bluuebunny/crossref_metadata_2025_split huggingface dataset:
YouTube marketing communication demographic and usage variables influence on Gen Y's cognitive attitudes in South Africa and Romania
Authors: Duffett Rodney Graeme , Edu Tudor , Negricea Iliuta Costel 
Published: May 2019

AbstractThe primary purposes of this study are to consider the influence of YouTube marketing communication (YMC) on awareness and knowledge among Generation (Gen) Y cohort respondents in South Africa (SA) and Romania (RO) and to establish if country, demographic, and usage (independent) variables have an effect on this cognitive attitudinal association. Multistage sampling was employed, and a survey was conducted among 400 respondents in SA and 400 respondents in RO. Structural equation modelling was used to investigate the hypothesized associations. The findings confirm that awareness had a favorable influence on knowledge for the total sample, SA and RO. The results also show that awareness displayed a significantly larger positive effect on knowledge among Romanian Gen Y in comparison with South African Gen Y. This study confirms that age (demographic variable) and access, usage length, log‐on frequency, log‐on duration, and advertisement viewership numbers (usage variables) have a significant effect on cognitive attitudinal responses due to YMC among Gen Y in SA and RO. Organizations should consider adapting YMC strategies to stimulate awareness, which will stimulate favorable knowledge attitudinal responses, as well as consider the aforementioned demographic and usage variables when targeting the infamously unpredictable Gen Y due to the positive cognitive attitudinal association in developing countries.
Pharmacy driven assessment of appropriate antibiotic selection in patients with reported beta‐lactam allergy
Authors: Holmes Ashley K. , Bennett Nicholas T. , Berry Timothy P. 
Published: May 2019

AbstractBackgroundReported beta‐lactam (BL) antibiotic allergies lead to the avoidance of BL antibiotics. Despite that less than 10% of patients reporting have a true allergy, the documentation often leads to an increased use of alternative antibiotics. These nonpreferred antibiotics (NPA) have a significant impact on cost, clinical outcomes, and antimicrobial resistance.ObjectiveThe primary objective of this study was to assess the impact of a pharmacy‐driven assessment on the prescribing frequency of penicillin or cephalosporin antibiotics in patients with a reported BL allergy.MethodsThis retrospective cohort analysis evaluated the effect of a best practice alert (BPA) and subsequent allergy assessment on BL use in patients with reported allergies at an integrated health system. The BPA notified pharmacy staff that a patient with a documented BL allergy was receiving a NPA. Pharmacy staff assessed previous BL tolerance and clarified reaction, severity, and timing of the documented allergy. Patients were identified for analysis if they had a documented BL allergy within the electronic medical record and received at least one antibiotic during the study period.ResultsA total of 418 patients were included in this analysis (180 preimplementation, 238 postimplementation). In the pharmacy‐driven assessment group, BL antibiotic use increased by 12.9% (P = .008) in patients with a previously documented BL allergy with the largest use increase in 3rd/4th generation cephalosporins (P = .045). Days of therapy for NPAs decreased in the postimplementation group, including aztreonam (P = .006) and vancomycin (P = .009).ConclusionsOur data suggests that a pharmacy‐driven allergy assessment using a BPA can increase appropriate use of BL antibiotics for hospitalized patients.
Regulatory role of Golgi brefeldin A resistance factor‐1 in amyloid precursor protein trafficking, cleavage and Aβ formation
Authors: Liu Kaifei , Liu Ying , Xu Yanting , Nandakumar Kutty Selva , Shen Xiaoyan , Lin Jiahe , Li Cuixian , He Chonghua , Zhou Chun 
Published: May 2019

Abstractβ‐amyloid peptide (Aβ) deposition derived from sequential cleavage of the amyloid precursor protein (APP) through the amyloidogenic pathway is an important characteristic feature of Alzheimer's disease (AD). During this process, cellular trafficking plays a crucial role. A large Sec7‐domain containing ADP‐ribosylation factor guanine nucleotide exchange factor (ARF‐GEF), Golgi brefeldin A resistance factor 1 (GBF1) has been reported to initiate the ADP‐ribosylation factor (Arf) activation cascade at trans‐Golgi network, which plays a crucial function at the endoplasmic reticulum‐Golgi interface. In this study, we investigated the role of GBF1 in APP transmembrane transport and Aβ formation. Using APP/PS1 (presenilin 1) overexpressing transgenic mice, we demonstrate that GBF1 has upregulated the expression of APP, indicating a role for GBF1 in APP physiological process. Knocking down of GBF1 using small interfering has significantly increased the intracellular but not the surface expression of APP. In contrast, overexpression of wild‐type (WT) and guanine nucleotide exchange factor (GEF) in the activated form but not the GEF deficient mutation induced continuous activation of GBF1, which subsequently increased the surface level of APP. Interestingly, inhibition of GBF1 by c(BFA) also impaired APP trafficking and induced endoplasmic reticulum (ER) stress in SH‐SY5Y cells. Our results thus for identified the role of GBF1 in APP trafficking and cleavage, and provide evidence for GBF1 as a possible therapeutic target in AD.
Biological and anti‐vascular activity evaluation of ethoxy‐erianin phosphate as a vascular disrupting agent
Authors: Yuan Wenshuang , Su Chang , Yang Xiaotong , Li Yueqi , Cao Yiou , Liang Xin , Liu Jianwen 
Published: May 2019

