Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

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

Review Article

Specificity and Continuity of Schizophrenia and Bipolar Disorder: Relation to Biomarkers

Author(s): Yuji Yamada, Madoka Matsumoto, Kazuki Iijima and Tomiki Sumiyoshi*

Volume 26, Issue 2, 2020

Page: [191 - 200] Pages: 10

DOI: 10.2174/1381612825666191216153508

open access plus

Abstract

Schizophrenia and bipolar disorder overlap considerably in terms of symptoms, familial patterns, risk genes, outcome, and treatment response. This article provides an overview of the specificity and continuity of schizophrenia and mood disorders on the basis of biomarkers, such as genes, molecules, cells, circuits, physiology and clinical phenomenology. Overall, the discussions herein provided support for the view that schizophrenia, schizoaffective disorder and bipolar disorder are in the continuum of severity of impairment, with bipolar disorder closer to normality and schizophrenia at the most severe end. This approach is based on the concept that examining biomarkers in several modalities across these diseases from the dimensional perspective would be meaningful. These considerations are expected to help develop new treatments for unmet needs, such as cognitive dysfunction, in psychiatric conditions.

Keywords: Schizophrenia, bipolar disorder, psychosis, differential diagnosis, RDoC, spectrum, cognitive dysfunction.

Next »
[1]
Pearlson GD, Clementz BA, Sweeney JA, Keshavan MS, Tamminga CA. Does biology transcend the symptom-based boundaries of psychosis? Psychiatr Clin North Am 2016; 39(2): 165-74.
[http://dx.doi.org/10.1016/j.psc.2016.01.001] [PMID: 27216897]
[2]
Ebert A, Bär KJ. Emil kraepelin: a pioneer of scientific understanding of psychiatry and psychopharmacology. Indian J Psychiatry 2010; 52(2): 191-2.
[http://dx.doi.org/10.4103/0019-5545.64591] [PMID: 20838510]
[3]
Kasanin J. The acute schizoaffective psychoses. 1933. Am J Psychiatry 1994; 151(6)(Suppl.): 144-54.
[http://dx.doi.org/10.1176/ajp.151.6.144] [PMID: 8192190]
[4]
van Os J, Kapur S. Schizophrenia. Lancet 2009; 374(9690): 635-45.
[http://dx.doi.org/10.1016/S0140-6736(09)60995-8] [PMID: 19700006]
[5]
Insel TR, Cuthbert BN. Endophenotypes: bridging genomic complexity and disorder heterogeneity. Biol Psychiatry 2009; 66(11): 988-9.
[http://dx.doi.org/10.1016/j.biopsych.2009.10.008] [PMID: 19900610]
[6]
Insel T, Cuthbert B, Garvey M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 2010; 167(7): 748-51.
[http://dx.doi.org/10.1176/appi.ajp.2010.09091379] [PMID: 20595427]
[7]
Clark LA, Cuthbert B, Lewis-Fernández R, Narrow WE, Reed GM. Three approaches to understanding and classifying mental disorder: ICD-11, DSM-5, and the national institute of mental health’s research domain criteria (RDoC). Psychol Sci Public Interest 2017; 18(2): 72-145.
[http://dx.doi.org/10.1177/1529100617727266] [PMID: 29211974]
[8]
Cardno AG, Owen MJ. Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder. Schizophr Bull 2014; 40(3): 504-15.
[http://dx.doi.org/10.1093/schbul/sbu016] [PMID: 24567502]
[9]
Kendler KS, Diehl SR. The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull 1993; 19(2): 261-85.
[http://dx.doi.org/10.1093/schbul/19.2.261] [PMID: 8322035]
[10]
Kendler KS, McGuire M, Gruenberg AM, O’Hare A, Spellman M, Walsh D. The roscommon family study. I. methods, diagnosis of probands, and risk of schizophrenia in relatives. Arch Gen Psychiatry 1993; 50(7): 527-40.
