bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ref-1 Redox Activity Alters Cancer Cell Metabolism in Pancreatic Cancer: Exploiting This Novel Finding as a Potential Target&nbsp;&nbsp;
Authors: Gampala Silpa , Shah Fenil , Lu Xiaoyu , Moon Hye-ran , Sandusky George , Hulsey Emily , Mosley Amber , Han Bumsoo , Ivan Mircea , Kelley Mark R , Zhang Chi , Fishel Melissa L 
Published: December 2020

Abstract
Background: Pancreatic cancer is a complex disease with a desmoplastic stroma, extreme hypoxia, and inherent resistance to therapy. Understanding the signaling and adaptive response of such an aggressive cancer is key to making advances in therapeutic efficacy. Redox factor-1 (Ref-1), a redox signaling protein, regulates the DNA binding activity of several transcription factors (TFs), including HIF-1α, STAT3 and NFκB . The conversion of these TFs from an oxidized to reduced state lead to enhancement of their DNA binding. In our previously published work, knockdown of Ref-1 under normoxia resulted in altered gene expression patterns on pathways including EIF2, protein kinase A, and mTOR. In this study, single cell RNA sequencing (scRNA-seq) and proteomics were used to explore the effects of Ref-1 on metabolic pathways under hypoxia.Methods: scRNA-seq comparing pancreatic cancer cells expressing less than 20% of the Ref-1 protein was analyzed using left truncated mixture Gaussian model and validated using proteomics and qRT-PCR. The impact of knocking down Ref-1 under hypoxia was dramatic on the mitochondria and metabolic pathways. Ref-1’s role in mitochondrial function was confirmed using mitochondrial function assays and qRT-PCR. Further, the effect of Ref-1 redox function inhibition against pancreatic cancer metabolism was assayed using 3D co-culture in vitro and xenograft studies in vivo and compared to Devimistat, a drug that disrupts mitochondrial metabolism.Results: Distinct transcriptional variation in central metabolism, cell cycle, apoptosis, immune response, and genes downstream of a series of signaling pathways and transcriptional regulatory factors were identified in Ref-1 knockdown vs Scrambled control from the scRNA-seq data. Mitochondrial DEG subsets downregulated with Ref-1 knockdown were significantly reduced following Ref-1 redox inhibition and more dramatically in combination with Devimistat in vitro. Mitochondrial function assays demonstrated that Ref-1 knockdown and Ref-1 redox signaling inhibition decreased utilization of TCA cycle substrates and slowed the growth of pancreatic cancer co-culture spheroids. In vivo xenograft studies demonstrated that tumor reduction was potent with Ref-1 redox inhibitor similar to Devimistat.Conclusion: Ref-1 redox signaling inhibition conclusively alters cancer cell metabolism by causing TCA cycle dysfunction while also reducing the pancreatic tumor growth in vitro as well as in vivo.
YYFZBJS&nbsp;Inhibits Colorectal Tumorigenesis by Remodeling Enterotoxigenic Bacteroides Fragilis Mediated M2 Macrophage Polarization in Vivo and in Vitro
Authors: Chai Ni , Cheng Yuelei , Xiong Yibai , Shi Wenfei , Yao Yiqing , Yang Limei , Sui Hua , Zhu Huirong 
Published: December 2020

