| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Zhu, RJ, et al.
(författare)
-
Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
-
Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:12, s. 1244-1262
-
Tidskriftsartikel (refereegranskat)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
|
|
| 5. |
|
|
| 6. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Wang, Q, et al.
(författare)
-
Systematic review of machine learning-based radiomics approach for predicting microsatellite instability status in colorectal cancer
- 2023
-
Ingår i: La Radiologia medica. - : Springer Science and Business Media LLC. - 1826-6983. ; 128:2, s. 136-148
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to systematically summarize the performance of the machine learning-based radiomics models in the prediction of microsatellite instability (MSI) in patients with colorectal cancer (CRC). It was conducted according to the preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guideline and was registered at the PROSPERO website with an identifier CRD42022295787. Systematic literature searching was conducted in databases of PubMed, Embase, Web of Science, and Cochrane Library up to November 10, 2022. Research which applied radiomics analysis on preoperative CT/MRI/PET-CT images for predicting the MSI status in CRC patients with no history of anti-tumor therapies was eligible. The radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) were applied to evaluate the research quality (full score 100%). Twelve studies with 4,320 patients were included. All studies were retrospective, and only four had an external validation cohort. The median incidence of MSI was 19% (range 8–34%). The area under the receiver operator curve of the models ranged from 0.78 to 0.96 (median 0.83) in the external validation cohort. The median sensitivity was 0.76 (range 0.32–1.00), and the median specificity was 0.87 (range 0.69–1.00). The median RQS score was 38% (range 14–50%), and half of the studies showed high risk in patient selection as evaluated by QUADAS-2. In conclusion, while radiomics based on pretreatment imaging modalities had a high performance in the prediction of MSI status in CRC, so far it does not appear to be ready for clinical use due to insufficient methodological quality.
|
|
| 24. |
|
|
| 25. |
- Zhan, YQ, et al.
(författare)
-
Predicting the prevalence of peripheral arterial diseases: modelling and validation in different cohorts
- 2016
-
Ingår i: VASA. Zeitschrift fur Gefasskrankheiten. - : Hogrefe Publishing Group. - 0301-1526. ; 45:1, s. 31-36
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract. Background: To develop models for prevalence estimation of peripheral arterial disease (PAD) and to validate them in an external cohort. Methods: Model training cohort was a population based cross-sectional survey. Age, sex, smoking status, body mass index, total cholesterol (TC), high density lipoprotein (HDL), TC/HDL ratio, low density lipoprotein, fasting glucose, diabetes, hypertension, pulse pressure, and stroke history were considered candidate predicting variables. Ankle brachial index ≤ 0.9 was defined as the presence of peripheral arterial disease. Logistic regression method was used to build the prediction models. The likelihood ratio test was applied to select predicting variables. The bootstrap method was used for model internal validation. Model performance was validated in an external cohort. Results: The final models included age, sex, pulse pressure, TC/HDL ratio, smoking status, diabetes, and stroke history. Area under receiver operating characteristics (AUC) with 95% confidence interval (CI) of the final model from the training cohort was 0.74 (0.70, 0.77). Model validation in another cohort revealed AUC (95% CI) of 0.72 (0.70, 0.73). P value of Hosmer-Lemeshow’s model goodness of fit test was 0.75 indicating good model calibration. Conclusions: The developed model yielded a moderate usefulness for predicting the prevalence of PAD in general population.
|
|
