bluuebunny/crossref_metadata_2025 huggingface dataset:
Installing Automobility
Authors: Gopakumar Govind
Published: April 2020

An examination of the process of prioritizing private motorized transportation in Bengaluru, a rapidly growing megacity of the Global South.

Automobiles and their associated infrastructures, deeply embedded in Western cities, have become a rapidly growing presence in the mega-cities of the Global South. Streets, once crowded with pedestrians, pushcarts, vendors, and bicyclists, are now choked with motor vehicles, many of them private automobiles. In this book, Govind Gopakumar examines this shift, analyzing the phenomenon of automobility in Bengaluru (formerly known as Bangalore), a rapidly growing city of about ten million people in southern India. He finds that the advent of automobility in Bengaluru has privileged the mobility needs of the elite while marginalizing those of the rest of the population.

Gopakumar connects Bengaluru's burgeoning automobility to the city's history and to the spatial, technological, and social interventions of a variety of urban actors. Automobility becomes a juggernaut, threatening to reorder the city to enhance automotive travel. He discusses the evolution of congestion and urban change in Bengaluru; the “regimes of congestion” that emerge to address the issue; an “infrastructurescape” that shapes the mobile behavior of all residents but is largely governed by the privileged; and the enfranchisement of an “automotive citizenship” (and the disenfranchisement of non-automobile-using publics). Gopakumar also finds that automobility in Bengaluru faces ongoing challenges from such diverse sources as waste flows, popular religiosity, and political leadership. These challenges, however, introduce messiness without upsetting automobility. He therefore calls for efforts to displace automobility that are grounded in reordering the mobility regime, relandscaping the city and its infrastructures, and reclaiming streets for other uses.

The open access edition of this book was made possible by generous funding from Arcadia – a charitable fund of Lisbet Rausing and Peter Baldwin.
Independent evolution of ancestral and novel defenses in a genus of toxic plants (Erysimum, Brassicaceae)
Authors: Züst Tobias , Strickler Susan R , Powell Adrian F , Mabry Makenzie E , An Hong , Mirzaei Mahdieh , York Thomas , Holland Cynthia K , Kumar Pavan , Erb Matthias , Petschenka Georg , Gómez José-María , Perfectti Francisco , Müller Caroline , Pires J Chris , Mueller Lukas A , Jander Georg
Published: April 2020

Phytochemical diversity is thought to result from coevolutionary cycles as specialization in herbivores imposes diversifying selection on plant chemical defenses. Plants in the speciose genus Erysimum (Brassicaceae) produce both ancestral glucosinolates and evolutionarily novel cardenolides as defenses. Here we test macroevolutionary hypotheses on co-expression, co-regulation, and diversification of these potentially redundant defenses across this genus. We sequenced and assembled the genome of E. cheiranthoides and foliar transcriptomes of 47 additional Erysimum species to construct a phylogeny from 9868 orthologous genes, revealing several geographic clades but also high levels of gene discordance. Concentrations, inducibility, and diversity of the two defenses varied independently among species, with no evidence for trade-offs. Closely related, geographically co-occurring species shared similar cardenolide traits, but not glucosinolate traits, likely as a result of specific selective pressures acting on each defense. Ancestral and novel chemical defenses in Erysimum thus appear to provide complementary rather than redundant functions.
The skin microbiome facilitates adaptive tetrodotoxin production in
poisonous newts
Authors: Vaelli Patric M , Theis Kevin R , Williams Janet E , O'Connell Lauren A , Foster James A , Eisthen Heather L
Published: April 2020

Rough-skinned newts (Taricha granulosa) use tetrodotoxin (TTX) to block
voltage-gated sodium (Nav) channels as a chemical defense against predation.
Interestingly, newts exhibit extreme population-level variation in toxicity
attributed to a coevolutionary arms race with TTX-resistant predatory
snakes, but the source of TTX in newts is unknown. Here, we investigated
whether symbiotic bacteria isolated from toxic newts could produce TTX. We
characterized the skin-associated microbiota from a toxic and non-toxic
population of newts and established pure cultures of isolated bacterial
symbionts from toxic newts. We then screened bacterial culture media for TTX
using LC-MS/MS and identified TTX-producing bacterial strains from four
genera, including Aeromonas, Pseudomonas, Shewanella, and Sphingopyxis.
Additionally, we sequenced the Nav channel gene family in toxic newts and
found that newts expressed Nav channels with modified TTX binding sites,
conferring extreme physiological resistance to TTX. This study highlights
the complex interactions among adaptive physiology, animal-bacterial
symbiosis, and ecological context.
A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in Caenorhabditis elegans
Authors: Fan Jiale , Ji Tingting , Wang Kai , Huang Jichang , Wang Mengqing , Manning Laura , Dong Xiaohua , Shi Yanjun , Zhang Xumin , Shao Zhiyong , Colón-Ramos Daniel A
Published: April 2020