Abstract
BackgroundThe occurrence of CRC is believed to be related to a variety of factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. Our previous studies indicated that the extract of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS), had potent anticancer activities by significantly inhibiting intestinal tumor development in ApcMin/+ mice. However, knowledge regarding the mechanism and effect of YYFZBJS in the prevention of colorectal cancer is limited.MethodsIn this study, we investigated the preventive effects of oral administration of YYFZBJS in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Here, the tumor load, tumor number, histology, and the severity of disease activity index (DAI) scores were reduced as expected.Resultsthe intragastric administration of YYFZBJS in AOM/DSS model significantly decreased ETBF abundance, immunity and some M2 macrophage markers, including CD206, Arg-1, IL-10, and TGF-β. Additionally, reversing polarized macrophages, which has been modified by YYFZBJS, could suppressed CRC cell proliferation and infiltration, as demonstrated by decreasing some tumor proliferation-related proteins in a dose-dependent manner, including c-Met, cyclinD1 and MMPs. Importantly, ETBF dysbiosis can contribute to the development of colon tumor by stimulating p-STAT3 medicated M2 macrophages polarization to promote chronic inflammation and adenoma malignant transformation, which effectively constrained by YYFZBJS.Conclusion﻿Altogether, we demonstrate that ETBF dysbiosis may contribute to M2 macrophages-promoted colon carcinogenesis and progression of CRC cells, and indicating that YYFZBJS could be employed as a promising protective agent against ETBF-mediated colorectal cancer.
Stromal Score-based Gene Signature: A Prognostic Prediction Model for Colon Cancer
Authors: Jia Jing , Dai Yuhan , Zhang Qing , Tang Peiyu , Fu Qiang , Xiong Guanying 
Published: December 2020

Abstract
BackgroundGrowing evidence has revealed the crucial roles of stromal cells in the microenvironment of various malignant tumors. However, efficient prognostic signatures based on stromal characteristics in colon cancer have not been well-established yet. The present study aimed to construct a stromal score-based multigene prognostic prediction model for colon cancer.MethodStromal scores were calculated based on the expression profiles of a colon cancer cohort from TCGA database applying the ESTIMATE algorithm. Linear models were used to identify differentially expressed genes between low-score and high-score groups by limma R package. Univariate and multivariate CoxPH regression analyses were used successively to select prognostic gene signature. An independent dataset from GEO was used as a validation cohort.ResultsLow stromal score was demonstrated to be a favorable factor to overall survival of colon cancer patients in TCGA cohort (log-rank test p = 0.0046). Three hundred and seven stromal score-related differentially expressed genes were identified. Through univariate and multivariate CoxPH regression analyses, a gene signature consisting of LEP, SYT3, NOG and IGSF11 was recognized to build a prognostic prediction model. Based on the predictive values estimated by the established integrated model, patients were divided into two groups with significantly different overall survival outcomes (log-rank test p < 0.0001). Time-dependent Receiver operating characteristic curve analyses suggested the satisfactory predictive efficacy for 5-year overall survival of the model (AUC value = 0.736). A nomogram with great predictive performance combining the multigene prediction model and clinicopathological factors was developed. The established model was verified to be of significant prognostic value for different subgroups in an independent colon cancer cohort from GEO database, which was demonstrated to be especially accurate for young patients (AUC value = 0.752). ConclusionThe well-established model based on stromal score-related gene signature might serve as a promising tool for the prognostic prediction of colon cancer.
Impact of Donation Physicians on Deceased Organ Donation: A Systematic Review
Authors: Squires Janet , Aloisio Laura D , Santos Wilmer John , Cho-Young Danielle , Taljaard Monica , Gritters Nills , Dhanani Sonny , Knoll Gregory 
Published: December 2020

Abstract
Background: An emerging strategy to increase deceased organ donation is to use dedicated donation physicians to champion organ donation. We sought to conduct a systematic review of the effectiveness of donation physicians in improving organ donation outcomes.Data Sources: A systematic review was conducted following Cochrane principles. MEDLINE, Embase, and CINHAL databases were searched from inception to March 26, 2020. Study Selection: Quantitative studies examining the effects of donation physicians on all deceased organ donation outcomes were considered for inclusion. Review articles, editorials and opinion articles, and case studies were excluded. Study selection was completed independently by two team members; all discrepancies were resolved by consensus.Data Extraction: Two team members independently extracted data from studies. Data Synthesis: A total of 1,017 studies were screened, and 12 met inclusion criteria. Included studies were published between 1994 and 2019. Half used an interrupted time series design (n = 6; 50%), three (25%) were cohort studies, and three (25%) used a before-and-after study design. Outcomes (reported in greater than 50% of included articles) included consent/refusal rate (n = 8; 67%), number of potential donors (n = 7; 58%), and number of actual donors (n = 7; 58%). Across studies and design types, there was an increase in potential organ donors ranging from 8 to 143% (Mdn = 33%), an increase in actual organ donors from 15 to 113% (Mdn = 27%), an increase in donor consent rate from -3 to 258% (Mdn = 12%) and an increase in deceased donor transplants from 13 to 24% (Mdn = 19%) following the introduction of donation physicians.Conclusions: Donation physicians have the potential to significantly improve deceased organ donation. Further implementation and evaluation of donation physician programs is warranted. However, implementation should be undertaken with a clear plan for a methodologically rigorous evaluation of outcomes.
Prognostic Value and Immune Infiltration of Novel Biomarkers in Glioma: Evidence From a Comprehensive Analysis of Tumor Microenvironment
Authors: Zhang Bolun , Guan Feng , Dai Bin , Zhu Guangtong , Mao Beibei , Liang Xin , Hu Zhiqiang 
Published: December 2020

