{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:33:05Z","timestamp":1777671185096,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.134906.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000}},{"DOI":"10.12688\/f1000research.134906.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000}}],"reference-count":41,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Polycystic kidney disease (PKD) has a complex phenotype partly explained by genetic variants related to this disease. Ultrasonography is a promising approach for defining clinical signs. This study aimed to assess kidney characteristics in cats with Polycystin-1 (PKD1) gene mutations and wild-type cats. Kidney characteristics were identified by ultrasonography. Methods A total of 108 cats of variable breeds aged an average of 37.01\u00b13.50 months were included. Blood examination and biochemical tests were evaluated. For cystic formation, renal ultrasound was performed. The PKD1 gene mutation was identified\n                    <ns3:italic>via<\/ns3:italic>\n                    polymerase chain reaction (PCR) and DNA sequencing. Matrix correlation and effectiveness of ultrasound for PKD1 mutation detection were determined. Results The results showed that 19.44% of cats had PKD1 mutations, a high prevalence in Persian and Persian-related breed cats. Our results demonstrated the characteristics of kidneys in wild-type cats and cats with gene mutations. Based on ultrasonography results, there was an association between cats with gene mutations and cyst formation. The findings indicated that ultrasound did not detect cysts in cats aged 4-36 months, supporting the evidence that PKD1 gene mutations may not be present. This study found high sensitivity and renal specificity ultrasound for PKD1 heterozygous mutation. Moreover, cystic formation\n                    <ns3:italic>via<\/ns3:italic>\n                    renal ultrasound showed an increased risk for PKD1 mutation 2,623 times compared to normal kidneys. Conclusions Ultrasonographic examination, coupled with genetic investigations, may help to clarify the phenotypic variability of PKD1. The phenotypic profile of PKD1 will guide therapeutic outcomes and reduce the prevalence of PKD morbidity and mortality in cats.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.134906.3","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T11:10:15Z","timestamp":1708686615000},"page":"760","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["PKD1 gene mutation and ultrasonographic characterization in cats with renal cysts"],"prefix":"10.12688","volume":"12","author":[{"given":"Kotchapol","family":"Jaturanratsamee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Palin","family":"Jiwaganont","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pratch","family":"Sukumolanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7552-937X","authenticated-orcid":false,"given":"Soontaree","family":"Petchdee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2548-2555","DOI":"10.1097\/01.ASN.0000141776.38527.BB","article-title":"Feline polycystic kidney disease mutation identified in PKD1.","volume":"15","author":"L Lyons","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"117-126","DOI":"10.1177\/030098589703400204","article-title":"Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats.","volume":"34","author":"K Eaton","year":"1997","journal-title":"Vet. Pathol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/vetsci8110269","article-title":"Feline polycystic kidney disease: an update.","volume":"8","author":"L Schirrer","year":"2021","journal-title":"Vet. Sci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"181-184","DOI":"10.1111\/j.1751-0813.2001.tb14573.x","article-title":"Feline polycystic kidney disease in Persian and other cats: a prospective study using ultrasonography.","volume":"79","author":"C Beck","year":"2001","journal-title":"Aust. Vet. J."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"257-259","DOI":"10.1111\/j.1751-0813.2001.tb11977.x","article-title":"Prevalence of autosomal dominant polycystic kidney disease in Persian cats and related-breeds in Sydney and Brisbane.","volume":"79","author":"V Barrs","year":"2001","journal-title":"Aust. Vet. J."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"345-347","DOI":"10.1016\/S1098-612X(03)00052-4","article-title":"Prevalence of polycystic kidney disease in Persian and Persian related cats in France.","volume":"5","author":"P Barthez","year":"2003","journal-title":"J. Feline Med. Surg."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"503-504","DOI":"10.1111\/j.1365-2052.2004.01213.x","article-title":"Genetic testing for feline polycystic kidney disease.","volume":"35","author":"R Grahn","year":"2004","journal-title":"Anim. Genet."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"585-589","DOI":"10.1111\/jsap.12327","article-title":"Polycystic kidney disease in four British shorthair cats with successful treatment of bacterial cyst infection.","volume":"56","author":"R Nivy","year":"2015","journal-title":"J. Small Anim. Pract."