ORIGINAL RESEARCH

https://doi.org/10.5005/jp-journals-10005-2660
International Journal of Clinical Pediatric Dentistry
Volume 16 | Issue S-2 | Year 2023

Evaluating the Thickness of the Root Canal Dentin Wall in Primary First Molars Using Cone-beam Computed Tomography

Carlos Justiniano-Navarro1https://orcid.org/0000-0003-4158-4754, Stefany Caballero-García2https://orcid.org/0000-0001-8672-9369, Gabriela L ópez-Rodriguez3https://orcid.org/0000-0002-0316-3775, Dafna Geller-Palti4https://orcid.org/0000-0002-2119-3433

1–4Faculty of Science Health, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru

Corresponding Author: Carlos Justiniano-Navarro, Faculty of Science Health, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru, Phone: +51 977 348 034, e-mail: carlos_3_234@hotmail.com

ABSTRACT

Aim: To evaluate the thickness of the root canal dentin wall in the cervical, middle, and apical third of primary first molars.

Materials and methods: Cross-sectional study consisting of 30 cone-beam computed tomography (CBCT) images of primary maxillary and mandibular first molars, with crown, and root integrity. The wall dentin thickness of each canal was measured in three axial views, divided into distal (D), mesial, lingual/palatine, and buccal surfaces.

Results: The smallest dentin wall thickness of the maxillary molar was located on the mesial surface of the mesiobuccal (MB) canal apical third (mean 0.55 ± 0.04 mm). The buccal and palatal (P) surfaces of the distobuccal (DB) and P canals showed the smallest dentin thickness on the cervical third (0.62 ± 0.02 mm). On the mandibular molar, we found the smallest dentin thickness on the apical third [lingual surface of the MB canal and buccal surface of the mesiolingual (ML) canal] with a mean of 0.41 ± 0.07 mm. Additionally, the dentin thickness is average of the D canal was about 0.67 ± 0.11 mm.

Conclusion: It is essential to understand the primary first molar’s anatomy to reduce possible complications in pediatric patients from instrumentation during root canal treatments.

Clinical significance: Pulpectomy is among the most challenging procedures in pediatric dentistry and the knowledge of the root anatomy of primary teeth allows the professional to make better clinical decisions and reduce possible risks during root canal treatment.

How to cite this article: Justiniano-Navarro C, Caballero-García S, López-Rodriguez G, et al. Evaluating the Thickness of the Root Canal Dentin Wall in Primary First Molars using Cone-beam Computed Tomography. Int J Clin Pediatr Dent 2023;16(S-2):S122–S127.

Source of support: Universidad Peruana de Ciencias Aplicadasexpost- 2022.

Conflict of interest: None

Keywords: Cone-beam computed tomography, Dentin, Endodontics, Molar, Primary tooth

INTRODUCTION

Pediatric dentistry is a dental branch responsible for averting and treating orofacial conditions in children.1,2 The scope of their responsibilities includes the preservation of primary teeth until their physiological exfoliation as they play an important role in the oral cavity conformation. However, one of the most common reasons for anticipated exfoliation is dental caries, which may compromise pulp vitality at more advanced stages.3,8 In that regard, complex treatments (i.e., pulpectomy) may be necessary to preserve the tooth’s structure, although it may affect the child’s quality of life.9 The primary and permanent dental anatomy differ in a range of characteristics. Such as in size and thickness of the dentin wall of the root and root canal, which is usually more curved and thinner. In addition, the permanent molar tooth germ is located between the roots of a primary molar (the interradicular space), which is considered a high-risk area due to the fragility and the smaller diameter of the dentin thickness.10-15

Previous research on primary root anatomy has employed cone-beam computed tomography (CBCT) because it is a high-technological tool that allows visualization of the internal characteristics of the molars and anatomical variations in comparison with the permanent dentition.16-20 In addition, this technique is reproducible, noninvasive, and allows visualization of the primary first molar in three dimensions (axial, coronal and sagittal). Thus, it is one of the most widely used techniques for root canal assessment due to the high resolution and precision it provides.3,10,16,19-29 Moreover, Acar et al.20 and Ahmed et al.29 found anatomical root canal variations of primary molars and their importance for clinical procedures.

