Predicting completion of clinical trials in pregnant women: Cox proportional hazard and neural network models.

This study aimed to develop a model for predicting the completion of clinical trials involving pregnant women using the Cox proportional hazard model and neural network model (DeepSurv) and to compare the predictive performance of both methods. We collected data on 819 clinical trials performed on pregnant women and intervention studies using at least one drug as intervention from 2009 to 2018 from ClinicalTrials.gov. The Cox proportional hazard model and DeepSurv were used to develop models that predict clinical trial completion. The concordance index (C-index) was used to evaluate the predictive performance. The Cox proportional hazard model revealed that a sample size of n ≥ 329 (hazard ratio [HR] = 0.53), very high human development index (HDI) country (HR = 0.28), abortion (HR = 3.30), labor (HR = 2.16), and iron deficiency anemia (HR = 2.29) were significantly related to the probability of clinical trial completion (all p value < 0.01). The C-index of the model development dataset and test dataset were 0.72 and 0.73, respectively. DeepSurv model consisted of one hidden layer with 16 nodes. DeepSurv showed the C-index comparable to the Cox proportional hazard model. The C-index of the training dataset and test dataset were 0.76 and 0.72, respectively. Further a nomogram that calculate a probability of clinical trial completion at 1 year, 3 years, and 5 years was developed. Both the Cox proportional hazard model and DeepSurv yielded sufficient predicting performance. We hope that this study will contribute to the execution of future clinical trials in pregnant women.

Involvement of cAMP in the Human Serum-Induced Migration of Adipose-Derived Stem Cells.

Previously we observed that human adipose-derived stem cells (hADSCs) could form aggregation during culture in the presence of human serum (HS). In the present study, we have examined if the aggregation might result from the cell migration and analyzed the difference of cell adhesivity after culture in various conditions. When cells were cultured in fetal bovine serum (FBS) alone, there was no morphological change. Similarly, cells pretreated with FBS for 1 day or cultured in a mixture of FBS and HS showed little change. In contrast, cells cultured in HS alone exhibited formation of cell-free area (spacing) and/or cell aggregation. When cells cultured in FBS or pretreated with FBS were treated with 0.06% trypsin, almost cells remained attached to the dish surfaces. In contrast, when cells cultured in HS alone were examined, most cells detached from the dish by the same treatment. Treatment of cells with forskolin, isobutylmethyl xanthine (IBMX) or LY294002 inhibited the formation of spacing whereas H89 or Y27632 showed little effect. When these cells were treated with 0.06% trypsin after culture, most cells detached from the dishes as cells cultured in HS alone did. However, cells treated with IBMX exhibited weaker adhesivity than HS alone. Based on these observations, it is suggested that HS treatment might decrease the adhesivity and induce three-dimensional migration of hADSCs, in the latter of which cAMP signaling could be involved.

Determination of acetamiprid residues in zucchini grown under greenhouse conditions: application to behavioral dynamics.

A simple analytical method was developed for the determination of acetamiprid residues in zucchini and zucchini leaves grown under greenhouse conditions using liquid chromatography. Residues were confirmed via tandem mass spectrometry in positive-ion electrospray ionization mode. The calibration curves were linear with correlation coefficients in excess of 0.999. The limits of detection and limits of quantification were 0.01 and 0.03 µg/g and 0.02 and 0.06 µg/g, for the zucchini and zucchini leaves, respectively. For validation purposes, recoveries studies were carried out at low and high levels, yielding recovery rates ranged from 85.7 to 92.2% in zucchini and from 90.5 to 101.9% in zucchini leaves, with a relative standard deviation of <12%. The results demonstrated that the pattern of acetamiprid dissipation followed pseudo first-order kinetics with a half-life of 1.9 and 2.5 days, respectively. The residues in zucchini leaves were substantially higher than in the zucchini plant itself. No residues were detected at 7 days post-application. The results of this study suggest that acetamiprid is acceptable for application in/on zucchini under the recommended dosage conditions.

In vitro inhibitory potential of decursin and decursinol angelate on the catalytic activity of cytochrome P-450 1A1/2, 2D15, and 3A12 isoforms in canine hepatic microsomes.

Danggui is one of the most popular herbal medicines consumed by patients in different clinical settings in Asian countries. In this study, the two major pyranocoumarin compounds extracted from the Korean Angelica gigas root decursin (DC) and decursinol angelate (DA) were examined in vitro with regard to their abilities to inhibit hepatic CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities in canine liver microsomes. The two components were capable of inhibiting CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities, but the potencies varied. DC and DA selectively and noncompetitively inhibited CYP1A1/2 activity, with K ( i ) values of 90.176 and 67.560 microM, respectively. On the other hand, they exhibited slight inhibitory effects on CYP2D15 and CYP3A12 with K ( i ) values of 666.180 and 872.502 microM, 990.500 and 909.120 microM (1'hydroxymidazolam, MDZ1'H), and 802.800 and 853.920 microM (4-hydroxymidazolam, MDZ4H), respectively. Additionally, they showed increased inhibition after preincubation, which suggests the involvement of a mechanism-based inhibition. In sum, this in vitro data should be heeded as a signal of possible in vivo interactions. The use of human liver preparations would considerably strengthen the practical impact of the data generated from this study.