| 1. |
- Cope, Jonathan E., et al.
(författare)
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Clear effects on root system architecture of winter wheat cultivars (Triticum aestivum L.) from cultivation environment and practices
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Roots play a pivotal role in the adaption of a plant to its environment, with different root traits adapting the plant to different stresses. The environment affects the Root System Architecture (RSA), but the genetic factors determine to what extent, and whether stress brought about by extreme environmental conditions is detrimental to a specific crop. This study aimed to identify differences in winter wheat RSA caused by cultivation region and practice, in the form of preceding crop (precrop), and to identify if modern cultivars used in Sweden differ in their reaction to these environments. This was undertaken using high-throughput phenotyping to assess the RSA. Clear differences in the RSA were observed between the Swedish cultivation regions, precrop treatments, and interaction of these conditions with each other and the genetics. Julius showed a large difference between cultivars, with 9.3-17.1% fewer and 12-20% narrower seminal roots. Standardized yield decreased when grown after wheat, 23% less compared to oilseed rape (OSR), and when grown in the Southern region, 14% less than the Central region. Additionally, correlations were shown between the root number, angle, and grain yield, with different root types being correlated depending on the precrop. Cultivars on the Swedish market show differences that can be adapted to the region-precrop combinations. The differences in precrop effect on RSA between regions show global implications and a need for further assessment. Correlations between RSA and yield, based on root-typexprecrop, indicate different needs of the RSA depending on the management practices and show the potential for improving crop yield through targeting genotypic and environmental conditions in a holistic manner. Understanding this RSA variance, and the mechanisms of conditional response, will allow targeted cultivar breeding for specific environments, increasing plant health and food security.
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| 2. |
- Cumlin, Tomas, et al.
(författare)
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From SARS-CoV-2 to Global Preparedness : A Graphical Interface for Standardised High-Throughput Bioinformatics Analysis in Pandemic Scenarios and Surveillance of Drug Resistance
- 2024
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:12
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic highlighted the need for a rapid, convenient, and scalable diagnostic method for detecting a novel pathogen amidst a global pandemic. While command-line interface tools offer automation for SARS-CoV-2 Oxford Nanopore Technology sequencing data analysis, they are inapplicable to users with limited programming skills. A solution is to establish such automated workflows within a graphical user interface software. We developed two workflows in the software Geneious Prime 2022.1.1, adapted for data obtained from the Midnight and Artic's nCoV-2019 sequencing protocols. Both workflows perform trimming, read mapping, consensus generation, and annotation on SARS-CoV-2 Nanopore sequencing data. Additionally, one workflow includes phylogenetic assignment using the bioinformatic tools pangolin and Nextclade as plugins. The basic workflow was validated in 2020, adhering to the requirements of the European Centre for Disease Prevention and Control for SARS-CoV-2 sequencing and analysis. The enhanced workflow, providing phylogenetic assignment, underwent validation at Uppsala University Hospital by analysing 96 clinical samples. It provided accurate diagnoses matching the original results of the basic workflow while also reducing manual clicks and analysis time. These bioinformatic workflows streamline SARS-CoV-2 Nanopore data analysis in Geneious Prime, saving time and manual work for operators lacking programming knowledge.
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| 3. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 4. |
- Häggström, Ida, 1982-, et al.
