bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Associated Macrophages Secret Exosomal miR-155 to Promote Metastasis of Non-Small-Cell Lung Cancer
Authors: Li Xiang , Chen Zhipeng , Ni Yaojun , Zhu Quan , Wu Weibing , He Zhicheng , Xia Yang , Chen Liang , Xie Xueying , Wang Jun 
Published: August 2020

Abstract
Background: Understanding the molecular basis underlying metastasis of non-small-cell lung cancer (NSCLC) may provide new therapeutic modality for the treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis still remain undefined.Methods: The role of macrophages in NSCLC was elucidated by gene set enrichment analysis via The Cancer Genome Atlas database (TCGA) database, and we further verified it through Quantitative real-time PCR and immunohistochemical staining. Exosomes from TAMs were extracted and co-cultured with A549 cells,the biological functions of miR-155 were evaluated through miRNAs sequencing, transwell assays,western blotting,fluorescence labeling,luciferase reporter assay, and animal experiments.Results: We found that M2 TAMs are abundant in metastatic tissues of NSCLC patients and exosomes secreted by M2 TAMs promote epithelial mesenchymal transition(EMT) and migration of A549 cells.Mechanistically,we demonstrated that miR-155 is the biomolecule in exosomes secreted by M2 TAMs and targets 3’-untranslated regions (UTRs) of RASSF4 to promote NSCLC metastasis.Conclusions: MiR-155 is the key functional molecule in M2 TAMs-released exosomes that promote EMT of NSCLC cells through targeting RASSF4. Our study suggests that miR-155 in TAMs and exosomes may serve as a novel therapeutic target in the treatment of lung cancer.
Zika Virus Public Health Crisis and the Perpetuation of Gender Inequality in Brazil
Authors: Coutinho Raquel Zanatta , Montalvo Aida Villanueva , Weitzman Abigail , Marteleto Letícia 
Published: August 2020

Abstract
Background: In 2015-2017, the Americas experienced a highly consequencial epidemics for pregnancy and childbearing. Mainly transmitted by the mosquito Aedes aegypti, but also through sexual intercourse, the Zika virus poses the risk of congenital Zika syndrome to fetus, which includes microcephaly and other child development complications. When a public health crisis taps directly into reproductive health, typically a feminine realm, gender systems may reproduce deeply-rooted gender norms, especially those linked to cultural beliefs and expectations. This paper investigated the role of gender in two relational contexts: public health messaging to prevent Zika infections and women’s Zika and pregnancy prevention negotiation with their sexual partners during the Zika outbreak. Methods: We conducted a systematic content analysis of 94 unique pieces, governmental agencies mass-produced public health communication campaigns promoting Zika awareness. Print and online materials were collected for one year (May 2016-May 2017), such as TV ads, Internet Pop-ups, and pamphlets. We also analyzed transcripts from 16 focus groups we conducted with reproductive-aged women (18-40) in Belo Horizonte and Recife, two large cities differently affected by the Zika outbreak. Women answered open-ended questions related to personal knowledge of and experiences with the Zika virus, the related experiences of their friends and acquaintances, their primary information sources, and their perceptions of public health efforts and women’s contraceptive use.Results: Campaign pieces handling pregnancy and microcephaly demonstrated robust gendering, drastically targeting women, placing on their shoulders the responsibility for protecting a potential fetus from the disease. Campaigns neglected male´s participation on Zika prevention and contraceptive management, and failed to address Brazil´s large proportion of unplanned pregnancies. Women were placed in a double bind by being expected to prevent pregnancy and Zika amidst a relationship power dynamic that included unprotected sexual intercourse and gender norms regarding division of labor. Conclusion: Government and individual responses to the epidemics reinforced gender roles, situating pregnant women as responsible for averting mosquito bites and microcephaly, emphasizing prevention of both disease and vector among women while excluding men. Since low-socioeconomic status women possessed fewer resources to preclude infection, we also find that beyond the gender divide, this subgroup faced more pronounced Zika prevention challenges.
Incidence and Predictors of Loss-to-follow-up Among Pregnant and Breastfeeding Women on Option B+ PMTCT Program in Northwest Ethiopia: a Retrospective Follow-up Study.
Authors: Azanaw Melkalem Mamuye , Baraki Adhanom Gebreegziabher , Yenit Melaku Kindie 
Published: August 2020

