Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Current Advances and Limitations of Deep Learning in Anticancer Drug Sensitivity Prediction

Author(s): Xian Tan, Yang Yu, Kaiwen Duan, Jingbo Zhang, Pingping Sun* and Hui Sun*

Volume 20, Issue 21, 2020

Page: [1858 - 1867] Pages: 10

DOI: 10.2174/1568026620666200710101307

Price: $65

Abstract

Anticancer drug screening can accelerate drug discovery to save the lives of cancer patients, but cancer heterogeneity makes this screening challenging. The prediction of anticancer drug sensitivity is useful for anticancer drug development and the identification of biomarkers of drug sensitivity. Deep learning, as a branch of machine learning, is an important aspect of in silico research. Its outstanding computational performance means that it has been used for many biomedical purposes, such as medical image interpretation, biological sequence analysis, and drug discovery. Several studies have predicted anticancer drug sensitivity based on deep learning algorithms. The field of deep learning has made progress regarding model performance and multi-omics data integration. However, deep learning is limited by the number of studies performed and data sources available, so it is not perfect as a pre-clinical approach for use in the anticancer drug screening process. Improving the performance of deep learning models is a pressing issue for researchers. In this review, we introduce the research of anticancer drug sensitivity prediction and the use of deep learning in this research area. To provide a reference for future research, we also review some common data sources and machine learning methods. Lastly, we discuss the advantages and disadvantages of deep learning, as well as the limitations and future perspectives regarding this approach.

Keywords: Deep learning, Cancer, Cancer cell lines, Anticancer drug screening, Computational biology, Bioinformatics.

Graphical Abstract

[1]
Mirnezami, R.; Nicholson, J.; Darzi, A. Preparing for precision medicine. N. Engl. J. Med., 2012, 366(6), 489-491.
[http://dx.doi.org/10.1056/NEJMp1114866] [PMID: 22256780]
[2]
Tannock, I.F.; Hickman, J.A. Limits to personalized cancer medicine. N. Engl. J. Med., 2016, 375(13), 1289-1294.
[http://dx.doi.org/10.1056/NEJMsb1607705] [PMID: 27682039]
[3]
Prasad, V. Perspective: The precision-oncology illusion. Nature, 2016, 537(7619), S63.
[http://dx.doi.org/10.1038/537S63a] [PMID: 27602743]
[4]
Subbiah, V.; Kurzrock, R. Debunking the delusion that precision oncology is an illusion. Oncologist, 2017, 22(8), 881-882.
[http://dx.doi.org/10.1634/theoncologist.2017-0040] [PMID: 28550030]
[5]
Stratton, M.R.; Campbell, P.J.; Futreal, P.A. The cancer genome. Nature, 2009, 458(7239), 719-724.
[http://dx.doi.org/10.1038/nature07943] [PMID: 19360079]
[6]
Lawrence, M.S.; Stojanov, P.; Polak, P.; Kryukov, G.V.; Cibulskis, K.; Sivachenko, A.; Carter, S.L.; Stewart, C.; Mermel, C.H.; Roberts, S.A.; Kiezun, A.; Hammerman, P.S.; McKenna, A.; Drier, Y.; Zou, L.; Ramos, A.H.; Pugh, T.J.; Stransky, N.; Helman, E.; Kim, J.; Sougnez, C.; Ambrogio, L.; Nickerson, E.; Shefler, E.; Cortés, M.L.; Auclair, D.; Saksena, G.; Voet, D.; Noble, M.; DiCara, D.; Lin, P.; Lichtenstein, L.; Heiman, D.I.; Fennell, T.; Imielinski, M.; Hernandez, B.; Hodis, E.; Baca, S.; Dulak, A.M.; Lohr, J.; Landau, D.A.; Wu, C.J.; Melendez-Zajgla, J.; Hidalgo-Miranda, A.; Koren, A.; McCarroll, S.A.; Mora, J.; Crompton, B.; Onofrio, R.; Parkin, M.; Winckler, W.; Ardlie, K.; Gabriel, S.B.; Roberts, C.W.M.; Biegel, J.A.; Stegmaier, K.; Bass, A.J.; Garraway, L.A.; Meyerson, M.; Golub, T.R.; Gordenin, D.A.; Sunyaev, S.; Lander, E.S.; Getz, G. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature, 2013, 499(7457), 214-218.
