bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India
Authors: Pathak Ashish , Mårtensson Andreas , Gawariker Sudhir , Sharma Ashish , Diwan Vishal , Purohit Manju , Ursing Johan 
Published: June 2020

Abstract
Background Artesunate plus sulfadoxine-pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and >80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015-2016 after 3-4 years of ASP use, are reported.Methods Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16-185, pfdhps 436-632 and K13 407-689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism. Results Sulfadoxine-pyrimethamine resistance-associated pfdhfr 108N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R+108N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively. Conclusion The frequency of P. falciparum with reduced susceptibility to sulfadoxine-pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.
Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer
Authors: Gu Yang , Zhang Shulan 
Published: June 2020

Abstract
Background: The molecular mechanisms of ovarian cancer (OC) remain unclear. We sought to comprehensively identify microRNAs (miRNAs) that are aberrantly expressed in metastatic OC. Methods: Differentially expressed miRNAs were screened from six pairs of primary and metastatic OC tissues; their possible functions were analyzed and target genes were predicted by bioinformatics. Then gene expression profiling results were established by reverse transcription quantitative polymerase chain reaction and western blot. Targeting relationship between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. CCK-8, Transwell assay, scratch test and flow cytometry were used for cell function detection after miR-7-5p overexpression. Results: Twelve miRNAs and 10 target mRNAs were differentially expressed in primary and metastatic OC tissues. ITGB3, TGFβ2 and TNC correlated to miRNA function in metastatic OC. Among all 7 miRNAs, expression of hsa-miR-141-3p, hsa-miR-7-5p, hsa-miR-187-5p, hsa-miR-200a-3p, and hsa-miR-200b-3p in metastatic OC tissues was obviously lower than that in primary OC tissues ( p < 0.05). Moreover, there was a significant correlation between hsa-miR-7-5p and TGFβ2 in OC tissues. Dual-luciferase reporter assay confirmed that hsa-miR-7-5p negatively targeted TGFβ2. After miR-7-5p overexpression, the OC cell viability and invasion were reduced, the cell cycle was blocked ( p < 0.05). Conclusions: Hsa-miR-141-3p, hsa-miR-187-5p, hsa-miR-7-5p, hsa-miR-200a-3p, and hsa-miR-200b-3p expression was prominently lower in metastatic OC than in primary OC, while TGFβ2 expression was markedly increased in metastatic OC tissues. Hsa-miR-7-5p bound to TGFβ2 3’-UTR to inhibit its expression. Hsa-miR-7-5p targeted TGFβ2 to inhibit cell proliferation, invasion and cell cycle entry.
Adjuvant Transarterial Chemoembolization does not Influence Recurrence-free and Overall survivals for Patients with Combined Hepatocellular Carcinoma and Cholangiocarcinoma after Curative Resection: a Propensity Score Matching Analysis
Authors: Liu Wei-Ren , Tian Meng-Xin , Tao Chen-Yang , Tang Zheng , Zhou Yu-Fu , Song Shu-Shu , Jiang Xi-Fei , Wang Han , Zhou Pei-Yun , Qu Wei-Feng , Fang Yuan , Ding Zhen-Bin , Zhou Jian , Fan Jia , Shi Ying-Hong 
Published: June 2020

