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| 2. |
- Ahlberg, Ernst, et al.
(author)
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Using conformal prediction to prioritize compound synthesis in drug discovery
- 2017
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In: Proceedings of Machine Learning Research. - Stockholm : Machine Learning Research. ; , s. 174-184
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Conference paper (peer-reviewed)abstract
- The choice of how much money and resources to spend to understand certain problems is of high interest in many areas. This work illustrates how computational models can be more tightly coupled with experiments to generate decision data at lower cost without reducing the quality of the decision. Several different strategies are explored to illustrate the trade off between lowering costs and quality in decisions.AUC is used as a performance metric and the number of objects that can be learnt from is constrained. Some of the strategies described reach AUC values over 0.9 and outperforms strategies that are more random. The strategies that use conformal predictor p-values show varying results, although some are top performing.The application studied is taken from the drug discovery process. In the early stages of this process compounds, that potentially could become marketed drugs, are being routinely tested in experimental assays to understand the distribution and interactions in humans.
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| 3. |
- Alsharari, Zayed, et al.
(author)
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Association between carbohydrate intake and fatty acids in the de novo lipogenic pathway in serum phospholipids and adipose tissue in a population of Swedish men
- 2020
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In: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 59:5, s. 2089-2097
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Journal article (peer-reviewed)abstract
- Purpose Fatty acid composition in blood and adipose tissue (AT) is a useful biomarker of dietary fat quality. However, circulating saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) have been proposed to also reflect carbohydrate-induced de novo lipogenesis (DNL) and stearoyl-CoA desaturase (SCD) activity. We aimed to test the hypothesis that high carbohydrate intake is related to SFA and MUFA in serum or AT in a Swedish population. Methods Fatty acid composition was measured in serum phospholipids (PL) and AT by gas chromatography in 63-year-old men (n = 299). Carbohydrate and alcohol intake was assessed (validated 7-day food records) in relation to total SFA, 16:0 (palmitate), 16:1 (palmitoleate), and estimated SCD activity (16:1n-7/16:0-ratio) in serum PL and in AT, respectively. Results Total carbohydrate intake was inversely associated with 16:0 in PL (P = 0.005), independently of BMI. Disaccharides were non-linearly (restricted cubic splines) and weakly associated with 16:1 and SCD activity in PL (nonlinear trend,P <= 0.02) but not AT. Carbohydrate intake and SCD expression were not associated (P >= 0.08,n = 81). Alcohol intake was, however, linearly associated with 16:0 in PL (P < 0.001), and with 16:1 (P < 0.001) and SCD activity (P <= 0.005) in both PL and AT. Conclusions Higher carbohydrate intake from sugar-rich foods or beverages was not clearly reflected by higher SFA or SCD activity in serum PL or AT. Alcohol was, however, associated with higher SFA and MUFA.
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| 4. |
- Alsharari, Zayed, et al.
(author)
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Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
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Other publication (other academic/artistic)abstract
- AbstractBackground: Fatty acid composition in blood and adipose tissue is useful to reflect dietary fatquality, although the utility of even-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) has been debated. Since SFA also can be produced via de novo lipogenesis (DNL), and desaturated to MUFA, it has been proposed that these fatty acids may reflect carbohydrate-induced DNL. We aimed to test the hypothesis that high carbohydrate intake, especially sugars, is related to SFA and MUFA in serum and adipose tissue.Methods: Validated 7-day food records were collected and fatty acid composition in serum phospholipids (PL) and adipose tissue (AT) were measured in 63-year-old men (n=299). Stearoyl-CoA desaturate (SCD) activities in AT and PL were estimated by the palmitoleic acid (16:1) to palmitic acid (16:0) ratio. Associations of dietary carbohydrate, disaccharides, monosaccharides, carbohydrate-to-fiber ratio, and alcohol with the sum of even-chain SFA, 16:0, 16:1, and SCD activity were assessed using linear regression models with and without adjustment for BMI. Non-linear trends were evaluated using restricted cubic splines. In a subsample (n=81) with RNA measured in AT biopsies, associations of dietary carbohydrate and alcohol with SCD gene expression were assessed using linear regression models.Results: In BMI-adjusted models, intake of carbohydrates was inversely associated with palmitic acid in PL (P=0.005). Disaccharide intake was non-linearly associated with 16:1 and SCD activity in PL (P for nonlinear trend ≤0.02), with the lowest values observed in the mid tertile. Alcohol intake was linearly associated with 16:0 in PL (P<0.001) and with 16:1 (P<0.001) and SCD activity (P ≤0.005) in AT. Alcohol intake was non-linear associated (P≤0.02) with 16:1 and SCD activity in PL; with initially stable levels at lower intakes that rapidly increased at intakes above median. In the subsample, we found no associations between carbohydrate intake and SCD gene expression (P ≥0.08).Conclusion: In this Swedish population, we found no evidence to suggest that higher carbohydrate intake or sugar-rich foods or beverages is reflected by higher SFA in PL and AT.Instead, alcohol was consistently associated with higher SFA and MUFA.
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| 5. |
- Alsharari, Zayed, et al.
(author)
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Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women
- 2017
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:1
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Journal article (peer-reviewed)abstract
- Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA- desaturase and Delta 6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, alpha-linolenic acid, docohexaenoic acid, and Delta 5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.
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| 6. |
- Andersson, Björn, 1977, et al.
(author)
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Decrease in adiponectin levels correlates to growth response in growth hormone-treated children.
