bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnesium Polysulfides: Synthesis, Disproportionation, and Impedance Response in Symmetrical Carbon Electrode Cells
Authors: Drvarič Talian Sara , Vizintin Alen , Bitenc Jan , Aquilanti Giuliana , Randon‐Vitanova Anna , Gaberšček Miran , Dominko Robert 
Published: January 2021

AbstractMagnesium polysulfides have a key role during the redox reaction in magnesium‐sulfur batteries. However, kinetics of the Mg polysulfide disproportionation, transport, and solubility in electrolytes are rarely studied. To fill this gap, we here report the synthesis of different chain‐length Mg polysulfides and their characterization with 1H NMR, ATR‐IR, and XANES spectroscopies. The tendency of polysulfides to disproportionate in solutions is confirmed with UV/Vis spectroscopy. To probe their reactivity and diffusivity, impedance spectroscopy is performed in symmetrical cells consisting of two planar glassy carbon or porous carbon electrodes containing Mg polysulfide catholyte. Several transport‐reaction parameters are obtained, such as exchange current densities, chemical diffusion coefficients, transference numbers of polysulfides, and conductivities. Moreover, we show that the solubility of Mg polysulfides in Mg(TFSI)2, MgCl2 ether‐based electrolyte is affected at rather moderate concentration of polysulfides, thereby having an impact on the cell performance.
Synthesis and Biological Activity of Ferrocenyl and Ruthenocenyl Analogues of Etoposide: Discovery of a Novel Dual Inhibitor of Topoisomerase II Activity and Tubulin Polymerization
Authors: Chrabąszcz Karolina , Błauż Andrzej , Gruchała Martyna , Wachulec Marcin , Rychlik Błażej , Plażuk Damian 
Published: January 2021

AbstractTwo series of the ferrocenyl and ruthenocenyl analogues of etoposide bearing 1,2,3‐triazolyl or aminoalkyl linker were synthesized and evaluated for their cytotoxic properties, influence on the cell cycle, ability to induce tubulin polymerization, and inhibition of topoisomerase II activity. We found that the replacement of the etoposide carbohydrate moiety with a metallocenyl group led to organometallic conjugates exhibiting differentiated antiproliferative activity. Biological studies demonstrated that two ferrocenylalkylamino conjugates were notably more active than etoposide, with submicromolar or low‐micromolar IC50 values towards SW620, etoposide‐resistant SW620E, and methotrexate‐resistant SW620M cancer cell lines. Moreover, the simplest ferrocenylmethylamino conjugate exerted dual inhibitory action against tubulin polymerization and topoisomerase II activity while other studied compounds affected only topoisomerase II activity.
Diastereoselective Synthesis of Functionalized 5‐Amino‐3,4‐Dihydro‐2H‐Pyrrole‐2‐Carboxylic Acid Esters: One‐Pot Approach Using Commercially Available Compounds and Benign Solvents
Authors: Meninno Sara , Carratù Mario , Overgaard Jacob , Lattanzi Alessandra 
Published: January 2021

AbstractA novel three‐step four‐transformation approach to highly functionalized 5‐amino‐3,4‐dihydro‐2H‐pyrrole‐2‐carboxylic acid esters, starting from commercially available phenylsulfonylacetonitrile, aldehydes, and N‐(diphenylmethylene)glycine tert‐butyl ester, was developed. The one‐pot strategy delivered this class of amidines bearing, for the first time, three contiguous stereocenters, in good to high yield and diastereoselectivity. The entire sequence was carried out using diethyl carbonate and 2‐methyl tetrahydrofuran as benign solvents, operating under metal‐free conditions. The process could be conveniently scaled‐up, and the synthetic utility of the products was demonstrated.
On the relevance of boundary conditions and viscosity models in blood flow simulations in patient‐specific aorto‐coronary bypass models
Authors: Jonášová Alena , Vimmr Jan 
Published: January 2021

