bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine effectiveness of the BNT162b2 mRNA COVID-19 vaccine against RT-PCR confirmed SARS-CoV-2 infections, hospitalisations and mortality in prioritised risk groups
Authors: Emborg Hanne-Dorthe , Valentiner-Branth Palle , Schelde Astrid Blicher , Nielsen Katrine Finderup , Gram Mie Agermose , Moustsen-Helms Ida Rask , Chaine Manon , Seidelin Ulla Holten , Nielsen Jens 
Published: June 2021

AbstractObjectiveTo estimate in a real life setting, the vaccine effectiveness of the BNT162b2 mRNA vaccine against confirmed SARS-CoV-2 infection, hospital admission, and death among five priority groups for vaccinationDesignCohort studySettingRoll-out of the BNT162b2 mRNA vaccine in DenmarkParticipants864,096 individuals who were first inline to receive the BNT162b2 mRNA vaccine: 46,101 long-term care facility (LTCF) residents, 61,805 individuals 65 years and older living at home but requiring practical help and personal care (65PHC), 98,533 individuals ≥85 years of age (+85), 425,799 health-care workers (HCWs), and 231,858 individuals with comorbidities that predispose for severe COVID-19 disease (SCD).Interventionvaccination with BNT162b2 mRNA vaccineMain outcome measuresRT-PCR confirmed SARS-CoV-2 infections, COVID-19 related admissions within 14 days after a confirmed SARS-CoV-2 infection, all-cause admission, COVID-19 related death within 30 days after confirmed SARS-CoV-2 infection, and all-cause death.ResultsBeyond 7 days after the second dose, the VE against SARS-CoV-2 infection in all groups ranged from 53-86%. In 65PHC, HCW and SCD, we observed a substantial reduction in risk of infection 0-7 days after the second dose ranging from 46-71%. The VE against COVID-19 related admissions ranged from 75-87% in all groups except +85 and HCWs where no events occurred. For COVID-19 related deaths, a significant VE was observed in LTCF residents (VE of 89%) and 65PHC (VE of 97%), whereas no events were observed in the three remaining groups. VE against all-cause death ranged from 26-73% in all groups except HCW where an insignificant VE was estimated. For all-cause admission, the VE ranged from 37-50% in all groups except in SCD where a negative VE was observed.ConclusionIn a real-life setting and more than 7 days after the second dose of BNT162b2 mRNA was administered to the most vulnerable individuals, the vaccine was associated with a reduction of SARS-CoV-2 infection (53-86%) and COVID-19 related admissions (≥75%) or deaths (≥89%).
Irradiation of UVC LED at 277 nm inactivates coronaviruses by photodegradation of spike protein
Authors: Ong Qunxiang , Ronnie Teo J. W. , Cruz Joshua Dela , Wee Elijah , Wee Winson , Han Weiping 
Published: June 2021

SUMMARYTo interrupt SARS-CoV-2 transmission chains, Ultraviolet-C (UVC) irradiation has emerged as a potential disinfection tool to aid in blocking the spread of coronaviruses. While conventional 254-nm UVC mercury lamps have been used for disinfection purposes, other UVC wavelengths have emerged as attractive alternatives but a direct comparison of these tools is lacking with the inherent mechanistic properties unclear. Our results using human coronaviruses, hCoV-229E and hCoV-OC43, have indicated that 277-nm UVC LED is most effective in viral inactivation, followed by 222-nm far UVC and 254-nm UVC mercury lamp. While UVC mercury lamp is more effective in degrading viral genomic content compared to 277-nm UVC LED, the latter results in a pronounced photo-degradation of spike proteins which potentially contributed to the higher efficacy of coronavirus inactivation. Hence, inactivation of coronaviruses by 277-nm UVC LED irradiation constitutes a more promising method for disinfection.
Systematic comparison of experimental assays and analytical pipelines for identification of active enhancers genome-wide
Authors: Yao Li , Liang Jin , Ozer Abdullah , Leung Alden King-Yung ,   ENCODE Consortium, Lis John T. , Yu Haiyuan 
Published: June 2021

