bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Aetiology and Outcomes of Acute Gastrointestinal Illness in Returning Travellers: a Retrospective Cohort Analysis
Authors: Lever Robert A , Tapper Louis , Skarbek Sophie , Chiodini Peter L , Armstrong Margaret , Bailey Robin L 
Published: March 2021

Abstract
Background: Gastrointestinal illness is a major cause of morbidity in travellers and is a common reason for presentation to healthcare services on return. Whilst the aetiology of imported gastrointestinal disease is predominantly infectious, outcomes are variable due to a range of phenomena such as post-infectious irritable bowel syndrome, drug resistance and occult pathology (both infectious and non-infectious). Previous studies have focussed on predictors of aetiology of gastrointestinal disease in travellers; we present a retrospective study combining both aetiological and early outcome data in a large cohort of returned travellers. Method: We identified 1450 patients who attended our post-travel walk-in clinic with gastrointestinal symptoms between 2010 and 2016. Demographic, travel, clinical and laboratory data was collected through case note review. Logistic regression analysis to examine correlates of aetiology and outcome were performed in R (CRAN Project 2017). Results: Of 1450 patients in our cohort 153 reported bloody diarrhoea and 1081 (74.6%) reported non-bloody diarrhoea. A definitive microbiological diagnosis was made in 310 (20.8%) of which 137 (9.4%) had a parasite identified and 111 (7.7%) had a bacterial cause identified. Factors associated with a parasitological diagnosis included history of travel to South Asia (aOR=2.55; 95%CI 1.75-3.70, p<0.0001) and absence of bloody diarrhoea (aOR=0.22; 95%CI 0.066-0.53, p<0.005). Factors associated with a bacteriological diagnosis included male gender (aOR=1.69; 95%CI 1.10-2.62, p<0.05), an age <37 years on presentation (aOR=2.04; 95%CI 1.25-3.43, p<0.01), white cells on stool microscopy (aOR=3.52; 95%CI 2.09-5.86, p<0.0001) and a C-reactive protein level of >5iu/dL (aOR=4.68; 95%CI 2.91-7.72, p<0.0001). The majority (1235/1450, 82.6%) reported full symptomatic resolution by the first follow up visit; factors associated with lack of symptomatic resolution included female gender (aOR=1.45 95%CI 1.06-1.99, p<0.05), dysenteric diarrhoea (aOR=2.14 (95%CI 1.38-3.25, p<0.0005) and elevated peripheral leukocyte count (aOR=1.58 95%CI 1.02-2.40, p<0.05).Conclusions: In a cohort of returned travellers, we were able to identify multiple factors that are correlated with both aetiology and outcome of imported gastrointestinal syndromes. We predict these data will be valuable in the development of diagnostic and therapeutic pathways for patients with imported gastrointestinal infections.
Exosomal Carboxypeptidase E (CPE) and CPE-shRNA&nbsp;Loaded Exosomes Control Growth and Invasion of Recipient Hepatocellular Carcinoma Cells
Authors: Hareendran Sangeetha , Albraidy Bassam , Yang Xuyu , Liu Aiyi , Breggia Anne , Chen Clark C , Loh Y. Peng 
Published: March 2021

