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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Research Article

Thyroidectomy and PTU-Induced Hypothyroidism: Effect of L-Thyroxine on Suppression of Spatial and Non-Spatial Memory Related Signaling Molecules

Author(s): Karem Alzoubi* and Karim Alkadhi

Volume 16, Issue 6, 2023

Published on: 03 November, 2022

Article ID: e200922208982 Pages: 10

DOI: 10.2174/1874467215666220920122039

Price: $65

Abstract

Background: The calcium/calmodulin protein kinase II (CaMKII) signaling cascade is crucial for hippocampus-dependent learning and memory. Hypothyroidism impairs hippocampus- dependent learning and memory in adult rats, which can be prevented by simple replacement therapy with L-thyroxine (thyroxine, T4) treatment. In this study, we compared animal models of hypothyroidism induced by thyroidectomy and treatment with propylthiouracil (PTU) in terms of synaptic plasticity and the effect on underlying molecular mechanisms of spatial and non-spatial types of memory.

Methods: Hypothyroidism was induced using thyroidectomy or treatment with propylthiouracil (PTU). L-thyroxin was used as replacement therapy. Synaptic plasticity was evaluated using in vivo electrophysiological recording. Training in the radial arm water maze (RAWM), where rats had to locate a hidden platform, generated spatial and non-spatial learning and memory. Western blotting measured signaling molecules in the hippocampal area CA1 area.

Results: Our findings show that thyroidectomy and PTU models are equally effective, as indicated by the identical plasma levels of thyroid stimulating hormone (TSH) and T4. The two models produced an identical degree of inhibition of synaptic plasticity as indicated by depression of long-term potentiation (LTP). For non-spatial memory, rats were trained to swim to a visible platform in an open swim field. Analysis of hippocampal area CA1 revealed that training, on both mazes, of control and thyroxine-treated hypothyroid rats, produced significant increases in the P-calcium calmodulin kinase II (P-CaMKII), protein kinase-C (PKCγ), calcineurin and calmodulin protein levels, but the training failed to induce such increases in untreated thyroidectomized rats.

Conclusion: Thyroxine therapy prevented the deleterious effects of hypothyroidism at the molecular level.

Keywords: TSH, T4 thyroidectomy, PTU, CaMKII, PKC, calmodulin, calcineurin, rat, LTP.

