bluuebunny/crossref_metadata_2025_split huggingface dataset:
Friend or foe—IDH1 mutations in glioma 10 years on
Authors: Huang L Eric 
Published: July 2019

AbstractThe identification of recurrent point mutations in the isocitrate dehydrogenase 1 (IDH1) gene, albeit in only a small percentage of glioblastomas a decade ago, has transformed our understanding of glioma biology, genomics and metabolism. More than 1000 scientific papers have been published since, propelling bench-to-bedside investigations that have led to drug development and clinical trials. The rapid biomedical advancement has been driven primarily by the realization of a neomorphic activity of IDH1 mutation that produces high levels of (d)-2-hydroxyglutarate, a metabolite believed to promote glioma initiation and progression through epigenetic and metabolic reprogramming. Thus, novel inhibitors of mutant IDH1 have been developed for therapeutic targeting. However, numerous clinical and experimental findings are at odds with this simple concept. By taking into consideration a large body of findings in the literature, this article analyzes how different approaches have led to opposing conclusions and proffers a counterintuitive hypothesis that IDH1 mutation is intrinsically tumor suppressive in glioma but functionally undermined by the glutamate-rich cerebral environment, inactivation of tumor-suppressor genes and IDH1 copy-number alterations. This theory also provides an explanation for some of the most perplexing observations, including the scarcity of proper model systems and the prevalence of IDH1 mutation in glioma.
A Sparse Probabilistic Code Underlies the Limits of Behavioral Discrimination
Authors: Sriram Balaji , Li Lillian , Cruz-Martín Alberto , Ghosh Anirvan 
Published: July 2019

AbstractThe cortical code that underlies perception must enable subjects to perceive the world at time scales relevant for behavior. We find that mice can integrate visual stimuli very quickly (&lt;100 ms) to reach plateau performance in an orientation discrimination task. To define features of cortical activity that underlie performance at these time scales, we measured single-unit responses in the mouse visual cortex at time scales relevant to this task. In contrast to high-contrast stimuli of longer duration, which elicit reliable activity in individual neurons, stimuli at the threshold of perception elicit extremely sparse and unreliable responses in the primary visual cortex such that the activity of individual neurons does not reliably report orientation. Integrating information across neurons, however, quickly improves performance. Using a linear decoding model, we estimate that integrating information over 50–100 neurons is sufficient to account for behavioral performance. Thus, at the limits of visual perception, the visual system integrates information encoded in the probabilistic firing of unreliable single units to generate reliable behavior.
Development and Analytical Validation of the Methodology for Vitamins in Tablets by Ultra-Performance Liquid Chromatography
Authors: d’Oliveira Giulio D C , Chaves Andréa R , Pérez Caridad N 
Published: July 2019

Abstract
In the present study, we developed a reliable and robust chromatographic method for the quantification of multivitamins in tablet samples by ultra-performance liquid chromatography (UPLC) with photodiode array detection. The vitamins nicotinamide, pyridoxine, riboflavin, and thiamin were analyzed and quantified in a total analysis time of 2.5 minutes, using hydrophilic interaction liquid chromatography stationary phase. Tocopherol acetate and cyanocobalamin were analyzed and quantified in a total analysis time of 2.5 minutes, using reversed-phase (RP)-UPLC. The analysis time reported here is lower than that of similar methods reported in the literature for single vitamin determination. The method linearity exhibits a good correlation coefficient (R2 = 0.998) with the relative residual standard deviation in the acceptable limit of 2.0%. The developed methods were validated, and the results demonstrated that the proposed analytical method showed to be selective, sensitive, accurate, and robust for the quantification of evaluated vitamins in multivitamin tablets. The work was fully developed in the quality control laboratory of a pharmaceutical industry in the Agroindustrial District of Anápolis (DAIA, Goiás, Brazil), where the product is manufactured.
Do Enterprise Zones have a role to play in delivering a place-based industrial strategy?
Authors: Hooton Christopher A , Tyler Peter 
Published: July 2019

