bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actions of colony-stimulating factor 3 on the maturing oocyte and developing embryo in cattle
Authors: Jannaman Elizabeth A , Xiao Yao , Hansen Peter J 
Published: April 2020

Abstract
Colony-stimulating factor 3 (CSF3), also known as granulocyte colony-stimulating factor, is used to reduce the incidence of mastitis in cattle. Here, we tested whether recombinant bovine CSF3 at 1, 10, or 100 ng/mL acts on the bovine oocyte during maturation or on the developing embryo to modify competence for development and characteristics of the resultant blastocyst. For experiment 1, oocytes were matured with or without CSF3. The resultant embryos were cultured in a serum-free medium for 7.5 d. There was no effect of CSF3 on cleavage or on development to the blastocyst stage except that 100 ng/mL reduced the percent of putative zygotes and cleaved embryos becoming blastocysts. Expression of transcripts for 93 genes in blastocysts was evaluated by RT-PCR using the Fluidigm platform. Transcript abundance was affected by one or more concentrations of CSF3 for four genes only (CYP11A1, NOTCH2, RAC1, and YAP1). For experiment 2, cumulus-oocyte complexes (COC) were fertilized with either X- or Y-sorted semen. Putative zygotes were cultured in medium containing CSF3 treatments added at the beginning of culture. There was no effect of CSF3, sex, or the interaction on the percent of putative zygotes that cleaved or on the percent of putative zygotes or cleaved embryos becoming a blastocyst. For experiment 3, CSF3 was added from day 4 to 7.5 of development. There was no effect of CSF3 on development to the blastocyst stage. Transcript abundance of 10 genes was increased by 100 ng/mL CSF3, including markers of epiblast (NANOG, SOX2), hypoblast (ALPL, FN1, KDM2B, and PDGFRA), epiblast and hypoblast (HNF4A) and trophectoderm (TJAP1). Results are indicative that concentrations of CSF3 higher than typical after therapeutic administration can reduce oocyte competence and act on the embryo to affect characteristics of the blastocyst.
Fibro-osseous pseudotumour of the digit—a diagnostic challenge
Authors: Rela Mariam , Bantick Giles 
Published: April 2020

Abstract
A 60-year-old right-hand dominant woman presented to the emergency department with a 3-week history of pain and swelling in her right thumb. The X-ray showed evidence of erosion at the tip of the distal phalanx. Her initial management included surgical debridement with bone biopsies and intravenous antibiotics. The initial working diagnosis was a soft tissue infection of the thumb tip, causing osteomyelitis of the distal phalanx. The X-ray findings also raised the suspicion of a possible bone tumour. She was treated as having osteomyelitis and attended ambulatory care for daily intravenous antibiotics for 2 weeks. Initial histology was reported as a spindle cell tumour; however, following discussion at the sarcoma MDT, a diagnosis of a fibro-osseous pseudotumour of the digit was made. This is a benign lesion that was managed non-operatively in this patient. This case emphasises the importance of considering all differential diagnoses, even in a common presentation.
Allopolyploid Speciation Accompanied by Gene Flow in a Tree Fern
Authors: Wang Jing , Dong Shiyong , Yang Lihua , Harris Aj , Schneider Harald , Kang Ming 
Published: April 2020

