Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

High Expression of SIRT1 Associates with the Doxorubicin Resistance of Breast Cancer through the Activation of Akt

Author(s): Xiaoxia Jin, Yingze Wei, Yushan Liu, Yali Chen, Bin Zhao, Jieyu Huang, Haiyan Yu and Chunsun Li*

Volume 20, Issue 1, 2020

Page: [94 - 102] Pages: 9

DOI: 10.2174/1871520619666191028100405

Price: $65

Abstract

Background and Purpose: Although limited by side effects and development of resistance, doxorubicin still represents the most common chemotherapy for breast cancer. Thus, the identification of critical molecules to alleviate doxorubicin resistance is crucial. Here, we provide a molecular rationale for the breast cancer patients potentially benefitting from doxorubicin based on the expression levels of SIRT1, an identified member of longevity genes.

Methods: SIRT1-overexpressed and SIRT1-knockdown breast cancer cells were established to investigate the functions of SIRT1 in regulating doxorubicin resistance both in vitro and in vivo. Cell proliferation was analyzed via CCK8 assay, cell apoptosis was studied by TUNEL analysis. Molecule interaction was analyzed through co-immunoprecipitation and immunofluorescence techniques. Sensibility to doxorubicin was assessed in vivo through the nude mice tumorigenicity experiment.

Results: First, SIRT1 was found higher-expressed in breast cancer doxorubicin-resistant cells MCF-7/ADR than that in the doxorubicin- sensitive cells MCF-7. Moreover, SIRT1-knockdown MCF-7/ADR cells showed higher susceptible to doxorubicin both in vitro and in vivo models, whereas overexpressing of SIRT1 inhibited this phenotype. Accordingly, SIRT1 was found interacted with Akt, consequently promoted the activity of Akt in MCF-7/ADR cells in vitro and positively correlated with the expression of P-Akt in vivo. Reversing the activity of Akt partially downturned the doxorubicin-resistant effects mediated by SIRT1.

Conclusion: This investigation suggested the value of SIRT1 as a biomarker of response to doxorubicin, leading to the development of new tools for the management of breast cancer patients.

Keywords: Breast cancer, doxorubicin resistance, doxorubicin-sensitive, SIRT1, Akt, P-Akt.

