bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oocyte and Embryo Manipulation and Epigenetics
Authors: Osman Emily , Franasiak Jason , Scott Richard 
Published: May 2019

AbstractRegulation of the epigenome is a mechanism by which the environment influences gene expression and consequently the health of the individual. The advent and refinement of novel assisted reproductive technology (ART) laboratory techniques, including vitrification, dynamic culture systems, oocyte in vitro maturation, laser-assisted hatching, intracytoplasmic sperm injection, and preimplantation genetic testing for aneuploidy have contributed to the success of ART. From fertilization through implantation, the epigenetic profile of the embryo changes dynamically. Concurrently with these changes, embryo development in vitro is dependent on laboratory intervention and manipulation to optimize outcomes. The impact of ART techniques on imprinting errors remains unclear, as the infertile population likely confers an independent risk factor for defects in expected epigenetic patterns. Alternations in epigenetic mechanisms may contribute to the incidence of aneuploidy as well as recurrent implantation failure of euploid embryos. Additional investigative efforts are needed to assess the contribution of oocyte and embryo manipulation on imprinting modifications in this vulnerable population. The development of diagnostic modalities involving the discovery of epigenetic alterations to improve in vitro fertilization outcomes is an exciting and promising area of future study.
12OHJA, 12OGlcJA, and JA-l-Val as airborne MeJA metabolites
Authors: Oki Katsunari , Masimbula Rishni , Miyawaki Kanji , Takata Yusuke , Takahashi Kosaku , Matsuura Hideyuki 
Published: May 2019

ABSTRACTIt has been reported that airborne methyl jasmonate (MeJA) was metabolized into jasmonic acid (JA) and jasmonoyl isoleucine (JA-l-Ile). In this report, jasmonoyl valine (JA-l-Val), 12-hydroxy JA (12OHJA), and 12-glucosyloxy JA (12OGlcJA) were identified as metabolites originating from airborne MeJA using tomato (Solanum lycopersicum). Furthermore, the preferable conversion of (-)-MeJA (natural form) into 12OHJA, 12OGlcJA, JA-l-Ile, and JA-l-Val was observed.
Employment Quality: An Overlooked Determinant of Workers’ Health and Well-being?
Authors: Vanroelen Christophe 
Published: May 2019

AbstractIn the past four decades, high-income countries have seen a thorough socio-economic restructuring with important implications for the jobs of many workers, including health- and safety-related aspects. Much attention has been paid to psychosocial risks related to intrinsic features of contemporary work tasks, while the occupational health and safety consequences of ‘new’ conditions and relations of employment have remained neglected. This relative neglect is unjustified given the disrupting nature of many contemporary forms of employment. In this commentary, I introduce the concept of ‘employment quality’ as a novel approach towards measuring employment-related OHS risks. Employment quality involves a ‘typological approach’ towards employment arrangements, identifying five employment types in European labour markets, showing a distinct profile in terms of health-related employment characteristics. Moreover, these types align with segmented labour market theory, have a clear socio-economic profile, and show strong associations with workers’ self-reported health.
Do patients with anomalous origin of the left coronary artery benefit from an early repair of the mitral valve?
Authors: Weixler Viktoria H M , Zurakowski David , Baird Christopher W , Guariento Alvise , Piekarski Breanna , del Nido Pedro J , Emani Sitaram 
Published: May 2019

Abstract

OBJECTIVES
The aim of this study was to determine mid-term outcomes of patients with anomalous origin of the left coronary artery from the pulmonary artery undergoing coronary repair only (group A) or simultaneous mitral valve repair (group B).

METHODS
Patients with anomalous origin of the left coronary artery from the pulmonary artery who underwent surgery from 2000 to 2017 were reviewed. Mitral regurgitation (MR) grade (none, mild, moderate, severe), left ventricular (LV) function [ejection fraction (EF): &lt;40%, 40–50%, &gt;50%] and LV Z-scores (long axis) were assessed preoperatively and at last visit. Outcomes were compared within/between the groups using the Wilcoxon signed-rank test.

