bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of a novel molecular classification incorporating oxidative stress and metabolism-related genes for stomach adenocarcinoma in the framework of predictive, preventive, and personalized medicine
Authors: Dong Ying , Yuan Qihang , Ren Jie , Li Hanshuo , Guo Hui , Guan Hewen , Jiang Xueyan , Qi Bing , Li Rongkuan 
Published: February 2023

BackgroundStomach adenocarcinoma (STAD) is one of the primary contributors to deaths that are due to cancer globally. At the moment, STAD does not have any universally acknowledged biological markers, and its predictive, preventive, and personalized medicine (PPPM) remains sufficient. Oxidative stress can promote cancer by increasing mutagenicity, genomic instability, cell survival, proliferation, and stress resistance pathways. As a direct and indirect result of oncogenic mutations, cancer depends on cellular metabolic reprogramming. However, their roles in STAD remain unclear.Method743 STAD samples from GEO and TCGA platforms were selected. Oxidative stress and metabolism-related genes (OMRGs) were acquired from the GeneCard Database. A pan-cancer analysis of 22 OMRGs was first performed. We categorized STAD samples by OMRG mRNA levels. Additionally, we explored the link between oxidative metabolism scores and prognosis, immune checkpoints, immune cell infiltration, and sensitivity to targeted drugs. A series of bioinformatics technologies were employed to further construct the OMRG-based prognostic model and clinical-associated nomogram.ResultsWe identified 22 OMRGs that could evaluate the prognoses of patients with STAD. Pan-cancer analysis concluded and highlighted the crucial part of OMRGs in the appearance and development of STAD. Subsequently, 743 STAD samples were categorized into three clusters with the enrichment scores being C2 (upregulated) &gt; C3 (normal) &gt; C1 (downregulated). Patients in C2 had the lowest OS rate, while C1 had the opposite. Oxidative metabolic score significantly correlates with immune cells and immune checkpoints. Drug sensitivity results reveal that a more tailored treatment can be designed based on OMRG. The OMRG-based molecular signature and clinical nomogram have good accuracy for predicting the adverse events of patients with STAD. Both transcriptional and translational levels of ANXA5, APOD, and SLC25A15 exhibited significantly higher in STAD samples.ConclusionThe OMRG clusters and risk model accurately predicted prognosis and personalized medicine. Based on this model, high-risk patients might be identified in the early stage so that they can receive specialized care and preventative measures, and choose targeted drug beneficiaries to deliver individualized medical services. Our results showed oxidative metabolism in STAD and led to a new route for improving PPPM for STAD.
Responses of crop production and soil health to chemical nitrogen fertilization in a maize-wheat rotation system
Authors: Deng Meihua , Ma Hua , Sadeghpour Amir , Yang Guiling , Hu Yan , Yang Dong 
Published: February 2023

Chemical nitrogen (N) fertilizer is generally applied at high rates to maximize crop yields and also many non-grain farmlands are being converted into grain production to ensure grain production safety in China now. To test the effects of chemical N on crop production and soil health, a 3-year trial with urea and controlled-release fertilizer was conducted in a maize (Zea mays L.)-wheat (Triticum aestivum L.) system shifted from vegetable farmland by evaluating the effects of N fertilization on crop yields, typical soil properties, and soil bacterial community using 16S rRNA gene sequencing. The maximum crop yield and aboveground N uptake efficiency was achieved at 150 kg N ha-1 for wheat and 200 kg N ha-1 for maize. After three cropping seasons, the soil N properties were notably altered. For each kg of N applied, soil pH decreased at a rate of 0.0004–0.0012 pH units. The soil total N (TN) and total carbon (TC) content reached a higher stability at certain cumulative N application rates. However, the C/N ratio linearly decreased as N rate increased. Consequently, N application significantly decreased soil bacterial diversity owing to the decrease of α-diversity indexes of Shannon and Pielou_e. At the phylum level, chemical N application significantly depleted members of Acidobacteria, Chloroflexi and Nitrospirae, but the growth of Actinobacteria, Gemmatimonadetes, Firmicutes and Patescibacteria were improved. Compared with urea, the controlled-release fertilizer did not significantly change crop yields, soil bacterial diversity, soil TN and TC content. Overall, our results indicated that chemical N promoted crop yields at optimum application rates, but excessive N application could result in a decline in soil health, specifically accelerated soil acidification, a decrease in soil bacterial diversity, and soil C and N imbalance.
Integrated analysis reveals common DNA methylation patterns of alcohol-associated cancers: A pan-cancer analysis
Authors: Liu Xingyu , Chen Jiarui , Li Jiali , Zeng Zihang , Jiang Xueping , Gao Yanping , Huang Zhengrong , Wu Qiuji , Gong Yan , Xie Conghua 
Published: February 2023

