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  • Wiley  (13)
  • 2020-2024  (13)
  • 2021  (13)
  • 1
    In: Clinical and Translational Science, Wiley, Vol. 14, No. 4 ( 2021-07), p. 1280-1291
    Abstract: This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT‐P17 to United States‐licensed adalimumab (US‐adalimumab) and European Union‐approved adalimumab (EU‐adalimumab). This double‐blind, parallel‐group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT‐P17, US‐adalimumab, or EU‐adalimumab. Primary end points were PK equivalence in terms of: area under the concentration–time curve from time zero to infinity (AUC 0–inf ); AUC from time zero to the last quantifiable concentration (AUC 0–last ); and maximum serum concentration (C max ). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80–125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT‐P17; 103 US‐adalimumab; 106 EU‐adalimumab), 308 subjects received study drug. AUC 0–inf , AUC 0–last , and C max were equivalent among CT‐P17, US‐adalimumab, and EU‐adalimumab, because 90% CIs for the ratios of GLSMs were within the 80–125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single‐dose administration of CT‐P17, EU‐adalimumab, and US‐adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars.
    Type of Medium: Online Resource
    ISSN: 1752-8054 , 1752-8062
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2433157-0
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  • 2
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  Diabetes, Obesity and Metabolism Vol. 23, No. 6 ( 2021-06), p. 1232-1241
    In: Diabetes, Obesity and Metabolism, Wiley, Vol. 23, No. 6 ( 2021-06), p. 1232-1241
    Abstract: To assess whether the use of evogliptin, a novel dipeptidyl peptidase‐4 inhibitor (DPP‐4i), was associated with an increased risk of cardiovascular events compared with glimepiride in patients with type 2 diabetes (T2D). Methods We conducted a population‐based cohort study using South Korea's nationwide healthcare database from 1 January 2014 to 31 December 2018. We identified a base cohort of patients with T2D who newly initiated metformin monotherapy, from which we identified a study cohort of patients who either added or switched to glimepiride or DPP‐4is (including evogliptin). Patients were followed up from initiation of DPP‐4is or glimepiride until the earliest of either outcome occurrence or 31 December 2018. Our primary outcome was hospitalization or an emergency visit for cardiovascular events, a composite endpoint comprised of cerebrovascular events, heart failure, myocardial infarction, transient ischaemic attack, angina pectoris and revascularization procedures; secondary outcomes were the individual components of the primary outcome. A multivariable Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of study outcomes associated with evogliptin compared with glimepiride. Results Our base and study cohorts had 317,307 and 128,788 patients, respectively, of which 100,038 were DPP‐4i users (2946 were evogliptin users) and 28,750 were glimepiride users within the study cohort. The median follow‐up was 195 days for evogliptin and 113 days for glimepiride users. Compared with glimepiride, evogliptin was associated with a reduced risk of the primary outcome (aHR 0.67, 95% CI 0.48–0.95) and cerebrovascular events (aHR 0.41, 95% CI 0.22–0.78) but showed non‐significant associations for myocardial infarction (aHR 0.63, 95% CI 0.27–1.46), heart failure (aHR 0.35, 95% CI 0.09–1.47), transient ischaemic attack (aHR 0.23, 95% CI 0.03–1.72) and angina pectoris (aHR 1.35, 95% CI 0.82–2.21). Conclusions Findings from this population‐based cohort study provide novel real‐world evidence that the use of evogliptin, compared with glimepiride, did not increase the risk of cardiovascular events, including cerebrovascular events, myocardial infarction, heart failure, transient ischaemic attack and angina pectoris.