RESULTS
Of 58 patients (67% women; median age 4.4 months), 39 patients were in group A (67%) and 19 patients in group B (33%). The median hospital stay (11 days, interquartile range 5–18) and average follow-up time (2.6 ± 0.5 years) did not differ significantly between the groups (P &gt; 0.05). Four patients in group A (10.3%) underwent mitral valve reintervention. The median MR grade differed significantly between the groups preoperatively (2 vs 3, P &lt; 0.001) but not at the last visit (2 vs 2, P = 0.88); both groups improved significantly (P = 0.021, P &lt; 0.001). EF grade (&lt;40%, 40–50%, &gt;50%) did not differ significantly between the groups at baseline (group A: 38%/23%/38% vs group B: 58%/10%/32%, P = 0.32) or at last visit (group A: 18%/15%/67% vs group B: 26%/16%/58%, P = 0.75); both groups improved significantly (P = 0.004, P = 0.014). The mean LV Z-scores for groups A and B were 3.1 ± 0.5 and 4.5 ± 0.6 before surgery (P &lt; 0.05) and 1.5 ± 0.3 and 2.7 ± 0.6 at last visit (P = 0.77).

CONCLUSIONS
The repair of anomalous origin of the left coronary artery from the pulmonary artery is associated with improvement in MR, EF and LV dimensions. However, in cases of ≥moderate MR, the risk of mitral valve reintervention may be higher in patients undergoing coronary transfer only.
The low return to English fluency during the Age of Mass Migration☆
Authors: Ward Zachary 
Published: May 2019

AbstractEnglish skills are highly valuable for today’s immigrants, but has this always been the case? I estimate the premium for English fluency and the rate of language acquisition in the early 20th century US using new linked data on over two hundred thousand immigrants. Few early 20th century immigrants arrived with English proficiency, yet many acquired language skills rapidly after arrival. Based on individual fixed effects, acquiring English fluency was associated with a small upgrade in occupational income. The results suggest that English fluency was less important for economic assimilation in the early 20th century than in recent decades.
A novel six-phage cocktail reducesPectobacterium atrosepticumsoft rot infection in potato tubers under simulated storage conditions
Authors: Carstens Alexander Byth , Djurhuus Amaru Miranda , Kot Witold , Hansen Lars Hestbjerg 
Published: May 2019

AbstractPectobacterium atrosepticum is a species of plant pathogenic bacteria responsible for significant losses in potato production worldwide. Pectobacterium atrosepticum can cause blackleg disease on potato stems as well as the tuber disease termed potato soft rot. Methods for the effective control of these diseases are limited and are primarily based on good agricultural practices. Bacteriophages, viruses of bacteria, could be used as an alternative, environmentally friendly, control measure. Here, we describe the isolation and characterization of 29 phages virulent to P. atrosepticum. The phages belong to 12 different species based on a 95% sequence identity cut-off. Furthermore, based on sequence diversity and propagation results, we selected six of these phages to form a phage cocktail. The phages in the cocktail was tested on a number of P. atrosepticum strains in order to determine their host range. The phages was found to lyse 93% of the tested strains. The cocktail was subsequently tested for its effectiveness in combatting potato soft rot under simulated storage conditions. Use of the phage cocktail reduced both disease incidence and disease severity by 61% and 64%, respectively, strongly indicating that phage biocontrol has the potential to reduce the economic impact of soft rot in potato production.
Ultra-deep, long-read nanopore sequencing of mock microbial community standards
Authors: Nicholls Samuel M , Quick Joshua C , Tang Shuiquan , Loman Nicholas J 
Published: May 2019

Abstract

Background
Long sequencing reads are information-rich: aiding de novo assembly and reference mapping, and consequently have great potential for the study of microbial communities. However, the best approaches for analysis of long-read metagenomic data are unknown. Additionally, rigorous evaluation of bioinformatics tools is hindered by a lack of long-read data from validated samples with known composition.

Findings
We sequenced 2 commercially available mock communities containing 10 microbial species (ZymoBIOMICS Microbial Community Standards) with Oxford Nanopore GridION and PromethION. Both communities and the 10 individual species isolates were also sequenced with Illumina technology. We generated 14 and 16 gigabase pairs from 2 GridION flowcells and 150 and 153 gigabase pairs from 2 PromethION flowcells for the evenly distributed and log-distributed communities, respectively. Read length N50 ranged between 5.3 and 5.4 kilobase pairs over the 4 sequencing runs. Basecalls and corresponding signal data are made available (4.2 TB in total). Alignment to Illumina-sequenced isolates demonstrated the expected microbial species at anticipated abundances, with the limit of detection for the lowest abundance species below 50 cells (GridION). De novo assembly of metagenomes recovered long contiguous sequences without the need for pre-processing techniques such as binning.