(författare)
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A Monte Carlo study of the dependence of early frame sampling on uncertainty and bias in pharmacokinetic parameters from dynamic PET
- 2015
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Ingår i: Journal of Nuclear Medicine Technology. - : Society of Nuclear Medicine. - 0091-4916 .- 1535-5675. ; 43:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Compartmental modeling of dynamic PET data enables quantifi- cation of tracer kinetics in vivo, through the calculated model parameters. In this study, we aimed to investigate the effect of early frame sampling and reconstruction method on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias and uncertainty (SD). Methods: The GATE Monte Carlo software was used to simulate 2 · 15 dynamic 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) brain PET studies, typical in terms of noise level and kinetic parameters. The data were reconstructed by both 3- dimensional (3D) filtered backprojection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6 dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15 s. Bias and SD were evaluated for fitted parameter estimates, calculated from regions of interest. Results: The 2-tissue-model parameter estimates K1, k2, and fraction of arterial blood in tissue depended on early frame sampling, and a sampling of 6–15 s generally minimized bias and SD. The shortest sampling of 1 s yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM, respectively, and a parameter uncertainty that was 10%–70% higher. The schemes from 4 to 15 s were generally not significantly different in regards to bias and SD. Typically, the reconstruction method 3DRP yielded less framesampling dependence and less uncertain results, compared with OSEM, but was on average more biased. Conclusion: Of the 6 sampling schemes investigated in this study, an early frame duration of 6–15 s generally kept both bias and uncertainty to a minimum, for both 3DRP and OSEM reconstructions. Veryshort frames of 1 s should be avoided because they typically resulted in the largest parameter bias and uncertainty. Furthermore, 3DRP may be p
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| 5. |
- Häggström, Ida, 1982-, et al.
(författare)
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Semi-automatic tumour segmentation by selective navigation in a three-parameter volume, obtained by voxel-wise kinetic modelling of C-11-acetate
- 2010
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 139:1-3, s. 214-218
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) is increasingly used for delineation of tumour tissue in, for example, radiotherapy treatment planning. The most common method used is to outline volumes with a certain per cent uptake over background in a static image. However, PET data can also be collected dynamically and analysed by kinetic models, which potentially represent the underlying biology better. In the present study, a three-parameter kinetic model was used for voxel-wise evaluation of C-11-acetate data of head/neck tumours. These parameters which represent the tumour blood volume, the uptake rate and the clearance rate of the tissue were derived for each voxel using a linear regression method and used for segmentation of active tumour tissue. This feasibility study shows that it is possible to segment images based on derived model parameters. There is, however, room for improvements concerning the PET data acquisition, noise reduction and the kinetic modelling. In conclusion, this early study indicates a strong potential of the method even though no 'true' tumour volume was available for validation.
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| 6. |
- Karlsson, Ida, et al.
(författare)
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Temporal and spatial dynamics of Fusarium spp. and mycotoxins in Swedish cereals during 16 years
- 2023
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Ingår i: Mycotoxin Research. - : Springer Berlin/Heidelberg. - 0178-7888 .- 1867-1632. ; 39:1, s. 3-18
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Tidskriftsartikel (refereegranskat)abstract
- We analysed the dynamics of Fusarium spp. and mycotoxin contamination in Swedish cereals during 2004-2018. More than 1400 cereal samples from field trials were included, collected in a monitoring programme run by the Swedish Board of Agriculture. Five Fusarium mycotoxins were quantified with LC-MS/MS and fungal DNA from four species was quantified using quantitative real-time PCR. Correlation analyses revealed that deoxynivalenol (DON) and zearalenone (ZEN) were mainly associated with Fusarium graminearum, but stronger correlations with F. culmorum was seen some years. Nivalenol (NIV) was associated with F. poae and the HT-2 and T-2 toxins with F. langsethiae. Clear differences in mycotoxin contamination between different cereal crops and geographical regions were identified. The highest levels of DON and ZEN were found in spring wheat in Western Sweden. For NIV, HT-2 and T-2 toxins, the levels were highest in spring oats and spring barley. Regional differences were not detected for NIV, while HT-2 and T-2 toxins were associated with the northernmost region. We found that delayed harvest was strongly associated with increased levels of DON and ZEN in several crops. However, harvest date did not influence the levels of NIV or HT-2 and T-2 toxins. Our results suggest similar distribution patterns of DON and ZEN, in contrast to NIV and HT-2 and T-2 toxins, probably mirroring the differences in the ecology of the toxin-producing Fusarium species. Timely harvest is important to reduce the risk of DON and ZEN contamination, especially for fields with other risk factors.
