bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of HIF-1α and high density of tumor associated macrophages predict tumor aggression, invasion and unfavorable prognosis of Kazakh esophageal squamous cell carcinomas
Authors: Jiang xianli , Xie Yufang , Jiang Xingran , Jiang Chenhao , Yuan Xin , Wang Xueli , Yang Lan , Liu Chunxia , Pang Lijuan , Liang Weihua , Cui Xiaobin , Shen Xihua , Gu Wenyi , Hu Jianming , Li Feng 
Published: July 2020

Abstract
Background

A hypoxic tumor microenvironment promotes the recruitment and transformation of macrophages and facilitates tumor progression. Hypoxia-induced factor-1α (HIF-1α) is a key factor in hypoxia. It is not clear whether HIF-1α and tumor associated macrophages (TAMs) play a synergistic role in neoplastic progression. Here we investigated potential synergism between HIF-1α and TAMs in the progression of Kazakh esophageal squamous cell carcinoma (ESCC).
Methods

We used immunohistochemistry (IHC) verify the expression of HIF-1α and vascular endothelial growth factor (VEGF) in tumor tissue. CD163 was used as a marker for TAMs, and the density of TAMs in tumor tissues were determined. Kazakh ESCC samples exhibited higher expression of HIF-1α and VEGF and greater density of TAMs compared to cancer adjacent normal (CAN) tissues.
Results

Overexpression of HIF-1α was significantly correlated with vascular invasion, lymph node metastasis and the clinical tumor stage of Kazakh ESCCs. Overexpression of HIF-1α was also associated with poor prognosis of Kazakh ESCC. Moreover, overexpression of HIF-1α was positively correlated with high TAM density and overexpression of VEGF (P < 0.05). Furthermore, the correlation between VEGF overexpression and high density of TAMs was very significant (P < 0.001).
Conclusions

These data suggest that overexpression of HIF-1α may increase the infiltration of TAMs in Kazakh ESCC, thereby increasing VEGF expression, which may in turn promote the progression of Kazakh ESCC.
Loss of tubal ciliated cells as a risk for “ovarian” or pelvic serous carcinoma
Authors: Wang Yue , Lin Wanrun , Wang Yiying , Wang Yan , Chambers Setsuko , Li Bo , Lea Jayanthi , Zheng Wenxin 
Published: July 2020

Abstract
Background

Recent advances suggest the fallopian tube as the main anatomic site for high-grade ovarian or pelvic serous carcinoma (O/PSC). Human fallopian tube is mainly lined by two cell types, secretory and ciliated cells. Large number of studies on the biologic role of tubal secretory cells in O/PSC have been performed in the last decade. However, the role of tubal ciliated cells in relation to the development of O/PSC has rarely been explored. The purpose of this study was to determine if change of the tubal ciliated cells shows difference in age and location and to examine their association with serous neoplasia.
Methods

Three groups (low-risk or benign control, high-risk, and O/PSC) of patients were age matched. The age data was stratified by 10-year intervals ranging from age 20 to older than 80. Ciliated cells from both tubal fimbria and ampulla segments were counted by microscopy and by tubulin immunohistochemical staining. The data was analyzed by standard contingency table, Poisson distribution methods, nonparametric Mann–Whitney U-tests and Spearman correlation analysis after age justification.
Results

The study revealed that the absolute number of tubal ciliated cells decreased significantly with age within each group. A reduction in ciliated cells within the fallopian tube remained a significant risk factor for serous neoplasia after age adjustment. A dramatic decrease of tubal ciliated cells in both tubal segments was identified in patients with high-risk and with O/PSC compared to those in the low-risk (benign control) group (p < 0.001). Further, within the fimbria segment, a reduced number of tubal ciliated cells was more prevalent in the high-risk group when compared to those in O/PSC group.
Conclusion

Our findings suggest that reduced number of ciliated cells within the fallopian tube represents a hallmark of early serous carcinogenesis. Findings also support a relationship between loss of tubal ciliated cells and aging, the presence of high-risk factors, and co-existing ovarian or pelvic high-grade serous cancers. This represents an early study identifying the role of tubal ciliated cells in the process of high-grade O/PSC development.
The Early-Life Risk Factors of Childhood Wheezing: Results from the NHANES During 2005-2012
Authors: Moradzadeh Rahmatollah , Zamanian Maryam 
Published: July 2020

