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Research Article

Demodex folliculorum and Skin Disease: A Case-Control Study

Shahla Talghini, Reihan Shenasi, Daniel F. Fouladi and Amir Hagigi
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Demodex mites are commensals of the pilosebaceous unit in human. This study aimed to investigate possible association of Demodex folliculorum with Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), melanoma, Discoid Lupus Erythematosus (DLE) and rosacea. In this case-control study, standardized skin surface biopsy samples were obtained from the cheeks of healthy individuals (n = 28); patients with BCC (n = 18), SCC (n = 13) and melanoma (n = 11) and patients with DLE (n = 28) and inflammatory rosacea (n = 34). Mite density (cm-2) and the rate of infestation (density ≥5) were compared. The rate of mite infestation (%) was comparable between the controls (21.4) and the patients with BCC (22.2, p = 0.95), SCC (18.8, p = 0.83), melanoma (9.1, p = 0.37) and DLE (17.9, p = 0.74). Infestation was significantly more frequent in the rosacea group (47.1, p = 0.04) than in the controls. While, the mean mite density (cm-2) was comparable between the control (4.07±2.06) and the groups with BCC (5.01±2.08, p = 0.68), SCC (3.17±1.29, p = 0.49) and DLE (3.26±1.04, p = 0.91); it was significantly higher in the group of rosacea (8.56±3.29, p = 0.03) and lower in the group of melanoma (1.45±0.58, p = 0.04) in comparison with the normal group. In conclusion, although Demodex folliculorum does not seem to play a role in the pathogenesis of BCC, SCC and DLE, it is apparently associated with rosacea and melanoma.

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Shahla Talghini, Reihan Shenasi, Daniel F. Fouladi and Amir Hagigi, 2014. Demodex folliculorum and Skin Disease: A Case-Control Study. Journal of Medical Sciences, 14: 229-234.

DOI: 10.3923/jms.2014.229.234

Received: March 20, 2014; Accepted: June 02, 2014; Published: August 11, 2014


Hair follicle mites, Demodex folliculorum and Demodex brevis are obligatory commensals of the pilosebaceous unit and the most common ectoparasites in human (Lacey et al., 2009).

Although, the presence of these mites in the skin is asymptomatic when their density is not considerable (<5 cm-2) (Dhingra et al., 2009), these two species of Demodex have been implicated in the pathogenesis of various skin diseases such as rosacea (Hsu et al., 2009), pityriasis (Baima and Sticherling, 2002), dermatitis (Karincaoglu et al., 2009), bacterial infections (Ozdemir et al., 2005), acne vulgaris (Karaman et al., 2008) and even more serious conditions such as Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC) (Erbagci and Erkilic, 2000; Sun et al., 2005) through provocation of inflammatory/immune reactions, mechanical obstruction of the follicles or acting as a vector for other pathogens (Powell, 2004).

Despite these evidences, there is still an ongoing debate on the connection between mites and skin diseases and a sheer coincidence is yet to be ruled out. These arguments are clinically critical, because the evidence linking Demodex to human disease has implications with regard to treatment (Elston, 2010).

The objective of this study is to investigate a possible association between the presence of Demodex folliculorum and its infestation with a number of malignant (BCC, SCC, melanoma) and nonmalignant (discoid lupus erythematosus, rosacea) skin diseases.


In this study, 135 patients with histopathologic diagnosis of BCC (n = 18), SCC (n = 16), melanoma (n = 11), discoid lupus erythematosus (DLE, n = 28) and inflammatory (papulopustular) rosacea (n = 34) were recruited from three referral centers from October 2008 to March 2013.

In these patients, the main lesion of BCC, SCC and melanoma was on their cheeks and in the groups with DLE and rosacea, the cheeks were clinically affected.

Twenty eight age and sex-matched healthy individuals without any dermatological diseases or telangiectases served as the controls.

None of the participants had received any topical/systemic antibiotic, topical acaricides or corticosteroid/immunosuppressive therapy within one month prior to enrollment or radiotherapy/chemotherapy before skin sampling.

This study was approved by the ethics committee of a local university and written informed consents were obtained from all participants.