AbstractMounting evidence supports the idea that transcriptional patterns serve as more specific identifiers of active enhancers than histone marks1,2; however, the optimal strategy to identify active enhancers both experimentally and computationally has not been determined. In this study, we compared 13 genome-wide RNA sequencing assays in K562 cells and showed that the nuclear run-on followed by cap-selection assay (namely, GRO/PRO-cap) has significant advantages in eRNA detection and active enhancer identification. We also introduced a new analytical tool, Peak Identifier for Nascent-Transcript Sequencing (PINTS), to identify active promoters and enhancers genome-wide and pinpoint the precise location of the 5’ transcription start sites (TSSs) within these regulatory elements. Finally, we compiled a comprehensive enhancer candidate compendium based on the detected eRNA TSSs available in 120 cell and tissue types. To facilitate the exploration and prioritization of these enhancer candidates, we also built a user-friendly web server (https://pints.yulab.org) for the compendium with various additional genomic and epigenomic annotations. With the knowledge of the best available assays and pipelines, this large-scale annotation of candidate enhancers will pave the road for selection and characterization of their functions in a time-, labor-, and cost-effective manner in the future.
3D-Scaffold: Deep Learning Framework to Generate 3D Coordinates of Drug-like Molecules with Desired Scaffolds
Authors: Joshi Rajendra P. , Gebauer Niklas W. A. , Bontha Mridula , Khazaieli Mercedeh , James Rhema M. , Brown Ben , Kumar Neeraj 
Published: June 2021

AbstractThe prerequisite of therapeutic drug design is to identify novel molecules with desired biophysical and biochemical properties. Deep generative models have demonstrated their ability to find such molecules by exploring a huge chemical space efficiently. An effective way to obtain molecules with desired target properties is the preservation of critical scaffolds in the generation process. To this end, we propose a domain aware generative framework called 3D-Scaffold that takes 3D coordinates of the desired scaffold as an input and generates 3D coordinates of novel therapeutic candidates as an output while always preserving the desired scaffolds in generated structures. We show that our framework generates predominantly valid, unique, novel, and experimentally synthesizable molecules that have drug-like properties similar to the molecules in the training set. Using domain specific datasets, we generate covalent and non-covalent antiviral inhibitors. To measure the success of our framework in generating therapeutic candidates, generated structures were subjected to high throughput virtual screening via docking simulations, which shows favorable interaction against SARS-CoV-2 main protease and non-structural protein endoribonuclease (NSP15) targets. Most importantly, our model performs well with relatively small volumes of training data and generalizes to new scaffolds, making it applicable to other domains.
Nuclear depletion of RNA binding protein ELAVL3 (HuC) in sporadic and familial amyotrophic lateral sclerosis
Authors: Diaz-Garcia Sandra , Ko Vivian I. , Vazquez-Sanchez Sonia , Chia Ruth , Arogundade Olubankole Aladesuyi , Rodriguez Maria J , Cleveland Don , Traynor Bryan J. , Ravits John 
Published: June 2021

AbstractAmyotrophic lateral sclerosis is a progressive fatal neurodegenerative disease caused by loss of motor neurons and characterized neuropathologically in almost all cases by nuclear depletion and cytoplasmic aggregation of TDP-43, a nuclear RNA binding protein (RBP). We identified ELAVL3 as one of the most downregulated genes in our transcriptome profiles of laser captured microdissection of motor neurons from sporadic ALS nervous systems and the top dysregulated RBPs. Neuropathological characterizations showed ELAVL3 nuclear depletion in a great percentage of remnant motor neurons, sometimes accompanied by cytoplasmic accumulations. These abnormalities were common in sporadic cases with and without intermediate expansions in ATXN2 and familial cases carrying mutations in C9orf72 and SOD1. Depletion of ELAVL3 occurred at both the RNA and protein levels and a short protein isoform was identified but it is not related to a TDP-43-dependent cryptic exon in intron 3. Strikingly, ELAVL3 abnormalities were more frequent than TDP-43 abnormalities and occurred in motor neurons still with normal nuclear TDP-43 present, but all neurons with abnormal TDP-43 also had abnormal ELAVL3. In a neuron-like cell culture model using SH-SY5Y cells, ELAVL3 mislocalization occurred weeks before TDP-43 abnormalities were seen. We interrogated genetic databases but did not identify association of ELAVL3 genetic structure associated with ALS. Taken together, these findings suggest that ELAVL3 is an important RBP in ALS pathogenesis acquired early and the neuropathological data suggest it is involved by loss of function rather than cytoplasmic toxicity.
An automated platform for structural analysis of membrane proteins through serial crystallography
Authors: Healey Robert D. , Basu Shibom , Humm Anne-Sophie , Leyrat Cedric , Cong Xiaojing , Golebiowski Jérome , Dupeux Florine , Pica Andrea , Granier Sébastien , Márquez José Antonio 
Published: June 2021

