Lebrikizumab is associated with improvements in patient-reported symptoms and quality-of-life measures across Eczema Area and Severity Index response categories: pooled results from phase-3 randomized ADvocate1 and ADvocate2 studies in patients with moderate-to-severe atopic dermatitis.

Background: Lebrikizumab monotherapy significantly improved signs and symptoms in patients with moderate-to-severe atopic dermatitis (AD) in phase 3 Advocate1 and ADvocate2 studies.

Objective: To evaluate improvements in patient-reported symptoms and quality-of-life (QoL) measures by Eczema Area and Severity Index (EASI) response categories using pooled Advocate1 and ADvocate2 data (post hoc analysis).

Methods: In the 52-week (W) (16-W induction + 36-W maintenance) double-blind, placebo-controlled ADvocate1 and ADvocate2 studies, patients were randomized (2:1) to receive subcutaneous lebrikizumab 250 mg or placebo every 2 weeks.

A High-Affinity Monoclonal Antibody Against the Pancreatic Ductal Adenocarcinoma Target, Anterior Gradient-2 (AGR2/PDIA17).

Background/objectives: Anterior Gradient-2 (AGR2/PDIA17) is a member of the protein disulfide isomerase (PDI) family of oxidoreductases. AGR2 is up-regulated in several solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Given the dire need for new therapeutic options for PDAC patients, we investigated the expression and function of AGR2 in PDAC and developed a novel series of affinity-matured AGR2-specific single-chain variable fragments (scFvs) and monoclonal antibodies.

Exploring racial and ethnic disparities in the hidradenitis suppurativa patient disease journey: Results from a real-world study in Europe and the USA.

Hidradenitis suppurativa (HS) is an inflammatory skin disease associated with high morbidity and disability that has limited treatment options. People from racial and ethnic minority groups may experience greater disease severity and delay to diagnosis. This study assessed the impact of race/ethnicity on HS diagnosis and management in real-world clinical settings.

Factors Associated With Treatment Escalation for Psoriasis: An Analysis of Electronic Health Records Data.

Background: Electronic health records (EHRs) offer the possibility of using data entry templates to simultaneously document routine clinical care and capture disease-specific measures as discrete data elements that can be used for health services research (HSR). The objective of this study was to determine factors associated with meaningful treatment escalation (MTE) of psoriasis as a pilot study for future real-world HSR studies.

Methods: We conducted a retrospective, observational cohort study of psoriasis patients by using data collected during routine clinical care from an EHR using EpiCare® SmartForms.

Economic Burden of Itch-Related Sleep Loss in Moderate-to-Severe Atopic Dermatitis in the United Kingdom.

Introduction: Atopic dermatitis is associated with intense itch, which has been shown to cause sleep disruption that significantly impacts the lives of patients with atopic dermatitis. Despite this, little is known about its burden to the healthcare system and society. This study aimed to quantify the economic burden of itch-related sleep loss in moderate-to-severe atopic dermatitis in the UK.

Sustained Improvements in Clinical and Patient-Reported Outcomes and Quality of Life Through 5 Years Among Ixekizumab-Treated Patients with Complete Clearance of Scalp Psoriasis by Week 60.

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment.

Formation of functional E3 ligase complexes with UBC2 and UEV1 of Leishmania mexicana.

In eukaryotic cells, molecular fate and cellular responses are shaped by multicomponent enzyme systems which reversibly attach ubiquitin and ubiquitin-like modifiers to target proteins. The extent of the ubiquitin proteasome system in Leishmania mexicana and its importance for parasite survival has recently been established through deletion mutagenesis and life-cycle phenotyping studies. The ubiquitin conjugating E2 enzyme UBC2, and the E2 enzyme variant UEV1, with which it forms a stable complex in vitro, were shown to be essential for the differentiation of promastigote parasites to the infectious amastigote form.

Ixekizumab Real-World Effectiveness at 24 Weeks in Patients with Psoriasis: Data from the United States Taltz Customer Support Program.

