Predicting Asthma Exacerbations Using Machine Learning Models.

Introduction: Although clinical, functional, and biomarker data predict asthma exacerbations, newer approaches providing high accuracy of prognosis are needed for real-world decision-making in asthma. Machine learning (ML) leverages mathematical and statistical methods to detect patterns for future disease events across large datasets from electronic health records (EHR). This study conducted training and fine-tuning of ML algorithms for the real-world prediction of asthma exacerbations in patients with physician-diagnosed asthma.

Effect of Tezepelumab on Sino-Nasal Outcome Test (SNOT)-22 Domain and Symptom-Specific Scores in Patients with Severe, Uncontrolled Asthma and a History of Chronic Rhinosinusitis with Nasal Polyps.

Introduction: Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2 years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes.

Biomarkers and clinical outcomes after tezepelumab cessation: Extended follow-up from the 2-year DESTINATION study.

Background: Long-term tezepelumab treatment in the DESTINATION study (NCT03706079) resulted in reduced asthma exacerbations, reduced biomarker levels, and improved lung function and symptom control in patients with severe, uncontrolled asthma.

Objective: To explore the time course of changes in biomarkers and clinical manifestations after treatment cessation after 2 years of tezepelumab treatment.

Methods: DESTINATION was a 2-year, phase 3, multicenter, randomized, placebo-controlled, double-blind study of tezepelumab treatment in patients (12-80 years old) with severe asthma.

Effect of Tezepelumab on the Humoral Immune Response to Seasonal Quadrivalent Influenza Vaccination in Patients with Moderate to Severe Asthma: The Phase 3b VECTOR Study.

Introduction: Annual influenza vaccinations are recommended for adolescents and adults with moderate to severe asthma. This study investigated the effect of tezepelumab, a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, on the humoral immune response to the quadrivalent seasonal influenza vaccine in patients with moderate to severe asthma.

Methods: VECTOR was a phase 3b, randomized, multicenter, double-blind, parallel-group, placebo-controlled study.

Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR.

Purpose: Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control versus placebo in adults and adolescents with severe, uncontrolled asthma. We assessed the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR.

Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study.

Background: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin. The drug has been tested previously in the phase 3 NAVIGATOR (NCT03347279) and SOURCE (NCT03406078) studies, and was subsequently approved as a treatment for severe asthma. This extension study recruited from NAVIGATOR and SOURCE and aimed to evaluate the long-term safety and efficacy of tezepelumab in individuals with severe, uncontrolled asthma.

Effect of Age on Efficacy and Safety of Fluticasone Furoate/Vilanterol (FF/VI), Umeclidinium (UMEC), and UMEC + FF/VI in Patients with Chronic Obstructive Pulmonary Disease: Analyses of Five Randomized Clinical Trials.

Introduction: Concerns have been raised about the practical use and clinical benefits of medications and inhalers in older patients with chronic obstructive pulmonary disease (COPD). Here, we report analyses according to age from five clinical trials evaluating medications administered using the ELLIPTA dry-powder inhaler (DPI).

Methods: Efficacy and safety according to age groups (<65 and ≥65 years) were assessed using data from five clinical trials in patients ≥40 years of age with symptomatic COPD.

Impact of clobetasol propionate 0.05% spray on health-related quality of life in patients with plaque psoriasis.

Psoriasis causes significant distress and impairment in health-related quality of life (QOL) in afflicted patients. For this reason, QOL is an essential and important measure of treatment outcome in patients with the disease. Clobetasol propionate is a super-highpotent class I topical corticosteroid.

Effectiveness and safety of once-daily doxycycline capsules as monotherapy in patients with rosacea: an analysis by Fitzpatrick skin type.

Rosacea is often under-recognized or misdiagnosed in patients with skin of color (Fitzpatrick Skin Types [FST] IV-VI). Subtle clinical features and a low index of suspicion likely contribute to less frequent diagnosis in this population. Clinical trials of therapeutic agents for rosacea generally include few patients from nonwhite racial/ethnic groups and therefore, potential differences in treatment outcomes have not been previously studied.

Digital videography assessment of patients' experiences using adapalene-benzoyl peroxide gel in the treatment of acne vulgaris.

Background: Acne profoundly affects patients' lives, but the effect of treatment is not fully characterized.

Objective: The purpose of this study was to explore patients' experiences and viewpoints regarding treatment for mild to moderate acne vulgaris.

Methods: This was an open-label, single-center study of 30 patients with mild to moderate acne vulgaris, treated with adapalene 0.

A comparison of the tolerability of adapalene 0.1% cream and adapalene 0.1% lotion in healthy individuals.

Two separate single-center, randomized, evaluator-blinded, bilateral (split-face) comparison studies compared the tolerability of adapalene 0.1% cream with adapalene 0.1% lotion in individuals with healthy skin treated once per day for 3 weeks.

Clobetasol propionate 0.05% spray for the management of moderate-to-severe plaque psoriasis of the scalp: results from a randomized controlled trial.

Background: Clobetasol propionate 0.05% spray is available for treating moderate-to-severe plaque psoriasis; however, there is limited information with plaque psoriasis of the scalp.

Objective: Evaluate the efficacy, safety, and quality-of-life impact of clobetasol propionate 0.

Expression of multidrug resistance proteins is localized principally to the Malpighian tubules in larvae of the cabbage looper moth, Trichoplusia ni.

