bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation into street, challenges, means of survival and perceived strategies to alleviate its plights among street children in Addis Ababa, Ethiopia 2019 A phenomenological study design
Authors: Chimdessa Ayana Fite 
Published: June 2020

Abstract
Background: There has been a major discrepancy in defining the term street children-where various stakeholders define in different ways. In spite of increasing in number, the life and health of street children is becoming a global concern. Even though a wide range of policies and strategies are available, they are poorly designed with helpless implementation. This made street children defenseless to harassments and denial of social protection services.Methods: A phenomenological study design was employed to explore difficulties of the street children and perceived strategies to prevent and alleviate plights. The study was conducted from January to March 2019. A Time-Space Sampling (TSS) was used to recruit participants. Pre-tested interview guide was used for data collection. Data was analyzed by using framework analysis software. Results: A total of 103 street children took part in the study. Complexity of push and pull factors pose to risk of flee into the street. Street children are facing widespread challenges i.e. social network fragmentation, child trafficking, harassments and shortage of coverage of basic needs. Furthermore, absences of comprehensive and contextualized strategies and less political value for this group worsening it. Thus, street children have been considered as felon, out laws and having a mentality of committing crime by both law keeping bodies and society. This in turn, affecting street children’s’ acceptance by their community and get legal protection under the law and made them more risk to denial of social protection services. To win street life struggles, they use different survival mechanisms by forming small group. Income Generating Activities (IGAs), shelter, community support, child protection, access to health education, health services, life coaching and by less extent reintegration are positively perceived strategies to address their problems. Conclusion: Lack/poorly designed policies and strategies targeting street children has made them prone to health and social problems. Furthermore, stigma by community, limited resources, lack of comprehensive standards and absence of political value of interventions exacerbating it. Therefore, call for different stakeholders in supporting to design and implement clear, case based and contextualized strategic policies to address and prevent plights; by considering positively perceived street children’s strategies.
Central venous pressure measurement is associated with improved outcomes in septic patients: an analysis of the MIMIC-III database
Authors: Chen Hui , Zhu Zhu , Zhao Chenyan , Guo Yanxia , Chen Dongyu , Wei Yao , Jin Jun 
Published: June 2020

Abstract
Purpose: Measurement of central venous pressure (CVP) can be a useful clinical tool. However, the formal utility of CVP measurement in preventing mortality in septic patients has never been proven.Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was searched to identify septic patients with and without CVP measurements. The primary outcome was 28-day mortality. Multivariate regression was used to elucidate the relationship between CVP measurement and 28-day mortality, and propensity score matching (PSM) and an inverse probability of treatment weighing (IPTW) were employed to validate our findings. Results: A total of 10275 patients were included in our study, of which 4516 patients (44%) underwent CVP measurement within 24 h of intensive care unit (ICU) admission. The risk of 28-day mortality was reduced in the CVP group (OR 0.60 (95% CI 0.51-0.70; p<0.001)). Patients in the CVP group received more fluid on day 1, and had a shorter duration of mechanical ventilation and vasopressor use, and the reduction in serum lactate was greater than that in the no CVP group. The mediating effect of serum lactate reduction was significant for the whole cohort (p=0.04 for the average causal mediation effect (ACME)) and patients in the CVP group with an initial CVP level below 8 mmHg (p=0.04 for the ACME).Conclusion: CVP measurement was associated with decreased risk-adjusted 28-day mortality among patients with sepsis and was proportionally mediated through serum lactate reduction.
Renal Hemangioblastoma with Mixed Mullerian tumor of endometrium: A tale of two rare primary tumors
Authors: Setia Aparna , Kumar Devender , Bains Lovenish , Sharma Pallavi , Tempe Anjali , Mallaya Varuna 
Published: June 2020

