Concept Drift in Japanese COVID-19 Infection Data.

In this study, we analyze concept drifts in the daily infection data of COVID-19 in Japan. A lockdown, the spread of vaccines, and the emergence of new variants of COVID-19 have had a significant impact on the number of daily infections. These changes, also known as concept drifts, make the prediction of COVID-19 infection rates difficult. Because the prediction of infection trends is crucial to protect people from the disease, this study aims to generate accurate predictions by handling concept drifts in the trend data. The key concept behind this method is a brute-force tuning of the training period. Although prior studies tended to require pre-tuned parameters to locate the drift points, this can be avoided through brute-force tuning. Experimental results show significant improvements in prediction accuracy. Furthermore, the extracted points where concept drifts occur appear to correspond to new COVID-19 variants and other important state changes.

Prediction of Soil Adsorption Coefficient in Pesticides Using Physicochemical Properties and Molecular Descriptors by Machine Learning Models.

The soil adsorption coefficient (KOC ) plays an important role in environmental risk assessment of pesticide registration. Based on this risk assessment, applied and registered pesticides can be allowed in the European Union. Almost 1 yr is required to study and obtain the KOC value of a pesticide. Furthermore, acquiring the KOC requires a large cost. It is necessary to efficiently estimate the KOC value in the early stages of pesticide development. In the present study, the experimental values of physicochemical properties and molecular descriptors of chemical structures were collected to develop a quantitative structure-property relationship (QSPR) model, and the prediction performance of the model was evaluated. More specifically, we compared the accuracies of models based on a gradient boosting decision tree, multiple linear regression, and support vector machine. The experimental results suggest that it is possible to develop a QSPR model with high accuracy using both the molecular descriptors calculated from the structural formula and experimental values of physicochemical properties from open literature and databases. Comparing to the previously established models, we achieved high prediction accuracy, fitness, and robustness by only using freeware. Therefore, our developed QSPR models can be useful preliminary risk assessment in the early developmental stages of pesticides. Environ Toxicol Chem 2020;39:1451-1459. © 2020 SETAC.

Evaluation of Drug Efficacy of GLP-1 Receptor Agonists and DPP-4 Inhibitors Based on Target Molecular Binding Occupancy.

Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, exenatide, lixisenatide) have recently been used as anti-diabetes drugs. We examined relationships of the binding occupancy of GLP-1 receptors (Φ) and their clinical efficacy after administration of GLP-1 receptor agonists. Next, by focusing on changes of GLP-1 concentration after administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, alogliptin, sitagliptin, linagliptin), we analyzed the relationship between Φ and clinical efficacy. Furthermore, using Φ as a common parameter, we compared the clinical efficacy elicited by GLP-1 receptor agonists and DPP-4 inhibitors using a theoretical analysis method. The present results showed that GLP-1 receptor agonists produced their clinical effect at a relatively low level of Φ (1.1-10.7%) at a usual dose. Furthermore, it was suggested that the drugs might achieve their full effect at an extraordinarily low level of Φ. It was also revealed that the Φ value of DPP-4 inhibitors (0.83-1.3%) was at the lower end or lower than that of GLP-1 receptor agonists at a usual dose. Accordingly, the predicted value for hemoglobin A1c (HbA1c) reduction after administration of the GLP-1 receptor agonists was higher than that of DPP-4 inhibitors. We clarified the differences between the therapeutic effects associated with GLP-1 receptor agonists and DPP-4 inhibitors theoretically. Together, the present findings provide a useful methodology for proper usage of GLP-1 receptor agonists and DPP-4 inhibitors.

Evaluation of drug efficacy of DPP-4 inhibitors based on theoretical analysis with pharmacokinetics and pharmacodynamics.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are used clinically as therapeutic agents for the treatment of diabetes. To determine the rate of DPP-4 inhibition induced by these inhibitors, pharmacokinetic and pharmacodynamic parameters were used to theoretically examine the relationship between the rate of DPP-4 inhibition and clinical efficacy following the administration of four different DPP-4 inhibitors (sitagliptin, vildagliptin, alogliptin, linagliptin) by focusing on the increase in the level of glucagon-like peptide-1 (GLP-1) induced by their administration. On the basis of the relationship shown, changes in clinical efficacy in association with dose change were examined in order to discuss clinical dosage from the standpoint of proper usage. The results indicate that a high rate of DPP-4 inhibition is necessary for the onset of the effect of an administered the DPP-4 inhibitor and that the average value for the DPP-4 inhibition rate can be utilized as a common parameter of clinical efficacy. Furthermore, the efficacy profiles of the present DPP-4 inhibitors could be demonstrated on the basis of an increase in the GLP-1 level. It is considered that the present findings provide useful information for promoting the proper clinical use of DPP-4 inhibitors. Copyright © 2016 John Wiley & Sons, Ltd.

Cytomegalovirus colitis in a patient undergoing postoperative adjuvant chemotherapy for lung adenocarcinoma with uracil-tegafur.

