bluuebunny/crossref_metadata_2025 huggingface dataset:
Major cardiovascular events at 5 years in surgical versus percutaneous revascularization for left main stem disease: an updated meta-analysis
Authors: Urso Stefano , Sadaba Rafel , Nogales Eliú , González Jesús María , Tena María Ángeles , Paredes Federico , González-Barbeito Miguel , Portela Francisco
Published: November 2020

The aim of the present study was to analyse the incidence of major adverse cardiovascular events in patients undergoing either coronary artery bypass grafting (CABG) or percutaneous coronary intervention with drug-eluting stents for left main stem disease. Five manuscripts publishing 5-year results of 4 trials (SYNTAX, PRECOMBAT, NOBLE and EXCEL) were included. Overall meta-analysis with inclusion of the 5-year results from the EXCEL trial using the protocol definition for myocardial infarction showed that CABG is associated with a significant reduction in the risk of major adverse cardiovascular events (MACE) (risk ratio = 0.74; 95% confidence interval = 0.68–0.80). When the universal definition was used to define myocardial infarction in the EXCEL trial, the analysis demonstrated a larger benefit of coronary surgery in terms of reduction in the risk of MACE (risk ratio = 0.70; 95% confidence interval = 0.63–0.76). Non-significant differences were detected in terms of risk of overall mortality, cardiac mortality or stroke. In conclusion, this meta-analysis shows that CABG significantly reduces the risk of MACE in patients with left main stem disease. The inclusion of the 5-year results of the EXCEL trial using third universal definition amplifies the benefit of CABG over percutaneous coronary intervention.
Theory and Method and the Stakes of a Fragmented Discipline: Or, What Economics Taught Me About the Study of Religion
Authors: Lewis Thomas A
Published: November 2020

As a discipline, the academic study of religion is strikingly fragmented, with little engagement or shared criteria of excellence across subfields. Although important recent developments have expanded the traditions and peoples studied as well as the methods used, the current extent of fragmentation limits the impact of this diversification and pluralization. At a moment when the global pandemic is catalyzing profound pressures on our universities and disciplines, this fragmentation makes it difficult to articulate to the public, to non-religious studies colleagues, and to students why the study of religion matters. We therefore too often fall back on platitudes. I argue for a revitalized methods and theories conversation that connects us even as it bears our arguments and disagreements about what we do and how. Courses in methods and theories in the study of religion represent the most viable basis we have for bringing the academic study of religion into the common conversation or argument that constitutes a discipline without sacrificing our pluralism.
Identification of a novel tetracycline resistance gene, tet(63), located on a multiresistance plasmid from Staphylococcus aureus
Authors: Zhu Yao , Wang Changzhen , Schwarz Stefan , Liu Wenyu , Yang Qin , Luan Tian , Wang Lingli , Liu Siguo , Zhang Wanjiang
Published: November 2020

Objectives

To identify and characterize a novel tetracycline resistance gene on a multiresistance plasmid from Staphylococcus aureus SA01 of chicken origin.

Methods

MICs were determined by broth microdilution according to CLSI recommendations. The whole genome sequence of S. aureus SA01 was determined via Illumina HiSeq and Oxford Nanopore platforms followed by a hybrid assembly. The new tet gene was cloned and expressed in S. aureus. The functionality of the corresponding protein as an efflux pump was tested by efflux pump inhibition assays.

Results

A novel tetracycline resistance gene, tet(63), was identified on a plasmid in S. aureus SA01. The cloned tet(63) gene was functionally expressed in S. aureus and shown to confer resistance to tetracycline and doxycycline, and a slightly elevated MIC of minocycline. The tet(63) gene encodes a 459 amino acid efflux protein of the major facilitator superfamily that consists of 14 predicted transmembrane helices. The results of efflux pump inhibitor assays confirmed the function of Tet(63) as an efflux protein. The deduced amino acid sequence of the Tet(63) protein exhibited 73.0% identity to the tetracycline efflux protein Tet(K). The plasmid pSA01-tet, on which tet(63) was located, had a size of 25664 bp and also carried the resistance genes aadD, aacA-aphD and erm(C).

Conclusions

A novel tetracycline resistance gene, tet(63), was identified in S. aureus. Its location on a multiresistance plasmid might support the co-selection of tet(63) under the selective pressure imposed by the use of macrolides, lincosamides and aminoglycosides.
G-quadruplex binding protein Rif1, a key regulator of replication timing
Authors: Alavi Sana , Ghadiri Hamed , Dabirmanesh Bahareh , Moriyama Kenji , Khajeh Khosro , Masai Hisao
Published: November 2020

DNA replication is spatially and temporally regulated during S phase to execute efficient and coordinated duplication of entire genome. Various epigenomic mechanisms operate to regulate the timing and locations of replication. Among them, Rif1 plays a major role to shape the ‘replication domains’ that dictate which segments of the genome are replicated when and where in the nuclei. Rif1 achieves this task by generating higher-order chromatin architecture near nuclear membrane and by recruiting a protein phosphatase. Rif1 is a G4 binding protein, and G4 binding activity of Rif1 is essential for replication timing regulation in fission yeast. In this article, we first summarize strategies by which cells regulate their replication timing and then describe how Rif1 and its interaction with G4 contribute to regulation of chromatin architecture and replication timing.
Comprehensive numerical study of the effect of nanoparticle additives on the cutting transport performance in horizontal boreholes
Authors: Minakov Andrey V , Mikhienkova Evgeniya I , Neverov Alexander L , Rudyak Valery Ya
Published: November 2020

