bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering the genetic mechanisms regulating panicle architecture in rice with GPWAS and GWAS
Authors: Zhong Hua , Liu Shuai , Meng Xiaoxi , Sun Tong , Deng Yujuan , Kong Weilong , Peng Zhaohua , Li Yangsheng 
Published: January 2021

Abstract
Background
The number of panicles per plant, number of grains per panicle, and 1000-grain weight are important factors contributing to the grain yield per plant in rice. The Rice Diversity Panel 1 (RDP1) contains a total of 421 purified, homozygous rice accessions representing diverse genetic variations within O. sativa. The release of High-Density Rice Array (HDRA, 700 k SNPs) dataset provides a new opportunity to discover the genetic variants of panicle architectures in rice.

Results
In this report, a new method genome-phenome wide association study (GPWAS) was performed with 391 individuals and 27 traits derived from RDP1 to scan the relationship between the genes and multi-traits. A total of 1985 gene models were linked to phenomic variation with a p-value cutoff of 4.49E-18. Besides, 406 accessions derived from RDP1 with 411,066 SNPs were used to identify QTLs associated with the total spikelets number per panicle (TSNP), grain number per panicle (GNP), empty grain number per panicle (EGNP), primary branch number (PBN), panicle length (PL), and panicle number per plant (PN) by GLM, MLM, FarmCPU, and BLINK models for genome-wide association study (GWAS) analyses. A total of 18, 21, 18, 17, 15, and 17 QTLs were identified tightly linked with TSNP, GNP, EGNP, PBN, PL, and PN, respectively. Then, a total of 23 candidate genes were mapped simultaneously using both GWAS and GPWAS methods, composed of 6, 4, 5, 4, and 4 for TSNP, GNP, EGNP, PBN, and PL. Notably, one overlapped gene (Os01g0140100) were further investigated based on the haplotype and gene expression profile, indicating this gene might regulate the TSNP or panicle architecture in rice.

Conclusions
Nearly 30 % (30/106) QTLs co-located with the previous published genes or QTLs, indicating the power of GWAS. Besides, GPWAS is a new method to discover the relationship between genes and traits, especially the pleiotropy genes. Through comparing the results from GWAS and GPWAS, we identified 23 candidate genes related to panicle architectures in rice. This comprehensive study provides new insights into the genetic basis controlling panicle architectures in rice, which lays a foundation in rice improvement.
Whole-genome characterization of Rosa chinensis AP2/ERF transcription factors and analysis of negative regulator RcDREB2B in Arabidopsis
Authors: Li Wei , Geng Ziwen , Zhang Cuiping , Wang Kuiling , Jiang Xinqiang 
Published: January 2021

Abstract
Background
Rose (Rosa chinensis) is a traditional famous flower with valuable ornamental characteristics. However, drought stress restricts its growth and development, leading to an abnormal phenotype. One of the main transcription factor (TF) protein groups in the plant kingdom are the APETALA2/ethylene-responsive factor (AP2/ERF) proteins and are potentially involved in the growth and stress responses of various plants.

Results
Our investigation mainly focused on exploring the genome of rose and thereby we discovered 135 apparent AP2/ERF TFs. Phylogenic analyses revealed that RcAP2/ERF genes are categorized into DREB, Soloist, AP2, and ERF subfamilies, and are further classified these into 17 groups, with the same as Malus domestica and Arabidopsis thaliana. The analysis of the gene structure revealed that the introns ranged from 0 to 9 in number. Pattern examination demonstrated that the RcAP2/ERF predominantly consists of typical AP2 domains, of which the 2nd motif is the most ubiquitous. Distributions of cis-acting elements indicated that members of the AP2/ERF family are frequently involved in growth and development, phytohormone and stress response in rose species. Also, the distribution mapping of the rose chromosomes indicated that AP2/ERF class genes are dispersed among all seven chromosomes. Additionally, we isolated a novel DREB A2 subgroup gene and named it RcDREB2B. Subsequently, the RcDREB2B transcript accumulation was repressed under the mild and severe drought stress in the root samples of rose. RcDREB2B was targeted to the nucleus and exhibited transactivation in yeast cells. The overexpression of RcDREB2B was found to promote sensitivity to a higher salt concentration, ABA, and PEG at the germination and post-germination stages. Twelve putative osmotic and ABA-related genes were impaired in RcDREB2B-overexpressing plants.

