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1.
  • Ge, Chenjie, et al. (författare)
  • Enlarged Training Dataset by Pairwise GANs for Molecular-Based Brain Tumor Classification
  • 2020
  • Ingår i: IEEE Access. - 2169-3536. ; 8:1, s. 22560-22570
  • 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.
2.
  • Toschke, Audré M., et al. (författare)
  • Paternal smoking is associated with a decreased prevalence of type 1 diabetes mellitus among offspring in two national British birth cohort studies (NCDS and BCS70)
  • 2007
  • Ingår i: Journal of Perinatal Medicine. - Berlin : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 35:1, s. 43-7
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>AB Aims: An association between paternal age and type 1 diabetes (IDDM) among their offspring was recently reported as well as transgenerational responses in humans. This paper aims to assess the association of markers for prenatal exposures with IDDM. Methods: We analysed data from two birth cohorts in Great Britain on 5214 cohort members from the National Child Development Study (NCDS) and 6068 members of the 1970 British Birth Cohort Study (BCS70) with full information on IDDM and explanatory variables using multivariate logistic regression. Results: IDDM prevalence was 0.7% (95% CI 0.5-1.0%; n = 38) in the NCDS and 0.4% (95% CI 0.3-0.6%; n = 27) in the BCS70 cohort. Paternal age was not associated with IDDM possibly due to lack of sample power. Unex-pectedly, a lowered prevalence of IDDM was observed among offspring of smoking fathers in both cohorts, with a combined odds ratio of 0.44 (95% CI 0.25-0.75). This association could not be explained by maternal smoking prior to, during or after pregnancy, number of siblings, parental social class, maternal and paternal age, or cohort. Maternal smoking in pregnancy did not alter the IDDM prevalence among offspring. Conclusions: This unexpected finding may be explained by germ-line mutations or other mechanisms associated with paternal smoking. This phenomenon should be investigated and these results should not be used as a justification for smoking. Paternal exposures may be important in determining IDDM risk.</p>
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3.
  • Johansson, Per, et al. (författare)
  • Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.
  • 2017
  • Ingår i: PloS one. - 1932-6203. ; 12:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The role of inflammation in Alzheimer’s disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples. Methods Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel. Results After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1–42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01). Conclusions Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
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7.
  • Petersson, Jesper, 1974- (författare)
  • Medicine At A Distance In Sweden: Spatiotemporal Matters In Accomplishing Working Telemedicine
  • 2011
  • Ingår i: Science Studies. - 0786-3012. ; 24:2, s. 43-62
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper examines the accomplishment of making technology work, using the discourse around telemedicine in Swedish healthcare during 1994-2003. The paper will compare four projects launched in the mid-1990s and policymakers’ visions of healthcare through telemedicine. I will employ a sociotechnical approach developed within Actor-Network Theory that understands functioning technology not as something intrinsic but as an outcome of an ongoing process of negotiations. In the paper, I will extend the sociotechnical approach of what constitutes working technology to include spatiotemporal matters. I will also approach the closely related issue of space that has become a concern of Actor-Network Theory scholars interested in the accomplishment and continued workings of technology as it travels. In this discussion, an emphasis on fixed relations (network space) has been challenged by investigations into changing relations (fluid space). This paper suggests that in order to travel well, technology must be both fixed and fluid.⁰
8.
  • Björkman, Kristoffer, et al. (författare)
  • Genotype-phenotype correlations in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1
  • 2014
  • Ingår i: Euromit 2014, 15-19 juni, Tampere, Finland.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Objectives: To study genotype-phenotype correlations in genes encoding complex I electron input module subunits. Materials and methods: We studied five patients with isolated complex I deficiency, three with NDUFS1 mutations and two with NDUFV1 mutations. A literature review of all reported cases of mutations in the affected genes was performed. Results: The literature review revealed pathological mutations in NDUFS1 for 18 patients in 17 families and correspondingly in NDUFV1 for 26 patients in 19 families. Unpublished clinical data for our five patients were added. Our study showed quite variable clinical courses; death before two years of age was seen in 41% of patients while 18% were alive at seven years. There was a significant difference between the NDUFS1 and NDUFV1 groups for clinical onset and life-span. Mutations in NDUFS1 were linked to a worse clinical course with earlier onset and earlier death. Conclusions: Genotype-phenotype correlations in patients with mutations affecting the genes that encode the electron input module of complex I vary, but patients with NDUFS1 mutation tend to have a worse clinical course than patients with NDUFV1 mutation. Identifying the mutations is of importance for accurate prognostic information and genetic counseling.
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9.
  • Paterson, R. W., et al. (författare)
  • A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.
  • 2016
  • Ingår i: Translational psychiatry. - 2158-3188. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.
10.
  • Lundin, Anna-Carin (författare)
  • Tendinosis in Trigger Finger
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.</p><p>We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.</p><p>Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.</p><p>Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.</p><p>We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.</p><p>In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.</p>
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