| 1. |
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| 2. |
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| 3. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Journal article (peer-reviewed)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.
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| 4. |
- Wang, Fang, et al.
(author)
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Emerging contaminants: A One Health perspective
- 2024
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In: Innovation. - 2666-6758. ; 5
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Research review (peer-reviewed)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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| 5. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 6. |
- Barregård, Lars, 1948, et al.
(author)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Journal article (peer-reviewed)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 7. |
- Chao, Guihua, et al.
(author)
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Tei index : The earliest detectable cardiac structural and functional abnormality detectable in Hb Bart's foetal edema.
- 2009
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 134:3, s. e150-154
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Premature death and still births are common in Hb Bart's foetal edema which carries significant risk to mothers. We aimed to identify early changes in cardiac structure and function in a cohort of HB Bart's foetuses, using Doppler echocardiography. METHODS: We studied 97 HB Bart's foetuses in different gestation groups; I (20-24 weeks),..., V (37-42 weeks) and compared them with age matched controls. We measured right and left atrial diameters as well as right and left ventricular diameters. From the Doppler filling and ejection velocities of the right and left ventricles we measured Tei index in 30 foetuses and compared them with age matched normal controls. RESULTS: The four cardiac chamber dimensions were not significantly different from the respective controls (p=NS for all). The right atrial diameter was enlarged in groups II, III, IV and V (p<0.05 vs normal controls). The right ventricle was significantly dilated in group III, IV and V (p<0.05-0.01) compared with normals. The left atrium and left ventricle were enlarged in groups III and IV, respectively (p<0.05 vs normals). Transmitral and transtricuspid E/A ratio was significantly less than normal in groups III (p<0.01), IV (p<0.05) and IV (p<0.05). LV and RV fractional shortening and stroke distance of group IV and V were significantly less than the respective normals (p<0.05 for all). LV and RV Tei index increased progressively from 20-week gestation (p<0.05) with respect to controls. CONCLUSIONS: In HB Bart's foetuses left and right ventricular asynchrony develop earlier than overt cavity dilatation and impairment of systolic function. The use of such markers of ventricular asynchronous function may play an important role in optimum management of these pregnancies.
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| 8. |
- Chen, Chao, et al.
(author)
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Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
- 2020
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In: Aging. - : Impact Journals, LLC. - 1945-4589. ; 12:11, s. 10642-10662
-
Journal article (peer-reviewed)abstract
- DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18×10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.
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| 9. |
- Chen, Zhishan, et al.
(author)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 10. |
- Cristea, Mirela, 1976-
(author)
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Expression of Manganese Lipoxygenase and Site-Directed Mutagenesis of Catalytically Important Amino Acids : Studies on Fatty Acid Dioxygenases
- 2006
-
Doctoral thesis (other academic/artistic)abstract
- Polyunsaturated fatty acids can be bioactivated by two families of dioxygenases, which either contain non-heme iron (lipoxygenases) or heme (cyclooxygenases, linoleate diol synthases and α-dioxygenases).Lipoxygenases and their products play important roles in the pathophysiology of plants and fungi. The only known lipoxygenase with catalytic manganese (Mn-lipoxygenase) is secreted by a devastating root pathogen of wheat, the Take-all fungus Gaeumannomyces graminis. Its mycelia also contains linoleate diol synthase (LDS), which can oxidize linoleic acid to sporulation hormones.Mn-lipoxygenase belongs to the lipoxygenase gene family. Recombinant Mn-lipoxygenase was successfully expressed in the yeast Pichia pastoris with an expression level of 30 mg/L in fermentor culture. The tentative metal ligands of Mn-lipoxygenase were studied by site-directed mutagenesis. The results show that four residues His-274, His-278, His-462 and the C-terminal Val-602 likely coordinate manganese, as predicted by sequence alignments with Fe lipoxygenases.Mn-lipoxygenase (~100 kDa) contains an Asp-Pro peptide bond in the N-terminal region, which appears to hydrolyze during storage and in the acidic media during Pichia expression to an active enzyme of smaller size, mini-Mn-lipoxygenase (~70 kDa). The active form of Mn-lipoxygenase can oxygenate fatty acids of variable chain length, suggesting that the fatty acids enter the catalytic site with the ω-end (“tail first”).Mn-lipoxygenase is an R-lipoxygenase with a conserved Gly316 residue known as a determinant of stereospecificity in other R/S lipoxygenases. The Gly316Ala mutant showed an increased hydroperoxide isomerase activity and transformed 18:3n-3 and 17:3n-3 to epoxyalcohols.The genome of the rice blast fungus, Magnaporthe grisea, contains putative genes of lipoxygenases and LDS. Mycelia of M. grisea were found to express LDS activity. This enzyme was cloned and sequenced and showed 65% amino acid identity with LDS from G.graminis. Take-all and the rice blast fungi represent a constant threat to staple foods worldwide. Mn-lipoxygenase and LDS might provide new means to combat these pathogens.
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| 11. |
- Cristea, Mirela, et al.