Synaptic positions underlie precise circuit connectivity. Synaptic positions can be established during embryogenesis and sustained during growth. The mechanisms that sustain synaptic specificity during allometric growth are largely unknown. We performed forward genetic screens in C. elegans for regulators of this process and identified mig-17, a conserved ADAMTS metalloprotease. Proteomic mass spectrometry, cell biological and genetic studies demonstrate that MIG-17 is secreted from cells like muscles to regulate basement membrane proteins. In the nematode brain, the basement membrane does not directly contact synapses. Instead, muscle-derived basement membrane coats one side of the glia, while glia contact synapses on their other side. MIG-17 modifies the muscle-derived basement membrane to modulate epidermal-glial crosstalk and sustain glia location and morphology during growth. Glia position in turn sustains the synaptic pattern established during embryogenesis. Our findings uncover a muscle-epidermis-glia signaling axis that sustains synaptic specificity during the organism’s allometric growth.
A halo of reduced dinoflagellate abundances in and around eelgrass beds
Authors: Jacobs-Palmer Emily , Gallego Ramón , Ramón-Laca Ana , Kunselman Emily , Cribari Kelly , Horwith Micah , Kelly Ryan P.
Published: April 2020

Seagrass beds provide a variety of ecosystem services, both within and outside the bounds of the habitat itself. Here we use environmental DNA (eDNA) amplicons to analyze a broad cross-section of taxa from ecological communities in and immediately surrounding eelgrass (Zostera marina). Sampling seawater along transects extending alongshore outward from eelgrass beds, we demonstrate that eDNA provides meter-scale resolution of communities in the field. We evaluate eDNA abundance indices for 13 major phylogenetic groups of marine and estuarine taxa along these transects, finding highly local changes linked with proximity to Z. marina for a diverse group of dinoflagellates, and for no other group of taxa. Eelgrass habitat is consistently associated with dramatic reductions in dinoflagellate abundance both within the contiguous beds and for at least 15 m outside, relative to nearby sites without eelgrass. These results are consistent with the hypothesis that eelgrass-associated communities have allelopathic effects on dinoflagellates, and that these effects can extend in a halo beyond the bounds of the contiguous beds. Because many dinoflagellates are capable of forming harmful algal blooms (HABs) toxic to humans and other animal species, the apparent salutary effect of eelgrass habitat on neighboring waters has important implications for public health as well as shellfish aquaculture and harvesting.
In vitro and in vivo Antioxidant Properties of Extracts from the Root of Curcuma longa Linn
Authors: Mohammed Abdulrashid , Usman Muhammad Ibrahim , Wudil Alhassan Muhammad , Alhassan Adamu Jibrin , Abubakar Salisu Maiwada , Lat Ngwen Anthony
Published: April 2020

Many plants possess antioxidants that exhibit additive or synergistic activities. The antioxidant activities of the root of Curcuma longa Linn extracts extracted different solvents were investigated by using several established in vitro systems: α,α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen Peroxide scavenging activity (HPSA), nitric oxide radical scavenging activity (NOSA) and ferric reducing antioxidant power (FRAP). The result showed that methanol extract exhibited greater antioxidant activity in vitro which was statistically significant compared to the other extracts. Based on the in vitro results, the methanol extract was subjected to column chromatography. Six pooled fractions (FI-FVI) were evaluated for in vivo antioxidant activity in liver and kidney of alloxan-induced diabetic rats using a total of forty-five (45) rats which were grouped into nine (9) groups of five (5) rats. The in vivo antioxidants showed a significant decrease in superoxide dismutase (SOD), catalase (CAT) and gluthatione peroxidase (GPx) levels in both liver and kidney of Alloxan-induced diabetic rats. These changes were significantly reversed after treatment with methanol fraction II and the standard drug. Thus, Curcuma longa Linn may be useful in the management of diabetes and oxidative stress.
Holographic description of M-branes via AdS2
Authors: Dibitetto Giuseppe , Lozano Yolanda , Petri Nicolò , Ramirez Anayeli
Published: April 2020

Abstract

We study AdS2
× S
4
× S
2
× Σ2 solutions in type IIB string theory arising from D1-D3-NS5 brane intersections. These backgrounds enjoy sixteen supercharges and the corresponding internal geometry is non-compact due to the specific form of the warping w.r.t. the Riemann surface Σ2. Even though a direct computation of the holographic free energy of the would-be dual CFT1 yields a divergent behaviour, it reveals the typical N
3 scaling of a 6d theory upon introducing a hard cut-off. We claim that such geometries may be interpreted as the gravity duals of M(atrix) models describing an IR phase of the (2, 0) theory of M5 branes, in presence of momentum and NUT charges. We discuss parallel AdS2 geometries describing longitudinal M2 branes in the UV, where the counting of the number of degrees of freedom correctly reproduces the expected N
3/2 behaviour of the dual field theory. These geometries provide explicit examples where deconstructed extra dimensions yield well-defined UV descriptions in terms of higher-dimensional CFTs.
RIGIDIFIED TORSOR COCYCLES, HYPERCOVERINGS AND BUNDLE GERBES
Authors: SCHRÖER STEFAN
Published: April 2020

We give a geometric interpretation of sheaf cohomology for higher degrees $n\geq 1$ in terms of torsors on the member of degree $d=n-1$ in hypercoverings of type $r=n-2$, endowed with an additional datum, the so-called rigidification. This generalizes the fact that cohomology in degree one is the group of isomorphism classes of torsors, where the rigidification becomes vacuous, and that cohomology in degree two can be expressed in terms of bundle gerbes, where the rigidification becomes an associativity constraint.
On the likelihood of Gravitational Wave emission during the Tidal Disruption of stars by Super Massive Black Holes
Authors: Toscani Martina , Lodato Giuseppe
Published: April 2020

