|Year : 2022 | Volume
| Issue : 3 | Page : 302-308
A questionnaire-based cross-sectional survey of Indian postgraduates and endodontists on awareness, attitude, and practice of using conventional syringe needle irrigation during root canal treatment
Kavalipurapu Venkata Teja1, Sindhu Ramesh1, Sahil Choudhari1, Krishnamachari Janani2, Jerry Jose1, Kaligotla Apoorva Vasundhara3
1 Department of Conservative Dentistry and Endodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India
2 Department of Conservative Dentistry and Endodontics, SRM Dental College, SRM Institute of Science and Technology, Ramapuram, Chennai, Tamil Nadu, India
3 Private Practitioner, Prosthodontist and Oral Implantologist, Hyderabad, Telangana, India
|Date of Submission||31-Jan-2022|
|Date of Decision||03-Apr-2022|
|Date of Acceptance||07-Apr-2022|
|Date of Web Publication||1-Sep-2022|
Dr. Sindhu Ramesh
Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, 162, Poonamallee High Road, Chennai - 600 077, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Introduction: Syringe needles of various gauges and vents have conventionally been used to irrigate the root canal system. This study aimed to collect data on the awareness, attitude, and practice among Indian postgraduates and endodontists of using conventional syringe needle irrigation (SNI) during root canal treatment.
Materials and Methods: The survey was performed between January 2019 and December 2021. A total of 1000 printed forms and 1500 electronic questionnaires were shared with postgraduate students and endodontists across India. After validation by three national and two international experts, the survey with 35 questions was formulated. The survey contained 2 demographic-based, 13 awareness-based, 10 attitude-based, and 10 practice-based questions. The Chi-square test was used to assess the data (P < 0.05).
Results: A total of 888 (35.5%) completed survey questionnaires were received (589 electronic and 299 printed). The respondents of the survey comprised 37% of postgraduate students and 63% of endodontic practitioners. In 24 out of the 35 questions, there was a statistical difference between postgraduate students and endodontists (P < 0.05). Ninety-one percent of the respondents were aware of the various SNI systems, while 7% were not much familiar and 2% were not aware. Sixty-six percent of the respondents strongly disagreed that SNI alone is sufficient for entire root canal disinfection, while 21% agreed to it. Eighty-eight percent of the respondents strongly agreed and 7% agreed that it is mandatory to activate the irrigant using agitation devices even after SNI, while 5% disagreed. Fifty-nine percent of the respondents used 30-gauge single side-vented closed-ended needles for conventional SNI, while 29% used needles for administration of local anesthesia.
Conclusion: The awareness among the postgraduates and endodontists on SNI is moderate and the attitude is positive.
Keywords: Disinfection, endodontics, root canal treatment, survey, syringe needle irrigation
|How to cite this article:|
Teja KV, Ramesh S, Choudhari S, Janani K, Jose J, Vasundhara KA. A questionnaire-based cross-sectional survey of Indian postgraduates and endodontists on awareness, attitude, and practice of using conventional syringe needle irrigation during root canal treatment. Saudi Endod J 2022;12:302-8
|How to cite this URL:|
Teja KV, Ramesh S, Choudhari S, Janani K, Jose J, Vasundhara KA. A questionnaire-based cross-sectional survey of Indian postgraduates and endodontists on awareness, attitude, and practice of using conventional syringe needle irrigation during root canal treatment. Saudi Endod J [serial online] 2022 [cited 2022 Oct 5];12:302-8. Available from: https://www.saudiendodj.com/text.asp?2022/12/3/302/354832
| Introduction|| |
Chemomechanical debridement is a crucial step in root canal therapy. Several investigations have revealed that the substantial areas of the root canal, especially at the apical third, are left undisturbed by the instruments., Root canal irrigation aids in the debridement of the uninstrumented surfaces of the root canal system. Syringe needles of various gauges and vents have conventionally been used to irrigate the root canal system. The depth of needle penetration in the canal is the most important determinant for positive pressure irrigation., Syringe needle irrigation (SNI) only distributes irrigant 1 mm beyond the needle tip, hence it alone might not be sufficient to eliminate the microbes from the intricate parts of the root canal system.
