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Programs to monitor radiographic quality have been established in several Canadian provinces. These quality assurance programs depend in part on the evaluation of technical radiographic errors. Interobserver variability in the assessment of these errors reduces the reliability of such information. This study examined the interoberserver variability of three dental specialists involved in documenting radiographic technical errors, and the need for retakes following the initial radiographic surveys of 200 children. Observers were trained and calibrated to standardize the evaluation of errors. The overall frequency at which errors were found in bitewing radiographs was consistent with the results of previous studies, but the number of periapical and panoramic technical errors was low. Interobserver variability occurred in the recording of radiographic technical errors, primarily in the recording of bitewing errors. There was also interobserver variability in the ordering of retakes. The interobserver variability in the assessment of radiographic quality could not be eliminated, despite prior observer training. This could indicate that the decision to retake a radiograph may be based on subjective criteria, especially in the absence of clinical information. [ABSTRACT FROM AUTHOR]

In vitro, low-passage clinical human immunodeficiency virus type 1 (HIV-1) isolates require up to 1000 times greater serum levels of recombinant soluble CD4 (rsCD4) than have ever been given. To determine if sufficient serum levels of rsCD4 provide in vivo inhibition of HIV-1, 4 HIV-1 plasma-viremic subjects were given single-dose boluses of 2, 4, 6, 8, and 10 rug/kg intravenous rsCD4. Plasma HIV-1 cultures were done after infusion. Three subjects demonstrated a dose-dependent reduction in plasma HIV-1 viremia. The inhibitory effect of rsCD4 on plasma HIV-1 viremia was associated with the in vitro ID90–95 of the isolate, not the ID50. These data demonstrate that extremely high doses of rsCD4 inactivate cell-free HIV-1 in vivo and suggest that high doses ofrsCD4 may have some short-term therapeutic utility, such as with accidental or occupational HIV-1 exposure. [ABSTRACT FROM PUBLISHER]

Background: The effect of closed-loop insulin delivery on the risk of acute diabetes complications in people with type 1 diabetes is unclear. We investigated whether the rates of severe hypoglycaemia and diabetic ketoacidosis are lower with hybrid closed-loop insulin therapy compared with sensor-augmented (open-loop) pump therapy in a large cohort of young people., Methods: In this population-based cohort study, we evaluated young people with type 1 diabetes from 250 diabetes centres in Germany, Austria, Switzerland, and Luxembourg participating in the Diabetes Prospective Follow-up (DPV) initiative. Included participants were aged 2-20 years, with diabetes duration of more than 1 year, and were treated between Jan 1, 2021, and Dec 31, 2023. The primary outcomes were the rates of severe hypoglycaemia and ketoacidosis in people using closed-loop therapy versus open-loop therapy. Key secondary outcomes were differences in HbA 1c levels, percentage of time in glucose range of 3·9-10·0 mmol/L, and glycaemic variability. To account for relevant confounders, we applied propensity score inverse probability of treatment weighting considering several baseline characteristics., Findings: 13 922 young people (median age 13·2 years [IQR 10·0 to 16·0]; 51% male) in the DPV database met inclusion criteria and were included in the analysis. 7088 used closed-loop therapy and 6834 used open-loop therapy, with a median observation time of 1·6 years [IQR 1·1 to 2·4]. Individuals using closed-loop therapy had a higher rate of ketoacidosis (1·74 per 100 patient-years) than those using open-loop therapy (0·96 per 100 patient-years; incidence rate ratio 1·81 [1·37 to 2·40], p<0·0001) and there was no significant difference between groups in the rate of severe hypoglycaemia (5·59 per 100 patient-years vs 6·63 per 100 patient-years; incidence rate ratio 0·84 [95% CI 0·69 to 1·03], p=0·089). Individuals using closed-loop therapy had a lower rate of hypoglycaemic coma (0·62 per 100 patient-years) compared with individuals using open-loop therapy (0·91 per 100 patient-years; incidence rate ratio 0·68 [95% CI 0·48 to 0·97], p=0·034). Those in the closed-loop therapy group also had a lower HbA 1c level (7·34% vs 7·50%; difference -0·16% [95% CI -0·20 to -0·13], p=0·0007), higher percentage of time in target glucose range of 3·9-10·0 mmol/L (64% vs 52%, difference 12% [10 to 14], p<0·0001), and less glycaemic variability (coefficient of variation 35·4% vs 38·3%; difference -2·9% [-3·3 to -2·5], p<0·0001) than those in the open-loop therapy group. The rate of ketoacidosis was particularly high in young people with HbA 1c of 8·5% or higher in the closed-loop therapy group (5·25 per 100 patient-years) compared with the open-loop therapy group (1·53 per 100 patient-years; incidence rate ratio 3·43 [95% CI 1·69 to 6·97], p<0·0001)., Interpretation: Hybrid closed-loop insulin delivery has no significant effect on the rate of severe hypoglycaemia, and is associated with an increased risk of diabetic ketoacidosis, but is associated with a reduced risk of hypoglycaemic coma and improved glycaemia. These findings indicate the need for additional educational measures for the use of closed-loop insulin delivery., Funding: German Center for Diabetes Research, German Diabetes Society, and Robert Koch Institute., Competing Interests: Declaration of interests The institution of TB received grants and services from Ypsomed and Dexcom, and grants from Vitalaire for clinical trials. TB received consulting fees from Ypsomed, honoraria for lectures from Insulet, Dexcom, Ypsomed, Vitalaire, and Abbott, and participated in advisory boards for Dexcom, Insulet, Medtronic, and Ypsomed. MT received consulting fees from Sanofi and Abbott Diabetes Care, honoraria for lectures from Eli Lilly, Medtronic, and Ypsomed, and his institution received support for attending meetings from Eli Lilly. AG and TB are members and TB is Treasurer of the Executive Board of the German Society of Paediatric and Adolescent Endocrinology and Diabetology (DGPAED). BK is member of the Executive Board of the German Diabetes Society (DDG). All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Conflicts of interest: N.A. received funding, travel support and/or personal honoraria for lectures from Novartis Pharma and Johnson & Johnson that were independent of the work submitted. F.G.B. has received honoraria for participation in advisory boards, in clinical trials, and/or as a speaker from AbbVie Inc., AbbVie Deutschland GmbH & Co. KG, Boehringer Ingelheim Pharma GmbH & Co. KG, Novartis Pharma GmbH, UCB Pharma, Incyte Corporation and JanssenCilag GmbH, MoonLake. E.S. has received lecture fees from Almirall, Leo, Pierre Favre and Philips. L.O. has received honoraria as a speaker and/or travel support from Novartis Pharma GmbH, Incyte Biosciences Corporation and Janssen. Y.H. declares no conflict of interest.

