Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Comparison of Cytokine Profile between Postmenopausal Women with and Without Osteoporosis – A Case-Control Study

Author(s): Geok Ting Soh, Affaf Hulma Mohammad, Sharifah Nur Liyana Syed Isa, Kok-Yong Chin* and Norazlina Mohamed*

Volume 23, Issue 6, 2023

Published on: 27 December, 2022

Page: [811 - 817] Pages: 7

DOI: 10.2174/1871530323666221114111029

Price: $65

Abstract

Background: Chronic low-grade inflammation is involved in the pathogenesis of postmenopausal osteoporosis, but the cytokines implicated remain elusive.

Objective: This study aimed to compare the difference in cytokine profile between postmenopausal women with and without osteoporosis in Klang Valley, Malaysia.

Methods: Postmenopausal women with (n = 20) and without osteoporosis (n = 20) were recruited for this study. Their bone health status was determined using dual-energy X-ray absorptiometry. Their fasting blood was collected for proteomic analysis. A protein array was performed for four subjects randomly selected from each group to screen the potential cytokines. Three cytokines at least 20% different between groups and consistently expressed by each subject were selected for validation using enzyme-linked immunosorbent assays (ELISA).

Results: The protein array screening demonstrated that platelet-derived growth factor-BB, interleukin- 6 receptor (IL-6R), and tissue inhibitor of metallopeptidase-2 were higher in women with osteoporosis than women without osteoporosis (n = 4 per group), and consistently expressed by all women. Only body mass index (BMI)-adjusted logarithmically transformed IL-6R levels were lower among postmenopausal women with osteoporosis compared to women with normal bone health (p = 0.026) (n = 16 per group) in the ELISA test.

Conclusion: IL-6R was lower among postmenopausal women with osteoporosis compared to women with normal bone health after adjusting for BMI. However, a large-scale epidemiological study with proteomic analysis needs to confirm the findings.

