bluuebunny/crossref_metadata_2025 huggingface dataset:
Thiocillin and Micrococcin Exploit the Ferrioxamine Receptor ofPseudomonas aeruginosafor Uptake
Authors: Chan Derek C. K. , Burrows Lori L.
Published: April 2020

Thiopeptides are a class of Gram-positive antibiotics that inhibit protein synthesis. They have been underutilized as therapeutics due to solubility issues, poor bioavailability, and lack of activity against Gram-negative pathogens. We discovered recently that a member of this family, thiostrepton, has activity againstPseudomonas aeruginosa and Acinetobacter baumanniiunder iron-limiting conditions. Thiostrepton uses pyoverdine siderophore receptors to cross the outer membrane, and combining thiostrepton with an iron chelator yielded remarkable synergy, significantly reducing the minimal inhibitory concentration. These results led to the hypothesis that other thiopeptides could also inhibit growth by using siderophore receptors to gain access to the cell. Here, we screened six thiopeptides for synergy with the iron chelator deferasirox againstP. aeruginosaand a mutant lacking the pyoverdine receptors FpvA and FpvB. Our findings suggest that thiopeptides such as thiocillin cross the outer membrane using FoxA, the ferrioxamine siderophore receptor. Other structurally related thiopeptides did not inhibit growth ofP. aeruginosa, but had greater potency against methicillin-resistantStaphylococcus aureusthan thiostrepton and related thiopeptides. These results suggest that thiopeptide structures have evolved with considerations for target affinity and entry into cells.
Cerebral cavernous malformation 1 determines YAP/TAZ signaling dependent metastatic hallmarks of prostate cancer cells
Authors: Park Sangryoung , Lee Ho-Yong , Park Hansol , Ju Young Seok , Kim Jayoung , Kim Eung-Gook , Kim Jaehong
Published: April 2020

Enhanced Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling is correlated with the extraprostatic extension of prostate cancer. However, the mechanism by which YAP/TAZ signaling becomes hyperactive and drives prostate cancer progression is currently unclear. In this study, we demonstrated that CCM1 induces the metastasis of multiple types of prostate cancer cells by regulating YAP/TAZ signaling. Mechanistically, CCM1, a gene mutated in cerebral cavernous malformation, suppresses DDX5, which regulates the PLK1-mediated suppression of YAP/TAZ signaling, indicating that CCM1 and DDX5 are novel upstream regulators of YAP/TAZ signaling. We also revealed that higher expression of CCM1, which is uniquely found in advanced prostate cancer, is inversely correlated with metastasis-free and overall survival in patients with prostate cancer. Our findings highlight the importance of CCM1-DDX5-PLK1-YAP/TAZ signaling in the metastasis of prostate cancer cells.

Statement of Significance

Our analysis of CCM1 expression and function represents a candidate predictive biomarker for prostate cancer metastasis and provides an evidence that abnormality of CCM1 can be pathogenic in prostate cancer. Importantly, CCM1 regulation of metastasis progression appears to a common molecular event in metastatic prostate cancer cells arising in disparate genetic backgrounds.
Charge-Driven Condensation of RNA and Proteins Suggests Broad Role of Phase Separation in Cytoplasmic Environments
Authors: Dutagaci Bercem , Nawrocki Grzegorz , Goodluck Joyce , Ashkarran Ali Akbar , Hoogstraten Charles G. , Lapidus Lisa J. , Feig Michael
Published: April 2020

Phase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well established drivers of liquid-liquid phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Condensates retain liquid character and phase diagrams are mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.

STATEMENT OF SIGNIFICANCE

Liquid-liquid phase separation has been recognized as a key mechanism for forming membrane-less organelles in cells. Commonly discussed mechanisms invoke a role of disordered peptides and specific multi-valent interactions. We report here phase separation of RNA and proteins based on a more universal principle of charge complementarity that does not require disorder or specific interactions. The findings are supported by coarse-grained simulations, theory, and experimental validation via microscopy and spectroscopy. The broad implication of this work is that condensate formation may be a universal phenomenon in biological systems.
The Viral Polymerase Complex Mediates the Interaction of vRNPs with Recycling Endosomes During SeV Assembly
Authors: Genoyer Emmanuelle , Kulej Katarzyna , Hung Chuan Tien , Thibault Patricia A. , Azarm Kristopher , Takimoto Toru , Garcia Benjamin A. , Lee Benhur , Lakdawala Seema , Weitzman Matthew D. , López Carolina B.
Published: April 2020

