Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Research Article

Metabolome Profiling of Malignant Ascites Identifies Candidate Metabolic Biomarkers of Hepatocellular Carcinoma

Author(s): Weijia Wang, Yue Wu, Qinsheng Zhang* and Peilin Cui*

Volume 31, Issue 13, 2024

Published on: 12 June, 2023

Page: [1769 - 1780] Pages: 12

DOI: 10.2174/0929867330666230324153552

Price: $65

Abstract

Background: Malignant ascites is one of the severe complications of hepatocellular carcinoma, which can be regarded as a unique tumor microenvironment of hepatocellular carcinoma. The identification of novel biomarkers in malignant ascites could be crucial to differentiate patients with hepatocellular carcinoma and cirrhotic ascites.

Objective: The study aimed to distinguish the metabolomics of malignant ascites in patients with hepatocellular carcinoma from that of non-malignant ascites (cirrhotic ascites).

Methods: Liquid chromatography-mass spectrometry was performed to analyze the differentially distributed biomarkers in patients with malignant ascites and hepatocellular carcinoma (n = 39), as well as in patients with cirrhotic ascites, which were taken as controls (n = 36).

Results: A total of 20 differential metabolites associated with malignant ascites were identified, of which 8 metabolites were upregulated and 12 metabolites were downregulated (ratio < 0.5 or > 1.5, respectively). Moreover, pathway and enrichment analyses revealed nitrogen metabolism, urea cycle, phenylalanine, and tyrosine metabolism to be implicated in the formation of malignant ascites in patients with hepatocellular carcinoma.

Conclusion: Our results suggest that the key factors associated with pathways, such as arachidonic acid, phenylalanine, and glutamic acid pathways, are potential ascitic fluidbased biomarkers for differentiating hepatocellular carcinoma with cirrhosis ascites; the results also provide a clinical pathophysiological interpretation of biomarkers and metabolic pathways relevant to disease status.

