bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biodecolorization and degradation of textile azo dyes using Lysinibacillus sphaericus MTCC 9523
Authors: Srinivasan Shantkriti , Bankole Paul Olusegun , Sadasivam Senthil Kumar 
Published: October 2022

Wastewater discharges by textile industries constitute a major environmental concern as they exert grave human health dangers. Innovative, cost-effective and economical strategy aimed at ameliorating the effect of textile effluent in the environment is highly desirable. Hence, this study investigated the decolorization efficiency of selective reactive azo dyes by textile effluent non-adapted Lysinibacillus sphaericus MTCC 9523 in optimized operational conditions. Visual color changes with 96.30% and 92.71% decolorization for Reactive Yellow F3R (RYF3R) and Joyfix Red RB (JRRB) elucidated by UV-visible spectrophotometric analysis affirmed decolorization of the dyes. Meanwhile, Fourier Transform Infrared (FTIR) Spectroscopy of the metabolites obtained after degradation further revealed the functional groups and loss of peak for azo group indicated the breaking of azo bond. On High-Performance Liquid Chromatography (HPLC) analysis, difference in control dye’s retention time compared to treated sample with peaks at 2.413 and 2.895 min for RYF3R and 2.466 min and 1.640 min for Joyfix Red RB supported biodegradation by this organism. The chemical identities of the metabolites revealed after Gas Chromatography-Mass Spectrometry (GC-MS) analysis was used in the prediction of each dye’s metabolic pathway of degradation based on their molecular weight and mass-to-charge ratio. They were found to be (2Z)-but-2-ene, 1,3,5-triazine, (3E)-penta-1,3-diene for RYF3R and (methylsulfonyl)benzene, phenol, buta-1,3-diene, 1,3,5-triazine-2,4(1H,3H)-dione, nitrobenzene for JRRB. Overall, the use of adapted and non-adapted microbes is highly promising as an efficient, cost-effective, time-saving and universal green strategy for biodegradation of textile effluent containing azo dyes.
Investigation of the biomarkers involved in ectopic ossification: The shared mechanism in ossification of the spinal ligament
Authors: Liu Jiachen , Chen Yunxia , Shan Xiuqi , Wang Huan 
Published: October 2022

Background: Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are multifactor diseases characterized by progressively ectopic ossification in the spinal ligament. However, the shared ossification mechanism of OPLL and OLF remains to be elucidated. The study aims to investigate the common biomarkers related to ectopic ossification and the potential molecular regulatory mechanism.Methods: Microarray and RNA-seq datasets were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) from OPLL and OLF were identified to construct the protein-protein interaction (PPI) network. Furthermore, the hub intersection genes were screened and the diagnostic performance was assessed in the external OLF and OPLL cohorts. We also depicted the landscape of immune cell infiltration and m6A modification meanwhile further estimating the relationship with BMP4.Results: A total of nine up-regulated DEGs and 11 down-regulated DEGs were identified to construct the PPI networks. The integrative bioinformatic analysis defined five hub genes (BMP4, ADAMTS4, HBEGF, IL11, and HAS2) as the common risk biomarkers. Among them, BMP4 was the core target. ROC analysis demonstrated a high diagnostic value of the hub genes. Moreover, activated B cells were recognized as shared differential immune infiltrating cells and significantly associated with BMP4 in OPLL and OLF. Meanwhile, a strong correlation was detected between the expression pattern of the m6A regulator METTL3 and BMP4.Conclusion: This study first identified BMP4 as the shared core biomarker in the development of OPLL and OLF. Activated B cells and m6A writer METTL3 might be involved in the osteogenesis process mediated by BMP4. Our findings provide insights into the pathogenesis in the ossification of the spinal ligament and unveil the potential therapeutic targets.
Regulatory T-cells and GARP expression are decreased in exercise-associated chikungunya viral arthritis flares
Authors: Dobbs John E. , Tritsch Sarah R. , Encinales Liliana , Cadena Andres , Suchowiecki Karol , Simon Gary , Mores Christopher , Insignares Silvana , Orozco Vierys Patricia Villamil , Ospino Mirna , Echavez Lil Avendano , Gomez Carlos Andres Herrera , Crespo Yerlenis Galvis , Amdur Richard , Jimenez Alberto David Cabana , Hernandez Carlos Alberto Perez , Zapata Jennifer Carolina Martinez , Hernandez Alfonso Sucerquia , Silvera Paula Bruges , Rosales Wendy , Mendoza Evelyn , Osorio-Llanes Estefanie , Castellar Jairo , Jimenez Dennys , Cooper Dan M. , Firestein Gary S. , Martins Karen , Chang Aileen Y. 
Published: October 2022

