| 1. |
|
|
| 2. |
- Juhlin, Kristina, et al.
(författare)
-
Outlier removal to uncover patterns in adverse drug reaction surveillance - a simple unmasking strategy
- 2013
-
Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 22:10, s. 1119-1129
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeThis study aimed to develop an algorithm for uncovering associations masked by extreme reporting rates, characterize the occurrence of masking by influential outliers in two spontaneous reporting databases and evaluate the impact of outlier removal on disproportionality analysis. MethodsWe propose an algorithm that identifies influential outliers and carries out parallel analysis after their omission. It considers masking of drugs as well as of adverse drug reactions (ADRs), uses a direct measure of the masking effect and makes no assumptions regarding the number of outliers per drug or ADR. The occurrence of masking is characterized in the WHO Global Individual Case Safety Report database, VigiBase and a regional collection of reports from Shanghai, China. ResultsFor WHO-ART critical terms such as myocardial infarction, rhabdomyolysis and hypoglycaemia outlier removal led to a 25-50% increase in the number of Statistics of Disproportionate Reporting (SDR) and gains in time to detection of 1-2years, while keeping the rate of spurious SDRs from the parallel analysis at 1%. Twenty-three per cent of VigiBase and 18% of Shanghai SRS reports listed an influential outlier. Twenty-seven per cent of the ADRs and 5% of the drugs in VigiBase, and 2% of the ADRs and 3% of the drugs in Shanghai SRS were involved in an outlier. The overall increase in the number of SDRs for both datasets was 3%. ConclusionMasking by outliers has substantial impact on specific ADRs including, in VigiBase, rhabdomyolysis, myocardial infarction and hypoglycaemia. It is a local phenomenon involving a fair number of reports but yielding a limited number of additional SDRs.
|
|
| 3. |
- Li, Xian, et al.
(författare)
-
GCDB-UNet : A novel robust cloud detection approach for remote sensing images
- 2022
-
Ingår i: Knowledge-Based Systems. - : Elsevier BV. - 0950-7051 .- 1872-7409. ; 238
-
Tidskriftsartikel (refereegranskat)abstract
- Cloud detection is a prerequisite in many remote sensing applications, and it has been tackled through different approaches from simple thresholding to complicated deep network training. On the other hand, existing approaches are susceptible to failures while handling thin clouds, largely because of their small sizes, sparse distributions, as well as high transparency and similarity to the non-cloud background regions. This paper presents global context dense block U-Net (GCDB-UNet), a robust cloud detection network that embeds global context dense block (GCDB) into the U-Net framework and is capable of detecting thin clouds effectively. GCDB consists of two feature extraction units for addressing the challenges in thin cloud detection, namely, a non-local self-attention unit that extracts sample correlation features by aggregating the sparsely distributed thin clouds and a squeeze excitation unit that extracts channel correlated features by differentiating their importance. In addition, a dense connection scheme is designed to exploit the multi-level fine-grained representations from the two types of extracted features and a recurrent refinement module is introduced for gradual enhancement of the predicted classification map. We also created a fully annotated cloud detection MODIS dataset that consists of 1192 training images, 80 validation images and 150 test images. Extensive experiments on Landsat8, SPARCS and MODIS datasets show that the proposed GCDB-UNet achieves superior cloud detection performance as compared with state-of-the-art methods. Our created MODIS cloud detection dataset is available at https://github.com/xiachangxue/MODIS-Dataset-for-Cloud-Detection.
|
|
| 4. |
- Nie, Man, et al.
(författare)
-
The dual role of CD70 in B‐cell lymphomagenesis
- 2022
-
Ingår i: Clinical and Translational Medicine. - : John Wiley & Sons. - 2001-1326. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundCD70 is a costimulatory molecule that is transiently expressed on a small set of activated lymphocytes and is involved in T-cell-mediated immunity. However, the role of CD70 in B-cell malignancies remains controversial.MethodsWe investigated the clinical relevance of CD70 genetic alterations and its protein expression in two diffuse large B-cell lymphoma (DLBCL) cohorts with different ethnic backgrounds. We also performed transcriptomic analysis to explore the role of CD70 alterations in tumour microenvironment. We further tested the blockade of CD70 in combination with PD-L1 inhibitor in a murine lymphoma model.ResultsWe showed that CD70 genetic aberrations occurred more frequently in the Chinese DLBCL cohort (56/233, 24.0%) than in the Swedish cohort (9/84, 10.8%), especially in those with concomitant hepatitis B virus (HBV) infection. The CD70 genetic changes in DLBCL resulted in a reduction/loss of protein expression and/or CD27 binding, which might impair T cell priming and were independently associated with poor overall survival. Paradoxically, we observed that over-expression of CD70 protein was also associated with a poor treatment response, as well as an advanced disease stage and EBV infection. More exhausted CD8+ T cells were furthermore identified in CD70 high-expression DLBCLs. Finally, in a murine lymphoma model, we demonstrated that blocking the CD70/CD27 and/or PD1/PD-L1 interactions could reduce CD70+ lymphoma growth in vivo, by directly impairing the tumour cell proliferation and rescuing the exhausted T cells.ConclusionsOur findings suggest that CD70 can play a role in either tumour suppression or oncogenesis in DLBCL, likely via distinct immune evasion mechanisms, that is, impairing T cell priming or inducing T cell exhaustion. Characterisation of specific dysfunction of CD70 in DLBCL may thus provide opportunities for the development of novel targeted immuno-therapeutic strategies.
|
|
| 5. |
- Pecori, Riccardo, et al.