The results of a numerical study of the effect of nanoparticle additives in the drilling fluid on the efficiency of cuttings removal from a horizontal well are presented. The rheological parameters of drilling fluids with nanoparticles (NPs) were set from the experiment. The SiO2 and Al2O3 NPs were used. The concentration of NPs in the drilling fluids varied from 0.25 to 2 wt%, while their average diameter ranged from 5 to 50 nm. The Eulerian granular media approach was used to simulate the cutting transport from the borehole. The numerical model was tested in detail on well-known experimental data on sand suspension flow in a round pipe. A good agreement with the experiment was obtained. A systematic computational study of the influence of several parameters on the efficiency of removing cuttings from the well was carried out. These parameters included the well's inclination angle from the vertical direction, the speed of rotation of the drill pipe, the flow rate of the drilling fluid, and the concentration, size, and composition of nanoparticles. It is shown that the 2 wt% concentration of nanoparticles in the drilling fluid results in a 2.7-fold increase in the cutting transport performance for horizontal boreholes. The positive effect of adding nanoparticles to the drilling fluid is enhanced with decreasing nanoparticle size.
How You Estimate Calories Matters: Calorie Estimation Reversals
Authors: Woolley Kaitlin , Liu Peggy J.
Published: November 2020

Consumers often form calorie estimates. How consumers estimate calories can systematically bias their calorie assessments. We distinguish between magnitude estimates—when consumers judge whether something has “very few” to “many” calories—and numeric estimates—when consumers estimate a number of calories. These two estimation modes lead to calorie estimate reversals when assessing calories in stimuli that trade off type and quantity, such as when assessing calories in a smaller portion of unhealthy food versus a larger portion of healthier food. When forming a “magnitude estimate,” people judge the larger, healthier food portion as containing fewer calories than the smaller, unhealthy food portion. However, when forming a “numeric estimate,” people often come to the opposite conclusion—judging the larger, healthier food portion as having more calories. This reversal occurs because these two estimation modes are differentially sensitive to information regarding a stimulus’ type (e.g., food healthiness), which is processed first, and quantity (e.g., food portion size), which is processed secondarily. Specifically, magnitude estimates are more sensitive to type, whereas numeric estimates attend to both type and quantity. Accordingly, this divergence between calorie estimation modes attenuates when: (1) quantity information is made primary or (2) in an intuitive (vs. deliberative) mindset.
Behavioral and Developmental Responses ofHabrobracon hebetor(Hymenoptera: Braconidae) to Larvae ofHelicoverpa armigera(Lepidoptera: Noctuidae) Inoculated With Various Concentrations ofBacillus thuringiensisvar.kurstaki(Bacillales: Bacillacae)
Authors: Allahyari Rahim , Aramideh Shahram , Michaud J P , Safaralizadeh Mohammad Hassan , Rezapanah Mohammad Reza
Published: November 2020

Bacillus thuringiensis Berliner subsp. kurstaki (Btk) and Habrobracon hebetor Say are both biological control agents of Helicoverpa armigera Hubner. The present study evaluated their compatibility for combined application against this pest by examining the acceptability of Btk-inoculated hosts for H. hebetor females and testing for negative life-history impacts on developing progeny. Second-instar H. armigera larvae fed for 72 h on potted chickpea plants treated with three concentrations of Btk (LC15, LC35, and LC70) and were then used in bioassays of parasitoid development and parasitism behavior. Survival of parasitoids was significantly reduced, and immature development prolonged, on hosts fed chickpea plants treated with LC35 and LC70  Btk, but not on plants treated with LC15  Btk. Parasitoids failed to discriminate against hosts treated with LC15 or LC35  Btk in choice tests, but attacked fewer hosts treated with LC70  Btk, paralyzing and parasitizing more healthy hosts, and laying more eggs on them. In contrast, a no-choice test revealed that more hosts treated with LC35 and LC70  Btk were paralyzed compared with control or LC15-treated hosts, but the numbers of hosts parasitized and eggs laid did not vary among Btk treatments. Thus, females required an experience with healthy hosts, as they had in the choice test, to discriminate against diseased ones. We conclude that H. hebetor and Btk are compatible for joint application against H. armigera, which could potentially improve biological control of this pest.
Improvement of predicting ecosystem productivity by modifying carbon–water–nitrogen coupling processes in a temperate grassland
Authors: Cheng Kaili , Hu Zhongmin , Li Shenggong , Guo Qun , Hao Yanbin , Yuan Wenping
Published: November 2020

Aims

Prediction of changes in ecosystem gross primary productivity (GPP) in response to climatic variability is a core mission in the field of global change ecology. However, it remains a big challenge for the model community to reproduce the interannual variation (IAV) of GPP in arid ecosystems. Accurate estimates of soil water content (SWC) and GPP sensitivity to SWC are the two most critical aspects for predicting the IAV of GPP in arid ecosystems.