[http://dx.doi.org/10.1001/archpsyc.1993.01820190029004] [PMID: 8317947]
[11]
Lichtenstein P, Yip BH, Björk C, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 2009; 373(9659): 234-9.
[http://dx.doi.org/10.1016/S0140-6736(09)60072-6] [PMID: 19150704]
[12]
Tsuang MT, Winokur G, Crowe RR. Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Br J Psychiatry 1980; 137: 497-504.
[http://dx.doi.org/10.1192/bjp.137.6.497] [PMID: 7214104]
[13]
Maier W, Lichtermann D, Minges J, et al. Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch Gen Psychiatry 1993; 50(11): 871-83.
[http://dx.doi.org/10.1001/archpsyc.1993.01820230041004] [PMID: 8215813]
[14]
Bertelsen A, Gottesman II. Schizoaffective psychoses: genetical clues to classification. Am J Med Genet 1995; 60(1): 7-11.
[http://dx.doi.org/10.1002/ajmg.1320600103] [PMID: 7485238]
[15]
Cardno AG, Gottesman II. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 2000; 97(1): 12-7.
[http://dx.doi.org/10.1002/(SICI)1096-8628(200021)97:1<12:AID-AJMG3>3.0.CO;2-U] [PMID: 10813800]
[16]
Cardno AG, Marshall EJ, Coid B, et al. Heritability estimates for psychotic disorders: the maudsley twin psychosis series. Arch Gen Psychiatry 1999; 56(2): 162-8.
[http://dx.doi.org/10.1001/archpsyc.56.2.162] [PMID: 10025441]
[17]
Van Snellenberg JX, de Candia T. Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch Gen Psychiatry 2009; 66(7): 748-55.
[http://dx.doi.org/10.1001/archgenpsychiatry.2009.64] [PMID: 19581566]
[18]
Ripke S, O’Dushlaine C, Chambert K, et al. Multicenter genetic studies of schizophrenia consortium; psychosis endophenotypes international consortium; wellcome trust case control consortium 2. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 2013; 45(10): 1150-9.
[http://dx.doi.org/10.1038/ng.2742] [PMID: 23974872]
[19]
Psychiatric GWAS consortium bipolar disorder working group. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011; 43(10): 977-83.
[http://dx.doi.org/10.1038/ng.943] [PMID: 21926972]
[20]
Sullivan PF, Daly MJ, O’Donovan M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet 2012; 13(8): 537-51.
[http://dx.doi.org/10.1038/nrg3240] [PMID: 22777127]
[21]
Kraguljac NV, Reid M, White D, et al. Neurometabolites in schizophrenia and bipolar disorder - a systematic review and meta-analysis. Psychiatry Res 2012; 203(2-3): 111-25.
[http://dx.doi.org/10.1016/j.pscychresns.2012.02.003] [PMID: 22981426]
[22]
Keshavan MS, Stanley JA, Pettegrew JW. Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings-part II. Biol Psychiatry 2000; 48(5): 369-80.
[http://dx.doi.org/10.1016/S0006-3223(00)00940-9] [PMID: 10978720]
[23]
Steen RG, Hamer RM, Lieberman JA. Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology 2005; 30(11): 1949-62.
[http://dx.doi.org/10.1038/sj.npp.1300850] [PMID: 16123764]
[24]
Yildiz-Yesiloglu A, Ankerst DP. Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30(6): 969-95.
[http://dx.doi.org/10.1016/j.pnpbp.2006.03.012] [PMID: 16677749]
[25]
Sager TN, Topp S, Torup L, Hanson LG, Egestad B, Møller A. Evaluation of CA1 damage using single-voxel 1H-MRS and un-biased stereology: Can non-invasive measures of N-acetyl-asparate following global ischemia be used as a reliable measure of neuronal damage? Brain Res 2001; 892(1): 166-75.
[http://dx.doi.org/10.1016/S0006-8993(00)03274-1] [PMID: 11172761]
[26]
Deicken RF, Pegues MP, Anzalone S, Feiwell R, Soher B. Lower concentration of hippocampal N-acetylaspartate in familial bipolar I disorder. Am J Psychiatry 2003; 160(5): 873-82.
[http://dx.doi.org/10.1176/appi.ajp.160.5.873] [PMID: 12727690]
