bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical outcomes of infective endocarditis in children: should we delay surgery for infective endocarditis?
Authors: Lee Jae Hong , Kwak Jae Gun , Cho Sungkyu , Kim Woong-Han , Lee Jeong Ryul , Kwon Hye Won , Song Mi Kyoung , Lee Sang-Yun , Kim Gi Beom , Bae Eun Jung 
Published: March 2021

Abstract

OBJECTIVES
We compared the surgical outcomes of infective endocarditis (IE) between early surgery and non-early surgery groups in children.

METHODS
From January 2000 to April 2020, we retrospectively reviewed 50 patients &lt;18years of age who underwent first surgery for IE. Early surgery was defined as that performed within 2 days for left-sided IE and 7 days for right-sided IE after diagnosis.

RESULTS
The median age and body weight at operation were 7.7 years [interquartile range (IQR), 2.3–13.2] and 23.7 kg (IQR, 10.3–40.7), respectively. The median follow-up duration was 9.5 years (IQR, 4.0–14.5). In 28 patients with native valve endocarditis, the native valve was preserved in 23 (82.1%). The most common causative microorganism was Streptococcus viridans (32.0%). The operative mortality was 2.0%, and 13 (26.0%) patients required reoperation most commonly for prosthesis failure (n = 7). There were no significant differences in patient characteristics and perioperative data between early surgery (n = 9) and non-early surgery (n = 36) groups, except for the interval between diagnosis and surgery (early surgery &lt; non-early surgery, P &lt; 0.001) and preoperative negative blood culture conversion (early surgery &lt; non-early surgery, P = 0.025). There were no significant differences in overall survival, recurrent IE, and reoperation rate between the groups. Early surgery and preoperative negative blood culture conversion were not found as significant factors for surgical adverse outcomes.

CONCLUSIONS
Surgical outcomes for IE in children were acceptable irrespective of the time of surgery. Our results suggest that it may not be required to delay surgery for IE and the potential benefit of early surgery could be expected in children.
Functional capacity assessment and Minimal Clinically Important Difference in post-acute cardiac patients: the role of Short Physical Performance Battery
Authors: Rinaldo Linda , Caligari Marco , Acquati Claudia , Nicolazzi Sabrina , Paracchini Giulio , Sardano Daniela , Giordano Andrea , Marcassa Claudio , Corrà Ugo 
Published: March 2021

Abstract

Background
The Short Physical Performance Battery (SPPB) test is a well-established tool to assess physical performance, and to identify frail patients. Assessment of the SPPB in a specific population of elder patients in cardiac rehabilitation phase after a cardiac event is missing.

Aim
The aim of this study was to correlate SPPB and the cardiac rehabilitation outcome in a group of elder patients after a cardiac event and to identify the Minimal Clinically Important Difference (MCID) of the SPPB.

Methods
Consecutive (n = 392) patients aged ≥75 years, in the rehabilitation phase after cardiac surgery (70.1%), congestive heart failure (7.4%), or acute coronary syndrome (22.5%), were enrolled. SPPB was performed twice: on admission and discharge. The MCID was assessed with the ‘anchor method’, and the Patient Global Impression of Change was employed as the anchor.

Results
On admission, SPPB classified 56, 117, 116, and 94 patients as severe, moderate, mild, or minimal/no limitations, respectively. Patients with the lower SPPB had the longer length of stay, and the higher complications rate. At receiver operating characteristic analysis, an SPPB improvement &gt;1 was identified as the MCID (area-under-curve 0.77, 95% CI 0.67–0.85). Overall, 285 patients (74.2%) had a ‘clinically significant’ improvement in SPPB, with a rate of improvement higher in patients with severe/moderate limitations (83.0%) and lower in those with mild (78.9%) or minimal/no limitations (53.6%).

