Reliability and Validity of the Arabic Version of the NOSE-Perf Scale

Summary

Objectives:

To assess the psychometric validity of the Arabic adaptation of the nasal obstruction symptom evaluation–perforation (NOSE-Perf) scale. To assess how reliable and valid the Arabic adaptation of the NOSE-Perf questionnaire is. Patients with septal perforations, particularly Arabic speakers, lack validated self-assessment tools for subjective symptom evaluation.

Methods:

Conducted between May 2024 and June 2025, the study included 100 participants—20 patients with septal perforation and 80 controls. Participants filled out a questionnaire consisting of demographic data as well as the Arabic forms of the Sino-Nasal Outcome Test-22 (SNOT-22), NOSE, and NOSE-Perf scales. Cronbach's alpha was applied to determine internal consistency, and the intraclass correlation coefficient (ICC) was utilized to verify test–retest reliability. Discriminative validity was evaluated by comparing score differences, while concurrent validity was analyzed through correlations with the NOSE and SNOT-22 scales.

Results:

Strong correlations were observed between the NOSE-Perf and the established NOSE (r = 0.920, p < 0.001) and SNOT-22 (r = 0.885, p < 0.001) measures, confirming the scale's concurrent validity. Discriminative validity was evident: NOSE-Perf scores were significantly higher in cases (29.8 ± 9.48) than controls (5.76 ± 8.10, p < 0.001; AUC = 0.856). NOSE scores also differed (cases: 68.1 ± 26.1; controls: 9.44 ± 21.9; p < 0.001; AUC = 0.931). SNOT-22 scores were 57.1 ± 24.2 in cases and 18.0 ± 18.4 in controls (p < 0.001; AUC = 0.32).

Conclusion:

The Arabic adaptation of the NOSE-Perf questionnaire exhibited reliability and validity as a tool for assessing subjective symptoms among individuals experiencing septal perforation.

Introduction

A nasal septal perforation (NSP) refers to a full-thickness defect of the nasal septum, the structure that separates the right and left nasal passages [1]. Globally, the prevalence of NSP is very low in the general community, but higher numbers have been observed in rhinology practice [2]. Data indicate that reports of septal perforations make up only approximately 1% of cases of nasal disorders and can be observed more frequently in patients who have undergone previous nasal injuries, surgeries, or drug abuse [2]. Etiologic factors can be traumatic, iatrogenic, infectious, inflammatory, autoimmune, and neoplastic [3]. The manifestations of nasal septal perforations may vary depending on the size and location of the defects. Common symptoms include nasal obstruction or congestion, epistaxis, nasal scabbing and dryness, whistling sounds during breathing, and foul-smelling nasal secretions.

Additionally, patients may experience an itching sensation, congestion in the nasal area, or pain in that region [1]. The treatment of NSP depends on the size and extent of the defects and, more importantly, on the patient's complaints [4]. Treatment options include observation. Stabilization of small perforations that do not cause any apparent clinical symptoms is not necessarily an indication for active surgical intervention [4]. Conservative management: Such measures include the use of saline drops, nasal ointments, and humidifiers or prosthesis placement to alleviate the sensations of dryness and crusting in the nasal passage [4]. Surgical Management, including septal perforation repair (SPT) using local flaps, is considered in cases of significant or symptomatic perforation [4, 5]. Evaluating the extent to which interventions improve the well-being of individuals with nasal septal perforation (NSP) is essential for determining their therapeutic efficacy and overall impact on patients' daily lives. Questionnaires can help quantify the extent of the symptom impact and how these symptoms interfere with daily activities, psychological health, and satisfaction with nasal function. The NOSE-Perf instrument was developed to assess the clinical outcomes of patients presenting with septal perforations [6]. The present study focused on validating and testing the reliability of the Arabic-translated version of the NOSE-Perf tool.

Methods

A prospective cohort design was used to investigate whether the Arabic NOSE-Perf questionnaire is a valid assessment tool. We recruited consecutive adult patients (≥18 years) diagnosed with septal perforation confirmed by nasal endoscopic examination (cases) in our rhinology clinic. We recruited respondents without nasal symptoms as the control group. The research was carried out at a leading tertiary medical center in Riyadh, Saudi Arabia, identified as King Fahad Medical City. All patients with septal perforation listed in the data registry of electronic health records were recruited for the study from September 2024 to May 2025, provided they met the inclusion criteria. Prior to data collection, ethical permission was granted by the College of Medicine's Institutional Review Board at King Saud University, Riyadh, Kingdom of Saudi Arabia. Prior to enrollment, each participant was provided with a detailed description of the study's purpose and methodology, and verbal consent was obtained. After consenting, they received an electronic link to the questionnaire, which they completed independently.