Paramyxoviruses are negative sense single-stranded RNA viruses that comprise many important human and animal pathogens, including human parainfluenza viruses. These viruses bud from the plasma membrane of infected cells after the viral ribonucleoprotein complex (vRNP) is transported from the cytoplasm to the cell membrane via Rab11a-marked recycling endosomes. The viral proteins that are critical for mediating this important initial step in viral assembly are unknown. Here we use the model paramyxovirus, murine parainfluenza virus 1, or Sendai virus (SeV), to investigate the roles of viral proteins in Rab11a-driven virion assembly. We previously reported that infection with SeV containing high levels of copy-back defective viral genomes (DVGs) generates heterogenous populations of cells. Cells enriched in full-length virus produce viral particles containing standard or defective viral genomes, while cells enriched in DVGs do not, despite high levels of defective viral genome replication. Here we take advantage of this heterogenous cell phenotype to identify proteins that mediate interaction of vRNPs with Rab11a. We examine the role of matrix protein and nucleoprotein and determine that they are not sufficient to drive interaction of vRNPs with recycling endosomes. Using a combination of mass spectrometry and comparative protein abundance and localization in DVG- and FL-high cells, we identify viral polymerase complex components L and, specifically, its cofactor C proteins as interactors with Rab11a. We find that accumulation of these proteins within the cell is the defining feature that differentiates cells that proceed to viral egress from cells which remain in replication phases.

IMPORTANCE

Paramyxoviruses are a family of viruses that include a number of pathogens with significant burdens on human health. Particularly, human parainfluenza viruses are an important cause of pneumonia and bronchiolitis in children for which there are no vaccines or direct acting antivirals. These cytoplasmic replicating viruses bud from the plasma membrane and coopt cellular endosomal recycling pathways to traffic viral ribonucleoprotein complexes from the cytoplasm to the membrane of infected cells. The viral proteins required for viral engagement with the recycling endosome pathway are still not known. Here we use the model paramyxovirus Sendai virus, or murine parainfluenza virus 1, to investigate the role of viral proteins in this initial step of viral assembly. We find that viral polymerase components large protein L and accessory C proteins are necessary for engagement with recycling endosomes. These findings are important in identifying viral proteins as potential targets for development of antivirals.
Spatio-temporal associations between deforestation and malaria incidence in Lao PDR
Authors: Rerolle Francois , Dantzer Emily , Lover Andrew A. , Marshall John M. , Hongvanthong Bouasy , Sturrock Hugh JW. , Bennett Adam
Published: April 2020

As countries in the Greater Mekong Sub-region (GMS) increasingly focus their malaria control and elimination efforts on forest-going populations, greater understanding of the relationship between deforestation and malaria incidence will be essential for programs to assess and meet their 2030 elimination goals. Leveraging village-level health facility surveillance data and forest cover data in a spatio-temporal modeling framework, we found evidence that deforestation is associated with short-term increases, but long-term decreases in confirmed malaria case incidence in Lao People’s Democratic Republic (Lao PDR). We identified strong associations with deforestation measured within 30 km of villages but not with deforestation in the near (10 km) and immediate (1 km) vicinity. Results appear driven by deforestation in densely forested areas and were more pronounced for infections with Plasmodium falciparum (P. falciparum) than for Plasmodium vivax (P. vivax). These findings highlight the influence of forest-going populations on malaria transmission in the GMS.
Structures of substrate- and product-bound forms of a multi-domain copper nitrite reductase shed light on the role of domain tethering in protein complexes
Authors: Sasaki Daisuke , Watanabe Tatiana F. , Eady Robert R. , Garratt Richard C. , Antonyuk Svetlana V. , Hasnain S. Samar
Published: April 2020

Copper-containing nitrite reductases (CuNiRs) are found in all three kingdoms of life and play a major role in the denitrification branch of the global nitrogen cycle where nitrate is used in place of dioxygen as an electron acceptor in respiratory energy metabolism. Several C- and N-terminal redox domain tethered CuNiRs have been identified and structurally characterized during the last decade. Our understanding of the role of tethered domains in these new classes of three-domain CuNiRs, where an extra cytochrome or cupredoxin domain is tethered to the catalytic two-domain CuNiRs, has remained limited. This is further compounded by a complete lack of substrate-bound structures for these tethered CuNiRs. There is still no substrate-bound structure for any of the as-isolated wild-type tethered enzymes. Here, structures of nitrite and product-bound states from a nitrite-soaked crystal of the N-terminal cupredoxin-tethered enzyme from the Hyphomicrobium denitrificans strain 1NES1 (Hd
1NES1NiR) are provided. These, together with the as-isolated structure of the same species, provide clear evidence for the role of the N-terminal peptide bearing the conserved His27 in water-mediated anchoring of the substrate at the catalytic T2Cu site. Our data indicate a more complex role of tethering than the intuitive advantage for a partner-protein electron-transfer complex by narrowing the conformational search in such a combined system.
Impact of the anion and chalcogen on the crystal structure and properties of 4,6-dimethyl-2-pyrimido(thio)nium halides
Authors: Okuniewski Andrzej , Rosiak Damian , Chojnacki Jarosław
Published: April 2020

