Using Three-Dimensional Information to Predict and Interpret the Facial Selectivities of Nucleophilic Additions to Cyclic Ketones.

In this study, we devised a new method to predict facial selectivity by quantifying steric and orbital factors for the nucleophile approaching both π-plane faces. Using this method, we quantified the total electron density and frontier orbital distributions of 163 cyclic ketones with various structures and quantitatively explained the surface selectivity of 323 reactions with eight nucleophiles (BH3, LiAlH4, NaBH4, LiAl(OMe)3H, MeLi, MeMgI, PhLi, and PnMgI). Importance analysis showed a large orbital effect for BH3, LiAlH4, and NaBH4 and the dominance of the steric effect for LiAl(OMe)3H, MeLi, MeMgI, PhLi, and PhMgI. Our method analyzes three-dimensional features based on Gaussian cube files, which can be easily obtained using mainstream computational chemistry software packages, and this approach should prove useful for predicting the rates and facial selectivity of other reactions.

DPPH Measurements and Structure-Activity Relationship Studies on the Antioxidant Capacity of Phenols.

The consumption of foods that are high in antioxidant capacity is believed to contribute to good health. Moreover, the addition of highly antioxidant compounds to foods is believed to prevent food deterioration. Among the known antioxidants in food, phenols have been identified as the primary antioxidants. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay is a simple, inexpensive, and rapid method widely used to evaluate the antioxidant capacity. Although the results of the DPPH assay depend on conditions such as the reaction time and concentration, the experimental conditions have not been standardized. Further, previous research that compared the antioxidant capacity determined through the DPPH assay largely focused on the differences in the specific substructures of approximately several dozen compounds. In this study, we conducted DPPH assays on 169 phenols under the same experimental conditions and summarized the correlation between their structures and activity. This DPPH assay study is the first single-laboratory investigation of the largest number of components in terms of their Trolox equivalent antioxidant capacities. Further, the analysis method was reproduced in an interlaboratory collaborative study, enabling its application in the reproduction and comparison of measurements in other laboratories.

Compound Classification and Consideration of Correlation with Chemical Descriptors from Articles on Antioxidant Capacity Using Natural Language Processing.

In recent times, there has been a substantial increase in the number of articles focusing on antioxidants. However, the development of a comprehensive estimator for antioxidant capacity remains elusive due to the challenge of integrating information from these articles. Furthermore, the complexity of the antioxidant mechanism, which involves a multitude of factors, makes it difficult to establish a simple equation or correlation. Hence, there is a pressing need for a model that can effectively interpret the collective knowledge from these articles, especially from a chemistry perspective. In this research, we employed natural language processing techniques, specifically Word2Vec, to analyze articles related to antioxidant capacity. We extracted representation vectors of compound names from these documents and organized them into 10 distinct clusters. In our investigation of two of these clusters, we unveiled that the majority of the compounds in question were flavonoids and flavonoid glycosides. To establish a link between the descriptors and clusters, we utilized kernel density estimation and generated scatter plots to visualize their similarity. These visualizations clearly indicated a strong relationship between the descriptors and clusters, affirming that a tangible connection exists between word vectors and compound descriptors through a document analysis conducted with natural language processing techniques. This study represents a pioneering approach that utilizes document analysis to shed light on the field of antioxidant capacity research, marking a significant advancement in this domain.

Feature Selection for the Interpretation of Antioxidant Mechanisms in Plant Phenolics.

Antioxidants, represented by plant phenolics, protect living tissues by scavenging reactive oxygen species through diverse reaction mechanisms. Research on antioxidants is often individualized, for example, focusing on the evaluation of their activity against a single reactive oxygen species or examining the antioxidant properties of compounds with similar structures. In this study, multivariate analysis was used to comprehensively examine antioxidant properties. Eighteen features were selected to explain the results of the antioxidant capacity tests. These selected features were then evaluated by supervised learning, using the results of the antioxidant capacity assays. Dimension-reduction techniques were also used to represent the compound space with antioxidants as a two-dimensional distribution. A small amount of data obtained from several assays provided us with comprehensive information on the relationships between the structures and activities of antioxidants.