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"13-23","DOI":"10.1681\/ASN.2017050483","article-title":"Genetic complexity of autosomal dominant polycystic kidney and liver diseases.","volume":"29","author":"E Cornec-Le Gall","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2407-2418","DOI":"10.1056\/NEJMoa1205511","article-title":"Tolvaptan in patients with autosomal dominant polycystic kidney disease.","volume":"367","author":"V Torres","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1140-1147","DOI":"10.1681\/ASN.2013101037","article-title":"Vasopressin-2 receptor signaling and autosomal dominant polycystic kidney disease: from bench to bedside and back again.","volume":"25","author":"M Rinschen","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1930-1942","DOI":"10.1056\/NEJMoa1710030","article-title":"Tolvaptan in later-stage autosomal dominant polycystic kidney disease.","volume":"377","author":"V Torres","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"488-493","DOI":"10.1038\/nm.3092","article-title":"Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy.","volume":"19","author":"I Rowe","year":"2013","journal-title":"Nat. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e505-e512","DOI":"10.1177\/1098612X221136815","article-title":"Renoprotective effects of docosahexaenoic acid in cats with early chronic kidney disease due to polycystic kidney disease: a pilot study.","volume":"24","author":"S Kobayashi","year":"2022","journal-title":"J. Feline Med. Surg."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"115-119","DOI":"10.1016\/j.jfms.2007.07.004","article-title":"Polycystic kidney disease: a review and occurrence in Slovenia with comparison between ultrasound and genetic testing.","volume":"10","author":"A Domanjko-Petri\u010d","year":"2008","journal-title":"J. Feline Med. Surg."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"993-996","DOI":"10.1016\/j.jfms.2009.07.002","article-title":"Evaluation of the repeatability of ultrasound scanning for detection of feline polycystic kidney disease.","volume":"11","author":"S Wills","year":"2009","journal-title":"J. Feline Med. Surg."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"669-692","DOI":"10.1016\/j.cvsm.2012.04.008","article-title":"Chronic kidney disease in dogs and cats.","volume":"42","author":"J Bartges","year":"2012","journal-title":"Vet. Clin. Small Anim. Pract."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"614-618","DOI":"10.1136\/vr.c4605","article-title":"Diagnosis of feline polycystic kidney disease by combining ultrasonographic examination and PKD1 gene analysis.","volume":"167","author":"Y Lee","year":"2010","journal-title":"Vet. Rec."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1-5","DOI":"10.1093\/oxfordjournals.jhered.a022945","article-title":"Inheritance of polycystic kidney disease in Persian cats.","volume":"87","author":"D Biller","year":"1996","journal-title":"J. Hered."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"430-434","DOI":"10.1016\/j.jfms.2008.10.003","article-title":"Comparison between ultrasound and genetic testing for the early diagnosis of polycystic kidney disease in Persian and Exotic Shorthair cats.","volume":"11","author":"M Bonazzi","year":"2009","journal-title":"J. Feline Med. Surg."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1079-1085","DOI":"10.1177\/1098612X13492164","article-title":"Maine Coon renal screening: ultrasonographical characterization and preliminary genetic analysis for common genes in cats with renal cysts.","volume":"15","author":"K Gendron","year":"2013","journal-title":"J. Feline Med. Surg."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"10058","DOI":"10.1038\/s41598-022-04908-6","article-title":"Age-and sex-specific reference intervals for blood urea nitrogen in Chinese general population.","volume":"11","author":"Q Liu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref22","first-page":"151","article-title":"Prevalence of polycystic kidney disease in Persian and Persian related-cats referred to Small Animal Hospital, University of Tehran, Iran.","volume":"20","author":"Z Noori","year":"2019","journal-title":"Iranian J. Vet. Res."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1220-1230","DOI":"10.1046\/j.1523-1755.2002.00250.x","article-title":"Caspases, Bcl-2 proteins and apoptosis in autosomal-dominant polycystic kidney disease.","volume":"61","author":"T Ecder","year":"2002","journal-title":"Kidney Int."},{"key":"ref24","doi-asserted-by":"crossref","first-page":"538-547","DOI":"10.1038\/ki.2014.84","article-title":"Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice.","volume":"86","author":"F Zeng","year":"2014","journal-title":"Kidney Int."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"109518","DOI":"10.1016\/j.cellsig.2019.109518","article-title":"Apoptosis and autophagy in polycystic kidney disease (PKD).","volume":"68","author":"K Nowak","year":"2020","journal-title":"Cell. Signal."