| 31. |
- Chen, Baoqing, et al.
(author)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Journal article (peer-reviewed)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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| 32. |
- Chen, Hui, et al.
(author)
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Age- and sex-specific modifiable risk factor profiles of dementia : evidence from the UK Biobank
- 2023
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 38:1, s. 83-93
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Journal article (peer-reviewed)abstract
- Dementia constitutes a worldwide concern. To characterize the age- and sex-specific modifiable risk factor profiles of dementia, we included 497,401 UK Biobank participants (mean age = 56.5 years) without dementia at baseline (2006–2010) and followed them until March 2021. Cox proportional hazard models were used to estimate the age- and sex-specific hazard ratios (HRs) of incident dementia associated with socioeconomic (less education and high Townsend deprivation index), lifestyle (non-moderate alcohol intake, current smoking, suboptimal diet, physical inactivity, and unhealthy sleep duration), and health condition factors (hypertension, diabetes, cardiovascular diseases, and depressive symptoms). We also calculated the population attributable fractions (PAFs) of these factors. During follow-up (mean = 11.6 years), we identified 6564 dementia cases. HRs for the risk factors were similar between the sexes, while most factors showed stronger associations among younger participants. For example, the HRs of smoking were 1.74 (95% CI: 1.23, 2.47) for individuals aged < 50 years, and 1.18 (1.05, 1.33) for those aged ≥ 65 years. Overall, 46.8% (37.4%, 55.2%) of dementia cases were attributable to the investigated risk factors. The PAFs of the investigated risk factors also decreased with age, but that for health condition risk factors decreased with lower magnitude than socioeconomic and lifestyle risk factors. The stronger associations and greater PAFs of several modifiable risk factors for dementia among younger adults than older participants underscored the importance of dementia prevention from an earlier stage across the adult life course.
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| 33. |
- Chen, Hui, et al.
(author)
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Association of Long-Term Body Weight Variability With Dementia : A Prospective Study
- 2021
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 77:10, s. 2116-2122
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Journal article (peer-reviewed)abstract
- Background: Body weight variability (BWV) refers to intraindividual weight loss and gain over a period. The association of long-term BWV with dementia remains unclear and whether this association is beyond body weight change is undetermined.Methods: In the Health and Retirement Study, a total of 5 547 dementia-free participants (56.7% women; mean [SD] age, 71.1 [3.2] years) at baseline (2008) were followed up to 8 years (mean = 6.8 years) to detect incident dementia. Body weight was self-reported biennially from 1992 to 2008. BWV was measured as the coefficient of variation utilizing the body weight reported 9 times across 16 years before baseline. Cox-proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI).Results: Among the 5 547 participants, a total of 427 incident dementia cases were identified during follow-up. Greater long-term BWV was significantly associated with a higher risk of dementia (HR comparing extreme quartiles: 2.01, 95% CI: 1.48-2.72; HR of each SD increment: 1.21, 95% CI: 1.10-1.32; p-trend < .001) independent of mean body weight and body weight change. This significant association was even observed for BWV estimated approximately 15 years preceding dementia diagnosis (HR of each SD increment: 1.13, 95% CI: 1.03-1.23) and was more pronounced for that closer to diagnosis.Conclusion: Our prospective study suggested that greater BWV may be a novel risk factor for dementia.
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| 34. |
- Chen, Hui, et al.
(author)
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Associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay diet with brain structural markers and their changes
- 2024
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In: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:2, s. 1190-1200
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear.METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations.RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654).DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation.
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| 35. |
- Chen, Wenjun, et al.
(author)
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A typological framework of non-floodplain wetlands for global collaborative research and sustainable use
- 2022
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 17:11
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Research review (peer-reviewed)abstract
- Non-floodplain wetlands (NFWs) are important but vulnerable inland freshwater systems that are receiving increased attention and protection worldwide. However, a lack of consistent terminology, incohesive research objectives, and inherent heterogeneity in existing knowledge hinder cross-regional information sharing and global collaboration. To address this challenge and facilitate future management decisions, we synthesized recent work to understand the state of NFW science and explore new opportunities for research and sustainable NFW use globally. Results from our synthesis show that although NFWs have been widely studied across all continents, regional biases exist in the literature. We hypothesize these biases in the literature stem from terminology rather than real geographical bias around existence and functionality. To confirm this observation, we explored a set of geographically representative NFW regions around the world and characteristics of research focal areas. We conclude that there is more that unites NFW research and management efforts than we might otherwise appreciate. Furthermore, opportunities for cross-regional information sharing and global collaboration exist, but a unified terminology will be needed, as will a focus on wetland functionality. Based on these findings, we discuss four pathways that aid in better collaboration, including improved cohesion in classification and terminology, and unified approaches to modeling and simulation. In turn, legislative objectives must be informed by science to drive conservation and management priorities. Finally, an educational pathway serves to integrate the measures and to promote new technologies that aid in our collective understanding of NFWs. Our resulting framework from NFW synthesis serves to encourage interdisciplinary collaboration and sustainable use and conservation of wetland systems globally.