(author)
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Expression of manganese lipoxygenase in Pichia pastoris and site-directed mutagenesis of putative manganese ligands
- 2005
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In: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861 .- 1096-0384. ; 434:1, s. 201-211
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Journal article (peer-reviewed)abstract
- Manganese lipoxygenase is secreted by the fungus Gaeumannomyces graminis. We expressed the enzyme in Pichia pastoris, which secreted approximately 30 mg Mn-lipoxygenase/L culture medium in fermentor. The recombinant lipoxygenase was N- and O-glycosylated (80-100 kDa), contained approximately 1 mol Mn/mol protein, and had similar kinetic properties (K(m) approximately 7.1 microM alpha-linolenic acid and V(max) 18 nmol/min/microg) as the native Mn-lipoxygenase. Mn-lipoxygenase could be quantitatively converted, presumably by secreted Pichia proteases, to a smaller protein (approximately 67 kDa) with retention of lipoxygenase activity (K(m) approximately 6.4 microM alpha-linolenic acid and V(max) approximately 12 nmol/min/microg). Putative manganese ligands were investigated by site-directed mutagenesis. The iron ligands of soybean lipoxygenase-1 are two His residues in the sequence HWLNTH, one His residue and a distant Asn residue in the sequence HAAVNFGQ, and the C-terminal Ile residue. The homologous sequences of Mn-lipoxygenase are H274VLFH278 and H462HVMN466QGS, respectively, and the C-terminal amino acid is Val-602. The His274Gln, His278Glu, His462Glu, and the Val-602 deletion mutants of Mn-lipoxygenase were inactive, and had lost >95% of the manganese content. His-463, Asn-466, and Gln-467 did not appear to be critical for Mn-lipoxygenase activity, as His463Gln, Asn466Gln, Asn466Leu, and Gln467Asn mutants metabolized alpha-linolenic acid to 11- and 13-hydroperoxylinolenic acids. We conclude that His-274, His-278, His-462, and Val-602 likely coordinate manganese.
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| 12. |
- Dong, Xuesi, et al.
(author)
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Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma
- 2019
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In: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:16, s. 6312-6335
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Journal article (peer-reviewed)abstract
- Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (Pdiscovery = 0.01 and Pvalidation = 2.71×10-3). Further, potential functional DNA methylation-gene expression-overall survival pathways were evaluated by causal mediation analysis. The effect of DNA methylation level on LUAD survival was significantly mediated through gene expression level. By adding DNA methylation and gene expression biomarkers to a model of only clinical data, the AUCs of the trans-omics model improved by 18.3% (to 87.2%) and 16.4% (to 85.3%) in discovery and validation phases, respectively. Further, concordance index of the nomogram was 0.81 and 0.77 in discovery and validation phases, respectively. Based on systematic review of published literatures, our model was superior to all existing models for early-stage LUAD. In summary, our trans-omics model may help physicians accurately identify patients with high mortality risk.
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| 13. |
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| 14. |
- Guo, Di, et al.
(author)
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Cholecystokinin-like peptide mediates satiety by inhibiting sugar attraction
- 2021
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:8
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Journal article (peer-reviewed)abstract
- Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.
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| 15. |
- Hendrikse, Natalie, et al.
(author)
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Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome
- 2021
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In: ISCIENCE. - : Elsevier BV. - 2589-0042. ; 24:3
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Journal article (peer-reviewed)abstract
- We show the successful application of ancestral sequence reconstruction to enhance the activity of iduronate-2-sulfatase (IDS), thereby increasing its therapeutic potential for the treatment of Hunter syndrome-a lysosomal storage disease caused by impaired function of IDS. Current treatment, enzyme replacement therapy with recombinant human IDS, does not alleviate all symptoms, and an unmet medical need remains. We reconstructed putative ancestral sequences of mammalian IDS and compared them with extant IDS. Some ancestral variants displayed up to 2-fold higher activity than human IDS in in vitro assays and cleared more substrate in ex vivo experiments in patient fibroblasts. This could potentially allow for lower dosage or enhanced therapeutic effect in enzyme replacement therapy, thereby improving treatment outcomes and cost efficiency, as well as reducing treatment burden. In summary, we showed that ancestral sequence reconstruction can be applied to lysosomal enzymes that function in concert with modern enzymes and receptors in cells.
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| 16. |
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| 17. |
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| 18. |
- Hörnsten, Lena, et al.
(author)
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Cloning of the manganese lipoxygenase gene reveals homology with the lipoxygenase gene family
- 2002
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In: Eur. J. Biochem. ; 269, s. 2690-7
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Journal article (peer-reviewed)abstract
- Manganese lipoxygenase was isolated to homogeneity from the take-all fungus, Gaeumannomyces graminis. The C-terminal amino acids and several internal peptides were sequenced, and the information was used to obtain a cDNA probe by RT/PCR. Screening of a genomic library of G. graminis yielded a full-length clone of the Mn-Lipoxygenase gene. cDNA analysis showed that the gene spanned 2.6 kb and contained one intron (133 bp). Northern blot analyses indicated two transcripts (2.7 and 3.1 kb). The deduced amino-acid sequence of the Mn-Lipoxygenase precursor (618 amino acids, 67.7 kDa) could be aligned with mammalian and plant lipoxygenases with 23-28% identity over 350-400 amino-acid residues of the catalytic domains. Lipoxygenases have one water molecule and five amino acids as Fe ligands. These are two histidine residues in the highly conserved 30 amino-acid sequence WLLAK-X15-H-X4-H-X3-E of alpha helix 9, one histidine and usually an asparaine residue in the sequence H-X3-N-X-G of alpha helix 18, and the carboxyl oxygen of the C-terminal isoleucine (or valine) residue. The homologous sequence of alpha helix 9 of Mn-Lipoxygenase [WLLAK-X14-H(294)-X3-H(297)-X3-E] contained two single-amino-acid gaps, but otherwise His294 and His297 aligned with the two His residues, which coordinate iron. Mn-Lipoxygenase [H(478)-X3-N(482)-X-G] could be aligned with the two metal ligands of alpha helix 18, and the C-terminal residue was Val618. We conclude that Mn-Lipoxygenase belongs to the lipoxygenase gene family and that its unique biochemical properties might be related to structural differences in the metal centre and alpha helix 9 of lipoxygenases rather than to the metal ligands.