Induced Radionuclides and Their Activity Concentration in Gel Dosimeters Irradiated by Carbon Ion Beam.

Radioactivity was measured in a micellar gel dosimeter, a polymer gel dosimeter, and water was irradiated by carbon ion beams at various beam energy conditions. Monte Carlo simulation was also performed to estimate the radioactivity. Short-lived positron-emitting nuclides were observed immediately after irradiation, but they decayed rapidly into the background. At 24 h post-irradiation, the dominant measured radioactivity was of 7Be. The simulation also showed minor activity of 24Na and 3H; however, they were not experimentally observed. The measured radioactivity was independent of the type of gel dosimeter under all irradiation conditions, suggesting that the radioactivity was induced by the interaction of carbon ions with water (the main component of the gel dosimeters). The ratio between the simulated and measured radioactivity was within 0.9-1.5. The activity concentration of 7Be was found to be less than 1/10 of the value derived using the exemption concept proposed by the International Atomic Energy Agency. This result should be applicable to irradiated gel dosimeters containing mainly water and 0-4 wt.% C and 0-1.7 wt.% N.

Hydrophilic oxygen radical absorbance capacity values of low-molecular-weight phenolic compounds containing carbon, hydrogen, and oxygen.

The antioxidant capacity of an antioxidant reflects its ability to remove reactive oxygen species (ROS). In this study, the hydrophilic oxygen radical absorbance capacity (H-ORAC) method was used to quantitatively evaluate the antioxidant capacities of natural phenols and their derivatives against peroxyl radicals. This method was comprehensively applied to low-molecular-weight phenols to construct a database. Although no macroscopic correlation was observed for values related to the antioxidant capacity expression, we observed a difference in the trend of the H-ORAC values for each functional group. Thus, this database will serve as a new benchmark and tool for molecular design.

Mechanism for the photodegradation of 9,10-dibutoxyanthracene in the presence of air.

The photoreactivity of anthracene has been previously verified for a range of its derivatives. 9,10-Dibutoxyanthracene is commonly used as an electron transfer sensitizer for photopolymerization because of its favorable optical properties. This study experimentally demonstrated that 9,10-dibutoxyanthracene produces an endoperoxide species upon reaction with the oxygen present in air. A secondary decomposition product formed during the photodecomposition of the endoperoxide species was also isolated and identified. The proposed reaction pathway is supported by singlet oxygen scavenger studies and calculations of the singlet-triplet transition energies. Our findings suggest that 9,10-dibutoxyanthracene can be used as a photo-induced oxygen scavenger.

Development of novel deep multimodal representation learning-based model for the differentiation of liver tumors on B-mode ultrasound images.

BACKGROUND AND AIM: Recently, multimodal representation learning for images and other information such as numbers or language has gained much attention. The aim of the current study was to analyze the diagnostic performance of deep multimodal representation model-based integration of tumor image, patient background, and blood biomarkers for the differentiation of liver tumors observed using B-mode ultrasonography (US). METHOD: First, we applied supervised learning with a convolutional neural network (CNN) to 972 liver nodules in the training and development sets to develop a predictive model using segmented B-mode tumor images. Additionally, we also applied a deep multimodal representation model to integrate information about patient background or blood biomarkers to B-mode images. We then investigated the performance of the models in an independent test set of 108 liver nodules. RESULTS: Using only the segmented B-mode images, the diagnostic accuracy and area under the curve (AUC) values were 68.52% and 0.721, respectively. As the information about patient background and blood biomarkers was integrated, the diagnostic performance increased in a stepwise manner. The diagnostic accuracy and AUC value of the multimodal DL model (which integrated B-mode tumor image, patient age, sex, aspartate aminotransferase, alanine aminotransferase, platelet count, and albumin data) reached 96.30% and 0.994, respectively. CONCLUSION: Integration of patient background and blood biomarkers in addition to US image using multimodal representation learning outperformed the CNN model using US images. We expect that the deep multimodal representation model could be a feasible and acceptable tool for the definitive diagnosis of liver tumors using B-mode US.