Participants filled out the Arabic NOSE-Perf questionnaire along with the Arabic versions of the SNOT-22 and NOSE scales to assess convergent validity. Demographic information was also collected, including age, sex, comorbidities, and septal perforation etiology. A subset of the patients completed the NOSE-Perf questionnaire again after 1–2 weeks for test–retest reliability assessment.

Validation of the NOSE-Perf scale

Translation process

We strictly followed established validation procedures from the literature to ensure effective cultural adaptation while validating the Arabic version of the NOSE-Perf questionnaire [7]. The translation from English to Arabic was executed by professional linguists who are native speakers of Arabic. Following an assessment of the translated version, modifications were implemented to better reflect the cultural setting. The Arabic questionnaire was subsequently translated back into English, and bilingual experts compared each item to the original NOSE-Perf scale to confirm that the meaning was maintained. Final approval was obtained after receiving input from senior authors. Fig. 1 illustrates the Arabic adaptation of the questionnaire.

Fig. 1.

Arabic version of the NOSE-Perf questionnaire.

Sino-Nasal Outcome Test-22

The SNOT-22 is an extensively used patient-reported questionnaire designed to evaluate how sinonasal disorders affect quality of life [8]. It consists of 22 questions covering nasal and non-nasal symptoms associated with chronic rhinosinusitis and other nasal disorders [8]. Patients rated each symptom on a scale from 0 (no problem) to 5 (as bad as possible). Participant responses were summed to calculate a composite index ranging from 0 to 110. Higher values corresponded to increased nasal symptom burden and poorer health status. A change of 8.9 points or more is considered clinically meaningful [8]. Although there is no universal cutoff, the scores are often interpreted as mild (8–20), moderate (21–50), or severe (51+) [8]. The SNOT-22 can also be divided into subscales for more detailed analysis, making it a versatile tool for assessing various aspects of sinonasal health both clinically and in research [8].

Nasal obstruction symptom evaluation scale

The NOSE instrument serves as a short, validated measure for quantifying the degree of nasal blockage [9]. Comprising five items, the scale uses a 0–4 rating system, with 0 signifying ‘no problem’ and 4 denoting a ‘severe problem’. These items evaluate nasal congestion, blockage, breathing difficulties, sleep disturbances, and air insufficiency during exercise. The total score was derived by adding the 5 item responses together and then multiplying the sum by 5, resulting in a range from 0 to 100. The scale interprets higher numerical values as representing progressively worse nasal airflow limitation, grouped into four levels: mild (0–25), moderate (26–50), severe (51–75), and very severe (76–100) [9]. A change of 10 points or more is typically considered clinically meaningful. The NOSE scale's focused nature makes it particularly useful for evaluating outcomes in patients undergoing surgery for nasal obstruction, such as septoplasty or turbinate reduction, allowing for effective pre- and postoperative comparisons [9]. The NOSE scale has been utilized to evaluate patient symptoms both preoperatively and postoperatively in those undergoing septal perforation repair (STP) [10].

NOSE-Perf scale

Developed as a condition-focused instrument, the NOSE-Perf scale is intended to assess symptoms linked to nasal septal perforation (NSP) [6]. It builds on the widely used NOSE scale by incorporating seven additional items related to NSP symptoms. The NOSE-Perf questionnaire consists of 12 items, each evaluated on a 5-point scale (0–4). The cumulative score, which ranges from 0 to 48, reflects the overall severity of nasal symptoms, with higher scores representing greater symptom burden. The NOSE-Perf scale proved dependable, exhibiting solid internal reliability and consistent results upon retesting, while successfully distinguishing subjects presenting nasal complaints from those without such symptoms [6].

