{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T01:10:53Z","timestamp":1782522653468,"version":"3.54.5"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005809","name":"Hyderabad Eye Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Higher-order aberrations (HOA\u2019s) are exaggerated in eyes with keratoconus but little is known about their impact on the retinal image quality (IQ) of these eyes. This computational study determined changes in IQ [peak IQ, best focus and depth of focus (DOF)] of 12 subjects with manifest keratoconus in both eyes (KCE cohort), 9 subjects with very asymmetric ectasia (VAE cohort) with and without their Rigid Gas Permeable contact lenses (RGP CL\u2019s) and 20 age-matched controls, using a HOA-based through-focus analysis performed on the logNS IQ metric over 5\u2009mm pupil diameter following cycloplegia. All IQ parameters were significantly worse in the KCE cohort with their native HOA\u2019s, relative to controls and in the ectatic eye of the VAE cohort, relative to the fellow non-ectatic eye (p\u2009\u2264\u20090.008 for all). Reduction in HOA\u2019s of these eyes with RGP CL\u2019s resulted in a significant improvement in all IQ parameters but they all remained significantly poorer than controls (p\u2009\u2264\u20090.02 for all). The inter-subject variability of best focus and the DOF range were inversely related to peak IQ in these eyes (r\u2009=\u20090.85; p\u2009&lt;\u20090.001). These results provide the optical basis for two clinical observations on keratoconus: (1) optical performance of keratoconic eyes are significantly better with RGP CL\u2019s than with spectacles or unaided conditions and (2) the endpoint of subjective refraction is elusive in keratoconic eyes, relative to healthy controls or to the non-ectatic eye in bilaterally asymmetric ectasia.<\/jats:p>","DOI":"10.1038\/s41598-020-57993-w","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T11:03:18Z","timestamp":1580209398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A computational analysis of retinal image quality in eyes with keratoconus"],"prefix":"10.1038","volume":"10","author":[{"given":"Vinay Kumar","family":"Nilagiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Metlapally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton M.","family":"Schor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikant R.","family":"Bharadwaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,28]]},"reference":[{"key":"57993_CR1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/0039-6257(84)90094-8","volume":"28","author":"JH Krachmer","year":"1984","unstructured":"Krachmer, J. H., Feder, R. S. & Belin, M. W. Keratoconus and related noninflammatory corneal thinning disorders. Surv. Ophthalmol. 28, 293\u2013322 (1984).","journal-title":"Surv. Ophthalmol."},{"key":"57993_CR2","doi-asserted-by":"publisher","first-page":"539","DOI":"10.3928\/1081-597X-20060601-05","volume":"22","author":"JL Alio","year":"2006","unstructured":"Alio, J. L. & Shabayek, M. H. Corneal higher order aberrations: a method to grade keratoconus. J. refractive surgery. 22, 539\u2013545 (2006).","journal-title":"J. refractive surgery."},{"key":"57993_CR3","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1097\/OPX.0b013e318249d727","volume":"89","author":"A Gordon-Shaag","year":"2012","unstructured":"Gordon-Shaag, A., Millodot, M., Ifrah, R. & Shneor, E. Aberrations and topography in normal, keratoconus-suspect, and keratoconic eyes. Optom. Vis. Sci. 89, 411\u2013418, https:\/\/doi.org\/10.1097\/OPX.0b013e318249d727 (2012).","journal-title":"Optom. Vis. Sci."},{"key":"57993_CR4","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1097\/OPX.0b013e31802e64f0","volume":"84","author":"JD Marsack","year":"2007","unstructured":"Marsack, J. D., Parker, K. E., Pesudovs, K., Donnelly, W. J. III & Applegate, R. A. Uncorrected wavefront error and visual performance during RGP wear in keratoconus. Optom. Vis. Sci. 84, 463\u2013470, https:\/\/doi.org\/10.1097\/OPX.0b013e31802e64f0 (2007).","journal-title":"Optom. Vis. Sci."