Applications of the CRISPR-Cas system for infectious disease diagnostics

References

• WHO. Global health estimates 2016: disease burden by cause, age, sex, by country and by religion, 2000–2016. Geneva: World Health Organization; 2018.
   Google Scholar
• Chen H, Liu K, Li Z, et al. Point of care testing for infectious diseases. Clin Chim Acta. 2019 Jun;493:138–147.
   PubMed Web of Science ®Google Scholar
• Hwang H, Hwang B-Y, Bueno J. Biomarkers in infectious diseases. Dis Markers. 2018;2018:1–2.
   Web of Science ®Google Scholar
• Nii-Trebi NI. Emerging and neglected infectious diseases: insights, advances, and challenges. Biomed Res Int. 2017;2017:5245021.
   PubMed Web of Science ®Google Scholar
• Weber DJ, Rutala WA, Fischer WA, et al. Emerging infectious diseases: focus on infection control issues for novel coronaviruses (severe acute respiratory syndrome-CoV and middle east respiratory syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9). Am J Infect Control. 2016 May 2;44(5 Suppl):e91–e100.
   PubMed Web of Science ®Google Scholar
• Morens DM, Fauci AS. Emerging pandemic diseases: how we got to COVID-19. Cell. 2020 Sep 3;182(5):1077–1092.
   PubMed Web of Science ®Google Scholar
• Banuls AL, Sanou A, Van Anh NT, et al. Mycobacterium tuberculosis: ecology and evolution of a human bacterium. J Med Microbiol. 2015 Nov;64(11):1261–1269.
   PubMedGoogle Scholar
• Brejt JA, Golightly LM. Severe malaria: update on pathophysiology and treatment. Curr Opin Infect Dis. 2019 Oct;32(5):413–418.
   PubMed Web of Science ®Google Scholar
• Muller DA, Depelsenaire AC, Young PR. Clinical and laboratory diagnosis of dengue virus infection. J Infect Dis. 2017 Mar 1;215(suppl_2):S89–S95.
   PubMedGoogle Scholar
• Bhattacharyya RP, Thakku SG, Hung DT. Harnessing CRISPR effectors for infectious disease diagnostics. ACS Infect Dis. 2018 Sep 14;4(9):1278–1282.
   PubMed Web of Science ®Google Scholar
• Caliendo AM, Gilbert DN, Ginocchio CC, et al. Better tests, better care: improved diagnostics for infectious diseases. Clin Infect Dis. 2013 Dec;57(Suppl 3):S139–70.
   PubMed Web of Science ®Google Scholar
• Yang S, Rothman RE. PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings. Lancet Infect Dis. 2004;4(6):337–348.
   PubMed Web of Science ®Google Scholar
• Obande GA, Banga Singh KK. Current and future perspectives on isothermal nucleic acid amplification technologies for diagnosing infections. Infect Drug Resist. 2020;13:455–483.
   PubMed Web of Science ®Google Scholar
• Matthijs G, Souche E, Alders M, et al. Guidelines for diagnostic next-generation sequencing. Eur J Hum Genet. 2016 Jan;24(1):2–5.
   PubMed Web of Science ®Google Scholar
• Kosack CS, Page AL, Klatser PR. A guide to aid the selection of diagnostic tests. Bull World Health Organ. 2017 Sep 1;95(9):639–645.
   PubMed Web of Science ®Google Scholar
• Pickar-Oliver A, Gersbach CA. The next generation of CRISPR-Cas technologies and applications. Nat Rev Mol Cell Biol. 2019 Aug;20(8):490–507.
   PubMed Web of Science ®Google Scholar
• Ishino Y, Shinagawa H, Makino K, et al. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987 Dec;169(12):5429–5433.
   PubMed Web of Science ®Google Scholar
• Jansen R, Embden JD, Gaastra W, et al. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol. 2002 Mar;43(6):1565–1575.
   PubMed Web of Science ®Google Scholar
• Barrangou R. CRISPR-Cas systems and RNA-guided interference. Wiley Interdiscip Rev RNA. 2013 May-Jun;4(3):267–278.
   PubMed Web of Science ®Google Scholar
• Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010 Jan 8;327(5962):167–170.
   PubMed Web of Science ®Google Scholar
• Brouns SJ, Jore MM, Lundgren M, et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science. 2008 Aug 15;321(5891):960–964.
   PubMed Web of Science ®Google Scholar
• Jinek M, East A, Cheng A, et al. RNA-programmed genome editing in human cells. Elife. 2013 Jan;29(2):e00471.
   Google Scholar
• Cong L, Ran FA, Cox D, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013 Feb 15;339(6121):819–823.