Tidal Disruption Events (TDEs) are a common feature between Active and Quiescent Galactic Nuclei; the study of these events is a very useful tool to probe phenomena that relate to the formation of an accretion disc or a jet. Also, the accretion rate at the beginning of the tidal flare is expected to be significantly super-Eddington and might result in high energy emission (in soft X-rays but sometimes up to the gamma regime, as in the the case of Swift J1644, see Komossa 2015). These events may even play an important role in the newborn field of the Multimessenger Astronomy. This work is set within this context. Indeed, it is a study of generation of Gravitational Waves (GWs) from the hot accreting torus resulting after a TDE. Since the torus has only formed recently, magnetic fields are not expected to be strong enough, so that the torus is likely to be unstable to the Papaloizou-Pringle Instability (PPI), producing a strongly varying mass quadrupole. Here, the study of the evolution of such tori is developed, using both analytical calculation and a Smoothed Particle Hydrodynamics simulation (SPH). In particular the goal of this work is to determine the GW waveform and to compute the characteristic strain of these GWs in order to see if they are detectable by the Laser Interferometer Space Antenna (LISA).
Radio-loud AGNs with peculiar shape of hard X-ray spectrum: figuring out the reasons
Authors: Fedorova E. , Hnatyk B. I. , Zhdanov V. I.
Published: April 2020

We analyze the hard X-ray properties of five radio-loud active galactic nuclei with peculiar spectral shape. High-energy exponential cut-offs (HEC) in their hard X-ray 3-500 keV spectra are too high for radio loud AGNs (above 100 keV) or even absent.The probable reason of such visible spectral “peculiarity” can be due to the “jet contamination”, i.e we see some mixture of the jet and nuclear emission, but not pure emission of the innermost nucleus. Here we try to estimate the jet and nuclear components of the spectra for a sample of “peculiar” RL AGNs to find out whether these are real or fake features.
Neutrino and γ-ray Emission from the Core of NGC1275 by Magnetic Reconnection: GRMHD Simulations and Radiative Transfer/Particle Calculations
Authors: Rodríguez-Ramírez J. C. , de Gouveia Dal Pino Elisabete M. , Alves Batista R.
Published: April 2020

Very high energy (VHE) emission has been detected from the radio galaxy NGC1275, establishing it as a potential cosmic-ray (CR) accelerator and a high energy neutrino source. We here study neutrino and γ-ray emission from the core of NGC1275 simulating the interactions of CRs assumed to be accelerated by magnetic reconnection, with the accreting plasma environment. To do this, we combine (i) numerical general relativistic (GR) magneto-hydrodynamics (MHD), (ii) Monte Carlo GR leptonic radiative transfer and, (iii) Monte Carlo interaction of CRs. A leptonic emission model that reproduces the SED in the [103-1010.5] eV energy range is used as the background target for photo-pion interactions+electromagnetic cascading. CRs injected with the power-law index Îº=1.3 produce an emission profile that matches the VHE tail of NGC1275. The associated neutrino flux, below the IceCube limits, peaks at ∼PeV energies. However, coming from a single source, this neutrino flux may be an over-estimation.
Arsenic–nucleotides interactions: an experimental and computational investigation
Authors: Cassone Giuseppe , Chillè Donatella , Mollica Nardo Viviana , Giuffrè Ottavia , Ponterio Rosina Celeste , Sponer Jiri , Trusso Sebastiano , Saija Franz , Foti Claudia
Published: April 2020

By means of state-of-the-art computational approaches and experiments we characterize the chelation process established by As(iii) with AMP, ADP, and ATP in aqueous solutions.
Novel “ruthenium cyclopentadienyl”–peptide conjugate complexes against human FGFR(+) breast cancer
Authors: Franco Machado João , Machuqueiro Miguel , Marques Fernanda , Robalo M. Paula , Piedade M. Fátima M. , Garcia M. Helena , Correia João D. G. , Morais Tânia S.
Published: April 2020

Synthesis of the first half-sandwich ruthenium(ii)-cyclopentadienyl peptide conjugates and their biological evaluation against human FGFR(+) and FGFR(−) breast cancer cells.
Visible light induced 3-position-selective addition of arylpropiolic acids with ethers via C(sp3)–H functionalization
Authors: Wan Zi-juan , Yuan Xiao-feng , Luo Jun
Published: April 2020

Although the 2-position-selective decarboxylative coupling or addition of arylpropiolic acids with cyclic ethers has been intensively investigated, selective functionalization of arylpropiolic acids at the 3-position is still a big challenge.
A meta-analysis of the vascular endothelial growth factor polymorphisms associated with the risk of pre-eclampsia
Authors: Duan Weicheng , Xia Chenlu , Wang Kang , Duan Yijie , Cheng Ping , Xiong Bo
Published: April 2020

Backgroud: Pre-eclampsia (PE) is a common pregnancy-induced hypertension disease. Some case–control studies reported the association between vascular endothelial growth factor (VEGF) gene polymorphisms (rs3025039, rs2010963) and PE risk. However, these associations were inconsistent in several studies. Therefore, we conducted this meta-analysis to assess the role of VEGF gene polymorphisms in PE more precisely.

