| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Kunnus, Kristjan, et al.
(författare)
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Vibrational wavepacket dynamics in Fe carbene photosensitizer determined with femtosecond X-ray emission and scattering
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The non-equilibrium dynamics of electrons and nuclei govern the function of photoactive materials. Disentangling these dynamics remains a critical goal for understanding photoactive materials. Here we investigate the photoinduced dynamics of the [Fe(bmip)2]2+ photosensitizer, where bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)-pyridine, with simultaneous femtosecond-resolution Fe Kα and Kβ X-ray emission spectroscopy (XES) and X-ray solution scattering (XSS). This measurement shows temporal oscillations in the XES and XSS difference signals with the same 278 fs period oscillation. These oscillations originate from an Fe-ligand stretching vibrational wavepacket on a triplet metal-centered (3MC) excited state surface. This 3MC state is populated with a 110 fs time constant by 40% of the excited molecules while the rest relax to a 3MLCT excited state. The sensitivity of the Kα XES to molecular structure results from a 0.7% average Fe-ligand bond length shift between the 1 s and 2p core-ionized states surfaces.
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| 3. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 4. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 5. |
- Ambrozic, A, et al.
(författare)
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Corrigendum
- 2017
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Ingår i: Journal of thrombosis and haemostasis : JTH. - : Elsevier BV. - 1538-7836. ; 15:6, s. 1236-1236
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Adhikari, Subash, et al.
(författare)
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A high-stringency blueprint of the human proteome
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 10. |
- Corona, Giovanni, et al.
(författare)
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Age-Related Changes in General and Sexual Health in Middle-Aged and Older Men: Results from the European Male Ageing Study (EMAS)
- 2010
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 7:4, s. 1362-1380
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Limited information is available concerning the general and sexual health status of European men. Aim. To investigate the age-related changes in general and sexual health in middle-aged and older men from different countries of the European Union. Methods. This is a cross-sectional multicenter survey performed on a sample of 3,369 community-dwelling men aged 40-79 years old (mean 60 +/- 11 years). Subjects were randomly selected from eight European centers including centers from nontransitional (Florence [Italy], Leuven [Belgium], Malmo [Sweden], Manchester [United Kingdom], Santiago de Compostela [Spain]) and transitional countries (Lodz [Poland], Szeged [Hungary], Tartu [Estonia]). Main Outcome Measures. Different parameters were evaluated including the Beck's Depression Inventory for the quantification of depressive symptoms, the Short Form-36 Health Survey for the assessment of the quality of life (QoL), the International Prostate Symptom Score for the evaluation of lower urinary tract symptoms, and the European Male Ageing Study sexual function questionnaire for the study of sexual function. Results. More than 50% of subjects reported the presence of one or more common morbidities. Overall, hypertension (29%), obesity (24%), and heart diseases (16%) were the most prevalent conditions. Around 30% of men reported erectile dysfunction (ED) and 6% reported severe orgasmic impairment, both of which were closely associated with age and concomitant morbidities. Only 38% of men reporting ED were concerned about it. Furthermore, concern about ED increased with age, peaking in the 50-59 years age band, but decreased thereafter. Men in transitional countries reported a higher prevalence of morbidities and impairment of sexual function as well as a lower QoL. Conclusion. Sexual health declined while concomitant morbidities increased in European men as a function of age. The burden of general and sexual health is higher in transitional countries, emphasizing the need to develop more effective strategies to promote healthy aging for men in these countries. Corona G, Lee DM, Forti G, O'Connor DB, Maggi M, O'Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, Finn JD, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean MEJ, Punab M, Silman AJ, Vanderschueren D, Wu FCW, and EMAS Study Group. Age-related changes in general and sexual health in middle-aged and older men: Results from the European Male Ageing Study (EMAS). J Sex Med 2010;7:1362-1380.
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| 11. |
- Hantal, Gyorgy, et al.
