bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and Safety of Porcine Circovirus-Free Human Rotavirus Vaccine in Healthy Infants: A Phase 3 Randomized Trial
Authors: Salamanca de la Cueva Ignacio , Pahud Barbara , Huang Li-Min , Leonardi Michael , Garcia-Sicilia José , Céspedes Javier , Abdelnour Arturo , Tamura Tsuyoshi , Kuroki Haruo , Chiu Nan-Chang , Virta Miia , Kokko Satu , Horn Michael , Panzer Falko , Kim Jong-Hyun , Lee Jin , Moerman Leentje , Debacq Christophe , Parra Jose , Ugarte Ana , Bi Dan ,   Rota-081 Study Group
Published: April 2020

Abstract

Background
Porcine circovirus type 1 (PCV-1) material was detected in the human rotavirus vaccine (HRV) in 2010. In this study we compared immunogenicity and safety of the PCV-free HRV vaccine (PCV-free HRV) with HRV. PCV-free HRV is an HRV with no detectable PCV-1 and PCV-2 according to the limit of detection of the tests used.

Methods
Healthy infants 6–12 weeks of age were randomized (1:1:1:1) to receive 2 doses of 1 of the 3 lots of PCV-free HRV or HRV. The study objectives were to demonstrate lot-to-lot consistency of the PCV-free HRV and noninferiority of PCV-free HRV as compared to HRV in terms of immunogenicity, 1–2 months post dose 2. Reactogenicity and safety were also assessed.

Results
Overall, 1612 infants were enrolled and 1545 completed the study. Study objectives were demonstrated because the predefined criteria were met. Among participants receiving PCV-free HRV and HRV, 79.27% and 81.76% seroconverted and geometric mean concentrations were 159.5 and 152.8 U/mL, respectively. The incidences of adverse events and serious adverse events were similar between the pooled PCV-free HRV and HRV groups.

Conclusions
The 3 PCV-free HRV lots demonstrated consistency and PCV-free HRV was noninferior compared to HRV in terms of immunogenicity.

Clinical trials registration
NCT02914184.
Challenges and Opportunities of Using Adoptive T-Cell Therapy as Part of an HIV Cure Strategy
Authors: Zhou Yuqi , Maldini Colby R , Jadlowsky Julie , Riley James L 
Published: April 2020

AbstractHIV-infected individuals successfully controlling viral replication via antiretroviral therapy often have a compromised HIV-specific T-cell immune response due to the lack of CD4 T-cell help, viral escape, T-cell exhaustion, and reduction in numbers due to the withdrawal of cognate antigen. A successful HIV cure strategy will likely involve a durable and potent police force that can effectively recognize and eliminate remaining virus that may emerge decades after an individual undergoes an HIV cure regimen. T cells are ideally suited to serve in this role, but given the state of the HIV-specific T-cell response, it is unclear how to best restore HIV-specific T-cell activity prior initiation of a HIV cure strategy. Here, we review several strategies of generating HIV-specific T cells ex vivo that are currently being tested in the clinic and discuss how infused T cells can be part of an HIV cure strategy.
Unique Approach to Quality Assurance in Viscoelastic Testing
Authors: Leadbetter Nicole H , Givens Thomas B , Viola Francesco 
Published: April 2020

Abstract

Background
The Quantra QPlus System is a novel viscoelastic testing (VET) device designed for the management of coagulation function in critical care settings. The system is indicated and approved for use at the point-of-care and designed for use by nonlaboratory personnel.

Methods
We describe the comprehensive set of internal QC checks implemented in the Quantra and demonstrate the system’s unique capabilities made possible by its ultrasound core technology. Single- and multisite precision testing were performed following Clinical Laboratory Standards Institute guidelines and included multiple days of testing, multiple instruments, multiple lots of cartridges and controls, and multiple operators.

Results
Percent CVs for total imprecision were 3.6% to 8.0% for all measured parameters. CVs for replicate imprecision (“repeatability”) were 2.7% to 7.7% for all measured parameters. Replicate imprecision was the largest component of variability for most parameters.

