| 1. |
- Sandstedt, Mikael, 1990, et al.
(author)
-
Regional transcriptomic profiling reveals immune system enrichment in nonfailing atria as well as all chambers of the failing human heart
- 2023
-
In: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 325:6, s. H1430-H1445
-
Journal article (peer-reviewed)abstract
- The different chambers of the human heart demonstrate regional physiological traits and may be differentially affected during pathologic remodeling, resulting in heart failure. Few previous studies have, however, characterized the different chambers at a transcriptomic level. We therefore conducted whole-tissue RNA sequencing and gene set enrichment analysis of biopsies collected from the four chambers of adult failing (n = 8) and nonfailing (n = 11) human hearts. Atria and ventricles demonstrated distinct transcriptional patterns. Compared to nonfailing ventricles, the transcriptional pattern of nonfailing atria was enriched for a large number of gene sets associated with cardiogenesis, the immune system and bone morphogenetic protein (BMP), transforming growth factor beta (TGF beta), MAPK/JNK and Wnt signaling. Differences between failing and nonfailing hearts were also determined. The transcriptional pattern of failing atria was distinct compared to that of nonfailing atria and enriched for gene sets associated with the innate and adaptive immune system, TGF beta/SMAD signaling, and changes in endothelial, smooth muscle cell and cardiomyocyte physiology. Failing ventricles were also enriched for gene sets associated with the immune system. Based on the transcriptomic patterns, upstream regulators associated with heart failure were identified. These included many immune response factors predicted to be similarly activated for all chambers of failing hearts. In summary, the heart chambers demonstrate distinct transcriptional patterns that differ between failing and nonfailing hearts. Immune system signaling may be a hallmark of all four heart chambers in failing hearts, and could constitute a novel therapeutic target.
|
|
| 2. |
|
|
| 3. |
- Ahmad, Shahzad, et al.
(author)
-
CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE ε4 carriers
- 2020
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- Many Alzheimer’s disease (AD) genes including Apolipoprotein E (APOE) are found to be expressed in blood-derived macrophages and thus may alter blood protein levels. We measured 91 neuro-proteins in plasma from 316 participants of the Rotterdam Study (incident AD = 161) using Proximity Extension Ligation assay. We studied the association of plasma proteins with AD in the overall sample and stratified by APOE. Findings from the Rotterdam study were replicated in 186 AD patients of the BioFINDER study. We further evaluated the correlation of these protein biomarkers with total tau (t-tau), phosphorylated tau (p-tau) and amyloid-beta (Aβ) 42 levels in cerebrospinal fluid (CSF) in the Amsterdam Dementia Cohort (N = 441). Finally, we conducted a genome-wide association study (GWAS) to identify the genetic variants determining the blood levels of AD-associated proteins. Plasma levels of the proteins, CDH6 (β = 0.638, P = 3.33 × 10−4) and HAGH (β = 0.481, P = 7.20 × 10−4), were significantly elevated in APOE ε4 carrier AD patients. The findings in the Rotterdam Study were replicated in the BioFINDER study for both CDH6 (β = 1.365, P = 3.97 × 10−3) and HAGH proteins (β = 0.506, P = 9.31 × 10−7) when comparing cases and controls in APOE ε4 carriers. In the CSF, CDH6 levels were positively correlated with t-tau and p-tau in the total sample as well as in APOE ε4 stratum (P < 1 × 10−3). The HAGH protein was not detected in CSF. GWAS of plasma CDH6 protein levels showed significant association with a cis-regulatory locus (rs111283466, P = 1.92 × 10−9). CDH6 protein is implicated in cell adhesion and synaptogenesis while HAGH protein is related to the oxidative stress pathway. Our findings suggest that these pathways may be altered during presymptomatic AD and that CDH6 and HAGH may be new blood-based biomarkers.
|
|
| 4. |
|
|
| 5. |
- Arvidsson, Ida, et al.
