bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic and transcriptome responses of RNAi-mediated AMPKα knockdown in Tribolium castaneum
Authors: Jiang Heng , Zhang Nan , Ji Caihong , Meng Xiangkun , Qian Kun , Zheng Yang , Wang Jianjun 
Published: September 2020

Abstract
Background The AMP-activated protein kinase (AMPK) is an intracellular fuel sensor for lipid and glucose metabolism. In addition to the short-term regulation of metabolic enzymes by phosphorylation, AMPK may also exert long-term effects on the transcription of downstream genes through the regulation of transcription factors and coactivators. In this study, RNA interference (RNAi) was conducted to investigate the effects of knockdown of TcAMPKα on lipid and carbohydrate metabolism in the red flour beetle, Tribolium castaneum, and the transcriptome profiles of dsTcAMPKα-injected and dsEGFP-injected beetles under normal conditions were compared by RNA-sequencing.Results RNAi-mediated suppression of TcAMPKα increased whole-body triglyceride (TG) level and the ratio between glucose and trehalose, as was confirmed by in vivo treatment with the AMPK-activating compound, 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR). A total of 1184 differentially expressed genes (DEGs) were identified between dsTcAMPKα-injected and dsEGFP-injected beetles. These include genes involved in lipid and carbohydrate metabolism as well as insulin/insulin-like growth factor signaling (IIS). Real-time quantitative polymerase chain reaction analysis confirmed the differential expression of selected genes. Interestingly, metabolism-related transcription factors such as sterol regulatory element-binding protein 1 (SREBP1) and carbohydrate response element-binding protein (ChREBP) were also significantly upregulated in dsTcAMPKα-injected beetles. Conclusions AMPK plays a critical role in the regulation of beetle metabolism. The findings of DEGs involved in lipid and carbohydrate metabolism provide valuable insight into the role of AMPK signaling in the transcriptional regulation of insect metabolism.
Peptidome analysis of cerebrospinal fluid in neonates with hypoxic-ischemic brain damage
Authors: Hou Xuewen , Yuan Zijun , Wang Xuan , Cheng Rui , Zhou Xiaoguang , Qiu Jie 
Published: September 2020

Abstract
Hypoxic-ischemic brain injury (HIBD) causes neonatal death and serious neurological disability; however, there are currently no promising therapies for it excepting cooling. Therefore, in this study, we used peptidome analysis to identify differentially expressed peptides in cerebrospinal fluid (CSF) of neonates with HIBD or controls, which may give a foundation for finding new promising drugs of neonatal HIBD. CSF samples were collected from neonates with HIBD (n=4) or controls (n=4). ITRAQ LC-MS/MS was used to identify differentially expressed peptides between two groups. Effects of the peptide from heat shock protein 90-alpha (HSP90α/HSP90AA1) on cell viability and pyroptosis under oxygen and glucose deprivation (OGD) were analyzed using cell counting kit-8 (CCK-8) assay and Annexin V-fluorescein isothiocyanate (FITC) Assay. Expressions of NLRP3, NLRP1, ASC and Caspase-1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Compared with the control group, one peptide significantly up-regulated and thirty-four peptides significantly down-regulated in the CSF of neonates with HIBD. A fragment of HSP90α/HSP90AA1 is the 2671.5Da peptide (HSQFIGYPITLFVEKER), one of the down-regulated peptides in neonatal HIBD. This peptide, we named it HIBDAP, inhibited pyroptosis of PC12 cells under OGD by suppressing expressions of NLRP3, ASC and Caspase-1 except NLRP1. The results of our study identified the characterization and expression profiles of peptides in CSF of neonatal HIBD. Several meaningful peptides such as HIBDAP may play significant roles in neonatal HIBD and provide new therapeutic targets for neonatal HIBD.
Human CD133-positive hematopoietic progenitor cells enhance the malignancy of breast cancer cells
Authors: Zhang Zhe , Zheng Qing Lian , Liu Yong Hui , Sun Lian Qing , Han Ping Ping , Wang Rui , Zhao Jiao , Hu Shan , Zhao Xin Han 
Published: September 2020