Graphical Abstract

[1]
DeSantis, C.E.; Ma, J.; Goding Sauer, A.; Newman, L.A.; Jemal, A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J. Clin., 2017, 67(6), 439-448.
[http://dx.doi.org/10.3322/caac.21412] [PMID: 28972651]
[2]
Akram, M.; Iqbal, M.; Daniyal, M.; Khan, A.U. Awareness and current knowledge of breast cancer. Biol. Res., 2017, 50(1), 33.
[http://dx.doi.org/10.1186/s40659-017-0140-9] [PMID: 28969709]
[3]
Kolahdooz, F.; Jang, S.L.; Corriveau, A.; Gotay, C.; Johnston, N.; Sharma, S. Knowledge, attitudes, and behaviours towards cancer screening in indigenous populations: a systematic review. Lancet Oncol., 2014, 15(11), e504-e516.
[http://dx.doi.org/10.1016/S1470-2045(14)70508-X] [PMID: 25281469]
[4]
Liu, M.; Yu, X.; Chen, Z.; Yang, T.; Yang, D.; Liu, Q.; Du, K.; Li, B.; Wang, Z.; Li, S.; Deng, Y.; He, N. Aptamer selection and applications for breast cancer diagnostics and therapy. J. Nanobiotechnology, 2017, 15(1), 81.
[http://dx.doi.org/10.1186/s12951-017-0311-4] [PMID: 29132385]
[5]
Zhang, X.H.; Hao, S.; Gao, B.; Tian, W.G.; Jiang, Y.; Zhang, S.; Guo, L.J.; Luo, D.L. A network meta-analysis for toxicity of eight chemotherapy regimens in the treatment of metastatic/advanced breast cancer. Oncotarget, 2016, 7(51), 84533-84543.
[http://dx.doi.org/10.18632/oncotarget.13023] [PMID: 27811367]
[6]
Ansari, L.; Shiehzadeh, F.; Taherzadeh, Z.; Nikoofal-Sahlabadi, S.; Momtazi-Borojeni, A.A.; Sahebkar, A.; Eslami, S. The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: a systematic review of clinical trials. Cancer Gene Ther., 2017, 24(5), 189-193.
[http://dx.doi.org/10.1038/cgt.2017.9] [PMID: 28409561]
[7]
Shafei, A.; El-Bakly, W.; Sobhy, A.; Wagdy, O.; Reda, A.; Aboelenin, O.; Marzouk, A.; El Habak, K.; Mostafa, R.; Ali, M.A.; Ellithy, M. A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer. Biomed. Pharmacother., 2017, 95, 1209-1218.
[http://dx.doi.org/10.1016/j.biopha.2017.09.059] [PMID: 28931213]
[8]
Prados, J.; Melguizo, C.; Ortiz, R.; Vélez, C.; Alvarez, P.J.; Arias, J.L.; Ruíz, M.A.; Gallardo, V.; Aranega, A. Doxorubicin-loaded nanoparticles: new advances in breast cancer therapy. Anticancer. Agents Med. Chem., 2012, 12(9), 1058-1070.
[http://dx.doi.org/10.2174/187152012803529646] [PMID: 22339066]
[9]
Guarente, L. Sir2 links chromatin silencing, metabolism, and aging. Genes Dev., 2000, 14(9), 1021-1026.
[PMID: 10809662]
[10]
Hwang, B.J.; Madabushi, A.; Jin, J.; Lin, S.Y.; Lu, A.L. Histoneprotein deacetylase SIRT1 is an anticancer. Am. J. Cancer Res., 2014, 4, 211-221.
[PMID: 24959376]
[11]
Wang, R.H.; Sengupta, K.; Li, C.; Kim, H.S.; Cao, L.; Xiao, C.; Kim, S.; Xu, X.; Zheng, Y.; Chilton, B.; Jia, R.; Zheng, Z.M.; Appella, E.; Wang, X.W.; Ried, T.; Deng, C.X. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell, 2008, 14(4), 312-323.
[http://dx.doi.org/10.1016/j.ccr.2008.09.001] [PMID: 18835033]
[12]
Roth, M.; Chen, W.Y. Sorting out functions of sirtuins in cancer. Oncogene, 2014, 33(13), 1609-1620.
[http://dx.doi.org/10.1038/onc.2013.120] [PMID: 23604120]
[13]
Wang, R.H.; Zheng, Y.; Kim, H.S.; Xu, X.; Cao, L.; Luhasen, T.; Lee, M.H.; Xiao, C.; Vassilopoulos, A.; Chen, W.; Gardner, K.; Man, Y.G.; Hung, M.C.; Finkel, T.; Deng, C.X. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol. Cell, 2008, 32(1), 11-20.
[http://dx.doi.org/10.1016/j.molcel.2008.09.011] [PMID: 18851829]
[14]
Olmos, Y.; Brosens, J.J.; Lam, E.W. Interplay between SIRT proteins and tumour suppressor transcription factors in chemotherapeutic resistance of cancer. Drug Resist. Updat., 2011, 14(1), 35-44.
[http://dx.doi.org/10.1016/j.drup.2010.12.001] [PMID: 21195657]
[15]
Choi, H.K.; Cho, K.B.; Phuong, N.T.; Han, C.Y.; Han, H.K.; Hien, T.T.; Choi, H.S.; Kang, K.W. SIRT1-mediated FoxO1 deacetylation is essential for multidrug resistance-associated protein 2 expression in tamoxifen-resistant breast cancer cells. Mol. Pharm., 2013, 10(7), 2517-2527.
[http://dx.doi.org/10.1021/mp400287p] [PMID: 23763570]
[16]
Sundaresan, N.R.; Pillai, V.B.; Wolfgeher, D.; Samant, S.; Vasudevan, P.; Parekh, V.; Raghuraman, H.; Cunningham, J.M.; Gupta, M.; Gupta, M.P. The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Sci. Signal., 2011, 4(182), ra46.
[http://dx.doi.org/10.1126/scisignal.2001465] [PMID: 21775285]
[17]
Pillai, V.B.; Sundaresan, N.R.; Gupta, M.P. Regulation of Akt signaling by sirtuins: its implication in cardiac hypertrophy and aging. Circ. Res., 2014, 114(2), 368-378.
[http://dx.doi.org/10.1161/CIRCRESAHA.113.300536] [PMID: 24436432]
[18]