(author)
-
Comparing a pre-defined versus deep learning approach for extracting brain atrophy patterns to predict cognitive decline due to Alzheimer’s disease in patients with mild cognitive symptoms
- 2024
-
In: Alzheimer's Research and Therapy. - 1758-9193. ; 16:1
-
Journal article (peer-reviewed)abstract
- Background: Predicting future Alzheimer’s disease (AD)-related cognitive decline among individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) is an important task for healthcare. Structural brain imaging as measured by magnetic resonance imaging (MRI) could potentially contribute when making such predictions. It is unclear if the predictive performance of MRI can be improved using entire brain images in deep learning (DL) models compared to using pre-defined brain regions. Methods: A cohort of 332 individuals with SCD/MCI were included from the Swedish BioFINDER-1 study. The goal was to predict longitudinal SCD/MCI-to-AD dementia progression and change in Mini-Mental State Examination (MMSE) over four years. Four models were evaluated using different predictors: (1) clinical data only, including demographics, cognitive tests and APOE ε4 status, (2) clinical data plus hippocampal volume, (3) clinical data plus all regional MRI gray matter volumes (N = 68) extracted using FreeSurfer software, (4) a DL model trained using multi-task learning with MRI images, Jacobian determinant images and baseline cognition as input. A double cross-validation scheme, with five test folds and for each of those ten validation folds, was used. External evaluation was performed on part of the ADNI dataset, including 108 patients. Mann-Whitney U-test was used to determine statistically significant differences in performance, with p-values less than 0.05 considered significant. Results: In the BioFINDER cohort, 109 patients (33%) progressed to AD dementia. The performance of the clinical data model for prediction of progression to AD dementia was area under the curve (AUC) = 0.85 and four-year cognitive decline was R2 = 0.14. The performance was improved for both outcomes when adding hippocampal volume (AUC = 0.86, R2 = 0.16). Adding FreeSurfer brain regions improved prediction of four-year cognitive decline but not progression to AD (AUC = 0.83, R2 = 0.17), while the DL model worsened the performance for both outcomes (AUC = 0.84, R2 = 0.08). A sensitivity analysis showed that the Jacobian determinant image was more informative than the MRI image, but that performance was maximized when both were included. In the external evaluation cohort from ADNI, 23 patients (21%) progressed to AD dementia. The results for predicted progression to AD dementia were similar to the results for the BioFINDER test data, while the performance for the cognitive decline was deteriorated. Conclusions: The DL model did not significantly improve the prediction of clinical disease progression in AD, compared to regression models with a single pre-defined brain region.
|
|
| 6. |
|
|
| 7. |
- Benner, Mats, et al.
(author)
-
Will the Center Hold? What Research Centers Do to Universities and to Societal Challenges
- 2024
-
In: Making Universities Matter. - Cham : Springer. - 2197-5698 .- 2197-5701. - 9783031487996 - 9783031487989 ; Part F2013, s. 123-140
-
Book chapter (peer-reviewed)abstract
- Research centers represent a specific organizational format for linking the traditional university organization with external actors, goals, and processes in time-limited, concentrated efforts of research and collaboration. Yet, the center format contains large variations, and centers act as interfaces between university organizations, societal actors, and research funders in multifaceted ways. In this chapter, we focus analytically on the organizational structuration of universities and the influence of external funding on the steering of work modes and orientations of academic research. We ask what centers do, how they affect universities’ operations, and why some centers are more successful than others in their missions. We address these questions through an analysis of six centers within the 10-year Vinn Excellence and Berzelii center schemes run by the Swedish innovation Agency Vinnova, drawing on interviews, evaluation reports, and a broad range of archival data. We highlight great variations in how universities are influenced by center funding, which is most effective when aligned with internal university strategies. Center success depends on the fit and integration of internal and external ambitions, university strategies, and partner orientations. However, such alignment is merely reinforced, rather than altered, by external center support.
|
|
| 8. |
- Björklund, Anders, et al.
