bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increase of foreign body and harmful substance ingestion and associated complications in children: a retrospective study of 1199 cases from 2005 to 2017
Authors: Speidel Arne , Woelfle Lena , Mayer Benjamin , Posovszky Carsten 
Published: July 2020

Abstract
Background
Children with a history of caustic or foreign body ingestions (FBI) are frequently presented at the emergency department. An uncertain case history, the different objects and diverse clinical presentation may complicate or delay a proper management and cause serious complications.
Methods
A structured retrospective data analysis of patients presented in between January 2005 and December 2017 at the University Medical Centre Ulm was performed. All patients up to 17 years of age with food impaction, foreign body or harmful substance ingestion were included by selection of the corresponding International Statistical Classification of Diseases and Related Health Problems (ICD10-GM) codes. Descriptive statistics, parametric or non-parametric tests, and linear regression analysis were performed.
Result
In total, 1199 cases were analysed; mean age 3.3 years (SD 3.12; range 7 days to 16 years), male to female ratio 1.15:1, thereof 194 (16.2%) were hospitalized. The majority (n = 619) had no symptoms, 244 out of 580 symptomatic patients complained retching or vomiting. The annually recorded cases increased from 66 in 2005 to 119 in 2017 with a rise of the percentage of all emergency cases by 0.52% since 2010 to 1.34% in 2017. Most frequently, coins were ingested (18,8%). Radiopaque objects accounted for 47.6%, and sharp objects for 10.5% of the FBI, which were significantly more often ingested by girls (p < 0.000015 and p < 0.000024, respectively). Button battery ingestion was recorded in 63 cases with a significant annual increase (R2 = 0.57; beta = 0,753; p < 0.003). The annual rate of complications raised significantly (R2 = 0.42; beta = 0,647; p < 0.017).
Conclusion
Children with FBI are increasingly presented at emergency departments. Special attention is necessary to prevent serious complications, especially in asymptomatic children. Further preventive measures within the home environment are needed to stop this trend.
A Cross-Sectional Study of Olfactory and Taste Disorders in COVID-19 Patients in China
Authors: Li Jianhui , Sun Yi , Li Meirong , Yuan Hu , Yang Changliang , Huang Chengcheng , Zhou Fengjie , Chen Ruiyao , Zhang Leibo , Yu Ning , Liu Qiong , He Jingjing , Zhou Xuejun , Fu Xiaobing , Yang Shiming 
Published: July 2020

Abstract
Objective To determine the prevalance and features of olfactory and taste disorders in coronavirus disease of 2019（CoVID-19）patients in China. Methods A cross-sectional study was performed from 3 April to 15 April 2020 in Wuhan. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection completed face-to-face interviews or telephone follow-up. Patients information including epidemiological, clinical, imaging, and serological records and treatment and outcomes data. Patients were further evaluated using questionnaires and visual analogue scale. Statistical analysis was performed with SPSS software (version 22.0). Results The enrolled 187 patients, 23 (12.3%) reported olfactory disorders, 42 (22.46%) reported taste disorders. Females are more prone to olfactory and taste disorders. Among patients that can clearly describe the fluctuation of olfactory and taste disfunctions, 4 (20.0%) and 7(18.92%) cases occurred before other symptoms appeared, the average number of days in advance was 3.5 and 3.57, respectively. The majority of patients can return to normal or basic normal, but in 4(17.39%) and 9(21.43%) cases olfactory and taste can not fully recoveried during the research period. Conclusions Prevalence of olfactory and taste disorders substantially lower in China cohorts compared to abroad COVID-19 cohorts. The prevalence of olfactory and taste disorders in COVID-19 patients was higher in females than in males. In some patients, olfactory and taste disorders precede other symptoms and can be used as a symbol for early screening and warning. The restoration of olfactory and taste function was independent of age; females recover more easily than males; olfactory or taste disorders was not easily recovered for patients with clinically classified as severe; when olfactory or taste disorders itself was serious, it was not easy to recover; olfactory or taste disorders occured early in the disease were more likely to be recovered, otherwise they were hard to be recovered.
Permeability of the Windows of the Brain: Feasibility of Dynamic Contrast-enhanced MRI of the Circumventricular Organs
Authors: Verheggen Inge C.M. , de Jong Joost J.A. , Boxtel Martin P.J. van , Postma Alida A. , Verhey Frans R.J. , Jansen Jacobus F.A. , Backes Walter H. 
Published: July 2020

