bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug‐induced shortening of the electromechanical window is an effective biomarker for in silico prediction of clinical risk of arrhythmias
Authors: Passini Elisa , Trovato Cristian , Morissette Pierre , Sannajust Frederick , Bueno‐Orovio Alfonso , Rodriguez Blanca 
Published: July 2019

Background and PurposeEarly identification of drug‐induced cardiac adverse events is key in drug development. Human‐based computer models are emerging as an effective approach, complementary to in vitro and animal models. Drug‐induced shortening of the electromechanical window has been associated with increased risk of arrhythmias. This study investigates the potential of a cellular surrogate for the electromechanical window (EMw) for prediction of pro‐arrhythmic cardiotoxicity, and its underlying ionic mechanisms, using human‐based computer models.Experimental ApproachIn silico drug trials for 40 reference compounds were performed, testing up to 100‐fold the therapeutic concentrations (EFTPCmax) and using a control population of human ventricular action potential (AP) models, optimised to capture pro‐arrhythmic ionic profiles. EMw was calculated for each model in the population as the difference between AP and Ca2+ transient durations at 90%. Drug‐induced changes in the EMw and occurrence of repolarisation abnormalities (RA) were quantified.Key ResultsDrugs with clinical risk of Torsade de Pointes arrhythmias induced a concentration‐dependent EMw shortening, while safe drugs lead to increase or small change in EMw. Risk predictions based on EMw shortening achieved 90% accuracy at 10× EFTPCmax, whereas RA‐based predictions required 100× EFTPCmax to reach the same accuracy. As it is dependent on Ca2+ transient, the EMw was also more sensitive than AP prolongation in distinguishing between pure hERG blockers and multichannel compounds also blocking the calcium current.Conclusion and ImplicationsThe EMw is an effective biomarker for in silico predictions of drug‐induced clinical pro‐arrhythmic risk, particularly for compounds with multichannel blocking action.
Mibefradil, a T‐type Ca2+ channel blocker also blocks Orai channels by action at the extracellular surface
Authors: Li Pengyun , Rubaiy Hussein N. , Chen Gui‐Lan , Hallett Thomas , Zaibi Nawel , Zeng Bo , Saurabh Rahul , Xu Shang‐Zhong 
Published: July 2019

Background and PurposeMibefradil, a T‐type Ca2+ channel blocker, has been investigated for treating solid tumours. However, its underlying mechanisms are still unclear. Here, we have investigated the pharmacological actions of mibefradil on Orai store‐operated Ca2+ channels.Experimental ApproachHuman Orai1‐3 cDNAs in tetracycline‐regulated pcDNA4/TO vectors were transfected into HEK293 T‐REx cells with stromal interaction molecule 1 (STIM1) stable expression. The Orai currents were recorded by whole‐cell and excised‐membrane patch clamp. Ca2+ influx or release was measured by Fura‐PE3/AM. Cell growth and death were monitored by WST‐1, LDH assays and flow cytometry.Key ResultsMibefradil inhibited Orai1, Orai2, and Orai3 currents dose‐dependently. The IC50 for Orai1, Orai2, and Orai3 channels was 52.6, 14.1, and 3.8 μM respectively. Outside‐out patch demonstrated that perfusion of 10‐μM mibefradil to the extracellular surface completely blocked Orai3 currents and single channel activity evoked by 2‐APB. Intracellular application of mibefradil did not alter Orai3 channel activity. Mibefradil at higher concentrations (>50 μM) inhibited Ca2+ release but had no effect on cytosolic STIM1 translocation evoked by thapsigargin. Inhibition on Orai channels by mibefradil was structure‐related, as other T‐type Ca2+ channel blockers with different structures, such as ethosuximide and ML218, had no or minimal effects on Orai channels. Moreover, mibefradil inhibited cell proliferation, induced apoptosis, and arrested cell cycle progression.Conclusions and ImplicationsMibefradil is a potent cell surface blocker of Orai channels, demonstrating a new pharmacological action of this compound in regulating cell growth and death, which could be relevant to its anti‐cancer activity.
Changes in whole metabolites after exenatide treatment in overweight/obese polycystic ovary syndrome patients
Authors: Tang Liang , Yuan Lei , Yang Gangyi , Wang Feng , Fu Mao , Chen Min , Liu Dongfang 
Published: July 2019

