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  • Oxford University Press (OUP)  (16)
  • 1
    Online Resource
    Online Resource
    Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial
    Oxford University Press (OUP) ; 2022
    In:  Clinical Infectious Diseases Vol. 74, No. 11 ( 2022-06-10), p. 1925-1932
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 74, No. 11 ( 2022-06-10), p. 1925-1932
    Abstract: Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. Methods Treatment-naive and experienced (not on treatment & gt;6 months) patients with chronic hepatitis B were eligible. Results A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group. Conclusions Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated. Clinical Trials registration NCT00230503 and China Drug Trials CTR2018042
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciab763
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2002229-3
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  • 2
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    Multi-copper oxidases SKU5 and SKS1 coordinate cell wall formation using apoplastic redox-based reactions in roots
    Oxford University Press (OUP) ; 2023
    In:  Plant Physiology Vol. 192, No. 3 ( 2023-07-03), p. 2243-2260
    Details
    In: Plant Physiology, Oxford University Press (OUP), Vol. 192, No. 3 ( 2023-07-03), p. 2243-2260
    Abstract: The primary cell wall is a fundamental plant constituent that is flexible but sufficiently rigid to support the plant cell shape. Although many studies have demonstrated that reactive oxygen species (ROS) serve as important signaling messengers to modify the cell wall structure and affect cellular growth, the regulatory mechanism underlying the spatial-temporal regulation of ROS activity for cell wall maintenance remains largely unclear. Here, we demonstrate the role of the Arabidopsis (Arabidopsis thaliana) multicopper oxidase-like protein skewed 5 (SKU5) and its homolog SKU5-similar 1 (SKS1) in root cell wall formation through modulating ROS homeostasis. Loss of SKU5 and SKS1 function resulted in aberrant division planes, protruding cell walls, ectopic deposition of iron, and reduced nicotinamide adeninedinucleotide phosphate (NADPH) oxidase-dependent ROS overproduction in the root epidermis–cortex and cortex–endodermis junctions. A decrease in ROS level or inhibition of NADPH oxidase activity rescued the cell wall defects of sku5 sks1 double mutants. SKU5 and SKS1 proteins were activated by iron treatment, and iron over-accumulated in the walls between the root epidermis and cortex cell layers of sku5 sks1. The glycosylphosphatidylinositol-anchored motif was crucial for membrane association and functionality of SKU5 and SKS1. Overall, our results identified SKU5 and SKS1 as regulators of ROS at the cell surface for regulation of cell wall structure and root cell growth.
    Type of Medium: Online Resource
    ISSN: 0032-0889 , 1532-2548
    URL: Article
    DOI: 10.1093/plphys/kiad207
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2004346-6
    detail.hit.zdb_id: 208914-2
    SSG: 12
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  • 3
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    Antiviral Activity and Pharmacokinetics of the Hepatitis B Virus (HBV) Capsid Assembly Modulator GLS4 in Patients With Chronic HBV Infection
    Oxford University Press (OUP) ; 2021
    In:  Clinical Infectious Diseases Vol. 73, No. 2 ( 2021-07-15), p. 175-182
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 2 ( 2021-07-15), p. 175-182
    Abstract: GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that can inhibit HBV replication by interfering with the assembly and disassembly of HBV nucleocapsid. Here, we evaluated its antiviral activity, pharmacokinetics, and tolerability in a double-blind, randomized, parallel, entecavir-controlled study. Methods Twenty-four patients with chronic HBV were randomized to receive a 28-day course of GLS4 (120 or 240 mg) and ritonavir (100 mg) combination (cohorts A and B, respectively) or entecavir treatment (cohort C) at a 1:1:1 ratio. Patients were followed up for 40 days in a phase 1b study. Results The GLS4/ritonavir combination was a tolerated combination for the treatment of chronic HBV infection. A total of 2, 3, and 3 subjects presented with alanine aminotransferase flare in cohorts A, B, and C, respectively. This contributed to the withdrawal of 1, 2, and 1 patient from cohorts A, B, and C, respectively. The mean Ctrough of GLS4 was 205–218 ng/mL, which was approximately 3.7–3.9 times the 90% effective concentration (55.8 ng/mL), with a lower accumulation (accumulation rate, 1.1–2.0). In cohorts A, B, and C, the mean declines in HBV DNA after 28 days of treatment were −1.42, −2.13, and −3.5 log10 IU/mL; in hepatitis B surface antigen were −0.06, −0.14, and −0.33 log10 IU/mL; in pregenomic RNA were −0.75, −1.78, and −0.96 log10 copies/mL; and in hepatitis B core antigen were −0.23, −0.5, and −0.44 log10 U/mL, respectively. Conclusions Treatment with 120 mg GLS4 was tolerated and had antiviral activity in patients with chronic HBV infection. Clinical Trials Registration Chinese Clinical Trial Registry; CTR20160068. http://www.chinadrugtrials.org.cn.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciaa961