Although the current literature claims irrigant activation techniques (IAT) to be superior to SNI in terms of inorganic smear removal, root canal debridement, and also on enhancing the endodontic treatment outcomes. SNI is still a primary mode of irrigant delivery during the preparatory phase of the root canal treatment. Although SNI has been practiced by various dental practitioners and specialists for decades, there is still ambiguity in the specific choice of needles, usage, optimization, and ideologies of using it in clinical practice. Especially, the improper protocol and usage of SNI cause the untoward irrigant extrusions, leading to sodium hypochlorite accidents. Hence, it is of utmost importance to know the current clinical scenario and ideology and practice of SNI among postgraduates and endodontists.
Literature from the in vitro- and ex vivo-based studies claim that various factors and parameters collectively play a role in controlling the output of syringe needle-based delivery systems. A recent systematic review highlighted that needle choice, needle placement, taper, and apical preparation sizes as the major factors that can be clinically altered during manual needle irrigation, to get the maximum benefit. When previous periapical pressure assessment-based studies on syringe needle-based irrigation systems are concerned, the optimal flow rates decided to be 4–6 ml/min., Clinically, an operator cannot maintain a constant irrigant flow rate continuously during the entire course of root canal irrigation.
Studies also claim that there are various factors such as root canal curvature and canal complexity that influence the manual syringe-based irrigation are not under the control of the operator. A clinically relevant ex vivo study by Boutsioukis et al. highlighted that clinically the irrigant flow rates vary based on the experience of the operator, gender, and also the syringe needle and barrel used for root canal irrigation. Hence, collectively taking all these factors, it was understood that there are various other clinical and operator-related factors, which vary from person to person and based on experience too. Hence, it urged us to survey practicing endodontists and postgraduates to know more about the awareness and clinical protocol of using SNI in their day-to-day practice.
Given these current findings, we were interested in assessing the current trends regarding SNI among postgraduate endodontic students and practicing endodontists in India. Previous survey-based literature among Indian endodontists assessed on the irrigation protocols employed and the use of various irrigation activation systems with no specific emphasis on the conventional SNI. Hence, the present survey aimed to collect data on the awareness, attitude, and practice among Indian postgraduates and endodontists of using conventional SNI during root canal treatment.
| Materials and Methods|| |
The Institutional Scientific Review Board granted the ethical approval (SRB/SD/MDS12/1710/19 ODS) and questionnaire framed based on the awareness, attitude, and practice on the manual SNI. The questionnaire contained demographic-, awareness-, attitude-, and practice-based questions. All questions framed were multiple-choice types.
The questions were prepared and forwarded to five endodontists for content validation (three national and two international). The final questionnaire was framed based on the suggestions by experts. The questionnaire contained 2 demographic-based, 13 awareness-based, 10 attitude-based, and 10 practice-based questions.
The sample size calculation was performed based on the recent survey using G*Power, version 3.1 (Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany). The sample size of 885 was calculated with an effect size of 0.11, alpha error set at 0.05, and power set at 95%. The questionnaire was made available to the participants in both printed and electronic formats. A total of 1000 printed forms were distributed at various national endodontic conferences. One thousand five hundred electronic questionnaires were shared with postgraduate students and endodontists across India. The questionnaires were distributed from January 2019 to December 2021. Data of the filled questionnaires were tabulated and stored in Microsoft Excel.
The Chi-square test was used to statistically analyze the data. The criteria for statistical significance were fixed at 0.05 levels. The analyses were done using SPSS 23.0 software (IBM SPSS Predictive Analytics Community, Armonk, New York, USA).
| Results|| |
Among the 2500 questionnaires shared, a total of 888 (35.5%) completed survey questionnaires were received (589 electronic and 299 printed). In 24 out of the 35 questions, a statistical difference existed between the two groups (P < 0.05). The respondents of the survey comprised 37% of postgraduate students and 63% of endodontic practitioners. Among endodontic practitioners, 30% had 1–2 years of experience, 17% had 2–5 years of experience, 8% had 5–10 years of experience, and 5% had 10–20 years of experience. Only 3% of the respondents had over 20 years of experience. Among the endodontic practitioners, 20% are involved in a multidisciplinary practice, 17% work in a university-based practice, and 15% work in a private practice. Six percent worked as full-time consultants and 2% worked as part-time consultants. Three percent of the practitioners are limited to only micro-endodontic practice.