Prediction and Chemical Interpretation of Singlet-Oxygen-Scavenging Activity of Small Molecule Compounds by Using Machine Learning.

A chemically explainable machine learning model was constructed with a small dataset to quantitatively predict the singlet-oxygen-scavenging ability. In this model, ensemble learning based on decision trees resulted in high accuracy. For explanatory variables, molecular descriptors by computational chemistry and Morgan fingerprints were used for achieving high accuracy and simple prediction. The singlet-oxygen-scavenging mechanism was explained by the feature importance obtained from machine learning outputs. The results are consistent with conventional chemical knowledge. The use of machine learning and reduction in the number of measurements for screening high-antioxidant-capacity compounds can considerably improve prediction accuracy and efficiency.

A Novel Non-invasive Method for Predicting Liver Fibrosis by Quantifying the Hepatic Vein Waveform.

The hepatic vein (HV) waveform by Doppler ultrasound reflects the severity of liver fibrosis. We conducted a proof-of-concept study of a new method for quantifying the HV waveform. We calculated the coefficient of variation (CV) of the HV flow velocity and created a new index "q-HV" (quantified HV) and analyzed its performance for predicting histologic liver fibrosis in 114 patients with chronic liver disease. The CV of the HV flow velocity was well associated with flattening of the waveform and the q-HV significantly increased with the progression of liver fibrosis. The areas under the curve for the prediction of fibrosis stage were 0.732 for F2, 0.772 for F3 and 0.805 for F4. Combined q-HV and FIB-4 index (widely used liver fibrosis score) increased the diagnostic accuracy for liver fibrosis. The q-HV showed good accuracy for predicting liver fibrosis; thus, q-HV is feasible and acceptable as a non-invasive tool for predicting liver fibrosis.

Effect of Side Chain Functional Groups on the DPPH Radical Scavenging Activity of Bisabolane-Type Phenols.

Methods for improving the antioxidant activity of phenolic compounds have been widely investigated; however, most studies have focused on the structure⁻activity correlations of substituents on the aromatic rings of catechols or flavonoids. We investigated the influence of side chain functional groups on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of xanthorrhizol and curcuphenol analogues. These compounds were synthesised by the side chain functional group conversion of curcumene, followed by direct oxidation of the aromatic ring. We determined the DPPH radical scavenging activity from the half-maximal effective concentration (EC50) obtained from a DPPH assay in methanol. The positional relationships of the side chain with the aromatic ring and phenolic OH group were determined using density functional theory calculations, and the stability of different conformations was compared. Electron transfer-proton transfer was determined to be the dominant mechanism in the DPPH reaction with xanthorrhizol analogues, based on the correlation between the EC50 and ionisation potential. The radical cation was greatly stabilised in the structure where the side chain functional group was close to the aromatic ring. Stabilisation also depended on the phenolic OH group position. In future antioxidant design, aromatic ring substituent conversion and the use of functional groups far from the OH group or ring should be explored.

Identification of liver fibrosis using the hepatic vein waveform in patients with Fontan circulation.

