Clinical assessment of skin phototypes: watch your words!

Fitzpatrick skin phototype classification is widely used to assess risk factors for skin cancers. This skin type evaluation is easy to use in clinical practice but is not always applied as initially described, nor practiced in a standardised way. This can have implications on the results of relevant dermato-epidemiological studies. To demonstrate, in a large multinational setting, that the phrasing of questions on sun sensitivity can have a strong impact on the perception and reporting of skin phototype, as well as the importance of a standardised procedure for phototype assessment. Using data collected from 48,258 screenees of the Euromelanoma campaign in six European countries from 2009 to 2011, we analysed the impact of change in the question phrasing on phototype classification in each country. Changing the wording of a question to assess the phototype of a person also significantly influenced the classification of phototypes in different countries (p<0.001 for each country). The difference essentially corresponded to a shift towards a less sun-sensitive skin type when a shorter question that did not include skin colour description was used. The only exception was Portugal where phototype was not patient-assessed and classification shifted towards a more sun-sensitive phototype. Results were statistically significant and highly consistent, irrespective of gender. The phrasing of questions on skin type is important and substantially influences reporting. A standardized procedure to classify phototypes should be used in order to obtain comparable data between studies

Non-invasive scoring of cellular atypia in keratinocyte cancers in 3D LC-OCT images using Deep Learning

Diagnosis based on histopathology for skin cancer detection is today's gold standard and relies on the presence or absence of biomarkers and cellular atypia. However it suffers drawbacks: it requires a strong expertise and is time-consuming. Moreover the notion of atypia or dysplasia of the visible cells used for diagnosis is very subjective, with poor inter-rater agreement reported in the literature. Lastly, histology requires a biopsy which is an invasive procedure and only captures a small sample of the lesion, which is insufficient in the context of large fields of cancerization. Here we demonstrate that the notion of cellular atypia can be objectively defined and quantified with a non-invasive in-vivo approach in three dimensions (3D). A Deep Learning (DL) algorithm is trained to segment keratinocyte (KC) nuclei from Line-field Confocal Optical Coherence Tomography (LC-OCT) 3D images. Based on these segmentations, a series of quantitative, reproducible and biologically relevant metrics is derived to describe KC nuclei individually. We show that, using those metrics, simple and more complex definitions of atypia can be derived to discriminate between healthy and pathological skins, achieving Area Under the ROC Curve (AUC) scores superior than 0.965, largely outperforming medical experts on the same task with an AUC of 0.766. All together, our approach and findings open the door to a precise quantitative monitoring of skin lesions and treatments, offering a promising non-invasive tool for clinical studies to demonstrate the effects of a treatment and for clinicians to assess the severity of a lesion and follow the evolution of pre-cancerous lesions over time.© 2022. The Author(s)

Comparison of reflectance confocal microscopy and line-field optical coherence tomography for the identification of keratinocyte skin tumours

Background: Reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT) are non-invasive imaging devices that can help in the clinical diagnosis of actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC). No studies are available on the comparison between these two technologies for the identification of the different features of keratinocyte skin tumours. Objectives: To compare RCM and LC-OCT findings in AK and SCC. Methods: A retrospective multicenter study was conducted. Tumours were imaged with RCM and LC-OCT devices before surgery, and the diagnosis was confirmed by histological examinations. LC-OCT and RCM criteria for AK/SCC were identified, and their presence/absence was evaluated in all study lesions. Gwet AC1 concordance index was calculated to compare RCM and LC-OCT. Results: We included 52 patients with 33 AKs and 19 SCCs. Irregular epidermis was visible in most tumours and with a good degree of agreement between RCM and LC-OCT (Gwet's AC1 0.74). Parakeratosis, dyskeratotic keratinocytes and both linear dilated and glomerular vessels were better visible at LC-OCT than RCM (p < 0.001). Erosion/ulceration was identified with both methods in more than half of the cases with a good degree of agreement (Gwet AC1 0.62). Conclusions: Our results suggest that both LC-OCT and hand-held RCM can help clinicians in the identification of AK and SCC, providing an in vivo and non-invasive identification of an irregular epidermis. LC-OCT proved to be more effective in identifying parakeratosis, dyskeratotic keratinocytes and vessels in this series

The effects of spatial resolution on Integral Field Spectrograph surveys at different redshifts. The CALIFA perspective