Abstract
Background: Although Ethiopia is implementing an option B+ program for the last seven years, lost to follow-up among HIV positive women remains the major problem for ART treatment. The study was conducted on lost to follow-up among human immunodeficiency virus infected pregnant and breastfeeding women after Option B+ modality since there was a scarcity of literatures in Northwest Ethiopia. The result is also expected to strengthen the effort to eliminate mother-to-child transmission of HIV to 5%. Methods: A retrospective follow-up study was conducted among 403 pregnant and breastfeeding women between June 2013 and December 2019 at the University of Gondar comprehensive specialized Hospital. Cox proportional hazards regression model was used for identifying predictors of lost-to-follow-up. Results were reported as hazard ratios with 95% confidence interval at a significance level of p=0.05. Results: The overall incidence rate of loss to follow-up was 9.4 per 1000 person-months of observation (95% confidence interval (CI): 7. 4‒11. 9). According to the multivariable Cox regression, rural residency (adjusted hazard ratio(AHR): 2.30; 95% CI:1.08‒4.88), being Muslim religion follower (AHR: 2.44; 95% CI:1.23‒4.81), having no baseline viral load measurement (AHR: 4.21; 95% CI:2.23–7.96, being on ART before enrolment (AHR: 0.30; 95% CI:0.15–0.62), having drug side effects (AHR: 1.82; 95% CI:1.01–3.33), same day ART initiation (AHR: 3.23; 95% CI:1.53–6.84) and having sub-optimal adherence level (AHR: 3.96; 95% CI:2.18–7.19) were significant predictors of lost to follow up.Conclusion: The incidence of lost to follow-up is lower as compared to evidence from most African countries but slightly higher than the WHO target. It is better to strength and expand viral load measurement for all women and giving attention to those women who are residing in a rural area and having fair/poor adherence level.
LncRNA CCAT1 Enhances Chemoresistance in Hepatocellular Carcinoma by Targeting QKI-5
Authors: Shi Jing , Guo Cao , Ma Junli 
Published: August 2020

Abstract
Background: A major reason for treatment failure of cancer is acquisition of drug resistance. The specific mechanisms underlying hepatocellular carcinoma (HCC) chemoresistance need to be fully elucidated. lncRNAs involve in drug resistance in some cancers, however, the exact functions of lncRNA colon cancer-associated transcript 1 (CCAT1) in oxaliplatin resistance in HCC need to be elucidated.Methods: Functional analysis of CCAT1 on oxaliplatin sensitivity was performed in HCC cell lines HCCLM3 and HepG2, and in a subcutaneous tumor model receiving OXA treatment. Furthermore, the downstream signaling targets of CCAT1 in HCC were explored. Results: CCAT1 promoted HCC proliferation and reduced the apoptosis induced by oxaliplatin. Knockout of CCAT1 could increased chemosensitivity in vitro and in vivo. Further study found that QKI-5 was an important mediator and blocking of QKI-5/p38 MAPK signaling pathway enhanced oxaliplatin sensitivity.Conclusions: CCAT1 promoted proliferation and oxaliplatin resistance by QKI-5/p38 MAPK signaling pathway in HCC. Targeting CCAT1 in combination with chemotherapeutics may be a promising alternative to reverse drug resistance in HCC treatment.
An 8-lncRNA Signature Predicts Survival of Triple-Negative Breast Cancer Patients Without Germline BRCA1/2 Mutation
Authors: Liu Minling , Dai Wei , Zhu Mengyuan , Li Xueying , Huang Shan , Wei Min , Li Lei , Fang Shuo 
Published: August 2020

