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PRKAA2 variation and the clinical characteristics of patients newly diagnosed with type 2 diabetes mellitus in Yogyakarta, Indonesia


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Chan JCN, Cho NH, Tajima N, Shaw J. Diabetes in the Western Pacific Region—past, present and future. Diabetes Res Clin Pract. 2014; 103:244–55. ChanJCN ChoNH TajimaN ShawJ Diabetes in the Western Pacific Region—past, present and future Diabetes Res Clin Pract 2014 103 244 55 10.1016/j.diabres.2013.11.01224418400 Search in Google Scholar

Ramachandran A, Snehalatha C, Shetty AS, Nandhita A. Trends in prevalence of diabetes in Asian countries. World J Diabetes. 2012; 3:110–17. RamachandranA SnehalathaC ShettyAS NandhitaA Trends in prevalence of diabetes in Asian countries World J Diabetes 2012 3 110 17 10.4239/wjd.v3.i6.110338270722737281 Search in Google Scholar

Suhadi R, Linawati Y, Wulandari ET, Virginia DM, Setiawan CH. The metabolic disorders and cardiovascular risk among lower socioeconomic subjects in Yogyakarta-Indonesia. Asian J Pharm Clin Res. 2017; 10:367–72. SuhadiR LinawatiY WulandariET VirginiaDM SetiawanCH The metabolic disorders and cardiovascular risk among lower socioeconomic subjects in Yogyakarta-Indonesia Asian J Pharm Clin Res 2017 10 367 72 10.22159/ajpcr.2017.v10i3.16310 Search in Google Scholar

Sirdah MM, Reading NS. Genetic predisposition in type 2 diabetes: a promising approach toward a personalized management of diabetes. Clin Genet. 2020; 98:525–47. SirdahMM ReadingNS Genetic predisposition in type 2 diabetes: a promising approach toward a personalized management of diabetes Clin Genet 2020 98 525 47 10.1111/cge.1377232385895 Search in Google Scholar

Leong A, Porneala B, Dupuis J, Florez JC, Meigs JB. Type 2 diabetes genetic predisposition, obesity, and all-cause mortality risk in the U.S.: a multiethnic analysis. Diabetes Care. 2016; 39:539–46. LeongA PornealaB DupuisJ FlorezJC MeigsJB Type 2 diabetes genetic predisposition, obesity, and all-cause mortality risk in the U.S.: a multiethnic analysis Diabetes Care 2016 39 539 46 10.2337/dc15-2080480677526884474 Search in Google Scholar

Xue A, Wu Y, Zhu Z, Zhang F, Kemper KE, Zheng Z, et al. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun. 2018; 9:2941. doi: 10.10138/s41467-018-04951-w XueA WuY ZhuZ ZhangF KemperKE ZhengZ Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes Nat Commun 2018 9 2941 10.10138/s41467-018-04951-w Open DOISearch in Google Scholar

Sim X, Ong RT-H, Suo C, Tay W-T, Liu J, Ng DP-K, et al. Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genet. 2011; 7:e1001363. doi: 10.1371/journal.pgen.1001363 SimX OngRT-H SuoC TayW-T LiuJ NgDP-K Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia PLoS Genet 2011 7 e1001363 10.1371/journal.pgen.1001363 307236621490949 Open DOISearch in Google Scholar

Meigs JB, Cupples LA, Wilson PWF. Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes. 2000; 49:2201–7. MeigsJB CupplesLA WilsonPWF Parental transmission of type 2 diabetes: the Framingham Offspring Study Diabetes 2000 49 2201 7 10.2337/diabetes.49.12.220111118026 Search in Google Scholar

Avery AR, Duncan GE. Heritability of type 2 diabetes in the Washington State Twin Registry. Twin Res Hum Genet. 2019; 22:95–8. AveryAR DuncanGE Heritability of type 2 diabetes in the Washington State Twin Registry Twin Res Hum Genet 2019 22 95 8 10.1017/thg.2019.11655711531124778 Search in Google Scholar

Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009; 461(7265):747–53. ManolioTA CollinsFS CoxNJ GoldsteinDB HindorffLA HunterDJ Finding the missing heritability of complex diseases Nature 2009 461 7265 747 53 10.1038/nature08494283161319812666 Search in Google Scholar

Stančáková A, Laakso M. Genetics of type 2 diabetes. In: Stettler C, Christ E, Diem P, editors. Novelties in Diabetes. Basel: Karger; 2016, p. 203–20. (Mullis P-E, series editor. Endocr Dev., Vol. 31). StančákováA LaaksoM Genetics of type 2 diabetes In: StettlerC ChristE DiemP editors. Novelties in Diabetes Basel Karger 2016 203 20 (Mullis P-E, series editor. Endocr Dev., Vol. 31). 10.1159/00043941826824439 Search in Google Scholar