- 2009
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In: Hormone research. - : S. Karger AG. - 1423-0046 .- 0301-0163. ; 71:4, s. 213-8
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Journal article (peer-reviewed)abstract
- Adiponectin is secreted by adipose tissue and circulates in human plasma at high levels. Decreased adiponectin levels are associated with insulin resistance and obesity. The aim of this study was to investigate whether changes in serum adiponectin levels are related to the growth response, insulin levels and insulin resistance during growth hormone (GH) treatment.
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| 7. |
- Carlsson, Axel, et al.
(author)
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Differences in anthropometric measures in immigrants and Swedish-born individuals : results from two community-based cohort studies
- 2014
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In: Preventive Medicine. - : Elsevier BV. - 0091-7435 .- 1096-0260. ; 69, s. 151-156
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Journal article (peer-reviewed)abstract
- AIM: To study differences in body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), waist-hip-height ratio (WHHR) and percent body fat in immigrants and Swedish-born men and women in two large population-based samples.METHODS: A cross-sectional analysis of 60-year-old individuals, n=4 232. To replicate the results, we also assessed another large independent cohort cross-sectionally, the Malmö Diet and Cancer Study (MDC, n=26 777). The data from both cohorts were collected in the 1990s in Sweden.RESULTS: Significant differences between Finnish-born, Middle Eastern and women from the rest of the world were seen for all anthropometric measures, using Swedish-born women as referent. However, WHHR was the only anthropometric measure that identified all these three groups of immigrant women as different from Swedish-born women with high statistical certainty (p<0.001). Apart from WHHR that identified differences in anthropometry in all immigrant groups of men using Swedish-born men as referent, few significant differences were seen in anthropometry among groups of immigrant men. These finding were observed in both cohorts, and remained after adjustments for smoking, physical activity and educational level.CONCLUSION: The present study confirms previous findings of more obesity among immigrants and is the first to report that WHHR measurements may detect anthropometric differences between different ethnic groups better than other anthropometrical measures.
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| 8. |
- Carlsson, Susanne, et al.
(author)
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Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface.
- 2007
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In: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 17:6, s. 663-76
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Journal article (peer-reviewed)abstract
- Galectin-8 has two different carbohydrate recognition domains (CRDs), the N-terminal Gal-8N and the C-terminal Gal-8C linked by a peptide, and has various effects on cell adhesion and signaling. To understand the mechanism for these effects further, we compared the binding activities of galectin-8 in solution with its binding and activation of cells. We used glycan array analysis to broaden the specificity profile of the two galectin-8 CRDs, as well as intact galectin-8s (short and long linker), confirming the unique preference for sulfated and sialylated glycans of Gal-8N. Using a fluorescence anisotropy assay, we examined the solution affinities for a subset of these glycans, the highest being 50 nM for NeuAcalpha2,3Lac by Gal-8N. Thus, carbohydrate-protein interactions can be of high affinity without requiring multivalency. More importantly, using fluorescence polarization, we also gained information on how the affinity is built by multiple weak interactions between different fragments of the glycan and its carrier molecule and the galectin CRD subsites (A-E). In intact galectin-8 proteins, the two domains act independently of each other in solution, whereas at a surface they act together. Ligands with moderate or weak affinity for the isolated CRDs on the array are bound strongly by intact galectin-8s. Also galectin-8 binding and signaling at cell surfaces can be explained by combined binding of the two CRDs to low or medium affinity ligands, and their highest affinity ligands, such as sialylated galactosides, are not required.
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| 9. |
- Ekbäck, Gustav, et al.
(author)
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Preoperative platelet-rich plasmapheresis and hemodilution with an autotransfusion device in total hip replacement surgery
- 2000
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In: Journal of clinical apheresis. - 0733-2459 .- 1098-1101. ; 15:4, s. 256-261
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Journal article (peer-reviewed)abstract
- The effectiveness of both preoperative autologous donation (PAD) and intraoperative autotransfusion (IAT) with an autotransfusion device has recently been questioned. Preoperative apheresis, with separation of concentrated platelet rich-plasma (c-PRP) and erythrocyte concentrate (ERC), represents an aggressive use of the autotransfusion device. Can such a procedure replace PAD in total hip replacement surgery (THR)? Eighty patients undergoing THR were investigated in a prospective and randomized study. Forty patients underwent PAD, and 2 units of ERC + plasma were retrieved within 4 weeks preoperatively. Another 40 patients underwent an immediately preoperative apheresis with a concomitant hemodilution with 4% albumin, retrieving c-PRP (30% of the platelet pool) and 2 units of ERC. Both groups used IAT up to 2 hours postoperatively, with 3% dextran-60 as a plasma substitute according to our standard of care. There were no differences in blood loss, B-hemoglobin or allogeneic transfusions between the groups: 85% of the patients did not receive allogeneic blood. Both apheresis and reinfusion of c-PRP had minor impact on the coagulation parameters. Platelet count increased slightly but significantly (P < 0.05) from 154 to 179 × 109/L after the c-PRP at wound closure. Preoperative apheresis with an autotransfusion device, separating platelet-rich plasma and erythrocyte concentrate, is a useful alternative for patients who are unable to utilize the PAD technique for either religious or practical reasons.
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| 10. |
- Gerdtham, Ulf, et al.
(author)
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Värdet av nya läkemedel: en förstudie
- 2011
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Conference paper (other academic/artistic)abstract
- Denna rapport redovisar en förstudie till SNS fleråriga forskningsprojekt som undersöker hur värdet av nya läkemedel kan bedömas ur ett brett samhällsperspektiv. En slutsats av förstudien är att det finns goda möjligheter att få bättre svar på många av de policyfrågor som ställs i läkemedelspolitiken, t ex om förskrivning och offentlig subventionering av nya läkemedel. De omfattande svenska patientregistren erbjuder unika möjligheter att studera det faktiska, realiserade värdet av läkemedel.
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