A non-invasive method for the Standardized Skin Surface Biopsy (SSSB) was used for detecting mites. For SSSB, a drop (about 0.05 mL) of cyanoacrylate glue was placed on a standard surface area of 1 cm2 that was drawn by a waterproof pen on a slide glass. The adhesive bearing surface was pressed onto to the skin for 1 min and then peeled off gently. Two drops of immersion oil were used for clarification of the samples and after the application of cover-slides, the specimens were immediately examined for mites under light microscopy (X40 and X100 magnification) by a skilled dermatopathologist unaware of the cohorts.

For the patients with BCC, SCC and melanoma, the samplings were performed from the skin of the cheek just next to the lesions, as well as, from the corresponding site on the contralateral (intact) cheek.

For normal subjects and the patients with DLE and rosacea, the sampling was performed from both cheeks. For comparisons between group, the results were obtained arbitrarily from the right cheeks were used in these groups.

The skin and slides were cleaned with ether prior to sampling (Forton and Song, 1998). Demodex density was established as the number of mites per square centimetre of the skin (Erbagci and Ozgoztasi, 1998; Karincaoglu et al., 2009). Infestation (positivity) was reported when the mite density was ≥5 (Forton and Seys, 1993).

Statistical analysis: The mite density and positivity rate were compared between the patients and the controls (between group comparison), as well as between left and right cheeks in each group (intra-group comparison). The SPSS Software for Windows (ver.18.0, SPSS Inc., IL, USA) was used for analysis. One-way analysis of variance (ANOVA), Tukey post hoc test, the independent samples t-test and the Chi-square (χ2) test were used for comparisons. A p-value ≤0.05 was considered statistically significant.


The patient groups were comparable with the normal group in terms of the participants’ age and gender (Table 1).

Image for - Demodex folliculorum and Skin Disease: A Case-Control Study
Fig. 1:
Mite positivity on the cheeks of the studied individuals. BCC: Basal cell carcinoma, DLE: Discoid lupus erythematosus, SCC: Squamous cell carcinoma

Table 1: Age and gender of the individuals in the studied groups
Image for - Demodex folliculorum and Skin Disease: A Case-Control Study
Significant at p≤0.05, *age, **gender. Data are presented as Mean±Standard deviation (age) and frequency (%) (gender)

Table 2: Mite density on the cheeks of the studied individuals
Image for - Demodex folliculorum and Skin Disease: A Case-Control Study
Significant p≤0.05, *patient vs. normal, **two sides. Data are presented as Mean±Standard error of mean

Mite infestation was established in 4 patients (22.2%) with BCC, 3 patients (18.8%) with SCC, 1 patient (9.1%) with melanoma, 5 patients (17.9%) with DLE, 16 patients (47.1%) with rosacea and 6 subjected (21.4%) in the normal group (Fig. 1).

Based on the results of χ2 test, the normal group was comparable with the groups of BCC (p = 0.95), SCC (p = 0.83), melanoma (p = 0.37) and DLE (p = 0.74), in terms of the mite infestation rate. The rate of mite infestation, however, was significantly higher in the group of patients with rosacea in comparison with that in the controls (χ2 test, p = 0.04; odds ratio = 3.26 with 95% confidence interval of 1.06-10.05).

The mean mite densities on the cheeks of the studied individuals in different groups are summarized in Table 2. Comparing the mean mite density between two sides in each group using the independent samples t-test showed no significant difference.

According to the results of one-way analysis of variance (ANOVA), a significant difference was present between the six studied groups in terms of the mean mite density on the involved (in BCC, SCC and melanoma groups) or right (in DLE, rosacea and normal groups) cheeks (p = 0.04).

Based on the results of post hoc analysis, this significant difference was related to two comparisons; normal vs. melanoma group (p = 0.04) and normal vs. rosacea group (p = 0.03) (Table 2).


In the present study, both mite density and the rate of mite infestation were significantly higher on the cheeks of the patients with rosacea in comparison with those in their unaffected counterparts.