   PubMed Web of Science ®Google Scholar
• Gupta D, Bhattacharjee O, Mandal D, et al. CRISPR-Cas9 system: a new-fangled dawn in gene editing. Life Sci. 2019 Sep 1;232:116636.
   PubMed Web of Science ®Google Scholar
• Kim HM, Colaiacovo MP. CRISPR-Cas9-guided genome engineering in caenorhabditis elegans. Curr Protoc Mol Biol. 2019 Dec;129(1):e106.
   PubMedGoogle Scholar
• Song R, Zhai Q, Sun L, et al. CRISPR/Cas9 genome editing technology in filamentous fungi: progress and perspective. Appl Microbiol Biotechnol. 2019 Sep;103(17):6919–6932.
   PubMed Web of Science ®Google Scholar
• Jiang W, Bikard D, Cox D, et al. RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol. 2013 Mar;31(3):233–239.
   PubMed Web of Science ®Google Scholar
• Javed MR, Sadaf M, Ahmed T, et al. CRISPR-Cas system: history and prospects as a genome editing tool in microorganisms. Curr Microbiol. 2018 Dec;75(12):1675–1683.
   PubMed Web of Science ®Google Scholar
• Oliva R, Ji C, Atienza-Grande G, et al. Broad-spectrum resistance to bacterial blight in rice using genome editing. Nat Biotechnol. 2019 Nov;37(11):1344–1350.
   PubMed Web of Science ®Google Scholar
• Wang M, Mao Y, Lu Y, et al. Multiplex gene editing in rice using the CRISPR-Cpf1 system. Mol Plant. 2017 Jul 5;10(7):1011–1013.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Qin W, Lu X, et al. Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system. Nat Commun. 2017 Jul 25;8(1):118.
   PubMedGoogle Scholar
• Fernandez JP, Vejnar CE, Giraldez AJ, et al. Optimized CRISPR-Cpf1 system for genome editing in zebrafish. Methods. 2018 Nov 1;150:11–18.
   PubMed Web of Science ®Google Scholar
• Hall B, Cho A, Limaye A, et al. Genome editing in mice using CRISPR/Cas9 technology. Curr Protoc Cell Biol. 2018 Dec;81(1):e57.
   PubMedGoogle Scholar
• Roper J, Tammela T, Akkad A, et al. Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation. Nat Protoc. 2018 Feb;13(2):217–234.
   PubMed Web of Science ®Google Scholar
• Chen S, Lee B, Lee AY, et al. Highly efficient mouse genome editing by CRISPR ribonucleoprotein electroporation of zygotes. J Biol Chem. 2016 Jul 8;291(28):14457–14467.
   PubMed Web of Science ®Google Scholar
• Bak RO, Dever DP, Porteus MH. CRISPR/Cas9 genome editing in human hematopoietic stem cells. Nat Protoc. 2018 Feb;13(2):358–376.
   PubMed Web of Science ®Google Scholar
• Richardson CD, Kazane KR, Feng SJ, et al. CRISPR-Cas9 genome editing in human cells occurs via the Fanconi anemia pathway. Nat Genet. 2018 Aug;50(8):1132–1139.
   PubMed Web of Science ®Google Scholar
• Salsman J, Dellaire G. Precision genome editing in the CRISPR era. Biochem Cell Biol. 2017 Apr;95(2):187–201.
   PubMedGoogle Scholar
• Pardee K, Green AA, Takahashi MK, et al. Rapid, Low-cost detection of zika virus using programmable biomolecular components. Cell. 2016 May 19;165(5):1255–1266.
   PubMed Web of Science ®Google Scholar
• Guk K, Keem JO, Hwang SG, et al. A facile, rapid and sensitive detection of MRSA using a CRISPR-mediated DNA FISH method, antibody-like dCas9/sgRNA complex. Biosens Bioelectron. 2017 Sep 15;95:67–71.
   PubMed Web of Science ®Google Scholar
• Gilbert LA, Larson MH, Morsut L, et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell. 2013 Jul 18;154(2):442–451.
   PubMed Web of Science ®Google Scholar
• Chen B, Gilbert LA, Cimini BA, et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell. 2013 Dec 19;155(7):1479–1491.
   PubMed Web of Science ®Google Scholar
• Ma H, Naseri A, Reyes-Gutierrez P, et al. Multicolor CRISPR labeling of chromosomal loci in human cells. Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):3002–3007.
   PubMed Web of Science ®Google Scholar
• Qin P, Parlak M, Kuscu C, et al. Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9. Nat Commun. 2017 Mar 14;8:14725.