Conclusions
We present ultra-deep, long-read nanopore datasets from a well-defined mock community. These datasets will be useful for those developing bioinformatics methods for long-read metagenomics and for the validation and comparison of current laboratory and software pipelines.
Postexposure Administration of a Yersinia pestis Live Vaccine for Potentiation of Second-Line Antibiotic Treatment Against Pneumonic Plague
Authors: Zauberman Ayelet , Gur David , Levy Yinon , Aftalion Moshe , Vagima Yaron , Tidhar Avital , Chitlaru Theodor , Mamroud Emanuelle 
Published: May 2019

Abstract
Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing contagious disease. In the plague mouse model, a single immunization with the EV76 live attenuated Y. pestis strain rapidly induced the expression of hemopexin and haptoglobin in the lung and serum, both of which are important in iron sequestration. Immunization against a concomitant lethal Y. pestis respiratory challenge was correlated with temporary inhibition of disease progression. Combining EV76-immunization and second-line antibiotic treatment, which are individually insufficient, led to a synergistic protective effect that represents a proof of concept for efficient combinational therapy in cases of infection with antibiotic-resistant strains.
Diagnosis and Management of Rhabdomyolysis in the Absence of Creatine Phosphokinase: A Medical Record Review
Authors: Chandel Abhimanyu , Brusher Kara , Hall Victoria , Howard Robin S , Clark Paul A 
Published: May 2019

AbstractIntroductionRhabdomyolysis is often encountered in austere environments where the diagnosis can be challenging due to the expense or unavailability of creatine phosphokinase (CPK) testing. CPK concentration ≥5,000 U/L has previously been found to be a sensitive marker for progression to renal failure. This study sought to propose a model utilizing an alternate biomarker to allow for the diagnosis and monitoring of clinically significant rhabdomyolysis in the absence of CPK.Materials and MethodsWe performed a retrospective chart review of 77 patients admitted to a tertiary medical center with a primary diagnosis of rhabdomyolysis. A linear regression model with aspartate aminotransferase (AST) as the independent variable was developed and used to predict CPK ≥5,000 U/L on admission and CPK values on subsequent hospital days. The study was approved and monitored by the Institutional Review Board at Walter Reed National Military Medical Center.ResultsLn(AST) explained over 80% of the variance in ln(CPK) (adjusted R2 = 0.802). The diagnostic accuracy to predict CPK ≥5,000 U/L was high (AUC 0.959; 95% CI: 0.921–0.997, P &lt; 0.001). A cut point of AST ≥110 U/L in our study population had a 97.1% sensitivity and an 85.7% specificity for the detection of a CPK value ≥5,000 U/L. The agreement between actual CPK and predicted CPK for subsequent days of hospitalization was fair with an intraclass correlation coefficient of 0.52 (95% CI: 0.38–0.63). The developed model based on day 1 data tended to overpredict CPK values on subsequent hospital days.ConclusionsWe propose a threshold concentration of AST that has an excellent sensitivity for detecting CPK concentration ≥5,000 U/L on day of admission in a patient population with a diagnosis of rhabdomyolysis. A formula with a fair ability to predict CPK levels based on AST concentrations on subsequent hospital days was also developed.
Mosquito and human hepatocyte infections with Plasmodium ovale curtisi and Plasmodium ovale wallikeri
Authors: Kristan Mojca , Thorburn Samuel G , Hafalla Julius C , Sutherland Colin J , Oguike Mary C 
Published: May 2019

Abstract

Background
Human ovale malaria is caused by the two closely related species, Plasmodium ovale curtisi and P. ovale wallikeri. Both species are known to relapse from quiescent hepatic forms months or years after the primary infection occurred. Although some studies have succeeded in establishing mosquito transmission for ovale malaria, none have specifically described transmission and human hepatocyte infection of both sibling species.

Methods
Here we describe a simplified protocol for successful transmission of both P. ovale curtisi and P. ovale wallikeri to Anopheles coluzzii mosquitoes and streamlined monitoring of infection using sensitive parasite DNA detection, by loop-activated amplification, in blood-fed mosquitoes.

Results
In one experimental infection with P. ovale curtisi and one with P. ovale wallikeri, viable sporozoites were isolated from mosquito salivary glands and used to successfully infect cultured human hepatocytes.

