Objectives Neuromas are aberrant axonal growths that may develop following amputations and contribute to residual-limb and/or phantom-limb pain. Burgeoning surgical approaches for treating neuroma pain include: targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI). However, little is known regarding functional outcomes, particularly post-operative prosthesis use. This scoping review aimed to examine prosthesis use and related outcomes among individuals with acquired amputations who underwent TMR/RPNI for neuromas. Design The study protocol was published on Open Science Framework. A comprehensive search was conducted across MEDLINE (OVID), EMBASE (OVID), CINAHL Plus (EBSCO), Cochrane Library, and Web of Science. An ascendancy approach was used to assess citation lists of select articles. Two reviewers independently screened abstracts and full texts following pilot testing, with input from a senior reviewer as needed. Results Nineteen studies were included. Studies predominantly assessed TMR (n=15), upper-extremity amputation only (n=13), traumatic amputation only (n=8), and many were case reports or case series (n=13). Thirteen studies reported pre- and post-operative prosthetic use. Eleven studies demonstrated positive prosthetic use outcomes, such as initiation of use, increased number of users, and increased frequency of use. Ten studies reported device-type post-operatively, nine of which exclusively described myoelectric prostheses. Conclusions Results suggest an increase in prosthesis use following TMR/RPNI, particularly with myoelectric devices. However, post-operative prosthetic outcome reporting is heterogeneous, and research on timing of prosthesis fitting, prosthesis tolerance, and barriers to prosthesis is limited. This scoping review highlights the need for larger studies to characterize prosthesis outcomes within the field. A clearer understanding of TMR/RPNI prosthetic use outcomes may assist in determining surgical candidacy and support the development of standardized pre-operative and post-operative rehabilitation protocols. More research is needed to ultimately improve neuroma management post limb-loss and increase patient prosthetic function and satisfaction. Research Study with Best Paper Award Abstract
Objectives: Neuromas are aberrant axonal growths that develop following nerve injury and can contribute to post-amputation pain.1,2 Prevalence estimates vary, with reports as high as 19% among lower-limb amputees,3 and 13% in upper-limb amputees.4 Management is challenging and non-operative strategies are numerous.2, 5-8 Traditional surgical approaches, such as traction neurectomy or “burying” the nerve, aim to distance axonal sprouts from the cutaneous surface but do not prevent regeneration and recurrence.2, 5, 7, 9 Newer techniques address this limitation by giving the nerve not only “somewhere to go” but “something to do”, namely reinnervate.9, 10 These include targeted muscle reinnervation (TMR) where nerve ends are coapted to an adjacent motor nerve, as well as regenerative peripheral nerve interface (RPNI) where nerve ends are placed in muscle/dermal grafts.6,9 Both techniques are known to reduce residual-limb pain,7, 10-12 yet their impact on prosthesis use remains poorly understood. Pain is cited as a reason for prosthetic abandonment in 20% of patients with upper-limb amputation,13 and 62% of lower-limb amputees who do not return to work cite amputation/prosthesis-related problems.14 Prostheses are a known predictor for quality-of-life among lower-limb amputees,15 and are associated with survival benefit through increased physical activity.16 Understanding how TMR/RPNI influences prosthesis outcomes is therefore clinically important.
Design: A scoping review was conducted to examine prosthesis outcomes among amputees who have undergone TMR/RPNI for neuromas. The review was conducted following the Joanna Briggs Institute framework,17 and reported in accordance with PRISMA.18 The protocol was registered with Open Science Framework.19 A preliminary search was conducted on MEDLINE (OVID) in November 2024. The preliminary search informed the final search strategy and was used as a means of validation by confirming the presence of select studies. The search string was translated between databases by the first reviewer and validated by an information specialist. The final search was conducted in January 2025 across MEDLINE (OVID), EMBASE (OVID), CINAHLS Plus (EBSCO), Cochrane Library, and Web of Science. The search yielded 783 results. Two reviewers pilot screened ten abstracts (70% inter-screener reliability) and ten full-texts (80% inter-screener reliability) prior to screening all records against pre-specified inclusion and exclusion criteria. Discrepancies were resolved through discussion and input from a senior reviewer as required. An ascendancy approach was used to assess citation lists of select articles. Data extraction and synthesis was performed by the first reviewer and validated by the second reviewer with input from senior reviewers as required. Data extraction items were determined a priori.
