3,152 research outputs found
Detection of temporal trends in atmospheric deposition of inorganic nitrogen and sulphate to forests in Europe
A recombinant positive control for serology diagnostic tests supporting elimination of Onchocerca volvulus
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Encapsulation of Inorganic Nanoparticles by Anionic Emulsion Polymerization of Diethyl Methylene Malonate for Developing Hybrid Microparticles with Tailorable Composition
Colloidal particle self-assembly into higher-ordered structures has been of great interest due to the promise of creating metamaterials with novel macroscopic properties. The physicochemical properties of these metamaterials can be tailored to achieve composites with tunable functionalities, either by controlling the assembly morphology and/or chemistry of the colloidal building blocks. This work describes a strategy of developing microparticles with a hybrid configuration that have an inorganic and an organic part. The inorganic part comprises functional nanoparticles, which are embedded within an organic polymer particle composed of diethyl methylene malonate polymer [p(DEMM)] prepared using anionic emulsion polymerization. DEMM polymerization is initiated entirely by the presence of hydroxyl anions and the resulting particle diameter can be tuned between 300 nm and 1 micrometer by reaction pH. Inorganic nanoparticles with varying chemistry (TiO2, CdTe, ZnO) can be loaded into the p(DEMM) particle with a controlled weight fraction, as confirmed by thermogravimetric analysis. The colloidal stability of the composite microparticles is seen to be dependent on the ligand coating attached to the inorganic constituent. These results provide a synthetic groundwork for creating hybrid, stimuli-responsive microparticles
Use of fecal genotyping to estimate population demographics in the North Interlake woodland caribou herd
A phase I, multicenter, open-label, first-in-human study of DS-6157a in patients with advanced gastrointestinal stromal tumor
PURPOSE: To evaluate DS-6157a, an antibody-drug conjugate targeting G protein-coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST).
PATIENTS AND METHODS: In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy.
RESULTS: A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses of 6.4 mg/kg, 9.6 mg/kg, and 12.8 mg/kg; the MTD was determined to be 6.4 mg/kg. Treatment-emergent adverse events (TEAE) grade ≥3 occurred in 17 patients (50.0%), including decreased platelet count (23.5%), anemia (20.6%), decreased neutrophil count (14.7%), and decreased white blood cell count (11.8%). Four patients (11.8%) experienced serious adverse events related to DS-6157a. Six patients died with 5 due to disease progression and 1 due to DS-6157a-related TEAE. Tumor shrinkage was observed in 7 patients (20.6%), and 1 patient (2.9%) achieved a partial response. Plasma concentrations and exposure of intact DS-6157a, DXd, and total anti-GPR20 antibody all demonstrated a dose-dependent profile. No treatment-emergent ADAs were observed.
CONCLUSIONS: Targeting GPR20 with DS-6157a was tolerated in patients with advanced GIST with tumor shrinkage demonstrated in KIT/PDGFRA wild-type GIST. However, the study did not proceed further due to lower efficacy outcomes than anticipated
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