| 861. |
- Guo, Yingying, et al.
(author)
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Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches
- 2018
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In: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 104:5, s. 865-889
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Research review (peer-reviewed)abstract
- This white paper examines recent progress, applications, and challenges in predicting unbound and total tissue and intra/subcellular drug concentrations using in vitro and preclinical models, imaging techniques, and physiologically based pharmacokinetic (PBPK) modeling. Published examples, regulatory submissions, and case studies illustrate the application of different types of data in drug development to support modeling and decision making for compounds with transporter-mediated disposition, and likely disconnects between tissue and systemic drug exposure. The goals of this article are to illustrate current best practices and outline practical strategies for selecting appropriate in vitro and in vivo experimental methods to estimate or predict tissue and plasma concentrations, and to use these data in the application of PBPK modeling for human pharmacokinetic (PK), efficacy, and safety assessment in drug development.
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| 862. |
- Hadjiev, V. G., et al.
(author)
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Symmetry of phonon, magnetic, and spin-phonon excitations in GdSr2RuCu2O8 single crystals
- 2001
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In: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 64
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Journal article (peer-reviewed)abstract
- We present a polarized Raman scattering study of GdSr2RuCu2O8 single crystals. In this compound, the RuO6 octahedra are rotated around the c axis that in turn gives some Raman activity of the oxygen (O-Ru) vibrations at 265 cm(-1) (A(1g)), 411 cm(-1) (B-2g) and 607 cm(-1) (B-1g). These vibrations, as well as those of the apical oxygen of RuO6, at 654 cm(-1) (A(1g)) and the Cu-plane oxygen at 318 cm(-1) (B-2g), clearly respond to the onset of magnetic ordering at T-m approximate to 140 K. In particular, the 265 cm(-1) mode hardens anomalously with decreasing temperature below T-m. Notably, the corresponding phonon line is absent in the Raman spectra of GdSr2NbCu2O8 (Nb5+:4d(0)), a compound isomorphic to GdSr2RuCu2O8 (Ru5+:4d(3)). We argue that the eigenvector of the 265 cm(-1) phonon (rotational mode) facilitates efficient modulation of the Ru(t(1g))-O-Ru (p) bands. This modulation gives both Raman scattering strength to the 265 cm(-1) mode and strong spin-phonon coupling.
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| 863. |
- Hawkes, Jeffrey A., et al.
(author)
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An international laboratory comparison of dissolved organic matter composition by high resolution mass spectrometry : Are we getting the same answer?
- 2020
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In: Limnology and Oceanography. - : Wiley. - 1541-5856. ; 18:6, s. 235-258
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Journal article (peer-reviewed)abstract
- High-resolution mass spectrometry (HRMS) has become a vital tool for dissolved organic matter (DOM) characterization. The upward trend in HRMS analysis of DOM presents challenges in data comparison and interpretation among laboratories operating instruments with differing performance and user operating conditions. It is therefore essential that the community establishes metric ranges and compositional trends for data comparison with reference samples so that data can be robustly compared among research groups. To this end, four identically prepared DOM samples were each measured by 16 laboratories, using 17 commercially purchased instruments, using positive-ion and negative-ion mode electrospray ionization (ESI) HRMS analyses. The instruments identified similar to 1000 common ions in both negative- and positive-ion modes over a wide range of m/z values and chemical space, as determined by van Krevelen diagrams. Calculated metrics of abundance-weighted average indices (H/C, O/C, aromaticity and m/z) of the commonly detected ions showed that hydrogen saturation and aromaticity were consistent for each reference sample across the instruments, while average mass and oxygenation were more affected by differences in instrument type and settings. In this paper we present 32 metric values for future benchmarking. The metric values were obtained for the four different parameters from four samples in two ionization modes and can be used in future work to evaluate the performance of HRMS instruments.
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| 864. |
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| 865. |
- Hidalgo, N. F., et al.
(author)
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Beta-Hemolytic Streptococcal Infective Endocarditis: Characteristics and Outcomes From a Large, Multinational Cohort
- 2020
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In: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 7:5
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Journal article (peer-reviewed)abstract
- Background. Beta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE. Methods. The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators. Results. Among 1336 definite cases of streptococcal IE, 823 were caused by VGS and 147 by BHS. Patients with BHS IE had a lower prevalence of native valve (P < .005) and congenital heart disease predisposition (P = .002), but higher prevalence of implantable cardiac device predisposition (P < .005). Clinically, they were more likely to present acutely (P < .005) and with fever (P = .024). BHS IE was more likely to be complicated by stroke and other systemic emboli (P < .005). The overall in-hospital mortality of BHS IE was significantly higher than that of VGS IE (P = .001). In univariate analysis, variables associated with in-hospital mortality for BHS IE were age (odds ratio [OR], 1.044; P = .004), prosthetic valve IE (OR, 3.029; P = .022), congestive heart failure (OR, 2.513; P = .034), and stroke (OR, 3.198; P = .009). Conclusions. BHS IE is characterized by an acute presentation and higher rate of stroke, systemic emboli, and in-hospital mortality than VGS IE. Implantable cardiac devices as a predisposing factor were more often found in BHS IE compared with VGS IE.
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| 866. |
- Hori, Masatsugu, et al.
(author)
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Dabigatran Versus Warfarin Effects on Ischemic and Hemorrhagic Strokes and Bleeding in Asians and Non-Asians With Atrial Fibrillation
- 2013
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In: Stroke. - 0039-2499 .- 1524-4628. ; 44:7, s. 1891-
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Journal article (peer-reviewed)abstract
- Background and Purpose-Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries. Methods-There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used. Results-Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3-4.7; P=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03-0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06-0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19-0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13-0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year). Conclusions-Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups.