(författare)
-
ADAR1-mediated RNA editing promotes B cell lymphomagenesis
- 2023
-
Ingår i: iScience. - : Cell Press. - 2589-0042. ; 26:6
-
Tidskriftsartikel (refereegranskat)abstract
- Diffuse large B cell lymphoma (DLBCL) is one of the most common types of aggressive lymphoid malignancies. Here, we explore the contribution of RNA editing to DLBCL pathogenesis. We observed that DNA mutations and RNA editing events are often mutually exclusive, suggesting that tumors can modulate pathway outcomes by altering sequences at either the genomic or the transcriptomic level. RNA editing targets transcripts within known disease-driving pathways such as apoptosis, p53 and NF-kappa B signaling, as well as the RIG-I-like pathway. In this context, we show that ADAR1-mediated editing within MAVS transcript positively correlates with MAVS protein expression levels, associating with increased interferon/NF-kappa B signaling and T cell exhaustion. Finally, using targeted RNA base editing tools to restore editing within MAVS 3 ' UTR in ADAR1-deficient cells, we demonstrate that editing is likely to be causal to an increase in downstream signaling in the absence of activation by canonical nucleic acid receptor sensing.
|
|
| 6. |
- Ren, Mengying, et al.
(författare)
-
Concentration-Response Relationship between PM2.5 and Daily Respiratory Deaths in China : A Systematic Review and Metaregression Analysis of Time-Series Studies
- 2017
-
Ingår i: BioMed Research International. - : Hindawi Publishing Corporation. - 2314-6133 .- 2314-6141.
-
Forskningsöversikt (refereegranskat)abstract
- The association between the particulate matters with aerodynamic diameter <= 2.5.mu m (PM2.5) and daily respiratory deaths, particularly the concentration-response pattern, has not been fully examined and established in China. We conducted a systematic review of time-series studies to compile information on the associations between PM2.5 concentration and respiratory deaths and used metaregression to assess the concentration-response relationship. Out of 1,957 studies screened, eleven articles in English and two articles in Chinese met the eligibility criteria. For single-day lags, per 10 mu g/m(3) increase in PM2.5 concentration was associated with 0.30 [95% confidence interval (CI): 0.10, 0.50] percent increase in daily respiratory deaths; for multiday lags, the corresponding increase in respiratory deaths was 0.69 (95% CI: 0.55, 0.83) percent. Difference in the effects was observed between the northern cities and the south cities in China. No statistically significant concentration-response relationship between PM2.5 concentrations and their effects was found. With increasingly wider location coverage for PM2.5 data, it is crucial to further investigate the concentration-response pattern of PM2.5 effects on respiratory and other cause-specific mortality for the refinement and adaptation of global and national air quality guidelines and targets.
|
|
| 7. |
- Ren, Weicheng, et al.
(författare)
-
Genetic and transcriptomic analyses of diffuse large B-cell lymphoma patients with poor outcomes within two years of diagnosis
- 2024
-
Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 38:2, s. 438-441
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the improvements in clinical outcomes for DLBCL, a significant proportion of patients still face challenges with refractory/relapsed (R/R) disease after receiving first-line R-CHOP treatment. To further elucidate the underlying mechanism of R/R disease and to develop methods for identifying patients at risk of early disease progression, we integrated clinical, genetic and transcriptomic data derived from 2805 R-CHOP-treated patients from seven independent cohorts. Among these, 887 patients exhibited R/R disease within two years (poor outcome), and 1918 patients remained in remission at two years (good outcome). Our analysis identified four preferentially mutated genes (TP53, MYD88, SPEN, MYC) in the untreated (diagnostic) tumor samples from patients with poor outcomes. Furthermore, transcriptomic analysis revealed a distinct gene expression pattern linked to poor outcomes, affecting pathways involved in cell adhesion/migration, T-cell activation/regulation, PI3K, and NF-kappa B signaling. Moreover, we developed and validated a 24-gene expression score as an independent prognostic predictor for treatment outcomes. This score also demonstrated efficacy in further stratifying high-risk patients when integrated with existing genetic or cell-of-origin subtypes, including the unclassified cases in these models. Finally, based on these findings, we developed an online analysis tool (https://lymphprog.serve.scilifelab.se/app/lymphprog) that can be used for prognostic prediction for DLBCL patients.