AIM: Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients. METHODS: We investigated the HV waveforms in 41 Fontan patients and assessed correlations with clinical parameters, liver fibrosis markers, and hemodynamic data. RESULTS: Based on our preliminary analysis of 64 adult patients with chronic liver disease who underwent liver biopsy, we classified HV waveforms into five types with reference to the degree of flattening (from type 1, normal triphasic waveform; to type 5, a monophasic waveform indicating cirrhosis), and confirmed a significant correlation between waveform pattern and fibrosis stage. Notably, we detected HV waveforms in all of the Fontan patients and classified them into five types. The HV waveform pattern positively correlated with γ-glutamyl transferase and hyaluronic acid levels, and negatively correlated with albumin level and platelet count, but did not correlate with central venous pressure or brain natriuretic peptide level, suggesting that HV waveform could reflect pathophysiological changes in the liver without being affected by hepatic congestion. The highest area under the receiver operating characteristic curve of the HV waveform for detecting advanced liver fibrosis, as defined by ultrasonic findings and clinical features, was 0.829 (81.8% sensitivity, 73.3% specificity), which was higher than that of other non-invasive fibrosis markers. CONCLUSIONS: Hepatic vein waveforms change in accordance with liver fibrosis progression in Fontan patients, and can be a useful indicator of liver fibrosis after the Fontan procedure.

A theoretical, dynamical evaluation method of the steric hindrance in nitroxide radicals using transition states of model reactions.

Steric hindrance is known to affect the stability, reactivity, and radical trapping ability of stable nitroxide radicals. Therefore, a quantitative evaluation and prediction model of steric hindrance is needed to select and design the optimum nitroxide radicals for specific applications. In this study, a dynamic parameter of steric hindrance (DPSH) is proposed and its characteristics are investigated. Unlike using only the equilibrium structure to evaluate the steric hindrance, DPSH is a dynamic value calculated from the theoretical activation enthalpies for two model reactions of radical addition to olefins. Using DPSH, the steric hindrance was evaluated for a total of 43 alkyl radicals, nitroxide radicals, and radicals derived from phenols, and the results were compared with those of other methods. The DPSH values for radicals can vary when the energy barrier for structural change varies, even if the equilibrium structures of the radicals have the same steric shielding. Finally, for radicals other than nitroxide radicals, the DPSH values were consistent with the predictions from their structures, which suggests that the DPSH has a wide range of applications. We expect DPSH to be used and developed in the analysis of steric factors in various reactions.

Optically transparent, high-toughness elastomer using a polyrotaxane cross-linker as a molecular pulley.

An elastomer is a three-dimensional network with a cross-linked polymer chain that undergoes large deformation with a small external force and returns to its original state when the external force is removed. Because of this hyperelasticity, elastomers are regarded as one of the best candidates for the matrix material of soft robots. However, the comprehensive performance required of matrix materials is a special challenge because improvement of some matrix properties often causes the deterioration of others. For example, an improvement in toughness can be realized by adding a large amount of filler to an elastomer, but to the impairment of optical transparency. Therefore, to produce an elastomer exhibiting optimum properties suitable for the desired purpose, very elaborate, complicated materials are often devised. Here, we have succeeded in creating an optically transparent, easily fabricated elastomer with good extensibility and high toughness by using a polyrotaxane (PR) composed of cyclic molecules and a linear polymer as a cross-linking agent. In general, elastomers having conventional cross-linked structures are susceptible to breakage as a result of loss of extensibility at high cross-linking density. We found that the toughness of the transparent elastomer prepared using the PR cross-linking agent is enhanced along with its Young's modulus as cross-linking density is increased.

Eradication of hepatitis C virus is associated with the attenuation of steatosis as evaluated using a controlled attenuation parameter.