This guideline was developed in close collaboration with multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF) and the European Organization for Research and Treatment of Cancer (EORTC). Recommendations for the diagnosis and treatment of melanoma were developed on the basis of systematic literature research and consensus conferences. Cutaneous melanoma (CM) is the most dangerous form of skin tumor and accounts for 90 % of skin cancer mortality. The diagnosis of melanoma can be made clinically and must always be confirmed by dermoscopy. If melanoma is suspected, a histopathological examination is always required. Sequential digital dermoscopy and whole-body photography can be used in high-risk patients to improve the detection of early-stage melanoma. If available, confocal reflectance microscopy can also improve the clinical diagnosis in special cases. Melanoma is classified according to the 8th version of the American Joint Committee on Cancer classification. For thin melanomas up to a tumor thickness of 0.8 mm, no further diagnostic imaging is required. From stage IB, lymph node sonography is recommended, but no further imaging examinations. From stage IIB/C, whole-body examinations with computed tomography or positron emission tomography CT in combination with magnetic resonance imaging of the brain are recommended. From stage IIB/C and higher, a mutation test is recommended, especially for the BRAF V600 mutation. It is important to perform a structured follow-up to detect relapses and secondary primary melanomas as early as possible. A stage-based follow-up regimen is proposed, which in the experience of the guideline group covers the optimal requirements, although further studies may be considered. This guideline is valid until the end of 2026., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amaral reports personal fees for advisory board membership from Delcath and Philogen; personal fees as an invited speaker from BMS, Neracare, Novartis and Pierre Fabre; personal fees for a writing engagement from CeCaVa and Medtrix; institutional fees as local principal investigator (PI) from Agenus Inc., AstraZeneca, BioNTech, BMS, HUYA Bioscience, Immunocore, IO Biotech, MSD, Pfizer, Philogen, Regeneron, Roche and University Hospital Essen; institutional fees as coordinating PI from Unicancer; institutional research grants from iFIT and Novartis; institutional funding from MNI - Naturwissenschaftliches und Medizinisches Institut, Neracare, Novartis, Pascoe, Sanofi and Skyline-Dx; non-remunerated membership of the American Society of Clinical Oncology (ASCO) and the Portuguese Society for Medical Oncology; and a role as clinical expert in the area of medical oncology for Infarmed. Dr. Arenberger reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, outside the submitted work. Dr Basset-Seguin has nothing to disclose. Dr. Bastholt reports personal fees for advisory boards from Bristol Myers-Squibb, Pierre Fabre, Merck MSD, Novartis and Roche, outside the submitted work. Dr. Bataille has nothing to disclose. Dr. Brochez has nothing to disclose. Dr. del Marmol reports grants and personal fees from BMS, grants and personal fees from SANOFI, personal fees from LEO Pharma, grants and personal fees from ALMIRALL, outside the submitted work. Dr. Dreno reports personal fees from MSD, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Fabre, outside the submitted work. A. Eggermont Consultant for: Agenus, Boehringer Ingelheim, BioInvent, BioNTech, Brenus, CatalYm, Eurobio, GenOway, IO Biotech, Imcheck, IQVIA, Merck&Co/MSD, Pfizer, QBiotics, Regeneron, Sairopa BV, ScanCell, Scorpion Therapeutics, Secarna, SkylineDx BV, Thermosome, Trained Immunity Discovery Speaker engagements: Merck/MSD, SkylineDx BVEquity: IO Biotech, Sairopa BV, SkylineDX BV. Dr. Fargnoli reports grants and personal fees from Almirall, personal fees from Leo Pharma, grants and personal fees from Janssen, personal fees from Novartis, personal fees from Lilly, personal fees from Sanofi, personal fees from UCB, personal fees from Abbvie, personal fees from AMGEN, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Sun Pharma, personal fees from BMS, personal fees from Kyowa Kyrin, personal fees from Pfizer, personal fees from MSD, outside the submitted work. Dr. Forsea has nothing to disclose. Dr. Garbe reports personal fees from CeCaVa, personal fees from MSD, personal fees from NeraCare, personal fees from Philogen, outside the submitted work. Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Highlight Therapeutics, personal fees from Iovance, personal fees from CureVac, personal fees from Xenthera, peronal fees from Agenus, personal fees from Almirall, and personal fees from Sun Pharma, outside the submitted work. Dr. Hoeller reports personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work. Dr. Kandolf reports personal fees for advisory boards from Bristol Myers-Squibb, MSD, Novartis Roche, Janssen, Abbvie, outside the submitted work. Dr. Kaufmann reports other from Abbvie, other from Almirall, other from Amgen, other from Astra Zeneca, other from Bionteck, other from BMS, other from Galderma, other from Incyte, other from Janssen, other from Leo, other from MSD, other from Novartis, other from Pfizer, other from Roche, other from Sanofi, outside the submitted work. Dr. Kelleners-Smeets reports personal fees from Sanofi, personal fees from Novartis, personal fees from MSD, personal fees from Sun Pharma, outside the submitted work. Dr. Lallas reports personal fees from Avene, personal fees from MSD, personal fees from Regeneron, personal fees from BMS, outside the submitted work. Dr. Lebbe reports personal fees from MSD, personal fees from Pierre Fabre, personal fees from BMS, personal fees from Sanofi, personal fees from immunocore, outside the submitted work. Dr. Leiter reports personal fees from Regeneron, Sanofi, personal fees from MSD, personal fees from Novartis, Almirall Hermal, personal fees from Sun Pharma, outside the submitted work. Dr. Longo has nothing to disclose. Dr. Lorigan reports grants and personal fees from Pierre Fabre, personal fees from MSD, grants and personal fees from BMS, personal fees from MLA diagnostics, outside the submitted work. Dr. Malvehy reports grants and personal fees from Almirall, personal fees from MSD, personal fees from Pierre Fabre, grants from Philogen, grants from Castle biosciences, grants from BMS, grants and personal fees from ISDIN, grants and personal fees from La Roche Posay, non-financial support and other from Vivascope, non-financial support and other from Damae medical, non-financial support and other from Canfield, non-financial support and other from Fotofinder, outside the submitted work. Dr. Mandala reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Regeneron, personal fees from Sun Pharma, outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Nathan reports personal fees from Novartis, grants and personal fees from Immunocore, personal fees from BMS, personal fees from SunPharma, personal fees from MSD, outside the submitted work; Dr. Pellacani has nothing to disclose. Dr. Peris reports personal fees from Abbvie, personal fees from Lilly, personal fees from Leo Pharma, personal fees from Sanofi, personal fees from Almirall, personal fees from Novartis, personal fees from Boehringer, personal fees from Amgen, outside the submitted work. Dr. Saiag reports personal fees from Novartis, MSD, NeraCare, BMS, Pierre Fabre, Merck, personal fees and grants from Damae Medical, outside the submitted work. Dr. Stockfleth has nothing to disclose. Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work. Dr. van Akkooi reports grants and personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from MSD-Merck, grants and personal fees from Merck-Pfizer, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Sirius Medical, personal fees from 4SC, personal fees from Genmab, personal fees from Menarini Silicon Biosystems, from Skyline Dx, outside the submitted work. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports personal fees from Philogen, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from La Roche Posay, personal fees from Sunpharma, personal fees from Biogena, personal fees from Cieffe Derma, outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

