bluuebunny/crossref_metadata_2025_split huggingface dataset:
The O‐methylated isoflavone, formononetin, inhibits human ovarian cancer cell proliferation by sub G0/G1 cell phase arrest through PI3K/AKT and ERK1/2 inactivation
Authors: Park Sunwoo , Bazer Fuller W. , Lim Whasun , Song Gwonhwa 
Published: May 2018

AbstractFormononetin is an isoflavone that is extracted from red clovers or soy. It has anti‐oxidant, anti‐proliferative, and anti‐tumor effects against cells in various diseases. Several cohort studies have indicated that phytoestrogen intake, including formononetin, could reduce the risk of various carcinogenesis. In fact, many case‐control studies have indicated the potential value of flavonoids as drug supplements in the treatment of many cancer patients. However, the toxic effects and the anti‐cancer mechanism of formononetin in ovarian cancer are unknown. We investigated the toxicological mechanism of formononetin in ES2 and OV90 ovarian cancer cells. Formononetin suppressed cell proliferation through sub G0/G1 phase arrest and increased apoptosis in both cell lines. Furthermore, it induced loss of mitochondrial membrane potential and generation of reactive oxygen species in ES2 and OV90 cells. The formononetin‐mediated regulation of cell proliferation and apoptosis involved decreased phosphorylation of ERK1/2, P90RSK, AKT, P70S6K, and S6 proteins, and increased phosphorylation of P38 protein in ES2 and OV90 cells. Co‐treatment of formononetin with pharmacological inhibitors (LY294002 or U0126) revealed additional anti‐proliferative effects on the two human ovarian cancer cell types. Conclusively, the results indicate the potential value of formononetin as an anti‐cancer agent in human ovarian cancer.
Pharmacokinetic/Pharmacodynamic Analysis of Isavuconazole Against Aspergillus spp. and Candida spp. in Healthy Subjects and Patients With Hepatic or Renal Impairment by Monte Carlo Simulation
Authors: Zheng Xiaowei , Xu Gaoqi , Zhu Liqin , Fang Luo , Zhang Yiwen , Ding Haiying , Tong Yinghui , Sun Jiao , Huang Ping 
Published: May 2018

AbstractThe aim of this pharmacokinetic/pharmacodynamic (PK/PD) study is to evaluate the efficacy of various isavuconazole dosing regimens for healthy individuals and patients with hepatic or renal impairment against Aspergillus spp. and Candida spp. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamics (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (AUC/MIC) targets of isavuconazole. A clinically recommended dosage regimen of isavuconazole (200 mg qd) obtained high cumulative fraction of response values of > 90% for all subjects against A. fumigatus, A. flavus, A. nidulans, A. terreus, A. versicolor, C. parapsilosis and C. tropicalis. For patients with mild or moderate hepatic impairment, the dosage should be halved only when treating invasive fungal infections caused by C. albicans, C. parapsilosis or C. tropicalis. However, dose adjustment is unlikely to be required in mild to severe renal impairment patients because all cumulative fraction of response values were similar to those of comparing with healthy subjects. Notably, all isavuconazole dosing regimens were not effective against C. glabrata and C. krusei in all subjects. These PK/PD‐based simulations rationalize and optimize the dosage regimens of isavuconazole for healthy individuals and patients with hepatic or renal impairment against Aspergillus spp. and Candida spp.
In Vivo Assessment of the Effect of CYP1A2 Inhibition and Induction on Pomalidomide Pharmacokinetics in Healthy Subjects
Authors: Li Yan , Liu Liangang , Wang Xiaomin , Zhang Chengyue , Reyes Josephine , Hoffmann Matthew , Palmisano Maria , Zhou Simon 
Published: May 2018

