| 1. |
- Turkki, Riku, et al.
(author)
-
Breast cancer outcome prediction with tumour tissue images and machine learning
- 2019
-
In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 177:1, s. 41-52
-
Journal article (peer-reviewed)abstract
- Purpose: Recent advances in machine learning have enabled better understanding of large and complex visual data. Here, we aim to investigate patient outcome prediction with a machine learning method using only an image of tumour sample as an input.Methods: Utilising tissue microarray (TMA) samples obtained from the primary tumour of patients (N=1299) within a nationwide breast cancer series with long-term-follow-up, we train and validate a machine learning method for patient outcome prediction. The prediction is performed by classifying samples into low or high digital risk score (DRS) groups. The outcome classifier is trained using sample images of 868 patients and evaluated and compared with human expert classification in a test set of 431 patients.Results: In univariate survival analysis, the DRS classification resulted in a hazard ratio of 2.10 (95% CI 1.33-3.32, p=0.001) for breast cancer-specific survival. The DRS classification remained as an independent predictor of breast cancer-specific survival in a multivariate Cox model with a hazard ratio of 2.04 (95% CI 1.20-3.44, p=0.007). The accuracy (C-index) of the DRS grouping was 0.60 (95% CI 0.55-0.65), as compared to 0.58 (95% CI 0.53-0.63) for human expert predictions based on the same TMA samples.Conclusions: Our findings demonstrate the feasibility of learning prognostic signals in tumour tissue images without domain knowledge. Although further validation is needed, our study suggests that machine learning algorithms can extract prognostically relevant information from tumour histology complementing the currently used prognostic factors in breast cancer.
|
|
| 2. |
- Adam, A, et al.
(author)
-
Abstracts from Hydrocephalus 2016.
- 2017
-
In: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
-
Journal article (peer-reviewed)
|
|
| 3. |
- Austin, Christine, et al.
(author)
-
Elemental Dynamics in Hair Accurately Predict Future Autism Spectrum Disorder Diagnosis : An International Multi-Center Study
- 2022
-
In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:23
-
Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed in approximately 2% of children. Reliance on the emergence of clinically observable behavioral patterns only delays the mean age of diagnosis to approximately 4 years. However, neural pathways critical to language and social functions develop during infancy, and current diagnostic protocols miss the age when therapy would be most effective. We developed non-invasive ASD biomarkers using mass spectrometry analyses of elemental metabolism in single hair strands, coupled with machine learning. We undertook a national prospective study in Japan, where hair samples were collected at 1 month and clinical diagnosis was undertaken at 4 years. Next, we analyzed a national sample of Swedish twins and, in our third study, participants from a specialist ASD center in the US. In a blinded analysis, a predictive algorithm detected ASD risk as early as 1 month with 96.4% sensitivity, 75.4% specificity, and 81.4% accuracy (n = 486; 175 cases). These findings emphasize that the dynamics in elemental metabolism are systemically dysregulated in autism, and these signatures can be detected and leveraged in hair samples to predict the emergence of ASD as early as 1 month of age.
|
|
| 4. |
|
|
| 5. |
- Curtin, Paul, et al.
(author)
-
Associations between Elemental Metabolic Dynamics and Default Mode Network Functional Connectivity Are Altered in Autism.
- 2023
-
In: Journal of clinical medicine. - : MDPI. - 2077-0383. ; 12:3
-
Journal article (peer-reviewed)abstract
- Autism is a neurodevelopmental condition associated with atypical social communication, cognitive, and sensory faculties. Recent advances in exposure biology suggest that biomarkers of elemental uptake and metabolism measured in hair samples can yield an effective signal predictive of autism diagnosis. Here, we investigated if elemental biomarkers in hair were associated with functional connectivity in regions of the default mode network (DMN) previously linked to autism. In a study sample which included twin pairs with concordant and discordant diagnoses for autism, our analysis of hair samples and neuroimaging data supported two general findings. First, independent of autism diagnosis, we found a broad pattern of association between elemental biomarkers and functional connectivity in the DMN, which primarily involved dynamics in zinc metabolism. Second, we found that associations between the DMN and elemental biomarkers, particularly involving phosphorus, calcium, manganese, and magnesium, differed significantly in autistic participants from control participants. In sum, these findings suggest that functional dynamics in elemental metabolism relate broadly to persistent patterns of functional connectivity in the DMN, and that these associations are altered in the emergence of autism.
|
|
| 6. |
- Dumitriu, Dani, et al.
(author)
-
Deciduous tooth biomarkers reveal atypical fetal inflammatory regulation in autism spectrum disorder.
- 2023
-
In: iScience. - : Cell Press. - 2589-0042. ; 26:3
-
Journal article (peer-reviewed)abstract
- Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured by developmentally archived C-reactive protein (CRP) in incremental layers of deciduous tooth dentin. In our discovery population, a group of Swedish twins, we found heightened inflammation in the third trimester in children with future ASD diagnosis relative to controls (n = 66; 14 ASD cases; critical window: -90 to -50 days before birth). In our replication study, in the US, we observed a similar increase in CRP in ASD cases during the third trimester (n = 47; 23 ASD cases; -128 to -21 days before birth). Our results indicate that the third trimester is a critical period of atypical fetal inflammatory regulation in ASD.
|
|
| 7. |
- Eliasson, Pernilla T., et al.
