bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thienopyrimidine‐based agents bearing diphenylurea: Design, synthesis, and evaluation of antiproliferative and antiangiogenic activity
Authors: Mohammadian Esmaeil , Oghabi Bakhshaiesh Tayebeh , Jouyban Abolghasem , Nazeri Elahe , Hasanvand Zaman , Moghimi Setareh , Motahari Rasoul , Firoozpour Loghman , Bijanzadeh Hamidreza , Alizadeh Sani Mahmood , Hosseinzadeh Elaheh , Esmaeili Rezvan , Foroumadi Alireza 
Published: November 2022

AbstractAn important role has been considered for the vascular endothelial growth factor receptor 2 (VEGFR‐2) in the angiogenesis process, so that its inhibition is an important scientific way for cancer treatment. In this work, new thienopyrimidine derivatives were synthesized and evaluated. Compared with sorafenib, the majority of the target compounds had antiproliferative activity against the PC3, HepG2, MCF7, SW480, and HUVEC cell lines, especially 9h with IC50 values of 4.5–15.1 μM, confirming the noticeable cytotoxic effects on the listed cell lines (PC3, HepG2, SW480, and HUVEC). Analyses by flow cytometry on SW480 and HUVEC cells revealed that 9n, 9k, 9h, and 9q led to apoptotic cell death. The result of the chick chorioallantoic membrane assay showed that 9h effectively reduced the number of corresponding blood vessels. Finally, the inhibitory effect on VEGFR‐2 phosphorylation was considered as the outcome of Western blot analysis of compound 9h.
Early Increase of Circulating Transitional B Cells and Autoantibodies to Joint‐Related Proteins in Patients With Metastatic Melanoma Developing Checkpoint Inhibitor–Induced Inflammatory Arthritis
Authors: Gatto Mariele , Bjursten Sara , Jonsson Charlotte A. , Agelii Monica Leu , Jonell Caroline , McGrath Sarah , Lönnblom Erik , Sareila Outi , Holmdahl Rikard , Rudin Anna , Levin Max , Gjertsson Inger 
Published: November 2022

ObjectiveTo investigate potential associations between B cell–related immunologic changes and development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICIs).MethodsPatients who developed ICI‐induced IA (ICI‐IA) and patients who did not develop immune‐related adverse events (non‐IRAE) after receiving ICIs to treat metastatic melanoma were consecutively recruited. Blood samples were collected at the time of ICI‐IA occurrence and at different time points during treatment. Peripheral blood B cell subsets during ICI treatment were analyzed by flow cytometry. Rheumatoid factor, anti–citrullinated protein antibodies, and antibodies against joint‐related proteins were measured.ResultsProportions of CD19+ B cells were higher in patients with ICI‐IA (n = 7) compared to patients with non‐IRAE (n = 15) (median 11.7% [interquartile range (IQR) 9.7–16.2%] versus 8.1% [IQR 5.7–11.0%]; P = 0.03). The proportion and absolute numbers of transitional CD19+CD10+CD24highCD38high B cells were increased in patients with ICI‐IA compared to non‐IRAE patients (median 8.1% [IQR 4.9–12.1%] versus 3.6% [IQR 1.9–4.9%]; median 10.7 cells/μl [IQR 8.9–19.6] versus 4.4 cells/μl [IQR 2.3–6.6]; P < 0.01 for both). In addition, higher levels of transitional B cells were associated with development of ICI‐IA (odds ratio 2.25 [95% confidence interval 1.03–4.9], P = 0.04). Transitional B cells increased before the onset of overt ICI‐IA and decreased between the active and quiescent stages of ICI‐IA (P = 0.02). Autoantibodies to type II collagen epitopes were detected in up to 43% of ICI‐IA patients compared to none of the non‐IRAE patients (P = 0.02).ConclusionDevelopment of ICI‐IA is accompanied by an increase in transitional B cells and by production of autoantibodies to joint‐related proteins. Monitoring of B cell–driven abnormalities upon ICI treatment may help earlier recognition of ICI‐IA.image
Aberrant Naive CD4–Positive T Cell Differentiation in Systemic Juvenile Idiopathic Arthritis Committed to B Cell Help
Authors: Kuehn Julia , Schleifenbaum Susanne , Hendling Michaela , Siebenhandl Sandra , Krainer Julie , Fuehner Sabrina , Hellige Antje , Park Carolin , Hinze Claas , Wittkowski Helmut , Holzinger Dirk , Thurner Lorenz , Weinhäusel Andreas , Foell Dirk , Kessel Christoph 
Published: November 2022

ObjectiveSystemic juvenile idiopathic arthritis (JIA) features characteristics of autoinflammation and autoimmunity, culminating in chronic arthritis. In this study, we hypothesized that aberrant or incomplete polarization of T helper cells contributes to disease pathology.MethodsCells or serum samples were obtained from healthy controls (n = 72) and systemic JIA patients (n = 171). Isolated naive T helper cells were cultured under Th1, Th17, and T follicular helper (Tfh) or T peripheral helper (Tph)—polarizing conditions and were partly cocultured with allogenic memory B cells. Cell samples were then analyzed for surface marker, transcription factor, and cytokine expression, as well as plasmablast generation. Serum samples were subjected to multiplexed bead and self‐antigen arrays and enzyme‐linked immunosorbent assays, and all data were compared to retrospective RNA profiling analyses.ResultsDifferentiation of systemic JIA–naive T helper cells toward Th1 cells resulted in low expression levels of interferon‐γ (IFNγ) and eomesodermin, which was associated in part with disease duration. In contrast, developing Th1 cells in patients with systemic JIA were found to produce elevated levels of interleukin‐21 (IL‐21), which negatively correlated with cellular expression of IFNγ and eomesodermin. In both in vitro and ex vivo analyses, IL‐21 together with programmed cell death 1 (PD‐1), inducible T cell costimulator (ICOS), and CXCR5 expression induced naive T helper cells from systemic JIA patients to polarize toward a Tfh/Tph cell phenotype. Retrospective analysis of whole‐blood RNA‐sequencing data demonstrated that Bcl‐6, a master transcription factor in Tfh/Tph cell differentiation, was overexpressed specifically in patients with systemic JIA. Naive T helper cells from systemic JIA patients which were stimulated in vitro promoted B cellular plasmablast generation, and self‐antigen array data indicated that IgG reactivity profiles of patients with systemic JIA differed from those of healthy controls.ConclusionIn the pathogenesis of systemic JIA, skewing of naive T helper cell differentiation toward a Tfh/Tph cell phenotype may represent an echo of autoimmunity, which may indicate the mechanisms driving progression toward chronic destructive arthritis.image
Inverse motion planning method for overhead crane systems with state constraints
Authors: Chen Qingrong , Yu Siyang , Cheng Wenming , Zhang Mao , Liu Jiahui , Gao Lingchong , Du Run , Yan Wei 
Published: November 2022

AbstractThe trajectory planning problem with state constraints of overhead crane systems is considered in this paper. A new method, that is, an inverse motion planning method, is proposed. On this basis, a new trajectory planner is designed. The payload swing angle trajectory is designed first, and then by substituting it into the dynamic equations, the trolley trajectory is derived. For any transportation tasks, the adjustable parameter of the planner is computed by solving the state constraints such that the system states; that is, the trolley acceleration, trolley speed, and payload swing angle will not exceed their predefined constraints. Several experimental tests are conducted to verify the swing elimination performance of the proposed method.
Nonparametric significance tests for imperfect repair
Authors: Gilardoni Gustavo L. , Colosimo Enrico A. , de Toledo Maria Luíza G. , Freitas Marta A. 
Published: November 2022

AbstractGiven the failure history for independent and identical repairable systems, a nonparametric procedure is presented to test the null hypothesis of minimal repair (MR) against the alternative of imperfect repair. The main idea is that, under non‐harmful (harmful) repair, systems that failed later (earlier) are more reliable than those that have failed (later). This fact allows one, at any moment in time, to rank the systems from more to less reliable and, hence, to define a vector that counts how many times the system ranked failed. When all the systems are time‐truncated at the same time , it is shown that, under the null hypothesis of MR, the vector of counts follows a multinomial distribution with class probabilities for . The test proceeds by computing a chi‐bar squared test statistic similar to the one used to test one‐sided alternatives in the multinomial setup, which allows us to compute ‐values using either asymptotic theory or a straightforward Monte Carlo simulation using the null multinomial distribution. Extension to the case of different truncation times is also discussed. The procedure is applied to two real datasets regarding equipment used in the mining industry.
Full Cell Lithium‐Ion Battery Manufacture by Electrophoretic Deposition
Authors: Bree Gerard , Tong John Low Chee 
Published: November 2022

AbstractElectrophoretic deposition (EPD) is a proven coating operation at an industrial scale. Initially designed for the automotive industry, it has expanded to other applications, notably ceramic coatings for surface protection, and has found promising application in the battery industry. Whilst fundamental half‐cell studies of EPD electrodes are numerous, their practical performance at full‐cell level is largely unknown. This study reports full‐cell lithium‐ion batteries in which anode and cathode are manufactured by EPD, using an exemplary Li4Ti5O12/LiFePO4 (LTO/LFP) chemistry. Investigations compatible with industry scalability were carried out including a) formulation of colloidal electrolytes for large area electrode manufacture, b) optimisation of EPD parameters providing high coating thickness and mass loading, c) comparison with slurry cast electrodes, d) scaling investigations to prototype large area pouch cells, and e) ease of manufacture with porous current collectors for high power applications. It was found that the practical performance of EPD electrodes outperformed slurry casting in various categories including lower resistances, more extractable capacity, higher power capability and stable cycling robustness.
Real‐time in‐situ electrochemical monitoring of Pseudomonas aeruginosa biofilms grown on air–liquid interface and its antibiotic susceptibility using a novel dual‐chamber microfluidic device
Authors: Zhang Ye , Gholizadeh Hanieh , Young Paul , Traini Daniela , Li Ming , Ong Hui Xin , Cheng Shaokoon 
Published: November 2022

AbstractBiofilms are communities of bacterial cells encased in a self‐produced polymeric matrix that exhibit high tolerance toward environmental stress. Despite the plethora of research on biofilms, most P. aeruginosa biofilm models are cultured on a solid–liquid interface, and the longitudinal growth characteristics of P. aeruginosa biofilm are unclear. This study demonstrates the real‐time and noninvasive monitoring of biofilm growth using a novel dual‐chamber microfluidic device integrated with electrochemical detection capabilities to monitor pyocyanin (PYO). The growth of P. aeruginosa biofilms on the air–liquid interface (ALI) was monitored over 48 h, and its antibiotic susceptibility to 6 h exposure of 50, 400, and 1600 µg/ml of ciprofloxacin solutions was analyzed. The biofilm was treated directly on its surface and indirectly from the substratum by delivering the CIP solution to the top or bottom chamber of the microfluidic device. Results showed that P. aeruginosa biofilm developed on ALI produces PYO continuously, with the PYO production rate varying longitudinally and peak production observed between 24 and 30 h. In addition, this current study shows that the amount of PYO produced by the ALI biofilm is proportional to its viable cell numbers, which has not been previously demonstrated. Biofilm treated with ciprofloxacin solution above 400 µg/ml showed significant PYO reduction, with biofilms being killed more effectively when treatment was applied to their surfaces. The electrochemical measurement results have been verified with colony‐forming unit count results, and the strong correlation between the PYO electrical signal and the viable cell number highlights the usefulness of this approach for fast and low‐cost ALI biofilm study and antimicrobial tests.
Degradation pathways and impurity profiling of the anticancer drug apalutamide by HPLC and LC–MS/MS and separation of impurities using Design of Experiments
Authors: Lakka Narasimha Swamy , Kuppan Chandrasekar , Vadagam Niroja , Reddamoni Sapthagiri Yadav , Muthusamy Chandru 
Published: November 2022

AbstractApalutamide, an androgen receptor inhibitor, is used to treat prostate cancer. A stability‐indicating high‐performance liquid chromatography method was developed for the estimation of assay and organic impurities of apalutamide in drug substance and in tablet dosages using Design of Experiments. The chromatographic separation was achieved within 30 min using Atlantis dC18, 100 × 4.6 mm, 3.0 μm and the binary gradient program (10 mm KH2PO4, pH 3.5; acetonitrile). The detection wavelength, flow rate, column temperature and injection volume used were 270 nm, 1.0 ml/min, 45°C and 10 μl, respectively. The interaction of independent variables (pH, column temperature and flow rate) and their influences on HPLC parameters were studied using a central composite design, and then the peak separation and elution behaviors between apalutamide and its seven impurities were determined. The method validation was performed for linearity, detection limit, quantitation limit, accuracy, precision and robustness as per the International Conference on Harmonization. A high‐quality recovery with good precision (91.7–106.0%) and correlations (r2 > 0.997) within a linear range of 0.12–2.24 μg/ml (0.05–0.3%, w/w) were achieved consistently for assay and organic impurities of apalutamide. The stability‐indicating characteristics of the proposed method were assessed through forced degradation and mass balance studies. An effort was made to figure out the chemical structures of newly formed degradation products (DP1–DP5) using LC–MS/MS.
The delivery of nanoparticles improves the pharmacokinetic properties of celecoxib to open a therapeutic window for oral administration of insoluble drugs
Authors: Qin Zhenmiao , Lv Geng , Wang Tong , Li Hailong , Zhao Beicheng , Chen Meili , Gang Hou , Tan Yinfeng , Jia Huanhuan 
Published: November 2022

AbstractA sensitive and reliable LC–MS/MS method is established and validated to determine the concentration of celecoxib, in the serum of cynomolgus monkey, using celecoxib‐D7 as an internal standard. The pharmacokinetic process was investigated after giving Celebrex, celecoxib nanoparticles (CXB‐NPs) and hyaluronic acid celecoxib nanoparticles (HA‐CXB‐NPs) by intragastric (i.g.) administration. Chromatographic separation was performed with a C18 column (2.1 × 100 mm, 2.6 μm) at 40°C with a mobile phase of 2‰ HCOOH in water and acetonitrile. The mass spectral acquisition was then performed in the multiple reaction monitoring mode, with negative ESI ion at m/z 380.0 → 316.0 and m/z 387.1 → 323.1 for celecoxib and celecoxib‐D7, respectively. Good linearity was observed over the concentration range from 3 to 2,000 ng/ml (R2 = 0.9954). The intra‐ and inter‐day precision and accuracy, matrix effect and extraction recovery, as well as stability, all met the determination requirements of biological samples. The pharmacokinetic parameters of Celebrex, CXB‐NPs and HA‐CXB‐NPs were determined as: area under the curve, 1,855.98 ± 346.59, 1,908.00 ± 1,130.24 and 2,164.48 ± 657.47 h·ng/ml; peak concentration, 261.08 ± 113.26, 261.12 ± 94.67 and 263.34 ± 151.78 μg/L; time to peak concentration, 2.00 ± 1.22, 4.00 ± 0.00 and 3.60 ± 0.89 h; half‐life, 4.39 ± 1.26, 2.33 ± 0.94 and 4.92 ± 3.13 h; relative bioavailability, 102.80 ± 49.62 and 116.63 ± 25.55%. The validated method was successfully applied to the pharmacokinetic study of celecoxib in cynomolgus monkey, after i.g. administration. The preparation of the nanoparticles of celecoxib and the modification of hyaluronic acid on the surface of nanoparticles could improve the bioavailability and prolong the circulation of celecoxib in vivo, which could lay the foundation for further development of celecoxib nanoparticles.
The determinants of green entrepreneurship: The perspectives of leadership, culture, and creativity
Authors: Chen Yu‐Shan , Lin Yi‐Hsiung , Lai Yi‐Ju 
Published: November 2022

AbstractThis study investigates the determinants of green entrepreneurship from the perspectives of leadership, culture, and creativity. We prove that environmental leadership of top managers positively influences green entrepreneurship directly, and it also positively affects green entrepreneurship indirectly via green creativity. Furthermore, environmental organizational culture cannot directly influence green entrepreneurship, but it can indirectly affect green entrepreneurship through green creativity positively. In addition, we verify that green creativity plays a partial mediator role on the relationship between environmental leadership of top managers and green entrepreneurship, as well as a full mediator role on the relationship between environmental organizational culture and green entrepreneurship. Moreover, we demonstrate that both of proactiveness and risk‐taking propensity of top managers moderate the positive relationship between green creativity and green entrepreneurship. The results suggest enterprises to improve environmental leadership of top managers, environmental organizational culture, and green creativity to improve green entrepreneurship. Additionally, firms must develop top managers' proactiveness and risk‐taking propensity to increase the extent of the positive relationship between green creativity and green entrepreneurship.
Cancer associated fibroblast derived gene signature determines cancer subtypes and prognostic model construction in head and neck squamous cell carcinomas
Authors: Wu Sangqing , Huang Cheng , Su Liangping , Wong Ping‐Pui , Huang Yongsheng , Chen Renhui , Lin Peiliang , Ye Yuchu , Song Pang , Han Ping , Huang Xiaoming 
Published: November 2022

AbstractBackgroundHead and neck squamous cell carcinomas (HNSCC) are the most common type of head and neck cancer with an unimproved prognosis over the past decades. Although the role of cancer‐associated‐fibroblast (CAF) has been demonstrated in HNSCC, the correlation between CAF‐derived gene expression and patient prognosis remains unknown.MethodsA total of 528 patients from TCGA database and 270 patients from GSE65858 database were contained in this study. After extracting 66 CAF‐related gene expression data from TCGA database, consensus clustering was performed to identify different HNSCC subtypes. Limma package was used to distinguish the differentially expression genes (DEGs) between these subtypes, followed by Lasso regression analysis to construct a prognostic model. The model was validated by performing Kaplan‐Meier survival, ROC and risk curve, univariate and multivariate COX regression analysis. GO, KEGG, GSEA, ESTIMATE and ssGSEA analyses was performed to explort the potential mechanism leading to different prognosis.ResultsBased on the 66 CAF‐related gene expression pattern we stratitied HNSCC patients into two previously unreported subtypes with different clinical outcomes. A prognostic model composed of 15 DEGs was constructed and validated. In addition, bioinformatics analysis showed that the prognostic risk of HNSCC patients was also negatively correlated to immune infiltration, implying the role of tumor immune escape in HNSCC prognosis and treatment option.ConclusionsThe study develops a reliable prognostic prediction tool and provides a theoretical treatment guidance for HNSCC patients.
Crisis communications plans can help to prevent legal trouble for colleges, universities
Authors: McCarthy Claudine 
Published: November 2022

