Skip to main content
PLOS One logoLink to PLOS One
. 2022 Aug 3;17(8):e0270487. doi: 10.1371/journal.pone.0270487

Assessing the impact of color blindness on the ability of identifying benign and malignant skin lesions by naked-eye examination

Mutasem Elfalah 1, Nesrin Sulyman 2, Anas Alrwashdeh 3, Sari Al Hajaj 4, Sonia Alrawashdeh 5, Asad Al-Rawashdeh 6, Saif Aldeen AlRyalat 1,*
Editor: Nikolas K Haass7
PMCID: PMC9348688  PMID: 35921375

Abstract

Background

Color vision deficiency describes the inability to distinguish certain shades of color. The aim of this study was to assess the impact of having color vision deficiency on the accuracy of distinguishing benign and malignant skin lesions by naked-eye examination.

Methods

This was a cross-sectional study conducted during the period August 2020 to February 2021. We randomly selected a total of 20 nevi and 20 melanoma images from an open access image database. The 40 images were divided into four sets of images, each set contained 5 benign and 5 malignant skin lesion images simulated as if they were seen by a protanope physician, deuteranope physician, tritanope physician, and a set of images presented without simulation. In an online survey, students who were in their final year of medical school or had newly graduated were asked to diagnose each image as benign or malignant.

Results

A total of 140 participants were included with a mean (SD) age of 24.88 (1.51). We found a significantly higher mean accuracy for non-simulated images compared to deuteranope simulated images (p< 0.001, mean difference = 11.07, 95% CI 8.40 to 13.74). We did not find a significant difference in accuracy classification for protanope simulated images (p = 0.066), nor for tritanope simulated images (p = 0.315). Classification accuracy for malignant lesions was higher than classification accuracy for benign lesions, with the highest difference belonging to deuteranope simulated images, with a difference in mean accuracy of classifying malignant lesions by 32.2 (95% CI 27.0 to 37.6).

Conclusion

Deuteranope participants (i.e., green color deficiency) had a significantly lower accuracy of distinguishing pigmented skin lesions as benign or malignant, an impact not found for other color vision deficiencies, which was mainly for misdiagnosing benign lesions as malignant.

Introduction

It has been almost 35 years since the introduction of the ABCD pneumonic to simplify and facilitate the detection and early recognition of malignant pigmented skin lesions [1]. The pneumonic originally described suspicious characteristics that may warrant referral to specialized dermatologists, including “A” for asymmetry, “B” for border irregularity, “C” for color variegation, and “D” for a diameter of more than 6 mm. Since then, several expert groups revisited the criteria, trying to increase its accuracy, by avoiding falsely classifying benign lesions as malignant (false positive), and more importantly, avoiding classifying malignant lesions as benign (false negative) [24]. They have also added the letter “E”, referring to evolution, a rapid change in shape, color, or size of the lesion [2]. Despite the need to put all lesion characteristics in the context, the color criterion was found to be among the top of the ABCDE criteria regarding accuracy of discriminating malignant lesions [4, 5]. Moreover, lesion pattern recognition, which mainly involved the color of the lesion, also played an important role in malignant lesion detection [6, 7].

Color vision deficiency originally described the inability to distinguish certain shades of color. On the other hand, the term "color blindness" is sometime used interchangeably [8]. Despite its relative high prevalence, people might be unaware of their color vision deficiency [9]. Physicians and healthcare professionals might also be affected by color vision deficiency without being aware of their condition, which might have a significant impact on their practice [10]. In a previous study, skin condition assessment was among the most difficult tasks for people with color vision deficiency [11].

Patients with skin lesions usually present to primary care physicians for evaluation, those lesions thought to be of malignant potential are usually referred to dermatology clinics for further evaluation and possible intervention. The diagnostic and referral accuracy of pigmented skin lesions were generally found to be low among primary care physicians compared to dermatologists [1214]. The impact of having color vision deficiency on distinguishing benign and malignant skin lesions has never been studied, despite the potential impact on lesion color, an integral part of the ABCDE criteria. The aim of this study was to assess the impact of having color vision deficiency on the accuracy of distinguishing benign and malignant skin lesions by naked-eye examination. We conducted this study on participants who were in their final year in medical school or had newly graduated, whom we believe depend more on lesion color criteria in distinguishing benign and malignant lesions.

Methods and materials

Design and participants

This was a cross-sectional study conducted during the period between August 2020 and February 2021. The study was approved by the institutional review board (IRB) and research committee at Jordan university hospital and the University of Jordan, and was conducted in concordance of the latest declaration of Helsinki. The study included participants who were either in their final year of medical school or had newly graduated and were working as general practitioners. Participants who did not have a dermatology rotation during their medical school were excluded at the beginning of the survey.

Using an online form, we detailed the nature of the project. Participants then provided their consent for participation. The rater was first asked to take an online Ishihara test to confirm the absence of preexisting color vision deficiency, and participants who had a score below 12/13 were asked not to proceed with the questionnaire. After that, the rater was provided a short online presentation on Medscape medical platform that explains how to differentiate between benign and malignant tumors [15].

Assessment

The questionnaire started by asking the participant if he/she took a dermatology rotation during medical school, where all Jordanian universities usually have a 2-week long dermatology rotation with an exam at the end of rotation to assess acquired knowledge. This was followed by Ishihara testing, as described above. After that, the questionnaire asked about the participant’s demographic variables (i.e., age, gender, and occupation).

Regarding benign and malignant lesions used in the survey, we used randomizer.org to randomly select a total of 20 nevi and 20 melanoma images from MED-NODE database [16]. The 40 images were divided into four sets of images, each set contain five images for benign and five images for malignant skin lesion. The four sets were:

  • Five benign and five malignant skin lesions to be simulated as if were seen by a protanope physician;

  • Five benign and five malignant skin lesion images to be simulated as if were seen by a deuteranope physician;

  • Five benign and five malignant skin lesion images to be simulated as if were seen by a tritanope physician.

  • Five benign and five malignant skin lesion images presented without simulation.

To transform images into what a protanope, deuteranope, and tritanope participant would see, we used Vischeck color blindness simulator implemented in Fiji software [17], which has been proven to be highly accurate in simulating color-blind images [18]. We used Google forms for data collection. In order to correct for any variabilities in the screens of the device’s, we compared the accuracy of non-simulated images with simulated images. (Fig 1) shows a benign skin lesion (i.e., nevus) simulated into what a protanope, deuteranope, and tritanope participant would see, and (Fig 2) shows a malignant skin lesion (i.e., superficial spreading melanoma) simulated into what a protanope, deuteranope, and tritanope participant would see. Both figures were not part of the MED-NODE images used in this study’s survey. The 40 images used in this study’s survey were deposited openly in Harvard Dataverse [19]. It is important to note that both images were collected from our hospital setting after proper consent had been obtained, so they were not a part of the images shown in the survey originally collected for this study. The 40 images were shuffled and were presented sequentially and individually. Images were standardized in size and resolution. The rater was asked to rate each image as either benign or malignant.