Methods: Eligible studies were searched in PubMed, Embase, Web of Science and Chinese (Chinese National Knowledge Infrastructure (CNKI) and WanFang) databases. Statistical analyses were performed by Stata 12.0 software. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. In addition, subgroup analyses, sensitive analyses and publication bias analyses were performed to further assess this meta-analysis.

Results: In total, 21 studies were included in the meta-analysis covering 2018 cases and 2632 controls. There were significant associations between VEGF polymorphisms (rs3025039, rs2010963) and PE risk in the overall populations. In the subgroup analyses, we found that rs3025039 polymorphism was associated with the increased risk of PE among Chinese. As for rs2010963 polymorphism, a significant association was observed in subgroup of Caucasian.

Conclusion: The present study suggested that the two VEGF gene polymorphisms (rs3025039, rs2010963) are associated with increased risk of PE in different ethnic groups, which means that the targets may be useful genetic markers for early prediction of PE.
Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis
Authors: Li Xiao-Song , Li Jun-Wei , Li Hui , Jiang Tao
Published: April 2020

The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12–1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85–1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81–2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20–3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16–1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54–0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55–0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06–10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.
Highly Efficient Chemoselective Synthesis of Pyrrolo[2,3-c]pyrazole Bearing Oxindole via Sequential Condensation–Michael Addition–Intramolecular Cyclization Reactions
Authors: Shaabani Ahmad , Nazeri Mohammad Taghi , Farhid Hassan , Javanbakht Siamak , Notash Behrouz
Published: April 2020

An efficient and highly chemoselective approach for the synthesis of novel scaffolds based on pyrrolo[2,3-c]pyrazole bearing oxindole is accomplished by the acid-promoted sequential reactions between benzoylacetonitriles, phenylhydrazine, and 3-phenacylideneoxindoles as readily available starting materials. This value structure is dexterously embraced with oxindole, pyrrole, and pyrazole heterocycles, which are famous for their enriched biological properties. Besides, this is an eco-friendly and atom-economy approach, and water is the only side product of the reaction. In this protocol, the requirement of column chromatography is completely avoided, and the products were isolated by recrystallization in crude reactions. These compounds due to their excellent fluorescence features and bioactive scaffolds may be attracted great interest in biomedical applications and clinical diagnostics in the future.
Thermodynamic stability and vibrational anharmonicity of black phosphorene—beyond quasi-harmonic analysis
Authors: Anees P
Published: April 2020

Thermodynamic stability and vibrational anharmonicity of single layer black phosphorene (SLBP) are studied using a spectral energy density (SED) method. At finite temperatures, SLBP sheet undergoes structural deformation due to the formation of thermally excited ripples. Thermal stability of deformed SLBP sheet is analyzed by computing finite temperature phonon dispersion, which shows that SLBP sheet is thermodynamically stable and survives the crumpling transition. To analyze the vibrational anharmonicity, temperature evolution of all zone center optic phonon modes are extracted, including experimentally forbidden IR and Raman active modes. Mode resolved phonon spectra exhibits red-shift in mode frequencies with temperature. The strong anharmonic phonon–phonon coupling is the predominant reason for the observed red-shift of phonon modes, the contribution of thermal expansion is marginal. Further, temperature sensitivity of all optic modes are analyzed by computing their first order temperature co-efficient (χ), and it can be expressed as B
2g >

A

g

2

>

B

3
g

1

>

B

3
g

2

> B
1g >

A

g

1

& B
2u > B
1u for Raman and IR active modes, respectively. The quasi-harmonic χ values are much smaller than the SED and experimental values; which substantiate that quasi-harmonic methods are inadequate, and a full anharmonic analysis is essential to explain structure and dynamics of SLBP at finite temperatures.
Fijian youth entrepreneurs: championing health through sustainable food systems
Authors: Conn Cath , Cammock Radilaite , Sa’u Lilo Losi , Nayar Shoba
Published: April 2020

The health of Pacific people is known to be at risk because of the onset of non-communicable diseases (NCDs), such as diabetes. The scale of the problem requires innovative approaches to bring about change. One such approach is the development of a sustainable food system in combination with the leadership of Pacific youth. This study sought to engage Pacific youth as part of the solution to reducing NCDs through social enterprise and championing of sustainable food systems. Four young Fijian vegetable and fruit entrepreneurs shared their stories as part of a participatory action research of Talanoa/storytelling, with social media workshops, networking and promotional opportunities. Findings revealed that youth entrepreneurs are passionate about food and health, family and tradition; some are already food influencers and champions and they are keen to grow their businesses. Yet, there is limited support for small business development with a social purpose and youth-led campaigns. The study indicates a growing potential to develop local youth-led social entrepreneurship and innovation to address NCDs in exciting new ways. There is an urgent need to support innovation interventions to advocate for sustainable food systems for the Pacific, that promote positive human health needs and address, more broadly, climate change effects.
Selling function: the advertising of sugar-containing beverages on Australian television
Authors: Brownbill Aimee L , Miller Caroline L , Smithers Lisa G , Braunack-Mayer Annette J
Published: April 2020