Conclusions
The Quantra QPlus System is a new-generation cartridge-based VET device that can operate with reduced oversight from the central laboratory while easily integrating into the Individualized Quality Control Plan framework.
The First Reported Case of a Synthetic Cannabinoid Ethyl Ester Detected in a Postmortem Blood Toxicological Analysis
Authors: Apirakkan Orapan , Hudson Simon , Couchman Lewis , Cowan David , Morley Stephen , Abbate Vincenzo 
Published: April 2020

Abstract
Metabolites of synthetic cannabinoids (SCs) are widely used as markers for identifying SCs’ intake. Polydrug use involving SCs and ethanol may generate new metabolites, namely SC ethyl esters, hereby shown for the first time as new blood markers of SC-alcohol concomitant abuse. We report a case involving both the presence of 5F-PB22 and ethanol and the detection of their transesterifcation product, namely 5F-PB22 ethyl ester, in a postmortem blood sample. This marker was found retrospectively in a preserved femoral blood analyzed via liquid chromatography–high-resolution mass spectrometry. A single-point calibration was used to estimate the concentration of 5F-PB22-Et in the sample, which found to be 0.4 μg/L. Retention time and fragment ions (within ±1 mmu extraction window) of 5F-PB22-Et in the sample gave a remarkable match with a synthetic reference material. To the best of our knowledge, this is the first case report of an SC ethyl ester in a biological sample to indicate SCs and ethanol co-consumption.
A UHPLC–MS-MS Method for the Determination of 84 Drugs of Abuse and Pharmaceuticals in Blood
Authors: Orfanidis Amvrosios , Gika Helen G , Theodoridis Georgios , Mastrogianni Orthodoxia , Raikos Nikolaos 
Published: April 2020

Abstract
The analysis of blood samples for forensic or clinical intoxication cases is a daily routine in an analytical laboratory. The list of ‘suspect’ drugs of abuse and pharmaceuticals that should be ideally screened is large, so multi-targeted methods for comprehensive detection and quantification are a useful tool in the hands of a toxicologist. In this study, the development of an ultra-high performance liquid chromatography (LC)–tandem mass spectrometry (MS-MS) method is described for the detection and quantification of 84 drugs and pharmaceuticals in postmortem blood. The target compounds comprise pharmaceutical drugs (antipsychotics, antidepressants, etc.), some of the most important groups of drugs of abuse: opiates, cocaine, cannabinoids, amphetamines, benzodiazepines and new psychoactive substances. Sample pretreatment was studied applying a modified Mini-QuEChERS single step, and the best results were obtained after adding a mixture of 20 mg MgSO4, 5 mg K2CO3 and 5 mg NaCl together with 600 μL of cold acetonitrile in 200 μL of sample. After centrifugation, the supernatant was collected for direct injection. LC–MS analysis took place on a C18 column with a gradient elution over 17 min. The method was found to be selective and sensitive, offering limits of detection ranging from 0.01 to 9.07 ng/mL. Validation included evaluation of limit of quantification, recovery, carryover, matrix effect, accuracy and precision of the method. The method performed satisfactorily in relation to established bioanalytical criteria and was therefore applied to the analysis of blood obtained postmortem from chronic drug abusers, offering unambiguous identification and quantitative determination of drugs in postmortem blood.
Media and Crime Perceptions: Evidence from Mexico
Authors: Ramírez-Álvarez Aurora Alejandra 
Published: April 2020

Abstract
This article examines whether individuals’ crime perceptions and crime avoidance behavior respond to changes in crime news coverage. I use data from Mexico, where major media groups agreed to reduce coverage of violence in March 2011. Using a unique dataset on national news content and machine learning techniques, I document that after the Agreement, crime news coverage on television, radio, and newspapers decreases relative to the national homicide rate. Using survey data, I find robust evidence that crime perceptions respond to this change in content. After the Agreement, individuals with higher media exposure are less likely to report that they feel insecure and that their country, state, or municipality is insecure, relative to individuals with lower media exposure. Finally, I show that smaller changes on conspicuous consumption and food consumed outside the home accompany these changes in crime perceptions; while I do not find effects on stated crime avoidance behavior. (JEL: D83, K42, L82).
The tale of caspase homologues and their evolutionary outlook: deciphering programmed cell death in cyanobacteria
Authors: Bhattacharjee Samujjal , Mishra Arun Kumar 
Published: April 2020