Liu, P.; Begley, M.; Michowski, W.; Inuzuka, H.; Ginzberg, M.; Gao, D.; Tsou, P.; Gan, W.; Papa, A.; Kim, B.M.; Wan, L.; Singh, A.; Zhai, B.; Yuan, M.; Wang, Z.; Gygi, S.P.; Lee, T.H.; Lu, K.P.; Toker, A.; Pandolfi, P.P.; Asara, J.M.; Kirschner, M.W.; Sicinski, P.; Cantley, L.; Wei, W. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature, 2014, 508(7497), 541-545.
[http://dx.doi.org/10.1038/nature13079] [PMID: 24670654]
[19]
Saini, K.S.; Loi, S.; de Azambuja, E.; Metzger-Filho, O.; Saini, M.L.; Ignatiadis, M.; Dancey, J.E.; Piccart-Gebhart, M.J. Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat. Rev., 2013, 39(8), 935-946.
[http://dx.doi.org/10.1016/j.ctrv.2013.03.009] [PMID: 23643661]
[20]
Jin, X.; Wei, Y.; Xu, F.; Zhao, M.; Dai, K.; Shen, R.; Yang, S.; Zhang, N. SIRT1 promotes formation of breast cancer through modulating Akt activity. J. Cancer, 2018, 9(11), 2012-2023.
[http://dx.doi.org/10.7150/jca.24275] [PMID: 29896286]
[21]
Lovitt, C.J.; Shelper, T.B.; Avery, V.M. Evaluation of chemotherapeutics in a three-dimensional breast cancer model. J. Cancer Res. Clin. Oncol., 2015, 141(5), 951-959.
[http://dx.doi.org/10.1007/s00432-015-1950-1] [PMID: 25773123]
[22]
Kahlem, P.; Dörken, B.; Schmitt, C.A. Cellular senescence in cancer treatment: friend or foe? J. Clin. Invest., 2004, 113(2), 169-174.
[http://dx.doi.org/10.1172/JCI20784] [PMID: 14722606]
[23]
Berns, A. Senescence: a companion in chemotherapy? Cancer Cell, 2002, 1(4), 309-311.
[http://dx.doi.org/10.1016/S1535-6108(02)00063-6] [PMID: 12086843]
[24]
Wang, Z.; Chen, W. Emerging roles of SIRT1 in cancer drug resistance. Genes Cancer, 2013, 4(3-4), 82-90.
[http://dx.doi.org/10.1177/1947601912473826] [PMID: 24019998]
[25]
Xiong, H.; Ni, Z.; He, J.; Jiang, S.; Li, X.; He, J.; Gong, W.; Zheng, L.; Chen, S.; Li, B.; Zhang, N.; Lyu, X.; Huang, G.; Chen, B.; Zhang, Y.; He, F. LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells. Oncogene, 2017, 36(25), 3528-3540.
[http://dx.doi.org/10.1038/onc.2016.521] [PMID: 28166203]
[26]
Chu, F.; Chou, P.M.; Zheng, X.; Mirkin, B.L.; Rebbaa, A. Control of multidrug resistance gene mdr1 and cancer resistance to chemotherapy by the longevity gene sirt1. Cancer Res., 2005, 65(22), 10183-10187.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2002] [PMID: 16288004]
[27]
Scheid, M.P.; Woodgett, J.R. PKB/AKT: functional insights from genetic models. Nat. Rev. Mol. Cell Biol., 2001, 2(10), 760-768.
[http://dx.doi.org/10.1038/35096067] [PMID: 11584303]
[28]
Cheng, G.Z.; Park, S.; Shu, S.; He, L.; Kong, W.; Zhang, W.; Yuan, Z.; Wang, L.H.; Cheng, J.Q. Advances of AKT pathway in human oncogenesis and as a target for anti-cancer drug discovery. Curr. Cancer Drug Targets, 2008, 8(1), 2-6.
[http://dx.doi.org/10.2174/156800908783497159] [PMID: 18288938]
[29]
D’Onofrio, N.; Servillo, L.; Balestrieri, M.L. SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection. Antioxid. Redox Signal., 2018, 28(8), 711-732.
[http://dx.doi.org/10.1089/ars.2017.7178] [PMID: 28661724]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version428msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[15:39:05] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[15:39:05] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[15:39:05] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (125ms)time
  • Application (303ms)time
  • 1 x Application (70.79%)
    303ms
    1 x Booting (29.21%)
    125ms
    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 duplicated223ms
    • 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 ('316595280','',1,1740497945,1740497945) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740497945
      1.09msalphaeurekaselec_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 ('316595280','/article/101940',1,1740497945,1740497945)
      190μsalphaeurekaselec_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 >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) 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 >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) 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 >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) 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 >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) 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 >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) 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 >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316595280 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316595280) limit 1
      11.42msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316595280
      • 1: 316595280
      • 2: 316595280
      • 3: 316595280
      • 4: 316595280
      • 5: 316595280
      • 6: 316595280
      • 7: 316595280
      • 8: 316595280
      • 9: 316595280