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| 19. |
- Ji, Xinyu, et al.
(author)
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Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early-stage NSCLC patients
- 2020
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In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 14:11, s. 2759-2774
-
Journal article (peer-reviewed)abstract
- Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas. The methylation of the CpG probe cg05293407TRIM27 was significantly associated with overall survival in patients with LUSC (HR = 1.65, 95% CI: 1.30–2.09, P = 4.52 × 10−5), but not in patients with LUAD (HR = 1.08, 95% CI: 0.87–1.33, P = 0.493). As incidence of LUSC is associated with higher smoking intensity compared to LUAD, we investigated whether smoking intensity impacted on the prognostic effect of cg05293407TRIM27 methylation in NSCLC. LUSC patients had a higher average pack-year of smoking (37.49LUAD vs 54.79LUSC, P = 1.03 × 10−19) and included a higher proportion of current smokers than LUAD patients (28.24%LUAD vs 34.09%LUSC, P = 0.037). cg05293407TRIM27 was significantly associated with overall survival only in NSCLC patients with medium–high pack-year of smoking (HR = 1.58, 95% CI: 1.26–1.96, P = 5.25 × 10−5). We conclude that cg05293407TRIM27 methylation is a potential predictor of LUSC prognosis, and smoking intensity may impact on its prognostic value across the various types of NSCLC.
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| 20. |
- Jianfeng, Lin, 1994, et al.
(author)
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Hydrodynamic performance of a rim-driven thruster improved with gap geometry adjustment
- 2023
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In: Engineering Applications of Computational Fluid Mechanics. - : Informa UK Limited. - 1994-2060 .- 1997-003X. ; 17:1
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Journal article (peer-reviewed)abstract
- The hubless rim-driven thruster (RDT) has become increasingly interesting for ship propulsion. Gap flow has been proven as the main feature of RDT that cannot be simply neglected. In this study, based on a classical hubless RDT, the effects of the gap geometry are studied by adjusting its axial passage length, and inlet and outlet oblique angles. The hydrodynamic characteristics of the RDT were simulated with OpenFOAM based on the k – ω shear stress transport turbulence model. Due to the pressure increase after the main flow passes through the rotating blades, the flow inside gap is driven upstream, which is opposite to the main flow direction. It is found that the hydrodynamic efficiency is increased as the gap axial passage length is shortened, which is realized by increasing the oblique angle with the fixed inlet and outlet positions. Moving the inlet and outlet to further downstream and upstream positions has negligible effects on the hydrodynamic efficiency and leads to recirculating flow within the gap near its inlet. These findings shed light on the design of the gap geometry to improve the RDT hydrodynamic performance.
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| 21. |
- Lin, Esther Ching-Lan, et al.
(author)
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Factors influencing patient-perceived quality of care in psychiatric hospitals in Taiwan
- 2021
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In: Archives of Psychiatric Nursing. - : Elsevier. - 0883-9417 .- 1532-8228. ; 35:1, s. 9-16
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Journal article (peer-reviewed)abstract
- Patient-perceived quality of inpatient/outpatient psychiatric care remains under-researched. A cross-sectional survey with purposive sampling comprising 567 inpatients and 549 outpatients was conducted among eight psychiatric care facilities in Taiwan to examine the factors influencing patient-perceived care quality. Inpatients and outpatients perceived moderate quality of care, where "Encounter" was reported as the highest dimension. Inpatients perceived "Secure environment" as the lowest; outpatients rated "Discharge/Referring" as the lowest. Hospital region and customer loyalty were significantly associated with patient-perceived care quality. Other significant factors were also identified: inpatient employment, perceived mental health and treatment effects, understanding diagnosis, previous treatment, and visited by appointment.
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| 22. |
- Lu, Xiaotian, et al.
(author)
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Climate change induced eutrophication of cold-water lake in an ecologically fragile nature reserve
- 2019
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In: Journal of Environmental Sciences (China). - : Elsevier BV. - 1001-0742 .- 1878-7320. ; 75, s. 359-369
-
Journal article (peer-reviewed)abstract
- © 2018 Aquatic ecosystem sustainability around the globe is facing crucial challenges because of increasing anthropogenic and natural disturbances. In this study, the Tianchi Lake, a typical cold-water lake and a UNESCO/MAB (Man and Biosphere) nature reserve located in high latitude and elevation with the relatively low intensity of human activity was chosen as a system to examine the linkages between climate change and eutrophication. As a part of the UNESCO Bogda Man and Biosphere Reserve, Tianchi Lake has been well preserved for prevention from human intervention, but why has it been infected with eutrophication recent years? Our results show that climate change played a significant role in the eutrophication in the Tianchi Lake. Increased temperature, changed precipitation pattern and wind-induced hydrodynamic fluctuations in the summer season were suggested to make a major contribution to the accelerated eutrophication. The results also showed that the local temperature and precipitation changes were closely linked to the large-scale atmospheric circulation, which opens the door for the method to be applied in other regions without local climatic information. This study suggests that there is an urgent need to take into consideration of climate change adaptation into the conservation and management of cold-water lakes globally.