Conclusion
A lower SPPB score is associated with a higher complications rate in the post-acute phase. An improvement &gt;1 point of SPPB was identified as the MCID; this reference value could serve as the goal for rehabilitation interventions.
Comparative transcriptome analyses of theDrosophilapupal eye
Authors: DeAngelis Miles W , Coolon Joseph D , Johnson Ruth I 
Published: March 2021

AbstractTissue function is dependent on correct cellular organization and behavior. As a result, the identification and study of genes that contribute to tissue morphogenesis is of paramount importance to the fields of cell and developmental biology. Many of the genes required for tissue patterning and organization are highly conserved between phyla. This has led to the emergence of several model organisms and developmental systems that are used to study tissue morphogenesis. One such model is the Drosophila melanogaster pupal eye that has a highly stereotyped arrangement of cells. In addition, the pupal eye is postmitotic that allows for the study of tissue morphogenesis independent from any effects of proliferation. While the changes in cell morphology and organization that occur throughout pupal eye development are well documented, less is known about the corresponding transcriptional changes that choreograph these processes. To identify these transcriptional changes, we dissected wild-type Canton S pupal eyes and performed RNA-sequencing. Our analyses identified differential expression of many loci that are documented regulators of pupal eye morphogenesis and contribute to multiple biological processes including signaling, axon projection, adhesion, and cell survival. We also identified differential expression of genes not previously implicated in pupal eye morphogenesis such as components of the Toll pathway, several non-classical cadherins, and components of the muscle sarcomere, which could suggest these loci function as novel patterning factors.
Chromosome inheritance and meiotic stability in allopolyploidBrassica napus
Authors: Xiong Zhiyong , Gaeta Robert T , Edger Patrick P , Cao Yao , Zhao Kanglu , Zhang Siqi , Pires J Chris 
Published: March 2021

AbstractHomoeologous recombination, aneuploidy, and other genetic changes are common in resynthesized allopolyploid Brassica napus. In contrast, the chromosomes of cultivars have long been considered to be meiotically stable. To gain a better understanding of the underlying mechanisms leading to stabilization in the allopolyploid, the behavior of chromosomes during meiosis can be compared by unambiguous chromosome identification between resynthesized and natural B. napus. Compared with natural B. napus, resynthesized lines show high rates of nonhomologous centromere association, homoeologous recombination leading to translocation, homoeologous chromosome replacement, and association and breakage of 45S rDNA loci. In both natural and resynthesized B. napus, we observed low rates of univalents, A–C bivalents, and early sister chromatid separations. Reciprocal homoeologous chromosome exchanges and double reductions were photographed for the first time in meiotic telophase I. Meiotic errors were non-uniformly distributed across the genome in resynthesized B. napus, and in particular homoeologs sharing synteny along their entire length exhibited multivalents at diakinesis and polysomic inheritance at telophase I. Natural B. napus appeared to resolve meiotic errors mainly by suppressing homoeologous pairing, resolving nonhomologous centromere associations and 45S rDNA associations before diakinesis, and reducing homoeologous cross-overs.
A zero altered Poisson random forest model for genomic-enabled prediction
Authors: Montesinos-López Osval Antonio , Montesinos-López Abelardo , Mosqueda-Gonzalez Brandon A , Montesinos-López José Cricelio , Crossa José , Ramirez Nerida Lozano , Singh Pawan , Valladares-Anguiano Felícitas Alejandra 
Published: March 2021

AbstractIn genomic selection choosing the statistical machine learning model is of paramount importance. In this paper, we present an application of a zero altered random forest model with two versions (ZAP_RF and ZAPC_RF) to deal with excess zeros in count response variables. The proposed model was compared with the conventional random forest (RF) model and with the conventional Generalized Poisson Ridge regression (GPR) using two real datasets, and we found that, in terms of prediction performance, the proposed zero inflated random forest model outperformed the conventional RF and GPR models.
Generalized gametic relationships for flexible analyses of parent-of-origin effects
Authors: Reinsch Norbert , Mayer Manfred , Blunk Inga 
Published: March 2021

