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  • Oxford University Press (OUP)  (55)
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  • 1
    Online Resource
    Online Resource
    Dual inhibition of DNA-PK and DNA polymerase theta overcomes radiation resistance induced by p53 deficiency
    Oxford University Press (OUP) ; 2020
    In:  NAR Cancer Vol. 2, No. 4 ( 2020-12-21)
    Details
    In: NAR Cancer, Oxford University Press (OUP), Vol. 2, No. 4 ( 2020-12-21)
    Abstract: TP53 deficiency in cancer is associated with poor patient outcomes and resistance to DNA damaging therapies. However, the mechanisms underlying treatment resistance in p53-deficient cells remain poorly characterized. Using live cell imaging of DNA double-strand breaks (DSBs) and cell cycle state transitions, we show that p53-deficient cells exhibit accelerated repair of radiomimetic-induced DSBs arising in S phase. Low-dose DNA-dependent protein kinase (DNA-PK) inhibition increases the S-phase DSB burden in p53-deficient cells, resulting in elevated rates of mitotic catastrophe. However, a subset of p53-deficient cells exhibits intrinsic resistance to radiomimetic-induced DSBs despite DNA-PK inhibition. We show that p53-deficient cells under DNA-PK inhibition utilize DNA polymerase theta (Pol θ)-mediated end joining repair to promote their viability in response to therapy-induced DSBs. Pol θ inhibition selectively increases S-phase DSB burden after radiomimetic therapy and promotes prolonged G2 arrest. Dual inhibition of DNA-PK and Pol θ restores radiation sensitivity in p53-deficient cells as well as in p53-mutant breast cancer cell lines. Thus, combination targeting of DNA-PK- and Pol θ-dependent end joining repair represents a promising strategy for overcoming resistance to DNA damaging therapies in p53-deficient cancers.
    Type of Medium: Online Resource
    ISSN: 2632-8674
    URL: Article
    DOI: 10.1093/narcan/zcaa038
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 3025038-9
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  • 2
    Online Resource
    Online Resource
    Prospective observational cohort study on grading the severity of postoperative complications in global surgery research
    Oxford University Press (OUP) ; 2019
    In:  British Journal of Surgery Vol. 106, No. 2 ( 2019-01-08), p. e73-e80
    Details
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 106, No. 2 ( 2019-01-08), p. e73-e80
    Abstract: The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    URL: Article
    DOI: 10.1002/bjs.11025
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2006309-X
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  • 3
    Online Resource
    Online Resource
    Ground-based calibration and characterization of LaBr3-SiPM-based gamma-ray detector on GECAM satellite: 8–160 keV
    Oxford University Press (OUP) ; 2023
    In:  Monthly Notices of the Royal Astronomical Society Vol. 525, No. 3 ( 2023-09-01), p. 3399-3412
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 525, No. 3 ( 2023-09-01), p. 3399-3412
    Abstract: As the main detector of the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor mission (GECAM), the calibration of the energy response and detection efficiency of the gamma-ray detector (GRD) is the main content of the ground-based calibration. This article mainly focuses on the calibration of the energy response and detection efficiency in the 8–160 keV with a refined measurement around the absorption edges of the lanthanum bromide crystal ($\rm {LaBr_3}$). The GRD performances for different crystal types, data acquisition modes, working modes, and incident positions are also analysed in detail. We show that the calibration campaign is comprehensive, the detector performance meets the flight requirements, and the calibration results generally agree with simulations as expected. The detector’s model was corrected by the ground-based calibration, which led to the establishment of the calibration data base.
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1093/mnras/stad2439
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 4
    Online Resource
    Online Resource
    The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder
    Oxford University Press (OUP) ; 2022
    In:  Psychoradiology Vol. 2, No. 1 ( 2022-06-09), p. 32-42
    Details
    In: Psychoradiology, Oxford University Press (OUP), Vol. 2, No. 1 ( 2022-06-09), p. 32-42
    Abstract: Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.