Abstract
BackgroundCircumventricular organs (CVOs) are small structures without a blood-brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood-brain barrier absence.MethodsTwenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter.ResultsIn both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer rates than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter.ConclusionsCurrent measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures.Trial registrationNetherlands Trial Register number: NL6358, date of registration: 2017-03-24
Camptothecin regulates microglia polarization and exerts neuroprotective effects via the AKT/Nrf2/HO-1-NF-κB signal axis in vivo and in vitro
Authors: he dewei , Liu Dianfeng , Zhou Ang , Gao Xiyu , Zhang Yufei , Su Yingchun , Huang Bingxu , Du Jian , Fu Shoupeng 
Published: July 2020

Abstract
Background

Parkinson's disease (PD), the second largest neurodegenerative disease seriously affects human health. Microglia, the main immune cells in the brain participate in the innate immune response in the central nervous system (CNS). Studies have shown that microglia can be polarized into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Accumulated evidences suggest that over-activated M1 microglia release pro-inflammatory mediators that damage neurons and lead to Parkinson's disease (PD). In contrast, M2 microglia release neuroprotective factors and exert the effects of neuroprotection. Camptothecin (CPT), an extract of the plant Camptotheca acuminate, has been reported to have anti-inflammation and antitumor effects. However the effect of CPT on microglia polarization and microglia-mediated inflammation responses has not been reported. Therefore, we aim to explore the effect of CPT on microglia polarization and its underlying mechanism on neuroinflammation.
Methods

C57BL/6 mice (25–30 g) were injected LPS or PBS into the substantia nigra (SN). Open-Field Test and Immunohistochemistry were performed to test the dyskinesia of mice and the loss of neurons in the substantia nigra (SN). Microglia cell line BV-2, the neuroblastoma SH-SY5Y and dopaminergic neuron MN9D cell were cultured. Cytotoxicity assay, reverse transcription quantitative real-time polymerase chain reaction (RT-PCR), Western blot, ELISA and Immunofluorescence staining were performed. All results were presented with mean ± SD.
Results

In vivo, CPT improved dyskinesia of mice, reduced the loss of neurons in the substantia nigra (SN) and inhibited neuro-inflammatory responses in LPS-injected mice. In vitro, CPT inhibited M1 polarization of microglia and promotes M2 polarization via the AKT/Nrf2/HO-1-NF-κB signal axis. Furthermore, CPT protected the neuroblastoma cell line SH-SY5Y and dopaminergic neuron cell line MN9D from neurotoxicity of mediated by microglia activation.
Conclusion

CPT regulates the microglia polarization phenotype via the AKT/Nrf2/HO-1-NF-κB signal axis, inhibits neuro-inflammatory responses and exerts neuroprotective effects in vivo and in vitro.
Study on the Demand and Utilization of Health Services for the Poor Elderly in China
Authors: Zeng Yanbing , Xu Weiqian , Luo Bei , Fang Ya 
Published: July 2020

Abstract
Background

Despite historic achievements in fighting poverty over recent decades, the unmet health needs of the poor elderly are still a severe problem in China. This paper investigates the demand and utilization status of health services among the poor elderly and examines the factors that affect healthcare service utilization.
Methods

According to the international poverty line of each year, we selected the poor elderly from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015 to create nationally representative estimates. The main outcome measures include utilization indicators for the probability and costs of outpatient/inpatient services. Based on a modified Andersen behaviour model, a two-part model is designed to investigate and analyse how predisposing factors, enabling factors, and need and health behaviour variables affect the health service utilization of the poor elderly. The prediction of marginal effect of the unconditional healthcare expenditure are estimated by jointing the model of probability and expenditure of health service utilization.
Results

The morbidity and chronic disease rates of the poor elderly were 16.93% and 79.43%, respectively. The visit rate of outpatient services increased from 15.05% in 2011 to 21.26% in 2015, and the hospitalization rate increased from9.87–16.89%. In terms of medical expenditures, the median cost of outpatient and inpatient services in 2015 for the poor elderly were 350 RMB and 10,000 RMB, respectively, and the out-of-pocket ratios were 85.2% and 53.3% respectively. Overall, 78.44% of the people who actually needed healthcare did not use health services, and the main reason was financial difficulties (42.32%). The two-part model showed that the poor elderly who are higher educated, have children, live in central regions, and have social security and a poor health status and who do not smoke or drink are more likely to use health services. Males who live in the eastern regions with poor self-reported health, physical disabilities and chronic diseases have more medical expenses. Margin effect analysis finds that the need factor is more important than other factors in determining health service utilization.
Conclusion

