bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug-target interaction prediction using semi-bipartite graph model and deep learning
Authors: Eslami Manoochehri Hafez , Nourani Mehrdad 
Published: July 2020

AbstractBackgroundIdentifying drug-target interaction is a key element in drug discovery. In silico prediction of drug-target interaction can speed up the process of identifying unknown interactions between drugs and target proteins. In recent studies, handcrafted features, similarity metrics and machine learning methods have been proposed for predicting drug-target interactions. However, these methods cannot fully learn the underlying relations between drugs and targets. In this paper, we propose anew framework for drug-target interaction prediction that learns latent features from drug-target interaction network.ResultsWe present a framework to utilize the network topology and identify interacting and non-interacting drug-target pairs. We model the problem as a semi-bipartite graph in which we are able to use drug-drug and protein-protein similarity in a drug-protein network. We have then used a graph labeling method for vertex ordering in our graph embedding process. Finally, we employed deep neural network to learn the complex pattern of interacting pairs from embedded graphs. We show our approach is able to learn sophisticated drug-target topological features and outperforms other state-of-the-art approaches.ConclusionsThe proposed learning model on semi-bipartite graph model, can integrate drug-drug and protein-protein similarities which are semantically different than drug-protein information in a drug-target interaction network. We show our model can determine interaction likelihood for each drug-target pair and outperform other heuristics.
Enhanced tolerance to Phytophthora root and stem rot by over-expression of the plant antimicrobial peptide CaAMP1 gene in soybean
Authors: Niu Lu , Zhong Xiaofang , Zhang Yuanyu , Yang Jing , Xing Guojie , Li Haiyun , Liu Dongbo , Ma Rui , Dong Yingshan , Yang Xiangdong 
Published: July 2020

Abstract
Background
Antimicrobial peptides play important roles in both plant and animal defense systems. Moreover, over-expression of CaAMP1 (Capsicum annuum antimicrobial protein 1), an antimicrobial protein gene isolated from C. annuum leaves infected with Xanthomonas campestris pv. vesicatoria, confers broad-spectrum resistance to hemibiotrophic bacterial and necrotrophic fungal pathogens in Arabidopsis. Phytophthora root and stem rot (PRR), caused by the fungus Phytophthora sojae, is one of the most devastating diseases affecting soybean (Glycine max) production worldwide.

Results
In this study, CaAMP1 was transformed into soybean by Agrobacterium-mediated genetic transformation. Integration of the foreign gene in the genome of transgenic soybean plants and its expression at the translation level were verified by Southern and western blot analyses, respectively. CaAMP1 over-expression (CaAMP1-OX) lines inoculated with P. sojae race 1 exhibited enhanced and stable PRR tolerance through T2–T4 generations compared with the wild-type Williams 82 plants. Gene expression analyses in the transgenic plants revealed that the expression of salicylic acid-dependent, jasmonic acid-dependent, and plant disease resistance genes (R-genes) were significantly up-regulated after P. sojae inoculation.

Conclusions
These results indicate that CaAMP1 over-expression can significantly enhance PRR tolerance in soybean by eliciting resistance responses mediated by multiple defense signaling pathways. This provides an alternative approach for developing soybean varieties with improved tolerance against soil-borne pathogenic PRR.
RNA-Seq of three free-living flatworm species suggests rapid evolution of reproduction-related genes
Authors: Brand Jeremias N. , Wiberg R. Axel W. , Pjeta Robert , Bertemes Philip , Beisel Christian , Ladurner Peter , Schärer Lukas 
Published: July 2020

