bluuebunny/crossref_metadata_2025_split huggingface dataset:
StackIL6: a stacking ensemble model for improving the prediction of IL-6 inducing peptides
Authors: Charoenkwan Phasit , Chiangjong Wararat , Nantasenamat Chanin , Hasan Md Mehedi , Manavalan Balachandran , Shoombuatong Watshara 
Published: April 2021

AbstractThe release of interleukin (IL)-6 is stimulated by antigenic peptides from pathogens as well as by immune cells for activating aggressive inflammation. IL-6 inducing peptides are derived from pathogens and can be used as diagnostic biomarkers for predicting various stages of disease severity as well as being used as IL-6 inhibitors for the suppression of aggressive multi-signaling immune responses. Thus, the accurate identification of IL-6 inducing peptides is of great importance for investigating their mechanism of action as well as for developing diagnostic and immunotherapeutic applications. This study proposes a novel stacking ensemble model (termed StackIL6) for accurately identifying IL-6 inducing peptides. More specifically, StackIL6 was constructed from twelve different feature descriptors derived from three major groups of features (composition-based features, composition-transition-distribution-based features and physicochemical properties-based features) and five popular machine learning algorithms (extremely randomized trees, logistic regression, multi-layer perceptron, support vector machine and random forest). To enhance the utility of baseline models, they were effectively and systematically integrated through a stacking strategy to build the final meta-based model. Extensive benchmarking experiments demonstrated that StackIL6 could achieve significantly better performance than the existing method (IL6PRED) and outperformed its constituent baseline models on both training and independent test datasets, which thereby support its excellent discrimination and generalization abilities. To facilitate easy access to the StackIL6 model, it was established as a freely available web server accessible at http://camt.pythonanywhere.com/StackIL6. It is anticipated that StackIL6 can help to facilitate rapid screening of promising IL-6 inducing peptides for the development of diagnostic and immunotherapeutic applications in the future.
Multi-view Multichannel Attention Graph Convolutional Network for miRNA–disease association prediction
Authors: Tang Xinru , Luo Jiawei , Shen Cong , Lai Zihan 
Published: April 2021

AbstractMotivation: In recent years, a growing number of studies have proved that microRNAs (miRNAs) play significant roles in the development of human complex diseases. Discovering the associations between miRNAs and diseases has become an important part of the discovery and treatment of disease. Since uncovering associations via traditional experimental methods is complicated and time-consuming, many computational methods have been proposed to identify the potential associations. However, there are still challenges in accurately determining potential associations between miRNA and disease by using multisource data.Results: In this study, we develop a Multi-view Multichannel Attention Graph Convolutional Network (MMGCN) to predict potential miRNA–disease associations. Different from simple multisource information integration, MMGCN employs GCN encoder to obtain the features of miRNA and disease in different similarity views, respectively. Moreover, our MMGCN can enhance the learned latent representations for association prediction by utilizing multichannel attention, which adaptively learns the importance of different features. Empirical results on two datasets demonstrate that MMGCN model can achieve superior performance compared with nine state-of-the-art methods on most of the metrics. Furthermore, we prove the effectiveness of multichannel attention mechanism and the validity of multisource data in miRNA and disease association prediction. Case studies also indicate the ability of the method for discovering new associations.
Resilience function uncovers the critical transitions in cancer initiation
Authors: Li Yan , Zhang Shao-Wu 
Published: April 2021

