bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis
Authors: WAN XIAOYU , TIAN XINBEI , DU JUN , LU YING , XIAO YONGTAO 
Published: August 2020

Abstract
Background: The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19 ) in the pathogenesis of IPF. Methods: Bleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction and western blot. H19 knockout ( H19 -/- ) mice were generated by CRISPR/Cas9 and used to investigate the roles of H19 in the pulmonary inflammation and fibrosis in vivo . Results: The expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19 -/- mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. Conclusions : Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for pulmonary fibrosis.
Asymptomatic “Exposers” and “Infectors” are Sources of Infection by SARS-CoV-2: Analysis based on Family Clustering
Authors: He Yu , Guo Yuanyuan , Liu Ping , Li Rui , Ouyang Liu , Wang Siyuan , Fu Dehao 
Published: August 2020

Abstract
Background: Previous studies have documented the clinical characteristics of patients with Coronavirus disease 2019(COVID-19) and presented evidence of person-to-person transmission. Limited data are available for patients with asymptomatic infections. Some asymptomatic carriers, whom we characterize as “exposers” or “infectors”, may be responsible for family clustering of COVID-19.Methods: A questionnaire survey and follow-up survey based on media reports were used to assess familial clustering of SARS-CoV-2 infection induced by asymptomatic exposers/infectors. Individual data were collected for all members of each tracked family. A transmission map was then drawn for each family.Results: Our study of 5 families indicated that individuals with no obvious symptoms of COVID-19, regardless of the PCR results, transmitted the virus to other family members who were community contained at home and had no contact with other infected individuals. There was one death case in Family No.3. Conclusion: Asymptomatic exposers/infectors of SARS-CoV-2 were all middle-aged (average age: 44.4 ± 14.9 years) who had no symptoms but had the ability to disseminate the virus. Medical staff participating in treatment of COVID-19 cases all had a high risk of infection, they should be quarantined so as to protect their families. The morbidity and mortality of Case 3.2 remind us that although these asymptomatic infected people have no symptoms, they are also infectious. It is not ruled out that the subsequent infected people are seriously ill or even die. Therefore, we should not take it lightly.
Scaling-up Community Self-reporting Rate for COVID-19: Implication for Assessing the Perceived Stigmatization of COVID-19 Survivors Among Residents of Agege Local Government, Lagos, Nigeria
Authors: Babatunde Olaniyan Akintunde , Amifofun Owoicho Samuel , Sola Sunday Thomas , Akande Abayomi , Besong Mathias , Yesufu Baqiah Morenike , Akanbi Ibukun Mary , Dairo Magbagbeola David 
Published: August 2020

Abstract
Objective: Coronavirus disease 2019 (COVID-19) is an emerging public health problem with over two million confirmed infections globally. Previous studies show that stigma impede the response activities. Therefore, this study was conducted to assess the perceived stigmatization of COVID-19 survivors among residents of Agege local government, Lagos State, Nigeria. We conducted a cross-sectional survey among 333 consenting residents recruited from Agege local government using multi-stage sampling technique. An interviewer-administered questionnaire was used to collect data on perceived stigmatization. Bivariate and multivariate analyses were done using Chi-square and logistic regression respectively.Results: The mean age of the respondents was 35.7 ± 13.6 years. The proportion of respondents with poor knowledge was 50.5% and awareness for COVID-19 was 95.2%. Television and radio were the two major sources of awareness for COVID-19. Higher likelihood of perceived stigmatization was found among those aged 25 – 49 years (aOR= 3.1, 95% CI = 1.4 – 6.7), ≥ 50 years (aOR= 2.1, 95% CI = 1.1 – 3.9) and married respondents (aOR= 1.8, 95% CI = 1.1 – 2.9). To reduce the effect of stigmatization, we recommend a holistic response plan designed with basic facts about COVID-19 using programmes targeting married respondents as well as the adults.
Incidence of Alzheimer’s Disease and Other Dementias: Results from the 2017 Global Burden of Disease Study
Authors: Guo Xiaojuan , He Hairong , Qu Yan , Liu Jie , Qu Qiumin , Lyu Jun 
Published: August 2020

Abstract
Background

The aim is to reveal the trends in the incidence of Alzheimer’s disease (AD) and other dementias at the global, region, and national levels using data from 2017 Global Burden of Disease Study (GBD 2017).
Methods