However, there is a lack of evidence on the anatomy of root canals in primary teeth, specifically dentin thickness of the root canal thickness measurements, which could cause the pediatric dentist to experience complications in instrumentation during pulpectomy, preventing clinical success. Therefore, this study aimed to evaluate the dentin thickness of primary first molars at the root canal wall level with CBCT.

MATERIALS AND METHODS

The study design was cross-sectional. A sample size formula for a single mean was utilized with a 95% confidence level and 80% power with the statistical software Epidat version 4.2 and using a pilot study’s means. As such, 30 tomography images were evaluated in two equally distributed groups. These were extracted from a database owned by a private radiological practice. The evaluation of the CBCT images was performed using a tomograph (CBCT Planmeca ProMax 3D Mid). This research study was exempted by the Ethics Board of the Peruvian University of Applied Sciences in Lima, Peru (CEI 383 - 11 - 19-PI237 - 19).

We included tomographic images of primary first molars with a minimum root length of 7.9 mm since a smaller measurement represented signs of root resorption.12 Consequently, we excluded those with external or internal resorption, with previous restorations or pulp treatment.

Training and calibration for tomographic analysis in the Planmeca Romexis Viewer® software (Planmeca, Finland) were carried out by the specialist in oral radiology. The degree of intraexaminer and interexaminer agreement was determined quantitively by κ statistical analysis, obtaining 0.82 (very good), and 0.63 (good), respectively.21

We measured the dentin thickness of the root canal walls by considering the root length of each canal in a sagittal view,12 subsequently dividing it into thirds. Hence, we measured 3 mm in the cervical third (most concave cervical line or amelocemental junction), 2 mm in the middle third (from the first line), and 3 mm in the apical third (from the second line toward the apical) as suggested by Montoya et al.13 The exact point of measurement was established in the center of each third (1.5 mm in the cervical third, 1 mm in the middle third, and 1.5 mm in the apical third). In this way, we sought to standardize the points measured in all the canals (Fig. 1).

Fig. 1: Sagittal view of a primary mandibular first molar

We identified canals in the maxillary molar as distobuccal (DB), mesiobuccal (MB), and palatal (P). In the mandibular molar, these were MB, mesiolingual (ML), and distal (D). We then divided each molar canal into three sections (cervical, middle, and apical third) from the amelocemental line to the root tip in the axial view of the tomography. Each third was divided into four surfaces (D, mesial, buccal, and P/lingual), and the dentin thickness was measured in millimeters (Fig. 2). In addition, in the MB and ML canals of the primary mandibular first molars, dentin junction was evidenced at the level of the thirds, between the lingual surface of the MB canal and the buccal surface of the ML canal in which it was decided to make a single measurement. Therefore, each had a dentin thickness corresponding only to the surface and the third (Fig. 3).

Fig. 2: Axial view at the level of the middle third of a primary mandibular first molar

Fig. 3: Axial view, measurements of the mesial canal (buccal-lingual) of the primary mandibular first molar

Statistical analysis was performed using Stata version 15 (Stata Corporation, College Station, Texas, United States of America). The average dentin thickness measurement was expressed in millimeters.

RESULTS

Tables 1 to 3 show the measurement of dentin thickness in millimeters of the primary maxillary first molars canals (MB, DB, and P), thirds, and surfaces (mesial, D, and P buccal). We found that in the MB canal, the smallest dentin thickness measurement was on the mesial surface of the apical third with a mean of 0.55 ± 0.04 mm. In the DB canal, the cervical third presented the smallest dentin thickness on the P surface (0.62 ± 0.02 mm). Similarly, in the P canal, a lower measurement was found on the buccal surface of the cervical third with a mean of 0.62 ± 0.02 mm.