Over the past decade, 3D optical spectroscopy has become the preferred tool for understanding the properties of galaxies and is now increasingly used to carry out galaxy surveys. Low redshift surveys include SAURON, DiskMass, ATLAS3D, PINGS and VENGA. At redshifts above 0.7, surveys such as MASSIV, SINS, GLACE, and IMAGES have targeted the most luminous galaxies to study mainly their kinematic properties. The on-going CALIFA survey ($z\sim0.02$) is the first of a series of upcoming Integral Field Spectroscopy (IFS) surveys with large samples representative of the entire population of galaxies. Others include SAMI and MaNGA at lower redshift and the upcoming KMOS surveys at higher redshift. Given the importance of spatial scales in IFS surveys, the study of the effects of spatial resolution on the recovered parameters becomes important. We explore the capability of the CALIFA survey and a hypothetical higher redshift survey to reproduce the properties of a sample of objects observed with better spatial resolution at lower redshift. Using a sample of PINGS galaxies, we simulate observations at different redshifts. We then study the behaviour of different parameters as the spatial resolution degrades with increasing redshift.Comment: 20 pages, 16 figures. Accepted for publication in A&

Position statement on classification of basal cell carcinomas. Part 1: unsupervised clustering of experts as a way to build an operational classification of advanced basal cell carcinoma based on pattern recognition

Background No simple classification system has emerged for 'advanced basal cell carcinomas', and more generally for all difficult-to-treat BCCs (DTT-BCCs), due to the heterogeneity of situations, TNM inappropriateness to BCCs, and different approaches of different specialists. Objective To generate an operational classification, using the unconscious ability of experts to simplify the great heterogeneity of the clinical situations into a few relevant groups, which drive their treatment decisions. Method Non-supervised independent and blinded clustering of real clinical cases of DTT-BCCs was used. Fourteen international experts from different specialties independently partitioned 199 patient cases considered 'difficult to treat' into as many clusters they want (<= 10), choosing their own criteria for partitioning. Convergences and divergences between the individual partitions were analyzed using the similarity matrix, K-mean approach, and average silhouette method. Results There was a rather consensual clustering of cases, regardless of the specialty and nationality of the experts. Mathematical analysis showed that consensus between experts was best represented by a partition of DTT-BCCs into five clusters, easily recognized a posteriori as five clear-cut patterns of clinical situations. The concept of 'locally advanced' did not appear consistent between experts. Conclusion Although convergence between experts was not granted, this experiment shows that clinicians dealing with BCCs all tend to work by a similar pattern recognition based on the overall analysis of the situation. This study thus provides the first consensual classification of DTT-BCCs. This experimental approach using mathematical analysis of independent and blinded clustering of cases by experts can probably be applied to many other situations in dermatology and oncology

CALIFA, the Calar Alto Legacy Integral Field Area survey: I. Survey presentation

We present here the Calar Alto Legacy Integral Field Area (CALIFA) survey, which has been designed to provide a first step in this direction.We summarize the survey goals and design, including sample selection and observational strategy.We also showcase the data taken during the first observing runs (June/July 2010) and outline the reduction pipeline, quality control schemes and general characteristics of the reduced data. This survey is obtaining spatially resolved spectroscopic information of a diameter selected sample of $\sim600$ galaxies in the Local Universe (0.005< z <0.03). CALIFA has been designed to allow the building of two-dimensional maps of the following quantities: (a) stellar populations: ages and metallicities; (b) ionized gas: distribution, excitation mechanism and chemical abundances; and (c) kinematic properties: both from stellar and ionized gas components. CALIFA uses the PPAK Integral Field Unit (IFU), with a hexagonal field-of-view of \sim1.3\sq\arcmin', with a 100% covering factor by adopting a three-pointing dithering scheme. The optical wavelength range is covered from 3700 to 7000 {\AA}, using two overlapping setups (V500 and V1200), with different resolutions: R\sim850 and R\sim1650, respectively. CALIFA is a legacy survey, intended for the community. The reduced data will be released, once the quality has been guaranteed. The analyzed data fulfill the expectations of the original observing proposal, on the basis of a set of quality checks and exploratory analysis. We conclude from this first look at the data that CALIFA will be an important resource for archaeological studies of galaxies in the Local Universe.Comment: 32 pages, 29 figures, Accepted for publishing in Astronomy and Astrophysic

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology

Phenylthiourea Specifically Reduces Zebrafish Eye Size

Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO) and sodium-iodide symporter (NIS), suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe