Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Association of High-Mobility Group Box-1 with Inflammationrelated Cytokines in the Aqueous Humor with Acute Primary Angle-Closure Eyes

Author(s): Wenjing He, Fan Xu*, Lifei Chen, Wei Huang, Li Jiang, Fen Tang, Wenya Yan, Shan Zhong, Chaolan Shen, Hui Huang, Jian Lv, Xiaonian Wu, Siming Zeng*, Min Li and Mingyuan Zhang*

Volume 21, Issue 3, 2021

Published on: 13 April, 2020

Page: [237 - 245] Pages: 9

DOI: 10.2174/1566524020666200413113107

Price: $65

Abstract

Aim: The aim of this study was to measure the levels of High-mobility group box-1 (HMGB1) and inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure glaucoma (APAG) and age-related cataract eyes (ARC).

Methods: Aqueous humor samples were obtained from 59 eyes of 59 Chinese subjects (APAG, 32 eyes; and ARC, 27eyes). The multiplex bead immunoassay technique was used to measure the levels of HMGB1 and IL-8, IL-6, G-CSF, MCP-3, VEGF, sVEGFR- 1, sVEFGR-2, TNF-α, PDGF, and IL-10 in aqueous. The data of Patients’ demographics and preoperative intraocular pressure (IOP) were also collected for detailed analysis.

Results: The APAG group showed significantly elevated concentrations of HMGB1, IL- 8, IL-6, G-CSF, VEGF, sVEGFR-1, and TNF-α than those in the ARC group. Aqueous HMGB1 level correlated significantly with IOP, IL-8, IL-6, G-CSF and sVEGFR-1 levels but not with age, TNF-α, or VEGF levels.

Conclusion: The aqueous level of HMGB1 is elevated in APAG and associated with aqueous level of inflammation-related cytokines, suggesting an association between elevated levels of HMGB1, APAC and certain inflammatory modulators which, of course, should lead to further investigations in order to demonstrate the cause and effect.

Keywords: High-Mobility Group Box-1, acute primary angle-closure, inflammation, cytokines, aqueous humor.

