Connecting the Kuramoto Model and the Chimera State

Since its discovery in 2002, the chimera state has frequently been described as a counter-intuitive, puzzling phenomenon. The Kuramoto model, in contrast, has become a celebrated paradigm useful for understanding a range of phenomena related to phase transitions, synchronization and network effects. Here we show that the chimera state can be understood as emerging naturally through a symmetry breaking bifurcation from the Kuramoto model's partially synchronized state. Our analysis sheds light on recent observations of chimera states in laser arrays, chemical oscillators, and mechanical pendula.Comment: 5 pages, 6 figure

Mind your head: two cases of mucosal metastasis of BRAF-mutated melanoma of the scalp

Mucosal melanomas are rare and only a small portion bear BRAF mutations while cutaneous melanomas have a much higher prevalence and often harbor BRAF mutations. We present two cases in which, after a malignant melanocytic mucosal lesion with a BRAF mutation was found, the primary cutaneous source was identified and clonality confirmed between the lesions. In both cases, primary lesions occurred on the scalp, an often-overlooked site. Both lesions showed signs of regression implying that in due time these lesions could have been fully regressed and might never have been detected. In that case, the metastatic mucosal lesion would erroneously be identified as a BRAF-mutated mucosal melanoma. These cases give warrant; a careful dermatological inspection should be instigated when confronted with a BRAF-mutated mucosal melanoma. We hypothesize that some BRAF-mutated mucosal melanomas might actually represent metastases of regressed cutaneous melanomas.MTG4Molecular tumour pathology - and tumour genetic

Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

BackgroundPatients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease- or treatment-related T- or B-cell dysfunction.MethodsAll advanced melanoma patients treated with anti-PD-1-based treatment or targeted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and melanoma-specific survival (MSS) were analysed for patients with HM (HM+) and without HM (HM−). A cox model was used to account for confounders associated with PFS and MSS.ResultsIn total, 4638 advanced melanoma patients received first-line anti-PD-1 monotherapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated patients, the median PFS was 2.8 months for HM+ and 9.9 months for HM− (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM− (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HRadj 1.62; 95% confidence interval [95% CI] 1.15–2.29; p = 0.006) and melanoma-related death (HRadj 1.74; 95% CI 1.09–2.78; p = 0.020). Median PFS and MSS for first-line BRAF(/MEK-) inhibitor-treated HM+ and HM− patients were not significantly different.ConclusionsPatients with HM and advanced melanoma show significantly worse melanoma-related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM.Analysis and support of clinical decision makin

First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis

Background: Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAFV600-mutant advanced melanoma. Until now, data are inconclusive on which therapy to use as first-line treatment. The aim of this study was to use propensity score matching to compare first-line anti-PD-1 monotherapy vs. BRAF/MEK inhibitors in advanced BRAFV600-mutant melanoma patients. Methods: We selected patients diagnosed between 2014 and 2017 with advanced melanoma and a known BRAFV600-mutation treated with first-line BRAF/MEK inhibitors or anti-PD-1 antibodies, registered in the Dutch Melanoma Treatment Registry. Patients were matched based on their propensity scores using the nearest neighbour and the optimal matching method. Results: Between 2014 and 2017, a total of 330 and 254 advanced melanoma patients received BRAF/MEK inhibitors and anti-PD-1 monotherapy as first-line systemic therapy. In the matched cohort, patients receiving anti-PD-1 antibodies as a first-line treatment had a higher median and 2-year overall survival compared to patients treated with first-line BRAF/MEK inhibitors, 42.3 months (95% CI: 37.3-NE) vs. 19.8 months (95% CI: 16.7–24.3) and 85.4% (95% CI: 58.1–73.6) vs. 41.7% (95% CI: 34.2–51.0). Conclusions: Our data suggest that in the matched BRAFV600-mutant advanced melanoma patients, anti-PD-1 monotherapy is the preferred first-line treatment in patients with relatively favourable patient and tumour characteristics

Histopathologische aspecten van het plaveiselcelcarcinoom van de huid.

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Role of tumor supressors in the pathogenesis and treatment of squamous skin tumors in renal transplant recipients.

Contains fulltext : 27040.pdf (publisher's version ) (Open Access)This thesis deals with new insights on the role of tumor suppressor proteins p53, p16, and p14 in (pre)malignant epidermal tumors of renal transplant recipients (RTRs) and immunocompetent individuals (ICIs). Expression of these tumor suppressor proteins in relation to important etiologic factors in cutaneous carcinogenesis, such as sun exposure, immune status, and Human Papilloma Virus are studied in epidermal skin tumors of both patient groups. Furthermore, the use of mutation analysis for p53 and INK4a-ARF is investigated in case of multiple primaries in patients with metastatic cutaneous squamous cell carcinoma. The last part of the thesis deals with systemic retinoid treatment in skin (pre)cancer in RTRs. Retinoids are known to influence proliferation and differentiation. The effects of systemic retinoids on expression of markers for differentiation, proliferation and tumor suppressor protein expression are studied in these transplant recipients. The introduction comprises a review on cutaneous squamous cell carcinogenesis in renal transplant recipients, and on the role of the tumor suppressors p53 and INK4a-ARF in cutaneous carcinogenesis. The main features of systemic retinoid treatment in skin malignancies will be reviewed.RU Radboud Universiteit Nijmegen, 19 december 2005Promotores : Ruiter, D.J., Kerkhof, P.C.M. van de Co-promotores : Jong, E.M.G.J. de, Wilde, P.C.M. de144 p

Moleculaire diagnostiek bij melanoom: meer dan BRAF-V600E en vemurafenib

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Congenitaal dermafibrosarcoma protuberans.

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Elastoderma: an uncommon cause of acquired hyperextensible skin.

Contains fulltext : 107729.pdf (publisher's version ) (Open Access)1 mei 201