A unique collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to two-centimeter safety margins. For a correct stage classification and treatment decision, a sentinel lymph node biopsy shall be offered in patients with tumor thickness ≥ 1.0 mm or ≥ 0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions should be primarily made by an interdisciplinary oncology team ("Tumor Board"). Adjuvant therapies can be proposed in completely resected stage IIB-IV. In stage II only PD-1 inhibitors are approved. In stage III anti-PD-1 therapy or dabrafenib plus trametinib for patients with BRAFV600 mutated melanoma can be discussed. In resected stage IV, nivolumab can be offered, as well as ipilimumab and nivolumab, in selected, high-risk patients. In patients with clinically detected macroscopic, resectable disease, neoadjuvant therapy with ipilimumab plus nivolumab followed complete surgical resection and adjuvant therapy according to pathological response and BRAF status can be offered. Neoadjuvant therapy with pembrolizumab followed by complete surgical resection and adjuvant pembrolizumab is also recommended. For patients with disease recurrence after (neo) adjuvant therapy, further treatment should consider the type of (neo) adjuvant therapy received as well as the time of recurrence, i.e., on or off therapy. In patients with irresectable stage III/IV disease systemic treatment is always indicated. For first line treatment PD-1 antibodies alone or in combination with CTLA-4 or LAG-3 antibodies shall be considered. In stage IV melanoma with a BRAFV600 mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy, in selected cases. In patients with primary resistance to immunotherapy and harboring a BRAFV600 mutation, this therapy shall be offered as second line. Other second line therapies include therapy with tumor infiltrating lymphocytes and combinations of immune checkpoint inhibitors not used in first line. This guideline is valid until the end of 2026., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amaral reports personal fees for advisory board membership from Delcath and Philogen; personal fees as an invited speaker from BMS, Neracare, Novartis and Pierre Fabre; personal fees for a writing engagement from CeCaVa and Medtrix; institutional fees as local principal investigator (PI) from Agenus Inc., AstraZeneca, BioNTech, BMS, HUYA Bioscience, Immunocore, IO Biotech, MSD, Pfizer, Philogen, Regeneron, Roche and University Hospital Essen; institutional fees as coordinating PI from Unicancer; institutional research grants from iFIT and Novartis; institutional funding from MNI - Naturwissenschaftliches und Medizinisches Institut, Neracare, Novartis, Pascoe, Sanofi and Skyline-Dx; non-remunerated membership of the American Society of Clinical Oncology (ASCO) and the Portuguese Society for Medical Oncology; and a role as clinical expert in the area of medical oncology for Infarmed. Dr. Arenberger reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, outside the submitted work. Dr Basset-Seguin has nothing to disclose. Dr. Bastholt reports personal fees for advisory boards from Bristol Myers-Squibb, Pierre Fabre, Merck MSD, Novartis and Roche, outside the submitted work. Dr. Bataille has nothing to disclose.Dr. Brochez has nothing to disclose.Dr. del Marmol reports grants and personal fees from BMS, grants and personal fees from SANOFI, personal fees from LEO Pharma, grants and personal fees from ALMIRALL, outside the submitted work.Dr. Dreno reports personal fees from MSD, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Fabre , outside the submitted work. Dr. Eggermont reports Consultant for: Agenus, Boehringer Ingelheim, BioInvent, BioNTech, Brenus, CatalYm, Eurobio, GenOway,IO Biotech, Imcheck, IQVIA, Merck&Co/MSD, Pfizer, QBiotics, Regeneron, Sairopa BV, ScanCell,Scorpion Therapeutics, Secarna, SkylineDx BV, Thermosome, Trained Immunity DiscoverySpeaker engagements: Merck/MSD, SkylineDx BVEquity: IO Biotech, Sairopa BV, SkylineDX BV. Dr. Fargnoli reports grants and personal fees from Almirall, personal fees from Leo Pharma, grants and personal fees from Janssen, personal fees from Novartis, personal fees from Lilly, personal fees from Sanofi, personal fees from UCB, personal fees from Abbvie, personal fees from AMGEN, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Sun Pharma, personal fees from BMS, personal fees from Kyowa Kyrin, personal fees from Pfizer, personal fees from MSD, outside the submitted work.Dr. Forsea has nothing to disclose.Dr. Garbe reports personal fees from CeCaVa, personal fees from MSD, personal fees from NeraCare, personal fees from Philogen, outside the submitted work.Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Highlight Therapeutics, personal fees from Iovance, personal fees from CureVac, personal fees from Xenthera, peronal fees from Agenus, personal fees from Almirall, and personal fees from Sun Pharma, outside the submitted work.Dr. Hoeller reports personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work.Dr. Kandolf reports personal fees for advisory boards from Bristol Myers-Squibb, MSD, Novartis Roche, Janssen, Abbvie, outside the submitted work.Dr. Kaufmann reports other from Abbvie, other from Almirall, other from Amgen, other from Astra Zeneca, other from Bionteck, other from BMS, other from Galderma, other from Incyte, other from Janssen , other from Leo, other from MSD, other from Novartis, other from Pfizer, other from Roche, other from Sanofi, outside the submitted work.Dr. Kelleners-Smeets reports personal fees from Sanofi, personal fees from Novartis, personal fees from MSD, personal fees from Sun Pharma, outside the submitted work.Dr. Lallas reports personal fees from Avene, personal fees from MSD, personal fees from Regeneron, personal fees from BMS, outside the submitted work.Dr. Lebbe reports personal fees from MSD, personal fees from Pierre Fabre, personal fees from BMS, personal fees from Sanofi, personal fees from immunocore, outside the submitted work.Dr. Leiter reports personal fees from Regeneron, Sanofi, personal fees from MSD, personal fees from Novartis, Almirall Hermal, personal fees from Sun Pharma, outside the submitted work.Dr. Longo has nothing to disclose.Dr. Lorigan reports grants and personal fees from Pierre Fabre, personal fees from MSD, grants and personal fees from BMS, personal fees from MLA diagnostics, outside the submitted work.Dr. Malvehy reports grants and personal fees from Almirall, personal fees from MSD, personal fees from Pierre Fabre, grants from Philogen, grants from Castle biosciences, grants from BMS, grants and personal fees from ISDIN, grants and personal fees from La Roche Posay, non-financial support and other from Vivascope, non-financial support and other from Damae medical, non-financial support and other from Canfield, non-financial support and other from Fotofinder, outside the submitted work.Dr. Mandala reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Regeneron, personal fees from Sun Pharma, outside the submitted work.Dr. Moreno-Ramírez has nothing to disclose.Dr. Nathan reports personal fees from Novartis, grants and personal fees from Immunocore, personal fees from BMS, personal fees from SunPharma, personal fees from MSD, outside the submitted work;Dr. Pellacani has nothing to disclose.Dr. Peris reports personal fees from Abbvie, personal fees from Lilly, personal fees from Leo Pharma, personal fees from Sanofi, personal fees from Almirall, personal fees from Novartis, personal fees from Boehringer, personal fees from Amgen, outside the submitted work.Dr. Saiag reports personal fees from Novartis, MSD, NeraCare, BMS, Pierre Fabre, Merck, personal fees and grants from Damae Medical, outside the submitted work.Dr. Stockfleth has nothing to disclose.Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work.Dr. van Akkooi reports grants and personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from MSD-Merck, grants and personal fees from Merck-Pfizer, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Sirius Medical, personal fees from 4SC, personal fees from Genmab, personal fees from Menarini Silicon Biosystems, from Skyline Dx, outside the submitted work.Dr. Vieira has nothing to disclose.Dr. Zalaudek reports personal fees from Philogen, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from La Roche Posay, personal fees from Sunpharma, personal fees from Biogena, personal fees from Cieffe Derma, outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