[1]
Pokhrel PK, Loftus SA. Ocular emergencies. Am Fam Physician 2007; 76(6): 829-36.
[PMID: 17910297]
[2]
Welge-Lüssen U, May CA, Neubauer AS, Priglinger S. Role of tissue growth factors in aqueous humor homeostasis. Curr Opin Ophthalmol 2001; 12(2): 94-9.
[http://dx.doi.org/10.1097/00055735-200104000-00003] [PMID: 11224714]
[3]
Curnow SJ, Falciani F, Durrani OM, et al. Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis. Invest Ophthalmol Vis Sci 2005; 46(11): 4251-9.
[http://dx.doi.org/10.1167/iovs.05-0444] [PMID: 16249505]
[4]
Kaneda S, Miyazaki D, Sasaki S, et al. Multivariate analyses of inflammatory cytokines in eyes with branch retinal vein occlusion: relationships to bevacizumab treatment. Invest Ophthalmol Vis Sci 2011; 52(6): 2982-8.
[http://dx.doi.org/10.1167/iovs.10-6299] [PMID: 21273540]
[5]
Jonas JB, Tao Y, Neumaier M, Findeisen P. Cytokine concentration in aqueous humour of eyes with exudative age-related macular degeneration. Acta Ophthalmol 2012; 90(5): e381-8.
[http://dx.doi.org/10.1111/j.1755-3768.2012.02414.x] [PMID: 22490043]
[6]
Sawada H, Fukuchi T, Tanaka T, Abe H. Tumor necrosis factor-alpha concentrations in the aqueous humor of patients with glaucoma. Invest Ophthalmol Vis Sci 2010; 51(2): 903-6.
[http://dx.doi.org/10.1167/iovs.09-4247] [PMID: 19737888]
[7]
Picht G, Welge-Luessen U, Grehn F, Lütjen-Drecoll E. Transforming growth factor beta 2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development. Graefes Arch Clin Exp Ophthalmol 2001; 239(3): 199-207.
[http://dx.doi.org/10.1007/s004170000252] [PMID: 11405069]
[8]
Huang W, Chen S, Gao X, et al. Inflammation-related cytokines of aqueous humor in acute primary angle-closure eyes. Invest Ophthalmol Vis Sci 2014; 55(2): 1088-94.
[http://dx.doi.org/10.1167/iovs.13-13591] [PMID: 24474267]
[9]
Kuchtey J, Rezaei KA, Jaru-Ampornpan P, Sternberg P Jr, Kuchtey RW. Multiplex cytokine analysis reveals elevated concentration of interleukin-8 in glaucomatous aqueous humor. Invest Ophthalmol Vis Sci 2010; 51(12): 6441-7.
[http://dx.doi.org/10.1167/iovs.10-5216] [PMID: 20592224]
[10]
Takai Y, Tanito M, Ohira A. Multiplex cytokine analysis of aqueous humor in eyes with primary open-angle glaucoma, exfoliation glaucoma, and cataract. Invest Ophthalmol Vis Sci 2012; 53(1): 241-7.
[http://dx.doi.org/10.1167/iovs.11-8434] [PMID: 22159018]
[11]
Hu DN, Ritch R, Liebmann J, Liu Y, Cheng B, Hu MS. Vascular endothelial growth factor is increased in aqueous humor of glaucomatous eyes. J Glaucoma 2002; 11(5): 406-10.
[http://dx.doi.org/10.1097/00061198-200210000-00006] [PMID: 12362079]
[12]
Gao X, Huang W, Zhang X, et al. Chemokine (C-C motif) ligand 2 and chemokine (C-C motif) ligand 7 in angle-closure glaucoma. Acta Ophthalmol 2016; 94(3): e220-4.
[http://dx.doi.org/10.1111/aos.12696] [PMID: 25726969]
[13]
Liu YM, Chen SD, Li XY, et al. Aqueous proinflammatory cytokines in acute primary angle-closure eyes. Int J Ophthalmol 2017; 10(5): 733-7.
[PMID: 28546929]
[14]
Bianchi ME, Manfredi AA. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev 2007; 220: 35-46.
[http://dx.doi.org/10.1111/j.1600-065X.2007.00574.x] [PMID: 17979838]
[15]
Harris HE, Andersson U, Pisetsky DS. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol 2012; 8(4): 195-202.
[http://dx.doi.org/10.1038/nrrheum.2011.222] [PMID: 22293756]
[16]
Janko C, Filipović M, Munoz LE, et al. Redox modulation of HMGB1-related signaling. Antioxid Redox Signal 2014; 20(7): 1075-85.
[http://dx.doi.org/10.1089/ars.2013.5179] [PMID: 23373897]
[17]
Zhu X, Messer JS, Wang Y, et al. Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation. J Clin Invest 2015; 125(3): 1098-110.
[http://dx.doi.org/10.1172/JCI76344] [PMID: 25642769]
[18]
Yang H, Antoine DJ, Andersson U, Tracey KJ. The many faces of HMGB1: molecular structure-functional activity in inflammation, apoptosis, and chemotaxis. J Leukoc Biol 2013; 93(6): 865-73.
[http://dx.doi.org/10.1189/jlb.1212662] [PMID: 23446148]
[19]
Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol 2011; 29: 139-62.
[http://dx.doi.org/10.1146/annurev-immunol-030409-101323] [PMID: 21219181]
[20]
Tirone M, Tran NL, Ceriotti C, et al. High mobility group box 1 orchestrates tissue regeneration via CXCR4. J Exp Med 2018; 215(1): 303-18.
[http://dx.doi.org/10.1084/jem.20160217] [PMID: 29203538]
[21]
Li LC, Gao J, Li J. Emerging role of HMGB1 in fibrotic diseases. J Cell Mol Med 2014; 18(12): 2331-9.