We collected information on the number of incident cases and on the age-standardized incidence rate (ASIR) of AD and other dementias during 1990–2017 from the GBD 2017. We also analyzed differences in the incidence among different age groups. The association of ASIR with the development level was explored using Pearson correlation analysis.
Results

In 2017, the number of incident cases of AD and other dementias was 73.01 million (95% uncertainty interval [CI] = 65.16–81.33 million). This represented an increase of 113.17% from 1990, and an ASIR of 97.46 per 100,000 persons (95% CI = 86.80–108.89 per 100,000 persons). The ASIR was highest in countries in the high-middle sociodemographic index (SDI) quintile, and lowest in low-SDI-quintile countries. The number of incident cases increased from 1990 to 2017, whereas ASIR showed a slight downward trend in most countries. Japan had the highest ASIR in 2017 and showed the largest increase in ASIR over the preceding 28 years. The ASIR increased rapidly with age among those older than 70 years, and was significantly associated with the SDI (P < 0.0001, ρ = 0.68).
Conclusion

The incidence rate of AD and other dementias has declined in recent decades, but the incidence still remains high. The present findings should be useful for resource allocation and planning health services for AD and other dementias.
The Association between Frequency of Eating Out with Overweight and Obesity Among Children Aged 6-17 in China: A National Cross-Sectional Study
Authors: Ma Yanning , Gong Weiyan , Ding Caicui , Song Chao , Yuan Fan , Fan Jing , Feng Ganyu , Chen Zheng , Liu Ailing 
Published: August 2020

Abstract
Background: In parallel with the increased prevalence of childhood overweight and obesity, the rate of eating out in China has increased dramatically in recent years. The purpose of the study was to explore the association between frequency of eating out with overweight and obesity among Chinese children.Methods: The representative sample of Chinese children aged 6-17 years (7685 boys; 7576 girls) was recruited from Chinese National Nutrition and Health Survey (CNNHS) in 2010-2012. Frequency of eating out was collected by interview-administered questionnaire and categorized as: less than once per week, once and twice per week, and three times or more per week. Height and weight were measured (body mass index was consequently calculated). Results：The prevalence of eating out among Chinese children aged 6-17 years old was 23.2%. Children who ate out 0, 1-2, ≥3 times per week were accounted for 76.8%, 10.9% and 12.3% respectively. Findings revealed that eating out three times per week or more was statistically significant associated with higher prevalence of overweight and obesity among boys (OR=1.20,95CI:1.04-1.38) compared with those ate out less than three times per week. However, no significantly association was observed among girls (OR=0.91, 95CI:0.78-1.01). In additional, Younger children, rural children, children from high income family, those with leisure exercises, leisure SB(>2h/d) were relatively more likely to eat out.Conclusions: The results illustrated that eating out three times or more had a significantly positive effect on overweight and obesity among boys in China.
Whole-Genome Sequencing of Bamei Mutton Sheep for Screening the Genes and SNPs Associated with Litter Size under Selection
Authors: Yao Yaxin , Pan Zhangyuan , Di Ran , Liu Qiuyue , Hu Wenping , Guo Xiaofei , He Xiaoyun , Gan Shangquan , Wang Xiangyu , Chu Mingxing 
Published: August 2020

Abstract
Background: Bamei mutton sheep is a Chinese domestic sheep breed developed by crossing German Mutton Merino sheep and indigenous Mongolian sheep for meat production. Here, we focused on increasing the litter size of this breed to improve the efficiency of mutton production.Results: We selected five high- and five low-fecundity Bamei mutton sheep for whole-genome resequencing to identify candidate genes for sheep prolificacy. We used the FST and XP-EHH statistical approach to detect the selective sweeps between these two groups. Combining the two selective sweep methods, the reproduction-related genes JUN, ITPR3, PLCB2, HERC5, and KDM4B were detected. JUN, ITPR3, and PLCB2 play vital roles in GnRH, oxytocin, and estrogen signaling pathway. Moreover, KDM4B, which had the highest FST value, exhibits demethylase activity. It can affect reproduction by binding the promoters of estrogen-regulated genes, such as FOXA1 and ESR1. Notably, one nonsynonymous mutation (p.S936A) specific to the high-prolificacy group was identified at the TUDOR domain of KDM4B.Conclusion: These observations provide a new opportunity to research the genetic variation influencing fecundity traits within a population evolving under artificial selection. The identified genomic regions of KDM4B that are responsible for litter size can in turn be used for further selection.
A Qualitative Content Analysis of "Problem Students": How Can We Identify and Manage Them?
Authors: Ahmady Soleiman , Khajeali nasrin , Kalantarion Masomeh , Amini Mitra 
Published: August 2020