Abstract
Background: Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment.Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm.Results:We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P=0.00018 and P =0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion.Conclusions: We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.
TRIM25 Regulates Oxaliplatin Resistance in Colorectal Cancer by Promoting EZH2 Stability
Authors: Zhou Sha , Peng Jianhong , Xiao Liuniu , Zhou Caixia , Fang Yujing , Ou Qingjian , Qin Jiayi , Liu Mengzhong , Pan Zhizhong , Hou Zhenlin 
Published: August 2020

Abstract
Background Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). TRIM25, an E3-ubiquitin ligase, has been reported to play a vital role in tumorigenesis. This project aims to explore the function and mechanism of TRIM25 in regulating oxaliplatin resistance in colorectal cancer.Methods The expression of TRIM25 in colorectal cancer tissues were examined by publicly available dataset, Immunohistochemistry and western blot. Further survival analysis was conducted using Kaplan-Meier method. CCK8 assay, colony-formation assay, Annexin V-FITC /PI staining and xenograft tumor models were used for evaluating sensitivity of CRC cells to oxaliplatin. Sphere-formation assay, RT-PCR and limiting dilution assay were used to evaluate the influence of TRIM25 on stem cell properties of CRC cells. Co-immunoprecipitation, polyubiquitination assay and western bolt elucidate the mechanism by which TRIM25 regulates EZH2.Results Patients with high expression of TRIM25 have significantly higher recurrence rate (28.9% vs. 15.0%, P = 0.012) and worse disease-free survival (P = 0.006) than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited while TRIM25 overexpression enhanced CRC cells survival after oxaliplatin treatment. In addition, TRIM25 promotes stem cell properties of CRC cells both in vitro and in vivo (8 mice per group). Importantly, we demonstrated that TRIM25 inhibits the binding of E3-ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2 and promoting oxaliplatin resistance. Conclusions Our study provides evidence that TRIM25 is a novel epigenetic regulator of oxaliplatin resistance. Targeting TRIM25 might be a promising strategy for CRC treatment.
High Rates of Multi-Drug Resistant Gram-Negative Organisms Associated With Surgical Site Infections in a Teaching Hospital in Ghana
Authors: Bediako-Bowan Antoinette Afua Asiadua , Kurtzhals Jørgen Anders Lindholm , Mølbak Kåre , Labi Appiah-Korang , Owusu Enid , Newman Mercy Jemima 
Published: August 2020

Abstract
Background There is limited data to guide the prevention and management of surgical site infections (SSI) in low- and middle-income countries. We prospectively studied aetiological agents associated with SSI and their corresponding antibiotic susceptibility patterns in a tertiary hospital in Ghana. Methods As part of a cohort study carried out at the surgical department of the Korle Bu Teaching Hospital (KBTH) from July 2017 to April 2019, wound swabs were collected from patients diagnosed with SSI. Isolates cultured from the wound swabs were identified by MALDI TOF and susceptibility testing was conducted according to EUCAST 2020 guidelines. Clinical data were monitored prospectively. Results Of 4577 patients, 438 developed an SSI and 352 microbial isolates were cultured. Isolates were predominantly Gram negative (286, 81%), a pattern seen for all kinds of surgery and all wound classes. The most common species included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Acinetobacter baumannii. The majority of organisms were multi-drug resistant including 86% of E. coli, 52% of A. baumannii and 86% of K. pneumoniae; and 65% (17/26) of the cefotaxime-resistant K. pneumoniae were extended spectrum β-lactamase producing. One of 139 E. coli, 15 of 49 P. aeruginosa, and 6 of 23 A. baumannii were meropenem resistant, but no clonal pattern was found. There was a 1% (5/428) prevalence of methicillin-resistant S. aureus. Conclusions The predominance of Gram-negative organisms and the high level of multi-drug resistance indicate a need to re-evaluate antibiotic prophylaxis and treatment protocols in surgical practice in low- and middle-income countries.
NHC-catalyzed Enantioselective Hetero-[10+2] Annulation
Authors: wang Jian , Peng Qiupeng , li shi-jun , Zhang Bei , Guo Donghui , Lan Yu 
Published: August 2020