AbstractPomalidomide is an immunomodulatory drug, and the dosage of 4 mg per day taken orally on days 1‐21 of repeated 28‐day cycles has been approved in the European Union and the United States to treat patients with relapsed/refractory multiple myeloma. In vitro data showed that pomalidomide is a substrate of multiple cytochrome P450 (CYP) isozymes and that its oxidative metabolism is mediated primarily by CYP1A2 and CYP3A4, with minor contributions from CYP2C19 and CYP2D6. The effect of CYP1A2 inhibition by fluvoxamine (a strong CYP1A2 inhibitor) and CYP1A2 induction by smoking on pomalidomide pharmacokinetics in healthy subjects has been assessed in 2 separate phase 1 open‐label, single‐dose studies. Following administration of a single oral dose of 4 mg pomalidomide, the plasma exposure when coadministered with fluvoxamine was 225.1% and 123.7% of that when administered alone for the total plasma exposure (AUC0‐inf) and the plasma peak exposure (Cmax), respectively. In smokers with elevated CYP1A2 activity demonstrated by high caffeine clearance (a marker of CYP1A2 induction), the AUC0‐inf was 32.3% lower, whereas the Cmax was 14.4% higher than that in nonsmokers. In addition, pomalidomide was safe and well tolerated as a single oral dose of 4 mg in healthy male smokers and nonsmokers ≥ 40 to ≤ 80 years old, and a single oral dose of 4 mg pomalidomide coadministered with multiple oral 50‐mg doses of the CYP1A2 inhibitor fluvoxamine compared with pomalidomide alone was safe and well tolerated by the healthy male subjects.
Risk of Hypoglycemia After Concomitant Use of Antidiabetic, Antihypertensive, and Antihyperlipidemic Medications: A Database Study
Authors: Gosho Masahiko 
Published: May 2018

AbstractHypoglycemia is the most important complication of antidiabetic medications. Most patients with diabetes mellitus take multiple medications. In this study, we explored clinical drug‐drug interactions that result in hypoglycemia by analyzing the Japanese Adverse Drug Event Report (JADER) database. The primary outcome was the report of hypoglycemia. The Norén and Gosho methods, which quantitatively measure the discrepancy between the observed and expected number of adverse events under the combination of 2 drugs, were used as the criteria for detecting drug‐drug interactions. The JADER database contained patient characteristics with 468 292 records, drug information with 2 973 172 records, and adverse reactions with 741 016 records. We noted that hypoglycemia was reported in 6208 patients. Concomitant use of linagliptin/glibenclamide, sitagliptin/glibenclamide, sitagliptin/buformin, exenatide/voglibose, mitiglinide/perindopril, repaglinide/barnidipine, alogliptin/cilnidipine, teneligliptin/barnidipine, teneligliptin/urapidil, exenatide/candesartan, voglibose/barnidipine, voglibose/guanabenz, or exenatide/tocopherol was noted using the 2 criteria for drug‐drug interactions. Concomitant use of teneligliptin and barnidipine produced the highest values for the 2 criteria. The second‐and third‐highest values were observed for teneligliptin/urapidil and exenatide/candesartan combinations, respectively. The same analysis was performed using the US Food and Drug Administration Adverse Event Reporting System database to assess the validity of the result from the JADER database. The concomitant use of sitagliptin/buformin, exenatide/voglibose, repaglinide/barnidipine, teneligliptin/barnidipine, teneligliptin/urapidil, exenatide/candesartan, voglibose/barnidipine, voglibose/guanabenz, or exenatide/tocopherol was detected in both the JADER and Food and Drug Administration Adverse Event Reporting System databases. Combination therapy with the drugs listed above would show potential interactions that could result in hypoglycemia in patients with diabetes mellitus.
ROSCAs as Lenders of Last Resort after Financial Crises: Lessons from Indonesia
Authors: Acquah Joseph Kofi , Dahal Roshani 
Published: May 2018

AbstractThis study investigated the lending capabilities of Rotating Savings and Credit Association (ROSCA) institutions in the 2 years following the 1998 Indonesian financial crisis. We found that lending increased threefold and resulted in 2 percent of ROSCA members securing ROSCA loans. Loans were small (US$28.8) with 92 percent of loan recipients reporting that they knew no other place to borrow. Factors that positively influenced lending capacities of ROSCA loans were ROSCA size (30–43 members) and diversity in employment sectors of ROSCA members. Additionally, members that participated in multiple ROSCAs and experienced hardships in 1998 were more likely to receive ROSCA loans. Copyright © 2018 John Wiley & Sons, Ltd.
Synthesis and characterization of a deuterium labeled stercobilin: A potential biomarker for autism
Authors: Coffey Jordan M. , Vadas Andrew J. , Puleo Thomas R. , Lewis Katelyn P. , Pirrone Gregory F. , Rudolph Heather L. , Helms Eric D. , Wood Troy D. , Flynn‐Charlebois Amber 
Published: May 2018