« Previous
[1]
Zheng, L.; Xu, M.; Xu, J.; Wu, K.; Fang, Q.; Liang, Y.; Zhou, S.; Cen, D.; Ji, L.; Han, W.; Cai, X. ELF3 promotes epithelial–mesenchymal transition by protecting ZEB1 from miR-141-3p-mediated silencing in hepatocellular carcinoma. Cell Death Dis., 2018, 9(3), 387.
[http://dx.doi.org/10.1038/s41419-018-0399-y] [PMID: 29523781]
[2]
El-Serag, H.B. Hepatocellular carcinoma. N. Engl. J. Med., 2011, 365(12), 1118-1127.
[http://dx.doi.org/10.1056/NEJMra1001683] [PMID: 21992124]
[3]
Pavlova, N.N.; Thompson, C.B. The emerging hallmarks of cancer metabolism. Cell Metab., 2016, 23(1), 27-47.
[http://dx.doi.org/10.1016/j.cmet.2015.12.006] [PMID: 26771115]
[4]
Cavazzoni, E.; Bugiantella, W.; Graziosi, L.; Franceschini, M.S.; Donini, A. Malignant ascites: Pathophysiology and treatment. Int. J. Clin. Oncol., 2013, 18(1), 1-9.
[http://dx.doi.org/10.1007/s10147-012-0396-6] [PMID: 22460778]
[5]
Watala, C.; Karolczak, K.; Kassassir, H.; Talar, M.; Przygodzki, T.; Maczynska, K.; Labieniec-Watala, M. How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Activation of circulating platelets and formation of “fibrinogen aggregates” in the presence of polycations. Int. J. Pharm., 2016, 503(1-2), 247-261.
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.073] [PMID: 26319628]
[6]
Pillai, R.C.; Fraser, J.F.; Ziegenfuss, M.; Bhaskar, B. Influence of circulating levels of fibrinogen and perioperative coagulation parameters on predicting postoperative blood loss in cardiac surgery: A prospective observational study. J. Card. Surg., 2014, 29(2), 189-195.
[http://dx.doi.org/10.1111/jocs.12255] [PMID: 24734282]
[7]
Moore, C.M.; Van Thiel, D.H. Cirrhotic ascites review: Pathophysiology, diagnosis and management. World J. Hepatol., 2013, 5(5), 251-263.
[http://dx.doi.org/10.4254/wjh.v5.i5.251] [PMID: 23717736]
[8]
Oberg, A.L.; Mahoney, D.W. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling. BMC Bioinformatics, 2012, 13(S16), 7.
[http://dx.doi.org/10.1186/1471-2105-13-S16-S7]
[9]
Thompson, J.W.; Forrester, M.T.; Moseley, M.A.; Foster, M.W. Solid-phase capture for the detection and relative quantification of S-nitrosoproteins by mass spectrometry. Methods, 2013, 62(2), 130-137.
[http://dx.doi.org/10.1016/j.ymeth.2012.10.001] [PMID: 23064468]
[10]
Mehrotra, S.; Goyal, V. Evaluation of designer crops for biosafety-A scientist’s perspective. Gene, 2013, 515(2), 241-248.
[http://dx.doi.org/10.1016/j.gene.2012.12.029] [PMID: 23266812]
[11]
Sauzay, C.; Petit, A.; Bourgeois, A.M.; Barbare, J.C.; Chauffert, B.; Galmiche, A.; Houessinon, A. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma. Clin Chim Acta, 2016, 463, 39-44.
[12]
Lindon, J.C.; Holmes, E.; Nicholson, J.K. Metabonomics in pharmaceutical R & D. FEBS J., 2007, 274(5), 1140-1151.
[http://dx.doi.org/10.1111/j.1742-4658.2007.05673.x] [PMID: 17298438]
[13]
Zhang, J.; Liang, R.; Wei, J.; Ye, J.; He, Q.; ChunlingYuan; Ye, J.; Li, Y.; Liu, Z.; Lin, Y. Identification of candidate biomarkers in malignant ascites from patients with hepatocellular carcinoma by iTRAQ-based quantitative proteomic analysis. BioMed Res. Int., 2018, 2018, 1-11.
[http://dx.doi.org/10.1155/2018/5484976] [PMID: 30345303]
[14]
Lee, S.S.; Min, H.J.; Choi, J.Y.; Cho, H.C.; Kim, J.J.; Lee, J.M.; Kim, H.J.; Ha, C.Y.; Kim, H.J.; Kim, T.H.; Kim, J.H.; Lee, O.J. Usefulness of ascitic fluid lactoferrin levels in patients with liver cirrhosis. BMC Gastroenterol., 2016, 16(1), 132.
[http://dx.doi.org/10.1186/s12876-016-0546-9] [PMID: 27733127]
[15]
