Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Meta-Analysis

Selective Vascular Endothelial Growth Factor Receptor Inhibitors Provide Limited Benefits for Metastatic Colorectal Cancer: A Meta-Analysis

Author(s): Qin Fan, Wenhao Lv, Yuexin Xu, Yuan Dong, Zhiqiang Xiang and Junjie Wang*

Volume 26, Issue 26, 2020

Page: [3171 - 3186] Pages: 16

DOI: 10.2174/1381612826666200218095932

Price: $65

Abstract

Background: Metastatic colorectal cancer (mCRC) is one of the most common and deadly cancers worldwide. For most patients diagnosed with mCRC and managed with 5-fluorouracil (5-FU)/leucovorin plus oxaliplatin (FOLFOX), the median survival time is still less than 2 years. Small molecule selective vascular endothelial growth factor receptor (VEGFR) inhibitors have been demonstrated to have strong anti-tumour activity in various cancer models.

Objective: To demonstrate the efficacy and safety of selective VEGFR inhibitors in the management of mCRC.

Methods: A comprehensive search in PubMed, EMBASE, Web of Science, Ovid MEDLINE, Google Scholar, Springer and Cochrane Central databases was performed for randomized controlled trials (RCTs) focusing on the effect of selective VEGFR inhibitors on mCRC. The primary outcome measures were progression-free survival (PFS) rates, overall survival (OS) rates, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rates (ORRs), disease control rates (DCRs) and adverse effect (AE) rates. The dates of the included studies ranged from the inception of the database to January 15, 2020.

Results: Twenty-two RCTs were included. A total of 9362 patients met the inclusion criteria. Compared with placebo, selective VEGFR inhibitors significantly increased the PFS rate, SD, PR and DCR, reduced PD, caused more treatment-emergent adverse events (TEAEs), hypertension, hand-foot skin reaction, diarrhoea, fatigue, and thrombocytopaenia and increased aspartate aminotransferase(AST) concentration. There was no significant difference between selective VEGFR inhibitors and placebo regarding OS rate, CR, ORR, proteinuria, hyperbilirubinaemia or alkaline phosphatase(ALP) concentration. Additionally, compared with FOLFOX4+placebo, FOLFOX4+ selective VEGFR inhibitors, clearly reduced PD, and caused more 3-4 AEs, serious AEs, hypertension, hand-foot syndrome, diarrhoea, nausea, vomiting, decreased appetite, dehydration, fatigue, dizziness, neutropaenia and thrombocytopaenia. For PFS rate, OS rate, CR, PR, SD, ORR, abdominal pain, peripheral sensory neuropathy, asthaenia, anaemia and hypokalaemia rates, there was no significant difference between FOLFOX4+ selective VEGFR inhibitors and FOLFOX4+placebo. However, compared with FOLFOX4+bevacizumab, FOLFOX4+selective VEGFR inhibitors, led to increased hypertension, neutropaenia, fatigue, thrombocytopaenia and asthaenia. There is no clear difference between FOLFOX4+selective VEGFR inhibitors and FOLFOX4+ bevacizumab with regard to PFS rate, OS rate, CR, PR, SD, PD, ORR, diarrhoea, nausea, vomiting, peripheral neuropathy and abdominal pain rates. Selective VEGFR inhibitors+cetuximab increased PFS and PR and reduced PD compared to cetuximab, but there was no statistical difference between the two groups for OS and SD.

Conclusion: Compared with placebo or cetuximab, selective VEGFR inhibitors alone or combined with cetuximab seemed to be more efficacious for mCRC respectively; however, the effects were not better than FOLFOX4 alone or when combined with bevacizumab for mCRC. Additionally, selective VEGFR inhibitors were not as safe as placebo or FOLFOX4 alone or in combination with bevacizumab in mCRC.

Keywords: Metastatic colorectal cancer, chemotherapy, VEGFR inhibitor, Bevacizumab, meta-analysis, randomized controlled trials.