   PubMed Web of Science ®Google Scholar
• Zetsche B, Gootenberg JS, Abudayyeh OO, et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell. 2015 Oct 22;163(3):759–771.
   PubMed Web of Science ®Google Scholar
• Shmakov S, Abudayyeh OO, Makarova KS, et al. Discovery and functional characterization of diverse class 2 CRISPR-Cas systems. Mol Cell. 2015 Nov 5;60(3):385–397.
   PubMed Web of Science ®Google Scholar
• Chen JS, Ma E, Harrington LB, et al. CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity. Science. 2018 Apr 27;360(6387):436–439.
   PubMed Web of Science ®Google Scholar
• Gootenberg JS, Abudayyeh OO, Lee JW, et al. Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017 Apr 28;356(6336):438–442.
   PubMed Web of Science ®Google Scholar
• Li SY, Cheng QX, Wang JM, et al. CRISPR-Cas12a-assisted nucleic acid detection. Cell Discov. 2018;4:20.
   PubMed Web of Science ®Google Scholar
• Zhang YM, Zhang Y, Xie K. Evaluation of CRISPR/Cas12a-based DNA detection for fast pathogen diagnosis and GMO test in rice. Mol Breed. 2020;40(1). DOI:10.1007/s11032-019-1092-2
   PubMed Web of Science ®Google Scholar
• Qin P, Park M, Alfson KJ, et al. Rapid and fully microfluidic ebola virus detection with CRISPR-Cas13a. ACS Sens. 2019 Apr 26;4(4):1048–1054.
   PubMed Web of Science ®Google Scholar
• Ackerman CM, Myhrvold C, Thakku SG, et al. Massively multiplexed nucleic acid detection with Cas13. Nature. 2020 Jun;582(7811):277–282.
   PubMed Web of Science ®Google Scholar
• Harrington LB, Burstein D, Chen JS, et al. Programmed DNA destruction by miniature CRISPR-Cas14 enzymes. Science. 2018 Nov 16;362(6416):839–842.
   PubMed Web of Science ®Google Scholar
• Cohen J. A cut above: pair that developed CRISPR earns historic award. Science. 2020 Oct 16;370(6514):271–272.
   PubMed Web of Science ®Google Scholar
• Garneau JE, Dupuis ME, Villion M, et al. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. 2010 Nov 4;468(7320):67–71.
   PubMed Web of Science ®Google Scholar
• Bhaya D, Davison M, Barrangou R. CRISPR-Cas systems in bacteria and archaea: versatile small RNAs for adaptive defense and regulation. Annu Rev Genet. 2011;45:273–297.
   PubMed Web of Science ®Google Scholar
• Hochstrasser ML, Doudna JA. Cutting it close: CRISPR-associated endoribonuclease structure and function. Trends Biochem Sci. 2015 Jan;40(1):58–66.
   PubMed Web of Science ®Google Scholar
• Charpentier E, Richter H, Van Der Oost J, et al. Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR-Cas adaptive immunity. FEMS Microbiol Rev. 2015 May;39(3):428–441.
   PubMed Web of Science ®Google Scholar
• Sternberg SH, Redding S, Jinek M, et al. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature. 2014 Mar 6;507(7490):62–67.
   PubMed Web of Science ®Google Scholar
• Sternberg SH, Richter H, Charpentier E, et al. Adaptation in CRISPR-Cas Systems. Mol Cell. 2016 Mar 17;61(6):797–808.
   PubMed Web of Science ®Google Scholar
• Koonin EV, Makarova KS, Zhang F. Diversity, classification and evolution of CRISPR-Cas systems. Curr Opin Microbiol. 2017 Jun;37:67–78.
   PubMed Web of Science ®Google Scholar
• Koonin EV, Makarova KS. Origins and evolution of CRISPR-Cas systems. Philos Trans R Soc Lond B Biol Sci. 2019 May 13;374(1772):20180087.
   PubMed Web of Science ®Google Scholar
• Makarova KS, Wolf YI, Iranzo J, et al. Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants. Nat Rev Microbiol. 2020 Feb;18(2):67–83.
   PubMed Web of Science ®Google Scholar
• Makarova KS, Zhang F, Koonin EV. SnapShot: class 1 CRISPR-Cas Systems. Cell. 2017 Feb 23;168(5):946–946 e1.
   PubMed Web of Science ®Google Scholar
• Liu TY, Doudna JA. Chemistry of Class 1 CRISPR-Cas effectors: binding, editing, and regulation. J Biol Chem. 2020 Oct 16;295(42):14473–14487.