AbstractObjectiveExenatide is a new agent for diabetes therapy, and its use in polycystic ovary syndrome (PCOS) has gradually increased; however, the clinical benefit and metabolic improvement need further evidence. This research aimed to study the changes in whole metabolites before and after exenatide treatment in overweight/obese PCOS patients to gain a better understanding of exenatide for the treatment of PCOS.MethodsSixty‐seven women, including 32 with PCOS and 35 age‐matched controls, were recruited. The metabolite changes were detected with nontargeted gas chromatography‐tandem mass spectrometry (NTGC‐MS) before and after exenatide treatment, and changes in clinical biochemical characteristics were also observed.ResultsA total of 62 metabolites were differentially expressed between the healthy and PCOS groups, and 31 differentially expressed metabolites were detected before and after exenatide treatment. Abnormal lipid metabolism and amino acid metabolism were the main metabolic disorders. Exenatide improved lipid and amino acid metabolism, especially amino acid metabolites. Three types of branched‐chain amino acids (valine, leucine and isoleucine), two types of aromatic amino acids (phenylalanine and tyrosine) and lysine are important potential metabolites for the therapeutic efficacy of exenatide. Many abnormal metabolic disorders are related to insulin resistance, oxidative stress and even ovulatory dysfunction. Moreover, in this small sample clinical study, we also found that exenatide improved insulin sensitivity, reduced body weight and improved glycolipid metabolism in PCOS.ConclusionsNTGC‐MS‐based metabolic pathway analysis revealed that exenatide has a beneficial effect on overweight/obese PCOS patients by regulating metabolic disorders, especially amino acid disorders.
The Embodied Penman: Effector‐Specific Motor–Language Integration During Handwriting
Authors: Afonso Olivia , Suárez‐Coalla Paz , Cuetos Fernando , Ibáñez Agustín , Sedeño Lucas , García Adolfo M. 
Published: July 2019

AbstractSeveral studies have illuminated how processing manual action verbs (MaVs) affects the programming or execution of concurrent hand movements. Here, to circumvent key confounds in extant designs, we conducted the first assessment of motor–language integration during handwriting—a task in which linguistic and motoric processes are co‐substantiated. Participants copied MaVs, non‐manual action verbs, and non‐action verbs as we collected measures of motor programming and motor execution. Programming latencies were similar across conditions, but execution was faster for MaVs than for the other categories, regardless of whether word meanings were accessed implicitly or explicitly. In line with the Hand‐Action‐Network Dynamic Language Embodiment (HANDLE) model, such findings suggest that effector‐congruent verbs can prime manual movements even during highly automatized tasks in which motoric and verbal processes are naturally intertwined. Our paradigm opens new avenues for fine‐grained explorations of embodied language processes.
Myth debunked: Keratinous pangolin scales do not contain the analgesic tramadol
Authors: Jacobs Rachel L. , McClure Pamela J. , Baker Barry W. , Espinoza Edgard O. 
Published: July 2019

AbstractConservation plans aiming to reduce the threat of illegal wildlife trade increasingly recognize the need for multifaceted approaches that include both enhanced enforcement and demand reduction initiatives. Both are complex issues that involve understanding consumer motives. Pangolins represent some of the most heavily trafficked species, largely due to high consumer demand for their scales for use in traditional medicines. Recent media reports also suggest that demand is related to the purported presence of the analgesic tramadol in scales. We examined chemotypes of scales from 104 individual pangolins representing all extant species. None of the specimens demonstrated the presence of tramadol. Given that demand for pangolins and their parts is decimating wild populations, it is imperative that such false claims be rectified. These results could be incorporated into demand reduction campaigns in areas where this misinformation is perpetuated.
The relation between subitizable symbolic and non‐symbolic number processing over the kindergarten school year
Authors: Hutchison Jane E. , Ansari Daniel , Zheng Samuel , De Jesus Stefanie , Lyons Ian M. 
Published: July 2019