Introduction: Ixekizumab, a highly selective interleukin-17A monoclonal antibody, was approved for the treatment of moderate-to-severe psoriasis (PsO) in 2016. Limited real-world data are available on its effectiveness from a patient's perspective shortly (2 to 4 weeks) after initiation and upon continuation for 24 weeks.

Objective: To describe patient-reported clinical and quality-of-life outcomes after initiating ixekizumab using data collected from the United States Taltz® Customer Support Program.

High-Grade, Stage 2 Mast Cell Tumors: Outcome in Dogs With Local and Systemic Therapy.

Canine mast cell tumors (MCTs) have highly variable clinical behavior, and predicting outcomes in individual dogs remains challenging. Many studies combine dogs with varying tumor grades, clinical stage, or treatments, confounding those results. The purpose of this retrospective study was to determine outcome and prognostic factors in a specific subset of dogs with high-grade, stage 2, cutaneous MCTs treated with adequate local control via surgery with or without radiation therapy and adjuvant cytotoxic chemotherapy.

Development of Psoriasis Assessment Tools Among Patients in the CorEvitas Psoriasis Registry.

Background: Dermatologists would benefit from an easy to use psoriasis severity assessment tool in the clinic.

Objective: To develop psoriasis assessment tools to predict PASI and Dermatology Life Quality Index (DLQI) using simple measures typically collected in clinical practice.

Methods: Data included 33 605 dermatology visits among plaque psoriasis patients enrolled in the CorEvitas Psoriasis Registry (4/15/15-7/11/20).

Commissioning of the novel Continuous Angle Multi-energy Analysis spectrometer at the Paul Scherrer Institut.

We report on the commissioning results of the cold neutron multiplexing secondary spectrometer CAMEA (Continuous Angle Multi-Energy Analysis) at the Swiss Spallation Neutron Source at the Paul Scherrer Institut, Switzerland. CAMEA is optimized for efficient data acquisition of scattered neutrons in the horizontal scattering plane, allowing for detailed and rapid mapping of low-energy excitations under extreme sample environment conditions.

Comparison of Real-World Costs, Healthcare Resource Utilization, and Comorbidity-Related Costs Between Ixekizumab and Secukinumab Among Biologic-Experienced Patients with Psoriasis Over 18 Months in the USA.

Background And Objective: Data on real-world healthcare costs for ixekizumab (IXE) and secukinumab (SEC) in biologic-experienced patients with psoriasis are limited. This study compared real-world costs and healthcare resource utilization between IXE and SEC in biologic-experienced patients with psoriasis over an 18-month follow-up period in the USA.

Methods: Adult patients with a diagnosis of psoriasis between 1 March, 2015 and 31 October, 2019 were identified using health insurance claims data from IBM Watson Health MarketScan.

Annual indirect costs savings in patients with episodic or chronic migraine: a post-hoc analysis of phase 3 galcanezumab clinical trials in the United States.

Background: Galcanezumab (GMB) improved quality-of-life and reduced disability of patients with episodic (EM) and chronic migraine (CM) in Phase 3 trials.

Aim: To estimate indirect cost savings associated with GMB treatment in patients with migraine in the United States (US).

Methods: We analyzed data of patients from the US from three randomized, Phase 3, double-blind, placebo (PBO)-controlled GMB studies: EVOLVE-1 and EVOLVE-2 (EM patients), REGAIN (CM patients).

In vitro Di-ubiquitin Formation Assay and E3 Cooperation Assay.

Ubiquitination is a post-translational modification conserved across eukaryotic species. It contributes to a variety of regulatory pathways, including proteasomal degradation, DNA repair, and cellular differentiation. The ubiquitination of substrate proteins typically requires three ubiquitination enzymes: a ubiquitin-activating E1, a ubiquitin-conjugating E2, and an E3 ubiquitin ligase.

Treatment Persistence of Ixekizumab in Adults with Moderate-to-Severe Plaque Psoriasis Participating in the Canadian Patient Support Program.

Introduction: Patients with psoriasis (PsO) should adhere to and be persistent with treatment to maintain disease control. Patient support programs (PSPs) are useful to support patients with disease management. We aimed to understand the real-world patient profile and persistence of ixekizumab-initiating Canadian patients with moderate-to-severe PsO using PSP data.

