| 1. |
- Böhmer, Jens, 1981, et al.
(författare)
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Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study.
- 2023
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874 .- 1432-2277. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.
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| 2. |
- Falk Erhag, Hanna, et al.
(författare)
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A Multidisciplinary Approach to Capability in Age and Ageing
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This open access book provides insight on how to interpret capability in ageing – one’s individual ability to perform actions in order to reach goals one has reason to value – from a multidisciplinary approach. With for the first time in history there being more people in the world aged 60 years and over than there are children below the age of 5, the book describes this demographic trends as well as the large global challenges and important societal implications this will have such as a worldwide increase in the number of persons affected with dementia, and in the ratio of retired persons to those still in the labor market. Through contributions from many different research areas, it discussed how capability depends on interactions between the individual (e.g. health, genetics, personality, intellectual capacity), environment (e.g. family, friends, home, work place), and society (e.g. political decisions, ageism, historical period). The final chapter by the editors summarizes the differences and similarities in these contributions. As such this book provides an interesting read for students, teachers and researchers at different levels and from different fields interested in capability and multidisciplinary research.
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| 3. |
- Ali, Muhaddisa Barat, 1986, et al.
(författare)
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A novel federated deep learning scheme for glioma and its subtype classification
- 2023
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Ingår i: Frontiers in Neuroscience. - 1662-4548 .- 1662-453X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep learning (DL) has shown promising results in molecular-based classification of glioma subtypes from MR images. DL requires a large number of training data for achieving good generalization performance. Since brain tumor datasets are usually small in size, combination of such datasets from different hospitals are needed. Data privacy issue from hospitals often poses a constraint on such a practice. Federated learning (FL) has gained much attention lately as it trains a central DL model without requiring data sharing from different hospitals. Method: We propose a novel 3D FL scheme for glioma and its molecular subtype classification. In the scheme, a slice-based DL classifier, EtFedDyn, is exploited which is an extension of FedDyn, with the key differences on using focal loss cost function to tackle severe class imbalances in the datasets, and on multi-stream network to exploit MRIs in different modalities. By combining EtFedDyn with domain mapping as the pre-processing and 3D scan-based post-processing, the proposed scheme makes 3D brain scan-based classification on datasets from different dataset owners. To examine whether the FL scheme could replace the central learning (CL) one, we then compare the classification performance between the proposed FL and the corresponding CL schemes. Furthermore, detailed empirical-based analysis were also conducted to exam the effect of using domain mapping, 3D scan-based post-processing, different cost functions and different FL schemes. Results: Experiments were done on two case studies: classification of glioma subtypes (IDH mutation and wild-type on TCGA and US datasets in case A) and glioma grades (high/low grade glioma HGG and LGG on MICCAI dataset in case B). The proposed FL scheme has obtained good performance on the test sets (85.46%, 75.56%) for IDH subtypes and (89.28%, 90.72%) for glioma LGG/HGG all averaged on five runs. Comparing with the corresponding CL scheme, the drop in test accuracy from the proposed FL scheme is small (−1.17%, −0.83%), indicating its good potential to replace the CL scheme. Furthermore, the empirically tests have shown that an increased classification test accuracy by applying: domain mapping (0.4%, 1.85%) in case A; focal loss function (1.66%, 3.25%) in case A and (1.19%, 1.85%) in case B; 3D post-processing (2.11%, 2.23%) in case A and (1.81%, 2.39%) in case B and EtFedDyn over FedAvg classifier (1.05%, 1.55%) in case A and (1.23%, 1.81%) in case B with fast convergence, which all contributed to the improvement of overall performance in the proposed FL scheme. Conclusion: The proposed FL scheme is shown to be effective in predicting glioma and its subtypes by using MR images from test sets, with great potential of replacing the conventional CL approaches for training deep networks. This could help hospitals to maintain their data privacy, while using a federated trained classifier with nearly similar performance as that from a centrally trained one. Further detailed experiments have shown that different parts in the proposed 3D FL scheme, such as domain mapping (make datasets more uniform) and post-processing (scan-based classification), are essential.
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| 4. |
- Ge, Chenjie, 1991, et al.
