bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gender-related variability in the pharmacokinetics and antiplasmodial activity of naphthoquine in rodents
Authors: Xie Yuewu , Liu Huixiang , Sun Yanhong , Xing Jie 
Published: February 2020

AbstractBackgroundNaphthoquine (NQ) is a suitable partner anti-malarial for the artemisinin-based combination therapy (ACT), which is recommended to be taken orally as a single-dose regimen. The metabolism of NQ was mainly mediated by CYP2D6, which is well-known to show gender-specific differences in its expression. In spite of its clinical use, there is limited information on the pharmacokinetics of NQ, and no data are available for females. In this study, the effect of gender on the pharmacokinetics and antiplasmodial efficacy of NQ in rodents was evaluated. The underlying factors leading to the potential gender difference, i.e., plasma protein binding and metabolic clearance, were also evaluated.MethodsThe pharmacokinetic profiles of NQ were investigated in healthy male or female rats after a single oral administration of NQ. The antiplasmodial efficacy of NQ was studied in male or female mice infected withPlasmodium yoelii. The recrudescence and survival time of infected mice were also recorded after drug treatment. Plasma protein binding of NQ was determined in pooled plasma collected from male or female mice, rat or human. In vitro metabolism experiments were performed in the liver microsomes of male or female mice, rat or human.ResultsThe results showed that the gender of rats did not affect NQ exposure (AUC0–tand Cmax) significantly (P > 0.05). However, a significant (P < 0.05) longer t1/2was found for NQ in male rats (192.1 ± 47.7), compared with female rats (143.9 ± 27.1). Slightly higher but not significant (P > 0.05) antiplasmodial activity was found for NQ in male mice (ED90, 1.10 mg/kg) infected withP. yoelii, compared with female mice (ED90, 1.67 mg/kg). The binding rates of NQ to plasma protein were similar in males and females. There was no metabolic difference for NQ in male and female mice, rat or human liver microsomes.ConclusionsThese results indicated that the pharmacokinetic profiles of NQ were similar between male and female rats, except for a longer t1/2in male rats. The difference was not associated with plasma protein binding or hepatic metabolic clearance. Equivalent antiplasmodial activity was found for NQ in male and female mice infected withP. yoelii. This study will be helpful for the rational design of clinical trials for NQ.
Tumor retractor: a simple and novel instrument for brain tumor surgery
Authors: Lim Jaejoon , Sung Kyoung Su , Hwang So Jung , Chun Duk-Hee , Cho Kyung Gi 
Published: February 2020

Abstract
Background
It is important to secure a surgical space during brain tumor surgery. One of the commonly used methods is to retract the brain. We hypothesized that the tumor can be retracted and that the normal brain tissue retraction can be minimized during surgery, and thus, the degree of collateral damage caused by brain retraction would be reduced.

Methods
The tumor retractor had a 90°, hard, and sharp tip for fixation of the tumor. The distal part of the retractor has a malleable and thin blade structure. By adjusting the angle of the distal malleable part of the tumor retractor, the operator can make the retracting angle additionally. Retractors with thin blade can be used in a conventional self-retraction system. To pull and hold the tumor constantly, the tumor retractor is held by a self-retraction system. The surgical technique using a tumor retractor is as follows: The first step is to fix the retractor to the tumor. The second step is to pull the retractor in the operator’s desired direction by applying force. After the tumor is pulled by adjusting the degree of force and angle, the surgical arm should be held in place to maintain the tumor retracted state.

Results
The tumor retractor was used to minimize the brain retraction, pulling the tumor in the opposite direction from the surrounding brain tissue. In clinical cases, we can apply the tumor retractor with good surgical outcomes.

Conclusions
A tumor retractor can be used to pull a tumor and minimize the brain retraction.
Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial
Authors: Shi Jing , Wei Mingqing , Ni Jingnian , Sun Feng , Sun Li , Wang Junfu , Yu Tao , Wang Kai , Lv Peiyuan , Wang Yunfu , Zhang Yulian , Gao Xuguang , Gao Xuanzhao , Luo Benyan , Mao Shanping , Zhang Baorong , Ren Xiangyang , Yu Fengchun , Hu Wenli , Yin Ping , Wu Nanjin , Liu Xianfeng , Bi Qi , Wang Yongyan , Tian Jinzhou ,   The CHASE Study Group
Published: February 2020

Abstract
Background and purpose
Tianzhi granule (TZ) is usually used for patients with vascular dementia (VaD) in China. The aim was to assess the effect of TZ by a randomized clinical trial (RCT).