Table 1: Measurement of dentin thickness in millimeters of primary maxillary first molar in MB canal, thirds, and surfaces (n = 15)
Canal Third Surface Mean Standard deviation 50th percentile Interquartile range
MB Cervical Mesial 0.83 0.04 0.83 0.80–0.87
D 0.62 0.03 0.62 0.60–0.64
P 1.48 0.04 1.49 1.46–1.51
Buccal 1.41 0.06 1.34 1.31–1.40
Middle Mesial 0.81 0.05 0.81 0.78–0.84
D 0.72 0.07 0.7 0.66–0.78
P 1.04 0.11 1.01 0.98–1.10
Buccal 1.01 0.09 0.99 0.95–1.10
Apical Mesial 0.55 0.04 0.56 0.52–0.59
D 0.63 0.03 0.62 0.61–0.65
P 0.98 0.07 0.97 0.92–1.02
Buccal 0.93 0.09 0.94 0.87–1.00
Table 2: Measurement of dentin thickness in millimeters of primary maxillary first molar in DB canal, thirds, and surfaces (n = 15)
Canal Third Surface Mean Standard deviation 50th percentile Interquartile range
DB Cervical Mesial 0.83 0.06 0.84 0.79–0.88
D 0.98 0.12 0.95 0.9–1.00
P 0.62 0.02 0.62 0.6–0.63
Buccal 1.79 0.02 1.79 1.78–1.80
Middle Mesial 0.78 0.03 0.78 0.76–0.81
D 0.85 0.04 0.85 0.82–0.89
P 0.69 0.07 0.68 0.65–0.74
Buccal 1.27 0.04 1.28 1.22–1.30
Apical Mesial 0.64 0.04 0.62 0.61–0.65
D 0.64 0.03 0.64 0.61–0.67
P 0.66 0.05 0.67 0.62–0.70
Buccal 0.95 0.05 0.95 0.90–1.00
Table 3: Measurement of dentin thickness in millimeters of primary maxillary first molar in P canal, thirds, and surfaces (n = 15)
Canal Third Surface Mean Standard deviation 50th percentile Interquartile range
P Cervical Mesial 1.41 0.06 1.39 1.36–1.46
D 1.15 0.07 1.17 1.08–1.20
P 1.71 0.08 1.69 1.62–1.77
Buccal 0.62 0.02 0.61 0.6–0.63
Middle Mesial 0.96 0.05 0.97 0.92–1.00
D 0.92 0.05 0.91 0.88–0.94
P 1.31 0.08 1.32 1.25–1.37
Buccal 0.72 0.07 0.68 0.65–0.74
Apical Mesial 0.81 0.02 0.81 0.79–0.82
D 0.71 0.07 0.71 0.65–0.77
P 1.01 0.16 1.01 0.92–1.15
Buccal 0.94 0.08 0.93 0.90–0.97

Table 4 to 6 illustrates the measurement of dentin thickness in millimeters of the primary mandibular first molars canals (MB, ML, and D), thirds, and surfaces (mesial, D, lingual, and buccal). We found that in the MB and ML canals, the smallest dentin thickness measurement was obtained in the apical third on its lingual surface (0.41 ± 0.07 mm). Similarly, in the D canal, a lower measurement was found in the apical third of the D surface (0.67 ± 0.11 mm).