ObjectiveChikungunya virus (CHIKV) causes persistent arthritis, and our prior study showed that approximately one third of CHIKV arthritis patients had exacerbated arthritis associated with exercise. The underlying mechanism of exercise-associated chikungunya arthritis flare (EACAF) is unknown, and this analysis aimed to examine the regulatory T-cell immune response related to CHIKV arthritis flares.MethodsIn our study, 124 Colombian patients with a history of CHIKV infection four years prior were enrolled and 113 cases with serologically confirmed CHIKV IgG were used in this analysis. Patient information was gathered via questionnaires, and blood samples were taken to identify total live peripheral blood mononuclear cells, CD4+ cells, T regulatory cells, and their immune markers. We compared outcomes in CHIKV patients with (n = 38) vs. without (n = 75) EACAF using t-tests to assess means and the Fisher’s exact test, chi-squared to evaluate categorical variables, and Kruskal-Wallis tests in the setting of skewed distributions (SAS 9.3).Results33.6% of CHIKV cases reported worsening arthritis with exercise. EACAF patients reported higher global assessments of arthritis disease ranging from 0-100 (71.2 ± 19.7 vs. 59.9 ± 28.0, p=0.03). EACAF patients had lower ratios of T regulatory (Treg)/CD4+ T-cells (1.95 ± 0.73 vs. 2.4 ± 1.29, p = 0.04) and lower percentage of GARP (glycoprotein-A repetitions predominant) expression per Treg (0.13 ± 0.0.33 vs. 0.16 ± 0.24 p= 0.020).ConclusionThese findings suggest relative decreases in GARP expression may indicate a decreased level of immune suppression. Treg populations in patients with CHIKV arthritis may contribute to arthritis flares during exercise, though current research is conflicting.
Integrated profiling of endoplasmic reticulum stress-related DERL3 in the prognostic and immune features of lung adenocarcinoma
Authors: Lin Lanlan , Lin Guofu , Lin Hai , Chen Luyang , Chen Xiaohui , Lin Qinhui , Xu Yuan , Zeng Yiming 
Published: October 2022

BackgroundDERL3 has been implicated as an essential element in the degradation of misfolded lumenal glycoproteins induced by endoplasmic reticulum (ER) stress. However, the correlation of DERL3 expression with the malignant phenotype of lung adenocarcinoma (LUAD) cells is unclear and remains to be elucidated. Herein, we investigated the interaction between the DERL3 and LUAD pathological process.MethodsThe Cancer Genome Atlas (TCGA) database was utilized to determine the genetic alteration of DERL3 in stage I LUAD. Clinical LUAD samples including carcinoma and adjacent tissues were obtained and were further extracted to detect DERL3 mRNA expression via RT-qPCR. Immunohistochemistry was performed to evaluate the protein expression of DERL3 in LUAD tissues. The GEPIA and TIMER website were used to evaluate the correlation between DERL3 and immune cell infiltration. We further used the t-SNE map to visualize the distribution of DERL3 in various clusters at the single-cell level via TISCH database. The potential mechanisms of the biological process mediated by DERL3 in LUAD were conducted via KEGG and GSEA.ResultsIt was indicated that DERL3 was predominantly elevated in carcinoma compared with adjacent tissues in multiple kinds of tumors from the TCGA database, especially in LUAD. Immunohistochemistry validated that DERL3 was also upregulated in LUAD tissues compared with adjacent tissues from individuals. DERL3 was preliminarily found to be associated with immune infiltration via the TIMER database. Further, the t-SNE map revealed that DERL3 was predominantly enriched in plasma cells of the B cell population. It was demonstrated that DERL3 high-expressed patients presented significantly worse response to chemotherapy and immunotherapy. GSEA and KEGG results indicated that DERL3 was positively correlated with B cell activation and unfolded protein response (UPR).ConclusionOur findings indicated that DERL3 might play an essential role in the endoplasmic reticulum-associated degradation (ERAD) process in LUAD. Moreover, DERL3 may act as a promising immune biomarker, which could predict the efficacy of immunotherapy in LUAD.
Postoperative neutrophil-lymphocyte ratio predicts unfavorable outcome of acute ischemic stroke patients who achieve complete reperfusion after thrombectomy
Authors: Feng Yao , Bai Xuesong , Li Wei , Cao Wenbo , Xu Xin , Yu Fan , Fu Zhaolin , Tian Qiuyue , Guo Xiaofan , Wang Tao , Sha Arman , Chen Yanfei , Gao Peng , Wang Yabing , Chen Jian , Ma Yan , Chen Fei , Dmytriw Adam A. , Regenhardt Robert W. , Lu Jie , Ma Qingfeng , Yang Bin , Jiao Liqun 
Published: October 2022