AbstractA long‐standing debate in the field of numerical cognition concerns the degree to which symbolic and non‐symbolic processing are related over the course of development. Of particular interest is the possibility that this link depends on the range of quantities in question. Behavioral and neuroimaging research with adults suggests that symbolic and non‐symbolic quantities may be processed more similarly within, relative to outside of, the subitizing range. However, it remains unclear whether this unique link exists in young children at the outset of formal education. Further, no study has yet taken numerical size into account when investigating the longitudinal influence of these skills. To address these questions, we investigated the relation between symbolic and non‐symbolic processing inside versus outside the subitizing range, both cross‐sectionally and longitudinally, in 540 kindergarteners. Cross‐sectionally, we found a consistently stronger relation between symbolic and non‐symbolic number processing within versus outside the subitizing range at both the beginning and end of kindergarten. We also show evidence for a bidirectional relation over the course of kindergarten between formats within the subitizing range, and a unidirectional relation (symbolic → non‐symbolic) for quantities outside of the subitizing range. These findings extend current theories on symbolic and non‐symbolic magnitude development by suggesting that non‐symbolic processing may in fact play a role in the development of symbolic number abilities, but that this influence may be limited to quantities within the subitizing range.
Modes of timing and spacing professional decisions: On the relationship between costing and caring in child protection work
Authors: Schrøder Ida 
Published: July 2019

AbstractWithin public sector accounting research, the question of how “costing” is implemented and how it transforms professional “caring” work has been widely studied and debated. Studies have, for instance, pointed to contextual variables that make cost information more or less useful in professional decision making. However, in doing so, scholars also assume that decision making follows a linear path that can be informed and transformed by cost information. In this paper, I take it as my starting point that both costing and caring vary as they are combined in professional decision‐making processes. I use the broad and processual definition of calculation from the work of Callon and Muniesa to analyze how distinctions about vulnerable children's situations are made relevant for the choice and delimitation of social services. This allows me to investigate how, when, and where distinctions between costing and caring are drawn rather than assuming that costing and caring are preexisting and stable practices that can be put to use or not.
Observation of irrigation‐induced climate change in the Midwest United States
Authors: Nocco Mallika A. , Smail Robert A. , Kucharik Christopher J. 
Published: July 2019

AbstractIrrigated agriculture alters near‐surface temperature and humidity, which may mask global climate change at the regional scale. However, observational studies of irrigation‐induced climate change are lacking in temperate, humid regions throughout North America and Europe. Despite unknown climate impacts, irrigated agriculture is expanding in the Midwest United States, where unconfined aquifers provide groundwater to support crop production on coarse soils. This is the first study in the Midwest United States to observe and quantify differences in regional climate associated with irrigated agricultural conversion from forests and rainfed agriculture. To this end, we established a 60 km transect consisting of 28 stations across varying land uses and monitored surface air temperature and relative humidity for 31 months in the Wisconsin Central Sands region. We used a novel approach to quantify irrigated land use in both space and time with a database containing monthly groundwater withdrawal estimates by parcel for the state of Wisconsin. Irrigated agriculture decreased maximum temperatures and increased minimum temperatures, thus shrinking the diurnal temperature range (DTR) by an average of 3°C. Irrigated agriculture also decreased the vapor pressure deficit (VPD) by an average of 0.10 kPa. Irrigated agriculture significantly decreased evaporative demand for 25% and 66% of study days compared to rainfed agriculture and forest, respectively. Differences in VPD across the land‐use gradient were highest (0.21 kPa) during the peak of the growing season, while differences in DTR were comparable year‐round. Interannual variability in temperature had greater impacts on differences in DTR and VPD across the land‐use gradient than interannual variability in precipitation. These regional climate changes must be considered together with increased greenhouse gas emissions, changes to groundwater quality, and surface water degradation when evaluating the costs and benefits of groundwater‐sourced irrigation expansion in the Midwest United States and similar regions around the world.
The blue economy: Identifying geographic concepts and sensitivities
Authors: Garland Michaela , Axon Stephen , Graziano Marcello , Morrissey John , Heidkamp C. Patrick 
Published: July 2019