AbstractHybridization in plants may result in hybrid speciation or introgression and, thus, is now widely understood to be an important mechanism of species diversity on an evolutionary timescale. Hybridization is particularly common in ferns, as is polyploidy, which often results from hybrid crosses. Nevertheless, hybrid speciation as an evolutionary process in fern lineages remains poorly understood. Here, we employ flow cytometry, phylogeny, genomewide single nucleotide polymorphism data sets, and admixture and coalescent modeling to show that the scaly tree fern, Gymnosphaera metteniana is a naturally occurring allotetraploid species derived from hybridization between the diploids, G. denticulata and G. gigantea. Moreover, we detected ongoing gene flow between the hybrid species and its progenitors, and we found that G. gigantea and G. metteniana inhabit distinct niches, whereas climatic niches of G. denticulata and G. metteniana largely overlap. Taken together, these results suggest that either some degree of intrinsic genetic isolation between the hybrid species and its parental progenitors or ecological isolation over short distances may be playing an important role in the evolution of reproductive barriers. Historical climate change may have facilitated the origin of G. metteniana, with the timing of hybridization coinciding with a period of intensification of the East Asian monsoon during the Pliocene and Pleistocene periods in southern China. Our study of allotetraploid G. metteniana represents the first genomic-level documentation of hybrid speciation in scaly tree ferns and, thus, provides a new perspective on evolution in the lineage.
A Whole-Genome Scan for Association with Invasion Success in the Fruit Fly Drosophila suzukii Using Contrasts of Allele Frequencies Corrected for Population Structure
Authors: Olazcuaga Laure , Loiseau Anne , Parrinello Hugues , Paris Mathilde , Fraimout Antoine , Guedot Christelle , Diepenbrock Lauren M , Kenis Marc , Zhang Jinping , Chen Xiao , Borowiec Nicolas , Facon Benoit , Vogt Heidrun , Price Donald K , Vogel Heiko , Prud’homme Benjamin , Estoup Arnaud , Gautier Mathieu 
Published: April 2020

Abstract
Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic variants associated with the status (invasive versus native) of the sampled populations based on a newly developed statistic, we called C2, that contrasts allele frequencies corrected for population structure. We evaluated this new statistical framework using simulated data sets and implemented it in an upgraded version of the program BayPass. We identified a relatively small set of single-nucleotide polymorphisms that show a highly significant association with the invasive status of D. suzukii populations. In particular, two genes, RhoGEF64C and cpo, contained single-nucleotide polymorphisms significantly associated with the invasive status in the two separate main invasion routes of D. suzukii. Our methodological approaches can be applied to any other invasive species, and more generally to any evolutionary model for species characterized by nonequilibrium demographic conditions for which binary covariables of interest can be defined at the population level.
Structural Phylogenetics with Confidence
Authors: Malik Ashar J , Poole Anthony M , Allison Jane R 
Published: April 2020

Abstract
For evaluating the deepest evolutionary relationships among proteins, sequence similarity is too low for application of sequence-based homology search or phylogenetic methods. In such cases, comparison of protein structures, which are often better conserved than sequences, may provide an alternative means of uncovering deep evolutionary signal. Although major protein structure databases such as SCOP and CATH hierarchically group protein structures, they do not describe the specific evolutionary relationships within a hierarchical level. Structural phylogenies have the potential to fill this gap. However, it is difficult to assess evolutionary relationships derived from structural phylogenies without some means of assessing confidence in such trees. We therefore address two shortcomings in the application of structural data to deep phylogeny. First, we examine whether phylogenies derived from pairwise structural comparisons are sensitive to differences in protein length and shape. We find that structural phylogenetics is best employed where structures have very similar lengths, and that shape fluctuations generated during molecular dynamics simulations impact pairwise comparisons, but not so drastically as to eliminate evolutionary signal. Second, we address the absence of statistical support for structural phylogeny. We present a method for assessing confidence in a structural phylogeny using shape fluctuations generated via molecular dynamics or Monte Carlo simulations of proteins. Our approach will aid the evolutionary reconstruction of relationships across structurally defined protein superfamilies. With the Protein Data Bank now containing in excess of 158,000 entries (December 2019), we predict that structural phylogenetics will become a useful tool for ordering the protein universe.
The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis
Authors: Wilcox Mark H , McGovern Barbara H , Hecht Gail A 
Published: April 2020

AbstractThe leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.
Clinical Outcomes and Risk Factors for Tunneled Hemodialysis Catheter-Related Bloodstream Infections
Authors: Martin Kylie , Lorenzo Yves S Poy , Leung Po Yee Mia , Chung Sheri , O’flaherty Emmet , Barker Nuala , Ierino Francesco 
Published: April 2020

Abstract
Diabetes and left internal jugular vein insertion site were significantly associated with increased risk of a catheter-related bloodstream infection from a tunneled hemodialysis catheter. Ex-smoker status was significantly associated with reduced risk.
Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients
Authors: Katthagen Teresa , Kaminski Jakob , Heinz Andreas , Buchert Ralph , Schlagenhauf Florian 
Published: April 2020