Franks PW, Shungin D. The interplay of lifestyle and genetic susceptibility in type 2 diabetes risk. Diabetes Manag. 2011; 1:299–307. FranksPW ShunginD The interplay of lifestyle and genetic susceptibility in type 2 diabetes risk Diabetes Manag 2011 1 299 307 10.2217/dmt.11.3 Search in Google Scholar

Wu L, Zhang L, Li B, Jiang H, Duan Y, Xie Z, et al. AMP-Activated protein kinase (AMPK) regulates energy metabolism through modulating thermogenesis in adipose tissue. Front Physiol. 2018; 9:122. doi: 10.3389/fphys.2018.00122 WuL ZhangL LiB JiangH DuanY XieZ AMP-Activated protein kinase (AMPK) regulates energy metabolism through modulating thermogenesis in adipose tissue Front Physiol 2018 9 122 10.3389/fphys.2018.00122 582632929515462 Open DOISearch in Google Scholar

Foretz M, Even PC, Viollet B. AMPK activation reduces hepatic lipid content by increasing fat oxidation in vivo. Int J Mol Sci. 2018; 19:2826. doi: 10.3390/ijms19092826 ForetzM EvenPC ViolletB AMPK activation reduces hepatic lipid content by increasing fat oxidation in vivo Int J Mol Sci 2018 19 2826 10.3390/ijms19092826 616495630235785 Open DOISearch in Google Scholar

Kjøbsted R, Hingst JR, Fentz J, Foretz M, Sans MN, Pehmøller C, et al. AMPK in skeletal muscle function and metabolism. FASEB J. 2018; 32:1741–77. KjøbstedR HingstJR FentzJ ForetzM SansMN PehmøllerC AMPK in skeletal muscle function and metabolism FASEB J 2018 32 1741 77 10.1096/fj.201700442R594556129242278 Search in Google Scholar

Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013; 123:2764–72. RudermanNB CarlingD PrentkiM CacicedoJM AMPK, insulin resistance, and the metabolic syndrome J Clin Invest 2013 123 2764 72 10.1172/JCI67227369653923863634 Search in Google Scholar

Tain Y-L, Hsu C-N. AMP-Activated protein kinase as a reprogramming strategy for hypertension and kidney disease of developmental origin. Int J Mol Sci. 2018; 19:1744. doi: 10.3390/ijms19061744 TainY-L HsuC-N AMP-Activated protein kinase as a reprogramming strategy for hypertension and kidney disease of developmental origin Int J Mol Sci 2018 19 1744 10.3390/ijms19061744 603213229895790 Open DOISearch in Google Scholar

Viollet B, Andreelli F, Jørgensen SB, Perrin C, Flamez D, Mu J, et al. Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. In: Hardie DG, Carling D, editors. AMPK 2002 – 2nd International Meeting on AMP-activated Protein Kinase. 2002 September 12–14, University of Dundee, Scotland, United Kingdom. Biochem Soc Trans. 2003; 31:216–9. ViolletB AndreelliF JørgensenSB PerrinC FlamezD MuJ Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. In: Hardie DG, Carling D, editors. AMPK 2002 – 2nd International Meeting on AMP-activated Protein Kinase. 2002 September 12–14, University of Dundee, Scotland, United Kingdom Biochem Soc Trans 2003 31 216 9 10.1042/bst031021612546688 Search in Google Scholar

Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes. 2014; 7:241–53. CoughlanKA ValentineRJ RudermanNB SahaAK AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes 2014 7 241 53 10.2147/DMSO.S43731407595925018645 Search in Google Scholar

Meng S, Cao J, He Q, Xiong L, Chang E, Rodovick S, et al. Metformin activates AMP-activated protein kinase by promoting formation of the αβγ heterotrimeric complex. J Biol Chem. 2015; 290:3793–802. MengS CaoJ HeQ XiongL ChangE RodovickS Metformin activates AMP-activated protein kinase by promoting formation of the αβγ heterotrimeric complex J Biol Chem 2015 290 3793 802 10.1074/jbc.M114.604421431904325538235 Search in Google Scholar

