| 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. |
- Wu, Jie, et al.
(författare)
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The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort : the Shanghai Aging Study
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers.METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted.RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001).CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.
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| 3. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 4. |
- Guo, Pengzhi, et al.
(författare)
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Twisted Alkylthiothien-2-yl Flanks and Extended Conjugation Length Synergistically Enhanced Photovoltaic Performance by Boosting Dielectric Constant and Carriers Kinetic Characteristics
- 2021
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Ingår i: Macromolecular Chemistry and Physics. - : Wiley. - 1022-1352 .- 1521-3935. ; 222:12
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Tidskriftsartikel (refereegranskat)abstract
- Alternating conjugated polymers (CPs), derived from 2-ethylhexylthiothiophen-2-yl (TS) or 2-ethylhexylthiophen-2-yl (T) flanked dithieno[3,2-d:3,2-d ']benzo[1,2-b:4,5-b ']dithiophene (DTBDT) and diketopyrrolo-pyrrole (DPP) termed as PDTBDT-TS-DPP and PDTBDT-T-DPP, are prepared and characterized. It is found that the PDTBDT-TS-DPP not only exhibits slightly deepening the highest occupied molecular orbital energy levels, and similar absorption, etc., but also presents higher dielectric constant (epsilon(r)) of 6.7 at 1 kHz in contrast to 3.2 for PDTBDT-T-DPP, which are even higher than those of 4.3 and 3.0 for PBDT-TS-DPP/PBDT-T-DPP generated from TS and T flanked benzo[1,2-b:4,5-bMODIFIER LETTER PRIME]dithiophene and DPP. Beyond that, the power conversion efficiency of 8.17% for the inverted photovoltaic devices from DPP-based CPs, is achieved from PDTBDT-TS-DPP. The alkylthio side chains are used in the DTBDT of the larger twisting angles of TS flanks and longer conjugation length, synergistically contribute to the highest dipole moments, and then lead to the enhancement of epsilon(r), thus devoted the modification exciton dissociation and charge carriers kinetic characteristics. To the authors' knowledge, it is the first time to report that epsilon(r) of the CPs is connected with the twisting angle of flanks and conjugation length of the building blocks, besides the use of functional side chains and atoms.
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| 5. |
- Qi, Di, et al.
(författare)
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Climate change drives rapid decadal acidification in the Arctic Ocean from 1994 to 2020
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 377:6614, s. 1544-1550
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Tidskriftsartikel (refereegranskat)abstract
- The Arctic Ocean has experienced rapid warming and sea ice loss in recent decades, becoming the first open-ocean basin to experience widespread aragonite undersaturation [saturation state of aragonite (Warag) < 1]. However, its trend toward long-term ocean acidification and the underlying mechanisms remain undocumented. Here, we report rapid acidification there, with rates three to four times higher than in other ocean basins, and attribute it to changing sea ice coverage on a decadal time scale. Sea ice melt exposes seawater to the atmosphere and promotes rapid uptake of atmospheric carbon dioxide, lowering its alkalinity and buffer capacity and thus leading to sharp declines in pH and Warag. We predict a further decrease in pH, particularly at higher latitudes where sea ice retreat is active, whereas Arctic warming may counteract decreases in Warag in the future.
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| 6. |
- Radamson, Henry H., et al.
(författare)
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State of the Art and Future Perspectives in Advanced CMOS Technology
- 2020
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Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:8
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Forskningsöversikt (refereegranskat)abstract
- The international technology roadmap of semiconductors (ITRS) is approaching the historical end point and we observe that the semiconductor industry is driving complementary metal oxide semiconductor (CMOS) further towards unknown zones. Today's transistors with 3D structure and integrated advanced strain engineering differ radically from the original planar 2D ones due to the scaling down of the gate and source/drain regions according to Moore's law. This article presents a review of new architectures, simulation methods, and process technology for nano-scale transistors on the approach to the end of ITRS technology. The discussions cover innovative methods, challenges and difficulties in device processing, as well as new metrology techniques that may appear in the near future.
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| 7. |
- Shi, Yongqiang, et al.