AbstractThere is currently no generally accepted definition for the “blue economy,” despite the term becoming common parlance over the past decade. The concept and practice have spawned a rich, and diverse, body of scholarly activity. Yet despite this emerging body of literature, there is ambiguity around what the blue economy is, what it encapsulates, and its practices. Thus far, the existing literature has failed to theorise key geographical concepts such as space, place, scale, and power relations, all of which have the potential to lead to uneven development processes and regional differentiation. Previous research has sought to clarify the ontological separation of land and sea or has conceptualised the blue economy as a complex governmental project that opens up new governable spaces and rationalises particular ways of managing marine and coastal regions. More recently, geographers have called for a critical—and practical—engagement with the blue economy. This paper critically examines the existing literature of the geographies of the blue economy through a structured meta‐analysis of published work, specifically its conceptualisations and applications to debates in the field. Results offer the potential to ground a bottom‐up definition of the blue economy. In so doing, this paper provides a clearly identifiable rubric of the key geographical concepts that are often overlooked by researchers, policymakers, and practitioners when promoting economic development and technological innovation in coastal and marine environments.
Microstructural evolution and fracture toughness of plasma sprayed CNT reinforced Yttria‐stabilized Hafnia coating
Authors: Pathak Abhishek , Mathiyalagam Sribalaji , Pandey Krishna Kant , Bijalwan Pavan , Dutta Monojit , Keshri Anup Kumar 
Published: July 2019

AbstractYttria (8 wt%)‐stabilized hafnia (YSH) and carbon nanotubes (CNTs) (1 wt%) reinforced yttria‐stabilized hafnia (YSHC) coatings were fabricated on alumina substrate using atmospheric plasma spray technique. Raman spectra confirmed the survival of CNTs in plasma sprayed YSHC coating and indicated about graphitization of CNTs. Whereas, the FE‐SEM micrograph infers the presence of few 2‐D graphene platelet‐like structure in plasma sprayed YSHC coating. Addition of 1 wt% CNTs has significantly increased the densification of YSH coating from 86% to 92%, whereas average hardness and elastic modulus increased by ~57% and ~16%, respectively. A phenomenal increase of ~125% in relative fracture toughness was observed in YSHC coating, which is attributed to three major factors viz. (a) Enhanced densification (b) High fraction of fully melted regions and (c) Various toughening mechanisms, like CNTs pull out, CNTs braiding, graphene splat wrapping, CNTs anchoring.
Bitter‐tasting hydrophobic peptides prepared from soy sauce using aqueous ethanol solutions influence taste sensation
Authors: Zhu Xiping , Sun‐Waterhouse Dongxiao , Chen Jiahui , Cui Chun , Wang Wei 
Published: July 2019

SummaryIn this study, bitter‐tasting hydrophobic peptides were prepared and purified from soy sauce using aqueous ethanol solutions and ion exchange resin, and analysed using RP‐HPLC and UPLC‐Q‐TOF‐MS/MS. Most of bitter fraction from soy sauce was obtained by treatments involving 80% ethanol and subsequent chromatographic separation. This fraction contained sixteen small peptides (molecular weight < 1000 Da; rich in hydrophobic amino acids with Lys‐Pro (KP), Glu‐Phe (EF), Glu‐Val (EV), Asp‐Leu (DL), Leu‐Trp (LW) and Asp‐Pro (DP)) capable of enhancing significantly (P < 0.05) umaminess and/or imparting kokumi effect in taste reconstitution experiments. Thus, the bitter peptides affected bitterness as well as other taste sensations like umaminess, kokuminess and saltiness. This was the first study to report the impacts of the bitter‐tasting hydrophobic peptides on soy sauce and solutions of salt, monosodium l‐glutamate.
Dye use in fresh meat preparations and meat products: a survey by a validated method based on HPLC‐UV‐diode array detection as a contribution to risk assessment
Authors: Iammarino Marco , Mentana Annalisa , Centonze Diego , Palermo Carmen , Mangiacotti Michele , Chiaravalle Antonio Eugenio 
Published: July 2019