Abstract
The higher-order cycloadditions are powerful strategies for construction of polycycles in one step, however an efficient and concise version for asymmetric induce is limited. N-heterocyclic carbenes are widely used organocatalysts for asymmetric synthesis and will be an ideal choice for enantioselective higher-order cycloadditions. Here we report an enantioselective [10+2] annulation between catalytically formed aza-benzofulvene intermediates and trifluoromethyl ketone derivatives. This protocol exhibits a wide scope, high yields and good ee values, reflecting a robust and efficient higher-order cycloaddition. Density functional theory (DFT) calculations provided an accurate prediction of the reaction enantioselectivity, and in-depth insight to the origins of stereocontrol.
rhEGF Treatment Improves EGFR Inhibitors-Induced Skin Barrier and Immune Defects
Authors: Kim Ji Min , Ji Jun Ho , Kim Young Saing , Lee Suee , Oh Sung Yong , Huh Seok Jae , Son Choon Hee , Kang Jung Hun , Ahn So Yun , Choo Jung Eun , Song Ki-Hoon , Roh Mee Sook 
Published: August 2020

Abstract
Background: The mechanisms of epidermal growth factor (EGF) effects EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF’s positive effects. Methods: Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). The expression levels of skin barrier related proteins, inflammatory cytokines, and antimicrobial peptides (AMPs) were measured by using RT qPCR, ELISA, immunohistochemical (IHC) stain, or immunofluorescence..Results: Using western blot assay, cetuximab decreased EGFR and phosphorylated EGFR (pEGFR) expression. In contrast, rhEGF increased EGFR and pEGFR expression. Also, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. Expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRIs -treated tissue. However, in rhEGF and EGFRIs co-treated tissue, those expressions were increased. Pro-inflammatory cytokines, including IL-1α, IL-8, and TNF-α expression, were increased by EGFRIs, and down-regulated by rhEGF. In patients’ tissue evaluation, compared with control, patients’ Ki-67 and EGFR expression were decreased (P=0.015, P=0.001). Patients’ IL-17 and TNF-α expression intensity was higher than that of control group (P=0.038, P=0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely patients’ proportions of IL-17 and TNF-α were decreased to low stain level.Conclusions: Treatment of rhEGF improved EGFRIs-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.
miR-4293 Upregulates lncRNA WFDC21P by Directly Suppressing mRNA-Decapping Enzyme 2 to Promote Lung Carcinoma Proliferation
Authors: Zhang Qian , Yan Yun-Fei , Lv Qing , Li You-Jie , Wang Ran-Ran , Sun Guang-Bin , Pan Li , Hu Jin-Xia , Xie Ning , Zhang Can , Tian Bao-Cheng , Jiao Fei , Xu Sen , Wang Ping-Yu , Xie Shu-Yang 
Published: August 2020

Abstract
Background: Emerging evidence shows that lncRNA WFDC21P could promote STAT3 phosphorylation and microRNA 4293 SNP is associated with the risk of carcinomas, but the oncogenic functions of WFDC21P and miR-4293 in lung carcinoma are unclear.Methods: mRNA sequencing of lung carcinoma and control para-carcinoma tissues was performed to screen the potential targets. WFDC21P and miR-4293 levels were evaluated in lung carcinoma cells and tissues by qRT-PCR. The function of WFDC21P and miR-4293 on proliferation, apoptosis and metastasis were assessed by MTT, FACS, western blot, transwell assays, colony formation assays and xenografts experiment. RNA immunoprecipitation assays were implemented to verify the relationship between WFDC21P and mRNA-decapping enzyme 2 (DCP2). Furthermore, gain/loss of miR-4293 functions were used to determine its targeting relationship of DCP2. Results: WFDC21P expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, WFDC21P promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified DCP2 can directly bind to WFDC21P and down-regulates its expression. DCP2 as a direct target of miR-4293 and its expression is suppressed by miR-4293. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With positive correlation to WFDC21P expression, miR-4293 also plays oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both WFDC21P and miR-4293. Conclusion: Our results establish oncogenic roles for both WFDC21P and miR-4293, and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in lung carcinoma pathogenesis.
Mental Health Problems and Related Factors in Chinese University Students During the COVID-19 Pandemic
Authors: Zhou Shuang-Jiang , Qi Meng , Wang Lei-Lei , Yang Xing-Jie , Gao Lan , Zhang Suo-Yuan , Zhang Li-Gang , Yang Rui , Chen Jing-Xu 
Published: August 2020

