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  • Wiley  (95)
  • Zhou, Yue  (95)
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  • Wiley  (95)
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  • 1
    In: Clinical Pharmacology & Therapeutics, Wiley
    Kurzfassung: The application of machine learning (ML) has shown promising results in precision medicine due to its exceptional performance in dealing with complex multidimensional data. However, using ML for individualized dosing of medicines is still in its early stage, meriting further exploration. A systematic review of study designs and modeling details of using ML for individualized dosing of different drugs was performed. We have summarized the status of the study populations, predictive targets, and data sources for ML modeling, the selection of ML algorithms and features, and the evaluation and validation of their predictive performance. We also used the Prediction model Risk of Bias Assessment Tool (PROBAST) to assess the risk of bias of included studies. Currently, ML can be used for both a priori and a posteriori dose selection and optimization, and it can also assist the implementation of therapeutic drug monitoring. However, studies are mainly focused on drugs with narrow therapeutic windows, predominantly immunosuppressants ( N  = 23, 35.9%) and anti‐infectives ( N  = 21, 32.8%), and there is currently only very limited attention for special populations, such as children ( N  = 22, 34.4%). Most studies showed poor methodological quality and a high risk of bias. The lack of external validation and clinical utility evaluation currently limits the further clinical implementation of ML for dose individualization. We therefore have proposed several ways to improve the clinical relevance of the studies and facilitate the translation of ML models into clinical practice.
    Materialart: Online-Ressource
    ISSN: 0009-9236 , 1532-6535
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2040184-X
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Cancer Medicine, Wiley, Vol. 9, No. 2 ( 2020-01), p. 575-585
    Kurzfassung: The poor outcome of patients with esophageal squamous cell carcinoma (ESCC) highlights the importance of the identification of novel effective prognostic biomarkers. We aimed to identify a clinically applicable prognostic immunohistochemistry (IHC) panel for ESCC. Methods An integrated analysis was performed to screen and establish a prognostic panel using exome sequencing profile from 81 pairs of ESCC samples and RNA expression microarray data from 119 ESCC subjects. Two independent ESCC cohorts were recruited as training and validation groups to test the prognostic value. Results Three genes were selected, namely, ANO1 , GAL, and MMP3 , which were aberrantly expressed in ESCC tumor tissues ( P   〈  .001). Among them, ANO1 and MMP3 were reserved for the construction of the prognostic panel due to their significant association with the prognosis of ESCC patients ( P  = .015 and P   〈  .001). Patients with both ANO1 + and MMP3 + had a poorer prognosis than that with ANO1 −/ MMP3 +, ANO1 +/ MMP3 −, or ANO1 −/ MMP3  − in both the training set and validation set ( P   〈  .001). Receiver operating characteristic analysis showed that the combination of IHC panel and eighth American Joint Commission on Cancer staging yielded a better prognostic predictive efficacy compared with the two indexes alone ( P   〈  .001, area under curve: 0.752). Finally, a nomogram was created by integrating the IHC markers and clinicopathological risk factors to predict prognosis with a C‐index of 0.695 (95% confidence interval: 0.657‐0.734). Conclusion Using an integrated multistage screening strategy, we identified and validated a valuable prognostic IHC panel for ESCC.
    Materialart: Online-Ressource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2020
    ZDB Id: 2659751-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Wiley ; 2019
    In:  Journal of Cellular Biochemistry Vol. 120, No. 8 ( 2019-08), p. 14076-14087
    In: Journal of Cellular Biochemistry, Wiley, Vol. 120, No. 8 ( 2019-08), p. 14076-14087
    Kurzfassung: Intermittent hypobaric hypoxia can produce a protective effect on both the nervous system and non‐nervous system tissues. Intermittent hypobaric hypoxia preconditioning has been shown to protect rats from cardiac ischemia‐reperfusion injury by decreasing cardiac iron levels and reactive oxygen species (ROS) production, thereby decreasing oxidative stress to achieve protection. However, the specific mechanism underlying the protective effect of hypobaric hypoxia is unclear. To shed light on this phenomenon, we subjected Sprague‐Dawley rats to hypobaric hypoxic preconditioning (8 hours/day). The treatment was continued for 4 weeks. We then measured the iron content in the heart, liver, spleen, and kidney. The iron levels in all of the assessed tissues decreased significantly after hypobaric hypoxia treatment, corroborating previous results that hypobaric hypoxia may produce its protective effect by decreasing ROS production by limiting the levels of catalytic iron in the tissue. We next assessed the expression levels of several proteins involved in iron metabolism (transferrin receptor, L‐ferritin, and ferroportin1 [FPN1]). The increased transferrin receptor and decreased L‐ferritin levels after hypobaric hypoxia were indicative of a low‐iron phenotype, while FPN1 levels remained unchanged. We also examined hepcidin, transmembrane serine proteases 6 (TMPRSS6), erythroferrone (ERFE), and erythropoietin (EPO) levels, all of which play a role in the regulation of systemic iron metabolism. The expression of hepcidin decreased significantly after hypobaric hypoxia treatment, whereas the expression of TMPRSS6 and ERFE and EPO increased sharply. Finally, we measured serum iron and total iron binding capacity in the serum, as well as red blood cell count, mean corpuscular volume, hematocrit, red blood cell distribution width SD, and red blood cell distribution width CV. As expected, all of these values increased after the hypobaric hypoxia treatment. Taken together, our results show that hypobaric hypoxia can stimulate erythropoiesis, which systemically draws iron away from nonhematopoietic tissue through decreased hepcidin levels.