    Type of Medium: Online Resource
    ISSN: 2634-4416
    URL: Article
    DOI: 10.1093/psyrad/kkac005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3076092-6
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  • 5
    Online Resource
    Online Resource
    Large expert-curated database for benchmarking document similarity detection in biomedical literature search
    Oxford University Press (OUP) ; 2019
    In:  Database Vol. 2019 ( 2019-01-01)
    Details
    In: Database, Oxford University Press (OUP), Vol. 2019 ( 2019-01-01)
    Abstract: Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
    Type of Medium: Online Resource
    ISSN: 1758-0463
    URL: Article
    DOI: 10.1093/database/baz085
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2496706-3
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  • 6
    Online Resource
    Online Resource
    Database Resources of the National Genomics Data Center in 2020
    Oxford University Press (OUP) ; 2019
    In:  Nucleic Acids Research ( 2019-11-08)
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), ( 2019-11-08)
    Abstract: The National Genomics Data Center (NGDC) provides a suite of database resources to support worldwide research activities in both academia and industry. With the rapid advancements in higher-throughput and lower-cost sequencing technologies and accordingly the huge volume of multi-omics data generated at exponential scales and rates, NGDC is continually expanding, updating and enriching its core database resources through big data integration and value-added curation. In the past year, efforts for update have been mainly devoted to BioProject, BioSample, GSA, GWH, GVM, NONCODE, LncBook, EWAS Atlas and IC4R. Newly released resources include three human genome databases (PGG.SNV, PGG.Han and CGVD), eLMSG, EWAS Data Hub, GWAS Atlas, iSheep and PADS Arsenal. In addition, four web services, namely, eGPS Cloud, BIG Search, BIG Submission and BIG SSO, have been significantly improved and enhanced. All of these resources along with their services are publicly accessible at https://bigd.big.ac.cn.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkz913
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Corrigendum to: The TianQin project: current progress on science and technology
    Oxford University Press (OUP) ; 2021
    In:  Progress of Theoretical and Experimental Physics Vol. 2021, No. 5 ( 2021-05-18)
    Details
    In: Progress of Theoretical and Experimental Physics, Oxford University Press (OUP), Vol. 2021, No. 5 ( 2021-05-18)
    Type of Medium: Online Resource
    ISSN: 2050-3911
    URL: Article
    DOI: 10.1093/ptep/ptaa165
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2705045-2
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  • 8
    Online Resource
    Online Resource
    The TianQin project: Current progress on science and technology
    Oxford University Press (OUP) ; 2021
    In:  Progress of Theoretical and Experimental Physics Vol. 2021, No. 5 ( 2021-05-18)
    Details
    In: Progress of Theoretical and Experimental Physics, Oxford University Press (OUP), Vol. 2021, No. 5 ( 2021-05-18)
    Abstract: TianQin is a planned space-based gravitational wave (GW) observatory consisting of three Earth-orbiting satellites with an orbital radius of about $10^5 \, {\rm km}$. The satellites will form an equilateral triangle constellation the plane of which is nearly perpendicular to the ecliptic plane. TianQin aims to detect GWs between $10^{-4} \, {\rm Hz}$ and $1 \, {\rm Hz}$ that can be generated by a wide variety of important astrophysical and cosmological sources, including the inspiral of Galactic ultra-compact binaries, the inspiral of stellar-mass black hole binaries, extreme mass ratio inspirals, the merger of massive black hole binaries, and possibly the energetic processes in the very early universe and exotic sources such as cosmic strings. In order to start science operations around 2035, a roadmap called the 0123 plan is being used to bring the key technologies of TianQin to maturity, supported by the construction of a series of research facilities on the ground. Two major projects of the 0123 plan are being carried out. In this process, the team has created a new-generation $17 \, {\rm cm}$ single-body hollow corner-cube retro-reflector which was launched with the QueQiao satellite on 21 May 2018; a new laser-ranging station equipped with a $1.2 \, {\rm m}$ telescope has been constructed and the station has successfully ranged to all five retro-reflectors on the Moon; and the TianQin-1 experimental satellite was launched on 20 December 2019—the first-round result shows that the satellite has exceeded all of its mission requirements.
    Type of Medium: Online Resource
    ISSN: 2050-3911
    URL: Article
    DOI: 10.1093/ptep/ptaa114
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2705045-2
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  • 9
    Online Resource
    Online Resource
    Database Resources of the National Genomics Data Center, China National Center for Bioinformation in 2021
    Oxford University Press (OUP) ; 2021
    In:  Nucleic Acids Research Vol. 49, No. D1 ( 2021-01-08), p. D18-D28
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 49, No. D1 ( 2021-01-08), p. D18-D28
    Abstract: The National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB), provides a suite of database resources to support worldwide research activities in both academia and industry. With the explosive growth of multi-omics data, CNCB-NGDC is continually expanding, updating and enriching its core database resources through big data deposition, integration and translation. In the past year, considerable efforts have been devoted to 2019nCoVR, a newly established resource providing a global landscape of SARS-CoV-2 genomic sequences, variants, and haplotypes, as well as Aging Atlas, BrainBase, GTDB (Glycosyltransferases Database), LncExpDB, and TransCirc (Translation potential for circular RNAs). Meanwhile, a series of resources have been updated and improved, including BioProject, BioSample, GWH (Genome Warehouse), GVM (Genome Variation Map), GEN (Gene Expression Nebulas) as well as several biodiversity and plant resources. Particularly, BIG Search, a scalable, one-stop, cross-database search engine, has been significantly updated by providing easy access to a large number of internal and external biological resources from CNCB-NGDC, our partners, EBI and NCBI. All of these resources along with their services are publicly accessible at https://bigd.big.ac.cn.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkaa1022
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Apolipoprotein E*Ɛ2 carriers exhibit high aspirin-treated platelet reactivity and low cardiovascular risk during long-term aspirin treatment
    Oxford University Press (OUP) ; 2022
    In:  Age and Ageing Vol. 51, No. 6 ( 2022-06-01)
    Details
    In: Age and Ageing, Oxford University Press (OUP), Vol. 51, No. 6 ( 2022-06-01)
    Abstract: Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown. Methods A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded. Results After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048–0.715, P = 0.014; HR = 0.435, CI: 0.234–0.812, P = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers. Conclusions Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation.
    Type of Medium: Online Resource
    ISSN: 0002-0729 , 1468-2834
    URL: Article
    DOI: 10.1093/ageing/afac119
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2065766-3
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