Abstract
Introduction: Renal hemangioblastoma (RH) is a very rare benign tumor. Hemangioblastoma most commonly occur in the central nervous system (CNS) and only few cases of RH have been reported as they occur most commonly as asymptomatic masses found incidentally. Mixed Mullerian Tumor (MMT) of the uterus is a rarer and aggressive form of uterine malignancy. The detection of two primary rare tumors incidentally is a rare entity. Case presentation: A 50 years female presented with abnormal uterine bleeding which on endometrial sampling was diagnosed as a rare variety of endometrial cancer i.e., MMT or uterine carcinosarcoma. On preoperative imaging, a renal mass was also detected which was highly vascular and was mimicking Renal Cell Carcinoma (RCC). Fine needle aspiration cytology (FNAC) was done from the renal mass to differentiate between RCC and metastasis but it showed only blood cells. Patient underwent staging laparotomy for endometrial cancer and frozen section examination of the renal mass which was inconclusive with few atypical cells and thus patient underwent radical nephrectomy too. Histopathological examination revealed it to be a RH which is a very rare benign tumor. Discussion: RH is a rare benign tumor which doesn’t require any treatment in majority of the patients. Only 26 cases of RH outside the CNS have been reported till date. MMT is a rare aggressive uterine tumor with an incidence of 1-2 % of all uterine neoplasms, which metastasizes early and thus early identification and treatment is the key. RH needs to be differentiated from RCC to avoid over treatment. Morphological findings are similar in both, preoperative FNAC, PET scan and intraoperative frozen section can be utilized to differentiate in between two in well circumcised tumors and in high suspicion. Occurrence of renal mass as an incidental finding in the preoperative work up of uterine malignancy directed us to the differentials of metastasis or another histologically distinct primary tumor. The presence of two rare primary tumors i.e., RH and MMT in the same patient which are unrelated is a rare entity.
Investigation of molecular mechanisms using integrated analysis of transcriptomes and cytokinome in dermatomyositis
Authors: Bai Jingjing , Wu Chanyuan , Zhong Danli , Xu Dong , Wang Qian , Zeng Xiaofeng 
Published: June 2020

Abstract
Background Pathomechanism of dermatomyositis (DM) remains yet fully elucidated. While several cytokines have been proved to participate in the progress of DM, few studies provided a comprehensive analysis of cytokinome in different DM clinical-serological subgroups and correlation with disease activity as well as interaction with DM tissue lesions.Methods Transcriptome datasets of DM skin and muscle were obtained from public database. Hub genes and signaling pathways were filtered by bioinformatic software. Serum cytokinome was measured in DM patients with different clinical-serological subgroups and correlation with disease activity indicators was analyzed. Cytokine interaction network was constructed.Results 6 hub genes, including STAT1, MX1, ISG15, IFIT3, GBP1 and OAS2 were identified as IFN signature in DM. Differently expressed genes (DEGs) identified in the skin and muscle datasets were significantly enriched in the type I interferon signaling pathway, defense response to virus and chemotaxis. 11 cytokines were significantly elevated in patients positive for melanoma differentiation-associated protein (MDA5) antibody. IFN-α, IFN-γ, MIP-1α, IP-10, MCP1, GRO-α, IL-6, IL-18 and IL-1RA were correlated with disease activity. MCP1/MIP-1α/RANTES/MCP2/CCR1 axes were filtered from cytokine interaction network.Conclusions The complexity of DM immunopathogenesis is mediated through interactions of multiple cytokines and signaling pathways. Type I interferon is the core participant in DM tissue damage. Serum upregulation of IFN-α, IFN-γ, MIP-1α, IP-10, MCP1, GRO-α, IL-6, IL-18 and IL-1RA could be used for disease activity assessment in DM patients positive for MDA5 antibody. Finally, MCP1/MIP-1α/RANTES/MCP2/CCR1 axes mediated monocytes attraction might be novel therapeutic targets in DM by chemokine network analysis.
Clinical and molecular spectrum of 46,XY disorders of sex development that harbourMAMLD1 variations: Case series and review of literature
Authors: Lele Li , Su Chang , Fan Lijun , Gao Fenqi , Liang Xuejun , Gong Chunxiu 
Published: June 2020