Factor analysis

The structure of the NOSE-Perf instrument was evaluated using exploratory factor analysis. Factor extraction was performed using maximum likelihood with promax rotation. Factors were considered for retention if their eigenvalues were above 1, and any items with factor loadings equal to or above 0.4 were deemed significant (Hair, 2009) [11]. Cronbach's alpha was calculated to evaluate internal consistency, and coefficients equal to or exceeding 0.7 were regarded as satisfactory for research purposes (Cronbach, 1951) [12]. Item–total correlations were calculated, and coefficients of 0.3 or greater were regarded as acceptable. The structural validity of the model was examined via confirmatory factor analysis, employing standard goodness-of-fit indices and their reference limits. (Hu & Bentler, 1999): [13] Following the initial CFA, indices were examined to improve the model. Error covariances were specified between three theoretically justified item pairs that shared similar symptom domains or measurement characteristics, allowing these items to covary beyond their relationship with the latent factors. This approach is consistent with established SEM practices when items share method variance or content overlap (Brown, 2015) [14].

Convergent and discriminant validity

Calculation of Pearson correlation coefficients between NOSE-Perf scores and the scores from the SNOT-22 and NOSE instruments was performed to assess convergent validity. Correlations ranging from 0.4 to 0.7 were interpreted as moderate, whereas values exceeding 0.7 indicated strong relationships. The ability of the NOSE-Perf scale to differentiate clinical cases from controls was investigated through analysis of mean score differences and receiver operating characteristic (ROC) curve evaluation, which quantified the measure's discriminative accuracy. Differences in NOSE-Perf scores between the two groups were analyzed using unpaired t-tests. The area under the curve (AUC) was interpreted such that values of 0.7–0.8 reflected acceptable accuracy, 0.8–0.9 denoted excellent performance, and scores above 0.9 represented outstanding discriminatory ability.

Data analysis

R software (version 4.3) was applied for statistical analysis. The analysis summarized categorical variables as frequency counts and relative percentages, evaluated through chi-square testing. The central tendency of continuous data was described through mean values accompanied by their standard deviations (SD) or through medians with interquartile ranges (IQR), according to the normality pattern of the data. For normally distributed data, Pearson correlation coefficients were applied, while Spearman coefficients were used when normality assumptions were not satisfied. Group differences in NOSE-Perf outcomes were assessed using independent t-testing, while within-subject variations between baseline and follow-up scores were examined through paired t-test analysis. A probability value (p) of less than 0.05 denoted statistical significance.

Results

Descriptive analysis

The median age of participants with nasal septal perforation (NSP) was 30.0 years [IQR: 27.5–33.0]. Females accounted for 60% (n = 12) of the sample, while males represented 40% (n = 8). The most commonly reported cause of perforation was iatrogenic (55%, n = 11), followed by idiopathic causes (35%, n = 7) and traumatic causes (10%, n = 2). Regarding comorbidities, 25.0% (n = 5) reported at least one condition. Perforation size data showed a median length of 1.50 cm [1.15–2.00] (n = 20) and a mean width of 1.70 ± 0.38 cm (n = 17). In terms of size categories (n = 20), medium-sized perforations (1–1.5 cm) were the most prevalent (40%, n = 8), followed by large (1.5–2 cm, 30%, n = 6), small (<1 cm, 20%, n = 4), and very large (>2 cm, 10%, n = 2) as as presented in Table 1.

Table 1.

Participant demographics and initial clinical features.

Characteristic	All (n = 100)	Cases (n = 20)	Controls (n = 80)	P-value
Age, mean (SD)	28.9 (9.91)	31.1 (10.1)	28.4 (9.84)	0.281
Age group, n (%)				0.244
≤20	8 (8.0)	2 (10.0)	6 (7.5)
21–30	66 (66.0)	10 (50.0)	56 (70.0)
31–40	12 (12.0)	5 (25.0)	7 (8.8)
41–50	9 (9.0)	2 (10.0)	7 (8.8)
>50	5 (5.0)	1 (5.0)	4 (5.0)
Gender, n (%)				0.174
Female	44 (44.0)	12 (60.0)	32 (40.0)
Male	56 (56.0)	8 (40.0)	48 (60.0)
Comorbidities, n (%)	14 (14.0)	5 (25.0)	9 (11.2)	0.147
Hypertension	4 (4.0)	2 (10.0)	2 (2.5)	0.330
Diabetes mellitus	5 (5.0)	1 (5.0)	4 (5.0)	0.922
Asthma	2 (2.0)	1 (5.0)	1 (1.2)	0.410
Prior nasal surgery, n (%)	21 (21.0)	11 (55.0)	10 (12.5)	<0.001
Current medications, n (%)	24 (24.0)	1 (5.0)	23 (28.7)	0.037
Perforation characteristics (cases only)
Cause of perforation, n (%)
Iatrogenic	–	11 (55.0)	–
Idiopathic	–	7 (35.0)	–
Traumatic	–	2 (10.0)	–
Perforation size, n (%)
Small (<1 cm)	–	4 (20.0)	–
Medium (1–1.5 cm)	–	8 (40.0)	–
Large (1.5–2 cm)	–	6 (30.0)	–
Very large (>2 cm)	–	2 (10.0)	–

Values that reached statistical significance (p < 0.05) appear in boldface for clarity.