AbstractBackgroundThe genusMacrostomumconsists of small free-living flatworms and containsMacrostomum lignano, which has been used in investigations of ageing, stem cell biology, bioadhesion, karyology, and sexual selection in hermaphrodites. Two types of mating behaviour occur within this genus. Some species, includingM. lignano, mate via reciprocal copulation, where, in a single mating, both partners insert their male copulatory organ into the female storage organ and simultaneously donate and receive sperm. Other species mate via hypodermic insemination, where worms use a needle-like copulatory organ to inject sperm into the tissue of the partner. These contrasting mating behaviours are associated with striking differences in sperm and copulatory organ morphology. Here we expand the genomic resources within the genus to representatives of both behaviour types and investigate whether genes vary in their rate of evolution depending on their putative function.ResultsWe present de novo assembled transcriptomes of threeMacrostomumspecies, namelyM. hystrix, a close relative ofM. lignanothat mates via hypodermic insemination,M. spirale, a more distantly related species that mates via reciprocal copulation, and finallyM. pusillum, which represents a clade that is only distantly related to the other three species and also mates via hypodermic insemination. We infer 23,764 sets of homologous genes and annotate them using experimental evidence fromM. lignano. Across the genus, we identify 521 gene families with conserved patterns of differential expression between juvenile vs. adult worms and 185 gene families with a putative expression in the testes that are restricted to the two reciprocally mating species. Further, we show that homologs of putative reproduction-related genes have a higher protein divergence across the four species than genes lacking such annotations and that they are more difficult to identify across the four species, indicating that these genes evolve more rapidly, while genes involved in neoblast function are more conserved.ConclusionsThis study improves the genusMacrostomumas a model system, by providing resources for the targeted investigation of gene function in a broad range of species. And we, for the first time, show that reproduction-related genes evolve at an accelerated rate in flatworms.
Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors
Authors: Labadie Julia D. , Elvers Ingegerd , Feigelson Heather Spencer , Magzamen Sheryl , Yoshimoto Janna , Dossey Jeremy , Burnett Robert , Avery Anne C. 
Published: July 2020

Abstract
Background
T zone lymphoma (TZL), a histologic variant of peripheral T cell lymphoma, represents about 12% of all canine lymphomas. Golden Retrievers appear predisposed, representing over 40% of TZL cases. Prior research found that asymptomatic aged Golden Retrievers frequently have populations of T zone-like cells (phenotypically identical to TZL) of undetermined significance (TZUS), potentially representing a pre-clinical state. These findings suggest a genetic risk factor for this disease and caused us to investigate potential genes of interest using a genome-wide association study of privately-owned U.S. Golden Retrievers.

Results
Dogs were categorized as TZL (n = 95), TZUS (n = 142), or control (n = 101) using flow cytometry and genotyped using the Illumina CanineHD BeadChip. Using a mixed linear model adjusting for population stratification, we found association with genome-wide significance in regions on chromosomes 8 and 14. The chromosome 14 peak included four SNPs (Odds Ratio = 1.18–1.19, p = .3 × 10− 5–5.1 × 10− 5) near three hyaluronidase genes (SPAM1, HYAL4, and HYALP1). Targeted resequencing of this region using a custom sequence capture array identified missense mutations in all three genes; the variant in SPAM1 was predicted to be damaging. These mutations were also associated with risk for mast cell tumors among Golden Retrievers in an unrelated study. The chromosome 8 peak contained 7 SNPs (Odds Ratio = 1.24–1.42, p = 2.7 × 10− 7–7.5 × 10− 5) near genes involved in thyroid hormone regulation (DIO2 and TSHR). A prior study from our laboratory found hypothyroidism is inversely associated with TZL risk. No coding mutations were found with targeted resequencing but identified variants may play a regulatory role for all or some of the genes.

Conclusions
The pathogenesis of canine TZL may be related to hyaluronan breakdown and subsequent production of pro-inflammatory and pro-oncogenic byproducts. The association on chromosome 8 may indicate thyroid hormone is involved in TZL development, consistent with findings from a previous study evaluating epidemiologic risk factors for TZL. Future work is needed to elucidate these mechanisms.
Pervasive duplication, biased molecular evolution and comprehensive functional analysis of the PP2C family in Glycine max
Authors: Fan Kai , Chen Yunrui , Mao Zhijun , Fang Yao , Li Zhaowei , Lin Weiwei , Zhang Yongqiang , Liu Jianping , Huang Jinwen , Lin Wenxiong 
Published: July 2020