    Materialart: Online-Ressource
    ISSN: 0730-2312 , 1097-4644
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2019
    ZDB Id: 1479976-5
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Small, Wiley
    Kurzfassung: Ni single‐atom catalysts (SACs) are appealing for electrochemical reduction CO 2 reduction (CO 2 RR). However, regulating the balance between the activity and conductivity remains a challenge to Ni SACs due to the limitation of substrates structure. Herein, the intrinsic performance enhancement of Ni SACs anchored on quasi‐one‐dimensional graphene nanoribbons (GNRs) synthesized is demonstrated by longitudinal unzipping carbon nanotubes (CNTs). The abundant functional groups on GNRs can absorb Ni atoms to form rich Ni–N 4 –C sites during the anchoring process, providing a high intrinsic activity. In addition, the GNRs, which maintain a quasi‐one‐dimensional structure and possess a high conductivity, interconnect with each other and form a conductive porous framework. The catalyst yields a 44 mA cm −2 CO partial current density and 96% faradaic efficiency of CO (FE CO ) at −1.1 V vs RHE in an H‐cell. By adopting a membrane electrode assembly (MEA) flow cell, a 95% FE CO and 2.4 V cell voltage are achieved at 200 mA cm −2 current density. This work provides a rational way to synthesize Ni SACs with a high Ni atom loading, porous morphology, and high conductivity with potential industrial applications.
    Materialart: Online-Ressource
    ISSN: 1613-6810 , 1613-6829
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2168935-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Small, Wiley, Vol. 19, No. 34 ( 2023-08)
    Kurzfassung: Although photodynamic immunotherapy has been promoted in the clinical practice of cholangiocarcinoma, the insensitivity to photodynamic immunotherapy remains to be a great problem. This can be largely attributed to an immune‐suppressive tumor microenvironment (TME) manifested as immature myeloid cells and exhausted cytotoxic T lymphocytes. Here, a three‐in‐one oncolytic adenovirus system PEG‐PEI‐Adv‐Catalase‐KillerRed (p‐Adv‐CAT‐KR) has been constructed to multiply, initiate, and enhance immune responses in photodynamic immunotherapy, using genetically‐engineered KillerRed as photosensitizer, catalase as in situ oxygen‐supplying mediator, and adenovirus as immunostimulatory bio‐reproducible carrier. Meanwhile, PEG‐PEI is applied to protect adenovirus from circulating immune attack. The administration of p‐Adv‐CAT‐KR induces increased antigen presenting cells, elevated T cell infiltrations, and reduced tumor burden. Further investigation into underlying mechanism indicates that hypoxia inducible factor 1 subunit alpha (Hif‐1α) and its downstream PD‐1/PD‐L1 pathway contribute to the transformation of immune‐suppressive TME in cholangiocarcinoma. Collectively, the combination of KillerRed, catalase, and adenovirus brings about multi‐amplified antitumor photo‐immunity and has the potential to be an effective immunotherapeutic strategy for cholangiocarcinoma.
    Materialart: Online-Ressource
    ISSN: 1613-6810 , 1613-6829
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2168935-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Clinical Pharmacology & Therapeutics, Wiley
    Kurzfassung: Continuous 6‐mercaptopurine (6‐MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose‐limiting hematopoietic toxicity. However, evidence‐based guidelines for gene‐based 6‐MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open‐label, active‐controlled clinical trial randomly assigned Chinese children with low‐ or intermediate‐risk ALL in a 1:1 ratio to receive TPMT – NUDT15 gene–based dosing of 6‐MP (N = 44, 10 to 50 mg/m 2 /day) or standard dosing (N = 44, 50 mg/m 2 /day) during maintenance therapy. The primary endpoint was the incidence of 6‐MP myelosuppression in both groups. Secondary endpoints included frequencies of 6‐MP hepatotoxicity, duration of myelosuppression and leukopenia, event‐free survival, and steady‐state concentrations of active metabolites (6‐thioguaninenucleotides and 6‐methylmercaptopurine nucleotides) in erythrocytes. A 2.2‐fold decrease in myelosuppression, the primary endpoint, was observed in the gene‐based–dose group using approximately 50% of the standard initial 6‐MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64; p = 0.003). Patients in the gene‐based–dose group had a significantly lower risk of developing thiopurine‐induced myelosuppression and leukopenia (p = 0.015 and p = 0.022, respectively). No significant differences were observed in the secondary endpoints of the incidence of hepatotoxicity and steady‐state concentrations of active metabolites in erythrocytes between the two groups. TPMT‐ and NUDT15 ‐based dosing of 6‐MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.