Abstract
Objectives: Wheezing is the most common cause of hospitalization during childhood. The aim of the present study was to identify early-life risk factors predisposing to childhood wheezing using directed acyclic graph (DAG) analysis.Methods: In this study, we used the National Health and Nutrition Examination Survey (NHANES) data to identify the risk factors associated with wheezing in children aged 1-15 years old in the United States. The data was related to four 2-year cycles from 2005 to 2012. All the adjusted analyses were based on the directed acyclic graph(DAG). The applied logistic regression was performed by survey analysis to adjust the weights of samples.Results: From 13203 children, 87.2% (n = 11 519) had not experienced wheezing during the past year, and 12.8% (n=1684) experienced wheezing during the same time. The mean ages (SD) were 6.6 (4.4) and 7.6 (4.4) years old in wheezing and healthy children respectively. Boys comprised a significantly higher ratio in wheezing compared with healthy children (P = 0.001). Mother smoking during pregnancy (MSDP) was a significant risk factor for childhood wheezing (OR= 1.42, 95% CI: 1.15-1.74, P = 0.001). All ethnicities other than the Mexican-American were established as significant risk factors for childhood wheezing. On the other hand, childhood wheezing was insignificantly associated with Socio-economic status, birth weight, maternal age at pregnancy, and exposure to smoke at home.Conclusion: After adjusting for established confounders, history of MSDP, as well as ethnicity delivered important risk factors for childhood wheezing in a large population of the US.
Demand for Family Planning among Poor Women in Uganda: Analysis of the Uganda Demographic and Health Surveys
Authors: Kabagenyi Allen , Kakande Pamela , Owayezu Vianney 
Published: July 2020

Abstract
Background: Family planning is one of the major cost-effective interventions to improve maternal health, reduce maternal and child mortality, and prevent unplanned pregnancies, yet its use remains low in sub-Saharan Africa, especially among the poor. In Uganda, little is known about the factors influencing the demand for family planning among the poor. This study examines the determinants of demand for family planning among poor women in a limited-resource setting.Methods: The study is based on data from the 2006, 2011, and 2016 Uganda Demographic and Health Surveys (UDHS). Multilevel binary logistic regressions were used to examine the influence of different demographic, behavioral, and socioeconomic factors on poor women’s demand for family planning.Results: Our findings showed demand for family planning was 56% in 2006, 60% in 2011, and 65% in 2016 among women in the poorest and poorer household health quintiles who were married or in union. In all three surveys, women age 25-39 had higher odds of demand for family planning compared with women age 15-24. Women with no education had lower odds of demand for family planning compared with those with secondary education. Also, in the 2011 UDHS, women who had heard about family planning on the radio had higher odds of demand for family planning compared with those who had not, and in the 2006 survey women who had discussed family planning at a health facility had higher odds of demand for family planning compared with women who had not done so.Conclusions: Demand for family planning is influenced by a woman’s age, educational attainment, religion, exposure to family planning messages on the radio, and discussion on family planning at a health facility. This study underscores the need for increased family planning counseling by health workers and more discussion about family planning at the health facility. The findings further suggest the need to provide increased adequate family planning services and information for the poor, uneducated, and rural women to meet the demand for family planning.
Differentiation of endogenous Erythropoietin and exogenous ESAs by Western blotting with deglycosylation
Authors: Yasuoka Yukiko , Fukuyama Takashi , Izumi Yuichiro , Yamashita Tetsuro , Nakayama Yushi , Inoue Hideki , Yanagita Kengo , Oshima Tomomi , Yamazaki Taiga , Uematsu Takayuki , Kobayashi Noritada , Shimada Yoshitaka , Nagaba Yasushi , Mukoyama Masashi , Sato Yuichi , Sands Jeff M. , Kawahara Katsumasa , Nonoguchi Hiroshi 
Published: July 2020

