| 1. |
|
|
| 2. |
- Mahajan, Anubha, et al.
(författare)
-
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
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.
|
|
| 3. |
- Mayo-Yáñez, Miguel, et al.
(författare)
-
Deep inferior epigastric artery perforator free flap in head and neck reconstruction : A systematic review
- 2021
-
Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier. - 1748-6815 .- 1878-0539. ; 74:4, s. 718-729
-
Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Perforator flaps yield the best results for the patient with the least morbidity, and they should be considered the gold standard in head and neck reconstruction. Although deep inferior epigastric perforator (DIEP) flap is considered as the gold standard in breast reconstruction, its use in head and neck reconstructive surgery does not seem so widespread. The objective of this study is to conduct a systematic review of the use, applications and results of the DIEP flap in the head and neck area.METHODS: Search was conducted in different indexed databases (PubMed/MEDLINE, the Cochrane Library, Scielo and Web of Science) and through meta-searcher Trip Database with deep inferior epigastric perforator flap AND head neck keywords. Studies on animal and human experiments published in peer-reviewed journals, where investigators assessed the use of DIEP flap, according to the Koshima criteria, in the head and neck area were considered.RESULTS: A total of 31 articles and 185 flaps with 95% of survival were found. Thrombosis or venous stasis is the most frequent cause of flap loss and 16.1% presented some type of complication, the most frequent being the dehiscence. The most use was in the reconstruction of glossectomy defect secondary to squamous cell carcinoma (30.51%), being able potentially to re-establish sensory innervation in oral cavity. The assessment of risk bias (National Institutes of Health) highlights the lack of uniformity, with no standardisation of the outcome variable collection and monitoring.DISCUSSION: By virtue of its versatility, reliable vascular supply and high flap survival rate, the DIEP flap reconstruction could be an option in complicated 3-dimensional head and neck defects while maintaining the standard of low donor site morbidity.
|
|
| 4. |
|
|
| 5. |
- Andres-Martin, Miguel, et al.
(författare)
-
Uncertainty in surface wind speed projections over the Iberian Peninsula: CMIP6 GCMs versus a WRF-RCM
- 2023
-
Ingår i: Annals of the New York Academy of Sciences. - 0077-8923 .- 1749-6632. ; 1529:1, s. 101-108
-
Tidskriftsartikel (refereegranskat)abstract
- This study assessed the projected near-surface wind speed (SWS) changes and variability over the Iberian Peninsula for the 21st century. Here, we compared Coupled Model Intercomparison Project Phase 6 global climate models (GCMs) with a higher spatial resolution regional climate model (RCM; ∼20km), known as WRF-CESM2, which was created by a dynamic downscaling of the Community Earth System Model version 2 (CESM2) using the Weather Research and Forecasting (WRF) model. Our analysis found that the GCMs tended to overestimate observed SWS for 1985–2014, while the higher spatial resolution of the WRF-CESM2 did not improve the accuracy and underestimated the SWS magnitude. GCMs project a decline of SWS under highshared socioeconomic pathways (SSPs) greenhouse concentrations, such as SSP370 and SSP585, while an interdecadal oscillation appears in SSP126 and SSP245 for the end of the century. The WRF-CESM2 under SSP585 predicts the opposite increasing SWS. Our results suggest that 21st-century projections of SWS are uncertain even for regionalized products and should be taken with caution.
|
|
| 6. |
- Artiach, Gonzalo, et al.
(författare)
-
Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease through the Resolvin E1 and ChemR23 Axis.
- 2020
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 142, s. 776-789
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in cardiovascular prevention have been recently demonstrated in a large randomized controlled trial. In addition, n-3 PUFA serve as the substrate for the synthesis of specialized pro-resolving mediators (SPMs), which are known by their potent beneficial anti-inflammatory, pro-resolving and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and SPMs on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA-derived SPMs in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe-/- mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in non-calcified regions compared with calcified regions. LC-MS-MS based lipid mediator lipidomics identified that the n-3 PUFA-derived SPM resolvin E1 (RvE1) was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe-/- mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1tgxApoe-/-), which enables the endogenous synthesis of n-3 PUFA, increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization and improved echocardiographic parameters. Finally, abrogation of the RvE1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived RvE1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression, and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.
|
|
| 7. |
- Azorin-Molina, Cesar, et al.
(författare)
-
Biases in wind speed measurements due to anemometer changes
- 2023
-
Ingår i: Atmospheric Research. - 0169-8095. ; 289
-
Tidskriftsartikel (refereegranskat)abstract
- This research presents a case study of the biases and discontinuities that were introduced in observed long-term mean wind-speed and gust data-series due to anemometer changes in a meteorological station in northern Spain, operated by the Spanish State Meteorological Agency: San Sebastian-Igueldo. Field and wind-tunnel experiments with predefined conditions have been presented in the literature, however this research uses a real case study to assess the impact of anemometer changes on wind speed measurements due to three factors being: (i) the 3-cup anemometer model (SEAC vs. THIES companies); (ii) sensor height (∼19.95 m vs. ∼20.45 m) and (iii) sensor age (20-years old vs. new). Our results show (a) substantial biases in the measured wind speed and daily peak wind gusts, with the new THIES anemometer reporting stronger surface winds than the old SEAC anemometer; (b) opposing biases under weak (negative) and moderate-strong (positive) winds; and (c) significant breakpoints in the long-term wind data-series, which highlight the importance of data homogenization. National Weather Services and climate assessment groups will benefit from these findings since errors in wind speed and gust measurements can be minimized by implementing systematic observation protocols. Robust anemometer observations provide a basis for accurate quantification of the magnitude of changes and the variability of surface winds.
|
|
| 8. |
- Brito-Zerón, Pilar, et al.
(författare)
-
Mortality risk factors in primary Sjögren syndrome : a real-world, retrospective, cohort study
- 2023
-
Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 61
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundWhat baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.MethodsIn this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.FindingsBetween January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27–2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22–2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01–1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22–1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16–2) were independent predictors of SjS-related death.InterpretationThe key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.
|
|
| 9. |
|
|
| 10. |
- Faux, Pierre, et al.
(författare)
-
Neanderthal introgression in SCN9A impacts mechanical pain sensitivity
- 2023
-
Ingår i: Communications Biology. - 2399-3642. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of similar to 123kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function. Neanderthal-derived variants in the SCN9A gene (encoding the voltage gated sodium channel, Nav1.7) are associated with enhanced experimental mechanical pain sensitivity in modern humans.
|
|