[http://dx.doi.org/10.1111/jcmm.12419] [PMID: 25284457]
[22]
Bianchi ME. HMGB1 loves company. J Leukoc Biol 2009; 86(3): 573-6.
[http://dx.doi.org/10.1189/jlb.1008585] [PMID: 19414536]
[23]
Riuzzi F, Sorci G, Donato R. The amphoterin (HMGB1)/receptor for advanced glycation end products (RAGE) pair modulates myoblast proliferation, apoptosis, adhesiveness, migration, and invasiveness. Functional inactivation of RAGE in L6 myoblasts results in tumor formation in vivo. J Biol Chem 2006; 281(12): 8242-53.
[http://dx.doi.org/10.1074/jbc.M509436200] [PMID: 16407300]
[24]
Tian J, Avalos AM, Mao SY, et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 2007; 8(5): 487-96.
[http://dx.doi.org/10.1038/ni1457] [PMID: 17417641]
[25]
Chang JH, McCluskey P, Wakefield D. Expression of toll-like receptor 4 and its associated lipopolysaccharide receptor complex by resident antigen-presenting cells in the human uvea. Invest Ophthalmol Vis Sci 2004; 45(6): 1871-8.
[http://dx.doi.org/10.1167/iovs.03-1113] [PMID: 15161852]
[26]
Fujimoto T, Sonoda KH, Hijioka K, et al. Choroidal neovascularization enhanced by Chlamydia pneumoniae via Toll-like receptor 2 in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 2010; 51(9): 4694-702.
[http://dx.doi.org/10.1167/iovs.09-4464] [PMID: 20393111]
[27]
Ko MK, Saraswathy S, Parikh JG, Rao NA. The role of TLR4 activation in photoreceptor mitochondrial oxidative stress. Invest Ophthalmol Vis Sci 2011; 52(8): 5824-35.
[http://dx.doi.org/10.1167/iovs.10-6357] [PMID: 21666244]
[28]
Jiang G, Sun D, Kaplan HJ, Shao H. Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells. PLoS One 2012; 7(7)e40510
[http://dx.doi.org/10.1371/journal.pone.0040510] [PMID: 22808176]
[29]
Ang LP, Aung T, Chew PT. Acute primary angle closure in an Asian population: long-term outcome of the fellow eye after prophylactic laser peripheral iridotomy. Ophthalmology 2000; 107(11): 2092-6.
[http://dx.doi.org/10.1016/S0161-6420(00)00360-2] [PMID: 11054339]
[30]
Campbell IL, Abraham CR, Masliah E, et al. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 1993; 90(21): 10061-5.
[http://dx.doi.org/10.1073/pnas.90.21.10061] [PMID: 7694279]
[31]
Maruo N, Morita I, Shirao M, Murota S. IL-6 increases endothelial permeability in vitro. Endocrinology 1992; 131(2): 710-4.
[PMID: 1639018]
[32]
Li J, Ang M, Cheung CM, et al. Aqueous cytokine changes associated with Posner-Schlossman syndrome with and without human cytomegalovirus. PLoS One 2012; 7(9)e44453
[http://dx.doi.org/10.1371/journal.pone.0044453] [PMID: 23028541]
[33]
Yuan J, Guo Q, Qureshi AR, et al. Circulating vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sVEGFR-1) are associated with inflammation and mortality in incident dialysis patients. Nephrol Dial Transplant 2013; 28(9): 2356-63.
[http://dx.doi.org/10.1093/ndt/gft256] [PMID: 23828162]
[34]
Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, et al. Vascular endothelial growth factor (VEGF), mast cells and inflammation. Int J Immunopathol Pharmacol 2013; 26(2): 327-35.
[http://dx.doi.org/10.1177/039463201302600206] [PMID: 23755748]
[35]
Pellegrini L, Foglio E, Pontemezzo E, Germani A, Russo MA, Limana F. HMGB1 and repair: Focus on the heart. Pharmacol Ther 2019; 196: 160-82.
[http://dx.doi.org/10.1016/j.pharmthera.2018.12.005] [PMID: 30529040]
[36]
Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285(5425): 248-51.
[http://dx.doi.org/10.1126/science.285.5425.248] [PMID: 10398600]
[37]
Hamada T, Torikai M, Kuwazuru A, et al. Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum 2008; 58(9): 2675-85.
[http://dx.doi.org/10.1002/art.23729] [PMID: 18759291]
[38]
Sappington PL, Yang R, Yang H, Tracey KJ, Delude RL, Fink MP. HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice. Gastroenterology 2002; 123(3): 790-802.
[http://dx.doi.org/10.1053/gast.2002.35391] [PMID: 12198705]
[39]
O’Connor KA, Hansen MK, Rachal Pugh C, et al. Further characterization of high mobility group box 1 (HMGB1) as a proinflammatory cytokine: Central nervous system effects. Cytokine 2003; 24(6): 254-65.
[http://dx.doi.org/10.1016/j.cyto.2003.08.001] [PMID: 14609567]
[40]
Hamada N, Maeyama T, Kawaguchi T, et al. The role of high mobility group box1 in pulmonary fibrosis. Am J Respir Cell Mol Biol 2008; 39(4): 440-7.
[http://dx.doi.org/10.1165/rcmb.2007-0330OC] [PMID: 18441281]
[41]
Ferhani N, Letuve S, Kozhich A, et al. Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 181(9): 917-27.
