Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 1 Impact of Genital and Non-Genital Psoriasis on Genital Self-Image, Quality of Life, and Sexual Dysfunction in Female Patients Hala Mohammed Elsadek1, Mona Sobh Ali1, Asmaa Mohamed Elaidy2 1 Department of Dermatology and Venereology, Faculty of medicine for girls, Al-azhar University, Cairo, Egypt 2 Department of Psychiatry, Faculty of medicine for girls, Al-azhar University, Cairo, Egypt Key words: psoriasis, genital psoriasis, sexual dysfunction, female sexual function Citation: Elsadek HM, Ali MS, Elaidy AM. Impact of Genital and Non-Genital Psoriasis on Genital Self-Image, Quality of Life, and Sexual Dysfunction in Female Patients. Dermatol Pract Concept. 2024;14(3):e2024159. DOI: https://doi.org/10.5826/dpc.1403a159 Accepted: February 14, 2024; Published: July 2024 Copyright: ©2024 Elsadek et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Asmaa M. Elaidy, Department of Psychiatry, Faculty of medicine for girls, Al-azhar University, Cairo, Egypt. Email: asmaamohamedelaidy.medg@azhar.edu.eg Introduction: Psoriasis is a chronic systemic inflammatory disease that affects millions of people worldwide. While its physical manifestations are well-documented, the psychosocial impact of psori- asis, particularly on female patients, is an area of growing concern. Feelings of shame, inferiority, and stigma are common among individuals with psoriasis, and these emotional burdens can be especially pronounced in females, particularly when the genital area is affected. Objectives: We aimed to shed light on the significance of genital psoriasis on the overall well-being of female patients. Methods: This cross-sectional, descriptive comparative study comprised 50 female participants diag- nosed with psoriasis: 25 with genital psoriasis, 25 without genital psoriasis, and 25 healthy women matched for age and sex who served as the control group. All participants underwent an assessment of disease severity using the Psoriasis Area and Severity Index in the psoriasis group and completed questionnaires for the assessment of the Female Sexual Function Index (FSFI). Additionally, quality of life was evaluated using the Dermatology Life Quality Index , and the Female Genital Self-Image Scale (FGSIS) was used to assess genital self-image. Results: We found that females with genital lesions, experience a notable decline in sexual health with higher levels of sexual distress compared to healthy individuals. In terms of the six FSFI domains, the psoriatic group scored lower than the control group in all areas, except for pain, which showed a significant increase. Psoriatic females also exhibited a significantly more negative FGSIS compared to the control group, and there was a highly significant difference in FGSIS between females with and without genital psoriasis. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 Introduction Psoriasis is a chronic systemic inflammatory disease that af- fects not only the skin but also nails and genitalia. Individu- als dealing with genital psoriasis often experience profound internalized stigma and psychological distress [1]. While the exact cause of psoriasis remains uncertain, it is believed to result from a combination of genetic predisposition, as well as various endogenous and exogenous factors, including emotional stress, trauma, infections, and medications [2]. The conspicuous nature of psoriasis skin manifestations can lead to stigmatization and diminished self-esteem among those affected [3]. Consequently, individuals with psoriasis frequently encounter difficulties in forming relationships, engaging in dating, and participating in social activities. Re- markably, research has revealed that up to 63% of patients develop psoriatic lesions in their genital area at some point in their lives. Regrettably, many avoid discussing these issues with their physicians due to shyness, embarrassment, or the fear of stigmatization. This reluctance to seek help can result in a significant decline in their quality of life (QoL), particu- larly in the context of romantic relationships, intimacy, and sexual function [4]. Female sexual dysfunction (FSD) encom- passes a range of issues that interfere with sexual satisfaction during the sexual response cycle. It includes problems related to sexual desire, arousal, orgasm, and pain [5]. Notably, one body image plays a pivotal role in sexual well-being. Women who have a positive body image tend to report more sexual activity, orgasms, and overall confidence in their sexual lives. Conversely, a negative body image is of- ten associated with a greater emphasis on physical attractive- ness, which can have adverse effects on sexual functioning and satisfaction [6]. Objectives This study aims to assess genital self-image in Egyptian fe- males with psoriasis and study its effects on their sexual function and QoL in relation to disease severity. Methods Study Design and Setting This cross-sectional descriptive comparative case-control study was conducted at Al-Zahraa University Hospital, Der- matology and Venereology Department, in collaboration with Psychiatry Department affiliated with the Faculty of Medicine for Girls, Al-Azhar University, Egypt. The study re- ceived approval from the Medical Ethics Committee (refer- ence number RHDIRB 2023021746), and written informed consent was obtained from all participants. Inclusion and Exclusion Criteria Participants included married and sexually active women diagnosed with psoriasis, aged 18 to 55 years. The control group consisted of age- and sex-matched healthy women. Exclusion criteria encompassed women with other dermato- logical, chronic/autoimmune diseases, psychiatric disorders, gynecological problems, recent psoriasis flare-ups, or those who received topical or systemic psoriasis treatment in the last 2-4 weeks. Additionally, pregnant, lactating, and meno- pausal women were excluded. Study Duration and Participants The study spanned a 6-month period, from February 2023 to July 2023. A total of 75 participants attending the outpa- tient clinic of the Dermatology and Venereology Department were included, comprising three groups: 25 female patients without genital psoriasis, 25 female patients with genital psoriasis, and 25 age-matched healthy women (nonrelatives of patients) as the control group. Data Collection Each participant underwent a comprehensive assessment, including: • Demographic and Clinical Information: age, education level, occupation, special habits, disease onset, course, duration, associated disorders, family history of psoriasis, and history of previous treatments. Additional details col- lected were the duration of marriage and sexual history. • Physical Examination: general and dermatological exam- inations were conducted to detect signs of associated sys- temic disorders, pinpoint the site of psoriatic lesions, assess clinical forms, and determine surface area involvement. • Questionnaires: • Psoriasis Severity Assessment: the Psoriasis Area and Se- verity Index (PASI) score was used to evaluate psoriasis severity. The PASI score considers lesion area and sever- ity, with scores ranging from 0 to 72. Higher scores indi- cate more severe psoriasis [7]. Severity categories were defined as mild (PASI < 10), moderate (PASI 10-20), and severe (PASI > 20) [8]. Conclusions: Understanding the impact of genital psoriasis on female sexual health and overall qual- ity of life is essential for comprehensive patient care. This research is instrumental in addressing the psychosocial aspects of psoriasis and enhancing patient well-being. Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 3 • Quality of Life Assessment: the Dermatology Life Qual- ity Index (DLQI), a 10-item questionnaire, assessed the impact of skin disease on various aspects of life, with scores ranging from 0 to 30. Higher scores indicated greater impairment in QoL [9]. • Female Sexual Function Assessment: the Arabic version of the Female Sexual Function Index (FSFI) question- naire evaluated sexual function across six domains: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. Individual domain scores were calculated, and a total score was derived, with lower scores indi- cating sexual dysfunction. Cutoff scores were used to classify dysfunction in each domain [10]). • Female Genital Self-Image Assessment: women feelings and beliefs about their own genitals were assessed using the 4-item Arabic version of the Female Genital Self-Image Scale (FGSIS) with a 4-point response scale [11]. • Assessment of Psychiatric Disorders by a Consultant Psy- chiatrist: the exclusion of other psychiatric disorders was carried out using the criteria outlined in the 5th Edition of the Diagnostic and Statistical Manual of Mental Disor- ders (DSM-5) [12]. Statistical Analysis Data were meticulously collected, reviewed, coded, and sub- sequently entered into IBM SPSS version 23 for analysis. Quantitative data were presented as means, standard devi- ations, and ranges when they met parametric assumptions. For non-parametric data, medians and inter-quartile ranges (IQR) were reported. Qualitative variables were summarized using frequencies and percentages. Results The studied groups, comprising 50 female participants diagnosed with psoriasis (25 with genital psoriasis, 25 without genital psoriasis, and 25 healthy controls), were well-matched in terms of age, sociocultural factors (including education, occupation, and residence), duration of disease, body mass index (BMI), and duration of mar- riage (Table  1). Regarding PASI scores, the genital pso- riasis group represented 14  (56.0%) cases of moderate psoriasis and 11 (44.0%) cases of severe psoriasis, while the non-genital group showed 3 (12.0%) cases of mild Table 1. Sociodemographic Data of the Studied Groups (N = 75) Control Group Non-Genital Psoriasis Genital Psoriasis Test Value P-Value SignificativityNo. = 25 No. = 25 No. = 25 Age Mean ± SD 35.72 ± 11.98 36.32 ± 10.95 37.24 ± 10.45 0.118 0.889 NS Range 19 – 55 19 – 55 18 – 55 18-29 y 9 (36.0%) 8 (32.0%) 6 (24.0%) 2.734 0.841 NS 30-39 y 7 (28.0%) 7 (28.0%) 10 (40.0%) 40-49 y 4 (16.0%) 7 (28.0%) 5 (20.0%) <50 y 5 (20.0%) 3 (12.0%) 4 (16.0%) BMI Mean±SD 23.02 ± 3.41 23.08 ± 4 24.6 ± 4.12 1.347 0.266 NS Range 18.5 – 30 19 – 31 19 – 31 Normal 17 (68.0%) 17 (68.0%) 13 (52.0%) 3.769 0.438 NS Overweight 7 (28.0%) 5 (20.0%) 7 (28.0%) Obese Class I 1 (4.0%) 3 (12.0%) 5 (20.0%) Obese Class II 0 (0.0%) 0 (0.0%) 0 (0.0%) Obese Class III 0 (0.0%) 0 (0.0%) 0 (0.0%) Residence Rural 12 (48.0%) 13 (52.0%) 13 (52.0%) 0.107 0.948 NS Urban 13 (52.0%) 12 (48.0%) 12 (48.0%) Education Illiterate 3 (12.0%) 5 (20.0%) 6 (24.0%) 2.857 0.943 NS Primary 2 (8.0%) 4 (16.0%) 2 (8.0%) Secondary 10 (40.0%) 9 (36.0%) 9 (36.0%) University 8 (32.0%) 6 (24.0%) 7 (28.0%) Postgraduate 2 (8.0%) 1 (4.0%) 1 (4.0%) Occupation Work 8 (32.0%) 8 (32.0%) 8 (32.0%) 0.000 1.000 NS Not work (Housewife) 17 (68.0%) 17 (68.0%) 17 (68.0%) Table 1 continues 4 Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 Table 2. Comparison between the PASI score in both genital and non-genital groups Control Group Non-Genital Psoriasis Genital Psoriasis Test Value P-Value SignificativityNo. = 25 No. = 25 No. = 25 PASI score Mild - 3 (12.0%) 0 (0.0%) 6.767 0.034 S Moderate - 18 (72.0%) 14 (56.0%) Severe - 4 (16.0%) 11 (44.0%) PASI = Psoriasis Area and Severity Index; S = significant. psoriasis, 18 (72.0%) cases of moderate psoriasis, and 4 (16.0%) cases of severe psoriasis. This difference was statistically significant (P < 0.05) (Table  2). In terms of FSFI, there was a highly statistically significant difference between the study groups. Approximately 24 females in the genital psoriasis group, 19 females in the non-genital psoriasis group, and 9 females in the control group exhib- ited sexual dysfunction (P value = 0.000). According to the FSFI, the total score in women with non-genital pso- riasis was 23.4 (18 - 25.6), in women with genital psori- asis was 20.5 (13.5 - 23.3), and in the control group was 28.4 (28 - 29.2), respectively. This difference affected all domains (arousal, desire, orgasm, satisfaction, and