bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Media Perceptions of Clubfoot Treatment: A Global Observational Study
Authors: Keil Evan J , Shaikh Hashim , Navarro Sergio M , Dube Andile , Yao Lilian E , Sheik-Ali Sharaf , Ncube Thando , Lavy Chris
Published: August 2020

Background: Clubfoot is a debilitating congenital anomaly that is often under treated in lower- and middle-income countries. There exists an active social media community with regards to clubfoot on both Instagram and Twitter. The purpose of this observational study was to investigate shared content related to clubfoot on social media. Methods: A search for public posts on social media regarding clubfoot was performed from October 31st, 2018 to October 31st, 2019. Three hashtags on Instagram and Twitter were analyzed: #clubfootsurgery, #clubfoot, and #clubfootmommas. Data was analyzed using Chi-squared tests with significance set to p<0.05.Results: Overall, 2050 posts with clubfoot-related hashtags were identified as publicly shared on these social media platforms over the 12-month period. 1992 met the inclusion criteria. Pictures consisted of 93.9% of posts which overwhelmingly had a positive tone, while only 16 posts were explicitly negative. On Instagram, personal accounts authored 95.5% of posts and on Twitter, organizations shared 99.4% of posts. Content related to active treatment was shared 32.7% of the time - of these posts, 94.8% showed Ponseti casting or Ponseti bracing. Chi-squared analysis was performed comparing Instagram with Twitter for media format, timing, tone, author, content, visibility, and topic reference. Statistically significant differences between the two (p<0.001) groups were found in each of these categories.Conclusions: Clubfoot treatment has a large social media presence with contributions from patients, treatment organizations, and physicians. Personal accounts on Instagram emphasize the patient experience, whereas organizations on Twitter focus primarily on education and increasing overall awareness.
Menarche and menopausal age changes over 40 years and its effective factors in women studied in Cohart Fasa population
Authors: Bazyar Neda , Jeihooni Ali Khani , moradi Zahra , Dehghan Azizollah , Farjam Mojtaba , Moradi Fatemeh
Published: August 2020

Background: Age at menarche and menopause is affected by various factors. A reduction has been observed in these ages over time. The present study aimed to determine the trend of changes in age at menarche and age at menopause among the women participating in Fasa Cohort Study over a 40-year period. Methods: This cross-sectional, descriptive-analytical study was conducted on 5545 women aged over 35 years in Fasa cohort population as a branch of the Persian cohort study. The participants were selected via census. The study data were obtained from the information registered in Fasa Cohort Center. Then, they were entered into the SPSS 22 software and were analyzed using descriptive statistics, chi-square test, correlation coefficient, and linear regression analysis. Results: The results showed that the mean age at menarche reduced from 14.66 to 13.40 years and the mean age at menopause decreased from 56.88 to 40.16 years over the 40-year period, and the reductions were statistically significant (p<0.001). Age at menarche was affected by body mass index and physical activity. Besides, age at menopause was affected by education level, marital status, diabetes, hypertension, cardiovascular diseases, cervical cancer, hysterectomy, and stillbirth (p<0.001). Conclusion: The results showed a decrease in age at menarche and age at menopause over the 40-year period.
rTMS modulates precuneus-hippocampal subregion circuit in subjective cognitive decline
Authors: Chen Jiu , Hu Guanjie , Xue Chen , Qi Wenzhang , Xu Wenwen , Chen Shanshan , Rao Jiang , Liu Wan , Zhang Fuquan , Zhang Xiangrong
Published: August 2020

Background: Hippocampal subregions (HIPsub) and their network connectivities are considered to be abnormal in subjective cognitive decline (SCD). This study aimed to identify whether repetitive transcranial magnetic stimulation (rTMS) could ameliorate the HIPsub network connectivity by modulating one node of HIPsub network in SCD subjects.Methods: In the first cohort (38 SCD and 55 healthy controls), we analyzed three HIPsub (i.e., hippocampal emotional, cognitive, and perceptual regions: HIPe, HIPc, and HIPp) functional connectivity to identify HIPsub network connectivity alterations that relate to SCD. And we further applied a support vector machine (SVM) approach using the alterations to identify how well this could distinguish SCD from CN. In the second cohort (13 SCD), rTMS with 5-day of once-daily for 2 weeks was used to modulate the altered HIPsub network connectivity in a sham-controlled design.Results: SCD subjects showed differently altered patterns of HIPsub network connectivity compared to controls. The SVM classifier showed that the abnormalities had a high power to discriminate SCD from CN, with an ACC of 86.0%, an AUC of 92.9%, 83.8% sensitivity, and 89.1% specificity. Restoration of HIPc connectivity with left parahippocampa gyrus and HIPp connectivity with left middle temporal gyrus corresponded to amelioration of episodic memory in SCD patients after 2 weeks of rTMS.Conclusion: rTMS can restore the posterior hippocampus connectivity by modulating the precuneus in SCD subjects. Correction of breakdown in HIPc and HIPp related to cognitive and perceptual processing can simultaneously ameliorate episodic memory in SCD subjects. Thus, these findings suggest that rTMS manipulation of precuneus-hippocampal circuit may prevent the disease progression by improving memory as the earliest at-risk state of AD in clinical trials.Trial registration: CCTR, ChiCTR2000034533. Registered 9 July 2020 - Retrospectively registered, http://www.chictr.org.cn
Exogenous melatonin enhances salt secretion from salt glands by upregulating the expression of ion transporter and vesicle transport genes in Limonium bicolor
Authors: Li Junpeng , Yuan Fang , Liu Yanlu , Zhang Mingjing , Liu Yun , Zhao Yang , Wang Baoshan , Chen Min
Published: August 2020