SummaryMembrane proteins are central to many pathophysiological processes yet remain very difficult to analyze at a structural level. Moreover, high-throughput structure-based drug discovery has not yet been exploited for membrane proteins due to lack of automation. Here, we present a facile and versatile platform for in meso membrane protein crystallization, enabling rapid atomic structure determination at both cryogenic and room temperature and in a single support. We apply this approach to two human integral membrane proteins, which allowed us to capture different conformational states of intramembrane enzyme-product complexes and analyze the structural dynamics of the ADIPOR2 integral membrane protein. Finally, we demonstrate an automated pipeline combining high-throughput microcrystal soaking, automated laser-based harvesting and serial crystallography enabling screening of small molecule libraries with membrane protein crystals grown in meso. This approach brings badly needed automation for this important class of drug targets and enables high-throughput structure-based ligand discovery with membrane proteins.HighlightsA fully automated, online workflow enables rapid determination of membrane protein structures by serial X-ray crystallography (SSX).High resolution room temperature and cryogenic structures of ADIPOR2 provide insights into the dynamic nature of receptor:ligand interactions.A web-based application allows remote user-guided experimental design and execution.An automated SSX-based ligand discovery pipeline for integral membrane proteins is introduced.
Cryo-EM structures reveal how ATP and DNA binding in MutS coordinate the sequential steps of DNA mismatch repair
Authors: Borsellini Alessandro , Kunetsky Vladislav , Friedhoff Peter , Lamers Meindert H. 
Published: June 2021

AbstractDNA mismatch repair detects and removes mismatches from DNA reducing the error rate of DNA replication a 100-1000 fold. The MutS protein is one of the key players that scans for mismatches and coordinates the repair cascade. During this, MutS undergoes multiple conformational changes that initiate the subsequent steps, in response to ATP binding, hydrolysis, and release. How ATP induces the different conformations in MutS is not well understood. Here we present four cryo-EM structures of Escherichia coli MutS at sequential stages of the ATP hydrolysis cycle. These structures reveal how ATP binding and hydrolysis induces a closing and opening of the MutS dimer, respectively. Additional biophysical analysis furthermore explains how DNA binding modulates the ATPase cycle by preventing hydrolysis during scanning and mismatch binding, while preventing ADP release in the sliding clamp state. Nucleotide release is achieved when MutS encounters single stranded DNA that is produced during the removal of the daughter strand. This way, the combination of the ATP binding and hydrolysis and its modulation by DNA enable MutS to adopt different conformations needed to coordinate the sequential steps of the mismatch repair cascade.
Early and late evoked brain responses differentially reflect feature encoding and perception in the flash-lag illusion
Authors: Keil Julian , Senkowski Daniel , Moran James K. 
Published: June 2021

