| 1. |
- 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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| 2. |
- Hahn, Jong Woo, et al.
(författare)
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Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis
- 2023
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Ingår i: eClinicalMedicine. - : ELSEVIER. - 2589-5370. ; 65
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Forskningsöversikt (refereegranskat)abstract
- Background Autoimmune hepatitis (AIH) varies significantly in incidence and prevalence across countries and regions. We aimed to examine global, regional, and national trends in incidence and prevalence of AIH from 1970 to 2022.Methods We conducted a thorough search of the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from database inception to August 9, 2023, using the search term "autoimmune hepatitis" in combination with "incidence," "prevalence," or "trend." Only general population-based observational studies with larger samples sizes were considered for inclusion. Studies that recruited convenience samples, and those with fewer than 50 participants were excluded. Summary data were extracted from published reports. A random effects model was used and pooled estimates with 95% CI were used to calculate the incidence and prevalence of AIH. Heterogeneity was evaluated using the I-2 statistic. The study protocol was registered with PROSPERO, CRD42023430138. Findings A total of 37 eligible studies, encompassing more than 239 million participants and 55,839 patients with AIH from 18 countries across five continents, were included in the analysis. Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I-2 = 99<middle dot>51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I-2 = 99<middle dot>75%; number of studies, 26; sample population, 217,178,684), respectively. The incidence of AIH was greater in countries with high Human Development Index (>0.92), in North America and Oceania (compared with Asia), among females, adults (compared with children), and high latitude (>45 degrees). Similar patterns in AIH prevalence were observed. Pooled AIH prevalence increased gradually from 1970 to 2019 (1970-1999; 9.95 [4.77-15.13], I-2 = 95<middle dot>58% versus 2015-2022; 27.91 [24.86-30.96], I-2 = 99<middle dot>32%; cases per 100,000 inhabitants). The overall incidence and prevalence of AIH, as well as some subgroup analyses of the studies, displayed asymmetry in the funnel plots, suggesting potential evidence of publication bias.Interpretation AIH incidence and prevalence have increased significantly and exhibit substantial variation across regions worldwide. Further research is required to assess the incidence and prevalence of AIH, specifically in South America and Africa.
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| 3. |
- Kwon, Hyuk Sung, et al.
(författare)
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Early increment of soluble triggering receptor expressed on myeloid cells 2 in plasma might be a predictor of poor outcome after ischemic stroke
- 2020
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Ingår i: Journal of clinical neuroscience. - : ELSEVIER SCI LTD. - 0967-5868 .- 1532-2653. ; 73, s. 215-218
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Tidskriftsartikel (refereegranskat)abstract
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is derived from cleavage of TREM2, which is expressed on the cell surface of microlgia and other tissue-specific macrophages. In the present study, the changes in the sTREM2 levels after ischemic stroke (IS) and their association with clinical outcomes were evaluated. A total of 43 patients diagnosed with non-cardioembolic IS between June 2011 and May 2014 were consecutively included in this study. Patients treated with intravenous thrombolysis or intra-arterial thrombectomy were excluded. Plasma samples were collected three times (days 1, 7, and 90) after ictus. The sTREM2 level was measured in the samples using the highly sensitive solid-phase proximity ligation assay (SP-PLA). Among the 43 subjects, higher initial NIH stroke scale (NIHSS) score (P = 0.005), early increment of sTREM2 (P < 0.001), and late decrement of sTREM2 (P = 0.002), were more common in patients with poor outcome. Based on multivariate analysis, initial NIHSS score (P = 0.015) and early increment of sTREM2 (P = 0.032) were independently associated with poor outcome. The results from the present study indicate that increment of sTREM2 level at the early phase was a predictor of poor outcome. Serial follow-up of sTREM2 may aid prognosis after stroke.
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| 4. |
- 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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| 5. |
- Liu, Ao, et al.
