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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

The Determinative Role of Cytokines in Retinopathy of Prematurity

Author(s): Seyed Ahmad Rasoulinejad* and Pegah Kiyamehr

Volume 23, Issue 1, 2023

Published on: 10 February, 2022

Page: [36 - 43] Pages: 8

DOI: 10.2174/1566524022666220117114920

Price: $65

Abstract

Retinopathy of prematurity (ROP) is a neonatal disease corresponding to vision impairment and blindness. Utilizing the pathogenesis of ROP and the risk factors affecting its progression can help prevent and reduce its incidence and lead to the emergence and development of new treatment strategies. Factors influencing retinopathy include growth and inflammatory factors that play an essential role in the pathogenesis of the ROP. This review summarizes the most critical factors in the pathogenesis of ROP.

Keywords: Retinopathy of prematurity, VEGF, IGF-1, inflammation, angiogenesis, pathogenesis.

[1]
Sen P, Wu W-C, Chandra P, Vinekar A, Manchegowda PT, Bhende P. Retinopathy of prematurity treatment: Asian perspectives. Eye (Lond) 2020; 34(4): 632-42.
[http://dx.doi.org/10.1038/s41433-019-0643-4] [PMID: 31664193]
[2]
Rivera JC, Sapieha P, Joyal J-S, et al. Understanding retinopathy of prematurity: update on pathogenesis. Neonatology 2011; 100(4): 343-53.
[http://dx.doi.org/10.1159/000330174] [PMID: 21968165]
[3]
Hansen ED, Hartnett ME. A review of treatment for retinopathy of prematurity. Expert Rev Ophthalmol 2019; 14(2): 73-87.
[http://dx.doi.org/10.1080/17469899.2019.1596026] [PMID: 31762784]
[4]
Bancalari A, Schade R. Update in the treatment of retinopathy of prematurity. Am J Perinatol 2020. Online ahead of print
[http://dx.doi.org/10.1055/s-0040-1713181] [PMID: 32544962]
[5]
Zin A, Gole GA. Retinopathy of prematurity-incidence today. Clin Perinatol 2013; 40(2): 185-200.
[http://dx.doi.org/10.1016/j.clp.2013.02.001] [PMID: 23719304]
[6]
Gilbert C, Fielder A, Gordillo L, et al. International NO-ROP Group. Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs. Pediatrics 2005; 115(5): e518-25.
[http://dx.doi.org/10.1542/peds.2004-1180] [PMID: 15805336]
[7]
Drack A. Retinopathy of prematurity. Adv Pediatr 2006; 53: 211-26.
[http://dx.doi.org/10.1016/j.yapd.2006.04.010] [PMID: 17089868]
[8]
Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LE. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci USA 1995; 92(3): 905-9.
[http://dx.doi.org/10.1073/pnas.92.3.905] [PMID: 7846076]
[9]
VanderVeen DK, Melia M, Yang MB, Hutchinson AK, Wilson LB, Lambert SR. Anti-vascular endothelial growth factor therapy for primary treatment of type 1 retinopathy of prematurity: a report by the American Academy of Ophthalmology. Ophthalmology 2017; 124(5): 619-33.
[http://dx.doi.org/10.1016/j.ophtha.2016.12.025] [PMID: 28341474]
[10]
Abcouwer SF. Angiogenic factors and cytokines in diabetic retinopathy. J Clin Cell Immunol Suppl 2013; 1(11): 1-12.
[http://dx.doi.org/10.4172/2155-9899] [PMID: 24319628]
[11]
Pierce EA, Foley ED, Smith LE. Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol 1996; 114(10): 1219-28.
[http://dx.doi.org/10.1001/archopht.1996.01100140419009] [PMID: 8859081]
[12]
Sonmez K, Drenser KA, Capone A Jr, Trese MT. Vitreous levels of stromal cell–derived factor 1 and vascular endothelial growth factor in patients with retinopathy of prematurity. Ophthalmology 2008; 115(6): 1065-70.
