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| 2. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 3. |
- Ben-Shabat, Ilan, et al.
(författare)
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Characteristics of in-hospital stroke patients in Sweden : a nationwide register-based study
- 2023
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Ingår i: European Stroke Journal. - : Sage Publications. - 2396-9873 .- 2396-9881. ; 8:3, s. 777-783
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Few studies have reported the characteristics of patients with in-hospital stroke (IHS) including the reason for hospitalization and invasive procedures before the stroke. We aimed to extend current knowledge.PATIENTS AND METHODS: All adult patients with IHS in Sweden during 2010-2019 registered in the Swedish Stroke Register (Riksstroke) were included. The cohort was cross-linked to the National Patient Register and data extracted on background diagnoses, main discharge diagnoses, and procedure codes for the hospitalization when IHS occurred and any hospital-based healthcare contacts within 30 days before IHS.RESULTS: 231,402 stroke cases were identified of which 12,551 (5.4%) were in-hospital and had corresponding entries in the National Patient Register. Of the IHS patients, 11,420 (91.0%) had ischemic stroke and 1131 (9.0%) hemorrhagic stroke; 5860 (46.7%) of the IHS patients had at least one invasive procedure prior to ictus. 1696 (13.5%) had a cardiovascular procedure and 560 (4.5%) a neurosurgical procedure. 1319 (10.5%) patients only had minimally invasive procedures such as blood product transfusion, hemodialysis, or central line insertion. Common discharge diagnosis in patients with no invasive procedures were cardiovascular disorders, injuries, and respiratory disorders.DISCUSSION AND CONCLUSION: One in every 17 strokes in Sweden occur in a hospital. In this unselected large cohort the previously reported major causes for in-hospital stroke, cardiovascular and neurosurgical procedures, preceded IHS in only 18.0% of cases suggesting that other etiologies are more common than previously reported. Future studies should aim at determining absolute risks of stroke after surgical procedures and ways of risk reduction.
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| 4. |
- Danielson, Mattias, et al.
(författare)
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Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study
- 2020
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 87:3, s. 370-382
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Tidskriftsartikel (refereegranskat)abstract
- Objective Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of >= 1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. Methods Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. Results Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). Interpretation Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort.
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| 5. |
- Danielsson, Mattias, et al.
(författare)
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Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.
- 2021
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Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 467-76
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.
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| 6. |
- Eriksson, Gustav, et al.
(författare)
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Boundary and interface methods for energy stable finite difference discretizations of the dynamic beam equation
- 2023
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Ingår i: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716. ; 476
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Tidskriftsartikel (refereegranskat)abstract
- We consider energy stable summation by parts finite difference methods (SBP-FD) for the homogeneous and piecewise homogeneous dynamic beam equation (DBE). Previously the constant coefficient problem has been solved with SBP-FD together with penalty terms (SBP-SAT) to impose boundary conditions. In this work, we revisit this problem and compare SBP-SAT to the projection method (SBP-P). We also consider the DBE with discontinuous coefficients and present novel SBP-SAT, SBP-P, and hybrid SBP-SAT-P discretizations for imposing interface conditions. To demonstrate the methodology for two-dimensional problems, we also present a discretization of the piecewise homogeneous dynamic Kirchoff-Love plate equation based on the hybrid SBP-SAT-P method. Numerical experiments show that all methods considered are similar in terms of accuracy, but that SBP-P can be more computationally efficient (less restrictive time step requirement for explicit time integration methods) for both the constant and piecewise constant coefficient problems.
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| 7. |
- Eriksson, Jonatan
(författare)
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Algorithms and Methods for Robust Processing and Analysis of Mass Spectrometry Data
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Liquid chromatography-mass spectrometry (LC-MS) and mass spectrometry imaging (MSI) are two techniques that are routinely used to study proteins, peptides, and metabolites at a large scale. Thousands of biological compounds can be identified and quantified in a single experiment with LC-MS, but many studies fail to convert this data to a better understanding of disease biology. One of the primary reasons for this is low reproducibility, which in turn is partially due to inaccurate and/or inconsistent data processing. Protein biomarkers and signatures for various types of cancer are frequently discovered with LC-MS, but their behavior in independent cohorts is often inconsistent to that in the discovery cohort. Biomarker candidates must be thoroughly validated in independent cohorts, which makes the ability to share data across different laboratories crucial to the future success of the MS-based research fields. The emergence and growth of public repositories for MSI data is a step in the rightdirection. Still, many of those data sets remain incompatible one another due to inaccurate or incompatible preprocessing strategies. Ensuring compatibility between data generated in different labs is therefore necessary to gain access to the full potential of MS-based research. In two of the studies that I present in this thesis, we used LC-MS to characterize lymph node metastases from individuals with melanoma. Furthermore, my thesis work has resulted in two novel preprocessing methods for MSI data sets. The first one is a peak detection method that achieves considerably higher sensitivity for faintly expressed compounds than existing methods, and the second one is a accurate, robust, and general approach to mass alignment. Both algorithms deliberately rely on centroid spectra, which makes them compatible with most shared data sets. I believe that the improvements demonstrated by these methods can lead to a higher reproducibility in the MS-based research fields, and, ultimately, to a better understanding of disease processes.
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| 8. |
- Eriksson, Jonatan O., et al.