[http://dx.doi.org/10.1038/nature12213] [PMID: 23770567]
[7]
Zack, T.I.; Schumacher, S.E.; Carter, S.L.; Cherniack, A.D.; Saksena, G.; Tabak, B.; Lawrence, M.S.; Zhsng, C.Z.; Wala, J.; Mermel, C.H.; Sougnez, C.; Gabriel, S.B.; Hernandez, B.; Shen, H.; Laird, P.W.; Getz, G.; Meyerson, M.; Beroukhim, R. Pan-cancer patterns of somatic copy number alteration. Nat. Genet., 2013, 45(10), 1134-1140.
[http://dx.doi.org/10.1038/ng.2760] [PMID: 24071852]
[8]
Cortes-Ciriano, I.; Mervin, L.H.; Bender, A. Current trends in drug sensitivity prediction. Curr. Pharm. Des., 2016, 22(46), 6918-6927.
[http://dx.doi.org/10.2174/1381612822666161026154430] [PMID: 27784247]
[9]
Pauli, C.; Hopkins, B.D.; Prandi, D.; Shaw, R.; Fedrizzi, T.; Sboner, A.; Sailer, V.; Augello, M.; Puca, L.; Rosati, R.; McNary, T.J.; Churakova, Y.; Cheung, C.; Triscott, J.; Pisapia, D.; Rao, R.; Mosquera, J.M.; Robinson, B.; Faltas, B.M.; Emerling, B.E.; Gadi, V.K.; Bernard, B.; Elemento, O.; Beltran, H.; Demichelis, F.; Kemp, C.J.; Grandori, C.; Cantley, L.C.; Rubin, M.A. Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov., 2017, 7(5), 462-477.
[http://dx.doi.org/10.1158/2159-8290.CD-16-1154] [PMID: 28331002]
[10]
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[http://dx.doi.org/10.1093/jnci/82.13.1107] [PMID: 2359136]
[11]
Tan, A.C.; Gilbert, D. Ensemble machine learning on gene expression data for cancer classification. Appl. Bioinformatics, 2003, 2(3)(Suppl.), S75-S83.
[PMID: 15130820]
[12]
Zupan, B.; Demsar, J.; Kattan, M.W.; Beck, J.R.; Bratko, I. Machine learning for survival analysis: a case study on recurrence of prostate cancer. Artif. Intell. Med., 2000, 20(1), 59-75.
[http://dx.doi.org/10.1016/S0933-3657(00)00053-1] [PMID: 11185421]
[13]
Riddick, G.; Song, H.; Ahn, S.; Walling, J.; Borges-Rivera, D.; Zhang, W.; Fine, H.A. Predicting in vitro drug sensitivity using Random Forests. Bioinformatics, 2011, 27(2), 220-224.
[http://dx.doi.org/10.1093/bioinformatics/btq628] [PMID: 21134890]
[14]
Knowles, D.A.; Bouchard, G.; Plevritis, S. Sparse discriminative latent characteristics for predicting cancer drug sensitivity from genomic features. PLOS Comput. Biol., 2019, 15(5)e1006743
[http://dx.doi.org/10.1371/journal.pcbi.1006743] [PMID: 31136571]
[15]
Menden, M.P.; Iorio, F.; Garnett, M.; McDermott, U.; Benes, C.H.; Ballester, P.J.; Saez-Rodriguez, J. Machine learning prediction of cancer cell sensitivity to drugs based on genomic and chemical properties. PLoS One, 2013, 8(4)e61318
[http://dx.doi.org/10.1371/journal.pone.0061318] [PMID: 23646105]
[16]
Hussain, S.; Ferzund, J.; Ul-Haq, R. Prediction of drug target sensitivity in cancer cell lines using apache spark. J. Comput. Biol., 2019, 26(8), 882-889.
[http://dx.doi.org/10.1089/cmb.2018.0102] [PMID: 31120327]
[17]
Dhruba, S.R.; Rahman, R.; Matlock, K.; Ghosh, S.; Pal, R. Application of transfer learning for cancer drug sensitivity prediction. BMC Bioinformatics, 2018, 19(Suppl. 17), 497.
[http://dx.doi.org/10.1186/s12859-018-2465-y] [PMID: 30591023]
[18]
Chen, T.H.; Sun, W. Prediction of cancer drug sensitivity using high-dimensional omic features. Biostatistics, 2017, 18(1), 1-14.
