bluuebunny/crossref_metadata_2025 huggingface dataset:
Virus discovery in all three major lineages of terrestrial arthropods highlights the diversity of single-stranded DNA viruses associated with invertebrates
Authors: Rosario Karyna , Mettel Kaitlin A , Benner Bayleigh E , Johnson Ryan , Scott Catherine , Yusseff-Vanegas Sohath Z , Baker Christopher CM , Cassill Deby L , Storer Caroline , Varsani Arvind , Breitbart Mya
Published: August 2018

Viruses encoding a replication-associated protein (Rep) within a covalently closed, single-stranded (ss)DNA genome are among the smallest viruses known to infect eukaryotic organisms, including economically valuable agricultural crops and livestock. Although circular Rep-encoding ssDNA (CRESS DNA) viruses are a widespread group for which our knowledge is rapidly expanding, biased sampling towards vertebrates and land plants has limited our understanding of their diversity and evolution. Here we screened terrestrial arthropods for CRESS DNA viruses and report the identification of 44 viral genomes and replicons associated with specimens representing all three major terrestrial arthropod lineages, namely Euchelicerata (spiders), Hexapoda (insects), and Myriapoda (millipedes). We identified virus genomes belonging to three established CRESS DNA viral families (Circoviridae, Genomoviridae, and Smacoviridae); however, over half of the arthropod-associated virus genomes are only distantly related to currently classified CRESS DNA viral sequences. Although members of viral and satellite families known to infect plants (Geminiviridae, Nanoviridae, Alphasatellitidae) were not identified in this study, these plant-infecting CRESS DNA viruses and replicons are transmitted by hemipterans. Therefore, members from six out of the seven established CRESS DNA viral families circulate among arthropods. Furthermore, a phylogenetic analysis of Reps, including endogenous viral sequences, reported to date from a wide array of organisms revealed that most of the known CRESS DNA viral diversity circulates among invertebrates. Our results highlight the vast and unexplored diversity of CRESS DNA viruses among invertebrates and parallel findings from RNA viral discovery efforts in undersampled taxa.
Comparing enzyme activity modifier equations through the development of global data fitting templates in Excel
Authors: Walsh Ryan
Published: August 2018

The classical way of defining enzyme inhibition has obscured the distinction between inhibitory effect and the inhibitor binding constant. This article examines the relationship between the simple binding curve used to define biomolecular interactions and the standard inhibitory term (1+([I]/Ki)). By understanding how this term relates to binding curves which are ubiquitously used to describe biological processes, a modifier equation which distinguishes between inhibitor binding and the inhibitory effect, is examined. This modifier equation which can describe both activation and inhibition is compared to standard inhibitory equations with the development of global data fitting templates in Excel and via the global fitting of these equations to simulated and previously published datasets. In both cases, this modifier equation was able to match or outperform the other equations by providing superior fits to the datasets. The ability of this single equation to outperform the other equations suggests an over-complication of the field. This equation and the template developed in this article should prove to be useful tools in the study of enzyme inhibition and activation.
Oscillation criteria for even order neutral difference equations
Authors: Selvarangam S. , Rupadevi S. A. , Thandapani E. , Pinelas S.
Published: August 2018

In this paper, we present some new sufficient conditions for oscillation of even order nonlinear neutral difference equation of the form \[\Delta^m(x_n+ax_{n-\tau_1}+bx_{n+\tau_2})+p_nx_{n-\sigma_1}^{\alpha}+q_nx_{n+\sigma_2}^{\beta}=0,\quad n\geq n_0\gt0,\] where \(m\geq 2\) is an even integer, using arithmetic-geometric mean inequality. Examples are provided to illustrate the main results.
Using paired serology and surveillance data to quantify dengue transmission and control during a large outbreak in Fiji
Authors: Kucharski Adam J , Kama Mike , Watson Conall H , Aubry Maite , Funk Sebastian , Henderson Alasdair D , Brady Oliver J , Vanhomwegen Jessica , Manuguerra Jean-Claude , Lau Colleen L , Edmunds W John , Aaskov John , Nilles Eric James , Cao-Lormeau Van-Mai , Hué Stéphane , Hibberd Martin L
Published: August 2018

Dengue is a major health burden, but it can be challenging to examine transmission and evaluate control measures because outbreaks depend on multiple factors, including human population structure, prior immunity and climate. We combined population-representative paired sera collected before and after the 2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such factors influence transmission and control in island settings. Our results suggested the 10–19 year-old age group had the highest risk of infection, but we did not find strong evidence that other demographic or environmental risk factors were linked to seroconversion. A mathematical model jointly fitted to surveillance and serological data suggested that herd immunity and seasonally varying transmission could not explain observed dynamics. However, the model showed evidence of an additional reduction in transmission coinciding with a vector clean-up campaign, which may have contributed to the decline in cases in the later stages of the outbreak.
Insights into centriole geometry revealed by cryotomography of doublet and triplet centrioles
Authors: Greenan Garrett A , Keszthelyi Bettina , Vale Ronald D , Agard David A
Published: August 2018