Competing Interests: Conflicts of interest Dr Abu Rached received funding, travel support, and/or personal honoraria for lectures from Novartis Pharma and Johnson & Johnson that were independent of the work submitted. Dr Hessam has received honoraria for participation in advisory boards, in clinical trials, and/or as a speaker from AbbVie Inc, AbbVie Deutschland GmbH & Co KG, Bristol-Myers Squibb GmbH & Co KGaA, Novartis Pharma GmbH, Bristol-Myers Squibb GmbH & Co. KGaA, Almirall Hermal GmbH. Prof Bechara has received honoraria for participation in advisory boards, in clinical trials, and/or as a speaker from AbbVie Inc, AbbVie Deutschland GmbH & Co KG, Boehringer Ingelheim Pharma GmbH & Co KG, Novartis Pharma GmbH, UCB Pharma, Incyte Corporation, and JanssenCilag GmbH, MoonLake. Prof Stockfleth has received lecture fees from Almirall, Leo, Pierre Favre and Philips. Dr Ocker has received honoraria as a speaker and/or travel support from Novartis Pharma GmbH, Incyte Biosciences Corporation, and Janssen. Prof Gambichler has received speakers and/or advisory board honoraria from BMS, Sanofi-Genzyme, MSD, Novartis Pharma, Roche, Abbvie, Almirall, Janssen, Lilly, Pfizer, Pierre Fabre, and Merck-Serono outside the submitted work. Drs Herbst and Skrygan have no conflicts of interest to declare.