AbstractProgrammed cell death (PCD), a genetically orchestrated mechanism of cellular demise, is paradoxically required to support life. As in lower eukaryotes and bacteria, PCD in cyanobacteria is poorly appreciated, despite recent biochemical and molecular evidence that supports its existence. Cyanobacterial PCD is an altruistic reaction to stressful conditions that significantly enhances genetic diversity and inclusive fitness of the population. Recent bioinformatic analysis has revealed an abundance of death-related proteases, i.e. orthocaspases (OCAs) and their mutated variants, in cyanobacteria, with the larger genomes of morphologically complex strains harbouring most of them. Sequence analysis has depicted crucial accessory domains along with the proteolytic p20-like sub-domain in OCAs, predicting their functional versatility. However, the cascades involved in sensing death signals, their transduction, and the downstream expression and activation of OCAs remain to be elucidated. Here, we provide a comprehensive description of the attempts to identify mechanisms of PCD and the existence and importance of OCAs based on in silico approaches. We also review the evolutionary and ecological significance of PCD in cyanobacteria. In the future, the analysis of cyanobacterial PCD will identify novel proteins that have varied functional roles in signalling cascades and also help in understanding the incipient mechanism of PCD morphotype(s) from where eukaryotic PCD might have originated.
The importance of accurate developmental staging
Authors: Ober Eric S , Howell Phil , Thomelin Pauline , Kouidri Allan 
Published: April 2020

This article comments on:
Fernández-Gómez J, Talle B, Tidy A, Wilson ZA. 2020. Accurate staging of reproduction development in Cadenza wheat by non-destructive spike analysis. Journal of Experimental Botany71, 3475–3484.
Reionization with galaxies and active galactic nuclei
Authors: Dayal Pratika , Volonteri Marta , Choudhury Tirthankar Roy , Schneider Raffaella , Trebitsch Maxime , Gnedin Nickolay Y , Atek Hakim , Hirschmann Michaela , Reines Amy 
Published: April 2020

ABSTRACT
In this work we investigate the properties of the sources that reionized the intergalactic medium (IGM) in the high-redshift Universe. Using a semi-analytical model aimed at reproducing galaxies and black holes in the first ∼1.5 Gyr of the Universe, we revisit the relative role of star formation and black hole accretion in producing ionizing photons that can escape into the IGM. Both star formation and black hole accretion are regulated by supernova feedback, resulting in black hole accretion being stunted in low-mass haloes. We explore a wide range of combinations for the escape fraction of ionizing photons (redshift-dependent, constant, and scaling with stellar mass) from both star formation ($\langle f_{\rm esc}^{\rm sf} \rangle$) and AGN ($f_{\rm esc}^{\rm bh}$) to find: (i) the ionizing budget is dominated by stellar radiation from low stellar mass ($M_*\lt 10^9 \, {\rm \rm M_\odot }$) galaxies at z &gt; 6 with the AGN contribution (driven by $M_{bh}\gt 10^6 \, {\rm \rm M_\odot }$ black holes in $M_* \gtrsim 10^9\, {\rm \rm M_\odot }$ galaxies) dominating at lower redshifts; (ii) AGN only contribute $10-25{{\ \rm per\ cent}}$ to the cumulative ionizing emissivity by z = 4 for the models that match the observed reionization constraints; (iii) if the stellar mass dependence of $\langle f_{\rm esc}^{\rm sf} \rangle$ is shallower than $f_{\rm esc}^{\rm bh}$, at z &lt; 7 a transition stellar mass exists above which AGN dominate the escaping ionizing photon production rate; (iv) the transition stellar mass decreases with decreasing redshift. While AGN dominate the escaping emissivity above the knee of the stellar mass function at z ∼ 6.8, they take-over at stellar masses that are a tenth of the knee mass by z = 4.
Visible and near-infrared observations of interstellar comet 2I/Borisov with the 10.4-m GTC and the 3.6-m TNG telescopes
Authors: de León J , Licandro J , de la Fuente Marcos C , de la Fuente Marcos R , Lara L M , Moreno F , Pinilla-Alonso N , Serra-Ricart M , De Prá M , Tozzi G P , Souza-Feliciano A C , Popescu M , Scarpa R , Font Serra J , Geier S , Lorenzi V , Harutyunyan A , Cabrera-Lavers A 
Published: April 2020

