18 research outputs found

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

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    Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    The Built Environment, Physical Activity, and Aging in the United States: A State of the Science Review

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    The article focuses on physical activity guidelines for older people in the U.S., and how built environment can affect health-related behavior. It is stated that physical activity offers several benefits for older adults, including preservation of muscle and bone mass, improving glucose control, cardiovascular health, and stability. It is stated that increasing physical activity is necessary to support successful aging, which includes reducing the chances of diseases

    Family burden of hospital-managed pediatric atopic dermatitis: a nationwide registry-based study

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    International audienceBACKGROUND: Parents of children with atopic dermatitis (AD) report reduced quality of life and higher stress level, which could increase risk of psychiatric and pain disorders, and medication use. METHODS: By use of Danish national registries, we identified family members of all first-born Danish children born between January 1(st) , 1995 and December 31(st) , 2013 with a hospital diagnosis of AD, matched them 1:10 with family members of children without AD, and followed the cohorts over time. RESULTS: Mothers of children with hospital-managed AD had higher risk of filling a prescription for medications for depression, anxiety, pain and sleep problems, and of consulting a psychologist, but most associations disappeared after full adjustment. Siblings had higher risk of receiving a diagnosis for adjustment disorder, and fathers showed increased risk of filling a prescription for pain medication and of divorce, in crude but not adjusted models. CONCLUSIONS: The increased risk of study endpoints seen in mothers of children with hospital-managed AD was not explained by pediatric AD alone. Rather, the total burden in these families including parent and child morbidity and socioeconomic resources seem to explain these observations. The burden in families of children with AD may potentially affect the overall management of their child’s AD

    Atopic dermatitis in the pediatric population: A cross-sectional, international epidemiologic study

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    © 2021 The Authors Background: Little is known on the current global prevalence of atopic dermatitis (AD) in the pediatric population. Objective: To estimate the real-world global prevalence of AD in the pediatric population and by disease severity. Methods: This international, cross-sectional, web-based survey of children and adolescents (6 months to \u3c18 years old) was conducted in the following 18 countries: North America (Canada, United States), Latin America (Argentina, Brazil, Columbia, Mexico), Europe (France, Germany, Italy, Spain, United Kingdom), Middle East and Eurasia (Israel, Saudi Arabia, Turkey, United Arab Emirates, Russia), and East Asia (Japan, Taiwan). Prevalence was determined using the following 2 definitions: (1) diagnosed as having AD according to the International Study of Asthma and Allergies in Childhood (ISAAC) criteria and self- or parent-report of ever being told by a physician that they or their child child had AD (eczema); and (2) reported AD based on the ISAAC criteria only. Severity was assessed using the Patient Global Assessment (PtGA) and Patient-Oriented Eczema Measure (POEM). Results: Among 65,661 responders, the 12-month diagnosed AD prevalence (ISAAC plus self-reported diagnosis) ranged from 2.7% to 20.1% across countries; reported AD (ISAAC only) was 13.5% to 41.9%. Severe AD evaluated with both PtGA and POEM was generally less than 15%; more subjects rated AD as mild on PtGA than suggested by POEM. No trends in prevalence were observed based on age or sex; prevalence was generally lower in rural residential settings than urban or suburban. Conclusion: This global survey in 18 countries revealed that AD affects a substantial proportion of the pediatric population. Although prevalence and severity varied across age groups and countries, less than 15% had severe AD
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