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  • Oxford University Press (OUP)  (31)
  • 2020-2024  (31)
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  • Oxford University Press (OUP)  (31)
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  • 2020-2024  (31)
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  • 1
    Online Resource
    Online Resource
    EMLI-ICC: an ensemble machine learning-based integration algorithm for metastasis prediction and risk stratification in intrahepatic cholangiocarcinoma
    Oxford University Press (OUP) ; 2022
    In:  Briefings in Bioinformatics Vol. 23, No. 6 ( 2022-11-19)
    Details
    In: Briefings in Bioinformatics, Oxford University Press (OUP), Vol. 23, No. 6 ( 2022-11-19)
    Abstract: Robust strategies to identify patients at high risk for tumor metastasis, such as those frequently observed in intrahepatic cholangiocarcinoma (ICC), remain limited. While gene/protein expression profiling holds great potential as an approach to cancer diagnosis and prognosis, previously developed protocols using multiple diagnostic signatures for expression-based metastasis prediction have not been widely applied successfully because batch effects and different data types greatly decreased the predictive performance of gene/protein expression profile-based signatures in interlaboratory and data type dependent validation. To address this problem and assist in more precise diagnosis, we performed a genome-wide integrative proteome and transcriptome analysis and developed an ensemble machine learning-based integration algorithm for metastasis prediction (EMLI-Metastasis) and risk stratification (EMLI-Prognosis) in ICC. Based on massive proteome (216) and transcriptome (244) data sets, 132 feature (biomarker) genes were selected and used to train the EMLI-Metastasis algorithm. To accurately detect the metastasis of ICC patients, we developed a weighted ensemble machine learning method based on k-Top Scoring Pairs (k-TSP) method. This approach generates a metastasis classifier for each bootstrap aggregating training data set. Ten binary expression rank-based classifiers were generated for detection of metastasis separately. To further improve the accuracy of the method, the 10 binary metastasis classifiers were combined by weighted voting based on the score from the prediction results of each classifier. The prediction accuracy of the EMLI-Metastasis algorithm achieved 97.1% and 85.0% in proteome and transcriptome datasets, respectively. Among the 132 feature genes, 21 gene-pair signatures were developed to establish a metastasis-related prognosis risk-stratification model in ICC (EMLI-Prognosis). Based on EMLI-Prognosis algorithm, patients in the high-risk group had significantly dismal overall survival relative to the low-risk group in the clinical cohort (P-value  & lt; 0.05). Taken together, the EMLI-ICC algorithm provides a powerful and robust means for accurate metastasis prediction and risk stratification across proteome and transcriptome data types that is superior to currently used clinicopathological features in patients with ICC. Our developed algorithm could have profound implications not just in improved clinical care in cancer metastasis risk prediction, but also more broadly in machine-learning-based multi-cohort diagnosis method development. To make the EMLI-ICC algorithm easily accessible for clinical application, we established a web-based server for metastasis risk prediction (http://ibi.zju.edu.cn/EMLI/).
    Type of Medium: Online Resource
    ISSN: 1467-5463 , 1477-4054
    URL: Article
    DOI: 10.1093/bib/bbac450
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2036055-1
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Identification and Functional Characterization of Metabolites for Skeletal Muscle Mass in Early Postmenopausal Chinese Women
    Oxford University Press (OUP) ; 2022
    In:  The Journals of Gerontology: Series A Vol. 77, No. 12 ( 2022-12-29), p. 2346-2355
    Details
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 77, No. 12 ( 2022-12-29), p. 2346-2355
    Abstract: Low skeletal muscle mass (SMM) is a crucial component of the sarcopenia phenotypes. In the present study, we aim to identify the specific metabolites associated with SMM variation and their functional mechanisms of decreased SMM in early postmenopausal women. We performed an untargeted metabolomics analysis in 430 early postmenopausal women to identify specific metabolite associated with skeletal muscle mass indexes (SMIes). Then, the potential causal effect of specific metabolite on SMM variation was accessed by one-sample Mendelian randomization (MR) analysis. Finally, in vitro experiments and transcriptomics bioinformatics analysis were conducted to explore the impact and potential functional mechanisms of specific metabolite on SMM variation. We detected 65 metabolites significantly associated with at least one SMI (variable importance in projection & gt; 1.5 by partial least squares regression and p & lt; .05 in multiple linear regression analysis). Remarkably, stearic acid (SA) was negatively associated with all SMIes, and subsequent MR analyses showed that increased serum SA level had a causal effect on decreased SMM (p & lt; .05). Further in vitro experiments showed that SA could repress myoblast’s differentiation at mRNA, protein, and phenotype levels. By combining transcriptome bioinformatics analysis, our study supports that SA may inhibit myoblast differentiation and myotube development by regulating the migration, adhesion, and fusion of myoblasts. This metabolomics study revealed specific metabolic profiles associated with decreased SMM in postmenopausal women, first highlighted the importance of SA in regulating SMM variation, and illustrated its potential mechanism on decreased SMM.
