TY  - JOUR
AU  - Životić, Ivan
AU  - Kolić, Ivana
AU  - Cvetković, Mirjana
AU  - Spasojević-Dimitrijeva, Brankica
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13223
AB  - Background Congenital anomalies of the kidney and urinary tract (CAKUT) represent a frequent cause of pediatric kidney failure. CNVs, as a major class of genomic variations, can also affect miRNA regions. Common CNV corresponding miRNAs (cCNV-miRNAs) are functional variants regulating crucial processes which could affect urinary system development. Thus, we hypothesize that cCNV-miRNAs are associated with CAKUT occurrence and its expressivity.  Methods The extraction and filtering of common CNVs, identified in control samples deposited in publicly available databases gnomAD v2.1 and dbVar, were coupled with mapping of miRNA sequences using UCSC Genome Browser. After verification of the mapped miRNAs using referent miRBase V22.1, prioritization of cCNV-miRNA candidates has been performed using bioinformatic annotation and literature research. Genotyping of miRNA gene copy numbers for MIR9-3, MIR511, and MIR1299, was conducted on 221 CAKUT patients and 192 controls using TaqMan™ technology.  Results We observed significantly different MIR9-3 and MIR1299 gene copy number distribution between CAKUT patients and controls (Chi-square, P = 0.006 and P = 0.0002, respectively), while difference of MIR511 copy number distribution showed nominal significance (Chi-square, P = 0.027). The counts of less and more than two of MIR1299 copy numbers were more frequent within CAKUT patients compared to controls (P = 0.01 and P = 0.008, respectively) and also in cohort of patients with anomalies of the urinary tract compared to controls (P = 0.016 and P = 0.003, respectively).  Conclusions Copy number variations of miRNA genes represent a novel avenue in clarification of the inheritance complexity in CAKUT and provide potential evidence about the association of common genetic variation with CAKUT phenotypes.
T2  - Pediatric Nephrology
T1  - Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT
DO  - 10.1007/s00467-024-06381-x
ER  - 

@article{
author = "Životić, Ivan and Kolić, Ivana and Cvetković, Mirjana and Spasojević-Dimitrijeva, Brankica and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan",
year = "2024",
abstract = "Background Congenital anomalies of the kidney and urinary tract (CAKUT) represent a frequent cause of pediatric kidney failure. CNVs, as a major class of genomic variations, can also affect miRNA regions. Common CNV corresponding miRNAs (cCNV-miRNAs) are functional variants regulating crucial processes which could affect urinary system development. Thus, we hypothesize that cCNV-miRNAs are associated with CAKUT occurrence and its expressivity.  Methods The extraction and filtering of common CNVs, identified in control samples deposited in publicly available databases gnomAD v2.1 and dbVar, were coupled with mapping of miRNA sequences using UCSC Genome Browser. After verification of the mapped miRNAs using referent miRBase V22.1, prioritization of cCNV-miRNA candidates has been performed using bioinformatic annotation and literature research. Genotyping of miRNA gene copy numbers for MIR9-3, MIR511, and MIR1299, was conducted on 221 CAKUT patients and 192 controls using TaqMan™ technology.  Results We observed significantly different MIR9-3 and MIR1299 gene copy number distribution between CAKUT patients and controls (Chi-square, P = 0.006 and P = 0.0002, respectively), while difference of MIR511 copy number distribution showed nominal significance (Chi-square, P = 0.027). The counts of less and more than two of MIR1299 copy numbers were more frequent within CAKUT patients compared to controls (P = 0.01 and P = 0.008, respectively) and also in cohort of patients with anomalies of the urinary tract compared to controls (P = 0.016 and P = 0.003, respectively).  Conclusions Copy number variations of miRNA genes represent a novel avenue in clarification of the inheritance complexity in CAKUT and provide potential evidence about the association of common genetic variation with CAKUT phenotypes.",
journal = "Pediatric Nephrology",
title = "Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT",
doi = "10.1007/s00467-024-06381-x"
}

Životić, I., Kolić, I., Cvetković, M., Spasojević-Dimitrijeva, B., Živković, M., Stanković, A.,& Jovanović, I.. (2024). Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT. in Pediatric Nephrology.
https://doi.org/10.1007/s00467-024-06381-x

Životić I, Kolić I, Cvetković M, Spasojević-Dimitrijeva B, Živković M, Stanković A, Jovanović I. Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT. in Pediatric Nephrology. 2024;.
doi:10.1007/s00467-024-06381-x .

