
[33]
Baldeiras I, Santana I, Leitão MJ, et al. Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer’s disease dementia in mild cognitive impairment. Alzheimers Res Ther 2018; 10(1): 33.
[http://dx.doi.org/10.1186/s13195-018-0362-2] [PMID: 29558986]
[34]
Verberk IMW, Slot RE, Verfaillie SCJ, et al. Plasma amyloid as prescreener for the earliest A lzheimer pathological changes. Ann Neurol 2018; 84(5): 648-58.
[http://dx.doi.org/10.1002/ana.25334] [PMID: 30196548]
[35]
Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: A diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol 2020; 19(5): 422-33.
[http://dx.doi.org/10.1016/S1474-4422(20)30071-5] [PMID: 32333900]
[36]
Janelidze S, Mattsson N, Palmqvist S, et al. Plasma P-tau181 in Alzheimer’s disease: Relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat Med 2020; 26(3): 379-86.
[http://dx.doi.org/10.1038/s41591-020-0755-1] [PMID: 32123385]
[37]
Pereira JB, Janelidze S, Stomrud E, et al. Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects. Brain 2021; 144(9): 2826-36.
[http://dx.doi.org/10.1093/brain/awab163] [PMID: 34077494]
[38]
Ashton NJ, Pascoal TA, Karikari TK, et al. Plasma p-tau231: A new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol 2021; 141(5): 709-24.
[http://dx.doi.org/10.1007/s00401-021-02275-6] [PMID: 33585983]
[39]
Barthélemy NR, Li Y, Joseph-Mathurin N, et al. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease. Nat Med 2020; 26(3): 398-407.
[http://dx.doi.org/10.1038/s41591-020-0781-z] [PMID: 32161412]
[40]
Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 2018; 14(10): 577-89.
[http://dx.doi.org/10.1038/s41582-018-0058-z] [PMID: 30171200]
[41]
Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with alzheimer disease. JAMA Neurol 2019; 76(7): 791-9.
[http://dx.doi.org/10.1001/jamaneurol.2019.0765] [PMID: 31009028]
[42]
Bridel C, van Wieringen WN, Zetterberg H, et al. Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology. JAMA Neurol 2019; 76(9): 1035-48.
[http://dx.doi.org/10.1001/jamaneurol.2019.1534] [PMID: 31206160]
[43]
Oeckl P, Halbgebauer S, Anderl-Straub S, et al. Glial fibrillary acidic protein in serum is increased in alzheimer’s disease and correlates with cognitive impairment. J Alzheimers Dis 2019; 67(2): 481-8.
[http://dx.doi.org/10.3233/JAD-180325] [PMID: 30594925]
[44]
Escartin C, Guillemaud O, Carrillo-de SMA. Questions and (some) answers on reactive astrocytes. Glia 2019; 67(12): 2221-47.
[http://dx.doi.org/10.1002/glia.23687] [PMID: 31429127]
[45]
Liddelow SA, Barres BA. Reactive astrocytes: Production, function, and therapeutic potential. Immunity 2017; 46(6): 957-67.
[http://dx.doi.org/10.1016/j.immuni.2017.06.006] [PMID: 28636962]
[46]
Verberk IMW, Thijssen E, Koelewijn J, et al. Combination of plasma amyloid beta((1-42/1-40)) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology. Alzheimers Res Ther 2020; 12: 118.
[http://dx.doi.org/10.1186/s13195-020-00682-7] [PMID: 32988409]
[47]
Benedet AL, Milà-Alomà M, Vrillon A, et al. Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the alzheimer disease continuum. JAMA Neurol 2021; 78(12): 1471-83.
[http://dx.doi.org/10.1001/jamaneurol.2021.3671] [PMID: 34661615]
[48]
Verghese PB, Castellano JM, Holtzman DM. Apolipoprotein E in Alzheimer’s disease and other neurological disorders. Lancet Neurol 2011; 10(3): 241-52.
[http://dx.doi.org/10.1016/S1474-4422(10)70325-2] [PMID: 21349439]
[49]
Jayachandran M, Miller VM, Heit JA, Owen WG. Methodology for isolation, identification and characterization of microvesicles in peripheral blood. J Immunol Methods 2012; 375(1-2): 207-14.
[http://dx.doi.org/10.1016/j.jim.2011.10.012] [PMID: 22075275]
[50]
O’Bryant SE, Zhang F, Petersen M, et al. Neurodegeneration from the AT(N) framework is different among Mexican Americans compared to non‐Hispanic Whites: A Health & Aging Brain among Latino Elders (HABLE) Study. Alzheimers Dement 2022; 14(1)e12267
[http://dx.doi.org/10.1002/dad2.12267] [PMID: 35155729]

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      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=136461
      12.01msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 66 limit 1
      1.12msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 66
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=66) and sj.journal_id!=66 group by `j`.`nid`) as `aggregate_table`
      890μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=66) and sj.journal_id!=66 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      700μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=66) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      388msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=66) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      7.13msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '136461'
      270μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 136461
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '136461'
      2.75msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 136461
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '136461' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      4.56msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 136461
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      260μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      520μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 66 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      33.78msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 66 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      17.75msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 66 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      8.81msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 136461 limit 1
      240μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 136461
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 136461 and content_type = 'article' order by status desc limit 1
      240μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 224121 limit 1
      180μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 224121
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      200μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CAR' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      270μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CAR
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '136461' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      1.57msalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '557' and is_uploaded = 1 and issue_id = 13001 order by cast(first_page as SIGNED) desc limit 1
      640μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 557
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '566' and is_uploaded = 1 and issue_id = 13001 order by cast(first_page as SIGNED) asc limit 1
      390μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 566
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      170μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      190μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 136461 limit 1
      2.35msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 136461
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 66 and `b`.`banner_from_date` <= 1740677064 and `b`.`banner_to_date` >= 1740677064 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.19msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 66
      • 3: 1740677064
      • 4: 1740677064
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 66 and `b`.`banner_from_date` <= 1740677064 and `b`.`banner_to_date` >= 1740677064 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.64msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 66
      • 3: 1740677064
      • 4: 1740677064
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='1b333a2e2a6e6f38c9c8972fa55ad9e5'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
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        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        status_code
        200
        
        status_text
        OK
        format
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        request_query
        []
        
        request_request
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        request_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-27 17:24:24GET/article/136461514311