Horikoshi M, Hara K, Ohashi J, Miyake K, Tokunaga K, Ito C, et al. A Polymorphism in the AMPKα2 subunit gene is associated with insulin resistance and type 2 diabetes in the Japanese population. Diabetes. 2006; 55: 919–23. HorikoshiM HaraK OhashiJ MiyakeK TokunagaK ItoC A Polymorphism in the AMPKα2 subunit gene is associated with insulin resistance and type 2 diabetes in the Japanese population Diabetes 2006 55 919 23 10.2337/diabetes.55.04.06.db05-072716567511 Search in Google Scholar

Keshavarz P, Inoue H, Nakamura N, Yoshikawa T, Tanahashi T, Itakura M. Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK α2-subunit (PRKAA2) and risk of type 2 diabetes. Mol Genet Metab. 2008; 93:200–9. KeshavarzP InoueH NakamuraN YoshikawaT TanahashiT ItakuraM Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK α2-subunit (PRKAA2) and risk of type 2 diabetes Mol Genet Metab 2008 93 200 9 10.1016/j.ymgme.2007.08.12517950019 Search in Google Scholar

Wang M-r, Li R, Zhang S-h. Investigation of AMPKα2 subunit gene polymorphism of type 2 diabetes mellitus in Han populations in Chongqing. Med J Chin PLA. 2014; 39:731–5. doi: 10.11855/j.issn.0577-7402.2014.09.11 [in Chinese, English abstract] WangM-r LiR ZhangS-h Investigation of AMPKα2 subunit gene polymorphism of type 2 diabetes mellitus in Han populations in Chongqing Med J Chin PLA 2014 39 731 5 10.11855/j.issn.0577-7402.2014.09.11 [in Chinese, English abstract] Open DOISearch in Google Scholar

Shen J-Z, Ge W-H, Fang Y, Liu H. A novel polymorphism in protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) is associated with type 2 diabetes in the Han Chinese population. J Diabetes. 2017; 9:606–12. ShenJ-Z GeW-H FangY LiuH A novel polymorphism in protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) is associated with type 2 diabetes in the Han Chinese population J Diabetes 2017 9 606 12 10.1111/1753-0407.1244927427333 Search in Google Scholar

Li Q, Li C, Li H, Zeng L, Kang Z, Mao Y, et al. Effect of AMP-activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population. J Diabetes. 2018; 10:43–9. LiQ LiC LiH ZengL KangZ MaoY Effect of AMP-activated protein kinase subunit alpha 2 (PRKAA2) genetic polymorphisms on susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a Chinese population J Diabetes 2018 10 43 9 10.1111/1753-0407.1255328322508 Search in Google Scholar

Gu HF. Genetic and epigenetic studies in diabetic kidney disease. Front Genet. 2019; 10:507. doi: 10.3389/fgene.2019.00507 GuHF Genetic and epigenetic studies in diabetic kidney disease Front Genet 2019 10 507 10.3389/fgene.2019.00507 656610631231424 Open DOISearch in Google Scholar

Jablonski KA, McAteer JB, de Bakker PIW, Franks PW, Pollin TI, Hanson RL, et al. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes. 2010; 59:2672–81. JablonskiKA McAteerJB de BakkerPIW FranksPW PollinTI HansonRL Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program Diabetes 2010 59 2672 81 10.2337/db10-0543327952220682687 Search in Google Scholar

Abdullah N, Attia J, Oldmeadow C, Scott RJ, Holliday EG. The architecture of risk for type 2 diabetes: understanding Asia in the context of global findings. Int J Endocrinol. 2014; 2014: 593982. doi: 10.1155/2014/593982 AbdullahN AttiaJ OldmeadowC ScottRJ HollidayEG The architecture of risk for type 2 diabetes: understanding Asia in the context of global findings Int J Endocrinol 2014 2014 593982 10.1155/2014/593982 397684224744783 Open DOISearch in Google Scholar

Garlo KG, White WB, Bakris GL, Zannad F, Wilson CA, Kupfer S, et al. Kidney biomarkers and decline in eGFR in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2018; 13:398–405. GarloKG WhiteWB BakrisGL ZannadF WilsonCA KupferS Kidney biomarkers and decline in eGFR in patients with type 2 diabetes Clin J Am Soc Nephrol 2018 13 398 405 10.2215/CJN.05280517596766729339356 Search in Google Scholar

Anutrakulchai S, Pongskul C, Sirivongs D, Tonsawan P, Thepsuthammarat K, Chanaboon S, et al. Factors associated with mortality and high treatment expense of adult patients hospitalized with chronic kidney disease in Thailand. Asian Biomed (Res Rev News). 2016; 10:15–24. AnutrakulchaiS PongskulC SirivongsD TonsawanP ThepsuthammaratK ChanaboonS Factors associated with mortality and high treatment expense of adult patients hospitalized with chronic kidney disease in Thailand Asian Biomed (Res Rev News) 2016 10 15 24 Search in Google Scholar