Syringe needle irrigation awareness
When asked about awareness of various SNI systems, 40% of endodontists and 30% of postgraduates responded yes, but they did not feel that it was important as they had irrigant agitation systems. Four percent of endodontists and 3% of postgraduates were not much aware of it.
Syringe needle irrigation research awareness and time of irrigation
Thirty-two percent of endodontists and 28% of postgraduates were aware of data on the wall contact time but were not aware of the time of SNI. Four percent of endodontists and 2% of postgraduates felt that 40 min of irrigation is sufficient for efficient root canal disinfection, whereas 3% of postgraduates and 1% of endodontists felt that 30 min of SNI was sufficient clinically. When asked about the awareness of postoperative pain, when the root canal treatment relies only on conventional needle irrigation, 68% of endodontists and 30% of postgraduates reported sufficient knowledge.
Awareness of needle placement during syringe needle irrigation
Forty-five percent of endodontists and 20% of postgraduates felt that the needle used for SNI should be placed 1–3 mm short of the working length. Thirteen percent of endodontists and 1% of postgraduates felt that the needle should be placed until it binds passively in the root canal. Whereas, 9% of postgraduates felt that needle placement is not an important factor during SNI.
Awareness on irrigant extrusion using syringe needle irrigation and its usage in minimally shaped canals
Sixty percent of endodontists and 39% of postgraduates were aware that inappropriate needle choice and placement can lead to irrigant extrusion. When asked about the efficacy of SNI in minimally shaped canals, 40% of endodontists and 27% of postgraduates felt that SNI can be done in minimally shaped and curved canals, but the efficiency would be compromised, whereas 18% of postgraduates and 3% of endodontists of the participants felt that SNI cannot be performed. Responses on various clinically used needle gauges, designs, and on the recommended optimal flow rates are mentioned in [Figure 1].
|Figure 1: (a) Pie chart showing the awareness on the recommended optimal flow rate to be maintained during syringe needle irrigation based on periapical pressure assessment models. (b) Bar graph showing the awareness on the various needle gauges and designs clinically used frequently for syringe needle irrigation. SNI: Syringe needle irrigation|
Click here to view
When asked if SNI is as important as irrigant activation during root canal treatment, 4% of endodontists and 1% of postgraduates strongly disagreed, 38% of endodontists and 30% of postgraduates disagreed, and 20% of postgraduates and 7% of endodontists agreed. When asked if it is mandatory to activate the irrigant using agitation devices even after SNI, 48% of endodontists and 40% of postgraduates strongly agreed, while 3% of postgraduates and 2% of endodontists disagreed. Other attitude-based responses are presented in [Figure 2].
|Figure 2: (a) Bar graph showing the attitude-based response if syringe needle irrigation alone is sufficient for complete root canal disinfection. (b) Bar graph showing the attitude-based response if apical extrusion is common with improper usage of syringe needle for root canal irrigation. (c) Bar graph showing the attitude-based response if syringe needle irrigation is important to enhance the therapeutic treatment outcomes. (d) Bar graph showing the attitude-based response on the reason for not using syringe needle irrigation. SNI: Syringe needle irrigation|
Click here to view
When respondents were asked if they practiced SNI and asked about the needle gauge and design they use, 32% of endodontists and 27% of postgraduates responded that they use 30-gauge single side-vented closed-ended needles, while 8% of postgraduates and 3% of endodontists used 31-gauge single side-vented closed-ended needles. Twenty-nine percent of postgraduates used syringe needles used for administering local anesthesia. Three percent of postgraduates did not practice SNI. Responses on reported procedural errors and various adjuncts to irrigation used by respondents are presented in [Figure 3].
|Figure 3: (a) Bar graph showing the practice-based response to the experience of procedural errors during syringe needle irrigation. (b) Pie chart showing the practice-based response on the various adjuncts to irrigation used by the respondents. SNI: Syringe needle irrigation|
Click here to view
| Discussion|| |
Manual SNI seems to be a difficult one to standardize in a clinical scenario. Especially, there is a large variation in the armamentarium choice or the SNI protocol as such among the endodontists worldwide. Hence, it is appropriate to know the current status of SNI employed among Indian postgraduates and specialists. Hence, the survey research would be an appropriate study design to know the current clinical status and the protocols employed by specialists in their clinical practice. Considering all these factors, we specifically formulated a custom questionnaire to assess the awareness and practice of SNI among Indian specialists and postgraduates. The present survey is unique in only obtaining data from clinicians on SNI, which is different from the previous survey designs which assessed the irrigation protocols and IAT among Indian practitioners.