Abstract
Doping tests for illegal use of erythropoiesis-stimulating agents (ESAs) have been developed. Here, we show a new Western blotting to distinguish endogenous erythropoietin (Epo, 35-38 kDa) and exogenous ESAs (epoetin alpha and beta; 38-42 kDa, darbepoetin alpha; 47-50 kDa, epoetin beta pegol; 93-110 kDa). In contrast, Liquid Chromatography/Mass Spectrometry analyzed all endogenous Epo and exogenous ESAs as delycosylated 22 kDa Epo, indicating that LC/MS analysis could not distinguish Epo and ESAs. We believe that our Western blotting is useful to protect against illegal use of ESAs.
Identification of core genes and pathways in melanoma metastasis via bioinformatics analysis
Authors: Li Yumei , Li Bifei , Chen Fan , Shen Weiyu , Katanaev Vladimir L. , jia lee 
Published: July 2020

Abstract
Background

Metastasis is the leading cause of melanoma mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. This study aimed to screen for the key core genes and molecular mechanisms related to the metastasis of melanoma.

Methods

Gene expression profile, GSE8401 including 31 primary melanoma and 52 metastatic melanoma clinical samples, was downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between metastatic melanoma and primary melanoma were screened using GEO2R. Assays of gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and protein-protein interaction (PPI) were performed to visualize these DEGs through Database for Annotation, Visualization and Integrated Discovery (DAVID) software and Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with Molecular Complex Detection (MCODE) plug-in tools. Top 10 genes with high degree were defined as hub genes. Furthermore, paired post-metastatic melanoma cells and pre-metastatic melanoma cells were established by experimental mouse model of melanoma metastasis to verify the expression of these hub genes.

Results

424 DEGs between the metastatic melanoma and primary melanoma were screened, including 60 upregulated genes enriched in ECM-receptor interaction and progesterone-mediated oocyte maturation and 364 downregulated genes enriched in amoebiasis, melanogenesis, and ECM-receptor interaction. CDH1, EGFR, KRT5, COL17A1, KRT14, IVL, DSP, DSG1, FLG and CDK1 were defined as the hub genes. . In addition, paired post-metastatic melanoma cells (A375M) and pre-metastatic melanoma cells (A375) were established and qRT-PCR analysis confirmed the expression of the hub genes during melanoma metastasis.

Conclusion

This bioinformatic study has provided a deeper understanding of the molecular mechanisms of melanoma metastasis. KRT5, IVL and COL17A1 have emerged as possible biomarkers and therapeutic targets in metastasis of melanoma.
What is The Main Problem in The Conservative Management of Complicated Appendicitis? A Meta-Analysis.
Authors: Zhang Chi , Ren Xuemeng , Gao Peng 
Published: July 2020

Abstract
Background: As one of the classified groups of appendicitis, complicated appendicitis has no standardized treatment methods for adults.Method: The efficacy of surgical treatment and conservative treatment for complicated appendicitis was evaluated based on the literatures systematically searched on PubMed, Cochrane and Web of Science. A focus was given to important aspects, such as the outcomes of the length of stay, operation time, postoperative complications and unplanned additional interventions. Result: A total of 14 studies were involved in the meta-analysis, which included 845 patients in the immediate operation group (IO) and 756 patients in the conservative management group (CM). The total hospitalization time for patients with surgical treatment was decreased by 1 day (WMD= -1.29, 95% CI [-2.42, -0.16], P= 0.03< 0.05) compared to that of patients with conservative treatment. The incidence of unplanned additional interventions in patients who underwent emergency surgery is lower than that of patients with conservative treatment (OR=0.18, 95%CI [0.11, 0.30], P<0.00001). Compared to patients with conservative treatment, patients who received surgery are more likely to develop complications such as wound infection (OR=2.41, 95%CI [1.08, 5.38], P=0.03<0.05) and intestinal obstruction (OR=4.14, 95%CI [2.21, 7.75], P<0.00001). The incidence of abdominal abscess in patients with surgery treatment was lower than that of patients with conservative treatment, but the difference was not statistically significant (OR=0.9, 95%CI [0.54, 1.47], P=0.66>0.05). Conclusion: In treating complicated appendicitis, patients who received immediate operation, when compared to patients managed under conservative treatment, have shorter hospitalization time and less unplanned interventions; hence significantly reduce the likelihood of readmission. This can decrease the requirements for follow-up treatments and ultimately lower the consumption of medical resources.
Validation of an Immune-Related Gene Pair Index as a Prognostic Marker of Lung Squamous Cell Carcinoma
Authors: Wang Zihao , Xiang Xuan , Wei Xiaoshan , Ye Linlin , Niu Yiran , Peng Wenbei , Li Yu , Wang Xu , Zhang Siyu , Zhou Qiong 
Published: July 2020