Abstract
Background: Exosomes from cancer cells prom­ote tumor growth and metastasis through intercellular communication. However, the exosomal bioactive molecules involved and the mechanism of action remain elusive. Carboxypeptidase E (CPE) is known to drive tumor progression in different cancers, including hepatocellular carcinoma (HCC), which is associated with high mortality rate. Here, we investigated if CPE is present within cancer cell exosomes and contributes to the molecular pathogenesis of HCC and other cancers by regulating tumor growth and invasion.Methods: Exosomes isolated from the culture media of cancer cells or human serum were analyzed for CPE mRNA and protein using quantitative PCR/ RT-PCR and western blot respectively. Low-metastatic HCC97L cells were incubated with exosomes derived from high-metastatic HCC97H cells. In other experiments, HCC97H cells were incubated with CPE-shRNA loaded exosomes isolated from HEK293T cells. The recipient HCC cells were assessed for proliferation and invasion using MTT cell proliferation, colony formation and matrigel invasion assays. Results: CPE mRNA and protein were found to be packaged within exosomes released from cancer cells. We observed elevated CPE mRNA levels in secreted exosomes from high versus low-malignant cells, from various cancer types including HCC, breast cancer and glioblastoma. In a pilot study, significantly higher CPE copy numbers were found in serum exosomes from cancer patients compared to healthy donors, suggesting that exosomal CPE mRNA could be a potential diagnostic biomarker. Low-malignant HCC97L cells treated with exosomes derived from HCC97H cells, displayed enhanced proliferation and invasion; however exosomes from HCC97H cells pre-treated with CPE-shRNA failed to promote proliferation. When HEK293T exosomes loaded with CPE-shRNA, were incubated with HCC97H cells, expression of CPE, Cyclin D1, a cell-cycle regulatory protein and c-MYC, a proto-oncogene, were suppressed, resulting in diminished proliferation of HCC97H cells. Conclusions: Our results identified CPE as a bioactive molecule in exosomes driving the growth and invasion of low-malignant HCC cells, and showed that CPE-shRNA loaded exosomes can inhibit malignant tumor cell proliferation via Cyclin D1 and c-MYC suppression. Thus, CPE is a key player in exosome transmission of tumorigenesis, and exosome-based delivery of CPE-shRNA offers a potential treatment for tumor progression.
SNHG9&nbsp;Promotes the Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a&nbsp;Axis
Authors: Bhandari Ramesh , Feng Sun Gui , Ya Liu , Zhixuan Bian , Quihui Pan , Jiabei Zhu , Sewi Mao , Ni Zhen , Jing Wang , Ji Ma , Fenyong Sun 
Published: March 2021

Abstract
Background: Hepatoblastoma is common hepatic tumors occurring children between 0 – 5 years. Accumulating studies has shown lncRNA potential role in distinct cancers progression and development including the hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated the progression of distinct human cancers but, it`s specific molecular mechanisms in hepatoblastoma not unknown. Methods:In this study, we estimated SNHG9 expression on hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated the SNHG9 expression in hepatoblastoma cell lines and then determined the cell proliferation (CCK-8), colony formation, cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pulls down and Spemann’s Pearson correlation coefficient assay were performed to establish the interaction between the SNHG9, WNt3a and miR-23a-5p. Xenograft in-vivo tumorgenicity test was performed to elucidate therole of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drugs resistance in hepatoblastoma was also determined. Results:SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogeneic while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. In Xenograft tumorgenicity test showed SNHG9 downregulation significantly reduced the tumor growth on mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma.Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.
Acquisition of Optimum Co-sources of Sulfur MAA&nbsp;Capped-ZnS&nbsp;Quantum Dots Conditions for Photoluminescence Chlorine Sensor
Authors: Elnady Jehan , Shaala Tosson , Soliman Moataz , Ebrahim Shaker , elshaer ahmed 
Published: March 2021

Abstract
ZnS quantum dots (QDs) has received a great attention due to its unique properties and wide applications. The objective of this work is to synthesize ZnS QDs by hydrothermal method and capped with mercaptoacetic acid (MAA) to be used as a chlorine sensor in the range from 1 to 35 mg/L. Optical, structural and morphological properties of MAA capped-ZnS QDs were investigated. MAA capped-ZnS QDs exhibited a cubic structure with an average diameter size of 8.8 nm. Photoluminescence (PL) spectra of the fabricated MAA capped-ZnS QDs revealed three basic emission peaks at 371, 423 and 486 nm due to level transitions involving of zinc vacancy, interstitial sulfur and zinc, respectively. The photostability of the MAA capped-ZnS QDs was examined after 14 months which retains 12% of the original PL intensity without any peak shift. The MAA capped-ZnS QDs PL intensity was changed linearly with the chlorine concentration in the range from 1 to 35 mg/L with correlation coefficient, sensitivity and limit of detection of 0.9782, 6.96×10-2 ppm-1 and 3.6 mg/L, respectively.
Based on network pharmacology and molecular docking to explore the mechanism of Achyranthis bidentate radix in the treatment of Renal cell carcinoma
Authors: Liu Yu , Li Mingquan , Teh LaiKuan , zhao Liangbin , Ye Naijing , Qu Bo , Lu Hongmei , Wu Ling , Wu Lihua , Tang Anqi 
Published: March 2021