Sui, Z.; Li, Q.; Zhu, L.; Wang, Z.; Lv, C.; Liu, R.; Xu, H.; He, B.; Li, Z.; Bi, K. An integrative investigation of the toxicity of Aconiti kusnezoffii radix and the attenuation effect of its processed drug using a UHPLC-Q-TOF based rat serum and urine metabolomics strategy. J. Pharm. Biomed. Anal., 2017, 145, 240-247.
[http://dx.doi.org/10.1016/j.jpba.2017.06.049] [PMID: 28668652]
[16]
Wang, X.; Zhang, A.; Sun, H. Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma. Hepatology, 2013, 57(5), 2072-2077.
[http://dx.doi.org/10.1002/hep.26130] [PMID: 23150189]
[17]
Jiang, M.; Lu, C.; Zhang, C.; Yang, J.; Tan, Y.; Lu, A.; Chan, K. Syndrome differentiation in modern research of traditional Chinese medicine. J. Ethnopharmacol., 2012, 140(3), 634-642.
[http://dx.doi.org/10.1016/j.jep.2012.01.033] [PMID: 22322251]
[18]
Zira, A.N.; Theocharis, S.E.; Mitropoulos, D.; Migdalis, V.; Mikros, E. (1)H NMR metabonomic analysis in renal cell carcinoma: A possible diagnostic tool. J. Proteome Res., 2010, 9(8), 4038-4044.
[http://dx.doi.org/10.1021/pr100226m] [PMID: 20527959]
[19]
Lu, X.; Zhao, X.; Bai, C.; Zhao, C.; Lu, G.; Xu, G. LC–MS-based metabonomics analysis. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2008, 866(1-2), 64-76.
[http://dx.doi.org/10.1016/j.jchromb.2007.10.022] [PMID: 17983864]
[20]
Jiang, W.; Qiu, Y.; Ni, Y.; Su, M.; Jia, W.; Du, X. An automated data analysis pipeline for GC-TOF-MS metabonomics studies. J. Proteome Res., 2010, 9(11), 5974-5981.
[http://dx.doi.org/10.1021/pr1007703] [PMID: 20825247]
[21]
Safaei, A.; Arefi Oskouie, A.; Mohebbi, S.R.; Rezaei-Tavirani, M.; Mahboubi, M.; Peyvandi, M.; Okhovatian, F.; Zamanian-Azodi, M. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases. Gastroenterol. Hepatol. Bed Bench, 2016, 9(3), 158-173.
[PMID: 27458508]
[22]
Cui, W.; Zhang, J.; Wu, D.; Zhang, J.; Zhou, H.; Rong, Y.; Liu, F.; Wei, B.; Xu, X. Ponicidin suppresses pancreatic cancer growth by inducing ferroptosis: Insight gained by mass spectrometry-based metabolomics. Phytomedicine, 2022, 98, 153943.
[http://dx.doi.org/10.1016/j.phymed.2022.153943] [PMID: 35104766]
[23]
Zhang, H.; Bian, S.; Xu, Z.; Gao, M.; Wang, H.; Zhang, J.; Zhang, M.; Ke, Y.; Wang, W.; Chen, Z.S.; Xu, H. The effect and mechanistic study of encequidar on reversing the resistance of SW620/AD300 cells to doxorubicin. Biochem. Pharmacol., 2022, 205, 115258.
[http://dx.doi.org/10.1016/j.bcp.2022.115258] [PMID: 36179932]
[24]
Jha, V.K.; Shenoy, G.; Borpujari, P.J.; Banerjee, M. Biomarkers of malignant ascites-a myth or reality. Med. J. Armed Forces India, 2011, 67(4), 398.
[http://dx.doi.org/10.1016/S0377-1237(11)60100-7] [PMID: 27365864]
[25]
Coloff, J.L.; Murphy, J.P.; Braun, C.R.; Harris, I.S.; Shelton, L.M.; Kami, K.; Gygi, S.P.; Selfors, L.M.; Brugge, J.S. Differential glutamate metabolism in proliferating and quiescent mammary epithelial cells. Cell Metab., 2016, 23(5), 867-880.
[http://dx.doi.org/10.1016/j.cmet.2016.03.016] [PMID: 27133130]
[26]
Prickett, T.D.; Samuels, Y. Molecular pathways: Dysregulated glutamatergic signaling pathways in cancer. Clin. Cancer Res., 2012, 18(16), 4240-4246.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1217] [PMID: 22648273]
[27]
Matsuda, K. Novel susceptibility loci for hepatocellular carcinoma in chronic HBV carriers. Hepatobiliary Surg. Nutr., 2012, 1(1), 59-60.
[PMID: 24570905]
[28]
Nahon, P.; Amathieu, R.; Triba, M.N.; Bouchemal, N.; Nault, J.C.; Ziol, M.; Seror, O.; Dhonneur, G.; Trinchet, J.C.; Beaugrand, M.; Le Moyec, L. Identification of serum proton NMR metabolomic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis. Clin. Cancer Res., 2012, 18(24), 6714-6722.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-1099] [PMID: 23136190]