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    URL: Article
    DOI: 10.1093/gerona/glac075
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2043927-1
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  • 3
    Online Resource
    Online Resource
    High-throughput single-microbe RNA sequencing reveals adaptive state heterogeneity and host-phage activity associations in human gut microbiome
    Oxford University Press (OUP) ; 2024
    In:  Protein & Cell ( 2024-05-23)
    Details
    In: Protein & Cell, Oxford University Press (OUP), ( 2024-05-23)
    Abstract: Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications in health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve comprehensive understanding of complex microbial communities together with their hosts is therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive responses states among species in Prevotella and Roseburia genus and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated the smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-word situations and promises new perspectives in the understanding of human microbiomes.
    Type of Medium: Online Resource
    ISSN: 1674-800X , 1674-8018
    URL: Article
    DOI: 10.1093/procel/pwae027
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2543451-2
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  • 4
    Online Resource
    Online Resource
    Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 3 ( 2021-04-12), p. 924-937
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 3 ( 2021-04-12), p. 924-937
    Abstract: Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer’s disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer’s disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer’s disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10−19, 2.49 × 10−23, 1.35 × 10−67, and 4.81 × 10−9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P  & lt; 5.0 × 10−8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer’s disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer’s disease, suggesting that our models can predict Alzheimer’s disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer’s disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer’s disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awaa364
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 5
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    Online Resource
    Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study
    Oxford University Press (OUP) ; 2023
    In:  The Oncologist Vol. 28, No. 2 ( 2023-02-08), p. 187-e114
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 28, No. 2 ( 2023-02-08), p. 187-e114
    Abstract: Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST). Methods Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR). Results No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade ≥3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both. Overall survival data were immature and not calculated. Conclusion Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939).
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1093/oncolo/oyac242
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2023829-0
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  • 6
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    Efficient extracellular production of recombinant proteins in E. coli via enhancing expression of dacA on the genome
    Oxford University Press (OUP) ; 2022
    In:  Journal of Industrial Microbiology and Biotechnology Vol. 49, No. 4 ( 2022-07-30)
    Details
    In: Journal of Industrial Microbiology and Biotechnology, Oxford University Press (OUP), Vol. 49, No. 4 ( 2022-07-30)
    Abstract: D, D-carboxypeptidase DacA plays an important role in the synthesis and stabilization of Escherichia coli cell wall peptidoglycan. The production level of extracellular recombinant proteins in E. coli can be enhanced by high D, D-carboxypeptidase activity. Construction of expression systems under optimal promoters is one of the main strategies to realize high protein production in E. coli. In this study, the promoter PdacA-3 from DacA on the genome of E. coli BL21 (DE3) was verified to be efficient for recombinant green fluorescent protein using the plasmid mutant pET28a-PdacA with PdacA-3. Meanwhile, the promoter PdacA-3 was engineered to increase the production level of proteins via inserting one or two Shine–Dalgarno (SD) sequences between the promoter PdacA-3 and the target genes. The expression level of dacA on the genome was increased by the improved transcription of the engineered promoters (especially after inserting one additional SD sequence). The engineered promoters increased cell membrane permeabilities to significantly enhance the secretion production of extracellular recombinant proteins in E. coli. Among them, the extracellular recombinant amylase activities in E. coli BL21::1SD-pET28a-amyK and E. coli BL21::2SD-pET28a-amyK were increased by 2.0- and 1.6-fold that of the control (E. coli BL21-pET28a-amyK), respectively. Promoter engineering also affected the morphology and growth of the E. coli mutants. It was indicated that the engineered promoters enhanced the expression of dacA on the genome to disturb the synthesis and structural stability of cell wall peptidoglycans.
    Type of Medium: Online Resource
    ISSN: 1367-5435 , 1476-5535
    URL: Article
    DOI: 10.1093/jimb/kuac016
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1482484-X
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  • 7
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    Toward Earth system modeling with resolved clouds and ocean submesoscales on heterogeneous many-core HPCs
    Oxford University Press (OUP) ; 2023
    In:  National Science Review Vol. 10, No. 6 ( 2023-05-10)
    Details
    In: National Science Review, Oxford University Press (OUP), Vol. 10, No. 6 ( 2023-05-10)
    Abstract: With the aid of the newly developed ‘Sunway’ heterogeneous-architecture supercomputer, which has world-leading HPC (high-performance computer) capability, a series of high-resolution coupled Earth system models (SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been developed. These models can meet the needs of multiscale interaction studies with different computational costs. Here we describe the progress of SW-HRESMs development, with an overview of the major advancements made by the international Earth science community in HR-ESMs. We also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean, stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions, and paving the way for further model development to resolve finer scales with even higher resolution and more realistic physics. Finally, in addition to increasing model resolution, the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discussed, laying out the major scientific directions of such a huge modeling advancement.
