bluuebunny/crossref_metadata_2025_split huggingface dataset:
GVDTI: graph convolutional and variational autoencoders with attribute-level attention for drug–protein interaction prediction
Authors: Xuan Ping , Fan Mengsi , Cui Hui , Zhang Tiangang , Nakaguchi Toshiya 
Published: October 2021

Abstract

Motivation
Identifying proteins that interact with drugs plays an important role in the initial period of developing drugs, which helps to reduce the development cost and time. Recent methods for predicting drug–protein interactions mainly focus on exploiting various data about drugs and proteins. These methods failed to completely learn and integrate the attribute information of a pair of drug and protein nodes and their attribute distribution.

Results
We present a new prediction method, GVDTI, to encode multiple pairwise representations, including attention-enhanced topological representation, attribute representation and attribute distribution. First, a framework based on graph convolutional autoencoder is constructed to learn attention-enhanced topological embedding that integrates the topology structure of a drug–protein network for each drug and protein nodes. The topological embeddings of each drug and each protein are then combined and fused by multi-layer convolution neural networks to obtain the pairwise topological representation, which reveals the hidden topological relationships between drug and protein nodes. The proposed attribute-wise attention mechanism learns and adjusts the importance of individual attribute in each topological embedding of drug and protein nodes. Secondly, a tri-layer heterogeneous network composed of drug, protein and disease nodes is created to associate the similarities, interactions and associations across the heterogeneous nodes. The attribute distribution of the drug–protein node pair is encoded by a variational autoencoder. The pairwise attribute representation is learned via a multi-layer convolutional neural network to deeply integrate the attributes of drug and protein nodes. Finally, the three pairwise representations are fused by convolutional and fully connected neural networks for drug–protein interaction prediction. The experimental results show that GVDTI outperformed other seven state-of-the-art methods in comparison. The improved recall rates indicate that GVDTI retrieved more actual drug–protein interactions in the top ranked candidates than conventional methods. Case studies on five drugs further confirm GVDTI’s ability in discovering the potential candidate drug-related proteins.

Contact
zhang@hlju.edu.cn Supplementary information: Supplementary data are available at Briefings in Bioinformatics online.
The Dangers of Using Cq to Quantify Nucleic Acid in Biological Samples: A Lesson From COVID-19
Authors: Evans Daniel , Cowen Simon , Kammel Martin , O’Sullivan Denise M , Stewart Graham , Grunert Hans-Peter , Moran-Gilad Jacob , Verwilt Jasper , In Jiwon , Vandesompele Jo , Harris Kathryn , Hong Ki Ho , Storey Nathaniel , Hingley-Wilson Suzie , Dühring Ulf , Bae Young-Kyung , Foy Carole A , Braybrook Julian , Zeichhardt Heinz , Huggett Jim F 
Published: October 2021

Abstract

Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA quantities, measured by reverse transcription quantitative PCR (RT-qPCR), have been proposed to stratify clinical risk or determine analytical performance targets. We investigated reproducibility and how setting diagnostic cutoffs altered the clinical sensitivity of coronavirus disease 2019 (COVID-19) testing.

Methods
Quantitative SARS-CoV-2 RNA distributions [quantification cycle (Cq) and copies/mL] from more than 6000 patients from 3 clinical laboratories in United Kingdom, Belgium, and the Republic of Korea were analyzed. Impact of Cq cutoffs on clinical sensitivity was assessed. The June/July 2020 INSTAND external quality assessment scheme SARS-CoV-2 materials were used to estimate laboratory reported copies/mL and to estimate the variation in copies/mL for a given Cq.

Results
When the WHO-suggested Cq cutoff of 25 was applied, the clinical sensitivity dropped to about 16%. Clinical sensitivity also dropped to about 27% when a simulated limit of detection of 106 copies/mL was applied. The interlaboratory variation for a given Cq value was &gt;1000 fold in copies/mL (99% CI).