Fig 1.

Fig 1

A nevus presented as an example of a benign skin lesion (A) simulated into what a protanope (B), deuteranope (C), and tritanope (D) participant would see. Note that the simulation included the lesion and the background skin, affecting the distinction at lesion borders. The image presented here is not a part of the MED-NODE database.

Fig 2.

Fig 2

A melanoma presented as an example of a malignant skin lesion (A) simulated into what a protanope (B), deuteranope (C), and tritanope (D) participant would see. The image presented here is not a part of the MED-NODE database. Figure adapted from Longo et al. study (non-simulated image) [20].

Statistical analysis

We used SPSS 26.0 in our statistical analysis. We used mean and standard deviation (SD) to describe continuous variables, and we used frequency (percentage) to describe categorical variables. The diagnosis for each image was scored as either correct (1) or incorrect (0). There were four sets of images, each containing images for five benign and five malignant lesions. Of the four sets, 3 were simulated into what a deuteranope, protanope, and tritanope participant would see, and the last set was not simulated. We calculated the accuracy score as a percentage for the benign and malignant images in each set, then the accuracy of image classification in the set (i.e., overall accuracy). We used Paired sample t-test to analyze the mean difference in accuracy between the four sets. We used independent sample t-test to analyze the accuracy score difference between men and women. We presented the data as mean difference and 95% confidence interval (CI). We used a p value threshold of 0.05 as our significance threshold.

Results

A total of 152 participants completed image classification. Among them, 12 participants did not have a dermatology rotation during their medical school, and thus were excluded from further analysis. For the 140 participants included in the analysis, the mean (SD) age was 24.88 (1.51). Among the participants were 86 men with a mean (SD) age of 25.2 (1.50), and 54 women with a mean (SD) age of 24.37 (1.40). Table 1 details the mean accuracy of classifying lesions presented in the images in each set (i.e., protanope, deuteranope, tritanope simulated images and non-simulated images) as either benign or malignant lesions. It also presents the mean difference in classification accuracy between images containing benign and malignant lesions.

Table 1. The mean accuracy of classifying lesions presented in the images in each set (i.e., protanope, deuteranope, tritanope simulated images and non-simulated images) as either benign or malignant lesions.

As well as, the mean difference in classification accuracy between images containing benign and malignant lesions.

Mean % Std. Deviation % p value Mean difference % 95% CI %
Protanope simulated images Accuracy of benign lesion classification 73.86 24.68 <0.001 8.4 4.0 to 12.8
Accuracy of malignant lesion classification 82.28 18.90
Deuteranope simulated images Accuracy of benign lesion classification 48.28 22.5 <0.001 32.2 27.0 to 37.6
Accuracy of malignant lesion classification 82.58 19.04
Tritanope simulated images Accuracy of benign lesion classification 70.0 26.98 <0.001 8.4 3.0 to 14.0
Accuracy of malignant lesion classification 78.42 21.6
Non-simulated images Accuracy of benign lesion classification 67.14 26.06 <0.001 16.7 10.6 to 22.8
Accuracy of malignant lesion classification 83.86 22.5

Upon comparing classification accuracy among protanope, deuteranope, and tritanope simulated images with non-simulated images, we found a significant difference in accuracy classification between deuteranope simulated images compared to non-simulated images (p< 0.001), with higher mean accuracy for non-simulated images (mean difference = 11.07, 95% CI 8.40 to 13.74). We did not find a significant difference in accuracy classification between protanope simulated images with non-simulated images (p = 0.066), nor between tritanope simulated images with non-simulated images (p = 0.315).

Upon comparing classification accuracy for benign and malignant lesions between each image simulation, we found significant differences for all images, where classification accuracy for malignant lesions was higher than classification accuracy for benign lesions. The highest difference was for deuteranope simulated images, where the accuracy of classifying malignant lesions was higher by a mean of 32.2 (95% CI 27.0 to 37.6), as shown in Table 1.

Upon comparing gender difference in regard to classification accuracy, there was no statistically significant difference between men and women for all groups, as shown in Table 2.

Table 2. Comparison in the accuracy of classifying lesions presented in the images in each set (i.e., protanope, deuteranope, tritanope simulated images and non-simulated images) between male and female participants.

Gender N Mean % Std. Deviation % p value
Protanope simulated images Male 86 79.42 18.68 0.257
Female 54 75.93 15.96
Deuteranope simulated images Male 86 63.49 14.61 0.301
Female 54 65.93 11.58
Tritanope simulated images Male 86 74.65 19.08 0.720
Female 54 73.52 16.62
Non-simulated images Male 86 73.49 16.36 0.058
Female 54 78.70 14.54

Discussion

This study tested the accuracy of classifying benign and malignant pigmented skin lesions among images simulated to appear as if seen by participants with different types of color vision deficiency, and we compared their accuracy with images that were not simulated. We found that the only color vision deficiency that affected classification accuracy was deuteranopia (i.e., green color deficiency). Upon performing our sub-group analysis to analyze if there was a difference in classification accuracy for benign or malignant lesions, we found that the classification accuracy for benign lesions was significantly lower for all images, with the highest magnitude arising from deuteranopia simulated images. In fact, non-simulated images had lower accuracy for the classification of benign lesions compared to protanopia and tritanopia simulated images. It was noted that the borders between the lesion and the surrounding skin is less distinct for deuteranopia-simulated images, which might increase the rater’s classification bias toward malignant lesions. This effect was also observed, but with a lesser degree, for protanopia-simulated images, but not for tritanopia-simulated images. This can be explained by previous studies’ observations, where the distinction of image borders increases for higher wavelength colors (i.e., toward the red colors) [21, 22], and deuteranopia- and protanopia-simulated images have more low-wavelength colors than normal or tritanopia-simulated images.

Due to the shortage of specialized dermatology clinics to diagnose and manage skin lesions, primary care physicians may need to depend on their skills and knowledge to diagnose and possibly conduct a biopsy on skin lesions [23]. Ensuring that those physicians can distinguish such lesions is of great importance. Here, we found that physicians with color vision deficiency will have a significantly higher frequency of false positives in their diagnosis’, thus, referring and performing procedures more than people without color vision deficiency, particularly those with green color deficiency. It is important to note that green color deficiency is the most common form of color vision deficiency [8].

