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  • Oxford University Press (OUP)  (24)
  • 1
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 11 ( 2021-12-06), p. e4154-e4165
    Abstract: Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren’t well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. Methods We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. Results Compared with children, older patients ( & gt;50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P & lt; .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P & lt; .025). Conclusions Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2002229-3
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  • 2
    In: Horticulture Research, Oxford University Press (OUP), Vol. 9 ( 2022-01-05)
    Abstract: Cissus is the largest genus in Vitaceae and is mainly distributed in the tropics and subtropics. Crassulacean acid metabolism (CAM), a photosynthetic adaptation to the occurrence of succulent leaves or stems, indicates that convergent evolution occurred in response to drought stress during species radiation. Here we provide the chromosomal level assembly of Cissus rotundifolia (an endemic species in Eastern Africa) and a genome-wide comparison with grape to understand genome divergence within an ancient eudicot family. Extensive transcriptome data were produced to illustrate the genetics underpinning C. rotundifolia’s ecological adaption to seasonal aridity. The modern karyotype and smaller genome of C. rotundifolia (n = 12, 350.69 Mb/1C), which lack further whole-genome duplication, were mainly derived from gross chromosomal rearrangements such as fusions and segmental duplications, and were sculpted by a very recent burst of retrotransposon activity. Bias in local gene amplification contributed to its remarkable functional divergence from grape, and the specific proliferated genes associated with abiotic and biotic responses (e.g. HSP-20, NBS-LRR) enabled C. rotundifolia to survive in a hostile environment. Reorganization of existing enzymes of CAM characterized as diurnal expression patterns of relevant genes further confer the ability to thrive in dry savannas.
    Type of Medium: Online Resource
    ISSN: 2052-7276
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2781828-7
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2017
    In:  Bioinformatics Vol. 33, No. 17 ( 2017-09-01), p. 2691-2698
    In: Bioinformatics, Oxford University Press (OUP), Vol. 33, No. 17 ( 2017-09-01), p. 2691-2698
    Abstract: Patient stratification or disease subtyping is crucial for precision medicine and personalized treatment of complex diseases. The increasing availability of high-throughput molecular data provides a great opportunity for patient stratification. Many clustering methods have been employed to tackle this problem in a purely data-driven manner. Yet, existing methods leveraging high-throughput molecular data often suffers from various limitations, e.g. noise, data heterogeneity, high dimensionality or poor interpretability. Results Here we introduced an Entropy-based Consensus Clustering (ECC) method that overcomes those limitations all together. Our ECC method employs an entropy-based utility function to fuse many basic partitions to a consensus one that agrees with the basic ones as much as possible. Maximizing the utility function in ECC has a much more meaningful interpretation than any other consensus clustering methods. Moreover, we exactly map the complex utility maximization problem to the classic K-means clustering problem, which can then be efficiently solved with linear time and space complexity. Our ECC method can also naturally integrate multiple molecular data types measured from the same set of subjects, and easily handle missing values without any imputation. We applied ECC to 110 synthetic and 48 real datasets, including 35 cancer gene expression benchmark datasets and 13 cancer types with four molecular data types from The Cancer Genome Atlas. We found that ECC shows superior performance against existing clustering methods. Our results clearly demonstrate the power of ECC in clinically relevant patient stratification. Availability and implementation The Matlab package is available at http://scholar.harvard.edu/yyl/ecc. Supplementary information Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4803 , 1367-4811
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 4
    In: JNCI Monographs, Oxford University Press (OUP), Vol. 2017, No. 52 ( 2017-11-01)
    Type of Medium: Online Resource
    ISSN: 1052-6773 , 1745-6614
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2044141-1
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  Environmental Entomology Vol. 47, No. 4 ( 2018-08-11), p. 781-787
    In: Environmental Entomology, Oxford University Press (OUP), Vol. 47, No. 4 ( 2018-08-11), p. 781-787
    Type of Medium: Online Resource
    ISSN: 0046-225X , 1938-2936
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2027540-7
    SSG: 12
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  • 6
    In: Protein & Cell, Oxford University Press (OUP), Vol. 6, No. 2 ( 2015-2), p. 152-156
    Type of Medium: Online Resource
    ISSN: 1674-800X , 1674-8018
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2543451-2
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  • 7
    In: Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 85, No. 4 ( 2009-04-01), p. 648-655
    Abstract: Chronic systemic inflammation links periodontal disease (PD) to increased incidence of cardiovascular disease. Activation of TLRs, particularly TLR4, promotes chronic inflammation in PD by stimulating myeloid cells. B cells from healthy individuals are generally refractory to TLR4 agonists as a result of low surface TLR4 expression. Unexpectedly, a significantly increased percentage of gingival and peripheral blood B cells from patients with PD expressed surface TLR4. Surface expression correlated with an active TLR4 promoter that mimicked the TLR4 promoter in neutrophils. B cells from PD patients were surface myeloid differentiation protein 2-positive and also packaged the enhancer of a proinflammatory cytokine, IL-1β, into an active structure, demonstrating that these cells harbor key characteristics of proinflammatory cell types. Furthermore, B cells lacked activating signatures of a natural IL-1β inhibitor, IL-1 receptor antagonist. Surprisingly, despite multiple signatures of proinflammatory cells, freshly isolated B cells from PD patients had decreased expression of TLR pathway genes compared with B cells from healthy individuals. Decreases in inflammatory gene expression were even more dramatic in B cells stimulated with a TLR4 ligand from a periodontal pathogen, Porphyromonas gingivalis LPS 1690. In contrast, B cell TLR4 was not activated by the prototypic TLR4 ligand Escherichia coli LPS. These findings raise the unexpected possibility that TLR4 engagement modulates B cell activation in PD patients.