The poor elderly in China, as the most vulnerable group, tends to have a worse health status and a heavier medical burden. Due to a variety of constraints, the poor elderly had a lower utilization of health services. Predisposing, enabling, need and health behaviour variables should be considered when making policy and taking measures to eliminate health inequalities to improve the health service utilization and the health of the poor elderly.
Characteristics and diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with drug-resistant clinical isolates of Acinetobacter baumannii
Authors: Salehi Bahare , Ghalavand Zohreh , Yadegar Abbas , Eslami Gita 
Published: July 2020

Abstract
Background
This study aimed to characterize the regulation and expression of three putative resistance-nodulation-cell division (RND)-type efflux systems and their contribution to multidrug efflux in clinical isolates of Acinetobacter baumannii.
Methods
Antimicrobial susceptibility testing (AST) of 95 A. baumannii isolates was determined by Kirby-Bauer disk diffusion for 18 antibiotics and minimum inhibitory concentration (MIC) of colistin was determined by broth microdilution method. Moreover, MIC of five classes of antibiotics was assessed using E-test strips in the presence and absence of phenylalanine-arginine beta-naphthylamide (PAβN). Regulatory genes of RND efflux pumps (AdeRS, AdeL, AdeN and BaeSR) were subjected to sequencing. The relative expression of adeB. adeG and adeJ genes was determined by quantitative real-time PCR (RT-PCR).
Results
Overall, majority of isolates (93%) were extensively drug-resistant (XDR). In the phenotypic assay, efflux pump activity was observed in 40% of isolates against multiple antibiotics mainly tigecycline, but not to imipenem. Several amino acid substitutions were detected in the regulatory genes; except in AdeN. Of note, A136V in AdeR and G186V in AdeS were found to be associated with overexpression of their relative efflux pumps. No insertion sequences (ISs) were detected.
Conclusions
Our findings outline the role of RND efflux pumps in resistance of A. baumannii against multiple antibiotics particularly tigecycline, and point out importance of a variety of single mutations in the corresponding regulatory systems. Even though it has been concluded that multidrug resistance occurs as a result of a complex sets of different resistant mechanisms.
Aberrant Methylation Modifications Reflect Specific Drug Responses in Small Cell Lung Cancer
Authors: Chen Peixin , Guo Haoyue , Liu Yu , Chen Bin , Zhao Sha , Wu Shengyu , Li Wei , Wang Lei , Jia Keyi , Wang Hao , Jiang Minlin , Tang Xuzhen , Qi Hui , Dai Chunlei , Ye Junyan , He Yayi 
Published: July 2020

Abstract
Background: Epigenetic alterations of specific genes are closely related to chemotherapeutic efficacy in various cancers. However, few comprehensive profiles of differentially methylated genes (DMGs) in small cell lung cancer (SCLC) were available. The current study aimed to explore the association between aberrant methylation modifications of coding and non-coding genes and chemotherapy insensitivity, thus constructing lncRNA-miRNA-mRNA regulatory network in SCLC.Methods: In this study, methylated DNA immunoprecipitation sequencing (MeDIP-Seq) and RNA sequencing (RNA-Seq) was employed to six SCLC patients who were sensitive and insensitive to first-line standard chemotherapy. Then, we verified the therapeutic predictive effects of DMGs in 62 SCLC cell lines and constructed lncRNA-miRNA-mRNA network on the basis of different cohorts and databases. Results: Of 4552 DMGs which were selected (fold change ≥ 2, p<0.01) between chemo-sensitive and chemo-insensitive group, coding genes constituted the largest percentage (3873/4551, 85.08%), followed by lncRNAs (479/4551, 10.52%) and miRNAs (162/4552, 3.56%). Further, both two groups demonstrated two methylation peaks near transcription start site and transcription end site. Two lncRNA-miRNA-mRNA networks which based on genes that showed opposite results in genetic expression and epigenetic modifications suggested the extensive genome connection between chemotherapy efficacy-related non-coding RNAs (ncRNAs) and mRNAs. Combing four DMGs, including hsa-miR-34a, LINC00461, LINC01018, and LINC01484 could effectively predict first-line chemotherapy response in SCLC, indicating that they might play vital roles in SCLC chemotherapy insensitivity. Conclusions: This study was the first to evaluate multiple drugs efficacy-related ncRNAs and mRNAs which were modified by methylation in SCLC. In addition, DMGs identified in our research might serve as predictors for chemotherapy effect and promising therapeutic targets to reverse drugs-insensitivity by complex lncRNA-miRNA-mRNA mechanisms in SCLC. Further comprehensive studies of these findings are worthy of expecting.
EBV Encoded miRNA BART8-3p Drives Radioresistance-Associated Metastasis in Nasopharyngeal Carcinoma
Authors: Zhou Xiaohan , Lin Yanling , Chen Yuting , Wang Lingzhi , Liao Jinrong , Zeng Hanyi , Luo Wenxiao , Wu Dehua , Cai Longmei 
Published: July 2020