By the reaction of urea or thiourea, acetylacetone and hydrogen halide (HF, HBr or HI), we have obtained seven new 4,6-dimethyl-2-pyrimido(thio)nium salts, which were characterized by single-crystal X-ray diffraction, namely, 4,6-dimethyl-2-oxo-2,3-dihydropyrimidin-1-ium bifluoride, C6H9N2O+·HF2
− or (dmpH)F2H, 4,6-dimethyl-2-oxo-2,3-dihydropyrimidin-1-ium bromide, C6H9N2O+·Br− or (dmpH)Br, 4,6-dimethyl-2-oxo-2,3-dihydropyrimidin-1-ium iodide, C6H9N2O+·I− or (dmpH)I, 4,6-dimethyl-2-oxo-2,3-dihydropyrimidin-1-ium iodide–urea (1/1), C6H9N2O+·I−·CH4N2O or (dmpH)I·ur, 4,6-dimethyl-2-sulfanylidene-2,3-dihydropyrimidin-1-ium bifluoride–thiourea (1/1), C6H9N2S+·HF2
−·CH4N2S or (dmptH)F2H·tu, 4,6-dimethyl-2-sulfanylidene-2,3-dihydropyrimidin-1-ium bromide, C6H9N2S+·Br− or (dmptH)Br, and 4,6-dimethyl-2-sulfanylidene-2,3-dihydropyrimidin-1-ium iodide, C6H9N2S+·I− or (dmptH)I. Three HCl derivatives were described previously in the literature, namely, 4,6-dimethyl-2-oxo-2,3-dihydropyrimidin-1-ium chloride, (dmpH)Cl, 4,6-dimethyl-2-sulfanylidene-2,3-dihydropyrimidin-1-ium chloride monohydrate, (dmptH)Cl·H2O, and 4,6-dimethyl-2-sulfanylidene-2,3-dihydropyrimidin-1-ium chloride–thiourea (1/1), (dmptH)Cl·tu. Structural analysis shows that in 9 out of 10 of these compounds, the ions form one-dimensional chains or ribbons stabilized by hydrogen bonds. Only in one compound are parallel planes present. In all the structures, there are charge-assisted N+—H...X
− hydrogen bonds, as well as weaker CAr
+—H...X
− and π+...X
− interactions. The structures can be divided into five types according to their hydrogen-bond patterns. All the compounds undergo thermal decomposition at relatively high temperatures (150–300 °C) without melting. Four oxopyrimidinium salts containing a π+...X
−...π+ sandwich-like structural motif exhibit luminescent properties.
Crystal structures of the flavonoid Oroxylin A and the regioisomers Negletein and Wogonin
Authors: De Grano Ruel Valerio Robles , Vashchenko Elena V. , Nisar Madiha , Sung Herman H.-Y. , Vashchenko Valerii V. , Williams Ian D.
Published: April 2020

The flavonoid Oroxylin A (6-methoxychrysin or 5,7-dihydroxy-6-methoxy-2-phenyl-4H-chromen-4-one, C16H12O5) and its regioisomers are of increasing interest for a variety of bioactive functions and their pharmaceutical formulation is of importance. Previous difficulties in the separation and misidentification of Oroxylin A from its regioisomers Wogonin (8-methoxychrysin or 5,7-dihydroxy-8-methoxy-2-phenyl-4H-chromen-4-one) and Negletein (5,6-dihydroxy-7-methoxyflavone or 5,6-dihydroxy-7-methoxy-2-phenyl-4H-chromen-4-one) render its full structural and powder X-ray characterization highly desirable. The low-temperature (100 K) crystal structures of Oroxylin A, Negletein and Wogonin sesquihydrate are reported for the first time. Wogonin crystallizes in two related but distinct hydrated forms. These have very similar powder diffractograms, indicating that such issues need to be addressed for its pharmaceutical formulation.
Hydrogen-bonding patterns in 2,2-bis(4-methylphenyl)hexafluoropropane pyridinium and ethylenediammonium salt crystals
Authors: Sugiyama Haruki
Published: April 2020

The crystal structures of two salt crystals of 2,2-bis(4-methylphenyl)hexafluoropropane (Bmphfp) with amines, namely, dipyridinium 4,4′-(1,1,1,3,3,3-hexafluoropropane-2,2-diyl)dibenzoate 4,4′-(1,1,1,3,3,3-hexafluoropropane-2,2-diyl)dibenzoic acid, 2C5H6N+·C17H8F6O42−·C17H10F6O4, (1), and a monohydrated ethylenediammonium salt ethane-1,2-diaminium 4,4′-(1,1,1,3,3,3-hexafluoropropane-2,2-diyl)dibenzoate monohydrate, C2H10N22+·C17H8F6O42−·H2O, (2), are reported. Compounds1and2crystallize, respectively, in space groupP21/cwithZ′ = 2 and in space groupPbcawithZ′ = 1. The crystals of compound1contain neutral and anionic Bmphfp molecules, and form a one-dimensional hydrogen-bonded chain motif. The crystals of compound2contain anionic Bmphfp molecules, which form a complex three-dimensional hydrogen-bonded network with the ethylenediamine and water molecules.
Bis(3-methyl-1-propyl-1H-imidazol-3-ium) bis(4,6-disulfanidyl-4,6-disulfanylidene-1,2,3,5,4,6-tetrathiadiphosphinane-κ3
S
2,S
4,S
6)nickel
Authors: Dalecky Lauren M. , Juillerat Christian A. , Cody Jason A.
Published: April 2020