« Previous
[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Siegel RL, Miller KD. Cancer statistics 2019; 69(1): 7-34.
[3]
Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-87.
[http://dx.doi.org/10.1016/j.ejca.2018.07.005] [PMID: 30100160]
[4]
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-32.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[5]
Sineshaw HM, Robbins AS, Jemal A. Disparities in survival improvement for metastatic colorectal cancer by race/ethnicity and age in the United States. Cancer Causes Control 2014; 25(4): 419-23.
[http://dx.doi.org/10.1007/s10552-014-0344-z] [PMID: 24445597]
[6]
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64(1): 9-29.
[http://dx.doi.org/10.3322/caac.21208] [PMID: 24399786]
[7]
Provenzale D, Jasperson K, Ahnen DJ, et al. Colorectal Cancer Screening, Version 1.2015. J Natl Compr Canc Netw 2015; 13(8): 959-68.
[http://dx.doi.org/10.6004/jnccn.2015.0116] [PMID: 26285241]
[8]
Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22(2): 229-37.
[http://dx.doi.org/10.1200/JCO.2004.05.113] [PMID: 14657227]
[9]
Jayson GC, Kerbel R, Ellis LM, Harris AL. Antiangiogenic therapy in oncology: current status and future directions. Lancet 2016; 388(10043): 518-29.
[http://dx.doi.org/10.1016/S0140-6736(15)01088-0] [PMID: 26853587]
[10]
Goel G, Sun W. Ramucirumab, another anti-angiogenic agent for metastatic colorectal cancer in second-line setting--its impact on clinical practice. J Hematol Oncol 2015; 8: 92.
[http://dx.doi.org/10.1186/s13045-015-0183-8] [PMID: 26215324]
[11]
Tampellini M, Sonetto C, Scagliotti GV. Novel anti-angiogenic therapeutic strategies in colorectal cancer. Expert Opin Investig Drugs 2016; 25(5): 507-20.
[http://dx.doi.org/10.1517/13543784.2016.1161754] [PMID: 26938715]
[12]
Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26(12): 2013-9.
[http://dx.doi.org/10.1200/JCO.2007.14.9930] [PMID: 18421054]
[13]
Gressett SM, Shah SR. Intricacies of bevacizumab-induced toxicities and their management. Ann Pharmacother 2009; 43(3): 490-501.
[http://dx.doi.org/10.1345/aph.1L426] [PMID: 19261963]
[14]
Motzer RJ, Nosov D, Eisen T, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol 2013; 31(30): 3791-9.
[http://dx.doi.org/10.1200/JCO.2012.47.4940] [PMID: 24019545]
[15]
Sun Q, Zhou J, Zhang Z, et al. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther 2014; 15(12): 1635-45.
[http://dx.doi.org/10.4161/15384047.2014.964087] [PMID: 25482937]
[16]
Moore K, Infante JR, Cotreau MM, et al. A Phase I cardiac safety and pharmacokinetic study of tivozanib hydrochloride in patients with advanced solid tumors. Clin Pharmacol Drug Dev 2014; 3(4): 284-9.
[http://dx.doi.org/10.1002/cpdd.113] [PMID: 27128834]
[17]
Hu-Lowe DD, Zou HY, Grazzini ML, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res 2008; 14(22): 7272-83.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0652] [PMID: 19010843]
[18]
Schmoll HJ, Cunningham D, Sobrero A, et al. Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III). J Clin Oncol 2012; 30(29): 3588-95.
[http://dx.doi.org/10.1200/JCO.2012.42.5355] [PMID: 22965961]
[19]
Infante JR, Reid TR, Cohn AL, et al. Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: a randomized phase 2 study. Cancer 2013; 119(14): 2555-63.
[http://dx.doi.org/10.1002/cncr.28112] [PMID: 23605883]
[20]
Xu RH, Li J, Bai Y, et al. Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. J Hematol Oncol 2017; 10(1): 22.
[http://dx.doi.org/10.1186/s13045-016-0384-9] [PMID: 28103904]
[21]
Grávalos C, Carrato A, Tobeña M, et al. A randomized phase II study of axitinib as maintenance therapy after first-line treatment for metastatic colorectal cancer. Clin Colorectal Cancer 2018; 17(2): e323-9.
[http://dx.doi.org/10.1016/j.clcc.2018.02.004] [PMID: 29551560]
[22]
Li J, Qin S, Xu RH, et al. Effect of Fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the fresco randomized clinical trial. JAMA 2018; 319(24): 2486-96.
[http://dx.doi.org/10.1001/jama.2018.7855] [PMID: 29946728]
[23]
Liao X, Li H, Liu Z, et al. Clinical efficacy and safety of apatinib in patients with advanced colorectal cancer as the late-line treatment. Medicine (Baltimore) 2018; 97(50)e13635
[http://dx.doi.org/10.1097/MD.0000000000013635] [PMID: 30558053]
[24]
Bendell JC, Tournigand C, Swieboda-Sadlej A, et al. Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study. Clin Colorectal Cancer 2013; 12(4): 239-47.
[http://dx.doi.org/10.1016/j.clcc.2013.09.001] [PMID: 24188685]
[25]
Cunningham D, Wong RP, D’Haens G, et al. Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer. Br J Cancer 2013; 108(3): 493-502.
[http://dx.doi.org/10.1038/bjc.2012.545] [PMID: 23299530]
[26]
