bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-1307-5p targeting TRAF3 upregulates the MAPK/NF-κB pathway and promotes lung adenocarcinoma proliferation
Authors: Du Xinyue , Wang Shuangmiao , Liu Xingyan , He Tao , Lin Xiangui , Wu Simin , Wang Dan , Li Jiao , Huang Wenhua , Yang Huiling 
Published: October 2020

Abstract
Background
Non-small cell lung cancer (NSCLC) includes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MicroRNA (miRNA) plays an important role in the regulation of post-transcriptional gene expression in animals and plants, especially in lung adenocarcinoma.

Methods
MiR-1307-5p is an miRNA with significant differences screened by the second generation of high-throughput sequencing in the early stage of our research group. In the current study, a series of in vitro and in vivo experiments were carried out. MiR-1307-5p mimic, miR-1307-5p inhibitor, and NC were transfected into A549 and H1299 lung adenocarcinoma cells. The correlation between miR-1307-5p and clinicopathological features in pathological samples was analyzed using a lung adenocarcinoma tissue microarray, and miR-1307-5p expression was detected by qPCR. CCK-8, EdU, colony formation, scratch test, and Transwell assays were used to observe cell proliferation and migration. Double luciferase assay, western blot, qPCR, and immunohistochemistry were employed in confirming the target relationship between miR-1307-5p and TRAF3. Western blotting was used to analyze the relationship between miR-1307-5p and the NF-κB/MAPK pathway. Finally, the effect of miR-1307-5p on tumor growth was studied using a subcutaneous tumorigenesis model in nude mice.

Results
Increased miR-1307-5p expression was significantly related to decreased overall survival rate of lung adenocarcinoma patients, revealing miR-1307-5p as a potential oncogene in lung adenocarcinoma. MiR-1307-5p mimic significantly promoted while miR-1307-5p inhibitor reduced the growth and proliferation of A549 and H1299 cells. MiR-1307-5p overexpression significantly enhanced the migration ability while miR-1307-5p inhibition reduced the migration ability of A549 and H1299 cells. Target binding of miR-1307-5p to TRAF3 was confirmed by double luciferase assay, western blot, qPCR, and immunohistochemistry. miR-1307-5p caused degradation of TRAF3 mRNA and protein. MiR-1307-5p targeted TRAF3 and activated the NF-κB/MAPK pathway. TRAF3 colocalized with p65 and the localization of TRAF3 and p65 changed in each treatment group. Tumor volume of the lv-miR-1307-5p group was significantly larger than that of the lv-NC group, and that of the lv-miR-1307-5p-inhibitor group was significantly smaller than that of the lv-NC group.

Conclusion
In conclusion, miR-1307-5p targets TRAF3 and activates the NF-κB/MAPK pathway to promote proliferation in lung adenocarcinoma.
Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria
Authors: Potluri Vijay , Shandil Radha K. , Gavara R. , Sambasivam Ganesh , Campo Brice , Wittlin Sergio , Narayanan Shridhar 
Published: October 2020

Abstract
Background
Emergence of anti-malarial drug resistance and perpetual increase in malaria incidence necessitates the development of novel anti-malarials. Histone deacetylases (HDAC) has been shown to be a promising target for malaria, despite this, there are no HDAC inhibitors in clinical trials for malaria treatment. This can be attributed to the poor pharmacokinetics, bioavailability and selectivity of the HDAC inhibitors.

Methods
A collection of HDAC inhibitors were screened for anti-malarial activity, and the best candidate was profiled in parasite-killing kinetics, growth inhibition of sensitive and multi-drug resistant (MDR) strains and against gametocytes. Absorption, distribution, metabolism and excretion pharmacokinetics (ADME-PK) parameters of FNDR-20123 were determined, and in vivo efficacy was studied in a mouse model for Plasmodium falciparum infection.