Životić, Ivan, Kolić, Ivana, Cvetković, Mirjana, Spasojević-Dimitrijeva, Brankica, Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan, "Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT" in Pediatric Nephrology (2024),
https://doi.org/10.1007/s00467-024-06381-x . .

TY  - JOUR
AU  - Cvetković, Mirjana
AU  - Živković, Maja
AU  - Bundalo, Maja M.
AU  - Gojković, Ivana
AU  - Spasojević-Dimitrijeva, Brankica
AU  - Stanković, Aleksandra
AU  - Kostić, Mirjana M.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1918
AB  - Background: The interindividual variability of cyclosporin A (CsA) pharmacokinetics might be explained by heterogeneity in the cytochrome P450 3A (CYP3A) subfamily. Altered CYP3A enzyme activity was associated with variant allele of P450 oxidoreductase gene (POR*28). The aim of this study was to assess the impact of age, CYP3A5*3, CYP3A4*22, and POR*28 alleles on CsA pharmacokinetics in pediatric renal transplant recipients. Methods: Renal transplant patients receiving CsA (n = 47) were genotyped for CYP3A5*3, CYP3A4*22, and POR*28. Results: CYP3A5 nonexpressers had higher overall dose-adjusted predose concentration (C0/dose; ng/mL per mg/kg) compared with expressers (31.48 +/- 12.75 versus 22.44 +/- 7.12, P = 0.01). CY-P3A5 nonexpressers carrying POR*28 allele had a lower overall dose-adjusted concentration (C2/dose) than those with POR*1/*1 genotype (165.54 +/- 70.40 versus 210.55 +/- 79.98, P = 0.02), with age as covariate. Children aged 6 years and younger had a lower overall C0/dose (18.82 +/- 4.72 versus 34.19 +/- 11.89, P = 0.001) and C2/dose (106.75 +/- 26.99 versus 209.20 +/- 71.57, P LT 0.001) compared with older children. Carriers of CYP3A5*3 allele aged LT = 6 years required higher dose of CsA and achieved lower C0/dose and C2/dose, at most time points, than older carriers of this allele. Carriers of POR*28 allele aged # 6 years required higher doses of CsA, whereas they achieved lower C0/dose and C2/dose, at most time points, in comparison to older carriers of this allele. The significant effect of age (P LT 0.002) and CYP3A5 variation (P, 0.02) was shown for overall C0/dose, whereas age (P LT 0.00001) and POR variation (P = 0.05) showed significant effect on C2/dose. Regression summary for overall C2/dose in patients aged 6 years younger showed a significant effect of both CYP3A5 and POR variations (P LT 0.016). Conclusions: Younger age, POR*28 allele, and CYP3A5*3 allele were associated with higher CsA dosing requirements and lower concentration/dose ratio. Pretransplant screening of relevant polymorphisms in accordance with age should be considered to adjust therapy.
T2  - Therapeutic Drug Monitoring
T1  - Effect of Age and Allele Variants of CYP3A5, CYP3A4, and POR Genes on the Pharmacokinetics of Cyclosporin A in Pediatric Renal Transplant Recipients From Serbia
VL  - 39
IS  - 6
SP  - 589
EP  - 595
DO  - 10.1097/FTD.0000000000000442
ER  - 

