bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of HMG‐CoA reductase inhibitory and antioxidant effects of various hydroxycoumarin derivatives
Authors: Ozalp Lalehan , Danış Özkan , Yuce‐Dursun Basak , Demir Serap , Gündüz Cihan , Ogan Ayse 
Published: July 2020

AbstractCardiovascular diseases are one of the primary causes of deaths worldwide, and the development of atherosclerosis is closely related to hypercholesterolemia. As the reduction of the low‐density lipoprotein cholesterol level is critical for treating these diseases, the inhibition of 3‐hydroxy‐3‐methyl‐glutaryl coenzyme A (HMG‐CoA) reductase, which is essentially responsible for cholesterol biosynthesis, stands out as a key solution to lower plasma cholesterol levels. In this study, we synthesized several dihydroxycoumarins and investigated their antioxidant and in vitro HMG‐CoA reductase inhibitory effects. Furthermore, we carried out in silico studies and examined the quantum‐chemical properties of the coumarin derivatives. We also performed molecular docking experiments and analyzed the binding strength of each coumarin derivative. Our results revealed that compound IV displayed the highest HMG‐CoA reductase inhibitory activity (IC50 = 42.0 µM) in vitro. Cupric‐reducing antioxidant capacity and ferric‐reducing antioxidant power assays demonstrated that coumarin derivatives exhibit potent antioxidant activities. Additionally, a close relationship was found between the lowest unoccupied molecular orbital energy levels and the antioxidant activities.
In vitro vascularized tumor platform for modeling tumor‐vasculature interactions of inflammatory breast cancer
Authors: Gadde Manasa , Phillips Caleb , Ghousifam Neda , Sorace Anna G. , Wong Enoch , Krishnamurthy Savitri , Syed Anum , Rahal Omar , Yankeelov Thomas E. , Woodward Wendy A. , Rylander Marissa N. 
Published: July 2020

AbstractInflammatory breast cancer (IBC), a rare form of breast cancer associated with increased angiogenesis and metastasis, is largely driven by tumor‐stromal interactions with the vasculature and the extracellular matrix (ECM). However, there is currently a lack of understanding of the role these interactions play in initiation and progression of the disease. In this study, we developed the first three‐dimensional, in vitro, vascularized, microfluidic IBC platform to quantify the spatial and temporal dynamics of tumor‐vasculature and tumor‐ECM interactions specific to IBC. Platforms consisting of collagen type 1 ECM with an endothelialized blood vessel were cultured with IBC cells, MDA‐IBC3 (HER2+) or SUM149 (triple negative), and for comparison to non‐IBC cells, MDA‐MB‐231 (triple negative). Acellular collagen platforms with endothelialized blood vessels served as controls. SUM149 and MDA‐MB‐231 platforms exhibited a significantly (p < .05) higher vessel permeability and decreased endothelial coverage of the vessel lumen compared to the control. Both IBC platforms, MDA‐IBC3 and SUM149, expressed higher levels of vascular endothelial growth factor (p < .05) and increased collagen ECM porosity compared to non‐IBCMDA‐MB‐231 (p < .05) and control (p < .01) platforms. Additionally, unique to the MDA‐IBC3 platform, we observed progressive sprouting of the endothelium over time resulting in viable vessels with lumen. The newly sprouted vessels encircled clusters of MDA‐IBC3 cells replicating a key feature of in vivo IBC. The IBC in vitro vascularized platforms introduced in this study model well‐described in vivo and clinical IBC phenotypes and provide an adaptable, high throughput tool for systematically and quantitatively investigating tumor‐stromal mechanisms and dynamics of tumor progression.
Genome‐scale modeling for Bacillus coagulans to understand the metabolic characteristics
Authors: Chen Yu , Sun Yan , Liu Zhihao , Dong Fengqing , Li Yuanyuan , Wang Yonghong 
Published: July 2020

