Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Survey of Drug Oxidation Activities in Hepatic and Intestinal Microsomes of Individual Common Marmosets, a New Nonhuman Primate Animal Model

Author(s): Shotaro Uehara, Toru Oshio, Kazuyuki Nakanishi, Etsuko Tomioka, Miyu Suzuki, Takashi Inoue, Yasuhiro Uno, Erika Sasaki and Hiroshi Yamazaki*

Volume 20, Issue 2, 2019

Page: [103 - 113] Pages: 11

DOI: 10.2174/1389200219666181003143312

Abstract

Background: Common marmosets (Callithrix jacchus) are potentially useful nonhuman primate models for preclinical studies. Information for major drug-metabolizing cytochrome P450 (P450) enzymes is now available that supports the use of this primate species as an animal model for drug development. Here, we collect and provide an overview of information on the activities of common marmoset hepatic and intestinal microsomes with respect to 28 typical human P450 probe oxidations.

Results: Marmoset P450 2D6/8-dependent R-metoprolol O-demethylation activities in hepatic microsomes were significantly correlated with those of midazolam 1′- and 4-hydroxylations, testosterone 6β-hydroxylation, and progesterone 6β-hydroxylation, which are probe reactions for marmoset P450 3A4/5/90. In marmosets, the oxidation activities of hepatic microsomes and intestinal microsomes were roughly comparable for midazolam and terfenadine. Overall, multiple forms of marmoset P450 enzymes in livers and intestines had generally similar substrate recognition functionalities to those of human and/or cynomolgus monkey P450 enzymes.

Conclusion: The marmoset could be a model animal for humans with respect to the first-pass extraction of terfenadine and related substrates. These findings provide a foundation for understanding individual pharmacokinetic and toxicological results in nonhuman primates as preclinical models and will help to further support understanding of the molecular mechanisms of human P450 function.

Keywords: Marmoset, CYP3A4, CYP2D6, CYP2C19, Polymorphism, PBPK.

