Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 3 appraisals
mAbs
Machine learning predictions of IgG1 and IgG4 self-association and high-concentration solution properties
To meet the widespread demand for subcutaneous delivery of antibody therapeutics, candidates with low viscosity, high solubility, and/or low aggregation propensity in concentrated formulations must be identified. Moreover, early identification of candidates with low self-association increases the likelihood of success at later stages of the development process. Here, we experimentally profile the self-association behavior of a panel of clinical-stage antibodies as a function of pH, excipient content, and antibody isotype. We find that acidic formulations (pH 5) with proline (200 mM) are most effective at suppressing self-association for both IgG1 and IgG4 variants. Moreover, our self-association measurements are correlated with antibody viscosity measurements and inversely correlated with antibody recovery after their concentration using membrane filters. Notably, we developed interpretable machine learning-based classifier and regressor models for predicting IgG1 and IgG4 self-association and demonstrated that they identify antibodies with favorable high-concentration properties. These findings are expected to improve the antibody development process by facilitating the identification of drug-like molecules during their discovery and optimization.
13 May 2026
Read appraisal →The pharmacogenomics journal
The role of cytochrome P450 polymorphisms in the pharmacokinetics of oral esketamine
Oral esketamine displays therapeutic potential for treatment-resistant depression. However, treatment is complicated by a low and variable bioavailability. Genetic polymorphisms in the cytochrome P450 (CYP) enzymes responsible for esketamine's metabolism may influence bioavailability. In a subsample of patients included in a placebo-controlled trial investigating repeated, low dose oral esketamine (N = 18), blood samples were collected four hours after dosing. CYP2B6 516 G > T, CYP3A4*22, and CYP3A5*3 genotyping was performed, and the plasma levels of esketamine and its metabolites were measured. CYP2B6 516 G > T carriers (Mdn = 5.1 µg/L) demonstrated higher esketamine plasma levels compared to non-carriers (Mdn = 2.1 µg/L) (U = 45.00, p = 0.032). No significant associations were observed for CYP3A4*22 carriership (n = 2) or CYP3A5*3 heterozygosity (n = 2), nor for esketamine's metabolites. In summary, CYP2B6 516 G > T is associated with higher esketamine plasma concentrations. Further research with more participants is warranted to draw conclusions about CYP3A4*22 and CYP3A5*3. Clinical trial registration: NTR6161 (Dutch Trial Register).
28 Apr 2026
Read appraisal →ACS sensors
Vertically Oriented Assembly of a Few-Layer Ti3C2Tx Grid by Electric Field Inducing and Freeze Drying for Wearable Levodopa Sensing in Sweat
Compared with the parallel assembly, the vertical assembly of MXene nanosheets on the substrate exhibits open three-dimensional porous structure, which is beneficial to the construction of high-performance electrodes. Herein, the vertically oriented assembly of Ti3C2Tx nanosheets is proposed by a novel preparation process of electric field inducing and freeze drying, resulting in the Ti3C2Tx grid with thin-wall and open porous structure. First, the electric field induces the formation of Ti3C2Tx hydrogel layer on the substrate. Second, freeze drying causes the growth of ice crystals for squeezing few-layer Ti3C2Tx nanosheets to stand up. More importantly, such a Ti3C2Tx grid with large surface area and intrinsic conductivity can effectively load electrocatalysts, resulting in the Au-Ti3C2Tx grid as a high-performance working electrode for the electrochemical detection of levodopa. The main parameters include 1-30 μM and 30-160 μM two-stage linear ranges and 37 nM detection limit. The structural advantages of Ti3C2Tx grid-based electrode materials are their three-dimensional conductive network and interconnected porous structure, which contribute to the penetration of the electrolyte, the diffusion of the analyte, and the electrocatalytic reaction. Furthermore, the self-adapting shape of the Ti3C2Tx grid leads to the fan-shaped Au-Ti3C2Tx grid collaborated with a self-designed leaf-like microfluidic. Ultimately, a wearable levodopa sensor composed of Au-Ti3C2Tx grid, microfluidic, flexible electronic system, and mobile phone client is established for detecting levodopa in human sweat, which is expected to help Parkinson's patients control the drug dosage. Our work proposes the vertically assembled Ti3C2Tx nanosheet loaded noble metal electrocatalysts to develop high-performance electrodes for electrochemical sensing.
26 Apr 2026
Read appraisal →