bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional targeting in mice reveals that hepatic homogentisate 1,2-dioxygenase activity is essential in reducing circulating homogentisic acid and for effective therapy in the genetic disease alkaptonuria
Authors: Hughes Juliette H , Liu Ke , Plagge Antonius , Wilson Peter J M , Sutherland Hazel , Norman Brendan P , Hughes Andrew T , Keenan Craig M , Milan Anna M , Sakai Takao , Ranganath Lakshminarayan R , Gallagher James A , Bou-Gharios George 
Published: October 2019

AbstractAlkaptonuria is an inherited disease caused by homogentisate 1,2-dioxygenase (HGD) deficiency. Circulating homogentisic acid (HGA) is elevated and deposits in connective tissues as ochronotic pigment. In this study, we aimed to define developmental and adult HGD tissue expression and determine the location and amount of gene activity required to lower circulating HGA and rescue the alkaptonuria phenotype.We generated an alkaptonuria mouse model using a knockout-first design for the disruption of the HGD gene. Hgd tm1a −/− mice showed elevated HGA and ochronosis in adulthood. LacZ staining driven by the endogenous HGD promoter was localised to only liver parenchymal cells and kidney proximal tubules in adulthood, commencing at E12.5 and E15.5 respectively. Following removal of the gene trap cassette to obtain a normal mouse with a floxed 6th HGD exon, a double transgenic was then created with Mx1-Cre which conditionally deleted HGD in liver in a dose dependent manner. 20% of HGD mRNA remaining in liver did not rescue the disease, suggesting that we need more than 20% of liver HGD to correct the disease in gene therapy.Kidney HGD activity which remained intact reduced urinary HGA, most likely by increased absorption, but did not reduce plasma HGA nor did it prevent ochronosis. In addition, downstream metabolites of exogenous 13C6-HGA, were detected in heterozygous plasma, revealing that hepatocytes take up and metabolise HGA.This novel alkaptonuria mouse model demonstrated the importance of targeting liver for therapeutic intervention, supported by our observation that hepatocytes take up and metabolise HGA.
Loss of the nucleoporin Aladin in central nervous system and fibroblasts of Allgrove Syndrome
Authors: Bitetto Giacomo , Ronchi Dario , Bonato Sara , Pittaro Alessandra , Compagnoni Giacomo Monzio , Bordoni Andreina , Salani Sabrina , Frattini Emanuele , Lopez Gianluca , Cribiù Fulvia Milena , Corti Stefania , Comi Giacomo P , Bresolin Nereo , Di Fonzo Alessio 
Published: October 2019

Abstract
Allgrove syndrome (AS) is a rare disease with broad neurological involvement. Neurodegeneration can affect spinal motor neurons, Purkinje cells, striatal neurons and the autonomic system. The mechanisms that lead to neuronal loss are still unclear. Recessive mutations in the AAAS gene affect the encoded protein Aladin, which would normally localize to the cytoplasmic face of the nuclear membrane as part of the nuclear pore complex (NPC). While the NPC is known to be a key factor for nucleocytoplasmic transport, the precise role of Aladin has not been elucidated yet. Here, we explored the consequences of the homozygous AAAS mutation c.464G&gt;A (p.R155H) in central nervous system tissues and fibroblasts of a novel AS patient presenting motor neuron disease, cerebellar ataxia and autonomic dysfunction. Neuropathological analyses showed severe loss of motor neurons and Purkinje cells, with significant reduction in the perinuclear expression of Aladin. A reduced amount of protein was detected in the nuclear membrane fraction of the patient’s brain. RNA analysis revealed a significant reduction of the transcript AAAS-1, while the AAAS-2 transcript was upregulated in fibroblasts. To our knowledge, this is the first study to demonstrate the effects of AAAS mutations in the human central nervous system.
Success of malaria chemoprophylaxis for outbound civil and military travellers in prevention of reintroduction of malaria in Sri Lanka
Authors: Fernando Sumadhya D , Ranaweera Dewanee , Weerasena Methnie S , Booso Rahuman , Wickramasekara Thamara , Madurapperuma Chirath P , Danansuriya Manjula , Rodrigo Chaturaka , Herath Hemantha 
Published: October 2019