Conclusions
The results provide comprehensive information regarding the gene structure, phylogenic, and distribution of the rose AP2/ERF family and bring insight into the complex transcriptional gene regulation of RcAP2/ERF. Findings in this study would also contribute to further understanding of the RcDREB2B gene in rose.
Analysis of histology and long noncoding RNAs involved in the rabbit hair follicle density using RNA sequencing
Authors: Ding Haisheng , Zhao Huiling , Zhao Xiaowei , Qi Yunxia , Wang Xiaofei , Huang Dongwei 
Published: January 2021

AbstractBackgroundHair follicle density influences wool fibre production, which is one of the most important traits of the Wan Strain Angora rabbit. However, molecular mechanisms regulating hair follicle density have remained elusive.ResultsIn this study, hair follicle density at different body sites of Wan Strain Angora rabbits with high and low wool production (HWP and LWP) was investigated by histological analysis. Haematoxylin-eosin staining showed a higher hair follicle density in the skin of the HWP rabbits. The long noncoding RNA (lncRNA) profile was investigated by RNA sequencing, and 50 and 38 differentially expressed (DE) lncRNAs and genes, respectively, were screened between the HWP and LWP groups. A gene ontology analysis revealed that phospholipid, lipid metabolic, apoptotic, lipid biosynthetic, and lipid and fatty acid transport processes were significantly enriched. Potential functional lncRNAs that regulate lipid metabolism, amino acid synthesis, as well as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and hedgehog signalling pathways, were identified. Consequently, five lncRNAs (LNC_002171, LNC_000797, LNC_005567, LNC_013595, and LNC_020367) were considered to be potential regulators of hair follicle density and development. Three DE lncRNAs and genes were validated by quantitative real-time polymerase chain reaction (q-PCR).ConclusionsLncRNA profiles provide information on lncRNA expression to improve the understanding of molecular mechanisms involved in the regulation of hair follicle density.
Ex vivo mRNA expression of toll-like receptors during latent tuberculosis infection
Authors: Alemnew Birhan , Hoff Soren T. , Abebe Tamrat , Abebe Markos , Aseffa Abraham , Howe Rawleigh , Wassie Liya 
Published: January 2021

Abstract
Background
Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their roles as potential diagnostic biomarkers.

Methods
Messenger RNA (mRNA) levels were analysed in a total of 64 samples collected from apparently healthy children and adolescents latently infected with tuberculosis (n = 32) or non-infected (n = 32). Relative expression in peripheral blood of selected genes encoding TLRs (TLR-1, TLR-2, TLR-4, TLR-6 and TLR-9) was determined with a quantitative real-time polymerase chain reaction (qRT-PCR) using specific primers and florescent labelled probes and a comparative threshold cycle method to define fold change. Data were analysed using Graph-Pad Prism 7.01 for Windows and a p-value less than 0.05 was considered statistically significant.

Results
An increased mean fold change in the relative expression of TLR-2 and TLR-6 mRNA was observed in LTBI groups relative to non-LTBI groups (p < 0.05), whereas a slight fold decrease was observed for TLR-1 gene.

Conclusions
An increased mRNA expression of TLR-2 and TLR-6 was observed in latently infected individuals relative to those non-infected, possibly indicating the roles these biomarkers play in sustenance of the steady state interaction between the dormant TB bacilli and host immunity.
Application of imiquimod-induced murine psoriasis model in evaluating interleukin-17A antagonist
Authors: Li Qingran , Liu Weiping , Gao Shidong , Mao Yao , Xin Yanfei 
Published: January 2021

Abstract
Background
Interleukin-17A (IL17A) is a proinflammatory cytokine critically involved in autoimmune diseases, and monoclonal antibodies of IL17A have been approved for clinical treatment of psoriasis. However, a usable psoriatic animal model has been always required for preclinical evaluation of IL17A antagonists. Imiquimod (IMQ)-induced psoriasis model is widely used in fundamental research, but it’s not able to accurately show anti-psoriatic effect of IL17A antagonists with conventional modelling condition.