[http://dx.doi.org/10.1164/rccm.200903-0340OC] [PMID: 20133931]
[42]
Tsung A, Tohme S, Billiar TR. High-mobility group box-1 in sterile inflammation. J Intern Med 2014; 276(5): 425-43.
[http://dx.doi.org/10.1111/joim.12276] [PMID: 24935761]
[43]
Dumitriu IE, Baruah P, Valentinis B, et al. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol 2005; 174(12): 7506-15.
[http://dx.doi.org/10.4049/jimmunol.174.12.7506] [PMID: 15944249]
[44]
Rao NA, Kimoto T, Zamir E, et al. Pathogenic role of retinal microglia in experimental uveoretinitis. Invest Ophthalmol Vis Sci 2003; 44(1): 22-31.
[http://dx.doi.org/10.1167/iovs.02-0199] [PMID: 12506051]
[45]
Jiang G, Ke Y, Sun D, Han G, Kaplan HJ, Shao H. Reactivation of uveitogenic T cells by retinal astrocytes derived from experimental autoimmune uveitis-prone B10RIII mice. Invest Ophthalmol Vis Sci 2008; 49(1): 282-9.
[http://dx.doi.org/10.1167/iovs.07-0371] [PMID: 18172104]
[46]
Chi W, Chen H, Li F, Zhu Y, Yin W, Zhuo Y. HMGB1 promotes the activation of NLRP3 and caspase-8 inflammasomes via NF-κB pathway in acute glaucoma. J Neuroinflammation 2015; 12: 137.
[http://dx.doi.org/10.1186/s12974-015-0360-2] [PMID: 26224068]
[47]
Liang Y, Hou C, Kong J, et al. HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2. Mol Cell Biochem 2015; 405(1-2): 63-71.
[http://dx.doi.org/10.1007/s11010-015-2396-0] [PMID: 25862459]
[48]
Park SY, Lee SW, Kim HY, Lee WS, Hong KW, Kim CD. HMGB1 induces angiogenesis in rheumatoid arthritis via HIF-1α activation. Eur J Immunol 2015; 45(4): 1216-27.
[http://dx.doi.org/10.1002/eji.201444908] [PMID: 25545169]
[49]
Malvitte L, Montange T, Vejux A, et al. Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs. Br J Ophthalmol 2007; 91(1): 29-32.
[http://dx.doi.org/10.1136/bjo.2006.101485] [PMID: 16943231]
[50]
Manni G, Centofanti M, Oddone F, Parravano M, Bucci MG. Interleukin-1beta tear concentration in glaucomatous and ocular hypertensive patients treated with preservative-free nonselective beta-blockers. Am J Ophthalmol 2005; 139(1): 72-7.
[http://dx.doi.org/10.1016/j.ajo.2004.08.028] [PMID: 15652830]
[51]
Baudouin C, Hamard P, Liang H, Creuzot-Garcher C, Bensoussan L, Brignole F. Conjunctival epithelial cell expression of interleukins and inflammatory markers in glaucoma patients treated over the long term. Ophthalmology 2004; 111(12): 2186-92.
[http://dx.doi.org/10.1016/j.ophtha.2004.06.023] [PMID: 15582072]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version383msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[18:17:26] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[18:17:26] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[18:17:26] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[18:17:26] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (91.82ms)time
  • Application (291ms)time
  • 1 x Application (76.01%)
    291ms
    1 x Booting (23.99%)
    91.82ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated217ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('314525270','',1,1739989046,1739989046) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739989046
      1.01msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('314525270','/article/105776',1,1739989046,1739989046)
      150μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 314525270 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314525270) limit 1
      11.46msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 314525270
      • 1: 314525270
      • 2: 314525270
      • 3: 314525270
      • 4: 314525270
      • 5: 314525270
      • 6: 314525270
      • 7: 314525270
      • 8: 314525270
      • 9: 314525270
      • 10: 314525270
      • 11: 314525270
      • 12: 314525270
      • 13: 314525270
      • 14: 314525270
      • 15: 314525270
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 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=105776
      680μsalphaeurekaselec_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` = 23 limit 1
      740μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 23
      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=23) and sj.journal_id!=23 group by `j`.`nid`) as `aggregate_table`
      850μsalphaeurekaselec_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=23) and sj.journal_id!=23 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      720μsalphaeurekaselec_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=23) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.76msalphaeurekaselec_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=23) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.48msalphaeurekaselec_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` = '105776'