Abstract
Background: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system.The incidence rate was increasing year by year, which has become a worldwide health problem. Achyranthis bidentate radix（ABR) is a traditional Chinese medicine that has been commonly reported on the prevention and treatment of RCC. However, the detailed mechanism of ABR is unclear. Therefore, this study aims to explore the possible molecular mechanism of ABR in the treatment of RCC based on network pharmacology and molecular docking.Methods: The main active compounds of ABR were obtained from pharmacology analysis platform of the Chinese Medicine System (TCMSP). The targets of ABR active compounds were obtained from TCMSP and Swiss Target Prediction. The targets of RCC were then screened in the Gene Cards and Online Mendelian Inheritance in Man (OMIM). The network of “medicine-ingredients-disease-targets” was established employing network pharmacology, and the key targets and core pathways were determined by R analysis. The molecular docking method was used to evaluate the binding activity between the target and the active compounds of ABR.Results: Twenty active compounds were found from ABR and are involving in 164 targets. The results of network analysis indicated that the targets mainly involve biological processes such as active oxygen metabolism, oxidative stress, cell proliferation, and apoptosis. ABR was able to treat RCC through regulating AGE-RAGE, PI3K-Akt, MAPK, JAK-STAT, NF-KB, and other major signaling pathways. Quercetin, baicalein, kaempferol had a strong binding to the target proteins of and MAPK1, AKT1, HSP90AA1.Conclusion: Flavonoids in ABR may be the material basis for its treatment of RCC. The mechanisms of action were through regulating active oxygen metabolism, inhibiting oxidative stress, cell proliferation, activating tumor cell apoptosis pathway, regulating protein kinase activity and nuclear receptor Activity, etc.
Therapeutic Administration of Etoposide Coincides With Reduced Systemic HMGB1 Levels in Macrophage Activation Syndrome
Authors: Palmblad Karin , Schierbeck Hanna , Sundberg Erik , Horne Anna-Carin , Harris Helena Erlandsson , Henter Jan-Inge , Andersson Ulf 
Published: March 2021

Abstract
Background: Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. HMGB1 is a nuclear protein released extracellularly during proinflammatory lytic cell death or secreted by activated macrophages, NK cells, and additional cell types during infection or sterile injury. Extracellular HMGB1 orchestrates central events in inflammation as a prototype alarmin. TLR4 and the receptor for advanced glycation end products operate as key HMGB1 receptors to mediate inflammation. Methods: Standard ELISA and cytometric bead array-based methods were used to examine the kinetic pattern for systemic release of HMGB1, ferritin, IL-18, IFN-γ, and MCP-1 before and during treatment of four children with critical MAS. Three of the patients with severe underlying systemic rheumatic diseases were treated with biologics including tocilizumab or anakinra when MAS developed. All patients required intensive care therapy due to life-threatening illness. Add-on etoposide therapy was administered due to insufficient clinical response with standard treatment. Etoposide promotes apoptotic rather than proinflammatory lytic cell death, conceivably ameliorating subsequent systemic inflammation. Results: This therapeutic intervention brought disease control coinciding with a decline of the increased systemic HMGB1, IFN-γ, IL-18, and ferritin levels whereas MCP-1 levels evolved independently. Conclusion: Systemic HMGB1 levels in MAS have not been reported before. Our results suggest that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of HMGB1 antagonists. They also advocate therapeutic etoposide administration in severe MAS and provide a possible biological explanation for its mode of action.
Synthesis, Spectroscopic Properties, Anti-Breast Cancer and Anti-Microbial Studies of Some Metal Complexes for New Schiff Base Ligand Derived From Anthranilic Acid.
Authors: El-Halim Hanan F. Abd , Mohamed Gehad , Mahmoud Walaa , El-Sayed Omnia 
Published: March 2021

