| 1. |
- Egevad, Lars, et al.
(författare)
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Prognostic Significance of Prostate Cancer with Seminal Vesicle Invasion on Radical Prostatectomy : A National Registry Study
- 2017
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Ingår i: Modern Pathology. - Karolinska Inst, Stockholm, Sweden. Univ Uppsala Hosp, Uppsala, Sweden. Univ Otago, Wellington Sch Med & Hlth Sci, Wellington, New Zealand. Aquesta Pathol, Brisbane, Qld, Australia. : NATURE PUBLISHING GROUP. - 0893-3952 .- 1530-0285. ; 97, s. 222A-222A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
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| 3. |
- Tessier-Cloutier, Basile, et al.
(författare)
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Cell of Origin (COO) of Diffuse Large B-Cell Lymphoma (DLBCL) in Patients with Systemic Lupus Erythematosus (SLE)
- 2017
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Ingår i: Modern Pathology. - Vancouver Gen Hosp, Vancouver, BC, Canada. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. Uppsala Univ, Uppsala, Sweden. British Columbia Canc Agcy, Vancouver, BC, Canada. Jewish Gen Hosp, Montreal, PQ, Canada. Med Univ South Carolina, Charleston, SC USA. Univ Calgary, Calgary, AB, Canada. Northwestern Univ, Chicago, IL 60611 USA. : NATURE PUBLISHING GROUP. - 0893-3952 .- 1530-0285. ; 97, s. 381A-381A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Andersson Sjöland, Annika, et al.
(författare)
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ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling.
- 2015
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837.
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary fibrosis is a grave diagnosis with insidious progression, generally considered as a consequence of aberrant epithelial wound healing and excessive scarring. This process is commonly modeled in animals by local bleomycin administration, resulting in peribronchial inflammation and subsequent fibrosis. We have previously described initiation and early development of distal pulmonary fibrosis following repeated subcutaneous bleomycin injections (systemic administration). The aim of this study was to identify mechanisms for the development of pulmonary fibrosis, which we hypothesize is related to endothelial stress and activation. Bleomycin was administered subcutaneously 3 times/week during 0.33-4w, and parenchymal alterations were studied. In addition, we used microvascular endothelial cells to investigate effects of bleomycin in vitro. Our results confirmed that systemic administration of bleomycin exerts oxidative stress indicated by an increase in Sod1 at 0.33, 1, and 4w (P<0.05). Endothelial cells were activated (increased CD106 expression) from 1w and onwards (P<0.05), and p21 expression was increased 2-3 times throughout the study (P<0.05) as were the number of β-catenin-positive nuclei (P<0.001). Wnt3a was increased at 0.33, 1, and 4w (P<0.01) and Wnt5a from 1w and onwards (P<0.001). The present study suggests that bleomycin-induced reactive oxygen species (ROS) causes DNA stress affecting the endothelial niche, initiating repair processes including Wnt signaling. The repeated systemic administrations disrupt a normally fine-tuned balance in the Wnt signaling. In addition, pericyte differentiation was affected, which may have significant effects on fibrosis due to their ability to differentiate into myofibroblasts. We conclude that the endothelial niche may have an important role in the development of pulmonary fibrosis and warrants further investigations.Laboratory Investigation advance online publication, 14 September 2015; doi:10.1038/labinvest.2015.100.
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| 5. |
- Balkenhol, Maschenka C. A., et al.
