Patients poorly recognize lesions of concern that are malignant melanomas: is self-screening the correct advice?

Background: Australia is known for its outdoor culture, with a large percentage of its population engaging in outdoor recreational activities, aquatic, non-aquatic and outdoor occupational activities. However, these outdoor enthusiasts face increased exposure to ultraviolet radiation (UVR), leading to a higher risk of skin cancer, including malignant melanoma (MM). Over the past 40 years, there has been a significant rise in skin cancer rates in Australia, with two out of three Australians expected to develop some form of skin cancer by age 70. Currently, skin cancer examinations are not endorsed in asymptomatic or low-risk individuals in Australia, with only high-risk individuals recommended to undergo regular skin examinations. Notably, the Melanoma Institute Australia suggests that one-half of patients identify MMs themselves, although this claim appears to be based on limited Australian data which may not reflect contemporary practice. Therefore this study sought to determine the percentage of patients who were able to self-identify MMs as lesions of concern when presenting for a skin cancer examination. Methods: Multi-site, cross-sectional study design incorporating a descriptive survey and total body skin cancer screening, including artificial intelligence by a skin cancer doctor. Results: A total of 260 participants with suspect MM lesions were biopsied, with 83 (31.9%) found to be melanomas. Of the true positive MMs only a small percentage of participants (21.7% specificity) correctly had concerns about the suspect lesion being a MM. These MMs were located primarily on the back (44.4%), shoulder (11.1%) and upper leg (11.1%). There was no significant difference in the size between those participants aware of a MM versus those who were not (P = 0.824, 24.6 vs 23.4 mm2). Significantly more males identified lesions of concern that were MMs as compared to females (P = 0.008, 61.1% vs 38.9%, respectively). With regard to true negatives males and females were similar (52.1% vs 47.9%, respectively). With regard to false negatives (n = 65), a greater percentage of males than females did not recognize the MM as a lesion of concern (66.2% vs 33.8%, respectively). Participants were more likely to correctly identify an invasive MM as opposed to an in situ MM (27.3% versus 21.3%). Conclusions: Only a small percentage of participants in this study were able to self-identify either in situ or invasive MM as a lesion of concern with a tendency to identify the more advanced, thicker MMs. Given that MM is associated with a high mortality and cost of treatment, particularly when invasive, the inability of lay persons to identify these cancerous lesions will likely lead to delayed treatment and a possible adverse outcome. We believe the current melanoma screening practices in Australian general practice should be revisited to improve patient outcomes with regard to MM. Additionally, prevention campaigns should include images and primary risk factors for MM.

Performance of Commercial Dermatoscopic Systems That Incorporate Artificial Intelligence for the Identification of Melanoma in General Practice: A Systematic Review.

BACKGROUND: Cutaneous melanoma remains an increasing global public health burden, particularly in fair-skinned populations. Advancing technologies, particularly artificial intelligence (AI), may provide an additional tool for clinicians to help detect malignancies with a more accurate success rate. This systematic review aimed to report the performance metrics of commercially available convolutional neural networks (CNNs) tasked with detecting MM. METHODS: A systematic literature search was performed using CINAHL, Medline, Scopus, ScienceDirect and Web of Science databases. RESULTS: A total of 16 articles reporting MM were included in this review. The combined number of melanomas detected was 1160, and non-melanoma lesions were 33,010. The performance of market-approved technology and clinician performance for classifying melanoma was highly heterogeneous, with sensitivity ranging from 16.4 to 100.0%, specificity between 40.0 and 98.3% and accuracy between 44.0 and 92.0%. Less heterogeneity was observed when clinicians worked in unison with AI, with sensitivity ranging between 83.3 and 100.0%, specificity between 83.7 and 87.3%, and accuracy between 86.4 and 86.9%. CONCLUSION: Instead of focusing on the performance of AI versus clinicians for classifying melanoma, more consistent performance has been obtained when clinicians' work is supported by AI, facilitating management decisions and improving health outcomes.

Implementation of artificial intelligence for the detection of cutaneous melanoma within a primary care setting: prevalence and types of skin cancer in outdoor enthusiasts.