HPV-associated dermatological diseases include benign lesions like cutaneous warts and external genital warts. In addition, HPV infection is associated with the development of epithelial skin cancers, in particular cutaneous squamous cell carcinoma (cSCC). In contrast to anogenital and oropharyngeal cancers caused by mucosal HPV types of genus alpha papillomavirus, cSCC-associated HPV types belong to the genus beta papillomavirus. Currently available HPV vaccines that target mucosal HPV types associated with anogenital cancer and genital warts are type-specific and provide no cross-protection against beta HPV. When implementing vaccination to beta HPV to prevent skin tumors, it must be considered that acquisition of these HPV types occurs early in childhood and that the risk for cSCC increases with growing age and decreasing immune surveillance. Thus, individuals considered for beta HPV vaccination usually have pre-existing infection and are largely immunocompromised. On the other hand, worldwide increasing incidence rates of epithelial skin cancer reflect an urgent need for skin cancer prevention measures. Based on the pathogenic involvement of beta HPV, vaccination may represent a promising prevention strategy. Indeed, various procedures of prophylactic and therapeutic vaccination have been developed, and some of them have shown efficiency in animal models. Thus far, however, none of these vaccine candidates has been approved for application in humans.

Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan-Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37-126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5-126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS ( p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores ( p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14-5.75; HR 2.94, 95% CI 1.42-6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms.

Sun exposure induces major skin alterations, but its effects on skin metabolites and lipids remain largely unknown. Using an original reconstructed human epidermis (RHE) model colonized with human microbiota and supplemented with human sebum, we previously showed that a single dose of simulated solar radiation (SSR) significantly impacted the skin metabolome and microbiota. In this article, we further analyzed SSR-induced changes on skin metabolites and lipids in the same RHE model. Among the significantly altered metabolites (log2-fold changes with p ≤ 0.05), we found several natural moisturizing factors (NMFs): amino acids, lactate, glycerol, urocanic acid, pyrrolidone carboxylic acid and derivatives. Analyses of the stratum corneum lipids also showed that SSR induced lower levels of free fatty acids and higher levels of ceramides, cholesterols and its derivatives. An imbalance in NMFs and ceramides combined to an increase of proinflammatory lipids may participate in skin permeability barrier impairment, dehydration and inflammatory reaction to the sun. Our skin model also allowed the evaluation of an innovative ultraviolet/blue light (UV/BL) broad-spectrum sunscreen with a high sun protection factor (SPF50+). We found that using this sunscreen prior to SSR exposure could in part prevent SSR-induced alterations in NMFs and lipids in the skin ecosystem RHE model., (© 2024 American Society for Photobiology.)

Executive functions are essential for adaptive behavior. One executive function is the so-called 'interference control' or conflict monitoring another one is inhibitory control (i.e., action restraint and action cancelation). Recent evidence suggests an interplay of these processes, which is conceptually relevant given that newer conceptual frameworks imply that nominally different action/response control processes are explainable by a small set of cognitive and neurophysiological processes. The existence of such overarching neural principles has as yet not directly been examined. In the current study, we therefore use EEG tensor decomposition methods, to look into possible common neurophysiological signatures underlying conflict-modulated action restraint and action cancelation as mechanism underlying response inhibition. We show how conflicts differentially modulate action restraint and action cancelation processes and delineate common and distinct neural processes underlying this interplay. Concerning the spatial information modulations are similar in terms of an importance of processes reflected by parieto-occipital electrodes, suggesting that attentional selection processes play a role. Especially theta and alpha activity seem to play important roles. The data also show that tensor decomposition is sensitive to the manner of task implementation, thereby suggesting that switch probability/transitional probabilities should be taken into consideration when choosing tensor decomposition as analysis method. The study provides a blueprint of how to use tensor decomposition methods to delineate common and distinct neural mechanisms underlying action control functions using EEG data., Competing Interests: Declaration of competing interest There are no conflicts of interest, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hidradenitis suppurativa (HS) is a debilitating, chronic inflammatory disease associated with multiple triggers. As the world struggles with the global COVID-19 pandemic, it is important to review the trigger factors for chronically ill HS patients during the COVID-19 pandemic. This work investigates the self-described trigger factors of HS patients that emerged during the COVID-19 outbreak. Methods : We anonymously surveyed 110 HS patients during the SARS-CoV-2 pandemic using a 25-question questionnaire that included trigger factors for deterioration. Demographic, personal, and HS-specific information was also collected to identify potential trigger factors for HS exacerbation. All HS patients were asked if their HS had worsened compared to the time before the pandemic. Results: Compared to before the pandemic, 20% of HS patients ( n = 22) reported a worsening of HS. Patients with an HS exacerbation were significantly more likely to avoid contact with a doctor than those without an exacerbation (45.5% vs. 18.2%; p = 0.007). HS involvement, severity, exercise activity, and BMI had no association with worsening HS ( p > 0.05). Interestingly, dietary changes and increased consumption of sweets and treats were associated with worsening HS ( p = 0.011 and p = 0.013). Specifically, eating more sweets and treats was associated with a 6-fold increased risk of worsening HS. The results suggest that diet has an important influence on HS relapses. Further investigation is needed to determine whether diet is a triggering factor independent of the SARS-CoV-2 pandemic. In addition, gluteal HS involvement was associated with a more than 4.3-fold risk of HS exacerbation. Conclusions: In the management of HS patients, it is important to consider that gluteal involvement and the consumption of sweets are more often associated with deterioration.

Actinic keratoses (AK) are common skin lesions associated with chronic exposure to sun. They are believed to be precursors of malignancy as they potentially may progress to invasive squamous cell carcinomas. The goal of current therapies is to reduce the number of AK and to prevent future cancer development. This review aims at providing an overview of the hallmarks of AK and skin field cancerization. We discuss epidemiology trends, risk factors and the state of the art and evidence of the current treatments. We review key figures of AK prevalence from different countries with regard to skin cancer risk and the associated economic burden of AK. We discuss the mutational status in AK lesions and the difficulties encountered by clinicians in evaluating AK visible and invisible lesions, referring to the concept of field cancerization. Based on a systematic literature review, we further evaluate the available treatment options. The presence of subclinical skin alterations in the periphery of visible AK lesions has gained a particular attention as those non-visible lesions are known to contain the same genetic changes as those found in the AK lesions themselves, prompting the concept of 'field cancerization'. Therefore, AK treatment guidelines now recognize the importance of treating the field in patients with AK. A recent systematic literature review and network meta-analysis showed that 5-FU interventions were associated with the best efficacy and a satisfactory acceptability profile compared with other field-directed therapies used in the treatment of AK. Although AK are considered quite common, they lack an accurate descriptive definition and conclusive epidemiologic data. Limited public awareness is a barrier to early and effective treatment, including prevention strategies. While different treatment options are available, there is still a limited understanding of long-term outcomes of treatment as measured by recurrence of cancer prevention., (© 2024 European Academy of Dermatology and Venereology.)

