| 1. |
- Smith, Gustav, et al.
(författare)
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Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure
- 2016
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
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| 2. |
- Wang, Xinchen, et al.
(författare)
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Design of High-Data-Density Chipless RFID Tag Embedded in QR Code
- 2022
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Ingår i: IEEE Transactions on Antennas and Propagation. - 0018-926X .- 1558-2221. ; 70:3, s. 2189-2198
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Tidskriftsartikel (refereegranskat)abstract
- A design scheme for embedding a chipless radio frequency identification (RFID) tag in a quick response (QR) code is proposed and demonstrated. By searching for QR modules that can be metalized to form a loop resonator in the edge area and to load the loop in the central area, the chipless RFID tag with an optimized loaded-loop resonator can be designed in the QR code. A specific loop genetic operator is proposed for optimization searching. The optimized loaded-loop resonator has a sharp dominant resonant peak at frequency as low as possible and a harmonic resonant peak at frequency as high as possible, which provides large space for data encoding of chipless RFID. By removing or demetalizing the metalized loading modules, the resonant frequency can be tuned conveniently for frequency shift keying (FSK) coding. For demonstration, the chipless RFID tag embedded in the QR code is designed and tested. It is shown that the RFID tag allows at least nine distinct resonant frequencies for simple FSK coding, which indicates a coding capacity of 3.17 bits and a normalization coding density of approximately 501.78 bits/ $\lambda _{\mathrm {g}}^{2}$ /GHz for the chipless RFID tag embedded in the QR code.
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| 3. |
- Liu, Qing, et al.
(författare)
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Maintenance proton pump inhibitor use and risk of colorectal cancer : a Swedish retrospective cohort study
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.DESIGN: Retrospective cohort study.SETTING: This research was conducted at the national level, encompassing the entire population of Sweden.PARTICIPANTS: This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years.INTERVENTIONS: Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use.PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use.RESULTS: Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05).CONCLUSIONS: Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.
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| 4. |
- Simin, Johanna, et al.
(författare)
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Prediagnostic use of estrogen-only therapy is associated with improved colorectal cancer survival in menopausal women : a Swedish population-based cohort study
- 2021
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 60:7, s. 881-887
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Menopausal hormone therapy (MHT) reduces the risk of developing colorectal cancer (CRC), yet it is largely unclear whether it could also influence survival in women with CRC. Therefore, we aimed to investigate the influence of prediagnostic MHT use on CRC-specific and all-cause mortality in women with CRC.METHODS: This nationwide nested cohort study, within a large population-based matched cohort, included all women diagnosed with incident CRC between January 2006 and December 2012 (N = 7814). A total of 1529 women had received at least one dispensed prescription of systemic MHT before CRC diagnosis, and 6285 CRC women with CRC did not receive MHT during the study period, as ascertained from the Swedish Prescribed Drug Registry. Multivariable Cox regression models provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality.RESULTS: Past use of prediagnostic estrogen-only therapy (E-MHT) was associated with lower CRC-specific (HR = 0.67, 95%CI 0.44-0.99) and all-cause mortality (HR = 0.68, 95%CI 0.59-0.93). However, all-cause mortality (HR = 1.23, 95%CI 1.02-1.48) was elevated among current prediagnostic E-MHT users who were 70+ years at diagnosis. Current estrogen combined progestin therapy (EP-MHT) was associated with higher CRC-specific mortality (HR = 1.61, 95%CI 1.06-2.44) in older women, but no association was shown for all-cause mortality.CONCLUSIONS: Our findings suggest that E-MHT, but not EP-MHT use, might be associated with improved CRC survival, indicating a potential role of estrogens in sex hormone-related cancers. However, association of MHT use with grade of cancer remains unclear.
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| 5. |
- Wang, Xinchen, et al.
(författare)
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Prenatal exposure to benzodiazepines and Z-drugs in humans and risk of adverse neurodevelopmental outcomes in offspring : A systematic review
- 2022
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier. - 0149-7634 .- 1873-7528. ; 137
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Forskningsöversikt (refereegranskat)abstract
- When used during pregnancy, benzodiazepines (BZDs) and related z-drugs could pass readily through the placenta and the foetal blood-brain barrier, where they can bind to γ-amino butyric acid (GABA) receptors in the developing foetal brain. Yet, data on long-term safety of prenatal BZD and z-drug use and its impact on offspring neurodevelopment are inconclusive. In this systematic review, we qualitatively synthetize the existing evidence on maternal exposure to various BZDs and z-drugs during pregnancy and offspring cognitive, emotional, behavioural, and motor skills developmental outcomes. Nineteen studies were included. We used harvest plots to visualize the directions of reported associations. Despite several associations between distinct types of BZDs and z-drugs and an increased risk of outcomes within different neurodevelopmental domains were observed, a remarkable scarcity of overall research on the topic and considerable discrepancies in methodology, particularly towards controlling for confounding by indication, precluded drawing conclusions with a reasonable degree of certainty. We outline various research strategies to mitigate methodological limitations and provide directions for future empirical studies on the topic. Systematic review registration: PROSPERO (ID: CRD42021265828).
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| 6. |
- Wang, Xinchen, et al.
(författare)
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Proton pump inhibitors and survival in patients with colorectal cancer : a Swedish population-based cohort study
- 2021
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 125:6, s. 893-900
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proton pump inhibitors (PPIs) are associated with microbiome changes of the gut, which in turn may affect the progression of colorectal cancer (CRC). This study aims to assess the associations between PPI use and all-cause and CRC-specific mortality.Methods: We selected all patients registered in the Swedish Prescribed Drug Registry who were diagnosed with CRC between 2006 and 2012 (N = 32,411, 54.9% PPI users) and subsequently followed them through register linkage to the Swedish Causes of Death Registry until December 2013. PPI users were patients with >= 1 post-diagnosis PPI dispensation. Time-dependent Cox-regression models were performed with PPI use as time-varying exposure.Results: Overall 4746 (14.0%) patients died, with an aHR of 1.38 (95% CI 1.32-1.44) for all-cause mortality comparing PPI users with PPI nonusers. Higher-magnitude associations were observed among male, cancer stage 0-I, rectal cancer and patients receiving CRC surgery. The PPI-all-cause mortality association was also more pronounced comparing new users to non-users (aHR = 1.47, 95%CI 1.40-1.55) than comparing continuous users to non-users (aHR = 1.32, 95%CI 1.24-1.39). The risk estimates for CRC-specific mortality comparing PPI users to PPI nonusers were similar to those for all-cause mortality.Conclusion: PPI use after the CRC diagnosis was associated with increased all-cause and CRC-specific mortality.
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