bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prominence of fossil energy resources in ecological sustainability of BRICS: The key role of institutional worth
Authors: Zhang Jie , Ullah Sami , Khan Karamat 
Published: January 2023

Introduction: The relationship between fossil fuel energy resources and environmental degradation has been quantified from theoretical and empirical perspectives. However, none of these studies has considered the conditioning role played by institutions in the nexus, especially for BRICS countries. Therefore, the current study examines the moderating role of institutional quality using annual data from 1996–2018 for BRICS countries.Method: The study employs the novel cross-sectional augmented autoregressive distributed lags (CS-ARDL) estimator, robust to cross-sectional dependency and heterogeneity, for short-run and long-run estimation. Moreover, augmented mean group (AMG) and common correlated effects mean group (CCEMG) estimators are used for robustness analysis.Results: The finding reveals that fossil fuel energy resources, globalization, and growth significantly positively affect the ecological footprint, whereas the institutional quality significantly negatively effects the ecological footprint in BRICS countries. Furthermore, the interaction term of institutional quality with fossil fuel energy resources significantly negatively moderates the fossil fuel energy-EFP nexus. Finally, we performed the Dumitrescu and Hurlin (DH) panel causality analysis to determine the causality direction between the variables. Except for intuitions quality and growth, we found a unidirectional causality for explanatory variables and EFP.Discussion: The study provides novel empirical evidence and recommends the importance of institutional quality for environmental sustainability.
Exploring the characteristics and driving forces of orchard expansion in ecological fragile region: A case study of three typical counties in the Loess Plateau
Authors: Hu Qiyuan , Gao Xiang , Wang Sijia , Wang Qihan , Qin Yuting , Zhang Weiyi , Lun Fei , Li Zhuo 
Published: January 2023

The Loess Plateau exemplifies the type of ecologically fragile region that faces severe poverty challenges in China. Orchards have expanded rapidly over the past few decades and now constitute a considerable part of local economy. Not only do the characteristics of orchard expansion affect local economic development, but also exert additional pressure on the ecological environment. Therefore, it is essential for sustainable development on the Loess Plateau to investigate the characteristics and driving forces of orchard expansion. The Fuxian, Luochuan, Huangling, three typical orchard planting counties were chosen as the study area. Firstly, the orchard was extracted from the land use/cover classification from 1990–2020. It broadens the research approach to the identification of expansion cash crops by using the combination of linear spectral mixture analysis (LSMA) and decision tree. Secondly, the spatiotemporal dynamics of orchard expansion were quantitatively investigated based on spatial geometry center shift, physical geographical features, landscape pattern and orchard planting suitability. Then, we constructed an evaluation indicators system to detect the feature importance and partial dependence of different factors by random forest regression. It is more innovative to employ the machine learning method to investigate driving forces. Finally, the linkages between planting suitability and orchard expansion were further discussed, and subsequent policies were proposed. Findings demonstrated the orchard had continuously expanded over the past 30 years, with the fastest expansion rate during 1990–2005. Increased cohesion was accompanied by a shift in the orchard’s spatial distribution to the north central region and highly suitable planting regions. Slope turned out to be the primary factor affecting the orchard expansion. In the future, regions with aging orchard but high planting suitability should be the preferred choice for orchard expansion. Additionally, the transportation connectivity and governmental assistance are crucial considerations for the future planning of the orchard.
Decomposing niche components reveals simultaneous effects of opposite deterministic processes structuring alpine small mammal assembly
Authors: Song Wen-Yu , Onditi Kenneth Otieno , Li Xue-You , Chen Zhong-Zheng , He Shui-Wang , Li Quan , Jiang Xue-Long 
Published: January 2023

