bluuebunny/crossref_metadata_2025_split huggingface dataset:
What's in a name: are cultured red blood cells ‘natural’?
Authors: King Emma , Lyall Catherine 
Published: March 2018

AbstractThe case of cultured red blood cells (RBCs) currently being grown in a laboratory for future use in human transfusion raises questions about the ontological status of such products of modern biotechnology. This paper presents results from a six‐year ethnographic study involving interviews, focus groups and other forms of engagement with the scientific research team and other stakeholders, including public groups, which sought to understand respondents’ reactions to cultured RBCs. These cells, derived from stem cell technology, have the potential to address the global shortage of donated blood. How these blood cells are situated within the spectrum of ‘natural’ to ‘synthetic’ will shape expectations and acceptance of this product, both within the scientific community and by wider publics: these blood cells are both novel and yet, at the same time, very familiar. Drawing on discussions related to classification and ‘anchoring’, we examine the contrasting discourses offered by our respondents on whether these blood cells are ‘natural’ or not and consider the impact that naming might have on both their future regulation and the eventual uptake of cultured RBCs by society.
Systematic Review and Meta‐analysis of Outcomes of Patients With Subsegmental Pulmonary Embolism With and Without Anticoagulation Treatment
Authors: Bariteau Adam , Stewart Lauren K. , Emmett Thomas W. , Kline Jeffrey A. 
Published: March 2018

AbstractBackgroundThis systematic review addresses the controversy over the decision to anticoagulate patients with subsegmental pulmonary embolism (SSPE).MethodsWe searched Ovid MEDLINE, PubMed, Embase, the Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, Google Scholar, and bibliographies in March 2017. Two authors reviewed and retained papers with symptomatic patients who underwent computerized tomographic pulmonary angiography and had sufficient information to determine SSPE; decision to treat (or not) with systemic anticoagulation; and outcomes of bleeding, venous thromboembolism (VTE) recurrence, and death. Papers were assessed for selection and publication bias and heterogeneity, with Eggers and the inconsistency indexes (I2).ResultsFrom 1,512 papers screened, we included 14 studies comprising 15,563 patients for full‐length review and analysis. Pooled data demonstrated I2 = 99% with an Eggers p < 0.001, suggesting significant publication bias. The pooled prevalence of SSPE was 4.6% (95% confidence interval [CI] = 1.8%–8.5%). The frequency of bleeding in SSPE patients treated with anticoagulation (n = 589) was 8.1% (95% CI = 2.8%–15.8%), with no available bleeding data in untreated patients (n = 126). The frequency of VTE recurrence within 90 days was 5.3% (95% CI = 1.6%–10.9%) for treated versus 3.9% (95% CI = 4.8%–13.4%) for untreated, while the frequency of death was 2.1% (95% CI = 3.4%–5.2%) for treated versus 3.0% (95% CI = 2.8%–8.6%) for untreated.ConclusionThis systematic review highlights the lack of any clinical trial to make a clear inference about harm or benefit of anticoagulation for SSPE. Comparison of pooled data from uncontrolled outcome studies shows no increase in VTE recurrence or death rates for patients who were not anticoagulated. These data suggest clinical equipoise for decision to anticoagulate or not anticoagulate patients with SSPE. However, this inference is limited by small numbers, imprecision, and the lack of a controlled clinical trial.
Assessing the Effect of a Medical Toxicologist in the Care of Rattlesnake‐envenomated Patients
Authors: Levine Michael , Offerman Steve , Vohra Rais , Wolk Brian , LaPoint Jeff , Quan Dan , Spyres Meghan , LoVecchio Frank , Thomas Stephen H. 
Published: March 2018