[http://dx.doi.org/10.1093/biostatistics/kxw022] [PMID: 27324412]
[19]
Kim, D.C.; Wang, X.; Yang, C.R.; Gao, J.X. A framework for personalized medicine: prediction of drug sensitivity in cancer by proteomic profiling. Proteome Sci., 2012, 10(Suppl. 1), S13.
[http://dx.doi.org/10.1186/1477-5956-10-S1-S13] [PMID: 22759571]
[20]
Suphavilai, C.; Bertrand, D.; Nagarajan, N. Predicting cancer drug response using a recommender system. Bioinformatics, 2018, 34(22), 3907-3914.
[http://dx.doi.org/10.1093/bioinformatics/bty452] [PMID: 29868820]
[21]
Zhang, L.; Chen, X.; Guan, N.N.; Liu, H.; Li, J.Q. A Hybrid interpolation weighted collaborative filtering method for anti-cancer drug response prediction. Front. Pharmacol., 2018, 9, 1017.
[http://dx.doi.org/10.3389/fphar.2018.01017] [PMID: 30258362]
[22]
Wei, D.; Liu, C.; Zheng, X.; Li, Y. Comprehensive anticancer drug response prediction based on a simple cell line-drug complex network model. BMC Bioinformatics, 2019, 20(1), 44.
[http://dx.doi.org/10.1186/s12859-019-2608-9] [PMID: 30670007]
[23]
Ruffalo, M.; Stojanov, P.; Pillutla, V.K.; Varma, R.; Bar-Joseph, Z. Reconstructing cancer drug response networks using multitask learning. BMC Syst. Biol., 2017, 11(1), 96.
[http://dx.doi.org/10.1186/s12918-017-0471-8] [PMID: 29017547]
[24]
Zhang, F.; Wang, M.; Xi, J.; Yang, J.; Li, A. A novel heterogeneous network-based method for drug response prediction in cancer cell lines. Sci. Rep., 2018, 8(1), 3355.
[http://dx.doi.org/10.1038/s41598-018-21622-4] [PMID: 29463808]
[25]
Yang, J.; Li, A.; Li, Y.; Guo, X.; Wang, M. A novel approach for drug response prediction in cancer cell lines via network representation learning. Bioinformatics, 2019, 35(9), 1527-1535.
[http://dx.doi.org/10.1093/bioinformatics/bty848] [PMID: 30304378]
[26]
Stanfield, Z.; Coşkun, M.; Koyutürk, M. Drug response prediction as a link prediction problem. Sci. Rep., 2017, 7, 40321.
[http://dx.doi.org/10.1038/srep40321] [PMID: 28067293]
[27]
Speyer, G.; Mahendra, D.; Tran, H.J.; Kiefer, J.; Schreiber, S.L.; Clemons, P.A.; Dhruv, H.; Berens, M.; Kim, S. Differential pathway dependency discovery associated with drug response across cancer cell lines. Pac. Symp. Biocomput., 2017, 22, 497-508.
[http://dx.doi.org/10.1142/9789813207813_0046] [PMID: 27897001]
[28]
Angermueller, C.; Pärnamaa, T.; Parts, L.; Stegle, O. Deep learning for computational biology. Mol. Syst. Biol., 2016, 12(7), 878.
[http://dx.doi.org/10.15252/msb.20156651] [PMID: 27474269]
[29]
Korotcov, A.; Tkachenko, V.; Russo, D.P.; Ekins, S. Comparison of deep learning with multiple machine learning methods and metrics using diverse drug discovery data sets. Mol. Pharm., 2017, 14(12), 4462-4475.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00578] [PMID: 29096442]
[30]
Wang, Y.; Li, M.; Zheng, R. Using deep neural network to predict drug sensitivity of cancer cell lines. In: Intelligent Computing Theories and Application; Springer: Berlin, 2018.
[http://dx.doi.org/10.1007/978-3-319-95933-7_27]
[31]
Xia, F.; Shukla, M.; Brettin, T.; Garcia-Cardona, C.; Cohn, J.; Allen, J.E.; Maslov, S.; Holbeck, S.L.; Doroshow, J.H.; Evrard, Y.A.; Stahlberg, E.A.; Stevens, R.L. Predicting tumor cell line response to drug pairs with deep learning. BMC Bioinformatics, 2018, 19(Suppl. 18), 486.