Abstract
Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients (n = 19) and healthy controls (n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Kicer), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Kicer. Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Kicer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Kicer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Kicer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.
Severe Necrotizing Pneumonia in Children: A Challenge to Intensive Care Specialist
Authors: Sharma Pradeep Kumar , Vinayak Nikhil , Aggarwal Girraj K , Srivastava R D , Aggarwal Pradeep Kumar , Kushwaha Anand Singh 
Published: April 2020

Abstract

Objective
Necrotizing pneumonia (NP) is recently recognized as a complication of pneumonia. The data on NP are scant from developing world and we aimed to describe the characteristic features of NP in our children.

Study design
Single center retrospective cohort analysis.

Patient selection
Institutional database of children treated for pneumonia between September 2014 and May 2018 was searched to identify children with NP.

Methods
The demographic characteristics, laboratory results, and clinical information were recorded for patients selected as NP and analyzed.

Results
In total, 10 patients (3.7%) of NP were identified out of 272 patients with pneumonia. Median age was 3 years (range: 3 months to 12years). All cases had severe respiratory distress and 70% required mechanical ventilation and inotropic support. The causative pathogens were identified in 6/10 children (60%) with Staphylococcus aureus being most common (4/10). Pleural effusion and pneumothorax were seen in six cases. Four cases had bilateral pleural effusion and three had bilateral pneumothorax. Intercostal drainage (ICD) was placed in 70% and bilateral ICD was placed in 40% cases. Bronchopleural fistula (BPF) developed in two cases and one had bilateral BPF. Median [inter quartile range] ICD days and hospital stay were 9 (6–14) and 13.5 (7.5–18.5) days, respectively. Mean (±SD) total antibiotic (in hospital plus outpatient) days were 28.8 ± 9.6 days. Four cases had airway hemorrhage and in three cases this was massive and fatal.

Conclusion
NP is a relatively rare but severe complication of pneumonia distinct from pediatric acute respiratory distress, pleural effusion and empyema. Airway hemorrhage is the most fatal complication.
Cybersecurity regulation in the financial sector: prospects of legal harmonization in the European Union and beyond
Authors: Didenko Anton N 
Published: April 2020

Abstract
Over the past several years, the cybersecurity regulatory landscape has undergone unprecedented change. Bespoke cybersecurity laws and regulations have replaced pre-existing general risk management and business continuity rules in a number of jurisdictions, including the European Union, Hong Kong, Russia, the USA, and Singapore. Cybersecurity has also become the focus of international rules and recommendations adopted by numerous international organizations. The financial sector lies at the centre of the new regulatory initiatives—which, in the absence of an agreed international approach, vary substantially across jurisdictions. This article analyses these emerging legal frameworks by (i) conducting a comparative study of the novel cybersecurity regulations in finance; (ii) identifying the common features of such frameworks; and (iii) assessing the prospect of their harmonization at an international level. It argues that international harmonization in this area is necessary to overcome the underlying regulatory challenges and outlines the scope of rules amenable, first, to initial (de minimis) and, second, subsequent (more expansive) harmonization. The article concludes with a list of main upcoming challenges in designing and harmonizing cybersecurity regulations in finance and practical recommendations for overcoming them.
Measuring Farm Labor: Survey Experimental Evidence from Ghana
Authors: Gaddis Isis , Oseni Gbemisola , Palacios-Lopez Amparo , Pieters Janneke 
Published: April 2020

Abstract
This study examines recall bias in farm labor through a randomized survey experiment in Ghana, comparing farm labor estimates from an end-of-season recall survey with data collected weekly throughout the agricultural season. Recall households report 10 percent more farm labor per person-plot, which can be explained by recall households’ underreporting of “marginal” plots and household workers. This “selective” omission by recall households, denoted as listing bias, alters the composition of plots and workers across treatment arms and inflates average farm labor hours per person-plot in the recall group. Since listing bias, in this setting, dominates other forms of recall bias at higher levels of aggregation (i.e., when farm labor per person-plot is summed at the plot, person, or household level), farm labor productivity is overestimated for recall households. Consistent with the notion that recall bias is linked to the cognitive burden of reporting on past events, there is no recall bias among more educated households.
Rapidin silicodesign of antibodies targeting SARS-CoV-2 using machine learning and supercomputing
Authors: Desautels Thomas , Zemla Adam , Lau Edmond , Franco Magdalena , Faissol Daniel 
Published: April 2020