Results: Nineteen studies were included. Thirteen studies provided information regarding pre- and post-operative prosthesis use.7, 12, 20-30 Eleven studies demonstrated positive interval change, such as initiation of prosthesis, increased number of prosthesis users, and increased frequency of use.7, 12, 20-24, 26, 28-30 Two studies indicated no interval change.25, 27 There was a dearth of data regarding the timing of prosthetic initiation post-operatively. Five studies described device type pre-operatively: myoelectric (n=2),22, 28 body-powered (n=1),24 “hybrid” (n=1),20 and both passive and myoelectric devices (n=1).27 Ten studies reported device type post-operatively - nine exclusively described myoelectric prostheses.20, 22, 24, 26-28, 30-32 Souza et al. described 23 of 26 patients using myoelectric prostheses, and 3 of 26 body-powered. It was unclear which of these patients underwent TMR for the purpose of neuroma pain rather than myoelectric control.7 Only two studies described the experience of prosthesis use. Chon et al. described post-operative ambulation of 30 minutes in a lower-extremity prosthetic user,21 and Rivedal et al. described the ability to wear an upper-extremity prosthesis for greater than 12 hours per day.26 Reasons for lack of prosthetic use post-operatively were not explicitly stated, however three studies discussed wound healing concerns post-operatively.12, 22, 33 Souza et al. described brachial plexopathy and financial challenges as barriers, though it was unclear which related specifically to patients pursuing TMR for neuroma pain.7
Conclusion: The scoping review suggests an overall increase in prosthesis use after TMR/RPNI, particularly myoelectric devices. Conceptually, these findings align with expectation given: 1) pain is an established barrier to prosthetic use and TMR/RPNI reduce neuroma pain;7, 10-13 2) these surgeries were originally developed to enhance control via myoelectric devices.34, 35 However, interpretation is guarded due to variable and limited follow-up which may underestimate eventual prosthetic rejection rates,36 and by lack of device type reporting in many studies. Furthermore, prosthesis use is nuanced as patients are advised to rotate between device types, and abandonment can involve factors extrinsic to the prosthesis.36, 37 Second, minimal guidance was available regarding timing of post-operative prosthesis initiation among included studies, and contrarian advice is present within the literature. For example, recommendations post-TMR include: immediate terminal-end device, delayed fitting at four-to-six weeks, or at three-to-six months.38-42 Formalized guidance is thus required to standardize care and support patients given that realistic expectations surrounding rehabilitation can lead to greater prosthesis acceptance.37 Third, only nineteen studies were included in the scoping review, likely reflecting the relative novelty of TMR/RPNI. Potential barriers may include limited awareness, variable adoption, and procedural cost compared to traditional approaches.43-45 The surgical landscape is also evolving with the advent of a combined procedure involving vascularized denervated muscle grafts placed at the site of TMR coaptation.9, 46, 47 Fourth, it is noted that surgeons may be less likely to recommend surgery for phantom-limb pain,43 despite the physiological overlap and difficulty distinguishing neuroma from phantom-limb pain.48, 49 As our understanding of these discrete categories continues to grow, recommended treatment approaches may evolve in conjunction. Limitations of this review include: overrepresentation of middle-aged males in case reports/series, upper-extremity and traumatic amputations, and TMR procedures; multiple surgical indications rather than neuroma pain exclusively; and co-interventions (e.g., osseointegration) that could potentially impact outcomes. Additionally, machine learning was used for translation and may have introduced interpretive errors. Overall, findings of this scoping review suggest that TMR/RPNI may enhance prosthesis use, particularly with upper-extremity myoelectric devices; however larger, well-designed studies with standardized prosthetic outcome reporting are needed. A clearer understanding of prosthesis wear patterns post-TMR/RPNI may support development of consistent, evidence-based surgical and rehabilitation protocols to ultimately improve patient comfort, function, and long-term prosthesis acceptance.