    Materialart: Online-Ressource
    ISSN: 0009-9236 , 1532-6535
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2040184-X
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: MedComm, Wiley, Vol. 4, No. 3 ( 2023-06)
    Kurzfassung: Lysine‐specific histone demethylase 1 (LSD1) is an attractive target for malignancies therapy. Nevertheless, its role in hepatocellular carcinoma (HCC) progression and the potential of its inhibitor in HCC therapy remains unclear. Here, we show that LSD1 overexpression in human HCC tissues is associated with HCC progression and poor patient survival. ZY0511, a highly selective and potent inhibitor of LSD1, suppressed human HCC cell proliferation in vitro and tumor growth in cell‐derived and patient‐derived HCC xenograft models in vivo. Mechanistically, ZY0511 induced mRNA expression of growth arrest and DNA damage‐inducible gene 45beta ( GADD45B ) by inducing histone H3 at lysine 4 (H3K4) methylation at the promoter of GADD45B , a novel target gene of LSD1. In human HCC tissues, LSD1 level was correlated with a decreased level of GADD45B, which was associated with HCC progression and predicted poor patient survival. Moreover, co‐administration of ZY0511 and DTP3, which specifically enhanced the pro‐apoptotic effect of GADD45B, effectively inhibited HCC cell proliferation both in vitro and in vivo. Collectively, our study revealed the potential value of LSD1 as a promising target of HCC therapy. ZY0511 is a promising candidate for HCC therapy through upregulating GADD45B, thereby providing a novel combinatorial strategy for treating HCC.
    Materialart: Online-Ressource
    ISSN: 2688-2663 , 2688-2663
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 3021470-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Wiley ; 2014
    In:  Chemistry - A European Journal Vol. 20, No. 11 ( 2014-03-10), p. 2998-3004
    In: Chemistry - A European Journal, Wiley, Vol. 20, No. 11 ( 2014-03-10), p. 2998-3004
    Materialart: Online-Ressource
    ISSN: 0947-6539
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2014
    ZDB Id: 1478547-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: International Journal of Cancer, Wiley, Vol. 150, No. 8 ( 2022-04-15), p. 1318-1328
    Kurzfassung: Osimertinib, as a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), showed more potent efficacy against brain metastasis (BM) in untreated EGFR‐mutant nonsmall cell lung cancer (NSCLC) in the FLAURA study. However, the overall survival (OS) benefit of osimertinib and clinical value of cranial local therapy (CLT) in these patients remain undetermined. Here we conducted a retrospective study involving untreated EGFR‐mutant NSCLC patients with BMs receiving first‐line osimertinib or first‐generation EGFR‐TKIs. Upfront CLT was defined as CLT performed before disease progression to the first‐line EGFR‐TKIs. Pattern of treatment failure and survival outcomes were extensively investigated. Among the 367 patients enrolled, first‐generation EGFR‐TKI was administered in 265, osimertinib in 102 and upfront CLT performed in 140. Patients receiving osimertinib had more ( P   〈  .001) and larger BMs ( P  = .003) than those receiving first‐generation EGFR‐TKIs. After propensity score matching, osimertinib was found to prolong OS (37.7 vs 22.2 months, P  = .027). Pattern of failure analyses found that 51.8% of the patients without upfront CLT developed their initial progressive disease (PD) in the brain and 59.0% of the cranial PD occurred at the original sites alone, suggesting potential clinical value of upfront CLT. Indeed, upfront stereotactic radiosurgery (SRS) and/or surgery was associated with improved OS among those receiving first‐generation EGFR‐TKIs ( P  = .019) and those receiving osimertinib ( P  = .041). In summary, compared to first‐generation EGFR‐TKIs, osimertinib is associated with improved OS in untreated EGFR‐mutant NSCLC with BMs. Meanwhile, upfront SRS and/or surgery may provide extra survival benefit, which needs to be verified in future studies.
    Materialart: Online-Ressource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2022
    ZDB Id: 218257-9
    ZDB Id: 1474822-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Small, Wiley, Vol. 11, No. 31 ( 2015-08), p. 3806-3806
    Materialart: Online-Ressource
    ISSN: 1613-6810 , 1613-6829
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2015
    ZDB Id: 2168935-0
    Standort Signatur Einschränkungen Verfügbarkeit
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