Generic placeholder image

Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Research Article

Preparation and Characterization of A Nanoliposomal Vaccine of pcLACK Candidate Against Cutaneous Leishmaniasis

Author(s): Hajar Ziaei Hezarjaribi, Masoud Soosaraei*, Mahdi Fakhar*, Javad Akhtari, Alireza Rafiei and Oghol Niaz Jorjani

Volume 21, Issue 4, 2021

Published on: 05 October, 2020

Page: [527 - 533] Pages: 7

DOI: 10.2174/1871526520666201005141159

Price: $65

Abstract

Background: Leishmaniasis is a public health problem and endemic in countries of the tropics and subtropics. An ongoing project with naked LACK (Leishmania homolog of receptors for activated C-kinase) demonstrated that this case of the gene is entirely susceptible to immune response and it does enter the cells effectively. This study aimed at developing a procedure to prepare a type of lipid nanoparticles overloaded with plasmid LACK (pcLACK) for usage as Leishmania major (L. major) nanoliposomal vaccine.

Materials and Methods: The single-gene expression plasmid of pcLACK was encoded in the LACK antigen. Nanoparticles were set up by thin film procedure using cationic lipids 1, 2-Dioleoyl- 3-Trimethylammonium propane (DOTAP), 1, 2-Dioleoyl-snGlycero-3-Phosphoethanolamine (DOPE), and cholesterol in a molar proportion of 2:1:1 molar ratio. Using dynamic light scattering, the particle diameters of empty and loaded lipoplexes were measured in triplicate. The zeta-potential (ζ) was measured with the same instrument using the zeta potential mode as the average of 20 measurements by diluting the particles into a low salt buffer.

Results: The results of the sustainability studies of Liposome-pcLACK formulation showed that there were no significant physical changes up to the 30th day of stability study at the storage condition of 4°C. However, there were significant changes in the formulation content during storage at 25°C for 30 days (204.2±0.90 at Day 30 compared with 207.2±0.26 nm at Day 0). It was observed that the prepared nanoliposomal formulation had more stability under refrigeration.

Conclusion: Immunostimulatory cationic lipids bearing a pcLACK encapsulation could serve as an effective delivery system.

Keywords: Leishmania major, nanoliposomal, vaccine, immunity, pcLACK, encapsulation.