Reducing population consumption of sugar-containing beverages has become a public health priority in many countries due to causal evidence between high consumption, weight gain and non-communicable diseases. This study aims to explore how sugar-containing beverages are associated with health and wellness in television advertisements. Our sample consisted of all televised advertisements from sugar-containing beverage manufacturers aired on free-to-air television from one Australian network (four channels) in 2016 (n = 30 unique advertisements). We transcribed advertisements for audio and visual information. We analysed data inductively using methods from thematic, discourse and multi-modal analysis. Advertisements for sugar-containing beverages reflected both traditional (physical health and reduced risk of disease) and broader (wellbeing) conceptualizations of health. Beverages were positioned in advertisements as contributing a functional role to promote and enhance health and wellbeing within the physical, mental and social domains. Beverages were advertised as correcting suboptimal states of being to achieve desirable outcomes, including relaxation, increased resistance to disease, enhanced performance, better cognitive functioning and improved social connections. Positioning beverages within a wider conceptualization of health and wellbeing aligns with how health and nutrition are increasingly being understood and sought out by consumers, creating increased opportunities for the marketing of sugar-containing beverages as ‘healthy’.
Thoracic aortic computed tomography angiography in swine: establishment of a baseline for endovascular evaluation of the ascending aorta
Authors: Tao Li , Xianhao Bao , Yuxi Zhao , Ziwen Li , Ziyi Xu , Zhaoxiang Zeng , Mingwei Wu , Yiming Li , Ding Xu , Jiaxuan Feng , Rui Feng , Jian Zhou , Zaiping Jing
Published: April 2020

OBJECTIVES

Our goal was to establish a baseline of computed tomography (CT) angiographic data for the porcine ascending thoracic aorta for endovascular evaluation of animal experiments and device development.

METHODS

Thoracic aortic CT angiography was conducted on 49 pigs with an average body weight of 60–65 kg. The CT angiographic scans were done on an imaging reconstruction workstation to obtain the specific aortic geometric data, including the diameters of the planes, the heights among the planes and the clock positions of target arteries.

RESULTS

Fourteen important planes were defined in the study for endograft customizing reference. The diameters of the planes were measured, and the heights among the planes were recorded. For endograft fenestrations, the right coronary artery ostium clock position was 100.11 ± 7.29°, and the brachiocephalic trunk ostium clock position was 74.72 ± 6.45°. The best projection angle of the tangent position of the left coronary artery was the right anterior oblique 17 ± 7° position. A pig with a rare congenital giant dilated aorta was found among the candidate experimental animals.

CONCLUSIONS

For experimental porcine models, CT angiography has proved to be a suitable imaging technique. The established baseline angiography of the swine can provide reference values for future animal experiments and device development.
Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data
Authors: Nijs Michel , Wajs Ewa , Aluisio Leah , Turkoz Ibrahim , Daly Ella , Janik Adam , Borentain Stephane , Singh Jaskaran B , DiBernardo Allitia , Wiegand Frank
Published: April 2020

Background

Esketamine nasal spray was recently approved for treatment-resistant depression. The current analysis evaluated the impact of symptom-based treatment frequency changes during esketamine treatment on clinical outcomes.

Methods

This is a post-hoc analysis of an open-label, long-term (up to 1 year) study of esketamine in patients with treatment-resistant depression (SUSTAIN 2). During a 4-week induction phase, 778 patients self-administered esketamine twice weekly plus a new oral antidepressant daily. In responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale total score from baseline), esketamine treatment frequency was thereafter decreased during an optimization/maintenance phase to weekly for 4 weeks and then adjusted to the lowest frequency (weekly or every other week) that maintained remission (Montgomery-Åsberg Depression Rating Scale ≤ 12) based on a study-defined algorithm. The relationship between treatment frequency and symptom response, based on clinically meaningful change in Clinical Global Impression–Severity score, was subsequently evaluated 4 weeks after treatment frequency adjustments in the optimization/maintenance phase.

Results

Among 580 responders treated with weekly esketamine for the first 4 weeks in the optimization/maintenance phase (per protocol), 26% continued to improve, 50% maintained clinical benefit, and 24% worsened. Thereafter, when treatment frequency could be reduced from weekly to every other week, 19% further improved, 49% maintained benefit, and 32% worsened. For patients no longer in remission after treatment frequency reduction, an increase (every other week to weekly) resulted in 47% improved, 43% remained unchanged, and 10% worsened.

Conclusions

These findings support individualization of esketamine nasal spray treatment frequency to optimize treatment response in real-world clinical practice.

Trial Registration

ClinicalTrials.gov identifier: NCT02497287
Peripheral Blood Mucosal-Associated Invariant T Cells in Tuberculosis Patients and Healthy Mycobacterium tuberculosis-Exposed Controls
Authors: Suliman Sara , Gela Anele , Mendelsohn Simon C , Iwany Sarah K , Tamara Kattya Lopez , Mabwe Simbarashe , Bilek Nicole , Darboe Fatoumatta , Fisher Michelle , Corbett Alexandra J , Kjer-Nielsen Lars , Eckle Sidonia B G , Huang Chuan-Chin , Zhang Zibiao , Lewinsohn David M , McCluskey James , Rossjohn Jamie , Hatherill Mark , León Segundo R , Calderon Roger I , Lecca Leonid , Murray Megan , Scriba Thomas J , Van Rhijn Ildiko , Moody D Branch
Published: April 2020

Background

In human blood, mucosal-associated invariant T (MAIT) cells are abundant T cells that recognize antigens presented on non-polymorphic major histocompatibility complex-related 1 (MR1) molecules. The MAIT cells are activated by mycobacteria, and prior human studies indicate that blood frequencies of MAIT cells, defined by cell surface markers, decline during tuberculosis (TB) disease, consistent with redistribution to the lungs.

