| 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. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 3. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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The Development of Swedish Military Healthcare System: Part II-Re-evaluating the Military and Civilian Healthcare Systems in Crises Through a Dialogue and Study Among Practitioners.
- 2021
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Ingår i: Military medicine. - : Oxford University Press (OUP). - 1930-613X .- 0026-4075. ; 186:3-4
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Tidskriftsartikel (refereegranskat)abstract
- Historical changes have transformed Sweden from being an offensive to a defensive and collaborative nation with national and international engagement, allowing it to finally achieve the ground for the civilian-military collaboration and the concept of a total defense healthcare. At the same time, with the decreasing number of international and interstate conflicts, and the military's involvement in national emergencies and humanitarian disaster relief, both the need and the role of the military healthcare system within the civilian society have been challenged. The recent impact of the COVID-19 in the USA and the necessity of military involvement have led health practitioners to anticipate and re-evaluate conditions that might exceed the civilian capacity of their own countries and the need to have collaboration with the military healthcare. This study investigated both these challenges and views from practitioners regarding the benefits of such collaboration and the manner in which it would be initiated.A primary study was conducted among responsive countries using a questionnaire created using the Nominal Group Technique. Relevant search subjects and keywords were extracted for a systematic review of the literature, according to the PRISMA model.The 14 countries responding to the questionnaire had either a well-developed military healthcare system or units created in collaboration with the civilian healthcare. The results from the questionnaire and the literature review indicated a need for transfer of military medical knowledge and resources in emergencies to the civilian health components, which in return, facilitated training opportunities for the military staff to maintain their skills and competencies.As the world witnesses a rapid change in the etiology of disasters and various crises, neither the military nor the civilian healthcare systems can address or manage the outcomes independently. There is an opportunity for both systems to develop future healthcare in collaboration. Rethinking education and training in war and conflict is indisputable. Collaborative educational initiatives in disaster medicine, public health and complex humanitarian emergencies, international humanitarian law, and the Geneva Convention, along with advanced training in competency-based skill sets, should be included in the undergraduate education of health professionals for the benefit of humanity.
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| 4. |
- Travaglini, Lorena, et al.
(författare)
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Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders
- 2013
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 21:10, s. 8-1074
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Tidskriftsartikel (refereegranskat)abstract
- Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain-hindbrain malformation known as the 'molar tooth sign'. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. We previously identified the INPP5E gene as causative of JSRD in seven families linked to the JBTS1 locus, yet the phenotypic spectrum and prevalence of INPP5E mutations in JSRD and MKS remain largely unknown. To address this issue, we performed INPP5E mutation analysis in 483 probands, including 408 JSRD patients representative of all clinical subgroups and 75 MKS fetuses. We identified 12 different mutations in 17 probands from 11 JSRD families, with an overall 2.7% mutation frequency among JSRD. The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS fetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus.
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