Centrioles are cylindrical assemblies comprised of 9 singlet, doublet, or triplet microtubules, essential for the formation of motile and sensory cilia. While the structure of the cilium is being defined at increasing resolution, centriolar structure remains poorly understood. Here, we used electron cryo-tomography to determine the structure of mammalian (triplet) and Drosophila (doublet) centrioles. Mammalian centrioles have two distinct domains: a 200 nm proximal core region connected by A-C linkers, and a distal domain where the C-tubule is incomplete and a pair of novel linkages stabilize the assembly producing a geometry more closely resembling the ciliary axoneme. Drosophila centrioles resemble the mammalian core, but with their doublet microtubules linked through the A tubules. The commonality of core-region length, and the abrupt transition in mammalian centrioles, suggests a conserved length-setting mechanism. The unexpected linker diversity suggests how unique centriolar architectures arise in different tissues and organisms.
Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription
Authors: Novais-Cruz Marco , Alba Abad Maria , van IJcken Wilfred FJ , Galjart Niels , Jeyaprakash A Arockia , Maiato Helder , Ferrás Cristina
Published: August 2018

Recent studies have challenged the prevailing dogma that transcription is repressed during mitosis. Transcription was also proposed to sustain a robust spindle assembly checkpoint (SAC) response. Here, we used live-cell imaging of human cells, RNA-seq and qPCR to investigate the requirement for de novo transcription during mitosis. Under conditions of persistently unattached kinetochores, transcription inhibition with actinomycin D, or treatment with other DNA-intercalating drugs, delocalized the chromosomal passenger complex (CPC) protein Aurora B from centromeres, compromising SAC signaling and cell fate. However, we were unable to detect significant changes in mitotic transcript levels. Moreover, inhibition of transcription independently of DNA intercalation had no effect on Aurora B centromeric localization, SAC response, mitotic progression, exit or death. Mechanistically, we show that DNA intercalating agents reduce the interaction of the CPC with nucleosomes. Thus, mitotic progression, arrest, exit or death is determined by centromere structural integrity, rather than de novo transcription.
How are we Measuring Up? Evaluating Research Data Services in Academic Libraries
Authors: Coates Heather L. , Carlson Jake , Clement Ryan , Henderson Margaret , Johnston Lisa R , Shorish Yasmeen
Published: August 2018

INTRODUCTION In the years since the emergence of federal funding agency data management and sharing requirements (http://datasharing.sparcopen.org/data), research data services (RDS) have expanded to dozens of academic libraries in the United States. As these services have matured, service providers have begun to assess them. Given a lack of practical guidance in the literature, we seek to begin the discussion with several case studies and an exploration of four approaches suitable to assessing these emerging services. DESCRIPTION OF PROGRAM This article examines five case studies that vary by staffing, drivers, and institutional context in order to begin a practice-oriented conversation about how to evaluate and assess research data services in academic libraries. The case studies highlight some commonly discussed challenges, including insufficient training and resources, competing demands for evaluation efforts, and the tension between evidence that can be easily gathered and that which addresses our most important questions. We explore reflective practice, formative evaluation, developmental evaluation, and evidence-based library and information practice for ideas to advance practice. NEXT STEPS Data specialists engaged in providing research data services need strategies and tools with which to make decisions about their services. These range from identifying stakeholder needs to refining existing services to determining when to extend and discontinue declining services. While the landscape of research data services is broad and diverse, there are common needs that we can address as a community. To that end, we have created a community-owned space to facilitate the exchange of knowledge and existing resources.
Captive gibbons (Hylobatidae) use different referential cues in an object-choice task: insights into lesser ape cognition and manual laterality
Authors: Caspar Kai R. , Mader Larissa , Pallasdies Fabian , Lindenmeier Miriam , Begall Sabine
Published: August 2018

Background

Utilization of visual referential cues by non-human primates is a subject of constant scientific interest. However, only few primate species, mostly great apes, have been studied thoroughly in that regard, rendering the understanding of phylogenetic influences on the underlying cognitive patterns difficult.

Methods

We tested six species of captive gibbons in an object-choice task (n = 11) for their ability to interpret two different pointing gestures, a combination of body orientation and gaze direction as well as glancing as referential cues. Hand preferences were tested in the object-choice task and in a bimanual tube task (n = 18).

Results

We found positive responses to all signals except for the glancing cue at the individual as well as at the group level. The gibbons’ success rates partially exceed results reported for great apes in comparable tests and appear to be similarly influenced by prior exposure to human communicative cues. Hand preferences exhibited by the gibbons in the object-choice task as well as in a bimanual tube task suggest that crested gibbons (Nomascussp.) are strongly lateralized at individual but not at population level for tasks involving object manipulation.

Discussion

Based on the available data, it can be assumed that the cognitive foundations to utilize different visual cues essential to human communication are conserved in extant hominoids and can be traced back at least to the common ancestor of great and lesser apes. However, future studies have to further investigate how the social environment of gibbons influences their ability to exploit referential signals. Gibbons’ manual laterality patterns appear to differ in several aspects from the situation found in great apes. While not extensive enough to allow for general conclusions about the evolution of hand preferences in gibbons or apes in general, our results add to the expanding knowledge on manual lateralization in the Hylobatidae.
Occurrence of virulent multidrug-resistantEnterococcus faecalisandEnterococcus faeciumin the pigs, farmers and farm environments in Malaysia
Authors: Tan Shiang Chiet , Chong Chun Wie , Teh Cindy Shuan Ju , Ooi Peck Toung , Thong Kwai Lin
Published: August 2018

Background

Enterococcus faecalisandEnterococcus faeciumare ubiquitous opportunistic pathogens found in the guts of humans and farmed animals. This study aimed to determine the occurrence, antimicrobial resistance, virulence, biofilm-forming ability and genotypes ofE. faecalisandE. faeciumfrom swine farms. Correlations between the genotypes, virulotypes, antibiotic resistance, and the environmental factors such as locality of farms and farm hygiene practice were explored.