[http://dx.doi.org/10.1016/j.ophtha.2007.08.050]
[13]
Barile GR, Schmidt AM. RAGE and its ligands in retinal disease. Curr Mol Med 2007; 7(8): 758-65.
[http://dx.doi.org/10.2174/156652407783220778] [PMID: 18331234]
[14]
Smith LE. IGF-1 and retinopathy of prematurity in the preterm infant. Biol Neonate 2005; 88(3): 237-44.
[http://dx.doi.org/10.1159/000087587] [PMID: 16210846]
[15]
Cheng Y, Zhu X, Linghu D, Xu Y, Liang J. Serum levels of cytokines in infants treated with conbercept for retinopathy of prematurity. Sci Rep 2020; 10(1): 12695.
[http://dx.doi.org/10.1038/s41598-020-69684-7] [PMID: 32728160]
[16]
Lee J, Dammann O. Perinatal infection, inflammation, and retinopathy of prematurity. In: Polin R, Randis T, Eds. Chorioamnionitis. Elsevier 2012; Vol. 17: pp. (1)26-9.
[http://dx.doi.org/10.1016/j.siny.2011.08.007]
[17]
Silveira RC, Fortes Filho JB, Procianoy RS. Assessment of the contribution of cytokine plasma levels to detect retinopathy of prematurity in very low birth weight infants. Invest Ophthalmol Vis Sci 2011; 52(3): 1297-301.
[http://dx.doi.org/10.1167/iovs.10-6279] [PMID: 21071735]
[18]
Yu H, Yuan L, Zou Y, et al. Serum concentrations of cytokines in infants with retinopathy of prematurity. APMIS 2014; 122(9): 818-23.
[http://dx.doi.org/10.1111/apm.12223] [PMID: 24479831]
[19]
Hartmann JS, Thompson H, Wang H, et al. Expression of vascular endothelial growth factor and pigment epithelial-derived factor in a rat model of retinopathy of prematurity. Mol Vis 2011; 17: 1577-87.
[PMID: 21738387]
[20]
Stahl A, Chen J, Joyal J-S, Smith LEH. The mouse model of oxygen-induced Retinopathy (OIR). In: Zudaire E, Cuttitta F, Eds. The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications. Dordrecht: Springer 2012; pp. 181-8.
[http://dx.doi.org/10.1007/978-94-007-4581-0_11]
[21]
Scott A, Fruttiger M. Oxygen-induced retinopathy: a model for vascular pathology in the retina. Eye (Lond) 2010; 24(3): 416-21.
[http://dx.doi.org/10.1038/eye.2009.306] [PMID: 20010791]
[22]
Smith LE, Hard A-L, Hellström A. The biology of retinopathy of prematurity: how knowledge of pathogenesis guides treatment. Clin Perinatol 2013; 40(2): 201-14.
[http://dx.doi.org/10.1016/j.clp.2013.02.002] [PMID: 23719305]
[23]
Vadlapatla RK, Vadlapudi AD, Mitra AK. Hypoxia-inducible factor-1 (HIF-1): A potential target for intervention in ocular neovascular diseases. Curr Drug Targets 2013; 14(8): 919-35.
[http://dx.doi.org/10.2174/13894501113149990015] [PMID: 23701276]
[24]
Madan A, Penn JS. Animal models of oxygen-induced retinopathy. Front Biosci 2003; 8: d1030-43.
[http://dx.doi.org/10.2741/1056] [PMID: 12700061]
[25]
Smith LE. Through the eyes of a child: understanding retinopathy through ROP the Friedenwald lecture. Invest Ophthalmol Vis Sci 2008; 49(12): 5177-82.
[http://dx.doi.org/10.1167/iovs.08-2584] [PMID: 18708611]
[26]
Ashton N, Ward B, Serpell G. Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. Br J Ophthalmol 1954; 38(7): 397-432.
[http://dx.doi.org/10.1136/bjo.38.7.397] [PMID: 13172417]
[27]
Stacker SA, Achen MG. The VEGF signaling pathway in cancer: the road ahead. Chin J Cancer 2013; 32(6): 297-302.