PurposeOnly approximately half of anterior circulation large vessel occlusion (LVO) patients receiving endovascular treatment (EVT) have a favorable outcome. The aim of this study was to explore the association of dynamic inflammatory markers (i.e., neutrophil to lymphocyte ratios, NLR, measured at different times after EVT) as well as other potential influencing factors with unfavorable outcome among acute ischemic stroke (AIS) patients who achieved complete reperfusion after EVT.MethodsPatients treated with EVT for LVO between January 2019 to December 2021 were prospectively enrolled. Complete reperfusion was defined as modified thrombolysis in cerebral infarction (mTICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3–6 was defined as unfavorable outcome (i.e., futile reperfusion). A logistic regression analysis was performed with unfavorable outcome as a dependent variable. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were then used to determine the diagnostic values of NLR and other relevant factors.Results170 patients with complete reperfusion (mTICI 3) were included in this study. Unfavorable outcome was observed in 70 (41.2%). Higher NLR within 24h (p=0.017) and at 3-7d (p=0.008) after EVT were an independent risk factors for unfavorable outcome at 3 months. In addition, older age, higher NIHSS scores, poor collaterals, and general anesthesia were independent predictors of unfavorable outcomes. When accounting for NLR, the diagnostic efficiency improved compared to conventional characteristics.ConclusionOur findings suggest that advanced age, increased stroke severity, poor collaterals, general anesthesia, and NLR are independent predictors for an unfavorable clinical outcome following complete reperfusion after EVT. Neuroinflammation may merit particular attention in future studies.
TP53I13 promotes metastasis in glioma via macrophages, neutrophils, and fibroblasts and is a potential prognostic biomarker
Authors: Ge Xinqi , Xu Manyu , Cheng Tong , Hu Nan , Sun Pingping , Lu Bing , Wang Ziheng , Li Jian 
Published: October 2022

BackgroundTP53I13 is a protein coding tumor suppression gene encoded by the tumor protein p53. Overexpression of TP53I13 impedes tumor cell proliferation. Nevertheless, TP53I13 role and expression in the emergence and progression of glioma (low-grade glioma and glioblastoma) are yet to be identified. Thus, we aim to use comprehensive bioinformatics analyses to investigate TP53I13 and its prognostic value in gliomas.MethodsMultiple databases were consulted to evaluate and assess the expression of TP53I13, such as the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GeneMANIA, and Gene Expression Profiling Interactive. TP53I13 expression was further explored using immunohistochemistry (IHC) and multiplex immunohistochemistry (mIHC). Through Gene Set Enrichment Analysis (GSEA), the biological functions of TP53I13 and metastatic processes associated with it were studied.ResultsThe expression of TP53I13 was higher in tumor samples compared to normal samples. In samples retrieved from the TCGA and CGGA databases, high TP53I13 expression was associated with poor survival outcomes. The analysis of multivariate Cox showed that TP53I13 might be an independent prognostic marker of glioma. It was also found that increased expression of TP53I13 was significantly correlated with PRS type, status, 1p/19q codeletion status, IDH mutation status, chemotherapy, age, and tumor grade. According to CIBERSORT (Cell-type Identification by Estimating Relative Subsets of RNA Transcript), the expression of TP53I13 correlates with macrophages, neutrophils, and dendritic cells. GSEA shows a close correlation between TP53I13 and p53 signaling pathways, DNA replication, and the pentose phosphate pathway.ConclusionOur results reveal a close correlation between TP53I13 and gliomas. Further, TP53I13 expression could affect the survival outcomes in glioma patients. In addition, TP53I13 was an independent marker that was crucial in regulating the infiltration of immune cells into tumors. As a result of these findings, TP53I13 might represent a new biomarker of immune infiltration and prognosis in patients with gliomas.
A novel hypoxia- and lactate metabolism-related signature to predict prognosis and immunotherapy responses for breast cancer by integrating machine learning and bioinformatic analyses
Authors: Li Jia , Qiao Hao , Wu Fei , Sun Shiyu , Feng Cong , Li Chaofan , Yan Wanjun , Lv Wei , Wu Huizi , Liu Mengjie , Chen Xi , Liu Xuan , Wang Weiwei , Cai Yifan , Zhang Yu , Zhou Zhangjian , Zhang Yinbin , Zhang Shuqun 
Published: October 2022