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| 36. |
- Chen, Zhi, et al.
(author)
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Large-Area Crystalline Zeolitic Imidazolate Framework Thin Films
- 2021
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:25, s. 14124-14130
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Journal article (peer-reviewed)abstract
- We report that continuous MOF films with highly controlled thickness (from 44 to 5100 nm) can be deposited over length scales greater than 80 centimeters by a facile, fast, and cost-effective spray-coating method. Such success relies on our discovery of unprecedented perfectly dispersed colloidal solutions consisting of amorphous MOF nanoparticles, which we adopted as precursors that readily converted to the crystalline films upon low-temperature in situ heating. The colloidal solutions allow for the fabrication of compact and uniform MOF films on a great deal of substrates such as fluorine-doped tin oxide, glass, SiO2, Al2O3, Si, Cu, and even flexible polycarbonate, widening their technological applications where substrates are essential. Despite the present work focuses on the fabrication of uniform cobalt-(2-methylimidazole)2 and zinc-(2-methylimidazole)2 films, our findings mark a great possibility in producing other high-quality MOF thin films on a large scale.
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| 37. |
- Chng, Kern Rei, et al.
(author)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
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Journal article (peer-reviewed)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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| 38. |
- Conti, David, V, et al.
(author)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 39. |
- Deng, Mingxin, et al.
(author)
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Efficient Parallel Polynomial-Based Compensation Structure for Frequency Response Mismatch in Two-Channel TI-ADCs
- 2024
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In: IEEE Transactions on Circuits and Systems - II - Express Briefs. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 1549-7747 .- 1558-3791. ; 71:2, s. 992-996
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Journal article (peer-reviewed)abstract
- This brief introduces a compensation structure for frequency response mismatch (FRM) errors in two-channel time-interleaved analog-to-digital converters (TI-ADCs) based on polynomial models of the channel frequency responses. It can be used for any Nyquist band and it comprises parallel error approximation branches (EABs), each branch consisting of a fixed differentiator of unique degree cascaded with a variable multiplier and a simple modulator. It suffices to alter the variable multipliers when the channels change, thereby avoiding online filter design. In addition, it achieves a lower latency and a significantly lower computational complexity compared to cascaded polynomial-based structures. Numerical simulations and comparisons are included, validating the efficacy of the proposed structure.
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| 40. |
- Fluckiger, Christoph, et al.
(author)
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The Reciprocal Relationship Between Alliance and Early Treatment Symptoms: A Two-Stage Individual Participant Data Meta-Analysis
- 2020
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In: Journal of Consulting and Clinical Psychology. - : AMER PSYCHOLOGICAL ASSOC. - 0022-006X .- 1939-2117. ; 88:9, s. 829-843
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Journal article (peer-reviewed)abstract
- Objective: Even though the early alliance has been shown to robustly predict posttreatment outcomes, the question whether alliance leads to symptom reduction or symptom reduction leads to a better alliance remains unresolved. To better understand the relation between alliance and symptoms early in therapy, we meta-analyzed the lagged session-by-session within-patient effects of alliance and symptoms from Sessions I to 7. Method: We applied a 2-stage individual participant data meta-analytic approach. Based on the data sets of 17 primary studies from 9 countries that comprised 5,350 participants, we first calculated standardized session-by-session within-patient coefficients. Second, we meta-analyzed these coefficients by using random-effects models to calculate omnibus effects across the studies. Results: In line with previous meta-analyses, we found that early alliance predicted posttreatment outcome. We identified significant reciprocal within-patient effects between alliance and symptoms within the first 7 sessions. Cross-level interactions indicated that higher alliances and lower symptoms positively impacted the relation between alliance and symptoms in the subsequent session. Conclusion: The findings provide empirical evidence that in the early phase of therapy. symptoms and alliance were reciprocally related to one other, often resulting in a positive upward spiral of higher alliance/lower symptoms that predicted higher alliances/lower symptoms in the subsequent sessions. Two-stage individual participant data meta-analyses have the potential to move the field forward by generating and interlinking well-replicable process-based knowledge.
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