Methods

We took a widely used model Biome-BGC as an example, to improve the model performances in a temperate grassland ecosystem. Firstly, we updated the estimation of SWC by modifying modules of evapotranspiration, SWC vertical profile and field capacity. Secondly, we modified the function of controlling water–nitrogen relation, which regulates the GPP–SWC sensitivity.

Important Findings

The original Biome-BGC overestimated the SWC and underestimated the IAV of GPP sensitivity, resulting in lower IAV of GPP than the observations, e.g. it largely underestimated the reduction of GPP in drought years. In comparison, the modified model accurately reproduced the observed seasonal and IAVs in SWC, especially in the surface layer. Simulated GPP–SWC sensitivity was also enhanced and became closer to the observations by optimizing parameter controlling nitrogen mineralization. Consequently, the model’s capability of reproducing IAV of GPP has been largely improved by the modifications. Our results demonstrate that SWC in the surface layer and the consequent effects on nitrogen availability should be among the first considerations for accurate modeling IAV of GPP in arid ecosystems.
An S-ribonuclease binding protein EBS1 and brassinolide signaling are specifically required for Arabidopsis tolerance to bicarbonate
Authors: Chen Jipeng , Li Xiaoxiao , Ye Xiaoxue , Guo Peng , Hu Zhubing , Qi Guoning , Cui Fuqiang , Liu Shenkui
Published: November 2020

Bicarbonate (NaHCO3) present in soils is usually considered to be a mixed stress for plants, with salts and high pH. NaHCO3-specific signaling in plants has rarely been reported. In this study, transcriptome analyses were conducted in order to identify NaHCO3-specific signaling in Arabidopsis. Weighted correlation network analysis was performed to isolate NaHCO3-specific modules in comparison with acetate treatment. The genes in the NaHCO3-root-specific module, which exhibited opposite expression to that in sodium acetate treatments, were further examined with their corresponding knock-out mutants. The gene Exclusively Bicarbonate Sensitive 1 (EBS1) encoding an S-ribonuclease binding protein, was identified to be specifically involved in plant tolerance to NaHCO3, but not to the other two alkaline salts, acetate and phosphate. We also identified the genes that are commonly regulated by bicarbonate, acetate and phosphate. Multiple brassinosteroid-associated gene ontology terms were enriched in these genes. Genetic assays showed that brassinosteroid signaling positively regulated plant tolerance to NaHCO3 stress, but negatively regulated tolerance to acetate and phosphate. Overall, our data identified bicarbonate-specific genes, and confirmed that alkaline stress is mainly dependent on the specificities of the weak acid ions, rather than high pH.
Trade Related Aspects of Intellectual Property Rights
Authors: Correa Carlos Maria
Published: November 2020

The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) is the most comprehensive and influential international treaty on intellectual property rights. It brings intellectual property rules into the framework of the World Trade Organization, obliging all WTO Member States to meet minimum standards of intellectual property protection and enforcement. This has required massive changes in some national laws, particularly in developing countries. This book provides an in-depth analysis of the principles and of the substantive and enforcement provisions of the TRIPS Agreement. It discusses the legal context in which the Agreement was negotiated, the objectives of their proponents and the nature of the obligations it created for the members of the World Trade Organization. In particular, it examines the minimum standards that must be implemented with regard to patents, trademarks, industrial designs, geographical indications, copyright and related rights, integrated circuits, trade-secrets and test data for pharmaceutical and agrochemical products. The book elaborates on the interpretation of provisions contained in said Agreement, in the light of the customary principles for the interpretation of international law. The analysis—which is supported by a review of the relevant GATT and WTO jurisprudence—identifies the policy space left to such members to implement their obligations in accordance with their own legal systems and public policy objectives, including in respect of complex issues such as patentability criteria, compulsory licenses, exceptions and limitations to copyright, border measures, injunctive relief and the protection of test data under the discipline of unfair competition.
1 The Court Over Sixty Years
Authors: Angelika Nussberger
Published: November 2020

This introductory chapter provides a background of the European Convention on Human Rights (ECHR), a multilateral treaty based on humanism and rule of law. Similar to the—albeit non-binding—Universal Declaration of Human Rights (UDHR), the ECHR is a document that marks a change in philosophy and gives a new definition of the responsibility of the State towards the individual. It fixes basic values in times of change and paves the way towards reconciliation in Europe. Unlike in a peace treaty, not all wartime enemies participate in its elaboration, but, one by one, all the European States accede to it, signalling their consent to the values fixed by a small community of States in the early 1950s. Seven decades later, forty-seven European States have ratified the Convention. Admittedly, the new start based on common values could not prevent the outbreak of violent conflicts between Member States. At the same time, the resurgence of anti-democratic tendencies could not be successfully banned in all Member States, but such tendencies could be stigmatized as grave human rights violations in binding judgments of the European Court of Human Rights (ECtHR). Thus, it is not surprising that the European model of human rights protection has been attractive and inspirational for other parts of the world. Nevertheless, there was and is a debate in some Member States to withdraw from the Convention as the Court’s jurisprudence is seen to be too intrusive on national sovereignty.
2 Organization, Personnel, and Procedure
Authors: Angelika Nussberger
Published: November 2020