Stercobilin is an end‐stage metabolite of hemoglobin, a component of red blood cells. It has been found that there is a significantly lower concentration of stercobilin in the urine of people diagnosed with autism spectrum disorders, suggesting potential use as a biomarker. In vitro, we have synthesized stercobilin from its precursor bilirubin through a reduction reaction proceeded by an oxidation reaction. In addition, we have isotopically labeled the stercobilin product with deuterium using this protocol. Nuclear magnetic resonance investigations show the products of the unlabeled stercobilin (Rxn 1) and the deuterated stercobilin (Rxn 2) both had a loss of signals in the 5.0‐ to 7.0‐ppm range indicating proper conversion to stercobilin. Changes in the multiplicity of the sp3 region of the proton nuclear magnetic resonance suggest proper deuterium incorporation. Mass spectrometry studies of Rxn 1 show a difference in fragmentation patterns than that of Rxn 2 proposing potential locations for deuterium incorporation. This isotopologue of stercobilin is stable (>6 mo), and further analysis permits investigation for its use as a biomarker and potential quantitative diagnostic probe for autism spectrum disorders.
Radiomics analysis of apparent diffusion coefficient in cervical cancer: A preliminary study on histological grade evaluation
Authors: Liu Ying , Zhang Yuwei , Cheng Runfen , Liu Shichang , Qu Fangyuan , Yin Xiaoyu , Wang Qin , Xiao Bohan , Ye Zhaoxiang 
Published: May 2018

BackgroundThe role of apparent diffusion coefficient (ADC)‐based radiomics features in evaluating histopathological grade of cervical cancer is unresolved.PurposeTo determine if there is a difference between radiomics features derived from center‐slice 2D versus whole‐tumor volumetric 3D for ADC measurements in patients with cervical cancer regarding tumor histopathological grade, and systematically assess the impact of the b value on radiomics analysis in ADC quantifications.Study TypeProspective.SubjectsIn all, 160 patients with histopathologically confirmed squamous cell carcinoma of uterine cervix.Field Strength/SequenceConventional and diffusion‐weighted MR images (b values = 0, 800, 1000 s/mm2) were acquired on a 3.0T MR scanner.AssessmentRegions of interest (ROIs) were drawn manually along the margin of tumor on each slice, and then the center slice of the tumor was selected with naked eyes in the course of whole‐tumor segmentation. A total of 624 radiomics features were derived from T2‐weighted images and ADC maps. We randomly selected 50 cases and did the reproducibility analysis.Statistical TestsParameters were compared using Wilcoxon signed rank test, Bland–Altman analysis, t‐test, and least absolute shrinkage and selection operator (LASSO) regression with crossvalidation.ResultsIn all, 95 radiomics features were insensitive to ROI variation among T2 images, ADC map of b800, and ADC map of b1000 (P > 0.0002). There was a significant statistical difference between the performances of 2D center‐slice and 3D whole‐tumor radiomics models in both ADC feature sets of b800 and b1000 (P < 0.0001, P < 0.0001). Compared with ADC features of b800 (0.3758 ± 0.0118), the model of b1000 ADC features appeared to be slightly lower in overall misclassification error (0.3642 ± 0.0162) (P = 0.0076).Data ConclusionSeveral radiomics features extracted from T2 images and ADC maps were highly reproducible. Whole‐tumor volumetric 3D radiomics analysis had a better performance than using the 2D center‐slice of tumor in stratifying the histological grade of cervical cancer. A b value of 1000 s/mm2 is suggested as the optimal parameter in pelvic DWI scans.Level of Evidence: 1Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2019;49:280–290.
Influence of plaque control on the relationship between rheumatoid arthritis and periodontal health status among Japanese rheumatoid arthritis patients
Authors: Hashimoto Hiroko , Hashimoto Shimpei , Muto Akinori , Dewake Nanae , Shimazaki Yoshihiro 
Published: May 2018

AbstractBackgroundFunctional disability of the finger joints in rheumatoid arthritis (RA) patients could affect their oral hygiene and periodontal status because of poor plaque control. We examined the influence of plaque control on the relationship between the severity of RA and periodontal status in RA patients.MethodsThis study recruited 89 Japanese RA patients who reported no difficulty in performing oral hygiene. We assessed RA severity using four indices: the Steinbrocker stage and class, the Health Assessment Questionnaire (HAQ) and the Disease Activity Score (DAS). Probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were taken as parameters of periodontal status. Oral hygiene status was assessed using the plaque index (PlI). We examined the association between the severity of RA and periodontal parameters using multivariable linear regression analyses.ResultsIn multivariable linear regression analyses not including PlI, Steinbrocker stage III–IV patients had significantly higher PlI scores and greater PD compared with those of stage I. The class III–IV patients had significantly higher PlI scores and greater PD. Patients with an HAQ score ≥0.5 had a significantly higher PlI score than those with an HAQ score of 0. However, when PlI was added to each multivariable model as an independent variable, no significant relationship between RA severity and periodontal status was observed.ConclusionsThis study suggests that it is important to consider the influence of plaque control when assessing the relationship between RA severity and periodontal health status in RA patients.
The evaluation of salivary oxidative stress in patients with familial Mediterranean fever and chronic periodontitis
Authors: Dinç Gözde , Fentoğlu Özlem , Doğru Atalay , İlhan İlter , Kırzıoğlu F. Yeşim , Orhan Hikmet 
Published: May 2018