(författare)
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Counterion and surface density dependence of the adsorption layer of ionic surfactants at the vapor-aqueous solution interface : A computer simulation study
- 2007
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 111:7, s. 1769-1774
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Tidskriftsartikel (refereegranskat)abstract
- To test the validity of currently used adsorption theories and understand the origin of the lack of their ability of adequately describing existing surface tension measurement data, we have performed a series of molecular dynamics simulations of the adsorption layer of alkali decyl sulfate at the vapor/aqueous solution interface. The simulations have been performed with five different cations (i.e., Li(+), Na(+), K(+), Rb(+), and Cs(+)) at two different surface concentrations (i.e., 2 mu mol/m(2) and 4 mu mol/m(2)). The obtained results clearly show that the thickness of the outer Helmholtz plate, a key quantity of the various adsorption theories, depends on two parameters, that is, the size of the cations and the surface density of the anionic surfactant. Namely, with increasing surface concentration, the electrostatic attraction between the two, oppositely charged, layers becomes stronger, leading to a considerable shrinking of the outer Helmholtz plate. Furthermore, this layer is found to be thicker in the presence of larger cations. The former effect could be important in understanding the anomalous shape of the adsorption isotherms of alkali alkyl sulfate surfactants, while the second effect seems to be essential in explaining the cation specificity of these isotherms.
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| 12. |
- Ivell, Richard, et al.
(författare)
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The Leydig cell biomarker INSL3 as a predictor of age-related morbidity : Findings from the EMAS cohort
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like peptide 3 (INSL3) is a constitutive hormone secreted in men by the mature Leydig cells of the testes. It is an accurate biomarker for Leydig cell functional capacity, reflecting their total cell number and differentiation status. Objectives: To determine the ability of INSL3 to predict hypogonadism and age-related morbidity using the EMAS cohort of older community-dwelling men. Materials & methods: Circulating INSL3 was assessed in the EMAS cohort and its cross-sectional and longitudinal relationships to hypogonadism, here defined by testosterone (T) <10.5nmol/l, and a range of age-related morbidities determined by correlation and regression analysis. Results & discussion: While INSL3 is an accurate measure of primary hypogonadism, secondary and compensated hypogonadism also indicate reduced levels of INSL3, implying that testicular hypogonadism does not improve even when LH levels are increased, and that ageing-related hypogonadism may combine both primary and secondary features. Unadjusted, serum INSL3, like calculated free testosterone (cFT), LH, or the T/LH ratio reflects hypogonadal status and is associated with reduced sexual function, bone mineral density, and physical activity, as well as increased occurrence of hypertension, cardiovascular disease, cancer, and diabetes. Using multiple regression analysis to adjust for a range of hormonal, anthropometric, and lifestyle factors, this relationship is lost for all morbidities, except for reduced bone mineral density, implying that INSL3 and/or its specific receptor, RXFP2, may be causally involved in promoting healthy bone metabolism. Elevated INSL3 also associates with hypertension and cardiovascular disease. When unadjusted, INSL3 in phase 1 of the EMAS study was assessed for its association with morbidity in phase 2 (mean 4.3 years later); INSL3 significantly predicts 7 out of 9 morbidity categories, behaving as well as cFT in this regard. In contrast, total T was predictive in only 3 of the 9 categories. Conclusion: Together with its low within-individual variance, these findings suggest that assessing INSL3 in men could offer important insight into the later development of disease in the elderly.
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| 13. |
- Lee, David M., et al.