AbstractBackgroundSri Lanka was certified as malaria-free in September 2016. However, the continuous presence of the malaria vector poses serious risks of reintroduction of the disease. Chemoprophylaxis and advice on malaria preventive behaviour for international travellers is a key strategy adopted to reduce the risk of imported malaria.MethodsWe conducted an efficiency study of malaria chemoprophylaxis for civilian and military travellers who requested travel advice from the Anti Malaria Campaign (AMC) prior to departure. The AMC is the only agency that can issue malaria chemoprophylaxis to travellers and hence this sample is representative of all such individuals seeking travel advice in Sri Lanka.ResultsA total of 544 (400 civilians and 144 military) travellers were interviewed prior to departure and after return. The majority travelled to African destinations (516/544 [94.8%]) and were prescribed mefloquine (517/544 [95%]). Chemoprophylaxis was well tolerated and discontinuation due to adverse events was minimal. Regular chemoprophylaxis was reported by 505 (92.8%) participants while overseas. The protective efficacy of chemoprophylaxis was 100% among those who complied with the full course.ConclusionsThe compliance with chemoprophylaxis and its protective efficacy were satisfactory in this study. It is an effective tool in preventing imported malaria to post-elimination Sri Lanka.
Policing Reality: Urban Disorder, Failure, and Expert Undoings
Authors: Machold Rhys 
Published: October 2019

AbstractThis article intervenes in discussions about the circulation of policing knowledge and the politics of expertise. As part of a broader conversation about transnational reconfigurations of state power, critical scholars have drawn attention to the influence of global policing “models” and “private” experts in shaping policy. They show how such figures and forms of knowhow symbolically enforce urban order and dispossess marginalized communities under conditions of neoliberal crisis. While incisive, these approaches can unduly portray expert authority as boundless and unassailable. This article argues that a sustained theoretical engagement with questions about controversies and failure opens up fruitful avenues to unsettle the perceived smoothness, inevitability, and omnipotence of experts in relation to politics and governing. Drawing on insights from actor-network theory (ANT), it situates deference to global experts as interventions that seek to enact and police the terms of “reality” concerning urban order. This approach allows us to better understand how such interventions work but also how they misfire and come undone. These claims are developed through a close reading of UK Prime Minister David Cameron's attempt to solicit policy advice from renowned global “supercop” William Bratton in the aftermath of the 2011 England riots.
Mutations that increase expression of the EmrAB-TolC efflux pump confer increased resistance to nitroxoline in Escherichia coli
Authors: Puértolas-Balint Fabiola , Warsi Omar , Linkevicius Marius , Tang Po-Cheng , Andersson Dan I 
Published: October 2019

AbstractObjectivesTo determine the mechanism of resistance to the antibiotic nitroxoline in Escherichia coli.MethodsSpontaneous nitroxoline-resistant mutants were selected at different concentrations of nitroxoline. WGS and strain reconstruction were used to define the genetic basis for the resistance. The mechanistic basis of resistance was determined by quantitative PCR (qPCR) and by overexpression of target genes. Fitness costs of the resistance mutations and cross-resistance to other antibiotics were also determined.ResultsMutations in the transcriptional repressor emrR conferred low-level resistance to nitroxoline [nitroxoline MIC (MICNOX) = 16 mg/L] by increasing the expression of the emrA and emrB genes of the EmrAB-TolC efflux pump. These resistant mutants showed no fitness reduction and displayed cross-resistance to nalidixic acid. Second-step mutants with higher-level resistance (MICNOX = 32–64 mg/L) had mutations in the emrR gene, together with either a 50 kb amplification, a mutation in the gene marA, or an IS upstream of the lon gene. The latter mutations resulted in higher-level nitroxoline resistance due to increased expression of the tolC gene, which was confirmed by overexpressing tolC from an inducible plasmid in a low-level resistance mutant. Furthermore, the emrR mutations conferred a small increase in resistance to nitrofurantoin only when combined with an nfsAB double-knockout mutation. However, nitrofurantoin-resistant nfsAB mutants showed no cross-resistance to nitroxoline.ConclusionsMutations in different genes causing increased expression of the EmrAB-TolC pump lead to an increased resistance to nitroxoline. The structurally similar antibiotics nitroxoline and nitrofurantoin appear to have different modes of action and resistance mechanisms.
Validity of social media for assessing treatment patterns in oncology patients: a case study in melanoma
Authors: McDonald Laura , Behl Varun , Sundar Vijayarakhavan , Mehmud Faisal , Malcolm Bill , Ramagopalan Sreeram 
Published: October 2019