Methods
A 24-week RCT was conducted in 16 centres. Participants were grouped into TZ, donepezil or placebo. The co-primary outcomes were the Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) and Clinician’s Interview-based Impression of Change-plus caregiver information (CIBIC-plus).

Results
A total of 543 patients with mild to moderate VaD were enrolled, of whom 242 took TZ granules, 241 took donepezil, and 60 took placebo. The least-squares mean changes from baseline and 95% CI were 6.20 (5.31, 7.09) (TZ group), 6.53 (5.63, 7.42) (donepezil group) and 3.47 (1.76, 5.19) (placebo group), both TZ and donepezil showed small but significantly improvement compared with placebo group. The percent of improvement on the global impression which was measured by CIBIC-plus was 73.71% in TZ and 58.18% in placebo, there was significant different between TZ and placebo group (P = 0.004). No significant differences were observed between TZ and donepezil. No significant differences of adverse events were found.

Conclusions
TZ and donepezil could bring symptomatic benefit for mild to moderate VaD.
Trial registration The protocol had retrospectively registered at clinical trial.gov, Unique identifier: NCT02453932, date of registration: May 27, 2015; https://www.clinicaltrials.gov/ct2/show/NCT02453932?term=NCT02453932&rank=1
Quantification of total apolipoprotein E and its isoforms in cerebrospinal fluid from patients with neurodegenerative diseases
Authors: Minta K. , Brinkmalm G. , Janelidze S. , Sjödin S. , Portelius E. , Stomrud E. , Zetterberg H. , Blennow K. , Hansson O. , Andreasson U. 
Published: February 2020

Abstract
Background
The human APOE gene, which codes for apolipoprotein E (apoE), has three major polymorphic alleles: ε2, ε3, and ε4 that give rise to amino acid substitutions. APOE-ε4 is a strong risk factor of sporadic Alzheimer’s disease (AD) but the reason why is still unknown despite intense research for more than 20 years. The aim of the study was to investigate if the concentrations of total apoE and the specific apoE isoforms in cerebrospinal fluid (CSF) differ between various neurodegenerative diseases and control individuals, as well as among the APOE genotypes.

Methods
Quantification of total apoE and specific apoE isoforms (E2, E3, and E4) in CSF was performed using high-resolution parallel reaction monitoring mass spectrometry. In total, 1820 individuals were involved in the study including clinically diagnosed AD patients (n = 228), cognitively unimpaired (CU) patients (n = 896), and patients with other neurodegenerative disorders (n = 696). Follow-up data was available for 100 individuals, assessed at two time points. Subjects were dichotomized based on an Aβ42/40 CSF concentration ratio cut-off into Aβ positive (Aβ+, < 0.091) and Aβ negative (Aβ−, > 0.091) groups.

Results
Even though there was a significant increase of total apoE in the amyloid β-positive (Aβ+) group compared with amyloid β-negative (Aβ−) individuals (p < 0.001), the magnitude of the effect was very small (AUC = 0.55). Moreover, CSF total apoE concentrations did not differ between Aβ− CU controls and clinically diagnosed AD patients. There was a difference in concentration between isoforms in heterozygous individuals in an isoform-dependent manner (E2 < E3 < E4) (p < 0.001, AUC = 0.64–0.69), and these associations remained when dichotomizing the samples into Aβ+ and Aβ− groups (p < 0.01, AUC = 0.63–0.74). In the cohort with follow-up samples, neither total apoE nor isoform-specific apoE concentrations differed between the two time points (p > 0.05).

Conclusions
The results indicate that neither the concentrations of total apoE nor the different apoE isoforms in CSF are associated with APOE-ε4 carrier status, Aβ status, or clinical dementia diagnoses.
Multipotency of mouse trophoblast stem cells
Authors: Hou Minmin , Han Junwen , Li Gu , Kwon Min-Young , Jiang Jiani , Emani Sirisha , Taglauer Elizabeth S. , Park Jin-Ah , Choi Eun-Bee , Vodnala Munender , Fong Yick W. , Emani Sitaram M. , Rosas Ivan O. , Perrella Mark A. , Liu Xiaoli 
Published: February 2020