AbstractBackgroundRattlesnake envenomation is an important problem in the United States, and the management of these envenomations can be complex. Despite these complexities, however, the majority of such cases are managed without the involvement of a medical toxicologist. The primary objective of this study was to evaluate the impact of a medical toxicology service (MTS) on the length of stay (LOS) of such patients.MethodsThe authors conducted a retrospective study at six centers in California. Patients were included if they were admitted in the 2 years before the establishment of a MTS (pre‐MTS) or in the 2 years after the creation of a MTS (post‐MTS).ResultsA total of 300 subjects were included (169 pre‐MTS, 131 post MTS). Baseline characteristics between the pre‐MTS and post‐MTS groups were very similar. The creation of a MTS was associated with a significant reduction in the mean (95% confidence interval) LOS (69.5 [59.1–79.9] hours vs. 48.1 [41.4–54.8] hours). This reduced LOS was not associated with any statistically significant change in readmission rates.ConclusionRattlesnake bite patients treated by a medical toxicologist have a significantly reduced LOS compared to those without direct involvement of a medical toxicologist.
Preclinical evidence for combining the 5‐HT2C receptor agonist lorcaserin and varenicline as a treatment for nicotine dependence
Authors: Fletcher Paul J. , Li Zhaoxia , Silenieks Leo B. , MacMillan Cam , DeLannoy Ines , Higgins Guy A. 
Published: March 2018

AbstractVarenicline, a nicotinic acetylcholine receptor partial agonist, is used to treat nicotine dependence. Lorcaserin, a 5‐HT2C receptor agonist has been approved in some countries to treat obesity. Based on preclinical and preliminary clinical evidence, lorcaserin may have potential to treat nicotine dependence. These experiments examined in rats the effects of combining varenicline (0.5 or 1 mg/kg) and lorcaserin (0.3, 0.6 and 1 mg/kg) on nicotine self‐administration, reinstatement of nicotine seeking, responding for food and impulsive action. Both drugs alone reduced nicotine self‐administration. Combining varenicline and 0.6 mg/kg lorcaserin reduced responding to a greater extent than either drug alone. In a relapse model, extinguished nicotine seeking was reinstated by a priming injection of nicotine and nicotine‐associated cues. Reinstatement was reduced by varenicline (1 mg/kg) and by lorcaserin (0.3 mg/kg). Combining lorcaserin (0.3 mg/kg) with varenicline (0.5 or 1 mg/kg) reduced reinstatement to a greater degree than either drug alone. Both drugs had minimal effects on responding for food, alone or in combination. In the five‐choice serial reaction time test, varenicline (0.5 or 1 mg/kg) increased impulsivity, measured as increased premature responding. This effect was reduced by lorcaserin (0.3 mg/kg). Plasma levels of varenicline or lorcaserin were not altered by co‐administration of the other drug. Varenicline and lorcaserin have additive effects on nicotine self‐administration, and on nicotine seeking. Lorcaserin prevents impulsivity induced by varenicline. This pattern of effects suggests that co‐administration of varenicline and lorcaserin has potential as a treatment for nicotine dependence that may exceed the value of either drug alone.
Bankrolling Repression? Modeling Third‐Party Influence on Protests and Repression
Authors: Chyzh Olga V. , Labzina Elena 
Published: March 2018

AbstractUkraine's anti‐government protests in 2013–2014, and the ensuing removal of President Yanukovich, raised much speculation about Russia's role in the outcome of the crisis, as well as more general questions related to third‐party influence on domestic protests and repression. Does third‐party assistance to the government increase the level of government repression or deter protesters? Does the leader removal indicate that foreign involvement was a failure? Or can a third party gain from involvement, even if its protégé leader is removed from power? We model external influence on the onset of protests and repression as a game between the government, the protesters, and a third party that supports the government. The main finding is that a third party may “bankroll” repression against the protesters, even at the risk of the removal of their protégé leader, with the goal of deterring future protests within its sphere of interest.
Accuracy of digital radiography: regional scaling factors for trauma
Authors: Drynan David , McArthur Milford , Vohora Ashray , Hinton Darren , Menegon Grant , Wilkinson Matthew P. R. 
Published: March 2018