Methods

E. faecalisandE. faeciumstrains were isolated from the oral, rectal and fecal samples of 140 pigs; nasal, urine and fecal samples of 34 farmers working in the farms and 42 environmental samples collected from seven swine farms located in Peninsular Malaysia. Antibiotic susceptibility test was performed using the disk diffusion method, and the antibiotic resistance and virulence genes were detected by Polymerase Chain Reaction. Repetitive Extragenic Palindromic-Polymerase Chain Reaction and Pulsed-Field Gel Electrophoresis were performed to determine the clonality of the strains. Crosstab/Chi-square test and DistLM statistical analyses methods were used to determine the correlations between the genotypes, virulence factors, antibiotic resistance, and the environmental factors.

Results

A total of 211E. faecalisand 42E. faeciumwere recovered from 140 pigs, 34 farmers and 42 environmental samples collected from seven swine farms in Peninsular Malaysia. Ninety-eight percent of the strains were multidrug-resistant (resistant to chloramphenicol, tetracycline, ciprofloxacin and erythromycin). Fifty-two percent of the strains formed biofilms. Virulence genesefa, asaI, gelE,esp,cylandacegenes were detected. Virulence genesefaandasaI were most prevalent inE. faecalis(90%) andE. faecium(43%), respectively. Cluster analyses based on REP-PCR and PFGE showed the strains were genetically diverse. Overall, the strains isolated from pigs and farmers were distinct, except for three highly similar strains found in pigs and farmers. The strains were regional- and host-specific.

Discussion

This study revealed alarming high frequencies of multidrug-resistant enterococci in pigs and swine farmers. The presence of resistance and virulence genes and the ability to form biofilm further enhance the persistence and pathogenicity of the strains. Although the overall clonality of the strains were regionals and host-specific, strains with high similarity were found in different hosts. This study reiterates a need of a more stringent regulation to ensure the proper use of antibiotics in swine husbandry to reduce the wide spread of multidrug-resistant strains.
Protein folding and quinary interactions: creating cellular organisation through functional disorder
Authors: Ribeiro Sara , Ebbinghaus Simon , Marcos João C.
Published: August 2018

The marginal stability of globular proteins in the cell is determined by the balance between excluded volume effect and soft interactions. Quinary interactions are a type of soft interactions involved in intracellular organisation and known to have stabilising or destabilising effects on globular proteins. Recent studies suggest that globular proteins have structural flexibility, exhibiting more than one functional state. Here, we propose that the quinary‐induced destabilisation can be sufficient to produce functional partially unfolded states of globular proteins. The biological relevance of this mechanism is explored, involving intracellular phase separation and regulatory stress response mechanisms.
Spatial versus temporal structure: Implications of inter‐haul variation and relatedness in the North‐east Atlantic spurdog Squalus acanthias
Authors: Thorburn James , Jones Rosie , Neat Francis , Pinto Cecilia , Bendall Victoria , Hetherington Stuart , Bailey David Mark , Leslie Noble , Jones Cath
Published: August 2018

Micropopulation processes, such as gene flow, operating within geographic regions are often poorly understood, despite their potential to affect stock structure and sustainability. This is especially true for highly mobile species, such as elasmobranchs, where the potential for spatial overlap of regional populations is increased as a result of greater movement capabilities. A lack of information on these processes means that management plans rarely consider spatio‐temporal structure.

Spurdog (Squalus acanthias) are globally distributed throughout temperate regions yet there is an apparent lack of gene flow between ocean basins. In the North‐east Atlantic there is little work on gene flow within the region, which is currently managed as a single stock that is estimated to be at 19% compared with 1905. Some evidence from this region suggests population processes that have the potential to cause structuring.

The population structure of the North‐east Atlantic spurdog was investigated using an 828‐bp fragment of the mitochondrial DNA control region and seven focal polymorphic microsatellite markers. Samples from 295 individuals from eight locations throughout UK waters were used in this study.

Overall, mitochondrial sequences suggest some regional differentiation. Genetic diversity was comparable with that reported in previous studies of spurdog. Haplotype diversity (0.782–1.000) is amongst the highest observed for an elasmobranch. Microsatellite markers suggest that a high level of relatedness was responsible for regional population structuring. There was no apparent spatial structure after removal of ‘full sibling’ relationships.

Inter‐haul variation from Celtic Sea samples is suggestive of subpopulations and aggregation events, which may have important implications for fisheries conservation of this and other elasmobranch species.
Switchable Dielectric Phase Transition Triggered by Pendulum‐Like Motion in an Ionic Co‐crystal
Authors: Wang Qing , Zhang Wan‐Ying , Shi Ping‐Ping , Ye Qiong , Fu Da‐Wei
Published: August 2018