Graphical Abstract

[1]
de Almeida, L.; Terumi Fujimura, A.; Del Cistia, M.L.; Fonseca-Santos, B.; Braga Imamura, K.; Michels, P.A.M.; Chorilli, M.; Graminha, M.A.S. Nanotechnological Strategies for Treatment of Leishmaniasis--A Review. J. Biomed. Nanotechnol., 2017, 13(2), 117-133.
[http://dx.doi.org/10.1166/jbn.2017.2349] [PMID: 29376626]
[2]
Mutiso, J.M.; Macharia, J.C.; Kiio, M.N.; Ichagichu, J.M.; Rikoi, H.; Gicheru, M.M. Development of Leishmania vaccines: predicting the future from past and present experience. J. Biomed. Res., 2013, 27(2), 85-102.
[PMID: 23554800]
[3]
Alvar, J.; Vélez, I.D.; Bern, C.; Herrero, M.; Desjeux, P.; Cano, J.; Jannin, J.; den Boer, M. Leishmaniasis worldwide and global estimates of its incidence. PLoS One, 2012, 7(5), e35671.
[http://dx.doi.org/10.1371/journal.pone.0035671] [PMID: 22693548]
[4]
Murray, H.W.; Berman, J.D.; Davies, C.R.; Saravia, N.G. Advances in leishmaniasis. Lancet, 2005, 366(9496), 1561-1577.
[http://dx.doi.org/10.1016/S0140-6736(05)67629-5] [PMID: 16257344]
[5]
Peacock, C.S.; Seeger, K.; Harris, D.; Murphy, L.; Ruiz, J.C.; Quail, M.A.; Peters, N.; Adlem, E.; Tivey, A.; Aslett, M.; Kerhornou, A.; Ivens, A.; Fraser, A.; Rajandream, M.A.; Carver, T.; Norbertczak, H.; Chillingworth, T.; Hance, Z.; Jagels, K.; Moule, S.; Ormond, D.; Rutter, S.; Squares, R.; Whitehead, S.; Rabbinowitsch, E.; Arrowsmith, C.; White, B.; Thurston, S.; Bringaud, F.; Baldauf, S.L.; Faulconbridge, A.; Jeffares, D.; Depledge, D.P.; Oyola, S.O.; Hilley, J.D.; Brito, L.O.; Tosi, L.R.; Barrell, B.; Cruz, A.K.; Mottram, J.C.; Smith, D.F.; Berriman, M. Comparative genomic analysis of three Leishmania species that cause diverse human disease. Nat. Genet., 2007, 39(7), 839-847.
[http://dx.doi.org/10.1038/ng2053] [PMID: 17572675]
[6]
Santos, D.O.; Coutinho, C.E.; Madeira, M.F.; Bottino, C.G.; Vieira, R.T.; Nascimento, S.B.; Bernardino, A.; Bourguignon, S.C.; Corte-Real, S.; Pinho, R.T.; Rodrigues, C.R.; Castro, H.C. Leishmaniasis treatment--a challenge that remains: a review. Parasitol. Res., 2008, 103(1), 1-10.
[http://dx.doi.org/10.1007/s00436-008-0943-2] [PMID: 18389282]
[7]
Croft, S.L.; Coombs, G.H. Leishmaniasis--current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol., 2003, 19(11), 502-508.
[http://dx.doi.org/10.1016/j.pt.2003.09.008] [PMID: 14580961]
[8]
Anversa, L.; Tiburcio, M.G.S.; Richini-Pereira, V.B.; Ramirez, L.E. Human leishmaniasis in Brazil: A general review. Rev Assoc Med Bras (1992), 2018, 64(3), 281-289.
[http://dx.doi.org/10.1590/1806-9282.64.03.281] [PMID: 29641786]
[9]
Hezarjaribi, H.Z.; Ghaffarifar, F.; Dalimi, A.; Sharifi, Z.; Jorjani, O. Effect of IL-22 on DNA vaccine encoding LACK gene of Leishmania major in BALB/c mice. Exp. Parasitol., 2013, 134(3), 341-348.
[http://dx.doi.org/10.1016/j.exppara.2013.03.012] [PMID: 23541883]
[10]
Jain, K.; Jain, N.K. Vaccines for visceral leishmaniasis: A review. J. Immunol. Methods, 2015, 422, 1-12.
[http://dx.doi.org/10.1016/j.jim.2015.03.017] [PMID: 25858230]
[11]
Courret, N.; Prina, E.; Mougneau, E.; Saraiva, E.M.; Sacks, D.L.; Glaichenhaus, N.; Antoine, J.C. Presentation of the Leishmania antigen LACK by infected macrophages is dependent upon the virulence of the phagocytosed parasites. Eur. J. Immunol., 1999, 29(3), 762-773.
[http://dx.doi.org/10.1002/(SICI)1521-4141(199903)29:03<762::AID-IMMU762>3.0.CO;2-4] [PMID: 10092078]
[12]
Schechtman, D.; Mochly-Rosen, D. Adaptor proteins in protein kinase C-mediated signal transduction. Oncogene, 2001, 20(44), 6339-6347.
[http://dx.doi.org/10.1038/sj.onc.1204778] [PMID: 11607837]
[13]
Plasmids for therapy and vaccination. Schleef, M; John Wiley & Sons, 2008.
[14]
Levine, M.M.; Sztein, M.B. Vaccine development strategies for improving immunization: the role of modern immunology. Nat. Immunol., 2004, 5(5), 460-464.
[http://dx.doi.org/10.1038/ni0504-460] [PMID: 15116108]
[15]
Li, L.; Saade, F.; Petrovsky, N. The future of human DNA vaccines. J. Biotechnol., 2012, 162(2-3), 171-182.
[http://dx.doi.org/10.1016/j.jbiotec.2012.08.012] [PMID: 22981627]
[16]