AbstractIn the flash-lag illusion (FLI), the position of a flash presented ahead of a moving bar is mislocalized, so the flash appears to lag the bar. Currently it is not clear whether this effect is due to early perceptual-related neural processes such as motion extrapolation or reentrant processing, or due to later feedback processing relating to postdiction, i.e. retroactively altered perception. We presented 17 participants with the FLI paradigm while recording EEG. A central flash occurred either 51ms (“early”) or 16ms (“late”) before the bar moving from left to right reached the screen center. Participants judged whether the flash appeared to the right (“no flash lag illusion”) or to the left (“flash-lag illusion”) of the bar. Using single-trial linear modelling, we examined the influence of timing (“early” vs. “late”) and perception (“illusion” vs. “no illusion”) on flash-evoked brain responses, and estimated the cortical sources underlying the FLI. Perception of the FLI was associated with a late window (368-452ms) in the ERP, with larger deflections for illusion than no illusion trials, localized to the left fusiform gyrus. An earlier frontal and occipital component (200-276ms) differentiated time-locked early vs. late stimulus presentation. Our results suggest a postdiction-related reconstruction of ambiguous sensory stimulation involving late processes in the occipito-temporal cortex, previously associated with temporal integration phenomena. This indicates that perception of the FLI relies on an interplay between ongoing stimulus encoding of the moving bar and feedback processing of the flash, which takes place at later integration stages.HighlightsFlash-lag illusion relates primarily to late evoked brain potentials (>300ms)Illusion vs. no-illusion trials showed difference in fusiform gyrusFlash-lag illusion could involve postdiction-driven integration of ongoing stimuli
Binding patterns of RNA binding proteins to repeat-derived RNA sequences reveal putative functional RNA elements
Authors: Onoguchi Masahiro , Zeng Chao , Matsumaru Ayako , Hamada Michiaki 
Published: June 2021

ABSTRACTRecent reports have revealed that repeat-derived sequences embedded in introns or long noncoding RNAs (lncRNAs) are targets of RNA binding proteins (RBPs) and contribute to biological processes such as RNA splicing or transcriptional regulation. These findings suggest that repeat-derived RNAs are important as scaffolds of RBPs and functional elements. However, the overall functional sequences of the repeat-derived RNAs are not fully understood. Here, we show the putative functional repeat-derived RNAs by analyzing the binding patterns of RBPs based on ENCODE eCLIP data. We mapped all eCLIP reads to repeat sequences and observed that 10.75 % and 7.04 % of reads on average were enriched (at least 2-fold over control) in the repeats in K562 and HepG2 cells, respectively. Using these data, we predicted functional RNA elements on the sense and antisense strands of long interspersed element 1 (LINE1) sequences. Furthermore, we found several new sets of RBPs on fragments derived from other transposable element (TE) families. Some of these fragments show specific and stable secondary structures and are found to be inserted into the introns of genes or lncRNAs. These results suggest that the repeat-derived RNA sequences are strong candidates for the functional RNA elements of endogenous noncoding RNAs.
Association between quinolone use in food animals and gonococcal resistance to ciprofloxacin: an ecological study
Authors: Gonzalez Natalia , Abdellati Said , Manoharan-Basil Sheeba , Kenyon Chris 
Published: June 2021

AbstractBackgroundConcentrations of fluoroquinolones up to 200-fold lower than the MIC have been shown to be able to select for antimicrobial resistance in E. coli and Salmonella spp. (the minimum selection concentration – MSC). We aimed to i) establish what the ciprofloxacin MSC is for Neisseria gonorrhoeae and ii) Assess at a country level if the prevalence of gonococcal ciprofloxacin resistance is associated with the concentration of quinolones used in food animal production (an important determinant of long-term low dose ciprofloxacin exposures in humans).Methodsi). To assess if sub-inhibitory ciprofloxacin concentrations could select for de novo generated resistant mutants, susceptible WHO-P was serially passaged at 1, 1/10, 1/100 and 1/1000 of the ciprofloxacin MIC of WHO-P (0.004mg/L) on GC agar plates. ii) Spearman’s correlation was used to assess the association between the prevalence of ciprofloxacin resistance in N. gonorrhoeae and the two independent variables – quinolone use for animals and quinolone consumption by humans.ResultsCiprofloxacin concentrations as low as 1/1000 of the MIC of WHO-P were able to select for ciprofloxacin resistance. The prevalence of ciprofloxacin resistance in N. gonorrhoeae was positively associated with quinolone use for food animals (ρ=0.47; P=0.004; N=34).ConclusionFurther individual level research is required to assess if low doses of ciprofloxacin from ingested foodstuffs are able to select for ciprofloxacin resistance in N. gonorrhoeae and other species.
Integrated design of fault-tolerant control for flight control systems using observer and fuzzy logic
Authors: Unal Gulay 
Published: June 2021

Purpose
Fault detection, isolation and reconfiguration of the flight control system is an important problem to obtain healthy flight. This paper aims to propose an integrated approach for aircraft fault-tolerant control.