BackgroundSurgical planning in trauma is essential for optimal patient care and best patient outcomes. Digital radiography has improved the availability, convenience and access to radiographs worldwide as used in every trauma centre in Australia. One shortcoming, however, is the variability in magnification error associated with different anatomic regions. Accurate assessment of radiographs is paramount to proper surgical planning.MethodsA retrospective review of 513 post‐operative trauma radiographs of implants at a single centre, collected from January 2015 to August 2016, was measured by the four individual investigators. A comparison of the digital calliper reading with the known implant size, taken from operation reports and company implant data, was conducted. Magnification scales were created for different anatomic regions: femur, tibia, humerus, elbow, wrist and hand, foot and ankle.ResultsPrecise regional scaling factors increase accuracy of digital radiography. Average magnification for hand, wrist, ankle and forearm is 5% (1–16%). Average magnification for foot, knee, tibia and elbow is 8% (3–11%). Humerus magnification is 10.3% (3–17%) and shoulder and femur approximately 15% (12–18%). Inter‐rater Pearson's R reliability testing is 0.985–0.995 and intra‐observer reliability is 0.998.DiscussionApplying regional scaling factors improves accuracy of digital imaging, therefore improving clinical decision‐making regarding fractures, distance from bony landmarks, component sizing and reduction assessment. Femoral and tibial fracture measurements with appropriate scaling factors allow the accurate estimation of nail diameter required for fixation and screw diameter for fragment fixation.
The relationship between increased oxidative stress and visual field defect progression in glaucoma patients with sleep apnoea syndrome
Authors: Yamada Erika , Himori Noriko , Kunikata Hiroshi , Omodaka Kazuko , Ogawa Hiromasa , Ichinose Masakazu , Nakazawa Toru 
Published: March 2018

AbstractPurposeSleep apnoea syndrome (SAS) is often associated with glaucoma, and intermittent hypoxia, present in SAS, can contribute to glaucoma pathogenesis. However, the relationships between SAS, high systemic oxidative stress and the speed of glaucoma progression are unclear. Thus, we investigated these relationships in glaucoma patients with and without SAS.MethodsPeripheral blood samples were collected from 166 eyes of 166 Japanese patients: 42 controls, 109 open‐angle glaucoma (OAG) patients without SAS and 15 OAG patients with SAS. Prognostic factors for visual field defect progression were determined with logistic regression. Diacron reactive oxygen metabolites (dROM) and biological antioxidant potential (BAP) were measured with a free radical analyser. Clinical parameters were also recorded. Intergroup comparisons used the Mann–Whitney U test.ResultsMultiple regression analysis showed that SAS was a statistically significant contributing factor to fast visual field defect progression, defined as mean deviation (MD) slope ≤−2.0 dB/Y (SAS: odds ratio (OR) = 14.48; p = 0.002). The non‐SAS and SAS groups had similar age, sex, intraocular pressure (IOP), axial length and antiglaucoma drug use. The SAS group had a significantly higher dROM level (p = 0.001), BAP level (p = 0.038) and steeper MD slope (p = 0.001) than the non‐SAS group.ConclusionGlaucoma patients with SAS have higher dROM, as well as steeper MD slope, than patients without SAS, suggesting that SAS may induce systemic oxidative stress and promote glaucomatous visual field defect progression.
Interaction of Sulfonylureas with Liver Uptake Transporters OATP1B1 and OATP1B3
Authors: Chen Yu , Chen Lin , Zhang Hong , Huang Shibo , Xiong Yuqing , Xia Chunhua 
Published: March 2018

AbstractSulfonylureas (SUs) such as glibenclamide, gliclazide, glimepiride, glipizide and gliquidone are one of the first oral medicines available for the treatment of type 2 diabetes and are widely used for the treatment of hyperglycaemia. The hepatic transporters, organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), play an important role in the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. Drug–drug interactions mediated by OATP1B1/1B3 may result in the hepatic transporting change for drug substrates. The inhibitory effects of glibenclamide and glimepiride on sulfobromophthalein (BSP) uptake have been previously studied, and glibenclamide has been reported as the substrate of OATP1B3, but it remains unclear whether other SUs such as gliclazide, glipizide and gliquidone are substrates of OATP1B1 and OATP1B3. Here, we investigated the relationship between the five most commonly applied SUs (glibenclamide, gliclazide, glimepiride, glipizide, gliquidone) and OATP1B1 and OATP1B3. We performed uptake and inhibition assays in HEK293T cells stably expressing OATP1B1 or OATP1B3, respectively, and established a liquid chromatography–mass spectrometry (LC‐MS) method for the simultaneous measurement of five SUs. We demonstrated that gliclazide and glimepiride are substrates of OATP1B1 and glibenclamide and glipizide are substrates of OATP1B3. We also confirmed the interaction between these SUs and rosuvastatin. No transporting was observed for gliquidone, suggesting that it is not a substrate of either transporter.
The Usefulness of Sperm Kinematics in Drug‐Induced Toxicity Assessment
Authors: Vicente‐Carrillo Alejandro 
Published: March 2018

