| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Cho, Eun, et al.
(författare)
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Clinical experience of tensor-valued diffusion encoding for microstructure imaging by diffusional variance decomposition in patients with breast cancer
- 2022
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Ingår i: Quantitative Imaging in Medicine and Surgery. - : AME Publishing Company. - 2223-4292 .- 2223-4306. ; 12:3, s. 2002-2017
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diffusion-weighted imaging plays a key role in magnetic resonance imaging (MRI) of breast tumors. However, it remains unclear how to interpret single diffusion encoding with respect to its link with tissue microstructure. The purpose of this retrospective cross-sectional study was to use tensor-valued diffusion encoding to investigate the underlying microstructure of invasive ductal carcinoma (IDC) and evaluate its potential value in a clinical setting. Methods: We retrospectively reviewed biopsy-proven breast cancer patients who underwent preoperative breast MRI examination from July 2020 to March 2021. We reviewed the MRI of 29 patients with 30 IDCs, including analysis by diffusional variance decomposition enabled by tensor-valued diffusion encoding. The diffusion parameters of mean diffusivity (MD), total mean kurtosis (MKT), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), macroscopic fractional anisotropy (FA), and microscopic fractional anisotropy (μFA) were estimated. The parameter differences were compared between IDC and normal fibroglandular breast tissue (FGBT), as well as the association between the diffusion parameters and histopathologic items. Results: The mean value of MD in IDCs was significantly lower than that of normal FGBT (1.07±0.27 vs. 1.34±0.29, P<0.001); however, MKT, MKA, MKI, FA, and μFA were significantly higher (P<0.005). Among all the diffusion parameters, MKI was positively correlated with the tumor size on both MRI and pathological specimen (rs=0.38, P<0.05 vs. rs=0.54, P<0.01), whereas MKT had a positive correlation with the tumor size in the pathological specimen only (rs=0.47, P<0.02). In addition, the lymph node (LN) metastasis group had significantly higher MKT, MKA, and μFA compared to the metastasis negative group (P<0.05). Conclusions: Tensor-valued diffusion encoding enables a useful non-invasive method for characterizing breast cancers with information on tissue microstructures. Particularly, μFA could be a potential imaging biomarker for evaluating breast cancers prior to surgery or chemotherapy.
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| 5. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 6. |
- Kim, Min-Jeong, et al.
(författare)
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Independent enhancement of the in-plane Seebeck effect in 2D PtSe2/PtSe2 homostructures via a facile interface tuning method
- 2024
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Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 268
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Tidskriftsartikel (refereegranskat)abstract
- Atomically thin two-dimensional (2D) transition-metal dichalcogenide (TMDC) films have emerged as promising semiconducting materials for use in thermoelectric (TE) applications. However, the utilization of such materials remains challenging owing to the relatively high intrinsic resistance as the size of the TMDC thin films increases to the centimeter scale. These 2D TMDC films can also form vertically stacked homo- or heterostructures at large interfaces with other 2D TMDC films, resulting in unique TE properties at room temperature. This article reports on the in-plane TE properties when the interfaces formed within a PtSe2/PtSe2 (3 nm/3 nm) homostructure are modulated as a function of O2 plasma treatment time. The results show enhanced Seebeck coefficients compared with that of the single-layer PtSe2 with the same thickness. The independent enhancement in the Seebeck coefficient while keeping the electrical conductivity leads to a substantial increase in the power factor. Such extra Seebeck voltage in 2D PtSe2/PtSe2 homostructures is mainly as a result of momentum exchange by charge carriers caused by the temperature gradient in the vertical direction, which occurs in-plane Seebeck coefficient measurements, at the interface between the PtSe2 layers in the in-plane temperature gradient along the samples. These results resemble the characteristics of the phonon drag effect at low temperatures, which can independently increase the Seebeck coefficient at room temperature.
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| 7. |
- Kim, Min-Jeong, et al.