In the comparison between cases (n = 20) and controls (n = 80), most variables did not show statistically significant differences. Cases had a somewhat higher average age (31.1 ± 10.1 years) compared to controls (28.4 ± 9.84 years); Nevertheless, the observed difference did not attain statistical significance. (p = 0.281). Similarly, age group distribution (p = 0.244), gender (p = 0.174), overall comorbidity presence (p = 0.147), and specific conditions such as hypertension (p = 0.330), diabetes (p = 0.922), and asthma (p = 0.410) were not significantly different between groups. However, two variables showed significant group differences: prior nasal surgery was markedly more common in cases (55%) than in controls (12.5%) (p < 0.001), and current medication use was lower in cases (5%) than in controls (28.7%) (p = 0.037), as shown in Table 1.

Factor analysis

The factor analysis of the NOSE-Perf scale identified a structure comprising 2 components. The first factor encompassed items related to whistling sounds from the nose (0.79), nasal discharge or postnasal drip (0.86), epistaxis (0.69), unpleasant odor (0.78), nasal crusting (0.73), facial discomfort or headache (0.60), and reduced olfactory sense (0.53), with factor loadings ranging from 0.53 to 0.86. The second factor included nasal stuffiness (0.69), blockage or obstruction (0.84), difficulty in nasal breathing (0.87), disturbed sleep (0.70), and shortness of breath on exertion (0.79), with loadings between 0.69 and 0.87. The internal consistency was high, with Cronbach's alpha coefficients of 0.93 for Factor 1 and 0.94 for Factor 2, demonstrating strong reliability across both components (Table 2).

Table 2.

Outcomes of factor analysis for the NOSE-Perf questionnaire.

Factor analysis	Factor 1	Factor 2
Nasal congestion or stuffiness	0.49	0.69
Nasal blockage or obstruction	0.39	0.84
Trouble breathing through my nose	0.33	0.87
Trouble sleeping	0.34	0.70
Unable to get enough air through my nose during exercise or exertion	0.40	0.79
Trouble with crusting in my nose	0.73	0.36
Whistling from my nose	0.79	0.49
Bleeding from my nose	0.69	0.25
Facial pain or headache	0.60	0.47
Decreased sense of smell	0.53	0.38
A foul or odd smell in my nose	0.78	0.32
Runny nose or post-nasal drip	0.86	0.46
Cronbach's α	0.93	0.94

The confirmatory factor analysis revealed two well-defined factors with excellent reliability (α = 0.93–0.94). Factor 1 (Structural/Sensory Symptoms) showed strong loadings (0.80-0.97), while Factor 2 (Functional/Obstructive Symptoms) demonstrated consistent loadings (0.69-0.91). The significant inter-factor correlation (r = 0.79, p < 0.001) indicates that these symptom domains are strongly related, supporting a meaningful 2-factor structure that captures distinct yet interconnected dimensions of nasal symptom experience as shown in Fig. 2.

Fig. 2.

Underlying factor structure for NOSE-Perf. Numbers represent the standardized factor loadings (squares) for items and correlations for factors (circles).

The initial CFA was refined by allowing three pairs of items to covary based on modification indices and theoretical considerations. The refined model indicated acceptable fit: χ² = 93.32 (df = 50, p < 0.001), CFI = 0.964, TLI = 0.953, SRMR = 0.048. The RMSEA was 0.093 (90% CI: 0.063-0.122, p-close = 0.012). Kenny et al (2015) [15] demonstrated that RMSEA systematically overestimates misfit in samples below 200 participants, particularly with df < 150, and that this inflation persists even in correctly specified models. The convergence of CFI, TLI, and SRMR within recommended thresholds, combined with the scale's strong psychometric properties across other validity assessments, supports adequate model fit.