AbstractLactic acid is widely used in many industries, especially in the production of poly‐lactic acid. Bacillus coagulans is a promising lactic acid producer in industrial fermentation due to its thermophilic property. In this study, we developed the first genome‐scale metabolic model (GEM) of B. coagulans iBag597, together with an enzyme‐constrained model ec‐iBag597. We measured strain‐specific biomass composition and integrated the data into a biomass equation. Then, we validated iBag597 against experimental data generated in this study, including amino acid requirements and carbon source utilization, showing that simulations were generally consistent with the experimental results. Subsequently, we carried out chemostats to investigate the effects of specific growth rate and culture pH on metabolism of B. coagulans. Meanwhile, we used iBag597 to estimate the intracellular metabolic fluxes for those conditions. The results showed that B. coagulans was capable of generating ATP via multiple pathways, and switched among them in response to various conditions. With ec‐iBag597, we estimated the protein cost and protein efficiency for each ATP‐producing pathway to investigate the switches. Our models pave the way for systems biology of B. coagulans, and our findings suggest that maintaining a proper growth rate and selecting an optimal pH are beneficial for lactate fermentation.
Evolution of an educational microprocessor
Authors: Mezei Ivan 
Published: July 2020

AbstractArising from the need to help students learn commercial assembly language programming more easily, Edulent microprocessor has evolved into an integrated educational tool. It is completely designed, developed, and verified targeting field‐programmable gate array (FPGA) and system on chip (SoC) implementations. Its evolution started almost two decades ago with a formal specification, continued through various implementations (both hardware and software) fulfilling several, mainly educational requirements. The educational impact on acquiring core learning outcomes in microprocessor architecture and assembly language programming is evaluated and assessed based on several questionnaires and results of laboratory assignments. The latest FPGA and SoC‐based implementations have shown further potential for students to acquire new knowledge in the field of microprocessor design, implementation, and verification.
Therapy preferences in melanoma treatment—Willingness to pay and preference of quality versus length of life of patients, physicians, healthy individuals and physicians with oncological disease
Authors: Weiss Julia , Kirchberger Michael Constantin , Heinzerling Lucie 
Published: July 2020

AbstractBackgroundIn recent years, monoclonal antibodies such as ipilimumab, nivolumab, and pembrolizumab have made a significant impact on the treatment of advanced melanoma. Combination of immune checkpoint inhibitors leads to improved survival and response rates of 58%‐61% as compared to monotherapy (36%‐44%). However, the price for the better response rates is also a higher frequency of severe adverse events (59%) as compared to monotherapy (17%‐21%). This study examines attitudes towards melanoma therapy options of physicians, healthy individuals, melanoma patients, and physicians with oncological disease, their willingness to pay, and preference of quality versus length of life.MethodsAfter obtaining ethical approval and informed consent surveys were conducted in 111 participants divided into four groups: melanoma patients (n = 30), healthy individuals as controls (n = 30), physicians (n = 27), and physicians with oncological disease (n = 24). Statistical analyses were conducted using SPSS statistics (version 25, IBM), applying the Pearson´s chi‐squared test, Spearman correlation coefficient, Wilcoxon‐Mann‐Whitney test, and Kruskal‐Wallis test.ResultsLife prolongation is more valued by melanoma patients and physicians with oncological disease compared to healthy controls and healthy physicians. In total, 30% of melanoma patients opt for a life prolonging therapy in all cases, even if this life prolongation is only marginal. Physicians are the strongest proponents of combination immunotherapy. ConclusionThe valuation of the different treatment options differs in the four study groups with affected people valuing life prolongation much more. The individual value of cancer therapies is high, but differs from the societal standpoint.
Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital‐based Cancer Registry
Authors: Okamoto Masanori , Matsuoka Masatake , Soma Tamotsu , Arai Ryuta , Kato Hidenori , Harabayashi Toru , Adachi Hirohumi , Shinohara Toshiki , Sagawa Tamotsu , Nishiyama Noriaki , Nambu Toshikazu , Sakai Wataru , Suzuki Hiroaki , Kato Hiroyuki , Hiraga Hiroaki 
Published: July 2020

AbstractBackgroundHepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type.MethodsFrom a Hospital‐based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow‐up periods of less than 1 month. SPSS 25 was used for statistical analysis.ResultsThe risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793‐12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782‐10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275‐9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280‐9.231). The 2‐year survival rate after hepatic metastasis was 21.7%.ConclusionsThe onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow‐up after treatment.
Detachment of a prosthetic valve due to infective endocarditis caused by Streptococcus pneumoniae
Authors: Nakamura Saori , Hanayama Naoji , Matushita Hiroshi , Sakaki Kenjiro 
Published: July 2020