The title salt, (PMIM)2[Ni(P2S8)2] (PMIM = 3-methyl-1-propyl-1H-imidazol-3-ium, C7H13N2
+), consists of a nickel–thiophosphate anion charge-balanced by a pair of crystallographically independent PMIM cations. It crystallizes in the monoclinic space group P21/n. The structure exhibits the known [Ni(P2S8)2]2− anion with two unique imidazolium cations in the asymmetric unit. Whereas one PMIM cation is well ordered, the other is disordered over two orientations with refined occupancies of 0.798 (2) and 0.202 (2). The salt was prepared directly from the elements in the ionic liquid [PMIM]CF3SO3. Whereas one of the PMIM cations is well behaved (it does not exhibit disorder even in the propyl side chain), the other is found in two overlapping positions. The refined occupancies for the two orientations are roughly 80:20. Here, too, there appears to be little disorder in the propyl arm.
Hybrid software reliability model with Pareto distribution and ant colony optimization (PD–ACO)
Authors: D Sudharson , Dr Prabha
Published: April 2020

Purpose

Software reliability models in the past few years attracted researchers to build an accurate model in the software engineering. Testing is an important factor in the software development cycle.

Design/methodology/approach

As testing improves quality and reliability of the application by identifying the bugs in it. Also, it defines the behavior and state of the product based on the defined principles and mechanisms. Conventional reliability models use statistical distributions to attain realistic features.

Findings

The ability to predict the bugs in the application during development phase itself is a proper testing practice which saves the time and increases the efficiency of the application. Efficient management and timely release of the product is based on this reliability testing and ant colony optimization (ACO)-based testing is an important optimization model which is available for testing the application.

Originality/value

Conventional ant colony optimization used test case generation as its common approach for testing the reliability of the application. ACO uses pheromone activity and it is related in testing of application and provides a simple positive mechanism by identifying the inactivity and precociousness.
Confirmation of a measurement model for manufacturing flexibility development practices
Authors: Mishra Ruchi
Published: April 2020

Purpose

The study aims to conceptualize and empirically develop an instrument to measure manufacturing flexibility development practices in firms.

Design/methodology/approach

Using a dataset of 315 responses, a series of procedures were used to develop, modify and refine item measures of constructs to enhance their reliability and validity. Further, following a competing model strategy, alternative models were compared to finalize the manufacturing flexibility development practices.

Findings

The study develops 36-item instrument capturing eight distinct constructs that influence manufacturing flexibility development, namely operational improvement practices, supplier integration practices, advanced manufacturing technologies, advanced human resource practices, supplier flexibility, customer integration practices, marketing and manufacturing integration practices and product-process technology integration. The derived factors exhibit an adequate level of consistency, reliability and validity.

Research limitations/implications

Since the external environment is always affected by externalities, tools and technologies used to develop flexibility may also vary over time. Therefore, the developed measurement instrument can be used over the medium term. Further, the statistical generalizability of this study cannot be drawn beyond the scope of this sample.

Practical implications

The derived items measure and their underlying factor structure facilitates practitioners to identify areas that need attention. Practically, practitioners should strive to improve multiple factors that influence manufacturing flexibility to arrive at the full realization of flexibility.

Originality/value

This study is probably the first to develop an instrument for assessing the factors influencing the potential of manufacturing flexibility.
Leveraging service design for healthcare transformation: toward people-centered, integrated, and technology-enabled healthcare systems
Authors: Patrício Lia , Sangiorgi Daniela , Mahr Dominik , Čaić Martina , Kalantari Saleh , Sundar Sue
Published: April 2020

Purpose

This paper explores how service design can contribute to the evolution of health service systems, moving them toward people-centered, integrated and technology-enabled care; the paper develops a research agenda to leverage service design research for healthcare transformation.

Design/methodology/approach

This conceptual study starts by analyzing healthcare challenges in terms of demographic trends and economic constraints, along with the problems of lack of people-centricity, dispersion of care and slowness in incorporating emerging technologies. Then, it examines the theoretical underpinnings of service design to develop a framework for exploring how a human-centered, transformative and service systems approach can contribute to addressing healthcare challenges, with illustrative cases of service design research in healthcare being given.

Findings

The proposed framework explores how a human-centered service design approach can leverage the potential of technology and advance healthcare systems toward people-centered care; how a transformative service design approach can go beyond explanatory research of healthcare phenomena to develop innovative solutions for healthcare change and wellbeing; and how a service systems perspective can address the complexity of healthcare systems, hence moving toward integrated care.

Originality/value

This paper systematizes and develops a framework for how service design can contribute to healthcare transformation. It identifies key healthcare application areas for future service design research and pathways for advancing service design in healthcare by using new interdisciplinary bridges, methodological developments and theoretical foundations.
Parameter sensitivity analysis of stability of T-shaped rigid frame bridge by adopting swivel construction method
Authors: Wang Jiawei , sun Quansheng
Published: April 2020

Purpose

In order not to affect the highway and railway traffic under the bridge during the construction process, bridges adopting swivel construction method are increasingly used at areas where the traffic is heavy. Previous studies are mostly conducted by assuming that the bridge is under its own stability conditions, without considering the impact of construction error, changes of external condition and wind-induced vibration on the stability of the bridge, which poses serious challenges to the bridge construction process. This paper aims to analyze the extent to which static load and fluctuating wind effect influence structural stability and to test the credibility of the structure.