Conclusion
While RT-qPCR has been instrumental in the response to COVID-19, we recommend Cq (cycle threshold or crossing point) values not be used to set clinical cutoffs or diagnostic performance targets due to poor interlaboratory reproducibility; calibrated copy-based units (used elsewhere in virology) offer more reproducible alternatives. We also report a phenomenon where diagnostic performance may change relative to the effective reproduction number. Our findings indicate that the disparities between patient populations across time are an important consideration when evaluating or deploying diagnostic tests. This is especially relevant to the emergency situation of an evolving pandemic.
Radiation dose to nurses, cardiologists, and patients during coronary angiography: a comparison of femoral and radial access
Authors: Wilson-Stewart Kelly S , Fontanarosa Davide , Malacova Eva , Trapp Jamie V 
Published: October 2021

Abstract

Background
Exposure to radiation during fluoroscopically guided cardiac procedures is a cause for concern for both the patient and staff.

Aims
This study sought to compare the occupational and patient radiation dose during femoral and radially accessed invasive coronary angiography (CA).

Methods and results
Occupational dose (µSv) was measured at the left temple of the cardiologist (n = 17), scrub (n = 27), and circulator nurse (n = 27) during 761 femoral and 671 radially accessed diagnostic coronary angiograms and percutaneous coronary intervention (PCI) procedures. Patient dose parameters of dose area product (DAP) (Gy.cm2) and air kerma (AK) (Gy) were also measured. Coronary angiography performed via the radial artery is associated with greater mean dose to the cardiologist, with the exception of procedures including only PCI. Results demonstrated that scrub nurses are exposed to higher mean doses than the cardiologist when using femoral access and similar doses during radial cases. Both AK and DAP were associated with a higher average dose for femoral PCI than radial, with DAP being significantly higher.

Conclusions
Awareness of factors that increase the dose to staff and patients is vital to inform and improve practice. This study has demonstrated that access route during diagnostic CA and PCI influences both patient and staff dose. Radiation dose to in-room staff other than the fluoroscopic operator should be a focus of future research. In addition, all staff present during X-ray guided procedures should be provided with radiation education and adopt dose minimization strategies to reduce occupational exposures.
Assessment of seismic tomographic models of the contiguous United States using intermediate-period 3-D wavefield simulation
Authors: Zhou Tong , Xi Ziyi , Chen Min , Li Jiaqi 
Published: October 2021

SUMMARYThe contiguous United States has been well instrumented with broad-band seismic stations due to the development of the EarthScope Transportable Array. Previous studies have provided various 3-D seismic wave speed models for the crust and upper mantle with improved resolution. However, discrepancies exist among these models due to differences in both data sets and tomographic methods, which introduce uncertainties on the imaged lithospheric structure beneath North America. A further model refinement using the best data coverage and advanced tomographic methods such as full-waveform inversion (FWI) is expected to provide better seismological constraints. Initial models have significant impacts on the convergence of FWIs. However, how to select an optimal initial model is not well investigated. Here, we present a data-driven initial model selection procedure for the contiguous US and surrounding regions by assessing waveform fitting and misfit functions between the observations and synthetics from candidate models. We use a data set of waveforms from 30 earthquakes recorded by 5820 stations across North America. The results suggest that the tested 3-D models capture well long-period waveforms while showing discrepancies in short periods especially on tangential components. This observation indicates that the smaller scale heterogeneities and radial anisotropy in the crust and upper mantle are not well constrained. Based on our test results, a hybrid initial model combining S40RTS or S362ANI in the mantle and US.2016 for Vsv and CRUST1.0 for Vsh in the crust is compatible for future FWIs to refine the lithospheric structure of North America.
Whither judicial dialogue after convergence? Finding transnational public law in nomos-building
Authors: Kuo Ming-Sung 
Published: October 2021

Abstract
One of the major themes emerging from the reinvigorated interest in legal comparativism in the burgeoning transnational legal phenomena is the transnational dialogue among judiciaries the world over, namely, the mutual referencing to judicial decisions across jurisdictional boundaries. This article aims to rethink the role of transnational judicial dialogue in the development of transnational public law by drawing upon Robert Cover’s discussion of the relationship between nomos and narratives. It is argued that the convergent legal doctrines and principles channeled through transnational judicial dialogue are “jurispathic” as they only generate “thin” transnational values with little power of persuasion. To contribute to the thriving of transnational public law, judicial dialogue should look beyond comparative constitutional jurisprudence, shifting the focus away from the convergence of constitutional doctrines to the building of a transnational nomos. By moving from the mutual learning of doctrines to the comparative articulation of nomos-making narratives—the way a specific doctrine or a legal principle is understood and gains its meaning in its legal culture—in transnational judicial dialogue, comparative constitutional law can enable a robust transnational public law enriched with meanings, which hold the key to persuasion.
Noisy bounded confidence models for opinion dynamics: the effect of boundary conditions on phase transitions
Authors: Goddard B D , Gooding B , Short H , Pavliotis G A 
Published: October 2021