[27]
Ohrmann P, Siegmund A, Suslow T, et al. Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res 2005; 73(2-3): 153-7.
[http://dx.doi.org/10.1016/j.schres.2004.08.021] [PMID: 15653258]
[28]
Frey BN, Stanley JA, Nery FG, et al. Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo 1H MRS study. Bipolar Disord 2007; 9(Suppl. 1): 119-27.
[http://dx.doi.org/10.1111/j.1399-5618.2007.00454.x] [PMID: 17543030]
[29]
Rüsch N, Tebartz van Elst L, Valerius G, et al. Neurochemical and structural correlates of executive dysfunction in schizophrenia. Schizophr Res 2008; 99(1-3): 155-63.
[http://dx.doi.org/10.1016/j.schres.2007.05.024] [PMID: 17616347]
[30]
Sharif-Barfeh Z, Beigoli S, Marouzi S, Sharif-Rad A, Asoodeh A, Chamani J. Multi-spectroscopic and HPLC studies of the interaction between estradiol and cyclophosphamide with human serum albumin: binary and ternary systems. J Solution Chem 2017; 46: 488-504.
[http://dx.doi.org/10.1007/s10953-017-0590-2]
[31]
Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry 2016; 21(12): 1696-709.
[http://dx.doi.org/10.1038/mp.2016.3] [PMID: 26903267]
[32]
Misiak B, Stańczykiewicz B, Kotowicz K, Rybakowski JK, Samochowiec J, Frydecka D. Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: a systematic review. Schizophr Res 2018; 192: 16-29.
[http://dx.doi.org/10.1016/j.schres.2017.04.015] [PMID: 28416092]
[33]
Gray LJ, Dean B, Kronsbein HC, Robinson PJ, Scarr E. Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder. Psychiatry Res 2010; 178(2): 374-80.
[http://dx.doi.org/10.1016/j.psychres.2008.07.012] [PMID: 20488553]
[34]
Ren X, Rizavi HS, Khan MA, Bhaumik R, Dwivedi Y, Pandey GN. Alteration of cyclic-AMP response element binding protein in the postmortem brain of subjects with bipolar disorder and schizophrenia. J Affect Disord 2014; 152-154: 326-33.
[http://dx.doi.org/10.1016/j.jad.2013.09.033] [PMID: 24148789]
[35]
Folsom TD, Thuras PD, Fatemi SH. Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders. Schizophr Res 2015; 165(2-3): 201-11.
[http://dx.doi.org/10.1016/j.schres.2015.04.012] [PMID: 25956630]
[36]
Leber SL, Llenos IC, Miller CL, Dulay JR, Haybaeck J, Weis S. Homer1a protein expression in schizophrenia, bipolar disorder, and major depression. J Neural Transm (Vienna) 2017; 124(10): 1261-73.
[http://dx.doi.org/10.1007/s00702-017-1776-x] [PMID: 28815330]
[37]
Torrey EF, Barci BM, Webster MJ, Bartko JJ, Meador-Woodruff JH, Knable MB. Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry 2005; 57(3): 252-60.
[http://dx.doi.org/10.1016/j.biopsych.2004.10.019] [PMID: 15691526]
[38]
Novikova SI, He F, Cutrufello NJ, Lidow MS. Identification of protein biomarkers for schizophrenia and bipolar disorder in the postmortem prefrontal cortex using SELDI-TOF-MS ProteinChip profiling combined with MALDI-TOF-PSD-MS analysis. Neurobiol Dis 2006; 23(1): 61-76.
[http://dx.doi.org/10.1016/j.nbd.2006.02.002] [PMID: 16549361]
[39]
Arnone D, Cavanagh J, Gerber D, Lawrie SM, Ebmeier KP, McIntosh AM. Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis. Br J Psychiatry 2009; 195(3): 194-201.
[http://dx.doi.org/10.1192/bjp.bp.108.059717] [PMID: 19721106]
[40]
Ellison-Wright I, Bullmore E. Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophr Res 2010; 117(1): 1-12.
[http://dx.doi.org/10.1016/j.schres.2009.12.022] [PMID: 20071149]
[41]
Maggioni E, Bellani M, Altamura AC, Brambilla P. Neuroanatomical voxel-based profile of schizophrenia and bipolar disorder. Epidemiol Psychiatr Sci 2016; 25(4): 312-6.