AbstractThe incidence of infective endocarditis (IE) due to S pneumoniae has decreased, thanks to antibiotics. However, when it does occur, it can be lethal. The present case provides a reminder of the potential lethality of this postoperative infection.
One‐Step Synthesis of Spin Crossover Nanoparticles Using Flow Chemistry and Supercritical CO2
Authors: Daro Nathalie , Vaudel Tony , Afindouli Luc , Marre Samuel , Aymonier Cyril , Chastanet Guillaume 
Published: July 2020

AbstractSwitchable materials are increasingly considered for implementation in devices or multifunctional composites leading to a strong need in terms of reliable synthetic productions of well‐defined objects. Here, an innovative and robust template‐free continuous process was developed to synthesize nanoparticles of a switchable coordination polymer, including the use of supercritical CO2, aiming at both quenching the particle growth and drying the powder. This all‐in‐one process offers a 12‐fold size reduction in a few minutes while maintaining the switching properties of the selected spin crossover coordination polymer.
Reversibly Switchable Fluorescent Molecular Systems Based on Metallacarborane–Perylenediimide Conjugates
Authors: Parejo Laura , Chaari Mahdi , Santiago Sara , Guirado Gonzalo , Teixidor Francesc , Núñez Rosario , Hernando Jordi 
Published: July 2020

AbstractIcosahedral metallacarboranes are θ‐shaped anionic molecules in which two icosahedra share one vertex that is a metal center. The most remarkable of these compounds is the anionic cobalt‐based metallacarborane [Co(C2B9H11)2]−, whose oxidation‐reduction processes occur via an outer sphere electron process. This, along with its low density negative charge, makes [Co(C2B9H11)2]− very appealing to participate in electron‐transfer processes. In this work, [Co(C2B9H11)2]− is tethered to a perylenediimide dye to produce the first examples of switchable luminescent molecules and materials based on metallacarboranes. In particular, the electronic communication of [Co(C2B9H11)2]− with the appended chromophore unit in these compounds can be regulated upon application of redox stimuli, which allows the reversible modulation of the emitted fluorescence. As such, they behave as electrochemically‐controlled fluorescent molecular switches in solution, which surpass the performance of previous systems based on conjugates of perylendiimides with ferrocene. Remarkably, they can form gels by treatment with appropriate mixtures of organic solvents, which result from the self‐assembly of the cobaltabisdicarbollide‐perylendiimide conjugates into 1D nanostructures. The interplay between dye π‐stacking and metallacarborane electronic and steric interactions ultimately governs the supramolecular arrangement in these materials, which for one of the compounds prepared allows preserving the luminescent behavior in the gel state.
Magnetic Correlation Engineering in Spin‐Sandwiched Layered Magnetic Frameworks
Authors: Fukunaga Hiroki , Kosaka Wataru , Nemoto Honoka , Taniguchi Kouji , Kawaguchi Shogo , Sugimoto Kunihisa , Miyasaka Hitoshi 
Published: July 2020

AbstractThe insertion of “sandwiched spins” between magnetic layers could efficiently affect the interlayer magnetic correlations, but doing so increases the complexity in the interlayer spin alignment because of competition between the inserted spin‐layer interaction JNNI and the interlayer through‐space interaction JNNNI if the magnitude of JNNI is of the same order as JNNNI with reciprocal signs of the respective interactions. Herein, systematic tuning of the magnetic phase variations by JNNI and JNNNI in two kinds of metal‐variable isostructural series of supramolecular pillared layer magnets [MCp*2][{Ru2II,II(2,3,5,6‐F4CO2)4}2(TCNQ)]⋅2 DCE (M=Co, Fe, Cr; 2,3,5,6‐F4PhCO2−=2,3,5,6‐tetrafluorobenzoate; TCNQ=7,7,8,8‐tetracyano‐p‐quinodimethane; DCE=1,2‐dichloroethane) and their DCE‐free series, in which [MCp*2]+ (Cp*=η5‐C5Me5) species with S=0, 1/2, and 3/2 for M=Co, Fe, Cr, respectively, are sandwiched between ferrimagnetic layers of [{Ru2}2(TCNQ)]−, is demonstrated. The results showed that the flexible magnetic natures of these magnets are changeable in dependence on JNNI and JNNNI, as well as on interlayer inserted spins M.
Enhancing Robustness of Sortase A by Loop Engineering and Backbone Cyclization
Authors: Zou Zhi , Mate Diana M. , Nöth Maximilian , Jakob Felix , Schwaneberg Ulrich 
Published: July 2020