AbstractWe study SDE and PDE models for opinion dynamics under bounded confidence, for a range of different boundary conditions, with and without the inclusion of a radical population. We perform exhaustive numerical studies with pseudo-spectral methods to determine the effects of the boundary conditions, suggesting that the no-flux case most faithfully reproduces the underlying mechanisms in the associated deterministic models of Hegselmann and Krause. We also compare the SDE and PDE models, and use tools from analysis to study phase transitions, including a systematic description of an appropriate order parameter.
International Non-State Humanitarian Actors outside of the International Legal System: Can there be any Legal Consequences for Humanitarian Actors?
Authors: McArdle Scarlett , Shucksmith-Wesley Christy 
Published: October 2021

Abstract
Humanitarians are saviours, people employed by organisations that were created to provide neutral and professional help in times of conflict, disaster or other emergencies. We assume that we can trust the humanitarians.1 This, at least, is the theory of humanitarianism. However, news outlets depict the actions of humanitarians somewhat differently. The accusations levied at humanitarian actors, including Oxfam and the International Committee of the Red Cross (ICRC) within the past three years, include that individuals have committed crimes against those they are meant to be helping, organisations have swept said abhorrent behaviour under the rug, and that the consequences for the individuals concerned are, at worst, being ‘let go’ or demoted. These scandals have besmirched the reputation of the humanitarian profession. In some instances, the scandals have undermined perceptions of humanitarian actors and, consequently, mired funding for the important work that they do. Although a multitude of actors’ act in the same spaces and places, including in armed conflict and disasters, only some are subject to accountability and responsibility on the international stage. Our question is what can and could be done at the international level to address the accusations and, in some cases, unlawful behaviour? This article explores avenues within and outside of the international legal system to ensure responsibility of those embroiled in illegal acts.
Standing the Test of Time: The Level Playing Field and Rebalancing Mechanism in the UK–EU Trade and Cooperation Agreement (TCA)
Authors: Collins David 
Published: October 2021

ABSTRACT
This article explores the dispute settlement elements of the UK–European Union Trade and Cooperation Agreement’s (TCA) novel Level Playing Field (LPF) rebalancing obligations, consisting of a requirement not to lower standards in areas of labour, the environment and subsidy policy such that an adverse material impact results to trade or investment flows between the parties. The test for violations of these provisions is narrowly framed, requiring strong evidence of significant harms and carefully calibrated retaliation. The system contemplates several avenues of dispute settlement including unilateral ex ante retaliation which may be levied against another sector. The article suggests that the substantive and procedural features of the TCA’s LPF mechanism affords reasonably wide opportunity for parties to practice regulatory divergence while evincing a commitment to shared values.
Risk Factors and Medical Resource Utilization of Respiratory Syncytial Virus, Human Metapneumovirus and Influenza Related Hospitalizations in Adults – A Global Study During the 2017-2019 Epidemic Seasons (Hospitalized Acute Respiratory Tract Infection [HARTI] Study)
Authors: Falsey Ann R , Walsh Edward E , House Stacey , Vandenijck Yannick , Ren Xiaohui , Keim Sofia , Kang Diye , Peeters Pascale , Witek James , Ispas Gabriela 
Published: October 2021

Abstract

Background
Respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza are respiratory pathogens leading to hospitalization in adults. Understanding disease burden is limited to data from single-center or one-season studies in elderly patients. The HARTI study allows comparison of risk factors for progression to severe disease and medical resources utilization (MRU) during and post-hospitalization in adults diagnosed with influenza, RSV, or hMPV.

Methods
This was a prospective global study in adults hospitalized with acute respiratory tract infection (40 centers, 12 countries). Participants with influenza, RSV, or hMPV were enrolled in a substudy and followed up to three months post-discharge.