      270μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 105776
      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` = '105776'
      500μsalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 105776
      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` = '105776' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.65msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 105776
      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
      230μsalphaeurekaselec_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
      470μsalphaeurekaselec_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 = 23 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      26.83msalphaeurekaselec_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 = 23 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.47msalphaeurekaselec_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 = 23 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      8.36msalphaeurekaselec_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` = 105776 limit 1
      250μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 105776
      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 = 105776 and content_type = 'article' order by status desc limit 1
      280μsalphaeurekaselec_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 a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 295 and cd.sub_disease_id = 300 and content_id!=105776 and cd.content_type = 'article' order by rand() limit 20
      130msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 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` = 180846 limit 1
      280μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 180846
      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
      220μsalphaeurekaselec_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` = 'CMM' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      280μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMM
      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 = '105776' 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) )
      350μsalphaeurekaselec_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 count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '10419' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      280μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 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 count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2978' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      270μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 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 j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2978) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2978) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2978)
      5.78msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 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.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10419) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10419) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10419)
      740μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 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.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 105776) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 105776) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314525270 and j.to_ip >=314525270 )) and ((j.from_date <= 1739989046 and j.to_date >= 1739989046 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 105776)
      580μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 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 `article` where `first_page` < '237' and is_uploaded = 1 and issue_id = 10419 order by cast(first_page as SIGNED) desc limit 1
      480μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 237
      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` > '245' and is_uploaded = 1 and issue_id = 10419 order by cast(first_page as SIGNED) asc limit 1
      380μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 245
      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'