@article{
author = "Cvetković, Mirjana and Živković, Maja and Bundalo, Maja M. and Gojković, Ivana and Spasojević-Dimitrijeva, Brankica and Stanković, Aleksandra and Kostić, Mirjana M.",
year = "2017",
abstract = "Background: The interindividual variability of cyclosporin A (CsA) pharmacokinetics might be explained by heterogeneity in the cytochrome P450 3A (CYP3A) subfamily. Altered CYP3A enzyme activity was associated with variant allele of P450 oxidoreductase gene (POR*28). The aim of this study was to assess the impact of age, CYP3A5*3, CYP3A4*22, and POR*28 alleles on CsA pharmacokinetics in pediatric renal transplant recipients. Methods: Renal transplant patients receiving CsA (n = 47) were genotyped for CYP3A5*3, CYP3A4*22, and POR*28. Results: CYP3A5 nonexpressers had higher overall dose-adjusted predose concentration (C0/dose; ng/mL per mg/kg) compared with expressers (31.48 +/- 12.75 versus 22.44 +/- 7.12, P = 0.01). CY-P3A5 nonexpressers carrying POR*28 allele had a lower overall dose-adjusted concentration (C2/dose) than those with POR*1/*1 genotype (165.54 +/- 70.40 versus 210.55 +/- 79.98, P = 0.02), with age as covariate. Children aged 6 years and younger had a lower overall C0/dose (18.82 +/- 4.72 versus 34.19 +/- 11.89, P = 0.001) and C2/dose (106.75 +/- 26.99 versus 209.20 +/- 71.57, P LT 0.001) compared with older children. Carriers of CYP3A5*3 allele aged LT = 6 years required higher dose of CsA and achieved lower C0/dose and C2/dose, at most time points, than older carriers of this allele. Carriers of POR*28 allele aged # 6 years required higher doses of CsA, whereas they achieved lower C0/dose and C2/dose, at most time points, in comparison to older carriers of this allele. The significant effect of age (P LT 0.002) and CYP3A5 variation (P, 0.02) was shown for overall C0/dose, whereas age (P LT 0.00001) and POR variation (P = 0.05) showed significant effect on C2/dose. Regression summary for overall C2/dose in patients aged 6 years younger showed a significant effect of both CYP3A5 and POR variations (P LT 0.016). Conclusions: Younger age, POR*28 allele, and CYP3A5*3 allele were associated with higher CsA dosing requirements and lower concentration/dose ratio. Pretransplant screening of relevant polymorphisms in accordance with age should be considered to adjust therapy.",
journal = "Therapeutic Drug Monitoring",
title = "Effect of Age and Allele Variants of CYP3A5, CYP3A4, and POR Genes on the Pharmacokinetics of Cyclosporin A in Pediatric Renal Transplant Recipients From Serbia",
volume = "39",
number = "6",
pages = "589-595",
doi = "10.1097/FTD.0000000000000442"
}

Cvetković, M., Živković, M., Bundalo, M. M., Gojković, I., Spasojević-Dimitrijeva, B., Stanković, A.,& Kostić, M. M.. (2017). Effect of Age and Allele Variants of CYP3A5, CYP3A4, and POR Genes on the Pharmacokinetics of Cyclosporin A in Pediatric Renal Transplant Recipients From Serbia. in Therapeutic Drug Monitoring, 39(6), 589-595.
https://doi.org/10.1097/FTD.0000000000000442

Cvetković M, Živković M, Bundalo MM, Gojković I, Spasojević-Dimitrijeva B, Stanković A, Kostić MM. Effect of Age and Allele Variants of CYP3A5, CYP3A4, and POR Genes on the Pharmacokinetics of Cyclosporin A in Pediatric Renal Transplant Recipients From Serbia. in Therapeutic Drug Monitoring. 2017;39(6):589-595.
doi:10.1097/FTD.0000000000000442 .

Cvetković, Mirjana, Živković, Maja, Bundalo, Maja M., Gojković, Ivana, Spasojević-Dimitrijeva, Brankica, Stanković, Aleksandra, Kostić, Mirjana M., "Effect of Age and Allele Variants of CYP3A5, CYP3A4, and POR Genes on the Pharmacokinetics of Cyclosporin A in Pediatric Renal Transplant Recipients From Serbia" in Therapeutic Drug Monitoring, 39, no. 6 (2017):589-595,
https://doi.org/10.1097/FTD.0000000000000442 . .

