bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Ferroptosis-related lncRNA Signature for Prognosis Prediction in Lung Squamous Cell Carcinoma
Authors: Cai Jiahao , Gu Jie , Ge Di , Xu Fengkai 
Published: November 2021

Abstract
BACKGROUNDThe incidence of lung cancer ranks first among malignant tumors all over the world. Based on the histological features, lung cancer could be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), of which non-small cell lung cancer accounts for about 80%. NSCLC mainly includes lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and large cell lung cancer (LLC). Most of the patients were diagnosed at a late stage, which means the 5-year overall survival rate for patients was shallow. According to the situation, new biomarkers are needed to recognize patients at high risk, which would help give them appropriate treatment to improve their outcomes.Ferroptosis, an important iron-dependent cell death driven by oxidative phospholipid damage and characterized by lipid peroxidation, was recently found to play a novel role in several cancers. Existing research have identified many genes related to ferroptosis in tumor tissues. However, research on ferroptosis-genes-related long non-coding RNA (lncRNA) in lung cancer is still insufficient. METHODSWe acquired the statistics from the public database TCGA Lung Squamous Cell Carcinoma (LUSC). Then a multi-lncRNA signature was constructed to recognize patients at high risk based on differentially expressed ferroptosis-genes-related lncRNAs in lung squamous cell carcinoma. RESULTSWe finally identified eight differently expressed ferroptosis-genes-related lncRNAs are predictive of outcomes in LUSC patients. Kaplan-Meier analyses revealed that the high-risk-related lncRNAs signature has strong predictive power for poor LUSC prognosis (AUC=0.686). Our risk-predictive model was superordinate to the traditional predictive method based on clinicopathological characteristics (Stage, AUC=0.563). Gene set enrichment analysis (GSEA) revealed signaling pathways that ferroptosis-genes-related lncRNAs may participate in. Further study of immune function-related gene sets showed that parainflammation, APC co-stimulation, inflammation-promoting, T cell co-stimulation, Type I and type II INF response were significantly associated with risk-related lncRNAs signature. Immune checkpoint-related genes such as PDCD-1, CD70, CD28, and CD27, etc., also expressed differently between the two risk groups.CONCLUSIONThe specific differentially expressed ferroptosis-related lncRNAs have a strong predictive effect on the prognosis in patients with lung squamous cell carcinoma.
WITHDRAWN: Qihuzha Granule Alleviated Cyclophosphamide-induced Immune Deficiency in Mice via IL-6 Related Signaling Pathways
Authors: Zhong Ting , Feng Min , Su Minzhi , Wu Hongshan , Li Qing , Luo Fang , Wang Haibo , Li Linzhen , Fan yanhua 
Published: November 2021

Abstract
BackgroundQihuzha granule (QHZG) is a Chinese patent medicine, composed of 11 kinds of edible medicinal plants, which is used to treat dyspepsia and anorexia in children caused by spleen and stomach deficiency syndrome. However, its role and mechanism in immunosuppression induced by cyclophosphamide remained unclear. The purpose of this study is to investigate the effect of QHZG on immunosuppression induced by cyclophosphamide in mice and its possible mechanism.MethodsThe immunosuppression injury model was induced by intraperitoneal injection of cyclophosphamide (100 mg/kg); the mRNA level of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3) were tested by QPCR; related protein levels were detected by western blotting; hematoxylin-eosin (HE) staining was employed to observe the histological alterations; macrophages and neutrophils in the mouse spleen were examined by immunofluorescence analysis. ResultsQHZG significantly increased the spleen index and thymus index of mice with immunodeficiency induced by cyclophosphamide and up-regulated the mRNA expression of cytokines (IL-2/4/6, IFN-γ) and critical targets of signaling pathways related to immune regulation (JNK, ERK, P38, JAK2, SRC and STAT3), which were decreased by cyclophosphamide treatment. The results of immunofluorescence staining and histological analysis showed that QHZG could also protect mice from immunosuppressive injury caused by cyclophosphamide via keeping structural integrity of spleen, and partially restoring the production levels of macrophages and monocytes in the spleen. Further studies indicated that QHZG could significantly counter the decline of phosphorylated protein levels of JAK2/SRC-STAT3 axes (P-JAK2, P-SRC and P-STAT3), and MAPK pathways (P-JNK, P-ERK and P-P38) induced by cyclophosphamide, suggesting that the protective effects of QHZG on immunosuppressive injury triggered by cyclophosphamide were involved in JAK2/SRC-STAT3 axes, and MAPK pathways. Meanwhile, we also found that QHZG could partially restore the vital phosphorylated proteins of PI3K/Akt/mTOR signaling pathway (P-Akt, P-mTOR), which were reduced by cyclophosphamide. The data implied that PI3K signaling pathway was also responsible for the protection of QHZG against the immunosuppression induced by cyclophosphamide in mice. ConclusionsOur study demonstrated that QHZG protected mice from cyclophosphamide-triggered immunosuppressive injury via IL-6 and its downstream signaling pathways including PI3K/Akt/mTOR signal pathway and JAK2-SRC/MAPK/STAT3 axes. These results suggested that QHZG might serve as a new drug for the treatment of the immunosuppression caused by cyclophosphamide therapy.
Specification of Interventions and Selection of Control in Acupuncture Randomized Controlled Trials: A Cross-Sectional Study
Authors: Liu Jiali , Li Ling , Luo Xiaochao , Qin Xuan , Zhao Ling , Zhao Jiping , Zhou Xu , Liu Yanmei , Deng Ke , Ma Yu , Zou Kang , Sun Xin 
Published: November 2021

