| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 5. |
- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 8. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 10. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 13. |
- Dalin, Martin, 1982, et al.
(författare)
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Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer.
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| 14. |
- Hussain, F., et al.
(författare)
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Electrochemical investigation of multi-fuel based low temperature nano-composite anode for solid oxide fuel cell
- 2019
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Ingår i: Journal of Power Sources. - : Elsevier B.V.. - 0378-7753 .- 1873-2755. ; 425, s. 147-152
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Tidskriftsartikel (refereegranskat)abstract
- Extensive efforts have been made in order to develop multi-fuel-based low temperature solid oxide fuel cell for direct conversion of hydrocarbons to electric power. It is extremely difficult to operate due to the C–H activation and its tremendously sluggish oxidation reduction in the low temperature range from 300 to 600 °C. The structural and electrochemical properties of novel anode material Ni 0.6 (Ba 0.3 Ce 0.2 Zn 0.5 ) 0.4 have been investigated in the presence of hydrogen, natural gas, ethanol, glucose, and sugar-cane at low temperature of 600 °C. Through sol-gel method the proposed oxide material is synthesized. The composite average crystalline size has been found 25–90 nm by both scanning electron microscopy and X-ray diffraction techniques. The ultraviolet– visible and Fourier transform infrared techniques are used to determine band gap and absorption spectrum respectively. The power density of the cell at various fuels has been observed and measurements indicate that it varies from 57 to 315 mWcm −2 at 600 °C among different fuels at anode side. The current study reveals that proposed anode Ni 0.6 (Ba 0.3 Ce 0.2 Zn 0.5 ) 0.4 is promising multi-fuel anode material for low-temperature solid oxide fuel cell, and it does not need to reform hydrocarbon fuels in order to fully utilize the advantage of these cells.
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| 15. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 16. |
- Muhammad, Riaz, et al.
(författare)
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Experimental and finite element method calculation of piezoelectric power generation from ZnO nanowire arrays grown on different substrates using high and low temperature methods
- 2008
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this paper we investigate the piezoelectric power generation from ZnO nanowire arrays grown using different methods. The ZnO nanowires are grown on n-SiC and n-Si substrates using both the high-temperature vapor liquid solid (VLS) and the lowtemperature aqueous chemical growth (ACG) methods. A conductive atomic force microscope (AFM) is used in contact mode to deflect the ZnO nanowire arrays. A piezoelectric potential across the nanowires is produced and then released via the rectifying behavior of the Schottky barrier at the platinum metal-ZnO interface. We do not observe any substrate effect but the growth method, crystal quality, density, length and diameter (aspect ratio) of the nanowires are found to affect the piezoelectric behavior. These parameters can significantly affect the performance manifested in the observed output voltage signal. Based on these parameters, we compare four nanogenerators under identical conditions. During the AFM scanning in contact mode without biased voltage, the ZnO nanowire arrays grown by the VLS method produce higher and larger output voltage signal of 35 mV compared to ZnO nanowires arrays grown by the ACG method, which produce smaller output voltage signal of 5 mV. We apply finite element (FE) method calculations to investigate the output voltage of ZnO nanowires based nanogenerators with different aspects ratios. From FE results we find that the output voltage of the nanogenerator is decreased above an aspect ratio 80 of ZnO nanowires.
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| 17. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 18. |
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| 19. |
- Riaz, M. A., et al.
(författare)
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Novel T-shaped resonator based chipless RFID tag
- 2017
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Ingår i: IEICE Electronics Express. - : Institute of Electronics Information Communication Engineers. - 1349-2543. ; 14:18
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Tidskriftsartikel (refereegranskat)abstract
- A novel, frequency selective surface (FSS) based, data encoding structure amenable to be used as a chipless RFID tag is proposed. The data encoding structure is made up of finite repetitions of a unit cell fabricated on commercially available grounded FR4 substrate having physical dimensions of 15 × 15mm2. The unit cell is composed of numerous T-shaped resonant elements arranged as two atypical sets of concentric nested loops. Alteration in geometry of the encoding circuit, attained by inclusion or omission of nested resonators, corresponds to a particular data sequence. Each encoded data sequence is manifested in the frequency domain as a distinct spectral signature. The proposed 10-bit tag is both compact and robust, and remains interrogable in response to illuminating electromagnetic waves at various angles of incidence.
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| 20. |
- Riaz, Z., et al.
(författare)
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Lung Tumor Image Segmentation from Computer Tomography Images Using MobileNetV2 and Transfer Learning
- 2023
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Ingår i: Bioengineering. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2306-5354. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung cancer is one of the most fatal cancers worldwide, and malignant tumors are characterized by the growth of abnormal cells in the tissues of lungs. Usually, symptoms of lung cancer do not appear until it is already at an advanced stage. The proper segmentation of cancerous lesions in CT images is the primary method of detection towards achieving a completely automated diagnostic system. Method: In this work, we developed an improved hybrid neural network via the fusion of two architectures, MobileNetV2 and UNET, for the semantic segmentation of malignant lung tumors from CT images. The transfer learning technique was employed and the pre-trained MobileNetV2 was utilized as an encoder of a conventional UNET model for feature extraction. The proposed network is an efficient segmentation approach that performs lightweight filtering to reduce computation and pointwise convolution for building more features. Skip connections were established with the Relu activation function for improving model convergence to connect the encoder layers of MobileNetv2 to decoder layers in UNET that allow the concatenation of feature maps with different resolutions from the encoder to decoder. Furthermore, the model was trained and fine-tuned on the training dataset acquired from the Medical Segmentation Decathlon (MSD) 2018 Challenge. Results: The proposed network was tested and evaluated on 25% of the dataset obtained from the MSD, and it achieved a dice score of 0.8793, recall of 0.8602 and precision of 0.93. It is pertinent to mention that our technique outperforms the current available networks, which have several phases of training and testing.
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| 21. |
- Yang, W., et al.
(författare)
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Immunogenic neoantigens derived from gene fusions stimulate T cell responses
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:5
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Tidskriftsartikel (refereegranskat)abstract
- Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. We identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. Using whole-genome sequencing and RNA sequencing, we identified a novel gene fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic T cell response. In a cohort of head and neck tumors with low mutation burden, minimal immune infiltration and prevalent gene fusions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses. Finally, analyzing additional datasets of fusion-positive cancers, including checkpoint-inhibitor-treated tumors, we found evidence of immune surveillance resulting in negative selective pressure against gene fusion-derived neoantigens. These findings highlight an important class of tumor-specific antigens and have implications for targeting gene fusion events in cancers that would otherwise be less poised for response to immunotherapy, including cancers with low mutational load and minimal immune infiltration.
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