IntroductionSpecies distribution in alpine areas is constrained by multiple abiotic and biotic stressors. This leads to discrepant assembly patterns between different locations and study objects as opposite niche-based processes—limiting similarity and habitat filtering—simultaneously structure communities, masking overall patterns. We aimed to address how these processes structure small mammal communities in the alpine tree line transition zone, one of the most distinct vegetation transitions between alpine and montane habitats.MethodsWe compiled a dataset of species checklist, phylogeny, and functional traits from field collection and published sources spanning 18 mountains in southwest China. We first examined hypothetical niche-based processes with frequently used phylogenetic and trait approaches using this dataset. The species traits were decomposed into different niche components to explore the respective effects of specific stressors. Indices representing evolutionary history, trait space, and pairwise species distance were estimated and compared with null model expectations. Linear mixed-effect models were used to assess the association patterns between diversity indices and elevation.ResultsThe results indicated that phylogenetic and functional richness were positively correlated with species richness. In contrast, distance-based indices were either negatively or weakly positively correlated with species richness. Null model analyses suggested no evidence of non-random phylogenetic or overall trait patterns. However, the resource acquisition niche tended to be more overdispersed (positive slopes), while the habitat affinity niche tended to be more clustered (negative slopes) beyond the high elevation tree line.DiscussionThese findings show that opposite niche-based processes simultaneously structure small mammal communities in alpine areas. Overall, the present study provides vital insights into the complexity of assembly processes in these habitats. It also highlights the importance of relating relevant traits to distinguish the influences of specific abiotic and biotic stressors.
The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study
Authors: Yu Xingxing , Zhang Yanyu , Lin Yuxiang , Zou Shuqing , Zhu Pingxiu , Song Mengjie , Fu Fangmeng , Yang Haomin 
Published: January 2023

Background: Despite the potential role of several chemokines in the migration of cytotoxic immune cells to prohibit breast cancer cell proliferation, a comprehensive view of chemokines and the risk and prognosis of breast cancer is scarce, and little is known about their causal associations.Methods: With a two-sample Mendelian randomization (MR) approach, genetic instruments associated with 30 plasma chemokines were created. Their genetic associations with breast cancer and its survival by molecular subtypes were extracted from the recent genome-wide association study of 133,384 breast cancer cases and 113,789 controls, with available survival information for 96,661 patients. We further tested the associations between the polygenic risk score (PRS) for chemokines and breast cancer in the UK Biobank cohort using logistic regression models, while the association with breast cancer survival was tested using Cox regression models. In addition, the association between chemokine expression in tumors and breast cancer survival was also analyzed in the TCGA cohort using Cox regression models.Results: Plasma CCL5 was causally associated with breast cancer in the MR analysis, which was significant in the luminal and HER-2 enriched subtypes and further confirmed using PRS analysis (OR = 0.94, 95% CI = 0.89–1.00). A potential causal association with breast cancer survival was only found for plasma CCL19, especially for ER-positive patients. Although not replicated in the UK Biobank, we still found an inverse association between CCL19 expression in tumors and breast cancer overall and relapse-free survival in the TCGA cohort (HR = 0.58, 95% CI = 0.35–0.95).Conclusion: We observed an inverse association between genetic predisposition to CCL5 and breast cancer, while CCL19 was associated with breast cancer survival. These associations suggested the potential of these chemokines as tools for breast cancer prevention and treatment.
Development and validation of a prognostic prediction model for iron metabolism-related genes in patients with pancreatic adenocarcinoma
Authors: Wei Wenhan , Cao Bin , Xu Dongchao , Liu Yusheng , Zhang Xiaofeng , Wang Yu 
Published: January 2023