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| 23. |
- Lu, Yonglong, et al.
(author)
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Interaction between pollution and climate change augments ecological risk to a coastal ecosystem
- 2018
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In: Ecosystem Health and Sustainability. - : American Association for the Advancement of Science (AAAS). - 2096-4129 .- 2332-8878. ; 4:7, s. 161-168
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Journal article (peer-reviewed)abstract
- Pollution and climate change are among the most challenging issues for countries with developing economies, but we know little about the ecological risks that result when these pressures occur together. We explored direct effects of, and interactions between, environmental pollution and climate change on ecosystem health in the Bohai Sea region of Northern China. We developed an integrated approach to assess ecological risks to this region under four scenarios of climate change. Although ecological risks to the system from pollution alone have been declining, interactions between pollution and climate change have enhanced ecological risks to this coastal/marine ecosystem. Our results suggest that current policies focused strictly on pollution control alone should be changed to take into account the interactive effects of climate change so as to better forecast and manage potential ecological risks.
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| 24. |
- Löwemark, Ludvig, et al.
(author)
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Variations in glacial and interglacial marine conditions over the last two glacial cycles off northern Greenland
- 2016
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 147:SI, s. 164-177
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Journal article (peer-reviewed)abstract
- Five sediment cores from the Lomonosov Ridge and the Morris Jesup Rise north of Greenland show the history of sea-ice coverage and primary productivity over the last two glacial cycles. Variations in Manganese content, benthic and planktonic foraminifera, bioturbation, and trace fossil diversity are interpreted to reflect differences in sea-ice cover and sediment depositional conditions between the identified interglacials. Marine Isotope Stage (MIS) 1 and MIS 2 are represented by thin (<< 5 cm) sediment units while the preceding interglacial MIS 5 and glacial MIS 6 are characterized by thick (10 -20 cm) deposits. Foraminiferal abundances and bioturbation suggest that MIS 1 was generally characterized by severe sea-ice conditions north of Greenland while MISS appears to have been considerably warmer with more open water, higher primary productivity, and higher sedimentation rates. Strengthened flow of Atlantic water along the northern continental shelf of Greenland rather than development of local polynyas is here suggested as a likely cause for the relatively warmer marine conditions during MIS 5 compared to MIS 1. The cores also suggest distinct differences between the glacial intervals MIS 2 and MIS 6. While MIS 6 is distinguished by a relatively thick sediment unit poor in foraminifera and with low Mn values, MIS 2 is practically missing. We speculate that this could be the effect from a paleocrystic sea-ice cover north of Greenland during MIS 2 that prevented sediment delivery from sea ice and icebergs. In contrast, the thick sequence deposited during MIS 6 indicates a longer glacial period with dynamic intervals characterized by huge drifting icebergs delivering ice rafted debris (IRD). A drastic shift from thinner sedimentary cycles where interglacial sediment parameters indicate more severe sea-ice conditions gave way to larger amplitude cycles with more open water indicators was observed around the boundary between MIS 7/8. This shift is in agreement with a sedimentary regime shift previously identified in the Eurasian Basin and may be an indicator for the growth of larger ice sheets on the Eurasian landmass during the penultimate glacial period.
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| 25. |
- Ma, Wing-Kin, et al.
(author)
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Some results on 16-QAM MIMO detection using semidefinite relaxation
- 2008
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In: 2008 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING. - 9781424414833 ; , s. 2673-2676
-
Conference paper (peer-reviewed)abstract
- Semidefinite relaxation (SDR) is a high-performance efficient approach to MIMO detection especially for the BPSK or QPSK constellations. Recently, a number of research endeavors have focused on extending SDR to the case of 16-QAM constellations. This paper reports two interesting and useful results on this problem. First, we show that two of the existing 16-QAM SDR receivers, namely the polynomial-inspired SDR (PI-SDR) and bound-constrained SDR (BC-SDR) methods, are equivalent. Second, we develop a specialized interior-point algorithm for the implementation of BC-SDR. The proposed algorithm is computationally efficient exploiting the BC-SDR structures, and enables us to handle larger problem sizes in practice.
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| 26. |
- Ma, Wing-Kin, et al.