[http://dx.doi.org/10.1186/s12859-018-2509-3] [PMID: 30577754]
[32]
Chiu, Y.C.; Chen, H.H.; Zhang, T.; Zhang, S.; Gorthi, A.; Wang, L.J.; Huang, Y.; Chen, Y. Predicting drug response of tumors from integrated genomic profiles by deep neural networks. BMC Med. Genomics, 2019, 12(Suppl. 1), 18.
[http://dx.doi.org/10.1186/s12920-018-0460-9] [PMID: 30704458]
[33]
Li, M.; Wang, Y.; Zheng, R. DeepDSC: A deep learning method to predict drug sensitivity of cancer cell lines. IEEE/ACM Trans. Comput. Biol. Bioinform., 2019. (Online ahead of print)
[http://dx.doi.org/10.1109/TCBB.2019.2919581]
[34]
Chang, Y.; Park, H.; Yang, H.J.; Lee, S.; Lee, K.Y.; Kim, T.S.; Jung, J.; Shin, J.M. Cancer drug response profile scan (cdrscan): a deep learning model that predicts drug effectiveness from cancer genomic signature. Sci. Rep., 2018, 8(1), 8857.
[http://dx.doi.org/10.1038/s41598-018-27214-6] [PMID: 29891981]
[35]
Liu, P.; Li, H.; Li, S.; Leung, K.S. Improving prediction of phenotypic drug response on cancer cell lines using deep convolutional network. BMC Bioinformatics, 2019, 20(1), 408.
[http://dx.doi.org/10.1186/s12859-019-2910-6] [PMID: 31357929]
[36]
Su, R.; Liu, X.; Wei, L.; Zou, Q. Deep-Resp-Forest: A deep forest model to predict anti-cancer drug response. Methods, 2019, 166, 91-102.
[http://dx.doi.org/10.1016/j.ymeth.2019.02.009] [PMID: 30772464]
[37]
Williams, S.P.; McDermott, U. The pursuit of therapeutic biomarkers with high-throughput cancer cell drug screens. Cell Chem. Biol., 2017, 24(9), 1066-1074.
[http://dx.doi.org/10.1016/j.chembiol.2017.06.011] [PMID: 28736238]
[38]
Covell, D.G.; Huang, R.; Wallqvist, A. Anticancer medicines in development: assessment of bioactivity profiles within the National Cancer Institute anticancer screening data. Mol. Cancer Ther., 2007, 6(8), 2261-2270.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0787] [PMID: 17699723]
[39]
Barretina, J.; Caponigro, G.; Stransky, N.; Venkatesan, K.; Margolin, A.A.; Kim, S.; Wilson, C.J.; Lehár, J.; Kryukov, G.V.; Sonkin, D.; Reddy, A.; Liu, M.; Murray, L.; Berger, M.F.; Monahan, J.E.; Morais, P.; Meltzer, J.; Korejwa, A.; Jané-Valbuena, J.; Mapa, F.A.; Thibault, J.; Bric-Furlong, E.; Raman, P.; Shipway, A.; Engels, I.H.; Cheng, J.; Yu, G.K.; Yu, J.; Aspesi, P., Jr; de Silva, M.; Jagtap, K.; Jones, M.D.; Wang, L.; Hatton, C.; Palescandolo, E.; Gupta, S.; Mahan, S.; Sougnez, C.; Onofrio, R.C.; Liefeld, T.; MacConaill, L.; Winckler, W.; Reich, M.; Li, N.; Mesirov, J.P.; Gabriel, S.B.; Getz, G.; Ardlie, K.; Chan, V.; Myer, V.E.; Weber, B.L.; Porter, J.; Warmuth, M.; Finan, P.; Harris, J.L.; Meyerson, M.; Golub, T.R.; Morrissey, M.P.; Sellers, W.R.; Schlegel, R.; Garraway, L.A. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature, 2012, 483(7391), 603-607.
[http://dx.doi.org/10.1038/nature11003] [PMID: 22460905]
[40]
Yang, W.; Soares, J.; Greninger, P.; Edelman, E.J.; Lightfoot, H.; Forbes, S.; Bindal, N.; Beare, D.; Smith, J.A.; Thompson, I.R.; Ramaswamy, S.; Futreal, P.A.; Haber, D.A.; Stratton, M.R.; Benes, C.; McDermott, U.; Garnett, M.J. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res., 2013, 41(Database issue), D955-D961.