The role of Demodex in the pathogeny of rosacea is not a new concept (Abd-El-Al et al., 1997; El-Shazly et al., 2001; Zhao et al., 2010; Lazaridou et al., 2011; Parodi et al., 2011; Jarmuda et al., 2012; Sattler et al., 2012). Several mechanisms have been proposed in this regard such as the obstruction of the hair follicle or sebaceous duct by increased mite density, direct damage to the follicular epithelia, induction of foreign body/hypersensitivity reactions and playing the role of a vector for bacteria like Staphylococcus albus and Bacillus oleronius (Crawford et al., 2004; Yamasaki and Gallo, 2009; Rios-Yuil and Mercadillo-Perez, 2013).

It should be noted that the patients recruited in the present study were affected with papulopustular form of rosacea. However, the pathologic role of Demodex folliculorum in rosacea is apparently irrespective of rosacea subtype (Casas et al., 2012).

Comparing the two groups of patients with DLE and normal subjects, we did not find a significant difference in terms of mite density and the rate of infestation.

In a recent study by Perrigouard et al. (2013) while over 75% of the specimens obtained from patients with rosacea involved Demodex, no mite was seen in lupus erythematosus cases.

In another study by Moravvej et al. (2007) Demodex spp. was found in 38.6% of rosacea biopsies and only in 21.3% of DLE biopsies.

In line with these finding, Roihu and Kariniemi (1998) also reported no significant difference in mite counts of infested follicles between DLE patients and their healthy counterparts.

Unlike in rosacea and DLE, available data regarding possible association between Demodex mites and malignant skin diseases are more conflicting.

Erbagci and Erkilic (2000) reported a higher infestation rate and mean density of Demodex mites in patients with BCC comparing with a normal sex and age matched group.

Sun et al. (2005) examined specimens of the facial skin obtained from patients with BCC, SCC and nonmalignant conditions (seborrheic keratosis and trichilemmoma) regarding the rate of mite infestation. Comparing with nonmalignant conditions, the rate of mite infestation was significantly higher in the BCC group and lower in the SCC patients.

In contrast, neither BCC nor SCC cases in the current study differed significantly in mean mite density and the rate of mite infestation with the controls.

Various possible factors may underlie this heterogeneity, such as patients’ age in different studies, lack of an appropriate control group, different time, site and method of sampling and dissimilar techniques in detecting mite and establishing its density.

It is thought that the likelihood of mite infestation and the mite density increase with advancing age (Erbagci et al., 2003; Aycan et al., 2007). In the present study, the groups of patients were matched with the normal subjects in terms of age. Although, there may not be a significant association between mite infestation and host gender, skin type, hygiene and use of cosmetics, (Andrews, 1982), the authors did their best to have homogenous groups in terms of these factors.

Since, incompetent immune system has been reported a risk factor for mite infestation (Akilov and Mumcuoglu, 2003, 2004), all samplings were performed before commencement of any treatment to ensure that the patients’ immune system was untouched. Furthermore, all samplings were performed on the cheek, because the highest density of mites has been found on this area of the face (Bonnar et al., 1993).

There are different methods available for skin sampling to examine Demodex mites such as using adhesive tape, skin impression/scraping, comedo extraction, hair epilation, skin biopsy and skin surface biopsy (Bonnar et al., 1993; Forton and Seys, 1993; Erbagci and Ozgoztasi, 1998). We preferred SSSB because it is noninvasive and more sensitive comparing with similar approaches in this regard (Forton and Song, 1998; Kligman and Christensen, 2011).

By comparison of the melanoma and control groups, although, the infestation rate of Demodex folliculorum was less than half of that in the controls, the comparison did not reach a level of significance (9.1% vs. 21.4%; p = 0.37). On the other hand, however, the mean mite density was significantly lower in the melanoma group comparing with the controls (1.45±0.58 vs. 4.07±2.06 mites cm-2; p = 0.04). To the best of our knowledge, the current study is apparently the first one that suggests an association between Demodex infestation and melanoma. This interesting finding may propose a shared point in immunological host defense against both melanoma and Demodex in human (Strohal et al., 1994; Thor Straten et al., 1999; Tsutsumi, 2004). Since the mite density was significantly higher in normal than in melanoma group, another possible hypothesis might be considering a protective role of infection with Demodex folliculorum against melanoma or vice versa. Further studies, particularly with larger sample size may better clarify this connection between mites and melanoma.

Performing an intra-group comparison of mite density and infestation rate between two sides of the face yielded no significant difference in all groups. This symmetry of mite distribution on the face has been also reported previously (Kligman and Christensen, 2011).