(author)
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The Equivalence of Semidefinite Relaxation MIMO Detectors for Higher-Order QAM
- 2009
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In: IEEE Journal on Selected Topics in Signal Processing. - 1932-4553. ; 3:6, s. 1038-1052
-
Journal article (peer-reviewed)abstract
- In multi-input multi-output (MIMO) detection, semidefinite relaxation (SDR) has been shown to be an efficient high-performance approach. For BPSK and QPSK, it has been found that SDR can provide near-optimal bit error probability performance. This has stimulated a number of recent research endeavors that aim to apply SDR to the high-order QAM cases. These independently developed SDRs are different in concept, structure and complexity, and presently no serious analysis has been given to compare these methods. This paper analyzes the relationship of three such SDR methods, namely the polynomial-inspired SDR (PI-SDR) by Wiesel et al., the bound-constrained SDR (BC-SDR) by Sidiropoulos and Luo, and the virtually-antipodal SDR (VA-SDR) by Mao et al. Rather unexpectedly, we prove that the three SDRs are equivalent in the following sense: The three SDRs yield the same optimal objective values, and their optimal solutions have strong correspondences. Specifically, we establish this solution equivalence between BC-SDR and VA-SDR for any 4(q)-QAM constellations, and that between BC-SDR and PI-SDR for 16-QAM and 64-QAM. Moreover, the equivalence result holds for any channel, problem size, and signal-to-noise ratio. Our theoretical findings are confirmed by simulations, where the three SDRs offer identical symbol error probabilities. Additional simulation results are also provided to demonstrate the effectiveness of SDR compared to some other MIMO detectors, in terms of complexity and symbol error performance.
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| 27. |
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| 28. |
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| 29. |
- Su, Chao
(author)
-
Characterization of two novel fatty acid dioxygenases : Linoleate diol synthase and manganese lipoxygenase
- 1999
-
Doctoral thesis (other academic/artistic)abstract
- Two classes of fatty acid dioxygenases, PGH synthases (hemeproteins) and lipoxygenases (non-heme iron proteins), are of eminent pharmacological importance. This thesis describes a PGH synthase-related dioxygenase designated linoleate diol synthase (LDS) and the first native occurring manganese-containing lipoxygenase.LDS was purified from the fungus Gaeumannomyces graminis as a hemeprotein with dioxygenase and hydroperoxide isomerase activities. It was previously known that the enzyme abstracts the pro-S hydrogen from the C-8 of linoleate and forms 8R-hydroperoxylinoleic acid that is sequentially isomerized to a diol, 7S,8S-dihydroxylinoleic acid. The pure enzyme was a homotetramer (520 kDa). It showed typical spectra of a high spin ferric hemeprotein, and contained at least 0.7 heme groups per monomer. A tyrosyl radical and ferryl intermediates were detected during catalysis by stopped-flow and electron paramagnetic resonance spectroscopy. With help of peptide sequence information and the reverse transcription polymerase chain reaction, the linoleate diol synthase gene was isolated from a genomic library. The gene contained three introns and spanned 3.2-kb corresponding to 978 amino acid residues. The deduced protein sequence showed homology with PGH synthases over the major catalytic domain. LDS and PGH synthases were thus found to have both structural and functional similarities.G. graminis was found to secret a lipoxygenase. The purified enzyme contained manganese and was designated manganese-lipoxygenase (Mn-LO). Mn-LO was highly glycosylated, with a protein mass of 73 kDa. It catalyzed the conversion of linoleate into 13R-hydroperoxylinoleic acid and 11S- hydroperoxylinoleic acid, a novel lipoxygenase metabolite, by initial abstraction of the pro- S hydrogen at C-11 and insertion of O2 at C-13 or C-11 in suprafacial way. In analogy with iron-lipoxygenases, Mn-LO contained a mononuclear metal center, which was Mn(II) and oxidized during catalysis. A hypothetical lipoxygenation model for Mn-LO was presented.In summary, LDS may belong to the same gene family as PGH synthases, the fatty acid heme dioxygenase family. The discovery of Mn-LO may have broadened our knowledge of lipoxygenases.
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| 30. |
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| 31. |
- Su, PJ, et al.
(author)
-
Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy
- 2016
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 31423-
-
Journal article (peer-reviewed)abstract
- The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted.
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| 32. |
- Tan, Chunlin, et al.
(author)
-
Acid-assisted hydrothermal synthesis of red fluorescent carbon dots for sensitive detection of Fe(III)
- 2017
-
In: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 7:65, s. 40952-40956
-
Journal article (peer-reviewed)abstract
- Red-emitting carbon dots (C-dots) were synthesized from p-phenylenediamine (p-PD) aqueous solution with nitric acid (HNO3) assistance by hydrothermal reaction at 200 degrees C for 2 h. p-PD aqueous solution can be transferred to C-dots (or poly(p-PD)) with (or without) the addition of acid. Different acid systems, such as HNO3, H3PO4 and HF, can directly synthesize red-emitting C-dots, and the fluorescence can be enhanced by increasing the strength of acids. N-CDs, 3.46 nm-average-sized C-dots, prepared in dilute HNO3, have a quantum yield of 15.8% with unique, excitation-wavelength independent emission in the red region (600 and 680 nm) and a broad visible excitation band. Carboxyl, ester and hydroxyl groups on the C-dots surface directly lead to red emission. N-CDs have a certain selective specificity for Fe3+ detection and the linear range is 10-300 nmol L-1 with a limit of determination of 1.9 nmol L-1.
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| 33. |
- Thalén, Niklas, 1985-, et al.
(author)
-
Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
-
Other publication (other academic/artistic)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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| 34. |
- Thalén, Niklas, et al.
(author)
-
Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold
- 2024
-
In: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 81, s. 157-166
-
Journal article (peer-reviewed)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.