Abstract
There is a need to understand how patients are managed in the real world to better understand disease burden and unmet need. Traditional approaches to gather these data include the use of electronic medical record (EMR) or claims databases; however, in many cases data access policies prevent rapid insight gathering. Social media may provide a potential source of real-world data to assess treatment patterns, but the limitations and biases of doing so have not yet been evaluated. Here, we assessed whether patient treatment patterns extracted from publicly available patient forums compare to results from more traditional EMR and claims databases. We observed that the 95% confidence intervals of proportions of treatments received at first, second, and third line for advanced/metastatic melanoma generated from unstructured social media data overlapped with 95% confidence intervals from proportions obtained from 1 or more traditional EMR/Claims databases. Social media may offer a valid data option to understand treatment patterns in the real world.
Attraction of Invasive Ambrosia Beetles (Coleoptera: Curculionidae: Scolytinae) to Ethanol-Treated Tree Bolts
Authors: Reding Michael E , Ranger Christopher M 
Published: October 2019

Abstract
Ethanol-treated bolts (tree stem sections) have potential as monitoring and pesticide screening tools for ambrosia beetles (Coleoptera: Curculionidae: Scolytinae). Bolts were infused with ethanol by immersing them for at least 24 h. Attacks on ethanol-treated bolts by Xylosandrus species were compared with captures in ethanol-baited traps. Bolts infused in ethanol were usually as attractive or more attractive to Xylosandrus germanus (Blandford) than ethanol-baited bottle traps. Xylosandrus crassiusculus (Motschulsky) were more attracted to bolts than trap in some experiments, but numbers were low and differences were usually not significant. Two techniques for treating bolts with ethanol were compared. Attraction of ambrosia beetles to ethanol-infused bolts were compared with bolts with a drilled cavity filled with ethanol. Drilled bolts filled with ethanol were attractive to X. germanus and were reliably attacked, but numbers of beetles were often lower than in traps and infused bolts. Aged and fresh ethanol-infused bolts were compared with evaluate residual attractiveness. Bolts aged 7 d usually had fewer X. germanus than fresh bolts and traps, and bolts aged 14 d had no beetles. Ethanol-infused bolts from different species of trees were compared. Xylosandrus germanus attacked all species tested with more attacks usually in red maple (Acer rubrum L.). Anisandrus maiche Stark was attracted to ethanol-infused bolts indicating it may attack trees emitting ethanol. Bolts attracted fewer nontarget species than traps, but residual attraction was much less. The selectivity of ethanol-treated bolts for Xylosandrus species should make them useful for monitoring and screening pesticides against those species.
Spatial Distributions of Thrips (Thysanoptera: Thripidae) in Cotton
Authors: Reay-Jones Francis P F , Greene Jeremy K , Bauer Philip J 
Published: October 2019

AbstractA 4-yr study was conducted to determine the degree of aggregation of thrips and injury in cotton, Gossypium hirsutum L., and their spatial association with a multispectral vegetation index (normalized difference vegetation index [NDVI]) and soil apparent electrical conductivity (ECa). Using the Spatial Analysis by Distance IndicEs analyses (SADIE), adult thrips were significantly (P &lt; 0.05) aggregated in 4 out of 24 analyses for adult thrips (17%), 4 out of 24 analyses for immature thrips (17%), and 2 out of 15 analyses for injury (13%). The SADIE association tool showed that NDVI values were associated with adult thrips in 2 out of 20 paired datasets (10%), with immature thrips in 3 out of 20 paired datasets (15%), and with thrips injury in 1 out of 14 paired datasets (7.1%). Soil ECa values were generally more associated with thrips variables than NDVI, with shallow ECa positively associated with adult thrips in 6 out of 21 paired datasets (28.6%), with immature thrips in 8 out of 21 paired datasets (40.0%), and with thrips injury in 8 out of 14 paired datasets (57.1%). The greater frequency of positive associations between thrips variables and soil ECa suggests a greater potential for site-specific management, particularly in the Coastal Plain of the southeastern United States, where soil types are highly variable.
Risk factors predicting Candida infective endocarditis in patients with candidemia
Authors: Foong Kap Sum , Sung Abby , Burnham Jason P , Kronen Ryan , Lian Qinghua , Salazar Zetina Ana , Hsueh Kevin , Lin Charlotte , Powderly William G , Spec Andrej 
Published: October 2019

