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- Hjort, Rebecka, et al.
(author)
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Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes
- 2020
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:11
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Journal article (peer-reviewed)abstract
- PURPOSE: Physical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated whether PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of human leukocyte antigen (HLA), transcription factor 7-like 2 (TCF7L2)-rs7903146, or the fat mass and obesity-associated gene, FTO-rs9939609. METHODS: We combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RRs) and 95% CI of diabetes in relation to high (≥ 30 minutes of moderate activity 3 times/week) self-reported leisure time PA, compared to sedentariness. RESULTS: High PA was associated with a reduced risk of LADA (RR 0.61; CI, 0.43-0.86), which was attenuated after adjustment for body mass index (BMI) (RR 0.90; CI, 0.63-1.29). The reduced risk applied only to noncarriers of HLA-DQB1 and -DRB1 (RR 0.49; CI, 0.33-0.72), TCF7L2 (RR 0.62; CI, 0.45-0.87), and FTO (RR 0.51; CI, 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49; CI, 0.42-0.56), irrespective of genotype. MAIN CONCLUSIONS: Our findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.
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| 2. |
- Magnusson, Louise, 1992-
(author)
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Peripheral immunity in patients with autoimmune endocrine diseases and the influence of physiological adaptions during pregnancy
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Type 1 diabetes (T1D), Hashimoto’s thyroiditis (HT), Graves’ disease (GD), and autoimmune Addison’s disease (AD) appear to share immunogenetic mechanisms. This idea is not novel, as “autoimmune tautology” is an established concept. An issue with previous studies is that no or few simultaneous comparisons between these autoimmune endocrine diseases have been made. Due to methodological limitations, immune deviations associated with these diseases have also been examined for a limited number of immune cell lineages and analytes. High-dimensional single-cell mass cytometry was thus employed to phenotypically characterise all peripheral CD45+ cell lineages, whilst immune-related proteins in plasma and cell supernatants were analysed by proximity extension assay. Patients with new-onset T1D, HT, and AD had altered frequencies of distinct clusters within antigen-presenting and cytotoxic cell lineages. Importantly, previously unreported alterations of rare cell subsets from patients with HT and AD were identified. The systemic immunoprofile of patients with autoimmune endocrine diseases was in general similar. However, an increased abundance of CDCP1 and SLAMF1 in plasma from patients with T1D, HT, and GD might reflect a higher degree of inflammation and lymphocyte activation.Pregnancy in healthy women entails two important features: 1) an increase in fractional β-cell area and 2) peripheral immunomodulation. The effects of pregnancy on T1D remain nevertheless equivocal, as there are conflicting results on β-cell function and longitudinal analyses on peripheral immunity are lacking. β-cell function and the plasma proteome in pregnant women with long-standing T1D (L-T1D) were therefore examined during three occasions: 1) first trimester, 2) third trimester, and 3) two months postpartum. An oral glucose tolerance test was performed to measure both fasting and stimulated C-peptide concentrations in plasma. Plasma proteins related to cell regulatory and immunological processes were analysed by proximity extension assay. Glucose-induced insulin secretion was regained in pregnant women with L-T1D, which decreased slowly after parturition. The plasma proteome was dynamic during gestation, although few analytes were functionally linked. A recovered β-cell function might be related to elevated plasma levels of prolactin, prokineticin-1, or glucagon. Moreover, reduced plasma levels of proteins related to leukocyte migration, T cell activation, and antigen-presentation might have further protected an improved β-cell function.
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| 5. |
- Andersson, Ola, et al.
(author)
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The impact of stay-at-home policies on individual welfare
- 2022
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In: Scandinavian Journal of Economics. - : Wiley. - 0347-0520 .- 1467-9442. ; 124:2, s. 340-362
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Journal article (peer-reviewed)abstract
- In this paper, we perform a choice experiment assessing the impact of stay-at-home policies on individual welfare. We estimate the willingness to accept compensation (WTA) for restricting non-working hours in Sweden during the COVID-19 pandemic. The WTA for a one-month stay-at-home policy is about US$480 per person, or 9.1 percent of Sweden's monthly per capita GDP. Stricter lockdowns require disproportionately higher compensation than more lenient ones, indicating that strict policies are cost-effective only if they are much more successful in slowing the spread of the disease. Moreover, older people have a higher WTA of staying home than the rest of the population.
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| 6. |
- Andersson, Ola, et al.