Graphical Abstract

[1]
Pouresmaeili F, Kamali Dehghan B, Kamarehei M, Yong MG. A comprehensive overview on osteoporosis and its risk factors. Ther Clin Risk Manag 2018; 14: 2029-49.
[http://dx.doi.org/10.2147/TCRM.S138000] [PMID: 30464484]
[2]
Shevroja E, Cafarelli FP, Guglielmi G, Hans D. DXA parameters, trabecular bone score (TBS) and bone mineral density (BMD), in fracture risk prediction in endocrine-mediated secondary osteoporosis. Endocrine 2021; 74(1): 20-8.
[http://dx.doi.org/10.1007/s12020-021-02806-x] [PMID: 34245432]
[3]
Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a World Health Organization Study Group. Geneva: World Health Organization 1994. Available from: https://apps.who.int/iris/handle/10665/39142
[4]
Subramaniam S, Chan CY, Soelaiman IN, et al. The performance of osteoporosis self-assessment tool for Asians (OSTA) in identifying the risk of osteoporosis among Malaysian population aged 40 years and above. Arch Osteoporos 2019; 14(1): 117.
[http://dx.doi.org/10.1007/s11657-019-0666-2] [PMID: 31781876]
[5]
Carlson BC, Robinson WA, Wanderman NR, et al. A review and clinical perspective of the impact of osteoporosis on the spine. Geriatr Orthop Surg Rehabil 2019; 10: 1-8.
[http://dx.doi.org/10.1177/2151459319861591] [PMID: 31360592]
[6]
Zhuang H, Wang P, Li Y, Lin J, Yao X, Xu H. Analysis of related factors of brittle hip fracture in postmenopausal women with osteoporosis. Orthop Surg 2020; 12(1): 194-8.
[http://dx.doi.org/10.1111/os.12605] [PMID: 31943831]
[7]
Chan CY, Subramaniam S, Mohamed N, et al. Determinants of bone health status in a multi-ethnic population in Klang Valley, Malaysia. Int J Environ Res Public Health 2020; 17(2): 384.
[http://dx.doi.org/10.3390/ijerph17020384] [PMID: 31936034]
[8]
Subramaniam S, Chan CY, Soelaiman IN, et al. Prevalence and predictors of osteoporosis among the Chinese population in Klang Valley, Malaysia. Appl Sci 2019; 9(9): 1820.
[http://dx.doi.org/10.3390/app9091820]
[9]
Drake MT, Khosla S. Sex steroids and the pathogenesis of osteoporosis. New Jersey: in: Primer on the Metabolic Bone Diseases And Disorders Of Mineral Metabolism. John Wiley & Sons, Inc. 2018; pp. 412-8.
[http://dx.doi.org/10.1002/9781119266594.ch52]
[10]
Kenkre JS, Bassett JHD. The bone remodelling cycle. Ann Clin Biochem 2018; 55(3): 308-27.
[http://dx.doi.org/10.1177/0004563218759371] [PMID: 29368538]
[11]
Khosla S, Pacifici R. Estrogen deficiency and the pathogenesis of osteoporosis. In: Dempster DW, Cauley JA, Bouxsein ML, Cosman F, Eds. Marcus and Feldman’s Osteoporosis. (5th ed.). Cambridge: Academic Press 2021; pp. 773-97.
[http://dx.doi.org/10.1016/B978-0-12-813073-5.00032-0]
[12]
Mohamad NV, Ima-Nirwana S, Chin KY. Are oxidative stress and inflammation mediators of bone loss due to estrogen deficiency? a review of current evidence. Endocr Metab Immune Disord Drug Targets 2020; 20(9): 1478-87.
[http://dx.doi.org/10.2174/1871530320666200604160614] [PMID: 32496996]
[13]
Azizieh F, Raghupathy R, Shehab D, Al-Jarallah K, Gupta R. Cytokine profiles in osteoporosis suggest a proresorptive bias. Menopause 2017; 24(9): 1057-64.
[http://dx.doi.org/10.1097/GME.0000000000000885] [PMID: 28609384]
[14]
Al-Daghri NM, Aziz I, Yakout S, et al. Inflammation as a contributing factor among postmenopausal Saudi women with osteoporosis. Medicine 2017; 96(4): e5780.
[http://dx.doi.org/10.1097/MD.0000000000005780] [PMID: 28121926]
[15]
Subramaniam S, Chan CY, Soelaiman IN, et al. Development of osteoporosis screening algorithm for population aged 50 years and above in Klang Valley, Malaysia. Int J Environ Res Public Health 2020; 17(7): 2526.
[http://dx.doi.org/10.3390/ijerph17072526] [PMID: 32272697]
[16]
Chan CY, Subramaniam S, Chin KY, et al. Levels of knowledge, beliefs, and practices regarding osteoporosis and the associations with bone mineral density among populations more than 40 years old in Malaysia. Int J Environ Res Public Health 2019; 16(21): 4115.
[http://dx.doi.org/10.3390/ijerph16214115] [PMID: 31731507]
[17]
Monteleone P, Mascagni G, Giannini A, Genazzani AR, Simoncini T. Symptoms of menopause - global prevalence, physiology and implications. Nat Rev Endocrinol 2018; 14(4): 199-215.
[http://dx.doi.org/10.1038/nrendo.2017.180] [PMID: 29393299]
[18]
Pelekanou V, Kampa M, Kiagiadaki F, et al. Estrogen anti-inflammatory activity on human monocytes is mediated through cross-talk between estrogen receptor ERα36 and GPR30/GPER1. J Leukoc Biol 2016; 99(2): 333-47.
[http://dx.doi.org/10.1189/jlb.3A0914-430RR] [PMID: 26394816]
[19]