Next »
Graphical Abstract

[1]
Nelson, D.R.; Zeldin, D.C.; Hoffman, S.M.G.; Maltais, L.J.; Wain, H.M.; Nebert, D.W. Comparison of cytochrome P450(CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics, 2004, 14, 1-18.
[2]
Guengerich, F.P. Cytochrome P450 and chemical toxicology. Chem. Res. Toxicol., 2008, 21(1), 70-83.
[3]
Sato, K.; Oiwa, R.; Kumita, W.; Henry, R.; Sakuma, T.; Ito, R.; Nozu, R.; Inoue, T.; Katano, I.; Sato, K.; Okahara, N.; Okahara, J.; Shimizu, Y.; Yamamoto, M.; Hanazawa, K.; Kawakami, T.; Kametani, Y.; Suzuki, R.; Takahashi, T.; Weinstein, E.J.; Yamamoto, T.; Sakakibara, Y.; Habu, S.; Hata, J.; Okano, H.; Sasaki, E. Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing. Cell Stem Cell, 2016, 19(1), 127-138.
[4]
Kurata, Y.; Makinodan, F.; Shimamura, N.; Katoh, M. Metabolism of di(2-ethylhexyl) phthalate(DEHP): Comparative study in juvenile and fetal marmosets and rats. J. Toxicol. Sci., 2012, 37(1), 33-49.
[5]
Shimizu, M.; Iwano, S.; Uno, Y.; Uehara, S.; Inoue, T.; Murayama, N.; Onodera, J.; Sasaki, E.; Yamazaki, H. Qualitative de novo analysis of full length cDNA and quantitative analysis of gene expression for common marmoset(Callithrix jacchus) transcriptomes using parallel long-read technology and short-read sequencing. PLoS One, 2014, 9(6), e100936.
[6]
Uehara, S.; Uno, Y.; Inoue, T.; Murayama, N.; Shimizu, M.; Sasaki, E.; Yamazaki, H. Activation and deactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by cytochrome P450 enzymes and flavin-containing monooxygenases in common marmosets (Callithrix jacchus). Drug Metab. Dispos., 2015, 43, 735-742.
[7]
Uno, Y.; Iwasaki, K.; Yamazaki, H.; Nelson, D.R. Macaque cytochromes P450: Nomenclature, transcript, gene, genomic structure, and function. Drug Metab. Rev., 2011, 43, 346-361.
[8]
Uno, Y.; Uehara, S.; Yamazaki, H. Utility of non-human primates in drug development: comparison of non-human primate and human drug-metabolizing cytochrome P450 enzymes. Biochem. Pharmacol., 2016, 121, 1-7.
[9]
Uehara, S.; Inoue, T.; Utoh, M.; Toda, A.; Shimizu, M.; Uno, Y.; Sasaki, E.; Yamazaki, H. Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol, and midazolam, in common marmosets (Callithrix jacchus). Xenobiotica, 2016, 46, 163-168.
[10]
Utoh, M.; Suemizu, H.; Mitsui, M.; Kawano, M.; Toda, A.; Uehara, S.; Uno, Y.; Shimizu, M.; Sasaki, E.; Yamazaki, H. Human plasma concentrations of cytochrome P450 probe cocktails extrapolated from pharmacokinetics in mice transplanted with human hepatocytes and from pharmacokinetics in common marmosets using physiologically based pharmacokinetic modeling. Xenobiotica, 2016, 46, 1049-1055.
[11]
Obach, R.S.; Lombardo, F.; Waters, N.J. Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug Metab. Dispos., 2008, 36(7), 1385-1405.
[12]
Uehara, S.; Uno, Y.; Inoue, S.; Kawano, M.; Shimizu, M.; Toda, A.; Utoh, M.; Sasaki, E.; Yamazaki, H. Novel marmoset cytochrome P450 2C19 in livers efficiently metabolizes human P450 2C9 and 2C19 substrates, S-warfarin, tolbutamide, flurbiprofen, and omeprazole. Drug Metab. Dispos., 2015, 43, 1408-1416.
[13]
Uehara, S.; Uno, Y.; Inoue, T.; Kawano, M.; Shimizu, M.; Toda, A.; Utoh, M.; Sasaki, E.; Yamazaki, H. Individual differences in metabolic clearance of S-warfarin efficiently mediated by polymorphic marmoset cytochrome P450 2C19 in livers. Drug Metab. Dispos., 2016, 44, 911-915.
[14]
Kusama, T.; Toda, A.; Shimizu, M.; Uehara, S.; Inoue, T.; Uno, Y.; Utoh, M.; Sasaki, E.; Yamazaki, H. Association with polymorphic marmoset cytochrome P450 2C19 of in vivo hepatic clearances of chirally separated R-omeprazole and S-warfarin using individual marmoset physiologically based pharmacokinetic models. Xenobiotica, 2018, 48(10), 1072-1077.
[15]
Toda, A.; Uehara, S.; Inoue, T.; Utoh, M.; Kusama, T.; Shimizu, M.; Uno, Y.; Mogi, M.; Sasaki, E.; Yamazaki, H. Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol, and midazolam in common marmosets genotyped for cytochrome P450 2C19. Xenobiotica, 2018, 48, 720-726.
[16]
Uehara, S.; Uno, Y.; Suzuki, T.; Inoue, S.; Utoh, M.; Sasaki, E.; Yamazaki, H. Strong induction of cytochrome P450 1A/3A, but not P450 2B, in cultured hepatocytes from common marmosets and cynomolgus monkeys by typical human P450 inducing agents. Drug Metab. Lett., 2016, 10, 244-253.
[17]
Uehara, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Substrate selectivities and catalytic activities of marmoset liver cytochrome P450 2A6 differed from those of human P450 2A6. Drug Metab. Dispos., 2015, 43, 969-976.
[18]
Uehara, S.; Uno, Y.; Hagihira, Y.; Murayama, N.; Shimizu, M.; Inoue, T.; Sasaki, E.; Yamazaki, H. Marmoset cytochrome P450 2D8 in livers and small intestines metabolizes typical human P450 2D6 substrates, metoprolol, bufuralol, and dextromethorphan. Xenobiotica, 2015, 45, 766-772.
[19]
Uehara, S.; Uno, Y.; Yuki, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. A new marmoset P450 4F12 enzyme expressed in small intestines and livers efficiently metabolizes an anti-histaminic drug ebastine. Drug Metab. Dispos., 2016, 44, 833-841.
