| 1. |
- Andersson, Martin, et al.
(författare)
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Thin film metal sensors in fusion bonded glass chips for high-pressure microfluidics
- 2017
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- High-pressure microfluidics offers fast analyses of thermodynamic parameters for compressed process solvents. However, microfluidic platforms handling highly compressible supercritical CO2 are difficult to control, and on-chip sensing would offer added control of the devices. Therefore, there is a need to integrate sensors into highly pressure tolerant glass chips. In this paper, thin film Pt sensors were embedded in shallow etched trenches in a glass wafer that was bonded with another glass wafer having microfluidic channels. The devices having sensors integrated into the flow channels sustained pressures up to 220 bar, typical for the operation of supercritical CO2. No leakage from the devices could be found. Integrated temperature sensors were capable of measuring local decompression cooling effects and integrated calorimetric sensors measured flow velocities over the range 0.5-13.8 mm/s. By this, a better control of high-pressure microfluidic platforms has been achieved.
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| 2. |
- Asp, Michaela, et al.
(författare)
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A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart
- 2019
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 179:7, s. 1647-
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Tidskriftsartikel (refereegranskat)abstract
- The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.
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| 3. |
- Berglund, Emelie, et al.
(författare)
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Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
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| 4. |
- Carlberg, Konstantin, et al.
(författare)
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Exploring inflammatory signatures in arthritic joint biopsies with Spatial Transcriptomics
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Lately it has become possible to analyze transcriptomic profiles in tissue sections with retained cellular context. We aimed to explore synovial biopsies from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients, using Spatial Transcriptomics (ST) as a proof of principle approach for unbiased mRNA studies at the site of inflammation in these chronic inflammatory diseases. Synovial tissue biopsies from affected joints were studied with ST. The transcriptome data was subjected to differential gene expression analysis (DEA), pathway analysis, immune cell type identification using Xcell analysis and validation with immunohistochemistry (IHC). The ST technology allows selective analyses on areas of interest, thus we analyzed morphologically distinct areas of mononuclear cell infiltrates. The top differentially expressed genes revealed an adaptive immune response profile and T-B cell interactions in RA, while in SpA, the profiles implicate functions associated with tissue repair. With spatially resolved gene expression data, overlaid on high-resolution histological images, we digitally portrayed pre-selected cell types in silico. The RA displayed an overrepresentation of central memory T cells, while in SpA effector memory T cells were most prominent. Consequently, ST allows for deeper understanding of cellular mechanisms and diversity in tissues from chronic inflammatory diseases.
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| 5. |
- Elfwen, Ludvig, et al.
(författare)
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Direct or subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)-An initial pilot-study of a randomized clinical trial
- 2019
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Ingår i: Resuscitation. - : ELSEVIER IRELAND LTD. - 0300-9572 .- 1873-1570. ; 139, s. 253-261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the 'DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest' (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods: Resuscitated bystander witnessed OHCA patients > 18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results: In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion: In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.
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| 6. |
- Lagedal, Rickard, et al.
(författare)
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Design of DISCO—Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest study
- 2018
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 197, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- Background Acute coronary syndrome is a common cause of out-of-hospital cardiac arrest (OHCA). In patients with OHCA presenting with ST elevation, immediate coronary angiography and potential percutaneous coronary intervention (PCI) after return of spontaneous circulation are recommended. However, the evidence for this invasive strategy in patients without ST elevation is limited. Observational studies have shown a culprit coronary artery occlusion in about 30% of these patients, indicating the electrocardiogram's (ECG's) limited sensitivity. The aim of this study is to determine whether immediate coronary angiography and subsequent PCI will provide outcome benefits in OHCA patients without ST elevation. Methods/design We describe the design of the DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest study (DISCO)—a pragmatic national, multicenter, randomized, clinical study. OHCA patients presenting with no ST elevation on their first recorded ECG will be randomized to a strategy of immediate coronary angiography or to standard of care with admission to intensive care and angiography after 3 days at the earliest unless the patient shows signs of acute ischemia or hemodynamic instability. Primary end point is 30-day survival. An estimated 1,006 patients give 80% power (α =.05) to detect a 20% improved 30-day survival rate from 45% to 54%. Secondary outcomes include good neurologic recovery at 30 days and 6 months, and cognitive function and cardiac function at 6 months. Conclusion This randomized clinical study will evaluate the effect of immediate coronary angiography after OHCA on 30-day survival in patients without ST elevation on their first recorded ECG.
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| 7. |
- Salmén, Fredrik, et al.
(författare)
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Multidimensional transcriptomics provides detailed information about immune cell distribution an identity in HER2+ breast tumors
- 2018
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The comprehensive analysis of tumor tissue heterogeneity is crucial for determining specific disease states and establishing suitable treatment regimes. Here, we analyze tumor tissue sections from ten patients diagnosed with HER2+ breast cancer. We obtain and analyze multidimensional, genome-wide transcriptomics data to resolve spatial immune cell distribution and identity within the tissue sections. Furthermore, we determine the extent of immune cell infiltration in different regions of the tumor tissue, including invasive cancer regions. We combine cross-sectioning and computational alignment to build three-dimensional images of the transcriptional landscape of the tumor and its microenvironment. The three-dimensional data clearly demonstrates the heterogeneous nature of tumor-immune interactions and reveal interpatient differences in immune cell infiltration patterns. Our study shows the potential for an improved stratification and description of the tumor-immune interplay, which is likely to be essential in treatment decisions.
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