Molecular‐based ionic co‐crystals, which have the merits of low‐cost/easy fabrication processes and flexible structure and functionality, have already exhibited tremendous potential in molecular memory switches and other electric devices. However, dipole (ON/OFF switching) triggering is a huge challenge. Here, we introduce a pendulum‐like dynamic strategy to induce the order–disorder transition of a co‐crystal [C5H7N3Cl]3[Sb2Br9] (compound 1). Here, the anion and cation act as a stator and a pendulum‐like rotor (the source of the dielectric switch), respectively. The temperature‐dependent dielectric and differential scanning calorimetry (DSC) analyses reveal that 1 undergoes a reversible phase transition, which stems from the order–disorder transition of the cations. The thermal ON/OFF switchable motions make 1 a promising candidate to promote the development of bulk crystals as artificial intelligent dielectric materials. In addition, the pendulum‐like molecular dynamics and distinct arrangements of two coexisting ions with a notable offset effect promotes/hinders dipolar reorientation after dielectric transition and provides a rarely observed but fairly useful and feasible strategy for understanding and modulating the dipole motion in crystalline electrically polarizable materials.
Life‐cycle greenhouse gas emissions of corn kernel fiber ethanol
Authors: Qin Zhangcai , Li Qianfeng , Wang Michael , Han Jeongwoo , Dunn Jennifer B.
Published: August 2018

Corn kernel fiber ethanol that can be produced concurrently with corn starch ethanol has recently been approved as cellulosic biofuel in the USA, suggesting that fiber ethanol could be eligible for a higher credit price than conventional starch ethanol due to its anticipated lower greenhouse gas (GHG) emissions. A life‐cycle analysis was conducted to quantify ethanol's GHG emissions. Here we show that fiber ethanol's life‐cycle GHG emissions (36–39 g CO2e MJ−1) are close to meeting the US cellulosic biofuel's legislative mandate of 60% GHG emissions reduction relative to gasoline (~94 g CO2e MJ−1), with slightly lower emissions under the nth plant mature fiber technology than under the state of technology (SOT). The co‐product, distiller's grain with solubles (DGS), can notably affect fiber ethanol's GHG emissions, and this impact may need to be further examined when evidence of DGS market impacts becomes available. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd
Understanding Animal Evolution: The Added Value of Sponge Transcriptomics and Genomics
Authors: Renard Emmanuelle , Leys Sally P. , Wörheide Gert , Borchiellini Carole
Published: August 2018

Sponges are important but often‐neglected organisms. The absence of classical animal traits (nerves, digestive tract, and muscles) makes sponges challenging for non‐specialists to work with and has delayed getting high quality genomic data compared to other invertebrates. Yet analyses of sponge genomes and transcriptomes currently available have radically changed our understanding of animal evolution. Sponges are of prime evolutionary importance as one of the best candidates to form the sister group of all other animals, and genomic data are essential to understand the mechanisms that control animal evolution and diversity. Here we review the most significant outcomes of current genomic and transcriptomic analyses of sponges, and discuss limitations and future directions of sponge transcriptomic and genomic studies.
Fluorescence‐Lifetime‐Sensitive Probes for Monitoring ATP Cleavage
Authors: Hammler Daniel , Marx Andreas , Zumbusch Andreas
Published: August 2018

Adenosine triphosphate (ATP) probes modified with fluorescence dyes that change their fluorescence properties upon cleavage are an interesting tool for monitoring enzymatic ATP turnover. As a readout parameter, fluorescence lifetime is attractive because it is nearly independent of concentration. In our study, we synthesised and investigated fifteen different ATP analogues, in which the fluorophores were attached to the γ‐phosphate of ATP. All analogues showed distinctly different fluorescence lifetimes compared to the corresponding values of the free fluorophores. Both increases and decreases in fluorescence lifetime were observed upon attachment to ATP. To shed light on the photophysical processes governing the lifetime changes, we performed photoelectron spectroscopy in air (PESA) to determine HOMO energy levels and time‐resolved fluorescence spectroscopy to obtain rate constants. We present evidence that fluorescence quenching in the compounds tested is dynamic and attributed to photoinduced electron transfer (PET), whereas fluorescence lifetime increases are caused by stacking interactions between chromophore and the nucleobase reducing non‐radiative relaxation. Finally, we demonstrate that enzymatic cleavage of the ATP analogues presented can be followed by continuous monitoring of fluorescence lifetime changes.
Tetrakis(phenylethynyl)tetracene: A New π‐Extended Rubrene Derivative
Authors: Kitamura Kei , Asahina Kenta , Nagai Yusaku , Sugiyama Haruki , Uekusa Hidehiro , Hamura Toshiyuki
Published: August 2018

An efficient synthetic route to 5,6,11,12‐tetrakis(arylethynyl)tetracenes, new π‐extended rubrene derivatives, was developed by means of [2+4] cycloaddition of dialkynylnaphthalyne and dialkynylisobenzofuran. Importantly, two alkynyl groups introduced into the aryne exerts a significant effect in lowering the LUMO energy, allowing practical access to sterically overcrowded polycyclic structures through an efficient HOMO–LUMO interaction. Study on the potential reactivity inherent in the peri‐ethynyl‐substituted tetracenes revealed several interesting reactivities. X‐ray analysis of these new π‐extended derivatives showed distorted structures to reduce steric repulsion due to the existence of the substituents at the peri‐positions.
Modeling the Catalytic Conversion of Steel Mill Gases Using the Example of Methanol Synthesis
Authors: Schlüter Stefan , Hennig Torsten
Published: August 2018

The conversion of steel mill off‐gases to base chemicals is a promising perspective to improve the financial return of steelmaking in Europe and fight CO2 emissions. In the Carbon2Chem® joint research project, mathematical models are developed to simulate operation scenarios of cross‐industrial networks and chemical plants embedded in a steel mill environment. Methodically, the modeling follows a multilevel approach combining models of different depth and origin in a common simulation framework. Here, the synthesis of methanol is simulated and analyzed for different gas conditioning scenarios.
The Project Carbon2Chem®
Authors: Deerberg Görge , Oles Markus , Schlögl Robert
Published: August 2018