Villa A, Rizzi N, Vegeto E, Ciana P, Maggi A. Estrogen accelerates the resolution of inflammation in macrophagic cells. Sci Rep 2015; 5(1): 15224.
[http://dx.doi.org/10.1038/srep15224] [PMID: 26477569]
[20]
Fischer V, Kalbitz M, Müller-Graf F, et al. Influence of menopause on inflammatory cytokines during murine and human bone fracture healing. Int J Mol Sci 2018; 19(7): 2070.
[http://dx.doi.org/10.3390/ijms19072070] [PMID: 30013010]
[21]
Wang Q, Ferreira DLS, Nelson SM, Sattar N, Ala-Korpela M, Lawlor DA. Metabolic characterization of menopause: Cross-sectional and longitudinal evidence. BMC Med 2018; 16(1): 17.
[http://dx.doi.org/10.1186/s12916-018-1008-8] [PMID: 29402284]
[22]
Wu D, Cline-Smith A, Shashkova E, Perla A, Katyal A, Aurora R. T-cell mediated inflammation in postmenopausal osteoporosis. Front Immunol 2021; 12: 687551.
[http://dx.doi.org/10.3389/fimmu.2021.687551] [PMID: 34276675]
[23]
Fang H, Zhang H, Wang Z, Zhou Z, Li Y, Lu L. Systemic immune‐inflammation index acts as a novel diagnostic biomarker for postmenopausal osteoporosis and could predict the risk of osteoporotic fracture. J Clin Lab Anal 2020; 34(1): e23016.
[http://dx.doi.org/10.1002/jcla.23016] [PMID: 31423643]
[24]
Liu Q, Zhou Y, Li Z. PDGF-BB promotes the differentiation and proliferation of MC3T3-E1 cells through the Src/JAK2 signaling pathway. Mol Med Rep 2018; 18(4): 3719-26.
[http://dx.doi.org/10.3892/mmr.2018.9351] [PMID: 30106097]
[25]
Xie H, Cui Z, Wang L, et al. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med 2014; 20(11): 1270-8.
[http://dx.doi.org/10.1038/nm.3668] [PMID: 25282358]
[26]
Hock JM, Canalis E. Platelet-derived growth factor enhances bone cell replication, but not differentiated function of osteoblasts. Endocrinology 1994; 134(3): 1423-8.
[http://dx.doi.org/10.1210/endo.134.3.8119182] [PMID: 8119182]
[27]
Hollinger JO, Hart CE, Hirsch SN, Lynch S, Friedlaender GE. Recombinant human platelet-derived growth factor: biology and clinical applications. J Bone Joint Surg Am 2008; 90(S1): 48-54.
[http://dx.doi.org/10.2106/JBJS.G.01231] [PMID: 18292357]
[28]
Tang L, Xia Z, Luo Z, Long H, Zhu Y, Zhao S. Low plasma PDGF-BB levels are associated with estradiol in postmenopausal osteoporosis. J Int Med Res 2017; 45(4): 1332-9.
[http://dx.doi.org/10.1177/0300060517706630] [PMID: 28606019]
[29]
Campana L, Iredale J. matrix metalloproteinases and their inhibitors. In: Gandhi CR, Pinzani M, Eds. Stellate Cells in Health and Disease. Boston: Academic Press 2015; pp. 107-24.
[http://dx.doi.org/10.1016/B978-0-12-800134-9.00007-5]
[30]
Azevedo A, Prado AF, Feldman S, de Figueiredo FAT, dos Santos MCG, Issa JPM. MMPs are involved in osteoporosis and are correlated with cardiovascular diseases. Curr Pharm Des 2018; 24(16): 1801-10.
[http://dx.doi.org/10.2174/1381612824666180604112925] [PMID: 29865998]
[31]
Valacca C, Tassone E, Mignatti P. TIMP-2 interaction with MT1-MMP activates the AKT pathway and protects tumor cells from apoptosis. PLoS One 2015; 10(9): e0136797.
[http://dx.doi.org/10.1371/journal.pone.0136797] [PMID: 26331622]
[32]
Lafleur MA, Handsley MM, Edwards DR. Metalloproteinases and their inhibitors in angiogenesis. Expert Rev Mol Med 2003; 5(23): 1-39.
[http://dx.doi.org/10.1017/S1462399403006628] [PMID: 14585170]
[33]
Shibutani T, Yamashita K, Aoki T, Iwayama Y, Nishikawa T, Hayakawa T. Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) stimulate osteoclastic bone resorption. J Bone Miner Metab 1999; 17(4): 245-51.
[http://dx.doi.org/10.1007/s007740050091] [PMID: 10575588]
[34]
Sobue T, Hakeda Y, Kobayashi Y, et al. Tissue inhibitor of metalloproteinases 1 and 2 directly stimulate the bone-resorbing activity of isolated mature osteoclasts. J Bone Miner Res 2001; 16(12): 2205-14.
[http://dx.doi.org/10.1359/jbmr.2001.16.12.2205] [PMID: 11760833]
[35]
Kramer FJ, Meyer M, Morgan D, et al. Tissue inhibitor of metalloproteinases II (TIMP-2) is an osteoanabolic factor in vitro and in vivo. Eur J Med Res 2008; 13(6): 292-8.
[PMID: 18558556]
[36]
Feng W, Liu H, Luo T, et al. Combination of IL-6 and sIL-6R differentially regulate varying levels of RANKL-induced osteoclastogenesis through NF-κB, ERK and JNK signaling pathways. Sci Rep 2017; 7(1): 41411.
[http://dx.doi.org/10.1038/srep41411] [PMID: 28128332]
[37]
Zhao R. Immune regulation of osteoclast function in postmenopausal osteoporosis: A critical interdisciplinary perspective. Int J Med Sci 2012; 9(9): 825-32.
[http://dx.doi.org/10.7150/ijms.5180] [PMID: 23136547]
[38]
Rose-John S. IL-6 trans-signaling via the soluble IL-6 receptor: Importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 2012; 8(9): 1237-47.