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| 867. |
- Huang, JJ, et al.
(author)
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Disease Burden, Risk Factors, and Recent Trends of Liver Cancer: A Global Country-Level Analysis
- 2021
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In: Liver cancer. - : S. Karger AG. - 2235-1795 .- 1664-5553. ; 10:4, s. 330-345
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> This study aimed to evaluate the updated disease burden, risk factors, and temporal trends of liver cancer based on age, sex, and country. <b><i>Methods:</i></b> We estimated the incidence of liver cancer and its attribution to hepatitis B virus (HBV) and hepatitis C virus (HCV) in 2018 based on the Global Cancer Observatory and World Health Organization (WHO) Cancer Causes database<i>.</i> We extracted the prevalence of risk factors from the WHO Global Health Observatory to examine the associations by weighted linear regression. The trend analysis used data from the <i>Cancer Incidence in Five Continents</i> and the WHO mortality database from 48 countries. Temporal patterns of incidence and mortality were calculated using average annual percent change (AAPC) by joinpoint regression analysis. <b><i>Results:</i></b> The global incidence of liver cancer was (age-standardized rate [ASR]) 9.3 per 100,000 population in 2018, and there was an evident disparity in the incidence related to HBV (ASR 0.2–41.2) and HCV (ASR 0.4–43.5). A higher HCV/HBV-related incidence ratio was associated with a higher level of alcohol consumption (β 0.49), overweight (β 0.51), obesity (β 0.64), elevated cholesterol (β 0.70), gross domestic product (β 0.20), and Human Development Index (HDI; β 0.45). An increasing trend in incidence was identified in many countries, especially for male individuals, population aged ≥50 years, and countries with a higher HCV/HBV-related liver cancer incidence ratio. Countries with the most drastic increase in male incidence were reported in India (AAPC 7.70), Ireland (AAPC 5.60), Sweden (AAPC 5.72), the UK (AAPC 5.59), and Norway (AAPC 4.87). <b><i>Conclusion:</i></b> We observed an overall increasing trend of liver cancer, especially among male subjects, older individuals, and countries with a higher prevalence of HCV-related liver cancer. More efforts are needed in enhancing lifestyle modifications and accessibility of antiviral treatment for these populations. Future studies should investigate the reasons behind these epidemiological changes.
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| 868. |
- Huang, JJ, et al.
(author)
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Global Burden, Risk Factors, and Trends of Esophageal Cancer: An Analysis of Cancer Registries from 48 Countries
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:1
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Journal article (peer-reviewed)abstract
- This study aimed to examine the global burden, risk factors, and trends of esophageal cancer based on age, sex, and histological subtype. The data were retrieved from cancer registries database from 48 countries in the period 1980–2017. Temporal patterns of incidence and mortality were evaluated by average annual percent change (AAPC) using joinpoint regression. Associations with risk factors were examined by linear regression. The highest incidence of esophageal cancer was observed in Eastern Asia. The highest incidence of adenocarcinoma (AC) was found in the Netherlands, the United Kingdom, and Ireland. A higher AC/squamous cell carcinoma (SCC) incidence ratio was associated with a higher prevalence of obesity and elevated cholesterol. We observed an incidence increase (including AC and SCC) in some countries, with the Czech Republic (female: AAPC 4.66), Spain (female: 3.41), Norway (male: 3.10), Japan (female: 2.18), Thailand (male: 2.17), the Netherlands (male: 2.11; female: 1.88), and Canada (male: 1.51) showing the most significant increase. Countries with increasing mortality included Thailand (male: 5.24), Austria (female: 3.67), Latvia (male: 2.33), and Portugal (male: 1.12). Although the incidence of esophageal cancer showed an overall decreasing trend, an increasing trend was observed in some countries with high AC/SCC incidence ratios. More preventive measures are needed for these countries.
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| 869. |
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| 870. |
- Huang, Shih-Wen, et al.
(author)
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Selective interlayer ferromagnetic coupling between the Cu spins in YBa2Cu3O7-x grown on top of La0.7Ca0.3MnO3.
- 2015
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Journal article (peer-reviewed)abstract
- Studies to date on ferromagnet/d-wave superconductor heterostructures focus mainly on the effects at or near the interfaces while the response of bulk properties to heterostructuring is overlooked. Here we use resonant soft x-ray scattering spectroscopy to reveal a novel c-axis ferromagnetic coupling between the in-plane Cu spins in YBa2Cu3O7-x (YBCO) superconductor when it is grown on top of ferromagnetic La0.7Ca0.3MnO3 (LCMO) manganite layer. This coupling, present in both normal and superconducting states of YBCO, is sensitive to the interfacial termination such that it is only observed in bilayers with MnO2 but not with La0.7Ca0.3O interfacial termination. Such contrasting behaviors, we propose, are due to distinct energetic of CuO chain and CuO2 plane at the La0.7Ca0.3O and MnO2 terminated interfaces respectively, therefore influencing the transfer of spin-polarized electrons from manganite to cuprate differently. Our findings suggest that the superconducting/ferromagnetic bilayers with proper interfacial engineering can be good candidates for searching the theorized Fulde-Ferrel-Larkin-Ovchinnikov (FFLO) state in cuprates and studying the competing quantum orders in highly correlated electron systems.
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