Design/methodology/approach

A finite element calculation method is used to analyze a T-shaped rigid frame swivel bridge. A full bridge model was built, and a local model of the turntable structure established; the two are then combined means of node coupling. Subsequently, the three sensitivity indexes – deflection rate, stress change rate and the change rate of spherical hinges – are used to evaluate in what way the bridge stability is influenced under various factors.

Findings

It is found that the stability of the swivel bridge is quite sensitive to unilateral overweight, steel beam tension and wind-induced vibration effects but less sensitive to the change of bulk density. Also found is that the change of elastic modulus exerts some effects on deflection but has negligible effects on other stability indexes. Furthermore, the transverse unbalanced torque on the bridge generated by wind-induced vibration is an important factor in determining the size of the turntable, indicating that it is not just controlled by the weight of the bridge.

Originality/value

All factors affecting the stability of swivel construction are analyzed, and solutions to reduce the influence are proposed. The influence of wind-induced vibration effects on swivel construction is analyzed for the first time. It is pointed out that wind-induced vibration effects have great influence on the structure, and its influence could not be neglected.
Sharing economy: a review of the literature and a framework for future research
Authors: Wang Xuequn , Lin Xiaolin , Abdullat Amjad
Published: April 2020

Purpose

As sharing economy has become increasingly popular, researchers from various disciplines begin to pay more attention to this important phenomenon. However, the current literature is fragmented and lacks a framework to integrate previous studies and guide future research. This study aims to systematically review the literature to better understand what one knows and what one need to know about sharing economy and provide a road map for future research in the context of sharing economy.

Design/methodology/approach

A systematic review was conducted with EBSCO and science direct database. In total, 91 studies were identified.

Findings

The review shows that previous studies focus on different stakeholders, including consumers, peer service providers, platform providers, and competitors. The authors further identify the main topics and limitations of the literature (integrated into a framework) and provide possible directions for future studies. For example, the authors find that few studies have examined individual and technical factors. The findings also show that consumers’ other activities and outcomes have received little attention. To address these limitations, future studies that examine how individual and technical characteristics influence sharing economy’s usage intention/behaviors are suggested. The authors also suggest future studies to explore other activities during the process of sharing economy services.

Research limitations/implications

The framework and directions provided can further the sharing economy research by addressing important gaps in the current literature.

Originality/value

This review identifies many opportunities for researchers to better understand the phenomenon of sharing economy.
The use of isothermal titration calorimetry to unravel chemotactic signalling mechanisms
Authors: Matilla Miguel A. , Martín‐Mora David , Krell Tino
Published: April 2020

Chemotaxis is based on the action of chemosensory pathways and is typically initiated by the recognition of chemoeffectors at chemoreceptor ligand‐binding domains (LBD). Chemosensory signalling is highly complex; aspect that is not only reflected in the intricate interaction between many signalling proteins but also in the fact that bacteria frequently possess multiple chemosensory pathways and often a large number of chemoreceptors, which are mostly of unknown function. We review here the usefulness of isothermal titration calorimetry (ITC) to study this complexity. ITC is the gold standard for studying binding processes due to its precision and sensitivity, as well as its capability to determine simultaneously the association equilibrium constant, enthalpy change and stoichiometry of binding. There is now evidence that members of all major LBD families can be produced as individual recombinant proteins that maintain their ligand‐binding properties. High‐throughput screening of these proteins using thermal shift assays offer interesting initial information on chemoreceptor ligands, providing the basis for microcalorimetric analyses and microbiological experimentation. ITC has permitted the identification and characterization of many chemoreceptors with novel specificities. This ITC‐based approach can also be used to identify signal molecules that stimulate members of other families of sensor proteins.
The Effect of Investment, LFA and Agri‐environmental Subsidies on the Components of Total Factor Productivity: The Case of Slovenian Farms
Authors: Baráth Lajos , Fertő Imre , Bojnec Štefan
Published: April 2020

The effect of subsidies on the performance of farms has received a great deal of attention in the literature, although results are inconclusive. Furthermore, much of the related literature examines the effect of subsidies only on technical efficiency (TE). We examine the effect of different types of subsidies on the different components of total factor productivity (TFP) in Slovenian agriculture over the period 2006–2013. We first estimate a Random Parameter Stochastic production frontier model. Then, based on the estimates of this model, we calculate and decompose the TFP index into TE, scale efficiency and technological change. Third, we apply combined difference‐in‐difference and a matching estimator to examine the effect of investment, less favoured area (LFA) and agri‐environmental (AE) subsidies on the different components of TFP. In our case, these subsidies are found to have no significant effect on either TFP or on its components.
Amur tiger stripes: individual identification based on deep convolutional neural network
Authors: SHI Chunmei , LIU Dan , CUI Yonglu , XIE Jiajun , ROBERTS Nathan James , JIANG Guangshun
Published: April 2020