[http://dx.doi.org/10.7150/ijbs.4989] [PMID: 23136552]
[39]
Rose-John S. The soluble interleukin 6 receptor: Advanced therapeutic options in inflammation. Clin Pharmacol Ther 2017; 102(4): 591-8.
[http://dx.doi.org/10.1002/cpt.782] [PMID: 28675418]
[40]
Chalaris A, Garbers C, Rabe B, Rose-John S, Scheller J. The soluble Interleukin 6 receptor: Generation and role in inflammation and cancer. Eur J Cell Biol 2011; 90(6-7): 484-94.
[http://dx.doi.org/10.1016/j.ejcb.2010.10.007] [PMID: 21145125]
[41]
Tamura T, Udagawa N, Takahashi N, et al. Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proc Natl Acad Sci 1993; 90(24): 11924-8.
[http://dx.doi.org/10.1073/pnas.90.24.11924] [PMID: 8265649]
[42]
Giuliani N, Sansoni P, Girasole G, et al. Serum interleukin-6, soluble interleukin-6 receptor and soluble gp130 exhibit different patterns of age- and menopause-related changes. Exp Gerontol 2001; 36(3): 547-57.
[http://dx.doi.org/10.1016/S0531-5565(00)00220-5] [PMID: 11250125]
[43]
Abrahamsen B, Bonnevie-Nielsen V, Ebbesen EN, Gram J, Beck-Nielsen H. Cytokines and bone loss in a 5-year longitudinal study--hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: The danish osteoporosis prevention study. J Bone Miner Res 2000; 15(8): 1545-54.
[http://dx.doi.org/10.1359/jbmr.2000.15.8.1545] [PMID: 10934653]
[44]
Nishimura R, Moriyama K, Yasukawa K, Mundy GR, Yoneda T. Combination of interleukin-6 and soluble interleukin-6 receptors induces differentiation and activation of JAK-STAT and MAP kinase pathways in MG-63 human osteoblastic cells. J Bone Miner Res 1998; 13(5): 777-85.
[http://dx.doi.org/10.1359/jbmr.1998.13.5.777] [PMID: 9610741]
[45]
d’Elia H, Mattsson LÅ, Ohlsson C, Nordborg E, Carlsten H. Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1. Arthritis Res 2003; 5(4): R202-9.
[http://dx.doi.org/10.1186/ar761] [PMID: 12823855]
[46]
Chin KY, Wong SK, Ekeuku SO, Pang KL. Relationship between metabolic syndrome and bone health – an evaluation of epidemiological studies and mechanisms involved. Diabetes Metab Syndr Obes 2020; 13: 3667-90.
[http://dx.doi.org/10.2147/DMSO.S275560] [PMID: 33116718]
[47]
Wong S, Chin KY, Suhaimi F, Ahmad F, Ima-Nirwana S. The relationship between metabolic syndrome and osteoporosis: A review. Nutrients 2016; 8(6): 347.
[http://dx.doi.org/10.3390/nu8060347] [PMID: 27338453]
[48]
Kuo FC, Huang YH, Lin FH, et al. Circulating soluble IL-6 receptor concentration and visceral adipocyte size are related to insulin resistance in taiwanese adults with morbid obesity. Metab Syndr Relat Disord 2017; 15(4): 187-93.
[http://dx.doi.org/10.1089/met.2016.0135] [PMID: 28346858]
[49]
Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: Significance for metabolic inflammation. PloS one 2015; 10(7): e0133494.
[50]
Pacifici R. Cytokines, estrogen, and postmenopausal osteoporosis - the second decade. Endocrinology 1998; 139(6): 2659-61.
[http://dx.doi.org/10.1210/endo.139.6.6087] [PMID: 9607769]
[51]
ter Horst R, Jaeger M, Smeekens SP, et al. Host and environmental factors influencing individual human cytokine responses. Cell 2016; 167(4): 1111-1124.e13.
[http://dx.doi.org/10.1016/j.cell.2016.10.018] [PMID: 27814508]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version399msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[15:36:20] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[15:36:20] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[15:36:20] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[15:36:20] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (141ms)time
  • Application (258ms)time
  • 1 x Application (64.63%)
    258ms
    1 x Booting (35.37%)
    141ms
    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
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated151ms
    • 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 ('316303896','',1,1740497780,1740497780) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740497780
      4.82msalphaeurekaselec_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 ('316303896','/article/127554',1,1740497780,1740497780)
      240μsalphaeurekaselec_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 >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) 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 >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) 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 >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) 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 >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) 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 >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) 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 >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) limit 1
