| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 4. |
- Zhang, Qi, et al.
(författare)
-
Scored-GLIM as an effective tool to assess nutrition status and predict survival in patients with cancer
- 2021
-
Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 40:6, s. 4225-4233
-
Tidskriftsartikel (refereegranskat)abstract
- Background & aims: The Global Leadership Initiative on Malnutrition (GLIM) released new universal criteria for diagnosing and grading malnutrition, and calls for further investigations not only in different clinical setting but also in GLIM itself including reference value, combination and weight of different GLIM criteria. This study aimed to weigh the GLIM criteria and develop a scored-GLIM system, and then validate as well as evaluate its application in nutritional assessment and survival prediction for patients with cancer. Design: A total of 3547 patients in the primary cohort and 415 patients in the validation cohort were included in the study. Patients' nutritional status were retrospectively assessed using the GLIM criteria. Kaplan-Meier survival curves and multivariate Cox regression analyses were performed to analyze the association between nutritional status and overall survival (OS). A nomogram was produced to quantify the GLIM criteria and develop the scored-GLIM system. C-index, receiver operating characteristic (ROC) curve and calibration curve analyses were performed to validate the predictive accuracy and discriminatory capacity of the scored-GLIM. Finally, a decision curve was applied to assess the clinical utility of the scored-GLIM system. Results: In the primary cohort, 70.3% of patients were diagnosed as malnutrition. The malnutrition severity grading according to the GLIM criteria were associated with the prognosis of patients with cancer (HR 1.42,1.23 to 1.65 for moderate malnutrition; HR 1.80,1.84 to 2.09 for severe malnutrition). The weight of each GLIM criteria was calculated, and unintentional weight loss was the most determining factor acting upon mortality (HR 1.82, 1.64 to 2.10 for stage II and HR 1.50, 1.31 to 1.73 for stage I). A nomogram was constructed by four factors of GLIM to weigh the GLIM criteria. The areas under the ROC curve were 65.3 (1-year ROC) and 65.5 (3-year ROC), and the C-index was 0.62, and the calibration curves fitted well. Decision curve analysis demonstrated the clinical usefulness of the scored-GLIM system. Conclusion: The accuracy and net clinical benefit of scored-GLIM system were similar to scored-PG-SGA but higher than GLIM both in nutrition assessment and in survival prediction for patients with cancer. These findings, along with its time-savings advantages over scored-PG-SGA, suggest scored-GLIM be a better nutritional assessment tool. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
|
|
| 5. |
- Zhang, Xi, et al.
(författare)
-
The GLIM criteria as an effective tool for nutrition assessment and survival prediction in older adult cancer patients
- 2021
-
Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 40:3, s. 1224-1232
-
Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Elderly cancer patients are at particularly high risk for malnutrition because both the disease and the old age threaten their nutritional status. The Global Leadership Initiative on Malnutrition (GLIM) released new universal criteria for diagnosing and grading malnutrition, but the validation of these criteria in elderly cancer population is not well documented. Our objective was to investigate the application of the GLIM criteria in nutrition assessment and survival prediction in elderly cancer patients. Methods: This retrospective cohort analysis was conducted on a primary cohort of 1192 cancer patients aged 65 years or older enrolled from a multi-institutional registry, and a validation cohort of 300 elderly cancer patients treated at the First Affiliated Hospital of Sun Yat-sen University. Patients considered at -risk for malnutrition based on the NRS-20 02 were assessed using the GLIM criteria. The association between the nutritional status and patients' overall survival (OS) was then analyzed by the Kaplan-Meier method and a Cox model. A nomogram was also established that included additional inde-pendent clinical prognostic variables. To determine the predictive accuracy and discriminatory capacity of the nomogram, the C-index, receiver operating characteristic (ROC) curve and calibration curve were evaluated. Results: The percentage of patients considered & ldquo;at-risk & rdquo; for malnutrition was 64.8% and 67.3% for the primary and validation cohorts, respectively. GLIM-defined malnutrition was diagnosed in 48.4% of pa-tients in the primary cohort and 46.0% in the validation cohort. In the primary cohort, patients at risk of malnutrition (NRS-20 02 > 3) showed a worse OS than those with a NRS-20 02 < 3 (HR 1.34, 1.10-1.64; p = 0.003). Additionally, patients with GLIM-defined severe malnutrition (HR1.71, 1.37-2.14; p < 0.001) or moderate malnutrition (HR1.35, 1.09-1.66; p = 0.006) showed a significantly shorter OS compared to those without malnutrition. The nomogram incorporating the domains of the GLIM with other variables was accurate, especially for predicting the 1-and 2-year overall survival rates. Conclusions: The GLIM criteria can be used in elderly cancer patients not only to assess malnutrition, but also to predict survival outcome. The nomogram developed based on the GLIM domains can provide a more accurate prediction of the prognosis than existing systems. (c) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
|
|
| 6. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
|
|
| 7. |
- Wang, Fei, et al.