AbstractPhysiologically realistic results are the aim of every blood flow simulation. This is not different in aorto‐coronary bypasses where the properties of the coronary circulation may significantly affect the relevance of the performed simulations. By considering three patient‐specific bypass geometries, the present article focuses on two aspects of the coronary blood flow – its phasic flow pattern and its behaviour affected by blood rheology. For the phasic flow property, a multiscale modelling approach is chosen as a means to assess the ability of five different types of coronary boundary conditions (mean arterial pressure, Windkessel model and three lumped parameter models) to attain realistic coronary haemodynamics. From the analysed variants of boundary conditions, the best option in terms of physiological characteristics and its potential for use in patient‐based simulations, is utilised to account for the effect of shear‐dependent viscosity on the resulting haemodynamics and wall shear stress stimulation. Aside from the Newtonian model, the blood rheology is approximated by two non‐Newtonian models in order to determine whether the choice of a viscosity model is important in simulations involving coronary circulation. A comprehensive analysis of obtained results demonstrated notable superiority of all lumped parameter models, especially in comparison to the constant outlet pressure, which regardless of bypass type gave overestimated and physiologically misleading results. In terms of rheology, it was noted that blood in undamaged coronary arteries behaves as a Newtonian fluid, whereas in vessels with atypical lumen geometry, such as that of anastomosis or stenosis, its shear‐thinning behaviour should not be ignored.
Safety, Pharmacokinetics, and Pharmacodynamics of Trazpiroben (TAK‐906), a Novel Selective D2/D3 Receptor Antagonist: A Phase 1 Randomized, Placebo‐Controlled Single‐ and Multiple‐Dose Escalation Study in Healthy Participants
Authors: Whiting Roger L. , Darpo Borje , Chen Chunlin , Fletcher Margaret , Combs Dan , Xue Hongqi , Stoltz Randall R. 
Published: January 2021

AbstractGastroparesis is a chronic neuromuscular disorder of the upper gastrointestinal tract in which episodic exacerbation can lead to frequent hospitalizations and severe disability. Dopamine D2/D3 receptor antagonists have been used to treat patients with gastroparesis with some efficacy; however, their chronic use is limited owing to associated central nervous system (CNS) or cardiovascular safety concerns. Trazpiroben (TAK‐906) is a dopamine D2/D3 receptor antagonist under development for the long‐term treatment of gastroparesis. Preclinical studies in rat and dog have shown trazpiroben to have minimal brain penetration and low affinity for the human ether‐à‐go‐go‐related gene (hERG) potassium channel (IC50, 15.6 µM), thereby reducing the risk of the CNS and cardiovascular adverse effects seen with other dopamine D2/D3 receptor antagonists. This phase 1 trial evaluated the safety, pharmacokinetics, and pharmacodynamics of trazpiroben in healthy participants. Trazpiroben was rapidly absorbed and eliminated (Tmax, ∼1.1 hours; t1/2, 4–11 hours) after administration of single (5–300 mg) and multiple (50 or 100 mg) doses. Receptor target engagement was confirmed for all doses, as indicated by an increase in serum prolactin levels compared with placebo (mean prolactin Cmax, 134.3 ng/mL after administration of trazpiroben 10 mg vs 16.1 ng/mL with placebo). Therapeutically relevant single and multiple doses of trazpiroben were well tolerated in healthy participants, and no clinically meaningful cardiovascular adverse effects were observed across the whole dose range. These data support the further development of trazpiroben for the treatment of gastroparesis.
A Randomized, Double‐Blind, Placebo‐Controlled, Multiple Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of ELX‐02 in Healthy Subjects
Authors: Leubitz Andi , Vanhoutte Frederic , Hu Ming‐yi , Porter Kaela , Gordon Efrat , Tencer Kathleen , Campbell Kathleen , Banks Kate , Haverty Tom 
Published: January 2021

AbstractELX‐02 is an investigational compound being developed as a therapy for genetic diseases caused by nonsense mutations such as cystic fibrosis. Structurally, ELX‐02 is an aminoglycoside analogue that induces read‐through of nonsense mutations through interaction with the ribosome, resulting in the production of full‐length functional proteins. This phase 1 multiple‐ascending‐dose trial evaluated the safety and pharmacokinetics of ELX‐02 in 62 healthy volunteers. ELX‐02 plasma exposure was dose proportional, with no apparent accumulation, and followed by renal elimination. The most reported adverse event was injection site reactions that were mild to moderate in severity. At the top dose of 5.0 mg/kg, 1 of 6 subjects experienced auditory threshold changes in which ototoxicity could not be clearly ruled out, and 2 of 6 had hearing threshold changes consistent with possible ototoxicity. Two of 3 subjects receiving placebo in the 5.0 mg/kg group also had significant hearing threshold changes. All observed hearing threshold changes resolved or were trending toward resolution after withdrawal of the study drug. No severe or serious adverse events were reported.The results of this study support the evaluation of ELX‐02 in phase 2 clinical trials with patients that have genetic diseases caused by nonsense mutations.
Pivotal Dose of Pembrolizumab: A Dose‐Finding Strategy for Immuno‐Oncology
Authors: Li Tommy R. , Chatterjee Manash , Lala Mallika , Abraham Anson K. , Freshwater Tomoko , Jain Lokesh , Sinha Vikram , de Alwis Dinesh P. , Mayawala Kapil 
Published: January 2021