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| 7. |
- Kvitne, Kine Eide, et al.
(författare)
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Digoxin Pharmacokinetics in Patients with Obesity Before and After a Gastric Bypass or a Strict Diet Compared with Normal Weight Individuals
- 2024
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Ingår i: Clinical Pharmacokinetics. - : Springer. - 0312-5963 .- 1179-1926. ; 63:1, s. 109-120
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: Several drugs on the market are substrates for P-glycoprotein (P-gp), an efflux transporter highly expressed in barrier tissues such as the intestine. Body weight, weight loss, and a Roux-en-Y gastric bypass (RYGB) may influence P-gp expression and activity, leading to variability in the drug response. The objective of this study was therefore to investigate digoxin pharmacokinetics as a measure of the P-gp phenotype in patients with obesity before and after weight loss induced by an RYGB or a strict diet and in normal weight individuals.Methods: This study included patients with severe obesity preparing for an RYGB (n = 40) or diet-induced weight loss (n = 40) and mainly normal weight individuals scheduled for a cholecystectomy (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day) followed by an additional 6 weeks of <800 kcal/day induced by an RYGB (performed at week 3) or a very-low-energy diet. Follow-up time was 2 years, with four digoxin pharmacokinetic investigations at weeks 0, 3, and 9, and year 2. Hepatic and jejunal P-gp levels were determined in biopsies obtained from the patients undergoing surgery.Results: The RYGB group and the diet group had a comparable weight loss in the first 9 weeks (13 +/- 2.3% and 11 +/- 3.6%, respectively). During this period, we observed a minor increase (16%) in the digoxin area under the concentration-time curve from zero to infinity in both groups: RYGB: 2.7 mu g h/L [95% confidence interval (CI) 0.67, 4.7], diet: 2.5 mu g h/L [95% CI 0.49, 4.4]. In the RYGB group, we also observed that the time to reach maximum concentration decreased after surgery: from 1.0 +/- 0.33 hours at week 3 to 0.77 +/- 0.08 hours at week 9 (-0.26 hours [95% CI -0.47, -0.05]), corresponding to a 25% reduction. Area under the concentration-time curve from zero to infinity did not change long term (week 0 to year 2) in either the RYGB (1.1 mu g h/L [-0.94, 3.2]) or the diet group (0.94 mu g h/L [-1.2, 3.0]), despite a considerable difference in weight loss from baseline (RYGB: 30 +/- 7%, diet: 3 +/- 6%). At baseline, the area under the concentration-time curve from zero to infinity was -5.5 mu g h/L [95% CI -8.5, -2.5] (-26%) lower in patients with obesity (RYGB plus diet) than in normal weight individuals scheduled for a cholecystectomy. Further, patients undergoing an RYGB had a 0.05 fmol/mu g [95% CI 0.00, 0.10] (29%) higher hepatic P-gp level than the normal weight individuals.Conclusions: Changes in digoxin pharmacokinetics following weight loss induced by a pre-operative low-energy diet and an RYGB or a strict diet (a low-energy diet plus a very-low-energy diet) were minor and unlikely to be clinically relevant. The lower systemic exposure of digoxin in patients with obesity suggests that these patients may have increased biliary excretion of digoxin possibly owing to a higher expression of P-gp in the liver.
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| 8. |
- Netterberg, Ida, 1988-, et al.