Conclusions
This protocol provides a method for the utilisation of pretreatment clinical blood samples from ovale malaria patients, collected in EDTA, for mosquito infection studies and generation of the hepatic life cycle stages of P. ovale curtisi and P. ovale wallikeri. We also demonstrate the utility of loop-activated amplification as a rapid and sensitive alternative to dissection for estimating the prevalence of infection in Anopheles mosquitoes fed with Plasmodium-infected blood.
FreeHi-C: high fidelity Hi-C data simulation for benchmarking and data augmentation
Authors: Zheng Ye , Keleş Sündüz 
Published: May 2019

AbstractAbility to simulate realistic high-throughput chromatin conformation (Hi-C) data is foundational for developing and benchmarking statistical and computational methods for Hi-C data analysis. We propose FreeHi-C, a data-driven Hi-C simulator for simulating and augmenting Hi-C datasets. FreeHi-C employs a non-parametric strategy for estimating interaction distribution of genome fragments from a given sample and simulates Hi-C reads from interacting fragments. Data from FreeHi-C exhibit higher fidelity to the biological Hi-C data compared with other tools in its class. FreeHi-C not only enables benchmarking a wide range of Hi-C analysis methods but also boosts the precision and power of differential chromatin interaction detection methods while preserving false discovery rate control through data augmentation.
OTUB1 is a key regulator of RIG-I dependent immune signalling and is targeted for proteasomal degradation by influenza A NS1
Authors: Jahan Akhee Sabiha , Biquand Elise , Muñoz-Moreno Raquel , Le Quang Agathe , Mok Chris Ka-Pun , Wong Ho Him , Teo Qi Wen , Doak Sophie , Chin Alex W. H. , Poon Leo Lit Man , te Velthuis Artejan , García-Sastre Adolfo , Demeret Caroline , Sanyal Sumana 
Published: May 2019

SummaryDeubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host innate immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, DUBs that regulate this pathway have not been identified. Using a ubiquitin C-terminal electrophile, we profiled DUBs that function during influenza A virus (IAV) infection, and isolated OTUB1 as a key regulator of RIG-I dependent antiviral responses. OTUB1 was interferon-inducible, and interacted with RIG-I, viral PB2 and NS1. Upon infection, OTUB1 relocalised from the nucleus to mitochondrial membranes, and activated the RIG-I signaling complex via hydrolysis of K48 polyubiquitin chains and by forming a repressive complex with UBCH5c. Using a reconstituted system composed of in vitro translated [35S]IRF3, purified RIG-I, mitochondrial membranes and cytosol expressing OTUB1 variants, we recapitulated the mechanism of OTUB1-dependent RIG-I activation. A wide range of IAV NS1 proteins triggered proteasomal degradation of OTUB1, thereby antagonizing the RIG-I signaling cascade and antiviral responses.HighlightsOTUB1 is induced during influenza A virus infections in an IFN-I dependent mannerOTUB1 regulates the RIG-I complex by hydrolysing K48-linked polyubiquitin chains and by sequestering UBCH5c to prevent K48 polyubiquitylationOptimal K63 versus K48 polyubiquitin chain concentrations determine RIG-I activationInfluenza NS1 targets OTUB1 for proteasomal degradation
SpCas9 activity prediction by DeepSpCas9, a deep learning-based model with unparalleled generalization performance
Authors: Kim Hui Kwon , Kim Younggwang , Lee Sungtae , Min Seonwoo , Bae Jung Yoon , Choi Jae Woo , Park Jinman , Jung Dongmin , Yoon Sungroh , Kim Hyongbum Henry 
Published: May 2019

AbstractWe evaluated SpCas9 activities at 12,832 target sequences using a high-throughput approach based on a human cell library containing sgRNA-encoding and target sequence pairs. Deep learning-based training on this large data set of SpCas9-induced indel frequencies led to the development of a SpCas9-activity predicting model named DeepSpCas9. When tested against independently generated data sets (our own and those published by other groups), DeepSpCas9 showed unprecedentedly high generalization performance. DeepSpCas9 is available athttp://deepcrispr.info/DeepCas9.
Frustration and Fidelity in Influenza Genome Assembly
Authors: Farheen Nida , Thattai Mukund 
Published: May 2019