There are various medical specialties to which a patient with a skin lesion can be presented to, including dermatology and plastic surgery, but most patients end up presenting to primary care clinics [24]. Primary care physicians play an important role in distinguishing skin lesions that warrant referral to specialized clinics, or even lesions that might need clinic based interventions [25, 26]. Many efforts have been evaluated for improving the diagnostic accuracy of primary care physicians for diagnosing malignant melanoma such as short training courses [13, 27, 28]. The most recent reviews of literature indicate that primary care physicians had sensitivities, specificities, and diagnostic accuracies ranging from 0.25 to 0.88, 0.26 to 0.71, and 0.49 to 0.80, respectively in comparison to 0.74 to 1.00, 0.56 to 0.95, and 0.85 to 0.89 sensitivities, specificities, and diagnostic accuracies for dermatologists [12]. Early referral to specialized dermatology clinics will lead to a decrease in the time from first diagnosis to excision and final histopathological diagnosis [29, 30], which in turn has significant impact on survival [31]. While the accuracy of distinguishing benign and malignant lesions was lower with color vision deficiency, it resulted in more lesions categorized as malignant and required further evaluation, rather than missing malignant lesions.

Even though the study included a relatively high number of participants with 40 instances from the openly accessible Med-NODE database to be assessed by each participant [32], with color vision deficiency simulation using high fidelity validated software, it still has limitations that need to be considered upon result’s interpretation. While we provided a short course for each participant on how to distinguish benign and malignant features, clinical decision on whether a lesion is benign or malignant is usually also dependent on clinical data, which was not provided in our case. Moreover, this study was not performed on specialized dermatologists, whom would have more experience and confidence in diagnosing benign lesions as benign depending on more lesion characteristics, other than color. Further studies in this regard might show if including experienced dermatologist might abolish such accuracy difference for participants with color vision deficiency. Another limitation to keep in mind is that participants used their own devices to complete the questionnaire, which might result in an impact from screen color and brightness on the classification accuracy.

Conclusion

Deuteranopia (i.e., green color deficiency) led to a significant decrease in accuracy of distinguishing pigmented skin lesions as benign or malignant on simulated images, an impact that was not found for other color vision deficiencies. We also found that the poor distinguishing accuracy was mainly for misdiagnosing benign lesions as malignant, which was also most prominent for deuteranopia simulated images.