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| 35. |
- Tian, Xue-Chan, et al.
(author)
-
Unique gene duplications and conserved microsynteny potentially associated with resistance to wood decay in the Lauraceae
- 2023
-
In: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 14
-
Journal article (peer-reviewed)abstract
- Wood decay resistance (WDR) is marking the value of wood utilization. Many trees of the Lauraceae have exceptional WDR, as evidenced by their use in ancient royal palace buildings in China. However, the genetics of WDR remain elusive. Here, through comparative genomics, we revealed the unique characteristics related to the high WDR in Lauraceae trees. We present a 1.27-Gb chromosome-level assembly for Lindera megaphylla (Lauraceae). Comparative genomics integrating major groups of angiosperm revealed Lauraceae species have extensively shared gene microsynteny associated with the biosynthesis of specialized metabolites such as isoquinoline alkaloids, flavonoid, lignins and terpenoid, which play significant roles in WDR. In Lauraceae genomes, tandem and proximal duplications (TD/PD) significantly expanded the coding space of key enzymes of biosynthesis pathways related to WDR, which may enhance the decay resistance of wood by increasing the accumulation of these compounds. Among Lauraceae species, genes of WDR-related biosynthesis pathways showed remarkable expansion by TD/PD and conveyed unique and conserved motifs in their promoter and protein sequences, suggesting conserved gene collinearity, gene expansion and gene regulation supporting the high WDR. Our study thus reveals genomic profiles related to biochemical transitions among major plant groups and the genomic basis of WDR in the Lauraceae.
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| 36. |
- Wang, Yangong, et al.
(author)
-
Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy
- 2024
-
In: NATURE MEDICINE. - 1078-8956 .- 1546-170X. ; 30, s. 1395-1405
-
Journal article (peer-reviewed)abstract
- Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making. Using exome sequencing data from one of the largest cohorts of children with cerebral palsy, the genetic diagnostic rates of single-nucleotide and copy number variants were assessed and a sizeable fraction found to be clinically actionable.
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| 37. |
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| 38. |
- Wang, Zhaoming, et al.
(author)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 39. |
- Wernersson, Erik, et al.
(author)
-
Deconwolf enables high-performance deconvolution of widefield fluorescence microscopy images
- 2024
-
In: Nature Methods. - 1548-7091 .- 1548-7105. ; 21:7, s. 1245-1256
-
Journal article (peer-reviewed)abstract
- Microscopy-based spatially resolved omic methods are transforming the life sciences. However, these methods rely on high numerical aperture objectives and cannot resolve crowded molecular targets, limiting the amount of extractable biological information. To overcome these limitations, here we develop Deconwolf, an open-source, user-friendly software for high-performance deconvolution of widefield fluorescence microscopy images, which efficiently runs on laptop computers. Deconwolf enables accurate quantification of crowded diffraction limited fluorescence dots in DNA and RNA fluorescence in situ hybridization images and allows robust detection of individual transcripts in tissue sections imaged with ×20 air objectives. Deconvolution of in situ spatial transcriptomics images with Deconwolf increased the number of transcripts identified more than threefold, while the application of Deconwolf to images obtained by fluorescence in situ sequencing of barcoded Oligopaint probes drastically improved chromosome tracing. Deconwolf greatly facilitates the use of deconvolution in many bioimaging applications.
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| 40. |
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| 41. |
- Xiao, Manjun, et al.
(author)
-
Approaching 19% efficiency and stable binary polymer solar cells enabled by a solidification strategy of solvent additive
- 2023
-
In: Science in China Series B. - : SCIENCE PRESS. - 1674-7291 .- 1869-1870. ; 66, s. 1500-1510
-
Journal article (peer-reviewed)abstract
- Additives play a crucial role in enhancing the photovoltaic performance of polymer solar cells (PSCs). However, the typical additives used to optimize blend morphology of PSCs are still high boiling-point solvents, while their trace residues may reduce device stability. Herein, an effective strategy of "solidification of solvent additive (SSA)" has been developed to convert additive from liquid to solid, by introducing a covalent bond into low-cost solvent diphenyl sulfide (DPS) to synthesize solid dibenzothiophene (DBT) in one-step, which achieves optimized morphology thus promoting efficiency and device stability. Owing to the fine planarity and volatilization of DBT, the DBT-processed films achieve ordered molecular crystallinity and suitable phase separation compared to the additive-free or DPS-treated ones. Importantly, the DBT-processed device also possesses improved light absorption, enhanced charge transport, and thus a champion efficiency of 11.9% is achieved in the PM6:Y6-based PSCs with an excellent additive component tolerance, reproducibility, and stability. Additionally, the DBT-processed PM6:L8-BO-based PSCs are further fabricated to study the universality of SSA strategy, offering an impressive efficiency approaching 19% as one of the highest values in binary PSCs. In conclusion, this article developed a promising strategy named SSA to boost efficiency and improve stability of PSCs.
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| 42. |
- Zhang, Chao, et al.