      18.79msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316303896
      • 1: 316303896
      • 2: 316303896
      • 3: 316303896
      • 4: 316303896
      • 5: 316303896
      • 6: 316303896
      • 7: 316303896
      • 8: 316303896
      • 9: 316303896
      • 10: 316303896
      • 11: 316303896
      • 12: 316303896
      • 13: 316303896
      • 14: 316303896
      • 15: 316303896
      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=127554
      1.2msalphaeurekaselec_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` = 59 limit 1
      1.28msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 59
      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=59) and sj.journal_id!=59 group by `j`.`nid`) as `aggregate_table`
      2.02msalphaeurekaselec_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=59) and sj.journal_id!=59 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.7msalphaeurekaselec_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=59) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      7.88msalphaeurekaselec_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=59) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      6.85msalphaeurekaselec_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` = '127554'
      370μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 127554
      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` = '127554'
      4.29msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 127554
      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` = '127554' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      4.39msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 127554
      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
      380μsalphaeurekaselec_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
      740μsalphaeurekaselec_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 = 59 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      45.32msalphaeurekaselec_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 = 59 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      13.11msalphaeurekaselec_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 = 59 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.24msalphaeurekaselec_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` = 127554 limit 1
      280μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 127554
      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 = 127554 and content_type = 'article' order by status desc limit 1
      370μsalphaeurekaselec_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` = 210876 limit 1
      280μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 210876
      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
      320μsalphaeurekaselec_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` = 'EMIDDT' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      450μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: EMIDDT
      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 = '127554' 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) )
      600μsalphaeurekaselec_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 = '12328' 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) )
      470μsalphaeurekaselec_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 = '3337' 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) )
      450μsalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3337) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3337) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3337)
      15.67msalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12328) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12328) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12328)
      710μsalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 127554) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 127554) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740497780 and j.to_date >= 1740497780 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 127554)
      650μsalphaeurekaselec_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` < '811' and is_uploaded = 1 and issue_id = 12328 order by cast(first_page as SIGNED) desc limit 1
      700μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 811
      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` > '817' and is_uploaded = 1 and issue_id = 12328 order by cast(first_page as SIGNED) asc limit 1