Results
A compound library of HDAC inhibitors (180 in number) was screened for anti-malarial activity, of which FNDR-20123 was the most potent candidate. The compound had been shown to inhibit Plasmodium HDAC with IC50 of 31 nM and human HDAC with IC50 of 3 nM. The IC50 obtained for P. falciparum in asexual blood-stage assay was 42 nM. When compared to atovaquone and pyrimethamine, the killing profiles of FNDR-20123 were better than atovaquone and comparable to pyrimethamine. The IC50 values for the growth inhibition of sensitive and MDR strains were similar, indicating that there is no cross-resistance and a low risk of resistance development. The selected compound was also active against gametocytes, indicating a potential for transmission control: IC50 values being 190 nM for male and > 5 µM for female gametocytes. FNDR-20123 is a stable candidate in human/mouse/rat liver microsomes (> 75% remaining post 2-h incubation), exhibits low plasma protein binding (57% in humans) with no human Ether-à-go–go-Related Gene (hERG) liability (> 100 µM), and does not inhibit any of the cytochrome P450 (CYP) isoforms tested (IC50 > 25 µM). It also shows negligible cytotoxicity to HepG-2 and THP-1 cell lines. The oral pharmacokinetics in rats at 100 mg/kg body weight shows good exposures (Cmax = 1.1 µM) and half-life (T1/2 = 5.5 h). Furthermore, a 14-day toxicokinetic study at 100 mg/kg daily dose did not show any abnormality in body weight or gross organ pathology. FNDR-20123 is also able to reduce parasitaemia significantly in a mouse model for P. falciparum infection when dosed orally and subcutaneously.

Conclusion
FNDR-20123 may be a suitable candidate for the treatment of malaria, which can be further developed.
High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018
Authors: Heinemann Melina , Phillips Richard O. , Vinnemeier Christof D. , Rolling Christina C. , Tannich Egbert , Rolling Thierry 
Published: October 2020

Abstract
Background
Ghana is among the high-burden countries for malaria infections and recently reported a notable increase in malaria cases. While asymptomatic parasitaemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce, and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season.

Methods
Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium species by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all Plasmodium ovale infections additional sub-species identification was performed.

Results
Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with P. ovale. The sub-species P. ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with P. falciparum.

Conclusions
Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with P. malariae, P. o. curtisi and P. o. wallikeri.
Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways
Authors: He Bin , Li Qi Yue , Wu Yuan Yuan , Ruan Jing Ling , Teng Xiao Ming , Li Da Jin , Tang Chuan Ling 
Published: October 2020

AbstractBackgroundTrophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis.MethodsJEG-3 cells were cocultured with H2O2and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting.ResultsCsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the H2O2-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with H2O2. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the H2O2-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis.ConclusionsThese results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways.
Association between telomere length in peripheral blood leukocytes and risk of ischemic stroke in a Han Chinese population: a linear and non-linear Mendelian randomization analysis
Authors: Cao Weijie , Zheng Deqiang , Zhang Jie , Wang Anxin , Liu Di , Zhang Jinxia , Singh Manjot , Maranga Isinta Elijah , Cao Mingyang , Wu Lijuan , Song Manshu , Wang Wei , Wang Youxin 
Published: October 2020

Abstract
Background
Many contradictory conclusions pertaining to the telomere length in peripheral leukocyte chromosomes as a potential biomarker for ischemic stroke (IS) risk have been reported by the various observational studies in previous years. This study aims to investigate whether the leukocyte telomere length is associated with an increased IS risk or not, based on the Mendelian randomization (MR) approach.

Methods
Based on the NHGRI-EBI GWAS Catalog database, the Chinese online genetic database as well as the previous published studies, twelve single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 were selected and the leukocyte telomere length was measured in 431 first-ever IS patients and 304 healthy controls (quantitative polymerase chain reaction). To explore linear and non-linear effect of telomere length on the IS risk, we preformed the linear MR analysis (the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method), and the non-linear MR analysis (semiparametric method with three tests for non-linearity, including the quadratic test, Cochran’s Q test, and the fractional polynomial test).