Background: The role of alcohol in carcinogenesis has received increasing attention in recent years. Evidence shows its impacts on various aspects, including epigenetics alteration. The DNA methylation patterns underlying alcohol-associated cancers are not fully understood.Methods: We investigated the aberrant DNA methylation patterns in four alcohol-associated cancers based on the Illumina HumanMethylation450 BeadChip. Pearson coefficient correlations were identified between differential methylated CpG probes and annotated genes. Transcriptional factor motifs were enriched and clustered using MEME Suite, and a regulatory network was constructed.Results: In each cancer, differential methylated probes (DMPs) were identified, and 172 hypermethylated and 21 hypomethylated pan-cancer DMPs (PDMPs) were examined further. Annotated genes significantly regulated by PDMPs were investigated and enriched in transcriptional misregulation in cancers. The CpG island chr19:58220189–58220517 was hypermethylated in all four cancers and silenced in the transcription factor ZNF154. Various biological effects were exerted by 33 hypermethylated and seven hypomethylated transcriptional factor motifs grouped into five clusters. Eleven pan-cancer DMPs were identified to be associated with clinical outcomes in the four alcohol-associated cancers, which might provide a potential point of view for clinical outcome prediction.Conclusion: This study provides an integrated insight into DNA methylation patterns in alcohol-associated cancers and reveals the corresponding features, influences, and potential mechanisms.
Development and validation of a pyroptosis-related genes signature for risk stratification in gliomas
Authors: Sun Penggang , Wang Xinyu , Zhong Junzhe , Yu Daohan , Xuan Hanwen , Xu Tianye , Song Dan , Yang Changxiao , Wang Pandeng , Liu Yuxiang , Meng Xiangqi , Cai Jinquan 
Published: February 2023

Background: Glioma is a highly heterogeneous disease, causing the prognostic prediction a challenge. Pyroptosis, a programmed cell death mediated by gasdermin (GSDM), is characterized by cell swelling and the release of inflammatory factors. Pyroptosis occurs in several types of tumor cells, including gliomas. However, the value of pyroptosis-related genes (PRGs) in the prognosis of glioma remains to be further clarified.Methods: In this study, mRNA expression profiles and clinical data of glioma patients were acquired from TCGA and CGGA databases, and one hundred and eighteen PRGs were obtained from the Molecular Signatures Database and GeneCards. Then, consensus clustering analysis was performed to cluster glioma patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to establish a polygenic signature. Functional verification of the pyroptosis-related gene GSDMD was achieved by gene knockdown and western blotting. Moreover, the immune infiltration status between two different risk groups were analyzed through the “gsva” R package.Results: Our results demonstrated that the majority of PRGs (82.2%) were differentially expressed between lower-grade gliomas (LGG) and glioblastoma (GBM) in the TCGA cohort. In univariate Cox regression analysis, eighty-three PRGs were shown to be associated with overall survival (OS). A five-gene signature was constructed to divide patients into two risk groups. Compared with patients in the low-risk group, patients in the high-risk group had obviously shorter OS (p &lt; 0.001). Also, we found that the high-risk group showed a higher infiltrating score of immune cells and immune-related functions. Risk score was an independent predictor of OS (HR &gt; 1, p &lt; 0.001). Furthermore, knockdown of GSDMD decreased the expression of IL-1β and cleaved caspase-1.Conclusion: Our study constructed a new PRGs signature, which can be used to predict the prognosis of glioma patients. Targeting pyroptosis might serve as a potential therapeutic strategy for glioma.
Risk of hospitalization and vaccine effectiveness among COVID-19 patients in the UAE during the Delta and Omicron outbreaks
Authors: Albreiki Mohammed , Mousa Mira , Azman Syafiq Kamarul , Vurivi Hema , Alhalwachi Zainab , Alshehhi Fatima , AlShamsi Safiya , Marzouqi Nada Al , Alawadi Tayba , Alrand Hussain , Oulhaj Abderrahim , Fikri Asma , Alsafar Habiba 
Published: February 2023