Abstract
A class of epigenetic inheritance patterns known as genomic imprinting allows alleles to influence the phenotype in a parent-of-origin-specific manner. Various pedigree-based parent-of-origin analyses of quantitative traits have attempted to determine the share of genetic variance that is attributable to imprinted loci. In general, these methods require four random gametic effects per pedigree member to account for all possible types of imprinting in a mixed model. As a result, the system of equations may become excessively large to solve using all available data. If only the offspring have records, which is frequently the case for complex pedigrees, only two averaged gametic effects (transmitting abilities) per parent are required (reduced model). However, the parents may have records in some cases. Therefore, in this study, we explain how employing single gametic effects solely for informative individuals (i.e., phenotyped individuals), and only average gametic effects otherwise, significantly reduces the complexity compared with classical gametic models. A generalized gametic relationship matrix is the covariance of this mixture of effects. The matrix can also make the reduced model much more flexible by including observations from parents. Worked examples are present to illustrate the theory and a realistic body mass data set in mice is used to demonstrate its utility. We show how to set up the inverse of the generalized gametic relationship matrix directly from a pedigree. An open-source program is used to implement the rules. The application of the same principles to phased marker data leads to a genomic version of the generalized gametic relationships.
Copper Availability Influences the Transcriptomic Response of Candida albicans to Fluconazole Stress
Authors: Hunsaker Elizabeth W , Yu Chen-Hsin Albert , Franz Katherine J 
Published: March 2021

Abstract
The ability of pathogens to maintain homeostatic levels of essential biometals is known to be important for survival and virulence in a host, which itself regulates metal availability as part of its response to infection. Given this importance of metal homeostasis, we sought to address how the availability of copper in particular impacts the response of the opportunistic fungal pathogen Candida albicans to treatment with the antifungal drug fluconazole. The present study reports whole transcriptome analysis via time-course RNA-seq of C. albicans cells exposed to fluconazole with and without 10 µM supplemental CuSO4 added to the growth medium. The results show widespread impacts of small changes in Cu availability on the transcriptional response of C. albicans to fluconazole. Of the 2359 genes that were differentially expressed under conditions of cotreatment, 50% were found to be driven uniquely by exposure to both Cu and fluconazole. The breadth of metabolic processes that were affected by cotreatment illuminates a fundamental intersectionality between Cu metabolism and fungal response to drug stress. More generally, these results show that seemingly minor fluctuations in Cu availability are sufficient to shift cells’ transcriptional response to drug stress. Ultimately, the findings may inform the development of new strategies that capitalize on drug-induced vulnerabilities in metal homeostasis pathways.
Comparative genome analyses suggest a hemibiotrophic lifestyle and virulence differences for the beech bark disease fungal pathogens Neonectria faginata and Neonectria coccinea
Authors: Salgado-Salazar Catalina , Skaltsas Demetra N , Phipps Tunesha , Castlebury Lisa A 
Published: March 2021

Abstract
Neonectria faginata and Neonectria coccinea are the causal agents of the insect-fungus disease complex known as beech bark disease (BBD), known to cause mortality in beech forest stands in North America and Europe. These fungal species have been the focus of extensive ecological and disease management studies, yet less progress has been made toward generating genomic resources for both micro- and macro-evolutionary studies. Here, we report a 42.1 and 42.7 mb highly contiguous genome assemblies of N. faginata and N. coccinea, respectively, obtained using Illumina technology. These species share similar gene number counts (12,941 and 12,991) and percentages of predicted genes with assigned functional categories (64 and 65%). Approximately 32% of the predicted proteomes of both species are homologous to proteins involved in pathogenicity, yet N. coccinea shows a higher number of predicted mitogen-activated protein kinase genes, virulence determinants possibly contributing to differences in disease severity between N. faginata and N. coccinea. A wide range of genes encoding for carbohydrate-active enzymes capable of degradation of complex plant polysaccharides and a small number of predicted secretory effector proteins, secondary metabolite biosynthesis clusters and cytochrome oxidase P450 genes were also found. This arsenal of enzymes and effectors correlates with, and reflects, the hemibiotrophic lifestyle of these two fungal pathogens. Phylogenomic analysis and timetree estimations indicated that the N. faginata and N. coccinea species divergence may have occurred at ∼4.1 million years ago. Differences were also observed in the annotated mitochondrial genomes as they were found to be 81.7 kb (N. faginata) and 43.2 kb (N. coccinea) in size. The mitochondrial DNA expansion observed in N. faginata is attributed to the invasion of introns into diverse intra- and intergenic locations. These first draft genomes of N. faginata and N. coccinea serve as valuable tools to increase our understanding of basic genetics, evolutionary mechanisms and molecular physiology of these two nectriaceous plant pathogenic species.
Transcriptome Expression of Biomineralization Genes inLittoraria flavaGastropod in Brazilian Rocky Shore Reveals Evidence of Local Adaptation
Authors: Santos Camilla A , Sonoda Gabriel G , Cortez Thainá , Coutinho Luiz L , Andrade Sónia C S 
Published: March 2021