Results
Two verified SNPs (rs11125529 and rs412658) were chosen as instrumental variables. In linear MR analysis, the adjusted odds ratios and 95% confidence intervals of IS for genetically predicted telomere lengths, based on the two SNPs, were 1.312 (0.979 to 1.759), 1.326 (0.932 to 1.888) and 1.226 (0.844 to 1.781) for the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method, respectively. Three tests for nonlinearity failed to reject the null exactly, indicating that the relationship between telomere length and IS risk is unlikely to be non-linear.

Conclusion
This MR study based on individual data does not provide strong evidence for a positive linear or non-linear effect of telomere length on the IS risk.
Midterm results of mitral valve repair for atrial functional mitral regurgitation: a retrospective study
Authors: Kaneyuki Daisuke , Nakajima Hiroyuki , Asakura Toshihisa , Yoshitake Akihiro , Tokunaga Chiho , Tochii Masato , Hayashi Jun , Takazawa Akitoshi , Izumida Hiroaki , Iguchi Atsushi 
Published: October 2020

Abstract
Background
Annular dilation by left atrial remodeling is considered the main cause of atrial function mitral regurgitation. Although acceptable outcomes have been obtained using mitral ring annuloplasty alone for atrial functional mitral regurgitation, data assessing outcomes of this procedure are limited. Therefore, we aimed to assess midterm outcomes of mitral valve repair in patients with atrial functional mitral regurgitation.

Methods
We retrospectively studied 40 patients (mean age: 69 ± 9 years) who had atrial fibrillation that persisted for > 1 year, preserved left ventricular ejection fraction of > 40%, and mitral valve repair for atrial functional mitral regurgitation. The mean clinical follow-up duration was 42 ± 24 months.

Results
Mitral ring annuloplasty was performed for all patients. Additional repair including anterior mitral leaflet neochordoplasty was performed for 22 patients. Concomitant procedures included maze procedure in 20 patients and tricuspid ring annuloplasty in 31 patients. Follow-up echocardiography showed significant decreases in left atrial dimensions and left ventricular end-diastolic dimensions. Recurrent mitral regurgitation due to ring detachment or leaflet tethering was observed in five patients and was seen more frequently among those with preoperative left ventricular dilatation. Three patients without tricuspid ring annuloplasty or sinus rhythm recovery by maze procedure developed significant tricuspid regurgitation. Five patients who underwent the maze procedure showed sinus rhythm recovery. Rates of freedom from re-admission for heart failure at 1 and 5 years after surgery were 95 and 86%, respectively.

Conclusions
Mitral valve repair is not sufficient to prevent recurrent atrial functional mitral regurgitation in patients with preoperative left ventricular dilatation. Tricuspid ring annuloplasty may be required for long-term prevention of significant tricuspid regurgitation.
Study of the effect of family communication and function, and satisfaction with body image, on psychological well-being of obese girls: the mediating role of self-esteem and depression
Authors: KavehFarsani Zabihollah , Kelishadi Roya , Beshlideh Kioumars 
Published: October 2020

Abstract
Background
Obesity has become a global problem in childhood and adolescence. The objective of the present study was to investigate the impact of family communication and function, and body image satisfaction, on psychological well-being by considering: the mediating role of self-esteem and depression.

Methods
In this cross sectional study, 173 obese and overweight female students were selected and evaluated based on body image satisfaction, self-esteem, depression, psychological well-being, functioning, and family Communication. The proposed model was evaluated through structural equation modeling, using AMOS and SPSS software.

Results
Results showed that family communication and function directly affected adolescents’ psychological well-being. In addition, family communication and function, as well body image satisfaction indirectly affected psychological well-being through self-esteem and depression.