The automatic individual identification of Amur tigers (Panthera tigris altaica) is important for population monitoring and making effective conservation strategies. Most existing research primarily relies on manual identification, which does not scale well to large datasets. In this paper, the deep convolution neural networks algorithm is constructed to implement the automatic individual identification for large numbers of Amur tiger images. The experimental data were obtained from 40 Amur tigers in Tieling Guaipo Tiger Park, China. The number of images collected from each tiger was approximately 200, and a total of 8277 images were obtained. The experiments were carried out on both the left and right side of body. Our results suggested that the recognition accuracy rate of left and right sides are 90.48% and 93.5%, respectively. The accuracy of our network has achieved the similar level compared to other state of the art networks like LeNet, ResNet34, and ZF_Net. The running time is much shorter than that of other networks. Consequently, this study can provide a new approach on automatic individual identification technology in the case of the Amur tiger.
Salt Flushing, Salt Storage, and Controls on Selenium and Uranium: A 31‐Year Mass‐Balance Analysis of an Irrigated, Semiarid Valley
Authors: Bern Carleton R. , Holmberg Michael J. , Kisfalusi Zachary D.
Published: April 2020

Salinity, selenium, and uranium pose water‐quality challenges for the Arkansas River in southeastern Colorado and other rivers that support irrigation in semiarid regions. This study used 31 years of continuous discharge and specific conductance (SC) monitoring data to assess interannual patterns in water quality using mass balance on a 120‐km reach of river. Discrete sampling data were used to link the SC records to salinity, selenium, and uranium. Several important patterns emerged. Consumptive use reduced discharge by a median value of 33% and drove corresponding increases in salinity and uranium concentrations. Increased water availability for irrigation from rainfall and upstream snowpack in 1995–1999 flushed additional salinity and uranium into the river in 1996–2000; average annual total dissolved solids (salinity) concentrations increased 25%, and loads increased 131%. Smaller flushing events have occurred, sometimes lagging an increase in water availability by about one year. The pattern indicates flushing of salts temporarily stored, evaporatively concentrated, or of geologic origin. Mobilization of selenium from the reach was minor compared to salinity and uranium, and net selenium removal from the river was suggested in some years. Several processes related to irrigation could be removing selenium. The results provide context for efforts to improve water quality in the Arkansas River and rivers in other semiarid regions.
Quality and access – Early experience of implementing a virtual stereotactic chart round across a national network
Authors: Fitzgerald Rhys , Pryor David , Aland Trent , Anderson Lee , Knesl Marcel , Fong Andrew , Lunn Dominic , Oar Andrew , Jackson James , Foote Matthew
Published: April 2020

Introduction

Stereotactic radiation therapy is a highly specialised technique which requires careful and structured implementation. As part of a national stereotactic programme implementation, protocols were developed and a national stereotactic chart round was formed, which strongly recommended attendance and presentation of all cases before treatment. Herein, we describe our experiences launching a national chart round and its importance in a stereotactic programme.

Method

Stereotactic chart rounds were held via videoconference between July 2018 and July 2019. Data collected included attendances, patient‐related information including, diagnosis, clinical background, treatment intent, prescribed dose and fractionation and technical approach. Consensus recommendations regarding changes to treatment approaches were also recorded.

Results

For the 12 months recorded, there were 1126 attendances, from 144 individual attendees, across 21 locations. In total, 285 cases (237 new cases, and 48 re‐presentations) were presented by 27 radiation oncologists (ROs) from 13 different locations. From the cases presented, 65 changes were recommended from 53 patients (22.3%), including 27 (11.4%) changes to contours, 18 (7.6%) changes to dose prescription/fractionation, 9 (3.8%) changes to plan dosimetry, 1 (0.4%) changes to treatment technique and 10 (4.2%) recommendations for which stereotactic radiation therapy was not advised. A significant inverse relationship was found between frequency of recommended changes and the individual RO’s stereotactic case load (P < 0.002).

Conclusion

The implementation of a national stereotactic chart held via videoconference has ensured national protocol compliance across the network of locations. Furthermore, the chart rounds have allowed the entire multidisciplinary team to be provided with mentorship and guidance. Increasing number of cases presented was associated with lower rates of recommended changes highlighting the impact of experience and the need for continued mentorship.
Accuracy of Signs and Symptoms for the Diagnosis of Community‐acquired Pneumonia: A Meta‐analysis
Authors: Ebell Mark H. , Chupp Hulme , Cai Xinyan , Bentivegna Michelle , Kearney Maggie
Published: April 2020

Background

Community‐acquired pneumonia (CAP) is an important source of morbidity and mortality. However, overtreatment of acute cough illness with antibiotics is an important problem, so improved diagnosis of CAP could help reduce inappropriate antibiotic use.

Methods

This was a meta‐analysis of prospective cohort studies of patients with clinically suspected pneumonia or acute cough that used imaging as the reference standard. All studies were reviewed in parallel by two researchers and quality was assessed using the QUADAS‐2 criteria. Summary measures of accuracy included sensitivity, specificity, likelihood ratios, the diagnostic odds ratio, and the area under the receiver operating characteristic curve (AUROCC) and were calculated using bivariate meta‐analysis.