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1171-1188","DOI":"10.1042\/BST20200757","article-title":"The cellular pathways and potential therapeutics of Polycystic Kidney Disease.","volume":"49","author":"T Richards","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"549-555","DOI":"10.1177\/1040638720935433","article-title":"Prevalence of PKD1 gene mutation in cats in Turkey and pathogenesis of feline polycystic kidney disease.","volume":"32","author":"N Bilgen","year":"2020","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref28","first-page":"81-100","article-title":"Polycystic kidney disease and renal fibrosis. Renal fibrosis: mechanisms and therapies.","author":"C Xue","year":"2019"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.3389\/fmolb.2022.971219","article-title":"Caspase-1 and the inflammasome promote polycystic kidney disease progression.","volume":"9","author":"K Swenson-Fields","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref30","first-page":"6954-6959","article-title":"Caspase inhibition reduces tubular apoptosis and proliferation, slowing disease progression in polycystic kidney disease.","volume":"102","author":"Y Tao","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"99-106","DOI":"10.1097\/MNH.0b013e3283262ab0","article-title":"Advances in the pathogenesis and treatment of polycystic kidney disease.","volume":"18","author":"V Patel","year":"2009","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"303-313","DOI":"10.1007\/s40265-019-1056-1","article-title":"Tolvaptan: a review in autosomal dominant polycystic kidney disease.","volume":"79","author":"H Blair","year":"2019","journal-title":"Drugs."},{"key":"ref33","first-page":"649-656","article-title":"Safety profile of Tolvaptan in the treatment of autosomal dominant polycystic kidney disease.","author":"I Bellos","year":"2021","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"711-724","DOI":"10.1111\/bph.14558","article-title":"The combination of metformin and 2-deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease.","volume":"176","author":"X Lian","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1323-1326","DOI":"10.1038\/nm935","article-title":"Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist.","volume":"9","author":"V Gattone","year":"2003","journal-title":"Nat. Med."},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.22957526.v1","author":"S Petchdee","year":"2023","journal-title":"figshare."},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.22957715.v1","author":"S Petchdee","year":"2023","journal-title":"figshare."},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.25230506.v1","author":"S Petchdee","year":"2024","journal-title":"figshare."},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.22958243.v1","author":"S Petchdee","year":"2023","journal-title":"figshare."},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.23123414.v1","author":"S Petchdee","year":"2023","journal-title":"figshare."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/12-760\/v3\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/12-760\/v3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/12-760\/v3\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T08:05:11Z","timestamp":1726646711000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/12-760\/v3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":41,"URL":"https:\/\/doi.org\/10.12688\/f1000research.134906.3","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.134906.2","asserted-by":"subject"},{"id-type":"doi","id":"10.12688\/f1000research.134906.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.162718.r306588","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.162718.r306588","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/12-760\/v3#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.157775.r218780, Leslie A. Lyons, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, 03 Nov 2023, version 2, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/12-760\/v2#referee-response-218780","order":0,"name":"referee-response-218780","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.157775.r222872, 224096, University of Kansas Medical Center, Kansas, 05 Feb 2024, version 2, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/12-760\/v2#referee-response-222872","order":1,"name":"referee-response-222872","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Soontaree Petchdee<\/b>; \n<i>Posted: 15 Feb 2024<\/i>; We have provided a point-by-point reply to each point raised by the reviewers as a separate file and indicated any changes or corrections within the text in blue on the resubmitted manuscript. Please see below for the list of changes. \n<b>Comments to the Author;<\/b> \n<b>Reviewer&nbsp;<\/b>\n<b>2: <\/b> \n<b>This portion of the manuscript is not clear to me: Of the total 108 cats examined by ultrasound, no cyst was found in 87 cats of the wild-type group. However, 19 cats were confirmed to have renal cysts, and in every cat with cysts found, a PKD1 mutation was present.<\/b>\n<b> An older domestic shorthair with cysts but no evidence of the relevant PKD1 mutation was reported elsewhere in the manuscript and should be addressed again at this point.