| 1. |
- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 2. |
- Teumer, A, et al.
(författare)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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| 3. |
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| 4. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 5. |
- Escadafal, C, et al.
(författare)
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Bacterial versus non-bacterial infections: a methodology to support use-case-driven product development of diagnostics
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- Acute febrile illness (AFI) is one of the most common reasons for seeking medical care in low-income and middle-income countries. Bacterial infections account for a relatively small proportion of AFIs; however, in the absence of a simple diagnostic test to guide clinical decisions, healthcare professionals often presume that a non-malarial febrile illness is bacterial in origin, potentially resulting in inappropriate antibiotic use. An accurate differential diagnostic tool for AFIs is thus essential, to both limit antibiotic use to bacterial infections and address the antimicrobial resistance crisis that is emerging globally, without resorting to multiple or complex pathogen-specific assays. The Biomarker for Fever-Diagnostic (BFF-Dx) study is one of the largest fever biomarker studies ever undertaken. We collected samples and classified disease aetiology in more than 1900 individuals, distributed among enrolment centres in three countries on two continents. Identical protocols were followed at each study site, and the same analyses were conducted in each setting, enabling like-with-like comparisons to be made among the large sample set generated. The BFF-Dx methodology can act as a model for other researchers, facilitating wider utility of the work in the future. The established sample collection is now accessible to researchers and companies and will facilitate the development of future fever-related diagnostic tests. Here, we outline the methodology used to determine the sample populations and to differentiate bacterial versus non-bacterial AFIs. Future publications will set out in more detail the study’s demographics, the causes of fever identified and the performance of selected biomarkers.
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| 6. |
- Kovtun, Yu., et al.
(författare)
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Overview of TOMAS plasma diagnostics
- 2023
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Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221 .- 1748-0221. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an overview of the TOMAS plasma diagnostics. The Langmuir probe method is employed to measure electron temperature, density and floating potential distributions. Two triple probes (horizontal and vertical distributions) and a single probe (horizontal distribution) are used. The measured plasma parameters by the triple and single probes are compared. The ion and neutral atom flux and energy distribution is respectively characterized with a Residual Field Energy Analyzer and a Time-of-Flight Neutral Particle Ana-lyzer. To determine the elemental/charge content of the plasma, the passive method of time-resolved optical emission spectroscopy is used. The time dependence of the integral flow of plasma emission from the discharge is registered by a photodetector. Using a filter allows the photodetector to measure spectral line intensities. To record a wide variety of plasma events several video diagnostics are used. It includes slow video cameras and one high-speed camera in the visible range including Hα.
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| 7. |
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| 8. |
- Schuettpelz, Eric, et al.
(författare)
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A community-derived classification for extant lycophytes and ferns
- 2016
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Ingår i: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 54:6, s. 563-603
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Tidskriftsartikel (refereegranskat)abstract
- Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predictive and stable. Here, we provide a modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community-based approach. We use monophyly as the primary criterion for the recognition of taxa, but also aim to preserve existing taxa and circumscriptions that are both widely accepted and consistent with our understanding of pteridophyte phylogeny. In total, this classification treats an estimated 11 916 species in 337 genera, 51 families, 14 orders, and two classes. This classification is not intended as the final word on lycophyte and fern taxonomy, but rather a summary statement of current hypotheses, derived from the best available data and shaped by those most familiar with the plants in question. We hope that it will serve as a resource for those wanting references to the recent literature on pteridophyte phylogeny and classification, a framework for guiding future investigations, and a stimulus to further discourse.
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| 9. |
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| 10. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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