   PubMed Web of Science ®Google Scholar
• Gong B, Shin M, Sun J, et al. Molecular insights into DNA interference by CRISPR-associated nuclease-helicase Cas3. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16359–16364.
   PubMed Web of Science ®Google Scholar
• Van Der Oost J, Westra ER, Jackson RN, et al. Unravelling the structural and mechanistic basis of CRISPR-Cas systems. Nat Rev Microbiol. 2014 Jul;12(7):479–492.
   PubMed Web of Science ®Google Scholar
• Xiao Y, Luo M, Hayes RP, et al. Structure basis for directional R-loop formation and substrate handover mechanisms in type I CRISPR-Cas system. Cell. 2017 Jun 29;170(1):48–60 e11.
   PubMed Web of Science ®Google Scholar
• Samai P, Pyenson N, Jiang W, et al. Co-transcriptional DNA and RNA cleavage during type III CRISPR-Cas immunity. Cell. 2015 May 21;161(5):1164–1174.
   PubMed Web of Science ®Google Scholar
• Liu T, Pan S, Li Y, et al. Type III CRISPR-Cas system: introduction and its application for genetic manipulations. Curr Issues Mol Biol. 2018;26:1–14.
   PubMed Web of Science ®Google Scholar
• Ozcan A, Pausch P, Linden A, et al. Type IV CRISPR RNA processing and effector complex formation in Aromatoleum aromaticum. Nat Microbiol. 2019 Jan;4(1):89–96.
   PubMed Web of Science ®Google Scholar
• Chylinski K, Makarova KS, Charpentier E, et al. Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res. 2014 Jun;42(10):6091–6105.
   PubMed Web of Science ®Google Scholar
• Jinek M, Chylinski K, Fonfara I, et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012 Aug 17;337(6096):816–821.
   PubMed Web of Science ®Google Scholar
• Yan WX, Hunnewell P, Alfonse LE, et al. Functionally diverse type V CRISPR-Cas systems. Science. 2019 Jan 4;363(6422):88–91.
   PubMed Web of Science ®Google Scholar
• Anantharaman V, Makarova KS, Burroughs AM, et al. Comprehensive analysis of the HEPN superfamily: identification of novel roles in intra-genomic conflicts, defense, pathogenesis and RNA processing. Biol Direct. 2013 Jun;15(8):15.
   Google Scholar
• Abudayyeh OO, Gootenberg JS, Essletzbichler P, et al. RNA targeting with CRISPR-Cas13. Nature. 2017 Oct 12;550(7675):280–284.
   PubMed Web of Science ®Google Scholar
• Cox DBT, Gootenberg JS, Abudayyeh OO, et al. RNA editing with CRISPR-Cas13. Science. 2017 Nov 24;358(6366):1019–1027.
   PubMed Web of Science ®Google Scholar
• O’Connell MR. Molecular mechanisms of RNA targeting by Cas13-containing type VI CRISPR-Cas systems. J Mol Biol. 2019 Jan 4;431(1):66–87.
   PubMed Web of Science ®Google Scholar
• Wang Q, Zhang B, Xu X, et al. CRISPR-typing PCR (ctPCR), a new Cas9-based DNA detection method. Sci Rep. 2018 Sep 20;8(1):14126.
   PubMed Web of Science ®Google Scholar
• Huang M, Zhou X, Wang H, et al. Clustered regularly interspaced short palindromic repeats/Cas9 triggered isothermal amplification for site-specific nucleic acid detection. Anal Chem. 2018 Feb 6;90(3):2193–2200.
   PubMed Web of Science ®Google Scholar
• Zhou W, Hu L, Ying L, et al. A CRISPR-Cas9-triggered strand displacement amplification method for ultrasensitive DNA detection. Nat Commun. 2018 Nov 27;9(1):5012.
   PubMedGoogle Scholar
• Quan J, Langelier C, Kuchta A, et al. FLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences. Nucleic Acids Res. 2019 Aug 22;47(14):e83.
   PubMed Web of Science ®Google Scholar
• Wang X, Xiong E, Tian T, et al. Clustered regularly interspaced short palindromic repeats/Cas9-mediated lateral flow nucleic acid assay. ACS Nano. 2020 Feb 25;14(2):2497–2508.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Qian L, Wei W, et al. Paired design of dCas9 as a systematic platform for the detection of featured nucleic acid sequences in pathogenic strains. ACS Synth Biol. 2017 Feb 17;6(2):211–216.
   PubMed Web of Science ®Google Scholar
• Qiu XY, Zhu LY, Zhu CS, et al. Highly effective and low-cost microRNA detection with CRISPR-Cas9. ACS Synth Biol. 2018 Mar 16;7(3):807–813.