(author)
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THE INDIVIDUAL WELFARE COSTS OF STAY-AT-HOME POLICIES
- 2020
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Other publication (other academic/artistic)abstract
- This paper reports the results of a choice experiment designed to estimate the private welfare costs of stay-at-home policies during the COVID-19 pandemic. The study is conducted on a large and representative sample of the Swedish population. The results suggest that the welfare cost of a one-month stay-at-home policy, restricting non-working hours away from home, amounts to 9.1 percent of qSweden's monthly GDP. The cost can be interpreted as 29,600 quality-adjusted life years (QALYs), which roughly corresponds to between 3,700 and 8,000 COVID-19 fatalities. Moreover, we find that stricter and longer lockdowns are disproportionately more costly than more lenient ones. This result indicates that strict stay-at-home policies are likely to be cost-effective only if they slow the spread of the disease much more than more lenient ones.
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| 7. |
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| 8. |
- Arvidsson McShane, Staffan, 1990-
(author)
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Confidence Predictions in Pharmaceutical Sciences
- 2023
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Doctoral thesis (other academic/artistic)abstract
- The main focus of this thesis has been on Quantitative Structure Activity Relationship (QSAR) modeling using methods producing valid measures of uncertainty. The goal of QSAR is to prospectively predict the outcome from assays, such as ADMET (Absorption, Distribution, Metabolism, Excretion), toxicity and on- and off-target interactions, for novel compounds. QSAR modeling offers an appealing alternative to laboratory work, which is both costly and time-consuming, and can be applied earlier in the development process as candidate drugs can be tested in silico without requiring to synthesize them first. A common theme across the presented papers is the application of conformal and probabilistic prediction models, which are used in order to associate predictions with a level of their reliability – a desirable property that is essential in the stage of decision making. In Paper I we studied approaches on how to utilize biological assay data from legacy systems, in order to improve predictive models. This is otherwise problematic since mixing data from separate systems will cause issues for most machine learning algorithms. We demonstrated that old data could be used to augment the proper training set of a conformal predictor to yield more efficient predictions while preserving model calibration. In Paper II we studied a new approach of predicting metabolic transformations of small molecules based on transformations encoded in SMIRKS format. In this work use used the probabilistic Cross-Venn-ABERS predictor which overall worked well, but had difficulty in modeling the minority class of imbalanced datasets. In Paper III we studied metabolomics data from patients diagnosed with Multiple Sclerosis and found a set of 15 discriminatory metabolites that could be used to classify patients from a validation cohort into one of two sub types of the disease with high accuracy. We further demonstrated that conformal prediction could be useful for tracking the progression of the disease for individual patients, which we exemplified using data from a clinical trial. In Paper IV we introduced CPSign – a software for cheminformatics modeling using conformal and probabilistic methods. CPSign was compared against other regularly used methods for this task, using 32 benchmark datasets, demonstrating that CPSign produces predictive accuracy on par with the best performing methods.
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| 9. |
- Balboa, Diego, et al.
(author)
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Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
- 2022
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In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 40:7, s. 1042-1055
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Journal article (peer-reviewed)abstract
- Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.
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| 10. |
- Bergengren, Oskar, et al.
(author)
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2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review
- 2023
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 84:2, s. 191-206
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Research review (peer-reviewed)abstract
- Context: Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and secondary prevention strategies.Objective: To systematically review and summarize the current evidence on the descrip-tive epidemiology, large screening studies, diagnostic techniques, and risk factors of PCa.Evidence acquisition: PCa incidence and mortality rates for 2020 were obtained from the GLOBOCAN database of the International Agency for Research on Cancer. A systematic search was performed in July 2022 using PubMed/MEDLINE and EMBASE biomedical databases. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42022359728).Evidence synthesis: Globally, PCa is the second most common cancer, with the highest incidence in North and South America, Europe, Australia, and the Caribbean. Risk factors include age, family history, and genetic predisposition. Additional factors may include smoking, diet, physical activity, specific medications, and occupational factors. As PCa screening has become more accepted, newer approaches such as magnetic resonance imaging (MRI) and biomarkers have been implemented to identify patients who are likely to harbor significant tumors. Limitations of this review include the evidence being derived from meta-analyses of mostly retrospective studies.Conclusions: PCa remains the second most common cancer among men worldwide. PCa screening is gaining acceptance and will likely reduce PCa mortality at the cost of over-diagnosis and overtreatment. Increasing use of MRI and biomarkers for the detection of PCa may mitigate some of the negative consequences of screening.
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