bioRxiv ScienceSearch

Biology subjects

Matsuzaki, T.

Publications and source records attributed to Matsuzaki, T..

2 recordsLinked to original sources

A machine learning model that emulates experts decision making in vancomycin initial dose planning

Vancomycin is a glycopeptide antibiotic that has been used primarily in the treatment of methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness and prevent nephrotoxicity, therapeutic drug monitoring (TDM) of trough concentrations is recommended. Initial vancomycin dosing regimens are determined based on patient characteristics such as age, body weight, and renal function, and dosing strategies to achieve therapeutic concentration windows at initial TDM have been extensively studied. Although numerous dosing nomograms for specific populations have been developed, no comprehensive strategy exists for individually tailoring initial dosing regimens; therefore, decision making regarding initial dosing largely depends on each clinicians experience and expertise. In this study, we applied a machine-learning (ML) approach to integrate clinician knowledge into a predictive model for initial vancomycin dosing. A dataset of vancomycin initial dose plans defined by pharmacists experienced in vancomycin TDM (i.e., experts) was used to build the ML model. The target trough concentration was attained at comparable rates with the model- and expert-recommended dosing regimens, suggesting that the ML model successfully incorporated the experts knowledge. The predictive model developed here will contribute to improved decision making for initial vancomycin dosing and early attainment of therapeutic windows.

pharmacology and toxicology

Micromanipulation of amyloplasts with optical tweezers in Arabidopsis stems

Intracellular sedimentation of highly dense, starch-filled amyloplasts toward the gravity vector is likely a key initial step for gravity sensing in plants. However, recent live-cell imaging technology revealed that most amyloplasts continuously exhibit dynamic, saltatory movements in the endodermal cells of Arabidopsis stems. These complicated movements led to questions about what type of amyloplast movement triggers gravity sensing. Here we show that a confocal microscope equipped with optical tweezers can be a powerful tool to trap and manipulate amyloplasts noninvasively, while simultaneously observing cellular responses such as vacuolar dynamics in living cells. A near-infrared ({lambda} = 1064 nm) laser that was focused into the endodermal cells at 1 mW of laser power attracted and captured amyloplasts at the laser focus. The optical force exerted on the amyloplasts was theoretically estimated to be up to 1 pN. Interestingly, endosomes and trans-Golgi networks were trapped at 30 mW but not at 1 mW, which is probably due to lower refractive indices of these organelles than that of the amyloplasts. Because amyloplasts are in close proximity to vacuolar membranes in endodermal cells, their physical interaction could be visualized in real time. The vacuolar membranes drastically stretched and deformed in response to the manipulated movements of amyloplasts by optical tweezers. Our new method provides deep insights into the biophysical properties of plant organelles in vivo and opens a new avenue for studying gravity-sensing mechanisms in plants.

plant biology