IntroductionA rapid increase in COVID-19 cases due to the spread of the Delta and Omicron variants in vaccinated populations has raised concerns about the hospitalization risk associated with, and the effectiveness of, COVID-19 vaccines.MethodThis case–control study aims to determine the hospitalization risk associated with the inactivated BBIBP-CorV (Sinopharm) and mRNA BNT162b2 (Pfizer–BionTech) vaccines, and their effectiveness reducing the rate of hospital admission between 28 May 2021 and 13 January 2022, during the Delta and Omicron outbreaks. The estimation of vaccine effectiveness of 4,618 samples was based on the number of patients hospitalized at different vaccination statuses, adjusted for confounding variables.ResultsHospitalization risk increases in patients affected with the Omicron variant if patients are aged ≤ 18 years (OR 6.41, 95% CI 2.90 to 14.17; p &lt; 0.001), and in patients affected with the Delta variant if they are aged &gt; 45 years (OR 3.41, 95% CI 2.21 to 5.50; p &lt; 0.001). Vaccine effectiveness reducing the rate of hospital admission for fully vaccinated participants infected with the Delta and Omicron variants was similar for both the BBIBP-CorV (94%, 95% CI 90% to 97%; 90%, 95% CI 74% to 96%) and BNT162b2 vaccines (95%, 95% CI 61% to 99.3%; 94%, 95% CI 53% to 99%), respectively.DiscussionThe BBIBP-CorV and BNT162b2 vaccines utilized in the UAE vaccination program were highly effective in reducing the rate of COVID-19-related hospitalization during the Delta and Omicron outbreaks, and further effort must be taken to achieve high vaccine coverage rates in children and adolescents in the global context to reduce the hospitalization risk associated with COVID-19 on an international scale.
Systemic inflammatory markers in patients with polyneuropathies
Authors: García-Fernández Patricia , Höfflin Klemens , Rausch Antonia , Strommer Katharina , Neumann Astrid , Cebulla Nadine , Reinhold Ann-Kristin , Rittner Heike , Üçeyler Nurcan , Sommer Claudia 
Published: February 2023

IntroductionIn patients with peripheral neuropathies (PNP), neuropathic pain is present in 50% of the cases, independent of the etiology. The pathophysiology of pain is poorly understood, and inflammatory processes have been found to be involved in neuro-degeneration, -regeneration and pain. While previous studies have found a local upregulation of inflammatory mediators in patients with PNP, there is a high variability described in the cytokines present systemically in sera and cerebrospinal fluid (CSF). We hypothesized that the development of PNP and neuropathic pain is associated with enhanced systemic inflammation.MethodsTo test our hypothesis, we performed a comprehensive analysis of the protein, lipid and gene expression of different pro- and anti-inflammatory markers in blood and CSF from patients with PNP and controls.ResultsWhile we found differences between PNP and controls in specific cytokines or lipids, such as CCL2 or oleoylcarnitine, PNP patients and controls did not present major differences in systemic inflammatory markers in general. IL-10 and CCL2 levels were related to measures of axonal damage and neuropathic pain. Lastly, we describe a strong interaction between inflammation and neurodegeneration at the nerve roots in a specific subgroup of PNP patients with blood-CSF barrier dysfunction.ConclusionIn patients with PNP systemic inflammatory, markers in blood or CSF do not differ from controls in general, but specific cytokines or lipids do. Our findings further highlight the importance of CSF analysis in patients with peripheral neuropathies.
Cell morphology as a biological fingerprint of chondrocyte phenotype in control and inflammatory conditions
Authors: Selig Mischa , Azizi Saman , Walz Kathrin , Lauer Jasmin C. , Rolauffs Bernd , Hart Melanie L. 
Published: February 2023