Liu, M.A. DNA vaccines: an historical perspective and view to the future. Immunol. Rev., 2011, 239(1), 62-84.
[http://dx.doi.org/10.1111/j.1600-065X.2010.00980.x] [PMID: 21198665]
[17]
Shah, M.A.; He, N.; Li, Z.; Ali, Z.; Zhang, L. Nanoparticles for DNA vaccine delivery. J. Biomed. Nanotechnol., 2014, 10(9), 2332-2349.
[http://dx.doi.org/10.1166/jbn.2014.1981] [PMID: 25992460]
[18]
Abbink, P.; Larocca, R.A.; De La Barrera, R.A.; Bricault, C.A.; Moseley, E.T.; Boyd, M.; Kirilova, M.; Li, Z.; Ng’ang’a, D.; Nanayakkara, O.; Nityanandam, R.; Mercado, N.B.; Borducchi, E.N.; Agarwal, A.; Brinkman, A.L.; Cabral, C.; Chandrashekar, A.; Giglio, P.B.; Jetton, D.; Jimenez, J.; Lee, B.C.; Mojta, S.; Molloy, K.; Shetty, M.; Neubauer, G.H.; Stephenson, K.E.; Peron, J.P.; Zanotto, P.M.; Misamore, J.; Finneyfrock, B.; Lewis, M.G.; Alter, G.; Modjarrad, K.; Jarman, R.G.; Eckels, K.H.; Michael, N.L.; Thomas, S.J.; Barouch, D.H. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science, 2016, 353(6304), 1129-1132.
[http://dx.doi.org/10.1126/science.aah6157] [PMID: 27492477]
[19]
Dhama, K.; Mahendran, M.; Gupta, P.K.; Rai, A. DNA vaccines and their applications in veterinary practice: current perspectives. Vet. Res. Commun., 2008, 32(5), 341-356.
[http://dx.doi.org/10.1007/s11259-008-9040-3] [PMID: 18425596]
[20]
Myhr, A.I. DNA vaccines: regulatory considerations and safety aspects. Curr. Issues Mol. Biol., 2017, 22, 79-88.
[http://dx.doi.org/10.21775/cimb.022.079] [PMID: 27705898]
[21]
Nakayama, Y.; Aruga, A. Comparison of current regulatory status for gene-based vaccines in the US, europe and japan. Vaccines (Basel), 2015, 3(1), 186-202.
[http://dx.doi.org/10.3390/vaccines3010186] [PMID: 26344953]
[22]
Gurram, I.; Kavitha, M.V.; Nagabhushnam, M.V.; Bonthagara, B.; Reddy, D.N. Overview of validation, basic concepts and analytical method process validation. Indo Am J Pharm Sci., 2017, 4(6), 1665-1680.
[23]
Kanuri, P. Science and risk based approach to the process validation. link from quality by design to process validation. Int. J. Pharm. Sci. Res., 2016, 7(3), 914-929.
[24]
Rathore, A.S.; Li, X.; Bartkowski, W.; Yeboah, S.; Sharma, A. Case study and application of process analytical technology (PAT) towards bioprocessing: Use of tryptophan DNA for vaccine and gene therapy: plasmid design, production, and purification. Enzyme Microb. Technol., 2003, 33, 865-883.
[25]
Li, L; Petrovsky, N Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines., 2016, 15(3), 313-329.
[http://dx.doi.org/10.1586/14760584.2016.1124762]
[26]
Šimčíková, M.; Prather, K.L.; Prazeres, D.M.; Monteiro, G.A. Towards effective non-viral gene delivery vector. Biotechnol. Genet. Eng. Rev., 2015, 31(1-2), 82-107.
[http://dx.doi.org/10.1080/02648725.2016.1178011] [PMID: 27160661]
[27]
Nguyen, D.N.; Green, J.J.; Chan, J.M.; Longer, R.; Anderson, D.G. Polymeric materials for gene delivery and DNA vaccination. Adv. Mater., 2009, 21(8), 847-867.
[http://dx.doi.org/10.1002/adma.200801478] [PMID: 28413262]
[28]
Grunwald, T; Ulbert, S. Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases., 2015.
[http://dx.doi.org/10.7774/cevr.2015.4.1.1]
[29]
Choi, Y.S.; Lee, M.Y.; David, A.E.; Park, Y.S. Nanoparticles for gene delivery: therapeutic and toxic effects. Mol. Cell. Toxicol., 2014, 10(1), 1-8.
[http://dx.doi.org/10.1007/s13273-014-0001-3]
[30]
Inoh, Y.; Nagai, M.; Matsushita, K.; Nakanishi, M.; Furuno, T. Gene transfection efficiency into dendritic cells is influenced by the size of cationic liposomes/DNA complexes. Eur. J. Pharm. Sci., 2017, 102, 230-236.
[http://dx.doi.org/10.1016/j.ejps.2017.03.023] [PMID: 28323115]
[31]
O’Hagan, D.T.; MacKichan, M.L.; Singh, M. Recent developments in adjuvants for vaccines against infectious diseases. Biomol. Eng., 2001, 18(3), 69-85.
[http://dx.doi.org/10.1016/S1389-0344(01)00101-0] [PMID: 11566599]
[32]
Rasoulianboroujeni, M.; Kupgan, G.; Moghadam, F.; Tahriri, M.; Boughdachi, A.; Khoshkenar, P.; Ambrose, J.J.; Kiaie, N.; Vashaee, D.; Ramsey, J.D.; Tayebi, L. Development of a DNA-liposome complex for gene delivery applications. Mater. Sci. Eng. C, 2017, 75, 191-197.
