Impact of gender, age, partnership and working status on patients’ preferences.

<p>(A) Men attached higher value to the probability of 50% and 90% improvement than women. (B) Probability of 50% and 90% improvement, time until response and treatment frequency became less important with increasing age whereas probability of severe AE and probability of ACR 20 response gained relevance. (C) Participants without a partner placed greater importance on the probability of 50% improvement while respondents with a partner valued the probability of ACR 20 response higher. (D) Compared to non-working participants, full-time working participants set higher priority to time until response, treatment location, and treatment frequency. The probability of 90% improvement was more important for full-time working than for part-time working participants. Part-time working participants considered the delivery method more important than non-working participants. Differences in RIS were tested for significance with ANOVA (A, C), 2-tailed t-test (B) or Bonferroni post-hoc tests (D). Bars: Means with standard deviations (A, C, D) or Pearson’s Correlations (B). RIS: Relative Importance Scores. * p≤0.05, ** p≤0.01.</p

Examples of discrete choice scenarios.

<p>Examples of discrete choice scenarios.</p

Relative Importance Scores (RIS) averaged across the study cohort.

<p>The probability of severe AE was evaluated as most important (RIS = 17.3), followed by the probability of 90% improvement (RIS = 14.0). Time until response (RIS = 4.5) and sustainability of the therapeutic success (RIS = 5.2) were least relevant. Bars: Means with standard deviations.</p

Outcome and process attributes and attribute levels used in the conjoint scenarios.

<p>¹ Probability of loss of response within one year</p><p>² per treatment session</p><p>AE: adverse events.</p><p>Outcome and process attributes and attribute levels used in the conjoint scenarios.</p

Impact of PASI and DLQI on Relative Importance Scores (RIS).

<p>With increasing PASI (A) and increasing DLQI (B), participants set greater value on treatment duration. The higher the DLQI score, the less importance was attached to probability of 50% improvement. Differences in RIS were tested for significance with 2-tailed t-tests. Bars: Pearson’s Correlations. * p≤0.05.</p

Characteristics of the study cohort.

<p>Characteristics of the study cohort.</p

Multiple linear regression models demonstrating impact of comorbidities on outcome attributes.

<p>Multiple linear regression models demonstrating impact of comorbidities on outcome attributes.</p

Multiple linear regression models showing the influence of comorbidities on process attributes.

<p>Multiple linear regression models showing the influence of comorbidities on process attributes.</p

Impact of comorbidities on preferences for outcome and process attributes of biologicals.

<p>(A) Participants with psoriatic arthritis attached higher value to probability of ACR 20 response and sustainability but less importance to time until response. (B) Respondents with cardiovascular disease prioritized avoidance of mild and severe AE as well as ACR 20 response. Time until response, treatment location, frequency and delivery method were less relevant for them than for other participants. (C) Participants with diabetes were particularly interested in short treatment duration. (D) Those with arterial hypertension attached special importance to a low risk of mild AE and a short treatment duration. Differences in RIS were tested for significance with one-way ANOVA or Brown-Forsythe tests. Bars: Means with standard deviations. AE: adverse events; art.: arterial; CV disease: cardiovascular disease; RIS: Relative Importance Scores. * p≤0.05, ** p≤0.01.</p

Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells

<div><p>During development and progression of malignant melanoma, an important role has been attributed to alterations of cell-cell adhesions, in particular, to a “cadherin switch” from E- to N-cadherin. We have previously shown that a subtype of melanoma cells express the desmosomal cadherin desmoglein 2 as non-junction-bound cell surface protein in addition to classical cadherins. To study the role of desmoglein 2 in melanoma cells, melanoma lines containing high endogenous amounts of desmoglein 2 were depleted of the protein by RNA interference. Transwell migration and scratch wounding assays showed markedly increased migration upon desmoglein 2 suppression whereas proliferation and viability remained unaltered. In gene expression profiles, desmoglein 2 depletion was associated with overexpression of migration-related genes. Strongest overexpression was found for secretogranin II which has not been reported in melanoma cells before. The bioactive peptide derived from secretogranin II, secretoneurin, is known to exert chemoattractive functions and was demonstrated here to stimulate melanoma cell migration. In summary, we show that desmoglein 2 expression attenuates migration of melanoma cells. The mechanism of desmoglein 2 impaired cell migration is mediated by downregulation of secretogranin II. Loss of desmoglein 2 increases expression of secretogranin II, followed by an enhanced migratory activity of melanoma cells. Our data add a new pathway of regulating melanoma cell migration related to a desmoglein 2 – secretogranin II axis.</p></div