An Updated Algorithm Integrated With Patient Data for the Differentiation of Atypical Nevi From Early Melanomas: the idScore 2021

Introduction: It is well known that multiple patient-related risk factors contribute to the development of cutaneous melanoma, including demographic, phenotypic and anamnestic factors. Objectives: We aimed to investigate which MM risk factors were relevant to be incorporated in a risk scoring-classifier based clinico-dermoscopic algorithm. Methods: This retrospective study was performed on a monocentric dataset of 374 atypical melanocytic skin lesions sharing equivocal dermoscopic features, excised in the suspicion of malignancy. Dermoscopic standardized images of 258 atypical nevi (aN) and 116 early melanomas (eMM) were collected along with objective lesional data (i.e., maximum diameter, specific body site and body area) and 7 dermoscopic data. All cases were combined with a series of 10 MM risk factors, including demographic (2), phenotypic (5) and anamnestic (3) ones. Results: The proposed iDScore 2021 algorithm is composed by 9 variables (age, skin phototype I/II, personal/familiar history of MM, maximum diameter, location on the lower extremities (thighs/legs/ ankles/back of the feet) and 4 dermoscopic features (irregular dots and globules, irregular streaks, blue gray peppering, blue white veil). The algorithm assigned to each lesion a score from 0 to 18, reached an area under the ROC curve of 92% and, with a score threshold ≥ 6, a sensitivity (SE) of 98.2% and a specificity (SP) of 50.4%, surpassing the experts in SE (+13%) and SP (+9%).Conclusions: An integrated checklist combining multiple anamnestic data with selected relevant dermoscopic features can be useful in the differential diagnosis and management of eMM and aN exhibiting with equivocal features

Fiabot!: design and evaluation of a mobile storytelling application for schools

This paper contributes to the ongoing debate about how digital technology can be integrated into the formal education system. Within a longitudinal research study, which lasted four years, we conducted an investigation on how mobile technology can support educational activities as defined by a school curriculum. Among the topics included in the school curriculum, we focused on the literary field and developed a Digital StoryTelling (DST) application, Fiabot!, to support this activity. Here, we describe the design of the application and how we evaluated its impact on educational activities. The application was designed and evaluated in two primary schools. The study had the objectives of exploring whether Fiabot! supports children in achieving educational objectives defined by the curriculum, how this effectively supports teachers, and to what extent children like using it for the creation and sharing of their stories. Our findings show that the application has a positive impact on curriculum enactment and effectively supports the related educational activities. Overall, Fiabot! wasdemonstrated to be very effective in stimulating children's discussion of a story's plot and characters. Thus, Fiabot! supported children not only in being creative but also in organizing their work and exploring a digital media opportunity. This resulted in the development of new skills and the better grounding of previously acquired knowledge, while teachers also had the opportunity to expand their teaching skills and get a taste of ICT's potential in education

Child-computer interaction, ubiquitous technologies, and big data

In this forum we celebrate research that helps to successfully bring the benefits of computing technologies to children, older adults, people with disabilities, and other populations that are often ignored in the design of mass-marketed products. The children’s technology landscape is changing quickly. The ubiquity of interactive technologies means children can access them just about anytime, anywhere. At the same time, these technologies constantly collect data from and about children, bringing them into the age of big data, voluntarily or not. These developments have the potential to significantly change children’s relationship to technology and the long-term impact of technology use. To discuss these changes, the child-computer-interaction community held a special interest group (SIG) meeting during the CHI 2018 conference

UVA-1 phototherapy as adjuvant treatment for eosinophilic fasciitis: in vitro and in vivo functional characterization

Introduction: Eosinophilic fasciitis (EF) is a rare autoimmune disease causing progressive induration of dermal, hypodermal, and muscularis fascia. The exact pathogenesis is yet to be fully understood, and a validated therapy protocol still lacks. We here aimed to realize a clinical–functional characterization of these patients. Materials and methods: A total of eight patients (five males, 45 years average) were treated with adjuvant high-dose UVA-1 phototherapy (90 J/cm), after having received the standard systemic immunosuppressive protocol (oral methylprednisolone switched to methotrexate). Body lesion mapping, Localized Scleroderma Assessment Tool (LoSCAT), Dermatology Life Quality Index (DLQI), High-Resolution Ultrasound (HRUS) (13-17MHz), and ultra HRUS (55–70 MHz) were performed at each examination time taking specific anatomical points. Gene expression analysis at a molecular level and in vitro UVA-1 irradiation was realized on lesional fibroblasts primary cultures. Results: The LoSCAT and the DLQI showed to decrease significantly starting from the last UVA-1 session. A significant reduction in muscularis fascia thickness (−50% on average) was estimated starting from 3 months after the last UVA-1 session and maintained up to 12 months follow-up. Tissues was detected by HRUS. The UVA-1 in vitro irradiation of lesional skin sites cells appeared not to affect their viability. Molecular genes analysis revealed a significant reduction of IL-1ß and of TGF-ß genes after phototherapy, while MMPs 1,2,9 gene expression was enhanced. Comment: These preliminary in vivo and in vitro findings suggest that UVA-1 phototherapy is a safe and useful adjuvant therapy able to elicit anti-inflammatory effects and stimulate tissue matrix digestion and remodeling at lesional sites

Myoimaging in the NGS era: The discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features -a case report