Results
On female C57BL/6 mice, with optimization on the usage of IMQ, positive control reagent and anti-mIL17A antibody, a 7-day model with proper testing window, acceptable disease severity as well as high repeatability was developed, and the efficacy of IL17A antagonist can be objectively evaluated by several qualitative and quantitative indices. Meanwhile, we validated the detailed involvement of IL17A signaling in disease progression, confirmed that the expression levels of IL17A and its related cytokines were induced by IMQ application, and its downstream cytokines can be inhibited by IL17A antagonist treatment. In further study, we revealed that IL17A was transient induced by IMQ and directly caused downstream signaling activation. This finding on the kinetical change of IL17A signaling will manifest the pharmacokinetics-pharmacodynamics investigation of IL17A antagonists.

Conclusions
Our work presents the application of a convenient psoriatic animal model in the research and development of IL17A antagonists, meanwhile providing extra evidence for understanding IL17A’s role in the progression of IMQ-induced psoriasis model, which manifest the research and development of IL17A antagonists.
Integrative transcriptomic, proteomic, and machine learning approach to identifying feature genes of atrial fibrillation using atrial samples from patients with valvular heart disease
Authors: Liu Yaozhong , Bai Fan , Tang Zhenwei , Liu Na , Liu Qiming 
Published: January 2021

Abstract
Background
Atrial fibrillation (AF) is the most common arrhythmia with poorly understood mechanisms. We aimed to investigate the biological mechanism of AF and to discover feature genes by analyzing multi-omics data and by applying a machine learning approach.

Methods
At the transcriptomic level, four microarray datasets (GSE41177, GSE79768, GSE115574, GSE14975) were downloaded from the Gene Expression Omnibus database, which included 130 available atrial samples from AF and sinus rhythm (SR) patients with valvular heart disease. Microarray meta-analysis was adopted to identified differentially expressed genes (DEGs). At the proteomic level, a qualitative and quantitative analysis of proteomics in the left atrial appendage of 18 patients (9 with AF and 9 with SR) who underwent cardiac valvular surgery was conducted. The machine learning correlation-based feature selection (CFS) method was introduced to selected feature genes of AF using the training set of 130 samples involved in the microarray meta-analysis. The Naive Bayes (NB) based classifier constructed using training set was evaluated on an independent validation test set GSE2240.

Results
863 DEGs with FDR < 0.05 and 482 differentially expressed proteins (DEPs) with FDR < 0.1 and fold change > 1.2 were obtained from the transcriptomic and proteomic study, respectively. The DEGs and DEPs were then analyzed together which identified 30 biomarkers with consistent trends. Further, 10 features, including 8 upregulated genes (CD44, CHGB, FHL2, GGT5, IGFBP2, NRAP, SEPTIN6, YWHAQ) and 2 downregulated genes (TNNI1, TRDN) were selected from the 30 biomarkers through machine learning CFS method using training set. The NB based classifier constructed using the training set accurately and reliably classify AF from SR samples in the validation test set with a precision of 87.5% and AUC of 0.995.

Conclusion
Taken together, our present work might provide novel insights into the molecular mechanism and provide some promising diagnostic and therapeutic targets of AF.
The association between serum copper concentrations and elevated blood pressure in US children and adolescents: National Health and Nutrition Examination Survey 2011–2016
Authors: Liu Changsong , Liao Yanfen , Zhu Zongyuan , Yang Lili , Zhang Qin , Li Li 
Published: January 2021

Abstract
Background
Copper is an essential trace metal with potential interest for cardiovascular effects. Few studies have explored the association between copper and blood pressure in children and adolescents.

Method
We conducted a cross-sectional analysis of 1242 children and adolescents aged 8–17 years who participated in the 2011 to 2016 National Health and Nutrition Examination Survey. Using 2017 American Academy of Pediatrics guidelines, elevated blood pressure (EBP) was defined as a mean systolic and/or diastolic blood pressure (BP) ≥ 90th percentile for sex, age, and height for children aged 1–12 years and systolic BP ≥ 120 mmHg or diastolic BP ≥ 80 mmHg for adolescent age 13–17 years. Mean serum copper was 114.17 μg/dL.

Results
After multiple adjustments, dose–response analyses revealed that EBP was associated with progressively higher serum copper concentrations in a nonlinear trend. In comparison with the lowest quartile of serum copper concentrations, the adjusted odds of EBP for the highest quartile was 5.26 (95% confidence interval, 2.76–10.03).

