Longitudinal monitoring of actinic keratosis (AK) is a part of patient management, scientific studies, and the development of new treatment strategies. Dynamic optical coherence tomography (D-OCT), an imaging method that enables noninvasive assessment of microvasculature, in conjunction with automated quantitative analysis, shows promise as an objective and robust method for monitoring AKs. Critical to quantitative longitudinal assessments is a dataset in which good-quality images are available at all time points. Yet, to date, few resources exist to train clinical researchers on how to ensure robust D-OCT data collection. In this study, we identify hallmarks of poor image quality to guide data curation and avoid biasing study results. We highlight strategies for imaging lesions with significant hyperkeratosis. Finally, we discuss characteristic features present in D-OCT images of AK that may complicate quantitative analysis. We hope that this work will facilitate the use of D-OCT in the objective longitudinal assessment of AK.

Background: Patient recruitment is a major cause of delays in randomized controlled trials (RCT). Online recruitment is evolving into an alternative to conventional in -clinic recruitment for RCT. The objective of this study was to test the effectiveness of online patient recruitment for an RCT on actinic keratosis (AK). Methods: In this proof -of -concept study, adults with AK were recruited for a Phase I/IIa RCT (NCT05164393) via social media using targeted advertising Interested users were directed to a landing page to learn about the study, respond to questionnaires, and upload self -obtained smartphone pictures of potential AK. Facebook Analytics was used to track the number of advertisement views, individual users exposed to the advertisement, and advertisement clicks. Following eligibility -review by remote dermatologists, candidates were contacted for an in -clinic visit. A review of pertinent RCTs on AK (2012-2022) was conducted to compare recruitment metrics. Results: The online campaign served 886,670 views, reached 309,000 users, and generated 27,814 clicks. A total of 556 users underwent eligibility review, leading to 140 pre -evaluated potential study subjects. The RCT's enrollment target of 60 patients (68.8 +/- 7.1 years, 43.3 % female) was reached in 53 days after screening 90 participants in -clinic, corresponding to a screen failure rate of 33.3 %. The total cost of this online recruitment campaign was 14,285 USD i.e. 238 USD per randomized patient. Compared to the existing literature (44 RCTs), our online approach resulted in 9 times more time -efficient recruitment per site. Conclusion: Using targeted advertisements, 60 patients with AK were recruited for a single -center Phase I/IIa RCT in 53 days. Social media appears to be an efficient platform for online recruitment of patients with low-grade AK for RCT.

The osteopontin-derived peptide FOL-005 stimulates hair growth. Using ligand-receptor glyco-capture technology we identified neuropilin-1 (NRP-1), a known co-receptor for vascular endothelial growth factor (VEGF) receptors, as the most probable receptor for FOL-005 and the more stable analogue FOL-026. X-ray diffraction and microscale thermophoresis analysis revealed that FOL-026 shares binding site with VEGF in the NRP-1 b1-subdomain. Stimulation of human umbilical vein endothelial cells with FOL-026 resulted in phosphorylation of VEGFR-2, ERK1/2 and AKT, increased cell growth and migration, stimulation of endothelial tube formation and inhibition of apoptosis in vitro. FOL-026 also promoted angiogenesis in vivo as assessed by subcutaneous Matrigel plug and hind limb ischemia models. NRP-1 knock-down or treatment of NRP-1 antagonist EG00229 blocked the stimulatory effects of FOL-026 on endothelial cells. Exposure of human coronary artery smooth muscle cells to FOL-026 stimulated cell growth, migration, inhibited apoptosis, and induced VEGF gene expression and VEGFR-2/AKT phosphorylation by an NRP-1-dependent mechanism. RNA sequencing showed that FOL-026 activated pathways involved in tissue repair. These findings identify NRP-1 as the receptor for FOL-026 and show that its biological effects mimic that of growth factors binding to the VEGF receptor family. They also suggest that FOL-026 may have therapeutical potential in conditions that require vascular repair and/or enhanced angiogenesis.

