bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crk and Crkl have shared functions in neural crest cells for cardiac outflow tract septation and vascular smooth muscle differentiation
Authors: Shi Lijie , Racedo Silvia E , Diacou Alexander , Park Taeju , Zhou Bin , Morrow Bernice E 
Published: October 2021

Abstract
CRK and CRKL encode cytoplasmic adaptors that contribute to the etiology of congenital heart disease. Neural crest cells (NCCs) are required for cardiac outflow tract (OFT) septation and aortic arch formation. The roles of Crk/Crkl in NCCs during mouse cardiovascular development remain unknown. To test this, we inactivated Crk and/or Crkl in NCCs. We found that the loss of Crk, rather than Crkl, in NCCs resulted in double outlet right ventricle, while loss of both Crk/Crkl in NCCs resulted in severe defects with earlier lethality due to failed OFT septation and severe dilation of the pharyngeal arch arteries (PAAs). We found that these defects are due to altered cell morphology resulting in reduced localization of NCCs to the OFT and failed integrity of the PAAs, along with reduced expression of Integrin signaling genes. Further, molecular studies identified reduced differentiation of vascular smooth muscle cells that may in part be due to altered Notch signaling. Additionally, there is increased cellular stress that leads to modest increase in apoptosis. Overall, this explains the mechanism for the Crk/Crkl phenotype.
Hybrid stochastic differential systems in pharmacokinetics
Authors: Baili Hana 
Published: October 2021

AbstractModelling patient medication poor compliance combined with the inherent uncertainty in a bioavailability trial leads recognizably to the fact that plasma concentration-time curve must be treated as a random process. We suggest for modelling a general class of hybrid stochastic differential systems (HSDS). Roughly speaking, a HSDS is a piecewise diffusion process with jumps of two types: spontaneous and predictable. The essential tasks for us afterwards are to identify the model ingredients and to derive its bearings; of interest are a couple of operators associated to every Markov process: the generating operator and the Fokker–Planck operator. The model induces a Fokker–Planck–Kolmogorov equation along with moment equations, and computations based on direct solutions of the latter make it possible to study the variability of the concentration around its mean as compared to the full compliance case and to assess the effect of some parameters such as the intake and elimination rates.
Phenotypic and genomic analysis reveals Riemerella anatipestifer as the potential reservoir of tet(X) variants
Authors: Li Ruichao , Jiang Yongjia , Peng Kai , Wang Yanhong , Wang Mianzhi , Liu Yuan , Wang Zhiqiang 
Published: October 2021

Abstract

Background
Tigecycline is regarded as one of the last-resort antimicrobials clinically. Emergence of plasmid-mediated tet(X) undermines such an important drug. However, the origins of tet(X) remain largely unexplored.

Methods
Riemerella anatipestifer strains were characterized by PCR, antimicrobial susceptibility testing, WGS and bioinformatics analysis. Functional analysis of tet(X) was verified by cloning experiments. Genomic structures of chromosome- and plasmid-mediated tet(X) were analysed.

Results
Thirty-eight R. anatipestifer strains were collected and found to be positive for tet(X). These strains were resistant to multiple antimicrobials; 55.3% (21/38) of the strains were resistant to tigecycline and all of the strains demonstrated resistance to tetracycline. The complete genome sequences of 18 representative strains were obtained. WGS analysis of 38 genomes identified 13 tet(X) variants located on chromosomes, which increased MICs of tigecycline (16–256-fold) for Escherichia coli, although most of them could not confer high-level resistance to tigecycline in the original R. anatipestifer hosts. Genomic environment analysis indicated that the occurrence of multiple tet(X) variants is common and other resistance genes, such as catB, tet(Q), floR, blaOXA, ereD and ermF, could be located in the same chromosomal regions. Two types of tet(X)-bearing segments were identified, one of which was floR-ISCR2-tet(X). This indicates that tet(X) variants were not conserved in chromosomal structures, but in regions with potential transferability. Furthermore, an MDR plasmid carrying tet(X18) was found in R. anatipestifer 20190305E2-2, different from the chromosomal tet(X21).