pain) in genital psoriasis and non-genital psoriasis compared to the control group, and this result is highly significant (Table 3) (Figure 1). Additionally, as shown in (Table 4), (Table 5) & (Table 6)a highly significant negative correlation was ob- served between FSFI and DQLI the age of the patient as shown in Figure 2 , and the PASI score in the psoriasis group (P values = 0.000, 0.002, and 0.000, respectively), with cor- relation coefficients (r) of -0.894, -0.348, and -0.900, respec- tively. Furthermore, a significant negative correlation was found between FSFI and both the duration of disease and BMI in patients with non-genital psoriasis (P values = 0.040 Control Group Non-Genital Psoriasis Genital Psoriasis Test Value P-Value SignificativityNo. = 25 No. = 25 No. = 25 Duration of marriage <5 yrs 7 (28.0%) 7 (28.0%) 7 (28.0%) 1.851 0.933 NS 5–<10 yrs 6 (24.0%) 4 (16.0%) 4 (16.0%) 10–20 yrs 3 (12.0%) 6 (24.0%) 6 (24.0%) >20 yrs 9 (36.0%) 8 (32.0%) 8 (32.0%) Female genital mutilation: Yes 21 (84.0%) 22 (88.0%) 22 (88.0%) 0.231 0.891 NS No 4 (16.0%) 3 (12.0%) 3 (12.0%) Duration of disease Median (IQR) - 7 (3 – 9) 5 (2 – 10) 0.371 0.711 NS Range - 1 - 15 1 - 15 BMI = Body Mass Index; IQR = interquartile range; NS = not significant; SD = standard deviation; yrs = years. Table 1. Sociodemographic Data of the Studied Groups (N = 75). (continued) and 0.002, respectively), with correlation coefficients of -0.303 and -0.380, respectively (Table 7) & (Table 8). Conclusions Psoriasis is a chronic inflammatory skin disease affecting ap- proximately 2% to 3% of the population [7]. The lifelong nature of psoriasis treatment can significantly impact emo- tional, social, and physical well-being, ultimately affecting patients QoL (6). Patients with psoriasis often experience feelings of shame, inferiority, and stigma, which can lead to hesitations about starting a family, particularly among women with psoriasis. Additionally, the psychological, phys- iological, and social effects of psoriasis can negatively impact female sexual function [7]. Sexual dysfunction (SD) is prev- alent in women with psoriasis, with studies reporting that 48.7% to 79.1% of them experience SD [13]. Risk factors associated with SD in psoriasis patients include disease se- verity, female sex, psoriatic arthritis, and age [14]. However, to date, no trials have compared the effects of vulvar and non-vulvar psoriasis on sexual function, female genital im- age, and dermatological quality of life within one gender. Ad- ditionally, only a limited number of studies have assessed the impact of psoriasis on sexual function and dermatological Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 5 However, other studies, such as Meeuwis et al [16], have indicated that genital lesions alone may not directly impair sexual function but may cause sexual distress due to feelings of physical unattractiveness. The variation in these findings could be attributed to physical signs and symptoms, such as stinging, bleeding, desquamation, itching, as well as psycho- logical factors like anxiety and joint involvement in psoriasis patients [17]. Itis worth noting that patients with genital psori- asis in our study had never used treatment for their genital le- sions, including systemic treatment, and almost half had never discussed the presence of genital lesions with their physicians, indicating the presence of stigmatization, shyness, or fear of judgment that may hinder patients from seeking help [4]. Our study revealed a highly significant reduction in over- all quality of life among psoriasis patients, both with and without genital involvement, compared to the control group. However, there was no significant difference in DLQI be- tween psoriatic females with or without genital involvement. These findings align with Nazik et al who reported that qual- ity of life was more negatively affected in the psoriasis group than in the control group [18]. However, they contrast with the findings of Kurd et al who suggested that the