Data Availability

This study used the MED-NOD dataset, an open access skin lesion image dataset available at their website: http://www.cs.rug.nl/~imaging/databases/melanoma_naevi/. The images used in this study, including simulated images, were deposited in Harvard dataverse at https://doi.org/10.7910/DVN/OX324U.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Friedman RJ, Rigel DS, Kopf AW. Early detection of malignant melanoma: the role of physician examination and self-examination of the skin. CA Cancer J Clin. 1985;35: 130–151. doi: 10.3322/canjclin.35.3.130 [DOI] [PubMed] [Google Scholar]
  • 2.Abbasi NR, Shaw HM, Rigel DS, Friedman RJ, McCarthy WH, Osman I, et al. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. JAMA. 2004;292: 2771–2776. doi: 10.1001/jama.292.22.2771 [DOI] [PubMed] [Google Scholar]
  • 3.Rigel DS, Russak J, Friedman R. The Evolution of Melanoma Diagnosis: 25 Years Beyond the ABCDs. CA Cancer J Clin. 2010;60: 301–316. doi: 10.3322/caac.20074 [DOI] [PubMed] [Google Scholar]
  • 4.Tsao H, Olazagasti JM, Cordoro KM, Brewer JD, Taylor SC, Bordeaux JS, et al. Early detection of melanoma: Reviewing the ABCDEs. J Am Acad Dermatol. 2015;72: 717–723. doi: 10.1016/j.jaad.2015.01.025 [DOI] [PubMed] [Google Scholar]
  • 5.Thomas L, Tranchand P, Berard F, Secchi T, Colin C, Moulin G. Semiological Value of ABCDE Criteria in the Diagnosis of Cutaneous Pigmented Tumors. Dermatology. 1998;197: 11–17. doi: 10.1159/000017969 [DOI] [PubMed] [Google Scholar]
  • 6.Gachon J, Beaulieu P, Sei JF, Gouvernet J, Claudel JP, Lemaitre M, et al. First Prospective Study of the Recognition Process of Melanoma in Dermatological Practice. Arch Dermatol. 2005;141: 434–438. doi: 10.1001/archderm.141.4.434 [DOI] [PubMed] [Google Scholar]
  • 7.Girardi S, Gaudy C, Gouvernet J, Teston J, Richard MA, Grob J-J. Superiority of a cognitive education with photographs over ABCD criteria in the education of the general population to the early detection of melanoma: A randomized study. Int J Cancer. 2006;118: 2276–2280. doi: 10.1002/ijc.21351 [DOI] [PubMed] [Google Scholar]
  • 8.Color vision deficiency. [cited 20 Feb 2021]. Available: https://www.aoa.org/healthy-eyes/eye-and-vision-conditions/color-vision-deficiency?sso=y
  • 9.Chan XBV, Goh SMS, Tan NC. Subjects with colour vision deficiency in the community: what do primary care physicians need to know? Asia Pac Fam Med. 2014;13: 10. doi: 10.1186/s12930-014-0010-3 [DOI] [Google Scholar]
  • 10.AlRyalat SA, Muhtaseb R, Alshammari T. Simulating a colour-blind ophthalmologist for diagnosing and staging diabetic retinopathy. Eye. 2020; 1–4. doi: 10.1038/s41433-020-01232-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Spalding JAB, Cole BL, Mir FA. Advice for medical students and practitioners with colour vision deficiency: a website resource. Clin Exp Optom. 2010;93: 39–41. doi: 10.1111/j.1444-0938.2009.00434.x [DOI] [PubMed] [Google Scholar]
  • 12.Corbo MD, Wismer J. Agreement between Dermatologists and Primary Care Practitioners in the Diagnosis of Malignant Melanoma: Review of the Literature. J Cutan Med Surg. 2012;16: 306–310. doi: 10.1177/120347541201600506 [DOI] [PubMed] [Google Scholar]
  • 13.Carli P, De Giorgi V, Crocetti E, Caldini L, Ressel C, Giannotti B. Diagnostic and referral accuracy of family doctors in melanoma screening: effect of a short formal training. Eur J Cancer Prev. 2005;14: 51–55. doi: 10.1097/00008469-200502000-00007 [DOI] [PubMed] [Google Scholar]
  • 14.Castillo-Arenas E, Garrido V, Serrano-Ortega S. Skin Conditions in Primary Care: An Analysis of Referral Demand. Actas Dermo-Sifiliográficas Engl Ed. 2014;105: 271–275. doi: 10.1016/j.adengl.2013.10.005 [DOI] [PubMed] [Google Scholar]
  • 15.Can You Recognize Benign Skin Lesions From Cancerous Ones? [cited 10 Aug 2021]. Available: https://reference.medscape.com/features/slideshow/suspicious-skin-lesions
  • 16.Giotis I, Molders N, Land S, Biehl M, Jonkman MF, Petkov N. MED-NODE: A computer-assisted melanoma diagnosis system using non-dermoscopic images. Expert Syst Appl. 2015;42: 6578–6585. doi: 10.1016/j.eswa.2015.04.034 [DOI] [Google Scholar]
  • 17.Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji—an Open Source platform for biological image analysis. Nat Methods. 2012;9. doi: 10.1038/nmeth.2019 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Lillo J, Alvaro L, Moreira H. An experimental method for the assessment of color simulation tools. J Vis. 2014;14: 15. doi: 10.1167/14.8.15 [DOI] [PubMed] [Google Scholar]
  • 19.AlRyalat SA. Cutaneous benign and malignant lesions simulated for color blindness. Harvard Dataverse; 2022. Available: 10.7910/DVN/OX324U [DOI] [Google Scholar]
  • 20.Longo C, Piana S, Lallas A, Moscarella E, Lombardi M, Raucci M, et al. Routine Clinical-Pathologic Correlation of Pigmented Skin Tumors Can Influence Patient Management. PloS One. 2015;10: e0136031. doi: 10.1371/journal.pone.0136031 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Kaiser PK, Lee BB, Martin PR, Valberg A. The physiological basis of the minimally distinct border demonstrated in the ganglion cells of the macaque retina. J Physiol. 1990;422: 153–183. doi: 10.1113/jphysiol.1990.sp017978 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Frome FS, Buck SL, Boynton RM. Visibility of borders: separate and combined effects of color differences, luminance contrast, and luminance level. J Opt Soc Am. 1981;71: 145–150. doi: 10.1364/josa.71.000145 [DOI] [PubMed] [Google Scholar]
  • 23.Chen SC, Pennie ML, Kolm P, Warshaw EM, Weisberg EL, Brown KM, et al. Diagnosing and Managing Cutaneous Pigmented Lesions: Primary Care Physicians Versus Dermatologists. J Gen Intern Med. 2006;21: 678–682. doi: 10.1111/j.1525-1497.2006.00462.x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Pereira da Veiga CR, Veiga C, Drummond-Lage AP, Alves Wainstein AJ, Cristina de Melo A. Melanoma Patient Journey: Understanding Resource Use and Bridging the Gap between Dermatologist, Surgeon and Oncologist in Different Healthcare Systems. Rochester, NY: Social Science Research Network; 2018. Feb. Report No.: ID 3279188. doi: 10.2139/ssrn.3279188 [DOI] [Google Scholar]
  • 25.Cummins DL, Cummins JM, Pantle H, Silverman MA, Leonard AL, Chanmugam A. Cutaneous Malignant Melanoma. Mayo Clin Proc. 2006;81: 500–507. doi: 10.4065/81.4.500 [DOI] [PubMed] [Google Scholar]
  • 26.Weinstock MA, Goldstein MG, Dubé CE, Rhodes AR, Sober AJ. Basic skin cancer triage for teaching melanoma detection. J Am Acad Dermatol. 1996;34: 1063–1066. doi: 10.1016/s0190-9622(96)90287-x [DOI] [PubMed] [Google Scholar]
  • 27.Grange F, Hédelin G, Halna J-M, Grall J-C, Kirstetter H, Guillaume J-C, et al. Évaluation d’une campagne de formation des médecins généralistes et des médecins du travail au dépistage du mélanome dans le Haut-Rhin. Ann Dermatol Vénéréologie. 2005;132: 956–961. doi: 10.1016/S0151-9638(05)79556-9 [DOI] [PubMed] [Google Scholar]
  • 28.Bedout VD, Williams N, Muñoz A, Londoño A, Munera M, Naranjo N-, et al. Skin Cancer and Dermoscopy Training for Primary Care Physicians: A Pilot Study. Dermatol Pract Concept. 2021; e2021145–e2021145. doi: 10.5826/dpc.1101a145 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Thilander K, Lee T, Kjellman P, Danielsdottir T, Brandberg Y, Backlund LM. Detection Rate and Lead Times for Diagnosis of Cutaneous Malignant Melanoma—a Cross-Sectional Study at Two Dermatology Clinics in Sweden. Clin Res Dermatol Open Access. 2016;3. Available: https://symbiosisonlinepublishing.com/dermatology/dermatology12.php [Google Scholar]
  • 30.Hajdarevic S, Hörnsten Å, Sundbom E, Isaksson U, Schmitt-Egenolf M. Health-Care Delay in Malignant Melanoma: Various Pathways to Diagnosis and Treatment. Dermatol Res Pract. 2014;2014: e294287. doi: 10.1155/2014/294287 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Conic RZ, Cabrera CI, Khorana AA, Gastman BR. Determination of the impact of melanoma surgical timing on survival using the National Cancer Database. J Am Acad Dermatol. 2018;78: 40–46.e7. doi: 10.1016/j.jaad.2017.08.039 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Dermatology database used in MED-NODE. [cited 20 Feb 2021]. Available: http://www.cs.rug.nl/~imaging/databases/melanoma_naevi/

Decision Letter 0

Nikolas K Haass

4 Aug 2021

PONE-D-21-20492

Assessing the impact of color blindness on the ability of identifying benign and malignant skin lesions

PLOS ONE

Dear Dr. AlRyalat,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

While understanding the impact of color blindness on the ability of diagnosing skin lesions, both clinically and dermoscopically, is certainly of major importance for the dermatology clinic, a study like this is only of use if (1) the right methodology is applied and (2) the data are interpreted without any bias. Thus, in accordance with the expert reviewers I have some conceptual and technical concerns that need to be addressed. Rather than repeat further points here, I refer you to the specific remarks (below) for details. 

Please submit your revised manuscript by Sep 18 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Nikolas K. Haass, MD/PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that Figure 1 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright.

We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:

a) You may seek permission from the original copyright holder of Figure 1 to publish the content specifically under the CC BY 4.0 license. 

We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:

“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”

Please upload the completed Content Permission Form or other proof of granted permissions as an "Other" file with your submission. 

In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].”

b) If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.

Additional Editor Comments:

While understanding the impact of color blindness on the ability of diagnosing skin lesions, both clinically and dermoscopically, is certainly of major importance for the dermatology clinic, a study like this is only of use if (1) the right methodology is applied and (2) the data are interpreted without any bias. Thus, in accordance with the expert reviewers I have some conceptual and technical concerns that need to be addressed. Rather than repeat further points here, I refer you to the specific remarks (below) for details. 

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Disclaimer: I am not a statistician and this manuscript should be reviewed by a statistician

Title: This should include “…by naked-eye examination” because in some countries dermatoscopic evaluation is standard of care for any assessment of pigmented skin lesions by any practitioner

Design

What is the duration of a “dermatology rotation” and what proportion of that rotation involves assessing skin lesions with respect to melanoma diagnosis?