Abstract
BackgroundHuman CD133+ hematopoietic progenitor cells (HPCs) are a specific subset of cells that can regulate tumor malignancy. However, the mechanism by which CD133+ HPCs affect the malignancy of human breast cancer has not been reported.MethodsCD133+ HPCs were isolated and purified from human umbilical cord blood (UCB) .We used in vitro culture of MCF-7 and MDA-MB-231 cell lines, and MCF-7 and MDA-MB-231 cells in nude mice to evaluate whether CD133+ HPCs affected the apoptosis, proliferation, invasion and epithelial mesenchymal transition EMT of breast cancer cells.ResultsCo-culture with CD133+ HPCs, but not UCB CD133- cells, promoted the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells, accompanied by reducing in vitro spontaneous apoptosis. Co-administration of these two lines with CD133+ HPCs significantly enhanced the growth of implanted breast cancer in vivo . Furthermore, co-culture with CD133+ HPCs, enhanced the invasion of breast cancer cells, N-cadherin and Vimentin expression, but reduced E-cadherin expression in breast cancer cells.ConclusionsOur study demonstrated that CD133+ HPCs enhance the malignancy of breast cancer cells by attenuating spontaneous apoptosis and promoting the process of epithelial mesenchymal transition. These findings may provide new insights into the role of human CD133+ HPCs in breast cancer pathogenesis. Therefore, CD133+ HPCs may be a new therapeutic target for inhibiting the progression of breast cancer.
Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis protocol
Authors: Niba Peter Thelma Ngwa , Nji Akindeh M. , Evehe Marie-Solange , Ali Innocent M. , Netongo Palmer Masumbe , Ngwafor Randolph , Moyeh Marcel N. , Ngum Lesley Ngum , Ndum Oliva Ebie , Acho Fon Abongwa , Mbu'u Cyrille Mbanwi , Fosah Dorothy A. , Atogho-Tiedeu Barbara , Achonduh-Atijegbe Olivia , Dadjeu Rosine , Chedjou Jean Paul Kengne , Bigoga Jude D. , Moukoko Carole Else Eboumbou , Ajua Anthony , Achidi Eric , Tallah Esther , Leke Rose G. F. , Tourgordi Alexis , Ringwald Pascal , Alifrangis Michael , Mbacham Wilfred F. 
Published: September 2020

Abstract
Background: Cameroon remains a country faced with high malaria burden despite enormous efforts made in the control of the disease. The rapid development and dispersal of mutations associated with anti-malarial drug resistance influenced policy changes from the use of chloroquine, amodiaquine and sulphadoxine-pyrimethamine to the adoption of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Different studies have identified the frequency of key markers in Plasmodium falciparum associated with drug resistance without a clear picture on the localisation of potential hotspots that may drive the emergence of resistance to the currently used ACTs. This systematic review and meta-analysis aims to determine the prevalence and distribution of P. falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from 1990 to present. Methods: The PRISMA, PRISMA-P and STREGA statements will be adopted in the quality assessments of studies to be included in this review. The electronic databases of Medline via Pubmed, EMBASE, Google Scholar and Science Direct will be searched by two independent researchers using different MeSH terms and Boolean operators (AND, OR). More so, unpublished data that will be sourced from academic libraries will also be extracted. Quantitative syntheses will be done using the “metaphor” and “meta” commands in the R statistical software package version 3.5.2. Heterogeneity will be assessed using the Cochrane Q and I2 statistics. The random effects model will be used as benchmark in the determination of heterogeneity between studies. Discussion: The primary outcome of this review is to identify and describe molecular markers conferring drug resistance in Plasmodium falciparum parasites that have been circulating for a period of over 30 years in Cameroon. This review will be able to pool data from previously published and unpublished studies on anti-malarial drug resistance gene mutations. This will provide evidence to support the continuous use of ACTs in the treatment of uncomplicated P. falciparum malaria. Moreover, it is also hoped that potential hotspots driving the emergence and spread of anti-malarial resistance markers will be identified. Systematic review registration: PROSPERO CRD42020162620
Outcomes of tissue reconstruction in distal lower leg fractures: a retrospective cohort study
Authors: Aydogan Emrah , Langer Stefan , Josten Christoph , Fakler Johannes Maria Karl , Henkelmann Ralf 
Published: September 2020