AbstractBackgroundIn a number of disease processes, the body is unable to repair injured tissue, promoting the need to develop strategies for tissue repair and regeneration, including the use of cellular therapeutics. Trophoblast stem cells (TSCs) are considered putative stem cells as they differentiate into other subtypes of trophoblast cells. To identify cells for future therapeutic strategies, we investigated whether TSCs have properties of stem/progenitor cells including self-renewal and the capacity to differentiate into parenchymal cells of fetal organs, in vitro and in vivo.MethodsTSCs were isolated using anti-CD117 micro-beads, from embryonic day 18.5 placentas. In vitro, CD117+TSCs were cultured, at a limiting dilution in growth medium for the development of multicellular clones and in specialized medium for differentiation into lung epithelial cells, cardiomyocytes, and retinal photoreceptor cells. CD117+TSCs were also injected in utero into lung, heart, and the sub-retinal space of embryonic day 13.5 fetuses, and the organs were harvested for histological assessment after a natural delivery.ResultsWe first identified CD117+cells within the labyrinth zone and chorionic basal plate of murine placentas in late pregnancy, embryonic day 18.5. CD117+TSCs formed multicellular clones that remained positive for CD117 in vitro, consistent with self-renewal properties. The clonal cells demonstrated multipotency, capable of differentiating into lung epithelial cells (endoderm), cardiomyocytes (mesoderm), and retinal photoreceptor cells (ectoderm). Finally, injection of CD117+TSCs in utero into lungs, hearts, and the sub-retinal spaces of fetuses resulted in their engraftment on day 1 after birth, and the CD117+TSCs differentiated into lung alveolar epithelial cells, heart cardiomyocytes, and retina photoreceptor cells, corresponding with the organs in which they were injected.ConclusionsOur findings demonstrate that CD117+TSCs have the properties of stem cells including clonogenicity, self-renewal, and multipotency. In utero administration of CD117+TSCs engraft and differentiate into resident cells of the lung, heart, and retina during mouse development.
Influence of inflammatory conditions provided by macrophages on osteogenic ability of mesenchymal stem cells
Authors: Vallés Gema , Bensiamar Fátima , Maestro-Paramio Leila , García-Rey Eduardo , Vilaboa Nuria , Saldaña Laura 
Published: February 2020

AbstractBackgroundThe mechanisms by which macrophage phenotype contributes to mesenchymal stem cells (MSC)-mediated bone repair remain unclear. In this work, we investigated the influence of factors released by human macrophages polarized to a pro-inflammatory or an anti-inflammatory phenotype on the ability of human MSC to attach, migrate, and differentiate toward the osteoblastic lineage. We focused on the role of TNF-α and IL-10, key pro-inflammatory and anti-inflammatory cytokines, respectively, in regulating MSC functions.MethodsMSC were treated with media conditioned by pro-inflammatory or anti-inflammatory macrophages to study their influence in cell attachment, migration, and osteogenic differentiation. The involvement of TNF-α and IL-10 in the regulation of MSC functions was investigated using neutralizing antibodies and recombinant cytokines.ResultsTreatment of MSC with media conditioned by pro-inflammatory or anti-inflammatory macrophages promoted cell elongation and enhanced MSC ability to attach and migrate. These effects were more noticeable when MSC were treated with media from pro-inflammatory macrophages. Interestingly, MSC osteogenic activity was enhanced by factors released by anti-inflammatory macrophages, but not by pro-inflammatory macrophages. Significant IL-10 levels originated from anti-inflammatory macrophages enhanced MSC osteogenesis by increasing ALP activity and mineralization in MSC layers cultured under osteogenic conditions. Moreover, macrophage-derived IL-10 regulated the expression of the osteogenic markersRUNX2,COL1A1, andALPL. Notably, low TNF-α levels secreted by anti-inflammatory macrophages increased ALP activity in differentiating MSC whereas high TNF-α levels produced by pro-inflammatory macrophages had no effects on osteogenesis. Experiments in which MSC were treated with cytokines revealed that IL-10 was more effective in promoting matrix maturation and mineralization than TNF-α.ConclusionsFactors secreted by pro-inflammatory macrophages substantially increased MSC attachment and migration whereas those released by anti-inflammatory macrophages enhanced MSC osteogenic activity as well as cell migration. IL-10 was identified as an important cytokine secreted by anti-inflammatory macrophages that potentiates MSC osteogenesis. Our findings provide novel insights into how environments provided by macrophages regulate MSC osteogenesis, which may be helpful to develop strategies to enhance bone regeneration.
Differences in virulence between the two more prevalent Staphylococcus aureus clonal complexes in rabbitries (CC121 and CC96) using an experimental model of mammary gland infection
Authors: Penadés Mariola , Viana David , García-Quirós Ana , Muñoz-Silvestre Asunción , Moreno-Grua Elena , Pérez-Fuentes Sara , Pascual Juan José , Corpa Juan M. , Selva Laura 
Published: February 2020