Introduction: Atopic dermatitis (AD) severity is traditionally evaluated during in-office consultations; however, this does not provide continuous monitoring and any intermittent fl are/remission cycles are usually not recorded. The aim was to apply smartphone technology to evaluate AD severity, to explore if severity based on highly frequent sampling of photographs is associated with patient reported outcomes, and to investigate disease fl uctuations and trigger associations based on passively collected environmental data. Methods: In this 12-week decentralized observational study, adult patients with AD were recruited online and used a tailored remote clinical trial platform app to perform all study tasks including capturing photographs and completing the Patient-Oriented Eczema Measure (POEM) weekly. AD severity was assessed based on photographs using the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD). Geographical location collected in the app was used to retrieve data on ambient temperature and carbon monoxide (CO), a common air pollutant. Results: A total of 42 patients (35 women) were recruited online. A total of 712 photographs were taken, with an average of 17 photographs per participant. Photographic SCORAD (r = 0.450) and EASI (r = 0.206) were significantly associated with subjective severity POEM. Patients experiencing AD fl uctuation (n = 10) based on SCORAD had significantly higher risk of also having a psychiatric disorder (60 vs. 17%, p = 0.008). Anxiety was significantly associated with disease fl uctuation based on EASI (40 vs. 7%, p = 0.01), and a tendency was observed for depression (40 vs. 13%, p = 0.06). Decreasing temperature was significantly associated with higher POEM (estimate - 0.18, p = 0.012) and EASI score (estimate - 0.14, p = 0.007), but not with SCORAD. High levels of CO were significantly associated with higher SCORAD (estimate 15.9, p < 0.001). Conclusion: In this small study with a predominance of young adults, primarily women, we were able to recruit patients and monitor AD entirely remotely via smartphoneenabled photographic assessments; patients reported outcomes and passively collected environmental data without physical contact between patient and investigator. (c) 2024 S. Karger AG, Basel

Hybrid trials are a new trend in dermatological research that leverage mobile health technologies to decentralize a subset of clinical trial elements and thereby reduce the number of in-clinic visits. In a Phase I/IIa randomized controlled hybrid trial, the safety and efficacy of an anti-proliferative and anti-inflammatory drug inhibiting cytosolic phospholipase A2 (AVX001) was tested using 1%, 3% or vehicle gel in 60 patients with actinic keratosis (AK) and assessed in-clinic as well as remotely. Over the course of 12 weeks, patients were assessed in-clinic at baseline, end of treatment (EOT) and end of study (EOS), as well as 9 times remotely on a weekly to biweekly basis. Safety outcomes comprising local skin reactions (LSR; 0-5), adverse events (AE) and cosmesis, were graded in-clinic and remotely using patient-obtained smartphone photographs (PSPs) and questionnaires; efficacy was assessed in-clinic based on clinically visible clearance of AK target area of >50%. A total of 55 participants (91.7%) completed the treatment course. The average submission rate of PSPs was high (>= 85%), of which 93% were of sufficient quality. No serious AE were reported and only two experienced temporary LSR >2 (scale 0-4) and cosmesis remained stable throughout the study. Based on the mild AE and LSR profile, daily application of AVX001 gel for 1 month appears safe, tolerable, and cosmetically acceptable for use in patients with AK. At EOT, AVX001 achieved a subtle treatment response with clearance of AK target area of >50% in 18% of patients. Remote and in-clinic assessments of LSRs were in high agreement, suggesting that the use of mobile health technologies in early-phase hybrid studies of AK does not compromise patient safety.

Background: Clinical trials often suffer from recruitment barriers and poor adherence, which increases costs and affects trial outcomes. Objective: To investigate the feasibility of Decentralized Clinical Trial (DCT) design elements to recruit, enroll, and engage patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM were recruited through a pharmacy and online recruitment using advert on Facebook, to 3 weeks monitoring of glucose and behaviometric parameters. Subjects recruited online could either complete an informed consent conversation in the pharmacy or through live video call managed by the study app. A continuous glucose monitoring (CGM) device to collect glucose data, and a hybrid smartwatch to monitor heart rate, track activity and sleep pattern were delivered by postal service to the participants’ home address. The devices were connected to a study specific app on the participant’s smartphone also capturing GPS data and questionnaire answers. Results: Twenty-six subjects (3 pharmacy, 23 online) with T2DM were recruited, 85% preferred online informed consent conversation. All participants were able to self-apply the CGM device, use the smartwatch, and download the app. GPS location was captured more than 100 times for each participant, and more than 90% completed all 3 questionnaires. All the participants felt safe with the informed consent process and they felt confident in participating from home. Three participants dropped-out during the study period leaving a retention rate at 87%. Conclusions: Use of DCT design elements to conduct a T2DM study is feasible regarding recruitment, data collection from various electronic devices, and participant engagement.