Abstract
Objectives: Problem students is one of the important issues in medical education. This qualitative study aimed to identify the problem students and the ways for managing these students from the educational experts view. Purposive sampling was used, and data collection continued until data saturation was achieved. The participants were 12 higher education experts and policymakers. Data analysis was performed by the content analysis method based on the Heidegger approach.Results: After data analysis, five main themes and 28 categories, and 164 codes were extracted. The reasons for changing a student to a problem students was: student self-regulation skills, multilayer interactions, curriculumfailure, identification policy and supportive solutions. The results indicated that despite revision in the curriculum, there were shortcomings in identification and management of problem students. This study emphasized that we could identify and manage this type of students with the best approach by faculty development, reviewing the faculty member recruitment, strengthening counseling centers, improving the exams, and screening the students on arrival.
CircRNA UBAP2 Serves as a Sponge of miR-1294 to Increase Tumorigenesis in Hepatocellular Carcinoma through Regulating c-Myc Expression
Authors: Yu Min-Cheng , Ding Guang-Yu , Fu Pei-Yao , Ma Peng , Zhu Xiao-Dong , Cai Jia-Bin , Shen Ying-Hao , Zhou Jian , Fan Jia , Sun Hui-Chuan , Kuang Ming , Huang Cheng 
Published: August 2020

Abstract
The authors have withdrawn this preprint due to author disagreement.
Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study
Authors: Yu Libo , Shi Qingtao , Jin Yan , Liu Zhixin , Li Jiaxin , Sun Wenzhou 
Published: August 2020

Abstract
Background: Activation of autophagy flux contributed to resistance of breast cancer (BC) cells to current chemotherapeutic drugs, which seriously limited their therapeutic efficacy and facilitated BC recurrence in clinic. However, the detailed mechanisms are still not fully understood. In the present study, we identified that inactivation of AMPK-ULK1 signaling cascade mediated protective autophagy sensitized BC cells to doxorubicin in vitro. Methods: Cell counting kit-8 (CCK-8) assay and colony formation assay were performed to evaluate cell proliferation abilities. Trypan blue staining assay was used to examine cell viability, and Annexin V-FITC/PI double staining method was conducted to determine cell apoptosis. The autophagosomes in BC cells were observed and photographed by electronic microscope (EM). Western Blot analysis was employed to examine genes expressions at protein levels.Results: The parental doxorubicin-sensitive BC (DS-BC) cells were exposed to increasing concentrations of doxorubicin to establish doxorubicin-resistant BC (DR-BC) cells, and the DR-BC cells were much more resistant to high-dose doxorubicin stimulation compared to the DS-BC cells (P < 0.05). Interestingly, high-dose doxorubicin specifically increased LC3B-II/I ratio, promoted autophagosomes formation and decreased p62 expression levels to facilitate autophagy in DR-BC cells, instead of DS-BC cells (P < 0.05), and the autophagy inhibitor 3-methyladenine (3-MA) enhanced the cytotoxic effects of high-dose doxorubicin on DR-BC cells (P < 0.05). In addition, we proved that high-dose doxorubicin triggered protective autophagy in DR-BC cells by activating AMPK-ULK1 pathway. Functionally, high-dose doxorubicin increased the expression levels of phosphorylated AMPK (p-AMPK) and ULK1 (p-ULK1) to activate AMPK-ULK1 pathway in DR-BC cells (P < 0.05), and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) blocked autophagy to promote cell death and slow down cell growth in DR-BC cells treated with high-dose doxorubicin (P < 0.05). Conclusions: Collectively, our in vitro data indicated that blockage of AMPK-ULK1 signaling cascade mediated protective autophagy might be a promising strategy to increase doxorubicin sensitivity for BC treatment.
Identification of Novel Transcription Factor-microRNA-mRNA Co-regulatory Networks in Pulmonary Large-cell Neuroendocrine Carcinomas
Authors: Cai Cunliang , Zhang Mingqiang , Mu Xiangdong 
Published: August 2020