<\/b>\n<b> Is it possible that the 51-month specimen represents a novel PKD1 mutation? Were the cysts in this animal unilateral or bilateral?<\/b> \n<b>Answer to <\/b>\n<b>the reviewer:<\/b>\n<b> <\/b>We apologize for the unclear on this point. We have edited this point in the revised manuscript in the discussion section. The 51-month-old cat may represent a PKD1 mutation, and it usually correlates with a bilateral cyst. The cysts detected are sufficient for a positive diagnosis in young cats up to 12 months of age. In addition, these criteria will help to determine a positive result for \n<i>PKD1<\/i> mutations if multiple bilateral cysts are detected (&gt;10 per kidney) or if cysts are not detected in older cats. The results from this study are similar to a previous study that reported a positive correlation between the detection of renal cysts and age, as cyst detection was increased in older animals. \n<b>Have additional PKD1 mutations been identified within cats, or is the c.10063 CA transversion the only mutation identified to date? If so then this is interesting given the very large number of unique PKD1 mutations in the ADPKD patient population, but raises a more fundamental question. The authors conclude that \u201cultrasonographic examination of cats will be a helpful tool for the routine identification of carriers of the mutated gene for polycystic kidney disease in cats.\u201d The manuscript reports <\/b>\n<b>a sensitivity of only 75% at 16 week<\/b>\n<b>s of age - isn\u2019t this close to sexual maturity? If there is a single founder mutation for PKD in cats then wouldn\u2019t a PCR-based assay (which could be performed well before sexual maturity) be much more useful for diagnosis than ultrasonography? The authors should discuss this and also note the age of sexual maturity in cats.<\/b> \n<b>Answer to <\/b>\n<b>the reviewer:<\/b> We apologize for the unclear on this point. We have edited this point in the revised manuscript in the discussion and conclusion section. Similar to our study, in the previous study, ultrasound provided more sensitivity when diagnosing cats of maturity age, which had a sensitivity of 91% when performed at 36 weeks of age. In our study, we suggested that ultrasonographic examination of cats will be a helpful tool for the routine identification of carriers of the mutated gene for polycystic kidney disease in mature cats. A previous study reported sexual maturation in the domestic cat\n<i> <\/i>based on histological examination of seminiferous tubules, cats were classified as juvenile (&lt;9 months; only spermatogonia and Sertoli cells present), pubertal (\u22659 months to &lt;1 year; complete spermatogenesis), and adult (&gt;2 years; spermiogenesis complete and cauda epididymis filled with spermatozoa). (Ref.) Sch&ouml;n, J., Neumann, S., Wildt, D. E., Pukazhenthi, B. S., &amp; Jewgenow, K. (2009). Localization of oestrogen receptors in the epididymis during sexual maturation of the domestic cat.&nbsp;\n<i>Reproduction in domestic animals = Zuchthygiene<\/i>,&nbsp;\n<i>44 Suppl 2<\/i>, 294\u2013301. https:\/\/doi.org\/10.1111\/j.1439-0531.2009.01391.x \n<b>The cats with mutant PKD1 are on average almost 17<\/b>\n<b> months older than the wild-type cats. This seems non-random. How were study animals selected, and has there been any consideration of whether there could be selection biases that affect <\/b>\n<b>the interpretation of the data?<\/b> \n<b>Answer to <\/b>\n<b>the reviewer:<\/b> We appreciate the helpful comment and apologize for the unclear on this point. The animals in this present study were truly randomized. We were random and blind in all the processes. The person who performed the ultrasounds, the person who recorded the genetic parameters, and the person who analyzed the data were different persons. \n<b>In Figure 3 B\/C are both labelled as Right Kidney. One should be the data for the left kidney.<\/b> \n<b>Answer to <\/b>\n<b>the reviewer:<\/b> We apologize for this point. We have edited this point in the revised manuscript \n<b>In Figure 4 the chemical name is listed as \u201calanine\u201d but it should be \u201cadenine\u201d. Please indicate the resulting protein mutation caused by this transversion.<\/b> \n<b>&nbsp;Answer to <\/b>\n<b>the reviewer:<\/b> We apologize for this point. We have edited this point in the revised manuscript \n<b>In Table 2 please indicate the percentage of cystic cats in which the cysts are unilateral vs bilateral.<\/b> \n<b>Answer to <\/b>\n<b>the reviewer:<\/b> We apologize for this point. We have edited this point in the revised manuscript Best regards Soontaree Petchdee Corresponding author","URL":"https:\/\/f1000research.com\/articles\/12-760\/v3#referee-comment-11073","order":2,"name":"referee-comment-11073","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.162718.r306588, Jin He, Zhejiang University, Hangzhou, Zhejiang, 05 Aug 2024, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/12-760\/v3#referee-response-306588","order":3,"name":"referee-response-306588","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}