[http://dx.doi.org/10.5732/cjc.012.10319] [PMID: 23419196]
[28]
Shibuya M. Vascular endothelial growth factor receptor-2: its unique signaling and specific ligand, VEGF-E. Cancer Sci 2003; 94(9): 751-6.
[http://dx.doi.org/10.1111/j.1349-7006.2003.tb01514.x] [PMID: 12967471]
[29]
Stuttfeld E, Ballmer-Hofer K. Structure and function of VEGF receptors. IUBMB Life 2009; 61(9): 915-22.
[http://dx.doi.org/10.1002/iub.234] [PMID: 19658168]
[30]
Wu A-L, Wu W-C. Anti-VEGF for ROP and pediatric retinal diseases. Asia Pac J Ophthalmol (Phila) 2018; 7(3): 145-51.
[http://dx.doi.org/10.22608/201837] [PMID: 29633587]
[31]
Mintz-Hittner HA, Kennedy KA, Chuang AZ. BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 2011; 364(7): 603-15.
[http://dx.doi.org/10.1056/NEJMoa1007374] [PMID: 21323540]
[32]
Pickens SR, Chamberlain ND, Volin MV, et al. Role of the CCL21 and CCR7 pathways in rheumatoid arthritis angiogenesis. Arthritis Rheum 2012; 64(8): 2471-81.
[http://dx.doi.org/10.1002/art.34452] [PMID: 22392503]
[33]
Yuan L-H, Chen X-L, Di Y, Liu M-L. CCR7/p-ERK1/2/VEGF signaling promotes retinal neovascularization in a mouse model of oxygen-induced retinopathy. Int J Ophthalmol 2017; 10(6): 862-9.
[http://dx.doi.org/10.18240/ijo.2017.06.06] [PMID: 28730075]
[34]
Rasoulinejad SA, Montazeri M. Retinopathy of prematurity in neonates and its risk factors: A seven year study in Northern Iran. Open Ophthalmol J 2016; 10: 17-21.
[http://dx.doi.org/10.2174/1874364101610010017] [PMID: 27014382]
[35]
Yoon S, Seger R. The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors 2006; 24(1): 21-44.
[http://dx.doi.org/10.1080/02699050500284218] [PMID: 16393692]
[36]
Eblen ST, Slack JK, Weber MJ, Catling AD. Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexes. Mol Cell Biol 2002; 22(17): 6023-33.
[http://dx.doi.org/10.1128/MCB.22.17.6023-6033.2002] [PMID: 12167697]
[37]
Rasoulinejad SA, Pourdad P, Pourabdollah A, Arzani A, Geraili Z, Roshan HY. Ophthalmologic outcome of premature infants with or without retinopathy of prematurity at 5-6 years of age. J Family Med Prim Care 2020; 9(9): 4582-6.
[http://dx.doi.org/10.4103/jfmpc.jfmpc_528_20] [PMID: 33209767]
[38]
Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002; 298(5600): 1911-2.
[http://dx.doi.org/10.1126/science.1072682] [PMID: 12471242]
[39]
Rasoulinejad SA, Maroufi F. A review of DNA and histone methylation alterations in the new era of diagnosis and treatment of retinal diseases. Curr Mol Med 2021; 21(8): 607-19.
[http://dx.doi.org/10.2174/1566524020666201209103603] [PMID: 33297915]
[40]
Chen CY, Su CM, Hsu CJ, et al. CCN1 promotes VEGF production in osteoblasts and induces endothelial progenitor cell angiogenesis by inhibiting miR‐126 expression in rheumatoid arthritis. J Bone Miner Res 2017; 32(1): 34-45.
[http://dx.doi.org/10.1002/jbmr.2926] [PMID: 27465842]
[41]
Di Y, Zhang Y, Yang H, Wang A, Chen X. The mechanism of CCN1-enhanced retinal neovascularization in oxygen-induced retinopathy through PI3K/Akt-VEGF signaling pathway. Drug Des Devel Ther 2015; 9: 2463-73.