AbstractThe genome of the influenza virus consists of eight distinct single-stranded RNA segments, each encoding proteins essential for the viral life cycle. When the virus infects a host cell these segments must be replicated and packaged into new budding virions. The viral genome is assembled with remarkably high fidelity: experiments reveal that most virions contain precisely one copy of each of the eight RNA segments. Cell-biological studies suggest that genome assembly is mediated by specific reversible and irreversible interactions between the RNA segments and their associated proteins. However, the precise inter-segment interaction network remains unresolved. Here we computationally predict that tree-like irreversible interaction networks guarantee high-fidelity genome assembly, while cyclic interaction networks lead to futile or frustrated off-pathway products. We test our prediction against multiple experimental datasets. We find that tree-like networks capture the nearest-neighbor statistics of RNA segments in packaged virions, as observed by EM tomography. Just eight tree-like networks (of a possible 262,144) optimally capture both the nearest-neighbor data as well as independently measured RNA-RNA contact propensities. These eight do not include the previously-proposed hub-and-spoke and linear networks. Rather, each predicted network combines hub-like and linear features, consistent with evolutionary models of interaction gain and loss.
Adrenergic-melatonin heteroreceptor complexes are key in controlling ion homeostasis and intraocular eye pressure and their disruption contributes to hypertensive glaucoma
Authors: Alkozi Hanan Awad , Navarro Gemma , Aguinaga David , Reyes-Resina Irene , Sanchez-Naves Juan , Perez de Lara Maria J , Franco Rafael , Pintor Jesus 
Published: May 2019

AbstractMelatonin regulates intraocular pressure (IOP) whose increase leads to glaucoma and eye nerve degeneration. Aiming at elucidating the role of melatonin receptors in humour production and IOP maintenance, we here demonstrate that glaucoma correlates with disassembly of α1-adrenergic/melatonin receptor functional units in cells producing the aqueous humour. Remarkably, α1-adrenoceptor-containing complexes do not coupled to the cognate Gq protein and, hence, phenylephrine activation of these receptors does not lead to Ca2+ mobilization. Functional complexes are significantly decreased in models of glaucoma and, more importantly, in human samples of glaucoma patients (GP). In such glaucomatous conditions phenylephrine produces, via α1-adrenoceptor activation, an increase in cytoplasmic [Ca2+] that is detrimental in glaucoma. The results led to hypothesize that using melatonin, a hypotensive agent, plus blockade of α1-adrenergic receptors may normalize pressure in glaucoma. Remarkably, co-instillation of melatonin and prazosin, a α1-adrenergic receptor antagonist, results in long-term decreases in IOP in a well-established animal model of glaucoma. The findings are instrumental to understand the physiological function of melatonin in the eye and its potential to address eye pathologies by targeting melatonin receptors and their complexes.
High throughput Characterization ofKCNB1variants Associated with Developmental and Epileptic Encephalopathy
Authors: Kang Seok Kyu , Vanoye Carlos G. , Misra Sunita N. , Echevarria Dennis M. , Calhoun Jeffrey D. , O’Connor John B. , Fabre Katarina L. , McKnight Dianalee , Demmer Laurie , Goldenberg Paula , Grote Lauren E. , Thiffault Isabelle , Saunders Carol , Strauss Kevin A. , Torkamani Ali , van der Smagt Jasper , van Gassen Koen , Carson Robert P. , Diaz Jullianne , Leon Eyby , Jacher Joseph E. , Hannibal Mark C. , Litwin Jessica , Friedman Neil R. , Schreiber Allison , Lynch Bryan , Poduri Annapurna , Marsh Eric D. , Goldberg Ethan M. , Millichap John J. , George Alfred L. , Kearney Jennifer A. 
Published: May 2019

ABSTRACTPathogenic variants inKCNB1, encoding the voltage-gated potassium channel Kv2.1, are associated with developmental and epileptic encephalopathies (DEE). Previous functional studies on a limited number ofKCNB1variants indicated a range of molecular mechanisms by which variants affect channel function, including loss of voltage sensitivity, loss of ion selectivity, and reduced cell-surface expression. We evaluated a series of 17KCNB1variants associated with DEE or neurodevelopmental disorder (NDD) to rapidly ascertain channel dysfunction using high-throughput functional assays. Specifically, we investigated the biophysical properties and cell-surface expression of variant Kv2.1 channels expressed in heterologous cells using high-throughput automated electrophysiology and immunocytochemistry-flow cytometry. Pathogenic variants exhibited diverse functional defects, including altered current density and shifts in the voltage-dependence of activation and/or inactivation, as homotetramers or when co-expressed with wild-type Kv2.1. Quantification of protein expression also identified variants with reduced total Kv2.1 expression or deficient cell-surface expression.Our study establishes a platform for rapid screening of functional defects ofKCNB1variants associated with DEE and other NDDs, which will aid in establishingKCNB1variant pathogenicity and may enable discovery of targeted strategies for therapeutic intervention based on molecular phenotype.