Abstract
BackgroundIn the glioma microenvironment, infiltrating immune cells has been shown to possess beneficial effects for tumor progression. Immune cells and stromal cells dominate the tumor microenvironment in glioma. The complex interplay between the tumor progression with immune cells or stromal cells was still unknown. MethodsIn this study, we used Estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) calculations to calculate the proportion of tumour-infiltrating immune cells (TIC) and the number of immune and stromal components in glioma cases from the cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Differentially expressed genes (DEG) were analyzed by COX regression analysis and protein-protein interaction (PPI) network construction. Then, JAK3, IL2RB and CD3E were identified as predictors by the intersection analysis of univariate COX and PPI, and further analysis showed that the expression of them were positively correlated with survival and clinicopathological characteristics of glioma patients. Finally, the Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) deconvolution algorithm was applied to quantify the fraction and infiltration of 22 types of immune cells in glioma. ResultsOur results showed that ESTIMATEScores Were Correlated with the Survival of glioma Patients, DEGs Shared by ImmuneScore and StromalScore were predominantly presented as the enrichment of immune-related genes gene set enrichment analysis (GSEA). The intersection analysis of PPI network and univariate COX regression enabled us to identify three genes (JAK3, IL2RB and CD3E) that had never been reported before, whose expression was correlated with clinical characteristics such as survival and WHO grading of these patients. CITICSORT analysis of TIC ratio showed that B cell memory and CD8 + T cells were positively correlated with JAK3, IL2RB and CD3E expression, suggesting that these genes may be responsible for maintaining the immunodominant state of TME. CIBERSORT analysis for the proportion of TICs revealed that the levels of JAK3, IL2RB and CD3E affected the immune activity of TME.ConclusionOur results confirmed that the JAK3, IL2RB and CD3E can be used as diagnostic and prognostic biomarkers for glioma and may be used as therapeutic targets in the future.
Needle Biopsy Compared With Surgical Biopsy: Pitfalls of Small Biopsy in Histologial Diagnosis of IgG4-related Disease
Authors: Liu Yanying , Yang Fei , Chi Xiying , Zhang Yuxin , Fu Jiangnan , Bian Wenjie , Shen Danhua , Li Zhanguo 
Published: December 2020