Background: There is enthusiasm for implementing artificial intelligence (AI) to assist clinicians detect skin cancer. Performance metrics of AI from dermoscopic images have been promising, with studies documenting sensitivity and specificity values equal to or superior to specialists for the detection of malignant melanomas (MM). Early detection rates would particularly benefit Australia, which has the worlds highest incidence of MM per capita. The detection of skin cancer may be delayed due to late screening or the inherent difficulty in diagnosing early skin cancers which often have a paucity of clinical features and may blend into sun damaged skin. Individuals who participate in outdoor sports and recreation experience high levels of intermittent ultraviolet radiation (UVR), which is associated with the development of skin cancer, including MM. This research aimed to assess the prevalence of skin cancer in individuals who regularly participate in activities outdoors and to report the performance parameters of a commercially available AI-powered software to assess the predictive risk of MM development. Methods: Cross-sectional study design incorporating a survey, total body skin cancer screening and AI-embedded software capable of predictive scoring of queried MM. Results: A total of 423 participants consisting of surfers (n = 108), swimmers (n = 60) and walkers/runners (n = 255) participated. Point prevalence for MM was highest for surfers (6.48%), followed by walkers/runners (4.3%) and swimmers (3.33%) respectively. When compared to the general Australian population, surfers had the highest odds ratio (OR) for MM (OR 119.8), followed by walkers/runners (OR 79.74), and swimmers (OR 61.61) rounded out the populations. Surfers and swimmers reported comparatively lower lifetime hours of sun exposure (5,594 and 5,686, respectively) but more significant amounts of activity within peak ultraviolet index compared with walkers/runners (9,554 h). A total of 48 suspicious pigmented lesions made up of histopathology-confirmed MM (n = 15) and benign lesions (n = 33) were identified. The performance of the AI from this clinical population was found to have a sensitivity of 53.33%, specificity of 54.44% and accuracy of 54.17%. Conclusions: Rates of both keratinocyte carcinomas and MM were notably higher in aquatic and land-based enthusiasts compared to the general Australian population. These findings further highlight the clinical importance of sun-safe protection measures and regular skin screening in individuals who spend significant time outdoors. The use of AI in the early identification of MM is promising. However, the lower-than-expected performance metrics of the AI software used in this study indicated reservations should be held before recommending this particular version of this AI software as a reliable adjunct for clinicians in skin imaging diagnostics in patients with potentially sun damaged skin.

Exploring Mycosporine-like Amino Acid UV-Absorbing Natural Products for a New Generation of Environmentally Friendly Sunscreens.

Human skin needs additional protection from damaging ultraviolet radiation (UVR: 280-400 nm). Harmful UVR exposure leads to DNA damage and the development of skin cancer. Available sunscreens offer chemical protection from detrimental sun radiation to a certain extent. However, many synthetic sunscreens do not provide sufficient UVR protection due to the lack of photostability of their UV-absorbing active ingredients and/or the lack of ability to prevent the formation of free radicals, inevitably leading to skin damage. In addition, synthetic sunscreens may negatively affect human skin, causing irritation, accelerating skin aging and even resulting in allergic reactions. Beyond the potential negative effect on human health, some synthetic sunscreens have been shown to have a harmful impact on the environment. Consequently, identifying photostable, biodegradable, non-toxic, and renewable natural UV filters is imperative to address human health needs and provide a sustainable environmental solution. In nature, marine, freshwater, and terrestrial organisms are protected from harmful UVR through several important photoprotective mechanisms, including the synthesis of UV-absorbing compounds such as mycosporine-like amino acids (MAAs). Beyond MAAs, several other promising, natural UV-absorbing products could be considered for the future development of natural sunscreens. This review investigates the damaging impact of UVR on human health and the necessity of using sunscreens for UV protection, specifically UV-absorbing natural products that are more environmentally friendly than synthetic UV filters. Critical challenges and limitations related to using MAAs in sunscreen formulations are also evaluated. Furthermore, we explain how the genetic diversity of MAA biosynthetic pathways may be linked to their bioactivities and assess MAAs' potential for applications in human health.

Critical disease burdens of Australian adults with cystic fibrosis: Results from an online survey.

BACKGROUND: The objective of this study was to conduct a web-based questionnaire to investigate self-reported phenotypes and disease burdens of individuals living in Australia and diagnosed with cystic fibrosis (CF) using a case-control study design. METHODS: An online questionnaire was distributed to individuals with CF and healthy control subjects. Overall health rating, medications, family history, education, clinical indicators of disease, and symptoms, including their severity and frequency, were evaluated. RESULTS: There was a total of 119 respondents consisting of 59 people living with CF and 60 controls. The CF cohort had significantly lower tertiary educational levels compared to controls. The analysis specific to the CF cohort depicted a significant correlation between the frequency of hospitalizations and the level of education in the CF cohort. Of the 26 self-reported symptoms of CF that were analyzed, 14 were significantly higher in the people living with CF. The CF cohort reporting symptoms of chronic pain (25%) described an increase in the burden of disease, depicting a 30% longer mean hospitalization, increased consumption of medications and significant relationships with four other symptoms, including muscle aches, digestive issues, pancreatic insufficiency, and abdominal swelling. CONCLUSIONS: The nationwide survey identified a diverse range of clinical manifestations experienced by the Australian CF population. Chronic pain, linked to aging and the changing landscape of disease, was a significant indicator of the burden of disease. A comprehensive understanding of the phenotypic profiles and symptom variability will contribute to future research and provide insights into the impacts of disease and the burden of therapy, particularly in children, at the start of their health journey.