Outcomes of Biologic Use in Asian Compared with Non-Hispanic White Adult Psoriasis Patients from the CorEvitas Psoriasis Registry.

Introduction: Real-world data are limited comparing Asian and White patients with psoriasis using biologic therapy. This study compared the 6-month effectiveness of biologic therapy between Asian and White plaque patients with psoriasis in the CorEvitas Psoriasis Registry.

Methods: Analyses included biologic initiations and 6-month follow-up visits from self-identified Asian (n = 293) and White (n = 2314) patients in the USA/Canada (4/2015-4/2020).

Outcomes in Ixekizumab Patients Following Exposure to Secukinumab and Other Biologics in the CorEvitas Psoriasis Registry.

Introduction: The aim of this work is to describe real-world biologic-experienced psoriasis patients initiating ixekizumab by prior biologic therapy status and compare the effectiveness of ixekizumab between patients who previously failed secukinumab and those who failed other biologics. We hypothesized that (1) clinical outcomes and patient-reported outcomes would improve following a switch to IXE, and (2) there would be no differences in responses between patients who previously failed secukinumab and those who failed other biologics.

Methods: Participants (n = 419) included adult psoriasis patients enrolled in the CorEvitas Psoriasis Registry through 9/10/20 who switched to ixekizumab after discontinuing another biologic.

Assessing the Cost-effectiveness of a Hypothetical Disease-modifying Therapy With Limited Duration for the Treatment of Early Symptomatic Alzheimer Disease.

Purpose: Clinical trials have produced promising results for disease-modifying therapies (DMTs) for Alzheimer's disease (AD); however, the evidence on their potential cost-effectiveness is limited. This study assesses the cost-effectiveness of a hypothetical DMT with a limited treatment duration in AD.

Methods: We developed a Markov state-transition model to estimate the cost-effectiveness of a hypothetical DMT plus best supportive care (BSC) versus BSC alone among Americans living with mild cognitive impairment (MCI) due to AD or mild AD.

Healthcare Costs Among Patients with Psoriasis Treated with Ixekizumab Versus Secukinumab in Real-World Settings Over 24 Months.

Objective: The aim of this study was to compare healthcare costs between ixekizumab (IXE)-treated and secukinumab (SEC)-treated patients with psoriasis over a 24-month follow-up period in the United States.

Methods: Patients with psoriasis diagnosis were identified from IBM Watson Health MarketScan Research Databases; those with one or more claim for index drug (IXE or SEC) between March 1, 2016 and October 31, 2019 were included. Included patients were ≥ 18 years old and had continuous enrollment with medical and pharmacy benefits ≥ 6 months before and ≥ 24 months after index date.

Ubiquitin and ubiquitin-like conjugation systems in trypanosomatids.

In eukaryotic cells, reversible attachment of ubiquitin and ubiquitin-like modifiers (Ubls) to specific target proteins is conducted by multicomponent systems whose collective actions control protein fate and cell behaviour in precise but complex ways. In trypanosomatids, attachment of ubiquitin and Ubls to target proteins regulates the cell cycle, endocytosis, protein sorting and degradation, autophagy and various aspects of infection and stress responses. The extent of these systems in trypanosomatids has been surveyed in recent reports, while in Leishmania mexicana, essential roles have been defined for many ubiquitin-system genes in deletion mutagenesis and life-cycle phenotyping campaigns.

Strengthening Mental Abilities with Relational Training (SMART) in multiple sclerosis (MS): study protocol for a feasibility randomised controlled trial.

Background: Multiple sclerosis (MS) is a chronic condition of the central nervous system, affecting around 1 in every 600 people in the UK, with 130 new diagnoses every week. Cognitive difficulties are common amongst people with MS, with up to 70% experiencing deficits in higher-level brain functions-such as planning and problem-solving, attention, and memory. Cognitive deficits make it difficult for people with MS to complete everyday tasks and limit their abilities to work, socialise, and live independently.