The specialists who participated in the survey were more aware as compared to the postgraduates. Most of the study participants had adequate knowledge on the influence of contact time of the irrigant exerted on the canal walls. They highlighted the current lacunae on specific irrigation time for a clinical case. When the literature is specifically analyzed, there is still lacking evidence on the exact time of needle irrigation required for a specific case. The majority of the survey participants felt that maintaining an optimal flow rate during root canal irrigation is not a clinically relevant factor that needs to be stressed. Although literature states an increase in periapical pressures at higher irrigant flow rates during SNI, a clinician cannot maintain a constant low irrigant flow rate in due course of root canal irrigation. Previous literature also specifically highlighted that irrigant flow rates vary based on clinical experience, gender, needle, and barrel choice. Hence, clinically, it is difficult for a clinician to perform efficient SNI. The majority of the participants were aware of apical vapor lock formation with SNI. Hence, they felt that syringe should be kept 1–3 mm short with continuous oscillations. Their views correlated with the current literature which stated the apical vapor lock formation with stationary needles during SNI.
In the present survey, more than half of the respondents preferred using 30-gauge side-vented close-ended needles, whereas in previous studies, 45% of the respondents used 27-gauge open-ended needles and 97% of the participants preferred using 26-gauge needles. The current literature claims that 30-gauge side-vented open-ended needles induce the least apical pressures. Hence, as there is wide variation and trend change in SNI from the previous years, the ideology would have also shifted among the specialists and practitioners which made them shift their interest toward the usage of 30-gauge needles. The participants felt that clinically the SNI can be performed with reduced efficiency in curved and narrow canals, their views correlated with a recent study that assessed minimally shaped canals, which stated the inefficiency of SNI in minimally shaped canals.
The majority of the participants felt that SNI alone is insufficient for effective root canal debridement, which was in correlation with the current literature evidence, which claims IAT as a mandatory adjunct to SNI., Participants of the current survey reported fatigue during SNI, which was in correlation with the previous literature. The participants in the current survey disagreed to prepare the root canal to larger sizes and tapers clinically to increase the efficiency of SNI, which is contradicting the current literature from in vitro studies., Due to the adjunctive usage activation techniques, many participants did not show interest in preparing the canals to greater sizes and tapers. The participants agreed that apical extrusion was quite common with SNI, which was in correlation with the previous literature.,, When the overall opinion on SNI was asked, the majority of the participants were skeptical and felt it was debatable.
Although the literature claims 40 min of total irrigation time during SNI to be effective for adequate root canal disinfection, the majority of the participants in our survey hardly irrigated for 15–30 min. The fatigue elicited during SNI was the answer given by a majority of the specialists and postgraduates. The reason for such fatigue would be the usage of larger barrel syringes with thinner gauge needles, leading to increased intrabarrel pressures causing earlier fatigue. Similarly, the majority of our participants reported using 5-ml barrel syringes for irrigating the root canal space, hence they elicited higher fatigues during SNI.
The majority of the participants preferred sodium hypochlorite as their primary choice. There is no current change in the ideology of practitioners as reported in the previous surveys conducted in India., The participants reported having separate syringes and barrels for various irrigating solutions and immediately dispose of after each case. While few postgraduates use the same local anesthetic syringe barrel for irrigation. The literature claims the thicker gauge syringe needles cause extrusion when wedged to the root canal walls and the literature also claims the possibility of precipitation, when the irrigants are contaminated or mixed. Hence, the survey results show that few postgraduates were not completely aware of these concepts and need to be aware of them. When data were obtained on the procedural accidents reported by participants on using SNI, three postgraduates and two specialists reported the occurrence of sodium hypochlorite accidents. Although the incidence of sodium hypochlorite accidents is reported to be <1% from the present survey, preferably clinicians should be aware of these accidents and prevent them in the near future.