AbstractBackgroundFamilial Mediterranean fever (FMF) is an inherent autoinflammatory disease and have a high prevalence in Mediterranean countries. The aim of this study was to evaluate salivary levels of oxidative stress parameters in patients with FMF and chronic periodontitis.MethodsThe study population consists of 81 patients with FMF and 85 systemically healthy controls. The test and control groups were classified as chronic periodontitis and periodontally healthy [FMF‐periodontitis (n = 37); FMF‐periodontally healthy (n = 44); systemically healthy‐periodontitis (n = 37); systemically and periodontally healthy (n = 48]. Total salivary samples were collected. Clinical periodontal parameters including plaque index, gingival index (GI), probing depth (PD), the percentage of bleeding on probing (BOP%), and clinical attachment level (CAL), were measured. Salivary total antioxidant status (TAS), total oxidant status (TOS), 8‐hydroxydeoxyguanosine (8‐OHdG), malondialdehyde (MDA), and oxidative stress index (OSI) were evaluated.ResultsThe FMF‐periodontitis group had significantly higher levels of 8‐OHdG, MDA, and OSI than that of the FMF‐periodontally healthy group. In the FMF‐periodontitis group, PD, 8‐OHdG, MDA, and OSI levels were significantly higher than in the systemically healthy‐periodontitis group (P = 0.035, P = 0.000, P = 0.000, and P = 0.000, respectively). 8‐OHdG values were significantly correlated with BOP% and GI, and TOS values were significantly correlated with PD and CAL in the FMF‐periodontitis group.ConclusionsIn the presence of FMF and chronic periodontitis, there were increased salivary levels of oxidative stress. Thus, oxidative stress could be an important inflammatory mechanism in the FMF and chronic periodontitis. Further studies need to clarify the oxidative mechanisms of FMF and chronic periodontitis.
The value of inflammation based prognostic scores in patients undergoing surgical resection for oesophageal and gastric carcinoma
Authors: Wen Jiaxin , Bedford Matthew , Begum Ruksana , Mitchell Harriet , Hodson James , Whiting John , Griffiths Ewen 
Published: May 2018

Background and ObjectivesSurgical interventions for oesophagogastric cancer carry a significant burden of morbidity and mortality. A range of inflammation based prognostic scores have been proposed in an attempt to predict outcome. This study evaluated five such prognostic scores in oesophageal and gastric carcinoma patients.MethodsThe modified Glasgow Prognostic Score (mGPS), Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI), and Prognostic Nutrition Index (PNI) were calculated for 723 consecutive patients undergoing oesophagectomy or gastrectomy at a single center. The predictive accuracy of each score was assessed using ROC curves and survival analyses.ResultsOverall, only PLR and PNI were significantly predictive of patient survival (both P < 0.001), with no significant association detected for mGPS (P = 0.480), NLR (P = 0.210), or PI (P = 0.808). Subgroup analysis found the predictive accuracy of PNI to be significantly greater in oesophagectomy than gastrectomy patients (hazard ratio 2.75 vs 1.39, P = 0.016) and mGPS to be predictive of patient survival only in oesophagectomies (P < 0.001).ConclusionsInflammation based prognostic scores may have a role in patients undergoing resection for oesophageal and gastric cancer. These scores are easily calculable from routinely collected data and could be used as an adjunct to existing staging modalities.
Ultra high performance liquid chromatography with tandem mass spectrometry method for determining dinotefuran and its main metabolites in samples of plants, animal‐derived foods, soil, and water
Authors: Zhang Ying , Wu Xiaohu , Duan Tingting , Xu Jun , Dong Fengshou , Liu Xingang , Li Xiaogang , Du Pengqiang , Zheng Yongquan 
Published: May 2018