(författare)
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Intrinsic Seebeck coefficients of 2D polycrystalline PtSe2 semiconducting films through two-step annealing
- 2023
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 11:11, s. 5714-5724
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Tidskriftsartikel (refereegranskat)abstract
- Because of the high contact resistance between a metal and a film, evaluating the intrinsic Seebeck coefficient of large-area two-dimensional (2D) semiconducting films with high-resistance is challenging. Here, we report a simple scheme to measure the large-area Seebeck coefficients of 2D polycrystalline platinum diselenide (PtSe2) thin films, whose electrical resistance (>2 M omega) is too high to measure the thermoelectric (TE) properties, by thermal annealing. As-prepared PtSe2 thin films deposited on sapphire substrates and treated by a two-step thermal annealing process at 574 K exhibited an intrinsic Seebeck coefficient > similar to 160 mu V K-1, which is 400% higher than that of the single-crystalline PtSe2 bulk, under a temperature gradient of up to 5 K along the samples. In addition, we confirm that the in-plane Seebeck coefficient of the two-step annealed samples was independent of the metal electrode. In addition, the role of thermal annealing in intrinsically-high-resistance 2D PtSe2 semiconducting films based on the atomic-scale crystallographic characteristics of these films and the measured contact resistance between the metal and PtSe2 layer is further discussed. Our finding represents an important achievement in understanding and measuring the Seebeck effect of high-TE-performance 2D layered transition metal dichalcogenide materials.
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| 8. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 9. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 10. |
- Cho, Wonkyung, et al.
(författare)
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Design of salmon calcitonin particles for nasal delivery using spray-drying and novel supercritical fluid-assisted spray-drying processes
- 2015
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 478:1, s. 288-296
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Tidskriftsartikel (refereegranskat)abstract
- The overall aim of this study was to prepare a nasal powder formulation of salmon calcitonin (sCT) using an absorption enhancer to improve its bioavailability. In this work, powder formulations for nasal delivery of sCT were studied using various absorption enhancers and stabilizers. Powders were prepared by two different methods: conventional spray-drying (SD) and novel supercritical fluid-assisted spray-drying (SASD) to investigate the role of CO2 in the particle formation process. The prepared sCT powder formulations were characterized by several analyses; powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), and the Fourier transform infrared (FT-IR) spectroscopy method. The particle size distribution was also evaluated. In vivo absorption tests were carried out in Sprague-Dawley rat using the prepared powder formulations, and the results were compared to those of raw sCT. Quantitative analysis by high-performance liquid chromatography (HPLC) indicated that sCT was chemically stable after both the SD and SASD processes. Results of PXRD, SEM, and FT-IR did not indicate a strong interaction or defragmentation of sCT. The in vivo absorption test showed that SD- and SASD-processed sCT powders increased the bioavailability of the drug when compared to the nasal administration of raw sCT. In addition, SASD-processed sCT exhibited higher nasal absorption when compared with SD-processed sCT in all formulations due to a reduction of particle size. The results from this study illustrate that the preparation of nasal powders using the SASD process could be a promising approach to improve nasal absorption of sCT.
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| 11. |
- Choi, Jae Won, et al.