[http://dx.doi.org/10.2147/DDDT.S79782] [PMID: 25995618]
[42]
Laron Z. Insulin-like growth factor 1 (IGF-1): A growth hormone. Mol Pathol 2001; 54(5): 311-6.
[http://dx.doi.org/10.1136/mp.54.5.311] [PMID: 11577173]
[43]
Yuan J, Yin Z, Tao K, Wang G, Gao J. Function of insulin-like growth factor 1 receptor in cancer resistance to chemotherapy. Oncol Lett 2018; 15(1): 41-7.
[http://dx.doi.org/10.3892/ol.2017.7276] [PMID: 29285186]
[44]
Heidary G, Vanderveen D, Smith LE, Eds. Retinopathy of prematurity: current concepts in molecular pathogenesis. Semin Ophthalmol 2009; 24(2): 77-81.
[http://dx.doi.org/10.1080/08820530902800314] [PMID: 19373690]
[45]
Hellstrom A, Perruzzi C, Ju M, et al. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci USA 2001; 98(10): 5804-8.
[http://dx.doi.org/10.1073/pnas.101113998] [PMID: 11331770]
[46]
Cavallaro G, Filippi L, Bagnoli P, et al. The pathophysiology of retinopathy of prematurity: An update of previous and recent knowledge. Acta Ophthalmol 2014; 92(1): 2-20.
[http://dx.doi.org/10.1111/aos.12049] [PMID: 23617889]
[47]
Smith LE, Shen W, Perruzzi C, et al. Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med 1999; 5(12): 1390-5.
[http://dx.doi.org/10.1038/70963] [PMID: 10581081]
[48]
Fukuda R, Hirota K, Fan F, Jung Y, Ellis LM, Semenza GL. IGF-1 induces HIF-1-mediated VEGF expression that is dependent on MAP kinase and PI-3-kinase signaling in colon cancer cells. J Biol Chem 2002; 277(41): 38205-11.
[http://dx.doi.org/10.1074/jbc.M203781200] [PMID: 12149254]
[49]
Rasoulinejad SA, Karkhah A, Paniri A, Saleki K, Pirzadeh M, Nouri HR. Contribution of inflammasome complex in inflammatory-related eye disorders and its implications for anti-inflammasome therapy. Immunopharmacol Immunotoxicol 2020; 42(5): 400-7.
[http://dx.doi.org/10.1080/08923973.2020.1808986] [PMID: 32791926]
[50]
Ahmadpour-Kacho M, Motlagh AJ, Rasoulinejad SA, Jahangir T, Bijani A, Pasha YZ. Correlation between hyperglycemia and retinopathy of prematurity. Pediatr Int 2014; 56(5): 726-30.
[http://dx.doi.org/10.1111/ped.12371] [PMID: 24803073]
[51]
Rivera JC, Dabouz R, Noueihed B, Omri S, Tahiri H, Chemtob S. Ischemic retinopathies: oxidative stress and inflammation. Oxid Med Cell Longev 2017; 2017
[http://dx.doi.org/10.1155/2017/3940241] [PMID: 29410732]
[52]
Stoll BJ, Hansen NI, Adams-Chapman I, et al. National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004; 292(19): 2357-65.
[http://dx.doi.org/10.1001/jama.292.19.2357] [PMID: 15547163]
[53]
Klinger G, Levy I, Sirota L, Boyko V, Lerner-Geva L, Reichman B. Israel Neonatal Network. Outcome of early-onset sepsis in a national cohort of very low birth weight infants. Pediatrics 2010; 125(4): e736-40.
[http://dx.doi.org/10.1542/peds.2009-2017] [PMID: 20231184]
[54]
Woo SJ, Park KH, Jung HJ, et al. Effects of maternal and placental inflammation on retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2012; 250(6): 915-23.
[http://dx.doi.org/10.1007/s00417-011-1648-2] [PMID: 21455777]
[55]
Mittal M, Dhanireddy R, Higgins RD. Candida sepsis and association with retinopathy of prematurity. Pediatrics 1998; 101(4 Pt 1): 654-7.