      • 10: 316595280
      • 11: 316595280
      • 12: 316595280
      • 13: 316595280
      • 14: 316595280
      • 15: 316595280
      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=101940
      700μsalphaeurekaselec_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` = 1 limit 1
      710μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 1
      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=1) and sj.journal_id!=1 group by `j`.`nid`) as `aggregate_table`
      1.14msalphaeurekaselec_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=1) and sj.journal_id!=1 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.2msalphaeurekaselec_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=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.03msalphaeurekaselec_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=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.56msalphaeurekaselec_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` = '101940'
      1.86msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 101940
      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` = '101940'
      2.6msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 101940
      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` = '101940' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.83msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 101940
      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
      240μsalphaeurekaselec_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
      490μsalphaeurekaselec_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 = 1 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      26.1msalphaeurekaselec_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 = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.97msalphaeurekaselec_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 = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.73msalphaeurekaselec_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` = 101940 limit 1
      320μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 101940
      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 = 101940 and content_type = 'article' order by status desc limit 1
      380μsalphaeurekaselec_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 = 16 and cd.sub_disease_id = 436 and content_id!=101940 and cd.content_type = 'article' order by rand() limit 20
      108msalphaeurekaselec_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` = 176218 limit 1
      230μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 176218
      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
      230μsalphaeurekaselec_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` = 'ACAMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      350μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: ACAMC
      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 = '101940' 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) )
      460μsalphaeurekaselec_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 = '9679' 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) )
      400μsalphaeurekaselec_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 = '2704' 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) )
      360μsalphaeurekaselec_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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2704) 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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2704) 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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2704)
      23.45msalphaeurekaselec_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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9679) 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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9679) 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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9679)
      820μsalphaeurekaselec_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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 101940) 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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 101940) 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 <= 316595280 and j.to_ip >=316595280 )) and ((j.from_date <= 1740497945 and j.to_date >= 1740497945 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 101940)
      770μsalphaeurekaselec_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` < '94' and is_uploaded = 1 and issue_id = 9679 order by cast(first_page as SIGNED) desc limit 1