Benson AB III, Kiss I, Bridgewater J, et al. BATON-CRC: A phase II randomized trial comparing tivozanib plus mFOLFOX6 with bevacizumab plus mFOLFOX6 in stage IV metastatic colorectal cancer. Clin Cancer Res 2016; 22(20): 5058-67.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-3117] [PMID: 27401244]
[27]
Hecht JR, Trarbach T, Hainsworth JD, et al. Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J Clin Oncol 2011; 29(15): 1997-2003.
[http://dx.doi.org/10.1200/JCO.2010.29.4496] [PMID: 21464406]
[28]
Kato T, Muro K, Yamaguchi K, et al. Cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer: results from the randomised phase II part of a phase I/II study. Ann Oncol 2012; 23(4): 933-41.
[http://dx.doi.org/10.1093/annonc/mdr359] [PMID: 21828378]
[29]
Van Cutsem E, Bajetta E, Valle J, et al. Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma. J Clin Oncol 2011; 29(15): 2004-10.
[http://dx.doi.org/10.1200/JCO.2010.29.5436] [PMID: 21464401]
[30]
Hoff PM, Hochhaus A, Pestalozzi BC, et al. Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II). J Clin Oncol 2012; 30(29): 3596-603.
[http://dx.doi.org/10.1200/JCO.2012.42.6031] [PMID: 22965965]
[31]
Galal KM, Khaled Z, Mourad AMM. Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer. Indian J Cancer 2011; 48(1): 47-54.
[http://dx.doi.org/10.4103/0019-509X.75825] [PMID: 21248446]
[32]
Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381(9863): 303-12.
[http://dx.doi.org/10.1016/S0140-6736(12)61900-X] [PMID: 23177514]
[33]
Carrato A, Swieboda-Sadlej A, Staszewska-Skurczynska M, et al. Fluorouracil, leucovorin, and irinotecan plus either sunitinib or placebo in metastatic colorectal cancer: a randomized, phase III trial. J Clin Oncol 2013; 31(10): 1341-7.
[http://dx.doi.org/10.1200/JCO.2012.45.1930] [PMID: 23358972]
[34]
Tabernero J, Garcia-Carbonero R, Cassidy J, et al. Sorafenib in combination with oxaliplatin, leucovorin, and fluorouracil (modified FOLFOX6) as first-line treatment of metastatic colorectal cancer: the RESPECT trial Clinical cancer research an official journal of the American Association for Cancer Research> 2013; 19(9): 2541-50..
[35]
Siu LL, Shapiro JD, Jonker DJ, et al. Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 Trial. J Clin Oncol 2013; 31(19): 2477-84.
[http://dx.doi.org/10.1200/JCO.2012.46.0543] [PMID: 23690424]
[36]
O’Neil BH, Cainap C, Van Cutsem E, et al. Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer. Clin Colorectal Cancer 2014; 13(3): 156-163.e2.
[http://dx.doi.org/10.1016/j.clcc.2014.04.001] [PMID: 25066269]
[37]
Li J, Qin S, Xu R, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16(6): 619-29.
[http://dx.doi.org/10.1016/S1470-2045(15)70156-7] [PMID: 25981818]
[38]
Van Cutsem E, Yoshino T, Lenz HJ, et al. Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): a phase III, international, randomized, placebo-controlled study. Ann Oncol 2018; 29(9): 1955-63.
[http://dx.doi.org/10.1093/annonc/mdy241] [PMID: 30010751]
[39]
Sanoff HK, Goldberg RM, Ivanova A, et al. Multicenter, randomized, double-blind phase 2 trial of FOLFIRI with regorafenib or placebo as second-line therapy for metastatic colorectal cancer. Cancer 2018; 124(15): 3118-26.
[http://dx.doi.org/10.1002/cncr.31552] [PMID: 29905927]
[40]
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109): 629-34.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[41]
Saif MW, Kim R. Incidence and management of cutaneous toxicities associated with cetuximab. Expert Opin Drug Saf 2007; 6(2): 175-82.
[http://dx.doi.org/10.1517/14740338.6.2.175] [PMID: 17367263]
[42]
Geng R, Song L, Li J, Zhao L. The safety of apatinib for the treatment of gastric cancer. Expert Opin Drug Saf 2018; 17(11): 1145-50.
[http://dx.doi.org/10.1080/14740338.2018.1535592] [PMID: 30324820]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version473msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[03:09:59] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[03:09:59] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[03:09:59] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (91.14ms)time
  • Application (382ms)time
  • 1 x Application (80.72%)
    382ms
    1 x Booting (19.28%)
    91.14ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated304ms
    • 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 ('51803705','',1,1739848199,1739848199) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739848199
      1.33msalphaeurekaselec_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 ('51803705','/article/104587',1,1739848199,1739848199)