Conclusions
This study confirmed that tet(X) is highly prevalent in R. anatipestifer. The transfer risk of tet(X) across R. anatipestifer to other clinical pathogens warrants further investigations.
Establishing a research informatics program in a public healthcare system: a case report with model documents
Authors: Meeker Daniella , Fu Paul , Garcia Gary , Dyer Irene E , Yadav Kabir , Fleishman Ross , Yee Hal F 
Published: October 2021

Abstract
While much is known about governance models for research informatics programs in academic medical centers and similarly situated cancer centers, community and public health systems have been less well-characterized. As part of implementing an enterprise research governance framework, leaders in the Los Angeles County Department of Health Services established a research informatics program, including research data warehousing. The strategy is focused on high-priority, patient-centered research that leverages the investment in health IT and an efficient, sustained contribution from 2 affiliated Clinical Translational Sciences Institutes. This case study describes the foundational governance framework and policies that were developed. We share the results of several years of planning, implementation, and operations of an academically funded research informatics service core embedded in a large, multicenter county health system. We include herein a Supplementary Appendix of governance documents that may serve as pragmatic models for similar initiatives.
FeedingSaccharomyces cerevisiaefermentation products lessens the severity of a viral–bacterial coinfection in preweaned calves
Authors: McDonald Paiton O , Schill Courtney , Maina Teresia W , Samuel Beulah , Porter Madison , Yoon Ilkyu , McGill Jodi L 
Published: October 2021

AbstractWe have previously reported that supplementation with Saccharomyces cerevisiae fermentation products (SCFP) ameliorates clinical signs and lung pathology following experimental bovine respiratory syncytial virus (BRSV) infection in preweaned dairy calves. The objectives of this study were to determine the effect of SCFP supplementation on the metabolic and endocrine responses, and disease outcome of a viral–bacterial coinfection in preweaned calves. Twenty-seven, 1- to 2-d-old Holstein-Angus cross calves were enrolled in the study; one SCFP calf was removed from the trial during the pre-challenge phase due to complications from nephritis. Calves were assigned to two treatment groups: control or SCFP-treated, base milk replacer with 1 g/d SCFP (Smartcare, soluble formula) and calf starter top dressed with 5 g/d SCFP (NutriTek, insoluble formula). Calves were infected with BRSV on day 21, followed 6 d later by intratracheal inoculation with Pasteurella multocida (PM). Calves were euthanized on day 10 post-viral infection. Calves receiving SCFP had reduced thoracic ultrasonography scores on day 7 post-viral infection (P = 0.03) and a tendency toward reduced scores on day 10 post-viral infection (P = 0.09). Calves receiving SCFP also had less severe lung pathology scores at necropsy (P = 0.06). No differences between treatments were observed in lung viral loads (P = 0.48) or bacterial lung recovery (P = 0.34); however, there was a distinction in the lung location for PM recovery, with PM isolated more frequently from the cranial lobes in SCFP-treated calves, but more frequently from the caudal lobes of control calves. Calves treated with SCFP tended (P = 0.07) to have higher serum IL-6 concentrations following the coinfection. Calves treated with SCFP had lower concentrations of serum nonesterified fatty acids and beta-hydroxybutyric acid compared with controls following experimental challenge (P = 0.03 and P = 0.08, respectively), suggesting metabolic changes favoring growth and development. There were no differences between groups in gene expression of insulin receptor, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), growth hormone receptor, or haptoglobin in the liver. Results from this study suggest that supplementing with SCFP may moderate the impact of a respiratory viral–bacterial coinfection on preweaned calves through metabolic and immune modifications.
Mitochondria as environments for the nuclear genome in Drosophila: mitonuclear G×G×E
Authors: Rand David M , Mossman James A , Spierer Adam N , Santiago John A 
Published: October 2021