(författare)
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Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men
- 2009
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:7, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although there is evidence that vitamin D inadequacy may be linked to adverse cognitive outcomes, results from studies on this topic have been inconsistent. The aim of this trial was to examine the association between 25-hydroxyvitamin D (25(OH) D) levels and cognitive performance in middle-aged and older European men. Methods: This population-based cross-sectional study included 3,369 men aged 40-79 years from eight centres enrolled in the European Male Ageing Study. Cognitive function was assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Camden Topographical Recognition Memory (CTRM) test and the Digit Symbol Substitution Test (DSST). Serum 25(OH) D levels were measured by radioimmunoassay. Additional assessments included measurement of physical activity, functional performance and mood/depression. Associations between cognitive function and 25(OH) D levels were explored using locally weighted and linear regression models. Results: In total, 3,133 men (mean (+/- SD) age 60 +/- 11 years) were included in the analysis. The mean (+/- SD) 25(OH) D concentration was 63 +/- 31 nmol/l. In age-adjusted linear regressions, high levels of 25(OH) D were associated with high scores on the copy component of the ROCF test (beta per 10 nmol/l = 0.096; 95% CI 0.049 to 0.144), the CTRM test (beta per 10 nmol/l= 0.075; 95% CI 0.026 to 0.124) and the DSST (beta per 10 nmol/l = 0.318; 95% CI 0.235 to 0.401). After adjusting for additional confounders, 25(OH) D levels were associated with only score on the DSST (beta per 10 nmol/l = 0.152; 95% CI 0.051 to 0.253). Locally weighted and spline regressions suggested the relationship between 25(OH) D concentration and cognitive function was most pronounced at 25(OH) D concentrations below 35 nmol/l. Conclusion: In this study, lower 25(OH) D levels were associated with poorer performance on the DSST. Further research is warranted to determine whether vitamin D sufficiency might have a role in preserving cognitive function in older adults.
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| 14. |
- Lee, David M., et al.
(författare)
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Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study
- 2010
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 162:6, s. 1155-1164
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Data remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men. Design: Community-based, cross-sectional study of 3369 men aged 40-79 years. Methods: Cognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE2) and 5 alpha-dihydrotestosterone were measured by gas chromatography-mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE2 were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping. Results: Total testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (beta=-0.011, P=0.02), although this was driven by subjects with DHEAS levels > 10 mu mol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (beta=-0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones. Conclusion: Our results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether 'high' DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.
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| 15. |
- Lee, David M., et al.
(författare)
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Lower vitamin D levels are associated with depression among community-dwelling European men
- 2011
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 25:10, s. 1320-1328
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Tidskriftsartikel (refereegranskat)abstract
- Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) Levels have been linked with depressive symptoms among adults in various clinical settings. Data in generally healthy, community-dwelling individuals remain inconclusive. We investigated whether depression was associated with 25(OH)D and/or PTH in a sample of middle-aged and older men (n = 3369; mean age 60 +/- 11) participating in the European Male Ageing Study, and whether any associations were explained by lifestyle and health factors. The Beck Depression Inventory-II (BDI-II) was used to screen for depression, and serum 25(OH)D and PTH levels measured by radioimmunoassay. Univariate analysis revealed that 25(OH)D levels were lower (p < 0.001) and PTH higher (p = 0.004) in people with depression. In age- and centre-adjusted linear regressions a higher BDI-II score was significantly associated with tower levels of 25(OH)D (p = 0.004). After adjustment for lifestyle and health factors this relationship was attenuated but remained significant (p = 0.01). Using multivariable logistic regression the odds for depression increased approximately 70% across decreasing 25(OH)D quartiles (p(trend) = 0.04). There was no independent association between PIN and depression in any of the muttivariable regressions. Our results reveal an inverse association between 25(OH)D levels and depression, largely independent of several lifestyle and health factors. Further studies are required to determine whether higher levels of vitamin D have an antidepressant effect in older adults.
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| 16. |
- Lee, David M., et al.