Abstract
Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare neuroendocrine neoplasm. Previous studies have shown that microRNAs can be widely involved in tumor regulation through targeting critical genes. However, it is unclear about which miRNAs play vital roles in LCNEC’s pathogenesis and how they interact with transcription factors (TFs) to regulate the cancer-related genes. Methods: To clarify the new TFs-miRNA-target gene feed-forward loops (FFLs) model of LCNEC, we integrated multi-omics data from GEO, TRRUST, TRED, and miRTarBase database. First, expression profile datasets for mRNAs (GSE1037) and miRNAs (GSE19945) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. The target genes of the FFL being obtained from the mirTarBase database, the GO and KEGG functional enrichment analysis was performed on the target gene. Then, we screened for key miRNAs in the FFL and perform gene regulatory network analysis based on key miRNAs. Finally, the TF-miRNA-target gene FFLs were constructed by the hypergeometric test.Results: A total of 343 DEGs and 60 DEMs were identified in LCNECs compared to normal tissues, including 210 downregulated, 133 upregulated genes and 29 downregulated, 31 upregulated miRNAs. Additionally, 55 DEMs were predicted through miRanda, mirDB, and TargetScan to be associated with the LCNEC 77 key genes. Finally, ETS1-miR195-CD36 and E2F3-miR195-CD36 from the TF-miRNA-mRNA FFLs were constructed and are significantly enriched in focal adhesion, cytokine-receptor interaction, hematopoietic cell lineage, and transforming growth factor (TGF)-β signaling pathways. Survival analysis showed that the differential expression of the multi-effect factors ETS1, CD36, and hsa-miR-195 in the FFL significantly affected the survival time of LCNEC patients.Conclusion: In summary, we construct the TF-miRNA-target regulatory network, which is helpful to understand the complex LCNEC regulatory mechanisms. The expression difference of regulated multi-effect target factors ETS1, CD36, and hsa-miR-195 has a significant impact on the survival and development of LCNEC.
Risk Factors for Unplanned Reintubation Caused by Acute Airway Compromise After General Anesthesia: A Case-control Study
Authors: CHEN SI , Zhang Yuelun , Che Lu , Shen Le , Huang Yuguang 
Published: August 2020

Abstract
Background: This study aimed to identify the risk factors and evaluate the prognosis of unplanned reintubation caused by acute airway compromise (AAC) after general anesthesia.Methods: This case-control study included surgical patients who underwent unplanned reintubation after general anesthesia during five years. Cases due to AAC were matched 1:4 with randomly selected controls.Results: Univariate analysis revealed that male sex, age >65, ASA physical status 3, heart disease history, cerebral infarction history, Cormack Lehane grade, surgery type, fresh frozen plasma infusion, increased intubation duration, white blood cell count, and creatinine clearance rate were significantly associated with AAC-caused unplanned reintubation. Multivariate analysis revealed that age >65 (OR=7.50, 95% CI=2.47-22.81, P<0.001), ASA physical status 3 (OR=6.51, 95% CI=1.18-35.92, P=0.032), head-neck surgery (OR=4.94, 95% CI=1.33-18.36, P=0.017) or thoracic surgery (OR=12.56, 95% CI=2.93-53.90, P<0.001), and a high fluid load (OR=3.04, 95% CI=1.16-7.99, P=0.024) were independent risk factors for AAC-caused unplanned reintubation. AAC-caused unplanned reintubation patients had longer postoperative hospital (OR=5.26, 95% CI=1.57-8.95, P<0.001) and intensive care unit days (OR=3.94, 95% CI=1.69-6.18, P<0.001).Conclusions: Age>65, ASA physical status 3, head-neck or thoracic surgery, and high fluid load were risk factors for AAC-caused unplanned reintubation, which was associated with increased postoperative hospital and ICU days.
Conservation Status and Historical Relatedness of South African Communal Indigenous Goat Populations Using Genome-Wide Snp Marker
Authors: Chokoe Tlou Caswell , Hadebe Khanyi , Muchadeyi Farai , Nephawe Khathutshelo , Dzomba Edgar , Mphahlele Tumudi , Matelele Tlou , Mtileni Bohani 
Published: August 2020