[http://dx.doi.org/10.1016/j.msec.2017.02.012] [PMID: 28415454]
[33]
Henriksen-Lacey, M.; Bramwell, V.W.; Christensen, D.; Agger, E.M.; Andersen, P.; Perrie, Y. Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen. J. Control. Release, 2010, 142(2), 180-186.
[http://dx.doi.org/10.1016/j.jconrel.2009.10.022] [PMID: 19874860]
[34]
Ureña-Búrquez, L.A.; García-Rendón, A.; Rochín-Wong, S.; Tejeda-Mansir, A. Preparation and characterization of a nanovaccine of pVAX1-NH36 for leishmaniasis. Fuel, 2019, 235, 1077-1082.
[http://dx.doi.org/10.1016/j.fuel.2018.08.070]
[35]
Lee, S.; Nguyen, M.T. Recent advances of vaccine adjuvants for infectious diseases. Immune Netw., 2015, 15(2), 51-57.
[http://dx.doi.org/10.4110/in.2015.15.2.51] [PMID: 25922593]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version346msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[04:54:44] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[04:54:44] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[04:54:44] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[04:54:44] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (106ms)time
  • Application (240ms)time
  • 1 x Application (69.48%)
    240ms
    1 x Booting (30.52%)
    106ms
    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 duplicated158ms
    • 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 ('316204442','',1,1740459284,1740459284) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740459284
      960μsalphaeurekaselec_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 ('316204442','/article/110443',1,1740459284,1740459284)
      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 >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) 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 >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) 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 >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) 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 >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) 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 >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) 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 >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316204442 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316204442) limit 1
      13.02msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316204442
      • 1: 316204442
      • 2: 316204442
      • 3: 316204442
      • 4: 316204442
      • 5: 316204442
      • 6: 316204442
      • 7: 316204442
      • 8: 316204442
      • 9: 316204442
      • 10: 316204442
      • 11: 316204442
      • 12: 316204442
      • 13: 316204442
      • 14: 316204442
      • 15: 316204442
      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=110443
      780μsalphaeurekaselec_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` = 54 limit 1
      850μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 54
      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=54) and sj.journal_id!=54 group by `j`.`nid`) as `aggregate_table`
      1.24msalphaeurekaselec_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=54) and sj.journal_id!=54 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.03msalphaeurekaselec_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=54) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      5.1msalphaeurekaselec_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=54) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      4.39msalphaeurekaselec_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` = '110443'
      1.57msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 110443
      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` = '110443'
      2.39msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 110443
      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` = '110443' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      4.77msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 110443