Abstract
Candida infective endocarditis (CIE) is a rare but serious complication of candidemia. Incidence and risk factors associated with CIE among candidemic patients are poorly defined from small cohorts. Identification of clinical predictors associated with this entity may guide more judicious use of cardiac imaging. We conducted a retrospective analysis of all inpatients aged ≥18 years diagnosed with candidemia at our institution. CIE was diagnosed by fulfilling two of the major Duke criteria: specifically a vegetation(s) on echocardiogram and positive blood cultures for Candida spp. We used univariable and multivariable regression analyses to identify risk factors associated with CIE. Of 1,873 patients with candidemia, 47 (2.5%) were identified to have CIE. In our multivariable logistic model, existing valvular heart disease was associated with a higher risk for CIE (adjusted odds ratio [aOR], 7.66; 95% confidence interval [CI], 2.95–19.84). Predictors that demonstrated a decreased risk of CIE included infection with C. glabrata (aOR, 0.17; 95% CI, 0.04–0.69), hematologic malignancy (aOR, 0.09; 95% CI, 0.01–0.68), and receipt of total parenteral nutrition (aOR, 0.38; 95% CI, 0.16–0.91). The 90-day crude mortality for CIE was 48.9%, similar to the overall non-CIE mortality of 41.9% (P = .338). We identified a set of clinical factors that can predict the presence of CIE among patient with candidemia. These findings may reduce the need for unnecessary expensive and invasive imaging studies in a subset of patients with a lower risk profile for endocarditis and alternative infection source.
Numerical simulation of helical jets at active region peripheries
Authors: Wyper Peter F , DeVore C Richard , Antiochos Spiro K 
Published: October 2019

ABSTRACT
Coronal jets are observed above minority-polarity intrusions throughout the solar corona. Some of the most energetic ones occur on the periphery of active regions where the magnetic field is strongly inclined. These jets exhibit a non-radial propagation in the low corona as they follow the inclined field, and often have a broad, helical shape. We present a three-dimensional magnetohydrodynamic simulation of such an active-region-periphery helical jet. We consider an initially potential field with a bipolar flux distribution embedded in a highly inclined magnetic field, representative of the field nearby an active region. The flux of the minority polarity sits below a bald-patch separatrix initially. Surface motions are used to inject free energy into the closed field beneath the separatrix, forming a sigmoidal flux rope that eventually erupts producing a helical jet. We find that a null point replaces the bald patch early in the evolution and that the eruption results from a combination of magnetic breakout and an ideal kinking of the erupting flux rope. We discuss how the two mechanisms are coupled, and compare our results with previous simulations of coronal-hole jets. This comparison supports the hypothesis that the generic mechanism for all coronal jets is a coupling between breakout reconnection and an ideal instability. We further show that our results are in good qualitative and quantitative agreement with observations of active-region-periphery jets.
The evolution of CNO isotopes: the impact of massive stellar rotators
Authors: Romano Donatella , Matteucci Francesca , Zhang Zhi-Yu , Ivison Rob J , Ventura Paolo 
Published: October 2019

ABSTRACT
Chemical abundances and abundance ratios measured in galaxies provide precious information about the mechanisms, modes, and time-scales of the assembly of cosmic structures. Yet, the nucleogenesis and chemical evolution of elements heavier than helium are dictated mostly by the physics of the stars and the shape of the stellar mass spectrum. In particular, estimates of CNO isotopic abundances in the hot, dusty media of high-redshift starburst galaxies offer a unique glimpse into the shape of the stellar initial mass function (IMF) in extreme environments that cannot be accessed with direct observations (star counts). Underlying uncertainties in stellar evolution and nucleosynthesis theory, however, may hurt our chances of getting a firm grasp of the IMF in these galaxies. In this work, we adopt new yields for massive stars, covering different initial rotational velocities. First, we implement the new yield set in a well-tested chemical evolution model for the Milky Way. The calibrated model is then adapted to the specific case of a prototype submillimetre galaxy (SMG). We show that, if the formation of fast-rotating stars is favoured in the turbulent medium of violently star-forming galaxies irrespective of metallicity, the IMF needs to be skewed towards high-mass stars in order to explain the CNO isotopic ratios observed in SMGs. If, instead, stellar rotation becomes negligible beyond a given metallicity threshold, as is the case for our own Galaxy, there is no need to invoke a top-heavy IMF in starbursts.
Coexistence of a planar magnetic structure and an Alfvén wave in the shock-sheath of an interplanetary coronal mass ejection
Authors: Shaikh Zubair I , Raghav Anil , Vichare Geeta 
Published: October 2019