[PMID: 23180760]
[41]
Seashore-Ludlow, B.; Rees, M.G.; Cheah, J.H.; Cokol, M.; Price, E.V.; Coletti, M.E.; Jones, V.; Bodycombe, N.E.; Soule, C.K.; Gould, J.; Alexander, B.; Li, A.; Montgomery, P.; Wawer, M.J.; Kuru, N.; Kotz, J.D.; Hon, C.S.; Munoz, B.; Liefeld, T.; Dančík, V.; Bittker, J.A.; Palmer, M.; Bradner, J.E.; Shamji, A.F.; Clemons, P.A.; Schreiber, S.L. Harnessing connectivity in a large-scale small-molecule sensitivity dataset. Cancer Discov., 2015, 5(11), 1210-1223.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0235] [PMID: 26482930]
[42]
Holbeck, S.L.; Camalier, R.; Crowell, J.A.; Govindharajulu, J.P.; Hollingshead, M.; Anderson, L.W.; Polley, E.; Rubinstein, L.; Srivastava, A.; Wilsker, D.; Collins, J.M.; Doroshow, J.H. The National Cancer Institute ALMANAC: A comprehensive screening resource for the detection of anticancer drug pairs with enhanced therapeutic activity. Cancer Res., 2017, 77(13), 3564-3576.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0489] [PMID: 28446463]
[43]
Bouhaddou, M.; DiStefano, M.S.; Riesel, E.A.; Carrasco, E.; Holzapfel, H.Y.; Jones, D.C.; Smith, G.R.; Stern, A.D.; Somani, S.S.; Thompson, T.V.; Birtwistle, M.R. Drug response consistency in CCLE and CGP. Nature, 2016, 540(7631), E9-E10.
[http://dx.doi.org/10.1038/nature20580] [PMID: 27905419]
[44]
Barrett, T.; Wilhite, S.E.; Ledoux, P.; Evangelista, C.; Kim, I.F.; Tomashevsky, M.; Marshall, K.A.; Phillippy, K.H.; Sherman, P.M.; Holko, M.; Yefanov, A.; Lee, H.; Zhang, N.; Robertson, C.L.; Serova, N.; Davis, S.; Soboleva, A. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res., 2013, 41(Database issue), D991-D995.
[PMID: 23193258]
[45]
Sherry, S.T.; Ward, M.H.; Kholodov, M.; Baker, J.; Phan, L.; Smigielski, E.M.; Sirotkin, K. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res., 2001, 29(1), 308-311.
[http://dx.doi.org/10.1093/nar/29.1.308] [PMID: 11125122]
[46]
Oughtred, R; Chatr-aryamontri, A; Breitkreutz, B.J. BioGRID: A resource for studying biological interactions in yeast. Cold Spring Harb. Protoc.,, 2016, 2016(1) , pdb.top080754
[http://dx.doi.org/10.1101/pdb.top080754]
[47]
Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; Jensen, L.J.; Mering, C.V. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res., 2019, 47(D1), D607-D613.
[http://dx.doi.org/10.1093/nar/gky1131] [PMID: 30476243]
[48]
Kanehisa, M.; Furumichi, M.; Tanabe, M.; Sato, Y.; Morishima, K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res., 2017, 45(D1), D353-D361.
[http://dx.doi.org/10.1093/nar/gkw1092] [PMID: 27899662]
[49]
Li, Q.; Cheng, T.; Wang, Y.; Bryant, S.H. PubChem as a public resource for drug discovery. Drug Discov. Today, 2010, 15(23-24), 1052-1057.
[http://dx.doi.org/10.1016/j.drudis.2010.10.003] [PMID: 20970519]
[50]
van de Wetering, M.; Francies, H.E.; Francis, J.M.; Bounova, G.; Iorio, F.; Pronk, A.; van Houdt, W.; van Gorp, J.; Taylor-Weiner, A.; Kester, L.; McLaren-Douglas, A.; Blokker, J.; Jaksani, S.; Bartfeld, S.; Volckman, R.; van Sluis, P.; Li, V.S.; Seepo, S.; Sekhar Pedamallu, C.; Cibulskis, K.; Carter, S.L.; McKenna, A.; Lawrence, M.S.; Lichtenstein, L.; Stewart, C.; Koster, J.; Versteeg, R.; van Oudenaarden, A.; Saez-Rodriguez, J.; Vries, R.G.; Getz, G.; Wessels, L.; Stratton, M.R.; McDermott, U.; Meyerson, M.; Garnett, M.J.; Clevers, H. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell, 2015, 161(4), 933-945.
