Over-Detection of Melanoma-Suspect Lesions by a CE-Certified Smartphone App: Performance in Comparison to Dermatologists, 2D and 3D Convolutional Neural Networks in a Prospective Data Set of 1204 Pigmented Skin Lesions Involving Patients’ Perception

The exponential increase in algorithm-based mobile health (mHealth) applications (apps) for melanoma screening is a reaction to a growing market. However, the performance of available apps remains to be investigated. In this prospective study, we investigated the diagnostic accuracy of a class 1 CE-certified smartphone app in melanoma risk stratification and its patient and dermatologist satisfaction. Pigmented skin lesions ≥ 3 mm and any suspicious smaller lesions were assessed by the smartphone app SkinVision® (SkinVision® B.V., Amsterdam, the Netherlands, App-Version 6.8.1), 2D FotoFinder ATBM® master (FotoFinder ATBM® Systems GmbH, Bad Birnbach, Germany, Version 3.3.1.0), 3D Vectra® WB360 (Canfield Scientific, Parsippany, NJ, USA, Version 4.7.1) total body photography (TBP) devices, and dermatologists. The high-risk score of the smartphone app was compared with the two gold standards: histological diagnosis, or if not available, the combination of dermatologists’, 2D and 3D risk assessments. A total of 1204 lesions among 114 patients (mean age 59 years; 51% females (55 patients at high-risk for developing a melanoma, 59 melanoma patients)) were included. The smartphone app’s sensitivity, specificity, and area under the receiver operating characteristics (AUROC) varied between 41.3–83.3%, 60.0–82.9%, and 0.62–0.72% according to two study-defined reference standards. Additionally, all patients and dermatologists completed a newly created questionnaire for preference and trust of screening type. The smartphone app was rated as trustworthy by 36% (20/55) of patients at high-risk for melanoma, 49% (29/59) of melanoma patients, and 8.8% (10/114) of dermatologists. Most of the patients rated the 2D TBP imaging (93% (51/55) resp. 88% (52/59)) and the 3D TBP imaging (91% (50/55) resp. 90% (53/59)) as trustworthy. A skin cancer screening by combination of dermatologist and smartphone app was favored by only 1.8% (1/55) resp. 3.4% (2/59) of the patients; no patient preferred an assessment by a smartphone app alone. The diagnostic accuracy in clinical practice was not as reliable as previously advertised and the satisfaction with smartphone apps for melanoma risk stratification was scarce. MHealth apps might be a potential medium to increase awareness for melanoma screening in the lay population, but healthcare professionals and users should be alerted to the potential harm of over-detection and poor performance. In conclusion, we suggest further robust evidence-based evaluation before including market-approved apps in self-examination for public health benefits

Educational level-dependent melanoma awareness in a high-risk population in Switzerland

IntroductionThe worldwide incidence of melanoma has been increasing rapidly in recent decades with Switzerland having one of the highest rates in Europe. Ultraviolet (UV) radiation is one of the main risk factors for skin cancer. Our objective was to investigate UV protective behavior and melanoma awareness in a high-risk cohort for melanoma.MethodsIn this prospective monocentric study, we assessed general melanoma awareness and UV protection habits in at-risk patients (≥100 nevi, ≥5 dysplastic nevi, known CDKN2A mutation, and/or positive family history) and melanoma patients using questionnaires. ResultsBetween 01/2021 and 03/ 2022, a total of 269 patients (53.5% at-risk patients, 46.5% melanoma patients) were included. We observed a significant trend toward using a higher sun protection factor (SPF) in melanoma patients compared with at-risk patients (SPF 50+: 48% [n=60] vs. 26% [n=37]; p=0.0016). Those with a college or university degree used a high SPF significantly more often than patients with lower education levels (p=0.0007). However, higher educational levels correlated with increased annual sun exposure (p=0.041). Neither a positive family history for melanoma, nor gender or Fitzpatrick skin type influenced sun protection behavior. An age of ≥ 50 years presented as a significant risk factor for melanoma development with an odd’s ratio of 2.32. Study participation resulted in improved sun protection behavior with 51% reporting more frequent sunscreen use after study inclusion. DiscussionUV protection remains a critical factor in melanoma prevention. We suggest that melanoma awareness should continue to be raised through public skin cancer prevention campaigns with a particular focus on individuals with low levels of education

Significant evidence for a heritable contribution to cancer predisposition: a review of cancer familiality by site

<p>Abstract</p> <p>Background/Aims</p> <p>Sound and rigorous well-established, and newly extended, methods for genetic epidemiological analysis were used to analyze population evidence for genetic contributions to risk for numerous common cancer sites in Utah. The Utah Population Database (UPDB) has provided important illumination of the familial contribution to cancer risk by cancer site.</p> <p>Methods</p> <p>With over 15 years of new cancer data since the previous comprehensive familial cancer analysis, we tested for excess familial clustering using an expanded Genealogical Index of Familiality (dGIF) methodology that provides for a more informative, but conservative test for the existence of a genetic contribution to familial relatedness in cancer.</p> <p>Results</p> <p>Some new cancer sites have been analyzed for the first time, having achieved sufficiently large sample size with additions to the UPDB. This new analysis has identified 6 cancer sites with significant evidence for a heritable contribution to risk, including lip, chronic lymphocytic leukemia, thyroid, lung, prostate, and melanoma.</p> <p>Conclusions</p> <p>Both environmentally and genetically-based familial clustering have clinical significance, and these results support increased surveillance for cancer of the same sites among close relatives of affected individuals for many more cancers than are typically considered.</p