Little J, Higgins JPT, Ioannidis JPA, Moher D, Gagnon F, von Elm E, et al. Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement. Hum Genet. 2009; 125:131–51. LittleJ HigginsJPT IoannidisJPA MoherD GagnonF von ElmE Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement Hum Genet 2009 125 131 51 10.1093/acprof:oso/9780195398441.003.0010 Search in Google Scholar

Li Q, Li C, Li H, Zeng L, Kang Z, Mao Y, et al. STK11 rs2075604 polymorphism is associated with metformin efficacy in Chinese type 2 diabetes mellitus. Int J Endocrinol. 2017; 2017:3402808. doi: 10.1155/2017/3402808 LiQ LiC LiH ZengL KangZ MaoY STK11 rs2075604 polymorphism is associated with metformin efficacy in Chinese type 2 diabetes mellitus Int J Endocrinol 2017 2017 3402808 10.1155/2017/3402808 552353928775741 Open DOISearch in Google Scholar

Applied Biosystems. TaqMan SNP Genotyping Assays [Internet]. Thermo Fisher Scientific; 2020 [cited 2021 July 09]. Available from: https://www.thermofisher.com/order/genome-database/?pearUXVerSuffix=pearUX2&elcanoForm=true#!/genotyping/assays/genotyping_all/?keyword=rs9803799 Applied Biosystems TaqMan SNP Genotyping Assays [Internet] Thermo Fisher Scientific 2020 [cited 2021 July 09]. Available from: https://www.thermofisher.com/order/genome-database/?pearUXVerSuffix=pearUX2&elcanoForm=true#!/genotyping/assays/genotyping_all/?keyword=rs9803799 Search in Google Scholar

Jeon S-M. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016; 48:e245. doi: 10.1038/emm.2016.81 JeonS-M Regulation and function of AMPK in physiology and diseases Exp Mol Med 2016 48 e245 10.1038/emm.2016.81 497331827416781 Open DOISearch in Google Scholar

Zhang Y, Chen J, Zeng Y, Huang D, Xu Q. Involvement of AMPK activation in the inhibition of hepatic gluconeogenesis by Ficus carica leaf extract in diabetic mice and HepG2 cells. Biomed Pharmacother. 2019; 109:188–94. ZhangY ChenJ ZengY HuangD XuQ Involvement of AMPK activation in the inhibition of hepatic gluconeogenesis by Ficus carica leaf extract in diabetic mice and HepG2 cells Biomed Pharmacother 2019 109 188 94 10.1016/j.biopha.2018.10.07730396076 Search in Google Scholar

Sun MW, Lee JY, De Bakker PIW, Burtt NP, Almgren P, Råstam L, et al. Haplotype structures and large-scale association testing of the 5′ AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 with type 2 diabetes. Diabetes. 2006; 55:849–55. SunMW LeeJY De BakkerPIW BurttNP AlmgrenP RåstamL Haplotype structures and large-scale association testing of the 5′ AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 with type 2 diabetes Diabetes 2006 55 849 55 10.2337/diabetes.55.03.06.db05-141816505254 Search in Google Scholar

Liu C-Y, Zhang W, Ji L-N, Wang J-G; ATTEND investigators. Comparison between newly diagnosed hypertension in diabetes and newly diagnosed diabetes in hypertension. Diabetol Metab Syndr. 2019; 11:69. doi: 10.1186/s13098-019-0465-3 LiuC-Y ZhangW JiL-N WangJ-G ATTEND investigators Comparison between newly diagnosed hypertension in diabetes and newly diagnosed diabetes in hypertension Diabetol Metab Syndr 2019 11 69 10.1186/s13098-019-0465-3 670824231462932 Open DOISearch in Google Scholar

Ha KH, Park CY, Jeong IK, Kim HJ, Kim SY, Kim WJ, et al. Clinical characteristics of people with newly diagnosed type 2 diabetes between 2015 and 2016: difference by age and body mass index. Diabetes Metab J. 2018; 42:137–46. HaKH ParkCY JeongIK KimHJ KimSY KimWJ Clinical characteristics of people with newly diagnosed type 2 diabetes between 2015 and 2016: difference by age and body mass index Diabetes Metab J 2018 42 137 46 10.4093/dmj.2018.42.2.137591151729676543 Search in Google Scholar