Abstract
We examine the body of evidence on Enterprise Zone policy with the objective of assessing its role in broader place-based industrial strategy. We conduct an extensive review, consolidate the empirical evidence into one place and examine it according to economic impact by zone type. We identify two gaps in the empirical knowledge that are systematically addressed through new research on several US Enterprise Zones to gain new evidence on their economic additionality. The article concludes by considering other, hitherto poorly explored, pathways by which zones may help an area to adapt to change and embrace longer-term economic futures.
Successful off-pump surgical release for extrinsic compression of outflow graft obstruction of a left ventricular assist device
Authors: Ushijima Tomoki , Tanoue Yoshihisa , Mitsuo Hiroshi , Shiose Akira 
Published: July 2019

Abstract
A 36-year-old woman had received support with the Jarvik 2000 left ventricular assist device for 3 years. Cardiac computed tomography revealed outflow graft obstruction, which appeared as external compression of the outflow graft. The patient underwent surgical release of the obstruction after resternotomy. Yellow sediment had become encrusted in the enclosed space between the covering graft and outflow graft and appeared to have been derived from plasma contents. Successful release of the obstruction was achieved by cutting open the covering graft without cardiopulmonary bypass. Neither pump exchange nor outflow graft exchange was required. This off-pump surgery can be a beneficial procedure in terms of less invasiveness and good curability.
Outcomes of transported and in-house patients on extracorporeal life support: a propensity score-matching study
Authors: Lee Heemoon , Sung Kiick , Suh Gee Young , Chung Chi Ryang , Yang Jeong Hoon , Jeon Kyeongman , Carriere Keumhee Chough , Ahn Joong Hyun , Cho Yang Hyun 
Published: July 2019

AbstractOBJECTIVESPatients on extracorporeal life support (ECLS), like other critically ill patients, are transported to other institutions for various reasons. However, little has been reported concerning the characteristics and clinical outcomes of transported patients compared with those of in-house patients.METHODSA total of 281 adult patients received ECLS between January 2014 and August 2016. Patients who underwent cannulation at another institution by our team were excluded. Patients were divided into 2 groups: transported group (N = 46) and in-house group (N = 235). All 46 patients were safely transported without serious adverse events. The mean travel distance was 206±140 km, with a mean travel time of 78 ± 57 min. Following propensity score matching, 44 transported patients were matched to 148 in-house patients.RESULTSIn the matched population, the mean age was 48 ± 13 years in the transported group and 49 ± 17 years in the in-house group (P = 0.70). The ECLS type (venoarterial/venovenous) comprised 35/9 (79.5/20.5%) in the transported group and 119/29 (80.4/19.6%) in the in-house group (P = 0.93). Seventeen (38.6%) extracorporeal cardiopulmonary resuscitations were performed in the transported group and 59 (39.9%) were performed in the in-house group (P = 0.91). The incidence of limb ischaemia and acute kidney injury was higher in the transported group (P = 0.007 and P = 0.001, respectively). However, the rate of survival to discharge did not differ between the groups (63.6% in the transported group vs 64.2% in the in-house group, P = 0.94) and there was no difference in overall mortality (P = 0.99).CONCLUSIONSAlthough transported patients had more complications than in-house ECLS patients, clinical outcomes were comparable in the matched population. Transporting ECLS patients to an experienced centre may be justified based on our experience.
Embodied Art: A Reading of A. S. Byatt’s ‘Body Art’
Authors: Mathews Peter D 
Published: July 2019

Abstract
This article examines the idea of an embodied art in A. S. Byatt’s short story ‘Body Art’. In order to contextualize this concept, the essay begins with a survey of Byatt’s earlier explorations of the link between mind and body, as well as an analysis of the small amount of secondary material relating to ‘Body Art’, a text that has received little critical attention. The article then explores the story’s ties to Dutch vanitas painting, a tradition that is intimately linked to the study of anatomy. The vanitas tradition shows how medicine and art were once a unified field, and explores the consequences of their modern division. This leads to a consideration of the influence of theological debates about mind and body and their effect, in particular, on Renaissance humanist art. The next section examines the shifting meaning of the archival collection, particularly in its significance for modern formations of subjectivity. This idea is particularly important in the context of the story’s allusions to Joseph Beuys, who views the artist’s body as a locus of creativity. Like Beuys, Byatt is interested in art that draws on the imaginative power of religious storytelling and imagery while rejecting its supernatural elements. Byatt draws together all of these elements in her story in order to articulate her vision of an embodied art, one that draws together the conceptual and the physical.
Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis
Authors: Ridker Paul M , MacFadyen Jean G , Thuren Tom , Libby Peter 
Published: July 2019