IntroductionLittle is known how inflammatory processes quantitatively affect chondrocyte morphology and how single cell morphometric data could be used as a biological fingerprint of phenotype.MethodsWe investigated whether trainable high-throughput quantitative single cell morphology profiling combined with population-based gene expression analysis can be used to identify biological fingerprints that are discriminatory of control vs. inflammatory phenotypes. The shape of a large number of chondrocytes isolated from bovine healthy and human osteoarthritic (OA) cartilages was quantified under control and inflammatory (IL-1β) conditions using a trainable image analysis technique measuring a panel of cell shape descriptors (area, length, width, circularity, aspect ratio, roundness, solidity). The expression profiles of phenotypically relevant markers were quantified by ddPCR. Statistical analysis, multivariate data exploration, and projection-based modelling were used for identifying specific morphological fingerprints indicative of phenotype.ResultsCell morphology was sensitive to both cell density and IL-1β. In both cell types, all shape descriptors correlated with expression of extracellular matrix (ECM)- and inflammatory-regulating genes. A hierarchical clustered image map revealed that individual samples sometimes responded differently in control or IL-1β conditions than the overall population. Despite these variances, discriminative projection-based modeling revealed distinct morphological fingerprints that discriminated between control and inflammatory chondrocyte phenotypes: the most essential morphological characteristics attributable to non-treated control cells was a higher cell aspect ratio in healthy bovine chondrocytes and roundness in OA human chondrocytes. In contrast, a higher circularity and width in healthy bovine chondrocytes and length and area in OA human chondrocytes indicated an inflammatory (IL-1β) phenotype. When comparing the two species/health conditions, bovine healthy and human OA chondrocytes exhibited comparable IL-1β-induced morphologies in roundness, a widely recognized marker of chondrocyte phenotype, and aspect ratio.DiscussionOverall, cell morphology can be used as a biological fingerprint for describing chondrocyte phenotype. Quantitative single cell morphometry in conjunction with advanced methods for multivariate data analysis allows identifying morphological fingerprints that can discriminate between control and inflammatory chondrocyte phenotypes. This approach could be used to assess how culture conditions, inflammatory mediators, and therapeutic modulators regulate cell phenotype and function.
Group B streptococcus virulence factors associated with different clinical syndromes: Asymptomatic carriage in pregnant women and early-onset disease in the newborn
Authors: Schindler Yulia , Rahav Galia , Nissan Israel , Treygerman Orit , Prajgrod George , Attia Bracha Zukerman , Raz Ronit , Valenci Gal Zizelski , Tekes-Manova Dorit , Maor Yasmin 
Published: February 2023

BackgroundGroup B streptococcus (GBS) harbors many virulence factors but there is limited data regarding their importance in colonization in pregnancy and early-onset disease (EOD) in the newborn. We hypothesized that colonization and EOD are associated with different distribution and expression of virulence factors.MethodsWe studied 36 GBS EOD and 234 GBS isolates collected during routine screening. Virulence genes (pilus-like structures-PI-1, PI-2a, PI-2b; rib and hvgA) presence and expression were identified by PCR and qRT-PCR. Whole genome sequencing (WGS) and comparative genomic analyses were used to compare coding sequences (CDSs) of colonizing and EOD isolates.ResultsSerotype III (ST17) was significantly associated with EOD and serotype VI (ST1) with colonization. hvgA and rib genes were more prevalent among EOD isolates (58.3 and 77.8%, respectively; p &lt; 0.01). The pilus loci PI-2b and PI-2a were more prevalent among EOD isolates (61.1%, p &lt; 0.01), while the pilus loci PI-2a and PI-1 among colonizing isolates (89.7 and 93.1% vs. 55.6 and 69.4%, p &lt; 0.01). qRT PCR analysis revealed that hvgA was barely expressed in colonizing isolates, even though the gene was detected. Expression of the rib gene and PI-2b was two-fold higher in EOD isolates compared to colonizing isolates. Transcription of PI-2a was three-fold higher in colonizing isolates compared to EOD isolates. ST17 isolates (associated with EOD) had a smaller genome size compared ST1 and the genome was more conserved relative to the reference strain and ST17 isolates. In a multivariate logistic regression analysis virulence factors independently associated with EOD were serotype 3, and PI-1 and PI-2a was protective.ConclusionThere was a significant difference in the distribution of hvg A, rib, and PI genes among EOD (serotype III/ST17) and colonizing (serotype VI/ST1) isolates suggesting an association between invasive disease and these virulence factors. Further study is needed to understand the contribution of these genes to GBS virulence.
Inhibitory effect of lactobacilli supernatants on biofilm and filamentation of Candida albicans, Candida tropicalis, and Candida parapsilosis
Authors: Poon Yeuklan , Hui Mamie 
Published: February 2023