},{"key":"57993_CR5","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1097\/OPX.0b013e318288c2b1","volume":"90","author":"JD Marsack","year":"2013","unstructured":"Marsack, J. D., Rozema, J. J., Koppen, C., Tassignon, M. J. & Applegate, R. A. Template-based correction of high-order aberration in keratoconus. Optom. Vis. Sci. 90, 324\u2013334, https:\/\/doi.org\/10.1097\/OPX.0b013e318288c2b1 (2013).","journal-title":"Optom. Vis. Sci."},{"key":"57993_CR6","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1097\/ICL.0b013e3181e52dd1","volume":"36","author":"A Jinabhai","year":"2010","unstructured":"Jinabhai, A., Radhakrishnan, H. & O\u2019Donnell, C. Visual acuity and ocular aberrations with different rigid gas permeable lens fittings in keratoconus. Eye Contact Lens. 36, 233\u2013237, https:\/\/doi.org\/10.1097\/ICL.0b013e3181e52dd1 (2010).","journal-title":"Eye Contact Lens."},{"key":"57993_CR7","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.ajo.2007.08.004","volume":"144","author":"K Negishi","year":"2007","unstructured":"Negishi, K., Kumanomido, T., Utsumi, Y. & Tsubota, K. Effect of higher-order aberrations on visual function in keratoconic eyes with a rigid gas permeable contact lens. Am. J. Ophthalmol. 144, 924\u2013929, https:\/\/doi.org\/10.1016\/j.ajo.2007.08.004 (2007).","journal-title":"Am. J. Ophthalmol."},{"key":"57993_CR8","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1097\/OPX.0000000000001205","volume":"95","author":"VK Nilagiri","year":"2018","unstructured":"Nilagiri, V. K., Kalaiselvan, P., Metlapally, S., Schor, C. M. & Bharadwaj, S. R. LogMAR and stereo acuity in keratoconus corrected with spectacles and RGP contact lenses. Optom. Vis. Sci. 95, 391\u2013398 (2018).","journal-title":"Optom. Vis. Sci."},{"key":"57993_CR9","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1097\/OPX.0000000000000253","volume":"91","author":"B Yang","year":"2014","unstructured":"Yang, B. et al. Contrast sensitivity function after correcting residual wavefront aberrations during RGP lens wear. Optom. Vis. Sci. 91, 1271\u20131277, https:\/\/doi.org\/10.1097\/OPX.0000000000000253 (2014).","journal-title":"Optom. Vis. Sci."},{"key":"57993_CR10","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1111\/opo.12133","volume":"34","author":"A Jinabhai","year":"2014","unstructured":"Jinabhai, A., O\u2019Donnell, C., Tromans, C. & Radhakrishnan, H. Optical quality and visual performance with customised soft contact lenses for keratoconus. Ophthalmic Physiol. Opt. 34, 528\u2013539, https:\/\/doi.org\/10.1111\/opo.12133 (2014).","journal-title":"Ophthalmic Physiol. Opt."},{"key":"57993_CR11","doi-asserted-by":"publisher","first-page":"E1172","DOI":"10.1097\/OPX.0b013e31818e8eaa","volume":"85","author":"JD Marsack","year":"2008","unstructured":"Marsack, J. D., Parker, K. E. & Applegate, R. A. Performance of wavefront-guided soft lenses in three keratoconus subjects. Optom. Vis. Sci. 85, E1172\u20131178, https:\/\/doi.org\/10.1097\/OPX.0b013e31818e8eaa (2008).","journal-title":"Optom. Vis. Sci."},{"issue":"6","key":"57993_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1167\/9.5.6","volume":"9","author":"R Sabesan","year":"2009","unstructured":"Sabesan, R. & Yoon, G. Visual performance after correcting higher order aberrations in keratoconic eyes. J Vis. 9(6), 1\u201310, https:\/\/doi.org\/10.1167\/9.5.6 (2009).","journal-title":"J Vis."},{"key":"57993_CR13","doi-asserted-by":"publisher","first-page":"3835","DOI":"10.1167\/iovs.09-4558","volume":"51","author":"R Sabesan","year":"2010","unstructured":"Sabesan, R. & Yoon, G. Neural compensation for long-term asymmetric optical blur to improve visual performance in keratoconic eyes. Investig. Ophthalmol. Vis. science. 