(författare)
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The association between different cognitive domains and age in a multi-centre study of middle-aged and older European men
- 2009
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 24:11, s. 1257-1266
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We determined levels of cognitive functioning in community dwelling men aged 40-79 (n = 3265) from eight European centres and investigated to what extent cognitive performance varied between centres, the association between different cognitive domains and age, educational level, co-morbidity and lifestyle factors and the respective contributions of centre and individual factors to cognitive performance. Methods Cognitive domains assessed were visuo-constructional ability and Visual memory (Rey-Osterrieth Complex Figure test, ROCF), topographical memory (Camden Topographical Recognition Memory test, CTRM) and processing speed (Digit-Symbol Substitution test, DSST). Results There were significant between-centre differences in all four cognitive test scores. Using multilevel linear regression analysis (MLRA), age, education, depression, physical performance and smoking were independent predictors of cognitive function and these variables explained 10-13% of the variation in cognitive scores between centres and 17-36% of the variation in scores between individuals within centres. Conclusion Our data suggest that although a proportion of the variance in cognitive function among European men is explained by individual level differences, a significant proportion is due to contextual phenomenon. Such contextual factors need to be considered when analysing multi-centre data and European men should not be treated as homogeneous when assessing cognitive performance using existing instruments. Copyright (C) 2009 John Wiley & Sons, Ltd.
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| 17. |
- Megyesfalvi, Zsolt, et al.
(författare)
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Unfolding the secrets of small cell lung cancer progression : Novel approaches and insights through rapid autopsies
- 2023
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Ingår i: Cancer Cell. - 1535-6108. ; 41:9, s. 1535-1540
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Tidskriftsartikel (refereegranskat)abstract
- The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.
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| 18. |
- O'Connor, Daryl B, et al.
(författare)
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Assessment of sexual health in aging men in Europe: Development and validation of the European Male Ageing Study sexual function questionnaire
- 2008
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 5:6, s. 1374-1385
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Assessment of male sexual dysfunction has been the focus of substantial scientific effort. Less research has focused on the development of instruments for the measurement of sexual functioning in aging men. Aim. The aims of this study were: (i) to characterize the psychometric properties of a new brief, reliable, and valid measure of male sexual functioning for use in a large population survey of middle-aged and elderly European men; and (ii) specifically, to determine whether the new instrument, the European Male Ageing Study-sexual function questionnaire (EMAS-SFQ), discriminates between men with high and low levels of circulating testosterone (T) (total T, free T, and bioavailable T). Method. One thousand six hundred men aged 40-79 years completed the self-administered EMAS-SFQ, the Beck depression inventory, and provided a blood sample for assessment of sex hormones. Eighty-five men aged 35-74 years completed the EMAS-SFQ twice, 2 weeks apart to examine the test-retest reliability of the instrument. Main Outcome Measures. Scores on the EMAS-SFQ in relation to age and T levels. Results. Principal component analysis showed that the EMAS-SFQ had four distinct domains (overall sexual functioning [OSF], masturbation, sexual functioning-related distress, and change in sexual functioning). The instrument demonstrated excellent internal and test-retest reliability, as well as convergent, divergent, and discriminant validity. Men with the lowest levels of total, free, and bioavailable T reported lower OSF scores compared to men with the highest T levels. Conclusion. The EMAS-SFQ is a valid and reproducible instrument, sensitive to age and T levels. It should be suitable for the assessment of sexual health in population samples of men in epidemiological studies of aging.
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| 19. |
- O'Connor, Daryl B, et al.
(författare)
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The Relationships between Sex Hormones and Sexual Function in Middle-Aged and Older European Men.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96, s. 1577-1587
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Tidskriftsartikel (refereegranskat)abstract
- Context: Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe. Objectives: The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men. Design: Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry. Setting: We conducted a community-based population survey in eight European centers. Main Outcome Measures: Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Results: Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau. Conclusions: These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.
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| 20. |
- Tajar, Abdelouahid, et al.
(författare)
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The Effect of Musculoskeletal Pain on Sexual Function in Middle-aged and Elderly European Men: Results from the European Male Ageing Study.