(författare)
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Article Modulation of vacancy-ordered double perovskite Cs(2)SnI(6 )for air-stable thin-film transistors
- 2022
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Ingår i: Cell Reports Physical Science. - : Elsevier. - 2666-3864. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Vacancy-ordered halide double perovskites are promising non-toxic and stable alternatives for their lead-and tin (II)-based counterparts in electronic and optoelectronic applications. Despite extensive theoretical studies on this emerging family of materials, efforts devoted to the chemical modulation of their thin-film properties and their potential application in electronic devices remain rare. Here, we develop a facile one-step solution processing strategy to tune the film quality of cesium tin (IV) iodide (Cs2SnI6) perovskite and demonstrate its feasibility in thin-film transistor (TFT) application. We reveal critical roles of precursor stoichiometric ratio and solvent engineering in achieving uniform and highly crystalline Cs2SnI6 films with superior electron mobility. We further modulate the electronic properties by incorporating an external manganese (Mn2+) dopant, achieving high-performance air-stable n-channel TFTs and all-perovskite complementary inverters. We anticipate that the present study would pave the way for expanding the environmentally friendly and stable perovskites toward widespread applications.
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| 6. |
- Zhu, Huihui, et al.
(författare)
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High-performance hysteresis-free perovskite transistors through anion engineering
- 2022
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Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite the impressive development of metal halide perovskites in diverse optoelectronics, progress on high-performance transistors employing state-of-the-art perovskite channels has been limited due to ion migration and large organic spacer isolation. Herein, we report high-performance hysteresis-free p-channel perovskite thin-film transistors (TFTs) based on methylammonium tin iodide (MASnI(3)) and rationalise the effects of halide (I/Br/Cl) anion engineering on film quality improvement and tin/iodine vacancy suppression, realising high hole mobilities of 20 cm(2) V-1 s(-1), current on/off ratios exceeding 10(7), and threshold voltages of 0 V along with high operational stabilities and reproducibilities. We reveal ion migration has a negligible contribution to the hysteresis of Sn-based perovskite TFTs; instead, minority carrier trapping is the primary cause. Finally, we integrate the perovskite TFTs with commercialised n-channel indium gallium zinc oxide TFTs on a single chip to construct high-gain complementary inverters, facilitating the development of halide perovskite semiconductors for printable electronics and circuits. Progress on high-performance transistor employing perovskite channels has been limited to date. Here, Zhu et al. report hysteresis-free tin-based perovskite thin-film transistors with high hole mobility of 20 cm(2)V(-1)S(-1), which can be integrated with commercial metal oxide transistors on a single chip.
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| 7. |
- Hyun, Gyu Hwan, et al.
(författare)
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Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity
- 2023
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 17:12, s. 11567-11582
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Tidskriftsartikel (refereegranskat)abstract
- Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation. Gal-NC is characterized as a carbohydrate nanoadjuvant with a macrophage-targeting feature. It is composed of repeating galactan glycopatterns derived from heteropolysaccharide structures of plant origin. The galactan repeats of Gal-NC function as multivalent pattern-recognition sites for Toll-like receptor 4 (TLR4). Functionally, Gal-NC-mediated TLR activation induces the repolarization of tumor-associated macrophages (TAMs) toward immunostimulatory/tumoricidal M1-like phenotypes. Gal-NC increases the intratumoral population of cytotoxic T cells, the main effector cells of antitumor immunity, via re-educated TAMs. These TME alterations synergistically enhance the T-cell-mediated antitumor response induced by αPD-1 administration, suggesting that Gal-NC has potential value as an adjuvant for immune checkpoint blockade combination therapies. Thus, the Gal-NC model established herein suggests a glycoengineering strategy to design a carbohydrate-based nanocomposite for advanced cancer immunotherapies.
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| 8. |
- Zhou, Jinyuan, et al.
(författare)
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Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T : Application to brain tumors
- 2022
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 88:2, s. 546-574
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Tidskriftsartikel (refereegranskat)abstract
- Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.
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