51, 3835\u20133839, https:\/\/doi.org\/10.1167\/iovs.09-4558 (2010).","journal-title":"Investig. Ophthalmol. Vis. science."},{"key":"57993_CR14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3928\/1081-597X-19970501-16","volume":"13","author":"RA Applegate","year":"1997","unstructured":"Applegate, R. A. & Howland, H. C. Refractive surgery, optical aberrations, and visual performance. J. refractive surgery. 13, 295\u2013299 (1997).","journal-title":"J. refractive surgery."},{"key":"57993_CR15","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1097\/01.opx.0000232842.60932.af","volume":"83","author":"RA Applegate","year":"2006","unstructured":"Applegate, R. A., Marsack, J. D. & Thibos, L. N. Metrics of retinal image quality predict visual performance in eyes with 20\/17 or better visual acuity. Optom. Vis. Sci. 83, 635\u2013640, https:\/\/doi.org\/10.1097\/01.opx.0000232842.60932.af (2006).","journal-title":"Optom. Vis. Sci."},{"key":"57993_CR16","doi-asserted-by":"publisher","first-page":"e0148085","DOI":"10.1371\/journal.pone.0148085","volume":"11","author":"S Sarkar","year":"2016","unstructured":"Sarkar, S., Vaddavalli, P. K. & Bharadwaj, S. R. Image Quality Analysis of Eyes Undergoing LASER Refractive Surgery. PLoS One. 11, e0148085, https:\/\/doi.org\/10.1371\/journal.pone.0148085 (2016).","journal-title":"PLoS One."},{"key":"57993_CR17","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1016\/j.visres.2011.05.006","volume":"51","author":"F Yi","year":"2011","unstructured":"Yi, F., Iskander, D. R. & Collins, M. Depth of focus and visual acuity with primary and secondary spherical aberration. Vis. Res. 51, 1648\u20131658, https:\/\/doi.org\/10.1016\/j.visres.2011.05.006 (2011).","journal-title":"Vis. Res."},{"issue":"3","key":"57993_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1167\/10.4.3","volume":"10","author":"F Yi","year":"2010","unstructured":"Yi, F., Iskander, D. R. & Collins, M. J. Estimation of the depth of focus from wavefront measurements. J. vision. 10(3), 1\u20139, https:\/\/doi.org\/10.1167\/10.4.3 (2010).","journal-title":"J. vision."},{"key":"57993_CR19","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1016\/j.visres.2011.10.003S0042-6989(11)00356-7","volume":"51","author":"Y Benard","year":"2011","unstructured":"Benard, Y., Lopez-Gil, N. & Legras, R. Optimizing the subjective depth-of-focus with combinations of fourth- and sixth-order spherical aberration. Vis. Res. 51, 2471\u20132477, https:\/\/doi.org\/10.1016\/j.visres.2011.10.003S0042-6989(11)00356-7 (2011).","journal-title":"Vis. Res."},{"key":"57993_CR20","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/OPX.0b013e3181d95217","volume":"87","author":"X Cheng","year":"2010","unstructured":"Cheng, X., Bradley, A., Ravikumar, S. & Thibos, L. N. Visual impact of Zernike and Seidel forms of monochromatic aberrations. Optometry Vis. science: Off. Publ. Am. Acad. Optometry. 87, 300\u2013312, https:\/\/doi.org\/10.1097\/OPX.0b013e3181d95217 (2010).","journal-title":"Optometry Vis. science: Off. Publ. Am. Acad. Optometry."},{"key":"57993_CR21","doi-asserted-by":"crossref","unstructured":"Cheng, X., Bradley, A. & Thibos, L. N. Predicting subjective judgment of best focus with objective image quality metrics. J Vis. 4, 310\u2013321, 10:1167\/4.4.74\/4\/7 (2004).","DOI":"10.1167\/4.4.7"},{"key":"57993_CR22","doi-asserted-by":"crossref","first-page":"S596","DOI":"10.3928\/1081-597X-20010901-19","volume":"17","author":"S Marcos","year":"2001","unstructured":"Marcos, S. Aberrations and visual performance following standard laser vision correction. J. refractive surgery. 17, S596\u2013S601 (2001).","journal-title":"J. refractive surgery."},{"key":"57993_CR23","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1016\/j.visres.2011.07.006S0042-6989(11)00243-4.