AbstractStaphylococcus aureus sortase A (SaSrtA) is widely used for site‐specific protein modifications, but it lacks the robustness for performing bioconjugation reactions at elevated temperatures or in presence of denaturing agents. Loop engineering and subsequent head‐to‐tail backbone cyclization of SaSrtA yielded the cyclized variant CyM6 that has a 7.5 °C increased melting temperature and up to 4.6‐fold increased resistance towards denaturants when compared to the parent rM4. CyM6 gained up to 2.6‐fold (vs. parent rM4) yield of conjugate in ligation of peptide and primary amine under denaturing conditions.
Metal/Metal Redox Isomerism Governed by Configuration
Authors: Ludwig Stephan , Helmdach Kai , Hüttenschmidt Mareike , Oberem Elisabeth , Rabeah Jabor , Villinger Alexander , Ludwig Ralf , Seidel Wolfram W. 
Published: July 2020

AbstractA pair of diastereomeric dinuclear complexes, [Tp′(CO)BrW{μ‐η2‐C,C′‐κ2‐S,P‐C2(PPh2)S}Ru(η5‐C5H5)(PPh3)], in which W and Ru are bridged by a phosphinyl(thiolato)alkyne in a side‐on carbon P,S‐chelate coordination mode, were synthesized, separated and fully characterized. Even though the isomers are similar in their spectroscopic properties and redox potentials, the like‐isomer is oxidized at W while the unlike‐isomer is oxidized at Ru, which is proven by IR, NIR and EPR‐spectroscopy supported by spectro‐electrochemistry and computational methods. The second oxidation of the complexes was shown to take place at the metal left unaffected in the first redox step. Finally, the tipping point could be realized in the unlike isomer of the electronically tuned thiophenolate congener [Tp′(CO)(PhS)W{μ‐η2‐C,C′‐κ2‐S,P‐C2(PPh2)S}Ru(η5‐C5H5)‐(PPh3)], in which valence trapped WIII/RuII and WII/RuIII cationic species are at equilibrium.
Effect of Mild and Moderate Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of a Single Dose of Oral Ivosidenib in Otherwise Healthy Participants
Authors: Fan Bin , Dai David , Cohen Marvin , Xu Huansheng , Yin Feng , Nagaraja Raj , Mobilia Michelle , Almon Caroline , Basile Frank G. , Yang Hua 
Published: July 2020

AbstractIvosidenib, a small‐molecule inhibitor of mutant isocitrate dehydrogenase 1, is primarily cleared by hepatic metabolism. This open‐label study investigated the impact of hepatic impairment on ivosidenib pharmacokinetics (ClinicalTrials.gov: NCT03282513). Otherwise healthy participants with mild (n = 9) or moderate (n = 8) hepatic impairment (Child‐Pugh score) and matched participants with normal hepatic function (n = 16) received 1 oral dose of 500‐mg ivosidenib. Mild hepatic impairment had a negligible effect on total ivosidenib plasma exposure, with geometric mean ratios (90% confidence interval [CI]) of 0.933 (0.715‐1.22) for maximum concentration (Cmax) and 0.847 (0.624‐1.15) for area under the plasma concentration–time curve (AUC) in participants with mild hepatic impairment versus matched controls. Moderate hepatic impairment reduced total ivosidenib exposure by 28% to 44%, with geometric mean ratios (90%CI) of 0.565 (0.419‐0.763) for Cmax and 0.716 (0.479‐1.07) for AUC, although the 90%CI for AUC included 1.00. The ivosidenib unbound fraction was concentration dependent and higher in participants with mild/moderate hepatic impairment compared with matched controls. There was no apparent trend to increasing unbound Cmax with increased hepatic impairment severity. A single 500‐mg ivosidenib dose was well tolerated, with no serious or severe adverse events and no adverse events leading to discontinuation. We conclude that mild/moderate hepatic impairment did not lead to clinically relevant changes in ivosidenib exposure following a single 500‐mg dose.
Generation of transgenic mice that conditionally express microRNA miR‐145
Authors: Sawant Dwitiya , Klevenow Emilie , Baeten Jeremy T. , Thomas Shelby , Manivannan Sathiyanarayanan , Conway Simon J. , Lilly Brenda 
Published: July 2020