Methods

We tested whether frequencies of blood MAIT cells were altered in patients with TB disease relative to healthy Mycobacterium tuberculosis-exposed controls from Peru and South Africa. We quantified their frequencies using MR1 tetramers loaded with 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil.

Results

Unlike findings from prior studies, frequencies of blood MAIT cells were similar among patients with TB disease and latent and uninfected controls. In both cohorts, frequencies of MAIT cells defined by MR1-tetramer staining and coexpression of CD161 and the T-cell receptor alpha variable gene TRAV1-2 were strongly correlated. Disease severity captured by body mass index or TB disease transcriptional signatures did not correlate with MAIT cell frequencies in patients with TB.

Conclusions

Major histocompatibility complex (MHC)-related 1-restrictied MAIT cells are detected at similar levels with tetramers or surface markers. Unlike MHC-restricted T cells, blood frequencies of MAIT cells are poor correlates of TB disease but may play a role in pathophysiology.
Exosomes Facilitate Transmission of Enterovirus A71 From Human Intestinal Epithelial Cells
Authors: Huang Hsing-I , Lin Jhao-Yin , Chiang Hsiao-Chu , Huang Pen-Nien , Lin Qing-Dong , Shih Shin-Ru
Published: April 2020

Background

Enterovirus A71 (EV-A71) has been noted for its tendency to lead to neurological manifestations in young children and infants. Although the alimentary tract has been identified as the primary replication site of this virus, how EV-A71 replicates in the gut and is transmitted to other organs remains unclear.

Methods

By using differentiated C2BBe1 cells as a model, we observed that intestinal epithelial cells (IECs) were permissive to EV-A71 infection, and viral particles were released in a nonlytic manner.

Results

The coexistence of active caspase 3 and EV-A71 protein was observed in the infected undifferentiated C2BBe1 and RD cells but not in the infected differentiated C2BBe1 cells. Furthermore, EV-A71 infection caused differentiated C2BBe1 and intestinal organoids to secrete exosomes containing viral components and have the ability to establish active infection. Inhibition of the exosome pathway decreased EV-A71 replication and release in IECs and increased the survival rates of infected animals.

Conclusions

Our findings showed that EV-A71 is able to be actively replicated in enterocytes, and that the exosome pathway is involved in the nonlytic release of viral particles, which may be useful for developing antiviral strategies.
In Utero Seasonal Food Insecurity and Cognitive Development: Evidence on Gender Imbalances From Ethiopia
Authors: Beshir Habtamu Ali , Maystadt Jean-François
Published: April 2020

Food insecurity is pervasive and highly seasonal in Ethiopia. In this study, we investigate the effect of seasonal food insecurity on child development. Exploiting the Young Lives Ethiopia dataset, we study the gender-specific impact of in utero exposure to seasonal food insecurity on cognitive development and the probability of being on the expected grade for children of age 8 up to 12. We find that at age 8, in utero exposure to food insecurity negatively affects cognitive development, only for boys. At age 12, such exposure significantly reduces cognitive development for all children, but with a significantly higher magnitude for boys. The impact is almost three times bigger compared to the one estimated for girls. Corroborated with other outcomes, we explain such gender imbalances by the accumulative nature of the scarring effect rather than the culling effect or gender differences in parental investment.
O-GlcNAc regulates gene expression by controlling detained intron splicing
Authors: Tan Zhi-Wei , Fei George , Paulo Joao A , Bellaousov Stanislav , Martin Sara E S , Duveau Damien Y , Thomas Craig J , Gygi Steven P , Boutz Paul L , Walker Suzanne
Published: April 2020

Intron detention in precursor RNAs serves to regulate expression of a substantial fraction of genes in eukaryotic genomes. How detained intron (DI) splicing is controlled is poorly understood. Here, we show that a ubiquitous post-translational modification called O-GlcNAc, which is thought to integrate signaling pathways as nutrient conditions fluctuate, controls detained intron splicing. Using specific inhibitors of the enzyme that installs O-GlcNAc (O-GlcNAc transferase, or OGT) and the enzyme that removes O-GlcNAc (O-GlcNAcase, or OGA), we first show that O-GlcNAc regulates splicing of the highly conserved detained introns in OGT and OGA to control mRNA abundance in order to buffer O-GlcNAc changes. We show that OGT and OGA represent two distinct paradigms for how DI splicing can control gene expression. We also show that when DI splicing of the O-GlcNAc-cycling genes fails to restore O-GlcNAc homeostasis, there is a global change in detained intron levels. Strikingly, almost all detained introns are spliced more efficiently when O-GlcNAc levels are low, yet other alternative splicing pathways change minimally. Our results demonstrate that O-GlcNAc controls detained intron splicing to tune system-wide gene expression, providing a means to couple nutrient conditions to the cell's transcriptional regime.
Role of stress in the development of rheumatoid arthritis: a case–control study
Authors: Germain Vincent , Scherlinger Marc , Barnetche Thomas , Pichon Clémence , Balageas Alexandre , Lequen Laurence , Shipley Emilie , Foret Jennifer , Dublanc Stéphanie , Capuron Lucile , Schaeverbeke Thierry ,   the Fédération Hospitalo-Universitaire ACRONIM
Published: April 2020

Objectives

The primary objective of this study was to assess the stressful life events preceding the onset of symptoms in RA. The secondary objectives were to assess how early RA patients perceive stress and cope with stressors.