Were the readers asked if they were colour-vision impaired and excluded for that reason and were any discovered on Ishihara testing? I ask this because in a cohort of 152 it might be expected that some males at least would have an impairment. I know that does vary with ethnicity but it is worth commenting on.

Discussion

I suggest including the following observation in the discussion re Figure 1:

In C the lesion is green and so is the background and in D the lesion is red and the background pink, whereas in B (deuteranope) the surrounding skin is similar to that of the unadjusted image (A)

As a result the colour contrast between the lesion and the surrounding skin is greater for Figure 1B than for C and D which makes irregular structures at the border (right side) more visible (similar as in A). This makes the lesion more clearly asymmetrical which may lean the reader towards a malignant diagnosis.

(The Figure legend should include the appropriate letter for each image respectively)

It would be interesting to see more images. At least a collage similar to Figure 1 but with a malignant lesion. This may or may not support what I have stated about the contrast between lesion and surrounding skin colour. I suggest that the authors evaluate this with every lesion and include those results in the manuscript.

Additional Limitations:

The readers were all inexperienced and an undefined proportion were not practising clinicians. There was a selection bias for suspicious lesions which may have influenced the readers (all lesions had been excised). This could in part explain the lower overall accuracy for benign lesions.

Reviewer #2: Dear Authors,

thank you for your manuscript "Assessing the impact of color blindness on the ability of identifying benign and malignant skin lesions". The idea behind your study is appreciated. However, there are some important issues to be adressed.

1) please improve the writing, there are many errors to be corrected (example: Page 1. Background: Color vision deficiencydescribes the inability to distinguish certain

shades of color. We found a significantlyhigher mean accuracyasthe accuracy of classifying)

2) diagnostic precision. You cite several sources to emphasize that "The diagnosis and referral accuracy of pigmented skin lesions are generally low among primary care physicians compared to dermatologists [12–14]." Despite that fact your study was conducted with participant in their final year in medical school or newly graduated. Please describe your intention to choose this group of participants and discuss a potential impact on the results.

3) "we used Vischeck color blindness simulator in Fiji software [16], which has been proved to be highly accurate in simulating color-blind images [17]".

It remains unclear how the whole process was conducted. Please specify how the images were presented (probably online via a private account shown on an uncertified screen). Especially the presentation of colors may vary and is dependent from many factors (model and age of the screen, contrast, intensity, surroundings etc). This might be crucial regarding the results.

Best regards and good luck!

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: Review.docx

PLoS One. 2022 Aug 3;17(8):e0270487. doi: 10.1371/journal.pone.0270487.r002

Author response to Decision Letter 0


11 Sep 2021

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Response: Thank you.

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Response: The statistical analysis was performed by an expert biostatistician.

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

Response: The data used in this study is openly and freely accessible at http://www.cs.rug.nl/~imaging/databases/melanoma_naevi/ with no restriction.

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Response: We performed further English language polishing to ensure the absence of any typographical or grammatical errors.

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Disclaimer: I am not a statistician and this manuscript should be reviewed by a statistician

Title: This should include “…by naked-eye examination” because in some countries dermatoscopic evaluation is standard of care for any assessment of pigmented skin lesions by any practitioner

Response: We agree with the reviewer, and we amended the title and further detailed this in the aim accordingly.

Design

What is the duration of a “dermatology rotation” and what proportion of that rotation involves assessing skin lesions with respect to melanoma diagnosis?

Response: We provided details on dermatology rotations at Jordanian universities: “all Jordanian universities usually have a 2-week long dermatology rotation with an exam at the end of rotation to assess acquired knowledge.”. Moreover, we provided a link for an optional educational slides on differentiating benign and malignant skin lesions:

https://reference.medscape.com/features/slideshow/suspicious-skin-lesions

Were the readers asked if they were colour-vision impaired and excluded for that reason and were any discovered on Ishihara testing? I ask this because in a cohort of 152 it might be expected that some males at least would have an impairment. I know that does vary with ethnicity but it is worth commenting on.

Response: We agree with the reviewer, we further explained this in the methodology, where any participant who had an Ishihara score below 12/13 should not proceed with the questionnaire.

Discussion

I suggest including the following observation in the discussion re Figure 1:

In C the lesion is green and so is the background and in D the lesion is red and the background pink, whereas in B (deuteranope) the surrounding skin is similar to that of the unadjusted image (A) As a result the colour contrast between the lesion and the surrounding skin is greater for Figure 1B than for C and D which makes irregular structures at the border (right side) more visible (similar as in A). This makes the lesion more clearly asymmetrical which may lean the reader towards a malignant diagnosis.

Response: We would like to than the reviewer for this important observation, which led us to more literature digging to find the basis to explain the observation. We found that the distinction of borders can be affected by colors at the border. However, the distinction is higher for high wavelength colors (i.e., red and green), and the distinction is lower for low-wavelength colors (i.e., blue). We provided this to the discussion to further explain this important point:

“It was noted that the borders between the lesion and the surrounding skin is less distinct for deuteranopia-simulated images, which might increase rater’s suspicion toward malignant lesion. This effect was also observed, but with a lesser degree, for protanopia-simulated images, but not for tritanopia-simulated images. This can be explained by previous studies’ observations, where the distinction of image borders increases for higher wavelength colors (i.e., toward the red colors) [19,20], and deuteranopia- and protanopia-simulated images have more low-wavelength colors than normal or tritanopia-simulated images.”.

(The Figure legend should include the appropriate letter for each image respectively)

Response: We added the letters referring to each simulation type.

It would be interesting to see more images. At least a collage similar to Figure 1 but with a malignant lesion. This may or may not support what I have stated about the contrast between lesion and surrounding skin colour. I suggest that the authors evaluate this with every lesion and include those results in the manuscript.

Response: We provided detailed discussion on the impact of contrast. As per journal’s request, we had to replace the image used from the database with a one from our own patients in order to publish the image under CC BY 4.0 license, so it was difficult to include an image for a malignant lesion.

Additional Limitations:

The readers were all inexperienced and an undefined proportion were not practising clinicians. There was a selection bias for suspicious lesions which may have influenced the readers (all lesions had been excised). This could in part explain the lower overall accuracy for benign lesions.

Response: We agree with the reviewer, and we explained this limitation at the end of discussion as follows:

“Moreover, this study was not performed on specialized dermatologist, whom would have more experience and confidence in diagnosing benign lesions as benign depending on more lesion characteristic, other than color. Further studies in this regard might show if including experienced dermatologist might abolish such accuracy difference for participants with color vision deficiency.”