Results
Overall, 366 influenza, 238 RSV, and 100 hMPV-infected participants enrolled in the substudy. RSV participants were older, had greater frequency of risk factors, and longer duration of symptoms prior to hospitalization than influenza participants. RSV and hMPV groups received more bronchodilators, corticosteroids, and oxygen supplementation. No significant differences in intensive care unit admissions or complications were observed. Readmission occurred in 20-33% of patients within three months post-discharge, with highest rates for RSV and hMPV. In-hospital death occurred in 2.5% RSV, 1.6% influenza, and 2% hMPV participants. In multivariate analyses, length of stay was independently associated with country, renal disease, and increased age; probability of receiving supplemental oxygen was associated with pathogen (hMPV&gt;RSV&gt;influenza), abnormal chest x-ray, and increased age.

Conclusions
Although influenza is more frequent, the HARTI study demonstrates greater frequency of underlying risk factors and MRU for RSV and hMPV versus influenza in hospitalized adults, indicating need for effective interventions.
Establishing Genetic Relationships between the Takidani Pluton and Two Large Silicic Eruptions in the Northern Japan Alps
Authors: Hartung Eva , Caricchi Luca , Floess David , Wallis Simon , Harayama Satoru 
Published: October 2021

AbstractThe Takidani pluton (1·1–1·6 Ma) represents a shallow magmatic reservoir at the base of an exhumed caldera floor. The deposits of two large caldera-forming eruptions, the Nyukawa Pyroclastic Flow Deposit (1·76 Ma; crystal-rich dacite) and the Chayano Tuff and Ebisutoge Pyroclastic Deposits (1·75 Ma; a sequence of crystal-poor rhyolite), are distributed concentrically around the pluton. We use major and trace element chemistry of whole-rock, glass and minerals to show that (1) the crystal-rich dacite (&gt;400 km3 DRE; dense rock equivalent) is the erupted portion of a shallow mush zone constituting the Takidani pluton and (2) the crystal-poor rhyolite (&gt;100 km3 DRE) was extracted from a deeper part of this vertically extended magmatic plumbing system. Whole-rock geochemistry indicates that the Nyukawa and Takidani compositions were produced dominantly through crystal fractionation of amphibole, pyroxene and plagioclase in the mid to lower crust and subsequently emplaced in the upper crust prior to eruption and solidification, respectively. The crystal-poor Chayano–Ebisutoge rhyolite (&gt;100 km3 DRE) is compositionally distinct from the Nyukawa and Takidani magmas and its generation is associated with a substantial contribution of crustal melts. However, plagioclase and orthopyroxene textures and chemistry provide strong evidence that the ascending rhyolite percolated through the upper Takidani–Nyukawa mush zone prior to eruption. Overgrowth of ‘rhyolitic plagioclase’ on ‘xenocrystic dacitic plagioclase’ typical of the Takidani–Nyukawa magmas indicates that the extraction and accumulation of the rhyolitic melts could have occurred in less than 10 kyr (i.e. the time between eruptions) prior to eruption, providing maximum timescales for pre-eruption storage. Overall, our findings show a progressive growth and thermal maturation of a vertically extended magmatic plumbing system over hundreds of thousands of years and imply that large volcanic eruptions can occur in relatively short succession without dramatic changes in the plumbing system, thus complicating the identification of signs of an impending large eruption.
Monkey Plays Pac-Man with Compositional Strategies and Hierarchical Decision-making
Authors: Yang Qianli , Lin Zhongqiao , Zhang Wenyi , Li Jianshu , Chen Xiyuan , Zhang Jiaqi , Yang Tianming 
Published: October 2021

AbstractHumans can often handle daunting tasks with ease by developing a set of strategies to reduce decision making into simpler problems. The ability to use heuristic strategies demands an advanced level of intelligence and has not been demonstrated in animals. Here, we trained macaque monkeys to play the classic video game Pac-Man. The monkeys’ decision-making may be described with a strategy-based hierarchical decision-making model with over 90% accuracy. The model reveals that the monkeys adopted the take-the-best heuristic by using one dominating strategy for their decision-making at a time and formed compound strategies by assembling the basis strategies to handle particular game situations. With the model, the computationally complex but fully quantifiable Pac-Man behavior paradigm provides a new approach to understanding animals’ advanced cognition.One-Sentence SummaryMacaque monkeys play Pac-Man with strategy-based hierarchical decision making, a cognitive capacity hitherto unknown in them.
Self-association configures the NAD+-binding site of plant NLR TIR domains
Authors: Burdett Hayden , Hu Xiahao , Rank Maxwell X. , Maruta Natsumi , Kobe Bostjan 
Published: October 2021