Table 4: Measurement of dentin thickness in millimeters of primary mandibular first molar in MB canal, thirds, and surfaces (n = 15)
Canal Third Surface Mean Standard deviation 50th percentile Interquartile range
MB Cervical Mesial 1.25 0.05 1.24 1.21–1.30
D 0.97 0.11 0.93 0.89–1.1
Lingual 0.42 0.07 0.42 0.36–0.48
Buccal 1.53 0.04 1.53 1.51–1.57
Middle Mesial 0.99 0.04 1.01 0.97–1.03
D 0.89 0.06 0.90 0.85–0.93
Lingual 0.44 0.06 0.43 0.39–0.49
Buccal 1.33 0.07 1.32 1.28–1.38
Apical Mesial 0.80 0.04 0.81 0.77–0.82
D 0.75 0.07 0.75 0.70–0.80
Lingual 0.41 0.07 0.42 0.36–0.45
Buccal 0.97 0.08 0.96 0.90–1.00
Table 5: Measurement of dentin thickness in millimeters of primary mandibular first molar in ML canal, thirds, and surfaces (n = 15)
Canal Third Surface Mean Standard deviation 50th percentile Interquartile range
ML Cervical Mesial 1.18 0.23 1.25 0.98–1.34
D 0.86 0.05 0.85 0.82–0.91
Lingual 1.50 0.07 1.50 1.45–1.56
Buccal 0.42 0.07 0.42 0.36–0.48
Middle Mesial 0.79 0.04 0.79 0.76–0.82
D 0.83 0.08 0.85 0.79–0.90
Lingual 0.99 0.10 0.95 0.90–1.10
Buccal 0.44 0.06 0.43 0.39–0.49
Apical Mesial 0.67 0.04 0.68 0.63–0.71
D 0.53 0.07 0.52 0.48–0.60
Lingual 0.80 0.07 0.81 0.78–0.83
Buccal 0.41 0.07 0.41 0.36–0.49
Table 6: Measurement of dentin thickness in millimeters of primary mandibular first molar in D canal, thirds, and surfaces (n = 15)
Canal Third Surface Mean Standard deviation 50th percentile Interquartile range
D Cervical Mesial 1.03 0.15 0.98 0.91–1.19
D 0.96 0.10 0.93 0.89–1.00
Lingual 1.42 0.09 1.43 1.36–1.50
Buccal 1.62 0.07 1.61 1.58–1.69
Middle Mesial 0.87 0.18 0.85 0.72–0.95
D 0.72 0.07 0.71 0.66–0.78
Lingual 1.21 0.10 1.26 1.18–1.28
Buccal 1.46 0.13 1.47 1.34–1.56
Apical Mesial 0.76 0.14 0.75 0.62–0.84
D 0.67 0.11 0.67 0.61–0.74
Lingual 0.95 0.12 0.91 0.84–1.09
Buccal 0.85 0.06 0.84 0.80–0.91

DISCUSSION

Our study is the first to report the dentin thickness of root canal walls at the cervical, middle, and apical third and mesial, D, P/lingual, and buccal surfaces of maxillary and mandibular primary first molars through a CBCT.

This study has shown the average dentin thickness of the primary root canal wall in millimeters, which can be informative and serve as a referential point for the biomechanical instrumentation (manual or rotary) of root canal treatments in primary teeth. Also, it complements previous studies on primary root anatomy and canal configuration.12,13,29 Espinoza et al. reported findings related to root canal diameter, with a value of 0.27 mm at the apical level (the lowest average) and 0.98 mm at the cervical level (the highest in the primary maxillary first molar).12 Montoya et al. evaluated root canal diameter using a microscopic technique and found values ranging from 0.50 mm at the cervical level, 0.38 mm in the middle third, and 0.19 mm in the apical third.13 However, pulp treatment guidelines do not define the canal thickness for instrumentation to obtain optimal obturation.3 Generally the files used in mesial, lingual, and buccal canals correspond to a #25 file and in D and palatine canals to a #30 file.30,31 Therefore, our findings could enable the delimitation of the file size employed during pulpectomy procedures and reduce the risk of canal perforation or over-instrumentation.

Additionally, Baik et al. highlight that prior to any pulp procedure, specialists should know the anatomy of primary root canals to avoid certain complications that may put the permanent tooth germ at risk.32 Ahmed et al.29 mentions that the changes and internal root anatomical variability of the primary molar may be due to physiological resorption and deposition of additional dentin. These changes may occur in the number, shape, and even the size of the root canal. Researchers support the importance of understanding the anatomical configuration of the root and root canal. One of the reasons is their great variability and that it will serve for the clinical development of pulpal therapies by providing an average of the instrumentation to be performed.33

One of the main limitations encountered was that the literature focuses on permanent dentition. Therefore, the collection of information and comparison with other studies on the primary dentition was cumbersome. However, when comparing the study with other studies related to the objective, reference is made to the anatomical variations of the root canals of primary first molars, mostly with accessory canals. Likewise, another limitation was related to data collection since the sample consisted of 30 CBCT scans and most of the primary molars presented root resorption and fracture, among other factors.

According to our findings, we suggest researchers continue to evaluate the dentin thickness of root canal walls of primary teeth and establish a protocol for the clinical management of root canals (especially on biomechanical instrumentation). As such, the success rate of the treatment would increase, presenting optimal results, and benefiting the quality of life of the pediatric patient.

CONCLUSION

Based on the results of this study, the following conclusions can be made:

Clinical Significance

Pulpectomy is among the most challenging procedures in pediatric dentistry and the knowledge of the root anatomy of primary teeth allows the professional to make better clinical decisions and reduce possible risks during root canal treatment.