Background
Salt, a common environmental stress factor, inhibits plant growth and reduces yields. Melatonin is a pleiotropic molecule that regulates plant growth and can alleviate environmental stress in plants. All previous research on this topic has focused on the use of melatonin to improve the relatively low salt tolerance of glycophytes by promoting growth and enhancing antioxidant ability. It is unclear whether exogenous melatonin can increase the salt tolerance of halophytes, particularly recretohalophytes, by enhancing salt secretion from the salt glands.
Results
To examine the mechanisms of melatonin-mediated salt tolerance, we explored the effects of exogenous applications of melatonin on the secretion of salt from the salt glands of Limonium bicolor (a kind of recretohalophyte) seedlings and on the expression of associated genes. A pretreatment with 5 µM melatonin significantly improved the growth of L. bicolor seedlings under 300 mM NaCl. Furthermore, exogenous melatonin significantly increased the dry weight and endogenous melatonin content of L. bicolor. In addition, this treatment reduced the content of Na+ and Cl− in leaves, but increased the K+ content. Both the salt secretion rate of the salt glands and the expression level of genes encoding ion transporters (LbHTK1, LbSOS1, LbPMA, and LbNHX1) and vesicular transport proteins (LbVAMP721, LbVAP27, and LbVAMP12) were significantly increased by exogenous melatonin treatment. These results indicate that melatonin improves the salt tolerance of the recretohalophyte L. bicolor via the upregulation of salt secretion by the salt glands.
Conclusions
Our results showed that melatonin can upregulate the expression of genes encoding ion transporters and vesicle transport proteins to enhance salt secretion from the salt glands. Combining the results of the current study with previous research, we formulated a novel mechanism by which melatonin increases salt secretion in L. bicolor. Melatonin binds to an unknown receptor located at the PM, which activates the downstream signaling pathway, and then a NO or ROS signaling pathway. This in turn upregulates the expression of genes encoding ion transporters and vesicle transport proteins. The ion transporters transport ions (mainly Na+) into the salt glands, which are subsequently secreted through the participation of various ion transporters and transport vesicles to maintain ionic homeostasis in the cells and alleviate NaCl-induced growth inhibition.
Diagnostic value of real-time shear wave elastography in children with chronic kidney disease
Authors: Liu Qin , Zhengrong Wang
Published: August 2020

Objective To investigate the diagnostic value of real-time shear wave elastography (SWE) in children with chronic kidney disease (CKD).Methods Children with CKD diagnosed by the ultrasound-guided biopsy between January 2018 and May 2019 were enrolled as the case group. Age- and sex- matched healthy children were selected as the control group. The Young’s Modulus (YM) of the renal cortex was measured by SWE after the traditional ultrasound examination. Variance analysis was performed to compare the values of YM between the two groups. Receiver operating characteristic curve (ROC) analysis was used to compare the values of YM, and explore the cut-offs of the YM.Results In the case group (n=60, 45% male, mean age of 9.2 years), the kidney YM modulus on the left side (16.8±4.8 Kpa vs. 8.3±2.1 Kpa) and the right side (16.0±4.7 Kpa vs. 8.3±2.4 Kpa) were both higher than the control group (all P values<0.001). With the progress of CKD, the YM value of the left and right kidneys gradually increased. ROC analysis showed that when the left and right kidney YM value was 11.7 KPa and 11.0Kpa, the diagnostic sensitivity and specificity were the highest (left: respectively 93.3% and 95.0%; right: respectively 93.3 % and 91.7%).Conclusion The increase of YM in CKD is related to the progression of renal dysfunction which may provide a new method for early diagnosis of CKD, dynamic monitoring of disease progression, and evaluation of curative effect and prognosis.
Nodal-Induced L1CAM/CXCR4 Subpopulation Sustains Tumor Growth and Metastasis in Colorectal Cancer Derived Organoids.
Authors: Cave Donatella Delle , Momblona Xavier Hernando , Sevillano Marta , Minchiotti Gabriella , Lonardo Enza
Published: August 2020

BackgroundColorectal cancer (CRC) is currently the third leading cause for cancer-related mortality. Cancer stem cells have been implicated in colorectal tumor growth, but their specific role in tumor biology, including metastasis, is still uncertain.MethodsIncreased expression of L1CAM, CXCR4 and NODAL was identified in tumor section of patients with CRC and in Patients-derived-organoids (PDOs). The expression of L1CAM, CXCR4 and NODAL was evaluated using quantitative real-time PCR, western blotting, immunofluorescence, immunohistochemistry and flow cytometry. The effects of the L1CAM, CXCR4 and NODAL on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo.Results We found that human colorectal cancer tissue contains cancer stem cells defined by L1CAMhigh/CXCR4high expression that is activated by Nodal in hypoxic microenvironment. This L1CAMhigh/CXCR4high population is tumorigenic, highly resistant to standard chemotherapy, and determines the metastatic phenotype of the individual tumor. Depletion of the L1CAMhigh/CXCR4high population drastically reduces the tumorigenic potential and the metastatic phenotype of colorectal tumors.ConclusionIn conclusion, we demonstrated that a subpopulation of migrating L1CAMhigh/CXCR4high is essential for tumor progression. Together, these findings suggest that strategies aimed at modulating the Nodal signaling could have important clinical applications to inhibit colorectal cancer-derived metastasis.
Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis
Authors: Shi Qin , Sun Baolan , Wang Di , Zhu Yi , Zhao Xinxin , Yang Xiaoqing , zhang yuquan
Published: August 2020