[20]
Uehara, S.; Uno, Y.; Inoue, T.; Suzuki, T.; Utoh, M.; Sasaki, E.; Yamazaki, H. Caffeine 7-N-demethylation and C-8-oxidation mediated by liver microsomal cytochrome P450 enzymes in common marmosets. Xenobiotica, 2016, 46, 573-578.
[21]
Uehara, S.; Kawano, M.; Murayama, N.; Uno, Y.; Utoh, M.; Inoue, T.; Sasaki, E.; Yamazaki, H. Oxidation of R- and S-omeprazole stereoselectively mediated by liver microsomal cytochrome P450 2C19 enzymes from cynomolgus monkeys and common marmosets. Biochem. Pharmacol., 2016, 120, 56-62.
[22]
Uehara, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Molecular cloning, tissue distribution, and functional characterization of marmoset cytochrome P450 1A1, 1A2, and 1B1. Drug Metab. Dispos., 2016, 46, 8-15.
[23]
Uehara, S.; Uno, Y.; Inoue, T.; Okamoto, E.; Sasaki, E.; Yamazaki, H. Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine. Xenobiotica, 2016, 46, 977-985.
[24]
Uehara, S.; Uno, Y.; Nakanishi, K.; Ishii, S.; Inoue, T.; Sasaki, E.; Yamazaki, H. Marmoset cytochrome P450 3A4 orthologue expressed in liver and small intestine tissues efficiently metabolizes midazolam, alprazolam, nifedipine, and testosterone. Drug Metab. Dispos., 2017, 45, 457-467.
[25]
Uehara, S.; Uno, Y.; Ishii, S.; Inoue, T.; Sasaki, E.; Yamazaki, H. Marmoset cytochrome P450 4A11, a novel arachidonic acid and lauric acid ω-hydroxylase expressed in liver and kidney tissues. Xenobiotica, 2017, 47, 553-561.
[26]
Uehara, S.; Uno, Y.; Tomioka, E.; Inoue, T.; Sasaki, E.; Yamazaki, H. Functional characterization and tissue expression of marmoset cytochrome P450 2E1. Biopharm. Drug Dispos., 2017, 38, 394-397.
[27]
Uehara, S.; Ishii, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Regio- and stereo-selective oxidation of a cardiovascular drug metoprolol mediated by cytochrome P450 2D and 3A enzymes in marmoset livers. Drug Metab. Dispos., 2017, 45, 896-899.
[28]
Nakanishi, K.; Uehara, S.; Kusama, T.; Inoue, T.; Shimura, K.; Kamiya, Y.; Murayama, N.; Shimizu, M.; Uno, Y.; Sasaki, E.; Yamazaki, H. In vivo and in vitro diclofenac 5-hydroxylation mediated primarily by cytochrome P450 3A enzymes in common marmoset livers genotyped for P450 2C19 variants. Biochem. Pharmacol., 2018, 152, 272-278.
[29]
Nakanishi, K.; Uehara, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Progesterone hydroxylation by cytochromes P450 2C and 3A enzymes in marmoset liver microsomes. Xenobiotica, 2018, 48, 757-763.
[30]
Oshio, T.; Uehara, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver. Xenobiotica, 2019, 49(3), 265-269.
[31]
Uehara, S.; Uno, Y.; Oshio, T.; Inoue, T.; Sasaki, E.; Yamazaki, H. Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and hepatic human P450 substrates. Xenobiotica, 2018, 48, 656-662.
[32]
Uehara, S.; Yuki, Y.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Terfenadine t-butyl hydroxylation catalyzed by human and marmoset cytochrome P450 3A and 4F enzymes in livers and small intestines. Xenobiotica, 2018, 48, 342-347.
[33]
Uehara, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Correction to “Molecular cloning, tissue distribution, and functional characterization of marmoset cytochrome P450 1A1, 1A2, and 1B1”. Drug Metab. Dispos., 2017, 45, 956.
[34]
Utoh, M.; Murayama, N.; Uno, Y.; Onose, Y.; Hosaka, S.; Fujino, H.; Shimizu, M.; Iwasaki, K.; Yamazaki, H. Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline. Xenobiotica, 2013, 43, 1037-1042.
[35]
Uehara, S.; Shimizu, M.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Marmoset flavin-containing monooxygenase 3 in liver is a major benzydamine and sulindac sulfide oxygenase. Drug Metab. Dispos., 2017, 45, 497-500.
[36]
Uehara, S.; Uno, Y.; Okamoto, E.; Inoue, T.; Sasaki, E.; Yamazaki, H. Molecular cloning and characterization of marmoset aldehyde oxidase. Drug Metab. Dispos., 2017, 45, 883-886.
[37]
Uehara, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Cloning and expression of a novel catechol-O-methyltransferase in common marmosets. J. Vet. Med. Sci., 2017, 79, 267-272.
[38]
Uehara, S.; Uno, Y.; Inoue, T.; Sasaki, E.; Yamazaki, H. Molecular cloning and tissue distribution of a novel marmoset ABC transporter. Biopharm. Drug Dispos., 2018, 39, 59-63.
[39]
Uehara, S.; Murayama, N.; Yamazaki, H.; Uno, Y. A novel CYP2A26 identified in cynomolgus monkey liver metabolizes coumarin. Xenobiotica, 2010, 40, 621-629.
[40]
Uno, Y.; Uehara, S.; Kohara, S.; Iwasaki, K.; Nagata, R.; Fukuzaki, K.; Utoh, M.; Murayama, N.; Yamazaki, H. Newly identified CYP2C93 is a functional enzyme in rhesus monkey, but not in cynomolgus monkey. PLoS One, 2011, 6, e16923.
[41]
Hosoi, Y.; Uno, Y.; Murayama, N.; Fujino, H.; Shukuya, M.; Iwasaki, K.; Shimizu, M.; Utoh, M.; Yamazaki, H. Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation. Biochem. Pharmacol., 2012, 84, 1691-1695.

© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version286msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[18:37:41] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[18:37:41] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[18:37:41] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (109ms)time
  • Application (177ms)time
  • 1 x Application (61.82%)
    177ms
    1 x Booting (38.18%)
    109ms
    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
    31 statements were executed, 4 of which were duplicates, 27 unique. Show only duplicated95.55ms
    • 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','',1,1740422261,1740422261) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740422261
      2.13msalphaeurekaselec_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/93400',1,1740422261,1740422261)
      660μsalphaeurekaselec_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
      18.32msalphaeurekaselec_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=93400
      800μsalphaeurekaselec_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` = 15 limit 1
      860μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 15
      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=15) and sj.journal_id!=15 group by `j`.`nid`) as `aggregate_table`
      1.07msalphaeurekaselec_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=15) and sj.journal_id!=15 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      890μsalphaeurekaselec_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=15) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.65msalphaeurekaselec_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=15) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.49msalphaeurekaselec_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` = '93400'
      1.85msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 93400
      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` = '93400'
      3.14msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 93400
      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` = '93400' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.38msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 93400
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      260μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      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 = 15 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      25.06msalphaeurekaselec_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 = 15 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      15.58msalphaeurekaselec_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 = 15 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      8.88msalphaeurekaselec_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` = 93400 limit 1
      1.36msalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 93400
      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 = 93400 and content_type = 'article' order by status desc limit 1
      300μsalphaeurekaselec_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` = 165907 limit 1
      230μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 165907
      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
      250μsalphaeurekaselec_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` = 'CDM' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      310μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CDM
      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 = '93400' 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) )
      390μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '103' and is_uploaded = 1 and issue_id = 9024 order by cast(first_page as SIGNED) desc limit 1
      440μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 103
      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` > '113' and is_uploaded = 1 and issue_id = 9024 order by cast(first_page as SIGNED) asc limit 1
      450μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 113
      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'
      180μsalphaeurekaselec_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` = 93400 limit 1
      2.43msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 93400
      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` = 15 and `b`.`banner_from_date` <= 1740422261 and `b`.`banner_to_date` >= 1740422261 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 15
      • 3: 1740422261
      • 4: 1740422261
      • 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` = 15 and `b`.`banner_from_date` <= 1740422261 and `b`.`banner_to_date` >= 1740422261 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 15
      • 3: 1740422261
      • 4: 1740422261
      • 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='e769ce032507d1c502c427d61b645b77'
      220μsalphaeurekaselec_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
        WyehCVZLAv2siULATiSd39l4J66QMLcY6qN5uMYq
        uc_cart_id
        e769ce032507d1c502c427d61b645b77
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/93400" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/93400
        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:8 [ "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
        []
        