Abstract
Background: The prognosis of patients with combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC) is usually poor, and effective adjuvant therapy is missing making it important to investigate whether these patients may benefit from adjuvant transarterial chemoembolization (TACE). We aimed to evaluate the efficiency of adjuvant TACE for long-term recurrence and survival after curative resection before and after propensity score matching (PSM) analysis.Methods: In this retrospective study, of 230 patients who underwent resection for CHC between January 1994 and December 2014, 46 (18.0%) patients received adjuvant TACE. Univariate and multivariate regression analyses were used to identify the independent predictive factors of survival. Cox regression analyses and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS) between patients who did or did not receive adjuvant TACE.Results: A total of 230 patients (mean age 52.2±11.9 years; 172 men) were enrolled, and 46 (mean age 52.7±11.1 years; 38 men) patients received TACE. Before PSM, in multivariate regression analysis, γ-glutamyl transpeptidase (γ-GT), tumour nodularity, macrovascular invasion (MVI), lymphoid metastasis, and extrahepatic metastasis were associated with OS. Alanine aminotransferase (ALT), MVI, lymphoid metastasis, and preventive TACE (HR: 2.763, 95% CI: 1.769-4.314, p <0.001) were independent prognostic factors for DFS. PSM created 46 pairs of patients. Before PSM, adjuvant preventive TACE was not associated with an increased risk of OS (HR: 0.911, 95% CI: 0.545-1.520, p =0.720) or DFS (HR: 3.345, 95% CI: 1.686-6.638, p =0.001). After PSM, the 5-year OS and DFS rates were comparable in the TACE group and the non-TACE group (OS: 22.7% vs 14.9%, respectively, p =0.75; DFS: 11.2% vs 14.4%, respectively, p =0.06).Conclusions: The present study identified that adjuvant preventive TACE did not influence DFS or OS after curative resection of CHC.
Anti-proliferative activities of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) using Ovarian Cancer Cell Lines
Authors: Ukwade Caroline E. , Ebuehi Osaretin Albert Taiwo , Adisa Rahmat A. , Singh Santosh K. , Singh Rajesh 
Published: June 2020

Abstract
Background Ovarian cancer (OvCa) is one of the most lethal tumors of gynecologic malignancies, due to lack of early detection, and a high rate of metastasis. The standard treatment for OvCa is surgery and cytotoxic chemotherapy. However, to overcome the high cost and side effects of these treatments, medicinal plants are widely used in developing countries to treat OvCa. Byrsocarpus coccineus plant preparation has been administered to patients traditionally in the management of tumors in Nigeria. In this study, we investigated the anti-proliferative effects of B. coccineus ethanol leaf extract against OVCAR3 and SW 626 OvCa cell lines. After the treatment of the two cell lines with the extracts, analyses were carried out to determine inhibition of proliferation and expression of cell cycle markers, pro-apoptotic, and anti-apoptotic markers. Results Results showed that B. coccineus ethanol leaf extract, significantly inhibited cell migration and colony formation in OVCAR3 and SW626 treated cells in a dose-dependent manner. Results also show that B. coccineus ethanol leaf extract modulated the expression of p53 gene, cell cycle progression, anti-apoptotic and pro-apoptotic genes. Conclusions These results suggest that B. coccineus have anti-proliferative properties and could induce apoptosis. Further investigation will be carried out to isolate bioactive compounds for the treatment of ovarian cancer.
Evaluating blood-brain barrier permeability in a rat model of type 2 diabetes
Authors: Qiao Ju , Lawson Christopher M , Rentrup Kilian FG , Kulkarni Praveen , Ferris Craig 
Published: June 2020

Abstract
Background: This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood-brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. Methods: The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood-brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas.Results: In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood-brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected. Conclusion: Small vessel disease as assessed by permeability in the blood-brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.
Insights into the phylogenetic relationship and drug targets of Babesia isolates infective to small ruminants from the mitochondrial genomes
Authors: Wang Xiaoxing , Wang Jinming , Liu Junlong , Liu Aihong , He Xin , Xiang Quanjia , Li Youquan , Yin Hong , Luo Jianxun , Guan Guiquan 
Published: June 2020