Standardized loadings were ≥0.7, indicating strong associations between indicators and their latent factors. The HTMT value was 0.829, staying under the conservative 0.85 threshold, thereby indicating adequate discriminant validity between the measured constructs.

Fit index criteria (Hu & Bentler, 1999): Model fit was deemed acceptable when CFI or TLI was at least 0.90, SRMR was no more than 0.08, and RMSEA was 0.08 or lower; a model was considered to have excellent fit if CFI or TLI reached at least 0.95, SRMR remained below 0.08, and RMSEA was 0.06 or less. To assess how accurately the model captured the observed data patterns, various fit indices were analyzed, including the Comparative Fit Index (CFI), Tucker–Lewis Index (TLI), Standardized Root Mean Square Residual (SRMR), and Root Mean Square Error of Approximation (RMSEA).

Concurrent (convergent) validity results

The NOSE-Perf scale showed strong evidence of convergent validity. A high correlation was observed with the SNOT-22 (Pearson r = 0.885, p < 0.001) and with the original NOSE scale (r = 0.920, p < 0.001). Similarly, the SNOT-22 showed a strong association with the NOSE scale (r = 0.873, p < 0.001). These findings indicate that the NOSE-Perf aligns closely with both a symptom-specific measure (NOSE) and a broader sinonasal quality-of-life instrument (SNOT-22). A significant association was found between NOSE-Perf and SNOT-22 scores in both participant groups. Among controls, the correlation was very strong (R = 0.81, p < 0.001), and among cases, it was also strong (R = 0.75, p = 0.00015). These statistically significant correlations indicate that higher NOSE-Perf scores are consistently associated with higher SNOT-22 scores.

Discriminant validity

For the NOSE-Perf, the mean score among cases was 29.8 ± 9.48, while controls reported a mean of 5.76 ± 8.10 (p < 0.001), yielding an AUC of 0.856. The NOSE scale showed a larger group difference, with cases scoring 68.1 ± 26.1 versus 9.44 ± 21.9 for controls (p < 0.001; AUC = 0.931). SNOT-22 scores were also elevated among cases (57.1 ± 24.2) compared to controls (18.0 ± 18.4), with a significant p-value (p < 0.001), though its discriminative ability was lower (AUC = 0.32). These results suggest that both the NOSE-Perf and NOSE scales effectively distinguish between cases and controls, with the NOSE scale showing the strongest performance, as presented in Table 3.

Table 3.

Comparison of total SNOT-22, NOSE-Perf, and NOSE scores between case and control groups.

	Cases	Controls
	N = 20	N = 80	P-overall	AUC
NOSE-Perf	29.8 ± 9.48	5.76 ± 8.10	<0.001	0.856
NOSE scale	68.1 ± 26.1	9.44 ± 21.9	<0.001	0.931
SNOT-22	57.1 ± 24.2	18.0 ± 18.4	<0.001	0.32

Analysis was performed using the unpaired t-test. Data were summarized using the mean (SD), AUC: Area under the curve.

Test-retest reliability

A subset of nine patients completed the NOSE-Perf questionnaire again after 1–2 weeks. The results for the NOSE-Perf questionnaire indicate excellent test-retest stability. The mean scores were very similar between test (32.33 ± 6.30) and retest (33.33 ± 7.25), with a small mean difference of 1.00 (SD = 4.50). Agreement limits were established between –7.82 and 9.82, indicating that there was minimal variation among individual score differences. The standard error of measurement (SEM) was determined to be 2.90, while the minimal detectable change at the 95% confidence level (MDC95) was estimated at 8.05. The paired t-test for the NOSE-Perf questionnaire showed a mean difference (MD) of 1.00 (SD_diff = 4.50) between test and retest scores, indicating a small average increase. However, the observed difference was not statistically significant (t = –0.67, df = 8, p = 0.52), and the 95% confidence interval (–4.46 to 2.46) included zero, indicating the absence of a meaningful change. For the NOSE-Perf scale, the intraclass correlation coefficient (ICC) reached 0.79, reflecting strong test-retest reliability (p < 0.001) Table 4.

Table 4.

Test–retest reliability results of the NOSE-Perf scale (n = 9).