Background Accumulating evidence indicates that mesenchymal stem cells (MSCs) exert tissue repair effects and therapeutic angiogenesis through their noncoding RNAs (ncRNAs). Our previous studies showed that MSCs derived from Wharton’s jelly (WJ-MSCs) can ameliorate damaged human endometrium by promoting angiogenesis. There is limited information on the functions and mechanism of ncRNAs in MSC-induced endometrial repair, and additional studies are needed for more insights.Methods Here, WJ-MSCs were cocultured with or without endometrial stromal cells (ESCs) damaged by mifepristone (cocultured group versus non-cocultured group). TUNEL staining assays, EdU proliferation assays, flow cytometry apoptosis assays, and western blot assays were performed to observe the reparative effect of WJ-MSCs on damaged ESCs. Subsequently, circular RNA (circRNA) and microRNA microarrays were performed between the two groups. A subset of top upregulated circRNAs was validated by qRT-PCR. The functions of circ6401 (hsa_circ_0006401) in WJ-MSCs were investigated using lentivirus-mediated circRNA overexpression assays. The subcellular localization of circ6401 and miR-29b-1-5p in WJ-MSCs was identified by double RNA fluorescence in situ hybridization. Dual-luciferase reporter assays and western blot assays were performed to elucidate the regulatory mechanisms among circ6401, miR-29b-1-5p, and RAP1B.Results WJ-MSCs significantly improved ESC proliferation and upregulated the expression of vascular angiogenesis markers. Circ6401 was upregulated in WJ-MSCs cocultured with damaged ESCs, while miR-29b-1-5p was significantly downregulated. Furthermore, circ6401 was found to bind to miR-29b-1-5p and prevent it from decreasing the level of RAP1B, a crucial protein involved in the VEGF signaling pathway, which promoted angiogenesis and stimulated the proliferation of ESCs.Conclusions Our results showed the abundance and regulation profiles of ncRNAs of WJ-MSCs during repair of damaged ESCs, and for the first time, clarified the underlying mechanism by which circ6401 promotes endometrial repair by WJ-MSCs; thus, demonstrating that circ6401 may serve as a potential therapeutic target.
Relationship between alcohol consumption and cancer in rural Chinese adults: 1 5- year follow-up cohort study
Authors: Zhang Yue , Li Jingyi , Cheng Nannan , Yang Jie , Ye Lijing , Lu Xiaofan , Zhou Ziyi , Wang Zhuo , Liu Lishun , Song Yun , Li Chuan , Lu Qian , Wang Gailing , Huang Xiao , Tang Genfu , Wang Binyan , Qin Xianhui , Zalloua Pierre , Zhang Huisheng , Yan Fangrong , Xu Xiping
Published: August 2020

Background：We aimed to evaluate the association between alcohol consumption and risk of cancer incidence among rural Chinese adults. Methods: We utilized data from a community-based cohort study in rural China enrolled in 2003 and followed up prospectively up to 2018. Generalized estimating equation models were used to obtain odds ratios (OR) and 95% confidence intervals (CI) to analyze the relationship between alcohol consumption and cancer incidence. Results: After an average of 15 years of follow-up, a total of 9870 adult participants were included in this study. The results of the regression analysis for males showed that former drinkers had a significantly increased risk of cancer compared to never drinkers ([OR]2.46,95%[CI](1.43-4.23)). The cancer risk for current drinkers with heavy alcohol consumption(>400g/week) significantly increased ([OR]1.66,95% [CI] (1.18-2.34))compared to never drinkers. Among current drinkers, for every 100g of alcohol consumed per week, the risk of cancer increased by 15%. Among current drinkers, those aged 53.5 years or older , had a significant increase in the risk of cancer ([OR]1.26,95% [CI](1.12-1.42), for those with triglycerides ≥150 mg/dL, the risk of cancer was even higher ([OR]1.50,95%[CI](1.20-1.88), P for interaction 0.018), and for those with high density lipoprotein cholesterol (HDLC)<40 mg/dL, the risk of cancer increased the greatest ([OR]2.03,95%[CI](1.36-3.04), P for interaction 0.005). Conclusions: Among middle-aged and elderly males in rural China, the risk of cancer significantly increased among former and heavy current drinkers compared with never drinkers. Age, triglycerides, and HDLC may increase the risk of cancer along with alcohol consumption.
Ovarian Cancer Cells Direct Monocyte Differentiation Through a Non-canonical Pathway
Authors: Fogg Kaitlin C. , Miller Andrew E. , Li Ying , Flanigan Will , Walker Alyssa , O’Shea Andrea , Kendziorski Christina , Kreeger Pamela
Published: August 2020