Abstract
Background: Specification of interventions and selection of control are two methodological determinants for a successful acupuncture trial. However, it is not fully understood about the current practice of these two determinants. We thus conduced a cross-sectional study to examine specification of interventions and selection of control among current acupuncture randomized controlled trials (RCTs). Methods: We searched PubMed for acupuncture RCTs published in the core clinical journals and complementary and alternative medicine (CAM) journals from January 2010 to December 2019 (10 years), and included RCTs that assessed treatment effects of acupuncture versus any type of control. Teams of methods-trained investigators who had experiences in acupuncture trials independently screened reports for eligibility and collected data, using a prespecified standardized questionnaire. We used network meta-analyses to investigate whether treatment effect was differential in patients with chronic pain when using sham acupuncture as a control versus using waiting-list or no treatment.Results: Of 319 eligible RCTs, most well specified style of acupuncture (86.8%), acupoint prescription (96.2%), type of needle stimulation (90.3%) and needle retention time (85.6%). However, other acupuncture details were less specified, including achievement of response sought (65.5%) and needle manipulation (50.5%), specification of number of needle insertions (21.9%), angle and direction of insertion (31.3%), patients posture (32.3%) and co-interventions (22.9%). Sham acupuncture (41.4%) was the most frequently used control, followed by waiting-list or no treatment (32.9%). There was no differential treatment effect when using sham acupuncture versus waiting-list/no treatment as a control (SMD = -0.15, 95% CI -0.91 to 0.62).Conclusions: Over a decade of research practice, important gaps remained in the specification of acupuncture interventions, including specification of response sought, needle manipulation, and co-interventions. While sham acupuncture was largely used, waiting-list or no treatment may also be used as an appropriate control.
Dietary Ellagic Acid Ameliorated Clostridium Perfringens-Induced Subclinical Necrotizing Enteritis In Broilers Via Regulating Inflammation Signaling Pathways And Cecal Microbiota to Inhibit Intestinal Barrier Damage
Authors: Tang Yu , Zhang Xinyue , Wang Yanan , Guo Yongpeng , Zhu Peiqi , Li Guiguan , Zhang Jianyun , Ma Qiugang , Zhao Lihong 
Published: November 2021