[http://dx.doi.org/10.1016/j.cell.2015.03.053] [PMID: 25957691]
[51]
Cherkasov, A.; Muratov, E.N.; Fourches, D.; Varnek, A.; Baskin, I.I.; Cronin, M.; Dearden, J.; Gramatica, P.; Martin, Y.C.; Todeschini, R.; Consonni, V.; Kuz’min, V.E.; Cramer, R.; Benigni, R.; Yang, C.; Rathman, J.; Terfloth, L.; Gasteiger, J.; Richard, A.; Tropsha, A. QSAR modeling: where have you been? Where are you going to? J. Med. Chem., 2014, 57(12), 4977-5010.
[http://dx.doi.org/10.1021/jm4004285] [PMID: 24351051]
[52]
Schmidhuber, J. Deep learning in neural networks: an overview. Neural Netw., 2015, 61, 85-117.
[http://dx.doi.org/10.1016/j.neunet.2014.09.003] [PMID: 25462637]
[53]
Tara, N. In:; Auto-encoder bottleneck features using deep belief networks, Proceedings of the Acoustics, Speech and Signal Processing (ICASSP), 2012 IEEE International Conference on IEEE, Hubei, China,. 2012.
[54]
Krizhevsky, A. ImageNet classification with deep convolutional neural networks. Advances in neural information processing systems , 2012, 25(2)
[http://dx.doi.org/10.1145/3065386]
[55]
Ozturk, K.; Dow, M.; Carlin, D.E.; Bejar, R.; Carter, H. The emerging potential for network analysis to inform precision cancer medicine. J. Mol. Biol., 2018, 430(18 Pt A), 2875-2899.
[http://dx.doi.org/10.1016/j.jmb.2018.06.016] [PMID: 29908887]
[56]
Sidorov, P.; Naulaerts, S.; Ariey-Bonnet, J.; Pasquier, E.; Ballester, P.J. Predicting synergism of cancer drug combinations using nci-almanac data. Front Chem., 2019, 7, 509.
[http://dx.doi.org/10.3389/fchem.2019.00509] [PMID: 31380352]
[57]
Preuer, K.; Lewis, R.P.I.; Hochreiter, S.; Bender, A.; Bulusu, K.C.; Klambauer, G. DeepSynergy: predicting anti-cancer drug synergy with Deep Learning. Bioinformatics, 2018, 34(9), 1538-1546.
[http://dx.doi.org/10.1093/bioinformatics/btx806] [PMID: 29253077]
[58]
Bayer, I.; Groth, P.; Schneckener, S. Prediction errors in learning drug response from gene expression data - influence of labeling, sample size, and machine learning algorithm. PLoS One, 2013, 8(7)e70294
[http://dx.doi.org/10.1371/journal.pone.0070294] [PMID: 23894636]
[59]
Goodspeed, A.; Heiser, L.M.; Gray, J.W.; Costello, J.C. Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Mol. Cancer Res., 2016, 14(1), 3-13.
[http://dx.doi.org/10.1158/1541-7786.MCR-15-0189] [PMID: 26248648]
[60]
Borrell, B. How accurate are cancer cell lines? Nature, 2010, 463(7283), 858.
[http://dx.doi.org/10.1038/463858a] [PMID: 20164888]
[61]
Hafner, M.; Niepel, M.; Chung, M.; Sorger, P.K. Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs. Nat. Methods, 2016, 13(6), 521-527.
[http://dx.doi.org/10.1038/nmeth.3853] [PMID: 27135972]
[62]
Kearnes, S.; McCloskey, K.; Berndl, M.; Pande, V.; Riley, P. Molecular graph convolutions: moving beyond fingerprints. J. Comput. Aided Mol. Des., 2016, 30(8), 595-608.
[http://dx.doi.org/10.1007/s10822-016-9938-8] [PMID: 27558503]
[63]
Kalinin, A.A.; Higgins, G.A.; Reamaroon, N.; Soroushmehr, S.; Allyn-Feuer, A.; Dinov, I.D.; Najarian, K.; Athey, B.D. Deep learning in pharmacogenomics: from gene regulation to patient stratification. Pharmacogenomics, 2018, 19(7), 629-650.