    Type of Medium: Online Resource
    ISSN: 0741-5400 , 1938-3673
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
    detail.hit.zdb_id: 2026833-6
    SSG: 12
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  • 8
    In: Briefings in Bioinformatics, Oxford University Press (OUP), Vol. 23, No. 2 ( 2022-03-10)
    Abstract: The lack of a reliable and easy-to-operate screening pipeline for disease-related noncoding RNA regulatory axis is a problem that needs to be solved urgently. To address this, we designed a hybrid pipeline, disease-related lncRNA–miRNA–mRNA regulatory axis prediction from multiomics (DLRAPom), to identify risk biomarkers and disease-related lncRNA–miRNA–mRNA regulatory axes by adding a novel machine learning model on the basis of conventional analysis and combining experimental validation. The pipeline consists of four parts, including selecting hub biomarkers by conventional bioinformatics analysis, discovering the most essential protein-coding biomarkers by a novel machine learning model, extracting the key lncRNA–miRNA–mRNA axis and validating experimentally. Our study is the first one to propose a new pipeline predicting the interactions between lncRNA and miRNA and mRNA by combining WGCNA and XGBoost. Compared with the methods reported previously, we developed an Optimized XGBoost model to reduce the degree of overfitting in multiomics data, thereby improving the generalization ability of the overall model for the integrated analysis of multiomics data. With applications to gestational diabetes mellitus (GDM), we predicted nine risk protein-coding biomarkers and some potential lncRNA–miRNA–mRNA regulatory axes, which all correlated with GDM. In those regulatory axes, the MALAT1/hsa-miR-144-3p/IRS1 axis was predicted to be the key axis and was identified as being associated with GDM for the first time. In short, as a flexible pipeline, DLRAPom can contribute to molecular pathogenesis research of diseases, effectively predicting potential disease-related noncoding RNA regulatory networks and providing promising candidates for functional research on disease pathogenesis.
    Type of Medium: Online Resource
    ISSN: 1467-5463 , 1477-4054
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2036055-1
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Diseases of the Esophagus Vol. 35, No. 7 ( 2022-07-12)
    In: Diseases of the Esophagus, Oxford University Press (OUP), Vol. 35, No. 7 ( 2022-07-12)
    Abstract: Mediastinal lymphadenectomy is of great importance during esophagectomy for esophageal squamous cell carcinoma. However, recurrent laryngeal nerve (RLN) injury is a severe complication caused by lymphadenectomy along the RLN. Intraoperative nerve monitoring (IONM) can effectively identify the RLN and reduce the incidence of postoperative vocal cord paralysis (VCP). Here, we describe the feasibility and effectiveness of IONM in minimally invasive McKeown esophagectomy. Methods A total of 150 patients who underwent minimally invasive McKeown esophagectomy from 2016 to 2020 were enrolled in this study. We divided the patients into two groups: a neuromonitoring group (IONM, n = 70) and a control group (control, n = 80). Clinical data, surgical variables, and postoperative complications were retrospectively analyzed and compared. Results There was no significant difference in baseline data between the two groups. Postoperative VCP occurred in six cases (8.6%) in the IONM group, which was lower than that in the control group (21.3%, P = 0.032). Postoperative pulmonary complications were found in five cases (7.1%) and 14 in the control group (18.8%, P = 0.037). The postoperative hospital stay in the IONM group was significantly shorter than that in the control group (8 vs. 12, median, P  & lt; 0.001). The number of RLN lymph nodes harvested in the IONM group was higher than that in the control group (13.74 ± 5.77 vs. 11.03 ± 5.78, P = 0.005). The sensitivity and specificity of IONM monitoring VCP were 83.8% and 100%, respectively. A total of 66.7% of patients with a reduction in signal showed transient VCP, whereas 100% with a loss of signal showed permanent VCP. Conclusion IONM is feasible in minimally invasive McKeown esophagectomy. It showed advantages for distinguishing RLN and achieving thorough mediastinal lymphadenectomy with less RLN injury. Abnormal IONM signals can provide an accurate prediction of postoperative VCP incidence.
    Type of Medium: Online Resource
    ISSN: 1120-8694 , 1442-2050
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2004949-3
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  • 10
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 8, No. 5 ( 2018-05-01), p. 1747-1754
    Abstract: The fat-1 gene from Caenorhabditis elegans encodes a fatty acid desaturase which was widely studied due to its beneficial function of converting n-6 polyunsaturated fatty acids (n-6PUFAs) to n-3 polyunsaturated fatty acids (n-3PUFAs). To date, many fat-1 transgenic animals have been generated to study disease pathogenesis or improve meat quality. However, all of them were generated using a random integration method with variable transgene expression levels and the introduction of selectable marker genes often raise biosafety concern. To this end, we aimed to generate marker-free fat-1 transgenic pigs in a site-specific manner. The Rosa26 locus, first found in mouse embryonic stem cells, has become one of the most common sites for inserting transgenes due to its safe and ubiquitous expression. In our study, the fat-1 gene was inserted into porcine Rosa 26 (pRosa26) locus via Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. The Southern blot analysis of our knock-in pigs indicated a single copy of the fat-1 gene at the pRosa26 locus. Furthermore, this single-copy fat-1 gene supported satisfactory expression in a variety of tissues in F1 generation pigs. Importantly, the gas chromatography analysis indicated that these fat-1 knock-in pigs exhibited a significant increase in the level of n-3PUFAs, leading to an obvious decrease in the n-6PUFAs/n-3PUFAs ratio from 9.36 to 2.12 (***P & lt; 0.0001). Altogether, our fat-1 knock-in pigs hold great promise for improving the nutritional value of pork and serving as an animal model to investigate therapeutic effects of n-3PUFAs on various diseases.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2629978-1
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