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2002229-3
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  • 4
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    A HYPOTHESIS OF RADIORESISTANCE AND CELL-SURVIVAL CURVE SHAPE BASED ON CELL-CYCLE PROGRESSION AND DAMAGE TOLERANCE
    Oxford University Press (OUP) ; 2019
    In:  Radiation Protection Dosimetry Vol. 183, No. 1-2 ( 2019-05-01), p. 107-110
    Details
    In: Radiation Protection Dosimetry, Oxford University Press (OUP), Vol. 183, No. 1-2 ( 2019-05-01), p. 107-110
    Type of Medium: Online Resource
    ISSN: 0144-8420 , 1742-3406
    URL: Article
    DOI: 10.1093/rpd/ncy247
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2121843-2
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  • 5
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    Structural Diversity and Differential Transcription of the Patatin Multicopy Gene Family During Potato Tuber Development
    Oxford University Press (OUP) ; 2006
    In:  Genetics Vol. 172, No. 2 ( 2006-02-01), p. 1263-1275
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 172, No. 2 ( 2006-02-01), p. 1263-1275
    Abstract: The patatin multicopy gene family encodes the major storage protein in potato tubers and is organized as a single cluster in the potato genome. We sequenced a 154-kb bacterial artificial chromosome (BAC) clone containing a portion of the patatin gene cluster. Two putatively functional patatin genes were found in this BAC. These two genes are embedded within arrays of patatin pseudogenes. Using a chromatin immunoprecipitation method we demonstrate that the dramatic increase of patatin gene expression during the transition from stolons to tubers coincides with an increase of histone H4 lysine acetylation. We used 3′ rapid amplification of cDNA ends to profile expression of different patatin genes during tuber development. The profiling results revealed differential expression patterns of specific patatin gene groups throughout six different stages of tuber development. One group of patatin gene transcripts, designated patatin gene group A, was found to be the most abundant group during all stages of tuber development. Other patatin gene groups, with a 48-bp insertion in the 3′-untranslated region, are not expressed in stolons but display a gradual increase in expression level following the onset of tuberization. These results demonstrate that the patatin genes exhibit alterations in chromatin state and differential transcriptional regulation during the developmental transition from stolons into tubers, in which there is an increased demand for protein storage.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1534/genetics.105.051219
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1477228-0
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  • 6
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    Long-Term Risk of Subsequent Malignant Neoplasms Among Childhood and Adolescent Lymphoma Survivors (1975-2013): A Population-Based Predictive Nomogram
    Oxford University Press (OUP) ; 2023
    In:  The Oncologist Vol. 28, No. 9 ( 2023-09-07), p. e765-e773
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 28, No. 9 ( 2023-09-07), p. e765-e773
    Abstract: Studies are needed to assess risk factors pertinent to the incidence of secondary malignancies among childhood and adolescent lymphoma survivors. We aimed to identify risk factors pertinent to the incidence of secondary malignancies and subsequently establish a clinically practical predictive nomogram. Methods A total of 5561 patients who were diagnosed with primary lymphoma below the age of 20 years between 1975 and 2013 and survived for at least 5 years were identified. Standardized incidence ratio (SIR) and excess risk (ER) analysis were performed by sex, age, and year when primary lymphoma was diagnosed, sites and types of primary lymphoma, and therapy strategies. Univariable and multivariable logistic regression were used to identify independent risk factors for adolescent and childhood lymphoma-related secondary malignancies. Based on 5 factors (age, time