Abstract
Considerable evidence suggests that during the progression of cancer initiation, the state transition from wellness to disease is not necessarily smooth but manifests switch-like nonlinear behaviors, preventing the cancer prediction and early interventional therapy for patients. Understanding the mechanism of such wellness-to-disease transitions is a fundamental and challenging task. Despite the advances in flux theory of nonequilibrium dynamics and ‘critical slowing down’-based system resilience theory, a system-level approach still lacks to fully describe this state transition. Here, we present a novel framework (called bioRFR) to quantify such wellness-to-disease transition during cancer initiation through uncovering the biological system’s resilience function from gene expression data. We used bioRFR to reconstruct the biologically and dynamically significant resilience functions for cancer initiation processes (e.g. BRCA, LUSC and LUAD). The resilience functions display the similar resilience pattern with hysteresis feature but different numbers of tipping points, which implies that once the cell become cancerous, it is very difficult or even impossible to reverse to the normal state. More importantly, bioRFR can measure the severe degree of cancer patients and identify the personalized key genes that are associated with the individual system’s state transition from normal to tumor in resilience perspective, indicating that bioRFR can contribute to personalized medicine and targeted cancer therapy.
Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice
Authors: Chen Yunxia , Zhang Xiaorong , Liu Zhihui , Yang Jiacai , Chen Cheng , Wang Jue , Yang Zengjun , He Lei , Xu Pengcheng , Hu Xiaohong , Luo Gaoxing , He Weifeng 
Published: April 2021

Abstract

Background
Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury. However, the systematic and detailed evaluation of the scald burn injury, including second-degree deep scald (SDDS) and third-degree scald (TDS), is still unclear. The present study aims to analyze the wound-healing speed, the formation of granulation tissue, and the healing quality after cutaneous damage.

Methods
In order to assess SDDS and TDS, the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice. Furthermore, an excisional wound was administered on the dorsal surface in mice (Cut group). The wound-healing rate was first analyzed at days 0, 3, 5, 7, 15 and 27, with the Cut group as a control. Then, on the full-thickness wounds, hematoxylin and eosin (H&E) staining, Masson staining, Sirius red staining, Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization, the formation of granulation tissue, vascularization, inflammatory infiltration and the healing quality at different time points in the Cut, SDDS and TDS groups.

Results
The presented data revealed that the wound-healing rate was higher in the Cut group, when compared with the SDDS and TDS groups. H&E staining showed that re-epithelialization, formation of granulation tissue and inflammatory infiltration were greater in the Cut group, when compared with the SDDS and TDS groups. Immunohistochemistry revealed that the number of CD31, vascular endothelial growth factor A, transforming growth factor-β and α-smooth muscle actin reached preferential peak in the Cut group, when compared with other groups. In addition, Masson staining, Sirius red staining, Victoria blue staining, Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III, reticular fibers, failure stress, Young’s modulus and failure length in the SDDS group were similar to those in the normal group, suggesting that healing quality was better in the SDDS group, when compared with the Cut and TDS groups.

Conclusion
Overall, the investigators first administered a comprehensive analysis in the Cut, SDDS and TDS groups through in vivo experiments, which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.
LEDet: A Single-Shot Real-Time Object Detector Based on Low-Light Image Enhancement
Authors: Hao Shijie , Wang Zhonghao , Sun Fuming 
Published: April 2021

Abstract
Recently, significant breakthroughs have been achieved in the field of object detection. However, existing methods mostly focus on the generic object detection task. Performance degradation can be unavoidable when applying the existing methods to some specific situations directly, e.g. a low-light environment. To address this issue, we propose a single-shot real-time object Detector based on Low-light image Enhancement, namely LEDet. LEDet adapts itself to the low-light detection task in three aspects. First, a low-light enhancement module is introduced as the image preprocessor, producing the augmented inputs from the low-light images. Second, two modules, i.e. low-light and enhanced features fusion module and the scale-aware channel attention dilated convolution module are designed. These two modules aim at learning robust and discriminative features from objects of various sizes hidden in the darkness. In experiments, we validate the effectiveness of each part of our LEDet model via several ablation studies. We also compare LEDet with various methods on the Exclusively Dark dataset, showing that our model achieves the state-of-the-art performance on the balance between speed and accuracy.
Aortic valve surgery in the UK, trends in activity and outcomes from a 15-year complete national series
Authors: Baghai Max , Wendler Olaf , Grant Stuart W , Goodwin Andrew T , Trivedi Uday , Kendall Simon , Jenkins David P 
Published: April 2021

Abstract

OBJECTIVES
Since the turn of the century, cardiac surgery has evolved quite notably. This study sought to investigate the trends in aortic valve surgery activity and subsequent outcomes in the UK by using a mandatory national cardiac surgical clinical database within the context of a comprehensive public healthcare system (National Health Service).