      520μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 817
      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'
      200μsalphaeurekaselec_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
      240μsalphaeurekaselec_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` = 127554 limit 1
      2.38msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 127554
      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` = 59 and `b`.`banner_from_date` <= 1740497780 and `b`.`banner_to_date` >= 1740497780 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.65msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 59
      • 3: 1740497780
      • 4: 1740497780
      • 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` = 59 and `b`.`banner_from_date` <= 1740497780 and `b`.`banner_to_date` >= 1740497780 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: 59
      • 3: 1740497780
      • 4: 1740497780
      • 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='fd509ab8c114b2eef7d676f859c05364'
      280μsalphaeurekaselec_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#?
        _token
        sEAyUo31SyG5OxxCsLS72b3bxuxvQEQKlqKKrVxT
        uc_cart_id
        fd509ab8c114b2eef7d676f859c05364
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/127554" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/127554
        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=eyJpdiI6IjhxZmtERFN6NkRkc2NweGVFMVkreWc9PSIsInZhbHVlIjoiOG8zUk9VOEdFcFgvNU9ZS3RmMDN5UUlYUXRiVzY5Y3VTd1hMbTh4MTl3TT0iLCJtYWMiOiJlMGI5Y2UzMWQyNDFlMzI2ZWMzYjc4MjgxNTgyZTA1NTQ0NmYwODZjZTY1NzgwOGRhYzQ2MjU5MTZiNmY1YmY3IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IjhxZmtERFN6NkRkc2NweGVFMVkreWc9PSIsInZhbHVlIjoiOG8zUk9VOEdFcFgvNU9ZS3RmMDN5UUlYUXRiVzY5Y3VTd1hMbTh4MTl3TT0iLCJtYWMiOiJlMGI5Y2UzMWQyNDFl" ] "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 => "Tue, 25 Feb 2025 15:36:20 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjN2cW1WL216bmRvQWttUjNFYUdBblE9PSIsInZhbHVlIjoic3VnMXk3VGVCanVKNGhkZi9KN3FTZE5WakREaWNQSUdSR3laeTBTZG1udGlIRGpwNGlQTU15OGljTmd2QjVKZ2crb0ZCM2wzOXZVY2RHdXMwZ3dkQVp1TWpkRUhmTk52bnkwTVh4Zk1sajBzWVZYeGZxcVMzczZEZ2ovYm9sRHgiLCJtYWMiOiIxZjY2MDMxOTQzZWU4OGJmNDdjYmFkMjE5MzJhYjhlNWVmYWZjYmZkZDEwN2Q4MjJkYWE1NzY5ZmUxMTJkYmNlIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 03:36:20 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjN2cW1WL216bmRvQWttUjNFYUdBblE9PSIsInZhbHVlIjoic3VnMXk3VGVCanVKNGhkZi9KN3FTZE5WakREaWNQSUdSR3laeTBTZG1udGlIRGpwNGlQTU15OGljTmd2QjVKZ2crb0ZCM" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImNXTERCa21EQ2RwYS84cUF2eUtFaXc9PSIsInZhbHVlIjoibUdwZkt2ajNYSG9LODlEenBUeHZwK0c2ek90bWthWVdGMXhXOHZvTnFvalF2dDlvRysyQXh6MHBSRk94SGJUTEw0VnJ5NWYvR28yb2Zub3dUb0JCMWVuS0ttSUoxK0RwOUFrb1AyVVZmM2ZCMmVScnY2WWVWaWtZcTc2VE5EbWIiLCJtYWMiOiI5ODA3M2RhZTNmYjcxOTAzNTdhZjJjYzA5YzE2NTlkMWZlMDg5YWQ4NWUzMDhjN2IxZjA0ODcyMmVmYjhmOWE1IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImNXTERCa21EQ2RwYS84cUF2eUtFaXc9PSIsInZhbHVlIjoibUdwZkt2ajNYSG9LODlEenBUeHZwK0c2ek90bWthWVdGMXhXOHZvTnFvalF2dDlvRysyQXh6MHB" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjN2cW1WL216bmRvQWttUjNFYUdBblE9PSIsInZhbHVlIjoic3VnMXk3VGVCanVKNGhkZi9KN3FTZE5WakREaWNQSUdSR3laeTBTZG1udGlIRGpwNGlQTU15OGljTmd2QjVKZ2crb0ZCM2wzOXZVY2RHdXMwZ3dkQVp1TWpkRUhmTk52bnkwTVh4Zk1sajBzWVZYeGZxcVMzczZEZ2ovYm9sRHgiLCJtYWMiOiIxZjY2MDMxOTQzZWU4OGJmNDdjYmFkMjE5MzJhYjhlNWVmYWZjYmZkZDEwN2Q4MjJkYWE1NzY5ZmUxMTJkYmNlIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 03:36:20 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjN2cW1WL216bmRvQWttUjNFYUdBblE9PSIsInZhbHVlIjoic3VnMXk3VGVCanVKNGhkZi9KN3FTZE5WakREaWNQSUdSR3laeTBTZG1udGlIRGpwNGlQTU15OGljTmd2QjVKZ2crb0ZCM" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImNXTERCa21EQ2RwYS84cUF2eUtFaXc9PSIsInZhbHVlIjoibUdwZkt2ajNYSG9LODlEenBUeHZwK0c2ek90bWthWVdGMXhXOHZvTnFvalF2dDlvRysyQXh6MHBSRk94SGJUTEw0VnJ5NWYvR28yb2Zub3dUb0JCMWVuS0ttSUoxK0RwOUFrb1AyVVZmM2ZCMmVScnY2WWVWaWtZcTc2VE5EbWIiLCJtYWMiOiI5ODA3M2RhZTNmYjcxOTAzNTdhZjJjYzA5YzE2NTlkMWZlMDg5YWQ4NWUzMDhjN2IxZjA0ODcyMmVmYjhmOWE1IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImNXTERCa21EQ2RwYS84cUF2eUtFaXc9PSIsInZhbHVlIjoibUdwZkt2ajNYSG9LODlEenBUeHZwK0c2ek90bWthWVdGMXhXOHZvTnFvalF2dDlvRysyQXh6MHB" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "sEAyUo31SyG5OxxCsLS72b3bxuxvQEQKlqKKrVxT" "uc_cart_id" => "fd509ab8c114b2eef7d676f859c05364" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/127554" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 15:36:20GET/article/127554414361