ABSTRACTIn this work, we present the results of an observational study of 2I/Borisov carried out with the 10.4-m Gran Telescopio Canarias (GTC) and the 3.6-m Telescopio Nazionale Galileo (TNG), both telescopes located at the Roque de Los Muchachos Observatory, in the island of La Palma (Spain). The study includes images in the visible and near-infrared, as well as visible spectra in the 3600–9200 Å wavelength range. N-body simulations were also performed to explore its orbital evolution and Galactic kinematic context. The comet’s dust continuum and near-infrared colours are compatible with those observed for Solar system comets. From its visible spectrum on the nights of 2019 September 24 and 26, we measured CN gas production rates Q(CN) = (2.3 ± 0.4) × 1024 mol s−1 and Q(CN) = (9.5 ± 0.2) × 1024 mol s−1, respectively, in agreement with measurements reported by other authors on similar nights. We also obtained an upper limit for the C2 production rate of Q(C2) &lt; (4.5 ± 0.1) × 1024 mol s−1. Dust modelling results indicate a moderate dust production rate of ∼50 kg s−1 at heliocentric distance rh = 2.6 au, with a differential power-law dust size distribution of index ∼–3.4, within the range reported for many comet comae. Our simulations show that the Galactic velocity of 2I/Borisov matches well that of known stars in the solar neighbourhood and also those of more distant regions of the Galactic disc.
Revealing thermodynamics of DNA origami folding via affine transformations
Authors: Majikes Jacob M , Patrone Paul N , Schiffels Daniel , Zwolak Michael , Kearsley Anthony J , Forry Samuel P , Liddle J Alexander 
Published: April 2020

AbstractStructural DNA nanotechnology, as exemplified by DNA origami, has enabled the design and construction of molecularly-precise objects for a myriad of applications. However, limitations in imaging, and other characterization approaches, make a quantitative understanding of the folding process challenging. Such an understanding is necessary to determine the origins of structural defects, which constrain the practical use of these nanostructures. Here, we combine careful fluorescent reporter design with a novel affine transformation technique that, together, permit the rigorous measurement of folding thermodynamics. This method removes sources of systematic uncertainty and resolves problems with typical background-correction schemes. This in turn allows us to examine entropic corrections associated with folding and potential secondary and tertiary structure of the scaffold. Our approach also highlights the importance of heat-capacity changes during DNA melting. In addition to yielding insight into DNA origami folding, it is well-suited to probing fundamental processes in related self-assembling systems.
AWSEM-Suite: a protein structure prediction server based on template-guided, coevolutionary-enhanced optimized folding landscapes
Authors: Jin Shikai , Contessoto Vinicius G , Chen Mingchen , Schafer Nicholas P , Lu Wei , Chen Xun , Bueno Carlos , Hajitaheri Arya , Sirovetz Brian J , Davtyan Aram , Papoian Garegin A , Tsai Min-Yeh , Wolynes Peter G 
Published: April 2020

Abstract
The accurate and reliable prediction of the 3D structures of proteins and their assemblies remains difficult even though the number of solved structures soars and prediction techniques improve. In this study, a free and open access web server, AWSEM-Suite, whose goal is to predict monomeric protein tertiary structures from sequence is described. The model underlying the server’s predictions is a coarse-grained protein force field which has its roots in neural network ideas that has been optimized using energy landscape theory. Employing physically motivated potentials and knowledge-based local structure biasing terms, the addition of homologous template and co-evolutionary restraints to AWSEM-Suite greatly improves the predictive power of pure AWSEM structure prediction. From the independent evaluation metrics released in the CASP13 experiment, AWSEM-Suite proves to be a reasonably accurate algorithm for free modeling, standing at the eighth position in the free modeling category of CASP13. The AWSEM-Suite server also features a front end with a user-friendly interface. The AWSEM-Suite server is a powerful tool for predicting monomeric protein tertiary structures that is most useful when a suitable structure template is not available. The AWSEM-Suite server is freely available at: https://awsem.rice.edu.
Structural disruption of exonic stem–loops immediately upstream of the intron regulates mammalian splicing
Authors: Saha Kaushik , England Whitney , Fernandez Mike Minh , Biswas Tapan , Spitale Robert C , Ghosh Gourisankar 
Published: April 2020

Abstract
Recognition of highly degenerate mammalian splice sites by the core spliceosomal machinery is regulated by several protein factors that predominantly bind exonic splicing motifs. These are postulated to be single-stranded in order to be functional, yet knowledge of secondary structural features that regulate the exposure of exonic splicing motifs across the transcriptome is not currently available. Using transcriptome-wide RNA structural information we show that retained introns in mouse are commonly flanked by a short (≲70 nucleotide), highly base-paired segment upstream and a predominantly single-stranded exonic segment downstream. Splicing assays with select pre-mRNA substrates demonstrate that loops immediately upstream of the introns contain pre-mRNA-specific splicing enhancers, the substitution or hybridization of which impedes splicing. Additionally, the exonic segments flanking the retained introns appeared to be more enriched in a previously identified set of hexameric exonic splicing enhancer (ESE) sequences compared to their spliced counterparts, suggesting that base-pairing in the exonic segments upstream of retained introns could be a means for occlusion of ESEs. The upstream exonic loops of the test substrate promoted recruitment of splicing factors and consequent pre-mRNA structural remodeling, leading up to assembly of the early spliceosome. These results suggest that disruption of exonic stem–loop structures immediately upstream (but not downstream) of the introns regulate alternative splicing events, likely through modulating accessibility of splicing factors.
Protein tolerance to random circular permutation correlates with thermostability and local energetics of residue-residue contacts
Authors: Atkinson Joshua T , Jones Alicia M , Nanda Vikas , Silberg Jonathan J 
Published: April 2020