TY  - CHAP
AU  - Živković, Maja
AU  - Stojković, Ljiljana S.
AU  - Spasojević-Dimitrijeva, Brankica
AU  - Kostić, Mirjana
AU  - Stanković, Aleksandra
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8882
PB  - IntechOpen
T2  - Recent Advances in the Field of Urinary Tract Infections
T1  - Genetic Factors Underlying Susceptibility to Acute Pyelonephritis and Post-infectious Renal Damage
VL  - Ch. 7
SP  - 1
EP  - 23
DO  - 10.5772/52852
ER  - 

@inbook{
author = "Živković, Maja and Stojković, Ljiljana S. and Spasojević-Dimitrijeva, Brankica and Kostić, Mirjana and Stanković, Aleksandra",
year = "2013",
publisher = "IntechOpen",
journal = "Recent Advances in the Field of Urinary Tract Infections",
booktitle = "Genetic Factors Underlying Susceptibility to Acute Pyelonephritis and Post-infectious Renal Damage",
volume = "Ch. 7",
pages = "1-23",
doi = "10.5772/52852"
}

Živković, M., Stojković, L. S., Spasojević-Dimitrijeva, B., Kostić, M.,& Stanković, A.. (2013). Genetic Factors Underlying Susceptibility to Acute Pyelonephritis and Post-infectious Renal Damage. in Recent Advances in the Field of Urinary Tract Infections
IntechOpen., Ch. 7, 1-23.
https://doi.org/10.5772/52852

Živković M, Stojković LS, Spasojević-Dimitrijeva B, Kostić M, Stanković A. Genetic Factors Underlying Susceptibility to Acute Pyelonephritis and Post-infectious Renal Damage. in Recent Advances in the Field of Urinary Tract Infections. 2013;Ch. 7:1-23.
doi:10.5772/52852 .

Živković, Maja, Stojković, Ljiljana S., Spasojević-Dimitrijeva, Brankica, Kostić, Mirjana, Stanković, Aleksandra, "Genetic Factors Underlying Susceptibility to Acute Pyelonephritis and Post-infectious Renal Damage" in Recent Advances in the Field of Urinary Tract Infections, Ch. 7 (2013):1-23,
https://doi.org/10.5772/52852 . .

TY  - JOUR
AU  - Spasojević-Dimitrijeva, Brankica
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Stojković, Ljiljana S.
AU  - Kostić, Mirjana M.
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4085
AB  - Urinary tract infections (UTI) are common in infants and children and may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the new markers in relation to acute pyelonephritis (APN) and its treatment is essential for designing interventions that would minimize tissue damage. This prospective study investigated the first UTI infection in 71 children (age range: 1-24 months) in respect to interleukin-6 (IL-6) -174G/C polymorphism and renal scarring. The patients were divided into an APN group and a lower UTI group according to dimercaptosuccinic acid (DMSA). The IL-6 -174G/C genotypes were determined by tetra-primer ARMSPCR. Serum IL-6 was significantly higher in the APN group than in the group with lower UTI (p LT 0.05). In both groups, the -174G/C genotype and allele frequencies did not differ significantly from the control group. The highest white blood cell (WBC) count was observed in the CC genotype (p LT 0.05). A non-significant trend toward higher serum IL-6 was observed in children with CC genotype. On follow-up DMSA imaging performed 6 months later, renal scarring was detected in 36.9% of APN children. We did not find the significant association of IL-6 -174G/C polymorphism with APN and/or postinfectious renal scarring. These results indicate that serum IL-6 concentrations were significantly higher in children with APN than in patients with lower UTI.
T2  - Pediatric Nephrology
T1  - The IL-6-174G/C polymorphism and renal scarring in children with first acute pyelonephritis
VL  - 25
IS  - 10
SP  - 2099
EP  - 2106
DO  - 10.1007/s00467-010-1587-x
ER  - 