(author)
-
A Combined α-Synuclein/Fibril (SynFib) Model of Parkinson-Like Synucleinopathy Targeting the Nigrostriatal Dopamine System
- 2022
-
In: Journal of Parkinson's Disease. - 1877-718X. ; 12:8, s. 2307-2320
-
Research review (peer-reviewed)abstract
- Injections of pre-formed α-synuclein fibrils (PFFs) or overexpression of α-synuclein using AAV vectors are commonly used as models of Parkinson-like synucleinopathy in rats and mice. In the modified method reviewed here, the "SynFib" model, the PFFs and the AAV vector are administered together unilaterally into the substantia nigra. This approach combines the key features of these two models, i.e., the generation of toxic α-synuclein aggregates and Lewy body-like inclusions, in combination with the increased vulnerability caused by increased cellular levels of α-synuclein. The combined AAV/PFF delivery offers several advantages over the standard PFF model due to the enhanced and accelerated α-synuclein pathology and microglial response induced by the PFF seeds in the presence of an elevated α-synuclein level. Injection of the AAV/PFF mixture into the substantia nigra makes it possible to target a larger proportion of the nigral dopamine neurons and obtain a level of dopamine cell loss (>60%) needed to induce significant impairments in drug-induced and spontaneous motor tests. The SynFib model shares attractive features of the standard 6-OHDA lesion model: a single unilateral stereotaxic intervention; pathology and cell loss developing over a short time span; and the possibility to monitor the degenerative changes using tests of motor behavior.
|
|
| 9. |
- Butler, Simon, et al.
(author)
-
An Exploration of Openness in Hardware and Software Through Implementation of a RISC-V Based Desktop Computer
- 2022
-
In: OpenSym '22. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450398459 - 9781450398466
-
Conference paper (peer-reviewed)abstract
- Open hardware and open source software platforms bring benefits to both implementers and users in the form of system adaptability and maintainability, and through the avoidance of lock-in, for example. Development of the \riscv\ Instruction Set Architecture and processors during the last ten years has made the implementation of a desktop computer using open hardware, including open processors, and open source software an approaching possibility. We use the SiFive Unmatched development board and Ubuntu Linux, and the recorded experiences of system builders using the Unmatched board to explore the extent to which it is possible to create an open desktop computer. The work identifies current limitations to implementing an open computer system, which lie mainly at the interface between the operating system and hardware components. Potential solutions to the challenges uncovered are proposed, including greater consideration of openness during the early stages of product design. A further contribution is made by an account of the synergies arising from open collaboration in a private-collective innovation process.
|
|
| 10. |
- Butler, Simon, et al.
(author)
-
Considerations and challenges for the adoption of open source components in software-intensive businesses
- 2022
-
In: Journal of Systems and Software. - : Elsevier. - 0164-1212 .- 1873-1228. ; 186
-
Journal article (peer-reviewed)abstract
- Component-Based Software Development is a conventional way of working for software-intensive businesses and OpenSource Software (OSS) components are frequently considered by businesses for adoption and inclusion in softwareproducts. Previous research has found a variety of practices used to support the adoption of OSS components, in-cluding formally specified processes and less formal, developer-led approaches, and that the practices used continue todevelop. Evolutionary pressures identified include the proliferation of available OSS components and increases in thepace of software development as businesses move towards continuous integration and delivery. We investigate workpractices used in six software-intensive businesses in the primary and secondary software sectors to understand currentapproaches to OSS component adoption and the challenges businesses face establishing effective work practices to eval-uate OSS components. We find businesses have established processes for evaluating OSS components and communitiesthat support more complex and nuanced considerations of the cost and risks of component adoption alongside matterssuch as licence compliance and functional requirements. We also found that the increasing pace and volume of softwaredevelopment within some businesses provides pressure to continue to evolve software evaluation processes.
|
|