Background: Pancreatic adenocarcinoma (PAAD) is one of the most aggressive tumors of the digestive tract, with low surgical resection rate and insensitivity to radiotherapy and chemotherapy. Existing evidence suggests that regulation of ferroptosis can induce PAAD cell death, inhibit tumor growth, and may synergistically improve the sensitivity of other antitumor drugs. However, there is little of systematic research on iron metabolism-related genes in PAAD. In this study, a risk-score system of PAAD iron metabolism-related genes was designed and tested, and verified to be robust.Materials and Methods: The TCGA database was used to download 177 PAAD patients’ message RNA (mRNA) expression profiles and clinical characteristics. By identifying dysregulated iron metabolism-related genes between PAAD related tissues and adjacent normal tissues, univariate Cox proportional hazards regression and LASSO regression algorithm were used to establish prognostic risk-score system and construct nomogram to estimate the 1-, 2-, 3-year survival in PAAD patients. Finally, selected genes were validated by quantitative PCR (q-PCR).Results: A 9-gene related to iron metabolism risk-score system of PAAD was constructed and validated. The clinicopathological characteristics of age, histologic grade, pathologic stage, T stage, residual tumor, and primary therapy outcome were all worse in patients with a higher risk-score. Further, immunohistochemistry results of SLC2A1, MBOAT2, XDH, CTSE, MOCOS, and ATP6V0A4 confirmed that patients with higher expression are more malignant. Then, a nomogram with 9-gene risk score system as a separate clinical factor was utilized to foretell the 1-, 2-, 3-year overall survival rate of PAAD patients. Results of q-PCR showed that 8 of the 9 genes screened were significantly up-regulated in at least one PAAD cell line, and one gene was significantly down-regulated in three PAAD cell lines.Conclusion: To conclude, we generated a nine-gene system linked to iron metabolism as an independent indicator for predicting PAAD prognosis, therefore presenting a possible prognostic biomarker and potential treatment targets for PAAD.
Gastroesophageal reflux disease and oral symptoms: A two-sample Mendelian randomization study
Authors: Jiang Shijing , Zheng Liang , Miao Zhiwei 
Published: January 2023

Background: The association between Gastroesophageal reflux disease (GERD) and oral symptoms has been reported in observational studies, but the causality of GERD to oral symptoms remained unknown. We aimed to assess the causal effect of GERD on five oral symptoms (mouth ulcers, toothache, loose teeth, bleeding gums, and periodontitis) using the two-sample Mendelian randomization (MR) method.Methods: Summary-level statistics for GERD and five oral symptoms were obtained from large-scale genome-wide association studies. Rigorous quality control of genetic instruments was conducted before MR analysis. Several analytical methods, including the inverse-variance weighted (IVW) method, MR-Egger regression, weighted median, maximum likelihood, and robust adjusted profile score (RAPS) were utilized, and the results of IVW were taken as the main results. The MR-Egger intercept test, Cochran’s Q test, and leave-one-out test were used as sensitivity analysis for quality control.Results: After Bonferroni, IVW detected a significant effect of GERD on mouth ulcers (OR = 1.008, 95% CI = 1.003–1.013, p = 0.003), loose teeth (OR = 1.009, 95% CI = 1.005–1.012, p = 9.20 × 10−7), and periodontitis (OR = 1.229, 95% CI = 1.081–1.398, p = 0.002). Consistent patterns of associations were observed across several MR models and sensitivity analysis found little evidence of bias. Nominal significant associations were observed in toothache and bleeding gums (p &lt; 0.05), and heterogeneity was detected.Conclusion: Our MR analyses supported the positive causal effect of GERD on oral symptoms, especially for mouth ulcers, loose teeth, and periodontitis. Our findings might shed light on the mechanism of oral disease and might imply that oral care should be enhanced in patients with GERD.
Inference of gene-environment interaction from heterogeneous case-parent trios
Authors: Ratnasekera Pulindu , Graham Jinko , McNeney Brad 
Published: January 2023