[29]
Han, M.; Xie, M.; Han, J.; Yuan, D.; Yang, T.; Xie, Y. Development and validation of a rapid, selective, and sensitive LC–MS/MS method for simultaneous determination of d- and l-amino acids in human serum: application to the study of hepatocellular carcinoma. Anal. Bioanal. Chem., 2018, 410(10), 2517-2531.
[http://dx.doi.org/10.1007/s00216-018-0883-3] [PMID: 29492623]
[30]
Keshet, R.; Szlosarek, P.; Carracedo, A.; Erez, A. Rewiring urea cycle metabolism in cancer to support anabolism. Nat. Rev. Cancer, 2018, 18(10), 634-645.
[http://dx.doi.org/10.1038/s41568-018-0054-z] [PMID: 30194362]
[31]
Kim, D.; Cho, E.; Yu, K.S.; Jang, I.J.; Yoon, J.H.; Park, T.; Cho, J.Y. Comprehensive metabolomic search for biomarkers to differentiate early stage hepatocellular carcinoma from cirrhosis. Cancers, 2019, 11(10), 1497.
[http://dx.doi.org/10.3390/cancers11101497] [PMID: 31590436]
[32]
Spinelli, J.B.; Yoon, H.; Ringel, A.E.; Jeanfavre, S.; Clish, C.B.; Haigis, M.C. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass. Science, 2017, 358(6365), 941-946.
[http://dx.doi.org/10.1126/science.aam9305] [PMID: 29025995]
[33]
Brosnan, M.E.; Brosnan, J.T. Hepatic glutamate metabolism: A tale of 2 hepatocytes. Am. J. Clin. Nutr., 2009, 90(3), 857S-861S.
[http://dx.doi.org/10.3945/ajcn.2009.27462Z] [PMID: 19625684]
[34]
Mian, A.; Lee, B. Urea-cycle disorders as a paradigm for inborn errors of hepatocyte metabolism. Trends Mol. Med., 2002, 8(12), 583-589.
[http://dx.doi.org/10.1016/S1471-4914(02)02437-1] [PMID: 12470992]
[35]
Gong, Z.G.; Zhao, W.; Zhang, J.; Wu, X.; Hu, J.; Yin, G.C.; Xu, Y.J. Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis. Oncotarget, 2017, 8(38), 63890-63900.
[http://dx.doi.org/10.18632/oncotarget.19173] [PMID: 28969038]
[36]
Yang, F.; Li, J.; Deng, H.; Wang, Y.; Lei, C.; Wang, Q.; Xiang, J.; Liang, L.; Xia, J.; Pan, X.; Li, X.; Long, Q.; Chang, L.; Xu, P.; Huang, A.; Wang, K.; Tang, N. GSTZ 1-1 deficiency activates NRF 2/ IGF 1R Axis in HCC via accumulation of oncometabolite succinylacetone. EMBO J., 2019, 38(15), e101964.
[http://dx.doi.org/10.15252/embj.2019101964] [PMID: 31267557]
[37]
Linkous, A.G.; Yazlovitskaya, E.M.; Hallahan, D.E. Cytosolic phospholipase A2 and lysophospholipids in tumor angiogenesis. J. Natl. Cancer Inst., 2010, 102(18), 1398-1412.
[http://dx.doi.org/10.1093/jnci/djq290] [PMID: 20729478]
[38]
Jee, S.H.; Kim, M.; Kim, M.; Yoo, H.J.; Kim, H.; Jung, K.J.; Hong, S.; Lee, J.H. Metabolomics profiles of hepatocellular carcinoma in a Korean prospective cohort: The Korean cancer prevention study-II. Cancer Prev. Res. (Phila.), 2018, 11(5), 303-312.
[http://dx.doi.org/10.1158/1940-6207.CAPR-17-0249] [PMID: 29500188]
[39]
Sun, X.M.; Dong, W.G.; Yu, B.P.; Luo, H.S.; Yu, J.P. Detection of type IV collagenase activity in malignant ascites. World J. Gastroenterol., 2003, 9(11), 2592-2595.
[http://dx.doi.org/10.3748/wjg.v9.i11.2592] [PMID: 14606104]
[40]
Kountouras, J.; Boura, P.; Tsapas, G.; Charisis, K.; Magoula, I.; Tsakiri, I. Value of ascitic fluid ferritin in the differential diagnosis of malignant ascites. Anticancer Res., 1993, 13(6B), 2441-2445.
[PMID: 8135481]
[41]
Wang, X.; Lin, G.; Huang, Y. Study on biomarkers of serum and ascites in patients with liver cirrhosis or liver cancer. World Chin. Digestion J., 1999, 7, 642-643.
[42]
Xu, P.; Zhu, B. Clinical significance of serum and ascites α-L-fucosylase in liver cancer. Jiangsu Med., 1990, 16(2), 91-92.