Abstract
Background Mastermind-like domain-containing 1 (MAMLD1) has previously been identified as a causative gene for "46,XY Disorders of Sex Development (DSD)". Recently, there has been some controversy regarding the causative role of MAMLD1 variations in DSDs. Here we describe a clinical series and review the reported cases to evaluate the role of MAMLD1 variants in children with 46,XY DSD. Cases of 46,XY DSD harbouring MAMLD1 variants from unrelated families were recruited from the Beijing Children’s Hospital in China (N = 10) or identified through a literature search (N = 26). The clinical manifestations and genetic variants of all the patients were evaluated.Results Hypospadias was the most prevalent phenotype among our 10 cases (8 out of 10 cases) and in all the previously reported ones. Central precocious puberty and isolated micropenis were observed for the first time. Among the 10 cases, nine variants were identified, including three nonsense (p.R356X, p.Q152X, and p.Q124X) and six missense (p.P334S, p.S662R, p.A421P,p.T992I, p.P542S, and p.R927L) variants. In silico analysis showed that the variants p.P334S, p.P542S, p.S662R, and p.R927Lmight lead to drastic changes in the interaction force of the amino acid chain and the flexibility of the spatial structure, and such changes may affect protein function.Conclusion Patients with 46,XY DSD harbouring MAMLD1variants manifest a broad spectrum of phenotypes and mostly present with hypospadias. The six novel variants reported here enrich the mutation database and contribute to our understanding of the pathogenesis of 46,XY DSD.
Prognostic factors of patients with pulmonary large-cell neuroendocrine carcinoma after surgery: a competing risk analysis
Authors: Huang Qian , Liu Jie , Cai Huifang , Zhang Qi , Wang Lina 
Published: June 2020

Abstract
Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare primary malignant tumor with a poor prognosis. Our aim was to determine the prognostic factors of patients with pulmonary LCNEC after surgery based on competing risk model. Methods: Patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database. For single outcome events, Kaplan-Meier method and Cox proportional risk model were used for analysis. Competing risk model was used in the analysis of multiple outcome events to adjust potential confounding factors. Competing risk model was used to calculate the cumulative incidence function of LCNEC-specific death. The Fine-Gray model was used for multivariate analysis to determine independent prognostic factors.Results: We finally screened 614 patients with pulmonary LCNEC who underwent surgery. The univariate analysis showed that T stage, N stage, M stage, regional nodes positive (RNP), and radiotherapy were significantly associated with the cumulative incidence of LCSD (P < 0.05). The Fine-Gray model showed that age, T stage, M stage, RNP, radiotherapy, and chemotherapy were independent prognostic factors for patients with pulmonary LCNEC after surgery (P < 0.05). Conclusion: Based on the competing risk model, we estimated a more accurate cumulative incidence of LCNEC-specific death and prognostic factors for patients with pulmonary LCNEC after surgery.
Using Osmotic Stress to Stabilize Mannitol Production in Synechocystis sp. PCC6803
Authors: Wu Wenyang , Du Wei , Gallego Ruth Perez , Hellingwerf Klaas J. , Woude Aniek D. van der , Santos Filipe Branco dos 
Published: June 2020

Abstract
Background

Mannitol is a C(6) polyol that is used in the food and medical sector as a sweetener and antioxidant, respectively. The sustainable production of mannitol, especially via the direct conversion of CO2 by photosynthetic cyanobacteria, has become increasingly appealing. However, previous work aiming to achieve mannitol production in the marine Synechococcus sp. PCC 7002 via heterologous expression of mannitol-1-phosphate-5-dehydrogenase (mtlD) and mannitol-1-phosphatase (m1p, in short: a ‘mannitol cassette’), proved to be genetically unstable. In this study, we aim to overcome this genetic instability by conceiving a strategy to stabilize mannitol production using Synechocystis sp. PCC 6803 as a model cyanobacterium.

Results

Here, we explore the stabilizing effect that mannitol production may have on cells faced with osmotic stress, in the freshwater cyanobacterium Synechocystis sp. PCC 6803. We first validated that mannitol can function as a compatible solute in Synechocystis sp. PCC 6803, and in derivative strains in which the ability to produce one or both of the native compatible solutes was impaired. Wild type Synechocystis, complemented with a mannitol cassette, indeed showed increased salt tolerance, which was even more evident in Synechocystis strains in which the ability to synthesize the endogenous compatible solutes was impaired. Next we tested the genetic stability of all these strains with respect to their mannitol productivity, with and without salt stress, during prolonged turbidostat cultivations. The obtained results show that mannitol production under salt stress conditions in the Synechocystis strain that cannot synthesize its endogenous compatible solutes is remarkably stable, while the control strain completely loses this ability in only 6 days. DNA sequencing results of the control groups that lost the ability to synthesize mannitol revealed that multiple types of mutation occurred in the mtlD gene that can explain the disruption of mannitol production.