(author)
-
Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release - a cohort study design combined with an experimental study
- 2019
-
In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
-
Journal article (peer-reviewed)abstract
- Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21-1.85) and 1.21 (1.02-1.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24-1.65) and women (aHR 1.41; 0.97-2.05). Former users did not confer a higher risk of tendinopathies. In vitro experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries.
|
|
| 8. |
- Eriksson Domellöf, Magdalena, et al.
(author)
-
Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson's disease
- 2017
-
In: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 38, s. 41-47
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Studies report that up to 90% of patients with idiopathic Parkinson's disease (PD) have olfactory dysfunction (hyposmia). Hyposmia has also been connected to cognitive impairment and dementia in PD, but no studies of newly diagnosed patients followed longer than three years exists. The present study investigates the prevalence of olfactory dysfunction at PD diagnosis, how it evolves over time and whether hyposmia increases the risk of dementia in Parkinson's disease.METHODS: Olfactory function was assessed with Brief Smell Identification Test (B-SIT) in 125 newly diagnosed patients with PD. They were followed for a maximum of 10 years (median six years) with extensive investigations at baseline, 12, 36, 60 and 96 months. Patients with B-SIT<9 were considered hyposmic.RESULTS: Hyposmia was found in 73% of the patients at diagnosis. During the follow up period of ten years 42 (46%) patients with hyposmia at baseline developed dementia compared to seven (21%) of the normosmic patients. Cox proportional hazards model showed that hyposmia at baseline (controlled for age, gender, UPDRS III and Mild Cognitive Impairment) increased the risk of developing dementia (hazard ratio (95%CI): 3.29 (1.44-7.52), p = 0.005). Only one of 22 patients with normal cognition and normal olfaction at baseline developed dementia.CONCLUSIONS: Olfactory dysfunction was common at the time of PD diagnosis and increased the risk of dementia up to ten years after PD diagnosis regardless of baseline cognitive function. Normal olfaction together with normal cognition at baseline predicted a benign cognitive course up to ten years after diagnosis.
|
|
| 9. |
- Forsslund, Jonas, 1983-
(author)
-
Preparing Spatial Haptics for Interaction Design
- 2016
-
Doctoral thesis (other academic/artistic)abstract
- Spatial haptics is a fascinating technology with which users can explore and modify3D computer graphics objects with the sense of touch, but its application potentialis often misunderstood. For a large group of application designers it is still unknown,and those who are aware of it often have either too high expectations of what is technicallyachievable or believe it is too complicated to consider at all. In addition, spatialhaptics is in its current form ill-suited to interaction design. This is partly because theproperties and use qualities cannot be experienced in an application prototype until asystem is fully implemented, which takes too much effort to be practical in most designsettings. In order to find a good match between a solution and a framing of aproblem, the designer needs to be able to mould/shape/form the technology into a solution,but also to re-frame the problem and question initial conceptual designs as shelearns more about what the technology affords. Both of these activities require a goodunderstanding of the design opportunities of this technology.In this thesis I present a new way of working with spatial haptic interaction design.Studying the serially linked mechanism from a well-known haptic device, and a forcereflectingcarving algorithm in particular, I show how to turn these technologies froman esoteric engineering form into a form ready for interaction design. The work isgrounded in a real application: an oral surgery simulator named Kobra that has beendeveloped over the course of seven years within our research group. Its design hasgone through an evolutionary process with iterative design and hundreds of encounterswith the audience; surgeon-teachers as users and potential customers. Some ideas, e.g.gestalting authentic patient cases, have as a result received increased attention by thedesign team, while other ideas, e.g. automatic assessment, have faded away.Simulation is an idea that leads to ideals of realism; that e.g. simulated instrumentsshould behave as in reality, e.g. a simulated dental instrument for prying teeth is expectedto behave according to the laws of physics and give force and torque feedback.If it does not, it is a bad simulation. In the present work it is shown how some of therealism ideal is unnecessary for creating meaningful learning applications and can actuallyeven be counter-productive, since it may limit the exploration of creative designsolutions. This result is a shift in perspective from working towards constantly improvingtechnological components, to finding and making use of the qualities of modern,but not necessarily absolute cutting-edge, haptic technology.To be able to work creatively with a haptic system as a design resource we needto learn its material qualities and how - through changing essential properties - meaningfulexperiential qualities can be modulated and tuned. This requires novel tools andworkflows that enable designers to explore the creative design space, create interactionsketches and tune the design to cater for the user experience. In essence, this thesisshows how one instance of spatial haptics can be turned from an esoteric technologyinto a design material, and how that can be used, and formed, with novel tools throughthe interaction design of a purposeful product in the domain of dental education.
|
|
| 10. |
- Franco, Irene, et al.
(author)
-
Somatic mutagenesis in satellite cells associates with human skeletal muscle aging
- 2018
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Journal article (peer-reviewed)abstract
- Human aging is associated with a decline in skeletal muscle (SkM) function and a reduction in the number and activity of satellite cells (SCs), the resident stem cells. To study the connection between SC aging and muscle impairment, we analyze the whole genome of single SC clones of the leg muscle vastus lateralis from healthy individuals of different ages (21-78 years). We find an accumulation rate of 13 somatic mutations per genome per year, consistent with proliferation of SCs in the healthy adult muscle. SkM-expressed genes are protected from mutations, but aging results in an increase in mutations in exons and promoters, targeting genes involved in SC activity and muscle function. In agreement with SC mutations affecting the whole tissue, we detect a missense mutation in a SC propagating to the muscle. Our results suggest somatic mutagenesis in SCs as a driving force in the age-related decline of SkM function.
|
|