The multidrug resistance proteins (MRPs) serve a number of important roles in development, physiological homeostasis and metabolic resistance. In insects, they may also contribute to resistance against xenobiotics including insecticides and plant secondary metabolites. To investigate their contribution to xenobiotic resistance, we have examined the tissue distribution of gene and protein expression of the multidrug resistance proteins TrnMRP1 and TrnMRP4 of the lepidopteran insect, Trichoplusia ni.

Genetic analysis of the xenobiotic resistance-associated ABC gene subfamilies of the Lepidoptera.

Some ATP-binding cassette (ABC) transporters of subfamilies B, C and G confer resistance to xenobiotics including insecticides. We identified genes of these subfamilies expressed by the lepidopterans Trichoplusia ni and Bombyx mori. The B.

Functional comparison of full-length and N-terminal-truncated octopamine transporters from Lepidoptera.

We have cloned two new lepidopteran octopamine transporters (OATs), members of the solute-linked carrier family 6 (SLC6) of nutrient transporters, from the CNS of the European corn borer Ostrinia nubilalis and the cabbage white Pieris rapae. Comparison of these sequences with the previously cloned OAT from the cabbage looper Trichoplusia ni showed that the T. ni OAT sequence previously reported was truncated by 74 amino acids at the N-terminus.

Ancestry of neuronal monoamine transporters in the Metazoa.

Selective Na(+)-dependent re-uptake of biogenic monoamines at mammalian nerve synapses is accomplished by three types of solute-linked carrier family 6 (SLC6) membrane transporter with high affinity for serotonin (SERTs), dopamine (DATs) and norepinephrine (NETs). An additional SLC6 monoamine transporter (OAT), is responsible for the selective uptake of the phenolamines octopamine and tyramine by insect neurons. We have characterized a similar high-affinity phenoloamine transporter expressed in the CNS of the earthworm Lumbricus terrestris.

A transporter for phenolamine uptake in the arthropod CNS.

Biogenic monoamines play central roles in the nervous control of physiological processes in both vertebrates and invertebrates, each using a suite of neurotransmitters tailored through evolution. Among the ancillary proteins necessary for the deployment of monoamine transmitters are membrane-bound transporters that enable the reuptake of synaptically released transmitters. Transporters responsible for monoamine uptake include a novel transporter discovered in a pest insect, the cabbage looper Trichoplusia ni, which has high affinity for the phenolamines octopamine and tyramine.

Molecular cloning and functional characterization of a neuronal choline transporter from Trichoplusia ni.

A cDNA encoding a high-affinity Na(+)-dependent choline transporter (TrnCHT) was isolated from the CNS of the cabbage looper Trichoplusia ni using an RT-PCR-based approach. The deduced amino acid sequence of the CHT cDNA predicts a 594 amino acid protein of 64.74 kDa prior to glycosylation.

Characterization of a chloride current in the larval epidermis of the beetle Tenebrio molitor.

Voltage-clamp analysis of single cuticle-attached epidermal cells dissected from the newly-ecdysed mealworm revealed the presence of a large inwardly-rectifying anion (i.e. outwardly-going) current.

Functionally distinct dopamine and octopamine transporters in the CNS of the cabbage looper moth.

A cDNA was cloned from the cabbage looper Trichoplusia ni based on similarity to other cloned dopamine transporters (DATs). The total nucleotide sequence is 3.8 kb in length and contains an open reading frame for a protein of 612 amino acids.

Cellular distribution of a high-affinity glutamate transporter in the nervous system of the cabbage looper Trichoplusia ni.

Glutamate functions as a neurotransmitter in the central nervous system (CNS) and neuromuscular junctions in insects. High-affinity glutamate transporters are responsible for keeping the resting levels of excitatory amino acids below the synaptic activation threshold by removing them from the extracellular fluid, thereby preventing them from reaching toxic levels. Peptides representing the N- and C-terminal regions of a glutamate transporter cloned from the cabbage looper caterpillar (Trichoplusia ni) were synthesized and used to generate polyclonal antibodies.

A high-affinity octopamine transporter cloned from the central nervous system of cabbage looper Trichoplusia ni.

A cDNA encoding a high-affinity Na(+)/anion(-)-dependent octopamine transporter (OAT) was isolated via an RT-PCR-based approach from caterpillars of the cabbage looper, Trichoplusia ni. The deduced amino acid sequence of the OAT cDNA predicts a 670 amino acid protein bearing strong homology to previously cloned monoamine transporters. The expression pattern of OAT mRNA in the central nervous system revealed by in situ hybridization closely resembles that of OA-ergic neurons identified by the presence of mRNA for tyramine beta-hydroxylase, a marker enzyme for OA-ergic neurons in invertebrates.

Insecticidal activity of glufosinate through glutamine depletion in a caterpillar.

The herbicide glufosinate-ammonium (GLA) is a competitive inhibitor of glutamine synthetase (GS), an enzyme converting glutamate to glutamine in both plants and animals. Because GS is essential for ammonia detoxification in plants, GLA treatment disrupts photorespiration by causing a build-up of ammonia and a loss of glutamine in plant tissues. This study reports that GLA applied to leaf surfaces is also toxic to 5th-instar caterpillars of the skipper butterfly Calpodes ethlius (LD50 = 400 mg kg-1).