(författare)
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Enlarged Training Dataset by Pairwise GANs for Molecular-Based Brain Tumor Classification
- 2020
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Ingår i: IEEE Access. - 2169-3536 .- 2169-3536. ; 8:1, s. 22560-22570
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Tidskriftsartikel (refereegranskat)abstract
- This paper addresses issues of brain tumor subtype classification using Magnetic Resonance Images (MRIs) from different scanner modalities like T1 weighted, T1 weighted with contrast-enhanced, T2 weighted and FLAIR images. Currently most available glioma datasets are relatively moderate in size, and often accompanied with incomplete MRIs in different modalities. To tackle the commonly encountered problems of insufficiently large brain tumor datasets and incomplete modality of image for deep learning, we propose to add augmented brain MR images to enlarge the training dataset by employing a pairwise Generative Adversarial Network (GAN) model. The pairwise GAN is able to generate synthetic MRIs across different modalities. To achieve the patient-level diagnostic result, we propose a post-processing strategy to combine the slice-level glioma subtype classification results by majority voting. A two-stage course-to-fine training strategy is proposed to learn the glioma feature using GAN-augmented MRIs followed by real MRIs. To evaluate the effectiveness of the proposed scheme, experiments have been conducted on a brain tumor dataset for classifying glioma molecular subtypes: isocitrate dehydrogenase 1 (IDH1) mutation and IDH1 wild-type. Our results on the dataset have shown good performance (with test accuracy 88.82%). Comparisons with several state-of-the-art methods are also included.
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| 5. |
- Tång Hallbäck, Erika, 1973, et al.
(författare)
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Outbreak of OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Western Sweden
- 2023
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 42:5, s. 597-605
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Tidskriftsartikel (refereegranskat)abstract
- In 2015, an outbreak caused by OXA-48-producing Enterobacteriaceae affected a neonatal intensive care unit at a Swedish University Hospital. The aim was to explore the transmission of OXA-48-producing strains between infants and the transfer of resistance plasmids between strains during the outbreak. Twenty-four outbreak isolates from ten suspected cases were whole-genome sequenced. A complete assembly was created for the index isolate (Enterobacter cloacae) and used as a mapping reference to detect its plasmids in the remaining isolates (17 Klebsiella pneumoniae, 4 Klebsiella aerogenes, and 2 Escherichia coli). Strain typing was performed using core genome MLST and SNP analysis. As judged from sequencing and clinical epidemiological data, the outbreak involved nine cases (two developed sepsis) and four OXA-48-producing strains: E. cloacae ST1584 (index case), K. pneumoniae ST25 (eight cases), K. aerogenes ST93 (two cases), and E. coli ST453 (2 cases). Two plasmids from the index strain, pEclA2 and pEclA4, carrying blaOXA48 and blaCMY-4, respectively, were traced to all K. pneumoniae ST25 isolates. Klebsiella aerogenes ST93 and E. coli ST453 harboured either only pEclA2, or both pEclA2 and pEclA4. One suspected case harbouring OXA-162-producing K. pneumoniae ST37 could be excluded from the outbreak. Once initiated by an E. cloacae strain, the outbreak was caused by the dissemination of a K. pneumoniae ST25 strain and involved inter-species horizontal transfer of two resistance plasmids, one of which carried blaOXA-48. To our knowledge, this is the first description of an outbreak of OXA-48-producing Enterobacteriaceae in a neonatal setting in northern Europe.
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| 6. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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| 7. |
- Barman, Malin, 1983, et al.
(författare)
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Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Serum Polyunsaturated Fatty Acid Composition and Development of Allergy (in a Swedish Birth Cohort).