Abstract
2,2’-((1Z-1’Z) (1,3-diphenylpropane-1,3-diylidene) bis (azanylylidene)) dibenzoic acid (H2L) Schiff base ligand, was obtained by condensation reaction between anthranilic acid and dibenzoyl methane in 2:1 ratio.A series of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes was resulted from 1:1 (ligand: metal salt) reaction.The structural features of the synthesized ligand and its metal complexes was determined by elemental analyses, IR, 1H NMR, UV-Vis, ESR, mass spectra, conductivity and magnetic susceptibility measurements as well as thermal (TG/DTG) analyses. The analytical and spectroscopic tools showed that the complexes had composition of ML type with octahedral geometry. The IR results confirmed the tetradendate binding of the ligand involving two azomethine nitrogen atoms and two carboxylate oxygens. The Schiff base and its complexes have been screened for their antimicrobial activity against several bacterial organisms as (Streptococcus pneumoniae and Bacillus subtilis; Pseudomonas aeruginosa and Escherichia coli) and fungi (Aspergillus fumigatus; Syncephalastrum racemosum; Geotricum candidum and Candida albicans) by disk diffusion method.All the metal complexes have potent antimicrobial activity than the free ligand. Anticancer activity of the ligand and its metal complexes was evaluated against human cancer (MCF-7 cells viability).
The Reflective Fostering Programme – improving the wellbeing of children in care through a group intervention for foster carers: a randomised controlled trial: study protocol for a randomised controlled trial.
Authors: Midgley Nick , Irvine Karen , Rider Beth , Byford Sarah , Cirasola Antonella , Ganguli Poushali , Katangwe Thando , Murdoch Jamie , Pond Martin , Pursch Benita , Redfern Sheila , Richards Zena-Louise , Shepstone Lee , Sims Erika , Smith Caroline , Sprecher Eva , Swart Ann Marie , Wyatt Solange , Wellsted David 
Published: March 2021

Abstract
Background: The needs of children in care are a government priority, yet the evidence-base for effective interventions to support the emotional wellbeing of children in care is still lacking. Research suggests that supporting the carer-child relationship, by promoting the carer’s reflective parenting, may be an effective approach to improving the well-being of these children.Methods: The study comprises a definitive, pragmatic, randomised control trial, with embedded process evaluation and economic evaluation, and an internal pilot, to evaluate the effectiveness, and cost effectiveness, of the Reflective Fostering Programme.The study is being conducted in local authority sites across England, and is targeted at foster carers (including kinship carers) looking after children aged four to 13. Consenting participants are randomly allocated to the Reflective Fostering Programme (intervention arm) in addition to usual support or usual support alone (control arm). The primary outcome is behavioural and emotional well-being of the child 12 months post-baseline, and secondary outcomes include: foster carer’s level of stress, quality of life, reflective capacity, compassion fatigue and burnout, placement stability, the quality of the child-carer relationship, child’s capacity for emotional regulation, and achievement of personalised goals set by the carer.Discussion: This study trials one of the first parenting programmes specifically targeting the reflective capacity of foster carers. A feasibility study has indicated effectiveness of the Programme in improving the child-carer relationship and emotional and behavioural wellbeing of children in care. This study will test the effectiveness and cost-effectiveness of implementing the Reflective Fostering Programme as an additional aid to the support already available to local authority foster carers.Trial Registration: ISRCTN 70832140
SUMOylation Regulates TDP-43 Splicing Activity and Nucleocytoplasmic Distribution
Authors: Maraschi AnnaMaria , Gumina Valentina , Dragotto Jessica , Colombrita Claudia , Monpeán Miguel , Buratti Emanuele , Silani Vincenzo , Feligioni Marco , Ratti Antonia 
Published: March 2021