AbstractIn vitro drug‐induced toxicity assessment demands the usability and validation of suitable cell models, obtained non‐invasively and pain‐free. Sperm suspensions, painlessly and easily obtained from breeding boars, have been proven as suitable biosensors for pre‐clinical toxicology screening and ranking of lead compounds in the drug development processes on a kinematics‐based assay. Having a limited number of mitochondria and depending on these mitochondria and on cytoplasmic glycolysis for the energy needed for motility and for plasma membrane functionality, spermatozoa become a suitable model for capturing multiple modes of action of drugs and other chemicals acting via measurements of sperm motility. In this MiniReview, the usability of boar spermatozoa as detectors of cytotoxicity based on sperm motility measurements is discussed.
Yoda1 analogue (Dooku1) which antagonizes Yoda1‐evoked activation of Piezo1 and aortic relaxation
Authors: Evans Elizabeth L , Cuthbertson Kevin , Endesh Naima , Rode Baptiste , Blythe Nicola M , Hyman Adam J , Hall Sally J , Gaunt Hannah J , Ludlow Melanie J , Foster Richard , Beech David J 
Published: March 2018

Background and PurposeThe mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small‐molecule agonist, but the pharmacology of these channels is otherwise limited.Experimental ApproachYoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in HUVECs, which natively express Piezo1. Isometric tension recordings were made from rings of mouse thoracic aorta.Key ResultsModification of the pyrazine ring of Yoda1 yielded an analogue, which lacked agonist activity but reversibly antagonized Yoda1. The analogue is referred to as Dooku1. Dooku1 inhibited 2 μM Yoda1‐induced Ca2+‐entry with IC50s of 1.3 μM (HEK 293 cells) and 1.5 μM (HUVECs) yet failed to inhibit constitutive Piezo1 channel activity. It had no effect on endogenous ATP‐evoked Ca2+ elevation or store‐operated Ca2+ entry in HEK 293 cells or Ca2+ entry through TRPV4 or TRPC4 channels overexpressed in CHO and HEK 293 cells. Yoda1 caused dose‐dependent relaxation of aortic rings, which was mediated by an endothelium‐ and NO‐dependent mechanism and which was antagonized by Dooku1 and analogues of Dooku1.Conclusion and ImplicationsChemical antagonism of Yoda1‐evoked Piezo1 channel activity is possible, and the existence of a specific chemical interaction site is suggested with distinct binding and efficacy domains.
A method for the quantification of biased signalling at constitutively active receptors
Authors: Hall David A , Giraldo Jesús 
Published: March 2018

Background and PurposeBiased agonism, the ability of an agonist to differentially activate one of several signal transduction pathways when acting at a given receptor, is an increasingly recognized phenomenon at many receptors. The Black and Leff operational model lacks a way to describe constitutive receptor activity and hence inverse agonism. Thus, it is impossible to analyse the biased signalling of inverse agonists using this model. In this theoretical work, we develop and illustrate methods for the analysis of biased inverse agonism.Experimental ApproachMethods were derived for quantifying biased signalling in systems that demonstrate constitutive activity using the modified operational model proposed by Slack and Hall. The methods were illustrated using Monte Carlo simulations.Key ResultsThe Monte Carlo simulations demonstrated that, with an appropriate experimental design, the model parameters are ‘identifiable’. The method is consistent with methods based on the measurement of intrinsic relative activity (RAi) (ΔΔlogR or ΔΔlog(τ/Ka)) proposed by Ehlert and Kenakin and their co‐workers but has some advantages. In particular, it allows the quantification of ligand bias independently of ‘system bias’ removing the requirement to normalize to a standard ligand.Conclusions and ImplicationsIn systems with constitutive activity, the Slack and Hall model provides methods for quantifying the absolute bias of agonists and inverse agonists. This provides an alternative to methods based on RAi and is complementary to the ΔΔlog(τ/Ka) method of Kenakin et al. in systems where use of that method is inappropriate due to the presence of constitutive activity.
Associations of insulin‐like growth factor‐I and insulin‐like growth factor binding protein‐3 with bone quality in the general adult population
Authors: Böker J. , Völzke H. , Nauck M. , Hannemann A. , Friedrich N. 
Published: March 2018