Has this work previously been presented or published? Presentations:
July 21 2025 - Sunnybrook Research Institute Research Day, Sunnybrook Health Sciences Centre, Toronto, Canada. December 5 2025 - Bionic Limb Reconstruction Symposium, Medical University of Vienna, Vienna, Austria.
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References for abstract:
Neumeister, M. W., & Winters, J. N. (2020). Neuroma. Clinics in Plastic Surgery, 47(2), 279–283. https://doi.org/10.1016/j.cps.2019.12.008
Peters, B. R., Russo, S. A., West, J. M., Moore, A. M., & Schulz, S. A. (2020). Targeted muscle reinnervation for the management of pain in the setting of major limb amputation. SAGE Open Medicine, 8, 2050312120959180. https://doi.org/10.1177/2050312120959180
Huang, Y. J., Assi, P. E., Drolet, B. C., Al Kassis, S., Bastas, G., Chaker, S., Manzanera Esteve, I. V., Perdikis, G., & Thayer, W. P. (2022). A Systematic Review and Meta-analysis on the Incidence of Patients With Lower-Limb Amputations Who Developed Symptomatic Neuromata in the Residual Limb. Annals of Plastic Surgery, 88(5), 574–580. https://doi.org/10.1097/SAP.0000000000002946
Chaker, S. C., Hung, Y.-C., Saad, M., Cardenas, D., Perdikis, G., & Thayer, W. P. (2024). Systematic Review and Meta-Analysis of Global Neuroma Incidence in Upper Extremity Amputees. Annals of Plastic Surgery, 92(1), 80–85. https://doi.org/10.1097/SAP.0000000000003742
Eberlin, K. R., & Ducic, I. (2018). Surgical Algorithm for Neuroma Management: A Changing Treatment Paradigm. Plastic and Reconstructive Surgery – Global Open, 6(10), e1952. https://doi.org/10.1097/GOX.0000000000001952
Ives, G. C., Kung, T. A., Nghiem, B. T., Ursu, D. C., Brown, D. L., Cederna, P. S., & Kemp, S. W. P. (2018). Current State of the Surgical Treatment of Terminal Neuromas. Neurosurgery, 83(3), 354–364. https://doi.org/10.1093/neuros/nyx500
Souza, J. M., Cheesborough, J. E., Ko, J. H., Cho, M. S., Kuiken, T. A., & Dumanian, G. A. (2014). Targeted muscle reinnervation: A novel approach to postamputation neuroma pain. Clinical Orthopaedics and Related Research, 472(10), 2984–2990. https://doi.org/10.1007/s11999-014-3528-7
Stokvis, A., van der Avoort, D.-J. J. C., van Neck, J. W., Hovius, S. E. R., & Coert, J. H. (2010). Surgical management of neuroma pain: A prospective follow-up study. PAIN®, 151(3), 862–869. https://doi.org/10.1016/j.pain.2010.09.032
Leach, G. A., Dean, R. A., Kumar, N. G., Tsai, C., Chiarappa, F. E., Cederna, P. S., Kung, T. A., & Reid, C. M. (2023). Regenerative Peripheral Nerve Interface Surgery: Anatomic and Technical Guide. Plastic and Reconstructive Surgery. Global Open, 11(7), e5127. https://doi.org/10.1097/GOX.0000000000005127
Dumanian, G. A., Potter, B. K., Mioton, L. M., Ko, J. H., Cheesborough, J. E., Souza, J. M., Ertl, W. J., Tintle, S. M., Nanos, G. P., Valerio, I. L., Kuiken, T. A., Apkarian, A. V., Porter, K., & Jordan, S. W. (2019). Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Annals of Surgery, 270(2), 238. https://doi.org/10.1097/SLA.0000000000003088
Hooper, R. C., Cederna, P. S., Brown, D. L., Haase, S. C., Waljee, J. F., Egeland, B. M., Kelley, B. P., & Kung, T. A. (2020). Regenerative Peripheral Nerve Interfaces for the Management of Symptomatic Hand and Digital Neuromas. Plastic and Reconstructive Surgery. Global Open, 8(6), e2792. https://doi.org/10.1097/GOX.0000000000002792