(author)
-
An Experimental Novel Study : Angelica sinensis Prevents Epidural Fibrosis in Laminectomy Rats via Downregulation of Hydroxyproline, IL-6, and TGF-beta 1
- 2013
-
In: Evidence-based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288. ; , s. 291814-
-
Journal article (peer-reviewed)abstract
- With laminectomy being widely accepted as the treatment for lumbar disorders, epidural fibrosis (EF) is a common complication for both the patients and the surgeons alike. Currently, EF is thought to cause recurrent postoperative pain after laminectomy or after discectomy. Angelica sinensis is a traditional Chinese medicine which has shown anti-inflammatory, antifibrotic, and antiproliferative properties. The object of this study was to investigate the effects of Angelica sinensis on the prevention of postlaminectomy EF formation in a rat model. A controlled double-blinded study was conducted in sixty healthy adult Wistar rats that underwent laminectomy at the L1-L2 levels. They were divided randomly into 3 groups according to the treatment method, with 20 in each group: (1) Angelica sinensis treatment group, (2) saline treatment group, and (3) sham group (laminectomy without treatment). All rats were euthanized humanely 4 weeks after laminectomy. The hydroxyproline content, Rydell score, vimentin cells density, fibroblasts density, inflammatory cells density, and inflammatory factors expressions all suggested better results in Angelica sinensis group than the other two groups. Topical application of Angelica sinensis could inhibit fibroblasts proliferation and TGF-beta 1 and IL-6 expressions and prevent epidural scar adhesion in postlaminectomy rat model.
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| 43. |
- Zhang, Chao, et al.
(author)
-
Clustered nuclei splitting via curvature information and gray-scale distance transform
- 2015
-
In: Journal of Microscopy. - : Wiley-Blackwell Publishing Inc.. - 0022-2720 .- 1365-2818. ; 259:1, s. 36-52
-
Journal article (peer-reviewed)abstract
- Clusters or clumps of cells or nuclei are frequently observed in two dimensional images of thick tissue sections. Correct and accurate segmentation of overlapping cells and nuclei is important for many biological and biomedical applications. Many existing algorithms split clumps through the binarization of the input images; therefore, the intensity information of the original image is lost during this process. In this paper, we present a curvature information, gray scale distance transform, and shortest path splitting line-based algorithm which can make full use of the concavity and image intensity information to find out markers, each of which represents an individual object, and detect accurate splitting lines between objects using shortest path and junction adjustment. The proposed algorithm is tested on both synthetic and real nuclei images. Experiment results show that the performance of the proposed method is better than that of marker-controlled watershed method and ellipse fitting method.
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| 44. |
- Zhang, Chao, et al.
(author)
-
Segmentation of clustered nuclei based on curvature-weighting
- 2012
-
In: Proceedings of the 27th Conference on Image and Vision Computing New Zealand. - New York, NY, USA : ACM. - 9781450314732 ; , s. 49-54
-
Conference paper (peer-reviewed)abstract
- Clusters of nuclei are frequently observed in thick tissue section images. It is very important to segment overlapping nuclei in many biomedical applications. Many existing methods tend to produce under segmented results when there is a high overlap rate. In this paper, we present a curvature weighting based algorithm which weights each pixel using the curvature information of its nearby boundaries to extract markers, each of which represents an object, from input images. Then we use marker-controlled watershed to obtain the final segmentation. Test results using both synthetic and real cell images are presented in the paper.
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| 45. |
- Zhang, Ruyang, et al.
(author)
-
EGLN2 DNA methylation and expression interact with HIF1A to affect survival of early-stage NSCLC
- 2019
-
In: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 14:2, s. 118-129
-
Journal article (peer-reviewed)abstract
- Hypoxia occurs frequently in human cancers and promotes stabilization and activation of hypoxia inducible factor (HIF). HIF-1α is specific for the hypoxia response, and its degradation mediated by three enzymes EGLN1, EGLN2 and EGLN3. Although EGLNs expression has been found to be related to prognosis of many cancers, few studies examined DNA methylation in EGLNs and its relationship to prognosis of early-stage non-small cell lung cancer (NSCLC). We analyzed EGLNs DNA methylation data from tumor tissue samples of 1,230 early-stage NSCLC patients, as well as gene expression data from The Cancer Genome Atlas. The sliding windows sequential forward feature selection method and weighted random forest were used to screen out the candidate CpG probes in lung adenocarcinomas (LUAD) and lung squamous cell carcinomas patients, respectively, in both discovery and validation phases. Then Cox regression was performed to evaluate the association between DNA methylation and overall survival. Among the 34 CpG probes in EGLNs, DNA methylation at cg25923056EGLN2 was identified to be significantly associated with LUAD survival (HR = 1.02, 95% CI: 1.01–1.03, P = 9.90 × 10–5), and correlated with EGLN2 expression (r =–0.36, P = 1.52 × 10–11). Meanwhile, EGLN2 expression was negatively correlated with HIF1A expression in tumor tissues (r =–0.30, P = 4.78 × 10–8) and significantly (P = 0.037) interacted with HIF1A expression on overall survival. Therefore, DNA methylation of EGLN2- HIF1A is a potential marker for LUAD prognosis and these genes are potential treatment targets for further development of HIF-1α inhibitors in lung cancer therapy.
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| 46. |
- Zhang, Ruyang, et al.