This review aimed at summarizing some of the key points that were discussed during the photoprotection session at the International Forum of Dermatology in 2022. This international conference was designed to address prominent topics of clinical dermatology in a holistic way, allowing to articulate multiple viewpoints. Therefore, this review does not claim to be exhaustive, but is instead intended to give an overview of recent developments and ongoing controversies in the field of photoprotection. Cumulative ultraviolet radiation (UVR) exposure is the major aetiological factor in the development of photoageing, photoimunosuppression and photocarcinogenesis. UVA (320-400 nm) penetrates into the dermis and damages DNA and other intracellular and acellular targets primarily by generating reactive oxygen species (ROS). It is the major contributor to photoageing, characterized by fine and coarse wrinkles, dyspigmentation and loss of elasticity. UVB (290-320 nm) is responsible for sunburns through direct damage to DNA by the formation of 6-4 cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts. Both UVA and UVB exposure increase the risk of basal cell carcinoma, squamous cell carcinoma and melanoma. In recent years, visible light (VL; 400-700 nm) has also been implicated in the exacerbation of conditions aggravated by sun exposure such as hyperpigmentation and melasma. Photoprotection is a critical health strategy to reduce the deleterious effects of UVR and VL. Comprehensive photoprotection strategies include staying in the shade when outdoors, wearing photoprotective clothing including a wide-brimmed hat, and sunglasses, and the use of sunscreen. Due to the absorption of UV filters, the safety of sunscreens has been questioned. Newer sunscreens are becoming available with filters with absorption even beyond the UV spectrum, offering enhanced protection compared with older products. Prevention of photocarcinogenesis, sun-induced or sunlight-exacerbated hyperpigmentary conditions and drug-induced photosensitivity is an important reason for adopting comprehensive photoprotection strategies., (© 2024 European Academy of Dermatology and Venereology.)

Objectives: The COVID-19 pandemic affected the mental health of children and adolescents in the general population, yet its impact on those with chronic conditions is relatively unknown. This study aimed to compare the incidences of comorbid mental disorders and substance misuse in children and adolescents with type 1 diabetes before and during the pandemic., Methods: A total of 42,975 patients aged 6-18 years from the multicentre DPV (Diabetes Prospective Follow-up) registry were included. Multivariable regression models were applied to compare newly diagnosed comorbid mental disorders, adjusted for demographic and clinical variables, among them the number of medical visits, during the pre-pandemic period (09/2017-02/2020) and the COVID-19 pandemic period (03/2020-08/2022)., Results: Analysing both sexes together, there were no differences in the incidence rates of overall mental disorders between the pandemic and the pre-pandemic period. However, girls showed an increased incidence rate (odds ratio 1.2, CI 1.1-1.3) during the pandemic. Adolescent girls also displayed higher incidence rates of depression, eating disorders, and self-harm. Substance misuse declined overall during the pandemic (odds ratio 0.8, CI 0.7-0.9)., Conclusions: During the COVID-19 pandemic, we found higher incidence rates of overall mental disorders in girls, but not in boys and not in the total study population of children and adolescents with type 1 diabetes. Adolescent girls displayed increased incidence rates of depression, eating disorders, and self-harm. Substance misuse declined substantially. Clinicians should be aware of the high-risk group of adolescent girls during times of increased strain., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised., (© 2024 European Academy of Dermatology and Venereology.)

Coping with distracting inputs during goal-directed behavior is a common challenge, especially when stopping ongoing responses. The neural basis for this remains debated. Our study explores this using a conflict-modulation Stop Signal task, integrating group independent component analysis (group-ICA), multivariate pattern analysis (MVPA), and EEG source localization analysis. Consistent with previous findings, we show that stopping performance is better in congruent (nonconflicting) trials than in incongruent (conflicting) trials. Conflict effects in incongruent trials compromise stopping more due to the need for the reconfiguration of stimulus-response (S-R) mappings. These cognitive dynamics are reflected by four independent neural activity patterns (ICA), each coding representational content (MVPA). It is shown that each component was equally important in predicting behavioral outcomes. The data support an emerging idea that perception-action integration in action-stopping involves multiple independent neural activity patterns. One pattern relates to the precuneus (BA 7) and is involved in attention and early S-R processes. Of note, three other independent neural activity patterns were associated with the insular cortex (BA13) in distinct time windows. These patterns reflect a role in early attentional selection but also show the reiterated processing of representational content relevant for stopping in different S-R mapping contexts. Moreover, the insular cortex's role in automatic versus complex response selection in relation to stopping processes is shown. Overall, the insular cortex is depicted as a brain hub, crucial for response selection and cancellation across both straightforward (automatic) and complex (conditional) S-R mappings, providing a neural basis for general cognitive accounts on action control., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

A reconstructed human epidermal model (RHE) colonized with human microbiota and sebum was developed to reproduce the complexity of the skin ecosystem in vitro. The RHE model was exposed to simulated solar radiation (SSR) with or without SPF50+ sunscreen (with UVB, UVA, long-UVA, and visible light protection). Structural identification of discriminant metabolites was acquired by nuclear magnetic resonance and metabolomic fingerprints were identified using reverse phase-ultra high-performance liquid chromatography-high resolution mass spectrometry, followed by pathway enrichment analysis. Over 50 metabolites were significantly altered by SSR (p < 0.05, log2 values), showing high skin oxidative stress (glutathione and purine pathways, urea cycle) and altered skin microbiota (branched-chain amino acid cycle and tryptophan pathway). 16S and internal transcribed spacer rRNA sequencing showed the relative abundance of various bacteria and fungi altered by SSR. This study identified highly accurate metabolomic fingerprints and metagenomic modifications of sun-exposed skin to help elucidate the interactions between the skin and its microbiota. Application of SPF50+ sunscreen protected the skin ecosystem model from the deleterious effects of SSR and preserved the physiological interactions within the skin ecosystem. These innovative technologies could thus be used to evaluate the effectiveness of sunscreen., (© 2023 American Society for Photobiology.)

