| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 3. |
- Englund, Oskar, et al.
(författare)
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Multifunctional perennial production systems for bioenergy: performance and progress
- 2020
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Ingår i: Wiley Interdisciplinary Reviews. - : Wiley. - 2041-8396 .- 2041-840X.
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Tidskriftsartikel (refereegranskat)abstract
- As the global population increases and becomes more affluent, biomass demands for food and biomaterials will increase. Demand growth is further accelerated by the implementation of climate policies and strategies to replace fossil resources with biomass. There are, however, concerns about the size of the prospective biomass demand and the environmental and social consequences of the corresponding resource mobilization, especially concerning impacts from the associated land-use change. Strategically integrating perennials into landscapes dominated by intensive agriculture can, for example, improve biodiversity, reduce soil erosion and nutrient emissions to water, increase soil carbon, enhance pollination, and avoid or mitigate flooding events. Such ?multifunctional perennial production systems? can thus contribute to improving overall land-use sustainability, while maintaining or increasing overall biomass productivity in the landscape. Seven different cases in different world regions are here reviewed to exemplify and evaluate (a) multifunctional production systems that have been established to meet emerging bioenergy demands, and (b) efforts to identify locations where the establishment of perennial crops will be particularly beneficial. An important barrier towards wider implementation of multifunctional systems is the lack of markets, or policies, compensating producers for enhanced ecosystem services and other environmental benefits. This deficiency is particularly important since prices for fossil-based fuels are low relative to bioenergy production costs. Without such compensation, multifunctional perennial production systems will be unlikely to contribute to the development of a sustainable bioeconomy.
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| 4. |
- Holmberg, Carl Jacob, et al.
(författare)
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The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
- 2022
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Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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| 5. |
- Karalexi, Maria A., et al.
(författare)
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Gender-affirming hormone treatment and cognitive function in transgender young adults : a systematic review and meta-analysis
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 119
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Forskningsöversikt (refereegranskat)abstract
- Background: Previous studies have examined whether steroid hormone treatment in transgender individuals may affect cognitive function; yet, their limited power does not allow firm conclusions to be drawn. We leveraged data from to-date literature aiming to explore the effect of gender-affirming hormone administration on cognitive function in transgender individuals.Methods: A search strategy of MEDLINE was developed (through June 1, 2019) using the key terms transgender, hormone therapy and cognitive function. Eligible were (i) cohort studies examining the longitudinal effect of hormone therapy on cognition, and (ii) cross-sectional studies comparing the cognitive function between treated and non-treated individuals. Standardized mean differences (Hedges' g) were pooled using random-effects models. Study quality was evaluated using the Newcastle-Ottawa Scale.Outcomes: Ten studies (seven cohort and three cross-sectional) were eligible representing 234 birth-assigned males (aM) and 150 birth-assigned females (aF). The synthesis of cohort studies (n = 5) for visuospatial ability following hormone treatment showed a statistically significant enhancement among aF (g = 0.55, 95% confidence intervals [CI]: 0.29, 0.82) and an improvement with a trend towards statistical significance among aM (g = 0.28, 95%CI: -0.01, 0.58). By contrast, no adverse effects of hormone administration were shown. No heterogeneity was evident in most meta-analyses.Interpretation: Current evidence does not support an adverse impact of hormone therapy on cognitive function, whereas a statistically significant enhancing effect on visuospatial ability was shown in aF. New longitudinal studies with longer follow-up should explore the long-term effects of hormone therapy, especially the effects on younger individuals, where there is greater scarcity of data.
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| 6. |
- Todisco, Gabriele, et al.
(författare)
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Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts
- 2023
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 29:20, s. 4256-4267
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Ring sideroblasts (RS) define the low-risk myelodysplastic neoplasm (MDS) subgroup with RS but may also reflect erythroid dysplasia in higher risk myeloid neoplasm. The benign behavior of MDS with RS (MDSRSþ) is limited to SF3B1-mutated cases without additional high-risk genetic events, but one third of MDSRSþ carry no SF3B1 mutation, suggesting that different molecular mechanisms may underlie RS formation. We integrated genomic and transcriptomic analyses to evaluate whether transcriptome profiles may improve current risk stratification. Experimental Design: We studied a prospective cohort of MDSRSþ patients irrespective of World Health Organization (WHO) class with regard to somatic mutations, copy-number alterations, and bone marrow CD34þ cell transcriptomes to assess whether transcriptome profiles add to prognostication and provide input on disease classification. Results: SF3B1, SRSF2, or TP53 multihit mutations were found in 89% of MDSRSþ cases, and each mutation category was associated with distinct clinical outcome, gene expression, and alternative splicing profiles. Unsupervised clustering analysis identified three clusters with distinct hemopoietic stem and progenitor (HSPC) composition, which only partially overlapped with mutation groups. IPSS-M and the transcriptome-defined proportion of megakaryocyte/erythroid progenitors (MEP) independently predicted survival in multivariable analysis. Conclusions: These results provide essential input on the molecular basis of SF3B1-unmutated MDSRSþ and propose HSPC quantification as a prognostic marker in myeloid neoplasms with RS.
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