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Abstract Background Edoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations. Case presentation This case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period. Conclusions This case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels.

Abstract Background Factors predicting the response to pembrolizumab plus platinum and pemetrexed combination therapy (Pemb‐Plt‐PEM) in nonsquamous non‐small cell lung cancer (non‐sq NSCLC) are unclear. We investigated the Glasgow Prognostic (GP) score, neutrophil‐to‐lymphocyte ratio (NLR), and body mass index (BMI) as predictors of response to initial treatment with combination therapy in individuals with advanced non‐sq NSCLC. Methods We retrospectively reviewed 236 patients who received initial treatment with combination therapy for non‐sq NSCLC at 13 institutions between December 2018 and December 2020. The usefulness of the GP score, NLR, and BMI as prognostic indicators was assessed. Cox proportional hazard models and the Kaplan–Meier method were used to compare progression‐free survival (PFS) and overall survival (OS). Results The response rate was 51.2% (95% CI: 44.9–57.5%). The median PFS and OS after beginning Pemb‐Plt‐PEM were 8.8 (95% CI: 7.0–11.9) months and 23.6 (95% CI: 18.7–28.6) months, respectively. The NLR independently predicted the efficacy of Pemb‐Plt‐PEM—the PFS and OS were more prolonged in individuals with NLR

Abstract Background In nasal or sinonasal tumors, orbital invasion beyond periorbita by the tumor is one of the important criteria in the selection of the surgical procedure. We investigated the usefulness of the convolutional neural network (CNN)-based deep learning technique for the diagnosis of orbital invasion, using computed tomography (CT) images. Methods A total of 168 lesions with malignant nasal or sinonasal tumors were divided into a training dataset (n = 119) and a test dataset (n = 49). The final diagnosis (invasion-positive or -negative) was determined by experienced radiologists who carefully reviewed all of the CT images. In a CNN-based deep learning analysis, a slice of the square target region that included the orbital bone wall was extracted and fed into a deep-learning training session to create a diagnostic model using transfer learning with the Visual Geometry Group 16 (VGG16) model. The test dataset was subsequently tested in CNN-based diagnostic models and by two other radiologists who were not specialized in head and neck radiology. At approx. 2 months after the first reading session, two radiologists again reviewed all of the images in the test dataset, referring to the diagnoses provided by the trained CNN-based diagnostic model. Results The diagnostic accuracy was 0.92 by the CNN-based diagnostic models, whereas the diagnostic accuracies by the two radiologists at the first reading session were 0.49 and 0.45, respectively. In the second reading session by two radiologists (diagnosing with the assistance by the CNN-based diagnostic model), marked elevations of the diagnostic accuracy were observed (0.94 and 1.00, respectively). Conclusion The CNN-based deep learning technique can be a useful support tool in assessing the presence of orbital invasion on CT images, especially for non-specialized radiologists.

Abstract In this study, we investigated the impact of single nucleotide polymorphisms in solute carrier (SLC) transporters, that is, SLC22A7 c.1586 + 206A > G, SLC22A2 c.808G > T, SLC22A3 c.1233G > A, SLC47A1 c.922‐158G > A, and SLC47A2 c.‐130G > A, on serum creatinine (SCr) concentrations. This cross‐sectional study included residents who participated as volunteers in a health promotion study. Lifestyle data, blood chemical analysis data, and SLC gene polymorphism information were collected from each participant. Univariate analyses were carried out to determine differences between groups and correlations in SCr. Stepwise multiple regression analysis was performed to confirm the independence of factors that were significantly different in the univariate analyses. In multiple regression analyses, muscle mass, serum cystatin C concentrations, body fat percentage, serum albumin concentrations, and SLC47A2 c.‐130G/G had the highest contribution to SCr concentrations, in that order (standardized regression coefficients = .505, .332, −.234, .123, and .084, respectively). The final model explained 72.2% of the variability in SCr concentrations. The SLC47A2 c.‐130G > A polymorphism may affect creatinine dynamics in the proximal tubules. Further studies are needed to determine the effects of SLC transporter gene polymorphisms on SCr concentrations in patients with various diseases in real‐world clinical settings.

Localized management based on multipoint measurements of crops and soil is expected to improve agricultural productivity. The difficulties with this process are as follows: it is time-consuming due to the many measurement points; it requires various sensors for various measurements; it can lead to unstable measurements due to sunlight and wind. To solve the above issues, the system we propose has the advantages of efficient measurements performed by a robot, various measurements performed through exchangeable sensor units, and stable measurements through protecting the crop from sunlight and wind. As a pilot study for the system, we conducted an experiment to simultaneously measure the crops and soil in a cabbage field. The robot achieved mobility in the field, >4 h of operation time, and the ability to obtain soil electrical conductivity measurements and crop imaging at 100 points. Furthermore, the stability of the measurement conditions within the sensor unit during the experiment was evaluated. Compared to the case without the covering, the illuminance became 280-fold stabler (standard deviation = 0.4 lx), and the wind-induced crop shaking became 20-fold lower (root mean square error of the image pixels = 0.5%). The potential impacts of this research include high reproducibility because of the shareable sensor unit and the expectation of new discoveries using precise indoor sensors.