Chronic hepatitis C virus (HCV) infection was shown to cause hepatic steatosis or suppression of serum lipid levels. However, little is known about the changes in hepatic steatosis following HCV eradication. We aimed to evaluate this issue using the controlled attenuation parameter (CAP), which was recently shown to provide a standardized non-invasive measure of hepatic steatosis. We enrolled 70 patients with chronic HCV infections and steatosis (CAP of over 248 dB/m) who had achieved a sustained viral response at 12 weeks after discontinuation of antiviral treatment using direct-acting antivirals (DAA). We then evaluated the state of hepatic steatosis before and after HCV eradication. We also investigated the changes in serum parameters such as cholesterol and glucose levels. The median value of CAP level decreased significantly after HCV eradication from 273 dB/m to 265 dB/m (P = 0.034). Also, LDL and HDL cholesterol levels increased significantly after HCV eradication (P = 0.002 and P = 0.027, respectively). In conclusion, a decrease in hepatic steatosis after HCV eradication with DAA was revealed in chronic hepatitis C patients with significant steatosis. Cancellation of the viral effect is a possible underlying cause of hepatic steatosis improvement and increase in HDL and LDL cholesterol levels.

[Evaluation of Radiochromic Gel Dosimeter and Optical CT].

Three-dimensional (3D) radiation dosimeter has received growing interest with the implementation of highly conformal radiotherapy treatments. Optical Computed tomography (CT) scanners have been developed for 3D quantitative measurement of optical attenuation. Malachite green and Leuco Crystal Violet (LCV) dye radiochromic gels were recently developed as radiation dosimeters in combination with optical CT scanners. Malachite green and LCV are colorless dyes and they become green or violet after irradiation, respectively. The dyes mixed with gelatin and surfactant became hardened and can be used as a 3D gel dosimeter. The radiochromic gels dosimeter with optical CT scanners provides many of desired features such as: low cost, easy to fabricate, low toxicity and fast readout. In this article, the fundamental characteristics of radiochromic gel dosimeter with optical CT scanners are reviewed.

Ultrasound evaluation of liver stiffness: accuracy of ultrasound imaging for the prediction of liver cirrhosis as evaluated using a liver stiffness measurement.

BACKGROUND AND AIMS: Because of the low penetration rate of transient elastography (TE) or its limitations in patients with obesity, narrow intercostal spaces, or ascites, the physical appearance of the liver as visualized using ultrasonography (US) is still thought to provide important information for the prediction of liver fibrosis. We examined the accuracy of various US signs when assessing the presence of liver cirrhosis, compared with TE. METHODS: We enrolled 189 patients who had undergone both conventional US and TE examinations. We then assessed the associations between US parameters of the liver (surface, edge, and parenchymal texture) or the US score (sum of each parameter score), and the presence of liver cirrhosis as determined based on a liver stiffness measurement (LSM) of >15. RESULTS: A significant increase in the LSM was observed according to the liver surface score (P < 0.001), liver edge score (P < 0.001), parenchymal texture score (P < 0.001), and US score (P < 0.001). The areas under the curves (AUROC) for the prediction of an LSM >15 for the liver surface, liver edge, parenchymal texture, and the US score were 0.859, 0.768, 0.837, and 0.902, respectively. The AUROC of the US score was higher than that of the APRI score (0.823) or the FIB-4 index (0.804). Using an optimal cut-off value of 3.5, the sensitivity and specificity of the US score were 0.815 and 0.858, respectively. CONCLUSIONS: The US score was clinically useful for the diagnosis of an LSM >15. The US score can be used as a substitute for TE data in patients with obesity, narrow intercostal spaces, or ascites or in hospitals where TE is unavailable.

Pancreatic cysts in general population on ultrasonography: Prevalence and development of risk score.