Methods

A case–control study was performed, comparing patients recently diagnosed with RA to age- and gender-matched control subjects recently hospitalized for an unplanned surgical procedure not known to be influenced by stress. The Social Readjustment Rating Scale assessed the cumulative stress induced by stressful life events in the year preceding the onset of symptoms. Coping strategies, stress and anxiety symptoms were evaluated using validated psychological scales.

Results

Seventy-six subjects were included in each group. The mean Social Readjustment Rating Scale score was twice as high in cases compared with controls [respectively, 167.0 (172.5) vs 83.3 (124.4), P < 0.001]. The association between cumulative stress and RA was statistically significant only in women, with a dose-dependent association between stress and RA. While female patients with RA attributed more often the onset of symptoms to a life event than female controls (70.2 vs 24.5%, P < 0.001), no significant difference was found when comparing male RA patients with male controls (26.9 vs 18.5%, respectively, P = 0.46). Increased perceived stress score (P = 0.04) and coping based on emotions (P = 0.001) were found in cases compared with controls.

Conclusion

Patients with early RA reported more life events in the year preceding the onset of symptoms than controls. Gender specificities were found with a significant association between cumulative stress and RA only in women.
Clinical phenotypes of IgG4-related disease reflect different prognostic outcomes
Authors: Lanzillotta Marco , Campochiaro Corrado , Mancuso Gaia , Ramirez Giuseppe Alvise , Capurso Gabriele , Falconi Massimo , Dagna Lorenzo , Della-Torre Emanuel
Published: April 2020

Introduction

Four clinical phenotypes of IgG4-related disease (IgG4-RD) have been recently identified by latent class analysis (LCA): pancreato-biliary (group 1); retroperitoneum/aortitis (group 2); head and neck limited (group 3); and Mikulicz/systemic (group 4). The reproducibility of this classification in clinical practice and its relevance for patient management, however, remain unknown.

Methods

The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA-derived phenotypes based on clinical judgement. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on an additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index (RI); history of atopy, diabetes, osteoporosis, relapses and malignancy; cumulative dose of glucocorticoids; and use of rituximab.

Results

Clinical judgement replicated LCA classification with strong agreement among IgG4-RD experts (κ = 0.841, P < 0.0005). At disease onset, group 1 showed the highest levels of serum IgG4 and IgE. Groups 2 and 4 had the lowest and highest IgG4-RD RI, respectively. At 2 years’ follow-up, group 3 received the highest cumulative dose of glucocorticoids, but higher incidences of diabetes mellitus were observed in groups 1 and 4, consistent with the higher likelihood of pancreatic involvement in groups 1 and 4. No difference among the four groups was observed in terms of disease recurrence, time to relapse and frequency of rituximab infusion.

Conclusion

Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes.
High prevalence, genetic diversity and a potentially novel genotype of Sapelovirus A (Picornaviridae) in enteric and respiratory samples in Hungarian swine farms
Authors: Boros Ákos , László Zoltán , Pankovics Péter , Marosi András , Albert Mihály , Cságola Attila , Bíró Hunor , Fahsbender Elizabeth , Delwart Eric , Reuter Gábor
Published: April 2020

All of the known porcine sapeloviruses (PSVs) currently belong to a single genotype in the genus Sapelovirus (family Picornaviridae). Here, the complete genome of a second, possibly recombinant, genotype of PSV strain SZ1M-F/PSV/HUN2013 (MN807752) from a faecal sample of a paraplegic pig in Hungary was characterized using viral metagenomics and RT-PCR. This sapelovirus strain showed only 64 % nucleotide identity in the VP1 region to its closest PSV-1 relative. Complete VP1 sequence-based epidemiological investigations of PSVs circulating in Hungary showed the presence of diverse strains found in high prevalence in enteric and respiratory samples collected from both asymptomatic and paraplegic pigs from 12 swine farms. Virus isolation attempts using PK-15 cell cultures were successful in 3/8 cases for the classic but not the novel PSV genotype. Sequence comparisons of faeces and isolate strains derived VP1 showed that cultured PSV strains not always represent the dominant PSVs found in vivo.
TEXS: in-vacuum tender X-ray emission spectrometer with 11 Johansson crystal analyzers
Authors: Rovezzi Mauro , Harris Alistair , Detlefs Blanka , Bohdan Timothy , Svyazhin Artem , Santambrogio Alessandro , Degler David , Baran Rafal , Reynier Benjamin , Noguera Crespo Pedro , Heyman Catherine , Van Der Kleij Hans-Peter , Van Vaerenbergh Pierre , Marion Philippe , Vitoux Hugo , Lapras Christophe , Verbeni Roberto , Kocsis Menhard Menyhert , Manceau Alain , Glatzel Pieter
Published: April 2020