Reviewer #2: Dear Authors,

thank you for your manuscript "Assessing the impact of color blindness on the ability of identifying benign and malignant skin lesions". The idea behind your study is appreciated. However, there are some important issues to be adressed.

1) please improve the writing, there are many errors to be corrected (example: Page 1. Background: Color vision deficiency describes the inability to distinguish certain

shades of color. We found a significantlyhigher mean accuracyasthe accuracy of classifying)

Response: We reviewed the manuscript for typographical or grammatical errors. The above-mentioned typographical error appeared due to pdf-HTML conversion by the editorial system.

2) diagnostic precision. You cite several sources to emphasize that "The diagnosis and referral accuracy of pigmented skin lesions are generally low among primary care physicians compared to dermatologists [12–14]." Despite that fact your study was conducted with participant in their final year in medical school or newly graduated. Please describe your intention to choose this group of participants and discuss a potential impact on the results.

Response: This is an important point to elaborate. We explained the rationale of including participant in their final year in medical school or newly graduated in the introduction as follows: “We conducted this study on participant in their final year in medical school or newly graduated, whom we believe depends more on lesion color criteria in distinguishing benign and malignant lesions. Moreover, it also enabled us to include a relatively larger sample size.”. However, including such sample resulted in a limitation compared to including experienced dermatologist, which we also detailed in study limitations as follows: “Moreover, this study was not performed on specialized dermatologist, whom would have more experience and confidence in diagnosing benign lesions as benign depending on more lesion characteristic, other than color. Further studies in this regard might show if including experienced dermatologist might abolish such accuracy difference for participants with color vision deficiency.”.

3) "we used Vischeck color blindness simulator in Fiji software [16], which has been proved to be highly accurate in simulating color-blind images [17]".

It remains unclear how the whole process was conducted. Please specify how the images were presented (probably online via a private account shown on an uncertified screen). Especially the presentation of colors may vary and is dependent from many factors (model and age of the screen, contrast, intensity, surroundings etc). This might be crucial regarding the results.

Response: We agree with the reviewer on the importance of elaboration on this part. We used Google forms for data collection. To account for device variability, we assessed data about skin lesion classification without simulation, in order to compare with classification accuracy for simulated images. However, as this does not eliminate the impact of device screen variability, we also added a limitation statement in this regard: “Another limitation to keep in mind is that participants used their own devices to complete the questionnaire, which might result in impact of screen color characteristic and brightness on classification accuracy.”

Best regards and good luck!

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: Response letter.docx

Decision Letter 1

Nikolas K Haass

10 Jan 2022

PONE-D-21-20492R1

Assessing the Impact of Color Blindness on the Ability of Identifying Benign and Malignant Skin Lesions by Naked-Eye Examination

PLOS ONE

Dear Dr. AlRyalat,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

In agreement with the expert reviewers, the authors have improved the manuscript in the revised version. However, there are still points that need to be addressed. Please see the reviewers' comments below for detail.

Please submit your revised manuscript by Feb 24 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Nikolas K. Haass, MD/PhD

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

********** 

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

********** 

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

********** 

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

********** 

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

********** 

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: See attachment for necessary formatting (bold italics re English grammar issues)

See attachment for necessary formatting (bold italics re English grammar issues)

Reviewer #2: Dear Authors,

thank you for improving your manuscript significantly. "We conducted this study on participant in their final year in medical school or newly graduated, whom we believe depends more on lesion color criteria in distinguishing benign and malignant lesions. Moreover, it also enabled us to include a relatively larger sample size." As far as I know the first statement is a hypothesis. The motivation to include a larger sample size might not justify to conduct such a study with graduating medical students instead of general practicioners or dermatolists. From a clinical stanpoint, conducting this study with general pracitioners would probably be ideal in order to simulate what you wanted to express.

********** 

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Alexander F. Scheuerle, MD

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: Review R1.docx

PLoS One. 2022 Aug 3;17(8):e0270487. doi: 10.1371/journal.pone.0270487.r004

Author response to Decision Letter 1


22 Jan 2022

Reviewer #1:

Page 16: The following confusing statement must be clarified:

“We calculated the score out of 5 for each of benign and malignant lesion images

correctly identified in each of the four sets and calculated the accuracy score as a percentage for each.” At face value this states that each image is scored out of 5 so there would be a maximum score of 50 for each set of 10 images.

The next sentence, on face value, describes a second calculation.

This does not make sense to me.

Reply: We agree with the reviewer that the statement was not clear, so we rewrote the statement as follows:

“Each image’s answer was scored as either correct (1) or incorrect (0). There were four sets of images, each containing images for five benign and five malignant lesions. Of the four sets, 3 were simulated into into what a deuteranope, protanope, and tritanope participan can see, and the last set was not simulated. We calculated accuracy score as a percentage for the benign and malignant images in each set, then accuracy of image classification in the set (aka., overall accuracy).”

Page 18: The following sentence does not make sense:

Table 2 details the mean accuracy of diagnosing benign and malignant lesions for each group the difference in accuracy between benign and malignant lesion classification. (the same sentence is repeated in the legend for Table 2.

Response: We rewrote the statement and figure legend to be better descriptive for the results:

“the mean accuracy of classifying lesions presented in the images in each set (i.e., protanope, deuteranope, tritanope simulated images and non-simulated images) as either benign or malignant lesions. It also present the mean difference in classification accuracy between images containing benign and malignant lesions.”

Table 2 presents the same data as Table 1 for benign and malignant accuracy, including values and Standard Deviation and essentially just adds a decimal point to the values and adds p-value, Mean Difference and 95% CI. This could be presented in a single table. An inconsistency between the two tables for malignant lesion accuracy for Deuteranope images is noted (80.6% vs. 82.58%)

Response: Thank you for the suggestion. We combined both tables into one as suggested and rechecked the numbers presented for accuracy.

The legend of Table 3 is not a complete sentence. I actually see no purpose in including Table 3 at all. The preceding sentence conveys the negative findings adequately.

Response: We completed the figure legend. Despite the absence of significant results in the table, we think it provides important descriptive data to be considered in gender comparison.

Discussion

Page 20: There is a major typo: This study tested the accuracy of diagnosing benign and malignant pigmented skin lesions among simulated images as if seen by patients with different types…

Response: Corrected, thank you.

Re this statement: “Upon performing our sub-group analysis to analyze if there was a difference in diagnosis accuracy for benign or malignant lesions, we found that the diagnostic accuracy for benign lesions were significantly lower for all images, with highest magnitude for deuteranopia simulated images” it is actually noted that non-simulated images were associated with a lower accuracy for benign lesions than both simulated groups except Deuteranope. This must be acknowledged and discussed.

Response: Thank you for this observation. We acknowledged this finding, however, it might be difficult to further elaborate on it due to the small difference in benign lesion diagnosis accuracy between non-simulated, and those protanopia and tritanopia simulated images.