Keeping carbon in the loop is a short sentence that describes the Carbon2Chem® project. Climate protection requires a reduction of CO2 emissions as well as less use of fossil fuels. In the project, a consortium from industry and science works on implementing a flexible carbon capture and utilization (CCU) concept for the carbon‐based industry. An example is the cross‐industrial network of steel industry, chemical industry, and energy industry. Instead of being harmful waste, top gases from the steel mill now serve as raw material for the production of synthetic fuels, plastics, and basic chemicals. This is possible through the systemic use of renewable energy.
Liver Transplant Listing in Pediatric Acute Liver Failure: Practices and Participant Characteristics
Authors: Squires James E. , Rudnick David A. , Hardison Regina M. , Horslen Simon , Ng Vicky L. , Alonso Estella M. , Belle Steven H. , Squires Robert H. ,   for the Pediatric Acute Liver Failure Study Group
Published: August 2018

Liver transplant (LT) decisions in pediatric acute liver failure (PALF) are complex. Three phases of the PALF registry, containing data on 1,144 participants over 15 years, were interrogated to characterize clinical features associated with listing status. A decrease in the cumulative incidence of listing (P < 0.005) and receiving (P < 0.05) LT occurred without an increase in the cumulative incidence of death (P = 0.67). Time to listing was constant and early (1 day; quartiles 1‐3 = 0‐2; P = 0.88). The most frequent reasons for not listing were “not sick enough” and “medically unsuitable.” Participants listed for LT were more likely male, with coma grade scores >0; had higher international normalized ratio, bilirubin, lactate, and venous ammonia; and had lower peripheral lymphocytes and transaminase levels compared to those deemed “not sick enough.” Participants listed versus those deemed “medically unsuitable” were older; had higher serum aminotransferase levels, bilirubin, platelets, and albumin; and had lower lactate, venous ammonia, and lymphocyte count. An indeterminate diagnosis was more prevalent in listed participants. Ventilator (23.8%) and vasopressor (9.2%) support occurred in a significant portion of listed participants but less frequently than in those who were not “medically suitable.” Removal from the LT list was a rare event. Conclusion: The cumulative incidence of listing for and receiving LT decreased throughout the PALF study without an increase in the cumulative incidence of death. While all participants fulfilled entry criteria for PALF, significant differences were noted between participants listed for LT and those deemed “not sick enough” as well as those who were “medically unsuitable.” Having an indeterminate diagnosis and a requirement for cardiopulmonary support appeared to influence decisions toward listing; optimizing listing decisions in PALF may reduce the frequency of LT without increasing the frequency of death.
Prospective Intraindividual Comparison of Magnetic Resonance Imaging With Gadoxetic Acid and Extracellular Contrast for Diagnosis of Hepatocellular Carcinomas Using the Liver Imaging Reporting and Data System
Authors: Min Ji Hye , Kim Jong Man , Kim Young Kon , Kang Tae Wook , Lee Soon Jin , Choi Gyu Seong , Choi Seo‐Youn , Ahn Soohyun
Published: August 2018

We intraindividually compared the efficacy of magnetic resonance imaging (MRI) with extracellular contrast agents (ECA‐MRI) and MRI with hepatobiliary agents (HBA‐MRI) for the diagnosis of hepatocellular carcinoma (HCC) using the Liver Imaging Reporting and Data System (LI‐RADS). Between November 2016 and November 2017, we enrolled 91 patients with chronic liver disease who underwent both ECA‐MRI and HBA‐MRI within a 1‐month interval for a first detected hepatic nodule on ultrasound. In total, 117 observations (95 HCCs, 19 benign lesions, and 3 other malignancies; median size, 18 mm) were identified with surgical resection. Two observers assessed two MRIs based on LI‐RADS v2017, with consensus by a third observer. We then compared the diagnostic performance of LR‐5 according to LI‐RADS and modified LI‐RADS. ECA‐MRI had higher sensitivity (77.9% versus 66.3%) and accuracy (82.1% versus 72.6%) than HBA‐MRI in the LR‐5 category (P < 0.001). When applying either modified washout on the portal venous phase (PVP)/transitional phase (TP) of HBA‐MRI or isointensity with a capsule during the PVP/delayed phase of ECA‐MRI (illusional washout), 13 HCCs on HBA‐MRI and 11 HCCs on ECA‐MRI were correctly classified as HCC, while achieving 100% specificity. One cholangiocarcinoma was accurately classified only with HBA‐MRI due to its targetoid appearance in the TP and hepatobiliary phase. Conclusion: ECA‐MRI showed better sensitivity and accuracy than HBA‐MRI for the diagnosis of HCC with LI‐RADS. We achieved better diagnostic performance when applying a modified washout on PVP/TP HBA‐MRI and an illusional washout on ECA‐MRI than we did with conventional criteria.
Short‐Duration AL‐335, Odalasvir, With or Without Simeprevir, in Patients With HCV GT1 or 3 Infection Without Cirrhosis
Authors: Gane Edward J. , Stedman Catherine A. , Schwabe Christian , Vijgen Leen , Chanda Sushmita , Kakuda Thomas N. , Fry John , Blatt Lawrence M. , McClure Matthew W.
Published: August 2018