from lymphoma diagnosis, gender, lymphoma type, and therapy), a nomogram for predicting the risk of a secondary malignancy for patients with childhood and adolescent primary lymphoma was established. Results Among 5561 lymphoma survivors, 424 developed a secondary malignancy. Females (SIR = 5.34, 95% CI, 4.73-5.99; ER = 50.58) exhibited a higher SIR and ER than males (SIR = 3.28, 95% CI, 2.76-3.87; ER = 15.53). Blacks were at a higher risk than Caucasians or others. Nodular lymphocyte-predominant Hodgkin lymphoma survivors exhibited typically high SIR (13.13, 95% CI, 6-24.92) and ER (54.79) among all lymphoma classifications. Lymphoma survivors who underwent radiotherapy, whether they received chemotherapy or not, had typically higher SIR and ER. Among all types of secondary malignancies, “bone and joint neoplasms” (SIR = 11.07, 95% CI, 5.52-19.81) and “soft tissue neoplasms” (SIR = 12.27, 95% CI, 7.59-18.76) presented significantly high SIR whereas “breast cancer” and “endocrine cancer” associated with higher ER. The median diagnosis age of secondary malignancies was 36 years old, and the median time interval between the diagnosis of two malignancies was 23 years. A nomogram was constructed to predict the risk of secondary malignancies in patients diagnosed with primary lymphoma before 20 years of age. After internal validation, the AUC and C-index of the nomogram are 0.804 and 0.804, respectively. Conclusion and Relevance The established nomogram provides a convenient and reliable tool for predicting the risk of a secondary malignancy among childhood and adolescent lymphoma survivors, concluding significant concern for lymphoma survivors with high-risk estimates.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1093/oncolo/oyad112
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2023829-0
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  • 7
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    PATH-23. GENOMIC LANDSCAPE OF IDH-MUTANT PRIMARY GLIOBLASTOMAS SHOWS DISTINCT CLINICAL AND MOLECULAR FEATURES AND THAT CDKN2A SHOULD BE SUPPLEMENTED WITH MGMTp AND G-CIMP FOR PRECISE PROGNOSTICATION
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii169-ii169
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii169-ii169
    Abstract: There have only been rare studies of IDH-mutant primary glioblastomas (IDH-mutant astrocytoma IV); there were one or two studies on secondary glioblastomas. In a cohort of 70 cases, we conducted clinical analysis, methylation profiling, RNA sequencing, targeted sequencing, and TERTp seqeuncing on available FFPE tissues. Median follow-up was 58.2 months (n= 60). IDH-mutant primary glioblastomas had longer median OS (30.4 months) and median PFS (25.9 months) than IDH-mutant secondary glioblastomas as in the literature or established databases. MGMTp methylated cases had better OS (p= 0.001) and it was an independent prognosticator. We previously showed G-CIMP to be an independent prognostic marker for IDH-mutant glioblastomas (NOA 2019). Although CDKN2A deletion was an independent prognostic marker for poorer OS (p= 0.036) and PFS (p= 0.005), MGMTp methylation had a trend of superseding CDKN2A deletion (p= 0.055) for prognostication and G-CIMP subgroups could similarly partially supersede CDKN2A deletion (p= 0.582). Hence, CDKN2A deletion should be supplemented with these two biomarkers for finer prognostication. Targeted sequencing (n= 55) showed that there were more ATRX (35/55, 64%), TP53 (31/55, 56%), KMT2D (18/55, 33%), POLE (11/55, 20%) and MSH6 (7/55, 13%) mutations, but fewer TERTp (3/69, 4%) and PTEN (1/55, 2%) mutations than IDH-wildtype glioblastomas as from literature and databases. CNVs revealed by methylomes (n= 53) and mutations (n= 55) showed that there were more PDGFRA (amplification: 9/53, 17%, mutation: 10/55, 18%) alterations, but fewer MET (amplification: 3/53, 6%, mutation: 4/55, 7%) alterations and hypermutated (6/55, 11%) cases than IDH-mutant secondary glioblastomas from literature. GISTIC analysis revealed amplifications of CCND2, CDK4, MYC, and PDGFRA, deletions of CDKN2A, RB1, and chromosome 10q to be significant CNVs (q & lt; 0.05). There were few EGFR amplifications (2/53, 4%), which was different from regular glioblastomas. RNA sequencing (n= 42) showed few fusions (4/42, 10%), which was different from IDH-mutant secondary glioblastomas.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.704
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 8
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    Rapid generation of ACE2 humanized inbred mouse model for COVID-19 with tetraploid complementation
    Oxford University Press (OUP) ; 2021
    In:  National Science Review Vol. 8, No. 2 ( 2021-02-10)