Introduction: In genetic epidemiology, log-linear models of population risk may be used to study the effect of genotypes and exposures on the relative risk of a disease. Such models may also include gene-environment interaction terms that allow the genotypes to modify the effect of the exposure, or equivalently, the exposure to modify the effect of genotypes on the relative risk. When a measured test locus is in linkage disequilibrium with an unmeasured causal locus, exposure-related genetic structure in the population can lead to spurious gene-environment interaction; that is, to apparent gene-environment interaction at the test locus in the absence of true gene-environment interaction at the causal locus. Exposure-related genetic structure occurs when the distributions of exposures and of haplotypes at the test and causal locus both differ across population strata. A case-parent trio design can protect inference of genetic main effects from confounding bias due to genetic structure in the population. Unfortunately, when the genetic structure is exposure-related, the protection against confounding bias for the genetic main effect does not extend to the gene-environment interaction term.Methods: We show that current methods to reduce the bias in estimated gene-environment interactions from case-parent trio data can only account for simple population structure involving two strata. To fill this gap, we propose to directly accommodate multiple population strata by adjusting for genetic principal components (PCs).Results and Discussion: Through simulations, we show that our PC adjustment maintains the nominal type-1 error rate and has nearly identical power to detect gene-environment interaction as an oracle approach based directly on population strata. We also apply the PC-adjustment approach to data from a study of genetic modifiers of cleft palate comprised primarily of case-parent trios of European and East Asian ancestry. Consistent with earlier analyses, our results suggest that the gene-environment interaction signal in these data is due to the self-reported European trios.
A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma
Authors: Yang Yanbing , Ye Xuenian , Zhang Haibin , Lin Zhaowang , Fang Min , Wang Jian , Yu Yuyan , Hua Xuwen , Huang Hongxuan , Xu Weifeng , Liu Ling , Lin Zhan 
Published: January 2023

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies with increasing incidence worldwide. The oncogenic roles of transcription factors (TFs) were increasingly recognized in various cancers. This study aimed to develop a predicting signature based on TFs for the prognosis and treatment of HCC.Methods: Differentially expressed TFs were screened from data in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Univariate and multivariate Cox regression analyses were applied to establish a TF-based prognostic signature. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the signature. Subsequently, correlations of the risk model with clinical features and treatment response in HCC were also analyzed. The TF target genes underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, followed by protein-protein-interaction (PPI) analysis.Results: A total of 25 differentially expressed TFs were screened, 16 of which were related to the prognosis of HCC in the TCGA-LIHC cohort. A 2-TF risk signature, comprising high mobility group AT-hook protein 1 (HMGA1) and MAF BZIP transcription factor G (MAFG), was constructed and validated to negatively related to the overall survival (OS) of HCC. The ROC curve showed good predictive efficiencies of the risk score regarding 1-year, 2-year and 3-year OS (mostly AUC &gt;0.60). Additionally, the risk score independently predicted OS for HCC patients both in the training cohort of TCGA-LIHC dataset (HR = 2.498, p = 0.007) and in the testing cohort of ICGC-LIRI-JP dataset (HR = 5.411, p &lt; 0.001). The risk score was also positively correlated to progressive characteristics regarding tumor grade, TNM stage and tumor invasion. Patients with a high-risk score were more resistant to transarterial chemoembolization (TACE) treatment and agents of lapatinib and erlotinib, but sensitive to chemotherapeutics. Further enrichment and PPI analyses demonstrated that the 2-TF signature distinguished tumors into 2 clusters with proliferative and metabolic features, with the hub genes belonging to the former cluster.Conclusion: Our study identified a 2-TF prognostic signature that indicated tumor heterogeneity with different clinical features and treatment preference, which help optimal therapeutic strategy and improved survival for HCC patients.
Exploring prognostic indicators in the pathological images of ovarian cancer based on a deep survival network
Authors: Wu Meixuan , Zhu Chengguang , Yang Jiani , Cheng Shanshan , Yang Xiaokang , Gu Sijia , Xu Shilin , Wu Yongsong , Shen Wei , Huang Shan , Wang Yu 
Published: January 2023