(författare)
-
Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level
- 2022
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-beta, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia.
|
|
| 8. |
- Zhou, Guang-Quan, et al.
(författare)
-
Automatic Myotendinous Junction Tracking in Ultrasound Images with Phase-Based Segmentation.
- 2018
-
Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
-
Tidskriftsartikel (refereegranskat)abstract
- Displacement of the myotendinous junction (MTJ) obtained by ultrasound imaging is crucial to quantify the interactive length changes of muscles and tendons for understanding the mechanics and pathological conditions of the muscle-tendon unit during motion. However, the lack of a reliable automatic measurement method restricts its application in human motion analysis. This paper presents an automated measurement of MTJ displacement using prior knowledge on tendinous tissues and MTJ, precluding the influence of nontendinous components on the estimation of MTJ displacement. It is based on the perception of tendinous features from musculoskeletal ultrasound images using Radon transform and thresholding methods, with information about the symmetric measures obtained from phase congruency. The displacement of MTJ is achieved by tracking manually marked points on tendinous tissues with the Lucas-Kanade optical flow algorithm applied over the segmented MTJ region. The performance of this method was evaluated on ultrasound images of the gastrocnemius obtained from 10 healthy subjects (26.0±2.9 years of age). Waveform similarity between the manual and automatic measurements was assessed by calculating the overall similarity with the coefficient of multiple correlation (CMC). In vivo experiments demonstrated that MTJ tracking with the proposed method (CMC = 0.97±0.02) was more consistent with the manual measurements than existing optical flow tracking methods (CMC = 0.79±0.11). This study demonstrated that the proposed method was robust to the interference of nontendinous components, resulting in a more reliable measurement of MTJ displacement, which may facilitate further research and applications related to the architectural change of muscles and tendons. [ABSTRACT FROM AUTHOR]
|
|
| 9. |
- Asayama, Kei, et al.
(författare)
-
Setting Thresholds to Varying Blood Pressure Monitoring Intervals Differentially Affects Risk Estimates Associated With White-Coat and Masked Hypertension in the Population
- 2014
-
Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 64:5, s. 935-942
-
Tidskriftsartikel (refereegranskat)abstract
- Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using >= 140/>= 90, >= 130/>= 80, >= 135/>= 85, and >= 120/>= 70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.
|
|
| 10. |
- Cui, Hao, et al.
(författare)
-
Heparanase expression upregulates platelet adhesion activity and thrombogenicity
- 2016
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:26, s. 39486-39496
-
Tidskriftsartikel (refereegranskat)abstract
- Heparanase is an endo-glucuronidase that specifically cleaves heparan sulfate (HS) and heparin polysaccharides. The enzyme is expressed at low levels in normal tissues, but is often upregulated under pathological conditions such as cancer and inflammation. Normal human platelets express exceptionally high levels of heparanase, but the functional consequences of this feature remain unknown. We investigated functional roles of heparanase by comparing the properties of platelets expressing high (Hpa-tg) or low (Ctr) levels of heparanase. Upon activation, Hpa-tg platelets exhibited a much stronger adhesion activity as compared to Ctr platelets, likely contributing to a higher thrombotic activity in a carotid thrombosis model. Furthermore, we found concomitant upregulated expression of both heparanase and CD62P (P-selectin) upon activation of mouse and human platelets. As platelets play important roles in tumor metastasis, these findings indicate contribution of the platelet heparanase to hyper-thrombotic conditions often seen in patients with metastatic cancer.
|
|