METHODS
The UK National Adult Cardiac Surgery Audit database provided data for aortic valve surgery procedures performed between 2002 and 2016, and the data were validated and cleaned using reproducible algorithms. The findings and trends in in activity and outcomes were then analysed by financial year.

RESULTS
During the study period, a total of 148 862 procedures were performed, with the number of cases per year peaking in 2014/2015 at 12 483. The mean in-hospital mortality rate for all aortic valve surgery has fallen from 5.6% to 3.4%, despite an increase in patient age and mean logistic EuroSCORE. While the number of isolated aortic valve replacements has remained stable at around 5000 per year, aortic valve replacement and coronary artery bypass graft have increased to over 3200 with transcatheter aortic valve implantation activity continuing to increase.

CONCLUSIONS
This study demonstrates that despite an increase in patient risk profile, there has been a consistent reduction in in-hospital mortality within all aortic valve surgery procedures performed in the UK over a 15-year period. Increasing catheter-based interventions have not yet resulted in a significant decrease in surgical aortic valve replacements in the UK.
Systematic engineering of Saccharomyces cerevisiae for D-lactic acid production with near theoretical yield
Authors: Watcharawipas Akaraphol , Sae-tang Kittapong , Sansatchanon Kitisak , Sudying Pipat , Boonchoo Kriengsak , Tanapongpipat Sutipa , Kocharin Kanokarn , Runguphan Weerawat 
Published: April 2021

Abstract
D-lactic acid is a chiral three-carbon organic acid that can improve the thermostability of polylactic acid. Here, we systematically engineered Saccharomyces cerevisiae to produce D-lactic acid from glucose, a renewable carbon source, at near theoretical yield. Specifically, we screened D-lactate dehydrogenase (DLDH) variants from lactic acid bacteria in three different genera and identified the Leuconostoc pseudomesenteroides variant (LpDLDH) as having the highest activity in yeast. We then screened single-gene deletions to minimize the production of the side products ethanol and glycerol as well as prevent the conversion of D-lactic acid back to pyruvate. Based on the results of the DLDH screening and the single-gene deletions, we created a strain called ASc-d789M which overexpresses LpDLDH and contains deletions in glycerol pathway genes GPD1 and GPD2 and lactate dehydrogenase gene DLD1, as well as downregulation of ethanol pathway gene ADH1 using the L-methionine repressible promoter to minimize impact on growth. ASc-d789M produces D-lactic acid at a titer of 17.09 g/L in shake-flasks (yield of 0.89 g/g glucose consumed or 89% of the theoretical yield). Fed-batch fermentation resulted in D-lactic acid titer of 40.03 g/L (yield of 0.81 g/g glucose consumed). Altogether, our work represents progress towards efficient microbial production of D-lactic acid.
Conservation of glp-1 Regulation and Function in Nematodes
Authors: Rudel David , Kimble Judith 
Published: April 2021

Abstract
The Caenorhabditis elegans (Ce) glp-1 gene encodes a Notch-like receptor. We have cloned glp-1 from C. briggsae (Cb) and C. remanei (Cr), two Caenorhabditis species that have diverged from C. elegans by roughly 20–40 million years. By sequence analysis, we find that the Cb-GLP-1 and Cr-GLP-1 proteins have retained the same motif architecture as Ce-GLP-1, including number of domains. In addition, two regions (CC-linker and regions flanking the ANK repeats) are as highly conserved as regions previously recognized as essential for signaling (e.g., ANK repeats). Phylogenetic analysis of glp-1 sequences suggests a C. briggsae/C. remanei clade with C. elegans as a sister taxon. Using RNAi to test biological functions, we find that Ce-glp-1, Cb-glp-1, and Cr-glp-1 are all required for proliferation of germline stem cells and for specifying blastomere fates in the embryo. In addition, certain biological roles of Cb-glp-1, e.g., in the vulva, have diverged from those of Ce-glp-1 and Cr-glp-1, suggesting a change in either regulation or function of the Cb-glp-1 gene during evolution. Finally, the regulation of glp-1 mRNA, previously analyzed for Ce-glp-1, is conserved in Cb-glp-1, and we identify conserved 3′ UTR sequences that may serve as regulatory elements.
Genetic Architecture of Mandible Shape in Mice: Effects of Quantitative Trait Loci Analyzed by Geometric Morphometrics
Authors: Klingenberg Christian Peter , Leamy Larry J , Routman Eric J , Cheverud James M 
Published: April 2021