- 2011
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 38, s. 370-377
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether musculoskeletal pain was associated with impaired sexual function in a population sample of middle-aged and older men. METHODS: The European Male Ageing Study (EMAS), a multicenter population-based study of men aged 40-79 years, was used to investigate this hypothesis. A questionnaire asked about the presence and duration of musculoskeletal pain, allowing subjects to be classified into 1 of 3 groups: those reporting chronic widespread pain (CWP), those reporting pain but not CWP ("some pain"), and those with no pain. Subjects completed a sexual function questionnaire from which 3 domains were considered: overall sexual functioning (OSF), sexual functioning-related distress (SFD), and change in sexual functioning compared to 1 year ago (CSF). RESULTS: A total of 3206 men [mean age 60 (SD 11) yrs] had complete data on pain status. Of these, 8.7% had CWP and 50.34% had "some pain." Pain was associated with lower OSF, and higher SFD and CSF scores. After adjustment for putative confounding factors, the associations became non-significant with OSF and CSF but persisted for SFD. Associations between pain status and some items within the sexual functioning domains, including frequency of sexual intercourse, frequency of morning erections, sexual desire, and orgasm were also significant, although these associations varied by pain status. CONCLUSION: Musculoskeletal pain is associated with several aspects of sexual functioning. These relationships differ depending on the extent of the pain (chronic or not) and are also largely confounded by other health-related factors, primarily depression.
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| 21. |
- Tournoy, Jos, et al.
(författare)
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Association of cognitive performance with the metabolic syndrome and with glycaemia in middle-aged and older European men: the European Male Ageing Study
- 2010
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Ingår i: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552. ; 26:8, s. 668-676
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims Metabolic syndrome has been reported to have adverse effects on cognition although the results are conflicting. We investigated the association between metabolic syndrome and cognitive function in a population sample of middle-aged and older European men and whether any observed association could be explained by lifestyle or other confounding factors. Methods A total of 3369 men in the 40-to 79-year age group were recruited from population registers in eight centres for participation in the European Male Ageing Study. The subjects completed a questionnaire instrument and several cognitive function tests including the Rey-Osterrieth Complex Figure test, the Camden Topographical Recognition Memory test and the Digit Symbol Substitution Test. Metabolic syndrome data were assessed at an invited visit and metabolic syndrome was defined by the National Cholesterol Education Program's Adult Treatment Panel-III criteria. Associations between cognitive performance and metabolic syndrome were explored using linear regression. Results Complete cognitive and metabolic syndrome data from 3152 subjects were included in the analysis, of whom 1007 (32%) fulfilled criteria for metabolic syndrome. After adjustment for putative health and lifestyle con-founders, no significant associations were found between any of the cognitive function scores and metabolic syndrome or between cognitive performance and high-sensitivity C-reactive protein. Analysis of the individual metabolic syndrome factors, however, revealed an inverse association between the level of glucose and cognitive performance. Conclusions Metabolic syndrome was not associated with cognitive impairment in this population. Of the individual components of the syndrome, diabetes was associated with poorer performances in memory, executive functions and processing speed, associations that warrant further investigation. Copyright (C) 2010 John Wiley & Sons, Ltd.
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| 22. |
- Vallejo-Vaz, Antonio J., et al.
(författare)
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Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
- 2018
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Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 277, s. 234-255
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in similar to 2/3 countries. Lipoprotein-apheresis is offered in similar to 60% countries, although access is limited. Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.
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| 23. |
- van Zuydam, NR, et al.
(författare)
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A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
- 2018
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 67:7, s. 1414-1427
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Tidskriftsartikel (refereegranskat)abstract
- Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10−8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
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| 24. |
- Vialas, Vital, et al.
(författare)
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A multicentric study to evaluate the use of relative retention times in targeted proteomics
- 2017
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 152, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. Biological significance From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.
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| 25. |
- Wan, Guihong, et al.
(författare)
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Development and validation of time-to-event models to predict metastatic recurrence of localized cutaneous melanoma
- 2024
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Ingår i: Journal of the American Academy of Dermatology. - 0190-9622. ; 90:2, s. 288-298
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. Objective: To develop time-to-event risk prediction models for melanoma metastatic recurrence. Methods: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. Results: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. Limitations: Retrospective nature and cohort from one geography. Conclusions: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.
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