This chapter discusses the organization, personnel, and procedures of the European Court of Human Rights (ECtHR), frequently referred to as the Strasbourg Court. The Member States are the masterminds for setting the framework of the Court’s organization, procedure, and personnel. The rules laid down in the original version of the European Convention on Human Rights (ECHR) in 1950 underwent substantial reform when the permanent Court was established in 1998 on the basis of Protocol No 11 to the Convention for the Protection of Human Rights and Fundamental Freedoms. The framework has been further modified by important additional protocols, especially Protocol No 14 allowing ‘single judges’ to adopt binding decisions, and Protocol No 16 introducing advisory opinions in addition to adversary procedures. However, not only the Member States make the rules. The Court itself has an important say in adapting the general set-up to its practical needs and in fine-tuning the regulations.
3 Convention Law and Basic Doctrine
Authors: Angelika Nussberger
Published: November 2020

This chapter examines the basic doctrine of the European Court of Human Rights (ECtHR). ‘Doctrine’ is a word the Court would rather avoid. The Court has preferred to develop ‘formula’ as a basis for discussing all relevant issues, formula which are repeated again and again, developed further in manifold scenarios, used as argumentation patterns, allowing to arrive at differentiated solutions, formula often linked to specific cases for which they were originally invented. With about 20,000 judgments, the case-law is rich and all-embracing and gives a lot of illustrative examples of how to understand these formula. What is called ‘basic doctrine’ is therefore something very specific. It cannot be compared to stare decisis in the British tradition or theoretical models in German constitutional law. Originating from a conglomerate of different legal cultures, the ECtHR has developed not only its own style, but also its own jurisprudential approach. If there is a ‘doctrine’, it denies being one. Yet, the non-doctrinal doctrine is very influential and has created notions such as ‘margin of appreciation’ and ‘European consensus’ which convey a certain message of the Court's mission and are widely discussed and disputed.
The LBT satellites of Nearby Galaxies Survey (LBT-SONG): the satellite population of NGC 628
Authors: Davis A Bianca , Nierenberg Anna M , Peter Annika H G , Garling Christopher T , Greco Johnny P , Kochanek Christopher S , Utomo Dyas , Casey Kirsten J , Pogge Richard W , Roberts Daniella M , Sand David J , Sardone Amy
Published: November 2020

We present the first satellite system of the Large Binocular Telescope Satellites Of Nearby Galaxies Survey (LBT-SONG), a survey to characterize the close satellite populations of Large Magellanic Cloud to Milky-Way-mass, star-forming galaxies in the Local Volume. In this paper, we describe our unresolved diffuse satellite finding and completeness measurement methodology and apply this framework to NGC 628, an isolated galaxy with ∼1/4 the stellar mass of the Milky Way. We present two new dwarf satellite galaxy candidates: NGC 628 dwA, and dwB with MV = −12.2 and −7.7, respectively. NGC 628 dwA is a classical dwarf while NGC 628 dwB is a low-luminosity galaxy that appears to have been quenched after reionization. Completeness corrections indicate that the presence of these two satellites is consistent with CDM predictions. The satellite colours indicate that the galaxies are neither actively star forming nor do they have the purely ancient stellar populations characteristic of ultrafaint dwarfs. Instead, and consistent with our previous work on the NGC 4214 system, they show signs of recent quenching, further indicating that environmental quenching can play a role in modifying satellite populations even for hosts smaller than the Milky Way.
Connecting cosmological accretion to strong Ly α absorbers
Authors: Theuns Tom
Published: November 2020

We present an analytical model for the cosmological accretion of gas on to dark matter haloes, based on a similarity solution applicable to spherical systems. Performing simplified radiative transfer, we compute how the accreting gas turns increasingly neutral as it self-shields from the ionizing background, and obtain the column density, $N_{\rm H\,{\small I}}$, as a function of impact parameter. The resulting column-density distribution function (CDDF) is in excellent agreement with observations. The analytical expression elucidates (1) why haloes over a large range in mass contribute about equally to the CDDF as well as (2) why the CDDF evolves so little with redshift in the range z = 2–5. We show that the model also predicts reasonable damped Lyman-αabsorber(DLA) line widths (v90), bias, and molecular fractions. Integrating over the CDDF yields the mass density in neutral gas, $\Omega _{\rm H\,{\small I}}$, which agrees well with observations. $\Omega _{\rm H\,{\small I}}(z)$ is nearly constant even though the accretion rate on to haloes evolves. We show that this occurs because the fraction of time that the inflowing gas is neutral depends on the dynamical time of the halo, which is inversely proportional to the accretion rate. Encapsulating results from cosmological simulations, the simple model shows that most Lyman-limit systems and DLAs are associated with the cosmological accretion of gas on to haloes.
Search for giant planets around seven white dwarfs in the Hyades cluster with the Hubble Space Telescope
Authors: Brandner Wolfgang , Zinnecker Hans , Kopytova Taisiya
Published: November 2020