Despite numerous publications emphasizing the value of dose finding, drug development in oncology is dominated by the mindset that higher dose provides higher efficacy. Examples of dose finding implemented by biopharmaceutical firms can change this mindset. The purpose of this article is to outline a pragmatic dose selection strategy for immuno‐oncology (IO) and other targeted monoclonal antibodies (mAbs). The approach was implemented for pembrolizumab. Selecting a recommended phase II dose (RP2D) with a novel mechanism of action is often challenging due to uncertain relationships between pharmacodynamics measurements and clinical end points. Additionally, phase I efficacy and safety data are generally inadequate for RP2D selection for IO mAbs. Here, the RP2D was estimated based on phase I (clinical study KN001 A and A2) pharmacokinetics data as the dose required for target saturation, which represents a surrogate for maximal pharmacological effect for antagonist mAbs. Due to limitations associated with collecting and analyzing tumor biopsies, characterizing intratumoral target engagement (TE) is challenging. To overcome this gap, a physiologically‐based pharmacokinetic model was implemented to predict intratumoral TE. As tumors are spatially heterogeneous, TE was predicted in well‐vascularized and poorly vascularized tumor regions. Additionally, impact of differences in target expression, for example, due to interindividual variability and cancer type, was simulated. Simulations showed that 200 mg every 3 weeks can achieve ≥ 90% TE in clinically relevant scenarios, resulting in the recommendation of 200 mg every 3 weeks as the RP2D. Randomized dose comparison studies (KN001 B2 and D) showing similar efficacy over a fivefold dose/exposure range confirmed the RP2D as the pivotal dose.
Pathological and immunological differences of arterial thrombi and wall caused by three different periodontal bacterial injections in rat models and proposals on the pathogeneses of vascular diseases
Authors: Iwai Takehisa , Matsui Yoshiki , Homma Kaori , Takemura Tamiko , Fujiwara Mutsunori , Aoyama Norio , Furukawa Asuka , Sato Hiroki , Izumi Yuichi 
Published: January 2021

AbstractObjectivesPeriodontal bacteria that have been studied show a strong connection to various vascular diseases. Among the many kinds of periodontal bacteria, Porphyromonas gingivalis (Pg) is well examined in the general aspects and in a rat model. However, whether other periodontal bacteria work or react differently is not studied well.Material and methodsWe chose Aggregatibacter actinomycetemcomitans (Aa) and Prevotella intermedia (Pi) as different types of periodontal bacteria. Low‐density and high‐density bacterial solutions were injected in the small artery of rats' groins using our rat model. Eighteen limbs of 9 SD male rats (500–650 g) were used. After 7 days, 14–18 days, and 28 days, the rats were sacrificed. A pathological and an immuno‐histochemical study was conducted and reported on the low‐density group with 12 limbs because the Pi group lacked a high‐density study. Immuno‐histochemical staining of live Pg was performed on three limbs of three rats at 1 h, 3 h, and 1 week after injection.ResultsThe appearances from the acute, at 7 days, to chronic phases, at 28 days, were observed. The differences of the species were certainly observed in the internal elastic lamina (IEL), and immuno‐histochemical reactions. The inflammatory reactions, such as cellular distribution or intra‐thrombus materials, were similar in all. One week later, we could not see any living bacteria in the specimen or immunological observation.ConclusionsThe three species were essentially the same, except for Aa's stronger disruption of IEL, and more CD3 (Pan T cell) in Pi and more CD79a (Pan B cell) in Pg. We propose a new concept of a possible mechanism of vascular diseases, in which the work of LPS (lipopolysaccharides) and a toll‐like receptor (TLR) is emphasized.
Sustainable human resources management in crisis contexts: Interaction of socially responsible labour practices for the wellbeing of employees
Authors: Sorribes Joan , Celma Dolors , Martínez‐Garcia Esther 
Published: January 2021