SummaryMicroRNAs are modulators of cellular phenotypes and their functions contribute to development, homeostasis, and disease. miR‐145 is a conserved microRNA that has been implicated in regulating an array of phenotypes. These include supporting smooth muscle differentiation, repression of stem cell pluripotency, and inhibition of tumor growth and metastasis. Previously, our lab demonstrated that miR‐145 acts to suppress cardiac fibrosis through inhibition of the TGF‐β signaling pathway. The range of effects that miR‐145 has on different cell types makes it an attractive microRNA for further study. Here we describe the generation of transgenic mice that conditionally express miR‐145 through Cre recombinase‐mediated activation. Characterization of individual founder lines indicates that overexpression of miR‐145 in the developing cardiovascular system has detrimental effects, with three independent miR‐145 transgenic lines exhibiting Cre‐dependent lethality. Expression analysis demonstrates that the transgene is robustly expressed and our analysis reveals a novel downstream target of miR‐145, Tnnt2. The miR‐145 transgenic mice represent a valuable tool to understand the role of miR‐145 in diverse cell types and to address its potential as a therapeutic mediator for the treatment of disease.
Minimum weighted clique cover on claw‐free perfect graphs
Authors: Bonomo Flavia , Oriolo Gianpaolo , Snels Claudia 
Published: July 2020

AbstractThe first combinatorial algorithm for the minimum weighted clique cover (MWCC) in a claw‐free perfect graph due to Hsu and Nemhauser dates back to 1984. It is essentially a “dual” algorithm as it relies on any algorithm for the maximum weighted stable set (MWSS) problem in claw‐free graphs and, taking into account the best‐known complexity for the latter problem, its complexity is . More recently, Chudnovsky and Seymour introduced a composition operation, strip composition, to define their structural results for claw‐free graphs; however, this composition operation is general and applies to nonclaw‐free graphs as well. In this paper, we show that an MWCC of a perfect strip‐composed graph, with the basic graphs belonging to a class , can be found in polynomial time, provided that the MWCC problem can be solved on in polynomial time. For the case of claw‐free perfect strip‐composed graphs, the algorithm can be tailored so that it never requires the computation of an MWSS on the strips and can be implemented as to run in time. Finally, building upon several results from the literature, we show how to deal with nonstrip‐composed claw‐free perfect graphs, and therefore compute an MWCC in a general claw‐free perfect graph in time.
Adult Sockeye Salmon Gastrically Tagged Near Spawning Grounds Exhibit Lower Survival Rates throughout the Spawning Period than Externally Tagged Conspecifics
Authors: Dick M. , Patterson D. A. , Robinson K. A. , Eliason E. J. , Hinch S. G. , Cooke S. J. 
Published: July 2020

Abstract
Telemetry is a common tool for studying the behavior and fate of migrating adult Pacific salmon Oncorhynchus spp., yet few field studies have compared behavior and fate associated with different tagging techniques. In this study, adult Harrison River (British Columbia) Sockeye Salmon O. nerka were captured in their natal river near spawning areas, radio-tagged by gastric insertion or external attachment in the dorsum, and released. Tagging occurred on 5 d spread over 3–8 weeks prior to spawning, thus encompassing fish in varying stages of maturity and freshwater residency. Tagged individuals were monitored over the spawning season by using fixed receiver stations and mobile tracking. The probability of fish moving upstream or downstream of the tagging site within 35 h of tagging was a function of tagging date but not tag type. Tag type significantly influenced fate, with almost twice as many externally tagged fish (41.6%; 42 of 101) surviving to reach spawning areas compared to gastrically tagged fish (22.4%; 21 of 94). The number of active externally tagged fish in the Harrison River system was consistently greater than the number of active gastrically tagged fish that received tags on the same date for four of the five tagging dates. External tag attachment may be a better approach than gastric insertion for studies that tag adult salmon near or on spawning areas.