Conclusions

Mannitol production in freshwater Synechocsytis sp. PCC6803 confers it with increased salt tolerance. Under this strategy, genetically instability which was the major challenge for mannitol production in cyanobacteria is tackled. This paper marks the first report of utilization of the response to salt stress as a factor that can increase the stability of mannitol production in a cyanobacterial cell factory.
Construction of a sensitive and specific lead biosensor using a genetically engineered bacterial system with a luciferase gene reporter controlled by pbr and cadA promoters
Authors: Nourmohammadi Esmail , Hosseinkhani Saman , Nedaeinia Reza , Khoshdel-Sarkarizi Hoda , Nedaeinia Mozhdeh , Ranjbar Maryam , Ebrahimi Neshat , Farjami Zahra , Nourmohammadi Mohammad , Mahmoudi Ali , Goli Mohammad , A.Ferns Gordon , Sadeghizadeh Majid 
Published: June 2020

Abstract
Background: A bacterial biosensor refers to genetically engineered bacteria that produce an assessable signal in the presence of a physical or chemical agent in the environment. Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase-reporter gene controlled by pbr and cadA promoters in Cupriavidus metallidurans (previously termed Ralstonia metallidurans) containing the CH34 and pI258 plasmids of Staphylococcus aureus, respectively, and that can be used for the detection of heavy metals. In the present study, we have produced and evaluated biosensor plasmids designated pGL3-luc/pbr-biosensor and pGL3-luc/cad-biosensor, that were based on the expression of luc+ under the control of the cad promoter and the cadC gene of S. aureus plasmid pI258 and pbr promoter and pbrR gene from plasmid pMOL30 of Cupriavidus metallidurans. Results: We found that the pGL3-luc/pbr-biosensor may be used to measure lead concentrations between 1-100 μM in the presence of other metals, including: zinc, cadmium, tin and nickel. The latter metals did not result in any significant signal. The pGL3-luc/cad-biosensor could detect lead concentrations between 10 nM to 10 μM. Conclusions: This biosensor was found to be a specific for measuring lead ions in both environmental and biological samples.
Exosomal miR-380 derived from alveolar macrophages in COPD is involved in enhanced proliferation of human bronchial epithelial cells
Authors: Fan Yunxin , Feng Xiumin , Zhang Jingxi , Bai Chong 
Published: June 2020

Abstract
Background Chronic obstructive pulmonary disease (COPD) is closely related to the occurrence of lung cancer. Both diseases involve changes in the biological function and structure of bronchial epithelial cells. Recently, the role of exosomes in intercellular communication has attracted increasing attention from researchers. As an important molecule carried by exosomes, the role of exosomal miRNAs in diseases such as COPD and lung cancer has also been gradually confirmed. The aim of this study is to investigate the effect of exosomal miRNA derived from macrophages on the proliferation of bronchial epithelial cells. Results After co-culture with alveolar macrophages from COPD, the proliferative activity and migration capacity of 16HBE was significantly enhanced compared with those from healthy controls. Alveolar macrophages from COPD promoted the production of MUC5AC, MUC5B and MUC2 as well as TNF - α and IL-6 in 16HBE. MiR-380 was up-regulated miRNA in exosomes derived from alveolar macrophages through miRNA array analysis. Exosomal miR-380 enhanced the proliferation and migration of 16HBE, promoted the expression of mucins such as MUC5AC, MUC5B and MUC2 of 16HBE, but inhibited the expression of CFTR protein. The target gene of miR-380 was CFTR. The proliferative activity and migration ability of 16HBE was enhanced by blocking CFTR. Conclusions Alveolar macrophages from COPD can enhance the proliferation and migration of 16HBE and promote the expression of mucin and proinflammatory mediators such as IL-6 and TNF-α. Exosomal miR-380 derived from macrophages in COPD was significantly up-regulated. The enhancement of proliferation and migration may be related to the down regulation of CFTR by exosomes delivering miR-380 to bronchial epithelial cells, opening a new way for the therapy and prevention in COPD and its complication.
CircRNA TADA2A relieves idiopathic pulmonary fibrosis by inhibiting proliferation and activation of fibroblasts
Authors: Li Juan , Li Ping , Zhang Guojun , Qin Pan , Zhang Da , Zhao Wei 
Published: June 2020