Only a small number of exoplanets have been identified in stellar cluster environments. We initiated a high angular resolution direct imaging search using the Hubble Space Telescope (HST) and its Near-Infrared Camera and Multi-Object Spectrometer (NICMOS) instrument for self-luminous giant planets in orbit around seven white dwarfs in the 625 Myr old nearby (≈45 pc) Hyades cluster. The observations were obtained with Near-Infrared Camera 1 (NIC1) in the F110W and F160W filters, and encompass two HST roll angles to facilitate angular differential imaging. The difference images were searched for companion candidates, and radially averaged contrast curves were computed. Though we achieve the lowest mass detection limits yet for angular separations ≥0.5 arcsec, no planetary mass companion to any of the seven white dwarfs, whose initial main-sequence masses were >2.8 M⊙, was found. Comparison with evolutionary models yields detection limits of ≈5–7 Jupiter masses (MJup) according to one model, and between 9 and ≈12 MJup according to another model, at physical separations corresponding to initial semimajor axis of ≥5–8 au (i.e. before the mass-loss events associated with the red and asymptotic giant branch phase of the host star). The study provides further evidence that initially dense cluster environments, which included O- and B-type stars, might not be highly conducive to the formation of massive circumstellar discs, and their transformation into giant planets (with m ≥ 6 MJup and a ≥6 au). This is in agreement with radial velocity surveys for exoplanets around G- and K-type giants, which did not find any planets around stars more massive than ≈3 M⊙.
The evolution of a circumplanetary disc with a dead zone
Authors: Chen Cheng , Yang (楊朝欽) Chao-Chin , Martin Rebecca G , Zhu Zhaohuan
Published: November 2020

We investigate whether the regular Galilean satellites could have formed in the dead zone of a circumplanetary disc. A dead zone is a region of weak turbulence in which the magnetorotational instability is suppressed, potentially an ideal environment for satellite formation. With the grid-based hydrodynamic code fargo3d, we examine the evolution of a circumplanetary disc model with a dead zone. Material accumulates in the dead zone of the disc leading to a higher total mass and but a similar temperature profile compared to a fully turbulent disc model. The tidal torque increases the rate of mass transport through the dead zone leading to a steady-state disc with a dead zone that does not undergo accretion outbursts. We explore a range of disc, dead zone, and mass inflow parameters and find that the maximum mass of the disc is around $0.001 M_{\rm J}$. Since the total solid mass of such a disc is much lower, we find that there is not sufficient material in the disc for in situ formation of the Galilean satellites and that external supplement is required.
A low-frequency radio halo survey of the South Pole Telescope SZ-selected clusters with the GMRT
Authors: Raja Ramij , Rahaman Majidul , Datta Abhirup , van Weeren Reinout J , Intema Huib T , Paul Surajit
Published: November 2020

The presence of non-thermal electrons and large-scale magnetic fields in the intracluster medium is known through the detection of megaparsec (Mpc) scale diffuse radio synchrotron emission. Although a significant amount of progress in finding new diffuse radio sources has happened in the last decade, most of the investigation has been constrained towards massive low-redshift clusters. In this work, we explore clusters with redshift z > 0.3 in search of diffuse radio emission, at 325 MHz with the Giant Metrewave Radio Telescope. This campaign has resulted in the discovery of two new radio haloes (SPT-CL J0013−4906 and SPT-CL J0304−4401) along with two other detections (SPT-CL J2031−4037 and SPT-CL J2248−4431), previously reported (at 325 MHz) in the literature. In addition, we detect a halo candidate in one cluster in our sample, and upper limits for haloes are placed in eight clusters where no diffuse emission is detected. In the P1.4–LX plane, the detected haloes follow the observed correlation, whereas the upper limits lie above the correlation line, indicating the possibility of future detection with sensitive observations.
CATH: increased structural coverage of functional space
Authors: Sillitoe Ian , Bordin Nicola , Dawson Natalie , Waman Vaishali P , Ashford Paul , Scholes Harry M , Pang Camilla S M , Woodridge Laurel , Rauer Clemens , Sen Neeladri , Abbasian Mahnaz , Le Cornu Sean , Lam Su Datt , Berka Karel , Varekova Ivana Hutařová , Svobodova Radka , Lees Jon , Orengo Christine A
Published: November 2020

CATH (https://www.cathdb.info) identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural and functional annotations. There are two levels: CATH-B, a daily snapshot of the latest domain structures and superfamily assignments, and CATH+, with additional derived data, such as predicted sequence domains, and functionally coherent sequence subsets (Functional Families or FunFams). The latest CATH+ release, version 4.3, significantly increases coverage of structural and sequence data, with an addition of 65,351 fully-classified domains structures (+15%), providing 500 238 structural domains, and 151 million predicted sequence domains (+59%) assigned to 5481 superfamilies. The FunFam generation pipeline has been re-engineered to cope with the increased influx of data. Three times more sequences are captured in FunFams, with a concomitant increase in functional purity, information content and structural coverage. FunFam expansion increases the structural annotations provided for experimental GO terms (+59%). We also present CATH-FunVar web-pages displaying variations in protein sequences and their proximity to known or predicted functional sites. We present two case studies (1) putative cancer drivers and (2) SARS-CoV-2 proteins. Finally, we have improved links to and from CATH including SCOP, InterPro, Aquaria and 2DProt.
MethHC 2.0: information repository of DNA methylation and gene expression in human cancer
Authors: Huang Hsi-Yuan , Li Jing , Tang Yun , Huang Yi-Xian , Chen Yi-Gang , Xie Yue-Yang , Zhou Zhe-Yuan , Chen Xin-Yi , Ding Si-Yuan , Luo Meng-Fan , Jin Chen-Nan , Zhao Le-Shan , Xu Jia-Tong , Zhou Ying , Lin Yang-Chi-Dung , Hong Hsiao-Chin , Zuo Hua-Li , Hu Si-Yao , Xu Pei-Yi , Li Xin , Huang Hsien-Da
Published: November 2020