Abstract
Background: Babesiosis, a tick-borne disease caused by protozoa of the genus Babesia, is widespread in subtropical and tropical countries. Mitochondria are essential organelles that are responsible for energy transduction and metabolism, calcium homeostasis and cell signaling. Mitochondrial genomes could provide new insight to help elucidate and investigate the biological features, genetic evolution and classification of the protozoa. Nevertheless, there are limited data on the mitochondrial genomes of ovine Babesia spp. in China.Methods: Herein, we sequenced, assembled and annotated the mitochondrial genomes of six ovine Babesia isolates; analyzed the genome size, gene content, genome structure and cytochrome b (cob) amino acid sequences; and performed comparative mitochondrial genomics and phylogenomic analyses among apicomplexan parasites.Results: The mitochondrial genomes range from 5767 to 5946 bp in length with a linear form and contain three protein-encoding genes, cytochrome c oxidase I (cox1), cytochrome c oxidase III (cox3) and cob, six large subunit rRNA genes (LSU), and two terminal inverted repeats (TIR) on both ends. The cob gene sequence analysis indicated the binding site of anti-Babesia drugs that targeted the cytochrome bc1 complex. Babesia microti and Babesia rodhaini have a dual flip-flop inversion of 184-1082 bp, whereas other Babesia spp. and Theileria spp. have one pair of TIRs, 25-1563 bp. Phylogenetic analysis indicated that the six ovine Babesia isolates were divided into two clades, Babesia sp. and Babesia motasi. B. motasi isolates were further separated into two small clades (B. motasi Hebei/Ningxian and B. motasi Tianzhu/Lintan).Conclusions: The data provided new insights into the taxonomic relationships and drug targets of apicomplexan parasites.
Measuring capital in active addiction and recovery: The development of the Strengths And Barriers Recovery Scale (SABRS)
Authors: Best David , Vanderplasschen Wouter , Nisic Mulka 
Published: June 2020

Abstract
Background: The international Life In Recovery (LiR) surveys have provided an important message to the public and policy makers about the reality of change from addiction to recovery, consistently demonstrating both that there are marked gains across a range of life domains and that the longer the person is in recovery the better their recovery strengths and achievements. However, to date, no attempt has been made to quantify the Life In Recovery scales and to assess what levels of change in removing barriers and building strengths is achieved at which point in the recovery journey. Methods: The current study undertakes a preliminary analysis of strengths and barriers from the Life in Recovery measure, using data from a European survey on drug users in recovery (n=480), and suggests that the instrument can be edited into a Strengths And Barriers Recovery Scale (SABRS). The new scale provides a single score for both current recovery strengths and barriers to recovery.Results: The resulting data analysis shows that there are stepwise incremental changes in recovery strengths at different recovery stages, but these occur with only very limited reductions in barriers to recovery, with even those in stable recovery typically having at least two barriers to their quality of life and wellbeing. Greater strengths in active addiction are associated with greater strengths and resources in recovery. Conclusion: As well as demonstrating population changes in each of the domains assessed, the current study has shown the potential of the Life In Recovery Scale as a measure of recovery capital that can be used to support recovery interventions and pathways.
Drp1 is widely, yet heterogeneously, distributed in the mouse central nervous system
Authors: Luo Ting-Ting , Dai Chun-Qiu , Wang Jia-Qi , Wang Zheng-Mei , Yang Yi , Zhang Kun-Long , Wu Fei-Fei , Yang Yan-Ling , Wang Ya-Yun 
Published: June 2020

Abstract
Objectives: Drp1 is widely expressed in the mouse central nervous system and plays a role in inducing the mitochondrial fission process. Many diseases are associated with Drp1 and mitochondria. However, since the exact distribution of Drp1 has not been specifically observed, it is difficult to determine the impact of anti-Drp1 molecules on the human body. Clarifying the specific Drp1 distribution could be a good approach to targeted treatment or prognosis. Methods: We visualized the distribution of Drp1 in different brain regions and explicated the relationship between Drp1 and mitochondria. GAD67-GFP knock-in mice were utilized to detect the expression patterns of Drp1 in GABAergic neurons. We also further analyzed Drp1 expression in human malignant glioma tissue. Results : Drp1 was widely but heterogeneously distributed in the central nervous system. Further observation indicated that Drp1 was highly and heterogeneously expressed in inhibitory neurons. Under transmission electron microscopy, the distribution of Drp1 was higher in dendrites than other areas in neurons, and only a small amount of Drp1 was localized in mitochondria. In human malignant glioma, the fluorescence intensity of Drp1 increased from grade I-III, while grade IV showed a declining trend. Conclusion: In this study, we observed a wide heterogeneous distribution of Drp1 in the central nervous system, which might be related to the occurrence and development of neurologic disease. We hope that the relationship between Drp1 and mitochondria may will to therapeutic guidance in the clinic.
Association of total bilirubin and indirect bilirubin content with metabolic syndrome among Kazakhs in Xinjiang
Authors: Hao Hao , Guo Heng , Ma Ru-lin , Yan Yi-zhong , Hu Yun-hua , Ma Jiao-long , Zhang Xiang-hui , Wang Xin-ping , Wang Kui , Mu La-ti , Song Yan-peng , Zhang Jing-yu , He Jia , Guo Shuxia 
Published: June 2020