Abstract
Background: Indigenous goats forms the majority of populations in smallholder; low input, low output production systems and are considered an important genetic resource due to their adaptability to different production environments and support communal farming. Effective population size (Ne), inbreeding levels, and the runs of homozygosity (ROHs) are effective tools for exploring the genetic diversity and understanding the demographic history in efforts to support breeding strategies to use and conserve genetic resources. Results: Across populations, the current Ne of Gauteng was the lowest at 371 animals, while the historical Ne across populations suggests that the ancestor Ne has decreased by 53.86%, 44.58%, 42.16% and 41.16% in Free State (FS), North West (NW), Limpopo (LP) and Gauteng (GP), respectively, over the last 971 generations. Genomic inbreeding levels related to ancient kinship (FROH >5Mb) was highest in FS (0.08±0.09) and lowest for Eastern Cape (EC) (0.02±0.02). A total of 871 ROH island regions which include important environmental adaptation and hermo-tolerance genes such as IL10RB, IL23A, FGF9, IGF1, EGR1, MTOR and MAPK3 were identified (occurring in over 20% of the samples) in FS (n = 37), GP (n = 42), NW (n = 2) populations only. The mean length of ROH across populations was 7.76Mb and ranged from 1.61Mb KwaZulu-Natal (KZN) to 98.05Mb (GP and NW). Distribution of ROH according to their size showed that the majority (n = 1949) of the detected ROH were >5Mb in length than the other categories. Assuming two hypothetical ancestral populations, the population from KZN and LP are revealed, supporting PC 1. The genomes of KZN and LP shared an origin but have substantial admixture from the EC and NW populations.Conclusions: These findings indicated a greater negative impact of inbreeding in recent times which is important for planning conservation strategies. It was revealed that the occurrence of high Ne and autozygosity varied largely across breeds in communal indigenous goat populations at different recent and ancient events when a genome-wide SNP marker was used.
In Vivo Vaccination with Cell Line-Derived Whole Tumor Lysates – Neoantigen Quality, Not Quantity Matters
Authors: Salewski Inken , Gladbach Yvonne Saara , Kuntoff Steffen , Irmscher Nina , Hahn Olga , Junghanss Christian , Maletzki Claudia 
Published: August 2020

Abstract
Background: Cancer vaccines provide a complex source of neoantigens. Still, increasing evidence reveals that the neoantigen quality rather than the quantity is predictive for treatment outcome. Methods: Using the preclinical Mlh1-/- tumor model, we performed a side-by side comparison of two autologous cell-line derived tumor lysates (namely 328 and A7450 T1 M1) harboring different tumor mutational burden (TMB; i.e. ultra-high: 328; moderate-high: A7450 T1 M1). Mice received repetitive prophylactic or therapeutic applications of the vaccine. Tumor incidence, immune responses and tumor microenvironment was examined.Results: Both tumor cell lysates delayed tumor formation in the prophylactic setting, with the A7450 T1 M1 lysate being more effective in decelerating tumor growth than the 328 lysate (median overall survival: 37 vs. 25 weeks). Comparable results were achieved in therapeutic setting and could be traced back to antigen-driven immune stimulation. Reactive T cells isolated from A7450 T1 M1-treated mice recognized autologous Mlh1−/− tumor cells in IFNγ ELISpot, but likewise YAC-1 cells, indicative for stimulation of both arms of the immune system. By deciphering local effects, vaccines shaped the tumor microenvironment differently. While A7450 T1 M1 prophylactically vaccinated tumors harbored low numbers of myeloid-derived suppressor cells (MDSC) and elevated CD8-T cell infiltrates, vaccination with the 328 lysate evoked MDSC infiltration. Similar effects were seen in the therapeutic setting with stable disease induction only upon A7450 T1 M1 vaccination. Untangling individual response profiles revealed strong infiltration with LAG3+ and PD-L1+ immune cells when treatments failed, but almost complete exclusion of checkpoint-expressing lymphocytes in long-term survivors. Conclusions: By applying two tumor cell lysates we demonstrate that neoantigen quality outranks quantity. This should be considered prior to designing cancer vaccine-based combination approaches.