Abstract
Background: Subclinical necrotizing enteritis (SNE) is a common intestinal disease caused by Clostridium perfringens in broilers, which cause chronic intestinal damage, affect the digestion and absorption of nutrients, and reduce production performance. Ellagic acid (EA) has been reported to have antioxidant and anti-inflammatory properties in many aspects. This study was conducted to evaluate the effect and mechanism of EA in relieving subclinical necrotizing enteritis in broilers induced by C. perfringens. Results: C. perfringens challenge decreased body weight (BW), average daily gain (ADG); jejunal villi height/crypt depth (V/C); the activity of catalase (CAT), and the mRNA expression of zonula occludens 1 (ZO-1) in jejunum mucosa of broilers. While it increased feed conversion ratios (FCR); jejunal crypt depth (CD); activities of myeloperoxidase (MPO) and diamine oxidase (DAO), as well as concentrations of interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) in serum; activities of inducible nitric oxide synthase (iNOs) and lysozyme (LZM), the concentration of malondialdehyde (MDA), and the mRNA expression of claudin-2, TNF-α, IL-1β, TLR4, TLR2, NF-κB, JAK3, STAT6 and iNOs in jejunum mucosa of broilers. Dietary EA supplement relieved these adverse effects, and heightened jejunal villi height (VH); the concentration of D-xylose in plasma; activities of superoxide dismutase (SOD), and the mRNA expression of occludin in jejunum mucosa of broilers. The alpha diversity of cecal microbiota exhibited dietary EA supplement increased observed species and Shannon index. C. perfringens challenge increased the relative abundance of Firmicutes and decreased the relative abundance of Desulfobacterota. Similarly, EA increased relative abundance of Firmicutes. LEfSe analysis showed that C. perfringens challenge harmed the cecal microbiota of broiler chickens, dietary EA supplementation led to a small beneficial effect, while the simultaneous effect of them seems to stimulate the immune function of broilers and made broilers possess a better cecal microbiota. Conclusions: Dietary EA ameliorated C. perfringens-induced SNE in broilers via regulating jejunal inflammation signaling pathways TLR/NF-κB and JAK3/STAT6, relieving jejunal oxidative stress, and balancing cecal microbiota to inhibit intestinal barrier damage, prevent systemic inflammatory response, and improve nutrient absorption capacity, finally protect and enhance growth performance of broilers.
Multi-Omics Analysis Identifies the Heterogeneity and Prognosis in Bladder Cancer
Authors: Ma Wenchao , Li Cheng , Liu Yuchao , Zhang Wentao , Guo Yadong , Yang Fuhan , Zhang Junfeng , Wang Hong , Jia Weihua , Yao Xudong , Xiao Jun , Yan Yang 
Published: November 2021

Abstract
Background

The multi-omics integrated analysis can help researchers understand the biological behavior of bladder cancer(BCa) in a more systematic and comprehensive manner, and further provide new clues for finding valuable tumor markers and therapeutic targets.
Methods

In this study, we applied the DNA methylation data to construct a prognosis classifier and stratified the BCa patients into high- and low-risk subtype. The differences of transcriptome, single nucleotide variants and copy number variations between two subgroups were explored for finding the changes of molecular mechanism.
Results

With 18 pairs DNA methylation samples, ten differentially methylated positions(DMPs) were identified and applied to evaluate the risk score of each sample. Kaplan-Meier survival analysis displayed that BCa patients with high risk had a poor prognosis than the lower(p<0.0001). In transcriptome analysis, many immune related pathways and biological process changed between high- and low-risk patients. The results also displayed that naive B cells, plasma cells, CD8+ T cells and T cell regulatory(Tregs) infiltrated less in high-risk patients and these patients were less sensitive to immunotherapy and chemotherapy. As for single nucleotide variants, we found that TP53, CDKN1A, STAG2 and other genes were more frequently mutated in high-risk BCa patients. Only copy number variation in high-risk patients were displayed for the limitation of TCGA data.
Conclusions

The high- and low-risk patients identified by DNA methylation data of bladder cancer were significant different in survival. The comprehensive comparison of multi-omics data between subgroups can help clinicians find the heterogeneity of tumor biological behavior and contribute to precision treatment in bladder cancer.
Affibody Molecule for Positron Emission Tomography Imaging of Human Epidermal Growth Factor Receptor: Validation in Mouse Models and Human Cancer Tissues
Authors: Chen Weizhi , Miao Shuang , Sun Yao , Liu Yang , Wang Chunhe , Liu Xiang , Cheng Zhen , Sun Xilin 
Published: November 2021

