Use of the semi-quantitative test with terbutaline sulfate for the identification of anhidrosis in Quarter Horses used in vaquejada events

Utilização do teste semi-quantitativo com sulfato de terbutalina para identificação de anidrose em equinos da raça Quarto de Milha utilizados em provas de vaquejada

ABSTRACT:

Anhidrosis, characterized by the partial or total reduction in sweat production, is a relevant condition in equines living in tropical climates, particularly those engaged in physical activity. This study evaluated the prevalence of anhidrosis in Quarter Horses used in the vaquejada sport, utilizing the semi-quantitative sweat test with terbutaline sulfate. Sixty Quarter Horses of both sexes, actively competing, were included in the study. The experimental procedure involved the intradermal application of a saline control solution and seven serial dilutions of terbutaline sulfate, ranging from 100 mg/L to 10^-6 mg/L, at predefined points in the cervical region. After solution application, the injection sites were assessed over a minimum of 20 minutes to observe the response to the test. The analysis criterion was based on the intensity of sweating at each concentration, enabling the classification of animals as healthy, partially anhidrotic, or completely anhidrotic. The study revealed a significant prevalence (75%) of partial anhidrosis among Quarter Horses. The results underscore the importance of accurate diagnosis of partial anhidrosis to understand its impact on equine health and performance.

Key words:
anhidrosis; exercise; sweat glands; thermoregulation

RESUMO:

A anidrose, caracterizada pela redução parcial ou total da produção de suor é uma condição relevante em equinos em clima tropical, especialmente naqueles sob atividade física. O objetivo deste estudo foi avaliar a prevalência de anidrose em equinos da raça Quarto de Milha utilizados na modalidade vaquejada, utilizando o teste semiquantitativo de sudorese com sulfato de terbutalina. Foram utilizados 60 equinos da raça Quarto de Milha, de ambos os sexos, em plena atividade fisíca. O procedimento experimental consistiu na aplicação intradérmica de uma solução salina controle e sete diluições seriadas de sulfato de terbutalina, variando de 100 mg/L a 10^-6 mg/L, em pontos previamente definidos na região cervical. Após a aplicação das soluções, os pontos de injeção foram avaliados durante um período mínimo de 20 minutos para verificar a resposta ao teste. O critério de análise baseou-se na intensidade da sudorese em cada concentração, permitindo a classificação dos animais como saudáveis, com anidrose parcial ou com anidrose completa. O estudo mostrou uma prevalência significativa (75%) de anidrose parcial em equinos da raça Quarto de Milha. Os resultados reforçam a importância de um diagnóstico preciso da anidrose parcial para compreender seus impactos na saúde e desempenho dos equinos.

Palavras-chave:
anidrose; exercício; glândulas sudoríparas; termorregulação

INTRODUCTION

Sweating plays a critical role in thermoregulation and water balance in horses, particularly in hot climates or during intense physical exertion. The evaporation of sweat from the skin is the primary mechanism of heat dissipation in these animals, accounting for the elimination of approximately 70% of the metabolic heat generated during exercise (JENKINSON et al., 2006; SOUSA et al., 2022; KANG et al., 2023). This process is indispensable for preventing severe hyperthermia, a condition that can result in collapse, seizures, and even death (JENKINSON et al., 2007; ROSA et al., 2021; SOUSA et al., 2022).

Anhidrosis, characterized by the reduction or absence of sweating, severely impairs thermoregulation, leading to increased body temperature, discomfort, and decreased athletic performance. It represents a significant concern for animal welfare (JENKINSON et al., 2007). This condition can be classified into acute anhidrosis and chronic idiopathic anhidrosis. The acute form occurs in response to specific environmental factors, such as extreme heat stress, lack of acclimatization, and electrolyte imbalances. In contrast, chronic idiopathic anhidrosis is marked by recurrent episodes of sweat absence, often linked to genetic predisposition and independent of environmental factors (ROSA et al., 2021).

The disease is more prevalent in hot and humid climates and can be triggered by inadequate acclimatization or genetic predisposition. Although, previously associated with horses subjected to strenuous activities, studies have indicated that non-athletic animals may also be affected (WARNER & MAYHEW, 1982; HUBERT et al., 2002).