Abstract
The nuclear RNA-binding protein TDP-43 forms abnormal cytoplasmic aggregates in the brains of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients and several molecular mechanisms promoting TDP-43 cytoplasmic mislocalization and aggregation have been proposed, including defects in nucleocytoplasmic transport, stress granules (SG) disassembly and post-translational modifications (PTM). SUMOylation is a PTM which regulates a variety of cellular processes and, similarly to ubiquitination, targets lysine residues. To investigate the possible regulatory effects of SUMOylation on TDP-43 activity and trafficking, we first assessed that TDP-43 is SUMO-conjugated in the nuclear compartment both covalently and non-covalently in the RRM1 domain at the predicted lysine 136 and SUMO-interacting motif (SIM, 106–110 residues), respectively. By using the SUMO-mutant TDP-43 K136R protein, we demonstrated that SUMOylation modifies TDP-43 splicing activity, specifically exon skipping, and influences its sub-cellular localization and recruitment to SG after oxidative stress. When promoting deSUMOylation by SENP1 enzyme over-expression or by treatment with the cell-permeable SENP1 peptide TS-1, the cytoplasmic localization of TDP-43 increased, depending on its SUMOylation. Moreover, deSUMOylation by TS-1 peptide favoured the formation of small cytoplasmic aggregates of the C-terminal TDP-43 fragment p35, still containing the SUMO lysine target 136, but had no effect on the already formed p25 aggregates. Our data suggest that TDP-43 can be post-translationally modified by SUMOylation which may regulate its splicing function and trafficking, indicating a novel and druggable mechanism to explore as its dysregulation may lead to TDP-43 pathological aggregation in ALS and FTD.
A Novel Decentralized Analytical Methodology for Cyber Physical Networks Attack Detection
Authors: Alqahtani Abdurrahman , Abuhasel Khaled Ali , Alquraish Mohammed 
Published: March 2021

Abstract
In many functional implementations of considerable engineering significance, cyber physical solutions have recently been developed where protection and privacy are essential. This led to the recent increase in interest in the development of advanced and emerging technology for anomaly and intrusion detection. The paper suggests a new frame for the distributed blind intrusion detection by modelling sensor measurements as the graph signal and using the statistical features of the graph signal for the detection of intrusion. The graphic similarity matrices is generated using the measured data of the sensors as well as the proximity of the sensors to completely take account of the underlying network structure. The scope of the collected data is modelled on the random field Gaussian Markov and the required precision matrix can be determined by adjusting to a graph called Laplacian matrix. For research statistics, the suggested technique for intrusion detection is based on the modified Bayesian probability ratio test and the closed-form expressions are derived. In the end, the time analysis of the actions of the network is calculated by computing the Bhattacharyya distance at consecutive times among the measurement distributions. Experiments are carried out, evaluated and equate the efficiency of the proposed system to the modern method. The findings indicate a detection value better than that offered by other existing systems via the proposed intrusion detection frame.
Isolation, purification and identification of biological compounds from Beauveria sp. and their evaluation as insecticidal effectiveness against Bemisia tabaci
Authors: An Ran , Ahmed Maqsood , Li Haiyan , Wang Yanbin , Zhang Aimin , Bi Yuhui , Yu Zhiguo 
Published: March 2021

Abstract
Bemisia tabaci is one of the most notorious agricultural pests in the world. A vicious circle among insect resistance, dose increased, environment and human body impaired as the overuse of synthetic pesticides are becoming increasingly evident. Entomopathogenic Beauveria sp. is known as an effective natural enemy to control B. tabaci. Therefore, this study aimed to purify and identify the biological compounds from Beauveria sp. LY2 via extensive chromatographic techniques, NMR and MS and evaluated for their insecticidal activities against B. tabaci via contact and stomach toxicity assay. The outcome identified that one new cerebroside, cerebroside F (1), nine known compounds, cerebroside B (2), bassiatin (3), methyl 1,4-dihydro-4-oxo-2-quinolinecarboxylate (4), cerevisterol (5), 9-hydroxycerevisterol (6), 6-dehydrocerevisterol (7), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (8), melithasterol B (9) and ergosterol peroxide (10) were isolated. Among the known compounds, methyl 1,4-dihydro-4-oxo- 2-quinolinecarboxylate (4) was isolated from natural origin for the first time. It is evident from the results that compounds 3, 4 and 7 strongly featured insecticidal activities against B. tabaci, being the LC50 value as 10.59, 19.05, 26.59 μg/mL respectively in contact as well as 11.42, 5.66, 5.65 μg/mL respectively in stomach experiment. The data from the current study has provided the foundation for the use of newly purified compounds against Bemisia tabaci as an alternative to synthetic chemical compounds.