Abstract
Background: Lung squamous cell carcinoma (LUSC) is one of the subtypes of non-small-cell lung cancer (NSCLC) and accounts for approximately 20 to 30% of all lung cancers. Methods: In this study, we developed an immune-related gene pair index (IRGPI) for LUSC from 8 public LUSC data sets, including The Cancer Genome Atlas LUSC cohort and Gene Expression Omnibus data sets, and explored the prognostic value of IRGPI for patients with LUSC. Results: IRGPI was constructed by 13 gene pairs consisting of 25 unique immune-related genes from the training cohort. Multivariate cox regression analysis showed that high risk based on IRGPI was an independent risk factor for poor prognosis of patients with LUSC in the training cohort (230 patients; HR= 3.40; 95%CI [2.34-4.94]; p<0.001), the testing cohort (228 patients; HR=2.11; 95%CI [1.48-3.01]; p<0.001) and the validation cohort (472 patients; HR=1.99; 95%CI [1.5-2.63]; p<0.001). The infiltrations of naïve B cells, plasma cells, CD8+ T cells, activated memory CD4+ T cells, gamma delta (γδ) T cells, M1 macrophages, and activated dendritic cells were lower in the high-risk group, as compared with the low-risk group in the TCGA cohort. The infiltrations of neutrophils, activated mast cells, and monocytes were higher in the high-risk group. Conclusions: IRGPI is a significant prognostic biomarker for predicting overall survival in LUSC patients. Combining clinical features with IRGPI will improve prognostic accuracy.
CLDN6 and CLDN10 are Associated with Immune Infiltration of Ovarian Cancer: A Study of Claudin Family
Authors: Gao Peipei , Peng Ting , Cao Canhui , Lin Shitong , Wu Ping , Huang Xiaoyuan , Wei Juncheng , Xi Ling , Yang Qin , Wu Peng 
Published: July 2020

Abstract
Background: Claudin family is a group of membrane proteins related to tight junction. There are many studies about them in cancer, but few studies pay attention to the relationship between them and the tumor microenvironment. In our research, we mainly focused on the genes related to the prognosis of ovarian cancer, and explored the relationship between them and the tumor microenvironment of ovarian cancer.Methods: The cBioProtal provided the genetic variation pattern of claudin gene family in ovarian cancer. The ONCOMINE database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to exploring the mRNA expression of claudins in cancers. The prognostic potential of these genes was examined via Kaplan-Meier plotter. Immunologic signatures were enriched by gene set enrichment analysis (GSEA). The correlations between claudins and the tumor microenvironment of ovarian cancer were investigated via Tumor Immune Estimation Resource (TIMER).Results: In our research, claudin genes were altered in 363 (62%) of queried patients/samples. Abnormal expression levels of claudins were observed in various cancers. Among them, we found that CLDN3, CLDN4, CLDN6, CLDN10, CLDN15 and CLDN16 were significantly correlated with overall survival of patients with ovarian cancer. GSEA revealed that CLDN6 and CLDN10 were significantly enriched in immunologic signatures about B cell, CD4 T cell and CD8 T cell. What makes more sense is that CLDN6 and CLDN10 were found related to the tumor microenvironment. CLDN6 expression was negatively correlated with immune infiltration level in ovarian cancer, and CLDN10 expression was positively correlated with immune infiltration level in ovarian cancer. Further study revealed the CLDN6 expression level was negatively correlated with gene markers of various immune cells in ovarian cancer. And, the expression of CLDN10 was positive correlated with gene markers of immune cells in ovarian cancer.Conclusions: CLDN6 and CLDN10 were prognostic biomarkers, and correlated with immune infiltration in ovarian cancer. Our results revealed new roles for CLDN6 and CLDN10, and they were potential therapeutic targets in the treatment of ovarian cancer.
“Taking Care of Your Pregnancy”: A Mixed-Methods Study of Group Antenatal Care in Kakamega County, Kenya
Authors: Somji Aleefia , Ramsey Kate , Dryer Sean , Makokha Fredrick , Ambasa Constance , Aryeh Brittany , Booth Kathleen , Xueref Serge , Moore Seneca , Mwenesi Ralpher , Rashid Shafia 
Published: July 2020