(författare)
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Circulating tumor cell counts is a better predictor of overall survival than dynamic tumor size changes – a quantitative modeling framework
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Quantitative relationships between treatment-induced changes in tumor size and circulating tumor cell (CTC) counts, and their links to overall survival (OS), are lacking. We here present a population modeling framework identifying and quantifying such relationships, based on longitudinal data collected in patients with metastatic colorectal cancer (mCRC) to evaluate the value of tumor size and CTC counts as predictors of OS.Experimental design: A pharmacometric approach (i.e., population pharmacodynamic modeling) was used to characterize the changes in tumor size and CTC count and evaluate them as predictors of OS in 451 patients with mCRC treated with chemotherapy and targeted therapy in a prospectively randomized phase 3 study (CAIRO2).Results: A tumor size model of tumor quiescence and drug-resistance, was used to characterize the tumor size time-course, and was, in addition to the total normalized dose (i.e., of all administered drugs) in a given cycle, related to the CTC counts through a negative binomial model (CTC model). A CTC count≥3/7.5 mL (hazard ratio=3.51, 95% confidence interval: 2.85-4.32), as described by the CTC model, was a better predictor of OS than tumor size changes. The modeling framework was applied to explore if dose-modifications (increased and reduced) would result in a CTC count below 3/7.5 mL after 1-2 weeks of treatment.Conclusions: Time-varying CTC counts can be useful for early predicting OS in patients with mCRC, and may therefore have potential for model-based treatment individualization. Although tumor size had a strong connection to CTC, its link to OS was weaker.
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| 9. |
- Netterberg, Ida, et al.
(författare)
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Comparing Circulating Tumor Cell Counts with Dynamic Tumor Size Changes as Predictor of Overall Survival : A Quantitative Modeling Framework
- 2020
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 26:18, s. 4892-4900
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Quantitative relationships between treatment-induced changes in tumor size and circulating tumor cell (CTC) counts, and their links to overall survival (OS), are lacking. We present a population modeling framework identifying and quantifying such relationships, based on longitudinal data collected in patients with metastatic colorectal cancer (mCRC) to evaluate the value of tumor size and CTC counts as predictors of OS. Experimental Design: A pharmacometric approach (i.e., population pharmacodynamic modeling) was used to characterize the changes in tumor size and CTC count and evaluate them as predictors of OS in 451 patients with mCRC treated with chemotherapy and targeted therapy in a prospectively randomized phase III study (CAIRO2). Results: A tumor size model of tumor quiescence and drug resistance was used to characterize the tumor size time-course, and was, in addition to the total normalized dose (i.e., of all administered drugs) in a given cycle, related to the CTC counts through a negative binomial model (CTC model). Tumor size changes did not contribute additional predictive value when themean CTC count was a predictor of OS. Treatment reduced the typical mean count from 1.43 to 0.477 (HR = 3.94). The modeling framework was applied to explore whether dose modifications (increased and reduced) would result in a CTC count below 1/7.5 mL after 1 to 2 weeks of treatment. Conclusions: Time-varying CTC counts can be useful for early predicting OS in patients with mCRC, and may therefore have potential for model-based treatment individualization. Although tumor size was connected to CTC, its link to OS was weaker.
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| 10. |
- Netterberg, Ida, et al.
(författare)
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Model-based prediction of myelosuppression and recovery based on frequent neutrophil monitoring
- 2017
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 80:2, s. 343-353
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To investigate whether a more frequent monitoring of the absolute neutrophil counts (ANC) during myelo-suppressive chemotherapy, together with model-based predictions, can improve therapy management, compared to the limited clinical monitoring typically applied today. Methods Daily ANC in chemotherapy-treated cancer patients were simulated from a previously published population model describing docetaxel-induced myelosuppression. The simulated values were used to generate predictions of the individual ANC time-courses, given the myelosuppression model. The accuracy of the predicted ANC was evaluated under a range of conditions with reduced amount of ANC measurements. Results The predictions were most accurate when more data were available for generating the predictions and when making short forecasts. The inaccuracy of ANC predictions was highest around nadir, although a high sensitivity (>= 90%) was demonstrated to forecast Grade 4 neutropenia before it occurred. The time for a patient to recover to baseline could be well forecasted 6 days (+/- 1 day) before the typical value occurred on day 17. Conclusions Daily monitoring of the ANC, together with model-based predictions, could improve anticancer drug treatment by identifying patients at risk for severe neutropenia and predicting when the next cycle could be initiated.
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