Woo, S. L., Kung, T. A., Brown, D. L., Leonard, J. A., Kelly, B. M., & Cederna, P. S. (2016). Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. Plastic and Reconstructive Surgery. Global Open, 4(12), e1038. https://doi.org/10.1097/GOX.0000000000001038
McFarland, L. V., Winkler, S. L. H., Heinemann, A. W., Jones, M., & Esquenazi, A. (2010). Unilateral upper-limb loss: Satisfaction and prosthetic-device use in veterans and servicemembers from Vietnam and OIF/OEF conflicts. The Journal of Rehabilitation Research and Development, 47(4), 299. https://doi.org/10.1682/jrrd.2009.03.0027
Fisher, K., Hanspal, R. S., & Marks, L. (2003). Return to work after lower limb amputation: International Journal of Rehabilitation Research, 26(1), 51–56. https://doi.org/10.1097/01.mrr.0000054806.81886.d7
Asano, M., Rushton, P., Miller, W. C., & Deathe, B. A. (2008). Predictors of quality of life among individuals who have a lower limb amputation. Prosthetics and Orthotics International, 32(2), 231–243. https://doi.org/10.1080/03093640802024955
Singh, R. K., & Prasad, G. (2016). Long-term mortality after lower-limb amputation. Prosthetics and Orthotics International, 40(5), 545–551. https://doi.org/10.1177/0309364615596067
Peters, M. D. J., Godfrey, C., McInerney, P., Khalil, H., Larsen, P., Marnie, C., Pollock, D., Tricco, A. C., & Munn, Z. (2022). Best practice guidance and reporting items for the development of scoping review protocols. JBI Evidence Synthesis, 20(4), 953. https://doi.org/10.11124/JBIES-21-00242
Rethlefsen, M. L., Kirtley, S., Waffenschmidt, S., Ayala, A. P., Moher, D., Page, M. J., Koffel, J. B., Blunt, H., Brigham, T., Chang, S., Clark, J., Conway, A., Couban, R., de Kock, S., Farrah, K., Fehrmann, P., Foster, M., Fowler, S. A., Glanville, J., … PRISMA-S Group. (2021). PRISMA-S: An extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. Systematic Reviews, 10(1), 39. https://doi.org/10.1186/s13643-020-01542-z
Saini, J., Yang, B., Mayo, A. (2025). Prosthetic use among amputees following TMR/RPNI for symptomatic neuromas: A scoping review. https://doi.org/10.17605/OSF.IO/7HGZK
Cheesborough, J. E., Smith, L. H., Kuiken, T. A., & Dumanian, G. A. (2015). Targeted muscle reinnervation and advanced prosthetic arms. Seminars in Plastic Surgery, 29(1), 62–72. https://doi.org/10.1055/s-0035-1544166
Chon, J., Franco, M. P., Luo, J., Vandevender, D., & Agnew, S. (2024). Targeted Muscle Reinnervation for a Symptomatic Neuroma in a Traumatic Transmetatarsal Amputee: A Case Report. JBJS Case Connector, 14(3). https://doi.org/10.2106/JBJS.CC.23.00657
Ernst, J., Hahne, J. M., Markovic, M., Schilling, A. F., Lorbeer, L., Grade, M., & Felmerer, G. (2023). Combining Surgical Innovations in Amputation Surgery-Robotic Harvest of the Rectus Abdominis Muscle, Transplantation and Targeted Muscle Reinnervation Improves Myocontrol Capability and Pain in a Transradial Amputee. Medicina, 59(12), 2134. https://doi.org/10.3390/medicina59122134
Felder, J. M., Pripotnev, S., Ducic, I., Skladman, R., Ha, A. Y., & Pet, M. A. (2022). Failed Targeted Muscle Reinnervation: Findings at Revision Surgery and Concepts for Success. Plastic and Reconstructive Surgery. Global Open, 10(4), e4229. https://doi.org/10.1097/GOX.0000000000004229
Harnoncourt, L., Gstoettner, C., Laengle, G., Boesendorfer, A., & Aszmann, O. (2024). [Prosthetic Fitting Concepts after Major Amputation in the Upper Limb—An Overview of Current Possibilities]. Handchirurgie, Mikrochirurgie, Plastische Chirurgie, 56(1), 84–92. https://doi.org/10.1055/a-2260-9842