[pii]","volume":"51","author":"J Martin","year":"2011","unstructured":"Martin, J., Vasudevan, B., Himebaugh, N., Bradley, A. & Thibos, L. Unbiased estimation of refractive state of aberrated eyes. Vis. Res. 51, 1932\u20131940, https:\/\/doi.org\/10.1016\/j.visres.2011.07.006S0042-6989(11)00243-4.[pii] (2011).","journal-title":"Vis. Res."},{"key":"57993_CR24","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1097\/00006324-200302000-00005","volume":"80","author":"RA Applegate","year":"2003","unstructured":"Applegate, R. A., Ballentine, C., Gross, H., Sarver, E. J. & Sarver, C. A. Visual acuity as a function of Zernike mode and level of root mean square error. Optometry Vis. science: Off. Publ. Am. Acad. Optometry. 80, 97\u2013105 (2003).","journal-title":"Optometry Vis. science: Off. Publ. Am. Acad. Optometry."},{"key":"57993_CR25","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1111\/j.1475-1313.2007.00488.x","volume":"27","author":"BJ Evans","year":"2007","unstructured":"Evans, B. J. Monovision: a review. Ophthalmic Physiol. Opt. 27, 417\u2013439, https:\/\/doi.org\/10.1111\/j.1475-1313.2007.00488.x (2007).","journal-title":"Ophthalmic Physiol. Opt."},{"key":"57993_CR26","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1016\/j.jcrs.2016.04.036","volume":"42","author":"S Ravikumar","year":"2016","unstructured":"Ravikumar, S., Bradley, A., Bharadwaj, S. & Thibos, L. N. Expanding binocular depth of focus by combining monovision with diffractive bifocal intraocular lenses. J. Cataract. Refract. Surg. 42, 1288\u20131296, https:\/\/doi.org\/10.1016\/j.jcrs.2016.04.036 (2016).","journal-title":"J. Cataract. Refract. Surg."},{"key":"57993_CR27","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1364\/BOE.4.000822","volume":"4","author":"EJ Fernandez","year":"2013","unstructured":"Fernandez, E. J., Schwarz, C., Prieto, P. M., Manzanera, S. & Artal, P. Impact on stereo-acuity of two presbyopia correction approaches: monovision and small aperture inlay. Biomed. Opt. Express. 4, 822\u2013830, https:\/\/doi.org\/10.1364\/BOE.4.000822 (2013).","journal-title":"Biomed. Opt. Express."},{"key":"57993_CR28","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1163\/187847511x579043","volume":"25","author":"J Qian","year":"2012","unstructured":"Qian, J., Adeseye, S. A., Stevenson, S. B., Patel, S. S. & Bedell, H. E. D(max) for stereoscopic depth perception with simulated monovision correction. Seeing Perceiving. 25, 399\u2013408, https:\/\/doi.org\/10.1163\/187847511x579043 (2012).","journal-title":"Seeing Perceiving."},{"key":"57993_CR29","doi-asserted-by":"publisher","first-page":"e0150118","DOI":"10.1371\/journal.pone.0150118","volume":"11","author":"PK Bandela","year":"2016","unstructured":"Bandela, P. K., Satgunam, P., Garg, P. & Bharadwaj, S. R. Corneal Transplantation in Disease Affecting Only One Eye: Does It Make a Difference to Habitual Binocular Viewing? PLoS One. 11, e0150118, https:\/\/doi.org\/10.1371\/journal.pone.0150118 (2016).","journal-title":"PLoS One."},{"key":"57993_CR30","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1111\/j.1475-1313.2011.00854.x","volume":"31","author":"A Benito","year":"2011","unstructured":"Benito, A., Redondo, M. & Artal, P. Temporal evolution of ocular aberrations following laser in situ keratomileusis. Ophthalmic Physiol. Opt. 31, 421\u2013428, https:\/\/doi.org\/10.1111\/j.1475-1313.2011.00854.x (2011).","journal-title":"Ophthalmic Physiol. Opt."},{"key":"57993_CR31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1097\/ICL.0000000000000270","volume":"43","author":"PS Mandathara","year":"2017","unstructured":"Mandathara, P. S., Stapleton, F. J. & Willcox, M. D. P. Outcome of Keratoconus Management: Review of the Past 20 Years\u2019 Contemporary Treatment Modalities. Eye Contact Lens. 43, 141\u2013154, https:\/\/doi.org\/10.1097\/ICL.0000000000000270 (2017).","journal-title":"Eye Contact Lens."