Abstract

Aims
The Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) established that targeting inflammation with interleukin-1β (IL-1β) inhibition can significantly reduce cardiovascular (CV) event rates in the absence of any beneficial effects on cholesterol. Yet, CANTOS participants treated with both high-intensity statins and canakinumab remain at considerable risk for recurrent CV events. Both interleukin-18 (IL-18, which like IL-1β requires the NLRP3 inflammasome for activation) and interleukin-6 (IL-6, a pro-inflammatory cytokine downstream of IL-1) may contribute to the recurrent events that occur even on canakinumab therapy, and thus represent novel targets for treating atherothrombosis.

Methods and results
Plasma samples from 4848 stable post-myocardial infarction patients who were assigned to active IL-1β inhibition or placebo within CANTOS underwent measurement of IL-18 and IL-6 both before and after initiation of canakinumab using validated ELISA. All participants were followed over a median 3.7-year period (maximum 5 years) for recurrent major adverse cardiovascular events (MACE) and for all-cause mortality. Compared to placebo, canakinumab significantly reduced IL-6 levels in a dose-dependent manner yielding placebo-subtracted median percent reductions in IL-6 at 3 months of 24.8%, 36.3%, and 43.2% for the 50, 150, and 300 mg doses, respectively (all P-values &lt;0.001). By contrast, no dose of canakinumab significantly altered IL-18 levels measured at 3 months (all effects &lt;1%, all P-values &gt; 0.05). Yet, despite these differential plasma effects, either baseline and on-treatment levels of IL-18 or IL-6 associated with rates of future CV events. For example, for MACE, each tertile increase in IL-18 measured 3 months after canakinumab initiation associated with a 15% increase in risk [95% confidence interval (CI) 3–29%, P = 0.016], while each tertile increase in IL-6 measured 3 months after canakinumab initiation associated with a 42% increase in risk (95% CI 26–59%, P &lt; 0.0001). Similar effects were observed for MACE-plus, CV death, all-cause mortality, and the for the combination endpoint of all vascular events inclusive of revascularization procedures and hospitalization for congestive heart failure. In baseline as well as on-treatment analyses, risks were highest among those with the highest levels of both IL-18 and IL-6.

Conclusion
There remains substantial residual inflammatory risk related to both IL-18 and IL-6 after IL-1β inhibition with canakinumab These data support further pharmacologic development of therapies for atherothrombosis that target IL-18 or IL-6 signalling, or that can simultaneously inhibit both IL-1β and IL-18 (such as NLRP3 inflammasome inhibitors).

Clinical trial registration
ClinicalTrials.gov NCT01327846.
High penetrance and similar disease progression in probands and in family members with arrhythmogenic cardiomyopathy
Authors: Chivulescu Monica , Lie Øyvind H , Popescu Bogdan A , Skulstad Helge , Edvardsen Thor , Jurcut Ruxandra O , Haugaa Kristina H 
Published: July 2019

Abstract

Aims
We aimed to assess structural progression in arrhythmogenic cardiomyopathy (AC) patients and mutation-positive family members and its impact on arrhythmic outcome in a longitudinal cohort study.

Methods and results
Structural progression was defined as the development of new Task Force imaging criteria from inclusion to follow-up and progression rates as annual changes in imaging parameters. We included 144 AC patients and family members (48% female, 47% probands, 40 ± 16 years old). At genetic diagnosis and inclusion, 58% of family members had penetrant AC disease. During 7.0 [inter-quartile range (IQR) 4.5–9.4] years of follow-up, 47% of family members without AC at inclusion developed AC criteria, resulting in a yearly new AC penetrance of 8%. Probands and family members had a similar progression rate of right ventricular outflow tract diameter (0.5 mm/year vs. 0.6 mm/year, P = 0.28) by mixed model analysis of 598 echocardiographic examinations. Right ventricular fractional area change progression rate was even higher in family members (−0.6%/year vs. −0.8%/year, P &lt; 0.01). Among 86 patients without overt structural disease or arrhythmic history at inclusion, a first severe ventricular arrhythmic event occurred in 8 (9%), of which 7 (88%) had concomitant structural progression. Structural progression was associated with higher incidence of severe ventricular arrhythmic events adjusted for age, sex, and proband status (HR 21.24, 95% CI 2.47–182.81, P &lt; 0.01).