This open‐label, phase IIa study assessed the safety, pharmacokinetics, and efficacy of direct‐acting antiviral agent (DAA) regimens in patients with chronic hepatitis C virus (HCV) infection. Multiple 6‐12‐week oral regimens of 400‐800 mg once daily (QD) AL‐335 + 50 mg QD/every other day odalasvir ± 75‐150 mg QD simeprevir were evaluated in treatment‐naïve, HCV genotype (GT)1/3‐infected patients without cirrhosis. Safety/pharmacokinetic parameters, HCV‐RNA, and sequencing data were assessed. Treatment regimens for later study cohorts were adjusted based on emerging data. In total, 112 patients were enrolled. Three serious treatment‐emergent adverse events occurred, one of which (a Mobitz type 1 second‐degree atrioventricular block [Wenckebach]) was possibly related to high odalasvir exposure and resulted in premature discontinuation of study drugs. No other clinically significant safety findings were identified. GT1‐infected patients receiving 3‐DAA for 6‐8 weeks achieved 100% sustained virologic response 12 weeks and 24 weeks after the end of treatment (sustained virologic response [SVR12/24]). GT1‐infected patients receiving 2‐DAA or GT3‐infected patients receiving 3‐DAA had SVR12/24 less than 90%, whether treated for 8 weeks or 12 weeks. Virologic failure was associated with the emergence of generally persistent NS5A and/or transient NS5B resistance‐associated substitutions in most patients. Pharmacokinetic characteristics of the three drugs were also elucidated. Conclusions: In treatment‐naïve subjects without cirrhosis, AL‐335 + odalasvir + simeprevir for 6‐8 weeks was generally safe and highly efficacious against HCV GT1. However, inadequate efficacy was observed for the 2‐DAA regimen in GT1‐infected subjects and the 3‐DAA regimen in GT3‐infected subjects.
Oxidized Albumin Triggers a Cytokine Storm in Leukocytes Through P38 Mitogen‐Activated Protein Kinase: Role in Systemic Inflammation in Decompensated Cirrhosis
Authors: Alcaraz‐Quiles José , Casulleras Mireia , Oettl Karl , Titos Esther , Flores‐Costa Roger , Duran‐Güell Marta , López‐Vicario Cristina , Pavesi Marco , Stauber Rudolf E. , Arroyo Vicente , Clària Joan
Published: August 2018

Decompensated cirrhosis is characterized by exuberant systemic inflammation. Although the inducers of this feature remain unknown, the presence of circulating forms of oxidized albumin, namely human nonmercaptalbumin 1 (HNA1) and HNA2, is a common finding in cirrhosis. The aim of this study was to explore the ability of these oxidized albumin forms to induce systemic inflammation by triggering the activation of peripheral leukocytes. We observed significantly higher plasma levels of HNA1 and HNA2 in patients with cirrhosis (n = 256) compared to healthy volunteers (n = 48), which gradually increased during the course from compensated to decompensated to acute‐on‐chronic liver failure. Plasma HNA1 and HNA2 levels significantly correlated with inflammatory markers (i.e., interleukin‐6 [IL‐6], IL‐1β, tumor necrosis factor‐alpha [TNF‐α] and IL‐8) in patients with cirrhosis. To directly test the inflammatory effects of HNA1 and HNA2 on leukocytes, these oxidized albumin forms were prepared ex vivo and their posttranslational modifications monitored by liquid chromatography (LC)–quadrupole time‐of‐flight/mass spectrometry (MS). HNA1, but not HNA2, increased IL‐1β, IL‐6, and TNF‐α mRNA and protein expression in leukocytes from both healthy volunteers and patients with cirrhosis. Moreover, HNA1 up‐regulated the expression of eicosanoid‐generating enzymes (i.e., cyclooxygenase‐2 [COX‐2] and microsomal prostaglandin E [PGE] synthase 1) and the production of inflammatory eicosanoids (PGE2, PGF2α, thromboxane B2, and leukotriene B4), as determined by LC–electrospray ionization–MS/MS. The inflammatory response to HNA1 was more pronounced in peripheral blood mononuclear cells (PBMCs) and marginal in polymorphonuclear neutrophils. Kinome analysis of PBMCs revealed that HNA1 induced the phosphorylation of p38 mitogen‐activated protein kinase, the inhibition of which blocked HNA1‐induced cytokine and COX‐2 induction. Conclusion: HNA1 triggers an inflammatory response in PBMCs, providing a rationale for its removal and replacement by reduced albumin in the prevention of systemic inflammation in patients with advanced liver disease.
Acne vulgaris severity graded by in vivo reflectance confocal microscopy and optical coherence tomography
Authors: Fuchs Christine S. K. , Andersen Amanda J. B. , Ardigo Marco , Philipsen Peter A. , Haedersdal Merete , Mogensen Mette
Published: August 2018

Introduction

Acne is an inflammatory disease of the pilosebaceous unit, which can be investigated in vivo using reflectance confocal microscopy (RCM) and optical coherence tomography (OCT).

Objectives

By means of RCM and OCT to identify morphological characteristics of acne that may be associated with clinical acne severity.

Methods

Patients with mild to moderate facial acne (n = 14, Investigators Global Assessment scale, IGA 1–3), and healthy participants (n = 7, IGA 0) were included in this explorative study. A total of 108 RCM image blocks and 54 OCT scans (each RCM and OCT image measuring 6 × 6 mm) were captured from lesional‐, perilesional, and lesion‐free skin areas. Acne lesions, infundibular regions of follicles and inflammation degree were compared in acne patients and healthy participants.