Graphical Abstract

[1]
Koromilas, C.; Liapi, C.; Schulpis, K.H.; Kalafatakis, K.; Zarros, A.; Tsakiris, S. Structural and functional alterations in the hippocampus due to hypothyroidism. Metab. Brain Dis., 2010, 25(3), 339-354.
[http://dx.doi.org/10.1007/s11011-010-9208-8] [PMID: 20886273]
[2]
Burmeister, L.A.; Ganguli, M.; Dodge, H.H.; Toczek, T.; Dekosky, S.T.; Nebes, R.D. Hypothyroidism and cognition: Preliminary evidence for a specific defect in memory. Thyroid, 2001, 11(12), 1177-1185.
[http://dx.doi.org/10.1089/10507250152741037] [PMID: 12186506]
[3]
He, X.S.; Ma, N.; Pan, Z.L.; Wang, Z.X.; Li, N.; Zhang, X.C.; Zhou, J.N.; Zhu, D.F.; Zhang, D.R. Functional magnetic resource imaging assessment of altered brain function in hypothyroidism during working memory processing. Eur. J. Endocrinol., 2011, 164(6), 951-959.
[http://dx.doi.org/10.1530/EJE-11-0046] [PMID: 21474509]
[4]
Ge, J.F.; Peng, L.; Hu, C.M.; Wu, T.N. Impaired learning and memory performance in a subclinical hypothyroidism rat model induced by hemi-thyroid electrocauterisation. J. Neuroendocrinol., 2012, 24(6), 953-961.
[http://dx.doi.org/10.1111/j.1365-2826.2012.02297.x] [PMID: 22324892]
[5]
Alzoubi, K.H.; Gerges, N.Z.; Aleisa, A.M.; Alkadhi, K.A. Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: Behavioral, electrophysiological, and molecular studies. Hippocampus, 2009, 19(1), 66-78.
[http://dx.doi.org/10.1002/hipo.20476] [PMID: 18680156]
[6]
Alzoubi, K.H.; Aleisa, A.M.; Gerges, N.Z.; Alkadhi, K.A. Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies. J. Neurosci. Res., 2006, 84(5), 944-953.
[http://dx.doi.org/10.1002/jnr.21014] [PMID: 16902999]
[7]
Gerges, N.Z.; Alzoubi, K.H.; Park, C.R.; Diamond, D.M.; Alkadhi, K.A. Adverse effect of the combination of hypothyroidism and chronic psychosocial stress on hippocampus-dependent memory in rats. Behav. Brain Res., 2004, 155(1), 77-84.
[http://dx.doi.org/10.1016/j.bbr.2004.04.003] [PMID: 15325781]
[8]
Rivas, M.; Naranjo, J.R. Thyroid hormones, learning and memory. Genes Brain Behav., 2007, 6(Suppl. 1), 40-44.
[http://dx.doi.org/10.1111/j.1601-183X.2007.00321.x] [PMID: 17543038]
[9]
Reid, R.E.; Kim, E.M.; Page, D.; O’Mara, S.M.; O’Hare, E. Thyroxine replacement in an animal model of congenital hypothyroidism. Physiol. Behav., 2007, 91(2-3), 299-303.
[http://dx.doi.org/10.1016/j.physbeh.2007.03.005] [PMID: 17445845]
[10]
Aghili, R.; Khamseh, M.E.; Malek, M.; Hadian, A.; Baradaran, H.R.; Najafi, L.; Emami, Z. Changes of subtests of Wechsler Memory Scale and cognitive function in subjects with subclinical hypothyroidism following treatment with levothyroxine. Arch. Med. Sci., 2012, 6(6), 1096-1101.
[http://dx.doi.org/10.5114/aoms.2012.32423] [PMID: 23319987]
[11]
Mennemeier, M.; Garner, R.D.; Heilman, K.M. Memory, mood and measurement in hypothyroidism. J. Clin. Exp. Neuropsychol., 1993, 15(5), 822-831.
[http://dx.doi.org/10.1080/01688639308402598] [PMID: 8276938]
[12]
Haggerty, J.J., Jr; Garbutt, J.C.; Evans, D.L.; Golden, R.N.; Pedersen, C.; Simon, J.S.; Nemeroff, C.B. Subclinical hypothyroidism: A review of neuropsychiatric aspects. Int. J. Psychiatry Med., 1990, 20(2), 193-208.
[http://dx.doi.org/10.2190/ADLY-1UU0-1A8L-HPXY] [PMID: 2203696]
[13]
Leentjens, A.F.G.; Kappers, E.J. Persistent cognitive defects after corrected hypothyroidism. Psychopathology, 1995, 28(5), 235-237.
[http://dx.doi.org/10.1159/000284933] [PMID: 8559946]
[14]
Samuels, M.H.; Schuff, K.G.; Carlson, N.E.; Carello, P.; Janowsky, J.S. Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J. Clin. Endocrinol. Metab., 2007, 92(7), 2545-2551.
[http://dx.doi.org/10.1210/jc.2007-0011] [PMID: 17473069]
[15]
Osterweil, D.; Syndulko, K.; Cohen, S.N.; Pettier-Jennings, P.D.; Hershman, J.M.; Cummings, J.L.; Tourtellotte, W.W.; Solomon, D.H. Cognitive function in non-demented older adults with hypothyroidism. J. Am. Geriatr. Soc., 1992, 40(4), 325-335.
[http://dx.doi.org/10.1111/j.1532-5415.1992.tb02130.x] [PMID: 1556359]
[16]
Yin, J.J.; Liao, L.M.; Luo, D.X.; Xu, K.; Ma, S.H.; Wang, Z.X.; Le, H.B.; Huang, R.R.; Cai, Z.L.; Zhang, J. Spatial working memory impairment in subclinical hypothyroidism: An FMRI study. Neuroendocrinology, 2013, 97(3), 260-270.
[http://dx.doi.org/10.1159/000343201] [PMID: 22986643]
[17]
Tong, H.; Chen, G.H.; Liu, R.Y.; Zhou, J.N. Age-related learning and memory impairments in adult-onset hypothyroidism in Kunming mice. Physiol. Behav., 2007, 91(2-3), 290-298.
[http://dx.doi.org/10.1016/j.physbeh.2007.03.008] [PMID: 17449072]
[18]
Alzoubi, K.H.; Gerges, N.Z.; Alkadhi, K.A. Levothyroxin restores hypothyroidism-induced impairment of LTP of hippocampal CA1: Electrophysiological and molecular studies. Exp. Neurol., 2005, 195(2), 330-341.
[http://dx.doi.org/10.1016/j.expneurol.2005.05.007] [PMID: 16004982]
[19]
Gerges, N.Z.; Alkadhi, K.A. Hypothyroidism impairs late LTP in CA1 region but not in dentate gyrus of the intact rat hippocampus: MAPK involvement. Hippocampus, 2004, 14(1), 40-45.
[http://dx.doi.org/10.1002/hipo.10165] [PMID: 15058481]
[20]
Beheshti, F.; Hosseini, M.; Shafei, M.N.; Soukhtanloo, M.; Ghasemi, S.; Vafaee, F.; Zarepoor, L. The effects of Nigella sativa extract on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. Nutr. Neurosci., 2017, 20(1), 49-59.
[http://dx.doi.org/10.1179/1476830514Y.0000000144] [PMID: 25087773]
[21]
Baghcheghi, Y.; Hosseini, M.; Beheshti, F.; Salmani, H.; Anaeigoudari, A. Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats. Arq. Neuropsiquiatr., 2018, 76(1), 32-40.
[http://dx.doi.org/10.1590/0004-282x20170182] [PMID: 29364392]
[22]
Gilbert, M.E. Impact of low-level thyroid hormone disruption induced by propylthiouracil on brain development and function. Toxicol. Sci., 2011, 124(2), 432-445.
[http://dx.doi.org/10.1093/toxsci/kfr244] [PMID: 21964421]
[23]
Abdi, H.; Amouzegar, A.; Azizi, F. Antithyroid drugs. Iran. J. Pharm. Res., 2019, 18(Suppl. 1), 1-12.
[PMID: 32802086]
[24]
Farrokhi, E.; Hosseini, M.; Beheshti, F.; Vafaee, F.; Hadjzadeh, M.A.; Dastgheib, S.S. Brain tissues oxidative damage as a possible mechanism of deleterious effects of propylthiouracil- induced hypothyroidism on learning and memory in neonatal and juvenile growth in rats. Basic Clin. Neurosci., 2014, 5(4), 285-294.
[PMID: 27284393]
[25]
Andersen, S.L.; Andersen, S. Antithyroid drugs and birth defects. Thyroid Res., 2020, 13(1), 11.
[http://dx.doi.org/10.1186/s13044-020-00085-8] [PMID: 32607131]
[26]
Jensovsky, J.; Ruzicka, E.; Spackova, N.; Hejdukova, B. Changes of event related potential and cognitive processes in patients with subclinical hypothyroidism after thyroxine treatment. Endocr. Regul., 2002, 36(3), 115-122.
[PMID: 12463967]
[27]
Baldini, I.M.; Vita, A.; Mauri, M.C.; Amodei, V.; Carrisi, M.; Bravin, S.; Cantalamessa, L. Psychopathological and cognitive features in subclinical hypothyroidism. Prog. Neuropsychopharmacol. Biol. Psychiatry, 1997, 21(6), 925-935.
[http://dx.doi.org/10.1016/S0278-5846(97)00089-4] [PMID: 9380789]
[28]
Monzani, F.; Del Guerra, P.; Caraccio, N.; Pruneti, C.A.; Pucci, E.; Luisi, M.; Baschieri, L. Subclinical hypothyroidism: Neurobehavioral features and beneficial effect of L-thyroxine treatment. Clin. Investig., 1993, 71(5), 367-371.
[PMID: 8508006]
[29]
Malenka, R.C.; Kauer, J.A.; Perkel, D.J.; Mauk, M.D.; Kelly, P.T.; Nicoll, R.A.; Waxham, M.N. An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation. Nature, 1989, 340(6234), 554-557.
[http://dx.doi.org/10.1038/340554a0] [PMID: 2549423]
[30]
Thomas, K.L.; Laroche, S.; Errington, M.L.; Bliss, T.V.P.; Hunt, S.P. Spatial and temporal changes in signal transduction pathways during LTP. Neuron, 1994, 13(3), 737-745.
[http://dx.doi.org/10.1016/0896-6273(94)90040-X] [PMID: 7917303]
[31]
Roberts, L.A.; Large, C.H.; Higgins, M.J.; Stone, T.W.; O’Shaughnessy, C.T.; Morris, B.J. Increased expression of dendritic mRNA following the induction of long-term potentiation. Brain Res. Mol. Brain Res., 1998, 56(1-2), 38-44.
[http://dx.doi.org/10.1016/S0169-328X(98)00026-6] [PMID: 9602046]
[32]
Pettit, D.L.; Perlman, S.; Malinow, R. Potentiated transmission and prevention of further LTP by increased CaMKII activity in postsynaptic hippocampal slice neurons. Science, 1994, 266(5192), 1881-1885.
[http://dx.doi.org/10.1126/science.7997883] [PMID: 7997883]
[33]
Giese, K.P.; Fedorov, N.B.; Filipkowski, R.K.; Silva, A.J. Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. Science, 1998, 279(5352), 870-873.
[http://dx.doi.org/10.1126/science.279.5352.870] [PMID: 9452388]
[34]
Lledo, P.M.; Hjelmstad, G.O.; Mukherji, S.; Soderling, T.R.; Malenka, R.C.; Nicoll, R.A. Calcium/calmodulin-dependent kinase II and long-term potentiation enhance synaptic transmission by the same mechanism. Proc. Natl. Acad. Sci. USA, 1995, 92(24), 11175-11179.
[http://dx.doi.org/10.1073/pnas.92.24.11175] [PMID: 7479960]
[35]
Frey, U.; Huang, Y.Y.; Kandel, E.R. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science, 1993, 260(5114), 1661-1664.
[http://dx.doi.org/10.1126/science.8389057] [PMID: 8389057]
[36]
Huang, Y.Y.; Li, X.C.; Kandel, E.R. cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase. Cell, 1994, 79(1), 69-79.
[http://dx.doi.org/10.1016/0092-8674(94)90401-4] [PMID: 7923379]
[37]
Alzoubi, K.H.; Aleisa, A.M.; Alkadhi, K.A. Nicotine prevents disruption of the late phase LTP-related molecular cascade in adult-onset hypothyroidism. Hippocampus, 2007, 17(8), 654-664.
[http://dx.doi.org/10.1002/hipo.20306] [PMID: 17523180]
[38]
Alzoubi, K.H.; Alkadhi, K.A. A critical role of CREB in the impairment of late-phase LTP by adult onset hypothyroidism. Exp. Neurol., 2007, 203(1), 63-71.
[http://dx.doi.org/10.1016/j.expneurol.2006.07.019] [PMID: 16952356]
[39]
Aleisa, A.M.; Alzoubi, K.H.; Alkadhi, K.A. Post-learning REM sleep deprivation impairs long-term memory: Reversal by acute nicotine treatment. Neurosci. Lett., 2011, 499(1), 28-31.
[http://dx.doi.org/10.1016/j.neulet.2011.05.025] [PMID: 21624432]
[40]
Alzoubi, K.H.; Khabour, O.F.; Ahmed, M. Pentoxifylline prevents post-traumatic stress disorder induced memory impairment. Brain Res. Bull., 2018, 139, 263-268.
[http://dx.doi.org/10.1016/j.brainresbull.2018.03.009] [PMID: 29559394]
[41]
Alzoubi, K.H.; Rababa’h, A.M.; Owaisi, A.; Khabour, O.F. L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation. Brain Res. Bull., 2017, 131, 176-182.
[http://dx.doi.org/10.1016/j.brainresbull.2017.04.004] [PMID: 28433816]
[42]
Khabour, O.F.; Alzoubi, K.H.; Alomari, M.A.; Alzubi, M.A. Changes in spatial memory and BDNF expression to simultaneous dietary restriction and forced exercise. Brain Res. Bull., 2013, 90, 19-24.
[http://dx.doi.org/10.1016/j.brainresbull.2012.08.005] [PMID: 23000024]
[43]
Mhaidat, N.M.; Alzoubi, K.H.; Khabour, O.F.; Tashtoush, N.H.; Banihani, S.A.; Abdul-razzak, K.K. Exploring the effect of vitamin C on sleep deprivation induced memory impairment. Brain Res. Bull., 2015, 113, 41-47.
[http://dx.doi.org/10.1016/j.brainresbull.2015.02.002] [PMID: 25724146]
[44]
Rababa’h, A.M.; Alzoubi, K.H.; Atmeh, A. Levosimendan enhances memory through antioxidant effect in rat model: Behavioral and molecular study. Behav. Pharmacol., 2018, 29(4), 344-350.
[PMID: 29176443]
[45]
Alkadhi, K.A.; Alzoubi, K.H. Comparison of effects of spatial and non-spatial memory acquisition on the CaMKII pathway during hypothyroidism and nicotine treatment. Mol. Neurobiol., 2020, 57(4), 1930-1937.
[http://dx.doi.org/10.1007/s12035-019-01865-6] [PMID: 31900862]
[46]
Al-Sawalha, N.; Alzoubi, K.; Khabour, O.; Alyacoub, W.; Almahmmod, Y.; Eissenberg, T. Effect of prenatal exposure to waterpipe tobacco smoke on learning and memory of adult offspring rats. Nicotine Tob. Res., 2018, 20(4), 508-514.
[http://dx.doi.org/10.1093/ntr/ntx142] [PMID: 28637174]
[47]
Alzoubi, K.H.; Khabour, O.F.; Alharahshah, E.A.; Alhashimi, F.H.; Shihadeh, A.; Eissenberg, T. The effect of waterpipe tobacco smoke exposure on learning and memory functions in the rat model. J. Mol. Neurosci., 2015, 57(2), 249-256.
[http://dx.doi.org/10.1007/s12031-015-0613-7] [PMID: 26160697]
[48]
Alzoubi, K.H.; Mayyas, F.A.; Mahafzah, R.; Khabour, O.F. Melatonin prevents memory impairment induced by high-fat diet: Role of oxidative stress. Behav. Brain Res., 2018, 336, 93-98.
[http://dx.doi.org/10.1016/j.bbr.2017.08.047] [PMID: 28866128]
[49]
Alhaider, I.A.; Aleisa, A.M.; Tran, T.T.; Alzoubi, K.H.; Alkadhi, K.A. Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity. Sleep, 2010, 33(4), 437-444.
[http://dx.doi.org/10.1093/sleep/33.4.437] [PMID: 20394312]
[50]
Alothaid, H.; Aldughaim, M.S.K.; Alamri, S.S.; Alrahimi, J.S.M.; Al-Jadani, S.H. Role of calcineurin biosignaling in cell secretion and the possible regulatory mechanisms. Saudi J. Biol. Sci., 2021, 28(1), 116-124.
[http://dx.doi.org/10.1016/j.sjbs.2020.08.042] [PMID: 33424288]
[51]
Chiovato, L.; Magri, F.; Carlé, A. Hypothyroidism in context: Where we’ve been and where we’re going. Adv. Ther., 2019, 36(Suppl. 2), 47-58.
[http://dx.doi.org/10.1007/s12325-019-01080-8] [PMID: 31485975]
[52]
Davis, J.D.; Tremont, G. Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol., 2007, 32(1), 49-65.
[PMID: 17353866]
[53]
Samuels, M.H. Psychiatric and cognitive manifestations of hypothyroidism. Curr. Opin. Endocrinol. Diabetes Obes., 2014, 21(5), 377-383.
[http://dx.doi.org/10.1097/MED.0000000000000089] [PMID: 25122491]
[54]
Chaalal, A.; Poirier, R.; Blum, D.; Gillet, B.; Le Blanc, P.; Basquin, M.; Buée, L.; Laroche, S.; Enderlin, V. PTU-induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer’s disease in the hippocampus and spatial memory impairments. Hippocampus, 2014, 24(11), 1381-1393.
[http://dx.doi.org/10.1002/hipo.22319] [PMID: 24978200]
[55]
Jolin, T.; Escobar, G.M.D.; Rey, F.E.D. Differential effects in the rat thyroidectomy, propylthiouracil and other goitrogens on plasma insulin and thyroid weight. Endocrinology, 1970, 87(1), 99-110.
[http://dx.doi.org/10.1210/endo-87-1-99] [PMID: 4192261]
[56]
Godini, A.; Ghasemi, A.; Karbalaei, N.; Zahediasl, S. The effect of thyroidectomy and propylthiouracil-induced hypothyroidism on insulin secretion in male rats. Horm. Metab. Res., 2014, 46(10), 710-716.
[http://dx.doi.org/10.1055/s-0034-1370962] [PMID: 24627102]
[57]
Gerges, N.Z.; Alzoubi, K.H.; Alkadhi, K.A. Role of phosphorylated CaMKII and calcineurin in the differential effect of hypothyroidism on LTP of CA1 and dentate gyrus. Hippocampus, 2005, 15(4), 480-490.
[http://dx.doi.org/10.1002/hipo.20073] [PMID: 15714506]
[58]
Alzoubi, K.H.; Aleisa, A.M.; Alkadhi, K.A. Molecular studies on the protective effect of nicotine in adult-onset hypothyroidism-induced impairment of long-term potentiation. Hippocampus, 2006, 16(10), 861-874.
[http://dx.doi.org/10.1002/hipo.20217] [PMID: 16897721]
[59]
Lisman, J.; Yasuda, R.; Raghavachari, S. Mechanisms of CaMKII action in long-term potentiation. Nat. Rev. Neurosci., 2012, 13(3), 169-182.
[http://dx.doi.org/10.1038/nrn3192] [PMID: 22334212]
[60]
Kim, J.J.; Yoon, K.S. Stress: Metaplastic effects in the hippocampus. Trends Neurosci., 1998, 21(12), 505-509.
[http://dx.doi.org/10.1016/S0166-2236(98)01322-8] [PMID: 9881846]
[61]
Alzoubi, K.H.; Aleisa, A.M.; Alkadhi, K.A. The sliding threshold of modification hypothesis: Application to the effect of hypothyroidism or chronic psychosocial stress and nicotine on synaptic plasticity. Neurosci. Lett., 2008, 430(3), 203-206.
[http://dx.doi.org/10.1016/j.neulet.2007.10.043] [PMID: 18063475]
[62]
Krebs, J. Implications of the thyroid hormone on neuronal development with special emphasis on the calmodulin-kinase IV pathway. Biochim. Biophys. Acta Mol. Cell Res., 2017, 1864(6), 877-882.
[http://dx.doi.org/10.1016/j.bbamcr.2016.12.004] [PMID: 27939430]
[63]
Blanquet, P.R.; Mariani, J.; Derer, P. A calcium/calmodulin kinase pathway connects brain-derived neurotrophic factor to the cyclic amp-responsive transcription factor in the rat hippocampus. Neuroscience, 2003, 118(2), 477-490.
[http://dx.doi.org/10.1016/S0306-4522(02)00963-6] [PMID: 12699783]
[64]
Bavarsad, K.; Hadjzadeh, M.A.R.; Hosseini, M.; Pakdel, R.; Beheshti, F.; Bafadam, S.; Ashaari, Z. Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer’s disease: The role of BDNF and oxidative stress. Drug Chem. Toxicol., 2020, 43(1), 57-63.
[http://dx.doi.org/10.1080/01480545.2018.1481085] [PMID: 29927658]
[65]
Hung, P.L.; Hsu, M.H.; Yu, H.R.; Wu, K.L.H.; Wang, F.S. Thyroxin protects white matter from hypoxic-ischemic insult in the immature sprague–dawley rat brain by regulating periventricular white matter and cortex BDNF and CREB pathways. Int. J. Mol. Sci., 2018, 19(9), 2573.
[http://dx.doi.org/10.3390/ijms19092573] [PMID: 30158497]
[66]
Villanueva, I.; Alva-Sánchez, C.; Pacheco-Rosado, J. The role of thyroid hormones as inductors of oxidative stress and neurodegeneration. Oxid. Med. Cell. Longev., 2013, 2013, 1-15.
[http://dx.doi.org/10.1155/2013/218145] [PMID: 24386502]
[67]
Aleisa, A.M.; Alzoubi, K.H.; Alkadhi, K.A. Nicotine prevents stress-induced enhancement of long-term depression in hippocampal area CA1: Electrophysiological and molecular studies. J. Neurosci. Res., 2006, 83(2), 309-317.
[http://dx.doi.org/10.1002/jnr.20716] [PMID: 16307449]
[68]
Alkadhi, K.A.; Alzoubi, K.H.; Srivareerat, M.; Tran, T.T. Chronic psychosocial stress exacerbates impairment of synaptic plasticity in β-amyloid rat model of Alzheimer’s disease: Prevention by nicotine. Curr. Alzheimer Res., 2011, 8(7), 718-731.
[http://dx.doi.org/10.2174/156720511797633188] [PMID: 21453245]
[69]
Srivareerat, M.; Tran, T.T.; Alzoubi, K.H.; Alkadhi, K.A. Chronic psychosocial stress exacerbates impairment of cognition and long-term potentiation in beta-amyloid rat model of Alzheimer’s disease. Biol. Psychiatry, 2009, 65(11), 918-926.
[http://dx.doi.org/10.1016/j.biopsych.2008.08.021] [PMID: 18849021]
[70]
Gilbert, M.E.; Mack, C.M. Field potential recordings in dentate gyrus of anesthetized rats: Stability of baseline. Hippocampus, 1999, 9(3), 277-287.
[http://dx.doi.org/10.1002/(SICI)1098-1063(1999)9:3<277:AID-HIPO7>3.0.CO;2-H] [PMID: 10401642]
[71]
Maren, S. Sexually dimorphic perforant path long-term potentiation (LTP) in urethane-anesthetized rats. Neurosci. Lett., 1995, 196(2), 177-180.
[http://dx.doi.org/10.1016/0304-3940(95)11869-X] [PMID: 7501277]