[http://dx.doi.org/10.2217/pgs-2018-0008] [PMID: 29697304]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version310msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[17:52:48] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[17:52:48] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[17:52:48] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (92.39ms)time
  • Application (218ms)time
  • 1 x Application (70.22%)
    218ms
    1 x Booting (29.78%)
    92.39ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated144ms
    • 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 ('51435153','',1,1739987568,1739987568) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739987568
      1.08msalphaeurekaselec_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 ('51435153','/article/108033',1,1739987568,1739987568)
      220μsalphaeurekaselec_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 >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) 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 >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) 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 >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) 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 >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) 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 >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) 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 >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51435153 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51435153) limit 1
      14.73msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51435153
      • 1: 51435153
      • 2: 51435153
      • 3: 51435153
      • 4: 51435153
      • 5: 51435153
      • 6: 51435153
      • 7: 51435153
      • 8: 51435153
      • 9: 51435153
      • 10: 51435153
      • 11: 51435153
      • 12: 51435153
      • 13: 51435153
      • 14: 51435153
      • 15: 51435153
      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=108033
      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` = 38 limit 1
      830μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 38
      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=38) and sj.journal_id!=38 group by `j`.`nid`) as `aggregate_table`
      1.25msalphaeurekaselec_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=38) and sj.journal_id!=38 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.04msalphaeurekaselec_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=38) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.99msalphaeurekaselec_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=38) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.06msalphaeurekaselec_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` = '108033'
      1.45msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 108033
      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` = '108033'
      3.4msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 108033
      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` = '108033' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.11msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 108033
      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
      360μsalphaeurekaselec_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
      710μsalphaeurekaselec_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 = 38 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      53.25msalphaeurekaselec_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 = 38 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      27.66msalphaeurekaselec_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 = 38 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      20.05msalphaeurekaselec_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` = 108033 limit 1
      260μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 108033
      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 = 108033 and content_type = 'article' order by status desc limit 1
      320μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 183610 limit 1
      210μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 183610
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      250μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CTMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      330μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CTMC
      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 = '108033' 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) )
      360μsalphaeurekaselec_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 = '10049' 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) )
      270μsalphaeurekaselec_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 = '2703' 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) )
      270μsalphaeurekaselec_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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2703) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2703) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2703)