SummaryObjectiveGrowth hormone (GH) and its main mediator, insulin‐like growth factor‐I (IGF‐I), play a significant role in bone metabolism. The relations betweenIGF‐I and bone mineral density (BMD) or osteoporosis have been assessed in previous studies but whether the associations are sex‐specific remains uncertain. Moreover, only a few studies examined bone quality assessed by quantitative ultrasound (QUS). We aimed to investigate these associations in the general population of north‐east Germany.Design and MeasurementsData from 1759 men and 1784 women who participated in the baseline examination of the Study of Health in Pomerania (SHIP)‐Trend were used.IGF‐I andIGF‐binding protein‐3 (IGFBP‐3) concentrations were measured on theIDS‐iSYSmultidiscipline automated analyser (Immunodiagnostic Systems Limited).QUSmeasurements were performed at the heel (Achilles InSight,GEHealthcare). Sex‐specific linear and multinomial logistic regression models adjusted for potential confounders were calculated.ResultsLinear regression analyses revealed significant positive associations betweenIGF‐I andIGF‐I/IGFBP‐3 ratio, a marker for freeIGF‐I, with allQUSparameters in men. Among women, we found an inverse association betweenIGF‐I and theQUS‐based fracture risk but no association with any otherQUSparameter. There was no association betweenIGFBP‐3 and theQUS‐based fracture risk.ConclusionsOur data suggest an important role ofIGF‐I on bone quality in men. The observed association ofIGF‐I with theQUS‐based stiffness index andQUS‐based fracture risk in this study might animate clinicians to refer patients with lowIGF‐I levels, particularly men, to a further evaluation of risk factors for osteoporosis and a detailed examination of the skeletal system.
Evaluating the Theoretic Adequacy and Applied Potential of Computational Models of the Spacing Effect
Authors: Walsh Matthew M. , Gluck Kevin A. , Gunzelmann Glenn , Jastrzembski Tiffany , Krusmark Michael 
Published: March 2018

AbstractThe spacing effect is among the most widely replicated empirical phenomena in the learning sciences, and its relevance to education and training is readily apparent. Yet successful applications of spacing effect research to education and training is rare. Computational modeling can provide the crucial link between a century of accumulated experimental data on the spacing effect and the emerging interest in using that research to enable adaptive instruction. In this paper, we review relevant literature and identify 10 criteria for rigorously evaluating computational models of the spacing effect. Five relate to evaluating the theoretic adequacy of a model, and five relate to evaluating its application potential. We use these criteria to evaluate a novel computational model of the spacing effect called the Predictive Performance Equation (PPE). Predictive Performance Equation combines elements of earlier models of learning and memory including the General Performance Equation, Adaptive Control of Thought—Rational, and the New Theory of Disuse, giving rise to a novel computational account of the spacing effect that performs favorably across the complete sets of theoretic and applied criteria. We implemented two other previously published computational models of the spacing effect and compare them toPPEusing the theoretic and applied criteria as guides.
Social Media and Participatory Authorship in Giant Screen Films
Authors: Nucci Mary 
Published: March 2018

AbstractAlthough the engagement with social media in the production of Hollywood films has been described in the literature, understanding whether social media has been adopted in the giant screen industry is unexamined. Giant screen film producers have an existing participatory relationship during film production with their “consumers”, which includes both the institutions that screen their films and the audiences who watch their films. Given that the advent of social media has created the opportunity for new ways for filmmakers to interact with consumers during film production, this research examined the role of social media in the production of these immersive films in light of the existing giant screen collaborative environment.