        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 => "Mon, 24 Feb 2025 18:37:41 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldRaUJOeHhFZXVpbkxobkZwdjI1dXc9PSIsInZhbHVlIjoiNnBublZwNFJtc0c0WktWL3g0OHc0NDlyK2FCUGU4NnVtMGFPUTd0NEp4Ujdjd0R2SjJEblE5WVdycERPSDFoVkZ1Q1lEQmxFYlFQLzFJNnlsRjFWQTFONW5iUEFwWVZ1c1JORHZLTWNFUnZDVFRrcnR4TzdXQ0dMMHkvNllvUTIiLCJtYWMiOiIwZjhiYmVmNmQzNDhjNmU1ODk2ODNkMTg0YzIxNzA2YWU4NzA0ZjE3MWIwYzdhZmJmNDJjMWM3MWUyODYxMzM3IiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 06:37:41 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IldRaUJOeHhFZXVpbkxobkZwdjI1dXc9PSIsInZhbHVlIjoiNnBublZwNFJtc0c0WktWL3g0OHc0NDlyK2FCUGU4NnVtMGFPUTd0NEp4Ujdjd0R2SjJEblE5WVdycERPSDFoVkZ1Q1lEQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6InpwaHNXOWQ0SS9TdGtFdXhWQUFWaXc9PSIsInZhbHVlIjoiOHdUa1B4WFg2SnJUeDlDTS91MGtJZmU0b3RGVUhmUk1SR1ZsUmp3S0taVzdHWkZydFZiYm51b1J1ZjY0Vzh1WVA4eDJjclZrMkx4SGl1eldlOXM4SEVYcjFxYllqcjg0NHBVam5Gc1BrUVA3MVpvZ2l2QklLVktUMWJuakhJUnoiLCJtYWMiOiI0NGExYWFiOWIxOWE1OGY2NjlmODk4NGNhODk3YWIyNDNjZjA0Y2RkZDdiN2IwYzAxNDJkZTMxYTViMzE5NmFjIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InpwaHNXOWQ0SS9TdGtFdXhWQUFWaXc9PSIsInZhbHVlIjoiOHdUa1B4WFg2SnJUeDlDTS91MGtJZmU0b3RGVUhmUk1SR1ZsUmp3S0taVzdHWkZydFZiYm51b1J" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldRaUJOeHhFZXVpbkxobkZwdjI1dXc9PSIsInZhbHVlIjoiNnBublZwNFJtc0c0WktWL3g0OHc0NDlyK2FCUGU4NnVtMGFPUTd0NEp4Ujdjd0R2SjJEblE5WVdycERPSDFoVkZ1Q1lEQmxFYlFQLzFJNnlsRjFWQTFONW5iUEFwWVZ1c1JORHZLTWNFUnZDVFRrcnR4TzdXQ0dMMHkvNllvUTIiLCJtYWMiOiIwZjhiYmVmNmQzNDhjNmU1ODk2ODNkMTg0YzIxNzA2YWU4NzA0ZjE3MWIwYzdhZmJmNDJjMWM3MWUyODYxMzM3IiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 06:37:41 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IldRaUJOeHhFZXVpbkxobkZwdjI1dXc9PSIsInZhbHVlIjoiNnBublZwNFJtc0c0WktWL3g0OHc0NDlyK2FCUGU4NnVtMGFPUTd0NEp4Ujdjd0R2SjJEblE5WVdycERPSDFoVkZ1Q1lEQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6InpwaHNXOWQ0SS9TdGtFdXhWQUFWaXc9PSIsInZhbHVlIjoiOHdUa1B4WFg2SnJUeDlDTS91MGtJZmU0b3RGVUhmUk1SR1ZsUmp3S0taVzdHWkZydFZiYm51b1J1ZjY0Vzh1WVA4eDJjclZrMkx4SGl1eldlOXM4SEVYcjFxYllqcjg0NHBVam5Gc1BrUVA3MVpvZ2l2QklLVktUMWJuakhJUnoiLCJtYWMiOiI0NGExYWFiOWIxOWE1OGY2NjlmODk4NGNhODk3YWIyNDNjZjA0Y2RkZDdiN2IwYzAxNDJkZTMxYTViMzE5NmFjIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InpwaHNXOWQ0SS9TdGtFdXhWQUFWaXc9PSIsInZhbHVlIjoiOHdUa1B4WFg2SnJUeDlDTS91MGtJZmU0b3RGVUhmUk1SR1ZsUmp3S0taVzdHWkZydFZiYm51b1J" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "WyehCVZLAv2siULATiSd39l4J66QMLcY6qN5uMYq" "uc_cart_id" => "e769ce032507d1c502c427d61b645b77" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/93400" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-24 18:37:41GET/article/93400314311