},{"key":"57993_CR32","doi-asserted-by":"publisher","first-page":"434","DOI":"10.3928\/1081597X-20170426-02","volume":"33","author":"R Ambrosio Jr.","year":"2017","unstructured":"Ambrosio, R. Jr. et al. Integration of Scheimpflug-Based Corneal Tomography and Biomechanical Assessments for Enhancing Ectasia Detection. J. refractive surgery. 33, 434\u2013443, https:\/\/doi.org\/10.3928\/1081597X-20170426-02 (2017).","journal-title":"J. refractive surgery."},{"key":"57993_CR33","unstructured":"Jack, J., Kanski, B. B. In Kanski\u2019s Clinical Ophthalmology: A Systematic Approach Ch. Chapter 06-Cornea, 213\u2013216 (Elsevier, 2015)."},{"key":"57993_CR34","unstructured":"Buxton, J. N., Buxton, D. F., Dias, A. K. & Scorsetti, D. H. In The CLAO guide to basic science and clinical practice. 3 101\u2013122 (Kendall\/Hunt, 1995)."},{"key":"57993_CR35","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1167\/iovs.10-5841iovs.10-5841","volume":"52","author":"N Visser","year":"2011","unstructured":"Visser, N. et al. Evaluation of the comparability and repeatability of four wavefront aberrometers. Investig. Ophthalmol. Vis. science. 52, 1302\u20131311, https:\/\/doi.org\/10.1167\/iovs.10-5841iovs.10-5841 (2011).","journal-title":"Investig. Ophthalmol. Vis. science."},{"key":"57993_CR36","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1364\/JOSAA.20.000209","volume":"20","author":"CE Campbell","year":"2003","unstructured":"Campbell, C. E. Matrix method to find a new set of Zernike coefficients from an original set when the aperture radius is changed. J. Optical Soc. America. A, Optics, image science, vision. 20, 209\u2013217 (2003).","journal-title":"J. Optical Soc. America. A, Optics, image science, vision."},{"key":"57993_CR37","doi-asserted-by":"crossref","unstructured":"Cheng, H. et al. A population study on changes in wave aberrations with accommodation. J Vis. 4, 272-280, 10.1167\/4.4.3 (2004).","DOI":"10.1167\/4.4.3"},{"key":"57993_CR38","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.clae.2012.01.006","volume":"35","author":"G Tyagi","year":"2012","unstructured":"Tyagi, G., Collins, M. J., Read, S. A. & Davis, B. A. Corneal changes following short-term rigid contact lens wear. Cont. Lens Anterior Eye. 35, 129\u2013136, https:\/\/doi.org\/10.1016\/j.clae.2012.01.006 (2012).","journal-title":"Cont. Lens Anterior Eye."},{"key":"57993_CR39","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1167\/4.4.9","volume":"4","author":"LN Thibos","year":"2004","unstructured":"Thibos, L. N., Hong, X., Bradley, A. & Applegate, R. A. Accuracy and precision of objective refraction from wavefront aberrations. J. Vis. 4, 329\u2013351, https:\/\/doi.org\/10.1167\/4.4.9 (2004).","journal-title":"J. Vis."},{"key":"57993_CR40","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1136\/bjo.2007.121715","volume":"92","author":"DAH Laidlaw","year":"2008","unstructured":"Laidlaw, D. A. H., Tailor, V., Shah, N., Atamian, S. & Harcourt, C. Validation of a computerised logMAR visual acuity measurement system (COMPlog): comparison with ETDRS and the electronic ETDRS testing algorithm in adults and amblyopic children. Br. J. Ophthalmol. 92, 241\u2013244 (2008).","journal-title":"Br. J. Ophthalmol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57993-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57993-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57993-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T06:13:08Z","timestamp":1670307188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57993-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,28]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["57993"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-57993-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,28]]},"assertion":[{"value":"11 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1321"}}