Results

We identified 17 studies, of which 12 were judged to be at low risk of bias and the remainder at moderate risk of bias. The prevalence of CAP was 10% in nine primary care studies and was 20% in seven emergency department studies. The probability of CAP is increased most by an abnormal overall clinical impression suggesting CAP (positive likelihood ratio [LR+] = 6.32, 95% CI = 3.58 to 10.5), egophony (LR+ = 6.17, 95% CI = 1.34 to 18.0), dullness to percussion (LR+ = 2.62, 95% CI = 1.14 to 5.30), and measured temperature (LR+ = 2.52, 95% CI = 2.02 to 3.20), while it is decreased most by the absence of abnormal vital signs (LR− = 0.25, 95% CI = 0.11 to 0.48). The overall clinical impression also had the highest AUROCC at 0.741.

Conclusions

While most individual signs and symptoms were unhelpful, selected signs and symptoms are of value for diagnosing CAP. Teaching and performing these high value elements of the physical examination should be prioritized, with the goal of better targeting chest radiographs and ultimately antibiotics.
Tissue‐resident CD8+T memory cells with unique properties are present in human decidua during early pregnancy
Authors: Huang Xixi , Liu Lu , Xu Chunfang , Peng Xiandong , Li Dajin , Wang Li , Du Meirong
Published: April 2020

Problem

Resident memory T (TRM) cells reside in the uterus during pregnancy may play an important role in balancing maternal‐fetal tolerance with anti‐infectious immunity. Although CD8+TRM and decidual CD8+T cells have been extensively characterized, the properties of decidual CD8+TRM (dTRM) cells remain poorly defined.

Method of study

We investigated the heterogeneity, phenotypes, and functions of dTRM cells, and compared the proportion of dTRM cells between normal pregnancy and recurrent spontaneous abortion (RSA) using flow cytometry. Moreover, we cocultured peripheral CD8+T (CD8+pT) cells with trophoblast, or decidual stomal cells (DSCs) in the presence or absence of anti‐TGF‐β antibody or TGF‐β type I receptor inhibitor to explore the effects of maternal‐fetal environment on decidual CD8+TRM cell formation.

Results

We found that CD69+CD103+TRM cells were abundant in CD8+dT cells but not in CD4+dT cells with effector‐memory (EM, CD45RA−CCR7−) phenotypes. The percentage of dTRM cells from RSA patients was significantly higher than that from normal pregnancy. Furthermore, dTRM cells showed increased expressions of chemokine receptors, T‐cell exhaustion‐related molecules, and produced more anti‐inflammatory cytokines and effector cytokines upon stimulation. Moreover, DSCs produced a considerable level of TGF‐β and upregulated CD103 expression on CD69+CD8+pT cells, which can be significantly reversed by blocking TGF‐β receptor.

Conclusion

Our findings demonstrate that TRM cells with unique properties are present in the decidua during human early pregnancy. They possess an enhanced capacity to produce effector cytokines and regulatory molecules, which might be important in the balance between maternal‐fetal immune tolerance and the capacity to aggressively respond to infections.
COVID19 coagulopathy in Caucasian patients
Authors: Fogarty Helen , Townsend Liam , Ni Cheallaigh Cliona , Bergin Colm , Martin‐Loeches Ignacio , Browne Paul , Bacon Christopher L. , Gaule Richard , Gillett Alexander , Byrne Mary , Ryan Kevin , O’Connell Niamh , O’Sullivan Jamie M. , Conlon Niall , O'Donnell James S.
Published: April 2020

Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role. Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3–4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.
Chronology and climate sensitivity of the post‐LGMglaciation in the Dunagiri valley, Dhauliganga basin, Central Himalaya, India
Authors: Kumar Vinit , Shukla Tanuj , Mishra Ajai , Kumar Anil , Mehta Manish
Published: April 2020

In this study, we reconstruct the style and timing of the late Quaternary glaciation pattern in a monsoon‐influenced precipitation‐deprived region (Dhauliganga basin) of the Central Himalaya, India. We present detailed glacial geomorphological mapping, aided by topographic maps, satellite data, Google Earth images, global positioning system survey, and fieldwork (2012–2016), supported by optically stimulated luminescence dating. Our estimations for the magnitude and timing of glaciations in the Dunagiri Glacier valley suggest five sets of glacial advances. The oldest and most extensive glaciation in the valley is Dunagiri Glacial Stage‐I (DGS‐I), represented by a discontinuous moraine ridge that extends down to ~10 km (~2700 m a.s.l.) from the present‐day snout and formed 13±3 ka ago. TheDGS‐IIstage is present in the form of a small moraine ridge (~3000 m a.s.l.) that formed 10±2 ka ago. TheDGS‐IIIandDGS‐IVglacial stages are 5–6 and 3.5 ka old, respectively. The youngest stage (DGS‐V) of glaciation belongs to the neoglaciation episode ~1 ka old.DGS‐I was the most extensive glaciation in the valley and corresponds to the global Last Glacial Maximum. The glaciation pattern has been correlated with the estimates of present‐day glacial sensitivity to climate and explained as forcing factors sensitive to temperature and/or precipitation changes in the region. The observations based on prevailing climate correlations aided with available glacial chronologies underline the fact that the glacial valleys situated in precipitation‐deprived regions have preserved a delayed response of glaciations to regional climatic events. Estimates for the timing and pattern of glaciation in the present study suggest a different glacial response for modern climatic changes than previously assumed. We suggest that individual glacier advances differ regionally and, therefore, should not be interpreted as being reflective of a change in the whole geographical belt.
Clinical efficiency and patient preference of digital and conventional workflow for single implant crowns using immediate and regular digital impression: A meta‐analysis
Authors: de Oliveira Nathalia R. Cunha , Pigozzo Monica N. , Sesma Newton , Laganá Dalva Cruz
Published: April 2020