QoL impact of genital psoriasis is serious and that these patients experi- ence higher levels of depression compared to those without genital involvement [19]. Several factors may contribute to the lower QoL in psoriasis patients. The chronic and recurring nature of the Table 3. Comparison Between the Studied Groups Regarding FSFI Total and Sub-items Level Distribution Control Group Non-Genital Psoriasis Genital Psoriasis Test Value P-Value SignificativityNo. = 25 No. = 25 No. = 25 FSFI Median (IQR) 28.4 (28 – 29.2) 23.4 (18 – 25.6) 20.5 (13.5 – 23.3) 38.836 0.000 HS Range 24.16 – 36 12 – 29 11.7 – 28.2 FSFI groups Normal 16 (64.0%) 6 (24.0%) 1 (4.0%) 21.948 0.000 HS Dysfunction 9 (36.0%) 19 (76.0%) 24 (96.0%) Desire Median (IQR) 4.8 (4.8 – 5.4) 4.2 (3.6 – 4.8) 3.6 (1.8 – 4.2) 32.970 0.000 HS Range 3.6 – 6 1.2 – 5.4 1.2 – 4.8 Arousal Median (IQR) 4.8 (4.8 – 5.1) 3.6 (2.8 – 4.8) 2.8 (2.1 – 3.6) 33.131 0.000 HS Range 3.6 – 6 1.8 – 4.8 1.2 – 4.8 Lubricant Median (IQR) 5.4 (4.8 – 5.4) 4.2 (4 – 4.8) 4 (2.4 – 4.2) 36.295 0.000 HS Range 4.2 – 6 1.2 – 5.4 1 – 5.4 Orgasm Median (IQR) 5.2 (5.2 – 5.6) 4 (2.7 – 4.8) 2.7 (2 – 4) 32.293 0.000 HS Range 4 – 5.6 0.68 – 5.6 1.6 – 5.2 Satisfaction Median (IQR) 5.2 (4.8 – 5.2) 3.6 (2.8 – 4.8) 2.8 (1.6 – 3.6) 31.325 0.001 HS Range 3.6 – 6 1.2 – 5.2 1.2 – 5.2 Pain Median (IQR) 2.8 (2.8 – 3.6) 3.6 (3.2 – 4.4) 4 (3.6 – 4.4) 15.028 0.000 HS Range 2.8 – 4.4 1.2 – 4.4 1 – 4.4 Range 1 – 2 1 – 15 2 – 22 FSFI = female sexual function index; HS = highly significant; IQR = interquartile range; NS = not significant. Figure 1. FSFI = Female Sexual Function Index. QoL. Therefore, our study aimed to evaluate the effects of psoriasis affecting both genital and non-genital areas on sex- ual dysfunction, female genital image, dermatological QoL, and their relationship with disease severity in female patients. In our study, we observed a highly statistically significant decrease in FSFI in psoriatic females, both with and with- out genital involvement, compared to healthy controls. This finding aligns with Molina-Leyva et al who found that the affected body parts play a crucial role in the development of SD [15]. Skin lesions on the genital areas and non-genital areas, such as thighs, abdomen, and back, were significantly associated with SD. 6 Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 Table 4. Comparison between the studied groups regarding DLQI and FGIS Control group Non-genital psoriasis Genital psoriasis Test value P-value Sig.No. = 25 No. = 25 No. = 25 DLQI No impairment 19 (76.0%) 3 (12.0%) 0 (0.0%) 51.165* 0.000 HS Mild impairment 6 (24.0%) 3 (12.0%) 3 (12.0%) Moderate 0 (0.0%) 11 (44.0%) 11 (44.0%) Severe 0 (0.0%) 8 (32.0%) 11 (44.0%) Extremely severe 0 (0.0%) 0 (0.0%) 0 (0.0%) FGIS Median (IQR) 15 (14 – 16) 12 (10 – 13) 8 (4 – 10) 46.366‡ 0.000 HS Range 12 – 16 8 – 16 4 – 12 DLQI Median (IQR) 1 (1 – 1) 7 (6 – 11) 10 (8 – 19) 44.967‡ 0.000 HS Range 1 – 2 1 – 15 2 – 22 DQLI = Dermatological quality life index; FSFI = female sexual function index. Table 5. Post hoc analysis between studied groups Post hoc analysis Control group versus non-genital psoriasis Control group versus genital psoriasis Non-genital psoriasis versus genital psoriasis DQLI 0.000 0.000 0.324 FSFI 0.000 0.000 0.014 FSFI groups 0.004 0.000 0.042 Desire 0.000 0.000 0.020 Arousal 0.000 0.000 0.017 Lubricant 0.000 0.000 0.009 Orgasm 0.000 0.000 0.064 Satisfaction 0.000 0.000 0.125 Pain 0.000 0.000 0.357 FGSIS 0.000 0.000 0.000 DQLI = Dermatological quality life index; FGSIS= female genital self-imagescale; FSFI = female sexual function index. Table 6. Correlation of FSFI with DLQI, Age of the patients, duration of disease, PASI score and BMI among psoriasis groups Psoriasis group Non genital psoriasis Genital psoriasis R P R P R P FSFI DQLI -0.894 0.000 -0.807 0.000 -0.651 0.000 FSFI Age -0.348 0.002 -0.443 0.027 -0.460* 0.021 FSFI Duration of disease -0.303 0.032 -0.413 0.040 -0.298 0.149 FSFI PASI score -0.900 0.000 -0.834 0.000 -0.888 0.000 FSFI BMI -0.380 0.001 -0.598 0.002 -0.261 0.207 BMI = body mass index; DQLI = Dermatological quality life index; FGSIS= female genital self-image scale; FSFI = female sexual function index; PASI = Psoriasis Area and Severity Index. disease often leads to a sense of hopelessness regarding a cure. Moreover, many psoriasis patients face social and psy- chological challenges related to their condition, which can lead to feelings of humiliation in situations like swimming, intimate relationships, using public showers, or living in en- vironments that lack privacy. Consequently, many patients feel the need to conceal their disease, further affecting their self-confidence [20]. Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 7 Figure 2. FSFI = Female Sexual Function Index. Table 7. Correlation of DLQI, with Age of the patients, duration of disease, PASI score and BMI among psoriasis groups Psoriasis group Non genital psoriasis Genital psoriasis R P R P R P DQLI Age 0.349 0.002 0.469 0.018 0.453 0.023 DQLI Duration of disease 0.345 0.014 0.507 0.010 0.310 0.132 DQLI PASI score 0.844 0.000 0.865 0.000 0.768 0.000 DQLI BMI 0.418 0.000 0.723 0.000 0.315 0.125 BMI = body mass index; DQLI = Dermatological quality life index; PASI = Psoriasis Area and Severity Index. Table 8. Correlation of PASI with Age of the patients, duration of disease and BMI among psoriasis groups Psoriasis group Non genital psoriasis Genital psoriasis R P R P R P PASI Age 0.442 0.001 0.538 0.006 0.390 0.054 PASI Duration of disease 0.293 0.039 0.502 0.011 0.233 0.263 PASI BMI 0.584 0.000 0.777 0.000 0.314 0.126 BMI = body mass index; PASI = Psoriasis Area and Severity Index. Our study demonstrated significant negative correlations between FSFI and various factors, including the DLQI, age, PASI score, duration of disease, and BMI among psoriasis patients. These findings are in line with studies by Alariny et al and Kędra et al reported negative impacts of psoria- sis on quality of life and sexual health [13,21]. Addition- ally, our study reported a significant negative correlation between FSFI and the age of the patient and duration of the disease, aligning with previous findings [18]. However, these results differ from those reported by Turel et al who found no significant relationship between age and sexual activity in psoriatic female patients [22]. Our findings revealed significant positive correlations between PASI score, age, and BMI among patients without genital psoriasis. This is consistent with Nazik et al, who re- ported positive correlations between PASI score, BMI, DLQI, sexual dysfunction, and the age of psoriatic patients [18]. They also found a significant relationship between increased BMI and waist size on one side and increased disease sever- ity on the other side [23]. These findings contradict those of Sobhan and Farshchian, who found no significant difference in psoriatic patients based on BMI and disease severity [24]. It is important to note that Sompogna et al reported that higher illness severity occurred in younger psoriasis patients [25]. The relatively small sample size, and absence of deter- mining causes of sexual dysfunction which could help in developing targeted interventions and treatments to address sexual health issues in this population are the main lim- itations of the study. We recommend further research with larger sample sizes to validate our results more robustly. In conclusion, our study emphasizes the significant im- pact of psoriasis on sexual health, particularly among women with genital psoriasis, who experience higher levels of sexual distress compared to healthy individuals. It is essential to ac- knowledge the multifaceted effects of psoriasis on the phys- ical, psychological, and emotional well-being of individuals. Healthcare professionals should address these aspects when managing psoriasis patients, aiming to improve not only their skin condition but also their overall QoL and sex- ual well-being. 8 Original Article | Dermatol Pract Concept. 2024;14(3):e2024159 15. 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