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.
Translational control of coronaviruses
Authors: de Breyne Sylvain , Vindry Caroline , Guillin Olivia , Condé Lionel , Mure Fabrice , Gruffat Henri , Chavatte Laurent , Ohlmann Théophile
Published: November 2020

Coronaviruses represent a large family of enveloped RNA viruses that infect a large spectrum of animals. In humans, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic and is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2002 and 2012, respectively. All viruses described to date entirely rely on the protein synthesis machinery of the host cells to produce proteins required for their replication and spread. As such, virus often need to control the cellular translational apparatus to avoid the first line of the cellular defense intended to limit the viral propagation. Thus, coronaviruses have developed remarkable strategies to hijack the host translational machinery in order to favor viral protein production. In this review, we will describe some of these strategies and will highlight the role of viral proteins and RNAs in this process.
The landscape of long noncoding RNA-involved and tumor-specific fusions across various cancers
Authors: Guo Mengbiao , Xiao Zhen-Dong , Dai Zhiming , Zhu Ling , Lei Hang , Diao Li-Ting , Xiong Yuanyan
Published: November 2020

The majority of the human genome encodes long noncoding RNA (lncRNA) genes, critical regulators of various cellular processes, which largely outnumber protein-coding genes. However, lncRNA-involved fusions have not been surveyed and characterized yet. Here, we present a systematic study of the lncRNA fusion landscape across cancer types and identify >30 000 high-confidence tumor-specific lncRNA fusions (using 8284 tumor and 6946 normal samples). Fusions positively correlated with DNA damage and cancer stemness and were specifically low in microsatellite instable (MSI)-High or virus-infected tumors. Moreover, fusions distribute differently among cancer molecular subtypes, but with shared enrichment in tumors that are microsatellite stable (MSS), with high somatic copy number alterations (SCNA), and with poor survival. Importantly, we find a potentially new mechanism, mediated by enhancer RNAs (eRNA), which generates secondary fusions that form densely connected fusion networks with many fusion hubs targeted by FDA-approved drugs. Finally, we experimentally validate functions of two tumor-promoting chimeric proteins derived from mRNA-lncRNA fusions, KDM4B–G039927 and EPS15L1–lncOR7C2–1. The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Our study completes the fusion landscape in cancers, sheds light on fusion mechanisms, and enriches lncRNA functions in tumorigenesis and cancer progression.
The topology of chromatin-binding domains in the NuRD deacetylase complex
Authors: Millard Christopher J , Fairall Louise , Ragan Timothy J , Savva Christos G , Schwabe John W R
Published: November 2020

Class I histone deacetylase complexes play essential roles in many nuclear processes. Whilst they contain a common catalytic subunit, they have diverse modes of action determined by associated factors in the distinct complexes. The deacetylase module from the NuRD complex contains three protein domains that control the recruitment of chromatin to the deacetylase enzyme, HDAC1/2. Using biochemical approaches and cryo-electron microscopy, we have determined how three chromatin-binding domains (MTA1-BAH, MBD2/3 and RBBP4/7) are assembled in relation to the core complex so as to facilitate interaction of the complex with the genome. We observe a striking arrangement of the BAH domains suggesting a potential mechanism for binding to di-nucleosomes. We also find that the WD40 domains from RBBP4 are linked to the core with surprising flexibility that is likely important for chromatin engagement. A single MBD2 protein binds asymmetrically to the dimerisation interface of the complex. This symmetry mismatch explains the stoichiometry of the complex. Finally, our structures suggest how the holo-NuRD might assemble on a di-nucleosome substrate.
SARS-CoV-2 Viral Load on Admission Is Associated With 30-Day Mortality
Authors: Bryan Andrew , Fink Susan L , Gattuso Meghan A , Pepper Gregory , Chaudhary Anu , Wener Mark H , Morishima Chihiro , Jerome Keith R , Mathias Patrick C , Greninger Alexander L
Published: November 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load on admission was associated with a significantly increased 30-day mortality (odds ratio [OR], 4.20; 95% CI, 1.62–10.86), and anti-SARS-CoV-2 nucleocapisid IgG seropositivity on admission trended toward a reduced 30-day mortality (OR, 0.43; 95% CI, 0.15–1.26). Reporting of quantitative SARS-CoV-2 viral load and serologic assays may offer prognostic clinical information.
L’utilisation sécuritaire des médicaments chez les enfants ayant des problèmes médicaux complexes
Authors: Huth Kathleen , Vandecruys Patricia , Orkin Julia , Patel Hema
Published: November 2020

