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| 2. |
- Avdic, H. B., et al.
(författare)
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Reduced effects of social feedback on learning in Turner syndrome
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Turner syndrome is a genetic condition caused by a complete or partial loss of one of the X chromosomes. Previous studies indicate that Turner syndrome is associated with challenges in social skills, but the underlying mechanisms remain largely unexplored. A possible mechanism is a reduced social influence on learning. The current study examined the impact of social and non-social feedback on learning in women with Turner syndrome (n=35) and a sex- and age-matched control group (n=37). Participants were instructed to earn points by repeatedly choosing between two stimuli with unequal probabilities of resulting in a reward. Mastering the task therefore required participants to learn through feedback which of the two stimuli was more likely to be rewarded. Data were analyzed using computational modeling and analyses of choice behavior. Social feedback led to a more explorative choice behavior in the control group, resulting in reduced learning compared to non-social feedback. No effects of social feedback on learning were found in Turner syndrome. The current study thus indicates that women with Turner syndrome may be less sensitive to social influences on reinforcement learning, than the general population.
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| 3. |
- Carter, Megan, et al.
(författare)
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Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Deregulated redox metabolism in cancer leads to oxidative damage to cellular components including deoxyribonucleoside triphosphates (dNTPs). Targeting dNTP pool sanitizing enzymes, such as MTH1, is a highly promising anticancer strategy. The MTH2 protein, known as NUDT15, is described as the second human homologue of bacterial MutT with 8-oxo-dGTPase activity. We present the first NUDT15 crystal structure and demonstrate that NUDT15 prefers other nucleotide substrates over 8-oxo-dGTP. Key structural features are identified that explain different substrate preferences for NUDT15 and MTH1. We find that depletion of NUDT15 has no effect on incorporation of 8-oxo-dGTP into DNA and does not impact cancer cell survival in cell lines tested. NUDT17 and NUDT18 were also profiled and found to have far less activity than MTH1 against oxidized nucleotides. We show that NUDT15 is not a biologically relevant 8-oxo-dGTPase, and that MTH1 is the most prominent sanitizer of the cellular dNTP pool known to date.
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| 4. |
- Ericsson, Malin, et al.
(författare)
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Childhood social class and cognitive aging in the Swedish Adoption/Twin Study of Aging
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:27, s. 7001-7006
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Tidskriftsartikel (refereegranskat)abstract
- In this report we analyzed genetically informative data to investigate within-person change and between-person differences in late-life cognitive abilities as a function of childhood social class. We used data from nine testing occasions spanning 28 y in the Swedish Adoption/Twin Study of Aging and parental social class based on the Swedish socioeconomic index. Cognitive ability included a general factor and the four domains of verbal, fluid, memory, and perceptual speed. Latent growth curve models of the longitudinal data tested whether level and change in cognitive performance differed as a function of childhood social class. Between-within twin-pair analyses were performed on twins reared apart to assess familial confounding. Childhood social class was significantly associated with mean-level cognitive performance at age 65 y, but not with rate of cognitive change. The association decreased in magnitude but remained significant after adjustments for level of education and the degree to which the rearing family was supportive toward education. A between-pair effect of childhood social class was significant in all cognitive domains, whereas within-pair estimates were attenuated, indicating genetic confounding. Thus, childhood social class is important for cognitive performance in adulthood on a population level, but the association is largely attributable to genetic influences.
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| 5. |
- Hagström, Hannes, et al.
(författare)
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Body composition measurements and risk of hematological malignancies : A population-based cohort study during 20 years of follow-up
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmo Diet and Cancer study conducted in Sweden between 1991-1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.
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| 6. |
- Haniffa, Muzlifah, et al.
(författare)
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A roadmap for the Human Developmental Cell Atlas
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597:7875, s. 196-205
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Tidskriftsartikel (refereegranskat)abstract
- This Perspective outlines the Human Developmental Cell Atlas initiative, which uses state-of-the-art technologies to map and model human development across gestation, and discusses the early milestones that have been achieved. The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.
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| 7. |
- Holmberg, Hans-Christer, et al.
(författare)
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Contribution of the legs to double-poling performance in elite cross-country skiers.
- 2006
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Ingår i: Medicine and science in sports and exercise. - : Ovid Technologies (Wolters Kluwer Health). - 0195-9131 .- 1530-0315. ; 38:10, s. 1853-60
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Tidskriftsartikel (refereegranskat)abstract
- In the classical style of cross-country skiing, the double-poling (DP) technique, which is regarded as an upper-body exercise, is used on the flatter parts of a course. Limited biomechanical and physiological data are available about DP compared with other cross-country skiing techniques. The purpose of the present study was to evaluate the possible role of the lower body during DP.Eleven elite cross-country skiers performed two incremental tests using DP roller skiing at 1 degree inclination on a treadmill with or without locking the knee and ankle joints (DPLOCKED and DPFREE). Maximal and peak oxygen uptake (VO2max and VO2peak) during classic diagonal skiing and DP, respectively, were measured. In addition, heart rate, blood lactate concentration, and maximal DP velocity (Vmax) were determined. Pole-ground reaction forces and joint angles (elbow, hip, knee, and ankle) were analyzed.The skiers obtained 7.7% higher VO2peak, 9.4% higher Vmax, and 11.7% longer time to exhaustion during DPFREE compared with DPLOCKED (all P < 0.05). There was a higher heart rate and blood lactate concentration in DPLOCKED at submaximal stages (all P < 0.05), with no difference in oxygen consumption. At 85% Vmax, corresponding to approximately 81% VO2peak FREE, the differences in physiological variables were accompanied by a 13.6% higher poling frequency, a 4.9% shorter poling phase, 13.3% shorter recovery phase, and 10.9% lower relative pole force in DPLOCKED (all P < 0.05).Movements of the knee and ankle joints are an integrative part in the skillful use of the DP technique, and restriction of the motion in these joints markedly affects both biomechanical and physiological variables, impairing DP performance.
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| 8. |
- Joling, Karlijn J., et al.
(författare)
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Quality indicators for community care for older people : A systematic review
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:1
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Forskningsöversikt (refereegranskat)abstract
- Background Health care systems that succeed in preventing long term care and hospital admissions of frail older people may substantially save on their public spending. The key might be found in high-quality care in the community. Quality Indicators (QIs) of a sufficient methodological level are a prerequisite to monitor, compare, and improve care quality. This systematic review identified existing QIs for community care for older people and assessed their methodological quality.Methods Relevant studies were identified by searches in electronic reference databases and selected by two reviewers independently. Eligible publications described the development or application of QIs to assess the quality of community care for older people. Information about the QIs, the study sample, and specific setting was extracted. The methodological quality of the QI sets was assessed with the Appraisal of Indicators through Research and Evaluation (AIRE) instrument. A score of 50% or higher on a domain was considered to indicate high methodological quality. Results Searches resulted in 25 included articles, describing 17 QI sets with 567 QIs. Most indicators referred to care processes (80%) and measured clinical issues (63%), mainly about follow-up, monitoring, examinations and treatment. About two-third of the QIs focussed on specific disease groups. The methodological quality of the indicator sets varied considerably. The highest overall level was achieved on the domain 'Additional evidence, formulation and usage' (51%), followed by 'Scientific evidence' (39%) and 'Stakeholder involvement' (28%).Conclusion A substantial number of QIs is available to assess the quality of community care for older people. However, generic QIs, measuring care outcomes and non-clinical aspects are relatively scarce and most QI sets do not meet standards of high methodological quality. This study can support policy makers and clinicians to navigate through a large number of QIs and select QIs for their purposes.
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| 9. |
- Järver, Peter, et al.
(författare)
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Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream ofTLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
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| 10. |
- Kirvalidze, Mariam, et al.
(författare)
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Estimating pairwise overlap in umbrella reviews : Considerations for using the corrected covered area (CCA) index methodology
- 2023
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Ingår i: Research Synthesis Methods. - : John Wiley & Sons. - 1759-2879 .- 1759-2887. ; 14:5, s. 764-767
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Forskningsöversikt (refereegranskat)abstract
- Umbrella reviews (reviews of systematic reviews) are increasingly used to synthesize findings from systematic reviews. One important challenge when pooling data from several systematic reviews is publication overlap, that is, the same primary publications being included in multiple reviews. Pieper et al. have proposed using the corrected covered area (CCA) index to quantify the degree of overlap between systematic reviews to be pooled in an umbrella review. Recently, this methodology has been integrated in Excel- or R-based tools for easier use. In this short letter, we highlight an important consideration for using the CCA methodology for pairwise overlap assessment, especially when reviews include varying numbers of primary publications, and we urge researchers to fine-tune this method and exercise caution when review exclusion decisions are based on its output.
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