Abstract
Background: The coronavirus disease-2019 (COVID-19) pandemic is a serious threat to global public health, including a wide range of metal health problems. Current research focuses mainly on mental health status and related factors among Chinese university students during the COVID-19 pandemic.Methods: Data from 11133 participants was obtained through an online survey of university students in mainland China. Depressive and anxiety symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9), and the 7-item Generalized Anxiety Disorder Scale (GAD-7), respectively.Results: In total, 37.0% of the subjects were experiencing depressive symptoms, 24.9% anxiety symptoms, 20.9% comorbid depressive and anxiety symptoms, and 7.3% suicidal ideation. Multivariable logistic regression analysis revealed an increased presence of mental health problems in female students, graduate students, and those with personal COVID-19 exposure. Living with family and awareness of COVID-19 were protective factors against depressive and anxiety symptoms. In addition, male, depressive and anxiety symptoms were risk factors for suicidal ideation. Living with family, graduate students, prevention and control measures and projections of COVID-19 trends were protective factors against suicidal ideation.Conclusions: The findings underlined that the mental health of university students should be monitored, and provided important information for healthcare planning during the COVID-19 pandemic.
The Tardigrade Hypsibius Exemplaris as an Emerging Model to Study the Mitochondrial Alternative Oxidase at Animal Organismal Level
Authors: Grobys Daria , Roszkowska Milena , Kaczmarek Łukasz , Jarmuszkiewicz Wiesława , Karachitos Andonis , Kmita Hanna 
Published: August 2020

Abstract
Background: Mitochondrial alternative oxidase (AOX) is suggested to be present in mitochondria of most invertebrates but not vertebrates. Independently of the reason concerning the enzyme occurrence in animal mitochondria, expression of AOX in human mitochondria is regarded as a potential therapeutic strategy in treatment of mitochondrial diseases caused by the mitochondrial respiratory chain (MRC) deficiency or blockage. Undoubtedly, development of AOX expression-based therapy requires explanation of AOX contribution to animal physiology. Till now the relevant data has been obtained mainly due to heterologous AOX expression in cells and animals that do not have natively expressed AOX. We think that application of animals natively expressing AOX could importantly contribute to the research and therapy development. Because the available genomic and transcriptomic data suggests the presence of functional AOX protein in mitochondria of the tardigrade Hypsibius exemplaris, we decided to investigate the possibility of the animal application as a model for AOX activity analysis at organismal level.Results: We observed that H. exemplaris tolerance to the blockage of the MRC complexes III and/or IV was diminished in the presence of AOX inhibitor and the inhibitor-sensitive respiration enabled the tardigrade respiration under condition of the blockage. Furthermore, although detection of H. exemplaris AOX at protein level and pronounced oxygraphic registration of its activity required the MRC complex III and/or IV blockage, the obtained data indicated that AOX clearly contributed to the animal functioning, also in the absence of the blockage. Conclusions: According to our best knowledge we demonstrated, for the first time, that AOX activity of small aquatic invertebrates, represented by the studied tardigrade species, can be monitored by measurement of intact specimen whole-body respiration. Furthermore, it was also possible to monitor the impact of the MRC complex IV blockage on AOX expression level and AOX inhibition in the absence of the blockage on animal functioning. Thus, H. exemplaris could be applied as a whole-animal model suitable to study activity and expression regulation of natively expressed animal AOX.