AbstractBackgroundSoybean (Glycine max) is an important oil provider and ecosystem participant. The protein phosphatase 2C (PP2C) plays important roles in key biological processes. Molecular evolution and functional analysis of the PP2C family in soybean are yet to be reported.ResultsThe present study identified 134 GmPP2Cs with 10 subfamilies in soybean. Duplication events were prominent in the GmPP2C family, and all duplicated gene pairs were involved in the segmental duplication events. The legume-common duplication event and soybean-specific tetraploid have primarily led to expanding GmPP2C members in soybean. Sub-functionalization was the main evolutionary fate of duplicated GmPP2C members. Meanwhile, massive genes were lost in the GmPP2C family, especially from the F subfamily. Compared with other genes, the evolutionary rates were slower in the GmPP2C family. The PP2C members from the H subfamily resembled their ancestral genes. In addition, some GmPP2Cs were identified as the putative key regulator that could control plant growth and development.ConclusionsA total of 134 GmPP2Cs were identified in soybean, and their expansion, molecular evolution and putative functions were comprehensively analyzed. Our findings provided the detailed information on the evolutionary history of the GmPP2C family, and the candidate genes can be used in soybean breeding.
Prognostic role of red blood cell distribution width in patients with sepsis: a systematic review and meta-analysis
Authors: Zhang Lin , Yu Cui-hua , Guo Kuan-peng , Huang Cai-zhi , Mo Li-ya 
Published: July 2020

Abstract
Background
Outcome prediction for patients with sepsis may be conductive to early aggressive interventions. Numerous biomarkers and multiple scoring systems have been utilized in predicting outcomes, however, these tools were either expensive or inconvenient.
We performed a meta-analysis to evaluate the prognostic role of red blood cell distribution width (RDW) in patients with sepsis.

Methods
The online databases of Embase, Web of science, Pubmed, Corchrane library, Chinese Wanfang database, CNKI database were systematically searched from the inception dates to June, 24th, 2020, using the keywords red cell distribution width and sepsis. The odds ratio (OR) or Hazards ratio (HR) with corresponding 95% confidence intervals (95%CI) were pooled to evaluate the association between baseline RDW and sepsis. A random-effects model was used to pool the data, and statistical heterogeneity between studies was evaluated using the I2 statistic. Sensitivity and subgroup analyses were performed to detect the publication bias and origin of heterogeneity.

Results
Eleven studies with 17,961 patients with sepsis were included in the meta-analysis. The pooled analyses indicated that increased baseline RDW was associated with mortality (HR = 1.14, 95%CI 1.09–1.20, Z = 5.78, P < 0.001) with significant heterogeneity (I2 = 80%, Pheterogeneity < 0.001). Similar results were found in the subgroup analysis stratified by site of infection, comorbidity, Newcastle-Ottawa Scale (NOS) score, study design, patients’ country. The predefined subgroup analysis showed that NOS score may be the origin of heterogeneity.

Conclusions
For patients with sepsis, baseline RDW may be a useful predictor of mortality, patients with increased RDW are more likely to have higher mortality.
Effects of red and blue light on leaf anatomy, CO2 assimilation and the photosynthetic electron transport capacity of sweet pepper (Capsicum annuum L.) seedlings
Authors: Li Yan , Xin Guofeng , Liu Chang , Shi Qinghua , Yang Fengjuan , Wei Min 
Published: July 2020

Abstract
Background
The red (R) and blue (B) light wavelengths are known to influence many plant physiological processes during growth and development, particularly photosynthesis. To understand how R and B light influences plant photomorphogenesis and photosynthesis, we investigated changes in leaf anatomy, chlorophyll fluorescence and photosynthetic parameters, and ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) and Calvin cycle-related enzymes expression and their activities in sweet pepper (Capsicum annuum L.) seedlings exposed to four light qualities: monochromatic white (W, control), R, B and mixed R and B (RB) light with the same photosynthetic photon flux density (PPFD) of 300 μmol/m2·s.

Results
The results revealed that seedlings grown under R light had lower biomass accumulation, CO2 assimilation and photosystem II (PSII) electron transportation compared to plants grown under other treatments. These changes are probably due to inactivation of the photosystem (PS). Biomass accumulation and CO2 assimilation were significantly enriched in B- and RB-grown plants, especially the latter treatment. Their leaves were also thicker, and photosynthetic electron transport capacity, as well as the photosynthetic rate were enhanced. The up-regulation of the expression and activities of Rubisco, fructose-1, 6-bisphosphatase (FBPase) and glyceraldehyde-phosphate dehydrogenase (GAPDH), which involved in the Calvin cycle and are probably the main enzymatic factors contributing to RuBP (ribulose-1, 5-bisphosphate) synthesis, were also increased.