Background: Alternatively-activated macrophages (AAMs), an anti-inflammatory macrophage subpopulation, have been implicated in the progression of high grade serous ovarian carcinoma (HGSOC). Increased levels of AAMs are correlated with poor HGSOC survival rates, and AAMs increase the attachment and spread of HGSOC cells in vitro. However, the mechanism by which monocytes in the HGSOC tumor microenvironment are differentiated and polarized to AAMs remains unknown. Methods: Using an in vitro co-culture device, we cultured naïve, primary human monocytes with a panel of five HGSOC cell lines over the course of seven days. An empirical Bayesian statistical method, EBSeq, was used to couple RNA-seq with observed monocyte-derived cell phenotype to explore which HGSOC-derived soluble factors supported differentiation to CD68+ macrophages and subsequent polarization towards CD163+ AAMs. Pathways of interest were interrogated using small molecule inhibitors, neutralizing antibodies, and CRISPR knockout cell lines. Results: HGSOC cell lines displayed a wide range of abilities to generate AAMs from naïve monocytes. Much of this variation appeared to result from differential ability to generate CD68+ macrophages, as most CD68+ cells were also CD163+. Differences in tumor cell potential to generate macrophages was not due to a MCSF-dependent mechanism, nor variance in established pro-AAM factors. TGFa was implicated as a potential signaling molecule produced by tumor cells that could induce macrophage differentiation, which was validated using a CRISPR knockout of TGFA in the OVCAR5 cell line. Conclusions: HGSOC production of TGFa drives monocytes to differentiate into macrophages, representing a central arm of the mechanism by which AAMs are generated in the tumor microenvironment.
The predictive value of preoperative positive urine cytology for development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma: A retrospective multi-center case-control study and meta-analysis
Authors: Fan Bo , Huang Yuanbin , Wen Shuang , Sun Min , Yang Xinrui , Sun Man , Chen Yuting , Huang Yan , Wang Yumei
Published: August 2020

Background: Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Urine cytology is a common clinical method for the early diagnosis of urologic neoplasms. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in Northeast China are rare. Methods: In this retrospective case-control study, we first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 142 patients with UUT-UC after radical nephroureterectomy (RNU). A nomogram model was established and we evaluated its effectiveness. Subsequently, after searching several databases, including PubMed, Embase, and Ovid, we quantitatively combined our results with the published data in a meta-analysis. Results: Our case-control study demonstrated that patients with muscle-invasive tumors (T2-T4) were more prone to preoperative positive urine cytology than those with non-muscle-invasive tumors (Tis-T1), suggesting that preoperative positive urine cytology may be associated with the aggressive form of UUT-UC. Kaplan-Meier curves demonstrated that the patients with positive urine cytology had significantly poorer intravesical recurrence-free survival (IV-RFS). Additionally, preoperative urine cytology (hazard ratio, HR=3.24) and lymph node status (HR=2.67) were validated as significant independent predictors of intravesical recurrence by multivariate analysis. Nomogram, calibration plots, AUC values and the C-index demonstrated that the predictive accuracy was significantly improved when preoperative urine cytology was combined. Subsequently, adding to our study, 11 eligible articles from 2010 to 2016 containing 2942 patients were sifted out for our meta-analysis. Overall analysis showed that preoperative positive urine cytology was associated with a 56% increased risk of intravesical recurrence (HR=1.56). In the subgroup analysis by region, study type, and sample size, the pooled HR was statistically significant for the Japan subgroup (HR=1.45), China subgroup (HR=1.66), cohort study subgroup (HR=1.44), and case-control study subgroup (HR=1.77), the subgroup with sample size greater than or equal to 100 (HR=1.42), and the subgroup with sample size less than 100 (HR=2.95). Conclusions: Preoperative urine cytology significantly correlated with intravesical recurrence in patients with UUT-UC after RNU, although these results need to be interpreted with caution. Large, prospective trials are required to further confirm its prognostic significance.
Dysregulation of ferroptosis may involve in the development of non-small cell lung cancer in Xuanwei area
Authors: Yang Zhang , Li Guangjian , Yang Jiapeng , Zhao Guangqiang , Shen Zhenghai , Yang Kaiyun , Tian Linwei , Zhou Qinghua , Peng Ren-Wang , Chen Ying
Published: August 2020

Background

The Xuanwei area of Yunnan Province, China is one of the regions with the highest incidence of lung cancer in the world. Local residents use bituminous coal as fuel for cooking and heating, which causes serious indoor air pollution. After the local government carried out furnace and stove reform work, the high incidence of lung cancer in residents continued. We herein wonder if there are specific mechanisms at protein level for the development of lung cancer in the area.
Methods

We investigated the changes of protein profiling in tumor of the patients from Xuanwei area. Tandem Mass Tag (TMT) were employed to screen the differential proteins between carcinoma and para-carcinoma tissues.
Results

We identified a total of 422 differentially-expressed proteins, among which 162 proteins were significantly upregulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially-expressed proteins were related to ECM-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, TXN2 and HP, showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumor in nude mice.
Conclusion

This study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.
Social Perspective of Female Genital Mutilation/Cutting in Khartoum State – Sudan 2020
Authors: Elnimeiri Mustafa Khidir Mustafa , Satti Shahenaz seifalseen Mustafa , Abdelrahim Taqwa Mohieldeen Hamid , Ibrahim Mohanad Kamaleldin Mahmoud , Abdelbasit Reem Mahmoud Mohamed , Mingaryous Dimetry Adel Dimetry
Published: August 2020