Conclusion

The study was not on distinguishing skin lesions, as stated , but on distinguishing images of skin lesions. That is significant and must be stated in the conclusion.

Response: We edited the conclusion and the manuscript throughout to ensure correct wording used.

The images presented in the revised manuscript (Figure 1) bear no reasonable resemblance at all to any skin lesion, benign or malignant.

Response: The database containing images used in the survey was provided in its respective database: http://www.cs.rug.nl/~imaging/databases/melanoma_naevi/

Due to copyright for the database, we can’t use any of its images as a figure. We obtained images for a benign (as in the figure 1), and for a malignant lesion (new figure 2) to show how simulation works. We agree with the reviewer that using images from the original database might be more reflective to what we used in this study, however, we could not obtain copyrights for database’s images.

English Grammar Issues

Page 12: Classification accuracy for malignant lesions were higher than…

Page 14: We conducted this study on participants in their final year in medical

school or newly graduated, whom we believe depends more on lesion color …

The study included participants who were either at their final year in medical school or newly graduated and were working as general practitioners.

Page 15: Using an online form, the nature of the project described and a consent to participate signed

Page 16: In order to correct for device’s screen variabilities, we compared the resulted

accuracy for none simulated images with simulated images.

(Fig 1) shows a benign skin lesion simulated into what a protanope, deuteranope, and tritanope participants can see. The 40 images were shuffled and presented sequentially each image alone.

Page 18: Upon comparing classification accuracy for benign and malignant lesions between each image simulation, we found significant differences for all images, where classification accuracy for malignant lesions were higher than classification accuracy for benign lesions

Page 20: Upon performing our sub-group analysis to analyze if there was a difference in

diagnosis accuracy for benign or malignant lesions, we found that the diagnostic accuracy for

benign lesions were significantly lower for all images, with highest magnitude for deuteranopia simulated images

Page 21: Many efforts has been evaluated…

Page 22: …it still has limitations that need to be considered upon result’s interpretation

Page 22: clinical decision to decide to wither a lesion is benign or…

Page 22: Moreover, this study was not performed on specialized dermatologist, whom would have more experience and confidence in diagnosing benign lesions as benign depending on more lesion characteristic, other than color

Page 22: Further studies in this regard might show if including experienced dermatologist might

Response: Thank you for going through the manuscript for English language. We went through the manuscript to correct the pointed mistakes and other missed ones.

Reviewer #2:

Thank you for improving your manuscript significantly. "We conducted this study on participant in their final year in medical school or newly graduated, whom we believe depends more on lesion color criteria in distinguishing benign and malignant lesions. Moreover, it also enabled us to include a relatively larger sample size." As far as I know the first statement is a hypothesis. The motivation to include a larger sample size might not justify to conduct such a study with graduating medical students instead of general practicioners or dermatolists. From a clinical stanpoint, conducting this study with general pracitioners would probably be ideal in order to simulate what you wanted to express.

Response: Thank you for this important point. We edited the manuscript accordingly.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Nikolas K Haass

27 Jan 2022

PONE-D-21-20492R2

Assessing the Impact of Color Blindness on the Ability of Identifying Benign and Malignant Skin Lesions by Naked-Eye Examination

PLOS ONE

Dear Dr. AlRyalat,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.I'd like to thank the authors for improving the manuscript. However, there are still some points that need to be addressed: (1) The point of the study is to assess the impact of colour deficiency on diagnosis of photos of pigmented skin lesions. Therefore, Figures 1 and 2 should be representative of the examined dataset and should thus be replaced with better examples (clinically). Secondly, the quality should be similar or better than that of the Figure in the original submission (the image quality of the new images is not sufficient), unless the quality of the actual dataset was similarly low as that of the new figures. The figure legend should contain the given diagnosis (e.g. compound naevus and superficial spreading melanoma). Moreover, and importantly, it should be made clear in text and legend that the lesions in Figures 1 and 2 are NOT included in the set of assessed lesions.  (2) ‘Each image’s answer’ should be corrected to ‘The diagnosis for each image’ (3) ‘aka. overall accuracy’ should be corrected to ‘i.e. overall accuracy’ (4) Table 2 should state ‘between males and female participants’ rather than ‘between males and females’ (5) ‘rater’s suspicion toward malignant’ should be ‘rater’s bias toward malignant’ (6) There are still multiple semantic and/or grammatical errors.

Please submit your revised manuscript by Mar 13 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Nikolas K. Haass, MD/PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments::

I'd like to thank the authors for improving the manuscript. However, there are still some points that need to be addressed:

(1) The point of the study is to assess the impact of colour deficiency on diagnosis of photos of pigmented skin lesions. Therefore, Figures 1 and 2 should be representative of the examined dataset and should thus be replaced with better examples (clinically). Secondly, the quality should be similar or better than that of the Figure in the original submission (the image quality of the new images is not sufficient), unless the quality of the actual dataset was similarly low as that of the new figures. The figure legend should contain the given diagnosis (e.g. compound naevus and superficial spreading melanoma). Moreover, and importantly, it should be made clear in text and legend that the lesions in Figures 1 and 2 are NOT included in the set of assessed lesions.

(2) ‘Each image’s answer’ should be corrected to ‘The diagnosis for each image’

(3) ‘aka. overall accuracy’ should be corrected to ‘i.e. overall accuracy’

(4) Table 2 should state ‘between males and female participants’ rather than ‘between males and females’

(5) ‘rater’s suspicion toward malignant’ should be ‘rater’s bias toward malignant’

(6) There are still multiple semantic and/or grammatical errors.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 Aug 3;17(8):e0270487. doi: 10.1371/journal.pone.0270487.r006

Author response to Decision Letter 2


15 Feb 2022

Response letter

Dear editor,

We are glad to submit our revised manuscript entitled:

Assessing the Impact of Color Blindness on the Ability of Identifying Benign and Malignant Skin Lesions by Naked-Eye Examination

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

I'd like to thank the authors for improving the manuscript. However, there are still some points that need to be addressed:

(1) The point of the study is to assess the impact of colour deficiency on diagnosis of photos of pigmented skin lesions. Therefore, Figures 1 and 2 should be representative of the examined dataset and should thus be replaced with better examples (clinically). Secondly, the quality should be similar or better than that of the Figure in the original submission (the image quality of the new images is not sufficient), unless the quality of the actual dataset was similarly low as that of the new figures. The figure legend should contain the given diagnosis (e.g. compound naevus and superficial spreading melanoma). Moreover, and importantly, it should be made clear in text and legend that the lesions in Figures 1 and 2 are NOT included in the set of assessed lesions.