AbstractMitochondria evolved from a union of microbial cells belonging to distinct lineages that were likely anaerobic. The evolution of eukaryotes required a massive reorganization of the 2 genomes and eventual adaptation to aerobic environments. The nutrients and oxygen that sustain eukaryotic metabolism today are processed in mitochondria through coordinated expression of 37 mitochondrial genes and over 1000 nuclear genes. This puts mitochondria at the nexus of gene-by-gene (G×G) and gene-by-environment (G×E) interactions that sustain life. Here we use a Drosophila model of mitonuclear genetic interactions to explore the notion that mitochondria are environments for the nuclear genome, and vice versa. We construct factorial combinations of mtDNA and nuclear chromosomes to test for epistatic interactions (G×G), and expose these mitonuclear genotypes to altered dietary environments to examine G×E interactions. We use development time and genome-wide RNAseq analyses to assess the relative contributions of mtDNA, nuclear chromosomes, and environmental effects on these traits (mitonuclear G×G×E). We show that the nuclear transcriptional response to alternative mitochondrial “environments” (G×G) has significant overlap with the transcriptional response of mitonuclear genotypes to altered dietary environments. These analyses point to specific transcription factors (e.g., giant) that mediated these interactions, and identified coexpressed modules of genes that may account for the overlap in differentially expressed genes. Roughly 20% of the transcriptome includes G×G genes that are concordant with G×E genes, suggesting that mitonuclear interactions are part of an organism’s environment.
Cancer among children, adolescents and young adults in the Hokushin region, Japan, between 2010 and 2015
Authors: Okura Eri , Nishino Yoshikazu , Sakashita Kazuo , Tanimoto Azusa , Hayashi Ryuji , Yoshida Yoshio , Nakada Mitsutoshi , Koizumi Tomonobu , Yano Seiji , Nakazawa Yozo 
Published: October 2021

Abstract
Adolescents and young adults with cancer encounter age-related challenges. Cancer treatment and support are not always tailored to the needs of each patient due to difficulty in the collection of accurate data. The present study aimed to investigate cancer among children and adolescents and young adults in the four adjacent prefectures of Japan (Toyama, Ishikawa, Fukui and Nagano) by analyzing data from a unique regional cancer database. We retrieved and analyzed the data of pediatric and adolescent and young adult patients aged between 0 and 39 years at cancer diagnosis (including carcinoma in situ), which was registered in the Hokushin Ganpro database between 2010 and 2015. A total of 5718 cases (1571 males and 4147 females) were identified during this period. The overall male-to-female ratio was 1:2.6. There was no distinct difference in the number of cancer cases per 100 000 population between males and females until 19 years of age. The difference became more pronounced after 20 years of age. The number of cancer cases (per 100 000 population) in the 0–14-, 15–19-, 20–29- and 30–39-year age groups was estimated to be 13.4, 14.5, 44.0 and 101.5, respectively. Carcinomas were the most common type of cancer in the adolescents and young adults (15–39 years) population (74%), whereas they were not the predominant cancer type in the pediatric (0–14 years) population. Although further research is needed to understand the needs of adolescents and young adults with cancer, we believe that our findings will help guide efforts to improve the management strategy for adolescents and young adults with cancer.
State Responsibility for the Conduct of Rebels in Situations of Unsuccessful Civil Wars: A Critical Analysis of the Cengiz v Libya Case
Authors: Dumberry Patrick 
Published: October 2021

Abstract
Based on an analysis of State practice and case law, this article examines one basic principle embodied in Article 10 of the International Law Commission Articles (ILC) on State responsibility: the wrongful acts committed by rebels during an insurrection or a civil war are not attributable to the State once the government defeats the insurgency. The article examines how investment tribunals can use Article 10 in the context of investor–State arbitration proceedings involving rebellions and civil wars. I will critically analyse the recent Cengiz v. Libya award rendered in the context of Libya’s civil war. I will show that the Tribunal failed to correctly applied Articles 4 and 10 of the ILC Articles. I will explain how the Tribunal could have made better use of the principles embodied in Article 10 to solve matters of State responsibility and attribution it was facing.
Action mechanisms of small microbial volatile compounds in plants
Authors: Gámez-Arcas Samuel , Baroja-Fernández Edurne , García-Gómez Pablo , Muñoz Francisco José , Almagro Goizeder , Bahaji Abdellatif , Sánchez-López Ángela María , Pozueta-Romero Javier 
Published: October 2021