      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
      320μsalphaeurekaselec_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
      640μsalphaeurekaselec_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 = 54 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      36.52msalphaeurekaselec_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 = 54 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      7.35msalphaeurekaselec_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 = 54 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      6.63msalphaeurekaselec_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` = 110443 limit 1
      360μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 110443
      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 = 110443 and content_type = 'article' order by status desc limit 1
      430μsalphaeurekaselec_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 = 295 and cd.sub_disease_id = 607 and content_id!=110443 and cd.content_type = 'article' order by rand() limit 20
      32.72msalphaeurekaselec_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` = 186606 limit 1
      280μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 186606
      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
      220μsalphaeurekaselec_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` = 'IDDT' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      290μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: IDDT
      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 = '110443' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      460μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '10741' 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) )
      350μsalphaeurekaselec_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 = '2994' 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) )
      350μsalphaeurekaselec_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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2994) 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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2994) 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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2994)
      23.05msalphaeurekaselec_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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10741) 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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10741) 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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10741)
      890μsalphaeurekaselec_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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 110443) 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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 110443) 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 <= 316204442 and j.to_ip >=316204442 )) and ((j.from_date <= 1740459284 and j.to_date >= 1740459284 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 110443)
      830μsalphaeurekaselec_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` < '527' and is_uploaded = 1 and issue_id = 10741 order by cast(first_page as SIGNED) desc limit 1
      820μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 527
      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` > '533' and is_uploaded = 1 and issue_id = 10741 order by cast(first_page as SIGNED) asc limit 1
      790μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 533
      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'
      280μsalphaeurekaselec_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
      290μsalphaeurekaselec_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` = 110443 limit 1
      3.96msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 110443