Abstract
Background: Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) expression status over time post challenges for the design of strategies for effective anti-EGFR monoclonal antibodies in the treatment of non-small-cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for real-time and comprehensive tumor EGFR profiling especially in lung cancer precision medicine trials. Radionuclide imaging of EGFR expression in tumors may screen patients for EGFR-targeting therapies and predict response or resistance to certain treatments.Methods: EGFR-specific Affibody molecule (ZEGFR:1907) was radiolabeled with 68Ga. The radioligands were characterized in vitro and in mice bearing subcutaneous tumors with varying levels of EGFR expression: HCC827 (EGFR overexpression), H1975 (moderate-high), A549 (moderate), H358 (low), and H520 (negative). In vivo tumor targeting activity using PET imaging and biodistribution were conducted in tumor-bearing nude mice. Autoradiography, western blot, immunofluorescence, and immunohistochemistry were performed in human tumor samples. Statistical analyses were performed using GraphPad Prism 7.0. One-way or two-way analysis of variance (ANOVA) followed by the Bonferroni’s multiple comparisons test was used. Statistical significance was set at P < 0.05.Results: 68Ga-NOTA-ZEGFR:1907 showed higher uptake in high EGFR-expressing cells (HCC827, H1975) when compared to cells with moderate to low EGFR (A549, H358) or without EGFR (H520). Radionuclide imaging showed probe accumulation was preferential in EGFR-expressing tumors, particularly in HCC827, H1975 xenografts. A549 and H358 xenografts were mildly and indistinctly visualized. EGFR-negative H520 xenografts were barely visible at any time-point. Biodistribution showed a significantly higher accumulation in HCC827 tumors when compared to H520 tumors (3.20 ± 0.10 %ID/g vs. 0.81 ± 0.08 %ID/g at 2h, P< 0.05). Specific binding to EGFR could be competitively blocked by excess un-radiolabeled affibody molecules in cell uptake, PET imaging and biodistribution assays. Autoradiography showed the regions with high radiotracer uptake partly overlapped with the area of positive EGFR immunofluorescence and immunohistochemistry. Finally, the overall accumulation of autoradiography was positively correlated with immunohistochemistry score.Conclusion: Affibody-based radiotracer 68Ga-NOTA-ZEGFR:1907 is suitable for identification of EGFR expression, showing great potential for further applications and clinical translation.
The Unvirtuous Cycle of Discrimination Affecting People with Hepatitis B
Authors: Freeland Catherine , Mendola Lindsay , Cheng Vivian , Cohen Chari , Wallace Jack 
Published: November 2021

Abstract
Background An estimated 296 million individuals live with chronic hepatitis B worldwide, most have not been diagnosed and remain at risk of liver disease and cancer. People with hepatitis B often face discrimination that denies them employment or education opportunities, results in unfair treatment at work or in school, limits their ability to emigrate to certain countries, and in some cases prohibits them from serving in the military. Discrimination specific to hepatitis B has not been widely documented within the literature. This study aims to investigate and describe hepatitis B related discrimination, document discrimination occurring around the globe, and provide initial recommendations for addressing discrimination using key informant interviews.MethodsPurposive and snowball sampling were used to identify potential key informants for qualitative interview. Key informants identified as community health leaders, public health scientists, doctors, and researchers, many of whom were also living with hepatitis B. Using a semi-structured guide, participants were asked to describe their experience and any challenges for people living with hepatitis B including marginalization and its’ consequences. A codebook was used to guide the organization of data for analysis, and all transcripts N=17 were double coded. Results The overarching themes identified from interviews demonstrate explicit experiences with discrimination of those directly affected, the psychological responses, and the negative health outcomes associated with the unvirtuous cycle of discrimination. All key informants reported on the substantial quality of life implications and often poorer health outcomes resulting from hepatitis B discrimination. Participants also identified the significant impact of hepatitis B discrimination occurring within a range of education-based services across several countries as well as military exclusion or removal if individuals are found to have hepatitis B. ConclusionOur data demonstrate that hepatitis B discrimination has a significant impact. Discrimination can occur in a cyclic nature at various points in life from education, to seeking employment, to marriage, to restrictions on entry, travel and stay in other countries. Hepatitis B discrimination impacts mental and physical health of those experiencing it and limits overall wellbeing, quality of life, can lead to poor health outcomes and avoidance of testing and management.
Optical Coherence Tomography Angiography in Herpetic Leucoma
Authors: Almeida Inês , Dias Libânia , Jesus Jeniffer , Fonseca Inês , Matias Maria João , Pedro João Carlos 
Published: November 2021