[http://dx.doi.org/10.1017/S2045796016000275] [PMID: 27095442]
[42]
Nenadic I, Maitra R, Langbein K, et al. Brain structure in schizophrenia vs. psychotic bipolar I disorder: a VBM study. Schizophr Res 2015; 165(2-3): 212-9.
[http://dx.doi.org/10.1016/j.schres.2015.04.007] [PMID: 25935815]
[43]
Brambilla P, Perlini C, Rajagopalan P, et al. Schizophrenia severity, social functioning and hippocampal neuroanatomy: three-dimensional mapping study. Br J Psychiatry 2013; 202(1): 50-5.
[http://dx.doi.org/10.1192/bjp.bp.111.105700] [PMID: 23284150]
[44]
Altamura AC, Bertoldo A, Marotta G, et al. White matter metabolism differentiates schizophrenia and bipolar disorder: a preliminary PET study. Psychiatry Res 2013; 214(3): 410-4.
[http://dx.doi.org/10.1016/j.pscychresns.2013.08.011] [PMID: 24144506]
[45]
O’Donoghue S, Holleran L, Cannon DM, McDonald C. Anatomical dysconnectivity in bipolar disorder compared with schizophrenia: a selective review of structural network analyses using diffusion MRI. J Affect Disord 2017; 209: 217-28.
[http://dx.doi.org/10.1016/j.jad.2016.11.015] [PMID: 27930915]
[46]
Stephan KE, Friston KJ, Frith CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 2009; 35(3): 509-27.
[http://dx.doi.org/10.1093/schbul/sbn176] [PMID: 19155345]
[47]
Ellison-Wright I, Bullmore E. Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophr Res 2009; 108(1-3): 3-10.
[http://dx.doi.org/10.1016/j.schres.2008.11.021] [PMID: 19128945]
[48]
Nortje G, Stein DJ, Radua J, Mataix-Cols D, Horn N. Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder. J Affect Disord 2013; 150(2): 192-200.
[http://dx.doi.org/10.1016/j.jad.2013.05.034] [PMID: 23810479]
[49]
Vederine FE, Wessa M, Leboyer M, Houenou J. A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35(8): 1820-6.
[http://dx.doi.org/10.1016/j.pnpbp.2011.05.009] [PMID: 21624424]
[50]
Baker JT, Holmes AJ, Masters GA, et al. Disruption of cortical association networks in schizophrenia and psychotic bipolar disorder. JAMA Psychiatry 2014; 71(2): 109-18.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.3469] [PMID: 24306091]
[51]
Bullmore E. Functional network endophenotypes of psychotic disorders. Biol Psychiatry 2012; 71(10): 844-5.
[http://dx.doi.org/10.1016/j.biopsych.2012.03.019] [PMID: 22520728]
[52]
De Peri L, Crescini A, Deste G, Fusar-Poli P, Sacchetti E, Vita A. Brain structural abnormalities at the onset of schizophrenia and bipolar disorder: a meta-analysis of controlled magnetic resonance imaging studies. Curr Pharm Des 2012; 18(4): 486-94.
[http://dx.doi.org/10.2174/138161212799316253] [PMID: 22239579]
[53]
Skudlarski P, Schretlen DJ, Thaker GK, et al. Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives. Am J Psychiatry 2013; 170(8): 886-98.
[http://dx.doi.org/10.1176/appi.ajp.2013.12111448] [PMID: 23771210]
[54]
Grace AA, Gomes FV. The circuitry of dopamine system regulation and its disruption in schizophrenia: insights into treatment and prevention. Schizophr Bull 2019; 45(1): 148-57.
[http://dx.doi.org/10.1093/schbul/sbx199] [PMID: 29385549]
[55]
Chai XJ, Whitfield-Gabrieli S, Shinn AK, et al. Abnormal medial prefrontal cortex resting-state connectivity in bipolar disorder and schizophrenia. Neuropsychopharmacology 2011; 36(10): 2009-17.
[http://dx.doi.org/10.1038/npp.2011.88] [PMID: 21654735]
[56]
Ongür D, Price JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 2000; 10(3): 206-19.
[http://dx.doi.org/10.1093/cercor/10.3.206] [PMID: 10731217]
[57]