Background: The catecholaminergic system influences response inhibition, but the magnitude of the impact of catecholaminergic manipulation is heterogeneous. Theoretical considerations suggest that the voluntary modulability of theta band activity can explain this variance. The study aimed to investigate to what extent interindividual differences in catecholaminergic effects on response inhibition depend on voluntary theta band activity modulation., Methods: A total of 67 healthy adults were tested in a randomized, double-blind, cross-over study design. At each appointment, they received a single dose of methylphenidate or placebo and performed a Go/Nogo task with stimuli of varying complexity. Before the first appointment, the individual's ability to modulate theta band activity was measured. Recorded EEG data were analyzed using temporal decomposition and multivariate pattern analysis., Results: Methylphenidate effects and voluntary modulability of theta band activity showed an interactive effect on the false alarm rates of the different Nogo conditions. The multivariate pattern analysis revealed that methylphenidate effects interacted with voluntary modulability of theta band activity at a stimulus processing level, whereas during response selection methylphenidate effects interacted with the complexity of the Nogo condition., Conclusions: The findings reveal that the individual's theta band modulability affects the responsiveness of an individual's catecholaminergic system to pharmacological modulation. Thus, the impact of pharmacological manipulation of the catecholaminergic system on cognitive control most likely depends on the existing ability to self-modulate relevant brain oscillatory patterns underlying the cognitive processes being targeted by pharmacological modulations., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Actinic keratosis is a lesion that develops in sun-exposed areas of the skin and is considered to be a precancerous condition or an early in situ squamous cell carcinoma. Treatment of actinic keratosis is important for reducing skin cancer risk, with treatment choice based on patient-, lesion- and treatment-related considerations. Of the topical treatments used for field-directed therapy, those containing 5-fluorouracil are among the most effective and widely prescribed. The most recently developed topical 5-fluorouracil preparation (Tolak®; Pierre Fabre, France) contains 4% 5-fluorouracil in an aqueous cream. This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors' expert opinion on issues associated with it use. The effect of the cream has been evaluated in phase 2 and 3 trials of adult patients with actinic keratosis on the face, ears or scalp. These trials included patients with severe baseline disease, defined by high lesion counts and large-size treatment fields, which possibly affected the proportion of patients who were able to achieve complete clearance. Other efficacy parameters (e.g. percentage change in lesion count, ≥ 75% clearance of lesions or clinically significant changes in validated severity scales) should also be assessed to fully evaluate 4% 5-fluorouracil treatment efficacy in these patients. Nevertheless, 4% 5-fluorouracil is associated with high efficacy, a low level of recurrence and a satisfactory safety profile.

Additive manufacturing of components using the material extrusion (MEX) of thermoplastics enables the integration of multiple materials into a single part. This can include functional structures, such as electrically conductive ones. The resulting functional structure properties depend on the process parameters along the entire manufacturing chain. The aim of this investigation is to determine the influence of process parameters in filament production and additive manufacturing on resistivity. Filament is produced from a commercially available composite of polylactide (PLA) with carbon nanotubes (CNT) and carbon black (CB), while the temperature profile and screw speed were varied. MEX specimens were produced using a full-factorial variation in extrusion temperature, layer height and deposition speed from the most and least conductive in-house-produced filament and the commercially available filament from the same composite. The results show that the temperature profile during filament production influences the resistivity. The commercially available filament has a lower conductivity than the in-house-produced filament, even though the starting feedstock is the same. The process parameters during filament production are the main factors influencing the resistivity of an additively manufactured structure. The MEX process parameters have a minimal influence on the resistivity of the used PLA/CNT/CB composite.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley-VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology developed updated recommendations on diagnosis and treatment of BCC. BCCs were categorised into 'easy-to-treat' (common) and 'difficult-to-treat' according to the new EADO clinical classification. Diagnosis is based on clinico-dermatoscopic features, although histopathological confirmation is mandatory in equivocal lesions. The first-line treatment of BCC is complete surgery. Micrographically controlled surgery shall be offered in high-risk and recurrent BCC, and BCC located on critical anatomical sites. Topical therapies and destructive approaches can be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial and low-risk nodular BCCs. Management of 'difficult-to-treat' BCCs should be discussed by a multidisciplinary tumour board. Hedgehog inhibitors (HHIs), vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCC. Immunotherapy with anti-PD1 antibodies (cemiplimab) is a second-line treatment in patients with a progression of disease, contraindication, or intolerance to HHI therapy. Radiotherapy represents a valid alternative in patients who are not candidates for or decline surgery, especially elderly patients. Electrochemotherapy may be offered when surgery or radiotherapy is contraindicated. In Gorlin patients, regular skin examinations are required to diagnose and treat BCCs at an early stage. Long-term follow-up is recommended in patients with high-risk BCC, multiple BCCs, and Gorlin syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Topical 5-fluorouracil (5-FU)-containing treatments are effective for actinic keratosis (AK); however, they frequently lead to transient local skin reactions (LSRs), which often result in treatment non-adherence., Methods: The aim of this international, phase IV clinical trial was to investigate whether addition of an emollient to topical 4% 5-FU would reduce the frequency and severity of LSRs over 4 weeks of treatment (intervention group) compared with 4% 5-FU alone (control group) in patients with AK. The primary objective was to assess the severity of LSRs (i.e. erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation and erosion/ulceration) at week 4 of treatment (or before, in case of a major local reaction). Key secondary objectives were LSR total scores at weeks 2 and 8, the scores of individual LSR items at each visit, and the proportions of patients with 100% and ≥ 75% AK lesion clearance at week 8., Results: In total, 141 patients were included in the efficacy analysis (71 in the intervention group and 70 in the control group). There were no statistically or clinically significant differences between the treatment groups in terms of LSR total score at week 4 (overall and by subgroups defined by the number of lesions and patient age at baseline), scores of individual LSR items at any time point, and AK lesion clearance rates at week 8. LSR scores with topical 4% 5-FU alone were lower than expected. Skin reactions were the most common treatment-emergent adverse events in both groups, leading to treatment discontinuation in nine patients (12.3%) in the intervention group and seven (9.9%) in the control group. No new safety signals were observed with the addition of an emollient to 4% 5-FU., Conclusions: Daily emollient applications during the 4-week treatment course did not impact the safety and efficacy profile of 4% 5-FU., (© 2023. The Author(s).)