ABSTRACT
The excess speed of coronal mass ejection over the ambient solar wind in interplanetary space generates a highly compressed, heated and turbulent shock-sheath. Here, for the first time, we present in situ observations of a unique and distinct feature of the shock-sheath, which exhibits the characteristics of a planar magnetic structure (PMS) and an Alfvén wave simultaneously. We have used standard techniques to confirm the presence of the PMS as described in Shaikh et al. We have employed the minimum variance analysis technique to estimate the properties of the PMS. The Walén test is used to confirm the presence of the Alfvén wave. Our study unambiguously proves the coexistence of the Alfvén wave and the PMS in the shock-sheath region. Further studies are essential to investigate the origin of such a peculiar shock-sheath and its effect on our view of solar-terrestrial physics.
Timing analysis of 2S 1417-624 observed with NICER and Insight-HXMT
Authors: Ji L , Doroshenko V , Santangelo A , Güngör C , Zhang S , Ducci L , Zhang S-N , Ge M-Y , Qu L J , Chen Y P , Bu Q C , Cao X L , Chang Z , Chen G , Chen L , Chen T X , Chen Y , Chen Y B , Cui W , Cui W W , Deng J K , Dong Y W , Du Y Y , Fu M X , Gao G H , Gao H , Gao M , Gu Y D , Guan J , Guo C C , Han D W , Hu W , Huang Y , Huo J , Jia S M , Jiang L H , Jiang W C , Jin J , Jin Y J , Kong L D , Li B , Li C K , Li G , Li M S , Li T P , Li W , Li X , Li X B , Li X F , Li Y G , Li Z J , Li Z W , Liang X H , Liao J Y , Liu C Z , Liu G Q , Liu H W , Liu S Z , Liu X J , Liu Y , Liu Y N , Lu B , Lu F J , Lu X F , Luo T , Ma X , Meng B , Nang Y , Nie J Y , Ou G , Sai N , Song L M , Song X Y , Sun L , Tan Y , Tao L , Tuo Y L , Wang G F , Wang J , Wang W S , Wang Y S , Wen X Y , Wu B B , Wu M , Xiao G C , Xiong S L , Xu H , Xu Y P , Yang Y R , Yang J W , Yang S , Yang Y J , Zhang A M , Zhang C L , Zhang C M , Zhang F , Zhang H M , Zhang J , Zhang Q , Zhang T , Zhang W , Zhang W C , Zhang W Z , Zhang Y , Zhang Y , Zhang Y F , Zhang Y J , Zhang Z , Zhang Z L , Zhao H S , Zhao J L , Zhao X F , Zheng S J , Zhu Y , Zhu Y X , Zou C L 
Published: October 2019

Abstract
We present a study of timing properties of the accreting pulsar 2S 1417-624 observed during its 2018 outburst, based on Swift/BAT, Fermi/GBM, Insight-HXMT and NICER observations. We report a dramatic change of the pulse profiles with luminosity. The morphology of the profile in the range 0.2-10.0 keV switches from double to triple peaks at ∼2.5 $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$ and from triple to quadruple peaks at ∼7 $\rm \times 10^{37}{\it D}_{10}^2\ erg\ s^{-1}$. The profile at high energies (25-100 keV) shows significant evolutions as well. We explain this phenomenon according to existing theoretical models. We argue that the first change is related to the transition from the sub to the super-critical accretion regime, while the second to the transition of the accretion disc from the gas-dominated to the radiation pressure-dominated state. Considering the spin-up as well due to the accretion torque, this interpretation allows to estimate the magnetic field self-consistently at ∼7 × 1012 G.