Reliability measure	Value	95% CI/SD
Descriptive satistics
Test 1 score, mean (SD)	32.33 (6.30)	–
Test 2 score, mean (SD)	33.33 (7.25)	–
Mean difference	1.00	SD = 4.50
Agreement analysis
Limits of agreement	-7.82 to 9.82	–
Standard error of measurement (SEM)	2.90	–
Minimal detectable change (MDC95)	8.05	–
Statistical tests
Paired t-test	t = -0.67	p = 0.52
Intraclass correlation coefficient (ICC)	0.79	0.36–0.95
F-statistic	8.64	p<0.001

Footnote: Test–retest interval: 1–2 weeks. According to the classification proposed by Koo and Li (2016), ICC values below 0.50 suggest poor reliability, between 0.50 and 0.75 indicate moderate reliability, between 0.75 and 0.90 denote good reliability, and greater than 0.90 imply excellent reliability. The paired t-test analysis revealed no statistically significant variation between the 2 administrations, thereby demonstrating consistent measurement performance. The broad confidence interval for the ICC likely reflects the limited size of the retest sample.

Discussion

The NOSE-Perf scale was created as a patient-reported instrument to assess the symptoms experienced by individuals with septal perforation [6]. Findings showed that the Arabic adaptation of the NOSE-Perf scale exhibited strong reliability and validity in assessing both the severity and functional impact of septal perforation symptoms among patients. Both factors of the NOSE-Perf demonstrated excellent internal consistency, and the total scale showed similarly high reliability, in line with accepted standards and matching prior validations in Spanish and Brazilian Portuguese [12,15,16,17,18]. The Arabic NOSE-Perf also correlated strongly with both the original NOSE scale and the SNOT-22, supporting its convergent validity. This is consistent with the Spanish version of the NOSE-Perf scale, which correlated 0.74 with the NOSE scale [17]. Furthermore, it demonstrated robust discriminant validity and satisfactory test–retest reliability, aligning with findings reported in the Spanish and Brazilian Portuguese adaptations of the NOSE-Perf questionnaire [17,18]. To strengthen the validity of this instrument, future evaluation of its responsiveness after perforation repair is necessary. This limitation should be addressed if a sufficient post-repair sample size is available. Taylor et al [19] previously have shown the tool's ability to detect clinical changes, with a marked decrease in NOSE-Perf scores from a preoperative mean of 25.3 to a postoperative mean of 7.9 (95% CI: 6.5–9.3), demonstrating its responsiveness. This investigation introduces the inaugural validated Arabic version of the NOSE-Perf questionnaire, anticipated to be a useful tool for clinicians assessing symptoms in Arabic-speaking individuals with septal perforation. Furthermore, Arabic ranks among the world's top 5 most spoken languages, with more than 400 million native speakers spanning over 35 countries [20]. Consequently, it is among the most widely spoken languages worldwide. Therefore, we believe that this Arabic-language instrument will be a significant asset for current international practices and ongoing scientific work.

This study faced a few constraints, particularly the limited participant number and missing responsiveness evaluation, which is largely attributable to the rarity of this condition. Our sample size (N = 100) is modest for CFA of a 12-item scale. While the subject-to-item ratio (8.3:1) exceeds the minimum threshold of 5:1 (Kline, 2016) [21], it falls below the recommended 200+ participants for optimal CFA stability. This limitation particularly affects the precision of RMSEA estimates (Kenny et al., 2015) [15]. However, the convergence of multiple fit indices (CFI, TLI, SRMR) and the strong discriminative validity support the overall model adequacy. The test-retest sample (n = 9) resulted in a wide confidence interval for the ICC (0.36–0.95), limiting the precision of the reliability estimate. Further research involving larger cohorts is warranted to verify these results. Nonetheless, the Arabic NOSE-Perf scale successfully differentiated patients from controls, even within a limited sample. It is also recommended that future investigations adapt and validate this instrument in additional languages to broaden its applicability.

In conclusion, due to the lack of a self-rating assessment tool for septal perforation symptoms in Arabic, this study introduced the Arabic NOSE-Perf scale. The instrument demonstrated strong validity and reliability in evaluating symptoms in patients with septal perforations.

Acknowledgement

The authors acknowledge Editage (www.editage.com) for English language editing.

Disclosure

AI tools were used exclusively for language and grammatical corrections. No AI tools were involved in the creation of images, data collection, or data analysis.

The authors have no conflict of interest.

This study was not supported or funded by any pharmaceutical or commercial organization.