Histological risk factors of AKs cannot be directly determined. Recent studies indicate that AKs restricted to the lower third of the epidermis (AK I), with marked basal proliferation (PRO III) and acantholysis, are associated with an increased risk of progression to invasive squamous cell carcinoma (iSCC). To confirm the aforementioned histological risk factors, this study compared AKs from solid organ transplant recipients (sOTRs), known to carry an up to 250-fold higher risk for progression into iSCC, to a matched immunocompetent control group (ICG). In total, 111 AKs from 43 sOTRs showed more AKs ( n = 54, 48.7%) graded as AK I compared to 35 AKs (31.5%) in the ICG ( p = 0.009). In line with these findings, 89 AKs (80.2%) from sOTRs showed pronounced basal proliferation (PRO III) compared to 37 AKs (33.3%) in the ICG ( p < 0.0001). Acantholysis was more frequent in sOTRs than the ICG (59.5% vs. 32.4%, p < 0.0001) and more frequently associated with advanced basal proliferation ( p < 0.0001). In conclusion, this study showed that acantholytic AKs graded as AK I and PRO III are predominantly found in a population at high risk of iSCC. Thus, AKs with marked basal proliferation and acantholysis should be assumed to be histological high-risk factors for the progression into iSCC.

Response inhibition and the ability to navigate distracting information are both integral parts of cognitive control and are imperative to adaptive behavior in everyday life. Thus far, research has only inconclusively been able to draw inferences regarding the association between response stopping and the effects of interfering information. Using a novel combination of the Simon task and a stop signal task, the current study set out to investigate the behavioral as well as the neurophysiological underpinnings of the relationship between response stopping and interference processing. We tested n  = 27 healthy individuals and combined temporal EEG signal decomposition with source localization methods to delineate the precise neurophysiological dynamics and functional neuroanatomical structures associated with conflict effects on response stopping. The results showed that stopping performance was compromised by conflicts. Importantly, these behavioral effects were reflected by specific aspects of information coded in the neurophysiological signal, indicating that conflict effects during response stopping are not mediated via purely perceptual processes. Rather, it is the processing of specific, stop-relevant stimulus features in the sensory regions during response selection, which underlies the emergence of conflict effects in response stopping. The findings connect research regarding response stopping with overarching theoretical frameworks of perception-action integration., (© The Author(s) 2023. Published by Oxford University Press.)

Merkel cell polyomavirus (MCPyV) is a ubiquitous virus replicating in human dermal fibroblasts. MCPyV DNA can be detected on healthy skin in 67−90% of various body sites, and intact virions are regularly shed from the skin. Infection occurs early in life, and seropositivity increases from 37 to 42% in 1- to 6-year-olds to 92% in adults. Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine tumor of the skin. It develops mainly on sun-exposed areas as a fast-growing, reddish nodule. Two MCC entities exist: about 80% of MCC are MCPyV-associated. Tumorigenesis is driven by viral integration into the host genome and MCPyV oncogene expression. In MCPyV-negative MCC, UV radiation causes extensive DNA damage leading to the deregulation of the cell cycle. In recent decades, MCC incidence rates have increased worldwide, e.g., in the United States, from 0.15 in 1986 to 0.7/100,000 in 2016. Risk factors for the development of MCC include male sex, older age (>75 years), fair skin, intense UV exposure, and immunosuppression. Projections suggest that due to aging populations, an increase in immunosuppressed patients, and enhanced UV exposure, MCC incidence rates will continue to rise. Early diagnosis and prompt treatment are crucial to reducing high MCC morbidity and mortality.

Aims: To investigate (1) daily, emotional, and physical caregiving burdens in parents of children with type 1 diabetes, (2) the sociodemographic and clinical predictors of three burdens, and (3) support measures that parents wish to receive., Methods: The study was a multicenter cross-sectional survey conducted in nine German pediatric diabetes centers. A questionnaire assessing three types of burdens and wishes for support was distributed to parents with a child with type 1 diabetes visiting one of the pediatric centers for a routine check-up., Results: Data from 1,107 parents (83% mothers) were analyzed. Parents reported significantly higher emotional burdens compared to daily and physical burdens ( p < 0.0001). Mothers felt more burdened than fathers did. Parents of younger children reported higher daily and physical burdens compared to the parents of older children, and similarly, parents of technology users reported higher daily and physical burdens compared to the parents of nontechnology users. However, emotional burdens did not differ in both comparisons. Other demographic factors (i.e., parent's age, migration status, and single-parent family status) predicted high levels of daily or physical burdens, but only HbA1c level and the parent's gender (mother) predicted a high emotional burden. Independent of the level of burden, 78% of parents wanted additional diabetes training., Conclusion: Despite parents reporting high emotional burdens in connection with diabetes care, HbA1c and the gender of the reporting parent were the only risk factors. As the child gets older, parents' daily and physical distress decrease but not the emotional burden. Diabetes training including regularly offered booster sessions as well as low-threshold interventions for mental health issues and practical self-care skills is recommended to provide continuous support for parents., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Heike Saßmann et al.)