[http://dx.doi.org/10.1542/peds.101.4.654] [PMID: 9521951]
[56]
Cohen T, Nahari D, Cerem LW, Neufeld G, Levi B-Z. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 1996; 271(2): 736-41.
[http://dx.doi.org/10.1074/jbc.271.2.736] [PMID: 8557680]
[57]
Liu P-M, Fang P-C, Huang C-B, et al. Risk factors of retinopathy of prematurity in premature infants weighing less than 1600 g. Am J Perinatol 2005; 22(2): 115-20.
[http://dx.doi.org/10.1055/s-2005-837276] [PMID: 15731992]
[58]
Rivera JC, Holm M, Austeng D, et al. Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies. J Neuroinflammation 2017; 14(1): 165.
[http://dx.doi.org/10.1186/s12974-017-0943-1] [PMID: 28830469]
[59]
Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340(6): 448-54.
[http://dx.doi.org/10.1056/NEJM199902113400607] [PMID: 9971870]
[60]
Pfeffer K. Biological functions of tumor necrosis factor cytokines and their receptors. Cytokine Growth Factor Rev 2003; 14(3-4): 185-91.
[http://dx.doi.org/10.1016/S1359-6101(03)00022-4] [PMID: 12787558]
[61]
Kociok N, Radetzky S, Krohne TU, Gavranic C, Joussen AM. Pathological but not physiological retinal neovascularization is altered in TNF-Rp55-receptor-deficient mice. Invest Ophthalmol Vis Sci 2006; 47(11): 5057-65.
[http://dx.doi.org/10.1167/iovs.06-0407] [PMID: 17065527]
[62]
Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992; 175(2): 323-9.
[http://dx.doi.org/10.1084/jem.175.2.323] [PMID: 1310100]
[63]
Zhou TE, Rivera JC, Bhosle VK, et al. Choroidal involution is associated with a progressive degeneration of the outer retinal function in a model of retinopathy of prematurity: Early role for IL-1β. Am J Pathol 2016; 186(12): 3100-16.
[http://dx.doi.org/10.1016/j.ajpath.2016.08.004] [PMID: 27768863]
[64]
Wooff Y, Man SM, Aggio-Bruce R, Natoli R, Fernando N. IL-1 family members mediate cell death, inflammation and angiogenesis in retinal degenerative diseases. Front Immunol 2019; 10: 1618.
[http://dx.doi.org/10.3389/fimmu.2019.01618] [PMID: 31379825]
[65]
Aouiss A, Anka Idrissi D, Kabine M, Zaid Y. Update of inflammatory proliferative retinopathy: Ischemia, hypoxia and angiogenesis. Curr Res Transl Med 2019; 67(2): 62-71.
[http://dx.doi.org/10.1016/j.retram.2019.01.005] [PMID: 30685380]
[66]
Ghasemi H, Ghazanfari T, Yaraee R, Faghihzadeh S, Hassan ZM. Roles of IL-8 in ocular inflammations: A review. Ocul Immunol Inflamm 2011; 19(6): 401-12.
[http://dx.doi.org/10.3109/09273948.2011.618902] [PMID: 22106907]
[67]
Powers MR, Davies MH, Eubanks JP. Increased expression of chemokine KC, an interleukin-8 homologue, in a model of oxygen-induced retinopathy. Curr Eye Res 2005; 30(4): 299-307.
[http://dx.doi.org/10.1080/02713680590923276] [PMID: 16020260]
[68]
Yoshida S, Yoshida A, Ishibashi T, Elner SG, Elner VM. Role of MCP-1 and MIP-1α in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization. J Leukoc Biol 2003; 73(1): 137-44.
[http://dx.doi.org/10.1189/jlb.0302117] [PMID: 12525571]
[69]
Maali A, Ferdosi-Shahandashti E, Sadeghi F, Aali E. The antihelminthic drug, mebendazole, induces apoptosis in adult t-cell leukemia/lymphoma cancer cells: In-vitro trial. Int J Hematol Oncol Stem Cell Res 2020; 14(4): 257-64.
[http://dx.doi.org/10.18502/ijhoscr.v14i4.4482] [PMID: 33603987]
[70]
Mitamura Y, Harada C, Harada T. Role of cytokines and trophic factors in the pathogenesis of diabetic retinopathy. Curr Diabetes Rev 2005; 1(1): 73-81.
[http://dx.doi.org/10.2174/1573399052952596] [PMID: 18220584]
[71]
Nakazawa T, Hisatomi T, Nakazawa C, et al. Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. Proc Natl Acad Sci USA 2007; 104(7): 2425-30.
[http://dx.doi.org/10.1073/pnas.0608167104] [PMID: 17284607]
[72]
Lukacs NW, Strieter RM, Elner VM, Evanoff HL, Burdick M, Kunkel SL. Intercellular adhesion molecule-1 mediates the expression of monocyte-derived MIP-1 alpha during monocyte-endothelial cell interactions. Blood 1994; 83(5): 1174-8.
[PMID: 7906962]
[73]
Maroufi F, Maali A, Abdollahpour-Alitappeh M, Ahmadi MH, Azad M. CRISPR-mediated modification of DNA methylation pattern in the new era of cancer therapy. Epigenomics 2020; 12(20): 1845-59.
[http://dx.doi.org/10.2217/epi-2020-0110] [PMID: 33185489]
[74]
Villalvilla A, Gomez R, Roman-Blas JA, Largo R, Herrero-Beaumont G. SDF-1 signaling: a promising target in rheumatic diseases. Expert Opin Ther Targets 2014; 18(9): 1077-87.
[http://dx.doi.org/10.1517/14728222.2014.930440] [PMID: 24950016]
[75]
Maali A, Maroufi F, Sadeghi F, et al. Induced pluripotent stem cell technology: Trends in molecular biology, from genetics to epigenetics. Epigenomics 2021; 13(8): 631-47.
[http://dx.doi.org/10.2217/epi-2020-0409] [PMID: 33823614]
[76]
Horuk R. Chemokine receptors. Cytokine Growth Factor Rev 2001; 12(4): 313-35.
[http://dx.doi.org/10.1016/S1359-6101(01)00014-4] [PMID: 11544102]
[77]
De Falco E, Porcelli D, Torella AR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood 2004; 104(12): 3472-82.
[http://dx.doi.org/10.1182/blood-2003-12-4423] [PMID: 15284120]
[78]
Salcedo R, Oppenheim JJ. Role of chemokines in angiogenesis: CXCL12/SDF-1 and CXCR4 interaction, a key regulator of endothelial cell responses. Microcirculation 2003; 10(3-4): 359-70.
[http://dx.doi.org/10.1080/mic.10.3-4.359.370] [PMID: 12851652]
[79]
Curnow SJ, Wloka K, Faint JM, et al. Topical glucocorticoid therapy directly induces up-regulation of functional CXCR4 on primed T lymphocytes in the aqueous humor of patients with uveitis. J Immunol 2004; 172(11): 7154-61.
[http://dx.doi.org/10.4049/jimmunol.172.11.7154] [PMID: 15153539]
[80]
Abu El-Asrar AM, Struyf S, Kangave D, Geboes K, Van Damme J. Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy. Eur Cytokine Netw 2006; 17(3): 155-65.
[PMID: 17194635]
[81]
Otsuka H, Arimura N, Sonoda S, et al. Stromal cell-derived factor-1 is essential for photoreceptor cell protection in retinal detachment. Am J Pathol 2010; 177(5): 2268-77.
[http://dx.doi.org/10.2353/ajpath.2010.100134] [PMID: 20889568]
[82]
He X, Cheng R, Benyajati S, Ma JX. PEDF and its roles in physiological and pathological conditions: Implication in diabetic and hypoxia-induced angiogenic diseases. Clin Sci (Lond) 2015; 128(11): 805-23.