Reply: Thank you for the clearly explained comment. We the main issue in the original image was the copyright of its deposition did not meet the copyright requirements of the Plos One journal, so we could not include one of the images used in the dataset as a figure in the manuscript. We made this point clear as requested in the figure legend. We discarded the previously included Fig.1 due to its low quality and we replaced it with a better figure with an improved quality and representation of the original dataset. The malignant lesion has similar characteristics to the images present within the MED_NOD dataset, so we just worked to improve its quality to meet journal’s requirements.

(2) ‘Each image’s answer’ should be corrected to ‘The diagnosis for each image’

Response: Done, thank you.

(3) ‘aka. overall accuracy’ should be corrected to ‘i.e. overall accuracy’

Response: Done, thank you.

(4) Table 2 should state ‘between males and female participants’ rather than ‘between males and females’

Response: Done, thank you.

(5) ‘rater’s suspicion toward malignant’ should be ‘rater’s bias toward malignant’

Response: Done, thank you.

(6) There are still multiple semantic and/or grammatical errors.

Response: We sent the manuscript for a professional medical English language professional.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 3

Nikolas K Haass

7 Jun 2022

PONE-D-21-20492R3Assessing the Impact of Color Blindness on the Ability of Identifying Benign and Malignant Skin Lesions by Naked-Eye ExaminationPLOS ONE

Dear Dr. AlRyalat,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Thank you very much for sending us the original sets of images used in the study. These photos certainly made a difference to the reviewers and me. In fact, I had two lengthy phone conversations with the reviewers today. As you can imagine from our previous communication, it would still be best to publish all 40 images of the test set as supplementary data, as this would allow not only us but also the reader to assess them and therefore make the paper more valuable to the community. Thus, I would encourage you (possibly together with the PLOS ONE editorial team) to have another strong attempt to get permission from the source of the photographs to publish them as supplementary information. If this is not possible, you should make a clear statement in the paper that the photographs are available from you on request at any time (the same way as you provided them to us privately). In any case, you will need to change the figures in the manuscript, as the point of the study is to assess the impact of colour deficiency on diagnosis of photos of pigmented skin lesions. Therefore, Figures 1 and 2 should be similar to the examined dataset and should thus be replaced with better examples. Figure 1 (benign lesion) looks reasonably similar to the benign lesions in the test sets. However, Figure 2 (melanoma) is structurally so different from Figure 1 that even a black-and-white image would suffice to see the difference (i.e. the difference between Figure 1 and 2 in the current version of the manuscript PONE-D-21-20492R3 is not relevant for the message of the study). Hence, a melanoma that is more similar to a naevus or a naevus that is more similar to a melanoma should be picked for illustration in Figures 1 and 2, to reflect the more subtle colour differences (relevant for colour deficient assessors) between benign and malignant lesions, rather than the less colour-dependent structural differences. Moreover, and importantly, it should be made clear in text and legend that the lesions in Figures 1 and 2 are NOT included in the set of assessed lesions.

Please submit your revised manuscript by Jul 22 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Nikolas K. Haass, MD/PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Dear Dr. AlRyalat, please accept my apologies for this delay and thank you very much for sending us the original sets of images used in the study. These photos certainly made a difference to the reviewers and me. In fact, I had two lengthy phone conversations with the reviewers today. As you can imagine from our previous communication, it would still be best to publish all 40 images of the test set as supplementary data, as this would allow not only us but also the reader to assess them and therefore make the paper more valuable to the community. Thus, I would encourage you (possibly together with the PLOS ONE editorial team) to have another strong attempt to get permission from the source of the photographs to publish them as supplementary information. If this is not possible, you should make a clear statement in the paper that the photographs are available from you on request at any time (the same way as you provided them to us privately). In any case, you will need to change the figures in the manuscript, as the point of the study is to assess the impact of colour deficiency on diagnosis of photos of pigmented skin lesions. Therefore, Figures 1 and 2 should be similar to the examined dataset and should thus be replaced with better examples. Figure 1 (benign lesion) looks reasonably similar to the benign lesions in the test sets. However, Figure 2 (melanoma) is structurally so different from Figure 1 that even a black-and-white image would suffice to see the difference (i.e. the difference between Figure 1 and 2 in the current version of the manuscript PONE-D-21-20492R3 is not relevant for the message of the study). Hence, a melanoma that is more similar to a naevus or a naevus that is more similar to a melanoma should be picked for illustration in Figures 1 and 2, to reflect the more subtle colour differences (relevant for colour deficient assessors) between benign and malignant lesions, rather than the less colour-dependent structural differences. Moreover, and importantly, it should be made clear in text and legend that the lesions in Figures 1 and 2 are NOT included in the set of assessed lesions.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Included in Editor Comments.

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2022 Aug 3;17(8):e0270487. doi: 10.1371/journal.pone.0270487.r008

Author response to Decision Letter 3


9 Jun 2022

We highly appreciate the time and effort Prof. Haass invested in our manuscript.

First, we deposited the images used in this study, including simulated images, in a separate database and we provided citation and link to the database:

AlRyalat, Saif Aldeen, 2022, "Cutaneous benign and malignant lesions simulated for color blindness", https://doi.org/10.7910/DVN/OX324U, Harvard Dataverse, V1

Second, we replaced figure two, where we used a new image for a melanoma previously reported in a Plos One article:

“Longo C, Piana S, Lallas A, Moscarella E, Lombardi M, Raucci M, Pellacani G, Argenziano G. Routine clinical-pathologic correlation of pigmented skin tumors can influence patient management. PLoS One. 2015 Sep 1;10(9):e0136031”

This image has a CC-BY copyright license. We used this image and we provided proper citation accordingly.

Third, we reiterated on the fact that the figures presented in this article (figures 1 and 2) were not used as part of the survey used for data collection.

We hope these changes satisfy the merit for publication in Plos One Journal.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 4

Nikolas K Haass

13 Jun 2022

Assessing the Impact of Color Blindness on the Ability of Identifying Benign and Malignant Skin Lesions by Naked-Eye Examination

PONE-D-21-20492R4

Dear Dr. AlRyalat,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Nikolas K. Haass, MD/PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have addressed all concerns.

Reviewers' comments:

Acceptance letter

Nikolas K Haass

15 Jun 2022

PONE-D-21-20492R4

Assessing the Impact of Color Blindness on the Ability of Identifying Benign and Malignant Skin Lesions by Naked-Eye Examination

Dear Dr. AlRyalat:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Prof Nikolas K. Haass

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Review.docx

    Attachment

    Submitted filename: Response letter.docx

    Attachment

    Submitted filename: Review R1.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    This study used the MED-NOD dataset, an open access skin lesion image dataset available at their website: http://www.cs.rug.nl/~imaging/databases/melanoma_naevi/. The images used in this study, including simulated images, were deposited in Harvard dataverse at https://doi.org/10.7910/DVN/OX324U.


    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES