bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis, and biological evaluation of imidazopyridine‐linked thiazolidinone as potential anticancer agents
Authors: Iqbal Md Azhar , Husain Asif , Alam Ozair , Khan Shah A. , Ahmad Aftab , Haider Md Rafi , Alam Md Aftab 
Published: July 2020

AbstractIn this study, two series of imidazopyridine‐linked thiazolidinone rings (5a–h and 6a–h) constituting 16 new compounds were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines, that is, MCF‐7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Three compounds, 5h, 6f, and 6h, exhibited remarkable results against all three cell lines, but compound 6h was found to be the most active one against the breast cancer cell line. Among all the synthesized compounds, 6h displayed the highest antioxidant results. Furthermore, the potent compounds 5h, 6f, and 6h showed no signs of toxicity at doses ranging from 50 to 500 mg/kg of animal body weight. The biochemical parameters (SGOT and SGPT) of compound 6h nearly matched the control in hepatotoxicity studies. The molecular docking and MM‐GBSADG binding studies are in agreement with the in vitro anticancer and antioxidant activity results. The most promising compound 6h was found to have the highest docking score and binding energy, and its absorption, distribution, metabolism, and excretion (ADME) parameters are in the acceptable range. Thus, it can be concluded that 6h, an imidazopyridine derivative endowed with a thiazolidinone ring system, has the potential to be developed as an anticancer agent.
PXR–ABC drug transporters/CYP‐mediated ursolic acid transport and metabolism in vitro and vivo
Authors: Jinhua Wen , Ying Zhou , Yuhua Li 
Published: July 2020

AbstractThe transporting kinetics and metabolic kinetics of ursolic acid were studied in transgenic cell models. Then, the pharmacokinetics features of ursolic acid and the expression of ATP‐binding cassette transporters (ABC transporter) and cytochrome P450 (CYP) enzymes in tissues after pregnane X receptor (PXR) activation by 5‐pregnen‐3β‐ol‐20‐one‐16α‐carbonitrile (PCN) were investigated in rats. After silencing of PXR in Caco2–siRNA–PXR cells, there was a decrease in the protein abundance of P‐glycoprotein, breast cancer‐resistant protein, multidrug resistance‐associated protein 2 (MRP2), and CYP2C9. The apparent permeability (PDR) values of 10, 20, and 50 µM ursolic acid in Caco2 cells were 2.19 ± 0.44, 1.40 ± 0.17, and 1.25 ± 0.07, respectively, whereas in Caco2–siRNA–PXR cells, they were 1.85 ± 0.36, 1.24 ± 0.11, and 1.19 ± 0.04, respectively. PXR–RXRα would significantly activate ABC transporter expression in Caco2 cells. Compared with Caco2 cells, when the concentrations of ursolic acid were 10, 20, and 50 µM, the PDR values increased in Caco2–PXR–RXRα cells after PXR activation: 1.60 ± 0.31 versus 1.97 ± 0.21, 1.46 ± 0.08 versus 2.01 ± 0.19, and 1.32 ± 0.26 versus 2.09 ± 0.22, respectively. Simultaneously, PXR–RXRα would activate the expression of CYP2C9; metabolic kinetics of ursolic acid in CYP metabolizing enzyme lysate of Caco2 cells and Caco2–PXR–RXR cells was studied and it was found that the Km values were 81.99 ± 44.32 and 60.05 ± 29.62 µg/ml, and Vmax values were 3.77 ± 0.86 and 3.41 ± 0.96 µg · ml−1 · min−1, respectively. However, in human CYP metabolizing recombinase, we found that both CYP2C9 and CYP34A were involved in the metabolism of ursolic acid. Vm and Km values for CYP3A4 and CYP2C9 were 3.57 ± 1.12 µg · ml−1 · min−1 and 81.71 ± 18.38 µg/ml, 3.85 ± 1.46 µg · ml−1 · min−1 and 62.18 ± 14.56 µg/ml, respectively. As a strong agonist for mouse pxr, PCN could significantly affect pharmacokinetics of ursolic acid in rats, and it showed discrepant effects on messenger RNA expression of cyp and transporters in tissues.
Bewehrungsstrategien für den Beton‐3D‐Druck
Authors: Kloft Harald , Empelmann Martin , Hack Norman , Herrmann Eric , Lowke Dirk 
Published: July 2020

AbstractDie Stahlbetonbauweise wurde in ihren Anfängen mit ingeniösen, materialsparenden Konstruktionen verbunden, entworfen aus dem Verständnis des kongenialen Zusammenwirkens der beiden Werkstoffe Beton und Stahl. Heutzutage ist Stahlbeton das am meisten eingesetzte Material im Bauwesen. Durch den Einsatz von Systemschalungen und einfach zu verlegenden Flächenbewehrungen werden Baukonstruktionen gefördert, die in Bezug auf Lohnkosten optimiert sind, aber oftmals eine ineffiziente Materialausnutzung aufweisen. Stefan Polónyi hat in diesem Zusammenhang immer wieder das mangelnde Verständnis der Ingenieure für das Zusammenwirken von Beton und Bewehrung kritisiert. Mit dem Beton‐3D‐Druck steht eine digitale Fertigungstechnologie bereit, die eine neue Gestaltungsfreiheit im Betonbau ermöglicht bei gleichzeitig ressourceneffizientem Materialeinsatz. Für die Integration der Bewehrung besteht die Chance für eine kraftflussgesteuerte Führung in den zugbeanspruchten Bereichen. Dies erfordert neue Strategien für die kombinierte Additive Fertigung von Beton und Bewehrung.
Information fraction estimation based on the number of events within the standard treatment regimen
Authors: Dang Ha M. , Alonzo Todd , Franklin Meredith , Mack Wendy J. , Krailo Mark D. , Eckel Sandrah P. 
Published: July 2020

AbstractFor a Phase III randomized trial that compares survival outcomes between an experimental treatment versus a standard therapy, interim monitoring analysis is used to potentially terminate the study early based on efficacy. To preserve the nominal Type I error rate, alpha spending methods and information fractions are used to compute appropriate rejection boundaries in studies with planned interim analyses. For a one‐sided trial design applied to a scenario in which the experimental therapy is superior to the standard therapy, interim monitoring should provide the opportunity to stop the trial prior to full follow‐up and conclude that the experimental therapy is superior. This paper proposes a method called total control only (TCO) for estimating the information fraction based on the number of events within the standard treatment regimen. Based on theoretical derivations and simulation studies, for a maximum duration superiority design, the TCO method is not influenced by departure from the designed hazard ratio, is sensitive to detecting treatment differences, and preserves the Type I error rate compared to information fraction estimation methods that are based on total observed events. The TCO method is simple to apply, provides unbiased estimates of the information fraction, and does not rely on statistical assumptions that are impossible to verify at the design stage. For these reasons, the TCO method is a good approach when designing a maximum duration superiority trial with planned interim monitoring analyses.
The influence of venous tumor thrombus combined with bland thrombus on the surgical treatment and prognosis of renal cell carcinoma patients
Authors: Liu Zhuo , Zhang Li , Hong Peng , Li Liwei , Tang Shiying , Zhao Xun , Zhang Qiming , Zhu Guodong , Peng Ran , Wang Binshuai , Chen Zhigang , Sun Zhenghui , Yang Feilong , Wang Guoliang , Tian Xiaojun , Zhang Shudong , Huang Yi , Zhang Hongxian , Liu Cheng , Wang Shumin , Ma Lulin 
Published: July 2020

AbstractObjectiveTo describe the clinical characteristics of renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and bland thrombus (BT), and to evaluate the influence of BT on surgical treatment and cancer‐specific survival (CSS) of RCC with VTT.MethodsWe retrospectively reviewed clinical data of 123 patients with RCC and VTT, who underwent surgical treatment in our center between February 2015 and May 2018. Patients were divided into the BT group (21 patients) and non‐BT group (102 patients). Chi‐square and Mann‐Whitney U test were used for categorical and continuous variables respectively. Univariable log‐rank tests and multivariable Cox regressions were conducted to evaluate the prognostic significance of each variable. Kaplan‐Meier plots were performed to evaluate the influence of BT.ResultsIn the delayed phase of enhanced magnetic resonance imaging (MRI), BT and VTT had difference. Patients were divided according to the relative position of BT: proximal end BT (one patients), contralateral renal vein BT (two patients), distal end BT (12 patients), and multiple BT (six patients). The average length of BT was 8.4 ± 5.8 cm (range: 0.6‐20.0 cm). Patients with BT had longer operative time (P = .001), more surgical blood loss (P = .004), higher proportion of open surgery (P = .006), more postoperative complications (P = .011). BT (hazard ratio [HR] = 3.323, P = .007) were independent risk factors for poor prognosis.ConclusionsIn the delayed phase of enhanced MRI, BT showed no obvious enhancement, while VTT usually showed enhancement. This was an important basis for preoperative imaging diagnosis of BT. The presence of BT increases the difficulty of surgery, and is correlated with adverse survival outcomes in patients with RCC and VTT.
Associations of multimorbidity and patient‐reported experiences of care with conservative management among elderly patients with localized prostate cancer
Authors: Fiano Ryan M. , Merrick Gregory S. , Innes Kim E. , Mattes Malcolm D. , LeMasters Traci J. , Shen Chan , Sambamoorthi Usha 
Published: July 2020

AbstractBackgroundMany elderly localized prostate cancer patients could benefit from conservative management (CM). This retrospective cohort study examined the associations of patient‐reported access to care and multimorbidity on CM use patterns among Medicare Fee‐for‐Service (FFS) beneficiaries with localized prostate cancer.MethodsWe used linked Surveillance, Epidemiology, and End Results cancer Registry, Medicare Claims, and the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) survey files. We identified FFS Medicare Beneficiaries (age ≥ 66; continuous enrollment in Parts A & B) with incident localized prostate cancer from 2003 to 2013 and a completed MCAHPS survey measuring patient‐reported experiences of care within 24 months after diagnosis (n = 496). We used multivariable models to examine MCAHPS measures (getting needed care, timeliness of care, and doctor communication) and multimorbidity on CM use.ResultsLocalized prostate cancer patients with multimorbidity were less likely to use CM (adjusted odds ratio (AOR)=0.42 (0.27‐ 0.66), P < .001); those with higher scores on timeliness of care (AOR = 1.21 (1.09, 1.35), P < .001), higher education attainment (3.21 = AOR (1.50,6.89), P = .003), and impaired mental health status (4.32 = AOR (1.86, 10.1) P < .001) were more likely to use CM.Conclusion(s)Patient‐reported experience with timely care was significantly and positively associated with CM use. Multimorbidity was significantly and inversely associated with CM use. Addressing specific modifiable barriers to timely care along the cancer continuum for elderly localized prostate cancer patients with limited life expectancy could reduce the adverse effects of overtreatment on health outcomes and costs.
Comprehensive analysis of copy number variance and sensitivity to common targeted therapy in clear cell renal cell carcinoma: In silico analysis with in vitro validation
Authors: Li Yuqing , Shen Yanyun , Zhu Zhidong , Wen Hui , Feng Chenchen 
Published: July 2020

AbstractBackgroundChromosomal rearrangements are common in clear cell renal cell carcinoma (ccRCC) and their roles in mediating sensitivity to tyrosine kinase inhibitors (TKIs) and mTOR inhibitors (mTORi) remain elusive.MethodsWe developed an in silico strategy by screening copy number variance (CNV) that was potentially related to TKI or mTORi sensitivity in ccRCC by reproducing the TCGA and GDSC datasets. Candidate genes should be both significantly prognostic and related to drug sensitivity or resistance, and were then validated in vitro.ResultsADCYAP1 loss and GNAS gain were associated with sensitivity and resistance and to Cabozantinib, respectively. ACRBP gain and CTBP1 loss were associated with sensitivity and resistance and to Pazopanib, respectively. CDKN2A loss and SULT1A3 gain were associated with sensitivity and resistance and to Temsirolimus, respectively. CCNE1 gain was associated with resistance to Axitinib and LRP10 loss was associated with resistance to Sunitinib. Mutivariate analysis showed ADCYAP1, GNAS, and CCNE1 remained independently prognostic when adjusted for the rest.ConclusionHere we show CNVs of several genes that are associated with sensitivity and resistance to commonly used TKIs and mTORi in ccRCC. Further validation and functional analyses are therefore needed.
Traces of cultural and personal values on sustainable consumption: An analysis of a small local swap event in Izmir, Turkey
Authors: Uckan Yuksel Can , Kaya Cigdem 
Published: July 2020

AbstractA shift to the use of more eco‐friendly products and production methods is not sufficient to reverse the negative impacts of the Anthropocene period. Irrational overconsumption and production patterns should be abolished and redesigned to remain within the Earth's carrying capacity. Over‐consumption in Turkey is a part of the problem. At the juncture of Europe and Asia, Turkey has a wide variety of consumer behaviors, ranging from conservative habits to shopping sprees, especially with the rapid transition to an open economy in developing cities with contemporized lifestyles. On the one hand, consumption and material culture have quickly diffused among the younger population, who have an important share in the demographic structure and who adopt new information technologies and follow global trends. On the other hand, sharing and collaboration are core elements of the established culture. With that notion in mind, Karsiyaka municipality and the alternative education cooperation BBOM Izmir organized a swap event. The aim of the research, was to discover the views of participants on sustainability and swapping as an alternative collaborative consumption method. The results of the interviews and observations from the swap event revealed the traces of personal and cultural values on the participants' perspectives on sustainability concept and swapping. The results also showed correlations and differences with the literature. The perceptions and expectations of local consumers about swap and the concept of sustainability are mismatched with what we profoundly need for our goal of sustainability.
Design, Synthesis, Molecular Docking, and Biological Evaluation of New Emodin Anthraquinone Derivatives as Potential Antitumor Substances
Authors: Li Yuying , Guo Fang , Chen Tinggui , Zhang Liwei , Wang Zhuanhua , Su Qiang , Feng Liheng 
Published: July 2020

AbstractThe emodin anthraquinone derivatives are generally used in traditional Chinese medicine due to their various pharmacological activities. In the present study, a series of emodin anthraquinone derivatives have been designed and synthesized, among which 1,3‐dihydroxy‐6,8‐dimethoxyanthracene‐9,10‐dione is a natural compound that has been synthesized for the very first time, and 1,3‐dimethoxy‐5,8‐dimethylanthracene‐9,10‐dione is a compound that has never been reported earlier. Interestingly, while total seven of these compounds showed neuraminidase inhibitory activity in influenza virus with inhibition rate more than 50 %, specific four compounds exhibited significant inhibition of tumor cell proliferation. The further results demonstrate that 1,3‐dimethoxy‐5,8‐dimethylanthracene‐9,10‐dione showed the best anticancer activity among all the synthesized compounds by inducing highest apoptosis rate to HCT116 cancer cells and arresting their G0/G1 cell cycle phase, through elevation of intracellular level of reactive oxygen species (ROS). Moreover, the binding of 1,3‐dimethoxy‐5,8‐dimethylanthracene‐9,10‐dione with BSA protein has thoroughly been investigated. Altogether, this study suggests the neuraminidase inhibitory activity and antitumor potential of the new emodin anthraquinone derivatives.
Transcatheter aortic valve implantation (TAVI) in cardiogenic shock: TAVI‐shock registry results
Authors: Fraccaro Chiara , Campante Teles Rui , Tchétché Didier , Saia Francesco , Bedogni Francesco , Montorfano Matteo , Fiorina Claudia , Meucci Francesco , De Benedictis Mauro , Leonzi Ornella , Barbierato Marco , Dumonteil Nicolas , Stolcova Miroslava , Maffeo Diego , Compagnone Miriam , Brito João , Chieffo Alaide , Tarantini Giuseppe 
Published: July 2020

AbstractObjectivesAim of this study is to evaluate safety, feasibility, and mid‐term outcome of transcatheter aortic valve implantation (TAVI) in cardiogenic shock (CS).BackgroundBalloon aortic valvuloplasty in patients with severe aortic valve stenosis (SAS) complicated by CS is indicated but associated with a grim prognosis. TAVI might be a more reasonable treatment option in this setting but data are scant.MethodsFrom March 2008 to February 2019, 51 patients with severe aortic valvulopathy (native SAS or degenerated aortic bioprosthesis) and CS treated by TAVI in 11 European centers were included in this multicenter registry. Demographic, clinical, and procedural data were collected, as well as clinical and echocardiographic follow‐up.ResultsThe mean age of our study population was 75.8 ± 13, 49% were women, and mean Society of Thoracic Surgeons (STS) score was 19 ± 15%. Device success was achieved in 94.1%, with a 5% incidence of moderate/severe paravalvular leak. The 30‐day events were mortality 11.8%, stroke 2.0%, vascular complications 5.9%, and acute kidney injury 34%. Valve Academic Research Consortium‐2 early safety endpoint was reached in 35.3% of cases. At 1‐year of follow‐up, the mortality rate was 25.7% and the readmission for congestive heart failure was 8.6%.ConclusionsTAVI seems to be a therapeutic option for patients with CS and SAS or degenerated aortic bioprosthesis in terms of both safety and efficacy at early and long‐term follow‐up.
Contributions of a modified electrodynamics to the molecular biochirality
Authors: Santos Alana C. L. , Muniz Celio R. , Oliveira Leonardo T. , Souza Jefferson T. 
Published: July 2020

AbstractIn this paper, we investigate the physical basis behind the molecular biochirality from the computation of a parity violation energy difference (PVED) in enantiomers of organic molecules (e.g., amino acids, which occur as levogyrous‐type in nature), by considering the influence of fundamental interactions beyond the standard model of elementary particles and interactions. Particularly, we study the role of a 4‐D Chern‑Simons theory at the origin of this PVED, the Carroll‑Field‑Jackiw electrodynamics, which violates both Lorentz and parity symmetries. Then, we consider terrestrial and Jovian scenarios where the influence of a modified (effective) magnetic field generated by the planets on the molecules is taken into account in the calculation of PVED. Besides this quantity, we also calculate the relative quantity excess of an enantiomer over the other in a thermal bath. Finally, we compare the obtained results with those ones from other models based on fundamental interactions.
Strictly periodic first: An optimal variant of LLF for scheduling tasks in a time‐critical cyber‐physical system
Authors: Kermia Omar 
Published: July 2020

SummaryCyber‐physical systems (CPSs) include time‐critical embedded systems where strict timing constraints are considered. These specific CPSs are dealing with close loop control functions, they are interfacing to sensors and actuators and have to fulfill safety critical real‐time constraints. To guarantee the timing correctness, a lot of work introduced the strict‐periodicity constraint. The latter is of great importance since it concerns sensors/actuators periodic tasks for which the relevancy of information they use is linked to the accuracy of their repetition. Applied to real‐time control systems, the strict‐periodicity constraint ensures much more stability and robustness. Therefore, the problem of scheduling real‐time strictly periodic tasks has been targeted by several works in the literature but all these works were interested in nonpreemptive systems. In this work, we consider as strictly periodic and nonpreemptive only the sensory subtask and the remaining portion of the task may be preempted. This way, input transaction of every task receives the highest priority when accessing processor resource which enhances system predictability. On the other hand, the preemption allows easing schedulability analysis and, most of the time, it leads to a better processor utilization. The article proposes an optimal such task scheduling algorithm, called SPF for Strictly Periodic First, based on the Least Laxity First (LLF) scheduler and an efficient schedulability analysis. Simulation experiments with randomly generated task sets allowed showing the effectiveness of the proposed approach.
Mood‐Stabilizing Antiepileptic Treatment Response in Bipolar Disorder: A Genome‐Wide Association Study
Authors: Ho Ada Man‐Choi , Coombes Brandon J. , Nguyen Thanh Thanh L. , Liu Duan , McElroy Susan L. , Singh Balwinder , Nassan Malik , Colby Colin L. , Larrabee Beth R. , Weinshilboum Richard M. , Frye Mark A. , Biernacka Joanna M. 
Published: July 2020

Several antiepileptic drugs (AEDs) have US Food and Drug Administration (FDA) approval for use as mood stabilizers in bipolar disorder (BD), but not all BD patients respond to these AED mood stabilizers (AED‐MSs). To identify genetic polymorphisms that contribute to the variability in AED‐MS response, we performed a discovery genome‐wide association study (GWAS) of 199 BD patients from the Mayo Clinic Bipolar Disorder Biobank. Most of these patients had been treated with the AED‐MS valproate/divalproex and/or lamotrigine. AED‐MS response was assessed using the Alda scale, which quantifies clinical improvement while accounting for potential confounding factors. We identified two genome‐wide significant single‐nucleotide polymorphism (SNP) signals that mapped to the THSD7A (rs78835388, P = 7.1E‐09) and SLC35F3 (rs114872993, P = 3.2E‐08) genes. We also identified two genes with statistically significant gene‐level associations: ABCC1 (P = 6.7E‐07; top SNP rs875740, P = 2.0E‐6), and DISP1 (P = 8.9E‐07; top SNP rs34701716, P = 8.9E‐07). THSD7A SNPs were previously found to be associated with risk for several psychiatric disorders, including BD. Both THSD7A and SLC35F3 are expressed in excitatory/glutamatergic and inhibitory/γ‐aminobutyric acidergic (GABAergic) neurons, which are targets of AED‐MSs. ABCC1 is involved in the transport of valproate and lamotrigine metabolites, and the SNPs in ABCC1 and DISP1 with the strongest evidence of association in our GWAS are strong splicing quantitative trait loci in the human gut, suggesting a possible influence on drug absorption. In conclusion, our pharmacogenomic study identified novel genetic loci that appear to contribute to AED‐MS treatment response, and may facilitate precision medicine in BD.
Tuning of the Oxygen Species Linker on the Surface of Polymeric Carbon Nitride to Promote the Photocatalytic Hydrogen Evolution Performance
Authors: Lei Qin , Chen Rongzhi , Zhao Yurong , Chen Huanyu , Long Xinxin , Tan Jihua , Wang Xinming 
Published: July 2020

AbstractInvited for this month's cover is the research group of Rongzhi Chen at the University of Chinese Academy of Sciences and Xinming Wang at Guangzhou Institute of Geochemistry, Chinese Academy of Sciences. The image proposes an effective strategy to tune bonded oxygen species of carbon nitride for improving photocatalytic hydrogen production. The Full Paper itself is available at 10.1002/cssc.202001027.