The design and first results of a large-solid-angle X-ray emission spectrometer that is optimized for energies between 1.5 keV and 5.5 keV are presented. The spectrometer is based on an array of 11 cylindrically bent Johansson crystal analyzers arranged in a non-dispersive Rowland circle geometry. The smallest achievable energy bandwidth is smaller than the core hole lifetime broadening of the absorption edges in this energy range. Energy scanning is achieved using an innovative design, maintaining the Rowland circle conditions for all crystals with only four motor motions. The entire spectrometer is encased in a high-vacuum chamber that allocates a liquid helium cryostat and provides sufficient space forin situcells andoperandocatalysis reactors.
Focusing with saw-tooth refractive lenses at a high-energy X-ray beamline
Authors: Shastri S. D. , Kenesei P. , Mashayekhi A. , Shade P. A
Published: April 2020

The Advanced Photon Source 1-ID beamline, operating in the 40–140 keV X-ray energy range, has successfully employed continuously tunable saw-tooth refractive lenses to routinely deliver beams focused in both one and two dimensions to experiments for over 15 years. The practical experience of implementing such lenses, made of silicon and aluminium, is presented, including their properties, control, alignment, and diagnostic methods, achieving ∼1 µm focusing (vertically). Ongoing development and prospects towards submicrometre focusing at these high energies are also mentioned.
Innovation of impairment loss allowance model of Indonesian financial accounting standards 71
Authors: Sugiarto Sugiarto , Suroso Suroso
Published: April 2020

Purpose

This study aims to develop a high-quality impairment loss allowance model in conformity with Indonesian Financial Accounting Standards 71 (PSAK 71) that has significant contribution to national interests and the banking industry.

Design/methodology/approach

The determination of the impairment loss allowance model is settled through 7 stages, using integration of some statistical methods such as Markov chain, exponential smoothing, time series analysis of behavioral inherent trends of probability of default, tail conditional expectation and Monte Carlo simulation.

Findings

The model which is developed by the authors is proven to be a high-quality and reliable model. By using the model, it can be shown that the implementation of the expected credit losses model on Indonesian Financial Accounting Standards 71 is more prudent than the implementation of the incurred loss model on Indonesian Financial Accounting Standards 55.

Research limitations/implications

Determination of defaults was based on days past due, and the analysis in this study did not touch the aspects of hedge accounting in general.

Practical implications

This developed model will contribute significantly to national interests as a source of reference for other banks operating in Indonesia in calculating impairment loss allowance (CKPN) and can be used by the Financial Services Authority of Indonesia (OJK) as a guideline in assessing the formation of impairment loss allowance for banks operating in Indonesia.

Originality/value

As so far there is not yet an available standardized model for calculating impairment loss allowance on the basis of Indonesian Financial Accounting Standards 71, the model developed by the authors will be a new breakthrough in Indonesia.
Evaluation of Commercial Molecular Diagnostic Methods for Detection and Determination of Macrolide Resistance in Mycoplasma pneumoniae
Authors: Leal Sixto M. , Totten Arthur H. , Xiao Li , Crabb Donna M. , Ratliff Amy , Duffy Lynn B. , Fowler Karen B. , Mixon Emily , Winchell Jonas M. , Diaz Maureen H. , Benitez Alvaro J. , Wolff Bernard J. , Qin Xuan , Tang Y.-W. , Gonzalez Mark , Selvarangan Raj , Hong Tao , Brooks Edward , Dallas Steve , Atkinson T. Prescott , Zheng Xiaotian , Dien Bard Jennifer , Waites Ken B.
Published: April 2020

We evaluated six commercial molecular tests targeting
Mycoplasma pneumoniae
, namely, the BioFire FilmArray respiratory panel (RP), the Meridian Alethia Mycoplasma Direct, the GenMark ePlex respiratory pathogen panel (RPP), the Luminex NxTAG RPP, the ELITech ELITe InGenius
Mycoplasma
MGB research use only (RUO) PCR, and the SpeeDx
Resistance Plus
MP assays. Laboratory-developed PCR assays at the University of Alabama at Birmingham and the Centers for Disease Control and Prevention were used as reference standards.
Genomic Epidemiology and Evolution of Diverse Lineages of Clinical Campylobacter jejuni Cocirculating in New Hampshire, USA, 2017
Authors: Park Cooper J. , Li Jinfeng , Zhang Xinglu , Gao Fengxiang , Benton Christopher S. , Andam Cheryl P.
Published: April 2020

Campylobacter jejuni
is one of the leading causes of bacterial gastroenteritis worldwide. In the United States, New Hampshire was one of the 18 states that reported cases in the 2016 to 2018 multistate outbreak of multidrug-resistant
C. jejuni
. Here, we aimed to elucidate the baseline diversity of the wider New Hampshire
C. jejuni
population during the outbreak. We used genome sequences of 52 clinical isolates sampled in New Hampshire in 2017, including 1 of the 2 isolates from the outbreak.