AbstractPeriods of recession and economic crisis pose great challenges to companies committed to quality of work and by extension to their human resources (HR) departments. The need for adjustments can be a great opportunity for the implementation of socially responsible labour practices for the wellbeing of employees and in line with sustainable development and sustainable development goals. This study analyses the effects of the interaction between different socially responsible human resource management labour practices on three variables of employee wellbeing: job satisfaction, job stress and trust in management. Prior to the application of various statistical models, a correlation analysis of labour practices is carried out. Two types of statistical models are used depending on the type of variable to be explained. The ordinal logit has been applied to variables ‘trust in management’ and ‘level of job stress,’ which are not continuous. And the linear regression model for the variable ‘job satisfaction,’ which is continuous. Based on the analysis of data from 1346 workers from the 2010 Quality of Life at Work Survey in Catalonia, the results show the effectiveness of the combination of applied practices related to personal quality of life aspects, such as work‐life balance, non‐discrimination or environmental workplace conditions, as a determining factor for generally increasing the wellbeing of employees in times of crisis. However, practices aimed at achieving greater employee involvement, are more effective when applied individually. The importance of job stability to increase employee wellbeing in times of crisis is to be highlighted.
Whether an innovation act as a catalytic moderator between corporate social responsibility performance and stated owned and non‐state owned enterprises' performance or not? An evidence from Pakistani listed firms
Authors: Tang Yingkai , Akram Aswad , Cioca Lucian‐Ionel , Shah Syed Ghulam Meran , Qureshi Muhammad Asim Ali 
Published: January 2021

AbstractThe objective of the study is to signify the impact of corporate social responsibility performance on state‐owned and non‐state‐owned enterprises' performance. The contributive concept of CSR performance has been formulated while contemplating total tax, staff expenditure, public welfare expenditure, social cost and total equity. To contemplate with deep insight, the moderating role of innovation input and output has been substantiated through empirical results. The data of 502 listed companies on Securities and Exchange Commission of Pakistan has been endorsed for years 2009–2018. Empirical underpinnings reveal that corporate social responsibility performance boosts the non‐state‐owned enterprises' performance vehemently while state‐owned enterprises have proclaimed insignificant results. Comprehensively, innovation input has decelerated the Non‐state owned Enterprises' performance while innovation output has remained insignificant. Specifically, leverage has been signified as the most deterrent vehicle for declining the Non‐State Owned Enterprises' performance. Intuitively, the theoretical contribution is manifested while deducing the implicative aspect of legitimacy theory which emphasizes on the adoption of corporate social responsibility. Implicatively, the study recommends to ameliorate the corporate structure of state‐owned enterprises comprehensively so that advantage of corporate social responsibility may be attained vigorously. Doubtlessly, empirical results are reliable and authenticated due to the execution of GMM and 2SLS instrumental regressions.
The Competing Demands of Patient Privacy and Clinical Research
Authors: Ulrich Connie M. , Grady Christine , Demiris George , Richmond Therese S. 
Published: January 2021

ABSTRACTPrivacy and confidentiality of personal medical information are cornerstones of ethical clinical care and ethical research. But real‐world research has challenged traditional ways of thinking about privacy and confidentiality of information. In today's world of “big data” and learning health care systems, researchers and others are combining multiple sources of information to address complex problems. We present a case study that highlights the ethical concerns that arise when a patient who is employed by an academic medical center learns through a research invitational letter that her private information was accessed at this center without her consent. We discuss the ethical challenges of balancing patient privacy with advancing clinical research and ask, what level of privacy and confidentiality can and should patients expect from their clinician providers, fellow research colleagues, and institutions?
Identification of novel bacterial biomarkers to detect bird scavenging by invasive rats
Authors: Muletz‐Wolz Carly R. , Wilson Rankin Erin , McGrath‐Blaser Sarah , Venkatraman Madhvi , Maldonado Jesús E. , Gruner Daniel S. , Fleischer Robert C. 
Published: January 2021