Objective

To assess whether digital workflow gives better results than the conventional one in the single implant crowns, when analyzing the impression time, patient preference, time efficiency, and adjustment time.

Material and methods

MEDLINE, Embase, and Cochrane were searched and supplemented via hand search up to June 19, 2019. Only clinical trials assessing conventional versus digital workflows for single implant crowns were included. Impression time was evaluated using random effects meta‐analysis, while patient preference, adjustment time, and time efficiency were reported descriptively.

Results

Among 1,334 publications identified, ten studies were included. The random effects models revealed statistically significant reduction in time in the digital impression group when compared to the conventional group by the mean meta‐analysis (MD: 8.22 [95% CI: 5.48, 10.96]). Analysis from immediate digital impression versus conventional (MD: 3.84 [95% CI: 3.30, 4.39]) and regular digital impression versus conventional (MD:10.67 [95% CI: 5.70, 15.65]) showed statistically significant reduction in time on using the digital impression. Impression time in the digital process ranged between 6 min 39 s and 20 min, whereas for conventional, it was between 11.7 and 28.47 min. Patients showed greater preference for digital impression. Adjustment time in the digital process ranged between 1.96 and 14 min, whereas for conventional, it was between 3.02 and 12 min. Time efficiency in the digital process ranged between 36.8 and 185.4 min, whereas for conventional, it was between 55.6 and 332 min.

Conclusion

The digital workflow has demonstrated better clinical efficiency considering impression time, patient preference, and time efficiency. According to the adjustment time, different results were presented.
Molecular and clinical characterization of PARP9 in gliomas: A potential immunotherapeutic target
Authors: Xu Hao , Chai Songshan , Wang Yihao , Wang Jiajing , Xiao Dongdong , Li Junjun , Xiong Nanxiang
Published: April 2020

Background

Glioma is a primary malignancy of the central nervous system (CNS). As biomedicine advances, an efficient molecular target is urgently needed for the diagnosis and treatment of glioma. Meanwhile, several studies have demonstrated that glioma development is closely related to immunity. PARP9 is an inactive mono‐ADP‐ribosyltransferase belonging to the poly‐ADP ribosyltransferase (ARTD) family. In this article, we aimed to reveal the relationship between PARP9 and glioma and explore the potential prognostic value and immunotherapeutic targetability of PARP9 in glioma.

Methods

PARP9 transcript levels were analyzed with TCGA and GEO databases. The clinicopathological information of patients with glioma in the TCGA database and gene expression profiles were analyzed to determine the relationship between the expression of PARP9 and clinicopathologic characteristics. Kaplan‐Meier survival analysis, univariate Cox regression analysis, and multivariate Cox regression analysis were used for survival analysis. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for bioinformatics analysis. Correlation analysis explored the relationships between PARP9, infiltrating inflammatory immune cells, and immune checkpoint molecules.

Results

PARP9 is highly expressed in glioma, and high expression of PARP9 is associated with poor prognosis and advanced clinicopathological features. Bioinformatics analysis showed that some immune‐related pathways were closely associated with high expression of PARP9. Correlation analysis indicated that PARP9 was closely related to inflammatory and immune responses, high immune cell infiltration, and immune checkpoint molecules.

Conclusions

PARP9 may serve as an unfavorable prognosis predictor for glioma and a potential immunotherapeutic target.
Accessibility of ‘essential’ alcohol in the time of COVID‐19: Casting light on the blind spots of licensing?
Authors: Reynolds Joanna , Wilkinson Claire
Published: April 2020

Among the Australian and UK governments' responses to the COVID‐19 pandemic has been the designation of outlets selling alcohol for off‐premise consumption as ‘essential’ services, allowing them to remain open while pubs, hotels and restaurants have been forced to close. In a context of restrictions on movement outside the home in both countries, and where alcohol providers are trying to find new ways to reach their customers, this may lead to an intensification of the social and health harms associated with home drinking. By examining the current situation in both Australia and the UK, we argue that heightened risks from home drinking amid COVID‐19 bring into sharp focus long‐standing weaknesses within licensing systems in both countries: the regulation of off‐premise outlets to minimise harms from drinking at home. We call for critical conversations on how licensing systems should be revised to take more responsibility for protecting people from the health and social harms associated with home drinking, both under COVID‐19 and in the future.