AbstractStaphylococcal mastitis is a major health problem in humans and livestock that leads to economic loss running in millions. This process is currently one of the main reasons for culling adult rabbit does. Surprisingly, the two most prevalent S. aureus lineages isolated from non-differentiable natural clinical mastitis in rabbits (ST121 and ST96) generate different immune responses. This study aimed to genetically compare both types of strains to search for possible dissimilarities to explain differences in immune response, and to check whether they showed similar virulence in in vitro tests as in experimental intramammary in vivo infection. The main differences were observed in the enterotoxin gene cluster (egc) and the immune-evasion-cluster (IEC) genes. While isolate ST121 harboured all six egc cluster members (seg, sei, selm, seln, selo, selu), isolate ST96 lacked the egc cluster. Strain ST96 carried a phage integrase Sa3 (Sa3int), compatible with a phage integrated into the hlb gene (β-haemolysin-converting bacteriophages) with IEC type F, while isolate ST121 lacked IEC genes and the hlb gene was intact. Moreover, the in vitro tests confirmed a different virulence capacity between strains as ST121 showed greater cytotoxicity for erythrocytes, polymorphonuclear leukocytes and macrophages than strain ST96. Differences were also found 7 days after experimental intramammary infection with 100 colony-forming units. The animals inoculated with strain ST121 developed more severe gross and histological mastitis, higher counts of macrophages in tissue and of all the cell populations in peripheral blood, and a significantly larger total number of bacteria than those infected by strain ST96.
Random field-aided tracking of autonomous kinetically passive wireless agents
Authors: Schlupkothen Stephan , Heidenblut Tim , Ascheid Gerd 
Published: February 2020

AbstractContinuous miniaturization of circuitry has open the door for various novel application scenarios of millimeter-sized wireless agents such as for the exploration of difficult-to-access fluid environments. In this context, agents are envisioned to be employed, e.g., for pipeline inspection or groundwater analysis. In either case, the demand for miniature sensors is incompatible with propulsion capabilities. Consequently, the agents are condemned to be kinetically passive and are, thus, subject to the fluid dynamics present in the environment. In these situations, the localization is complicated by the fact that unknown external forces (e.g., from the fluid) govern the motion of the agents. In this work, a comprehensive framework is presented that targets the simultaneous estimation of the external forces stemming from the fluid and the agents’ positions which are traversing the environment. More precisely, a Bayesian hierarchical model is proposed that models’ relevant characteristics of the fluid via a spatial random field and incorporates this as control input into the motion model. The random field model facilitates the consideration of spatial correlation among the agents’ trajectories and, thereby, improves the localization significantly. Additionally, this is combined with multiple particle filtering to account for the fact that within such underground fluid environments, only a localization based on distance and/or bearing measurements is feasible. In the results provided in this work, which are based on realistic computational fluid dynamics simulations, it is shown that—via the proposed spatial model—significant improvements in terms of localization accuracy can be achieved.
Long-term effects of alcohol consumption on cognitive function: a systematic review and dose-response analysis of evidence published between 2007 and 2018
Authors: Brennan Sue E. , McDonald Steve , Page Matthew J. , Reid Jane , Ward Stephanie , Forbes Andrew B. , McKenzie Joanne E. 
Published: February 2020

AbstractBackgroundUnderstanding the long-term health effects of low to moderate alcohol consumption is important for establishing thresholds for minimising the lifetime risk of harm. Recent research has elucidated the dose-response relationship between alcohol and cardiovascular outcomes, showing an increased risk of harm at levels of intake previously thought to be protective. The primary objective of this review was to examine (1) whether there is a dose-response relationship between levels of alcohol consumption and long-term cognitive effects, and (2) what the effects are of different levels of consumption.MethodsThe review was conducted according to a pre-specified protocol. Eligible studies were those published 2007 onwards that compared cognitive function among people with different levels of alcohol consumption (measured ≥ 6 months prior to first follow-up of cognition). Major cognitive impairment was excluded. Searches were limited to MEDLINE, Embase and PsycINFO (January 2007 to April 2018). Screening, data extraction, and risk of bias assessment (ROBINS-I) were piloted by three authors, then completed by a single author and checked by a second. Analyses were undertaken to identify and characterise dose-response relationships between levels of alcohol consumption and cognition. Certainty of evidence was assessed using GRADE.ResultsWe included 27 cohort studies (from 4786 citations). Eighteen studies examined the effects of alcohol consumption at different levels (risk of bias 16 serious, 2 critical). Ten studies provided data for dose-response analysis. The pooled dose-response relationship showed a maximum standardised mean difference (SMD) indicating slightly better cognition among women with moderate alcohol consumption compared to current non-drinkers (SMD 0.18, 95%CI 0.02 to 0.34, at 14.4 grams/day; 5 studies, very low certainty evidence), and a trivial difference for men (SMD 0.05, 95% CI 0.00 to 0.10, at 19.4 grams/day; 6 studies, very low certainty evidence).ConclusionsMajor limitations in the design and reporting of included studies made it impossible to discern if the effects of ‘lower’ levels of alcohol intake are due to bias. Further review of the evidence is unlikely to resolve this issue without meta-analysis of individual patient data from cohort studies that address biases in the selection of participants and classification of alcohol consumption.
The mir-767-105 cluster: a crucial factor related to the poor prognosis of hepatocellular carcinoma
Authors: Rui Tao , Xu Siyi , Feng Shi , Zhang Xueyou , Huang Haitao , Ling Qi 
Published: February 2020

AbstractMiRNAs have been widely reported as the therapeutic target for hepatocellular carcinoma (HCC). However, mirna clusters, as the more impressive tumor regulatory factors, have received little attention. By deeply digging the Cancer Genome Atlas (TCGA) database, we aimed to explore the vital mirna cluster that regulated the poor prognosis of HCC. The results showed that the upregulation of mirna cluster-767-105 in HCC was the most significant, compared with the non-tumor tissues. Besides, high expression of all three members of the cluster was positively correlated with poor prognosis of HCC and the resistance of sorafenib. Cox analysis proved that all the three mirnas were independent prognostic factors, while the mir-767 was the most compelling (HR value 8.388, 95%CI 2.524–27.897). The higher expression of the three-mirna signature also significantly indicated the worse prognosis. Through bioinformatics analysis, we screened their common potential target genes, which were highly correlated with tumor regulation. These results supported that the mirna cluster-767-105 promoted the poor outcome of HCC and could be a robust target for the therapy of HCC patients.
Simultaneous removals of cadmium(II) ions and reactive yellow 4 dye from aqueous solution by bone meal-derived apatite: kinetics, equilibrium and thermodynamic evaluations
Authors: Ofudje Edwin A. , Adeogun Idowu A. , Idowu Mopelola A. , Kareem Sarafadeen O. , Ndukwe Nelly A. 
Published: February 2020

AbstractThe simultaneous removal of Cadmium ions and reactive yellow 4 dye (RY4 dye) by bone meal-derived apatite (BMDA) were investigated in a batch process. The structural elucidation of the prepared BMDA was done using TEM, XRD, FT-IR and EDX to evaluate the structures of the adsorbent. Different experimental features such as the agitation time, BMDA dosage, temperature, initial adsorbate concentration and pH of the solution were examined on the uptake pattern of the pollutants. The mechanism of adsorption was examined with Elovich, pseudo-first-order, intraparticle diffusion and pseudo-second-order kinetic models, while Langmuir, Dubinin-Radushkevich (D-R), Freundlich and Tempkin isotherms were exploited in order to describe the behaviour of the equilibrium process. Analysis from XRD revealed peaks corresponding to single phase apatite powder, while the various forces responsible for the interactions between the BMDA surface and the pollutants were obtained to CO32−, OH− and PO43− as observed by FT-IR analysis. SEM and TEM investigations confirmed a round-like morphology which agglomerated together upon the adsorption of pollutants.The kinetic modelling of the adsorption data were well illustrated with the pseudo-first-order model with correlation coefficient (R2) values ranging from 0.997 to 0.999. Isotherms studies revealed that best fit was achieved with Langmuir isotherm with adsorption capacities of 94.85 and 116.16 mg/g for RY4 dye and Cd(II) ions respectively. Thermodynamic study signified the uptake of the pollutants to be spontaneous, feasible and endothermic in nature. The values of entropy change (ΔS) for the sorption processes calculated are 86.57 and 60.16 J/mol/K for Cd(II) and RY4 dye, respectively.