SummaryRapidly responding to novel pathogens, such as SARS-CoV-2, represents an extremely challenging and complex endeavor. Numerous promising therapeutic and vaccine research efforts to mitigate the catastrophic effects of COVID-19 pandemic are underway, yet an efficacious countermeasure is still not available. To support these global research efforts, we have used a novel computational pipeline combining machine learning, bioinformatics, and supercomputing to predict antibody structures capable of targeting the SARS-CoV-2 receptor binding domain (RBD). In 22 days, using just the SARS-CoV-2 sequence and previously published neutralizing antibody structures for SARS-CoV-1, we generated 20 initial antibody sequences predicted to target the SARS-CoV-2 RBD. As a first step in this process, we predicted (and publicly released) structures of the SARS-CoV-2 spike protein using homology-based structural modeling. The predicted structures proved to be accurate within the targeted RBD region when compared to experimentally derived structures published weeks later. Next we used ourin silicodesign platform to iteratively propose mutations to SARS-CoV-1 neutralizing antibodies (known not to bind SARS-Cov-2) to enable and optimize binding within the RBD of SARS-CoV-2. Starting from a calculated baseline free energy of −48.1 kcal/mol (± 8.3), our 20 selected first round antibody structures are predicted to have improved interaction with the SARS-CoV-2 RBD with free energies as low as −82.0 kcal/mole. The baseline SARS-CoV-1 antibody in complex with the SARS-CoV-1 RBD has a calculated interaction energy of −52.2 kcal/mole and neutralizes the virus by preventing it from binding and entering the human ACE2 receptor. These results suggest that our predicted antibody mutants may bind the SARS-CoV-2 RBD and potentially neutralize the virus. Additionally, our selected antibody mutants score well according to multiple antibody developability metrics. These antibody designs are being expressed and experimentally tested for binding to COVID-19 viral proteins, which will provide invaluable feedback to further improve the machine learning–driven designs. This technical report is a high-level description of that effort; the Supplementary Materials includes the homology-based structural models we developed and 178,856in silicofree energy calculations for 89,263 mutant antibodies derived from known SARS-CoV-1 neutralizing antibodies.
On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2
Authors: Corrêa Giron Carolina , Laaksonen Aatto , Barroso da Silva Fernando L. 
Published: April 2020

ABSTRACTA new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.
The Framework for the Prediction of the Critical Turning Period for Outbreak of COVID-19 Spread in China based on the iSEIR Model1
Authors: Yuan George Xianzhi , Di Lan , Gu Yudi , Qian Guoqi , Qian Xiaosong 
Published: April 2020

AbstractThe goal of this study is to establish a general framework for predicting the so-called critical “Turning Period” in an infectious disease epidemic such as the COVID-19 outbreak in China early this year. This framework enabled a timely prediction of the turning period when applied to Wuhan COVID-19 epidemic and informed the relevant authority for taking appropriate and timely actions to control the epidemic. It is expected to provide insightful information on turning period for the world’s current battle against the COVID-19 pandemic.The underlying mathematical model in our framework is the individual Susceptible-Exposed-Infective-Removed (iSEIR) model, which is a set of differential equations extending the classic SEIR model. We used the observed daily cases of COVID-19 in Wuhan from February 6 to 10, 2020 as the input to the iSEIR model and were able to generate the trajectory of COVID-19 cases dynamics for the following days at midnight of February 10 based on the updated model, from which we predicted that the turning period of CIVID-19 outbreak in Wuhan would arrive within one week after February 14. This prediction turned to be timely and accurate, providing adequate time for the government, hospitals, essential industry sectors and services to meet peak demands and to prepare aftermath planning.Our study also supports the observed effectiveness on flatting the epidemic curve by decisively imposing the “Lockdown and Isolation Control Program” in Wuhan since January 23, 2020. The Wuhan experience provides an exemplary lesson for the whole world to learn in combating COVID-19.