- 2015
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 7:12, s. 10100-10115
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to polyunsaturated fatty acids (PUFA) influences immune function and may affect the risk of allergy development. Long chain PUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by FADS and ELOVL genes. In 211 subjects, we investigated whether polymorphisms in the FADS gene cluster and the ELOVL2 gene were associated with allergy or PUFA composition in serum phospholipids in a Swedish birth-cohort sampled at birth and at 13 years of age; allergy was diagnosed at 13 years of age. Minor allele carriers of rs102275 and rs174448 (FADS gene cluster) had decreased proportions of 20:4 n-6 in cord and adolescent serum and increased proportions of 20:3 n-6 in cord serum as well as a nominally reduced risk of developing atopic eczema, but not respiratory allergy, at 13 years of age. Minor allele carriers of rs17606561 in the ELOVL2 gene had nominally decreased proportions of 20:4 n-6 in cord serum but ELOVL polymorphisms (rs2236212 and rs17606561) were not associated with allergy development. Thus, reduced capacity to desaturase n-6 PUFAs due to FADS polymorphisms was nominally associated with reduced risk for eczema development, which could indicate a pathogenic role for long-chain PUFAs in allergy development.
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| 8. |
- Gryska, Emilia, 1992, et al.
(författare)
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Deep learning for automatic brain tumour segmentation on MRI: evaluation of recommended reporting criteria via a reproduction and replication study.
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- To determine the reproducibility and replicability of studies that develop and validate segmentation methods for brain tumours on MRI and that follow established reproducibility criteria; and to evaluate whether the reporting guidelines are sufficient.Two eligible validation studies of distinct deep learning (DL) methods were identified. We implemented the methods using published information and retraced the reported validation steps. We evaluated to what extent the description of the methods enabled reproduction of the results. We further attempted to replicate reported findings on a clinical set of images acquired at our institute consisting of high-grade and low-grade glioma (HGG, LGG), and meningioma (MNG) cases.We successfully reproduced one of the two tumour segmentation methods. Insufficient description of the preprocessing pipeline and our inability to replicate the pipeline resulted in failure to reproduce the second method. The replication of the first method showed promising results in terms of Dice similarity coefficient (DSC) and sensitivity (Sen) on HGG cases (DSC=0.77, Sen=0.88) and LGG cases (DSC=0.73, Sen=0.83), however, poorer performance was observed for MNG cases (DSC=0.61, Sen=0.71). Preprocessing errors were identified that contributed to low quantitative scores in some cases.Established reproducibility criteria do not sufficiently emphasise description of the preprocessing pipeline. Discrepancies in preprocessing as a result of insufficient reporting are likely to influence segmentation outcomes and hinder clinical utilisation. A detailed description of the whole processing chain, including preprocessing, is thus necessary to obtain stronger evidence of the generalisability of DL-based brain tumour segmentation methods and to facilitate translation of the methods into clinical practice.
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| 9. |
- Ekegren, Titti, et al.
(författare)
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Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience: exemplified in amyotrophic lateral sclerosis biomarker discovery research.
- 2008
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1076-5174 .- 1096-9888. ; 43:5, s. 559-71
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Forskningsöversikt (refereegranskat)abstract
- Biomarker discovery is a central application in today's proteomic research. There is an urgent need for valid biomarkers to improve diagnostic tools and treatment in many disorders, such as the rapidly progressing neurodegenerative disorder amyotrophic lateral sclerosis (ALS) that has a fatal outcome in about 3 years and yet no curative treatment. Screening for clinically relevant biomarkers puts high demands on high-throughput, rapid and precise proteomic techniques. There is a large variety in the methods of choice involving mainly gel-based approaches as well as chromatographic techniques for multi-dimensional protein and peptide separations followed by mass spectrometry (MS) analysis. This special feature article will discuss some important aspects of MS-based clinical proteomics and biomarker discovery in the field of neurodegenerative diseases and ALS research respectively, with the aim to provide a prospective view on current and future research aspects in the field. Furthermore, examples for application of high-resolution MS-based proteomic strategies for ALS biomarker discovery will be demonstrated with two studies previously reported by our group. These studies include among others, utilization of capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) for advanced protein pattern classification in cerebrospinal fluid (CSF) samples of ALS patients as well as highly sensitive protein identification in minimal amounts of postmortem spinal cord tissue and laser micro-dissected motor neurons using FT-ICR-MS in conjunction with nanoflow LC coupled to matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (LC-MALDI-TOF-TOF-MS).
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| 10. |
- Culverhouse, R. C., et al.
(författare)
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Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:1, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
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