|
|
| 8. |
- Ye, Xiaofei
(författare)
-
Characterization of the genome and tumor microenvironment of human B-cell lymphoma
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non-Hodgkin lymphoma (NHL) is the 13th most common type of cancer worldwide in 2020 and consists mainly of human B-cell lymphoma (approximately 85%). Diffuse large B-cell lymphoma (DLBCL) is the most common NHL subtype (approximately 30%). Several factors have been suggested to be associated with DLBCL lymphomagenesis and unfavorable outcomes, including cell of origin, viral infection, aberrant activation-induced cytidine deaminase (AID) activity, tumor microenvironment (TME) pattern, and immunodeficiency. In the last decade, high-throughput next-generation sequencing (NGS) has made it possible to study genetic variations and transcription genome-wide. Using NGS on the genomes and transcriptomes of DLBCL at the bulk tissue or single-cell level, we investigated the associations between these factors and DLBCL. In study I, we explored the associations between HBV infection (surface antigen positive, HBsAg+) and DLBCL. We observed increased mutagenesis rates and different sets of mutated genes in HBsAg+ DLBCL genomes, which were associated with APOBEC and AID activities. We found that highly expressed genes in HBsAg+ DLBCL were enriched with genes regulated by BCL6, FOXO1, and ZFP36L1. Our data suggest that HBV-associated DLBCL can be considered as a distinct subtype. In study II, we identified seven genomic mutational signatures in DLBCL and follicular lymphoma (FL), including a novel signature related to aberrant somatic hypermutation (SHM). For the localized clustered mutations (kataegis), we characterized two major mutational signatures (K1 and K2), which resulted from AID and DNA polymerase η activities, respectively. K1 was related to mutations/translocations in the immunoglobulin (Ig) switch region and the ABC subtype of DLBCL. In contrast, K2 was associated with mutations in the Ig variable region and the GCB subtype of DLBCL and FL. Our data suggested that mutations associated with aberrant AID activity could be related to distinct developmental paths for the two major cell-of-origin subtypes of B-cell lymphoma. In study III, we studied malignant and infiltrating immune cells in DLBCL at the single-cell level. We revealed high intra- and intertumor heterogeneity and showed that activated MAPK signaling is associated with the relapse of DLBCL. We have also identified a dynamic TME in DLBCL, which may further contribute to disease heterogeneity. Furthermore, we discovered unique features in HBsAg+ DLBCL, with a higher expression level of major histocompatibility complex class II genes in malignant cells, stronger CD40-mediated interaction between malignant cells and CD4+ T cells, and a more immunosuppressive TME. In study IV, we performed an in-depth analysis of lymphoma genomes derived from inborn errors of immunity (IEI). We identified a novel mutation target, BRWD3, that is highly mutated in a subgroup of activated p110δ syndrome patients. We characterized five genomic mutational signatures in IEI-associated lymphomas, including two DNA repair deficiency-related signatures. In conclusion, we presented comprehensive genomic and transcriptomic studies that may help to understand the complex mechanism underlying B cell lymphomagenesis. The genetic alterations and gene expression profiles identified in these studies pave the way for the development of novel therapeutic strategies for lymphoma patients
|
|
| 9. |
- Zhai, Yinghong, et al.
(författare)
-
Atrial fibrillation increases the risk of all-cause dementia, Alzheimer's disease, and vascular dementia : A cohort study of 373, 415 participants in the UK Biobank
- 2024
-
Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 351, s. 323-330
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Accumulated evidence has highlighted the association between atrial fibrillation and the risk of developing dementia.METHODS: This current cohort study utilized data from the UK Biobank to explore the association between atrial fibrillation (AF) and all-cause dementia (ACD), encompassing its main subtypes (Alzheimer's disease (AD), and vascular dementia (VD)). Cox proportional hazards models were applied to examine the association of AF and dementia with its primary subtypes after adjusting for different sets of covariates. Hazard ratios (HRs) with 95 % confidential intervals (CIs) were estimated to quantify the associated risks. Competing risk model was applied in sensitivity analysis.RESULTS: After exclusion, 373, 415 participants entered the primary analysis. Among these, 27, 934 (7.48 %) were with a history AF at baseline, while 345, 481 (92.52 %) were without. During a mean follow-up of 13.45 years, ACD was diagnosed in 1215 individuals with AF and 3988 individuals without AF. Participants with AF had higher risks of ACD (1.79 [1.67-1.91]), AD (1.48 [1.32-1.65]), and VD (2.46 [2.17-2.80]) in the fully adjusted Cox regression models. Results of subgroup and sensitivity analyses predominantly aligned with the positive associations in primary analysis.LIMITATIONS: The applicability of our findings to diverse ethnicities might require careful consideration and the behind biological mechanisms need to be further revealed.CONCLUSIONS: It indicated that people with atrial fibrillation had an increased future risk of all-cause dementia, Alzheimer's disease, vascular dementia. Atrial fibrillation screening and prevention strategies should take into account to prevent and delay the onset of dementia.
|
|
| 10. |
- Zhai, Yinghong, et al.
(författare)
-
Cardiovascular Toxicity of Carfilzomib : The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States
- 2021
-
Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.
|
|