BACKGROUND: Pancreatic cysts are related to the presence of ductal adenocarcinomas elsewhere in the pancreas, and are also associated with an increased risk of pancreatic adenocarcinoma in the future. Most of the previous studies that investigated the prevalence of pancreatic cysts focused on patients within a hospital or out-patient setting, which may not be representative of the general population. We investigated the prevalence and predictive factors for the presence of pancreatic cysts within a large number of subjects via general health examination. METHODS: Between December 2007 and December 2013, a total of 5198 subjects were enrolled that underwent ultrasonography (US) on general health examination. We established a scoring system for predicting the presence of one or more pancreatic cysts using a split-sample method. RESULTS: Among the enrolled subjects, the prevalence of a pancreatic cyst was 3.5 %. In multivariate analysis, the prevalence was significantly increased with older age, female sex, and the presence of gall bladder adenomyomatosis (GB-ADM). Based on multivariate analysis in the training sample (n = 2,599), we established the scoring system consisting of age, sex, and the presence of GB-ADM to predict the presence of pancreatic cysts. This scoring system was validated in the testing sample (n = 2,599) and produced an area under the curve of 0.711. CONCLUSIONS: The prevalence of pancreatic cyst detected by US was 3.5 % in the general population, and increased with age, female sex, and the presence of GB-ADM. A new scoring system developed in the present study may help to identify better candidates for further examination when the pancreas is not visible by US.

Two Reaction Mechanisms via Iminium Ion Intermediates: The Different Reactivities of Diphenylprolinol Silyl Ether and Trifluoromethyl-Substituted Diarylprolinol Silyl Ether.

The reactions of α,ß-unsaturated aldehydes with cyclopentadiene in the presence of diarylprolinol silyl ethers as catalyst proceed via iminium cations as intermediates, and can be divided into two types; one involving a Michael-type reaction (type A) and one involving a cycloaddition (type B). Diphenylprolinol silyl ethers and trifluoromethyl-substituted diarylprolinol silyl ethers, which are widely used proline-type organocatalysts, have been investigated in this study. As the LUMO of the iminium ion derived from trifluoromethyl-substituted diarylprolinol silyl ether is lower in energy than that derived from diphenylprolinol silyl ether, as supported by ab initio calculations, the trifluoromethyl-substituted catalyst is more reactive in a type B reaction. The iminium ion from an α,ß-unsaturated aldehyde is generated more quickly with diphenylprolinol silyl ether than with the trifluoromethyl-substituted diarylprolinol silyl ether. When the generation of the iminium ion is the rate-determining step, the diphenylprolinol silyl ether catalyst is the more reactive. Because acid accelerates the generation of iminium ions and reduces the generation of anionic nucleophiles in the Michael-type reaction (type A), it is necessary to select the appropriate acid for specific reactions. In general, diphenylprolinol silyl ether is a superior catalyst for type A reactions, whereas the trifluoromethyl-substituted diarylprolinol silyl ether catalyst is preferred for type B reactions.

Potential associations between perihepatic lymph node enlargement and liver fibrosis, hepatocellular injury or hepatocarcinogenesis in chronic hepatitis B virus infection.

AIM: Although perihepatic lymph node enlargement (PLNE) is frequently observed in chronic liver disease, little is known about PLNE in chronic hepatitis B virus (HBV) infection. We aimed to evaluate this issue. METHODS: We originally enrolled a consecutive 502 patients with chronic HBV infection. Among them, 288 patients without history of interferon-based or nucleoside analog treatment and hepatocellular carcinoma (HCC) were primarily analyzed. RESULTS: PLNE was detected in 27 of 288 (9.4%) patients, which was fewer than that in chronic hepatitis C patients but more than that in subjects undertaking a general health examination as previously reported. The presence of PLNE was significantly associated with a higher probability of having an aspartate aminotransferase (AST) platelet ratio index of more than 1.5 (11.1% vs 1.5%, P = 0.01), a higher AST level (38.0 vs 26.8 U/L, P = 0.001), a higher alanine aminotransferase level (50.1 vs 28.0 U/L, P < 0.0001), and a lower platelet count (18.6 vs 20.6 × 10(4) /µL, P = 0.048) after adjustment for sex and age. However, in our original sample (n = 502), PLNE was observed in 1.4% of the patients with HCC and/or its history whereas 9.2% of the patients without HCC, and the proportion was significantly lower in patients with HCC and/or its history (P = 0.03). CONCLUSION: PLNE was associated with liver fibrosis and hepatocellular injury, but was negatively associated with HCC in chronic HBV infection.