Background Female genital cutting( FGC) comprises all procedures that involve partial or total removal of the external female genitalia, or other injury to the female genital organs for non-medical reasons and it is considered as violation of human rights of girls and women. The overall objective of this study was to explore the social factors contributing in the persistence of this practice despite of the efforts for eradication in Khartoum State-Methods: This was a community based cross-sectional study conducted in Khartoum State- Sudan including the three localities. The study included 920 females within the reproductive age, sampled proportionate to size using multistage cluster sampling The data were collected using standardized administered questionnaire, Data were analyzed using statistical package for social science's version 21. Analysis was composed of descriptive data and Multinominal Regression Test to study the associations between variables of interest.Results: 62% of the participants considered female genital cutting as a violation of girls’ and women’s rights, 20% of them mentioned rejection by husbands as the main risk if daughters were not subjected to female genital cutting ,71% of the participants considered female genital cutting as a harmful traditional practice while 26% did not consider it as such . ] Multinomial logistic regression estimates of daughters have been subjected to any form of female genital cutting and reasons of conduct of female genital cutting and the risk encountered when girls are not subjected to female genital cutting showed ,“the risk encountered when girls are not subjected to female genital cutting” ranked the first place in influence as the regression coefficient of this variable is 68.779, while the main reason for the conduct of female genital cutting ranked the second place in influence as the regression coefficient of this variable is .089.Conclusions: FGC is a cultural practice recognized as a violation of human rights. These findings support the social coordination norm model, and results indicate the widely prevailing misconceptions about FGC/M among the study participants especially among those participants supporting the continuation of FGC/M. Key words Female genital cutting, Social Factors, Violation, Sudan
Left ventricular fractional shortening as a novel predictor of clinical outcomes in patients with coronary artery disease after undergoing PCI: A Retrospective Cohort Study
Authors: Guo Qian-Qian , Tang Jun-Nan , Yang Xu-Ming , Zhang Jian-Chao , Cheng Meng-Die , Song Feng-Hua , Liu Zhi-Yu , Wang Kai , Jiang Li-Zhu , Fan Lei , Yue Xiao-Ting , Bai Yan , Dai Xin-Ya , Zhang Zeng-Lei , Zheng Ru-Jie , Zheng Ying-Ying , Zhang Jin-Ying
Published: August 2020

Background: Even though great advances have been made in the treatment of coronary artery disease (CAD) owing to coronary revascularization and modern antiremodeling therapy, it remains the major cause of cardiac morbidity and mortality worldwide. Risk stratification in CAD patients is primarily based on left ventricular ejection fraction (LVEF), risk scores, and some serum markers. The value of baseline Left ventricular fractional shortening (LVFS) level in predicting the clinical outcomes has not yet been determined.Methods: In this retrospective cohort study, a total of 3561 patients were enrolled in Clinical Outcomes and Risk Factors of Patients with CAD after percutaneous coronary intervention (PCI), from January 2013 to December 2017. After excluding patients without echocardiography data, we finally enrolled 2787 patients. These patients were divided into two groups according to LVFS value. The lower group (LVFS <31%, n=741), the higher group (LVFS≥31%, n=2046). The average follow-up time were 37.59±22.24 months.Results: We found that there were significant differences between the two groups in the incidence of all-cause mortality (ACM) (P<0.001), cardiac mortality (CM) (P<0.001), major adverse cardiovascular events (MACEs) (P<0.05) and major adverse cardiovascular and cerebrovascular events (MACCEs) (P<0.05). Multivariate Cox regression analyses showed that LVFS was an independent predictor for ACM (hazard ratio [HR]:0.473 [95% confidence interval [CI]:0.290-0.772],P=0.003), CM (HR: 0.393 [95% CI:0.213-0.725],P=0.003) in acute coronary syndrome (ACS) patients but that it was an independent predictor for only the incidence of CM (HR: 0.153 [95% CI:0.046-0.504],P=0.002) in stable CAD patients.Conclusion This study indicates that baseline LVFS is an independent and novel predictor of adverse long-term outcomes in CAD patients who underwent PCI.
Analysis Using Random Forest and Data Integration Methods of Non-promoter Methylation and Expression Data Identifies Dysregulated Genes in Central Carbon Metabolism Pathway in Oral Cancer
Authors: Majumder Partha P. , Mukhopadhyay Srija , Ghosh Sahana , Das Debodipta , Arun P. , Roy Bidyut , Biswas Nidhan K. , Maitra Arindam
Published: August 2020