Genome Mining as an Alternative Way for Screening the Marine Organisms for Their Potential to Produce UV-Absorbing Mycosporine-like Amino Acid.

Mycosporine-like amino acids (MAAs) are small molecules with robust ultraviolet (UV)-absorbing capacities and a huge potential to be used as an environmentally friendly natural sunscreen. MAAs, temperature, and light-stable compounds demonstrate powerful photoprotective capacities and the ability to capture light in the UV-A and UV-B ranges without the production of damaging free radicals. The biotechnological uses of these secondary metabolites have been often limited by the small quantities restored from natural resources, variation in MAA expression profiles, and limited success in heterologous expression systems. Overcoming these obstacles requires a better understanding of MAA biosynthesis and its regulatory processes. MAAs are produced to a certain extent via a four-enzyme pathway, including genes encoding enzymes dehydroquinate synthase, enzyme O-methyltransferase, adenosine triphosphate grasp, and a nonribosomal peptide synthetase. However, there are substantial genetic discrepancies in the MAA genetic pathway in different species, suggesting further complexity of this pathway that is yet to be fully explored. In recent years, the application of genome-mining approaches allowed the identification of biosynthetic gene clusters (BGCs) that resulted in the discovery of many new compounds from unconventional sources. This review explores the use of novel genomics tools for linking BGCs and secondary metabolites based on the available omics data, including MAAs, and evaluates the potential of using novel genome-mining tools to reveal a cryptic potential for new bioproduct screening approaches and unrevealing new MAA producers.

Point prevalence of non-melanoma and melanoma skin cancers in Australian surfers and swimmers in Southeast Queensland and Northern New South Wales.

Background: Surfing and swimming are two popular outdoor aquatic activities in Australia with an estimated 2.7 million surfers and three million swimmers; however, these activities are associated with intermittent exposure to ultraviolet radiation. Our aim was to determine the point prevalence of pre-skin cancer (actinic keratosis (PSC)), non-melanoma (NMSC) and melanoma skin cancers (MSC) in Australian surfers and swimmers. Methods: This cross-sectional study involved Australian surfers who completed a survey that included physiological demographics, aquatic activity-specific demographics, history of skin cancer followed by screening. Results: A total of 171 surfers (n = 116) and swimmers (n = 55) participated in the study. Both groups were identified as having a history of skin cancer (surfers 41.4%, swimmers 36.4%) and a family history of skin cancer (surfers 52.6%, swimmers 43.6%). The majority of both groups reported using a high percentage of a chemical or physical skin cancer prevention strategy (surfers 100%, Swimmers 92.7%, P = 0.003). Significantly more surfers were identified with a skin cancer of any type vs. swimmers (50% vs. 27.3%; OR 2.67; P = 0.005) with most the common skin cancer being PSC (44.7% vs. 11.3%, P = 0.076) followed by basal cell carcinoma (BCC) (24.2% vs. 7.6%, P = 0.068). There was a total of seven MSC identified in surfers and swimmers (4.6% vs. 0.8%, respectively, P = 0.137). Most skin cancers in surfers were located on the face (28.0%) followed by the arm and back (12.1% each), whereas in swimmers, the majority of skin cancers were identified on the face (17.3%), followed by the arm and lower leg (15.4% each). The highest number of melanomas were identified in surfers (n = 6) and mainly located on the face (n = 2) and back (n = 2). There was a single melanoma identified on the back in a swimmer. With the groups combined, the majority (42.9%) of melanomas were identified on the back in participants, followed by the face (28.6%). Rates per 100,000 of NMSC and MSC in surfers and swimmers (respectively) were BCC (11,206 vs. 14,545), squamous cell carcinoma (SCC) in situ (13,793 vs. 12,727), SCC (1,724 vs. 3,636) and MSC (5,172 vs. 1,818). When compared to the general Australian population, surfers and swimmers had higher odds ratios (OR), which included BCCs (OR 7.3 and 9.4, respectively), SCCs (OR 1.7 and 3.5, respectively) and MSC (OR 96.7 and 18.8, respectively). Conclusion: Surfers and swimmers had consistently higher rates of PSC, NMSC and MSC than the general Australian population. Point prevalence of MSC (groups combined) was 76-fold higher than the general Australian population. These findings highlight the clinical importance of regular skin cancer screenings in individuals who surf or swim for early detection and treatment of skin cancer. Additionally, these aquatic enthusiasts should be advised of the benefits of sun protection strategies such as chemical and physical barriers to reduce the likelihood of developing skin cancer.