Design/methodology/approach
The integrated structure includes a Kalman filter to obtain without noise, a full order observer for sensor fault detection, a GOS (generalized observer scheme) for sensor fault isolation and a fuzzy controller to reconfigure of the healthy sensor. This combination is simulated using the state space model of a lateral flight control system in case of disturbance and under sensor fault scenario.

Findings
Using a dedicated observer scheme, the detection and time of sensor fault are correct, but the sensor fault isolation is evaluated incorrectly while the faulty sensor is isolated correctly using GOS. The simulation results show that the suggested approach works affectively for sensor faults with disturbance.

Originality/value
This paper proposes an integrated approach for aircraft fault-tolerant control. Under this framework, three units are designed, one is Kalman filter for filtering and the other is GOS for sensor fault isolation and another is fuzzy logic for reconfiguration. An integrated approach is sensitive to faults that have disturbances. The simulation results show the proposed integrated approach can be used for any linear system.
International higher education brand alliance: the role of brand fit and world-mindedness
Authors: Kim Kyung-Min , Nobi Benjamin , Lee Sangwon , Milewicz Chad 
Published: June 2021

PurposeThis research investigates three major research questions. First, how does brand alliance type, defined by a partner's location and brand quality, affect consumers' emotional value perceptions of higher education brand alliances for dual-degree programs? Second, does perceived brand fit mediate the relationship between brand alliance type and emotional value perceptions? Third, do individual differences in world-mindedness moderate the influence of brand alliance type on emotional value perceptions?Design/methodology/approachIn total, two experiments are performed. Experiment one examines the effect of brand alliance type, at varying combinations of partner brand quality and partner location (domestic or foreign), on consumers' emotional value perceptions. Experiment two examines the moderating role of world-mindedness in the relationship between brand alliance type and consumers' emotional value perceptions.FindingsResults provide evidence that consumers' perception of brand fit mediates the relationship between brand alliance type and consumers' emotional value perceptions of the alliance. Results also indicate that world-mindedness moderates the relationship between brand alliance type and emotional value perceptions.Originality/valueThis research extends the previous literature on higher education dual-degree brand alliances and introduces world-mindedness as an important consumer-based characteristic to consider in this line of research. It answers calls for more research on higher education branding and calls for research into the potential mediating role and importance of brand fit. It provides several theoretical and managerial implications relevant to the higher education brand alliances, particularly in dual-degree programs.
Speed of internationalization and firm performance: the moderating role of potential slack and knowledge assets
Authors: Zhang Banruo , Li Zijie , Li Xiaomeng , Liu Ziqi 
Published: June 2021

PurposeThe speed of internationalization is an important research topic in the process of internationalization. This paper aims to answer two questions: first, what is the relationship between the speed of internationalization of Chinese multinational firms and their performance? Second, how do potential slack and knowledge assets of firms affect this relationship?Design/methodology/approachThe authors choose Chinese A-share listed manufacturing firms from 2009–2018 as the research sample and use the fixed-effect regression model to test the proposed hypotheses.FindingsFirstly, there is an inverted U-shaped relationship between the speed of internationalization and firm performance (SI-P). Secondly, the potential slack and knowledge assets of firms moderate the inverted U-shaped relationship. Firms with a higher level of potential slack or knowledge assets have a flatter inverted U-shaped relationship between SI-P.Originality/valueFirst, the authors develop and extend Penrose’s theory of firm growth to the research topic of speed of internationalization. Second, this paper incorporates the time dimension into the research on the internationalization process and locates the research context in emerging market firms (EMFs). This is a step forward in clarifying the complex relationship of SI-P. Third, the authors show that the SI-P relationship of EMFs is inverted U-shaped and integrate previous studies, which argue that rapid internationalization positively or negatively affects firm performance. Fourth, starting from inside the firm, the authors provide more contextual factors for better understanding and analysis of the SI-P relationship.