Wang S, Ma W, Yuan Z, Wang S-M, Yi X, Jia H, Xue F. Association between obesity indices and type 2 diabetes mellitus among middle-aged and elderly people in Jinan, China: a cross-sectional study. BMJ Open. 2016; 6:e012742. doi: 10.1136/bmjopen-2016-012742 WangS MaW YuanZ WangS-M YiX JiaH XueF Association between obesity indices and type 2 diabetes mellitus among middle-aged and elderly people in Jinan, China: a cross-sectional study BMJ Open 2016 6 e012742 10.1136/bmjopen-2016-012742 512904727810975 Open DOISearch in Google Scholar

Nature Education. Hardy-Weinberg equilibrium [Internet]. Scitable by Nature Education; 2014 [cited 2021 Feb 23]. Available from: https://www.nature.com/scitable/definition/hardy-weinberg-equilibrium-122/ Nature Education Hardy-Weinberg equilibrium [Internet] Scitable by Nature Education 2014 [cited 2021 Feb 23]. Available from: https://www.nature.com/scitable/definition/hardy-weinberg-equilibrium-122/ Search in Google Scholar

Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017; 12:2032–45. AlicicRZ RooneyMT TuttleKR Diabetic kidney disease: challenges, progress, and possibilities Clin J Am Soc Nephrol 2017 12 2032 45 10.2215/CJN.11491116571828428522654 Search in Google Scholar

de Boer IH, Bangalore S, Benetos A, Davis AM, Michos ED, Muntner P, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017; 40:1273–84. de BoerIH BangaloreS BenetosA DavisAM MichosED MuntnerP Diabetes and hypertension: a position statement by the American Diabetes Association Diabetes Care 2017 40 1273 84 10.2337/dci17-002628830958 Search in Google Scholar

Rajani R, Pastor-Soler NM, Hallows KR. Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease. Curr Opin Nephrol Hypertens. 2017; 26:375–83. RajaniR Pastor-SolerNM HallowsKR Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease Curr Opin Nephrol Hypertens 2017 26 375 83 10.1097/MNH.000000000000034928614117 Search in Google Scholar

Schneider H, Schubert KM, Blodow S, Kreutz C-P, Erdogmus S, Wiedenmann M, et al. AMPK dilates resistance arteries via activation of SERCA and BKCa channels in smooth muscle. Hypertension. 2015; 66:108–16. SchneiderH SchubertKM BlodowS KreutzC-P ErdogmusS WiedenmannM AMPK dilates resistance arteries via activation of SERCA and BKCa channels in smooth muscle Hypertension 2015 66 108 16 10.1161/HYPERTENSIONAHA.115.0551426034200 Search in Google Scholar

Cuschieri S. The genetic side of type 2 diabetes: a review. Diabetes Metab Syndr. 2019; 13:2503–6. CuschieriS The genetic side of type 2 diabetes: a review Diabetes Metab Syndr 2019 13 2503 6 10.1016/j.dsx.2019.07.01231405668 Search in Google Scholar

Mambiya M, Shang M, Wang Y, Li Q, Liu S, Yang L, et al. The play of genes and non-genetic factors on type 2 diabetes. Front Public Health. 2019; 7:349. doi: 10.3389/fpubh.2019.00349 MambiyaM ShangM WangY LiQ LiuS YangL The play of genes and non-genetic factors on type 2 diabetes Front Public Health 2019 7 349 10.3389/fpubh.2019.00349 687773631803711 Open DOISearch in Google Scholar

American Diabetes Association. 1. Strategies for improving care. Diabetes Care. 2016; 39(Suppl 1):S6–12. American Diabetes Association 1. Strategies for improving care Diabetes Care 2016 39 Suppl 1 S6 12 10.2337/dc16-S00426696683 Search in Google Scholar

Mahendradhata Y, Trisnantoro L, Listyadewi S, Soewondo P, Marthias T, et al. The Republic of Indonesia Health System Review. Asia Pacific Observatory on Health Systems and Policies. World Health Organization Regional Office for South-East Asia: New Delhi 110 002, India; 2017. (Hort K, Patcharanarumol W, series editors. Health Systems in Transition, Vol. 7(1)). MahendradhataY TrisnantoroL ListyadewiS SoewondoP MarthiasT The Republic of Indonesia Health System Review Asia Pacific Observatory on Health Systems and Policies. World Health Organization Regional Office for South-East Asia New Delhi 110 002, India 2017 (Hort K, Patcharanarumol W, series editors. Health Systems in Transition, Vol. 7(1)). Search in Google Scholar

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