Abstract
ObjectiveThe growing utilization of needle biopsy has challenged the current pathology consensus of IgG4-related disease (IgG4-RD). The aims of this study were to identify the histological characteristics of needle biopsy and surgical specimens, and evaluate the ability of needle biopsy in histological diagnosis of IgG4-RD.MethodsBiopsies from patients who were referred to as IgG4-RD by the 2019 ACR/EULAR IgG4-RD classification criteria in Peking University People’s Hospital from 2012 to 2019 were re-evaluated. Typical histological features and diagnostic categories were compared between needle biopsy and surgical biopsy.ResultsIn total, 69 patients met the 2019 ACR/EULAR classification criteria and 72 biopsies of them were re-evaluated. All cases showed lymphoplasmacytic infiltrate, while storiform fibrosis and obliterative phlebitis were only present in 35 (48.6%) and 23 (31.9%) specimens, respectively. Storiform fibrosis was more likely to be seen in retroperitoneum lesion (P=0.033). Surgical biopsy showed significantly higher IgG4+ plasma cells/high power field (IgG4/HPF) count (P<0.01) and higher proportion of IgG4/HPF>10 (P<0.01). No significant difference was observed with regard to the ratio of IgG4+/IgG+ cells (IgG4/IgG) (P=0.399), storiform fibrosis (P=0.739), and obliterative phletibis (P=0.153). According to the 2011 comprehensive diagnostic criteria, patients who performed a needle biopsy were less likely to be probable IgG4-RD (P=0.045). Based on the 2011 pathology consensus, needle biopsy was tougher to be diagnosed as IgG4-RD (P<0.01), especially to be highly suggestive IgG4-RD (P<0.01). Only 1/18 (5.6%) needle salivary specimens fulfilled the cutoff of IgG4/HPF>100, which was significantly less than 15/23 (65.2%) of surgical ones (P<0.01).ConclusionsNeedle biopsy shows an inferiority in detecting IgG4/HPF count but not in IgG4/IgG ratio, storiform fibrosis and obliterative phlebitis. Compared with surgical samples, it is tougher for needle biopsy to obtain a histological diagnosis of IgG4-RD. A different IgG4/HPF threshold for needle biopsy of salivary glands may be considered.
Perceived Stress Among University Students in South-East Serbia During the COVID-19 Outbreak
Authors: Kostic Jelena , Zikić Olivera , Đorđevic Vladimir , Krivokapic Zilijeta 
Published: December 2020

Abstract
Background The COVID-19 pandemic has brought into focus the mental health the student population. The study aimed to analyze the psychological response to the COVID-19 outbreak in terms of perceived stress and its related factors among university students in the southeastern Serbia. The study was conducted during the increasing rate of the coronavirus disease in Serbia. Method A total of 434 students from the public university in South-East Serbia enrolled in the study and completed the measures of socio-demographical data, the Perceived stress scale (PSS-10), the Coping Strategy Indicator (CSI) and the General Health Questionnaire (GHQ-28). The data were analyzed through quantitative and qualitative methods. Results Study findings suggest that the mean perceived stress score was placed to 20.43 (±7.67), suggesting that the students showed high stress level during the COVID-19 outbreak. Our model showed that female gander, higher scores on anxiety/insomnia and depression subscales as well as the coping strategy avoidance predicted higher level of perceived stress, while higher scores on social dysfunction were related to the reduced perceived stress scores. Conclusion Besides limitation of the study, findings provided authentic data of stress reactions of students in South-East Serbia during the COVID-19 outbreak. The findings confirm the need to examine the experience of students in states of emergencies and crisis as well as introduce a plan for support programs aimed at preventing a decline in education efficacy in the long run, together with preventing the occurrence of mental disorders.
Assessing Frequency and Clinical Outcomes of BRCA Mutated Ovarian Cancer in Saudi Women
Authors: Agha Naela , Alshamsan Bader , Al-Farsi Sharifa , Ateya Heba Aly , Almugbel Fahed A , Alotaibi Hazem Abdullah , Omar Ayman , Mohamed Amgad Shahin , Alharthy Hanan , Elhassan Tusneem , Salem Hany , Alhussainia Hamed 
Published: December 2020

Abstract
Background: BRCA gene mutations (BRCAm) had an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women.This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. The objective response rate (ORR) of the first line and subsequent lines for BRCAm and BRCAw were evaluated using Response Evaluation Criteria in Solid Tumors Version 1. The disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier methods and compared by log-rank tests.Result: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The majority were BRCA 1 (92%), and the most common deleterious germline BRCA1 mutation was c.1140dupG (39%), followed by c.5530del (13%) and c.5095C>T (8%). Most women (72%) had no family history of cancers, all had high-grade serous carcinoma, and 82% had advanced stage at presentation. Regardless of BRCA mutations, an optimal ORR to first-line treatment has been achieved although most cases relapsed after the first line of management (84%) and the majority were platinum-sensitive relapse (85%). The ORR was higher in BRCAm in subsequent lines compared to BRCAw type. BRCAm women experienced longer median DFS (25 vs 17 months, p = 0.02) and a higher five-year OS rate (90.9% vs 66.7%, p = 0.19) than BRCAw.Conclusion: The prevalence of BRCAm of OC was higher in Saudi women when compared with the regional and most of the international figures. The better clinical outcomes of BRCAm women is in concordance with the reported evidence. Further studies on BRCA mutations of OC, education, genetic counseling, and free access to genetic testing are highly recommended.
A Multiplex PCR Assay for Six Aedini Species, Including Aedes albopictus
Authors: Bang Woo Jun , Won Min Hyeok , Cho Seong Tae , Ryu Jihun , Choi Kwang Shik 
Published: December 2020