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version498msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[08:58:14] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[08:58:14] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[08:58:14] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[08:58:14] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[08:58:14] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (148ms)time
  • Application (351ms)time
  • 1 x Application (70.37%)
    351ms
    1 x Booting (29.63%)
    148ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated244ms
    • 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 ('873341851','',1,1740473894,1740473894) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740473894
      2.17msalphaeurekaselec_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 ('873341851','/article/130349',1,1740473894,1740473894)
      260μsalphaeurekaselec_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 >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) 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 >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) 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 >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) 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 >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) 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 >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) 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 >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 873341851 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873341851) limit 1
      18.36msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 873341851
      • 1: 873341851
      • 2: 873341851
      • 3: 873341851
      • 4: 873341851
      • 5: 873341851
      • 6: 873341851
      • 7: 873341851
      • 8: 873341851
      • 9: 873341851
      • 10: 873341851
      • 11: 873341851
      • 12: 873341851
      • 13: 873341851
      • 14: 873341851
      • 15: 873341851
      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=130349
      980μsalphaeurekaselec_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` = 25 limit 1
      40.71msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 25
      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=25) and sj.journal_id!=25 group by `j`.`nid`) as `aggregate_table`
      2.28msalphaeurekaselec_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=25) and sj.journal_id!=25 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.82msalphaeurekaselec_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=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      5.54msalphaeurekaselec_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=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      4.74msalphaeurekaselec_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` = '130349'
      300μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 130349
      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` = '130349'
      4.38msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 130349
      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` = '130349' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.04msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 130349
      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
      340μsalphaeurekaselec_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
      680μsalphaeurekaselec_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 = 25 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      48.65msalphaeurekaselec_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 = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      54.52msalphaeurekaselec_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 = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      31.99msalphaeurekaselec_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` = 130349 limit 1
      300μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 130349
      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 = 130349 and content_type = 'article' order by status desc limit 1
      310μsalphaeurekaselec_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` = 214960 limit 1
      270μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 214960
      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
      300μsalphaeurekaselec_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` = 'CMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      660μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMC
      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 = '130349' 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) )
      420μsalphaeurekaselec_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 = '13043' 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) )
      410μsalphaeurekaselec_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 = '3436' 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) )
      370μsalphaeurekaselec_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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3436) 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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3436) 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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3436)
      10.19msalphaeurekaselec_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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13043) 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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13043) 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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13043)