    Type of Medium: Online Resource
    ISSN: 1462-8902 , 1463-1326
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2004918-3
    detail.hit.zdb_id: 1454944-X
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  • 3
    In: Liver International, Wiley, Vol. 41, No. 4 ( 2021-04), p. 743-753
    Abstract: Elevated liver enzymes are associated with later development of type 2 diabetes mellitus. The objective of this study was to assess the association between prepregnancy liver enzyme levels and subsequent risk of gestational diabetes mellitus. Methods Data from a total of 236,109 women who participated in the National Health Screening Examination between 2011 and 2015 was analysed. Multivariate logistic regression analyses were performed to estimate the risk of developing gestational diabetes mellitus in relation to pregravid liver enzyme levels. Subgroup analyses were performed according to pregravid obesity and metabolic syndrome (MetS). Results Approximately 5.7% and 1.1% of women developed gestational diabetes mellitus with and without insulin treatment requirement respectively. Pregravid gamma‐glutamyl transferase and alanine aminotransferase levels with greater than or equal to the 4th quartile were associated with significantly increased risks of gestational diabetes mellitus requiring insulin treatment in women with obesity and with MetS, (odds ratios [ORs] with 6.228 and 9.505, respectively, P   〈  .001 for both). In women without obesity and without MetS, the risks of gestational diabetes mellitus requiring insulin treatment were also significant (ORs with 2.837 and 3.029, respectively, P   〈  .001 for both). The elevated pregravid liver enzymes were associated with gestational diabetes mellitus without insulin treatment requirement, but minimally. Conclusions/interpretation The elevated pregravid liver enzyme levels were significantly associated with the subsequent risk of gestational diabetes mellitus, especially gestational diabetes mellitus requiring insulin treatment, not only in women with obesity or MetS, but also in women without obesity or MetS.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2102783-3
    detail.hit.zdb_id: 2124684-1
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  • 4
    In: Advanced Therapeutics, Wiley, Vol. 4, No. 4 ( 2021-04)
    Abstract: It is demonstrated that nuclear transfer embryonic stem cells (NT‐ESCs) can be transformed into mesenchymal progenitor cells (NtMPCs) via culture under appropriate conditions and it is proposed that NtMPCs can be used for bone regeneration instead of bone marrow‐derived mesenchymal stem cells (BMSCs). In a 2‐dimensional culture, NtMPCs undergo chondrogenic and adipogenic differentiation more readily than BMSCs upon culture in appropriate media. However, the osteogenic differentiation ability of NtMPCs is lower than that of BMSCs. 3‐dimensional (3D) biologically active scaffolds (BAs) comprising poly(lactic‐co‐glycolic acid) (PLGA) microspheres are constructed to improve osteogenic differentiation. To generate BAs, nanoparticles containing an l ‐Arginyl‐Glycyl‐ l ‐Aspartic acid (RGD) sequence (RGD‐NPs) and dexamethasone (DEX), a drug used to control differentiation and inflammation, are simultaneously encapsulated by PLGA to form particles measuring 150–250 µm. After that, bone morphogenetic protein 2 (BMP2) is immobilized on the surface of polyethylenimine (PEI)‐coated microspheres via formation of ionic bonds between O‐sulfate and N‐sulfate in heparin with lysine/arginine residues of BMP2. Gene expression profiling is performed via QuantSeq 3′ mRNA‐sequencing in mice transplanted with BAs containing NtMPCs and BMSCs. Expression of the osteogenic differentiation‐related genes collagen Type I Alpha 2 (COL1A2), Homeobox protein MSX‐2 (MSX2), Runt‐related transcription factor 2 (RUNX2), and bone morphogenetic protein 2 (BMP2) is 2–3‐fold higher in mice transplanted with BAs containing NtMPCs than in mice transplanted with BAs containing BMSCs.
    Type of Medium: Online Resource
    ISSN: 2366-3987 , 2366-3987
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2920320-X
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  • 5
    In: Thoracic Cancer, Wiley, Vol. 12, No. 2 ( 2021-01), p. 235-244
    Abstract: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA. Methods We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP−, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP−. Results The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP− group ( P   〈  0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups ( P   〈  0.001, all comparisons for S/MP+ vs. S/MP−; P  ≤ 0.01, all comparisons for S/MP5 vs. S/MP−). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer‐related death than the S/MP− group( P   〈  0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA. Conclusions The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed. Key points Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma. What this study adds: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2559245-2
    detail.hit.zdb_id: 2625856-0
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  • 6
    In: Cancer Medicine, Wiley, Vol. 10, No. 23 ( 2021-12), p. 8451-8461
    Abstract: Although skeletal muscle index (SMI) and radiodensity (SMD) are well‐known prognostic factors, the clinical impact of the integrated measure, known as skeletal muscle gauge (SMG), has been limited in patients with colorectal cancer (CRC). Patients and Methods A total of 727 and 268 patients with CRC at two tertiary centers were included and allocated into the training and test sets, respectively. Preoperative slice computed tomography images of the third lumbar area were evaluated for SMI and SMD. SMG was calculated as SMI × SMD and expressed as an arbitrary unit (AU). The optimal cutoff SMG value was determined to maximize the overall survival (OS) difference between the groups with respect to sex in the training set. The multivariate Cox proportional hazard model evaluated the association of its clinical significance. Results With regard to SMG, 1640 and 1523 AU were identified as cutoff values for males and females, respectively. The patients with low SMG values showed significantly worse 5‐year OS than those with high SMG values in the two datasets (both p  〈  0.001). In the multivariate analysis, low SMG was identified as an independent poor prognostic factor of OS in the training set (hazard ratio 2.18, 95% confidence interval 1.43–3.32, p  〈  0.001) and test set (hazard ratio 1.79, 95% confidence interval 1.07–3.00, p  = 0.025), whereas SMI and SMD were not. Conclusion SMG acts synergistically to improve its prognostic predictive accuracy as compared with SMI or SMD alone in patients with CRC. Additional research is warranted to define its significance in different ethnic groups.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2659751-2
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  • 7
    In: Emergency Medicine International, Wiley, Vol. 2021 ( 2021-4-24), p. 1-7
    Abstract: Objective. Excessive daytime sleepiness (EDS) in emergency medicine (EM) residents is associated with patient safety. However, studies regarding EDS in EM residents are limited. The objective of this study was to identify the prevalence of EDS and its associated factors among EM residents. Methods. Epworth sleepiness scale scores, working hours per week (WHW), night working days per month, working environment, and depression were analyzed using data from the 2019 Korean Emergency Medicine Resident Survey. Results. The survey response rate was 63.8% (384/601). Among 241 respondents, the prevalence rate of EDS was 32.4%. Multivariable logistic regression analysis demonstrated that WHW (odds ratio [OR] = 1.03, 95% confidence interval [CI]  = 1.01–1.06) and depression (OR = 3.64, 95% CI = 1.91–6.96) had increased ORs for EDS. Conclusions. Approximately one-third of EM residents had EDS. Depression and WHW were the associated factors.