AbstractRapid advances in genomic tools for use in ecological contexts and non‐model systems allow unprecedented insight into interactions that occur beyond direct observation. We developed an approach that couples microbial forensics with molecular dietary analysis to identify species interactions and scavenging by invasive rats on native and introduced birds in Hawaii. First, we characterized bacterial signatures of bird carcass decay by conducting 16S rRNA high‐throughput sequencing on chicken (Gallus gallus domesticus) tissues collected over an 11‐day decomposition study in natural Hawaiian habitats. Second, we determined if field‐collected invasive black rats (Rattus rattus; n = 51, stomach and fecal samples) had consumed birds using molecular diet analysis with two independent PCR assays (mitochondrial Cytochrome Oxidase I and Cytochrome b genes) and Sanger sequencing. Third, we characterized the gut microbiome of the same rats using 16S rRNA high‐throughput sequencing and identified 15 bacterial taxa that were (a) detected only in rats that consumed birds (n = 20/51) and (b) were indicative of decaying tissue in the chicken decomposition experiment. We found that 18% of rats (n = 9/51) likely consumed birds as carrion by the presence of bacterial biomarkers of decayed tissue in their gut microbiome. One species of native bird (Myadestes obscurus) and three introduced bird species (Lophura leucomelanos, Meleagris gallopavo, Zosterops japonicus) were detected in the rats’ diets, with individuals from these species (except L. nycthemera) likely consumed through scavenging. Bacterial biomarkers of bird carcass decay can persist through rat digestion and may serve as biomarkers of scavenging. Our approach can be used to reveal trophic interactions that are challenging to measure through direct observation.
Energetic efficiency of foraging mediates bee niche partitioning
Authors: Balfour Nicholas J. , Shackleton Kyle , Arscott Natalie A. , Roll‐Baldwin Kimberley , Bracuti Anthony , Toselli Gioelle , Ratnieks Francis L.W. 
Published: January 2021

AbstractRevitalizing our understanding of species distributions and assembly in community ecology requires greater use of functional (physiological) approaches based on quantifiable factors such as energetics. Here, we explore niche partitioning between bumble and honey bees by comparing a measure of within‐patch foraging efficiency, the ratio of flower visitation rate (proportional to energy gain) to body mass (energy cost). This explained a remarkable 74% of the variation in the proportions of bumble to honey bees across 22 plant species and was confirmed using detailed energy calculations. Bumble bees visited flowers at a greater rate (realizing greater energy benefits) than honey bees, but were heavier (incurring greater energy costs) and predominated only on plant species where their benefit : cost ratio was higher than for honey bees. Importantly, the competition between honey bees and bumble bees had no consistent winner, thus highlighting the importance of plant diversity to the coexistence of competing bees. By contrast, tongue : corolla‐tube‐length ratio explained only 7% of the variation (non‐significant). Our results confirm the importance of energetics in understanding community ecology and bee foraging niche and highlight the energetic tightrope navigated by foraging bees, since approximately half the nectar energy gained was expended in its collection.
Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis
Authors: Pius‐Sadowska Ewa , Machaliński Bogusław 
Published: January 2021

AbstractCardiac innervation density generally reflects the levels of nerve growth factor (NGF) produced by the heart—changes in NGF expression within the heart and vasculature contribute to neuronal remodelling (e.g. sympathetic hyperinnervation or denervation). Its synthesis and release are altered under different pathological conditions. Although NGF is well known for its survival effects on neurons, it is clear that these effects are more wide ranging. Recent studies reported both in vitro and in vivo evidence for beneficial actions of NGF on cardiomyocytes in normal and pathological hearts, including prosurvival and antiapoptotic effects. NGF also plays an important role in the crosstalk between the nervous and cardiovascular systems. It was the first neurotrophin to be implicated in postnatal angiogenesis and vasculogenesis by autocrine and paracrine mechanisms. In connection with these unique cardiovascular properties of NGF, we have provided comprehensive insight into its function and potential effect of NGF underlying heart sustainable/failure conditions. This review aims to summarize the recent data on the effects of NGF on various cardiovascular neuronal and non‐neuronal functions. Understanding these mechanisms with respect to the diversity of NGF functions may be crucial for developing novel therapeutic strategies, including NGF action mechanism‐guided therapies.