AbstractUnderstanding how selection shapes population differentiation and local adaptation in marine species remains one of the greatest challenges in the field of evolutionary biology. The selection of genes in response to environment-specific factors and microenvironmental variation often results in chaotic genetic patchiness, which is commonly observed in rocky shore organisms. To identify these genes, the expression profile of the marine gastropod Littoraria flava collected from four Southeast Brazilian locations in ten rocky shore sites was analyzed. In this first L. flava transcriptome, 250,641 unigenes were generated, and 24% returned hits after functional annotation. Independent paired comparisons between 1) transects, 2) sites within transects, and 3) sites from different transects were performed for differential expression, detecting 8,622 unique differentially expressed genes. Araçá (AR) and São João (SJ) transect comparisons showed the most divergent gene products. For local adaptation, fitness-related differentially expressed genes were chosen for selection tests. Nine and 24 genes under adaptative and purifying selection, respectively, were most related to biomineralization in AR and chaperones in SJ. The biomineralization-genes perlucin and gigasin-6 were positively selected exclusively in the site toward the open ocean in AR, with sequence variants leading to pronounced protein structure changes. Despite an intense gene flow among L. flava populations due to its planktonic larva, gene expression patterns within transects may be the result of selective pressures. Our findings represent the first step in understanding how microenvironmental genetic variation is maintained in rocky shore populations and the mechanisms underlying local adaptation in marine species.
Transcriptional Control of the Production of Aspergillus fumigatus Conidia-Borne Secondary Metabolite Fumiquinazoline C Important for Phagocytosis Protection
Authors: Rocha Marina Campos , Fabri João Henrique Tadini Marilhano , Silva Lilian Pereira , Angolini Célio Fernando Figueiredo , Bertolini Maria Célia , da Cunha Anderson Ferreira , Valiante Vito , Goldman Gustavo Henrique , Fill Taicia Pacheco , Malavazi Iran 
Published: March 2021

Abstract
Aspergillus fumigatus produces diverse secondary metabolites whose biological functions and regulation remain to be understood. Despite the importance of the conidia for this fungus, the role of the conidia-born metabolite fumiquinazoline C (FqC) is unclear. Here, we describe a dual function of the cell-wall integrity pathway in regulating FqC biosynthesis dictated by the MAPK kinase MpkA, which phosphorylates one of the nonribosomal peptide synthetases enzymes of the cluster (FmqC), and the transcription factor RlmA, which directly regulates the expression of fmq genes. Another level of crosstalk between the FqC regulation and the cell physiology is described since the deletion of the stress-responsive transcription factor sebA provokes derepression of the fmq cluster and overproduction of FqC. Thus, we describe a mechanism by which A. fumigatus controls FqC biosynthesis orchestrated by MpkA-RlmA and SebA and hence enabling survival and adaptation to the environmental niche, given that FqC is a deterrent of ameba predation.
Detecting de novo mitochondrial mutations in angiosperms with highly divergent evolutionary rates
Authors: Broz Amanda K , Waneka Gus , Wu Zhiqiang , Fernandes Gyorfy Matheus , Sloan Daniel B 
Published: March 2021