Abstract
Adenylate kinase (AK) orthologs with a range of thermostabilities were subjected to random circular permutation, and deep mutational scanning was used to evaluate where new protein termini were nondisruptive to activity. The fraction of circularly permuted variants that retained function in each library correlated with AK thermostability. In addition, analysis of the positional tolerance to new termini, which increase local conformational flexibility, showed that bonds were either functionally sensitive to cleavage across all homologs, differentially sensitive, or uniformly tolerant. The mobile AMP-binding domain, which displays the highest calculated contact energies, presented the greatest tolerance to new termini across all AKs. In contrast, retention of function in the lid and core domains was more dependent upon AK melting temperature. These results show that family permutation profiling identifies primary structure that has been selected by evolution for dynamics that are critical to activity within an enzyme family. These findings also illustrate how deep mutational scanning can be applied to protein homologs in parallel to differentiate how topology, stability, and local energetics govern mutational tolerance.
cRel expression regulates distinct transcriptional and functional profiles driving fibroblast matrix production in systemic sclerosis
Authors: Worrell Julie C , Leslie Jack , Smith Graham R , Zaki Marco Y W , Paish Hannah L , Knox Amber , James Michelle L , Cartwright Tyrell N , O’Reilly Steven , Kania Gabriela , Distler Oliver , Distler Jörg H W , Herrick Ariane L , Jeziorska Maria , Borthwick Lee A , Fisher Andrew J , Mann Jelena , Mann Derek A , Oakley Fiona 
Published: April 2020

AbstractObjectivesNF-κB regulates genes that control inflammation, cell proliferation, differentiation and survival. Dysregulated NF-κB signalling alters normal skin physiology and deletion of cRel limits bleomycin-induced skin fibrosis. This study investigates the role of cRel in modulating fibroblast phenotype in the context of SSc.MethodsFibrosis was assessed histologically in mice challenged with bleomycin to induce lung or skin fibrosis. RNA sequencing and pathway analysis was performed on wild type and Rel−/− murine lung and dermal fibroblasts. Functional assays examined fibroblast proliferation, migration and matrix production. cRel overexpression was investigated in human dermal fibroblasts. cRel immunostaining was performed on lung and skin tissue sections from SSc patients and non-fibrotic controls.ResultscRel expression was elevated in murine lung and skin fibrosis models. Rel−/− mice were protected from developing pulmonary fibrosis. Soluble collagen production was significantly decreased in fibroblasts lacking cRel while proliferation and migration of these cells was significantly increased. cRel regulates genes involved in extracellular structure and matrix organization. Positive cRel staining was observed in fibroblasts in human SSc skin and lung tissue. Overexpression of constitutively active cRel in human dermal fibroblasts increased expression of matrix genes. An NF-κB gene signature was identified in diffuse SSc skin and nuclear cRel expression was elevated in SSc skin fibroblasts.ConclusioncRel regulates a pro-fibrogenic transcriptional programme in fibroblasts that may contribute to disease pathology. Targeting cRel signalling in fibroblasts of SSc patients could provide a novel therapeutic avenue to limit scar formation in this disease.
Acute abdominal pain from epiploic appendagitis
Authors: Peña Santiago , Wilkin Zebulon 
Published: April 2020

ABSTRACT
Evaluating patients for abdominal pain is common in the ED and can involve many differential diagnoses and treatment options. This case report describes a 35-year-old active duty military man whose abdominal pain evaluation at a military treatment facility led to the diagnosis of epiploic appendagitis.
Care coordination for children with medical complexity
Authors: Cady Rhonda , Bushaw Andrea , Davis Heidi , Mills Julie , Thomasson Deana 
Published: April 2020

Abstract:
Children with medical complexity have complex health management and care coordination needs. Care models that address these needs rely on interprofessional teams that include NPs. Understanding these care models allows NPs from all disciplines to support the care of this growing patient population in pediatric and adult settings.