Phillips ML, Ladouceur CD, Drevets WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry 2008; 13(9): 829-57.
[http://dx.doi.org/10.1038/mp.2008.82] [PMID: 18574483]
[58]
Versace A, Thompson WK, Zhou D, et al. Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: state versus trait vulnerability markers of depression in bipolar disorder. Biol Psychiatry 2010; 67(5): 422-31.
[http://dx.doi.org/10.1016/j.biopsych.2009.11.025] [PMID: 20159144]
[59]
Gilbert SJ, Spengler S, Simons JS, et al. Functional specialization within rostral prefrontal cortex (area 10): a meta-analysis. J Cogn Neurosci 2006; 18(6): 932-48.
[http://dx.doi.org/10.1162/jocn.2006.18.6.932] [PMID: 16839301]
[60]
Vinogradov S, Luks TL, Schulman BJ, Simpson GV. Deficit in a neural correlate of reality monitoring in schizophrenia patients. Cereb Cortex 2008; 18(11): 2532-9.
[http://dx.doi.org/10.1093/cercor/bhn028] [PMID: 18321870]
[61]
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124: 1-38.
[http://dx.doi.org/10.1196/annals.1440.011] [PMID: 18400922]
[62]
Du Y, Pearlson GD, Lin D, et al. Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder. Hum Brain Mapp 2017; 38(5): 2683-708.
[http://dx.doi.org/10.1002/hbm.23553] [PMID: 28294459]
[63]
Ivleva EI, Bidesi AS, Keshavan MS, et al. Gray matter volume as an intermediate phenotype for psychosis: bipolar-schizophrenia network on intermediate phenotypes (B-SNIP). Am J Psychiatry 2013; 170(11): 1285-96.
[http://dx.doi.org/10.1176/appi.ajp.2013.13010126] [PMID: 24185241]
[64]
Argyelan M, Ikuta T, DeRosse P, et al. Resting-state fMRI connectivity impairment in schizophrenia and bipolar disorder. Schizophr Bull 2014; 40(1): 100-10.
[http://dx.doi.org/10.1093/schbul/sbt092] [PMID: 23851068]
[65]
Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996; 153(3): 321-30.
[http://dx.doi.org/10.1176/ajp.153.3.321] [PMID: 8610818]
[66]
Daban C, Martinez-Aran A, Torrent C, et al. Specificity of cognitive deficits in bipolar disorder versus schizophrenia. A systematic review. Psychother Psychosom 2006; 75(2): 72-84.
[http://dx.doi.org/10.1159/000090891] [PMID: 16508342]
[67]
Bora E, Yucel M, Pantelis C. Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord 2009; 113(1-2): 1-20.
[http://dx.doi.org/10.1016/j.jad.2008.06.009] [PMID: 18684514]
[68]
Burdick KE, Goldberg JF, Harrow M. Neurocognitive dysfunction and psychosocial outcome in patients with bipolar I disorder at 15-year follow-up. Acta Psychiatr Scand 2010; 122(6): 499-506.
[http://dx.doi.org/10.1111/j.1600-0447.2010.01590.x] [PMID: 20637012]
[69]
Reichenberg A, Harvey PD, Bowie CR, et al. Neuropsychological function and dysfunction in schizophrenia and psychotic affective disorders. Schizophr Bull 2009; 35(5): 1022-9.
[http://dx.doi.org/10.1093/schbul/sbn044] [PMID: 18495643]
[70]
Hill SK, Ragland JD, Gur RC, Gur RE. Neuropsychological profiles delineate distinct profiles of schizophrenia, an interaction between memory and executive function, and uneven distribution of clinical subtypes. J Clin Exp Neuropsychol 2002; 24(6): 765-80.
[http://dx.doi.org/10.1076/jcen.24.6.765.8402] [PMID: 12424651]
[71]
Burdick KE, Goldberg TE, Cornblatt BA, et al. The MATRICS consensus cognitive battery in patients with bipolar I disorder. Neuropsychopharmacology 2011; 36(8): 1587-92.
[http://dx.doi.org/10.1038/npp.2011.36] [PMID: 21451499]
[72]
Burdick KE, Russo M, Frangou S, et al. Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications. Psychol Med 2014; 44(14): 3083-96.
[http://dx.doi.org/10.1017/S0033291714000439] [PMID: 25065409]

© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version424msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[18:24:55] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[18:24:55] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[18:24:55] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (127ms)time
  • Application (297ms)time
  • 1 x Application (70.03%)
    297ms
    1 x Booting (29.97%)
    127ms
    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
    32 statements were executed, 4 of which were duplicates, 28 unique. Show only duplicated221ms
    • 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 ('316381173','',1,1740421495,1740421495) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740421495
      940μsalphaeurekaselec_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 ('316381173','/article/103017',1,1740421495,1740421495)
      180μsalphaeurekaselec_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 >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) 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 >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) 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 >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) 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 >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) 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 >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) 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 >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316381173 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316381173) limit 1
      21.16msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316381173
      • 1: 316381173
      • 2: 316381173
      • 3: 316381173
      • 4: 316381173
      • 5: 316381173
      • 6: 316381173
      • 7: 316381173
      • 8: 316381173
      • 9: 316381173
      • 10: 316381173
      • 11: 316381173
      • 12: 316381173
      • 13: 316381173
      • 14: 316381173
      • 15: 316381173
      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=103017
      940μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 29 limit 1
      1.07msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 29
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid`) as `aggregate_table`
      1.43msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.16msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.55msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.41msalphaeurekaselec_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` = '103017'
      1.38msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 103017
      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` = '103017'
      3.73msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 103017
      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` = '103017' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.89msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 103017
      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
      290μsalphaeurekaselec_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
      650μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 29 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      60.87msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      67.02msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      33.94msalphaeurekaselec_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` = 103017 limit 1
      190μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 103017
      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 = 103017 and content_type = 'article' order by status desc limit 1
      420μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 281 and cd.sub_disease_id = 508 and content_id!=103017 and cd.content_type = 'article' order by rand() limit 20
      11.02msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 177556 limit 1
      190μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 177556
      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
      210μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CPD' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      290μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPD
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '103017' 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) )