ORCID

Carlos Justiniano-Navarro https://orcid.org/0000-0003-4158-4754

Stefany Caballero-García https://orcid.org/0000-0001-8672-9369

Gabriela López-Rodriguez https://orcid.org/0000-0002-0316-3775

Dafna Geller-Palti https://orcid.org/0000-0002-2119-3433

ACKNOWLEDGMENT

This work is original, there are no conflicts of interest, and it was self-financed: UPC-expost-2022-2.

REFERENCES

1. American Academy of Pediatric Dentistry. Overview. The Reference Manual of Pediatric Dentistry. Chicago, Illinois: American Academy of Pediatric Dentistry; 2021.

2. American Academy of Pediatric Dentistry. Management of the developing dentition and occlusion in pediatric dentistry. The Reference Manual of Pediatric Dentistry. Chicago, Illinois: American Academy of Pediatric Dentistry; 2021.

3. American Academy of Pediatric Dentistry. Pulp therapy for primary and immature permanent teeth. The Reference Manual of Pediatric Dentistry. Chicago, Illinois: American Academy of Pediatric Dentistry; 2021.

4. Brustolin JP, Mariath AA, Ardenghi TM, et al. Survival and factors associated with failure of pulpectomies performed in primary teeth by dental students. Braz Dent J 2017;28(1):121–128. DOI: 10.1590/0103-6440201601009

5. Arhakis A, Athanasiadou E, Vlachou C. Social and psychological aspects of dental trauma, behavior management of young patients who have suffered dental trauma. Open Dent J 2017;11:41–47. DOI: 10.2174/1874210601711010041

6. Ebrahimi M, Janani A, Majidinia S, et al. Are self-etch adhesives reliable for primary tooth dentin? A systematic review and meta-analysis. J Conserv Dent 2018;21(3):243–250. DOI: 10.4103/JCD.JCD_287_17

7. Goldberg M. Deciduous tooth and dental caries. Ann Pediatr Child Health 2017;5(1):1120–1125.

8. Zoremchhingi, Joseph T, Varma B, et al. A study of root canal morphology of human primary molars using computerised tomography: an in vitro. J Indian Soc Pedod Prev Dent 2013;23(1):7–12.

9. Abanto J, Tsakos G, Olegario IC, et al. Pulpectomy is a better option than extraction for primary molars: evidence from a randomised clinical trial. Int J Paediatr Dent 2022.

10. Fumes AC, Sousa-Neto MD, Leoni GB, et al. Root canal morphology of primary molars: a micro-computed tomography study. Eur Arch Paediatr Dent 2014;15(5):317–326. DOI: 10.1007/s40368-014-0117-0

11. Costa B, Iwamoto AS, Puppin-Rontani RM, et al. Comparative analysis of root dentin morphology and structure of human versus bovine primary teeth. Microsc. Microanal 2015;21(3):689–694. DOI: 10.1017/S1431927615000434

12. Espinoza A, Velasquez C, Suarez A, et al. Longitud y diámetro del conducto radicular en primeros molares superiores deciduos usando tomografía computarizada cone beam: estudio in vitro. Odontol Sanmarquina 2016;19(2):7–11. DOI: 10.15381/os.v19i2.12910

13. Montoya J, Torres G, Blanco D, et al. Consideraciones anatómicas para la preparación de conductos radiculares en la primera molar inferior decidua. Odontol Pediatr 2016;15(1):41–52.

14. Ulu Güzel KG, Kirzioğlu Z, Özkorucuklu S. Dentin permeability of carious primary teeth. Niger J Clin Pract 2017;20(12):1566–1570. DOI: 10.4103/1119-3077.196078

15. Krishnamurthy NH, Jacob CD, Thimmegowda U, et al. Anatomical configuration of roots and canal morphology of primary mandibular first molars: a CBCT study. J clin diagn 2017;11(11):9–11. DOI: 10.7860/JCDR/2017/32284.10838

16. Van Acker JW, Martens LC, Aps JK. Cone-beam computed tomography in pediatric dentistry, a retrospective observational study. Clin Oral Investig 2016;20(5):1003–1010. DOI: 10.1007/s00784-015-1592-3

17. Dhillon J, Kalra G. Cone beam computed tomography: an innovative tool in pediatric dentistry. J Pediatr Dent 2013;1(2):27–31. DOI: 10.4103/WKMP-0028.117440

18. Wang Y, Chang H, Kuo C, et al. A study on the root canal morphology of primary molars by high-resolution computed tomography. J Dent Sci 2013;8(3):321–327. DOI: 10.1016/j.jds.2013.04.002

19. Saggena G, Anandaraj S, Issac JS, et al. Rotatory endodontics in primary teeth—a review. Saudi J Dent 2016;28(1):12–7. DOI: 10.1016/j.sdentj.2015.08.004

20. Acar B, Kamburoğlu K, Tatar İ, et al. Comparison of micro-computerized tomography and cone-beam computerized tomography in the detection of accessory canals in primary molars. Imaging Sci Dent 2015;45(4):205–211. DOI: 10.5624/isd.2015.45.4.205

21. Dettori JR, Norvell DC. Kappa and beyond: is there agreement. Global Spine J 2020;10(4):499–501. DOI: 10.1177/2192568220911648

22. Wolf TG, Paqué F, Zeller M, et al. Root canal morphology and configuration of 118 mandibular first molars by means of micro-computed tomography: an ex vivo study. J Endod 2016;42(4):610–614. DOI: 10.1016/j.joen.2016.01.004

23. Senan EM, Madfa AA, Alhadainy HA. Root and canal configuration of mandibular first molars in a yemeni population: a cone-beam computed tomography. Eur Endod J 2020;5(1):10–17. DOI: 10.14744/eej.2020.99609

24. Datta P, Zahir S, Kundu GK, et al. An in vitro study of root canal system of human primary molars by using multidetector computed tomography. J Indian Soc Pedod Prev Dent 2019;37(2):120–126. DOI: 10.4103/1319-2442.261339

25. Deshpande AN, Joshi NH, Naik KS. In vitro comparative evaluation of cleaning efficacy and volumetric filling in primary molars: cone beam computed tomography evaluation. Contemp Clin Dent 2017;8(1):33–37. DOI: 10.4103/0976-237X.205064

26. Demiriz L, Bodrumlu EH, Icen M. Evaluation of root canal morphology of human primary mandibular second molars by using cone beam computed tomography. Niger J Clin Pract 2018;21(4):462–467. DOI: 10.4103/njcp.njcp_85_17

27. Musale PK, Jain KR, Kothare SS. Comparative assessment of dentin removal following hand and rotary instrumentation in primary molars using cone-beam computed tomography. J Indian Soc Pedod Prev Dent 2019;37(1):80–86. DOI: 10.4103/JISPPD.JISPPD_210_18

28. Jiménez EV, Muñoz EH, Domínguez LC. Características de los canales radiculares de molares temporales. Int J Odontostomat 2015;9(1):159–164. DOI: 10.4067/S0718-381X2015000100024

29. Ahmed HMA, Musale PK, Shahawy OI, et al. Application of a new system for classifying tooth, root and canal morphology in the primary dentition. Int Endod J 2020;53(1):27–35. DOI: 10.1111/iej.13199

30. Ramezanali F, Afkhami F, Soleimani A, et al. Comparison of cleaning efficacy and instrumentation time in primary molars: mtwo rotary instruments vs. hand K-files. Iran Endod J 2015;10(4):240–243. DOI: 10.7508/iej.2015.04.006

31. Katge F, Chimata VK, Poojari M, et al. Comparison of cleaning efficacy and instrumentation time between rotary and manual instrumentation techniques in primary teeth: an in vitro study. Int J Clin Pediatr Dent 2016;9(2):124–127. DOI: 10.5005/jp-journals-10005-1347

32. Baik SA, Mkenah AA, Khan A, et al. Pulpotomy vs. pulpectomy techniques, indications and complications. Int J Community Med Public Health 2018;5(11):1–4. DOI: 10.18203/2394-6040.ijcmph20184261

33. Ahmed HM, Khamis MF, Gutmann JL. Seven root canals in a deciduous maxillary molar detected by the dental operating microscope and micro-computed tomography. Scanning 2016;38(6):554–557. DOI: 10.1002/sca.21299

________________________
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.