(författare)
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MSIWarp : A General Approach to Mass Alignment in Mass Spectrometry Imaging
- 2020
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 92:24, s. 16138-16148
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Tidskriftsartikel (refereegranskat)abstract
- Mass spectrometry imaging (MSI) is a technique that provides comprehensive molecular information with high spatial resolution from tissue. Today, there is a strong push toward sharing data sets through public repositories in many research fields where MSI is commonly applied; yet, there is no standardized protocol for analyzing these data sets in a reproducible manner. Shifts in the mass-to-charge ratio (m/z) of molecular peaks present a major obstacle that can make it impossible to distinguish one compound from another. Here, we present a label-free m/z alignment approach that is compatible with multiple instrument types and makes no assumptions on the sample's molecular composition. Our approach, MSIWarp (https://github.com/horvatovichlab/MSIWarp), finds an m/z recalibration function by maximizing a similarity score that considers both the intensity and m/z position of peaks matched between two spectra. MSIWarp requires only centroid spectra to find the recalibration function and is thereby readily applicable to almost any MSI data set. To deal with particularly misaligned or peak-sparse spectra, we provide an option to detect and exclude spurious peak matches with a tailored random sample consensus (RANSAC) procedure. We evaluate our approach with four publicly available data sets from both time-of-flight (TOF) and Orbitrap instruments and demonstrate up to 88% improvement in m/z alignment.
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| 9. |
- Lundin, Jonatan
(författare)
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Shaping thought through action : A study of the use and design of technical information
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation deals with the design of technical information, such as a user manual for an industrial device, based on the searching and reading behaviour of process operators and maintenance technicians. Such industrial professionals, who use tools like measuring equipment, are sometimes unable to get the support they need from searching and reading in a text- and image-based tool manual in order to perform work tasks. If such a manual is the only available source of information, the user will either give up or attempt a workaround which ends up compromising the safety, quality, satisfaction, efficiency or effectiveness of the work task. Research within technical communication and human-computer interaction suggests how manuals can be designed to support users in accomplishing tasks. These suggestions are based upon studies of how users approach the use of tools and tool manuals, as well as how the design of procedural and declarative information supports users. However, there is limited knowledge about how users search and read manuals, and how manuals can be designed to support such searching and reading behaviour. This dissertation aims to contribute knowledge to technical communicators about how technical information can be designed to support industrial professionals in accomplishing their work tasks. An ethnographic research method was selected to study the behaviour exhibited by process operators and maintenance technicians’ while they search and read sources of information in order to perform work tasks with tools. The results show that some participants were unable to perform a task after searching and reading the manual. The empirical material has been analysed using Vygotsky’s sociocultural theory. This was to gain a deeper understanding of how thought and language influence—and are influenced by—searching and reading behaviours, as well as the task behaviours during tool use. This dissertation's contribution is a design method for technical communicators that will enable them to support users in the shaping of mental representations about what results are possible to accomplish with a tool. The method involves the design of tangible tokens that signify the results and components of a tool. As the end-user arranges these symbols into a result model they are supported in their process of shaping a mental representation.
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| 10. |
- Mulder, Skander, et al.
(författare)
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A metabolomics-based molecular pathway analysis of how the sodium-glucose co-transporter-2 inhibitor dapagliflozin may slow kidney function decline in patients with diabetes
- 2020
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Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326. ; 22:7, s. 1157-1166
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate which metabolic pathways are targeted by the sodium-glucose co-transporter-2 inhibitor dapagliflozin to explore the molecular processes involved in its renal protective effects. Methods An unbiased mass spectrometry plasma metabolomics assay was performed on baseline and follow-up (week 12) samples from the EFFECT II trial in patients with type 2 diabetes with non-alcoholic fatty liver disease receiving dapagliflozin 10 mg/day (n = 19) or placebo (n = 6). Transcriptomic signatures from tubular compartments were identified from kidney biopsies collected from patients with diabetic kidney disease (DKD) (n = 17) and healthy controls (n = 30) from the European Renal cDNA Biobank. Serum metabolites that significantly changed after 12 weeks of dapagliflozin were mapped to a metabolite-protein interaction network. These proteins were then linked with intra-renal transcripts that were associated with DKD or estimated glomerular filtration rate (eGFR). The impacted metabolites and their protein-coding transcripts were analysed for enriched pathways. Results Of all measured (n = 812) metabolites, 108 changed (P < 0.05) during dapagliflozin treatment and 74 could be linked to 367 unique proteins/genes. Intra-renal mRNA expression analysis of the genes encoding the metabolite-associated proteins using kidney biopsies resulted in 105 genes that were significantly associated with eGFR in patients with DKD, and 135 genes that were differentially expressed between patients with DKD and controls. The combination of metabolites and transcripts identified four enriched pathways that were affected by dapagliflozin and associated with eGFR: glycine degradation (mitochondrial function), TCA cycle II (energy metabolism), L-carnitine biosynthesis (energy metabolism) and superpathway of citrulline metabolism (nitric oxide synthase and endothelial function). Conclusion The observed molecular pathways targeted by dapagliflozin and associated with DKD suggest that modifying molecular processes related to energy metabolism, mitochondrial function and endothelial function may contribute to its renal protective effect.
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