Abstract
Background: Open and closed fractures can be associated with posttraumatic or postoperative soft tissue defects caused by initial trauma, operative procedures, or infections. This study evaluated the postoperative outcomes in patients with open or closed lower leg fractures, related soft tissue defects, and subsequent flap coverage.Methods: We performed a retrospective single-center cohort study in a level 1 trauma center. We analyzed the patients treated from January 2012 through December 2017 and recorded demographics, treatment, and outcome data. The outcome data were measured via patient-reported Foot and Ankle Outcomes Scores (FAOS) and EQ-5D-5L scores.Results: We included 22 patients with complicated fractures (11 open and 11 closed) and subsequent soft tissue defects and flap coverages. The mean follow-up time was 41.2 months. Twenty-one patients developed infections, and necrosis at the site of surgery manifested in all closed fractures. Therefore, all patients needed soft tissue reconstructions. Preoperatively, 16 patients underwent arterial examinations via angiography and six underwent ultrasound examinations of the venous system. Ten patients had complications involving the flaps due to ischemia and consequent necrosis. The mean EQ-5D index was 0.62 ± 0.27, and EQ-5D VAS score was 57.7 ± 20.2. The mean FAOS was 60.7 ± 22.2; in particular, quality of life was 32.3 ± 28.8. The rate of returning to work in our patient group was 37.5% after one year.Conclusions: Distal tibial fractures often require revisions and soft tissue reconstruction. The evaluated patient population had poor outcomes in terms of function, quality of life, and return to work. Furthermore, patients suffering from flap ischemia have worse outcomes than those without flap ischemia.
A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status
Authors: Wang Changpeng , Zhang Siwei , Zou Yuefei , Ma Hongzhao , Jiang Donglang , Sheng Lei , Sang Shaoming , Jin Lirong , Guan Yihui , Gui Yuan , Xu Zhihong , Zhong Chunjiu 
Published: September 2020

Abstract
Background: Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff-Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods: A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 minutes after injection as represented by the area under the curve (AUC) and blood thiamine levels were investigated. Results: The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61±0.53 in the liver within 1 minute, 18.67±7.04 in the kidney within half a minute. The SUV dropped to 0.72±0.05 and 0.77±0.35 after 60 minutes of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 minutes after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 minutes was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = - 0.985, p = 0.015).Conclusion: The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.
Uncertainty analysis of tumour absorbed dose calculations in Molecular Radiotherapy
Authors: Finocchiaro Domenico , Gear Jonathan I , Fioroni Federica , Flux Glenn D , Murray Iain , Castellani Gastone , Versari Annibale , Iori Mauro , Grassi Elisa 
Published: September 2020

Abstract
Background: Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results. Recently, the EANM published a practical guidance on uncertainty analysis for molecular radiotherapy based on the application of the law of propagation of uncertainty. In this study, we investigated the overall uncertainty on a sample of patient following the EANM guidelines. The aim of this study was to provide an indication of the typical uncertainties that may be expected from performing dosimetry, to determine parameters that have the greatest effect on the accuracy of calculations and to consider the potential improvements that could be made if these effects were reduced.Results: Absorbed doses and the relative uncertainties were calculated for a sample of 49 patients and a total of 154 tumours. A wide range of relative absorbed dose uncertainty values was observed (14 - 102%). Uncertainties associated with each quantity along the absorbed dose calculation chain (i.e. Volume, Recovery Coefficient, Calibration Factor, Activity, Time-Activity Curve Fitting, Time-Integrated Activity and Absorbed Dose) were estimated. An equation was derived to describe relationship between the uncertainty in the absorbed dose and the volume. The largest source of error was the VOI delineation. By postulating different values of FWHM, the impact of the imaging system spatial resolution on the uncertainties was investigated.Discussion: To the best of our knowledge, this is the first analysis of uncertainty in molecular radiotherapy based on a cohort of clinical cases. Wide inter-lesion variability of absorbed dose uncertainty was observed. Hence, a proper assessment of the uncertainties associated with the calculations should be considered as a basic scientific standard. A model for a quick estimate of uncertainty without implementing the entire error propagation schema, which may be useful in clinical practice, was presented. Ameliorating spatial resolution may be in future the key factor for accurate absorbed dose assessment.
Protective CD8+ T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epitope peptides in HLA-A2.1/Kb transgenic mice
Authors: Ma Ying , Tang Kang , Zhang Yusi , Zhang Chunmei , Cheng Linfeng , Zhang Fanglin , Zhuang Ran , Jin Boquan , Zhang Yun 
Published: September 2020

Abstract
Background: An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods: Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results: The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo.Conclusions: This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.
Genetic diversity and complexity of Plasmodium falciparum infections in the microenvironment among siblings of the same household in North-Central Nigeria
Authors: Oyedeji Segun Isaac , Bassi Peter Usman , Oyedeji Samuel Adeola , Ojurongbe Olusola , Awobode Henrietta Oluwatoyin 
Published: September 2020