Abstract
Background: Some studies have shown that a high level of bilirubin is a protective factor against metabolic syndrome (MS), while a high level of transaminase is a risk factor for MS. However, the existing results are inconsistent and few cohort studies have been published. Methods: Using an ambispective cohort study, 565 Kazakhs from Xinjiang, China were selected as the study subjects. The baseline serum bilirubin and transaminase levels of the subjects were divided into quartiles and the relationship between these values and the incidence of MS was analyzed. The definition of MS was based on the Joint Interim Statement (JIS) diagnostic criteria. Results: The average follow-up time for the subjects was 5.72 years. The cumulative incidence of MS was 36.11% (204 of the 565 subjects), and the incidence density was 63.10/1000 person-years. Multivariate Cox regression analysis showed that the levels of total bilirubin (TBIL) and indirect bilirubin (IBIL) were negatively correlated with the occurrence of MS, Compared to the lowest quartile level (Q1), the hazard ratios of MS the TBIL levels at the Q2-Q4 quartiles were: 0.47 (0.31-0.71), 0.53 (0.35-0.79), and 0.48 (0.32-0.72), respectively, while IBIL levels at the Q2-Q4 quartiles showed an MS hazard ratio of 0.48 (0.32-0.72), 0.54(0.36-0.81), and 0.52 (0.35-0.77), respectively, all at a 95% confidence level. However, no relationship was found between transaminase levels and the incidence of MS. Conclusion: Serum TBIL and IBIL levels were negatively correlated with the incidence of MS in a Kazakh population in China.
The thermochemical non-equilibrium scale effects of the high enthalpy nozzle
Authors: Shen Junmou , Lu Hongbo , Li Ruiqu , Chen Xing , Ma Handong 
Published: June 2020

Abstract
The high enthalpy nozzle converts the high enthalpy stagnation gas into the hypervelocity free flow. The flow region of the high enthalpy nozzle consists of three parts: an equilibrium region upstream of the throat, a non-equilibrium region near the throat, and a frozen region downstream of the throat. Here we propose to consider the thermochemical non-equilibrium scale effects in the high enthalpy nozzle. With numerical solving axisymmetric compressible Navier-Stokes equations coupling with Park’s two-temperature model, the fully non-equilibrium solution is employed throughout the entire nozzle. Calculations are performed at different stagnation conditions with the different absolute scales and expansion ratio. The results of this study contain twofold. Firstly, as the absolute scale and expansion ratio increase, the freezing position is delayed, and the flow approaches equilibrium. Secondly, the vibrational temperature and Mach number decrease with the increase in the nozzle scale and expansion ratio，while the speed of sound, static pressure, and translational temperature increase as the nozzle scale and expansion ratio increase.
Residual stress variation in SiCf/SiC composite during heat treatment and its effects on mechanical behavior
Authors: Chen Xiaowu , Cheng Guofeng , Zhang Junmin , Guo Feiyu , Zhou Haijun , Liao Chunjin , Wang Hongda , Zhang Xiangyu , Dong Shaoming 
Published: June 2020