Abstract
The excessive activation and proliferation of lung fibroblasts are responsible for the abundant deposition of extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF), while its specific mechanism is still unknown. This study focuses on the role of circRNA (circ) TADA2A in functional abnormalities of lung fibroblasts and aims to elaborate its regulatory mechanism. In the present study, circTADA2A was down-regulated in both IPF primary human lung fibroblasts and human IPF fibroblastic cell lines. Functionally, the overexpression of circTADA2A repressed the activation and proliferation of normal human fibroblastic cell line induced by several fibrogenic growth factors. Using fluorescence in situ hybridization (FISH), luciferase reporter assays, and RNA pull-down, circTADA2A was confirmed to function as sponges of miR-526b and miR-203, thus releasing the expression of Caveolin (Cav)-1 and Cav-2. The overexpression of circTADA2A suppressed lung fibroblasts activation via Cav-1 and reduced lung fibroblasts proliferation via Cav-2. In vivo experiments also confirmed that the overexpression of circTADA2A decreased fibrogenic responses induced by bleomycin in lung fibrosis mice. Collectively, circTADA2A repressed lung fibroblasts activation via miR-526b/Cav-1 and reduced lung fibroblasts proliferation via miR-203/Cav-2, thus inhibiting the excessive deposition of ECM and relieving IPF.
Identifying the Biomarkers of Spinal Cord Injury and the effects of Neurotrophin-3 Based on MicroRNA and mRNA Signature
Authors: Qi Shuang , Li Zinan , Yu Shanshan 
Published: June 2020

Abstract
Background

To gain a better understanding of the molecular mechanisms of spinal cord injury and the effects of Neurotrophin-3, differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed.
Methods

The miRNA transcription profile of GSE82195 and the mRNA transcription profile of GSE82196 were downloaded from the Gene Expression Omnibus (GEO). Then, DERs were identified using limma. The noise-robust soft clustering of the intersection DERs was performed using Mfuzz package. Additionally, the integrated miRNAs–targets regulatory network was constructed using Cytoscape. Finally, the Comparative Toxicogenomics Database 2019 update was used to search the central nervous system injury related pathway.
Results

A total of 444 DERs including 382 DEGs and 62 DEmiRNAs were screened between group injury and group none whlie 576 DERs including 523 DEGs and 55 DEmiRNAs were screened between group NT-3 and group injury. Moreover, 80 intersections DERs were identified. DREs in cluster 1 were firstly significantly down-regulated in group injury and subsequently were significantly up-regulated in group NT-3. DERs in cluster 2 were firstly up-regulated in group injury and subsequently down-regulated in group NT-3. OPRL1 and GHSR were enriched in the KEGG pathway of Neuroactive ligand-receptor interaction. OPRL1 was involved in the chemical homeostasis and ion homeostasis while GHSR was related to the regulation of fatty acid metabolic process and regulation of cellular ketone metabolic process.
Conclusion

rno-miR-3072 and rno-miR-667-5p and OPRL1 and GHSR might participate in the pathogenesis of neurological injury and the neurotrophin-3 treatment.
Natural compounds as potential inhibitors of novel coronavirus (COVID-19) main protease: An in silico study
Authors: Mishra Amaresh , Pathak Yamini , Choudhir Gourav , Kumar Anuj , Mishra Surabhi Kirti , Tripathi Vishwas 
Published: June 2020

Abstract
COVID-19 pandemic has now expanded over 213 nations across the world. To date, there is no specific medication available for SARS CoV-2 infection. The main protease (Mpro) of SARS CoV-2 plays a crucial role in viral replication and transcription and thereby considered as an attractive drug target for the inhibition of COVID-19,. Natural compounds are widely recognised as valuabe source of antiviral drugs due to their structural diversity and safety. In the current study, we have screened twenty natural compounds having antiviral properties to discover the potential inhibitor molecules against Mpro of COVID-19. Systematic molecular docking analysis was conducted using AuroDock 4.2 to determine the binding affinities and interactions between natural compounds and the Mpro. Out of twenty molecules, four natural metabolites namely, amentoflavone, guggulsterone, puerarin, and piperine were found to have strong interaction with Mpro of COVID-19 based on the docking analysis. These selected natural compounds were further validated using combination of molecular dynamic simulations and molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations. During MD simulations, all four natural compounds bound to Mpro on 50ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands have stable and favourable energies causing strong binding with binding site of Mpro protein. These four natural compounds have passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property as well as Lipinski’s rule of five. Our promising findings based on in-silico studies warrant further clinical trials in order to use these natural compounds as potential inhibitors of Mpro protein of COVID.