Horses with anhidrosis exhibit clinical signs such as prolonged tachypnea, hyperthermia, and the absence of sweat in response to appropriate stimuli. The typical progression involves an initial phase of profuse sweating, followed by gradual restriction to specific areas, including the neck, base of the ears, and under the saddle (JENKINSON et al., 2007).

Factors such as sudden climatic changes, heat stress, and genetic predisposition influence the development of anhidrosis. ROSA et al. (2021) emphasized that the condition can occur in horses acclimated to tropical climates as well as in those transferred from colder regions. Additionally, there is a significant association between chronic idiopathic anhidrosis and family history, particularly in breeds such as Quarter Horses, Paint Horses, Appaloosas, and Thoroughbreds.

The occurrence of anhidrosis in horses used for “vaquejada” (a traditional Brazilian equestrian sport) is often reported anecdotally within the equestrian community. However, diagnoses are frequently based solely on clinical observation of prolonged tachypnea and lack of sweating. In the field, veterinarians commonly rely on hormonal assays for diagnostic confirmation, often associating these clinical signs with suspected hypothyroidism.

The use of diagnostic tests with greater sensitivity and specificity, such as sweat stimulation tests, is rarely performed, either due to a lack of technical knowledge or the unavailability of specific drugs for such procedures. Given this scenario, this study investigated the occurrence of total or partial anhidrosis in vaquejada athlete horses in the state of Rio Grande do Norte.

MATERIALS AND METHODS

The study was conducted in the state of Rio Grande do Norte, Brazil, between August and November 2024, and included 60 Quarter Horses of both sexes, with a mean age of 8.49 ± 3.23 years, all in full physical activity and all born in the region where the study was carried out. Prior to testing, the owners were asked about their horses’ habitual sweating patterns and were requested to identify the body regions where sweating was most frequently observed. The tests were conducted at the animals’ home properties, and none of the horses had undergone routine exercise in the 24-48 hours preceding the examination. None of the evaluated horses were under pharmacological treatment at the time of the assessment; although, they received regular supplementation consisting of amino acids, electrolytes, and mineral salts. The diet included fresh grass, dry hay, and pelleted feed, with unrestricted access to drinking water.

The experimental procedure involved the intradermal application of a control saline solution and seven serial dilutions of terbutaline sulfate, ranging from 100 mg/L (positive control) to 10^-6 mg/L, at predetermined points on the lateral cervical region, either on the right or left side, according to the methodology described by MACKAY (2008). The positive control (PC) refers to an expected and well-established response to the administration of the sweat-stimulating agent, terbutaline sulfate, without any dilution factor. The PC is essential for validating the effectiveness of the procedure, ensuring that the test was performed correctly and that the stimulant used is active. The absence of sweating at the positive control point would indicate a technical error in the test rather than the presence of anhidrosis.

The application area was sanitized with an antiseptic solution prior to injection. Standardized volumes of 0.1 mL per point were administered, with regular spacing between injection sites. To ensure precision and minimize discomfort, 25G needles were used. The horses were not subjected to physical restraint, such as twitching or stocks, nor were they sedated. The only restraint applied was a halter, handled by caretakers familiar with the animals.

Following the application of the solutions, the injection sites were evaluated over a 20-minute period to assess the sudorific response. The analysis criteria were based on the intensity of sweating at each concentration, enabling the classification of horses as healthy, partially anhidrotic, or completely anhidrotic (Table 1).

Table 1
Classification of responses to the sweating test using intradermal terbutaline sulfate injection.

1. Absence of anhidrosis:	Animals showed a positive sweating response at all tested concentrations, with a dose-dependent intensity.
2. Partial anhidrosis:	Limited sweating response, present only at higher concentrations (10-1 to 10-4 mg/L), and may be absent at lower concentrations (≤10-6 mg/L).
3. Complete anhidrosis:	No sweating response observed at any concentration of terbutaline sulfate tested.

In healthy horses, focal sweating was observed at all concentrations of terbutaline sulfate except at the saline control site (Figure 1), with intensity following a dose-dependent pattern, being more pronounced at higher concentrations. In completely anhidrotic horses, no sweating response was observed at any tested concentration. In cases of partial anhidrosis (Figure 2), sweating was restricted to higher concentrations and reduced or absent at intermediate and lower dilutions.