@article{
author = "Spasojević-Dimitrijeva, Brankica and Živković, Maja and Stanković, Aleksandra and Stojković, Ljiljana S. and Kostić, Mirjana M.",
year = "2010",
abstract = "Urinary tract infections (UTI) are common in infants and children and may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the new markers in relation to acute pyelonephritis (APN) and its treatment is essential for designing interventions that would minimize tissue damage. This prospective study investigated the first UTI infection in 71 children (age range: 1-24 months) in respect to interleukin-6 (IL-6) -174G/C polymorphism and renal scarring. The patients were divided into an APN group and a lower UTI group according to dimercaptosuccinic acid (DMSA). The IL-6 -174G/C genotypes were determined by tetra-primer ARMSPCR. Serum IL-6 was significantly higher in the APN group than in the group with lower UTI (p LT 0.05). In both groups, the -174G/C genotype and allele frequencies did not differ significantly from the control group. The highest white blood cell (WBC) count was observed in the CC genotype (p LT 0.05). A non-significant trend toward higher serum IL-6 was observed in children with CC genotype. On follow-up DMSA imaging performed 6 months later, renal scarring was detected in 36.9% of APN children. We did not find the significant association of IL-6 -174G/C polymorphism with APN and/or postinfectious renal scarring. These results indicate that serum IL-6 concentrations were significantly higher in children with APN than in patients with lower UTI.",
journal = "Pediatric Nephrology",
title = "The IL-6-174G/C polymorphism and renal scarring in children with first acute pyelonephritis",
volume = "25",
number = "10",
pages = "2099-2106",
doi = "10.1007/s00467-010-1587-x"
}

Spasojević-Dimitrijeva, B., Živković, M., Stanković, A., Stojković, L. S.,& Kostić, M. M.. (2010). The IL-6-174G/C polymorphism and renal scarring in children with first acute pyelonephritis. in Pediatric Nephrology, 25(10), 2099-2106.
https://doi.org/10.1007/s00467-010-1587-x

Spasojević-Dimitrijeva B, Živković M, Stanković A, Stojković LS, Kostić MM. The IL-6-174G/C polymorphism and renal scarring in children with first acute pyelonephritis. in Pediatric Nephrology. 2010;25(10):2099-2106.
doi:10.1007/s00467-010-1587-x .

Spasojević-Dimitrijeva, Brankica, Živković, Maja, Stanković, Aleksandra, Stojković, Ljiljana S., Kostić, Mirjana M., "The IL-6-174G/C polymorphism and renal scarring in children with first acute pyelonephritis" in Pediatric Nephrology, 25, no. 10 (2010):2099-2106,
https://doi.org/10.1007/s00467-010-1587-x . .

TY  - CONF
AU  - Spasojević-Dimitrijeva, Brankica
AU  - Kostic, M.
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Peco-Antic, A.
AU  - Cvetković, M.
AU  - Paripovic, D.
AU  - Milosevski-Lomic, G.
AU  - Kruscic, D.
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3757
C3  - Pediatric Nephrology
T1  - Il-1beta, Il-6 and Angiotensin Converting Enzyme (Ace) Genotype Polymorphisms, Inflammatory Markers in Urinary Tract Infection and Scar Formation
VL  - 24
IS  - 9
SP  - 1870
EP  - 1870
UR  - https://hdl.handle.net/21.15107/rcub_vinar_3757
ER  - 

@conference{
author = "Spasojević-Dimitrijeva, Brankica and Kostic, M. and Živković, Maja and Stanković, Aleksandra and Peco-Antic, A. and Cvetković, M. and Paripovic, D. and Milosevski-Lomic, G. and Kruscic, D.",
year = "2009",
journal = "Pediatric Nephrology",
title = "Il-1beta, Il-6 and Angiotensin Converting Enzyme (Ace) Genotype Polymorphisms, Inflammatory Markers in Urinary Tract Infection and Scar Formation",
volume = "24",
number = "9",
pages = "1870-1870",
url = "https://hdl.handle.net/21.15107/rcub_vinar_3757"
}