Behind every legal issue facing your institution are communications issues that need to be addressed. The way you choose to address these issues will influence how they're perceived by others, whether such issues might become entangled in the legal process, and the potential reputational damage to your department and institution. That's according to James F. Haggerty, J.D., Crisis Communications Consultant and President and CEO of PRCG/Haggerty LLC, a strategic communications firm, and the author of Chief Crisis Officer: Structure and Leadership for Effective Communications Response and In the Court of Public Opinion: Winning Strategies for Litigation Communications. He spoke at Stetson University's National Conference on Law and Higher Education.
Design, Synthesis, α‐Amylase/α‐Glucosidase Inhibition Assay, Induced Fit Docking Study of New Hybrid Compounds Containing 4H‐Pyrano[2,3‐d]pyrimidine, 1H‐1,2,3‐Triazole and D‐Glucose Components
Authors: Toan Vu Ngoc , Thanh Nguyen Dinh , Huyen Le Thi , Hanh Nguyen Thi , Hai Do Son , Anh Hoang Huu , Giang Nguyen Thi Kim , Van Hoang Thi Kim 
Published: November 2022

AbstractIn this study, the click chemistry between N‐propargyl derivatives of substituted 4H‐pyrano[2,3‐d]pyrimidines and tetra‐O‐acetyl‐α‐d‐glucopyranosyl azide carried out under catalytic conditions using catalyst CuI@Montmorillonite and additive N,N‐diisopropylethylamine (DIPEA). The yields of obtained hybrid compounds having 4H‐pyrano[2,3‐d]pyrimidine connected to 1H‐1,2,3‐triazole rings were about 85–94 %. All these synthesized hybrid compounds were examined for in vitro α‐amylase (with IC50 values in the range of 103.63±1.13 μM to 295.45±1.11 μM) and α‐glucosidase (with IC50 values in the range of 45.63±1.14 μM to 184.52±1.15) inhibitory activity. Amongst this series, ethyl ester 8m showed the best inhibitory activity against α‐amylase with IC50 of 103.63±1.13 μM, while ethyl ester 8t exhibited the highest activity against α‐glucosidase with IC50 of 45.63±1.14 μM. The kinetics of the inhibition of compound 8t showed the competitive α‐glucosidase inhibitor property of this compound. Furthermore, the most potent compounds had any cytotoxicity against human normal cells. Induced fit docking and molecular dynamics simulation calculations indicated that the inhibition potential compounds 8m and 8t had the active interactions with the residues in receptors of corresponding tested enzymes. The calculated binding free energy from MM‐GBSA approach showed that the major energy components contributed to the active binding of these studied inhibitors, including Coulomb, lipophilic and van der Waals energy. Further, 300 ns MD simulation showed that studied ligand‐protein complexes were stable and indicated the structural observations into mode of binding in these complexes.
Six New Constituents from the Fruit of Hypericum patulum and Their Anti‐Inflammatory Activity
Authors: Xue Jing‐Yi , Jiang Wei , Li Li , Lu Ding‐Yan , Ma Xue , Lu Yuan , Liu Ting , Huang Yong , Wang Yong‐Lin , Li Yong‐Jun 
Published: November 2022

AbstractFour new xanthone glucosides, 3‐hydroxy‐2‐methoxyxanthone‐4‐O‐β‐D‐glucopyranoside (1), 4,8‐dihydroxy‐2‐methoxyxanthone‐3‐O‐β‐D‐glucopyranoside (2), 2‐methoxyxanthone‐5‐O‐β‐D‐glucopyranoside (3), 4‐hydroxy‐2‐methoxyxanthone‐3‐O‐β‐D‐glucopyranoside (4), a new phenolic acid, 4,4′‐dihydroxy‐3,3′‐imino‐di‐benzoic acid monomethyl ester (5), and a new isoquinoline, methyl 6‐hydroxy‐1‐oxo‐1,2,3,4‐tetrahydroisoquinoline‐4‐carboxylate (6) were isolated from the fruit of Hypericum patulum. The structural elucidation of the isolated compounds was primarily based on HR‐ESI‐MS, UV, IR, 1D and 2D NMR. All compounds were evaluated for their inhibitory effect against LPS‐induced NO production in RAW 264.7 cells. Compound 2, 3 exhibited moderate inhibitory activity against NO production.