Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

Background: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating.

A center-based, ambulatory care concept for hidradenitis suppurativa improves patient outcomes and is also cost-effectiveness.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting approximately 1% of the population. The patient journey through the German health care system leads to high disease burden and substantial treatment costs. The EsmAiL study showed that an innovative, interprofessional, multimodal care-concept reduces disease activity and burden of HS compared to standard care.

Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project.

Background: A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. The Rare Genomes Project (RGP) is a direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis and gene discovery.

Guselkumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa: A phase 2 randomized study.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that causes substantial physical, emotional and psychological burdens. Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin-23, has demonstrated high levels of efficacy in the treatment of inflammatory diseases, including psoriasis and psoriatic arthritis.

Objective: To evaluate the effect of guselkumab on the treatment of HS, a phase 2, multicentre, randomized, placebo-controlled, double-blind, proof-of-concept study was conducted.

PARP1 negatively regulates MAPK signaling by impairing BRAF-X1 translation.

In human cells BRAF oncogene is invariably expressed as a mix of two coding transcripts: BRAF-ref and BRAF-X1. These two mRNA isoforms, remarkably different in the sequence and length of their 3'UTRs, are potentially involved in distinct post-transcriptional regulatory circuits. Herein, we identify PARP1 among the mRNA Binding Proteins that specifically target the X1 3'UTR in melanoma cells.

A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy.

Background: The ability to increase their degree of pigmentation is an adaptive response that confers pigmentable melanoma cells higher resistance to BRAF inhibitors (BRAFi) compared to non-pigmentable melanoma cells.

Methods: Here, we compared the miRNome and the transcriptome profile of pigmentable 501Mel and SK-Mel-5 melanoma cells vs. non-pigmentable A375 melanoma cells, following treatment with the BRAFi vemurafenib (vem).

Real-world outcomes using PD-1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland.

Background: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland.

A randomised controlled multicentre investigator-blinded clinical trial comparing efficacy and safety of surgery versus complex physical decongestive therapy for lipedema (LIPLEG).

Background: Lipedema is a chronic disorder of the adipose tissue that affects mainly women, characterised by symmetrical, excessive fatty tissue on the legs and pain. Standard conservative treatment is long-term comprehensive decongestive therapy (CDT) to alleviate lipedema-related pain and to improve psychosocial well-being, mobility and physical activity. Patients may benefit from surgical removal of abnormally propagated adipose tissue by liposuction.

Tomato Bushy Stunt Virus Nanoparticles as a Platform for Drug Delivery to Shh-Dependent Medulloblastoma.

Medulloblastoma (MB) is a primary central nervous system tumor affecting mainly young children. New strategies of drug delivery are urgent to treat MB and, in particular, the SHH-dependent subtype-the most common in infants-in whom radiotherapy is precluded due to the severe neurological side effects. Plant virus nanoparticles (NPs) represent an innovative solution for this challenge.

Perceived naturalness of facial expression after hyaluronic acid filler injection in nasolabial folds and lower face.

Background: In addition to having a younger and more attractive appearance after facial aesthetic treatment, patients desire natural-looking and long-lasting results.

Objective: To evaluate perceived naturalness of dynamic facial expressions after treatment with hyaluronic acid fillers in nasolabial folds (NLFs) and lower face wrinkles and folds.

Methods: Subjects requiring treatment of moderate-to-severe NLFs and at least one other lower face indication were treated with hyaluronic acid fillers.

Prevention of Progression of Lipedema With Liposuction Using Tumescent Local Anesthesia: Results of an International Consensus Conference.

Background: Lipedema is a chronic, progressive disorder of subcutaneous adipose tissue that usually affects the lower extremities of women. Also known as "two-body syndrome," the fat accumulations in lipedema are unsightly and painful. The disorder is well-known in Europe but is largely unrecognized and underdiagnosed in the United States.

Evaluating Perceived Naturalness of Facial Expression After Fillers to the Nasolabial Folds and Lower Face With Standardized Video and Photography.

Background: Hyaluronic acid (HA) fillers are commonly used in treating facial wrinkles and folds but have not been studied with standardized methodology to include assessment of standard facial expressions.

Objective: To assess perceived naturalness of facial expression after treatment with 2 HA fillers manufactured with XpresHAn Technology (also known as Optimal Balance Technology).

Materials And Methods: Treatment was directed to the nasolabial folds (NLFs) and at least 1 additional lower face wrinkle or fold.

Melanoma and tattoos: a case report and review of the literature.

Background: Malignant melanoma cases arising in tattoos have been increasingly described, however, there is no clear relationship between this practice and the development of cutaneous malignancies.

Objectives: We report a new case of melanoma in a dark-blue tattoo and we review all cases of melanoma reported in the medical literature from 1938 to date.

Materials & Methods: Pubmed and Google Scholar were searched using the terms "melanoma tattoo", "tattoo skin tumour" and "ink melanoma".

Superiority of occipital donor sites for split-thickness skin grafting in dermatosurgery: Results of a prospective randomized controlled study.

Background: Split-thickness skin grafts are commonly used in dermatosurgery. For occipital donor sites, retrospective studies have shown good results with respect to graft take and healing rates. Nevertheless, the majority of grafts in dermatosurgery are harvested from the thigh.

A 12-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Severe Nasolabial Folds.

Background: Hyaluronic acid (HA) filler injection is an increasingly popular aesthetic procedure.

Objective: To compare the effectiveness and safety of two HA fillers (HAED and HAPER) for the treatment of severe nasolabial folds (NLFs).

Materials And Methods: This was an evaluator-blinded and subject-blinded split-face study.

An 18-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Moderate Nasolabial Folds.

Background: Hyaluronic acid (HA) filler injection is a popular nonsurgical aesthetic procedure.

Objective: To compare the effectiveness and safety of 2 hyaluronic acid fillers (HAEC and HARES) for treatment of moderate nasolabial folds (NLFs).

Materials And Methods: This was an evaluator- and subject-blinded split-face study.

S1 guideline: microscopically controlled surgery (MCS).

When using procedures that enable complete examination of surgical margins (3D histology), microscopically controlled surgery (MCS) represents a safe and proven method to confirm R0 resection of infiltrating tumors, especially at problematic sites, while preserving the adjacent tissue. This allows for excellent or good aesthetic results that are superior (cryosurgery, short-range irradiation) or equivalent (PDT) to nonsurgical and less safe procedures (PDT).

Exposure to Carbon Ions Triggers Proinflammatory Signals and Changes in Homeostasis and Epidermal Tissue Organization to a Similar Extent as Photons.

The increasing application of charged particles in radiotherapy requires a deeper understanding of early and late side effects occurring in skin, which is exposed in all radiation treatments. We measured cellular and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure. Model systems for human skin from healthy donors of different complexity, i.

Intermittent High-Dose Intravenous Interferon Alfa-2b for Adjuvant Treatment of Stage III Melanoma: Final Analysis of a Randomized Phase III Dermatologic Cooperative Oncology Group Trial.

Purpose: To evaluate the efficacy, safety, tolerability, and quality of life (QoL) in patients receiving intravenous, intermittent high-dose interferon alfa-2b (IFN-α-2b [iHDI]) compared with standard high-dose IFN-α-2b (HDI).

Patient And Methods: Patients with stage III resected lymph node or in-transit metastasis from cutaneous malignant melanoma were randomly assigned to receive either a standard HDI regimen or three courses of IFN-α-2b 20 MIU/m(2) administered intravenously 5 days a week for 4 weeks then repeated every 4 months. Distant metastasis-free survival was the primary end point for efficacy analysis.