BackgroundBreast cancer is the most common cancer worldwide. Hypoxia and lactate metabolism are hallmarks of cancer. This study aimed to construct a novel hypoxia- and lactate metabolism-related gene signature to predict the survival, immune microenvironment, and treatment response of breast cancer patients.MethodsRNA-seq and clinical data of breast cancer from The Cancer Genome Atlas database and Gene Expression Omnibus were downloaded. Hypoxia- and lactate metabolism-related genes were collected from publicly available data sources. The differentially expressed genes were identified using the “edgeR” R package. Univariate Cox regression, random survival forest (RSF), and stepwise multivariate Cox regression analyses were performed to construct the hypoxia-lactate metabolism-related prognostic model (HLMRPM). Further analyses, including functional enrichment, ESTIMATE, CIBERSORTx, Immune Cell Abundance Identifier (ImmuCellAI), TIDE, immunophenoscore (IPS), pRRophetic, and CellMiner, were performed to analyze immune status and treatment responses.ResultsWe identified 181 differentially expressed hypoxia-lactate metabolism-related genes (HLMRGs), 24 of which were valuable prognostic genes. Using RSF and stepwise multivariate Cox regression analysis, five HLMRGs were included to establish the HLMRPM. According to the medium-risk score, patients were divided into high- and low-risk groups. Patients in the high-risk group had a worse prognosis than those in the low-risk group (P &lt; 0.05). A nomogram was further built to predict overall survival (OS). Functional enrichment analyses showed that the low-risk group was enriched with immune-related pathways, such as antigen processing and presentation and cytokine-cytokine receptor interaction, whereas the high-risk group was enriched in mTOR and Wnt signaling pathways. CIBERSORTx and ImmuCellAI showed that the low-risk group had abundant anti-tumor immune cells, whereas in the high-risk group, immunosuppressive cells were dominant. Independent immunotherapy datasets (IMvigor210 and GSE78220), TIDE, IPS and pRRophetic analyses revealed that the low-risk group responded better to common immunotherapy and chemotherapy drugs.ConclusionsWe constructed a novel prognostic signature combining lactate metabolism and hypoxia to predict OS, immune status, and treatment response of patients with breast cancer, providing a viewpoint for individualized treatment.
A non-traditional crystal-based compound screening method targeting the ATP binding site of Plasmodium falciparum GRP78 for identification of novel nucleoside analogues
Authors: Mrozek Alexander , Antoshchenko Tetyana , Chen Yun , Zepeda-Velázquez Carlos , Smil David , Kumar Nirbhay , Lu Hua , Park Hee-Won 
Published: October 2022

Drug resistance to front-line malarial treatments represents an ongoing threat to control malaria, a vector borne infectious disease. The malarial parasite, Plasmodium falciparum has developed genetic variants, conferring resistance to the current standard therapeutic artemisinin and its derivatives commonly referred to as artemisinin-combination therapies (ACTs). Emergence of multi-drug resistance parasite genotypes is a warning of potential treatment failure, reaffirming the urgent and critical need to find and validate alternate drug targets to prevent the spread of disease. An attractive and novel drug target includes glucose-regulated protein 78 kDa (GRP78, or BiP), an essential molecular chaperone protein involved in the unfolded protein response that is upregulated in ACT treated P. falciparum parasites. We have shown that both sequence and structure are closely related to human GRP78 (hGRP78), a chaperone belonging to the HSP70 class of ATPase proteins, which is often upregulated in cellular stress responses and cancer. By screening a library of nucleoside analogues, we identified eight ‘hit’ compounds binding at the active site of the ATP binding domain of P. falciparum GRP78 using a high-throughput ligand soaking screen using x-ray crystallography. These compounds were further evaluated using protein thermal shift assays to assess target binding activity. The nucleoside analogues identified from our screen provide a starting point for the development of more potent and selective antimalarial inhibitors. In addition, we have established a well-defined, high-throughput crystal-based screening approach that can be applied to many crystallizable P. falciparum proteins for generating anti-Plasmodium specific compounds.
A population-based predictive model identifying optimal candidates for primary and metastasis resection in patients with colorectal cancer with liver metastatic
Authors: Jin Xin , Wu Yibin , Feng Yun , Lin Zhenhai , Zhang Ning , Yu Bingran , Mao Anrong , Zhang Ti , Zhu Weiping , Wang Lu 
Published: October 2022