      680μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 94
      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` > '102' and is_uploaded = 1 and issue_id = 9679 order by cast(first_page as SIGNED) asc limit 1
      580μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 102
      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
      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` = 101940 limit 1
      3.69msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 101940
      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` = 1 and `b`.`banner_from_date` <= 1740497945 and `b`.`banner_to_date` >= 1740497945 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.75msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740497945
      • 4: 1740497945
      • 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` = 1 and `b`.`banner_from_date` <= 1740497945 and `b`.`banner_to_date` >= 1740497945 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.5msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1740497945
      • 4: 1740497945
      • 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='0aa6d6687dafb7988f9dfc7f9abc885f'
      360μsalphaeurekaselec_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
        eqQfa0L2vZFqgLH4ivJNGYzUDf7mcagsZk3ghwgu
        uc_cart_id
        0aa6d6687dafb7988f9dfc7f9abc885f
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/101940" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/101940
        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=eyJpdiI6InpUMXBOdmVJdDBjeHBBQUMybXBJbWc9PSIsInZhbHVlIjoiaU9QQ2NmeU5nV213RzYwUlhENklhUE9wU09OUE9NcFEzMm8yTXMxb2FsWT0iLCJtYWMiOiJmZWEyMjhiYjE3MjVjMzZkZmUxNGE0YmEwNTk1YzNlYjAyYTJkYTM1Zjk4NTM4ZTIzOWMwNjE3ZDlkYTY3N2Y2IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InpUMXBOdmVJdDBjeHBBQUMybXBJbWc9PSIsInZhbHVlIjoiaU9QQ2NmeU5nV213RzYwUlhENklhUE9wU09OUE9NcFEzMm8yTXMxb2FsWT0iLCJtYWMiOiJmZWEyMjhiYjE3MjVj" ] "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 15:39:05 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ik92TldoRmxMZHJRb2ZJWGp4d09PdWc9PSIsInZhbHVlIjoiTnR1aklzZWNMYXZUVGg5RzcydG1iYkdVN1BOZWNsZGpKMEJkTkdpQm84YXZBc1BpQktKRng4VG1sbnlkMEZQd1dacExRQ2VLRHR0NjdZOWtCaDZSRlF4YzZMMnJRa0FMdGQyRzhaMmd0OGxFM0xmR21SOGwxUHdPYS8xZnYxY1ciLCJtYWMiOiI1MGE4ZTM1NmMwZWI2NzNjNTM1ZDY2YjBiOWRlZDdkN2RmNjJlNGUzNzliOGZhZmNlY2E3YTNjODA3YzU4ODk5IiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 03:39:05 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Ik92TldoRmxMZHJRb2ZJWGp4d09PdWc9PSIsInZhbHVlIjoiTnR1aklzZWNMYXZUVGg5RzcydG1iYkdVN1BOZWNsZGpKMEJkTkdpQm84YXZBc1BpQktKRng4VG1sbnlkMEZQd1dacExRQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ijdic1I1ejNrQ0YzdGNNUnprNDhwL1E9PSIsInZhbHVlIjoibkJKM1orcW0wYW9neG1Mci9namtCV3BlSGtUOXpndkpaK3Q4UVRvNUFLeGxyT0hKRFlUYXU1TWcwRFhpSXhtTXNCbnRIL003TlVML3FzQTByRHJSQnVEc285Wk81VVpTNWN4dC9jRUZzTTdHdzlmYkttakdaUXlBbVZMMFNyckoiLCJtYWMiOiIyMGE4NGVlZDdhZTdkMTFiNDBiYzdiYTViYTg2NjgyNGQwYTQ4ZjlhNTZlNmVhODBkYjMxYjk2YmE3Y2NkNmZlIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Ijdic1I1ejNrQ0YzdGNNUnprNDhwL1E9PSIsInZhbHVlIjoibkJKM1orcW0wYW9neG1Mci9namtCV3BlSGtUOXpndkpaK3Q4UVRvNUFLeGxyT0hKRFlUYXU1TWc" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ik92TldoRmxMZHJRb2ZJWGp4d09PdWc9PSIsInZhbHVlIjoiTnR1aklzZWNMYXZUVGg5RzcydG1iYkdVN1BOZWNsZGpKMEJkTkdpQm84YXZBc1BpQktKRng4VG1sbnlkMEZQd1dacExRQ2VLRHR0NjdZOWtCaDZSRlF4YzZMMnJRa0FMdGQyRzhaMmd0OGxFM0xmR21SOGwxUHdPYS8xZnYxY1ciLCJtYWMiOiI1MGE4ZTM1NmMwZWI2NzNjNTM1ZDY2YjBiOWRlZDdkN2RmNjJlNGUzNzliOGZhZmNlY2E3YTNjODA3YzU4ODk5IiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 03:39:05 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Ik92TldoRmxMZHJRb2ZJWGp4d09PdWc9PSIsInZhbHVlIjoiTnR1aklzZWNMYXZUVGg5RzcydG1iYkdVN1BOZWNsZGpKMEJkTkdpQm84YXZBc1BpQktKRng4VG1sbnlkMEZQd1dacExRQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ijdic1I1ejNrQ0YzdGNNUnprNDhwL1E9PSIsInZhbHVlIjoibkJKM1orcW0wYW9neG1Mci9namtCV3BlSGtUOXpndkpaK3Q4UVRvNUFLeGxyT0hKRFlUYXU1TWcwRFhpSXhtTXNCbnRIL003TlVML3FzQTByRHJSQnVEc285Wk81VVpTNWN4dC9jRUZzTTdHdzlmYkttakdaUXlBbVZMMFNyckoiLCJtYWMiOiIyMGE4NGVlZDdhZTdkMTFiNDBiYzdiYTViYTg2NjgyNGQwYTQ4ZjlhNTZlNmVhODBkYjMxYjk2YmE3Y2NkNmZlIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Ijdic1I1ejNrQ0YzdGNNUnprNDhwL1E9PSIsInZhbHVlIjoibkJKM1orcW0wYW9neG1Mci9namtCV3BlSGtUOXpndkpaK3Q4UVRvNUFLeGxyT0hKRFlUYXU1TWc" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "eqQfa0L2vZFqgLH4ivJNGYzUDf7mcagsZk3ghwgu" "uc_cart_id" => "0aa6d6687dafb7988f9dfc7f9abc885f" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/101940" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 15:39:05GET/article/101940314371