Background: Tumor pathology can assess patient prognosis based on a morphological deviation of tumor tissue from normal. Digitizing whole slide images (WSIs) of tissue enables the use of deep learning (DL) techniques in pathology, which may shed light on prognostic indicators of cancers, and avoid biases introduced by human experience.Purpose: We aim to explore new prognostic indicators of ovarian cancer (OC) patients using the DL framework on WSIs, and provide a valuable approach for OC risk stratification.Methods: We obtained the TCGA-OV dataset from the NIH Genomic Data Commons Data Portal database. The preprocessing of the dataset was comprised of three stages: 1) The WSIs and corresponding clinical data were paired and filtered based on a unique patient ID; 2) a weakly-supervised CLAM WSI-analysis tool was exploited to segment regions of interest; 3) the pre-trained model ResNet50 on ImageNet was employed to extract feature tensors. We proposed an attention-based network to predict a hazard score for each case. Furthermore, all cases were divided into a high-risk score group and a low-risk one according to the median as the threshold value. The multi-omics data of OC patients were used to assess the potential applications of the risk score. Finally, a nomogram based on risk scores and age features was established.Results: A total of 90 WSIs were processed, extracted, and fed into the attention-based network. The mean value of the resulting C-index was 0.5789 (0.5096–0.6053), and the resulting p-value was 0.00845. Moreover, the risk score showed a better prediction ability in the HRD + subgroup.Conclusion: Our deep learning framework is a promising method for searching WSIs, and providing a valuable clinical means for prognosis.
Genetic heritability as a tool to evaluate the precision of 24-hour recall dietary questionnaire variables in UK Biobank
Authors: Cole Joanne B. , Westerman Kenneth E. , Manning Alisa K. , Florez Jose C. , Hirschhorn Joel N. 
Published: January 2023

A variety of statistical approaches in nutritional epidemiology have been developed to enhance the precision of dietary variables derived from longitudinal questionnaires. Correlation with biomarkers is often used to assess the relative validity of these different approaches, however, validated biomarkers do not always exist and are costly and laborious to collect. We present a novel high-throughput approach which utilizes the modest but importantly non-zero influence of genetic variation on variation in dietary intake to compare different statistical transformations of dietary variables. Specifically, we compare the heritability of crude averages with Empirical Bayes weighted averages for 302 correlated dietary variables from multiple 24-hour recall questionnaires in 177 K individuals in UK Biobank. Overall, the crude averages for frequency of consumption are more heritable than their Empirical Bayes counterparts only when the reliability of that item across questionnaires is high (measured by intra-class correlation), otherwise, the Empirical Bayes approach (for both unreliably measured frequencies and for average quantities independent of reliability) leads to higher heritability estimates. We also find that the more heritable versions of each dietary variable lead to stronger underlying statistical associations with specific genetic loci, many of which have well-known mechanisms, further supporting heritability as an alternative metric for relative validity in nutritional epidemiology and beyond.
Proteome changes of dairy calves rumen epithelium from birth to postweaning
Authors: Zheng Kaizhi , Wu Jianliang , Ullah Saif , Cao Yang , Jiang Yongqing , Huang Xin , Jiang Junfang 
Published: January 2023

Background: Rumen epithelium plays a central role in absorbing, transporting, and metabolizing of short-chain fatty acids. For dairy calves, the growth of rumen papillae greatly enhances the rumen surface area to absorb nutrients. However, the molecular mechanism underlying dairy calves rumen postnatal development remains rarely understood.Results: Here, we firstly describe the histological change of rumen epithelium from birth to day 90 of age. Then, a shotgun approach and bioinformatics analyses were used to investigate and compare proteomic profiles of Holstein calve rumen epithelium on day 0, 30, 60 and 90 of age. A total of 4372 proteins were identified, in which we found 852, 342, 164 and 95 differentially expressed proteins between D0 and D30, between D30 and D60, between D60 and D90, respectively. Finally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to provide a comprehensive proteomic landscape of dairy calves rumen development at tissue level.Conclusion: To conclude, our data indicated that keratinocyte differentiation, mitochondrion formation, the establishment of urea transport and innate immune system play central roles during rumen epithelium development. Tetrahydrobiopterin (BH4) presents an important role in rumen epithelial keratinization. The biological processes of BH4 biosynthesis and molecular function of nicotinamide adenine dinucleotide phosphate binding participate in mitochondrial cristae formation. The proposed datasets provide a useful basis for future studies to better comprehend dairy calves rumen epithelial development.