Abstract
BackgroundMosquitoes, as vectors of various human pathogens, are significant drivers of serious human illness. In particular, those species in the Aedini tribe, which typically transmit dengue virus, Chikungunya fever virus, and Zika virus, are increasing their range because of climate change and international commerce. In order to prevent mosquito-borne disease, accurate mosquito species identification and monitoring are needed. The goal of this work was to develop a rapid and simple molecular diagnostic method for six morphologically similar Aedini species (Aedes flavopictus, Aedes albopictus, Ochlerotatus koreicus, Ochlerotatus japonicus, Ochlerotatus togoi, and Ochlerotatus hatorii) in Korea.MethodsIn total, 109 samples were used in this study. The internal transcribed spacer 2 (ITS2) regions from all six species were amplified, sequenced and analyzed using Mega 6. Once regions that were consistently different in sequence between all six species were identified, multiplex primers were designed to amplify them to generate species-specific fragments distinguishable by their size. ResultsUniquely sized fragments were generated in Aedes flavopictus (495bp), Aedes albopictus (438bp), Ochlerotatus koreicus (361bp), Ochlerotatus togoi (283bp), Ochlerotatus hatorii (220bp), and Ochlerotatus japonicus (160bp). Pairwise distance analysis showed that the difference was 35.0±1.5% between Aedes spp. and Ochlerotatus spp., 17.4±0.2% between Aedes albopictus and Aedes flavopictus, and 11.1±0.3% between Ochlerotatus koreicus and Ochlerotatus japonicus.ConclusionsIn this study, a multiplex PCR assay for six species of the Aedini tribe was developed. This assay is more accurate than morphological identification and will be useful for monitoring and controlling these vector mosquitoes.
Effectiveness of multicomponent treatment in patients with fibromyalgia: Protocol for a systematic review and meta-analysis
Authors: Araya-Quintanilla Felipe , Gutierrez-Espinoza Hector , Fuentes Jorge , Prieto-Lafrentz Fernanda , Pavez Leonardo , Cristi-Montero Carlos , Cavero-Redondo Ivan , Alvarez-Bueno Celia 
Published: December 2020

Abstract
Background
The purpose of this protocol is to provide new and clear data on the systematic review with meta-analysis with the current Cochrane methodology to compare the effectiveness of multicomponent treatment versus other interventions for patients with fibromyalgia.
Methods
This protocol conforms to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and the recommendations of the Cochrane Collaboration Handbook. An electronic search will be conducted in MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL, LILACS, CINAHL, and PEDro, from the inception until January 2021. There will be no language restrictions. The Cochrane Collaboration tool for assessing the risk of bias (RoB2) will be used. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scale will be used to evaluate the strength of the evidence. The DerSimonian and Laird random effects of Mantel-Haenszel fixed effects methods will be used, depending on the heterogeneity. To compute a pooled estimate of mean difference (MD) or standardized mean difference (SMD), and respective 95% confidence intervals (CI) for pain intensity, physical function, pain catastrophizing, kinesiophobia, quality of life, sleep quality, and level of depression.
Discussion
This systematic review will synthesize evidence on the effectiveness of multicomponent treatment in patients with fibromyalgia. This systematic review could add important evidence in the treatment of FM that could improve the clinical practice and the making of decisions and actions in this field. The novel statistical analysis will try to show the effects of multicomponent treatment by type and dose of exercise in patients with FM. The results will be disseminated by publication in a peer-reviewed journal. Ethics approval will not be needed because the data used for this systematic review will be obtained from individual trials and there will be no concerns about privacy.
PROSPERO systematic review registration number:
CRD42020142082