AbstractTIR domains are signalling domains present in plant nucleotide-binding leucine-rich repeat receptors (NLRs), with key roles in plant innate immunity. They are required for the induction of a hypersensitive response (HR) in effector-triggered immunity, but the mechanism by which this occurs is not yet fully understood. It has been recently shown that the TIR domains from several plant NLRs possess NADase activity. The oligomeric structure of TIR-containing NLRs ROQ1 and RPP1 reveals how the TIR domains arrange into an active conformation, but low resolution around the NAD+ binding sites leaves questions unanswered about the molecular mechanisms linking self-association and NADase activity. In this study, a number of crystal structures of the TIR domain from the grapevine NLR RUN1 reveal how self-association and enzymatic activity may be linked. Structural features previously proposed to play roles involve the “AE interface” (mediated by helices A and E), the “BB-loop” (connecting β-strand B and helix B in the structure), and the “BE interface” (mediated by the BB-loop from one TIR and the “DE surface” of another). We demonstrate that self-association through the AE interface induces conformational changes in the NAD+-binding site, shifting the BB-loop away from the catalytic site and allowing NAD+ to access the active site. We propose that an intact “DE surface” is necessary for production of the signalling product (variant cyclic ADPR), as it constitutes part of the active site. Addition of NAD+ or NADP+ is not sufficient to induce self-association, suggesting that NAD+ binding occurs after TIR self-association. Our study identifies a mechanistic link between TIR self-association and NADase activity.
Dynamic Allostery Highlights the Evolutionary Differences between the CoV-1 and CoV-2 Main Proteases
Authors: Campitelli P. , Lu J. , Ozkan S. B. 
Published: October 2021

ABSTRACTThe SARS-CoV-2 coronavirus has become one of the most immediate and widely-studied systems since its identification and subsequent global outbreak from 2019-2020. In an effort to understand the biophysical changes as a result of mutations, the mechanics of multiple different proteins within the SARS-CoV-2 virus have been studied and compared with SARS-CoV-1. Focusing on the main protease (mPro), we first explored the long range dynamic-relationship, particularly in cross-chain dynamics, using the Dynamic Coupling Index (DCI) to investigate the dynamic coupling between the catalytic site residues and the rest of the protein, both inter and intra chain for the CoV-1 and CoV-2 mPro. We found that there is significant cross-chain coupling between these active sites and distal residues in the CoV-2 mPro but it was missing in CoV-1. The enhanced long distance interactions, particularly between the two chains, suggest subsequently enhanced cooperativity for CoV-2. A further comparative analysis of the dynamic flexibility using the Dynamic Flexibility Index (DFI) between the CoV-1 and CoV-2 mPros shows that the inhibitor binding near active sites induces change in flexibility to a distal region of the protein, opposite in behavior between the two systems; this region becomes more flexible upon inhibitor binding in CoV-1 while it becomes less flexible in the CoV-2 mPro. Upon inspection, we show that, on average, the dynamic flexibility of the sites substituted from CoV-1 to CoV-2 changes significantly less than the average calculated across all residues within the structure, indicating that the differences in behaviors between the two systems is likely the result of allosteric influence, where the new substitutions in COV-2 induce flexibility and dynamical changes elsewhere in the structure.SIGNIFICANCEHere we have conducted a comparative analysis between the SARS-CoV-1 and SARS-CoV-2 mPro systems to shed mechanistic insight on the biophysical changes associated with the mutations between these two enzymes. Our work shows that the CoV-2 mPro system exhibits enhanced cross-chain communication between catalytic site residues and the rest of the structure. Further, both dynamic coupling and dynamic flexibility analyses indicates that, largely, the dynamic changes as evaluated by DCI and DFI occur at sites other than the mutation sites themselves, indicating that the functional differences between these two proteins are a result of dynamic allostery