Abstract
This study introduces a new multivariate approach for analyzing the effects of quantitative trait loci (QTL) on shape and demonstrates this method for the mouse mandible. We quantified size and shape with the methods of geometric morphometrics, based on Procrustes superimposition of five morphological landmarks recorded on each mandible. Interval mapping for F2 mice originating from an intercross of the LG/J and SM/J inbred strains revealed 12 QTL for size, 25 QTL for shape, and 5 QTL for left-right asymmetry. Multivariate ordination of QTL effects by principal component analysis identified two recurrent features of shape variation, which involved the positions of the coronoid and angular processes relative to each other and to the rest of the mandible. These patterns are reminiscent of the knockout phenotypes of a number of genes involved in mandible development, although only a few of these are possible candidates for QTL in our study. The variation of shape effects among the QTL showed no evidence of clustering into distinct groups, as would be expected from theories of morphological integration. Further, for most QTL, additive and dominance effects on shape were markedly different, implying overdominance for specific features of shape. We conclude that geometric morphometrics offers a promising new approach to address problems at the interface of evolutionary and developmental genetics.
Haldane's Sieve and Adaptation From the Standing Genetic Variation
Authors: Orr H Allen , Betancourt Andrea J 
Published: April 2021

Abstract
We consider populations that adapt to a sudden environmental change by fixing alleles found at mutation-selection balance. In particular, we calculate probabilities of fixation for previously deleterious alleles, ignoring the input of new mutations. We find that “Haldane's sieve”—the bias against the establishment of recessive beneficial mutations—does not hold under these conditions. Instead probabilities of fixation are generally independent of dominance. We show that this result is robust to patterns of sex expression for both X-linked and autosomal loci. We further show that adaptive evolution is invariably slower at X-linked than autosomal loci when evolution begins from mutation-selection balance. This result differs from that obtained when adaptation uses new mutations, a finding that may have some bearing on recent attempts to distinguish between hitchhiking and background selection by contrasting the molecular population genetics of X-linked vs. autosomal loci. Last, we suggest a test to determine whether adaptation used new mutations or previously deleterious alleles from the standing genetic variation.
Joint Linkage and Linkage Disequilibrium Mapping in Natural Populations
Authors: Wu Rongling , Zeng Zhao-Bang 
Published: April 2021

AbstractA new strategy for studying the genome structure and organization of natural populations is proposed on the basis of a combined analysis of linkage and linkage disequilibrium using known polymorphic markers. This strategy exploits a random sample drawn from a panmictic natural population and the open-pollinated progeny of the sample. It is established on the principle of gene transmission from the parental to progeny generation during which the linkage between different markers is broken down due to meiotic recombination. The strategy has power to simultaneously capture the information about the linkage of the markers (as measured by recombination fraction) and the degree of their linkage disequilibrium created at a historic time. Simulation studies indicate that the statistical method implemented by the Fisher-scoring algorithm can provide accurate and precise estimates for the allele frequencies, recombination fractions, and linkage disequilibria between different markers. The strategy has great implications for constructing a dense linkage disequilibrium map that can facilitate the identification and positional cloning of the genes underlying both simple and complex traits.
An Incremental Approach to Filling Protection Gaps in Equality Rights for Persons with Disabilities
Authors: Richards Jane 
Published: April 2021