Abstract
Background Plasmodium falciparum parasites are known to exhibit extensive genetic diversity in areas of high transmission intensity and infected individuals in such communities often harbour several complex mixtures of parasite clones with different genetic characteristics. However, in the micro-environment, the extent of genetic diversity of P. falciparum parasites remain largely unknown. In this study therefore, the complexity of P. falciparum infections in households was investigated among symptomatic siblings, living under the same roof in north-central Nigeria.Methods Children were enrolled into the study if they were at least two from a household and presented with symptoms of uncomplicated malaria. Clinical malaria was confirmed by light microscopy of Giemsa-stained thick and thin blood films. Genomic DNA was isolated from blood spots on filter paper. Molecular characterization of P. falciparum isolates was done by allele-specific nested PCR of the highly polymorphic merozoite surface protein-2 (msp-2) gene.Results Ninety-three children from 43 households were enrolled into this study. A total of 26 different msp-2 alleles were identified from 215 fragments (range: 180-480 bp). Majority of the isolates (65.6% (n=61)) were polyclonal infections consisting of 2-6 clones and were significantly more common with the FC27 allelic family (p = 0.036). The multiplicity of infection (MOI) per household ranged from 1.0 to 4.5 while the overall MOI in the study population was 2.31. The pattern of distribution of msp-2 allele types among the households fell into two categories: households where both msp-2 allele types (FC27 and 3D7) were present; households where only one msp-2 allele type (FC27 or 3D7) was present. Majority of the households (88.4% (n=38)), had both msp-2 allele types but they were disproportionately distributed among the children while in a few households (11.6% (n=5)), all the children were infected with only one type of msp-2 allele.Conclusion These findings showed that P. falciparum isolates exhibit remarkable degree of genetic diversity in the micro-environment and are composed mainly of multiclonal infections, which is an indication of a high ongoing parasite transmission. This suggests that the micro-environment is an important area of focus for malaria control interventions and for evaluating intervention programmes.
Full Snapshot Reconstruction in Hybrid Architecture Antenna Arrays
Authors: Trigka Maria , Mavrokefalidis Christos , Berberidis Kostas 
Published: September 2020

Abstract
In the context of this research work, we study the so-called problem of full snapshot reconstruction in hybrid antenna array structures that are utilized in mmWave communication systems. It enables the recovery of the snapshots that would have been obtained if a conventional (non-hybrid) Uniform Linear Antenna (ULA) array was employed. The problem is considered at the receiver side where the hybrid architecture exploits in a novel way the antenna elements of a uniform linear array. To this end, the recommended scheme is properly designed so as to be applicable to overlapping and non-overlapping architectures. Moreover, the full snapshot recoverability is addressed for two cases, namely, for time-varying and constant signal sources. Simulation results are also presented to illustrate the consistency between the theoretically predicted behaviors and the simulated results, and the performance of the proposed scheme in terms Angle-of-Arrival (AoA) estimation, when compared to the conventional MUSIC algorithm and a recently proposed hybrid version of MUSIC (H-MUSIC).
Plasma Lipid Levels and Risk of Primary Open Angle Glaucoma: A Genetic Study Using Mendelian Randomization
Authors: Xu Mengqiao , Li Shengguo , Zhu Jundong , Luo Dawei , Song Weitao , Zhou Minwen 
Published: September 2020

Abstract
Background: The causal effects of plasma lipid concentrations and the risk of primary open angle glaucoma (POAG) are still unclear. Thus, the purpose of this study was to identify, applying a two-sample Mendelian randomization (MR) analysis, whether plasma lipid concentrations are causally associated with the risk of POAG.Methods Two-sample MR analysis of data from a genome-wide association study (GWAS) was performed to investigate the causal role of plasma lipid levels and POAG. A total of 185 independent single-nucleotide polymorphisms (SNPs) associated with plasma lipid levels were selected as instrumental variables (IVs). The SNPs were obtained from a meta-analysis of GWAS based on 188,577 European-ancestry individuals for MR analyses. Association with POAG for the SNPs was obtained from a GWAS conducted among the United Kingdom (UK) Biobank study participants with a total of 463,010 European-ancestry individuals. Four MR methods (inverse variance weighted [IVW], weighted mode, weighted median, and MR-Egger regression) were applied to obtain the overall causal estimate for multiple, instrumental SNPs.Results Using the IVW analysis method, no evidence was found to support a causal association between plasma LDL-C level and POAG risk (β=-0.00026; 95% CI=-0.00062, 0.00011; P=0.165) with no significant heterogeneity among SNPs. The overall causal estimate between plasma LDL-C level and POAG was consistent using the other three MR methods. Using the four MR methods, no evidence of an association between plasma HDL-C (β=0.00023; 95% CI=-0.00015, 0.00061; P=0.238; IVW method) or TG levels (β=-0.00028; 95% CI=-0.00071, 0.00015; P=0.206; IVW method) and POAG risk was found. Sensitivity analyses did not reveal any sign of directional pleiotropy.Conclusions The present study did not find any evidence for a causal association between plasma lipid levels and POAG risk. Further research is needed to elucidate the potential biological mechanisms to provide a reasonable interpretation for these results.