   PubMed Web of Science ®Google Scholar
• Hajian R, Balderston S, Tran T, et al. Detection of unamplified target genes via CRISPR-Cas9 immobilized on a graphene field-effect transistor. Nat Biomed Eng. 2019 Jun;3(6):427–437.
   PubMed Web of Science ®Google Scholar
• Li L, Li S, Wu N, et al. HOLMESv2: a CRISPR-Cas12b-assisted platform for nucleic acid detection and DNA methylation quantitation. ACS Synth Biol. 2019 Oct 18;8(10):2228–2237.
   PubMed Web of Science ®Google Scholar
• Teng F, Guo L, Cui T, et al. CDetection: CRISPR-Cas12b-based DNA detection with sub-attomolar sensitivity and single-base specificity. Genome Biol. 2019 Jul 1;20(1):132.
   PubMed Web of Science ®Google Scholar
• Dai Y, Somoza RA, Wang L, et al. Exploring the trans-cleavage activity of CRISPR-Cas12a (cpf1) for the development of a universal electrochemical biosensor. Angew Chem Int Ed Engl. 2019 Nov 25;58(48):17399–17405.
   PubMed Web of Science ®Google Scholar
• Khan MZ, Haider S, Mansoor S, et al. Targeting plant ssDNA viruses with engineered miniature CRISPR-Cas14a. Trends Biotechnol. 2019 Aug;37(8):800–804.
   PubMed Web of Science ®Google Scholar
• Gootenberg JS, Abudayyeh OO, Kellner MJ, et al. Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science. 2018 Apr 27;360(6387):439–444.
   PubMed Web of Science ®Google Scholar
• Myhrvold C, Freije CA, Gootenberg JS, et al. Field-deployable viral diagnostics using CRISPR-Cas13. Science. 2018 Apr 27;360(6387):444–448.
   PubMed Web of Science ®Google Scholar
• Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1–23.
   PubMedGoogle Scholar
• Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016 Jun;24(6):490–502
   PubMed Web of Science ®Google Scholar
• Malik YS, Kumar N, Sircar S, et al. Coronavirus disease pandemic (COVID-19): challenges and a global perspective. Pathogens. 2020 Jun 28;9:7.
   Web of Science ®Google Scholar
• Latinne A, Hu B, Olival KJ, et al. Origin and cross-species transmission of bat coronaviruses in China. Nat Commun. 2020 Aug 25;11(1):4235.
   PubMed Web of Science ®Google Scholar
• Arumugam A, Faron ML, Yu P, et al. A rapid SARS-CoV-2 RT-PCR assay for low resource settings. Diagnostics (Basel). 2020;10(10). doi:10.3390/diagnostics10100739.
   PubMedGoogle Scholar
• Pillay S, Giandhari J, Tegally H, et al. Whole genome sequencing of SARS-CoV-2: adapting illumina protocols for quick and accurate outbreak investigation during a pandemic. Genes (Basel). 2020 17;11(8):949.
   Web of Science ®Google Scholar
• Zhang F, Abudayyeh OO, Gootenberg JS. A protocol for detection of COVID-19 using CRISPR diagnostics. 2020.
   Google Scholar
• Ding X, Yin K, Li Z, et al. All-in-one dual CRISPR-Cas12a (AIOD-CRISPR) assay: a case for rapid, ultrasensitive and visual detection of novel coronavirus SARS-CoV-2 and HIV virus. bioRxiv. 2020.
   Google Scholar
• Broughton JP, Deng X, Yu G, et al. CRISPR–Cas12-based detection of SARS-CoV-2. Nat Biotechnol. 2020;38(7):870–874.
   PubMed Web of Science ®Google Scholar
• Krammer F, Hou T, Zeng W, et al. Development and evaluation of a rapid CRISPR-based diagnostic for COVID-19. PLoS Pathog. 2020;16(8).
   Web of Science ®Google Scholar
• Ali Z, Aman R, Mahas A, et al. iSCAN: an RT-LAMP-coupled CRISPR-Cas12 module for rapid, sensitive detection of SARS-CoV-2. Virus Res. 2020 Oct 15;288:198129.
   PubMed Web of Science ®Google Scholar
• Lotfi M, Rezaei N. CRISPR/Cas13: a potential therapeutic option of COVID-19. Biomed Pharmacother. 2020 Nov;131:110738.
   PubMed Web of Science ®Google Scholar
• Liang M, Li Z, Wang W, et al. A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules. Nat Commun. 2019 Aug 14;10(1):3672.
   PubMedGoogle Scholar