Figure 1
Anhidrosis test. Animal with a normal sweating response, characterized by the presence of perspiration at all evaluated points (CP: positive control; 10^-1 to 10^-6: serial dilutions of terbutaline sulfate), except at the negative control point, where 0.9% saline solution was used (CN). Note the more intense response in the positive control and higher dilutions.

Figure 2
Partial anhidrosis test. Animal with partial sweating response, evidenced by the presence of perspiration only at the points corresponding to the positive control (CP) and the 10^-1 and 10^-2 dilutions of terbutaline sulfate, with absence of response at the lower dilutions (10^-3 to 10^-6).

The saline control (physiological solution) served as a reference parameter for all horses. No sweating response was expected at this site, and any positive response was indicative of technical error or contamination. This control ensured the validity of the results obtained and allowed for precise identification of sweating alterations, reinforcing the reliability of the applied method.

The data obtained was exclusively subjected to descriptive statistical analysis, using frequency distribution to characterize and describe the observed results.

RESULTS

Regarding sex distribution, of the 60 horses evaluated, 32 were males, and 28 were females, indicating a slight predominance of males among the individuals analyzed in the study. Concerning bloodline classification, Purebred Quarter Horses predominated, accounting for 71.7% (n = 43) of the sample. Crossbred horses represented 26.7% (n = 16), while only one horse was classified as Appendix, corresponding to 1.6% (n = 1) of the analyzed population.

Among the tested animals, the response to the anhidrosis test, conducted with terbutaline dilutions, indicated some degree of anhidrosis in 75% (45/60) of the horses, comprising 41.7% of the males (25 animals) and 33.4% of the females (20 animals). Conversely, 25% (15/60) exhibited normal responses to all terbutaline dilutions, representing 10% of the males (6 animals) and 15% of the females (9 animals).

Among the partially anhidrotic horses, 3 (6.67%) responded only up to the 10^-1 dilution, 10 (22.22%) up to the 10^-2 dilution, 11 (24.44%) up to the 10^-3 dilution, 9 (20%) up to the 10^-4 dilution, and 12 (26.67%) up to the 10^-5 dilution.

In 100% of the animals classified as having partial anhidrosis, the owners reported that after exercise periods, sweating was restricted to the areas at the base of the ears, neck, and under the saddle, corroborating the clinical findings observed during the sweating test with terbutaline sulfate.

Table 2 presents the distribution of positive results according to the bloodline classification of the horses, showing that the highest prevalence of positive responses was observed among purebred horses.

Table 2
Results of animals positive for partial anhidrosis according to bloodline.

Bloodline	Number	Frequency (%)
Purebred Quarter Horse	32	71.2
1/2 Quarter Horse crossbreed	10	22.2
3/4 Quarter Horse crossbred	2	4.4
7/8 Quarter Horse crossbred	1	2.2
Total	45	100%

DISCUSSION

Anhidrosis is the loss of the ability to sweat in response to appropriate stimuli (BREUHAUS, 2009). A poorly understood disease in horses, idiopathic anhidrosis has been reported to affect 2% of the equine population in Florida (JOHNSON et al., 2010). However, reports of its occurrence in Brazil are scarce.

BASHIR & RASEDEE (2009) studied the prevalence of anhidrosis in horses living in hot climates and its relationship with physical performance and heat stress. The study indicated that anhidrosis primarily occurs in regions with hot and humid climates and is frequently associated with intensely trained horses, findings similar to those of the present study. The research also highlighted that the disease’s prevalence is not influenced by breed, age, or sex but rather by the genetic predisposition of the animals. It is worth noting that; although, all animals in this study belonged to the Quarter Horse breed, this does not necessarily imply a racial predisposition, as the Quarter Horse is the predominant breed used in rodeo events.

Although, both studies present a significant prevalence of partial anhidrosis in horses, the research by BASHIR & RASEDEE (2009) focused mainly on the disease’s relationship with acclimatization and heat stress. It is important to highlight that, despite the inference by BASHIR & RASEDEE (2009) that anhidrosis is an acclimatization-related issue, the present study predominantly involved animals born in the Northeastern region of Brazil, where most of the equine population is exposed to a hot climate. This factor could influence both the prevalence and the underlying mechanisms of the disease.