Abstract
Background: Traditional antenatal care (ANC) models often do not meet women’s needs for information, counseling, and support, resulting in gaps in quality and coverage. Group ANC (GANC) provides an alternative, person-centered approach where pregnant women of similar gestational age meet with the same health provider for facilitated discussion. There are few studies that show associations between GANC and various outcomes. Methods: We used mixed methods to evaluate a contextualized GANC model (Lea Mimba Pregnancy Clubs) and to understand implementation experiences at six health facilities in Kakamega County, Kenya. Between April 2018 and January 2019, we tracked 1,652 women who were assigned to 162 GANC cohorts to assess ANC retention. Using an intention-to-treat approach, we conducted baseline (N = 112) and endline surveys (N = 360) with women attending immunization visits to assess outcomes and used time diaries to assess wait times. At endline, we conducted 29 in-depth interviews (IDIs) and three focus group discussions with women who were currently and previously participating in GANC, and 15 IDIs with stakeholders.Results: GANC was associated with enhanced social support, with some evidence for improved knowledge, adoption of healthy behaviors, enhanced self-efficacy, and improved experience of care. Quantitatively, we found strong associations with knowledge of danger signs, women who shared their feelings with other women, knowledge and competence of health workers, respect shown by ANC providers, overall quality of care, and birth preparations. No changes were seen in knowledge of positive behaviors, empowerment, several aspects of the experience of care, ANC retention, early ANC, and other healthy behaviors. Qualitatively, women and stakeholders noted improvements in interactions between health providers and women, improved counseling, increased feelings of empowerment to ask questions and speak freely, and strengthened social networks and enhanced social cohesion among women. Both wait times and counseling times increased in GANC compared to traditional ANC.Conclusions: This is one of the few mixed-methods studies evaluating GANC and offers new measures for experience of care, empowerment, and adoption of healthy behaviors. While more research is required, GANC holds promise for enhancing women’s experiences during pregnancy. Modifications are needed for sustainability and scalability.
Identification of hub genes associated with accumulation of extracellular matrix as biomarkers of diabetic nephropathy
Authors: Feng Song-Tao , Gao Yue-Ming , Yin Di , Lv Lin-Li , Wen Yi , Li Zuo-Lin , Wang Bin , Wu Min , Liu Bi-Cheng 
Published: July 2020

Abstract
Background

Diabetic nephropathy (DN) remains a major cause of end stage renal disease (ESRD). The development of novel biomarkers and early diagnosis of DN are of great clinical importance. The goal of this study was to identify hub genes with diagnostic potential for DN by weighted gene co-expression network analysis (WGCNA).
Methods

Gene Expression Omnibus (GEO) database was searched for microarray data including distinct types of chronic kidney diseases (CKD). Gene co-expression network was constructed and modules specific for DN were identified by WGCNA. Gene Ontology (GO) analysis was performed and the hub genes were screened out within the selected gene modules. Furthermore, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic values of hub genes. In addition, an external validation was performed in an independent dataset.
Results

Dataset GSE99339 was selected and a total of 179 microdissected glomeruli samples were analyzed, including DN, normal control and 7 groups of other glomerular diseases. 23 modules of the total 10947 genes were grouped by WGCNA and a module was specifically correlated with DN (r = 0.54, 9e-15). GO analysis showed that module genes were mainly enriched in the accumulation of extracellular matrix (ECM). LUM, ELN, FBLN1, MMP2, FBLN5 and FMOD were identified as hub genes. Furthermore, levels of hub genes were the highest in DN compared to other groups, which could differentially diagnose DN (AUC, 0.67 ~ 0.95). External verification showed hub genes were higher in DN group and were negatively correlated with eGFR.
Conclusions

By using WGCNA approach, we identified 6 hub genes, LUM, ELN, FBLN1, MMP2, FBLN5 and FMOD, related to ECM accumulation and were specific for DN. These genes may represent potential candidate diagnostic biomarkers of DN.