Results

Combined use of RCM and OCT demonstrated infundibular morphology, acne lesions, and blood flow. RCM images of perilesional‐ and lesion‐free skin in acne patients revealed follicle infundibula with hyperkeratinized borders and abundant keratin plugs, contrasting skin of healthy participants. Higher acne severity related to increased number of follicles with hyperkeratotic borders (P = 0.04) and keratin plugs (P = 0.006), increased infundibulum diameter (P < 0.001), increased density of inflammatory cells (P < 0.001), and blood flow (P = 0.03). Acne lesion morphology was not associated with acne severity.

Conclusion

Combined use of RCM and OCT elucidated distinctive follicle infundibulum characteristics and inflammation degree that were associated with acne severity. Future trials may apply imaging techniques to support clinical acne grading, and monitor treatment efficacy. Lasers Surg. Med. 51:104–113, 2019. © 2018 Wiley Periodicals, Inc.
TGF‐β1 and connexin‐43 expression in neurogenic bladder from rats with sacral spinal cord injury
Authors: Zhao Jimao , Wu Menghua , Chen Siyang , Ji Zhengguo , Zheng Xin
Published: August 2018

Aims

Sacral spinal cord injury (SCI) could induce underactive bladder (UAB). Malfunction of connexin 43 (CX43) regulated by TGF‐β1 might involve in urinary bladder dysfunction. We studied the changes of CX43 and TGF‐β1/Smad3 signaling in detrusor of neurogenic bladder (NB) in sacral SCI rats.

Methods

Sacral SCI was produced by hemisection (SSCH) or transection (SSCT) of spinal cord between L4 and L5 in female Wistar rats. BBB scores, residual urine volume and bladder weight as well as characteristic cystometric parameters at 6th week were used to confirm the successful establishment of NB. Western blotting and qRT‐PCR were used to exam the protein and mRNA expression levels of CX43, CX45, TGF‐β1, and Smad3 in detrusor.

Results

BBB scores were significantly decreased, with the lowest in SSCT rats (P < 0.01). The residual urine volume, mean bladder weight, and cystometric parameters were increased, with the highest in SSCT rats. CX43 and phospho‐CX43 protein levels were significantly decreased, but those of TGF‐β1, Smad3, and phospho‐Smad3 were significantly increased. It was the protein and mRNA levels of CX43 but not those of CX45 which were decreased in negative accordance with those of TGF‐β1 and Smad3. Those changes were more significant in SSCT than in SSCH rats.

Conclusions

This study indicates that voiding dysfunction is related to the decreased CX43 function in detrusor from NB. TGF‐β1/Smad3 signaling might be involved in the down‐regulation of CX43 in SCI rats. Early regulation of CX43 might be beneficial to patients with voiding dysfunction.
The Nature of Lithium‐Ion Transport in Low Power Consumption LiFePO4 Resistive Memory with Graphite as Electrode
Authors: Zhang Lei , Wu Cheng , Liu Jun , Zhao Xiaoning , Wang Zhongqiang , Xu Haiyang , Wang Liancheng , Liu Yichun
Published: August 2018

Lithium‐ion migration modulated by electric field in carbon‐based materials has been reported extensively in lithium‐ion batteries, which will also offer potential application in ion‐migration‐related resistive switching (RS) memories. Inspired by this, lithium iron phosphate (LiFePO4)‐based RS memory (Au/LiFePO4/G) is developed with Au and graphite sheet as electrodes. The devices can be operated with a low power consumption (<30 µW) by controlling the compliance currents. The RS mechanism is ascribed to lithium concentration‐related reversible conductivity switching inLiFePO4 due to lithium ions insertion/extraction through the graphite electrode as verified by temperature‐dependent resistance, time‐of‐flight secondary ion mass spectrometry, and Raman spectra. As indicated by the experiments, LiFePO4 is potentially useful for future low power nonvolatile memory applications.
Disseminated Cryptococcus gattii infection preceding onset of pulmonary alveolar proteinosis
Authors: Quah Jessica , Low Teck Boon , Fong Raymond
Published: August 2018

A 50‐year‐old immunocompetent man presented with intracranial space‐occupying lesions and a right lung mass. This was found to be disseminated Cryptococcus gattii infection. Following 15 months of anti‐fungal therapy, imaging showed reduction in the size of the pulmonary cryptococcoma and new multi‐lobar ground‐glass opacities interspersed with a crazy‐paving pattern. Surgical lung biopsy was performed after bronchoscopic evaluation was non‐yielding. Histology showed intra‐alveolar accumulation of foamy macrophages and airspaces containing periodic acid Schiff‐positive amorphous eosinophilic material with strong immune positivity for surfactant A, consistent with a diagnosis of pulmonary alveolar proteinosis (PAP). The majority of adult‐onset PAP is due to the presence of anti‐granulocyte macrophage colony‐stimulating factor antibodies. Opportunistic fungal and mycobacterial infections are known to occur in these patients due to alveolar macrophage and neutrophilic dysfunction. The onset of PAP may occur concurrently with, or be temporally distinct from, opportunistic infections. For patients with respiratory failure, whole lung lavage is a therapeutic strategy.
Formability of 800 MPa Grade Hot‐Dip Galvanized Steel Sheet
Authors: Song Renbo , Zhang Kai , Gao Yi
Published: August 2018