Background: Studies of epigenomic alterations associated with diseases primarily focus on methylation profiles of promoter regions of genes, but not of other genomic regions. In our past work (Das et al. 2019) on patients suffering from gingivo-buccal oral cancer – the most prevalent form of cancer among males in India – we have also focused on promoter methylation changes and resultant impact on transcription profiles. Here, we have investigated alterations in non-promoter (gene-body) methylation profiles and have carried out an integrative analysis of gene-body methylation and transcriptomic data of oral cancer patients. Methods: Tumor and adjacent normal tissue samples were collected from 40 patients. Data on methylation in the non-promoter (gene-body) regions of genes and transcriptome profiles were generated and analyzed. Because of high dimensionality and highly correlated nature of these data, we have used Random Forest (RF) and other data-analytical methods.Results: Our integrative analysis of non-promoter methylation and transcriptome data has revealed significant methylation-driven alterations in some genes that also significantly impact on their transcription levels. These changes result in enrichment of the Central Carbon Metabolism (CCM) pathway, primarily by dysregulation (overexpression) of (a) NTRK3, which plays a dual role as an oncogene and a tumor suppressor; (b) SLC7A5 (LAT1) which is a transporter dedicated to essential amino acids, and is overexpressed in cancer cells to meet the increased demand for nutrients that include glucose and essential amino acids; and, (c) EGFR which has been earlier implicated in progression, recurrence, and stemness of oral cancer, but we provide evidence of epigenetic impact on overexpression of this gene for the first time. Conclusions: In rapidly dividing cancer cells, metabolic reprogramming from normal cells takes place to enable enhanced proliferation. In the present analysis, we have identified that among oral cancer patients, genes in the CCM pathway – that plays a fundamental role in metabolic reprogramming – are significantly dysregulated because of perturbation of methylation in non-promoter regions of the genome. This result compliments our previous result that perturbation of promoter methylation results in significant changes in key genes that regulate the feedback process of DNA methylation for the maintenance of normal cell division.
Eating alone at each meal and associated health status by cohabitation situation among Japanese community-dwelling elderly: a cross-sectional analysis of the KAGUYA study
Authors: Kushida Osamu , Moon Jong-Seong , Matsumoto Daisuke , Yamasaki Naomi , Takatori Katsuhiko
Published: August 2020

Background: This study investigated the association between eating alone at each meal and health status including functional capacity according to cohabitation situation among Japanese community-dwelling elderly.Methods: This was a cross-sectional analysis of baseline data from the Keeping Active across Generations Uniting the Youth and the Aged (KAGUYA) study in Japan. A self-administered questionnaire was mailed to all 8004 residents aged 65 or older residing in the same Japanese town the participants in March 2016. Eating alone was assessed by first asking whether participants ate three separate meals each day (i.e., breakfast, lunch, and dinner), and those who answered affirmatively were then asked how many people were usually present at each meal. Health status was assessed in terms of subjective health, medical history, care needs, body mass index, depression, and functional capacity.Results: Data from 3057 respondents were analyzed. Among those living with others, those who reported not being in good subjective health and a history of hypertension were significantly more likely to eat alone at breakfast (odds ratio 1.27; 95% confidence interval 1.01–1.61, and 1.26; 1.06–1.49). Depressive symptoms and many subscales of functional capacity were also significantly associated with eating alone at breakfast, lunch, and dinner (P < 0.05). Among those living alone, those eating alone at breakfast had lower scores for indicators of functional capacity including information practice (P = 0.010) and total scores (P = 0.049).Conclusions: For both cohabitation situations, many health status indicators were related to eating alone at each meal, especially breakfast.
Genetic background contributions to the disproportion of vitamin A deficiency in pregnant women of certain ethnicities in populations of the United States.
Authors: Suzuki Masako , Wang Tao , Garretto Diana J , Isasi Carmen R. , Cardoso Wellington V , Greally John M. , Quadro Loredana
Published: August 2020

Vitamin A is an essential micronutrient that plays critical roles in many biological functions of the body. Limited access to vitamin A-rich food or supplements severely affects tissue and blood levels of vitamin A. Therefore, low serum vitamin A and poverty levels are strongly associated in vitamin A deficiency (VAD) studies that have focused mainly on developing countries. The current national prevalence rate of vitamin A deficiency in the United States is reported to be very low (< 1%). However, several studies, including ours, have suggested that people from certain ethnic groups still face a higher proportion of vitamin A deficiency. Here, we re-analyzed two different datasets of serum retinol levels of pregnant females to assess the VAD status differences between women of different ancestries. We found that pregnant females with non-Hispanic Black and with Latin American/Afro-Caribbean ancestry have strikingly high proportions of vitamin A deficiency. Moreover, we identified candidate genetic variants that associate with the disproportions between these different ancestries. Maternal vitamin A deficiency increases the risk of adverse health outcomes for both the mother and offspring later in life. Measuring serum retinol levels of pregnant women in the higher risk groups and provision of food interventions based on genetic information to improve the vitamin A status of at-risk women are needed. Our study strongly suggests that emergency actions need to be taken to reduce vitamin A deficiency in specific, at-risk ethnic groups.
A prognostic nomogram in AFP-negative hepatocellular carcinoma based on LASSO Cox regression
Authors: Zhou Dong dong , Liu Xiao li , Wang Xin hui , Yan Feng na , Wang Peng , Yan Hui wen , Jiang Yu yong , Yang Zhi yun
Published: August 2020

PurposeHepatocellular carcinoma (HCC) patients with alpha-fetoprotein (AFP)-negative (<8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of HCC patients with AFP-negative.Materials and MethodsA total of 410 AFP-negative patients with clinical diagnosed with HCC as a primary cohort; 148 AFP-negative HCC patients as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by univariate and multivariate Cox hazard analysis were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort.ResultsThe C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847) and good calibration. The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively.ConclusionsNovel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-negative HCC. This model could help AFP-negative HCC facilitate a personalized prognostic evaluation.
Seamless Data Analysis, Visualizations and Sharing: Perspective from IRRI’s Rainfed Rice Breeding Program
Authors: Hussain Waseem , Bhosale Sankalp , Catolos Margaret , Anumalla Mahender , Khanna Apurva , Cruz Ma Teresa Sta. , Ramos Joie
Published: August 2020