Conclusion
Our results suggested that high serum copper concentrations were significantly associated with EBP in US children and adolescents.
Dietary patterns and risk of non-alcoholic fatty liver disease
Authors: Salehi-sahlabadi Ammar , Sadat Samaneh , Beigrezaei Sara , Pourmasomi Makan , Feizi Awat , Ghiasvand Reza , Hadi Amir , Clark Cain C. T. , Miraghajani Maryam 
Published: January 2021

AbstractBackgroundNutrition is a modifiable risk factor that plays an important role in the prevention or delaying of the onset of non-alcoholic fatty liver disease (NAFLD). Previous studies have focused on NAFLD and individual nutrients, which does not take into account combinations of food that are consumed. Therefore, we aimed to investigate the relationship between major dietary patterns and NAFLD.MethodsThis case–control study was conducted on 225 newly diagnosed NAFLD patients and 450 healthy controls. Usual dietary intake over the preceding year was assessed using a validated 168-item semi-quantitative food frequency questionnaire. Major dietary patterns were determined by exploratory factor analysis.ResultsThree dietary patterns, including "western dietary pattern", "healthy dietary pattern", and "traditional dietary pattern" were identified. Subjects in the highest tertile of healthy dietary pattern scores had a lower odds ratio for NAFLD than those in the lowest tertile. Compared with those in the lowest tertile, people in the highest tertile of “western dietary pattern” scores had greater odds for NAFLD. After adjusting for potential confounding factors, “western dietary pattern” had a positive significant effect on NAFLD occurrence. In contrast, “healthy dietary pattern” was associated with a decreased risk of NAFLD. Furthermore, Higher consumption of the “traditional dietary pattern” was significantly associated with NAFLD, albeit in the crude model only.ConclusionThis study indicated that healthy and western dietary patterns may be associated with the risk of NAFLD. The results can be used for developing interventions in order to promote healthy eating for the prevention of NAFLD.
Long‐term prognosis of enteral feeding and parenteral nutrition in a population aged 75 years and older: a population‐based cohort study
Authors: Tsugihashi Yukio , Akahane Manabu , Nakanishi Yasuhiro , Myojin Tomoya , Kubo Shinichiro , Nishioka Yuichi , Noda Tatsuya , Hayashi Shuichiro , Furihata Shiori , Higashino Tsuneyuki , Imamura Tomoaki 
Published: January 2021

Abstract
Background
Enteral feeding and parenteral nutrition (PN) using gastrostomy (GS) and a nasogastric tube feeding (NGT) and PN should be initiated for older patients based on their prognoses. This study aimed to investigate the long-term prognosis of patients aged ≥75 years who underwent enteral feeding via GS and NGT as well as PN.

Methods
A population-based cohort study was conducted using Japan’s universal health insurance claims in the Nara Prefecture. This study enrolled 3,548 patients aged ≥75 years who received GS (N=770), NGT (N=2,370), and PN (N=408) during hospital admissions between April 2014 and March 2016. The GS group was further categorized into secondary GS (N=400) with preceding NGT or PN within 365 days and primary GS (N=370) without preceding NGT or PN groups. In the secondary GS group, 356 (96%) patients received NGT (versus PN). The outcome was mortality within 730 days after receiving GS, NGT, and PN. Cox regression analyses in cases with or without malignant diseases, adjusted for sex, age, comorbidity, and hospital type, were performed to compare mortality in the groups.

Results
Of the 3,548 participants, 2,384 (67%) died within 730 days after the initiation of GS and NGT and PN. The 2-year mortality rates in the secondary GS, primary GS, NGT, and PN groups were 58%, 66%, 68%, and 83% in patients without malignancies and 67%, 71%, 74%, and 87% in those with malignancies, respectively. In the non-malignant group, Cox regression analysis revealed that secondary GS (hazard ratio (HR) = 0.43, 95% CI: 0.34–0.54), primary GS (HR = 0.51, 95% CI: 0.40–0.64), and NGT (HR = 0.71, 95% CI: 0.58-0.87) were statistically significantly associated with lower mortality compared with PN.

