| 1. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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- Guintivano, Jerry, et al.
(författare)
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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
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| 4. |
- Lebedev, A. V., et al.
(författare)
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Psychedelic drug use and schizotypy in young adults
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n=1032) with a special focus on young (18-35 years) and healthy individuals (n=701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n=39). We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen's d=0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen's d=0.13) and a higher sensitivity of fear responses (Cohen's d=1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance. Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.
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- El Khoury, A, et al.
(författare)
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Decreased plasma prolactin release in euthymic lithium-treated women with bipolar disorder
- 2003
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 48:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- In order to evaluate the effect of treatment with citalopram (CIT) and lithium (Li) on hormone levels in women with bipolar disorder, morning plasma prolactin (PRL) and cortisol (CORT) were measured in 14 nonmedicated depressed patients, 13 depressed patients responding to CIT treatment, 17 euthymic patients on long-term Li treatment, and 11 healthy controls. Plasma PRL values in the Li group were significantly lower than those of the three other groups, suggesting a net inhibitory impact of augmentative effects of Li on dopaminergic activity and serotonergic neurotransmission in the central nervous system. Plasma CORT values in nonmedicated depressed patients were significantly higher than those of healthy controls, indicating hyperactivity of the hypothalamic-pituitary-adrenal system in depression, which appears to be a state-dependent phenomenon, and is normalized upon successful treatment with Li and CIT.
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- Karlen, A, et al.
(författare)
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Nogo receptor 1 regulates formation of lasting memories
- 2009
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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. ; 106:48, s. 20476-20481
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Tidskriftsartikel (refereegranskat)abstract
- Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked to memory formation and storage, and postulated this to be required for formation of lasting memories. We now show that mice with inducible overexpression of NgR1 in forebrain neurons have normal long-term potentiation and normal 24-h memory, but severely impaired month-long memory in both passive avoidance and swim maze tests. Blocking transgene expression normalizes these memory impairments. Nogo, Lingo-1, Troy, endogenous NgR1, and BDNF mRNA expression levels were not altered by transgene expression, suggesting that the impaired ability to form lasting memories is directly coupled to inability to down-regulate NgR1. Regulation of NgR1 may therefore serve as a key regulator of memory consolidation. Understanding the molecular underpinnings of synaptic rearrangements that carry lasting memories may facilitate development of treatments for memory dysfunction.
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| 21. |
- Hugoson, Anders, et al.
(författare)
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Caries prevalence and distribution in 3-20-year-olds in Jönköping, Sweden, in 1973, 1978, 1983, and 1993.
- 2000
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Ingår i: Community Dentistry and Oral Epidemiology. - 0301-5661 .- 1600-0528. ; 28:2, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- Four cross-sectional studies were carried out in 1973, 1978, 1983, and 1993 to collect clinical and radiographic epidemiological data on the dental health status of the inhabitants of Jönköping, Sweden. The aim of the present paper was to use these data to analyze trends in the development of caries among children and adolescents between 1973 and 1993. Approximately 500 randomly selected individuals evenly distributed among the age groups 3, 5, 10, 15, and 20 years participated in each study. The main results show that the numbers of caries-free individuals increased in all age groups. In 1993, the mean number of decayed and filled tooth surfaces in the primary (dfs) and the permanent (DFS) dentition in all age groups was less than half of that found in 1973. Most of this decrease took place during the first 5 years, i.e., between 1973 and 1978. Between 1978 and 1983, only minor changes were observed. There was a further reduction of approximately 30%-50% in dfs/DFS between 1983 and 1993 in 3-, 5-, 10-, and 20-year-olds. The frequency distributions of dfs/DFS for 5- and 15-year-olds revealed an increasing skewness over time: in 1993, a large majority of the children and adolescents had a low or moderate caries severity while only a small group had high scores of dfs/DFS.
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| 35. |
- Aberg, B, et al.
(författare)
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Delayed left ventricular free wall rupture complicating coronary artery bypass surgery. A case report.
- 1985
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Ingår i: Scandinavian journal of thoracic and cardiovascular surgery. - : Informa UK Limited. - 0036-5580. ; 19:3, s. 273-7
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Tidskriftsartikel (refereegranskat)abstract
- Rupture of the left ventricular free wall is a not uncommon life-threatening complication of acute myocardial infarction and after prosthetic mitral valve replacement. To our knowledge, no case of left ventricular rupture after coronary artery bypass surgery has been reported. A case is now described in which coronary artery bypass grafting was complicated by delayed rupture, which was successfully repaired. Different etiologic factors are discussed, but the cause considered most likely was trauma from elevation of and traction on the heart in exposure of its posterior aspect.
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| 36. |
- Aberg, D, et al.
(författare)
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Implantation temperature dependent deep level defects in 4H-SiC
- 2001
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Ingår i: Materials Science Forum, Vols. 353-356. ; , s. 443-446
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Konferensbidrag (refereegranskat)abstract
- Deep level transient spectroscopy spectra of the near Z-defect region (150-350K) were investigated for B implanted samples of low doses (10(8)-10(9) cm(-2)). For 300 degreesC implantation, a level at an energy of 0.41 eV below the conduction hand edge was found, referred to as the S-level. The S-center was shown to form in both implanted and electron irradiated 4H-SiC, either after room temperature (R.T.) implantation followed by mild heat treatments or lung R.T. storage (several months) or after 200-300 degreesC implantations/irradiations. The S-center was found to anneal out at temperatures above 250 degreesC.
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- Balocco, C, et al.
(författare)
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Microwave detection at 110 GHz by nanowires with broken symmetry
- 2005
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 5:7, s. 1423-1427
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Tidskriftsartikel (refereegranskat)abstract
- By using arrays of nanowires with intentionally broken symmetry, we were able to detect microwaves up to 110 GHz at room temperature. This is, to the best of our knowledge, the highest speed that has been demonstrated in different types of novel electronic nanostructures to date. Our experiments showed a rather stable detection sensitivity over a broad frequency range from 100 MHz to 110 GHz. The novel working principle enabled the nanowires to detect microwaves efficiently without a dc bias. In principle, the need for only one high-resolution lithography step and the planar architecture allow an arbitrary number of nanowires to be made by folding a linear array as many times as required over a large area, for example, a whole wafer. Our experiment on 18 parallel nanowires showed a sensitivity of approximately 75 mV dc output/mW of nominal input power of the 110 GHz signal, even though only about 0.4% of the rf power was effectively applied to the structure because of an impedance mismatch. Because this array of nanowires operates simultaneously, low detection noise was achieved, allowing us to detect -25 dBm 110 GHz microwaves at zero bias with a standard setup.
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| 50. |
- Bender, Michael, et al.
(författare)
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Future of nuclear fission theory
- 2020
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:11
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Forskningsöversikt (refereegranskat)abstract
- There has been much recent interest in nuclear fission, due in part to a new appreciation of its relevance to astrophysics, stability of superheavy elements, and fundamental theory of neutrino interactions. At the same time, there have been important developments on a conceptual and computational level for the theory. The promising new theoretical avenues were the subject of a workshop held at the University of York in October 2019; this report summarises its findings and recommendations.
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