Conclusions
Mixed R and B light altered plant photomorphogenesis and photosynthesis, mainly through its effects on leaf anatomy, photosynthetic electron transportation and the expression and activities of key Calvin cycle enzymes.
Inhibition of multiple defense responsive pathways by CaWRKY70 transcription factor promotes susceptibility in chickpea under Fusarium oxysporum stress condition
Authors: Chakraborty Joydeep , Sen Senjuti , Ghosh Prithwi , Jain Akansha , Das Sampa 
Published: July 2020

Abstract
Background
Suppression and activation of plant defense genes is comprehensively regulated by WRKY family transcription factors. Chickpea, the non-model crop legume suffers from wilt caused by Fusarium oxysporum f. sp. ciceri Race1 (Foc1), defense response mechanisms of which are poorly understood. Here, we attempted to show interaction between WRKY70 and several downstream signaling components involved in susceptibility/resistance response in chickpea upon challenge with Foc1.

Results
In the present study, we found Cicer arietinum L. WRKY70 (CaWRKY70) negatively governs multiple defense responsive pathways, including Systemic Acquired Resistance (SAR) activation in chickpea upon Foc1 infection. CaWRKY70 is found to be significantly accumulated at shoot tissues of susceptible (JG62) chickpea under Foc1 stress and salicylic acid (SA) application. CaWRKY70 overexpression promotes susceptibility in resistant chickpea (WR315) plants to Foc1 infection. Transgenic plants upon Foc1 inoculation demonstrated suppression of not only endogenous SA concentrations but expression of genes involved in SA signaling. CaWRKY70 overexpressing chickpea roots exhibited higher ion-leakage and Foc1 biomass accumulation compared to control transgenic (VC) plants. CaWRKY70 overexpression suppresses H2O2 production and resultant reactive oxygen species (ROS) induced cell death in Foc1 infected chickpea roots, stem and leaves. Being the nuclear targeted protein, CaWRKY70 suppresses CaMPK9-CaWRKY40 signaling in chickpea through its direct and indirect negative regulatory activities. Protein-protein interaction study revealed CaWRKY70 and CaRPP2-like CC-NB-ARC-LRR protein suppresses hyper-immune signaling in chickpea. Together, our study provides novel insights into mechanisms of suppression of the multiple defense signaling components in chickpea by CaWRKY70 under Foc1 stress.

Conclusion
CaWRKY70 mediated defense suppression unveils networking between several immune signaling events negatively affecting downstream resistance mechanisms in chickpea under Foc1 stress.
Physical activity and the risk of sudden cardiac death: a systematic review and meta-analysis of prospective studies
Authors: Aune Dagfinn , Schlesinger Sabrina , Hamer Mark , Norat Teresa , Riboli Elio 
Published: July 2020

Abstract
Background
Physical activity has been associated with a significant reduction in risk of sudden cardiac death in epidemiological studies, however, the strength of the association needs clarification. We conducted a systematic review and meta-analysis to summarize the available data from population-based prospective studies.

Methods
PubMed and Embase databases were searched for studies of physical activity and sudden cardiac death from inception to March 26th 2019. Prospective studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of sudden cardiac death associated with physical activity were included. A random effects model was used to estimate summary RRs (95% CIs).

Results
Thirteen prospective studies were included in the systematic review. Eight prospective studies with 1193 sudden cardiac deaths among 136,298 participants were included in the meta-analysis of physical activity and sudden cardiac death and the summary RR for highest vs. lowest level of physical activity was 0.52 (95% CI: 0.45–0.60, I2 = 0%, pheterogeneity = 0.72). The association was similar in men and women and among American and European studies. In the dose-response analysis the summary RR was 0.68 (95% CI: 0.55–0.86, I2 = 44%, n = 3) per 20 MET-hours/week. Although the test for nonlinearity was not significant, pnonlinearity = 0.18, there was no further reduction in risk beyond 20–25 MET-hours/week. The summary RR was 0.58 (95% CI: 0.41–0.81, I2 = 0%, pheterogeneity = 0.65, n = 2) for the highest vs. the lowest level of cardiorespiratory fitness.