Abstract
Background: Herpes simplex virus (HSV) keratitis remains a leading infectious cause of blindness worldwide. This study instends to investigate the potential of Optical Coherence Tomography Angiography (OCTA) device to image and describe quantitatively the vascularization in eyes diagnosed with herpetic leucoma and to discuss and review the usefulness of this technique in this pathology. Methods: A Cross-sectional study was made, including 17 eyes of 15 patients with leucoma secondary to herpetic keratitis. All eyes underwent anterior segment Slit-Lamp photography (SLP), and Optical Coherence Tomography Angiography (OCT) with en-face, b-scans and c-scans imaging. The vessel density (VD) was analyzed in the inferior, nasal and temporal corneal margin in all patients, and in the central area, in eyes with central corneal neovascularization (CoNV). The measurements were calculated after binarization with ImageJ software, using OCTA scans with 6x6 mm in a depth of 800 μm. Results: Patients included had a mean age 53.267±21.542 (years±SD). The mean total vessel area was 50.907±3.435%. VD was higher in the nasal quadrant (51.156±4.276) but there were no significant differences between the three analyzed areas (p=0.940). OCTA was able to identify abnormal vessels when SLP apparently showed no abnormal vessels; OCTA was able to distinguish between larger and smaller vessels even in central cornea; OCTA scans allowed the investigation of several corneal planes and the relation of them with clinical findings. Conclusions: OCTA can be useful in both qualitative and quantitative follow-up of patients and may become a non-invasive alternative to objectively monitor treatment response in eyes with corneal vascularization due to herpetic infection.
Based on Network Pharmacology to Explore the Mechanisms of Radix Astragali Combined with Prepared Radix Rehmanniain for Treating Osteoporosis
Authors: Kang Wenqian , Liu Chunyu , Tang Yu , Geng Zhixin , Zhang Jiahao , Li Min , Gao Feng , Ou Li , Wei Peifeng 
Published: November 2021

Abstract
Background: With the improvement of people's living standards, the aging population in China has gradually increased, and the treatment of osteoporosis (OP) has become a major problem afflicting the medical field. Radix Astragali(RA) and Prepared Radix Rehmannia(PRR) are commonly used Chinese herbal medicines. The combination of them can achieve a synergistic effect in the treatment of osteoporosis. However, its mechanism of action remains uncertain.Objective: This study aims to investigate the possible molecular mechanism of RA combined with PRR in the treatment of OP using an integrated strategy of network pharmacology and experimental validation.Methods: The active ingredients of RA combined with PRR were searched and screened by TCMSP database, and the targets of active ingredients were predicted and supplemented by TCMSP and SwissTargetPrediction databases. The target genes related to OP diseases were searched in GeneCards and OMIM comprehensive databases. The intersection targets of drugs and diseases were imported into String database to obtain the interaction information of intersection target genes. Cytoscape3.7.1 software was used to construct the protein interaction network diagram and "drug component-target-disease" network diagram. Then DAVID database was used for GO gene enrichment analysis and KEGG metabolic pathway analysis. Finally, in vivo experiments were also performed to validate the findings of network pharmacology.Results: A total of 98 active components of RA combined with PRR were finally retrieved and integrated into the TCMSP database, 1700 target genes related to OP were obtained through the disease database, 149 gene targets were obtained by taking the intersection of disease genes, and drug targets, 122 core targets and 514 interaction relationships were obtained after protein interaction network and topology analysis. GO analysis and KEGG pathway enrichment analysis showed that RA combined with PRR intervention for OP mainly through multiple pathways such as PI3K-Akt, MAPK, TNF, Rap1, and Toll-like receptors. In addition, in vivo experiments confirmed that RA combined with PRR could significantly increase bone mineral density, reduce bone spacing, improve bone tissue structure, and improve osteoporosis in ovariectomized rats.Conclusion: In this study, the network pharmacological approach was used to reveal the potential targets and key signal pathways of RA combined with PRR in treating osteoporosis. This study was also verified by animal experiments, which provided a reliable basis for clinical application.