When the final note on adjunct agitation protocol was asked to the participants, the majority of them preferred ultrasonic, followed by sonic irrigation. The present survey results were contradictory to the previous survey on IAT, where manual dynamic activation was most preferred as compared to other adjuncts. The reason for such variation was the inclusion of the participants in the present survey, where 63% of the participants were practicing endodontists with less inclusion of postgraduates. Among the included specialists, 30% of them had experience of 1–2 years and run their private practice. Hence, they were aware of the recent advances and equipped with better adjunct activation aids in their clinical practice.
When the limitations of the present survey were considered, the survey has not specifically highlighted the gender- and experience-wise opinions of the survey participants on SNI and protocols of SNI in their clinical practice. As previous literature clearly states the variations on irrigant flow rates elicited based on gender and experience too, it would be better to reconsider these factors. The other limitation was not considering the questionnaire on patient difficulties. A recent report highlighted the patient's difficulties in opening their mouth for a quite long time during dental and endodontic treatments. Hence, this might be another reason which might have caused the specialists and postgraduates to shift from conventional SNI to more advanced IAT. Hence, future survey questionnaires should ideally focus on collecting data on the patient's opinion and satisfaction with using SNI. The current trend has tremendously shifted in analyzing optimal shapes., Hence, future surveys should better focus on collecting information on irrigation protocols employed for minimally invasive endodontic treatments. As the present literature evidence shows the inefficiency of current aids in debridement of minimally shaped root canal system, future survey-based research should better focus on analyzing collective data from clinicians on debridement strategies employed by clinicians for minimally shaped root canal systems.
| Conclusion|| |
It can be concluded from the present survey that most of the respondents perform SNI and the awareness among postgraduates and endodontists on SNI is moderate and the attitude is positive.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Siqueira JF Jr., Pérez AR, Marceliano-Alves MF, Provenzano JC, Silva SG, Pires FR, et al.
What happens to unprepared root canal walls: A correlative analysis using micro-computed tomography and histology/scanning electron microscopy. Int Endod J 2018;51:501-8.
Silva AA, Belladonna FG, Rover G, Lopes RT, Moreira EJ, De-Deus G, et al.
Does ultraconservative access affect the efficacy of root canal treatment and the fracture resistance of two-rooted maxillary premolars? Int Endod J 2020;53:265-75.
Topçuoğlu HS, Topçuoğlu G, Arslan H. The effect of apical positive and negative pressure irrigation methods on postoperative pain in mandibular molar teeth with symptomatic irreversible pulpitis: A randomized clinical trial. J Endod 2018;44:1210-5.
Romualdo PC, de Oliveira KM, Nemezio MA, Küchler EC, Silva RA, Nelson-Filho P, et al.
Does apical negative pressure prevent the apical extrusion of debris and irrigant compared with conventional irrigation? A systematic review and meta-analysis. Aust Endod J 2017;43:129-37.
Mandorah A. Effect of irrigation needle depth in smear layer removal: Scanning electron microscope study. Saudi Endod J 2013;3:114. [Full text]
Susila A, Minu J. Activated irrigation vs. conventional non-activated irrigation in endodontics – A systematic review. Eur Endod J 2019;4:96-110.
Virdee SS, Seymour DW, Farnell D, Bhamra G, Bhakta S. Efficacy of irrigant activation techniques in removing intracanal smear layer and debris from mature permanent teeth: A systematic review and meta-analysis. Int Endod J 2018;51:605-21.
Ng WN, Marruganti C, Grandini S, Neelakantan P. Root canal debridement by negative pressure irrigation, ultrasonically activated irrigation and their combination. J Oral Sci 2021;63:286-8.
Konstantinidi E, Psimma Z, Chávez de Paz LE, Boutsioukis C. Apical negative pressure irrigation versus syringe irrigation: A systematic review of cleaning and disinfection of the root canal system. Int Endod J 2017;50:1034-54.
Sujith IL, Teja KV, Ramesh S. Assessment of irrigant flow and apical pressure in simulated canals of single-rooted teeth with different root canal tapers and apical preparation sizes: An ex vivo
study. J Conserv Dent 2021;24:314-22. [Full text]
Guivarc'h M, Ordioni U, Ahmed HM, Cohen S, Catherine JH, Bukiet F. Sodium hypochlorite accident: A systematic review. J Endod 2017;43:16-24.
Teja KV, Ramesh S, Battineni G, Vasundhara KA, Jose J, Janani K. The effect of various in-vitro
parameters on irrigant flow and apical pressure using manual syringe needle irrigation: Systematic review. Saudi Dent J 2022;34:87-99.
Park E, Shen Y, Khakpour M, Haapasalo M. Apical pressure and extent of irrigant flow beyond the needle tip during positive-pressure irrigation in an in vitro
root canal model. J Endod 2013;39:511-5.
Khan S, Niu LN, Eid AA, Looney SW, Didato A, Roberts S, et al.
Periapical pressures developed by nonbinding irrigation needles at various irrigation delivery rates. J Endod 2013;39:529-33.
Teja KV, Ramesh S, Vasundhara KA, Janani KC, Jose J, Battineni G. A new innovative automated root canal device for syringe needle irrigation. J Taibah Univ Med Sci 2022;17:155-8.
Boutsioukis C, Lambrianidis T, Kastrinakis E, Bekiaroglou P. Measurement of pressure and flow rates during irrigation of a root canal ex vivo
with three endodontic needles. Int Endod J 2007;40:504-13.
Gopikrishna V, Pare S, Pradeep Kumar A, Lakshmi Narayanan L. Irrigation protocol among endodontic faculty and post-graduate students in dental colleges of India: A survey. J Conserv Dent 2013;16:394-8.
] [Full text]
Natanasabapathy V, Durvasulu A, Krithikadatta J, Namasivayam A, Deivanayagam K, Manali S, et al.
Current trends in the use of irrigant activation techniques among endodontists & post-graduate dental students in India –A knowledge, attitude and practice based survey. Eur Endod J 2020;5:73-80.
Retamozo B, Shabahang S, Johnson N, Aprecio RM, Torabinejad M. Minimum contact time and concentration of sodium hypochlorite required to eliminate Enterococcus faecalis
. J Endod 2010;36:520-3.
Boutsioukis C, Kastrinakis E, Lambrianidis T, Verhaagen B, Versluis M, van der Sluis LW. Formation and removal of apical vapor lock during syringe irrigation: A combined experimental and computational fluid dynamics approach. Int Endod J 2014;47:191-201.
Boutsioukis C, Gutierrez Nova P. Syringe irrigation in minimally shaped root canals using 3 endodontic needles: A computational fluid dynamics study. J Endod 2021;47:1487-95.
Alkahtani A, Al Khudhairi TD, Anil S. A comparative study of the debridement efficacy and apical extrusion of dynamic and passive root canal irrigation systems. BMC Oral Health 2014;14:12.
Boutsioukis C, Psimma Z, van der Sluis LW. Factors affecting irrigant extrusion during root canal irrigation: A systematic review. Int Endod J 2013;46:599-618.
Silva PB, Krolow AM, Pilownic KJ, Casarin RP, Lima RK, Leonardo Rde T, et al.
Apical extrusion of debris and irrigants using different irrigation needles. Braz Dent J 2016;27:192-5.
Psimma Z, Boutsioukis C, Kastrinakis E, Vasiliadis L. Effect of needle insertion depth and root canal curvature on irrigant extrusion ex vivo
. J Endod 2013;39:521-4.
Basrani BR, Manek S, Sodhi RN, Fillery E, Manzur A. Interaction between sodium hypochlorite and chlorhexidine gluconate. J Endod 2007;33:966-9.
Sahebi S, Moazami F, Afsa M, Nabavi Zade MR. Effect of lengthy root canal therapy sessions on temporomandibular joint and masticatory muscles. J Dent Res Dent Clin Dent Prospects 2010;4:95-7.
Teja KV, Ramesh S. Shape optimal and clean more. Saudi Endod J 2019;9:235. [Full text]
Ordinola-Zapata R, Crepps JT, Neelakantan P. Root canal debridement and disinfection in minimally invasive preparation. In: Plotino G, editor. Minimally Invasive Approaches in Endodontic Practice. Cham: Springer International Publishing; 2021. p. 93-107.
[Figure 1], [Figure 2], [Figure 3]