Conclusion
The current finding suggests that the psychological well-being of obese adolescent girls is associated with many factors, including family functioning and communication, body image satisfaction, self-esteem, and depression. The factors identified in this study may be helpful for mental health policy-makers, in planning and implementing preventive and therapeutic intervention programs.
Novel insights into extrachromosomal DNA: redefining the onco-drivers of tumor progression
Authors: Gu Xiang , Yu Jie , Chai Peiwei , Ge Shengfang , Fan Xianqun 
Published: October 2020

AbstractExtrachromosomal DNA (ecDNA), gene-encoding extrachromosomal particles of DNA, is often present in tumor cells. Recent studies have revealed that oncogene amplification via ecDNA is widespread across a diverse range of cancers. ecDNA is involved in increasing tumor heterogeneity, reverting tumor phenotypes, and enhancing gene expression and tumor resistance to chemotherapy, indicating that it plays a significant role in tumorigenesis. In this review, we summarize the characteristics and genesis of ecDNA, connect these characteristics with their concomitant influences on tumorigenesis, enumerate the oncogenes encoded by ecDNA in multiple cancers, elaborate the roles of ecDNA in tumor pathogenesis and progression, and propose the considerable research and therapeutic prospects of ecDNA in cancer.
Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study
Authors: Villa Gianluca , Romagnoli Stefano , De Rosa Silvia , Greco Massimiliano , Resta Marco , Pomarè Montin Diego , Prato Federico , Patera Francesco , Ferrari Fiorenza , Rotondo Giuseppe , Ronco Claudio 
Published: October 2020

Abstract
Background
Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19.

Aim
Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties.

Methods
An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events.

Results
The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001).
Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement.

Conclusions
EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.
Meta-analysis of cyathostomin species-specific prevalence and relative abundance in domestic horses from 1975–2020: emphasis on geographical region and specimen collection method
Authors: Bellaw Jennifer L. , Nielsen Martin K. 
Published: October 2020

AbstractBackgroundCyathostomins infect virtually all horses, and concomitant infections with 10 or more species per horse is standard. Species-specific knowledge is limited, despite potential species bias in development of disease and anthelmintic resistance. This is the first meta-analysis to examine effects of geographical region and cyathostomin collection method on reported composition of cyathostomin communities.MethodsThirty-seven articles published in English in 1975 or later, in which adults of individual species were systematically enumerated, were included. Seven regions; North America, South America, eastern Europe, western Europe, northern Europe, southern Africa, and Oceania, and three cyathostomin collection methods; (i) standard necropsy recovery from the large intestine, (ii) critical test collection from post-treatment feces and necropsy, and (iii) diagnostic deworming recovery solely from post-treatment feces, were considered. Generalized mixed linear models analyzed the effects of region and collection method on species-specific prevalence and relative abundance. Species richness was analyzed by mixed linear models.ResultsDefinitively, the most prevalent and relatively abundant species wereCylicocyclus nassatus(prevalence = 93%, relative abundance = 20%),Cylicostephanus(Cys.)longibursatus(93%, 20%), andCyathostomum catinatum(90%, 16%). A bias toward horses with high infection intensities and cyathostomin collection from feces resulted in North American critical tests and eastern European diagnostic deworming overestimating the species-specific prevalence and underestimating the relative abundance of rare/uncommon species compared to respective intra-regional standard necropsies. North American critical tests underestimated species richness due partially to identification key errors. Inter-regional standard necropsy comparisons yielded some species-specific regional differences, including a significantly higherCys. longibursatusprevalence and relative abundance in North America (92%, 33%) than in eastern Europe (51%, 7%) (P > 0.0001). Localization of critical tests to North America and diagnostic deworming to Eastern Europe precluded expansive ‘region by collection method’ interaction analyses.ConclusionWe provide substantial data to inform study design, e.g. effect and study size, for cyathostomin research and highlight necessity for method standardization and raw data accessibility for optimalpost-factumcomparisons.