Conclusion
More than half of family members had AC criteria at genetic diagnosis and yearly AC penetrance was 8%. Structural progression was similar in probands and family members and was associated with higher incidence of severe ventricular arrhythmic events.
A non-perturbative method for gravitational potential calculations within heterogeneous and aspherical planets
Authors: Maitra Matthew , Al-Attar David 
Published: July 2019

SUMMARY
We present a numerically exact method for calculating the internal and external gravitational potential of aspherical and heterogeneous planets. Our approach is based on the transformation of Poisson’s equation into an equivalent equation posed on a spherical computational domain. This new problem is solved in an efficient iterative manner based on a hybrid pseudospectral/spectral element discretization. The main advantage of our method is that its computational cost reflects the planet’s geometric and structural complexity, being in many situations only marginally more expensive than boundary perturbation theory. Several numerical examples are presented to illustrate the method’s efficacy and potential range of applications.
Rotating double-diffusive convection in stably stratified planetary cores
Authors: Monville R , Vidal J , Cébron D , Schaeffer N 
Published: July 2019

SUMMARYIn planetary fluid cores, the density depends on temperature and chemical composition, which diffuse at very different rates. This leads to various instabilities, bearing the name of double-diffusive convection (DDC). We investigate rotating DDC (RDDC) in fluid spheres. We use the Boussinesq approximation with homogeneous internal thermal and compositional source terms. We focus on the finger regime, in which the thermal gradient is stabilizing whereas the compositional one is destabilizing. First, we perform a global linear stability analysis in spheres. The critical Rayleigh numbers drastically drop for stably stratified fluids, yielding large-scale convective motions where local analyses predict stability. We evidence the inviscid nature of this large-scale double-diffusive instability, enabling the determination of the marginal stability curve at realistic planetary regimes. In particular, we show that in stably stratified spheres, the Rayleigh numbers Ra at the onset evolve like Ra ∼ Ek−1, where Ek is the Ekman number. This differs from rotating convection in unstably stratified spheres, for which Ra ∼ Ek−4/3. The domain of existence of inviscid convection thus increases as Ek−1/3. Secondly, we perform non-linear simulations. We find a transition between two regimes of RDDC, controlled by the strength of the stratification. Furthermore, far from the RDDC onset, we find a dominating equatorially antisymmetric, large-scale zonal flow slightly above the associated linear onset. Unexpectedly, a purely linear mechanism can explain this phenomenon, even far from the instability onset, yielding a symmetry breaking of the non-linear flow at saturation. For even stronger stable stratification, the flow becomes mainly equatorially symmetric and intense zonal jets develop. Finally, we apply our results to the early Earth core. Double diffusion can reduce the critical Rayleigh number by four decades for realistic core conditions. We suggest that the early Earth core was prone to turbulent RDDC, with large-scale zonal flows.
Stir it up: how master-apprentice relationships affect the similarity of product offerings in high-end restaurants
Authors: Castellucci Fabrizio , Slavich Barbara 
Published: July 2019

AbstractThis work explores the determinants of decisions by former apprentices to present product offerings similar to those of their masters. Using a quantitative study of 194 international chefs, this article argues that there is a negative association between the degree to which a master rebels against the rules and conventions of a field and master-apprentice similarity. It also shows that master status and a creative professional’s career stage during an apprenticeship moderate the association between master rebellion and master-apprentice similarity. The work concludes by outlining some implications for the career development and creativity of creative professionals and the emergence of new styles.
Opportunities in Novel Psychotropic Drug Design from Natural Compounds
Authors: Tang Siu Wa , Tang Wayne H 
Published: July 2019