Spasojević-Dimitrijeva, B., Kostic, M., Živković, M., Stanković, A., Peco-Antic, A., Cvetković, M., Paripovic, D., Milosevski-Lomic, G.,& Kruscic, D.. (2009). Il-1beta, Il-6 and Angiotensin Converting Enzyme (Ace) Genotype Polymorphisms, Inflammatory Markers in Urinary Tract Infection and Scar Formation. in Pediatric Nephrology, 24(9), 1870-1870.
https://hdl.handle.net/21.15107/rcub_vinar_3757

Spasojević-Dimitrijeva B, Kostic M, Živković M, Stanković A, Peco-Antic A, Cvetković M, Paripovic D, Milosevski-Lomic G, Kruscic D. Il-1beta, Il-6 and Angiotensin Converting Enzyme (Ace) Genotype Polymorphisms, Inflammatory Markers in Urinary Tract Infection and Scar Formation. in Pediatric Nephrology. 2009;24(9):1870-1870.
https://hdl.handle.net/21.15107/rcub_vinar_3757 .

Spasojević-Dimitrijeva, Brankica, Kostic, M., Živković, Maja, Stanković, Aleksandra, Peco-Antic, A., Cvetković, M., Paripovic, D., Milosevski-Lomic, G., Kruscic, D., "Il-1beta, Il-6 and Angiotensin Converting Enzyme (Ace) Genotype Polymorphisms, Inflammatory Markers in Urinary Tract Infection and Scar Formation" in Pediatric Nephrology, 24, no. 9 (2009):1870-1870,
https://hdl.handle.net/21.15107/rcub_vinar_3757 .

TY  - CONF
AU  - Spasojević-Dimitrijeva, Brankica
AU  - Kostic, M.
AU  - Peco-Antic, A.
AU  - Stanic, M.
AU  - Živković, Maja
AU  - Afgan, Naim H.
AU  - Topalov, D.
AU  - Mitrović, J.
PY  - 2008
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3492
C3  - Pediatric Nephrology
T1  - Proinflamatory cytokines IL-1 beta, IL-6 and procalcitonin in children with acute pyelonephritis
VL  - 23
IS  - 9
SP  - 1705
EP  - 1705
UR  - https://hdl.handle.net/21.15107/rcub_vinar_3492
ER  - 

@conference{
author = "Spasojević-Dimitrijeva, Brankica and Kostic, M. and Peco-Antic, A. and Stanic, M. and Živković, Maja and Afgan, Naim H. and Topalov, D. and Mitrović, J.",
year = "2008",
journal = "Pediatric Nephrology",
title = "Proinflamatory cytokines IL-1 beta, IL-6 and procalcitonin in children with acute pyelonephritis",
volume = "23",
number = "9",
pages = "1705-1705",
url = "https://hdl.handle.net/21.15107/rcub_vinar_3492"
}

Spasojević-Dimitrijeva, B., Kostic, M., Peco-Antic, A., Stanic, M., Živković, M., Afgan, N. H., Topalov, D.,& Mitrović, J.. (2008). Proinflamatory cytokines IL-1 beta, IL-6 and procalcitonin in children with acute pyelonephritis. in Pediatric Nephrology, 23(9), 1705-1705.
https://hdl.handle.net/21.15107/rcub_vinar_3492

Spasojević-Dimitrijeva B, Kostic M, Peco-Antic A, Stanic M, Živković M, Afgan NH, Topalov D, Mitrović J. Proinflamatory cytokines IL-1 beta, IL-6 and procalcitonin in children with acute pyelonephritis. in Pediatric Nephrology. 2008;23(9):1705-1705.
https://hdl.handle.net/21.15107/rcub_vinar_3492 .

Spasojević-Dimitrijeva, Brankica, Kostic, M., Peco-Antic, A., Stanic, M., Živković, Maja, Afgan, Naim H., Topalov, D., Mitrović, J., "Proinflamatory cytokines IL-1 beta, IL-6 and procalcitonin in children with acute pyelonephritis" in Pediatric Nephrology, 23, no. 9 (2008):1705-1705,
https://hdl.handle.net/21.15107/rcub_vinar_3492 .