      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` = 54 and `b`.`banner_from_date` <= 1740459284 and `b`.`banner_to_date` >= 1740459284 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.59msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 54
      • 3: 1740459284
      • 4: 1740459284
      • 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` = 54 and `b`.`banner_from_date` <= 1740459284 and `b`.`banner_to_date` >= 1740459284 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.57msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 54
      • 3: 1740459284
      • 4: 1740459284
      • 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='13e49022f8b6d85b9c9aaccd92f7aefd'
      290μsalphaeurekaselec_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
        7qCBtLoNdgmZtZ6ORA49IE6d17Tx5ZGVjL5Dnjt6
        uc_cart_id
        13e49022f8b6d85b9c9aaccd92f7aefd
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/110443" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/110443
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6ImRWZ3V6SlJnWUZqSFlxT0JXT0JlR0E9PSIsInZhbHVlIjoiV1pLSnVuRXQ3YzJqUGhGS093dG12L1FPemlEUTQzNTJSM0k1aG0vSEdqbz0iLCJtYWMiOiI5YjFlNTE1OTRkMGY5MDk5NzAyMmUxM2UwMjIyNmJhZGU1YTI5M2NiMTRkNTVjZTlkNWI2YWY5Mzg2MWM5NWNhIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImRWZ3V6SlJnWUZqSFlxT0JXT0JlR0E9PSIsInZhbHVlIjoiV1pLSnVuRXQ3YzJqUGhGS093dG12L1FPemlEUTQzNTJSM0k1aG0vSEdqbz0iLCJtYWMiOiI5YjFlNTE1OTRkMGY5" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 04:54:44 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InlkN0w0V3BWQUNWVHNmc01wUUFucGc9PSIsInZhbHVlIjoiT1A2cy85anVpSmNpQ3dZS20yL3ZTMThlYXc0WG9Gaml4TWRVS3NRamE5V3pGeGZDa3RJakNKRjBjZzcveWR2MkxWTUdtYnNXUnJlMjZUeVRhVGF4KzVnVExwZXVsZHMyRUcrUGY4aHNEN1ZuS0NyTnQ1WDliS2ZyR2xMaytWUE0iLCJtYWMiOiI3NWUyN2RkYWY2ODlkNjcwNzRlMTMzNTAyN2U4ZTVlZTI4ZmFjYTVmMzk0ZTQ5MjNlZmU3OTA4Y2EyMWEzYTQxIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 16:54:44 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InlkN0w0V3BWQUNWVHNmc01wUUFucGc9PSIsInZhbHVlIjoiT1A2cy85anVpSmNpQ3dZS20yL3ZTMThlYXc0WG9Gaml4TWRVS3NRamE5V3pGeGZDa3RJakNKRjBjZzcveWR2MkxWTUdtY" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im9ZSTJlU25yYVV5R1ZVUDE0S3RGaHc9PSIsInZhbHVlIjoidzB2U1RMNWhoSWJEVmZCdG1UQlIyaDRVZzYxc0RQWnduZ1FLUVhMNlE5RzNoaDVpdnVCQ0FWaE5nRUdON3lROHlBaTUvKzhWK1plRktTcmZ4YkF4OFY5R3VPWmxjY0RnU2hsTERPV1RqVHZwU0tmNkVFVWxaVVNPUHFrc0M3M2ciLCJtYWMiOiJmZDUzYmY2Y2FjYTE1NjQ4ODE5OWU5NzMyMmQ5NmZmNWU3OTY3MDBlMzE3OGRkOThmM2RmZTMzOWEzN2Y3NzA0IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Im9ZSTJlU25yYVV5R1ZVUDE0S3RGaHc9PSIsInZhbHVlIjoidzB2U1RMNWhoSWJEVmZCdG1UQlIyaDRVZzYxc0RQWnduZ1FLUVhMNlE5RzNoaDVpdnVCQ0FWaE5" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InlkN0w0V3BWQUNWVHNmc01wUUFucGc9PSIsInZhbHVlIjoiT1A2cy85anVpSmNpQ3dZS20yL3ZTMThlYXc0WG9Gaml4TWRVS3NRamE5V3pGeGZDa3RJakNKRjBjZzcveWR2MkxWTUdtYnNXUnJlMjZUeVRhVGF4KzVnVExwZXVsZHMyRUcrUGY4aHNEN1ZuS0NyTnQ1WDliS2ZyR2xMaytWUE0iLCJtYWMiOiI3NWUyN2RkYWY2ODlkNjcwNzRlMTMzNTAyN2U4ZTVlZTI4ZmFjYTVmMzk0ZTQ5MjNlZmU3OTA4Y2EyMWEzYTQxIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 16:54:44 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InlkN0w0V3BWQUNWVHNmc01wUUFucGc9PSIsInZhbHVlIjoiT1A2cy85anVpSmNpQ3dZS20yL3ZTMThlYXc0WG9Gaml4TWRVS3NRamE5V3pGeGZDa3RJakNKRjBjZzcveWR2MkxWTUdtY" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im9ZSTJlU25yYVV5R1ZVUDE0S3RGaHc9PSIsInZhbHVlIjoidzB2U1RMNWhoSWJEVmZCdG1UQlIyaDRVZzYxc0RQWnduZ1FLUVhMNlE5RzNoaDVpdnVCQ0FWaE5nRUdON3lROHlBaTUvKzhWK1plRktTcmZ4YkF4OFY5R3VPWmxjY0RnU2hsTERPV1RqVHZwU0tmNkVFVWxaVVNPUHFrc0M3M2ciLCJtYWMiOiJmZDUzYmY2Y2FjYTE1NjQ4ODE5OWU5NzMyMmQ5NmZmNWU3OTY3MDBlMzE3OGRkOThmM2RmZTMzOWEzN2Y3NzA0IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Im9ZSTJlU25yYVV5R1ZVUDE0S3RGaHc9PSIsInZhbHVlIjoidzB2U1RMNWhoSWJEVmZCdG1UQlIyaDRVZzYxc0RQWnduZ1FLUVhMNlE5RzNoaDVpdnVCQ0FWaE5" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "7qCBtLoNdgmZtZ6ORA49IE6d17Tx5ZGVjL5Dnjt6" "uc_cart_id" => "13e49022f8b6d85b9c9aaccd92f7aefd" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/110443" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 04:54:44GET/article/110443414371