Background: Myosin heavy chain 7 related myopathies are rare disorders characterized by a wide phenotypic spectrum and heterogeneous pathological features. In the present study, we performed clinical, morphological, genetic and imaging investigations in three relatives affected by autosomal dominant distal myopathy. Whilst earlier traditional Sanger investigations had pointed to the wrong gene as disease causative, next-generation sequencing allowed us to obtain the definitive molecular genetic diagnosis in the family.Case presentation: The proposita, being found to harbor a novel heterozygous mutation in the RYR1 gene (p. Glu294Lys), was initially diagnosed with core myopathy. Subsequently, consideration of muscle magnetic resonance imaging (MRI) features and extension of family study led this diagnosis to be questioned. Use of next-generation sequencing analysis identified a novel mutation in the MYH7gene (p.Ser1435Pro) that segregated in the affected family members.Conclusions: This study identified a novel mutation in MYH7 in a family where the conclusive molecular diagnosis was reached through a complicated path. This case report might raise awareness, among clinicians, of the need to interpret NGS data in combination with muscle MRI patterns so as to facilitate the pinpointing of the main molecular etiology in inherited muscle disorders

Phenotypic definition and genotype-phenotype correlates in pmpca-related disease

Background: Peptidase mitochondrial processing alpha (PMPCA) biallelic mutations cause a spectrum of disorders ranging from severe progressive multisystemic mitochondrial encephalopathy to a milder non-progressive cerebellar ataxia with or without intellectual disability. Recently, we and others described an intermediate phenotype in two unrelated patients. Methods: We report a second Italian patient carrying novel PMPCA variants (p.Trp278Leu; p.Arg362Gly). Molecular modeling, dynamics simulation, RT-qPCR, and Western blotting were performed to predict the pathogenic impact of variants in the two Italian patients and attempt genotype-phenotype correlates. Results: In line with the two patients with intermediate phenotypes, our case presented global psychomotor delay with regression, intellectual disability, spastic-ataxic gait, and hyperkinetic movements, with cerebellar atrophy and bilateral striatal hyperintensities. However, blood lactate, muscle biopsy, and MRI spectroscopy were normal. PMPCA protein levels were significantly higher than controls despite normal cDNA levels. Dynamics simulation of several PMPCA missense variants showed a variable impact on the flexibility of the glycine rich loop and, for some cases, on the overall protein stability, without clear genotype-phenotype correlates. Conclusion: We confirm the expansion of PMPCA phenotypic spectrum including an intermediate phenotype of progressive encephalopathy without systemic involvement. The association of cerebellar atrophy with “Leigh-like” striatal hyperintensities may represent a “red flag” for this condition

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 combination of dermoscopy and reflectance confocal microscopy increases the diagnostic confidence of amelanotic/hypomelanotic lentigo maligna

The dermoscopic diagnosis of amelanotic/hypomelanotic lentigo maligna/lentigo maligna melanoma (AHLM/LMM) may be very difficult in its early stages because of lack of pigment. Reflectance confocal microscopy (RCM) is an imaging technique that is especially helpful for the diagnosis of lentigo maligna. To determine the diagnostic performances of dermoscopy and RCM in the diagnosis of AHLM/LMMs we evaluated dermoscopic and RCM images of consecutive cases of histopathologically confirmed AHLM/LMMs, amelanotic/hypomelanotic basal cell carcinoma and squamous cell carcinoma (AHBCCs/AHSCCs), amelanotic/hypomelanotic benign lesions (AHBLs), and actinic keratoses (AKs) from five participating centers. Sensitivity, specificity, accuracy, predictive values, and level of diagnosis confidence were calculated for both diagnostic procedures. Both dermoscopy and RCM showed diagnostic performance >97% in the diagnosis of AHLM/LMMs versus AHBCC/AHSCCs and their combination slightly improved diagnostic performance, with accuracy increasing from 98.0% to 99.1%. Similarly, RCM in combination with dermoscopy showed a tiny increase in the diagnostic performance in the diagnosis of AHLM/LMMs versus AHBLs (accuracy increased from 87.2% to 88.8%) and versus AKs (accuracy increased from 91.4% to 93.4%). Although the increase in diagnostic performance due to RCM was modest, the combination of dermoscopy and RCM greatly increased the level of confidence; high confidence in the diagnosis of AHLM/LMMs versus AHBLs increased from 36.2% with dermoscopy alone to 76.6% with dermoscopy plus RMC. Based on our results, dermoscopy and RCM should be complementary to improve not only diagnostic accuracy but also the level of diagnostic certainty in the diagnosis of AHLM/LMMs

Novel COX11 Mutations Associated with Mitochondrial Disorder: Functional Characterization in Patient Fibroblasts and Saccharomyces cerevisiae

Genetic defects in the nuclear encoded subunits and assembly factors of cytochrome c oxidase (mitochondrial complex IV) are very rare and are associated with a wide variety of phenotypes. Biallelic pathogenic variants in the COX11 protein were previously identified in two unrelated children with infantile-onset mitochondrial encephalopathies. Through comprehensive clinical, genetic and functional analyses, here we report on a new patient harboring novel heterozygous variants in COX11, presenting with Leigh-like features, and provide additional experimental evidence for a direct correlation between COX11 protein expression and sensitivity to oxidative stress. To sort out the contribution of the single mutations to the phenotype, we employed a multi-faceted approach using Saccharomyces cerevisiae as a genetically manipulable system, and in silico structure-based analysis of human COX11. Our results reveal differential effects of the two novel COX11 mutations on yeast growth, respiration, and cellular redox status, as well as their potential impact on human protein stability and function. Strikingly, the functional deficits observed in patient fibroblasts are recapitulated in yeast models, validating the conservation of COX11's role in mitochondrial integrity across evolutionarily distant organisms. This study not only expands the mutational landscape of COX11-associated mitochondrial disorders but also underscores the continued translational relevance of yeast models in dissecting complex molecular pathways

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)