      190μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) 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 >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) 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 >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) 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 >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) 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 >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) 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 >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51803705 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51803705) limit 1
      18.91msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51803705
      • 1: 51803705
      • 2: 51803705
      • 3: 51803705
      • 4: 51803705
      • 5: 51803705
      • 6: 51803705
      • 7: 51803705
      • 8: 51803705
      • 9: 51803705
      • 10: 51803705
      • 11: 51803705
      • 12: 51803705
      • 13: 51803705
      • 14: 51803705
      • 15: 51803705
      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=104587
      850μsalphaeurekaselec_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` = 29 limit 1
      780μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 29
      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=29) and sj.journal_id!=29 group by `j`.`nid`) as `aggregate_table`
      1.06msalphaeurekaselec_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=29) and sj.journal_id!=29 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      900μsalphaeurekaselec_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=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.13msalphaeurekaselec_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=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.04msalphaeurekaselec_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` = '104587'
      2.09msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 104587
      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` = '104587'
      3.87msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 104587
      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` = '104587' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.56msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 104587
      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
      280μsalphaeurekaselec_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 = 29 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      34.01msalphaeurekaselec_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 = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      54.59msalphaeurekaselec_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 = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      45.62msalphaeurekaselec_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` = 104587 limit 1
      2.09msalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 104587
      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 = 104587 and content_type = 'article' order by status desc limit 1
      1.3msalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 258 and cd.sub_disease_id = 402 and content_id!=104587 and cd.content_type = 'article' order by rand() limit 20
      98.15msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 179472 limit 1
      990μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 179472
      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
      270μsalphaeurekaselec_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` = 'CPD' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      390μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPD
      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 = '104587' 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 = '9996' 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) )
      320μsalphaeurekaselec_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 = '2790' 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) )
      250μsalphaeurekaselec_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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2790) 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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2790) 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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2790)
      20.94msalphaeurekaselec_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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9996) 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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9996) 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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9996)
      610μsalphaeurekaselec_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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 104587) 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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 104587) 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 <= 51803705 and j.to_ip >=51803705 )) and ((j.from_date <= 1739848199 and j.to_date >= 1739848199 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 104587)
      600μsalphaeurekaselec_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` < '3171' and is_uploaded = 1 and issue_id = 9996 order by cast(first_page as SIGNED) desc limit 1
      580μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 3171
      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` > '3186' and is_uploaded = 1 and issue_id = 9996 order by cast(first_page as SIGNED) asc limit 1
      470μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 3186
      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'
      190μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      230μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 104587 limit 1
      2.43msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 104587
      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` = 29 and `b`.`banner_from_date` <= 1739848199 and `b`.`banner_to_date` >= 1739848199 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.16msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1739848199
      • 4: 1739848199
      • 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` = 29 and `b`.`banner_from_date` <= 1739848199 and `b`.`banner_to_date` >= 1739848199 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: 29
      • 3: 1739848199
      • 4: 1739848199
      • 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='e89eb67d91a151df8c8cb7be9fa56d5c'
      350μsalphaeurekaselec_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
        QiuptOYFoUYV83Aw2yj7iBYUECDqOO7sOMVu9ruz
        uc_cart_id
        e89eb67d91a151df8c8cb7be9fa56d5c
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/104587" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/104587
        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 => "Tue, 18 Feb 2025 03:09:59 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ik04UnpxSUpqbWdJWGJsMTNFdFpLR0E9PSIsInZhbHVlIjoibERXQVdkeUFQRVZKT005QTZQSy9oekJzWlFTaFh1Vy92MEhLRHBEdUZFckhwR01aOCs2WGFENHJuei9aSWt0dS9LNHNPc2lKWnNaM0tpYnl0em0xaGYyMDRMckx2anZ3K3VPWFhHeHdaczk1N2ZrODBPY2FLeWlZOVJoQlNjbWwiLCJtYWMiOiI5NDU4YmFiMTU4ZWFkNjQzNGI4MTRiNjgzOTcwMWRlMTBiYzQwMGMwZDBhZTY0NzY2ZTQyNTA4NDg1MzNiMmRhIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 15:09:59 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Ik04UnpxSUpqbWdJWGJsMTNFdFpLR0E9PSIsInZhbHVlIjoibERXQVdkeUFQRVZKT005QTZQSy9oekJzWlFTaFh1Vy92MEhLRHBEdUZFckhwR01aOCs2WGFENHJuei9aSWt0dS9LNHNPc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IllZWFlRUGtDU1h0QjFHczRPYW0xbGc9PSIsInZhbHVlIjoiOERiWmpLbjBzSmhOSFZ1K3Y0dG1MTEtEQit1VWtqemtWWjJpVGpGZzlMWi9GZlg5dUlDYUtLS3dqMjBqMytoOEVnakJ2SXIrSHRkV1R6aG05QitibFcwV2FBTWRlZk5VQXpaaER0M3NsVzhaWHFmdGpGV0FHc0pOa0grUG1NZzYiLCJtYWMiOiI2ZTJmN2YzNzc3ZWU1ZDMyMmM1ZWY0NWYwMDFlNzdkMjk1NmRmNTVhZWU2ZDAxYzcxNDM0ZjNmNTlkZTNiMTgxIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IllZWFlRUGtDU1h0QjFHczRPYW0xbGc9PSIsInZhbHVlIjoiOERiWmpLbjBzSmhOSFZ1K3Y0dG1MTEtEQit1VWtqemtWWjJpVGpGZzlMWi9GZlg5dUlDYUtLS3d" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ik04UnpxSUpqbWdJWGJsMTNFdFpLR0E9PSIsInZhbHVlIjoibERXQVdkeUFQRVZKT005QTZQSy9oekJzWlFTaFh1Vy92MEhLRHBEdUZFckhwR01aOCs2WGFENHJuei9aSWt0dS9LNHNPc2lKWnNaM0tpYnl0em0xaGYyMDRMckx2anZ3K3VPWFhHeHdaczk1N2ZrODBPY2FLeWlZOVJoQlNjbWwiLCJtYWMiOiI5NDU4YmFiMTU4ZWFkNjQzNGI4MTRiNjgzOTcwMWRlMTBiYzQwMGMwZDBhZTY0NzY2ZTQyNTA4NDg1MzNiMmRhIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 15:09:59 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Ik04UnpxSUpqbWdJWGJsMTNFdFpLR0E9PSIsInZhbHVlIjoibERXQVdkeUFQRVZKT005QTZQSy9oekJzWlFTaFh1Vy92MEhLRHBEdUZFckhwR01aOCs2WGFENHJuei9aSWt0dS9LNHNPc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IllZWFlRUGtDU1h0QjFHczRPYW0xbGc9PSIsInZhbHVlIjoiOERiWmpLbjBzSmhOSFZ1K3Y0dG1MTEtEQit1VWtqemtWWjJpVGpGZzlMWi9GZlg5dUlDYUtLS3dqMjBqMytoOEVnakJ2SXIrSHRkV1R6aG05QitibFcwV2FBTWRlZk5VQXpaaER0M3NsVzhaWHFmdGpGV0FHc0pOa0grUG1NZzYiLCJtYWMiOiI2ZTJmN2YzNzc3ZWU1ZDMyMmM1ZWY0NWYwMDFlNzdkMjk1NmRmNTVhZWU2ZDAxYzcxNDM0ZjNmNTlkZTNiMTgxIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IllZWFlRUGtDU1h0QjFHczRPYW0xbGc9PSIsInZhbHVlIjoiOERiWmpLbjBzSmhOSFZ1K3Y0dG1MTEtEQit1VWtqemtWWjJpVGpGZzlMWi9GZlg5dUlDYUtLS3d" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "QiuptOYFoUYV83Aw2yj7iBYUECDqOO7sOMVu9ruz" "uc_cart_id" => "e89eb67d91a151df8c8cb7be9fa56d5c" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/104587" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:09:59GET/article/104587314371