    Type of Medium: Online Resource
    ISSN: 2090-2859 , 2090-2840
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2596429-X
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  • 8
    In: Clinical and Translational Science, Wiley, Vol. 14, No. 5 ( 2021-09), p. 1747-1755
    Abstract: DHP107 is a newly developed lipid‐based oral formulation of paclitaxel. We evaluated the in vivo tissue pharmacokinetics (PKs) of DHP107 in mice and patients using positron emission tomography (PET). Radioisotope‐labeled [ 3 H]DHP107 and [ 18 F]DHP107 for oral administration were formulated in the same manner as the manufacturing process of DHP107. In vivo tissue PK were assessed in healthy ICR mice and breast cancer xenografted SCID mice. Two patients with metastatic breast cancer were clinically evaluated for absorption at the target lesion after internal absorbed dose estimation. Whole‐body PET/computed tomography data were acquired in healthy and xenografted mice and in patients up to 10–24 h after administration. Tissue [ 18 F]DHP107 signals were plotted against time and PK parameters were determined. The amounts of radioactivity in various organs an d excreta were determined using a beta‐counter and are expressed as the percentage of injected dose (ID). Oral [ 18 F]DHP107 was well‐absorbed and reached the target lesion in mice and patients with breast cancer. Significant amounts of radioactivity were found in the stomach, intestine, and liver after oral administration of [ 3 H]‐ and [ 18 F]DHP107 in healthy mice. The [ 18 F]DHP107 reached a peak distribution of 0.7–0.8%ID in the tumor at 5.6–7.3 h in the xenograft model. The [ 18 F]DHP107 distribution in patients with metastatic breast cancer was the highest at 3–4 h postadministration. Systemic exposures after administration of a DHP107 therapeutic dose were comparable with those in previous studies. PET using radioisotope‐labeled drug candidates is useful for drug development and can provide valuable information that can complement plasma PK data, particularly in early phase clinical trials.
    Type of Medium: Online Resource
    ISSN: 1752-8054 , 1752-8062
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2433157-0
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  • 9
    In: Pediatric Pulmonology, Wiley, Vol. 56, No. 10 ( 2021-10), p. 3310-3320
    Abstract: Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age‐related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. Methods Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%–75%) and clinical information were gathered from three population‐based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) ( z score: −1.64) were compared with the expected value 5%. GLI z scores were assessed according to low ( 〈 −2), normal (≥−2 and ≤2), and high ( 〉 2) BMI z score groups. Results Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27] ) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (−0.23 [−0.31, −0.15] and −0.26 [−0.36, −0.16] , respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81] ), and forced expiratory flow at 25%–75% of forced vital capacity (FEF25%–75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60] ) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups. Conclusion GLI equations marginally differ from real‐world values, which should be considered by pulmonologists in practice or research.
    Type of Medium: Online Resource
    ISSN: 8755-6863 , 1099-0496
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 632784-9
    detail.hit.zdb_id: 1491904-7
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  • 10
    In: Advanced Functional Materials, Wiley, Vol. 31, No. 29 ( 2021-07)
    Abstract: MXenes are interesting 2D materials that have been considered as attractive frontier materials for potential applications in the fields of energy and electronic devices due to their excellent optoelectronic properties including metallic conductivity and high optical transparency. However, it is still challenging to achieve compatibility for the as‐synthesized MXene nanosheets with simple solution‐deposition and patterning processes because of their limited solubility in many solvents. Here, a promising strategy is developed for obtaining alcohol‐dispersible MXene nanosheets suitable for all‐printed electronics while enhancing their electrical conductivity. This strategy includes a trifluoroacetic acid treatment—applied in order to contribute to the modification of intercalants between the MXene nanosheets—and achieves long‐term dispersion of the MXene in alcoholic media and balanced jetting conditions during the electrohydrodynamic printing process. Furthermore, the high conductivity levels of the treated MXenes allow their printed patterns to be applied as gate and source/drain electrodes in all‐printed logic circuits, displaying good and robust operation in transistors, inverters, and NAND, and NOR logic gates. This study provides a promising approach for modifying MXene nanosheets with the purpose of achieving desirable properties suitable for large‐area printing processes, suggesting the feasibility of using MXene in practical applications involving all‐printed electronics.
    Type of Medium: Online Resource
    ISSN: 1616-301X , 1616-3028
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2029061-5
    detail.hit.zdb_id: 2039420-2
    SSG: 11
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