[http://dx.doi.org/10.1042/CS20130463] [PMID: 25881671]
[83]
Tombran-Tink J, Aparicio S, Xu X, et al. PEDF and the serpins: phylogeny, sequence conservation, and functional domains. J Struct Biol 2005; 151(2): 130-50.
[http://dx.doi.org/10.1016/j.jsb.2005.05.005] [PMID: 16040252]
[84]
Karakousis PC, John SK, Behling KC, et al. Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues. Mol Vis 2001; 7(154): 154-63.
[PMID: 11438800]
[85]
Michalczyk ER, Chen L, Fine D, et al. Pigment epithelium-derived factor (PEDF) as a regulator of wound angiogenesis. Sci Rep 2018; 8(1): 11142.
[http://dx.doi.org/10.1038/s41598-018-29465-9] [PMID: 30042381]
[86]
Huang Q, Wang S, Sorenson CM, Sheibani N. PEDF-deficient mice exhibit an enhanced rate of retinal vascular expansion and are more sensitive to hyperoxia-mediated vessel obliteration. Exp Eye Res 2008; 87(3): 226-41.
[http://dx.doi.org/10.1016/j.exer.2008.06.003] [PMID: 18602915]
[87]
McColm JR, Geisen P, Hartnett ME. VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: Relevance to clinical ROP. Mol Vis 2004; 10: 512-20.
[PMID: 15303088]
[88]
Moradi Z, Maali A, Shad JS, et al. Updates on novel erythropoiesis-stimulating agents: Clinical and molecular approach. Indian J Hematol Blood Transfus 2020; 36(1): 26-36.
[http://dx.doi.org/10.1007/s12288-019-01170-1] [PMID: 32174689]
[89]
Zhang SX, Wang JJ, Gao G, Parke K, Ma JX. Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J Mol Endocrinol 2006; 37(1): 1-12.
[http://dx.doi.org/10.1677/jme.1.02008] [PMID: 16901919]
[90]
Dehghanifard A, Kaviani S, Abroun S, et al. Various signaling pathways in multiple myeloma cells and effects of treatment on these pathways. Clin Lymphoma Myeloma Leuk 2018; 18(5): 311-20.
[http://dx.doi.org/10.1016/j.clml.2018.03.007] [PMID: 29606369]
[91]
Maali A, Atashi A, Ghaffari S, Kouchaki R, Abdolmaleki F, Azad M. A review on leukemia and ipsc technology: application in novel treatment and future. Curr Stem Cell Res Ther 2018; 13(8): 665-75.
[http://dx.doi.org/10.2174/1574888X13666180731155038] [PMID: 30068283]
[92]
Konson A, Pradeep S, D’Acunto CW, Seger R. Pigment epithelium-derived factor and its phosphomimetic mutant induce JNK-dependent apoptosis and p38-mediated migration arrest. J Biol Chem 2011; 286(5): 3540-51.
[http://dx.doi.org/10.1074/jbc.M110.151548] [PMID: 21059648]
[93]
Putzbach W, Haluck-Kangas A, Gao QQ, et al. CD95/Fas ligand mRNA is toxic to cells. eLife 2018; 7: e38621.
[http://dx.doi.org/10.7554/eLife.38621] [PMID: 30324908]
[94]
Volpert OV, Zaichuk T, Zhou W, et al. Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nat Med 2002; 8(4): 349-57.
[http://dx.doi.org/10.1038/nm0402-349] [PMID: 11927940]
[95]
Kaplan HJ, Leibole MA, Tezel T, Ferguson TA. Fas ligand (CD95 ligand) controls angiogenesis beneath the retina. Nat Med 1999; 5(3): 292-7.
[http://dx.doi.org/10.1038/6509] [PMID: 10086384]
[96]
Aurora AB, Biyashev D, Mirochnik Y, et al. NF-kappaB balances vascular regression and angiogenesis via chromatin remodeling and NFAT displacement. Blood 2010; 116(3): 475-84.