Grâce aux progrès de la médecine et aux innovations en technologies de la santé, de nombreux enfants atteints d’affections au pronostic réservé vivent désormais plus longtemps. Ces enfants sont souvent qualifiés d’« enfants ayant des problèmes médicaux complexes », parce qu’ils ont des affections chroniques, utilisent davantage les soins de santé et sont dépendants de la technologie. La complexité de leurs soins et leur fragilité intrinsèque entraînent des risques plus élevés d’erreurs de médication, autant dans un contexte ambulatoire qu’hospitalier. Le taux élevé de fragmentation des soins, de mauvaise communication et de polypharmacie chez les enfants ayant des problèmes médicaux complexes accroissent les possibilités d’erreurs, particulièrement au moment de changer de milieu de soins et de praticiens. Il n’existe pas de données sur les facteurs qui contribuent à un risque plus élevé d’erreurs de médication dans cette population et sur les meilleures mesures pour les éviter. Le présent point de pratique fournit des directives cliniques aux professionnels de la santé afin de s’assurer d’une utilisation sécuritaire des médicaments auprès des enfants ayant des problèmes médicaux complexes et s’attarde sur des stratégies pratiques applicables à la fois en soins ambulatoires et hospitaliers.
Diagnosis and management of severe sepsis in the paediatric patient
Authors: Farrell Catherine A
Published: November 2020

Sepsis is a systemic inflammatory response to suspected or proven infection. Given its importance in terms of morbidity and mortality, a number of initiatives by several professional societies in recent years have led to the development of guidelines for the recognition and timely management of sepsis. The principal elements of the most recent guidelines are summarized in this practice point. These elements include recognition of changes in clinical condition and vital signs, such as fever, tachycardia, and changes in peripheral perfusion, which should raise concern for sepsis; initial stabilization of airway, breathing, and circulation; timely administration of empiric antimicrobial therapy; use of fluid boluses and vasoactive medications; and specific considerations in patients with underlying medical conditions, such as the use of corticosteroids for possible adrenal insufficiency due to hypothalamic-adrenal suppression. Two changes from previous guidelines are the concern for fluid overload, implying the need for clinical re-assessment after administration of each fluid bolus, and the removal of dopamine as the initial vasoactive agent for use in hypotensive paediatric patients, with recommendations for the use of epinephrine or norepinephrine as dictated by the clinical context. This practice point focuses primarily on sepsis management in older infants, children, and youth.
EP03 Parechovirus in a pathologist
Authors: Masih Claire , Dologhan Michael , Cairns Andrew
Published: November 2020

Case report - Introduction

A 42-year-old pathologist presented with a 1-week history of muscle pain and subjective weakness. CK level on 2 occasions was >3000.

The patient was systemically well with no past medical history, medication, or foreign travel. He had 1-day history of shivering with no recorded pyrexia. He reported pain in his proximal muscles and neck and subjective muscle weakness and lack of finger dexterity with no objective findings.

Case report - Case description

Autoantibody panel and inflammatory markers were performed which were normal. Full blood count with differential white cell count including eosinophils was normal. There was a modest rise in transaminases. Myositis panel was negative. Full viral screen was positive for parechovirus with titre of 30 on several samples. MRI proximal musculature showed increased fluid signal in the perifascial region of both thighs primarily involving the hamstrings, not definitive for myositis but suggestive of fasciitis.

Case report - Discussion

Parechovirus is a picornavirus, often causing mild gastrointestinal or respiratory illness but has been associated with epidemic myalgia and myositis during outbreaks of parechovirus in a Japanese population.

The patient improved spontaneously with CK reduced to 187 and improved symptoms after 1 week. We expect a good outcome and will review on patient's request if necessary.

Case report - Key learning points

Parechovirus can cause myofasciitis which is usually mild and self-limiting. It can be associated with elevated CK, transaminases and MRI findings and can be confirmed on respiratory viral swab.
EP16 Challenges in treating new onset systemic lupus erythematosus with lupus nephritis and COVID-19 infection overlap
Authors: Dahou Selma , Leach Tim , Bostock Kathryn , Louden Jonathan , Raj Jonathan , Ghedia Shivan
Published: November 2020

Case report - Introduction

COVID-19 infection caused by a novel coronavirus SARS-coV-2 has made the diagnosis and the treatment of inflammatory diseases incredibly challenging. On the one hand, because of its pro-inflammatory state, that may aggravate or trigger flares in autoimmune diseases such as systemic lupus erythematosus (SLE). On the other hand, the risk of an immunosuppressive therapy during the active phase SARS-coV-2 infection that may lead to catastrophic outcomes. We report a case of a 24-year-old female newly diagnosed with SLE during COVID-19 pandemic who developed COVID-19 infection during her induction treatment for lupus nephritis.