Recent advances in the discovery of novel marine natural products and mycosporine-like amino acid UV-absorbing compounds.

Bioactive compounds from marine environments represent a rich source of bioproducts for potential use in medicine and biotechnology. To discover and identify novel marine natural products (MNPs), evaluating diverse biological activities is critical. Increased sensitivity and specificity of omics technologies, especially next-generation high-throughput sequencing combined with liquid chromatography-mass spectrometry and nuclear magnetic resonance, are speeding up the discovery of novel bioactive compounds. Mycosporine-like amino acids (MAAs) isolated from many marine microorganisms are among highly promising MNPs characterized by ultraviolet radiation (UV) absorbing capacities and are recognized as a potential source of ecologically friendly sunscreens. MAAs absorb damaging UV radiation with maximum absorption in the range of 310-360 nm, including both UVA and UVB ranges. MAAs are also characterized by other biological activities such as anti-oxidant, anti-cancer, and anti-inflammatory activities. The application of modern omics approaches promoted some recent developments in our understanding of MAAs' functional significance and diversity. This review will summarize the various modern tools that could be applied during the identification and characterization of MNPs, including MAAs, to further their innovative applications. KEY POINTS: • New omics technologies are speeding up the discovery of novel bio-products • The vast diversity of bioactive capacities of marine natural products described • Marine microorganisms as a source of environmentally friendly sunscreens.

Phylogenetic analysis of genes involved in mycosporine-like amino acid biosynthesis in symbiotic dinoflagellates.

Mycosporine-like amino acids (MAAs) are multifunctional secondary metabolites involved in photoprotection in many marine organisms. As well as having broad ultraviolet (UV) absorption spectra (310-362 nm), these biological sunscreens are also involved in the prevention of oxidative stress. More than 20 different MAAs have been discovered so far, characterized by distinctive chemical structures and a broad ecological distribution. Additionally, UV-screening MAA metabolites have been investigated and used in biotechnology and cosmetics. The biosynthesis of MAAs has been suggested to occur via either the shikimate or pentose phosphate pathways. Despite their wide distribution in marine and freshwater species and also the commercial application in cosmetic products, there are still a number of uncertainties regarding the genetic, biochemical, and evolutionary origin of MAAs. Here, using a transcriptome-mining approach, we identify the gene counterparts from the shikimate or pentose phosphate pathway involved in MAA biosynthesis within the sequences of the reef-building coral symbiotic dinoflagellates (genus Symbiodinium). We also report the highly similar sequences of genes from the proposed MAA biosynthetic pathway involved in the metabolism of 4-deoxygadusol (direct MAA precursor) in various Symbiodinium strains confirming their algal origin and conserved nature. Finally, we reveal the separate identity of two O-methyltransferase genes, possibly involved in MAA biosynthesis, as well as nonribosomal peptide synthetase and adenosine triphosphate grasp homologs in symbiotic dinoflagellates. This study provides a biochemical and phylogenetic overview of the genes from the proposed MAA biosynthetic pathway with a focus on coral endosymbionts.

Validation of housekeeping genes for gene expression studies in Symbiodinium exposed to thermal and light stress.

Unicellular photosynthetic algae (dinoflagellate) from the genus Symbiodinium live in mutualistic symbiosis with reef-building corals. Cultured Symbiodinium sp. (clade C) were exposed to a range of environmental stresses that included elevated temperatures (29°C and 32°C) under high (100 µmol quanta m(-2) s(-1) Photosynthetic Active Radiation) and low (10 µmol quanta m(-2) s(-1)) irradiances. Using real-time RT-PCR the stability of expression for the nine selected putative housekeeping genes (HKGs) was tested. The most stable expression pattern was identified for cyclophilin and S-adenosyl methionine synthetase (SAM) followed by S4 ribosomal protein (Rp-S4), Calmodulin (Cal), and Cytochrome oxidase subunit 1 (Cox), respectively. Thermal stress alone resulted in the highest expression stability for Rp-S4 and SAM, with a minimum of two reference genes required for data normalization. For Symbiodinium exposed to both, light and thermal stresses, at least five reference genes were recommended by geNorm analysis. In parallel, the expression of Hsp90 for Symbiodinium in culture and in symbiosis within coral host (Acropora millepora) was evaluated using the most stable HKGs. Our results revealed a drop in Hsp90 expression after an 18 h-period and a 24 h-period of exposure to elevated temperatures indicating the similar Hsp90 expression profile in symbiotic and non-symbiotic environments. This study provides the first list of the HKGs and will provide a useful reference in future gene expression studies in symbiotic dinoflagellates.