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  • warninglog[06:05:55] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[06:05:55] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[06:05:55] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[06:05:55] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (172ms)time
  • Application (336ms)time
  • 1 x Application (66.08%)
    336ms
    1 x Booting (33.91%)
    172ms
    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 duplicated215ms
    • 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 ('59833132','',1,1740549955,1740549955) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740549955
      12.84msalphaeurekaselec_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 ('59833132','/article/126439',1,1740549955,1740549955)
      240μsalphaeurekaselec_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 >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) 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 >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) 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 >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) 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 >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) 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 >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) 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 >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59833132 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59833132) limit 1
      31.15msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59833132
      • 1: 59833132
      • 2: 59833132
      • 3: 59833132
      • 4: 59833132
      • 5: 59833132
      • 6: 59833132
      • 7: 59833132
      • 8: 59833132
      • 9: 59833132
      • 10: 59833132
      • 11: 59833132
      • 12: 59833132
      • 13: 59833132
      • 14: 59833132
      • 15: 59833132
      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=126439
      1.06msalphaeurekaselec_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` = 98 limit 1
      1.14msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 98
      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=98) and sj.journal_id!=98 group by `j`.`nid`) as `aggregate_table`
      1.4msalphaeurekaselec_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=98) and sj.journal_id!=98 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.1msalphaeurekaselec_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=98) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.25msalphaeurekaselec_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=98) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      6.16msalphaeurekaselec_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` = '126439'
      4.97msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 126439
      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` = '126439'
      11.68msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 126439
      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` = '126439' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      26.4msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 126439
      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
      400μsalphaeurekaselec_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
      730μsalphaeurekaselec_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 = 98 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      65.41msalphaeurekaselec_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 = 98 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      4.72msalphaeurekaselec_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 = 98 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      4.38msalphaeurekaselec_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` = 126439 limit 1
      10.21msalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 126439
      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 = 126439 and content_type = 'article' order by status desc limit 1
      480μsalphaeurekaselec_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` = 208982 limit 1
      340μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 208982
      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
      360μsalphaeurekaselec_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` = 'CMP' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      430μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMP
      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 = '126439' 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) )
      600μsalphaeurekaselec_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 = '12344' 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) )
      490μsalphaeurekaselec_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 = '3386' 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) )
      480μsalphaeurekaselec_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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3386) 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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3386) 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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3386)
      3.12msalphaeurekaselec_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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12344) 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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12344) 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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12344)
      1.01msalphaeurekaselec_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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 126439) 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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 126439) 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 <= 59833132 and j.to_ip >=59833132 )) and ((j.from_date <= 1740549955 and j.to_date >= 1740549955 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 126439)
      3.13msalphaeurekaselec_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` < '654' and is_uploaded = 1 and issue_id = 12344 order by cast(first_page as SIGNED) desc limit 1
      650μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 654
      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` > '663' and is_uploaded = 1 and issue_id = 12344 order by cast(first_page as SIGNED) asc limit 1
      630μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 663
      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'
      220μsalphaeurekaselec_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
      330μsalphaeurekaselec_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` = 126439 limit 1
      4.01msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 126439
      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` = 98 and `b`.`banner_from_date` <= 1740549955 and `b`.`banner_to_date` >= 1740549955 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      4.78msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 98
      • 3: 1740549955
      • 4: 1740549955
      • 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` = 98 and `b`.`banner_from_date` <= 1740549955 and `b`.`banner_to_date` >= 1740549955 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      3.99msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 98
      • 3: 1740549955
      • 4: 1740549955
      • 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='cc50b8fe3bc624a266dc30954e6d1dce'
      4.63msalphaeurekaselec_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
        nyuM046nMWAFrMMUhvOsytbwoJ6LqKamSof2KpZ7
        uc_cart_id
        cc50b8fe3bc624a266dc30954e6d1dce
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/126439" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/126439
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Imc4WHNMUWNiWkhWSHNVdzdjZlNvQXc9PSIsInZhbHVlIjoiNEhsbGMxZUNHcHlGQkRVTys0dXNteUphTElqeG5DOHFFR2lodHBrM3B6RT0iLCJtYWMiOiIyMGZmZWQ2MjhkMWZlYjZmYzFjZTYyYTg4ZGIwNjE5YjYzMTllNzNkNzBmMzQyOGU5NmY1ZjhiMTcxNTJiNGU4IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Imc4WHNMUWNiWkhWSHNVdzdjZlNvQXc9PSIsInZhbHVlIjoiNEhsbGMxZUNHcHlGQkRVTys0dXNteUphTElqeG5DOHFFR2lodHBrM3B6RT0iLCJtYWMiOiIyMGZmZWQ2MjhkMWZl" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
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