(författare)
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Interface-driven seebeck effect in two-dimensional trilayer-stacked PtTe2/MoS2/MoS2 heterostructures via electron-electron interactions
- 2023
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Ingår i: Nano Energy. - : Elsevier. - 2211-2855 .- 2211-3282. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional (2D) platinum telluride (PtTe2), which is one of the promising metallic transition metal dichalcogenides, has been proven as an essential candidate for electronic devices, magnetic devices, type-II Dirac fermions, topological superconductors, and other optoelectronic applications. However, the formation and thermal transport as important thermoelectric (TE) device applications have not been realized in large-area 2D PtTe2 films due to their semi-metallic properties. Here, we report an innovative approach to enhance the in-plane TE power factors by piling the metallic PtTe2 films on high-resistance (> 10 MO) intrinsic MoS2 films to form bilayer-PtTe2/MoS2 (5 nm/7 nm)//sapphire and trilayer-PtTe2/MoS2/MoS2 (5 nm/7 nm/7 nm)//sapphire heterostructures via wet-transfer stacking method. Such approaches can be achieved by utilizing 2D/2D heterostructure to increase the electron effective mass due to the strong electron-electron interaction at interface under temperature gradient along the samples and ultimately increase Seebeck coefficients via interface-driven Seebeck effect along with a metallic high-conductivity top-PtTe2 films. The trilayer-stacked PtTe2/MoS2/MoS2 heterostructures exhibit an extremely high Seebeck coefficient of 21.6 mu V/K and power factor of similar to 0.2 mW/m.K-2, which are 231 % and similar to 727 %, higher than those of the metallic 5-nm-thick single PtTe2 film on the sapphire substrate, respectively. Our new physics and observation can pave the way toward an effective strategy for understating 2D/2D TMDC heterostructure materials for high Fig.-of-merit TE energy harvesting devices.
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| 12. |
- Jung, Min-Sook, et al.
(författare)
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Bioavailability of indomethacin-saccharin cocrystals
- 2010
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 62:11, s. 1560-1568
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee (R).MethodsScale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.Key findingsThe bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee (R) at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P < 0.05) than that of IND but not significantly different from Indomee (R) (ANOVA, P > 0.05).ConclusionsThe study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.
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| 13. |
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| 14. |
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| 15. |
- Shin, Jiho, et al.
(författare)
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Targeted Synthesis of Two Super-Complex Zeolites with Embedded Isoreticular Structures
- 2016
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 55:16, s. 4928-4932
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Tidskriftsartikel (refereegranskat)abstract
- A novel structural coding approach combining structure solution, prediction, and the targeted synthesis of new zeolites with expanding complexity and embedded isoreticular structures was recently proposed. Using this approach, the structures of two new zeolites in the RHO family, PST-20 and PST-25, were predicted and synthesized. Herein, by extending this approach, the next two higher generation members of this family, PST-26 and PST-28, have been predicted and synthesized. These two zeolites have much larger unit cell volumes (422 655 Å3 and 614 912 Å3, respectively) than those of the lower generations. Their crystallization was confirmed by a combination of both powder X-ray and electron diffraction techniques. Aluminate and water concentrations in the synthetic mixture were found to be the two most critical factors influencing the structural expansion of embedded isoreticular zeolites under the synthetic conditions studied herein.
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| 16. |
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| 17. |
- Cho, Sung Min, et al.
(författare)
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Development of Novel VEGFR2 Inhibitors Originating from Natural Product Analogues with Antiangiogenic Impact
- 2021
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:21, s. 15858-15867
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Tidskriftsartikel (refereegranskat)abstract
- A novel natural small molecule, voacangine (Voa), has been discovered as a potent antiangiogenic compound. Notably, Voa directly binds the kinase domain of the vascular endothelial growth factor receptor 2 (VEGFR2) and thereby inhibits downstream signaling. Herein, we developed synthetic small molecules based on the unique chemical structure of Voa that directly and specifically target and modulate the kinase activity of VEGFR2. Among these Voa structure analogues, Voa analogue 19 (V19) exhibited increased antiangiogenic potency against VEGF-induced VEGFR2 phosphorylation without cytotoxic effects. Moreover, treatment with V19 resulted in significant tumor cell death in a mouse xenograft model. In conclusion, this new VEGFR2 modulator, inspired from the rigid scaffold of a natural compound, Voa, is presented as a potent candidate in the development of new antiangiogenic agents.
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| 18. |
- Kassebaum, Nicholas J., et al.
(författare)
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Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
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Tidskriftsartikel (refereegranskat)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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| 19. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 20. |
- Wen, Wanqing, et al.
(författare)
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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