(författare)
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Deep learning assisted mitotic counting for breast cancer
- 2019
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Ingår i: Laboratory Investigation. - : NATURE PUBLISHING GROUP. - 0023-6837 .- 1530-0307. ; 99:11, s. 1596-1606
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Tidskriftsartikel (refereegranskat)abstract
- As part of routine histological grading, for every invasive breast cancer the mitotic count is assessed by counting mitoses in the (visually selected) region with the highest proliferative activity. Because this procedure is prone to subjectivity, the present study compares visual mitotic counting with deep learning based automated mitotic counting and fully automated hotspot selection. Two cohorts were used in this study. Cohort A comprised 90 prospectively included tumors which were selected based on the mitotic frequency scores given during routine glass slide diagnostics. This pathologist additionally assessed the mitotic count in these tumors in whole slide images (WSI) within a preselected hotspot. A second observer performed the same procedures on this cohort. The preselected hotspot was generated by a convolutional neural network (CNN) trained to detect all mitotic figures in digitized hematoxylin and eosin (Hamp;E) sections. The second cohort comprised a multicenter, retrospective TNBC cohort (n = 298), of which the mitotic count was assessed by three independent observers on glass slides. The same CNN was applied on this cohort and the absolute number of mitotic figures in the hotspot was compared to the averaged mitotic count of the observers. Baseline interobserver agreement for glass slide assessment in cohort A was good (kappa 0.689; 95% CI 0.580-0.799). Using the CNN generated hotspot in WSI, the agreement score increased to 0.814 (95% CI 0.719-0.909). Automated counting by the CNN in comparison with observers counting in the predefined hotspot region yielded an average kappa of 0.724. We conclude that manual mitotic counting is not affected by assessment modality (glass slides, WSI) and that counting mitotic figures in WSI is feasible. Using a predefined hotspot area considerably improves reproducibility. Also, fully automated assessment of mitotic score appears to be feasible without introducing additional bias or variability.
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| 7. |
- Dave, Vivek Priy, et al.
(författare)
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MicroRNA amplification and detection technologies : opportunities and challenges for point of care diagnostics
- 2018
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Ingår i: Laboratory Investigation. - : Nature Publishing Group. - 0023-6837 .- 1530-0307. ; 99:4, s. 452-469
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Forskningsöversikt (refereegranskat)abstract
- The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC. However, the most widely used methods for analyzing miRNAs, including Northern blot-based platforms, in situ hybridization, reverse transcription qPCR, microarray, and next-generation sequencing, are still far from being used as ideal POC diagnostic tools, due to considerable time, expertize required for sample preparation, and in terms of miniaturizations making them suitable platforms for centralized labs. In this review, we highlight various existing and upcoming technologies for miRNA amplification and detection with a particular emphasis on the POC testing industries. The review summarizes different miRNA targets and signals amplification-based assays, from conventional methods to alternative technologies, such as isothermal amplification, paper-based, oligonucleotide-templated reaction, nanobead-based, electrochemical signaling-based, and microfluidic chip-based strategies. Based on critical analysis of these technologies, the possibilities and feasibilities for further development of POC testing for miRNA diagnostics are addressed and discussed.
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| 8. |
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| 9. |
- Hofvander, Jakob, et al.
(författare)
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RNA sequencing of sarcomas with simple karyotypes: identification and enrichment of fusion transcripts.
- 2015
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837. ; 95:6, s. 603-609
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Tidskriftsartikel (refereegranskat)abstract
- Gene fusions are neoplasia-associated mutations arising from structural chromosomal rearrangements. They have a strong impact on tumor development and constitute important diagnostic markers. Malignant soft tissue tumors (sarcomas) constitute a heterogeneous group of neoplasms with >50 distinct subtypes, each of which is rare. In addition, there is considerable morphologic overlap between sarcomas and benign lesions. Several subtypes display distinct gene fusions, serving as excellent biomarkers. The development of methods for deep sequencing of the complete transcriptome (RNA-Seq) has substantially improved the possibilities for detecting gene fusions. With the aim of identifying new gene fusions of biological and clinical relevance, eight sarcomas with simple karyotypes, ie, only one or a few structural rearrangements, were subjected to massively parallel paired-end sequencing of mRNA. Three different algorithms were used to identify fusion transcripts from RNA-Seq data. Three novel (KIAA2026-NUDT11, CCBL1-ARL1, and AFF3-PHF1) and two previously known fusions (FUS-CREB3L2 and HAS2-PLAG1) were found and could be verified by other methods. These findings show that RNA-Seq is a powerful tool for detecting gene fusions in sarcomas but also suggest that it is advisable to use more than one algorithm to analyze the output data as only two of the confirmed fusions were reported by more than one of the gene fusion detection software programs. For all of the confirmed gene fusions, at least one of the genes mapped to a chromosome band implicated by the karyotype, suggesting that sarcomas with simple karyotypes constitute an excellent resource for identifying novel gene fusions.Laboratory Investigation advance online publication, 13 April 2015; doi:10.1038/labinvest.2015.50.
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