Abstract
Residual stress originated from thermal expansion mismatch determines the mechanical properties of ceramic matrix composites (CMCs). Here, continuous SiC fiber reinforced SiC matrix (SiCf/SiC) composites were fabricated by nano-infiltration and transient eutectic-phase (NITE) method, and the residual stress of the composites was investigated using high-temperature Raman spectrometer. With temperature increasing from room temperature to 1400℃, the residual stresses of the matrix and the fiber decrease from 1.29 GPa to 0.62 GPa and from 0.84 GPa to 0.55 GPa in compression respectively, while that of the interphase decreases from 0.16 GPa to 0.10 GPa in tension. The variation of residual stress shows little effect in the tensile strength of the composites, while causes a slight decrease in the tensile strain. The suppression of fiber/matrix debonding and fiber pulling-out caused by the residual stress reduction in the interphase is responsible for the decreasing tensile strain. This work can open up new alternatives for residual stress analysis in CMCs.
Population structure and geographic segregation of Cryptosporidium parvum IId subtypes in cattle in China
Authors: Zhang Zhenjie , Hu Suhui , Zhao Wentao , Guo Yaqiong , Li Na , Zheng Zezhong , Zhang Longxian , Kvac Martin , Xiao Lihua , Feng Yaoyu 
Published: June 2020

Abstract
Background: Cryptosporidium parvum is a zoonotic pathogen worldwide. Extensive genetic diversity and complex population structures exist in C. parvum in different geographic regions and hosts. Unlike the IIa subtype family, which is responsible for most zoonotic C. parvum infections in industrialized countries, IId is identified as the dominant subtype family in farm animals, rodents, and humans in China. Thus far, the population genetic characteristics of IId subtypes in calves in China are not clear.Methods: In the present study, 46 C. parvum isolates from dairy and beef cattle in six provinces and regions, China were characterized using sequence analysis of eight genetic loci, including msc6-7, rpgr, msc6-5, dz-hrgp, chom3t, hsp70, mucin1, and gp60. They belonged to three IId subtypes in the gp60 gene, including IIdA20G1 (n = 17), IIdA19G1 (n = 24) and IIdA15G1 (n = 5). The data generated were analyzed for population genetic structures of C. parvum using DnaSP and LIAN, and subpopulation structures using STRUCTURE, RAxML, Arlequin, GENALEX and Network.Results: Seventeen multilocus genotypes were identified. The results of linkage disequilibrium analysis indicated the presence of an epidemic genetic structure in the C. parvum IId population. When isolates of various geographical areas were treated as individual subpopulations, maximum likelihood inference of phylogeny, pairwise genetic distance analysis, sub-structure analysis, principal component analysis and network analysis all provided evidence for geographic segregation of subpopulations in Heilongjiang, Hebei, and Xinjiang. In contrast, isolates from Guangdong, Shanghai, and Jiangsu were genetically like each other.Conclusions: Data from the multilocus analysis have revealed a much higher genetic diversity of C. parvum than gp60 sequence analysis. Despite an epidemic population structure, there is apparent geographic segregation in C. parvum subpopulations within China.
Intraventricular IL-17A administration activates microglia and alters their localization in the mouse embryo cerebral cortex
Authors: Sasaki Tetsuya , Tome Saki , Takei Yosuke 
Published: June 2020

Abstract
Viral infection during pregnancy has been suggested to increase the probability of autism spectrum disorder (ASD) in offspring via the phenomenon of maternal immune activation (MIA). This has been modeled in rodents. Maternal T helper 17 cells and the effector cytokine, interleukin 17A (IL-17A), play a central role in MIA-induced behavioral abnormalities and cortical dysgenesis, termed cortical patch. However, it is unclear how IL-17A acts on fetal brain cells to cause ASD pathologies. To assess the effect of IL-17A on cortical development, we directly administered IL-17A into the lateral ventricles of the fetal mouse brain. We analyzed injected brains focusing on microglia, which express IL-17A receptors. We found that IL-17A activated microglia and altered their localization in the cerebral cortex. Our data indicate that IL-17A activates cortical microglia, which leads to a cascade of ASD-related brain pathologies, including excessive phagocytosis of neural progenitor cells in the ventricular zone.