    Details
    In: National Science Review, Oxford University Press (OUP), Vol. 8, No. 2 ( 2021-02-10)
    Type of Medium: Online Resource
    ISSN: 2095-5138 , 2053-714X
    URL: Article
    DOI: 10.1093/nsr/nwaa285
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2745465-4
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  • 9
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    Association of Nirmatrelvir/Ritonavir Treatment on Upper Respiratory Severe Acute Respiratory Syndrome Coronavirus 2 Reverse Transcription-Polymerase Chain Reaction (SARS-Cov-2 RT-PCR) Negative Conversion Rates Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19)
    Oxford University Press (OUP) ; 2023
    In:  Clinical Infectious Diseases Vol. 76, No. 3 ( 2023-02-08), p. e148-e154
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 3 ( 2023-02-08), p. e148-e154
    Abstract: Acceleration of negative respiratory conversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) might reduce viral transmission. Nirmatrelvir/ritonavir is a new antiviral agent recently approved for treatment of COVID-19 that has the potential to facilitate negative conversion. Methods A cohort of hospitalized adult patients with mild-to-moderate COVID-19 who had a high risk for progression to severe disease were studied. These patients presented with COVID-19 symptoms between 5 March and 5 April 2022. The time from positive to negative upper respiratory reverse transcription-polymerase chain reaction (RT-PCR) conversion was assessed by Kaplan-Meier plots and Cox proportional hazards regression with the adjustment for patients’ baseline demographic and clinical characteristics. Results There were 258 patients treated with nirmatrelvir/ritonavir and 224 nontreated patients who had mild-to-moderate COVID-19. The median (interquartile range) time for patients who converted from positive to negative RT-PCR was 10 days (7–12 days) in patients treated ≤5 days after symptom onset and 17 days (12–21 days) in nontreated patients. The proportions of patients with a negative conversion at day 15 were 89.7% and 42.0% in treated patients and nontreated patients, corresponding to a hazard ratio of 4.33 (95% confidence interval, 3.31–5.65). Adjustment for baseline differences between the groups had little effect on the association. Subgroup analysis on treated patients suggests that time to negative conversion did not vary with the patients’ baseline characteristics. Conclusions This cohort study of high-risk patients with mild-to-moderate COVID-19 found an association between nirmatrelvir/ritonavir treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion that might reduce the risk of viral shedding and disease transmission.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciac600
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002229-3
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  • 10
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    Phosphorylation and ubiquitination of OsWRKY31 are integral to OsMKK10-2-mediated defense responses in rice
    Oxford University Press (OUP) ; 2023
    In:  The Plant Cell Vol. 35, No. 6 ( 2023-05-29), p. 2391-2412
    Details
    In: The Plant Cell, Oxford University Press (OUP), Vol. 35, No. 6 ( 2023-05-29), p. 2391-2412
    Abstract: Mitogen-activated protein kinase (MPK) cascades play vital roles in plant innate immunity, growth, and development. Here, we report that the rice (Oryza sativa) transcription factor gene OsWRKY31 is a key component in a MPK signaling pathway involved in plant disease resistance in rice. We found that the activation of OsMKK10-2 enhances resistance against the rice blast pathogen Magnaporthe oryzae and suppresses growth through an increase in jasmonic acid and salicylic acid accumulation and a decrease of indole-3-acetic acid levels. Knockout of OsWRKY31 compromises the defense responses mediated by OsMKK10-2. OsMKK10-2 and OsWRKY31 physically interact, and OsWRKY31 is phosphorylated by OsMPK3, OsMPK4, and OsMPK6. Phosphomimetic OsWRKY31 has elevated DNA-binding activity and confers enhanced resistance to M. oryzae. In addition, OsWRKY31 stability is regulated by phosphorylation and ubiquitination via RING-finger E3 ubiquitin ligases interacting with WRKY 1 (OsREIW1). Taken together, our findings indicate that modification of OsWRKY31 by phosphorylation and ubiquitination functions in the OsMKK10-2-mediated defense signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1040-4651 , 1532-298X
    URL: Article
    DOI: 10.1093/plcell/koad064
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 623171-8
    detail.hit.zdb_id: 2004373-9
    SSG: 12
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