Conclusion
This meta-analysis suggest that a high compared to a low level of physical activity may reduce the risk of sudden cardiac death in the general population. Further studies are needed to clarify the dose-response relationship between specific subtypes and intensities of physical activity in relation to sudden cardiac death.
Identification of candidate genes in ischemic cardiomyopathy by gene expression omnibus database
Authors: Dang Haiming , Ye Yicong , Zhao Xiliang , Zeng Yong 
Published: July 2020

AbstractBackgroundIschemic cardiomyopathy (ICM) is one of the most usual causes of death worldwide. This study aimed to find the candidate gene for ICM.MethodsWe studied differentially expressed genes (DEGs) in ICM compared to healthy control. According to these DEGs, we carried out the functional annotation, protein-protein interaction (PPI) network and transcriptional regulatory network constructions. The expression of selected candidate genes were confirmed using a published dataset and Quantitative real time polymerase chain reaction (qRT-PCR).ResultsFrom three Gene Expression Omnibus (GEO) datasets, we acquired 1081 DEGs (578 up-regulated and 503 down-regulated genes) between ICM and healthy control. The functional annotation analysis revealed that cardiac muscle contraction, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy were significantly enriched pathways in ICM. SNRPB, BLM, RRS1, CDK2, BCL6, BCL2L1, FKBP5, IPO7, TUBB4B and ATP1A1 were considered the hub proteins. PALLD, THBS4, ATP1A1, NFASC, FKBP5, ECM2 and BCL2L1 were top six transcription factors (TFs) with the most downstream genes. The expression of 6 DEGs (MYH6, THBS4, BCL6, BLM, IPO7 and SERPINA3) were consistent with our integration analysis and GSE116250 validation results.ConclusionsThe candidate DEGs and TFs may be related to the ICM process. This study provided novel perspective for understanding mechanism and exploiting new therapeutic means for ICM.
Multi-state analysis of hypertension and mortality: application of semi-Markov model in a longitudinal cohort study
Authors: Ramezankhani Azra , Blaha Michael J. , Mirbolouk Mohammad hassan , Azizi Fereidoun , Hadaegh Farzad 
Published: July 2020

Abstract
Background
Most previous research has studied the association of hypertension with cardiovascular disease (CVD) and all-cause mortality by focusing on the transition from the initial state to a single outcome. We investigated the impact of hypertension, defined according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) (new) and the Seventh Report of the Joint National Committee (JNC7) (old), on CVD death and all-cause mortality considering non-fatal CVD as an intermediate event between two CVD-free and mortality states.

Methods
A total of 3002 Iranian population (47.4% men), aged ≥50 years were followed from 1999 to 2014. Two multi-state semi-Markov models with three transitions were defined for CVD death and all-cause mortality as two outcomes. The multivariable Cox model was used to estimate the effect of hypertension on transition hazards. The mean of 15-year life expectancy of participants in each transition was estimated using the restricted mean survival time.

Results
The ACC/AHA guideline increased the prevalence of hypertension from 43.3 to 68.6%. Among CVD-free individuals, hypertension was significantly associated with increased risk of non-fatal CVD [Hazard Ratio, 1.52 (1.28–1.81) and 1.48 (1.21–1.80)], CVD death [2.96 (2.06–4.25) and 1.98 (1.30–3.04)] and all-cause mortality [1.64 (1.32–2.05) and 1.31 (1.01–1.69)] according the old and new guidelines, respectively. However, after incident non-fatal CVD, the association between hypertension and mortality events was not significant according to both definitions. Hypertensive participants experienced a first non-fatal CVD about 0.9 and 0.6 years earlier than normotensive population according to JNC7 and the 2017 ACC/AHA guidelines, respectively.

Conclusion
Hypertension, according to JNC7 and the ACC/AHA guidelines, significantly increased the risk of mortality events among CVD-free population although the risk was attenuated using ACC/AHA guideline. Hypertension also decreased the number of years lived without CVD and early onset of CVD, and consequently, an increase in the time spent with these diseases. After non-fatal CVD, hypertension had no significant impact on mortality risk according to both guidelines.