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  • Oxford University Press (OUP)  (17)
  • 2020-2024  (17)
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  • Oxford University Press (OUP)  (17)
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  • 2020-2024  (17)
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  • 1
    Online Resource
    Online Resource
    A Gene-Expression Predictor for Efficacy of Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
    Oxford University Press (OUP) ; 2021
    In:  JNCI: Journal of the National Cancer Institute Vol. 113, No. 4 ( 2021-04-06), p. 471-480
    Details
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 113, No. 4 ( 2021-04-06), p. 471-480
    Abstract: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. Methods We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. Results We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. Conclusions The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    URL: Article
    DOI: 10.1093/jnci/djaa100
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 2
    Online Resource
    Online Resource
    Importance of healthy lifestyle factors and ideal cardiovascular health metrics for risk of heart failure in Chinese adults
    Oxford University Press (OUP) ; 2022
    In:  International Journal of Epidemiology Vol. 51, No. 2 ( 2022-05-09), p. 567-578
    Details
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 51, No. 2 ( 2022-05-09), p. 567-578
    Abstract: The relative importance of healthy lifestyle factors and cardiovascular health metrics for the risk of heart failure is uncertain in Chinese populations. We aimed to compare the strength of associations between healthy lifestyle factors and ideal cardiovascular health metrics in the risk of heart failure in middle-aged Chinese adults. Methods A healthy lifestyle score (HLS) was constructed using smoking, drinking, physical activity, diet, body mass index and waist circumference, and compared with a more comprehensive set of metrics that included cardiovascular-disease risk biomarkers (blood pressure, blood glucose and blood lipids) in addition to the HLS. This broader set of factors [called ‘ideal cardiovascular health metrics’ (ICVHMs)] was evaluated in 487 197 participants in the China Kadoorie Biobank. Results A total of 4208 incident cases of heart failure were recorded during a median follow-up of 10 years. Both HLS [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.85, 0.91] and ICVHMs (0.87: 0.84, 0.89) were inversely associated with risk of heart failure (P  & lt; 0.001 for linear trend). Compared with participants with 0–1 HLS, the multivariable-adjusted HR of those with 4–5 HLS was 0.68 (0.59, 0.77). Compared with participants with 0–2 ICVHMs, the adjusted HR (95% CIs) of those who had 7–8 ICVHMs was 0.47 (0.36, 0.60). ICVHMs were more strongly predictive of risk of heart failure (area under curve, 0.61 vs 0.58, P  & lt; 0.001) than healthy lifestyle factors alone. Conclusions Higher levels of healthy lifestyle factors and ICVHMs were each inversely associated with heart failure, and lifestyle factors combined with cardiometabolic factors improved the prediction of heart failure compared with healthy lifestyle factors alone.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    URL: Article
    DOI: 10.1093/ije/dyab236
    RVK:
    XF 4100
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1494592-7
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  • 3
    Online Resource
    Online Resource
    PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations
    Oxford University Press (OUP) ; 2024
    In:  European Journal of Preventive Cardiology ( 2024-01-10)
    Details
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), ( 2024-01-10)
    Abstract: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition. Methods and results In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)]. Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque [n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45–0.83); P = 0.0015] , major occlusive vascular events [n = 15 752; 0.80 (0.67–0.95); P = 0.011], and ischaemic stroke [n = 11 467; 0.80 (0.66–0.98); P = 0.029] . However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease [COPD: n = 6836; 1.38 (1.08–1.76); P = 0.0089] and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD [n = 730; 3.61 (1.71–7.60); P = 7.3 × 10−4] . We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) [pooled OR after meta-analysis of 1.87 (1.38–2.54); P = 5.4 × 10−5] and self-reported asthma [pooled OR of 1.17 (1.04–1.30); P = 0.0071] . There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI. Conclusion The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections. Lay summary Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease.