Abstract
Background: Radiotherapy plays an important role in the treatment of nasopharyngeal carcinoma (NPC), however, 20 % of patients with NPC exhibit unusual radioresistance. Patients with radioresistance are at risk of recurrence, so it is imperative to explore the mechanism of resistance to radiotherapy. In the past, studies on the mechanism of radioresistance have been restricted to DNA damage and related cell cycle remodeling or apoptosis. So far, no studies have explored the relationship between radioresistance and metastasis. Methods: We analyzed the metastasis rate of patients with recurrent NPC and that of patients with primary NPC. Constructing an acquired radioresistant NPC cell line and detect their metastatic ability in vivo and in vitro. RNA-deep sequencing was performed to predict the targeted host genes of EBV-miR-BART8-3p. Western blotting, real-time PCR and immunochemistry were conducted to investigate the relationship of clinicopathologic features and EBV-miR-BART8-3p or PAG1. Results:Through the analysis of clinical samples, we observed that the metastasis rate of recurrent NPC was much higher than that of primary patients. In vitro and in vivo experiments showed that NPC cells with acquired radioresistance exhibited a stronger ability for invasion and metastasis. Mechanistically, we found that the Epstein–Barr virus (EBV)-encoded miRNA BART8-3p was increased in patients with NPC and its expression was positively correlated with adverse prognostic factors, such as radioresistance. Besides, miR-BART8-3p promoted the epithelial-mesenchymal transition (EMT), invasion, and metastasis of radioresistant NPC cells by targeting and inhibiting their PAG1 host gene. Conclusion: These results demonstrated a correlation between radioresistance and metastasis in NPC, which depended on the elevated levels of the EBV-encoded miRNA BART8-3p and the inhibition of the PAG1 host gene. These findings suggested a novel role for EBV-miR-BART8-3p and PAG1 in recurrence NPC and highlighted their potential value as prognostic indicators or therapeutic targets.
TMPRSS2, a SARS-CoV-2 Internalization Protease is Downregulated in Head and Neck Cancer Patients.
Authors: Sacconi Andrea , Donzelli Sara , Pulito Claudio , Ferrero Stefano , Morrone Aldo , Rigoni Marta , Pimpinelli Fulvia , Ensoli Fabrizio , Sanguineti Giuseppe , Pellini Raul , Agrawal Nishant , Izumchenko Evgeny , Ciliberto Gennaro , Giannì Aldo , Muti Paola , Strano Sabrina , Blandino Giovanni 
Published: July 2020

Abstract
Background: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas.Methods: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC.Results: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation.Conclusions: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.
Characterization of Neoplastic Cells in the Cystic Space of Invasive Micropapillary Carcinoma of the Canine Mammary Gland.
Authors: Rodrigues Michele Angela , Caldeira-Brant Andre L. , Gomes Dawidson Assis , Silveira Tatiany L. , Chiarini-Garcia Hélio , Cassali Geovanni Dantas 
Published: July 2020

Abstract
Background: Invasive micropapillary carcinoma (IMPC) is a rare breast malignant tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the canine mammary gland and the human breast. There is a progressed recognition of the importance of the tumor microenvironment in cancer development, but little is known about cell types expressed in the cystic space of canine IMPC. This study aimed to investigate the neoplastic and stromal cells surrounding the cystic space in IMPC. Methods: It was used immunohistochemistry (IHC), immunofluorescence (IF), super-resolution microscope and transmission electron microscopy (TEM) to access the localization and morphology of both stromal cells and epithelial cells in canine IMPC cystic areas.Results: Cells surrounding the cystic space in IMPC were positive for the mesenchymal marker's alpha-smooth muscle actin (aSMA), Vimentin, and S100A4. Furthermore, myoepithelial cell marker p63 was negative on IMPC. Tumoral reversal polarity was observed using MUC1 for the first time in IMPC from the canine mammary gland. MUC1 is known to have a role in lumen formation and has an inhibitory role in the cell to stroma interaction. TEM showed that cells lining the IMPC cystic space were modified myoepithelial cells. Conclusion: The present work demonstrates, for the first time, a characterization of the cystic space compound on IMPC from the canine mammary gland. These findings could be useful to understand better the cellular microenvironment in invasive tumors of the mammary gland to improve cancer treatment.