(författare)
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Thiazole Imide-Based All-Acceptor Homopolymer with Branched Ethylene Glycol Side Chains for Organic Thermoelectrics
- 2022
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773. ; 61:51
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Tidskriftsartikel (refereegranskat)abstract
- n-Type semiconducting polymers with high thermoelectric performance remain challenging due to the scarcity of molecular design strategy, limiting their applications in organic thermoelectric (OTE) devices. Herein, we provide a new approach to enhance the OTE performance of n-doped polymers by introducing acceptor-acceptor (A-A) type backbone bearing branched ethylene glycol (EG) side chains. When doped with 4-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-N,N-dimethylbenzenamine (N-DMBI), the A-A homopolymer PDTzTI-TEG exhibits n-type electrical conductivity (sigma) up to 34 S cm(-1) and power factor value of 15.7 mu W m(-1) K-2. The OTE performance of PDTzTI-TEG is far greater than that of homopolymer PBTI-TEG (sigma=0.27 S cm(-1)), indicating that introducing electron-deficient thiazole units in the backbone further improves the n-doping efficiency. These results demonstrate that developing A-A type polymers with EG side chains is an effective strategy to enhance n-type OTE performance.
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| 8. |
- Tahmasian, Masoud, et al.
(författare)
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ENIGMA-Sleep : Challenges, opportunities, and the road map
- 2021
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:6
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Forskningsöversikt (refereegranskat)abstract
- Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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| 9. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 10. |
- Zhu, Zheng, et al.
(författare)
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TOMM40 and APOE variants synergistically increase the risk of Alzheimer's disease in a Chinese population
- 2021
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Ingår i: Aging Clinical and Experimental Research. - : Springer. - 1594-0667 .- 1720-8319. ; 33:6, s. 1667-1675
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Tidskriftsartikel (refereegranskat)abstract
- Background: The apolipoprotein E (APOE) epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD) in Caucasian and African American populations. It suggests that other genetic factors may modulate AD pathogenesis in Chinese populations, among which the frequency of this allele is reduced but the AD prevalence is maintained. The translocase of outer mitochondrial membrane 40 (TOMM40), which is located adjacent to APOE,may play an APOE-dependent role in modulating AD pathogenesis.Aims: This work aimed to investigate whether TOMM40 polymorphisms modulate AD risk independently of, or in conjunction with APOE polymorphisms in Chinese populations.Methods: We conducted a case-control study including 834 patients with AD recruited from the Memory Clinic and 643 cognitively normal participants recruited from the community. The Taqman SNP method was used for APOE genotyping, while TOMM40 polymorphism genotyping was conducted via a polymerase chain reaction-ligase detection reaction.Results: TheTOMM40 rs10119 and rs71352238 alleles were associated with AD independently of the patient APO status. The rs10119 AA genotype and rs71352238 CC genotype were risk genotypes of AD. Individuals carrying a TOMM40 rs10119 GG/APOE epsilon 4+ (OR, 3.73; 95% CI 1.49-9.37;P = 0.005), TOMM40 rs10119 AG/APOE epsilon 4+ (OR, 4.16; 95% CI 3.30-5.24;P < 0.001), or TOMM40 rs10119 AA/APOE epsilon 4+ (OR, 14.78; 95% CI 8.56-25.54;P < 0.001) genotype exhibited a significantly higher AD risk. Those carrying a TOMM40 rs71352238 TT/APOE epsilon 4+ (OR, 3.82; 95% CI 2.32-6.29;P < 0.001), TOMM40 rs71352238 CT/APOE epsilon 4+ (OR, 4.40; 95% CI 3.46-5.56;P < 0.001), or TOMM40 rs71352238 CC/APOE epsilon 4+ (OR, 14.02; 95% CI 7.81-25.17;P < 0.001) genotype also exhibited a significantly increased AD risk.Discussion and conclusions: This study provides invaluable insights into the mechanisms underlying the prevalence of AD in Chinese populations, and supports that simultaneous TOMM40 and APOE genotyping in the clinical setting may identify individuals at high risk of developing AD.
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