Abstract
Microorganisms communicate with plants by exchanging chemical signals throughout the phytosphere. Before direct contact with plants occurs, beneficial microorganisms emit a plethora of volatile compounds that promote plant growth and photosynthesis as well as developmental, metabolic, transcriptional, and proteomic changes in plants. These compounds can also induce systemic drought tolerance and improve water and nutrient acquisition. Recent studies have shown that this capacity is not restricted to beneficial microbes; it also extends to phytopathogens. Plant responses to microbial volatile compounds have frequently been associated with volatile organic compounds with molecular masses ranging between ~ 45Da and 300Da. However, microorganisms also release a limited number of volatile compounds with molecular masses of less than ~45Da that react with proteins and/or act as signaling molecules. Some of these compounds promote photosynthesis and growth when exogenously applied in low concentrations. Recently, evidence has shown that small volatile compounds are important determinants of plant responses to microbial volatile emissions. However, the regulatory mechanisms involved in these responses remain poorly understood. This review summarizes current knowledge of biochemical and molecular mechanisms involved in plant growth, development, and metabolic responses to small microbial volatile compounds.
Belowground plant–microbe communications via volatile compounds
Authors: Sharifi Rouhallah , Jeon Je-Seung , Ryu Choong-Min 
Published: October 2021

AbstractVolatile compounds play important roles in rhizosphere biological communications and interactions. The emission of plant and microbial volatiles is a dynamic phenomenon that is affected by several endogenous and exogenous signals. Diffusion of volatiles can be limited by their adsorption, degradation, and dissolution under specific environmental conditions. Therefore, rhizosphere volatiles need to be investigated on a micro and spatiotemporal scale. Plant and microbial volatiles can expand and specialize the rhizobacterial niche not only by improving the root system architecture such that it serves as a nutrient-rich shelter, but also by inhibiting or promoting the growth, chemotaxis, survival, and robustness of neighboring organisms. Root volatiles play an important role in engineering the belowground microbiome by shaping the microbial community structure and recruiting beneficial microbes. Microbial volatiles are appropriate candidates for improving plant growth and health during environmental challenges and climate change. However, some technical and experimental challenges limit the non-destructive monitoring of volatile emissions in the rhizosphere in real-time. In this review, we attempt to clarify the volatile-mediated intra- and inter-kingdom communications in the rhizosphere, and propose improvements in experimental design for future research.
Dual functionality of natural mixtures of bacterial volatile compounds on plant growth
Authors: Song Geun Cheol , Jeon Je-Seung , Sim Hee-Jung , Lee Soohyun , Jung Jihye , Kim Sang-Gyu , Moon Sun Young , Ryu Choong-Min 
Published: October 2021

AbstractBacteria emit volatile compounds that modulate plant growth. Previous studies reported the impacts of bacterial volatile compounds on plant growth; however, the results varied depending on bacterial nutrient availability. We investigated whether the effects of plant growth–inhibiting volatiles (PGIVs) and plant growth–promoting volatiles (PGPVs) depended on the perceived dose by evaluating the growth of Arabidopsis thaliana seedlings placed at 7, 14, and 21 cm away from Bacillus amyloliquefaciens GB03 colonies growing in rich medium. A large bacterial colony (500 μl inoculum) inhibited plant growth at 7 cm and promoted growth at 21 cm, whereas a small bacterial colony (100 μl inoculum) induced the opposite pattern of response. We identified pyrazine and 2,5-dimethylpyrazine as candidate PGIVs that significantly reduced plant growth at a distance of 7 cm. PGIV effects were validated by exposing plants to synthetic 2,5-dimethylpyrazine and bacteria emitting PGPVs, which showed that PGIVs overwhelm PGPVs to rapidly increase salicylic acid content and related gene expression. This is referred to as the defence-growth trade-off. Our results indicate that high PGIV concentrations suppress plant growth and promote immunity, whereas low PGPV concentrations promote growth. This study provides novel insights into the complex effects of bacterial volatile mixtures and fine-tuning of bacteria-plant interactions.
Pneumocystis jirovecii genetic diversity in a Spanish tertiary hospital
Authors: Goterris Lidia , Pasic Lana , Guerrero Murillo Mercedes , Kan Alex , Anton Andres , Aguilar Company Juan , Ruiz-Camps Isabel , Meyer Wieland , Martin-Gomez María Teresa 
Published: October 2021