Although, this finding may indicate a systemic rather than a local phenomenon in relating skin diseases with Demodex mites, more studies merit to be carried out in this regard. The authors acknowledge small sample size in some groups particularly melanoma, as a limitation of the present study. This limitation is largely due to the criterion of including cases with involvement of a particular site on the face (the cheek) which was considered to the detriment of sample size and very time-consuming process of data collection. Nevertheless, the results of comparison between melanoma and normal groups are so interesting that make this limitation negligible.

Based on the findings on the present study, there is apparently no association between Demodex folliculorum and BCC, SCC and DLE. In conformity with previous reports, both Demodex mite density and infestation rate may be considered as risk factors for rosacea. Conversely, infestation rate and density of Demodex folliculorum are lower in patients with melanoma comparing with their healthy counterparts. Nevertheless, multicentric studies are required to establish the hypothesis.

The role of age in dermatological diseases (Babaeinejad et al., 2011; Amirnia et al., 2012; Khodaeiani et al., 2012, 2013; Babaeinejad and Fouladi, 2013) should also be considered in this regard.


According to the results of the present study, Demodex folliculorum doesn’t play a significant role in the pathogenesis of basal cell carcinoma, squamous cell carcinoma and discoid lupus erythematosus. Infection with Demodex folliculorum may be associated with melanoma.


1:  Abd-El-Al, A.M., A.M. Bayoumy and E.A. Abou Salem, 1997. A study on Demodex folliculorum in rosacea. J. Egypt. Soc. Parasitol., 27: 183-195.
PubMed  |  

2:  Akilov, O.E. and K.Y. Mumcuoglu, 2003. Association between human demodicosis and HLA class I. Clin. Exp. Dermatol., 28: 70-73.
CrossRef  |  PubMed  |  Direct Link  |  

3:  Akilov, O.E. and K.Y. Mumcuoglu, 2004. Immune response in demodicosis. J. Eur. Acad. Dermatol. Venereol., 18: 440-444.
CrossRef  |  PubMed  |  Direct Link  |  

4:  Amirnia, M., E. Khodaeiani, R.F. Fouladi and A. Hashemi, 2012. Topical steroids versus PUVA therapy in moderate plaque psoriasis: A clinical trial along with cost analysis. J. Dermatol. Treat., 23: 109-111.
CrossRef  |  Direct Link  |  

5:  Andrews, J.R., 1982. The prevalence of hair follicle mites in Caucasian New Zealanders. N. Z. Med. J., 95: 451-453.
PubMed  |  Direct Link  |  

6:  Aycan, O.M., G.H. Otlu, U. Karaman, N. Daldal and M. Atambay, 2007. Frequency of the appearance of Demodex sp. In various patient and age groups. Turk. Soc. Parasitol., 31: 115-118.
PubMed  |  Direct Link  |  

7:  Babaeinejad, S., E. Khodaeiani and R.F. Fouladi, 2011. Comparison of therapeutic effects of oral doxycycline and azithromycin in patients with moderate acne vulgaris: What is the role of age? J. Dermatol. Treat., 22: 206-210.
CrossRef  |  PubMed  |  Direct Link  |  

8:  Babaeinejad, S.H. and R.F. Fouladi, 2013. The efficacy, safety and tolerability of adapalene versus benzoyl peroxide in the treatment of mild acne vulgaris: A randomized trial. J. Drugs Dermatol., 12: 1033-1038.
PubMed  |  Direct Link  |  

9:  Baima, B. and M. Sticherling, 2002. Demodicidosis revisited. Acta Dermato-Venereologica, 82: 3-6.
PubMed  |  

10:  Bonnar, E., P. Eustace and F.C. Powell, 1993. The Demodex mite population in Rosacea. J. Am. Acad. Dermatol., 28: 443-448.
PubMed  |  

11:  Casas, C., C. Paul, M. Lahfa, B. Livideanu and O. Lejeune et al., 2012. Quantification of Demodex folliculorum by pcr in rosacea and its relationship to skin innate immune activation. Exp. Dermatol., 21: 906-910.
CrossRef  |  PubMed  |  Direct Link  |  