The results obtained in this study contrast with the findings reported by RASHEED et al. (2010) in a population of 290 horses in Pakistan. While this study, using a semiquantitative anhidrosis test, found a prevalence of 75%, RASHEED et al. (2010) reported a prevalence of 12.41%, based solely on clinical signs for diagnosis. This discrepancy may be attributed to the sensitivity and specificity of the method used for detecting anhidrosis. The semiquantitative sweating test with terbutaline sulfate, employed in the present study, is more sensitive and specific, allowing for a more precise detection of the condition, particularly in cases where clinical signs may be less evident or atypical. This approach provides a more reliable diagnostic tool, enabling the identification of subclinical cases or those with less pronounced signs, which could be overlooked in diagnoses based solely on clinical observation.

There is a widespread belief among breeders, owners, and professionals that anhidrosis is associated with the acclimatization of animals originating from temperate climates. However, the results of the present study refute this hypothesis, as only three of the evaluated animals were from the Southeastern region, while the remaining horses were born in the region where the research was conducted. This finding suggested that the problem is not solely restricted to climatic adaptation.

The study by MAYHEW & FERGUSON (1987) on anhidrosis complements this analysis, showing that/ although, the disease is often observed in regions with hot and humid climates, it also affects native horses. This data reinforces the idea that anhidrosis is not exclusively related to the acclimatization of animals from temperate climates, as suggested by BASHIR & RASEDEE (2009), but instead to multifactorial factors such as heat stress, genetics, and possibly alterations in the endocrine system and energy metabolism of affected horses.

Furthermore, the study by MAYHEW & FERGUSON (1987) points out that intensely trained horses, especially those engaged in high-performance activities such as racing or physically demanding work, are more susceptible to anhidrosis, although, a small proportion of affected horses are directly involved in performance activities. While the findings of this study align with this observation, it should be noted that only athletic horses were evaluated.

ROSA et al. (2021) conducted a genome-wide association study (GWAS) that revealed specific variants associated with anhidrosis in horses, such as the KCNE4 gene, which regulates potassium currents and plays a critical role in the cellular function of sweat glands. The identification of the nonsynonymous variant rs68643109, which alters the protein structure of the potassium channel β-subunit, highlights a potential genetic cause of anhidrosis. This suggested that alterations in this channel may impair the function of sweat glands in horses. These findings support the hypothesis of genetic predisposition in the disease’s etiology, suggesting that the results of the present study are linked to the higher susceptibility of Quarter Horses to anhidrosis, especially in tropical and subtropical climates.

The results of an epidemiological analysis conducted in Florida revealed a strong association between a family history of anhidrosis and the risk of developing the condition (JOHNSON et al., 2010). In two separate analyses, horses with a family history of anhidrosis were nearly seven times more likely to develop compared to those without such a history.

The study by MACKAY (2008) revealed that the sweating test using terbutaline injection, a sudorific agent, is an effective method for diagnosing total or partial anhidrosis in horses. The intradermal injection of terbutaline promotes a measurable increase in sweating in healthy horses, and the absence of this response at certain concentrations can indicate the presence of anhidrosis, particularly at higher concentrations of terbutaline.

In the context of the present study, which employed a semiquantitative test, we observed that the terbutaline-based approach proposed by MACKAY (2008) could add value to the investigation of anhidrosis in horses by providing a more precise assessment of sweat intensity in response to the sudorific agent. Additionally, MACKAY (2008) demonstrated the method’s safety, with no significant adverse effects observed, reinforcing its feasibility for use in anhidrosis investigations in horses.

This study is pioneering in investigating the prevalence of anhidrosis in horses in Brazil, particularly in a specific hot and/or humid climate scenario, such as that of the Northeastern region. Although, there have been reports of the condition affecting horses from the region, this is the first to provide an analysis of its prevalence in a specific population of Brazilian horses, contributing to the understanding of the disease in a regional context. However, the main limitation of this study was the low number of animals evaluated. Additionally, the use of athletic horses overemphasizes the prevalence of anhidrosis in animals under athletic training, which does not allow for a comparison with non-athletic animals. A future study evaluating both athletic and non-athletic animals would provide a more comprehensive understanding of the prevalence and risk factors associated with anhidrosis. The findings presented here will serve as a foundation for future studies, expanding the knowledge about anhidrosis in horses and enabling the development of more effective management strategies for controlling and preventing this condition in intensively trained animals.