      1.06msalphaeurekaselec_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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 130349) 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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 130349) 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 <= 873341851 and j.to_ip >=873341851 )) and ((j.from_date <= 1740473894 and j.to_date >= 1740473894 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 130349)
      950μsalphaeurekaselec_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` < '1769' and is_uploaded = 1 and issue_id = 13043 order by cast(first_page as SIGNED) desc limit 1
      750μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1769
      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` > '1780' and is_uploaded = 1 and issue_id = 13043 order by cast(first_page as SIGNED) asc limit 1
      660μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1780
      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'
      240μsalphaeurekaselec_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
      280μsalphaeurekaselec_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` = 130349 limit 1
      3.86msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 130349
      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` = 25 and `b`.`banner_from_date` <= 1740473894 and `b`.`banner_to_date` >= 1740473894 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.55msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740473894
      • 4: 1740473894
      • 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` = 25 and `b`.`banner_from_date` <= 1740473894 and `b`.`banner_to_date` >= 1740473894 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.47msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740473894
      • 4: 1740473894
      • 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='08ebd652f1112d60a73ef6fa0e5eae53'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        c9ChYNclWAnGGgWlDsZ0Ky5rjhpuvfvQ3Vxju8Jy
        uc_cart_id
        08ebd652f1112d60a73ef6fa0e5eae53
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/130349" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/130349
        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:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InZUajk5V0Q2akY1aWtyN3YrQVpBaGc9PSIsInZhbHVlIjoiS0N4ZkVnakFoaFZNUktSL1pWZmJ6TmYzMGpuUnlocVIvUUNxN3F1WlZGQT0iLCJtYWMiOiJhNjgyZTRiNDcyZWJhYTJkMzE2NzNlNjA3MDc1NjUzNTk2NTFmNzQ5YjM3OTk3ZGE3Yzc1ZWFkN2UyOWMwNWY1IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InZUajk5V0Q2akY1aWtyN3YrQVpBaGc9PSIsInZhbHVlIjoiS0N4ZkVnakFoaFZNUktSL1pWZmJ6TmYzMGpuUnlocVIvUUNxN3F1WlZGQT0iLCJtYWMiOiJhNjgyZTRiNDcyZWJh" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "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" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        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 08:58:14 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjNRd0tTZWx2c2dNdHozSFd0NFpaa0E9PSIsInZhbHVlIjoibFYxdmxsRHROQkZOdFJIYm5CaWxBaXJkUVRGVmsvRmoxYm1aM21lWkltWkhpT3BwMHpFYW1WNDZaaGt0SDNBMS9teTJTVW9xUWZaMjZpNzByaU9DbTNqalBnTFpsYWZYSWUrMUNKWThsN1lLdE5CSnVscE5iVTl2YjJYVnZsOWgiLCJtYWMiOiJkODdiYjVhNTRjMWUwYTRmYzRmNjk5NTFlMDc2ZGM3OTIzN2I3MDdjMzY4M2ViNDg5YzZlMTZiNWJkYmY2NmE5IiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 20:58:14 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjNRd0tTZWx2c2dNdHozSFd0NFpaa0E9PSIsInZhbHVlIjoibFYxdmxsRHROQkZOdFJIYm5CaWxBaXJkUVRGVmsvRmoxYm1aM21lWkltWkhpT3BwMHpFYW1WNDZaaGt0SDNBMS9teTJTV" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZtaTIrem1DNFdyS0p4ejJSejdqTGc9PSIsInZhbHVlIjoiVVlHcGg5YlpsTnpvNFZtM21oYUtqcVF0TEVHN1ptTS9jTnk4T2x5blV3UXZNZjlpTGZ0cDRPMDVqNEhmd2tNNU5STTlKL3lBZFE4TUV4bDZ0b2tRcmVhRjBJNW5NRlZmQndTY2NJdGpPeU1BVTMxL0FOQzQzci9sYytmZ3dzcGkiLCJtYWMiOiIzMzkwZTlkMGFmZjJmNTU0YTA4MWI2ODliYjBhNzFlZTliMjI2Y2M5MjAyOWI4MzI3ZDQ0MjNiNzEzY2ZhNjk5IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InZtaTIrem1DNFdyS0p4ejJSejdqTGc9PSIsInZhbHVlIjoiVVlHcGg5YlpsTnpvNFZtM21oYUtqcVF0TEVHN1ptTS9jTnk4T2x5blV3UXZNZjlpTGZ0cDRPMDV" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjNRd0tTZWx2c2dNdHozSFd0NFpaa0E9PSIsInZhbHVlIjoibFYxdmxsRHROQkZOdFJIYm5CaWxBaXJkUVRGVmsvRmoxYm1aM21lWkltWkhpT3BwMHpFYW1WNDZaaGt0SDNBMS9teTJTVW9xUWZaMjZpNzByaU9DbTNqalBnTFpsYWZYSWUrMUNKWThsN1lLdE5CSnVscE5iVTl2YjJYVnZsOWgiLCJtYWMiOiJkODdiYjVhNTRjMWUwYTRmYzRmNjk5NTFlMDc2ZGM3OTIzN2I3MDdjMzY4M2ViNDg5YzZlMTZiNWJkYmY2NmE5IiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 20:58:14 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjNRd0tTZWx2c2dNdHozSFd0NFpaa0E9PSIsInZhbHVlIjoibFYxdmxsRHROQkZOdFJIYm5CaWxBaXJkUVRGVmsvRmoxYm1aM21lWkltWkhpT3BwMHpFYW1WNDZaaGt0SDNBMS9teTJTV" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZtaTIrem1DNFdyS0p4ejJSejdqTGc9PSIsInZhbHVlIjoiVVlHcGg5YlpsTnpvNFZtM21oYUtqcVF0TEVHN1ptTS9jTnk4T2x5blV3UXZNZjlpTGZ0cDRPMDVqNEhmd2tNNU5STTlKL3lBZFE4TUV4bDZ0b2tRcmVhRjBJNW5NRlZmQndTY2NJdGpPeU1BVTMxL0FOQzQzci9sYytmZ3dzcGkiLCJtYWMiOiIzMzkwZTlkMGFmZjJmNTU0YTA4MWI2ODliYjBhNzFlZTliMjI2Y2M5MjAyOWI4MzI3ZDQ0MjNiNzEzY2ZhNjk5IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InZtaTIrem1DNFdyS0p4ejJSejdqTGc9PSIsInZhbHVlIjoiVVlHcGg5YlpsTnpvNFZtM21oYUtqcVF0TEVHN1ptTS9jTnk4T2x5blV3UXZNZjlpTGZ0cDRPMDV" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "c9ChYNclWAnGGgWlDsZ0Ky5rjhpuvfvQ3Vxju8Jy" "uc_cart_id" => "08ebd652f1112d60a73ef6fa0e5eae53" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/article/130349" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 08:58:14GET/article/130349514361