AbstractMultiple initiatives at the national and international level support natural drug discovery. Psychiatrists and patients are not well informed about natural psychotropics in general. Existing antidepressant and antipsychotic drugs were developed from atropine, a natural product. Subsequent drug developments were largely based on extension and modification of earlier molecular scaffolds. This limits their mechanisms of action to similar neuropathways. Natural psychotropic substances, particularly those with hallucinogenic and psychedelic properties and different chemical structures, may serve as new paths to novel psychotropic drug development.
An Intranasal Exposure Model of Lethal Nipah Virus Infection in African Green Monkeys
Authors: Geisbert Joan B , Borisevich Viktoriya , Prasad Abhishek N , Agans Krystle N , Foster Stephanie L , Deer Daniel J , Cross Robert W , Mire Chad E , Geisbert Thomas W , Fenton Karla A 
Published: July 2019

Abstract
Due to the difficulty in conducting clinical trials for vaccines and treatments against Nipah virus (NiV), licensure will likely require animal models, most importantly non-human primates (NHPs). The NHP models of infection have primarily relied on intratracheal instillation or small particle aerosolization of NiV. However, neither of these routes adequately models natural mucosal exposure to NiV. To develop a more natural NHP model, we challenged African green monkeys with the Bangladesh strain of NiV by the intranasal route using the laryngeal mask airway (LMA) mucosal atomization device (MAD). LMA MAD exposure resulted in uniformly lethal disease that accurately reflected the human condition.
The Fat Body of the Hematophagous Insect, Panstrongylus megistus (Hemiptera: Reduviidae): Histological Features and Participation of the β-Chain of ATP Synthase in the Lipophorin-Mediated Lipid Transfer
Authors: Fruttero Leonardo L , Leyria Jimena , Moyetta Natalia R , Ramos Fabian O , Settembrini Beatriz P , Canavoso Lilián E 
Published: July 2019

AbstractIn insects, lipid transfer to the tissues is mediated by lipophorin, the major circulating lipoprotein, mainly through a nonendocytic pathway involving docking receptors. Currently, the role of such receptors in lipid metabolism remains poorly understood. In this work, we performed a histological characterization of the fat body of the Chagas’ disease vector, Panstrongylus megistus (Burmeister), subjected to different nutritional conditions. In addition, we addressed the role of the β-chain of ATP synthase (β-ATPase) in the process of lipid transfer from lipophorin to the fat body. Fifth-instar nymphs in either fasting or fed condition were employed in the assays. Histological examination revealed that the fat body was composed by diverse trophocyte phenotypes. In the fasting condition, the cells were smaller and presented a homogeneous cytoplasmic content. The fat body of fed insects increased in size mainly due to the enlargement of lipid stores. In this condition, trophocytes contained abundant lipid droplets, and the rough endoplasmic reticulum was highly developed and mitochondria appeared elongated. Immunofluorescence assays showed that the β-ATPase, a putative lipophorin receptor, was located on the surface of fat body cells colocalizing partially with lipophorin, which suggests their interaction. No changes in β-ATPase expression were found in fasting and fed insects. Blocking the lipophorin–β-ATPase interaction impaired the lipophorin-mediated lipid transfer to the fat body. The results showed that the nutritional status of the insect influenced the morphohistological features of the tissue. Besides, these findings suggest that β-ATPase functions as a lipophorin docking receptor in the fat body.
‘Father, father, where are you going?’: Epicurean Deism and Absent Fathers in Blake’s Songs of Innocence and of Experience
Authors: Codsi Stephanie 
Published: July 2019

Abstract
This article explores the connection between the absent deity of Epicurean Deism and the father figure in Blake's Songs of Innocence and of Experience (1789–1794). The absent, elusive or indifferent God – which I trace back to Epicurean theology and its theory of atoms – plays out in Blake's depiction of a father whose absence or neglect is an implied cause of man's alienation. The article firstly looks at the inheritance of Epicureanism in 17–18th century Deist texts, then considers Blake s references to Epicureanism in his works, and finally argues that Blake critiques such concepts of God and fatherhood in a selection of Songs.