AbstractAn ultra high‐performance liquid chromatography with tandem triple quadrupole mass spectrometry residue method was developed and validated for the quantification and identification of dinotefuran and its main metabolites 1‐methyl‐3‐(tetrahydro‐3‐furylmethyl) urea and 1‐methyl‐3‐(tetrahydro‐3‐furylmethyl) guanidine in fruit (watermelon), vegetable (cucumber), cereal (rice), animal‐derived foods (milk, egg, and pork), soil, and water. The samples were extracted with acetonitrile containing 15% v/v acetic acid and purified with dispersive solid‐phase extraction with octadecylsilane, primary secondary amine, graphitized carbon black, or zirconia‐coated silica prior to analysis. The method had an excellent linearity (R2 ≥ 0.9942, 1–500 μg/L) and satisfactory recoveries (73–102%) at five spiked levels (0.001, 0.01, 0.05, 0.5, and 2 mg/kg) with intra‐ or interday precision in the range of 0.8–9.5% and 3.0–12.8% for the three compounds in the eight matrices. The limits of quantification were 10 μg/kg for 1‐methyl‐3‐(tetrahydro‐3‐furylmethyl) guanidine and 1 μg/kg for 1‐methyl‐3‐(tetrahydro‐3‐furylmethyl) urea and dinotefuran. The applicability of the developed method was demonstrated by determining the occurrence of dinotefuran, 1‐methyl‐3‐(tetrahydro‐3‐furylmethyl) guanidine, and 1‐methyl‐3‐(tetrahydro‐3‐furylmethyl) urea in various samples from plants, animal‐derived foods, and the environment. From 80 samples, 70 contained dinotefuran (0.8–11.7 μg/kg), among which six also contained 1‐methyl‐3‐(tetrahydro‐3‐furylmethyl) urea (water and rice, 0.5–0.9 μg/kg).
Diagnostic Performance of Shear Wave Elastography in Patients With Autoimmune Liver Disease
Authors: Li Changtian , Dhyani Manish , Bhan Atul K. , Grajo Joseph R. , Pratt Daniel S. , Gee Michael S. , Samir Anthony E. 
Published: May 2018

ObjectivesTo assess performance of shear wave elastography for evaluation of fibrosis and the histologic stage in patients with autoimmune liver disease (ALD) and to validate previously established advanced fibrosis cutoff values in this cohort.MethodsShear wave elastography was performed on patients with ALD with an Aixplorer ultrasound system (SuperSonic Imagine, Aix‐en‐Provence, France) using an SC6‐1 transducer. The median estimated tissue Young modulus was calculated from sets of 8 to 10 elastograms. A blinded, subspecialty‐trained pathologist reviewed biopsy specimens. The METAVIR classification was used to stage liver fibrosis and necroinflammation. Steatosis was graded from 0 to 4+. The Kendall τ‐b correlation test was performed to identify the correlation between the estimated tissue Young modulus and fibrosis, steatosis, and the necroinflammatory score. The Spearman correlation test was performed to identify the correlation between the estimated tissue Young modulus and clinical data. The diagnostic performance of shear wave elastography for differentiating METAVIR stage F2 or higher from F0 and F1 fibrosis was evaluated by a receiver operating characteristic (ROC) curve analysis.ResultsFifty‐one patients with ALD were analyzed. The estimated tissue Young modulus was positively correlated with the fibrosis stage and necroinflammation score (r = 0.386; P < .001; r = 0.338; P = .002, respectively) but not steatosis (r = −0.091; P = .527). Serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin values were positively correlated with the estimated tissue Young modulus (r = 0.501; P < .001; r = 0.44; P = .001; r = 0.291; P = .038). The serum albumin value was negatively correlated (r = −0.309; P = .033). The area under the ROC curve was 0.781 (95% confidence interval, 0.641–0.921) for distinguishing F2 or greater fibrosis from F0 and F1 fibrosis. Based on the ROC curve, an optimal cutoff value of 9.15 kPa was identified (sensitivity, 83.3%; specificity, 72.7%).ConclusionsShear wave elastography is a novel noninvasive adjunct to liver biopsy in evaluation and staging of patients with ALD, showing the potential for serial evaluations of disease progression and treatment responses.
Boundedness in a fully parabolic chemotaxis‐consumption system with nonlinear diffusion and sensitivity, and logistic source
Authors: Marras Monica , Viglialoro Giuseppe 
Published: May 2018

AbstractIn this paper we study the zero‐flux chemotaxis‐system
urn:x-wiley:0025584X:media:mana201700172:mana201700172-math-0001Ω being a convex smooth and bounded domain of , , and where , and . For any the chemotactic sensitivity function is assumed to behave as the prototype , with and . We prove that for nonnegative and sufficiently regular initial data and , the corresponding initial‐boundary value problem admits a unique globally bounded classical solution provided μ is large enough.