Abstract
Although plant mitochondrial genomes typically show low rates of sequence evolution, levels of divergence in certain angiosperm lineages suggest anomalously high mitochondrial mutation rates. However, de novo mutations have never been directly analyzed in such lineages. Recent advances in high-fidelity DNA sequencing technologies have enabled detection of mitochondrial mutations when still present at low heteroplasmic frequencies. To date, these approaches have only been performed on a single plant species (Arabidopsis thaliana). Here, we apply a high-fidelity technique (Duplex Sequencing) to multiple angiosperms from the genus Silene, which exhibits extreme heterogeneity in rates of mitochondrial sequence evolution among close relatives. Consistent with phylogenetic evidence, we found that Silene latifolia maintains low mitochondrial variant frequencies that are comparable with previous measurements in Arabidopsis. Silene noctiflora also exhibited low variant frequencies despite high levels of historical sequence divergence, which supports other lines of evidence that this species has reverted to lower mitochondrial mutation rates after a past episode of acceleration. In contrast, S. conica showed much higher variant frequencies in mitochondrial (but not in plastid) DNA, consistent with an ongoing bout of elevated mitochondrial mutation rates. Moreover, we found an altered mutational spectrum in S. conica heavily biased towards AT→GC transitions. We also observed an unusually low number of mitochondrial genome copies per cell in S. conica, potentially pointing to reduced opportunities for homologous recombination to accurately repair mismatches in this species. Overall, these results suggest that historical fluctuations in mutation rates are driving extreme variation in rates of plant mitochondrial sequence evolution.
Aging Changes in Bladder Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Are Associated With Increasing Heterogeneity of Adrenergic/Mucosal Influence on Detrusor Control in the Mouse
Authors: Hardy Cara C , Al-Naggar Iman M , Kuo Chia-Ling , Kuchel George A , Smith Phillip P 
Published: March 2021

Abstract
A geroscience-informed approach to the increasing prevalence of bladder control problems in older adults requires understanding the impact of aging on dynamic mechanisms that ensure resilience in response to stressors challenging asymptomatic voluntary control over urine storage and voiding. Bladder control is predicated on sensory neural information about bladder volume. Modulation of volume-induced bladder wall tensions by autonomic and mucosal factors controls neural sensitivity to bladder volume. We hypothesized that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels integrate these factors and thereby mediate adrenergic detrusor tension control. Furthermore, loss of HCN expression compromises that integration and could result in loss of precision of detrusor control. Using a life-span mouse model, reverse transcription quantitative real-time PCR and pharmacologic studies in pretensioned intact and mucosa-denuded bladder strips were made. The dominant hcn1 expression declines with maturation and aging; however, aging is also associated with increased variance around mean values. In strips from Mature animals, isoproterenol had less effect in denuded muscle strips than in intact strips, and HCN blockade diminished isoproterenol responsiveness. With aging, variances about mean response values significantly increased, paralleling hcn1 expression. Our findings support a role for HCN in providing neuroendocrine/paracrine integration and suggest an association of increased heterogeneity of HCN expression in aging with reductions in response precision to neuroendocrine control. The functional implication is an increased risk of dysfunction of brainstem/bladder regulation of neuronal sensitivity to bladder volume. This supports the clinical model of the aging bladder phenotype as an expression of loss of resilience, and not as emerging bladder pathology with aging.
Constructing time in foreign policy-making: Brexit's timing entrepreneurs, malcontemps and apparatchiks
Authors: Hom Andrew , Beasley Ryan 
Published: March 2021

Abstract
Temporal considerations play a role in many models of foreign policy analysis, particularly those focused on decision-making processes. While time features prominently as a background feature against which sequence, cadence and psychological consequence are measured, little attention has been given to how foreign policy agents actively construct their temporal environments. We propose that different foreign policy-making actors develop distinct relationships with time, and that variations in these relationships can help account for the ways in which ‘events’ are transformed into routine practices, change opportunities or full-blown foreign policy crises. We advance a novel conception of time in foreign policy-making through our development of timing theory and the linguistic constructions of ‘time’ by foreign policy actors. We propose a typology of timing agency, which highlights the impact of these orientations on decision-making processes as well as the characteristics of foreign policy behaviours. Using the case of Brexit, we elaborate differences in actors' temporal orientations and show how such differences impact the making of foreign policy.