Phenotypic data analysis is a key component in crop breeding to extract meaningful insights from data in making better breeding decisions. Each year the rainfed rice breeding (RRB) program at IRRI conducts trials in the national agricultural research and extension systems (NARES) network-partner sites across South Asia, Southeast Asia and Africa. Analyzing the data from the network trials and sharing the results with the partners in the best possible format is a daunting task. It is crucial to demystify data analysis to the NARES partners for making better breeding decisions. Here, we provide an overview of how RRB program at IRRI has leveraged R computational power with open-source resource tools like R Markdown, plotly , LaTeX and HTML to develop a unique data analysis workflow and redesigned it to a reproducible document for better interpretation, visualization and seamlessly sharing with partners. The generated report is the state-of-the-art implementation of analysis workflow and outputs either in text, tables or graphics in a unified way as one document. The analysis is highly reproducible and can be regenerated based at any time. The plots are built with enhanced dynamic and interactive visualizations to aid in better understanding and extract information with ease. Tables are highly interactive and manageable rendering liberty to be exported within the document in numerous formats. The source code and demo data set for download and use is available at https://github.com/whussain2/Analysis-pipeline . Conclusively, the analysis workflow and document we presented is not limited to IRRI’s RRB program but is applicable to any organization or institute with full-fledged breeding programs.
Dynamic Changes in the Rhizosphere Bacterial Community in Monoculture and Intercropped Corn and Soybean During Various Crop Growth Stages
Authors: Li Han , Luo Luyun , Tang Bin , Guo Huanle , Cao Zhongyang , Zeng Qiang , Chen Songlin , Chen Zhihui
Published: August 2020

Although rhizosphere microorganisms have been studied for a long time, rhizosphere microbial communities based on monoculture and intercropped soybean and corn have rarely been studied. To define the effect of crop monoculture and intercropping on soil physicochemical properties and rhizosphere microbial communities, field experiments were conducted using corn and soybean cultivars at five different crop growth stages. The pH and soil organic matter (SOM) were the key factors affecting crop rhizosphere soil microorganisms. The content of available phosphorus(AP) in the intercropped soybean/corn soil samples was higher than that in the monoculture soil samples at five different growth stages.The content of available cadmium(ACd) in monoculture soybean rhizosphere soil samples decreased and then increased, but the intercropped soybean soil samples indicated an opposite trend.Proteobacteria, Chloroﬂexi, Acidobacteria, Actinobacteria, and Firmicutes were the dominant phyla in the soybean and cornrhizosphere soil samples. Crops of the same plant species showed little difference in the bacterial community diversity under the two planting modes. The results showed that the cadmium content in cadmium-polluted soil could be reduced by the soybean/corn intercropping system. The crop rhizosphere bacterial community is not only regulated by the crop itself but also influenced by the planting pattern.
LncRNA LEF1-AS1/LEF1/FUT8 Axis Mediates Colorectal Cancer Progression by Regulating α1, 6-Fucosylation via Wnt/β-Catenin Pathway
Authors: Qi Yu , Shan Yujia , Li Shuangda , Huang Yiran , Guo Yanru , Huang Tong , Jia Li
Published: August 2020

Background: Fucosylation alteration is involved in several steps of human cancer pathogenesis. Dysregulated long noncoding RNA (lncRNA) often leads to malignancy in colorectal cancer (CRC). Methods: Differential levels of LEF1-AS1, LEF1 and FUT8 are analyzed by qRT-PCR and western blot. Chip, RIP, EMSA and luciferase reporter assay confirm the direct interaction among LEF1-AS1, MLL1, H3K4me3, LEF1 and FUT8. Functionally, CRC cell proliferation, proliferation, migration and invasion are analyzed by CCK8 assay, colony formation assay, transwell assay and flow cytometry. The xenografts nude mice models, lung metastasis and liver metatstasis are established to determine the effect of LEF1-AS1/LEF1/FUT8 axis on CRC progression in vivo.Results: Here, we identify that LEF1-AS1 and LEF1 are higher in CRC tissues than that in adjacent tissues, as well as upregulated in CRC cell lines than that in normal colorectal cells. Altered levels of LEF1-AS1 modulate LEF1 expression, while altered LEF1 could not regulate LEF1-AS1. LEF1-AS1 recruits MLL1 to the promoter region of LEF1, induces H3K4me3 methylation modification and mediates LEF1 transcription. Furthermore, α1-6 fucosyltransferase FUT8 is overexpressed in CRC tissues and positively correlated to LEF1. FUT8 is a direct target of transcription factor LEF1, which regulates FUT8 level. Altered FUT8 also regulates the core fucosylation of CRC cells, and LEF1-AS1 mediates FUT8 level through activation of Wnt/β-catenin/LEF1 pathway, thereby resulting in β-catenin nuclear translocation. In addition, LEF1-AS1 mediates the proliferation, migration and invasion of CRC cells in vitro. LEF1-AS1 silence hinders the tumorigenesis, liver and lung metastasis of SW620 cells in vivo, while overexpressed FUT8 abolishes the suppressive impact of LEF1-AS1 repression on the biological behavior of SW620 cells. Conclusion: Our studies uncovered a novel mechanism for constitutive LEF1-AS1/LEF1/FUT8 axis in CRC progression by regulating α1, 6-fucosylation via Wnt/β-catenin pathway, and consequently, as a potential therapeutic target in CRC.
Irradiation-Induced Polyploidy Giant Cancer Cells Mediate Tumor Cell Repopulation via Neosis
Authors: Zhang Zhengxiang , He Sijia , Xiao Feng , Cheng Jin , Wang Yiwei , Zhao Minghui , Zhao Yucui , Li Chuanyuan , Huang Qian
Published: August 2020