      150μsalphaeurekaselec_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
      230μsalphaeurekaselec_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` = 105776 limit 1
      3.18msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 105776
      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` = 23 and `b`.`banner_from_date` <= 1739989046 and `b`.`banner_to_date` >= 1739989046 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.52msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 23
      • 3: 1739989046
      • 4: 1739989046
      • 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` = 23 and `b`.`banner_from_date` <= 1739989046 and `b`.`banner_to_date` >= 1739989046 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 23
      • 3: 1739989046
      • 4: 1739989046
      • 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='de2cd10883b4277d74b9157ceb403c83'
      230μsalphaeurekaselec_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#?
    App\Models\MultiLangArticle
    1MultiLangArticle.php#?
        _token
        tM8CNdVm3wTfJJ0kbb5ZmBp8fyOLRGBq83NGmpe4
        uc_cart_id
        de2cd10883b4277d74b9157ceb403c83
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/105776" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/105776
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Ino1c1FsSzZoNytEelJYQVVlT0RCZUE9PSIsInZhbHVlIjoiUmkwcTVjVWcwOUJYRUMwcjY1bm9WUXlDTFN0cmxNQnRTWkFZVzUyMk9scz0iLCJtYWMiOiI2NzM0NmZkNTM1NzMzNDhkYTk0OWM5OTc2YTYyOTZlMGRlZTIwYmI5MzhmY2E4ZjkyODljMzRiMmIyMDM0MWE3IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Ino1c1FsSzZoNytEelJYQVVlT0RCZUE9PSIsInZhbHVlIjoiUmkwcTVjVWcwOUJYRUMwcjY1bm9WUXlDTFN0cmxNQnRTWkFZVzUyMk9scz0iLCJtYWMiOiI2NzM0NmZkNTM1NzMz" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 18:17:26 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InVHSXZHRWozMC9wTVRpYW9XM2d3Y2c9PSIsInZhbHVlIjoiUTAybkxvZHdwUncyUXV1SEthd0xwZStmM29hWk1MZkI1Znc0SVBEOTdBNHNXTlVsZTZBbHIxRmcrTmNwbnNmMGRERDNDZ01GdTRoLzZydFgvcndXVnV0ZVRVaXpPdWJJaHZFZnVGUnN4UHBtMHNTUktyMm9QK1Y2YzhTYlVtMUkiLCJtYWMiOiI5MjAyMTIxZDUxZDc4YmEwZmU0M2Q4N2NhNjM5YjU1OTk2YjZhMzk4YTg5YWE2NmM1NzEyOGUyNmNiNjA2N2QyIiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:17:26 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InVHSXZHRWozMC9wTVRpYW9XM2d3Y2c9PSIsInZhbHVlIjoiUTAybkxvZHdwUncyUXV1SEthd0xwZStmM29hWk1MZkI1Znc0SVBEOTdBNHNXTlVsZTZBbHIxRmcrTmNwbnNmMGRERDNDZ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjhId2h0WmdsYWtzRWZIa1BQdDBNMGc9PSIsInZhbHVlIjoiTzNHUHlvNEVQRkJ6cWNIK254bHNPRElxcjVnekl6WkZnMGplOXlWTWlJTnAxUU5TQzUzSGkvNEpnWHBLc1VObUJEMWtYNjE5SFVldUJzV0JpUHpRTktIWTFNUkZsVDlXOHVhWXoyYVNSUHlwMDdtc0IxZy9laEllY3RMaUdqOTQiLCJtYWMiOiJiOWE1YzIwYzg2NTg2MzE0NGFhNThlM2RmZjZlNzkxNGMxZjI1MzU5MWIzOTFkYTEwZTcwMjhkOTIwM2FiMTgwIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjhId2h0WmdsYWtzRWZIa1BQdDBNMGc9PSIsInZhbHVlIjoiTzNHUHlvNEVQRkJ6cWNIK254bHNPRElxcjVnekl6WkZnMGplOXlWTWlJTnAxUU5TQzUzSGkvNEp" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InVHSXZHRWozMC9wTVRpYW9XM2d3Y2c9PSIsInZhbHVlIjoiUTAybkxvZHdwUncyUXV1SEthd0xwZStmM29hWk1MZkI1Znc0SVBEOTdBNHNXTlVsZTZBbHIxRmcrTmNwbnNmMGRERDNDZ01GdTRoLzZydFgvcndXVnV0ZVRVaXpPdWJJaHZFZnVGUnN4UHBtMHNTUktyMm9QK1Y2YzhTYlVtMUkiLCJtYWMiOiI5MjAyMTIxZDUxZDc4YmEwZmU0M2Q4N2NhNjM5YjU1OTk2YjZhMzk4YTg5YWE2NmM1NzEyOGUyNmNiNjA2N2QyIiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:17:26 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InVHSXZHRWozMC9wTVRpYW9XM2d3Y2c9PSIsInZhbHVlIjoiUTAybkxvZHdwUncyUXV1SEthd0xwZStmM29hWk1MZkI1Znc0SVBEOTdBNHNXTlVsZTZBbHIxRmcrTmNwbnNmMGRERDNDZ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjhId2h0WmdsYWtzRWZIa1BQdDBNMGc9PSIsInZhbHVlIjoiTzNHUHlvNEVQRkJ6cWNIK254bHNPRElxcjVnekl6WkZnMGplOXlWTWlJTnAxUU5TQzUzSGkvNEpnWHBLc1VObUJEMWtYNjE5SFVldUJzV0JpUHpRTktIWTFNUkZsVDlXOHVhWXoyYVNSUHlwMDdtc0IxZy9laEllY3RMaUdqOTQiLCJtYWMiOiJiOWE1YzIwYzg2NTg2MzE0NGFhNThlM2RmZjZlNzkxNGMxZjI1MzU5MWIzOTFkYTEwZTcwMjhkOTIwM2FiMTgwIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjhId2h0WmdsYWtzRWZIa1BQdDBNMGc9PSIsInZhbHVlIjoiTzNHUHlvNEVQRkJ6cWNIK254bHNPRElxcjVnekl6WkZnMGplOXlWTWlJTnAxUU5TQzUzSGkvNEp" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "tM8CNdVm3wTfJJ0kbb5ZmBp8fyOLRGBq83NGmpe4" "uc_cart_id" => "de2cd10883b4277d74b9157ceb403c83" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/105776" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:17:26GET/article/105776414372