    Type of Medium: Online Resource
    ISSN: 2095-5138 , 2053-714X
    URL: Article
    DOI: 10.1093/nsr/nwad069
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2745465-4
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  • 8
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    Dynamic cell transition and immune response landscapes of axolotl limb regeneration revealed by single-cell analysis
    Oxford University Press (OUP) ; 2021
    In:  Protein & Cell Vol. 12, No. 1 ( 2021-01), p. 57-66
    Details
    In: Protein & Cell, Oxford University Press (OUP), Vol. 12, No. 1 ( 2021-01), p. 57-66
    Type of Medium: Online Resource
    ISSN: 1674-800X , 1674-8018
    URL: Article
    DOI: 10.1007/s13238-020-00763-1
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2543451-2
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  • 9
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    GABAA receptor β3 subunit mutation D120N causes Lennox–Gastaut syndrome in knock-in mice
    Oxford University Press (OUP) ; 2020
    In:  Brain Communications Vol. 2, No. 1 ( 2020-01-01)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 2, No. 1 ( 2020-01-01)
    Abstract: The Lennox–Gastaut syndrome is a devastating early-onset epileptic encephalopathy, associated with severe behavioural abnormalities. Its pathophysiology, however, is largely unknown. A de novo mutation (c.G358A, p.D120N) in the human GABA type-A receptor β3 subunit gene (GABRB3) has been identified in a patient with Lennox–Gastaut syndrome. To determine whether the mutation causes Lennox–Gastaut syndrome in vivo in mice and to elucidate its mechanistic effects, we generated the heterozygous Gabrb3+/D120N knock-in mouse and found that it had frequent spontaneous atypical absence seizures, as well as less frequent tonic, myoclonic, atonic and generalized tonic–clonic seizures. Each of these seizure types had a unique and characteristic ictal EEG. In addition, knock-in mice displayed abnormal behaviours seen in patients with Lennox–Gastaut syndrome including impaired learning and memory, hyperactivity, impaired social interactions and increased anxiety. This Gabrb3 mutation did not alter GABA type-A receptor trafficking or expression in knock-in mice. However, cortical neurons in thalamocortical slices from knock-in mice had reduced miniature inhibitory post-synaptic current amplitude and prolonged spontaneous thalamocortical oscillations. Thus, the Gabrb3+/D120N knock-in mouse recapitulated human Lennox–Gastaut syndrome seizure types and behavioural abnormalities and was caused by impaired inhibitory GABAergic signalling in the thalamocortical loop. In addition, treatment with antiepileptic drugs and cannabinoids ameliorated atypical absence seizures in knock-in mice. This congenic knock-in mouse demonstrates that a single-point mutation in a single gene can cause development of multiple types of seizures and multiple behavioural abnormalities. The knock-in mouse will be useful for further investigation of the mechanisms of Lennox–Gastaut syndrome development and for the development of new antiepileptic drugs and treatments.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcaa028
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 3020013-1
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  • 10
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    Metagenomic surveillance in Jinan, China, reveals serum microbiome and biochemistry features in fever of unknown origin (FUO) patients
    Oxford University Press (OUP) ; 2023
    In:  Letters in Applied Microbiology Vol. 76, No. 6 ( 2023-06-01)
    Details
    In: Letters in Applied Microbiology, Oxford University Press (OUP), Vol. 76, No. 6 ( 2023-06-01)
    Abstract: Here we aim to build up a metagenomics-centered surveillance on the infectious microbiome showing in the fever of unknown origin (FUO) patients. We collected venous blood, bronchoalveolar lavage fluid, cerebrospinal fluid, tissue block, sputum, bone marrow biopsy, and purulent liquid samples from 123 patients. Metagenomic sequencing (mNGS) for both DNA and RNA sequences was performed to profile the total pathogenic microbiome in the samples. A large pool of infectious or conditional infectious bacteria was found, belonging to Enterobacteriaceae, Staphylococcaceae (10.55%), Burkholderiaceae (10.05%), and Comamonadaceae (4.25%). The major virus families detected from mNGS analysis include Adenoviridae, Anelloviridae, Peribunyaviridae, Flaviviridae, and Herpesviridae, showing up in 34.96%, 47.37%, 30.89%, 5.69%, 3.25%, and 1.63% of patients, respectively. Using the Ward clustering method, two clusters of patients were organized: high-variety group and low-variety group. The patients in the high-variety group demonstrated higher levels of immune cells and inflammatory indicators such as lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. The patients in the low-variety group showed higher levels of inflammatory lipids such as 13,14-dihy-15-keto PGE2 (fold  & gt; 10, P = 0.021); tetra-PGDM (fold = 5.29, P = 0.037); and 20-HETE (fold  & gt; 10, P = 0.02). The mNGS surveillance system demonstrated remarkable potential in preventing infectious diseases using mNGS data.
    Type of Medium: Online Resource
    ISSN: 1472-765X
    URL: Article
    DOI: 10.1093/lambio/ovad060
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2020629-X
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