      340μsalphaeurekaselec_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 * from `article` where `first_page` < '191' and is_uploaded = 1 and issue_id = 9697 order by cast(first_page as SIGNED) desc limit 1
      380μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 191
      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` > '200' and is_uploaded = 1 and issue_id = 9697 order by cast(first_page as SIGNED) asc limit 1
      380μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 200
      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'
      160μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      170μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 103017 limit 1
      2.28msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 103017
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 29 and `b`.`banner_from_date` <= 1740421495 and `b`.`banner_to_date` >= 1740421495 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.52msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1740421495
      • 4: 1740421495
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 29 and `b`.`banner_from_date` <= 1740421495 and `b`.`banner_to_date` >= 1740421495 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.47msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1740421495
      • 4: 1740421495
      • 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='38c70a06065adb734a85b5d0ed0c977d'
      250μsalphaeurekaselec_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
        jU593mLGFMKZaDIL4IH2Ixc9uAu1QKfXsdjHYqGw
        uc_cart_id
        38c70a06065adb734a85b5d0ed0c977d
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/103017" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/103017
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 24 Feb 2025 18:24:55 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkNTWm14bmtTRkI2b3orUFNxcFgxM1E9PSIsInZhbHVlIjoiWlpPRS85MHJhdEdpU3gvQk05aXRnLzJGbFJaRWMxVlNub2xkODZYSkY4eWJ3RHdwRFRQVjNWQ1VRcG1LU1BxRGRGUVd2KzNFbUVZRHlTTGQ3YzNXWm9HeW9udjF2QlI3a3cycVdKL0JrT0lMd0FnSHdlVzFkNHBSZGdmOEl2U1UiLCJtYWMiOiJlMzNhYzdlNjU3OWRhYWE4ZDkyZWYwZTVkYWEzZGQxMzc3ODczNTQ1OGFkODQ4ZTg3OWM3YjY4OTAwZjhkMzc0IiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 06:24:55 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkNTWm14bmtTRkI2b3orUFNxcFgxM1E9PSIsInZhbHVlIjoiWlpPRS85MHJhdEdpU3gvQk05aXRnLzJGbFJaRWMxVlNub2xkODZYSkY4eWJ3RHdwRFRQVjNWQ1VRcG1LU1BxRGRGUVd2K" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ill2VlRHbktrQkcwVWpSdUhJRTZ3RWc9PSIsInZhbHVlIjoid05KS2tNcTVsOUhha3p2cjFxSnVQTWx4OU1QNDdHaE1MekxaYkNCclZnSU4yWGdXNk83azk0Vlo0OXFnb3RqVVY2RzAwQ1pXOVlRRXZGeFFzcVhxZDhzb1djQmhGbXNsNVh3V2hYcHVTbStCT1B4NUNjRlQvR0QwczVKNGo1UDAiLCJtYWMiOiI2YzM4Y2M3NWUyNDFmNmVhOGEzYWMxMzEwZTYwZWU4OWU1OTY2YmQ2Nzc1OGRmMmI4OGMwYmQ3NmQ1MDc0NTYxIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Ill2VlRHbktrQkcwVWpSdUhJRTZ3RWc9PSIsInZhbHVlIjoid05KS2tNcTVsOUhha3p2cjFxSnVQTWx4OU1QNDdHaE1MekxaYkNCclZnSU4yWGdXNk83azk0Vlo" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkNTWm14bmtTRkI2b3orUFNxcFgxM1E9PSIsInZhbHVlIjoiWlpPRS85MHJhdEdpU3gvQk05aXRnLzJGbFJaRWMxVlNub2xkODZYSkY4eWJ3RHdwRFRQVjNWQ1VRcG1LU1BxRGRGUVd2KzNFbUVZRHlTTGQ3YzNXWm9HeW9udjF2QlI3a3cycVdKL0JrT0lMd0FnSHdlVzFkNHBSZGdmOEl2U1UiLCJtYWMiOiJlMzNhYzdlNjU3OWRhYWE4ZDkyZWYwZTVkYWEzZGQxMzc3ODczNTQ1OGFkODQ4ZTg3OWM3YjY4OTAwZjhkMzc0IiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 06:24:55 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkNTWm14bmtTRkI2b3orUFNxcFgxM1E9PSIsInZhbHVlIjoiWlpPRS85MHJhdEdpU3gvQk05aXRnLzJGbFJaRWMxVlNub2xkODZYSkY4eWJ3RHdwRFRQVjNWQ1VRcG1LU1BxRGRGUVd2K" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ill2VlRHbktrQkcwVWpSdUhJRTZ3RWc9PSIsInZhbHVlIjoid05KS2tNcTVsOUhha3p2cjFxSnVQTWx4OU1QNDdHaE1MekxaYkNCclZnSU4yWGdXNk83azk0Vlo0OXFnb3RqVVY2RzAwQ1pXOVlRRXZGeFFzcVhxZDhzb1djQmhGbXNsNVh3V2hYcHVTbStCT1B4NUNjRlQvR0QwczVKNGo1UDAiLCJtYWMiOiI2YzM4Y2M3NWUyNDFmNmVhOGEzYWMxMzEwZTYwZWU4OWU1OTY2YmQ2Nzc1OGRmMmI4OGMwYmQ3NmQ1MDc0NTYxIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Ill2VlRHbktrQkcwVWpSdUhJRTZ3RWc9PSIsInZhbHVlIjoid05KS2tNcTVsOUhha3p2cjFxSnVQTWx4OU1QNDdHaE1MekxaYkNCclZnSU4yWGdXNk83azk0Vlo" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "jU593mLGFMKZaDIL4IH2Ixc9uAu1QKfXsdjHYqGw" "uc_cart_id" => "38c70a06065adb734a85b5d0ed0c977d" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/103017" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-24 18:24:55GET/article/103017314321