SummaryThe use of dyes in meats has to be monitored, due to food safety concerns. The presence of twelve dyes (Amaranth, Ponceau 4R, Carmine, Ponceau SX, Ponceau 3R, Allura Red AC, Carmoisine, Erythrosine, Sudan I, Sudan II, Sudan III and Sudan IV) in meat was investigated in 130 meat product and fresh meat preparation samples, and the dietary exposure was estimated. Carmine and Ponceau 4R were the identified dyes. Except for one sample of salami, they were regularly indicated on the label, and their concentrations were in the range 1.3–8.1 and 6.2–86.4 mg kg−1 for Ponceau 4R and Carmine, respectively. Concerning fresh meat preparations, Carmine was detected in three samples, confirming that this dye is still used, although it is no longer authorised in these products. Regarding dietary exposure estimate, the daily intake from meat product consumption resulted lower than 1% of the ADI, both for Carmine and Ponceau 4R.
Full blood count and white cell differential count reference ranges obtained from a healthy urban South African population residing in the Western Cape of South Africa
Authors: Smit Francois C. , Davison Glenda M. , Hoffmann Mariza , Erasmus Rajiv T. , Davids Saarah , Matsha Tandi E. 
Published: July 2019

AbstractBackgroundResearch has suggested that individuals of African descent have lower white cell and neutrophil counts than Caucasians. These differences could lead to incorrect clinical decisions, and therefore, ethnic‐specific reference ranges are required. The Western Cape region of South Africa is uniquely diverse, comprising Caucasian, Mixed Ancestry and those of African descent. The aim of this study was to compare the full blood count and differential counts across the three major ethnic groups residing in this area and to propose appropriate RIs.MethodsThe study formed part of the international project led by the Committee on Reference Intervals and Decision Limits (C‐RIDL), and therefore, the strict guidelines laid out by the committee were followed. Full blood count and differential counts were performed on a Beckman Coulter ACT 5 diff AL analyser within 2‐4 hours of collection and were reported as mean (standard deviation), 2.5th and 97.5th percentiles. Comparisons were analysed using Spss v25 and Statistica v13, and a P value of < 0.05 was considered significant.ResultsReference ranges for Caucasian and Mixed Ancestry individuals were similar while white cell (P = 0.016), monocyte (P < 0.001), neutrophil (P = 0.034) and red cell indices were significantly different amongst the three population groups. There were however no statistical and clinical significant differences between the eosinophil, lymphocyte, red cell and platelet counts across the three groups.ConclusionIn conclusion, subjects of Mixed Ancestry, in this region, have similar reference intervals to those of European descent, while lower white cell and neutrophil counts in Africans have been confirmed.
Circular RNA circABCC4 as the ceRNA of miR‐1182 facilitates prostate cancer progression by promoting FOXP4 expression
Authors: Huang Changkun , Deng Huanghao , Wang Yinhuai , Jiang Hongyi , Xu Ran , Zhu Xuan , Huang Zhichao , Zhao Xiaokun 
Published: July 2019

AbstractIn recent years, circular RNAs (circRNAs) have been identified to be essential regulators of various human cancers. However, knowledge of the functions of circRNAs in prostate cancer remains very limited. The correlation between circABCC4 and human cancer is largely unknown. This study aims to investigate the biological functions of circABCC4 in prostate cancer progression and illustrate the underlying mechanism. We found that circABCC4 was remarkably up‐regulated in prostate cancer tissues and cell lines and promoted FOXP4 expression by sponging miR‐1182 in prostate cancer cells. CircABCC4 knockdown markedly suppressed prostate cancer cell proliferation, cell‐cycle progression, migration and invasion in vitro. Furthermore, silencing of the circRNA also delayed tumor growth in vivo. Taken together, our findings indicated that circABCC4 facilitates the malignant behaviour of prostate cancer by promoting FOXP4 expression through sponging of miR‐1182. The circABCC4–miR‐1182‐FOXP4 regulatory loop may be a promising therapeutic target for prostate cancer intervention.