IntroductionProbiotic Lactobacillus strains had been investigated for the potential to protect against infection caused by the major fungal pathogen of human, Candida albicans. Besides antifungal activity, lactobacilli demonstrated a promising inhibitory effect on biofilm formation and filamentation of C. albicans. On the other hand, two commonly isolated non-albicans Candida species, C. tropicalis and C. parapsilosis, have similar characteristics in filamentation and biofilm formation with C. albicans. However, there is scant information of the effect of lactobacilli on the two species.MethodsIn this study, biofilm inhibitory effects of L. rhamnosus ATCC 53103, L. plantarum ATCC 8014, and L. acidophilus ATCC 4356 were tested on the reference strain C. albicans SC5314 and six bloodstream isolated clinical strains, two each of C. albicans, C. tropicalis, and C. parapsilosis.Results and Discussion:Cell-free culture supernatants (CFSs) of L. rhamnosus and L. plantarum significantly inhibited in vitro biofilm growth of C. albicans and C. tropicalis. L. acidophilus, conversely, had little effect on C. albicans and C. tropicalis but was more effective on inhibiting C. parapsilosis biofilms. Neutralized L. rhamnosus CFS at pH 7 retained the inhibitory effect, suggesting that exometabolites other than lactic acid produced by the Lactobacillus strain might be accounted for the effect. Furthermore, we evaluated the inhibitory effects of L. rhamnosus and L. plantarum CFSs on the filamentation of C. albicans and C. tropicalis strains. Significantly less Candida filaments were observed after co-incubating with CFSs under hyphae-inducing conditions. Expressions of six biofilm-related genes (ALS1, ALS3, BCR1, EFG1, TEC1, and UME6 in C. albicans and corresponding orthologs in C. tropicalis) in biofilms co-incubated with CFSs were analyzed using quantitative real-time PCR. When compared to untreated control, the expressions of ALS1, ALS3, EFG1, and TEC1 genes were downregulated in C. albicans biofilm. In C. tropicalis biofilms, ALS3 and UME6 were downregulated while TEC1 was upregulated. Taken together, the L. rhamnosus and L. plantarum strains demonstrated an inhibitory effect, which is likely mediated by the metabolites secreted into culture medium, on filamentation and biofilm formation of C. albicans and C. tropicalis. Our finding suggested an alternative to antifungals for controlling Candida biofilm.
Discrimination of psychrophilic enzymes using machine learning algorithms with amino acid composition descriptor
Authors: Huang Ailan , Lu Fuping , Liu Fufeng 
Published: February 2023

IntroductionPsychrophilic enzymes are a class of macromolecules with high catalytic activity at low temperatures. Cold-active enzymes possessing eco-friendly and cost-effective properties, are of huge potential application in detergent, textiles, environmental remediation, pharmaceutical as well as food industry. Compared with the time-consuming and labor-intensive experiments, computational modeling especially the machine learning (ML) algorithm is a high-throughput screening tool to identify psychrophilic enzymes efficiently.MethodsIn this study, the influence of 4 ML methods (support vector machines, K-nearest neighbor, random forest, and naïve Bayes), and three descriptors, i.e., amino acid composition (AAC), dipeptide combinations (DPC), and AAC + DPC on the model performance were systematically analyzed.Results and discussionAmong the 4 ML methods, the support vector machine model based on the AAC descriptor using 5-fold cross-validation achieved the best prediction accuracy with 80.6%. The AAC outperformed than the DPC and AAC + DPC descriptors regardless of the ML methods used. In addition, amino acid frequencies between psychrophilic and non-psychrophilic proteins revealed that higher frequencies of Ala, Gly, Ser, and Thr, and lower frequencies of Glu, Lys, Arg, Ile,Val, and Leu could be related to the protein psychrophilicity. Further, ternary models were also developed that could classify psychrophilic, mesophilic, and thermophilic proteins effectively. The predictive accuracy of the ternary classification model using AAC descriptor via the support vector machine algorithm was 75.8%. These findings would enhance our insight into the cold-adaption mechanisms of psychrophilic proteins and aid in the design of engineered cold-active enzymes. Moreover, the proposed model could be used as a screening tool to identify novel cold-adapted proteins.