When we examine a patient with symptoms of acute enteritis in the course of chemotherapy with oral fluoropyrimidines such as uracil-tegafur (often referred to as UFT), we usually suspect 5-fluorouracil-induced enterocolitis. In case of persistent clinical symptoms despite discontinuation of chemotherapy, cytomegalovirus colitis should be considered in the differential diagnosis of chemotherapy-induced enterocolitis. We herein report the case of a patient who underwent surgery for lung adenocarcinoma followed by postoperative adjuvant chemotherapy with uracil-tegafur and was diagnosed as having cytomegalovirus colitis during the therapy. In the course of chemotherapy, cytomegalovirus colitis occasionally occurs even though the patient does not experience severe myelosuppression; thus, it is necessary that we recognize its potential occurrence.

Three cases of acute or fulminant hepatitis E caused by ingestion of pork meat and entrails in Hokkaido, Japan: Zoonotic food-borne transmission of hepatitis E virus and public health concerns.

AIM: In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission. METHODS: Three patients with non-A, B and C acute hepatitis, two of whom presented in a critical condition, were assessed for HEV infection using polymerase chain reaction and their route of infection; the genome sequences of the infecting HEV were also analyzed. A phylogenetic tree based on the full, or near full, HEV RNA sequences were constructed by neighbor-joining method. RESULTS: All three patients ingested grilled pork meat and entrails at the same barbecue restaurant in Abashiri, Hokkaido, Japan. When comparing partial to entire, or nearly entire, nucleotide sequences of HEV detected in these patients, they were 99.9-100% identical to each other. These genotype 4 isolates had great resemblance to the genome sequences of the isolates from the mini-outbreak in 2004 in Kitami, a city adjacent to Abashiri. These Kitami/Abashiri strains were segregated into a single cluster on the phylogenetic tree of HEV genotype 4 indigenous to Japan. CONCLUSION: Indigenous HEV transmission via a zoonotic food-borne route has been demonstrated in Kitami and Abashiri via pork meat and entrails contaminated with virulent HEV strains. Because a similar outbreak can recur in the future, infection sources and distribution routes should be clarified rapidly for public health.

Improvement in symptoms after H2-receptor antagonist-based therapy for eradication of H pylori infection.

AIM: To investigate the therapeutic effects of triple therapy combining lafutidine with clarithromycin and amoxicillin on H pylori infection and the resolution of gastroesophageal symptoms after eradication. METHODS: We conducted a randomized, multicenter, open-label controlled trial to compare the effectiveness of a triple therapy of lafutidine, clarithromycin, and amoxicillin (lafutidine group) with that of a triple therapy of lansoprazole, clarithromycin, and amoxicillin (lansoprazole group) in patients with H pylori infection. The study group comprised 22 patients with gastric ulcers and 18 patients with duodenal ulcers who had H pylori infection. RESULTS: H pylori eradication rates were similar in the lafutidine group (14/20, 70%) and the lansoprazole group (14/20, 70%). Gastroesophageal reflux and abdominal symptoms improved after eradication therapy in both groups, whereas abdominal discomfort, diarrhea, and constipation were unchanged. H pylori status had no apparent effect on improvement of gastroesophageal reflux or abdominal symptoms after treatment. Adverse events were similar in both groups. CONCLUSION: The triple therapy including lafutidine is equivalent to triple therapy including lansoprazole in terms of H pylori eradication rates and improvement in gastroesophageal reflux and abdominal symptoms. These results are attributed to the fact that lafutidine has strong, continuous antisecretory activity, unaffected by CYP2C19 polymorphisms.

Patterns of spiral tip motion in cardiac tissues.

In support of the spiral wave theory of reentry, simulation studies and animal models have been utilized to show various patterns of spiral wave tip motion such as meandering and drifting. However, the demonstration of these or any other patterns in cardiac tissues have been limited. Whether such patterns of spiral tip motion are commonly observed in fibrillating cardiac tissues is unknown, and whether such patterns form the basis of ventricular tachycardia or fibrillation remain debatable. Using a computerized dynamic activation display, 108 episodes of atrial and ventricular tachycardia and fibrillation in isolated and intact canine cardiac tissues, as well as in vitro swine and myopathic human cardiac tissues, were analyzed for patterns of nonstationary, spiral wave tip motion. Among them, 46 episodes were from normal animal myocardium without pharmacological perturbations, 50 samples were from normal animal myocardium, either treated with drugs or had chemical ablation of the subendocardium, and 12 samples were from diseased human hearts. Among the total episodes, 11 of them had obvious nonstationary spiral tip motion with a life span of >2 cycles and with consecutive reentrant paths distinct from each other. Four patterns were observed: (1) meandering with an inward petal flower in 2; (2) meandering with outward petals in 5; (3) irregularly concentric in 3 (core moving about a common center); and (4) drift in 1 (linear core movement). The life span of a single nonstationary spiral wave lasted no more than 7 complete cycles with a mean of 4.6+/-4.3, and a median of 4.5 cycles in our samples. Conclusion: (1) Patently evident nonstationary spiral waves with long life spans were uncommon in our sample of mostly normal cardiac tissues, thus making a single meandering spiral wave an unlikely major mechanism of fibrillation in normal ventricular myocardium. (2) A tendency toward four patterns of nonstationary spiral tip motion was observed. (c) 1998 American Institute of Physics.