CONCLUSION

The results of the present study indicated that anhidrosis can affect horses native to hot climates and is not restricted to animals originating from temperate regions, challenging previous conceptions regarding its etiology and prevalence.

ACKNOWLEDGMENTS

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasil - Finance code 001.

REFERENCES

• BASHIR, A.; RASEDEE, A. Plasma catecholamines, sweat electrolytes and physiological responses of exercised normal, partial anhidrotic and anhidrotic horses. American Journal of Animal and Veterinary Sciences, v.4, n.1, p.26-31, 2009. Available from: <Available from: https://scidoc.thescipub.com/pdf/ajavsp.2009.26.31.pdf >. Accessed: Nov. 20, 2024. doi: 10.3844/ajavsp.2009.26.31.
  » https://doi.org/10.3844/ajavsp.2009.26.31.» https://scidoc.thescipub.com/pdf/ajavsp.2009.26.31.pdf
• BREUHAUS, B. A. Thyroid function in anhidrotic horses. Journal of Veterinary Internal Medicine, v.23, n.1, p.168-173, 2009. Available from: <Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2008.0217.x >. Accessed: Nov. 18, 2024. doi: 10.1111/j.1939-1676.2008.0217.x.
  » https://doi.org/10.1111/j.1939-1676.2008.0217.x.» https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2008.0217.x
• HUBERT, J. D. et al. Equine anhidrosis. Veterinary Clinics of North America: Equine Practice, v.18, n.2, p.355-369, 2002. Available from: <Available from: https://www.vetequine.theclinics.com/article/S0749-0739(02)00016-0/abstract >. Accessed: Nov. 03, 2024. doi: 10.1016/s0749-0739(02)00016-0.
  » https://doi.org/10.1016/s0749-0739(02)00016-0.» https://www.vetequine.theclinics.com/article/S0749-0739(02)00016-0/abstract
• JENKINSON, D. M. et al. Equine sweating and anhidrosis Part 1: equine sweating. Veterinary Dermatology, v.17, n.6, p.361-392, 2006. Available from: <Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-3164.2006.00545.x >. Accessed: Oct. 15, 2024. doi: 10.1111/j.1365-3164.2006.00545.x.
  » https://doi.org/10.1111/j.1365-3164.2006.00545.x.» https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-3164.2006.00545.x
• JENKINSON, D. M. et al. Equine sweating and anhidrosis Part 2: anhidrosis. Veterinary Dermatology, v.18, n.1, p.2-11, 2007. Available from: <Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-3164.2007.00571.x?msockid=1e05ebbad3bb62d917befeffd2ea63db >. Accessed: Oct. 15, 2024. doi: 10.1111/j.1365-3164.2007.00571.x.
  » https://doi.org/10.1111/j.1365-3164.2007.00571.x.» https://onlinelibrary.wiley.com/doi/10.1111/j.1365-3164.2007.00571.x?msockid=1e05ebbad3bb62d917befeffd2ea63db
• JOHNSON, E. B. et al. An epidemiologic study of anhidrosis in horses in Florida. Journal of the American Veterinary Medical Association, v.236, n.10, p.1091-1097, 2010. Available from: <https://pubmed.ncbi.nlm.nih.gov/20470071/>. Accessed: doi: 10.2460/javma.236.10.1091.
  » https://doi.org/10.2460/javma.236.10.1091.» https://pubmed.ncbi.nlm.nih.gov/20470071/
• KANG, H. et al. Heat stress in horses: a literature review. International Journal of Biometeorology, v.67, n.6, p.957-973, 2023. Available from: <Available from: https://link.springer.com/article/10.1007/s00484-023-02467-7 >. Accessed: Oct. 08, 2024. doi: 10.1007/s00484-023-02467-7.
  » https://doi.org/10.1007/s00484-023-02467-7.» https://link.springer.com/article/10.1007/s00484-023-02467-7
• MACKAY, R. J. Quantitative intradermal terbutaline sweat test in horses. Equine Veterinary Journal, v.40, n.5, p.518-520, 2008. Available from: <Available from: https://beva.onlinelibrary.wiley.com/doi/abs/10.2746/042516408X322409 >. Accessed: Oct. 08, 2024. doi: 10.2746/042516408X322409.
  » https://doi.org/10.2746/042516408X322409.» https://beva.onlinelibrary.wiley.com/doi/abs/10.2746/042516408X322409
• MAYHEW, I. G.; FERGUSON, H. O. Clinical, clinicopathologic, and epidemiologic features of anhidrosis in central Florida Thoroughbred horses. Journal of Veterinary Internal Medicine, v.1, n.3, p.136-141, 1987. Available from: <Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1939-1676.1987.tb02001.x?msockid=1e05ebbad3bb62d917befeffd2ea63db >. Accessed: Oct. 08, 2024. doi: 10.1111/j.1939-1676.1987.tb02001.x.
  » https://doi.org/10.1111/j.1939-1676.1987.tb02001.x.» https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1939-1676.1987.tb02001.x?msockid=1e05ebbad3bb62d917befeffd2ea63db
• RASHEED, S. U. et al. A study on prevalence and treatment of anhidrosis in horses. Journal of Animal & Plant Sciences, v.20, n.1, p.70-72, 2010. Available from: <Available from: https://www.researchgate.net/publication/262561578_A_study_on_prevalence_and_treatment_of_anhidrosis_in_horses >. Accessed: Nov. 30, 2024.
  » https://www.researchgate.net/publication/262561578_A_study_on_prevalence_and_treatment_of_anhidrosis_in_horses
• ROSA, L. et al. Genomic Association of Chronic Idiopathic Anhidrosis to a Potassium Channel Subunit in a Large Animal Model. The Journal of Investigative dermatology, v.141, n.11, p.2639-2645, 2021. Available from: <Available from: https://www.jidonline.org/article/S0022-202X(21)01307-5/pdf >. Accessed: Oct. 08, 2024. doi: 10.1016/j.jid.2021.05.014.
  » https://doi.org/10.1016/j.jid.2021.05.014.» https://www.jidonline.org/article/S0022-202X(21)01307-5/pdf
• SOUSA, R. F. et al. Aspectos fisiológicos da termorregulação em equinos. Revista Brasileira de Medicina Equina, v.103, n.1, p.16-20, 2022. Available from: <Available from: https://www.researchgate.net/publication/364301409_Aspectos_fisiologicos_da_termor regulacao_em_equinos >. Accessed: Nov. 23, 2024.
  » https://www.researchgate.net/publication/364301409_Aspectos_fisiologicos_da_termor regulacao_em_equinos
• WARNER, A. E.; MAYHEW, I. G. Equine anhidrosis: a survey of affected horses in Florida. Journal of the American Veterinary Medical Association, v.180, n.6, p.627-629, 1982.