Background and AimsA better understanding of distinct subgroups in atopic dermatitis (AD) is warranted. The aim was to identify and determine characteristics of clusters based on anatomical location of AD. MethodsIn this 8-week, observational, decentralized study, patients with AD completed a baseline questionnaire about anatomical location and severity of AD, and a principal component analysis (PCA) was applied to identify clusters. The Patient-Oriented Eczema Measure (POEM) was completed weekly and photographs of affected body areas were captured by the participants' own smartphones. From the weekly photographs, the AD severity was evaluated using the intensity part of the SCORing Atopic Dermatitis. ResultsFifty-five participants were recruited, of which 53 completed the baseline questionnaire with a mean POEM of 14.5 (SD: 5.6). The PCA analysis revealed three clusters, with AD predominantly on the shins, knees, and genitals (Cluster 1), with involvement of the upper body (Cluster 2), and with AD on the hands and feet (Cluster 3). Cluster 1 had a lower mean POEM score (11.12, SD: 5.3) compared with Clusters 2 (12.64, SD: 4.5) and 3 (15.98, SD: 4.7), respectively (p = 0.007). Further, Cluster 1 had the highest age of AD onset (mean 9.5 vs. 2.5 and 4.7 years, p = 0.02) and the lowest proportion of asthma/allergy (47% vs. 82% and 90%, p = 0.01). ConclusionThree clusters of patients with AD based on affected body areas were identified. The cluster with involvement of legs and genitals was characterized by the oldest age of AD onset and the lowest prevalence of asthma/allergy.

Background: Remote monitoring was used to assess and manage skin diseases. Objective: To investigate to what extent smartphone photographs along with a self -reported body region (BR) score can be used to evaluate psoriasis severity. Methods: Psoriasis severity was assessed in the clinic using the psoriasis area and severity index and the physician's global assessment. On the same day, the patients took a photograph of a representative lesion from 4 BR (head/neck, upper limbs, trunk, and lower limbs) and completed a questionnaire about BR score. The photographs were rated by 5 dermatologists. Intraclass correlation coefficients with 95% CIs were calculated. Results: Overall, 32 were included, of which 6% had almost clear, 69% had mild, and 25% had moderate psoriasis. Perfect agreement between the self -reported and the doctors' BR score was observed for 59%, and near -perfect agreement (deviation of maximum 1 score) was 92%. The intraclass correlation coefficient between clinical and photographic psoriasis area and severity index was 0.78 (95% CI, 0.55-0.90), and for physician's global assessment, perfect agreement was 53%. Conclusions: The agreement between psoriasis severity assessed clinically and by photographs was good in a study setting. This gives the opportunity to remotely assess psoriasis severity by combining photographs with self -reported BR scores. ( JAAD Int 2023;11:129-36.)

Selection of further investigated targets.

Time course experiment for gene expression analysis of IL13RA2 and IL1R2.

Gene expression analysis of IM-treated primary keratinocytes and patient-derived SCC cells; pathways analysis; validation of specific genes

Effect of IM on fibroblasts and melanoma cells and effect of TPA on SCC13 cells.

BACKGROUND:Wide-ranging patient recruitment not restricted to the location of the investigator will provide a better representation of the patient population in clinical studies.OBJECTIVE:Our goal was to assess the feasibility of a broad web-based recruitment strategy in an 8-week observational study of 500 study participants with psoriasis and healthy controls from locations remote from the investigator and to assess the cost associated with each participant.METHODS:A decentralized team in Denmark recruited patients with psoriasis and healthy controls using Google and Facebook advertisements and posts to Facebook groups. All individuals were screened via the internet, and patients diagnosed with psoriasis were included. Questionnaires regarding itch and sleep were completed by both groups at inclusion, week 4, and week 8.RESULTS:During a 2-week recruitment period, 12,887 unique advertisement views were registered, and 839 participants were enrolled, of which 507 completed the study (220 with psoriasis and 287 healthy controls) with a retention rate of 60.4%. Participants were recruited from 11 different countries on 4 separate continents, mainly from the United States, Canada, and the United Kingdom. The recruitment rate was 59.9 participants per day, and the conversion rate was 57.2%. Recruitment costs were US $13 per enrolled participant and US $22 per participant completing the study.CONCLUSIONS:It is feasible and rapid to recruit a large number of participants from locations different from the investigator and to retain patients in an observational study with no visits to a clinical site at low costs.