[http://dx.doi.org/10.1182/blood-2009-07-232132] [PMID: 20203265]
[97]
Zaichuk TA, Shroff EH, Emmanuel R, Filleur S, Nelius T, Volpert OV. Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med 2004; 199(11): 1513-22.
[http://dx.doi.org/10.1084/jem.20040474] [PMID: 15184502]
[98]
Micheau O. Cellular FLICE-inhibitory protein: An attractive therapeutic target? Expert Opin Ther Targets 2003; 7(4): 559-73.
[http://dx.doi.org/10.1517/14728222.7.4.559] [PMID: 12885274]

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Request history8.2.27PHP Version296msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[23:40:38] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
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  • Application (205ms)time
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    205ms
    1 x Booting (30.77%)
    91.03ms
    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
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    • layouts._login_access_login_access.blade.php#?blade
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    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 duplicated121ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316303896','',1,1740526838,1740526838) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740526838
      1.01msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316303896','/article/120213',1,1740526838,1740526838)
      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 >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316303896 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316303896) limit 1
      12.38msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316303896
      • 1: 316303896
      • 2: 316303896
      • 3: 316303896
      • 4: 316303896
      • 5: 316303896
      • 6: 316303896
      • 7: 316303896
      • 8: 316303896
      • 9: 316303896
      • 10: 316303896
      • 11: 316303896
      • 12: 316303896
      • 13: 316303896
      • 14: 316303896
      • 15: 316303896
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=120213
      630μsalphaeurekaselec_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` = 23 limit 1
      780μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 23
      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=23) and sj.journal_id!=23 group by `j`.`nid`) as `aggregate_table`
      820μsalphaeurekaselec_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=23) and sj.journal_id!=23 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      700μsalphaeurekaselec_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=23) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.6msalphaeurekaselec_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=23) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.16msalphaeurekaselec_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` = '120213'
      240μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 120213
      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` = '120213'
      4.05msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 120213
      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` = '120213' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      600μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 120213
      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
      210μsalphaeurekaselec_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
      410μsalphaeurekaselec_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 = 23 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      35.93msalphaeurekaselec_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 = 23 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      18.38msalphaeurekaselec_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 = 23 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      11.9msalphaeurekaselec_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` = 120213 limit 1
      280μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 120213
      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 = 120213 and content_type = 'article' order by status desc limit 1
      330μsalphaeurekaselec_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` = 200291 limit 1
      250μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 200291
      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
      310μsalphaeurekaselec_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` = 'CMM' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      370μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMM
      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 = '120213' 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) )
      470μsalphaeurekaselec_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 = '11772' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      410μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3305' 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) )
      380μsalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3305) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3305) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3305)
      14.12msalphaeurekaselec_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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11772) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11772) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11772)
      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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 120213) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 120213) 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 <= 316303896 and j.to_ip >=316303896 )) and ((j.from_date <= 1740526838 and j.to_date >= 1740526838 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 120213)
      820μsalphaeurekaselec_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` < '36' and is_uploaded = 1 and issue_id = 11772 order by cast(first_page as SIGNED) desc limit 1
      660μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 36
      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` > '43' and is_uploaded = 1 and issue_id = 11772 order by cast(first_page as SIGNED) asc limit 1
      610μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 43
      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'
      230μsalphaeurekaselec_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` = 120213 limit 1
      3.78msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 120213
      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` = 23 and `b`.`banner_from_date` <= 1740526838 and `b`.`banner_to_date` >= 1740526838 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.6msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 23
      • 3: 1740526838
      • 4: 1740526838
      • 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` = 23 and `b`.`banner_from_date` <= 1740526838 and `b`.`banner_to_date` >= 1740526838 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.56msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 23
      • 3: 1740526838
      • 4: 1740526838
      • 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='fa5eeb758ed09bc4a8c445ec02609be6'
      310μsalphaeurekaselec_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
        ouAfSp7Et7U8ar43Yr2IUcdRZUETqrktGslqsero
        uc_cart_id
        fa5eeb758ed09bc4a8c445ec02609be6
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/120213" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
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