BIOETHICS AND BIOSECURITY COMMITTEE APPROVAL

• CR-2025-0008.R1
• We authors of the article entitled “Use of the semi-quantitative test with terbutaline sulfate for the identification of anhidrosis in Quarter Horses used in vaquejada events” declared, for all due purposes, the project that gave rise to the present data has not been submitted for evaluation to the Ethics Committee of the Centro Universitário Maurício de Nassau, but we are aware of the content of the Brazilian resolutions of the Conselho Nacional de Controle de Experimentação Animal - CONCEA if it involves animals. Thus, the authors assume full responsibility for the presented data and are available for possible questions, should they be required by the competent authorities
• DATA AVAILABILITY STATEMENT
  Not applicable.
• DECLARATION OF USE OF ARTIFICIAL INTELLIGENCE
  Artificial intelligence tools were used to improve the quality of the manuscript.

Edited by

• ASSOCIATE EDITOR:
  Rudi Weiblen (0000-0002-1737-9817)

• SCIENTIFIC EDITOR:
  Gustavo Miranda Zanotto (0000-0001-8498-5246)

Data availability

Not applicable.

Publication Dates

• Publication in this collection
  17 Nov 2025
• Date of issue
  2026

History

• Received
  08 Jan 2025
• Accepted
  28 May 2025
• Reviewed
  18 Sept 2025