      1.97msalphaeurekaselec_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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10049) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10049) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10049)
      550μsalphaeurekaselec_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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108033) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108033) 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 <= 51435153 and j.to_ip >=51435153 )) and ((j.from_date <= 1739987568 and j.to_date >= 1739987568 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 108033)
      560μsalphaeurekaselec_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` < '1858' and is_uploaded = 1 and issue_id = 10049 order by cast(first_page as SIGNED) desc limit 1
      430μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1858
      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` > '1867' and is_uploaded = 1 and issue_id = 10049 order by cast(first_page as SIGNED) asc limit 1
      370μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1867
      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'
      170μsalphaeurekaselec_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
      170μsalphaeurekaselec_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` = 108033 limit 1
      2.44msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 108033
      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` = 38 and `b`.`banner_from_date` <= 1739987568 and `b`.`banner_to_date` >= 1739987568 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 38
      • 3: 1739987568
      • 4: 1739987568
      • 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` = 38 and `b`.`banner_from_date` <= 1739987568 and `b`.`banner_to_date` >= 1739987568 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.07msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 38
      • 3: 1739987568
      • 4: 1739987568
      • 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='e9b1e37a527384fb1cb499d04cda6639'
      240μsalphaeurekaselec_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
        0nm7l5yQQtBNuo4zX9f9g2FuEMYjzf6ZLqPPh5qi
        uc_cart_id
        e9b1e37a527384fb1cb499d04cda6639
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/108033" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/108033
        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 => "Wed, 19 Feb 2025 17:52:48 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlRPSVdUR1lLTlh1WUlYMTB3VWpXa1E9PSIsInZhbHVlIjoiVks0cmVhWGRHc1p0KzBhU1FPOG8xejRGUU9QaitNY0JLMHVibEFMazRtUzBvN1F5UlZGVVFGTXFnVzBUN0VDbTZSblFEUkFWOVRSRWdGd1pzL0JaTUZtV0tFVzF3UlcvV1Y2aUEwZE83bFNlQXRnT3cwZml4NytiQm5XYlpWR20iLCJtYWMiOiI0N2ViNGMzN2U4ZjBlZTMwZTg1MWEzNDRjOGU0NWQwNTc3MzY2NmI2NmUyYzMxYzhiNmJjMGY1MzNhZjMxMTU5IiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 05:52:48 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlRPSVdUR1lLTlh1WUlYMTB3VWpXa1E9PSIsInZhbHVlIjoiVks0cmVhWGRHc1p0KzBhU1FPOG8xejRGUU9QaitNY0JLMHVibEFMazRtUzBvN1F5UlZGVVFGTXFnVzBUN0VDbTZSblFEU" 1 => "alphaeurekaselectnet_session=eyJpdiI6InBtcDF6eWRjNEZUQ1pIRXFOWGZCcXc9PSIsInZhbHVlIjoiaUUzS3g3K09ndkVPM0N1cFNDZy9SOUhFSk5yZ3ZpSllQbTFaZHJWdVVocnNmUUlET3lKa0xoNjQ4ajJlN25aUEE0UStxQ0I0L2t3YnRUUklxdXg0SllxLzhqV3dCZXNsL1N4N29yeDZkaEphT3VDWktQR29TbUw4OWNySDB1bm4iLCJtYWMiOiI3ZDI4NTFlMDg5YmY5OWI1NjEyYjZhZjU2MTkwNTdjZTczN2Y5NmExNDJlZGEwZmRmYzhjYTdkOTM5NjMwYzJjIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InBtcDF6eWRjNEZUQ1pIRXFOWGZCcXc9PSIsInZhbHVlIjoiaUUzS3g3K09ndkVPM0N1cFNDZy9SOUhFSk5yZ3ZpSllQbTFaZHJWdVVocnNmUUlET3lKa0xoNjQ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlRPSVdUR1lLTlh1WUlYMTB3VWpXa1E9PSIsInZhbHVlIjoiVks0cmVhWGRHc1p0KzBhU1FPOG8xejRGUU9QaitNY0JLMHVibEFMazRtUzBvN1F5UlZGVVFGTXFnVzBUN0VDbTZSblFEUkFWOVRSRWdGd1pzL0JaTUZtV0tFVzF3UlcvV1Y2aUEwZE83bFNlQXRnT3cwZml4NytiQm5XYlpWR20iLCJtYWMiOiI0N2ViNGMzN2U4ZjBlZTMwZTg1MWEzNDRjOGU0NWQwNTc3MzY2NmI2NmUyYzMxYzhiNmJjMGY1MzNhZjMxMTU5IiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 05:52:48 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlRPSVdUR1lLTlh1WUlYMTB3VWpXa1E9PSIsInZhbHVlIjoiVks0cmVhWGRHc1p0KzBhU1FPOG8xejRGUU9QaitNY0JLMHVibEFMazRtUzBvN1F5UlZGVVFGTXFnVzBUN0VDbTZSblFEU" 1 => "alphaeurekaselectnet_session=eyJpdiI6InBtcDF6eWRjNEZUQ1pIRXFOWGZCcXc9PSIsInZhbHVlIjoiaUUzS3g3K09ndkVPM0N1cFNDZy9SOUhFSk5yZ3ZpSllQbTFaZHJWdVVocnNmUUlET3lKa0xoNjQ4ajJlN25aUEE0UStxQ0I0L2t3YnRUUklxdXg0SllxLzhqV3dCZXNsL1N4N29yeDZkaEphT3VDWktQR29TbUw4OWNySDB1bm4iLCJtYWMiOiI3ZDI4NTFlMDg5YmY5OWI1NjEyYjZhZjU2MTkwNTdjZTczN2Y5NmExNDJlZGEwZmRmYzhjYTdkOTM5NjMwYzJjIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InBtcDF6eWRjNEZUQ1pIRXFOWGZCcXc9PSIsInZhbHVlIjoiaUUzS3g3K09ndkVPM0N1cFNDZy9SOUhFSk5yZ3ZpSllQbTFaZHJWdVVocnNmUUlET3lKa0xoNjQ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "0nm7l5yQQtBNuo4zX9f9g2FuEMYjzf6ZLqPPh5qi" "uc_cart_id" => "e9b1e37a527384fb1cb499d04cda6639" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/108033" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 17:52:48GET/article/108033314361