Background Tumor repopulation generally describes the phenomenon that residual tumor cells surviving therapies tenaciously proliferate and reestablish the tumor, presenting an embarrassing plight for cancer treatment. However, the cellular and molecular mechanisms underlying this process remains poorly understood. In this study, we proposed polyploidy giant cancer cells (PGCCs)-mediated and neosis-based tumor repopulation after radiotherapy.Methods The formation of PGCCs after irradiation was examined in vitro and in vivo. The demise of X-ray irradiated cells was detected by flow cytometry, clonogenic cell survival assay and transmission electron microscopy. Western blot was used to test cell proliferation and death related protein expression level of these irradiated cells. Time lapse microscopy was adopted to observe the destiny of PGCCs. The property of these PGCCs was identified by TUNEL assay, Brdu chasing assay, western blot, immunocytochemical and immunofluorescence staining. The relationship of HMGB1 with PGCCs-derived tumor repopulation was conducted via HMGB1 chemical inhibitors. Finally, animal model was used to verify the formation of PGCCs, and the relevance of HMGB1 in this process was investigated by immunohistochemical staining.Results The majority of PGCCs induced by irradiation move towards cell demise, whereas some of them intriguingly possessed proliferative property. Utilizing time-lapse microscopy and single-cell cloning assay, we observed that neosis derived from those PGCCs with proliferative capacity contributed to tumor cell repopulation after irradiation. Using the conditioned media collected from dying tumor cells to perform single-cell cloning assay, we unexpectedly demonstrated that HMGB1 released from dying tumor cells participated the process of neosis-based tumor repopulation. In irradiation treated animal tumor bearing model, the expression level of HMGB1 increased after irradiation compare with non-irradiated group. Moreover, some PGCCs presented high HMGB1 expression. Interestingly, we also observed that the proliferation potential of PGCCs varied. Some PGCCs proliferated at early stage, while some PGCCs proliferated at late stage.Conclusion X-ray irradiation could induce the formation of PGCCs, which could move towards both cell death and survival; irradiation-generating PGCCs mediated tumor cell repopulation after irradiation via neosis; HMGB1 released from dying cells stimulated the process of neosis and participated in tumor repopulation after irradiation.
CircCDKN2B-AS1 Interacts with IMP3 to Stabilize Hexokinase 2 mRNA and Facilitate Cervical Squamous Cell Carcinoma Aerobic Glycolysis Progression
Authors: Zhang Yanan , Zhao Lu , Yang Shizhou , Cen Yixuan , Zhu Tingjia , Wang Lingfang , Xia Lili , Liu Yuwan , Zou Jian , Xu Junfen , Li Yang , Cheng Xiaodong , Lu Weiguo , Wang Xinyu , Xie Xing
Published: August 2020

Background: Circular RNAs(circRNAs) have been reported to play key roles in the development of various cancers. However, the biological function and clinical significance of most circRNAs are still elusive. The purpose of this study is to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development, and its potential value in clinic. Methods: The qRT-PCR array was conducted to verify the expression level of circCDKN2B-AS1. CCK8 assay, transwell assay, and FCM were undertaken to detect cellular proliferation, migration, and apoptosis, respectively. Seahorse XFe 96 analyzer was used to measure the glycolysis metabolism level. RNA pulldown, RIP, actinomycin-D adding assay and Western Blot were used to screen and elucidate the potential mechanisms. BALB/c nude mice and zebrafish embryo（AB,WT） were used as animal models to investigate tumorigenesis capability.18FDG-microPET/CT was used to detect the glucose metabolism level of subcutaneous tumor in nude mice. Results: CircCDKN2B-AS1, circular isoform of lncRNA CDKN2B-AS1, was upregulated in cervical cancer and precancer tissues. We found that circCDKN2B-AS1 associated with IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2(HK2) mRNA, the rate-limiting enzyme of aerobic glycolysis pathway. The expression level of circCDKN2B-AS1 fated the binding of IMP3 to 3’UTR of HK2 mRNA, consequently affects cell malignant phenotypes and aerobic glycolysis of cervical cancer in vitro and in vivo. Mutant circCDKN2B-AS1 lacking of the IMP3 binding site didn’t have such effects. Utilizing an inhibitory peptide to block the interaction between circCDKN2B-AS1 and IMP3 protein impeded the binding of IMP3 to 3’UTR of HK2 mRNA and suppressed aerobic glycolysis in cervical cancer cells.Conclusions: Our findings demonstrate that circCDKN2B-AS1 facilitates aerobic glycolysis by sponging IMP3 protein to stabilize HK2 mRNA, consequently promotes malignant phenotypes in cervical cancer, which may provide a potential approach for cervical cancer therapeutics.