Hot‐dip galvanized steel sheets are widely used for their better corrosion resistance. With the development of steel materials and the need for higher performance of galvanized steel, it is urgent to carry out research on the formability of 800 MPa or even higher grade hot‐dip galvanized steel sheets. In this paper, forming limit diagram (FLD) is assessed in laboratory by stretch‐forming galvanized sheets with a hemispherical punch. The intersection of forming limit curve (FLC) and the major strain axis is around 0.28. By comparison to zinc layer removed samples, galvanized samples have higher yield strength and lower strain hardening coefficient. Formability of experimental galvanized sheets declines significantly attributed to the existence of brittle intermetallic Fe–Zn phase. The original positions of cracking in zinc layer are microcracks and voids around the zinc grain boundaries. During punch forming, the crack networks are formed by the microcracks from the different layers of the zinc coating and may accumulate and propagate to the surface. Forming failure including cracks and flaking makes the zinc layer thinner and increases the tendency of matrix to be exposed.
Modified Starches as Direct Compression Excipients – Effect of Physical and Chemical Modifications on Tablet Properties: A Review
Authors: Lawal Mariam V.
Published: August 2018

Starch is an abundant natural polymer with unique properties that make it amenable to various kinds of treatments. This deliberate attempt at altering the character of native starch results in modified starches. Starches are extensively used in the pharmaceutical industry, especially as excipients in tablet formulation. It is now widely acknowledged that starches in their native form have functional limitations. Modification is a means of enhancing the functionality of native starch for a wide variety of applications. The importance of modified starches as excipients for pharmaceutical direct compression has been identified. Although, there is a wealth of information on starch modification, characterization and applications in the literature, there does not appear to be as yet, any attempt at a methodological analysis of physical and chemical modification techniques as they apply to pharmaceutical direct compression. This review aims at addressing these gaps. It describes a range of physical and chemical techniques employed in producing modified starches and their potentials as excipients for direct compression. The effect of modification on the morphological and functional properties of starch in various direct compression formulations is also reviewed.
A synchronous program algebra: a basis for reasoning about shared-memory and event-based concurrency
Authors: Hayes Ian J. , Meinicke Larissa A. , Winter Kirsten , Colvin Robert J.
Published: August 2018

In this paper we introduce an abstract algebra for reasoning about concurrent programs, that includes an abstract algebra of atomic steps, with sub-algebras of program and environment steps, and an abstract synchronisation operator. We show how the abstract synchronisation operator can be instantiated as a synchronous parallel operator with interpretations in rely-guarantee concurrency for shared-memory systems, and in process algebras CCS and CSP. It is also instantiated as a weak conjunction operator, an operator that is useful for the specification of rely and guarantee conditions in rely/guarantee concurrency. The main differences between the parallel and weak conjunction instantiations of the synchronisation operator are how they combine individual atomic steps. Lemmas common to these different instantiations are proved once using the axiomatisation of the abstract synchronous operator. Using the sub-algebras of program and environment atomic steps, rely and guarantee conditions, as well as Morgan-style specification commands, are defined at a high-level of abstraction in the program algebra. Lifting these concepts from rely/guarantee concurrency to a higher level of abstraction makes them more widely applicable. We demonstrate the practicality of the algebra by showing how a core law from rely-guarantee theory, the parallel introduction law, can be abstracted and verified easily in the algebra. In addition to proving fundamental properties for reasoning about concurrent shared-variable programs, the algebra is instantiated to prove abstract process synchronisation properties familiar from the process algebras CCS and CSP. The algebra has been encoded in Isabelle/HOL to provide a basis for tool support for concurrent program verification based on the rely/guarantee technique. It facilitates simpler, more general, proofs that allow a higher level of automation than what is possible in low-level, model-specific interpretations.
Utility of the Addenbrooke’s Cognitive Examination in Amyotrophic Lateral Sclerosis
Authors: Chenji Sneha , Mah Dennell , Johnston Wendy , Camicioli Richard , Fisher Nancy , Kalra Sanjay
Published: August 2018

Objective

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that primarily affects motor neurons. Cognitive changes are reported in 25%-50% of patients, secondary to frontotemporal involvement. The objective of this study was to evaluate the utility of a screening tool, the Addenbrooke’s Cognitive Examination (ACE), in ALS patients.

Methods

In this retrospective cross-sectional study, performance on the ACE was compared between 55 ALS patients and 49 healthy controls. The validation of the ACE in ALS patients was explored using a neuropsychometric battery. Correlations between the ACE and clinical variables such as the ALS Functional Rating Scale-Revised (ALSFRS-R) and forced vital capacity were computed.

Results

A higher percentage of patients were below cut-off scores, although this remained non-significant between the patient and control groups. The ACE did not reveal significant differences between ALS patients and controls. The scores on the ACE displayed moderate correlations with our neuropsychometric battery for some domains, whereas others showed poor or no associations. Poor ACE Total was associated with lower ALSFRS-R and finger-tapping scores.

Conclusions

Performance on the ACE was comparable between patients and controls. Associations with motor function pose a challenge to accurate interpretation of ACE performance. It is likely that patients with poor cognition have greater disability, or that poor ACE performance reflects reduced motor ability to perform the task. This raises concern for the utility of the ACE as a screening tool in ALS patients, especially since recent versions of the ACE continue to include motor-based tasks.