Abstract The effects of inflammatory responses and polymorphisms of the genes encoding cytochrome P450 (CYP) (CYP2C19 and CYP3A5), flavin‐containing monooxygenase 3 (FMO3), pregnane X receptor (NR1I2), constitutive androstane receptor (NR1I3), and CYP oxidoreductase (POR) on the ratio of voriconazole (VRCZ) N‐oxide to VRCZ (VNO/VRCZ) and steady‐state trough concentrations (C0h) of VRCZ were investigated. A total of 56 blood samples were collected from 36 Japanese patients. Results of multiple linear regression analyses demonstrated that the presence of the extensive metabolizer CYP2C19 genotype, the dose per administration, and the presence of the NR1I2 rs3814057 C/C genotype were independent factors influencing the VNO/VRCZ ratio in patients with CRP levels of less than 40 mg/L (standardized regression coefficients (SRC) = 0.448, −0.301, and 0.390, respectively; all p

In the winter pruning operation of deciduous fruit trees, the number of pruning branches and the structure of the main branches greatly influence the future growth of the fruit trees and the final harvest volume. Terrestrial laser scanning (TLS) is considered a feasible method for the 3D modeling of trees, but it is not suitable for large-scale inspection. The simultaneous localization and mapping (SLAM) technique makes it possible to move the lidar on the ground and model quickly, but it is not useful enough for the accuracy of plant detection. Therefore, in this study, we used UAV-SfM and 3D lidar SLAM techniques to build 3D models for the winter pruning of peach trees. Then, we compared and analyzed these models and further proposed a method to distinguish branches from 3D point clouds by spatial point cloud density. The results showed that the 3D lidar SLAM technique had a shorter modeling time and higher accuracy than UAV-SfM for the winter pruning period of peach trees. The method had the smallest RMSE of 3084 g with an R2 = 0.93 compared to the fresh weight of the pruned branches. In the branch detection part, branches with diameters greater than 3 cm were differentiated successfully, regardless of whether before or after pruning.

Antifibrotic agents have been widely used in patients with idiopathic pulmonary fibrosis (IPF). Long-term continuation of antifibrotic therapy is required for IPF treatment to prevent disease progression. However, antifibrotic treatment has considerable adverse events, and the continuation of treatment is uncertain in many cases. Therefore, we examined and compared the continuity of treatment between pirfenidone and nintedanib in patients with IPF. We retrospectively enrolled 261 consecutive IPF patients who received antifibrotic treatment from six core facilities in Gunma Prefecture from 2009 to 2018. Among them, 77 patients were excluded if the antifibrotic agent was switched or if the observation period was less than a year. In this study, 134 patients treated with pirfenidone and 50 treated with nintedanib were analyzed. There was no significant difference in patient background, discontinuation rate of antifibrotic treatment over time, and survival rate between the two groups. However, the discontinuation rate due to adverse events within one year of antifibrotic treatment was significantly higher in the nintedanib group than in the pirfenidone group (76% vs. 37%, p < 0.001). Furthermore, the discontinuation rate due to adverse events in nintedanib was higher than that of pirfenidone treatment throughout the observation period (70.6% vs. 31.2%, p = 0.016). The pirfenidone group tended to be discontinued due to acute exacerbation or transfer to another facility. The results of this study suggest that better management of adverse events with nintedanib leads to more continuous treatment that prevents disease progression and acute exacerbations, thus improving prognosis in patients with IPF.

Strawberries are an economically valuable fruit in Japan; hence, their production must be maintained throughout the year. In this study, we investigated the effect of temperature on the number of days required for each fruit growth and ripening stage in order to obtain a basic knowledge for the highly accurate prediction and control of fruit harvest time. We planted the 'Koiminori' variety in artificial climate chambers, and then the effect of the average air temperature on the number of days required for each stage was analysed in four stages. The results showed that the correlation between temperature and the number of days required for fruit maturity was high at the white stage, moderate at the flowering and turning stages, and weak at the green stage. In comparing our proposed method which estimates the entire maturation period of the strawberries by totalling the predicted number of days required for each stage with the conventional method of estimating the entire maturation period at once, our proposed method significantly reduced the mean absolute error. However, the difference was slight at 0.18 days. This result suggests that the number of days required for each stage should be optimized for prediction by adding parameters other than air temperature as independent variables. [ABSTRACT FROM AUTHOR]

The article presents a study which surveyed the status of medication guidance for the physical and psychological symptoms of patients receiving palliative care and compared the medication guidance provided by certified and uncertified pharmacists. Topics include requirements for board certification as a pharmacist in palliative pharmacy, intervention guidance in relieving symptoms other than pain, and background characteristics of pharmacists.