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    URL: Article
    DOI: 10.1093/eurjpc/zwae009
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2646239-4
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  • 4
    Online Resource
    Online Resource
    Deletion of Schizophrenia Susceptibility Gene Ulk4 Leads to Abnormal Cognitive Behaviors via Akt-GSK-3 Signaling Pathway in Mice
    Oxford University Press (OUP) ; 2022
    In:  Schizophrenia Bulletin Vol. 48, No. 4 ( 2022-06-21), p. 804-813
    Details
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 48, No. 4 ( 2022-06-21), p. 804-813
    Abstract: Despite of strenuous research in the past decades, the etiology of schizophrenia (SCZ) still remains incredibly controversial. Previous genetic analysis has uncovered a close association of Unc-51 like kinase 4 (ULK4), a family member of Unc-51-like serine/threonine kinase, with SCZ. However, animal behavior data which may connect Ulk4 deficiency with psychiatric disorders, particularly SCZ are still missing. Methods We generated Emx1-Cre:Ulk4flox/flox conditional knockout (CKO) mice, in which Ulk4 was deleted in the excitatory neurons of cerebral cortex and hippocampus. Results The cerebral cellular architecture was maintained but the spine density of pyramidal neurons was reduced in Ulk4 CKO mice. CKO mice showed deficits in the spatial and working memories and sensorimotor gating. Levels of p-Akt and p-GSK-3α/β were markedly reduced in the CKO mice indicating an elevation of GSK-3 signaling. Mechanistically, Ulk4 may regulate the GSK-3 signaling via putative protein complex comprising of two phosphatases, protein phosphatase 2A (PP2A) and 1α (PP1α). Indeed, the reduction of p-Akt and p-GSK-3α/β was rescued by administration of inhibitor acting on PP2A and PP1α in CKO mice. Conclusions Our data identified potential downstream signaling pathway of Ulk4, which plays important roles in the cognitive functions and when defective, may promote SCZ-like pathogenesis and behavioral phenotypes in mice.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    URL: Article
    DOI: 10.1093/schbul/sbac040
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial
    Oxford University Press (OUP) ; 2020
    In:  JNCI: Journal of the National Cancer Institute Vol. 112, No. 2 ( 2020-02-01), p. 145-153
    Details
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 112, No. 2 ( 2020-02-01), p. 145-153
    Abstract: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    URL: Article
    DOI: 10.1093/jnci/djz074
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 6
    Online Resource
    Online Resource
    Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients†
    Oxford University Press (OUP) ; 2020
    In:  Biology of Reproduction Vol. 103, No. 1 ( 2020-06-23), p. 4-6
    Details
    In: Biology of Reproduction, Oxford University Press (OUP), Vol. 103, No. 1 ( 2020-06-23), p. 4-6
    Type of Medium: Online Resource
    ISSN: 0006-3363 , 1529-7268
    URL: Article
    DOI: 10.1093/biolre/ioaa050
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1469812-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Wastewater surveillance and an automated robot: effectively tracking SARS-CoV-2 transmission in the post-epidemic era
    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: Wastewater-based epidemiology (WBE) has exhibited great utility in the early and rapid identification of SARS-CoV-2. However, the efficacy of wastewater surveillance under China's previous strict epidemic prevention policy remains to be described. We collected the WBE data of wastewater treatment plants (WWTPs) in the Third People's Hospital of Shenzhen and several communities to determine the significant effectiveness of routine wastewater surveillance in monitoring the local spread of SARS-CoV-2 under tight containment of the epidemic. The results of 1 month of continuous wastewater surveillance showed that positive signals for SARS-CoV-2 RNA were detected in the wastewater samples, and a significant positive correlation was observed between the virus concentration and the number of daily cases. In addition, the community's domestic wastewater surveillance results were confirmed even 3 days before, or simultaneously with, the infected patient being confirmed as having the virus. Meanwhile, an automated sewage virus detection robot, ShenNong No.1 robot, was developed, showing a high degree of agreement with experimental data, offering the possibility of large-scale multi-point surveillance. Overall, our results illustrated the clear indicative role of wastewater surveillance in combating COVID-19 and provided a practical basis for rapidly expanding the feasibility and value of routine wastewater surveillance for future emerging infectious diseases.
    Type of Medium: Online Resource
    ISSN: 2095-5138 , 2053-714X
    URL: Article
    DOI: 10.1093/nsr/nwad089
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2745465-4
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  • 8
    Online Resource
    Online Resource
    MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty
    Oxford University Press (OUP) ; 2021
    In:  Nucleic Acids Research Vol. 49, No. 7 ( 2021-04-19), p. 3796-3813
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 49, No. 7 ( 2021-04-19), p. 3796-3813
    Abstract: The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkab155
    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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  • 9
    Online Resource
    Online Resource
    Genomic consequences of population decline in critically endangered pangolins and their demographic histories
    Oxford University Press (OUP) ; 2020
    In:  National Science Review Vol. 7, No. 4 ( 2020-04-01), p. 798-814
    Details
    In: National Science Review, Oxford University Press (OUP), Vol. 7, No. 4 ( 2020-04-01), p. 798-814
    Abstract: Pangolins are among the most critically endangered animals due to heavy poaching and worldwide trafficking. However, their demographic histories and the genomic consequences of their recent population declines remain unknown. We generated high-quality de novo reference genomes for critically endangered Malayan (Manis javanica, MJ) and Chinese (M. pentadactyla, MP) pangolins and re-sequencing population genomic data from 74 MJs and 23 MPs. We recovered the population identities of illegally traded pangolins and previously unrecognized genetic populations that should be protected as evolutionarily distinct conservation units. Demographic reconstruction suggested environmental changes have resulted in a population size fluctuation of pangolins. Additionally, recent population size declines due to human activities have resulted in an increase in inbreeding and genetic load. Deleterious mutations were enriched in genes related to cancer/diseases and cholesterol homeostasis, which may have increased their susceptibility to diseases and decreased their survival potential to adapt to environmental changes and high-cholesterol diets. This comprehensive study provides not only high-quality pangolin reference genomes, but also valuable information concerning the driving factors of long-term population size fluctuations and the genomic impact of recent population size declines due to human activities, which is essential for pangolin conservation management and global action planning.
    Type of Medium: Online Resource
    ISSN: 2095-5138 , 2053-714X
    URL: Article
    DOI: 10.1093/nsr/nwaa031
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2745465-4
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  • 10
    Online Resource
    Online Resource
    Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn’s Disease: A Potentially Novel Mesenteric Creeping Fat Index
    Oxford University Press (OUP) ; 2021
    In:  Journal of Crohn's and Colitis Vol. 15, No. 7 ( 2021-07-05), p. 1161-1173
    Details
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 15, No. 7 ( 2021-07-05), p. 1161-1173
    Abstract: Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn’s disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. Methods MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30] . The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. Results In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate–severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC]  = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of & gt; 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000] . Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. Conclusions MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    URL: Article
    DOI: 10.1093/ecco-jcc/jjab005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2389631-0
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