Abstract

Pneumocystis jirovecii is associated with non-noxious colonization or severe pneumonia in immunocompromised hosts. Epidemiological investigations have been hampered by the lack of a standardized typing scheme. Thus, only partial molecular data on Spanish P. jirovecii cases are available. Recently, a new ISHAM consensus multilocus sequence typing scheme (MLST) targeting β-TUB, mt26S, CYB, and SOD with a publicly accessible database has been launched to overcome this problem.
The molecular epidemiology of P. jirovecii from immunocompromised patients either colonized (n = 50) or having pneumonia (n = 36) seen between 2014 and 2018 at a single center in Barcelona, Spain, was studied. The new ISHAM consensus MSLT scheme was used to investigate the local epidemiology and identify possible unnoticed outbreaks. Mutations in the DHPS gene, not included in the scheme but giving information about potential sulfa treatment failure, were also studied. The study assigned 32 sequence types (ST) to 72.2% pneumonia and 56% colonization cases. The most frequent STs were ST21 (18.5%), ST22 (14.8%), and ST37(14.8%). For non-unique STs, ST3, ST30 and ST31 were found only in pneumonia cases, whereas ST27 was associated exclusively to colonizations. Despite 38 patients sharing similar STs, only two were involved in a potential cross transmission event. No DHPS mutations were identified. The new consensus typing scheme was useful to ascertain the molecular epidemiology of P. jirovecii in our center revealing a high genetic diversity and the potential association of specific STs to colonization and pneumonia cases.

Lay Summary
A newly described MLST scheme aims at providing a standardized tool to study and compare Pneumocystis jirovecii epidemiology. A high diversity among P. jirovecii isolates from patients in Barcelona, Spain, and a potential association between specific STs and infection/colonization were identified.
Indicator power spectra: surgical excision of non-linearities and covariance matrices for counts in cells
Authors: Repp Andrew , Szapudi István 
Published: October 2021

ABSTRACT
We here introduce indicator functions, which identify regions of a given density in order to characterize the density dependence of clustering. After a general introduction to this tool, we show that indicator-function power spectra are biased versions of the linear spectrum on large scales. We provide a calculation from first principles for this bias, we show that it reproduces simulation results, and we provide a simple functional form for the translinear portion of the indicator-function spectra. We also outline two applications: First, these spectra facilitate surgical excision of non-linearity, and thus, significantly increase the reach of linear theory. Second, indicator-function spectra permit calculation of theoretical covariance matrices for counts-in-cells (CIC), facilitating parameter estimation with complementary CIC methods.
Convolutional deep denoising autoencoders for radio astronomical images
Authors: Gheller C , Vazza F 
Published: October 2021

ABSTRACT
We apply a Machine Learning technique known as Convolutional Denoising Autoencoder to denoise synthetic images of state-of-the-art radio telescopes, with the goal of detecting the faint, diffused radio sources predicted to characterize the radio cosmic web. In our application, denoising is intended to address both the reduction of random instrumental noise and the minimization of additional spurious artefacts like the sidelobes, resulting from the aperture synthesis technique. The effectiveness and the accuracy of the method are analysed for different kinds of corrupted input images, together with its computational performance. Specific attention has been devoted to create realistic mock observations for the training, exploiting the outcomes of cosmological numerical simulations, to generate images corresponding to LOFAR HBA 8 h observations at 150 MHz. Our autoencoder can effectively denoise complex images identifying and extracting faint objects at the limits of the instrumental sensitivity. The method can efficiently scale on large data sets, exploiting high-performance computing solutions, in a fully automated way (i.e. no human supervision is required after training). It can accurately perform image segmentation, identifying low brightness outskirts of diffused sources, proving to be a viable solution for detecting challenging extended objects hidden in noisy radio observations.