Abstract
The Convention on the Rights of Persons with Disabilities (CRPD) guarantees that persons with disabilities (‘PWD’) are to be equal before and under the law. There are almost identical equality guarantees in the Canadian Charter of Rights and Freedoms and Hong Kong's mini constitution – the Basic Law. Australia boasts similar legislative equality guarantees for PWD. The CRPD Committee has interpreted the right broadly, whereas constitutional courts have taken a proportionality approach, balancing the right to substantive equality against competing concerns. The tension between these methods of rights protection means the CRPD is being positioned as an alternative model of rights protection, but it is not an alternative mechanism for enforcement. This article calls on the Committee to modify its guidance to make suggestions to state parties as to how incremental advances in rights protection can be immediately implemented, even if in the short-term, these advances fall short of full inclusion.
Dynamic hedging in incomplete markets using risk measures
Authors: Gaillardetz Patrice , Hachem Saeb 
Published: April 2021

Abstract
In this paper, we consider the pricing of financial derivatives that involve dynamic hedging strategies and payments within the planning horizon. Equity-indexed annuities (EIAs), guaranteed investment certificates (GICs) and American and barrier options are typical examples of these products. Our exploration involves the use and comparison of alternative models that use risk measures. Although the hedging is done for each observation of the input stochastic process, the appropriate mix of risk measures and state dynamic equations helps the issuer to appropriately tailor the overall risk exercise. These different models are solved by a unified backward stochastic dynamic programming framework that we imbed with parametric techniques to shorten the running time and manage the curse of dimensionality in dynamic programming. To demonstrate the flexibility of this framework we present numerical examples featuring GICs and point-to-point EIAs. Finally, by using sampling techniques, optimal hedging strategies and specific indicators of the hedging performance, we make recommendations on how to fine tune the risk measure parameters.
Development of a Selective Agar for Improving Campylobacter jejuni Detection in Food
Authors: Ha Jimyeong , Seo Yeongeun , Kim Yujin , Choi Yukyung , Oh Hyemin , Lee Yewon , Park Eunyoung , Kang Joohyun , Lee Heeyoung , Lee Soomin , Yoon Yohan 
Published: April 2021

Abstract

Background
Campylobacter jejuni is a major gastroenteritis-causing foodborne pathogen. However, it is difficult to isolate when competing bacteria or cold-damaged cells are present.

Objective
Herein, a medium (Campylobacter selective agar, CSA) was developed and supplemented with catalase, L-serine, L-cysteine, and quercetin for the selective detection of C. jejuni in food.

Method
The C. jejuni-detection efficiency in media broth and chicken tenders was evaluated. The pathogen was enumerated on modified charcoal–cefoperazone–deoxycholate agar (mCCDA), CSA supplemented with 4 µM catalase (CSA-C4), 8 µM catalase (CSA-C8), 20 mM L-serine (CSA-S20) or 50 mM L-serine (CSA-S50), and mCCDA supplemented with 0.5 mM L-cysteine (mCCDA-LC0.5), 1 mM L-cysteine (mCCDA-LC1), 40 µM quercetin (mCCDA-Q40) or 320 µM quercetin (mCCDA-Q320). The detection efficiency was then evaluated by counting colonies on the selective agar media. Quantitative assessment was also performed using chicken and duck carcasses.

Results
The C. jejuni detection efficiencies were higher (P &lt; 0.05) in the groups CSA-C4 or CSA-C8, and CSA-S20 or CSA-S50, than mCCDA, and the detection efficiencies were maintained even in the presence of Acinetobacter baumannii, a competing bacterium. In the quantitative test, CSA-C8 and CSA-S50 demonstrated higher C. jejuni-detection efficiencies than mCCDA (control).

Conclusions
Therefore, CSA-C8 and CSA-S50 improved the detection efficiency of C. jejuni in poultry products by promoting the recovery of cold-damaged cells.

Highlights
When using CSA-C8 or CSA-S50 developed in this study for detection of C. jejuni in food, detection efficiency was higher than mCCDA.