12:  Crawford, G.H., M.T. Pelle and W.D. James, 2004. Rosacea: I. Etiology, pathogenesis and subtype classification. J. Am. Acad. Dermatol., 51: 327-341.
CrossRef  |  PubMed  |  Direct Link  |  

13:  Dhingra, K.K., V. Saroha, P. Gupta and N. Khurana, 2009. Demodex-associated dermatologic conditions: A coincidence or an etiological correlate. Review with a report of a rare case of sebaceous adenoma. Pathol. Res. Pract., 205: 423-426.
CrossRef  |  PubMed  |  Direct Link  |  

14:  El-Shazly, A.M., B.M. Ghaneum, T.A. Morsy and H.E. Aaty, 2001. The pathogenesis of Demodex folliculorum (hair follicular mites) in females with and without rosacea. J. Egypt. Soc. Parasitol., 31: 867-875.
PubMed  |  Direct Link  |  

15:  Elston, D.M., 2010. Demodex mites: Facts and controversies. Clin. Dermatol., 28: 502-504.
CrossRef  |  

16:  Erbagci, Z., I. Erbagci and S. Erkilic, 2003. High incidence of demodicidosis in eyelid basal cell carcinomas. Int. J. Dermatol., 42: 567-571.
CrossRef  |  PubMed  |  Direct Link  |  

17:  Erbagci, Z. and S. Erkilic, 2000. Basal cell carcinoma and demodicidosis: Is there an etiologic or coincidental relationship? Turk. J. Cancer, 30: 111-118.
Direct Link  |  

18:  Erbagci, Z. and O. Ozgoztasi, 1998. The significance of Demodex folliculorum density in rosacea. Int. J. Dermatol., 37: 421-425.
CrossRef  |  PubMed  |  Direct Link  |  

19:  Forton, F. and B. Seys, 1993. Density of Demodex folliculorum in rosacea: A case-control study using standardized skin-surface biopsy. Br. J. Dermatol., 128: 650-659.
CrossRef  |  PubMed  |  Direct Link  |  

20:  Forton, F. and M. Song, 1998. Limitations of standardized skin surface biopsy in measurement of the density of Demodex folliculorum. A case report. Br. J. Dermatol., 139: 697-700.
CrossRef  |  PubMed  |  Direct Link  |  

21:  Hsu, C.K., M.M.L. Hsu and J.Y.Y. Lee, 2009. Demodicosis: A clinicopathological study. J. Am. Acad. Dermatol., 60: 453-462.
CrossRef  |  PubMed  |  Direct Link  |  

22:  Jarmuda, S., N. O'Reilly, R. Zaba, O. Jakubowicz, A. Szkaradkiewicz and K. Kavanagh, 2012. Potential role of Demodex mites and bacteria in the induction of rosacea. J. Med. Microbiol., 61: 1504-1510.
CrossRef  |  PubMed  |  Direct Link  |  

23:  Karaman, U., T. Celik, S. Calik, S. Sener, N.E. Aydin and U.N. Daldal, 2008. Demodex spp. In hairy skin biopsy specimens. Turkiye Parazitoloji Dernegi, 32: 343-345.
PubMed  |  

24:  Karincaoglu, Y., B. Tepe, B. Kalayci, M. Atambay and M. Seyhan, 2009. Is Demodex folliculorum an aetiological factor in seborrhoeic dermatitis? Clin. Exp. Dermatol., 34: e516-e520.
CrossRef  |  PubMed  |  Direct Link  |  

25:  Khodaeiani, E., R.F. Fouladi, M. Amirnia, M. Saeidi and E.R. Karimi, 2013. Topical 4% nicotinamide vs. 1% clindamycin in moderate inflammatory acne vulgaris. Int. J. Dermatol., 52: 999-1004.
CrossRef  |  PubMed  |  Direct Link  |  

26:  Khodaeiani, E., R.F Fouladi, N. Yousefi, M. Amirnia, S. Babaeinejad and J. Shokri, 2012. Efficacy of 2% metronidazole gel in moderate acne vulgaris. Indian J. Dermatol., 57: 279-281.
CrossRef  |  PubMed  |  Direct Link  |  