Conclusions
Approximately 58% to 87% patients aged ≥75 years died within 730 days after initiation of nutrition through GS, NGT, or PN. Patients with non-malignant diseases who received secondary GS exhibited better 2-year prognosis than those who received NGT or PN. Healthcare professionals should be aware of the effectiveness and limitations of enteral feeding and PN when considering their initiation.
Integrating Xpert MTB/RIF for TB diagnosis in the private sector: evidence from large-scale pilots in Patna and Mumbai, India
Authors: Deo Sarang , Jindal Pankaj , Papineni Sirisha 
Published: January 2021

Abstract
Background
Xpert MTB/RIF (Xpert) has been recommended by WHO as the initial diagnostic test for TB and rifampicin-resistance detection. Existing evidence regarding its uptake is limited to public health systems and corresponding resource and infrastructure challenges. It cannot be readily extended to private providers, who treat more than half of India’s TB cases and demonstrate complex diagnostic behavior.

Methods
We used routine program data collected from November 2014 to April 2017 from large-scale private sector engagement pilots in Mumbai and Patna. It included diagnostic vouchers issued to approximately 150,000 patients by about 1400 providers, aggregated to 18,890 provider-month observations. We constructed three metrics to capture provider behavior with regards to adoption of Xpert and studied their longitudinal variation: (i) Uptake (ordering of test), (ii) Utilization for TB diagnosis, and (iii) Non-adherence to negative results. We estimated multivariate linear regression models to assess heterogeneity in provider behavior based on providers’ prior experience and Xpert testing volumes.

Results
Uptake of Xpert increased considerably in both Mumbai (from 36 to 60.4%) and Patna (from 12.2 to 45.1%). However, utilization of Xpert for TB diagnosis and non-adherence to negative Xpert results did not show systematic trends over time. In regression models, cumulative number of Xpert tests ordered was significantly associated with Xpert uptake in Patna and utilization for diagnosis in Mumbai (p-value< 0.01). Uptake of Xpert and its utilization for diagnosis was predicted to be higher in high-volume providers compared to low-volume providers and this gap was predicted to widen over time.

Conclusions
Private sector engagement led to substantial increase in uptake of Xpert, especially among high-volume providers, but did not show strong evidence of Xpert results being integrated with TB diagnosis. Increasing availability and affordability of a technically superior diagnostic tool may not be sufficient to fundamentally change diagnosis and treatment of TB in the private sector. Behavioral interventions, specifically aimed at, integrating Xpert results into clinical decision making of private providers may be required to impact patient-level outcomes.
Gender difference in quality of life (QoL) among outpatients with schizophrenia in a tertiary care setting
Authors: Shafie Saleha , Samari Ellaisha , Jeyagurunathan Anitha , Abdin Edimansyah , Chang Sherilyn , Chong Siow Ann , Subramaniam Mythily 
Published: January 2021

Abstract
Background
Patients with mental illness report lower quality of life (QoL) compared to the general population. Prior research has found several differences in clinical features and experiences of male and female patients with schizophrenia. Given these differences, it is also important to explore if there are any gender differences in terms of their QoL. This study aimed to investigate differences in QoL between and within each gender among outpatients with schizophrenia in Singapore.

Methods
A total of 140 outpatients were recruited through convenience sampling at the Institute of Mental Health, Singapore. QoL was measured using the brief version of World Health Organization Quality of Life (WHOQOL-BREF) which consists of four domains: physical health, psychological health, social relationships, and environment. QoL scores of males and females were compared using independent t-tests, and multiple linear regressions were used to examine sociodemographic correlates of QoL in the overall sample and within each gender.

Results
There was no significant difference in QoL domain scores between genders. Among males, Indian ethnicity (versus Chinese ethnicity) was positively associated with physical health (β=3.03, p=0.018) while males having Technical Education/ Diploma/ A level education (versus Degree and above) were positively associated with social relationships domain (β=2.46, p=0.047).
Among females, Malay ethnicity (versus Chinese ethnicity) was positively associated with physical health (β=1.95, p=0.026) psychological health (β=3.21, p=0.001) social relationships (β=2.17, p=0.048) and environment (β=2.69, p=0.006) domains, while females who were separated/divorced (versus single) were inversely associated with psychological health (β=− 2.80, p=0.044) and social relationships domains (β=− 4.33, p=0.011). Females who had Secondary and below education (versus Degree and above) were inversely associated with social relationships (β=− 2.29, p=0.028) and environment domains (β=− 1.79, p=0.048).

Conclusions
The findings show the importance of treatments targeting QoL to attend to both the clinical features of the illness as well patient’s sociodemographic characteristics.