Case report - Case description

A 24-year-old Nepali female, with no past medical history of note, presented to her regional hospital with a history of flu-like symptoms few days ago, peripheral oedema, acute kidney injury with proteinuria and hypertension. Further investigations showed a high titre of double-stranded DNA antibodies, anti-cardiolipin IgM and B2 microglobulin positive and low C3. She also developed a haemolytic anaemia and thrombocytopenia during her admission. She received pulsed steroid therapy and was started on mycophenolate mofetil (MMF) for a probable lupus nephritis awaiting the results of biopsy, which showed later a lupus nephritis Class IV-G with active lesions. She then developed symptoms of COVID-19 infection and had a positive PCR leading to an interruption of her induction therapy. She was recruited to the RECOVERY trial on the lopinavir-ritonavir arm and made a good recovery.

Case report - Discussion

It is well known that viruses can trigger or aggravate auto-immune response in patients predisposed genetically. However, the role of SARS-coV-2 is not elucidated yet. The EULAR COVID-19 registry showed that rheumatoid arthritis and SLE were the most prevalent rheumatic diseases, and there was an increased risk in those who are on moderate to high dose corticosteroids. In patients with SLE and COVID-19 infection, it is agreed by all the national and international rheumatology societies to interrupt their immunosuppressive therapy until the symptoms resolve, especially those with renal involvement or an active disease. Which is the case in our patient. Luckily, she resumed her MMF a month later after a negative PCR and her renal function has continued to improve.

Case report - Key learning points

Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE. It requires an early immunosuppressive treatment to induce remission.

Randomized clinical trials showed that MMF is at least equally effective as cyclophosphamide in inducing remission and that it has been associated with a reduced risk of infection and amenorrhea. It seems to be a suitable alternative in women of childbearing age. In patients with concomitant COVID-19 disease, immunosuppressive therapy should be paused until the symptoms improve.
Economic-State Variation in Uncertainty-Yield Dynamics
Authors: Connolly Robert A , Dubofsky David , Stivers Chris
Published: November 2020

We show there is a much stronger negative, dynamic relation between changes in economic uncertainty and Treasury yields over weaker economic times since at least 1990. We document this economic-state variation in uncertainty-yield dynamics for weekly and monthly change horizons, for nominal yields and real-yield proxies, for multiple economic-state identification methods, and for different economic uncertainty metrics. We present additional findings that suggest short-term fluctuations in precautionary-savings and consumption-smoothing forces are more impactful on interest rate dynamics during weaker economic times, especially relying on surveys of expected economic growth and inflation.

Received February 8, 2019; editorial decision August 24, 2020 by Editor Nikolai Roussanov. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Comparison between low cost USB nailfold capillaroscopy and videocapillaroscopy: a pilot study
Authors: Berks Michael , Dinsdale Graham , Marjanovic Elizabeth , Murray Andrea , Taylor Chris , Herrick Ariane L
Published: November 2020

Objectives

Universal serial bus (USB) microscopy (capillaroscopy) could provide all rheumatologists with an easy-to-use, low-cost tool to examine the nailfold capillaries to facilitate early diagnosis of SSc. The objectives of this pilot study were to examine the feasibility of acquiring and analysing images using USB microscopy and to compare results to videocapillaroscopy.

Methods

Videocapillaroscopy and USB microscope images were obtained from the right and left ring fingers of 20 patients with SSc and 20 healthy control subjects. In addition to generating panoramic capillary mosaics from across the whole nailbed, custom software made fully automated measurements of vessel structure including capillary width and density. The area under the receiver operating characteristic curve (AZ) was used to measure separation between the SSc and healthy control groups.

Results

High quality images could be generated from the USB microscope, with reconstructed USB images comparing very favourably with those obtained using videocapillaroscopy. Using USB microscope images, the receiver operating characteristic curve AZ for group separation based on mean width was 0.81 (standard error 0.120) compared with 0.81 (standard error 0.095) for the (gold standard) videocapillaroscopy. The receiver operating characteristic curve AZ for group separation using capillary density was 0.48 (standard error 0.16) for USB microscope images, compared with 0.70 (standard error 0.10) for videocapillaroscopy.

Conclusion

In this pilot study, USB capillaroscopy was able to discriminate between patients with SSc and controls as well as videocapillaroscopy on the basis of capillary width. This finding, together with the high-quality images obtained, highlights the potential of USB capillaroscopy as a low-cost, easily accessible clinical and research tool.
The evolutionary diversity of barnacles, with an updated classification of fossil and living forms
Authors: Chan Benny K K , Dreyer Niklas , Gale Andy S , Glenner Henrik , Ewers-Saucedo Christine , Pérez-Losada Marcos , Kolbasov Gregory A , Crandall Keith A , Høeg Jens T
Published: November 2020

We present a comprehensive revision and synthesis of the higher-level classification of the barnacles (Crustacea: Thecostraca) to the genus level and including both extant and fossils forms. We provide estimates of the number of species in each group. Our classification scheme has been updated based on insights from recent phylogenetic studies and attempts to adjust the higher-level classifications to represent evolutionary lineages better, while documenting the evolutionary diversity of the barnacles. Except where specifically noted, recognized taxa down to family are argued to be monophyletic from molecular analysis and/or morphological data. Our resulting classification divides the Thecostraca into the subclasses Facetotecta, Ascothoracida and Cirripedia. The whole class now contains 14 orders, 65 families and 367 genera. We estimate that barnacles consist of 2116 species. The taxonomy is accompanied by a discussion of major morphological events in barnacle evolution and justifications for the various rearrangements we propose.