| 1. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 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. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 2. |
- Malloch, Margaret, et al.
(författare)
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Vocational Education andTraining in Cuba : A Process ofChanges Towards Learning inthe Workplace
- 2010
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Ingår i: The SAGE Handbook of Learning and Work. - : Sage Publications. - 9781446248416
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Bokkapitel (refereegranskat)abstract
- Cuba, a country with an estimated populationof 11,326,616 inhabitants (Worldometer,2020), which has been ruled by a one-partysystemsince 1959, and whose developmenthas been marked by a trade embargo imposedby the United States since 1960 and the fallof the Soviet Union in 1991 (Binns,1996) isarguably a land of contradictions and of significantpolitical polarization. Standpointstowards Cuban society are often mediated byindividual political positions and consequentlydiffer.The very word, Cuba, conjures images ofclassic American cars, faded colonial mansions,colorful music and dancing, lush greenfields, and cigars and rum. Looking deeper,this country, which has experienced colonialrule, revolution and economic isolation,remains resilient and innovative. The threeheroes, José Martí, Fidel Castro and ErnestoChe Guevara, have influenced the values ofthe Cuba of today.This is particularly evident in education. From their speeches, and especiallythose of Martí, the theme of educationis that it is the only means to be saved fromslavery (Chávez Rodríguez, 2011). Between1959 and 1961, the structure of ‘a national,coherent and harmonious school system’(Chávez Rodríguez, 2011, p.45) was established,reinforced by the Declaration of Cubaas a Territory Free of Illiteracy in 1961. Thiswas the beginning of the establishment of asocialist education.The accomplishments of the Cuban educationsystem are widely acknowledged internationally(Wolf, Hernández Penton, Beltrán& Romero, 2011). Education became a corestrategic priority in the policies of the revolutionarygovernment that came to power in1959 and continued as a priority until thepresent time (2020). The literacy campaignof 1961 laid the foundations of the subsequenteducational development of the country(López, 2011). Cuba is also recognizedfor its inclusive and free education system(Breidlid, 2007).
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| 3. |
- Peterlongo, Paolo, et al.
(författare)
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FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5345-5355
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Tidskriftsartikel (refereegranskat)abstract
- Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.
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