Parental attributions of control for child behaviour and their relation to discipline practices in parents of children with and without developmental delays

Children with developmental delays (DD) are at risk for developing behavior problems. Research suggests that parents’ causal attributions for child behavior are related to parenting. This study investigated this association in parents of children with DD compared to parents of typically developing (TD) children. It specifically focused on attributions of child control by separating these from attributions of responsibility, blame and intent, and from attributions of parent control and responsibility. Fifty-one parents of children with DD and 69 parents of TD children completed two questionnaires. The Written Analogue Questionnaire measured causal attributions. The Parenting Scale measured dysfunctional discipline practices. Parents of children with DD viewed the child’s role in problematic behavior more positively while also viewing misbehavior as more fixed than parents of TD children. Parents of TD children who viewed their child as more in control over misbehavior used less dysfunctional discipline, but this association was not found for parents of children with DD. The results advance understanding of how parents perceive behavior problems in children with DD and the important role these perceptions play in parental behavior management strategies. More importantly, these perceptions relate to discipline practices differently for parents of children with DD compared to parents of TD children, highlighting that parent interventions should be adapted to the specific needs of parents of children with DD

Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI

Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents viral gene expression through the assembly of repressive chromatin remodeling complexes targeting incoming viral genomes. However, it has remained unclear how initial transcriptional activation of the adenoviral genome is achieved. Here we show that Daxx mediated repression of the immediate early Ad E1A promoter is efficiently counteracted by the capsid protein VI. This requires a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses were also shown to activate the Ad E1A promoter independent of Ad gene expression and support virus replication. Our results show how Ad entry is connected to transcriptional activation of their genome in the nucleus. Our data further suggest a common principle for genome activation of DNA viruses by counteracting Daxx related repressive mechanisms through virion proteins

Co-Stimulation of BCR and Toll-Like Receptor 7 Increases Somatic Hypermutation, Memory B Cell Formation, and Secondary Antibody Response to Protein Antigen

The goal of immunization is to produce both a flood of antibodies to neutralize antigen and memory cells to accelerate the secondary response. To enhance the generation of memory B cells, we examined the effect of co-engaging BCR and toll-like receptor (TLR) 7 receptors by immunizing mice with a hapten-protein antigen, NP-CGG, and a ligand, R837 (imiquimod). During the early and late primary responses, there was no augmentation with R837 on the number of germinal center B cells or serum antibody. However, in the niche of germinal centers, R837 increased somatic hypermutation in the canonical VH1-72 gene that encodes NP-specific antibody. Increased mutation was not due to enhanced expression of activation-induced deaminase, but was likely a result of selection for high-affinity B cells with altered codons in the gene. This correlated with the appearance of antigen-specific B cells with a memory phenotype, which was intrinsic to TLR7 on B cells. To determine if these memory cells produced a recall response after a secondary challenge, spleen cells from mice that were immunized with NP-CGG and R837 were adoptively transferred into muMT recipients, and boosted with NP-CGG. Cells from mice that initially received both antigen and R837 generated a robust increase in germinal center B cells, plasmablasts, plasma cells, and serum antibody, compared with their cohorts who received antigen alone. These results support the use of co-immunization with TLR7 ligands to promote vigorous memory B cell responses to protein antigens

Phenotypic and Nodule Microbial Diversity among Crimson Clover (Trifolium incarnatum L.) Accessions

Crimson clover (Trifolium incarnatum L.) is the most common legume cover crop in the United States. Previous research found limited genetic variation for crimson clover within the National Plant Germplasm System (NPGS) collection. The aim of this study was to assess the phenotypic and nodule microbial diversity within the NPGS crimson clover collection, focusing on traits important for cover crop performance. Experiments were conducted at the Beltsville Agricultural Research Center (Maryland, USA) across three growing seasons (2012&ndash;2013, 2013&ndash;2014, 2014&ndash;2015) to evaluate 37 crimson clover accessions for six phenotypic traits: fall emergence, winter survival, flowering time, biomass per plant, nitrogen (N) content in aboveground biomass, and proportion of plant N from biological nitrogen fixation (BNF). Accession effect was significant across all six traits. Fall emergence of plant introductions (PIs) ranged from 16.0% to 70.5%, winter survival ranged from 52.8% to 82.0%, and growing degree days (GDD) to 25% maturity ranged from 1470 GDD to 1910 GDD. Biomass per plant ranged from 1.52 to 6.51 g, N content ranged from 1.87% to 2.24%, and proportion of plant N from BNF ranged from 50.2% to 85.6%. Accessions showed particularly clear differences for fall emergence and flowering time, indicating greater diversity and potential for selection in cover crop breeding programs. Fall emergence and winter survival were positively correlated, and both were negatively correlated with biomass per plant and plant N from BNF. A few promising lines performed well across multiple key traits, and are of particular interest as parents in future breeding efforts, including PIs 369045, 418900, 561943, 561944, and 655006. In 2014&ndash;2015, accessions were also assessed for nodule microbiome diversity, and 11 genera were identified across the sampled nodules. There was large variation among accessions in terms of species diversity, but this diversity was not associated with observed plant traits, and the functional implications of nodule microbiome diversity remain unclear