Morgan, E. N., Kyle Potter, B., Souza, J. M., Tintle, S. M., & Nanos, G. P. (2016). Targeted Muscle Reinnervation for Transradial Amputation: Description of Operative Technique. Techniques in Hand & Upper Extremity Surgery, 20(4), 166–171. https://doi.org/10.1097/BTH.0000000000000141
Rivedal, D. D., Guo, M., Sanger, J., & Morgan, A. (2021). Revision Targeted Muscle Reinnervation Improves Secondary Pain Insult in an Upper Extremity Amputee: A Case Report. Hand, 16(6), NP15–NP18. https://doi.org/10.1177/1558944721992467
Takagi, T., Ogiri, Y., Kato, R., Kodama, M., Yamanoi, Y., Nishino, W., Masakado, Y., & Watanabe, M. (2020). Selective motor fascicle transfer and neural-machine interface: Case report. Journal of Neurosurgery, 132(3), 825–831. https://doi.org/10.3171/2018.10.JNS181865
Vincitorio, F., Staffa, G., Aszmann, O. C., Fontana, M., Brånemark, R., Randi, P., Macchiavelli, T., & Cutti, A. G. (2020). Targeted Muscle Reinnervation and Osseointegration for Pain Relief and Prosthetic Arm Control in a Woman with Bilateral Proximal Upper Limb Amputation. World Neurosurgery, 143, 365–373. https://doi.org/10.1016/j.wneu.2020.08.047
Anderson, S. R., Gupta, N., Johnson, E. A., & Johnson, R. M. (2022). Disruption of targeted muscle reinnervation due to heterotopic ossification in an amputated lower extremity. BMJ Case Reports, 15(5), e249705. https://doi.org/10.1136/bcr-2022-249705
Vu, P. P., Vaskov, A. K., Irwin, Z. T., Henning, P. T., Lueders, D. R., Laidlaw, A. T., Davis, A. J., Nu, C. S., Gates, D. H., Gillespie, R. B., Kemp, S. W. P., Kung, T. A., Chestek, C. A., & Cederna, P. S. (2020). A regenerative peripheral nerve interface allows real-time control of an artificial hand in upper limb amputees. Science Translational Medicine, 12(533), eaay2857. https://doi.org/10.1126/scitranslmed.aay2857
Salminger, S., Sturma, A., Roche, A. D., Mayer, J. A., Gstoettner, C., & Aszmann, O. C. (2019). Outcomes, Challenges, and Pitfalls after Targeted Muscle Reinnervation in High-Level Amputees: Is It Worth the Effort? Plastic and Reconstructive Surgery, 144(6), 1037e–1043e. https://doi.org/10.1097/PRS.0000000000006277
Yin, H.-W., Feng, J.-T., Shen, Y.-D., Wang, Y.-S., Zhang, D.-G., & Xu, W.-D. (2021). Using posterior part of the deltoid muscle as receptor and quality control with intra-operative electrophysiological examination in targeted muscle reinnervation for high-level upper extremity amputees. Chinese Medical Journal, 134(9), 1129–1131. https://doi.org/10.1097/CM9.0000000000001261
Kang, N. V., Woollard, A., Michno, D. A., Al-Ajam, Y., Tan, J., & Hansen, E. (2022). A consecutive series of targeted muscle reinnervation (TMR) cases for relief of neuroma and phantom limb pain: UK perspective. Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS, 75(3), 960–969. https://doi.org/10.1016/j.bjps.2021.09.068
Kuiken, T. A., Dumanian, G. A., Lipschutz, R. D., Miller, L. A., & Stubblefield, K. A. (2004). The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthetics and Orthotics International, 28(3), 245–253. https://doi.org/10.3109/03093640409167756
Woo, S. L., Urbanchek, M. G., Cederna, P. S., & Langhals, N. B. (2014). Revisiting Nonvascularized Partial Muscle Grafts: A Novel Use for Prosthetic Control. Plastic and Reconstructive Surgery, 134(2), 344e. https://doi.org/10.1097/PRS.0000000000000317
Biddiss, E. A., & Chau, T. T. (2007). Upper limb prosthesis use and abandonment: A survey of the last 25 years. Prosthetics and Orthotics International, 31(3), 236–257. https://doi.org/10.1080/03093640600994581
Østlie, K., Lesjø, I. M., Franklin, R. J., Garfelt, B., Skjeldal, O. H., & Magnus, P. (2012). Prosthesis rejection in acquired major upper-limb amputees: A population-based survey. Disability and Rehabilitation: Assistive Technology, 7(4), 294–303. https://doi.org/10.3109/17483107.2011.635405
Chappell, A. G., Jordan, S. W., & Dumanian, G. A. (2020). Targeted Muscle Reinnervation for Treatment of Neuropathic Pain. Clinics in Plastic Surgery, 47(2), 285–293. https://doi.org/10.1016/j.cps.2020.01.002
Rogers, M. J., Daryoush, J. R., & Kazmers, N. H. (2022). Contemporary Review: Targeted Muscle Reinnervation for Foot and Ankle Applications. Foot & Ankle International, 43(12), 1595–1605. https://doi.org/10.1177/10711007221129990
Johnson, C. C., Loeffler, B. J., & Gaston, R. G. (2021). Targeted Muscle Reinnervation: A Paradigm Shift for Neuroma Management and Improved Prosthesis Control in Major Limb Amputees. The Journal of the American Academy of Orthopaedic Surgeons, 29(7), 288–296. https://doi.org/10.5435/JAAOS-D-20-00044
Bowen, J. B., Wee, C. E., Kalik, J., & Valerio, I. L. (2017). Targeted Muscle Reinnervation to Improve Pain, Prosthetic Tolerance, and Bioprosthetic Outcomes in the Amputee. Advances in Wound Care, 6(8), 261–267. https://doi.org/10.1089/wound.2016.0717
Ganesh Kumar, N., & Kung, T. A. (2021). Regenerative Peripheral Nerve Interfaces for the Treatment and Prevention of Neuromas and Neuroma Pain. Hand Clinics, 37(3), 361–371. https://doi.org/10.1016/j.hcl.2021.05.003
Létourneau, S. G., & Hendry, J. M. (2020). Managing Neuroma and Phantom Limb Pain in Ontario: The Status of Targeted Muscle Reinnervation. Plastic and Reconstructive Surgery. Global Open, 8(12), e3287. https://doi.org/10.1097/GOX.0000000000003287
Loewenstein, S. N., Cuevas, C. U., & Adkinson, J. M. (2022). Utilization of Techniques for Upper Extremity Amputation Neuroma Treatment and Prevention. Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS, 75(5), 1551–1556. https://doi.org/10.1016/j.bjps.2021.11.077
Zamore, Z., Yesantharao, P. S., Aravind, P., & Dellon, A. L. (2024). Economic Cost-Benefit Analysis of Nerve Implanted into Muscle versus Targeted Muscle Reinnervation versus Regenerative Peripheral Nerve Interface, for Treatment of the Painful Neuroma. Journal of Reconstructive Microsurgery, 40(8), 642–647. https://doi.org/10.1055/a-2273-3940
Kurlander, D., Wee, C., Chepla, K., Lineberry, K., Long, T., Gillis, J., Valerio, I., & Khouri, J. (2020). TMRpni: Combining Two Peripheral Nerve Management Techniques. Plastic and Reconstructive Surgery. Global Open, 8, e3132. https://doi.org/10.1097/GOX.0000000000003132
Valerio, I., Schulz, S. A., West, J., Westenberg, R. F., & Eberlin, K. R. (2020). Targeted Muscle Reinnervation Combined with a Vascularized Pedicled Regenerative Peripheral Nerve Interface. Plastic and Reconstructive Surgery Global Open, 8(3), e2689. https://doi.org/10.1097/GOX.0000000000002689
Watson, J., Gonzalez, M., Romero, A., & Kerns, J. (2010). Neuromas of the hand and upper extremity. The Journal of Hand Surgery, 35(3), 499–510. https://doi.org/10.1016/j.jhsa.2009.12.019
Tanner, N., & Ayalon, O. (2023). The neurobiology of targeted muscle reinnervation for post-amputation pain. Plastic and Aesthetic Research, 10(11). https://doi.org/10.20517/2347-9264.2022.95