27:  Kligman, A.M. and M.S. Christensen, 2011. Demodex folliculorum: Requirements for understanding its role in human skin disease. J. Invest. Dermatol., 131: 8-10.
CrossRef  |  PubMed  |  Direct Link  |  

28:  Lacey, N., K. Kavanagh and S.C. Tseng, 2009. Under the lash: Demodex mites in human diseases. Biochemist, 31: 2-6.
PubMed  |  

29:  Lazaridou, E., C. Giannopoulou, C. Fotiadou, E. Vakirlis, A. Trigoni and D. Ioannides, 2011. The potential role of microorganisms in the development of rosacea. J. German Soc. Dermatol., 9: 21-25.
CrossRef  |  PubMed  |  Direct Link  |  

30:  Moravvej, H., M. Dehghan-Mangabadi, M.R. Abbasian and G. Meshkat-Razavi, 2007. Association of rosacea with demodicosis. Arch. Iran. Med., 10: 199-203.
PubMed  |  

31:  Ozdemir, M.H., U. Aksoy, E. Sonmez, C. Aksu, C. Yorulmaz and A. Hilal, 2005. Prevalence of Demodex in health personnel working in the autopsy room. Am. J. Forensic Med. Pathol., 26: 18-23.
PubMed  |  Direct Link  |  

32:  Parodi, A., F. Drago, S. Paolino, E. Cozzani and R. Gallo, 2011. Treatment of rosacea. Annales Dermatologie Venereologie, 138: S211-S214.
CrossRef  |  Direct Link  |  

33:  Perrigouard, C., B. Peltre and B. Cribier, 2013. A histological and immunohistological study of vascular and inflammatory changes in rosacea. Annal. Dermatol. Venereol., 140: 21-29.
CrossRef  |  

34:  Powell, F.C., 2004. Rosacea and the Pilosebaceous follicle. Cutis, 74: 9-12.
PubMed  |  

35:  Rios-Yuil, J.M. and P. Mercadillo-Perez, 2013. Evaluation of Demodex folliculorum as a risk factor for the diagnosis of rosacea in skin biopsies: Mexico's general hospital (1975-2010). Indian J. Dermatol., 58: 157-157.
PubMed  |  

36:  Roihu, T. and A.L. Kariniemi, 1998. Demodex mites in acne rosacea. J. Cutaneous Pathol., 25: 550-552.
CrossRef  |  PubMed  |  Direct Link  |  

37:  Sattler, E.C., T. Maier, V.S. Hoffmann, J. Hegyi, T. Ruzicka and C. Berking, 2012. Noninvasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy. Br. J. Dermatol., 167: 1042-1047.
CrossRef  |  PubMed  |  Direct Link  |  

38:  Strohal, R., K. Marberger, H. Pehamberger and G. Stingl, 1994. Immunohistological analysis of anti-melanoma host responses. Arch. Dermatol. Res., 287: 28-35.
CrossRef  |  PubMed  |  Direct Link  |  

39:  Sun, J., X. Gui, J. He, H.M. Liu, H.Y. Yu, C.Y. Xia and Y. Xu, 2005. The relationship between infestation of Demodex folliculorum and epidermal neoplasm on face. Chinese J. Parasitol. Parasitic Dis., 23: 428-431.
PubMed  |  Direct Link  |  

40:  Thor Straten, P., J.C. Becker, P. Guldberg and J. Zeuthen, 1999. In situ T cells in melanoma. Cancer Immunol. Immunother., 48: 386-395.
CrossRef  |  Direct Link  |  

41:  Tsutsumi, Y., 2004. Deposition of igd, alpha-1-antitrypsin and alpha-1-antichymotrypsin on Demodex folliculorum and D. brevis infesting the pilosebaceous unit. Pathol. Int., 54: 32-34.
CrossRef  |  PubMed  |  Direct Link  |  

42:  Yamasaki, K. and R.L. Gallo, 2009. The molecular pathology of rosacea. J. Dermatol. Sci., 55: 77-81.
CrossRef  |  PubMed  |  Direct Link  |  

43:  Zhao, Y.E., L.P. Wu, Y. Peng and H. Cheng, 2010. Retrospective analysis of the association between Demodex infestation and rosacea. Arch. Dermatol., 146: 896-902.
CrossRef  |  PubMed  |  Direct Link  |  

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