Despite a rapidly growing interest in use of teledermatology, validation of conventional in-clinic scoring systems for remote assessment of actinic keratosis (AK) fails to keep pace. In this paper, we describe the level of agreement between in-clinic and remote assessments of AK using two different conventional scoring systems. The results of our proof-of-concept study encourage the use of patient-obtained smartphone photographs for standardized remote assessment but highlight the need for adjustments to the currently available scoring systems to improve their reliability. The results of this study may pave the road for the implementation of remote assessments of AK in a clinical management plan.

Conformation of knock-down for siRNA experiments.

Chemical structure of ingenol mebutate. Confirmation of inhibition by MEK and ERK inhibitor,

ERK is activated after IM treatment in a PKC-dependent manner.

Figure legend for supplementary figures.

Several external and internal triggers may cause a flare up of atopic dermatitis (AD), and psychological stress is well known to have an impact on AD disease activity. Stress levels are either self-reported or require complicated monitoring setups of pulse, blood pressure, and hormone levels. Research into voice analysis has revealed that human emotions, such as stress, can be extrapolated from voice biomarkers exploiting that psychological states alter the characteristics of one’s voice. 1 In this 12-week decentralized longitudinal study, we aimed to explore the association between selected voice biomarkers and measures of objective and subjective AD disease activity. captureapplication(Imagine,LEOInnovationLab,Denmark),andcom-plete an online questionnaire including Skindex Mini questionnaire, 2 a numeric ranking scale (NRS) for self-perceived daily stress, and the patient-oriented eczema measure (POEM). 3 patients were askedtoperforma59-svoicerecordingwiththeirownmobiledevice.A layeredvoiceanalysisplatform(Nemesysco,Israel)wasusedtoextract the sub-acoustic/low-amplitude features from the recorded voice samples. All photographs were evaluated by a board-certified derma-tologist.Eachphotographwasscoredaccordingtotheintensitypartof SCORing Atopic Dermatitis (SCORAD) as per the presence and intensity of the following characteristics, erythema,

Introduction Actinic keratosis (AK) is the most common precancerous skin condition caused by long-term UV exposure. Given the high recurrence rate of 15%–53%, identifying safe and effective treatment options is warranted. AVX001, a cytosolic phospholipase A2α (cPLA2α) enzyme inhibitor, is a novel anti-inflammatory drug for field-directed, self-administered, topical therapy of AK. Methods and analysis This study is a single-centre, randomised, vehicle-controlled, double-blind, parallel-group hybrid clinical trial in adults with multiple AK lesions Olsen grade 1 or 2. The hybrid design combines decentralised participant tasks and assessments with conventional in-clinic visits. Recruitment using targeted advertising on social media and eligibility prescreening are conducted via the Studies&Me online recruitment platform. Participants (n=60) are randomly assigned to 1 of 3 treatment arms: AVX001 gel 1%, AVX001 gel 3% or vehicle gel. The trial consists of a 4-week treatment period with daily field-directed topical application of the gel and an 8-week follow-up period. Participants attend in-clinic visits at baseline, week 4 and week 12. The remote participant trial tasks include questionnaires and upload of smartphone-obtained photos of the treated skin area using a study-specific web-based app. Both remote and in-clinic assessments of safety and efficacy will be performed. The primary objective is to evaluate the local tolerability of daily application of AVX001 gel (1% or 3%) compared with vehicle gel. Secondary objectives include safety, efficacy, dose–response efficacy relationship, treatment satisfaction and cosmetic outcome. Exploratory objectives include evaluations of tolerability and efficacy assessed by dermatologists using smartphone photos uploaded by participants, comparisons of in-clinic and remote assessments and assessment of AK-related skin changes by non-invasive optical imaging. Ethics and dissemination Approved by the Ethics Committee of the Capital Region of Denmark (H-21018064) and the Danish Medicines Agency (2021032485). Results will be submitted for publication in peer-reviewed scientific journals. Trial registration numbers 2021-000934-32; NCT05164393.