(author)
-
Independent Validation of Early-Stage Non-Small Cell Lung Cancer Prognostic Scores Incorporating Epigenetic and Transcriptional Biomarkers With Gene-Gene Interactions and Main Effects
- 2020
-
In: Chest. - : Elsevier BV. - 0012-3692. ; 158:2, s. 808-819
-
Journal article (peer-reviewed)abstract
- Background: DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. Research Question: Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomics data, improve the accuracy of cancer prognosis? Study Design and Methods: Biomarker screening and model validation were used to construct and validate a prognostic prediction model. NSCLC prognosis-associated biomarkers were identified on the basis of either their main effects or interactions with two types of omics data. A prognostic score incorporating epigenetic and transcriptional biomarkers, as well as clinical information, was independently validated. Results: Twenty-six pairs of biomarkers with G×G interactions and two biomarkers with main effects were significantly associated with NSCLC survival. Compared with a model using clinical information only, the accuracy of the epigenetic and transcriptional biomarker-based prognostic model, measured by area under the receiver operating characteristic curve (AUC), increased by 35.38% (95% CI, 27.09%-42.17%; P = 5.10 × 10–17) and 34.85% (95% CI, 26.33%-41.87%; P = 2.52 × 10–18) for 3- and 5-year survival, respectively, which exhibited a superior predictive ability for NSCLC survival (AUC3 year, 0.88 [95% CI, 0.83-0.93]; and AUC5 year, 0.89 [95% CI, 0.83-0.93]) in an independent Cancer Genome Atlas population. G×G interactions contributed a 65.2% and 91.3% increase in prediction accuracy for 3- and 5-year survival, respectively. Interpretation: The integration of epigenetic and transcriptional biomarkers with main effects and G×G interactions significantly improves the accuracy of prognostic prediction of early-stage NSCLC survival.
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| 47. |
- Zhang, Ruyang, et al.
(author)
-
SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival : an epigenomic–smoking interaction analysis
- 2019
-
In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 13:5, s. 1235-1248
-
Journal article (peer-reviewed)abstract
- Smoking cessation prolongs survival and decreases mortality of patients with non-small-cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed. Here, we conducted an epigenome-wide interaction analysis between DNA methylation and smoking cessation on NSCLC survival. We used a two-stage study design to identify DNA methylation–smoking cessation interactions that affect overall survival for early-stage NSCLC. The discovery phase contained NSCLC patients from Harvard, Spain, Norway, and Sweden. A histology-stratified Cox proportional hazards model adjusted for age, sex, clinical stage, and study center was used to test DNA methylation–smoking cessation interaction terms. Interactions with false discovery rate-q ≤ 0.05 were further confirmed in a validation phase using The Cancer Genome Atlas database. Histology-specific interactions were identified by stratification analysis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. We identified one CpG probe (cg02268510 SIPA 1L3 ) that significantly and exclusively modified the effect of smoking cessation on survival in LUAD patients [hazard ratio (HR) interaction = 1.12; 95% confidence interval (CI): 1.07–1.16; P = 4.30 × 10 –7 ]. Further, the effect of smoking cessation on early-stage LUAD survival varied across patients with different methylation levels of cg02268510 SIPA 1L3 . Smoking cessation only benefited LUAD patients with low methylation (HR = 0.53; 95% CI: 0.34–0.82; P = 4.61 × 10 –3 ) rather than medium or high methylation (HR = 1.21; 95% CI: 0.86–1.70; P = 0.266) of cg02268510 SIPA 1L3 . Moreover, there was an antagonistic interaction between elevated methylation of cg02268510 SIPA 1L3 and smoking cessation (HR interaction = 2.1835; 95% CI: 1.27–3.74; P = 4.46 × 10 −3 ). In summary, smoking cessation benefited survival of LUAD patients with low methylation at cg02268510 SIPA 1L3 . The results have implications for not only smoking cessation after diagnosis, but also possible methylation-specific drug targeting.
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| 48. |
- Zhao-Hai, He, et al.
(author)
-
Characters of the magnetotail plasma injection surveyed from Cluster observation
- 2008
-
In: Chinese Journal of Geophysics. - 0001-5733. ; 51:2, s. 307-315
-
Journal article (peer-reviewed)abstract
- The properties of proton (0 eV < E < 40 keV) in the plasma sheet are examined by means of a superposed epoch analysis, using 115 magnetotail plasma injection events which are identified from Cluster magnetotail orbit time in between 2001 and 2004. All events distribute in magnetic local time from 20 p.m. to 04 a. in. Five classes of magnetotail injection events are found to be similar with the geosynchronous observation: (1) pure ion injections; (2) ion injections followed a few minutes later by an electron injection; (3) simultaneous ion and electron injections; (4) electron injections followed a few minutes later by an ion injection; (5) pure electron injections. Proton shows a significant increase in temperature and density at the onset, and injects earthward with an increasing velocity more than the pre-injection average one. Super-posed epoch analysis on the simultaneous observation data of dusk-dawn electric field from the EFW (Electric Field and Waves) instrument, we found two different electric field configurations: ( I) electric field increases suddenly at the onset and the value is positive; (2) electric field changes the direction at the onset, and turns into a negative value. The simulation results of velocity vector after injection in equatorial plain, calculated in static magnetic (T89c) and electric (Volland-Stern) field models, agree with the statistical results mostly, and that suggests the electric drift caused by dawn-dusk convection electric field is one of the mechanisms of the particles injected earthward in magnetotail(-18 R-E < R < -10R(E)).
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