BackgroundThe survival benefit of primary and metastatic resection for patients with colorectal cancer with liver metastasis (CRLM) has been observed, but methods for discriminating which individuals would benefit from surgery have been poorly defined. Herein, a predictive model was developed to stratify patients into sub-population based on their response to surgery.MethodsWe assessed the survival benefits for adults diagnosed with colorectal liver metastasis by comparing patients with curative surgery vs. those without surgery. CRLM patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were identified for model construction. Other data including CRLM patients from our center were obtained for external validation. Calibration plots, the area under the curve (AUC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram compared with the tumor–node–metastasis (TNM) classification. The Kaplan–Meier analysis was performed to examine whether this model would distinguish patients who could benefit from surgery.ResultsA total of 1,220 eligible patients were identified, and 881 (72.2%) underwent colorectal and liver resection. Cancer-specific survival (CSS) for the surgery group was significantly better than that for the no-surgery group (41 vs. 14 months, p &lt; 0.001). Five factors were found associated with CSS and adopted to build the nomograms, i.e., age, T stage, N stage, neoadjuvant chemotherapy, and primary tumor position. The AUC of the CRLM nomogram showed a better performance in identifying patients who could obtain benefits in the surgical treatment, compared with TNM classification (training set, 0.826 [95% CI, 0.786–0.866] vs. 0.649 [95% CI, 0.598–0.701]; internal validation set, 0.820 [95% CI, 0.741–0.899] vs. 0.635 [95% CI, 0.539–0.731]; external validation set, 0.763 [95% CI, 0.691–0.836] vs. 0.626 [95% CI, 0.542–0.710]). The calibration curves revealed excellent agreement between the predicted and actual survival outcomes. The DCA showed that the nomogram exhibited more clinical benefits than the TNM staging system. The beneficial and surgery group survived longer significantly than the non-beneficial and surgery group (HR = 0.21, 95% CI, 0.17–0.27, p &lt; 0.001), but no difference was observed between the non-beneficial and surgery and non-surgery groups (HR = 0.89, 95% CI, 0.71–1.13, p = 0.344).ConclusionsAn accurate and easy-to-use CRLM nomogram has been developed and can be applied to identify optimal candidates for the resection of primary and metastatic lesions among CRLM patients.
EPDR1 levels and tumor budding predict and affect the prognosis of bladder carcinoma
Authors: Yang Yue , Xu Hong , Zhu Han , Yuan Dan , Zhang Hanchao , Liu Zhengdao , Zhao Faliang , Liang Guobiao 
Published: October 2022

BackgroundBladder carcinoma is a common malignancy of the urinary system. The previous study showed that EPDR1 expression was significantly related to the carcinogenesis and progression of bladder carcinomaMethodsWe retrospectively reviewed the records of 621 patients who were newly diagnosed with bladder carcinoma between January 2018 and August 2020 at The Affiliated Hospital of Zunyi Medical University. We conducted immunohistochemistry of EPDR1 in tumor tissues. Meanwhile, tumor budding evaluation was also carried out by 2 independent experienced pathologists.Results80 patients were included in this study with a median age of 66 years (range; 42–88 years). 45% of the patients (36/80) were non-muscle-invasive bladder carcinoma patients, while 55% of muscle-invasive bladder carcinoma(44/80). The follow-up time was from 6 months to 36 months. We found that there were significant differences in expression of EPDR1 in the tumor pT stages(p&lt;0.05), pM stages(p&lt;0.05), and pN stages(p&lt;0.05). Meanwhile, a higher expression of EPDR1 indicated a worse outcome for the patient(p&lt;0.05). A tendency toward a worse status of the patient was accompanied by a high positive rate (p&lt;0.001). Moreover, the IOD of EPDR1 had a positive relationship with TB (p&lt;0.05). Furthermore, we found that EPDR1 and tumor budding could be crucial factors for affecting the prognosis of bladder carcinoma, even better than pTMN(Riskscore=(0.724)* pT_stage +(4.960) *EPDR1+(4.312)*TB).ConclusionIn conclusion, bladder cancer patients with higher expression levels of EPDR1 had worse survival outcomes. The combination of TB and EPDR1 levels could predict the prognosis for muscle-invasive bladder cancer patients.