AbstractThe effects of ethoxy‐erianin phosphate (EBTP) on cell proliferation, mitotic cell arrest, migration, infiltration, and endothelial tubular structures were evaluated in this study. The antiproliferative activity of EBTP and combretastatin A‐4P (CA4P) was analyzed on several tumor cells (including MCF‐7, HeLa, 2LL, and 2LL‐IDO) and on an endothelial cell (human umbilical vein endothelial cells [HUVECs]) as well as a human normal liver cell (L02). The results showed that EBTP possessed antiproliferative activity in the micromole range and was relatively less toxic than CA4P. Treating HUVECs with EBTP caused cell accumulation in the G2/M phase, and wound‐healing assays indicated that EBTP inhibited cell migration. Furthermore, EBTP and CA4P destroyed the vasculature in endothelial cells and showed vascular disrupting activity of the chorioallantoic membrane in fertilized chicken eggs. In addition, we found that EBTP suppressed the expression of indoleamine 2,3‐dioxygenase (IDO) and significantly inhibited IDO‐induced migration and infiltration of 2LL‐IDO cells. Administration of EBTP blocked vasculogenic mimicry in 2LL‐IDO cells, which was typically observed in tube formation assays of 2LL‐IDO cells. Moreover, the results of Lewis lung carcinoma in mice showed a high inhibition rate of EBTP. EBTP is an effective vascular disrupting agent that is superior to CA4P and may prevent and treat malignancy by inhibiting the expression of IDO.
Inhibition of CTRP6 prevented survival and migration in hepatocellular carcinoma through inactivating the AKT signaling pathway
Authors: Wan Xiaolong , Zheng Caixia , Dong Lei 
Published: May 2019

AbstractC1qTNF‐related proteins (CTRPs) are a member of the adiponectin paralogs family, which are implicated in regulation of various biological processes. Recently, CTRP6 was found upregulated in human hepatocellular carcinomas (HCC). However, the specific roles and molecular mechanisms of CTRP6 in HCC remain unclear. Here, we investigated the effects of CTRP6 on the vitality, apoptosis, migration, and invasion of HCC cells. Firstly, we measured the levels of CTRP6 in HCC tissues and cell lines. Our results showed that CTRP6 was markedly upregulated in HCC tissues and Hep3B cells. Then, the CTRP6 siRNA was transfected into Hep3B cells. Cell counting kit‐8 (CCK‐8) assay and flow cytometry analysis revealed that silencing CTRP6‐induced cell viability inhibition, and apoptosis. The wound‐healing and transwell assay showed that CTRP6 deficiency suppressed the migration and invasion of Hep3B cells. Meanwhile, the AKT phosphorylation level was reduced by CTRP6 silencing. Next, Hep3B cells were pretreated with insulin‐like growth factor‐1 (IGF‐1) (an activator of AKT), and then transfected with CTRP6 siRNA, and the cell vitality, apoptosis, migration, and invasion were measured again. We found that all these alterations caused by CTRP6 inhibition could be reversed by IGF‐1 treatment. Taken together, CTRP6 suppression blocked cell survival, migration, and invasion and promoted cell apoptosis through inactivating the AKT signaling pathway. Our findings present a novel potential molecular target for HCC therapy.
EMP1 regulates cell proliferation, migration, and stemness in gliomas through PI3K‐AKT signaling and CD44
Authors: Wang Junxiang , Li Xuetao , Wu Haibin , Wang Hao , Yao Lin , Deng Zhitong , Zhou Youxin 
Published: May 2019

AbstractGlioblastoma multiforme (GBM) is an intracranial tumor; the feature is higher malignant and poorer prognosis. The search for therapeutic targets for gliomas has always been a focus of research in the field of neurology. The unusual expression of epithelial membrane protein 1 (EMP1) has been proved in most tumors. In our study, we determined the expression level of EMP1 expression in glioma tissues. There were higher levels of EMP1 in glioma tissues—particularly GBM tissues—than those in normal brain tissues. Then we discovered that silencing EMP1 inhibited glioma cell invasion and proliferation through inhibiting the PI3K‐AKT signaling pathway. Subsequently, we investigated the function of EMP1 on glioma stem cells and found that it regulates the expression of CD44 in such cells to promote stemness. Taken together, the new strategies for the treatment of glioma may be provided by these finding, thereby improving the prognosis associated with it.
MicroRNA‐628‐5p inhibits cell proliferation in glioma by targeting DDX59
Authors: Xie Peng , Wang Yan , Liao Yuanmei , Han Qiu , Qiu Zhichao , Chen Yinbing , Zuo Xiaohua 
Published: May 2019

AbstractRecent study has reported that microRNA‐628‐5p (miR‐628‐5p) is involved in the development of epithelial ovarian cancer; however, the mechanisms of miR‐628‐5p in glioma remain unclear. In this study, we explored the potential biological roles of miR‐628‐5p in glioma. First, we found that miR‐628‐5p was decreased in the tissues and cells (U87 and T98) of glioma. Second, overexpressing miR‐628‐5p reduced the ability of glioma cells' proliferation and induced glioma cells' cycle arrest in G1. Then, we found that miR‐628‐5p directly bound to the 3′‐untranslated region of DDX59 and decreased the protein level of DDX59. The decrease of DDX59 was found to lead to the decrease of p‐AKT. Mechanistic studies revealed that restoring the expression of DDX59 alleviated miR‐628‐5p‐induced inhibition of proliferation of glioma. These findings suggest that the miR‐628‐5p/DDX59 axis has a key role in the development of glioma, and miR‐628‐5p might be a new therapeutic target against glioma.
Long noncoding RNA CPS1‐IT1 suppresses melanoma cell metastasis through inhibiting Cyr61 via competitively binding to BRG1
Authors: Zhou Xiaobo , Rao Yamin , Sun Qilin , Liu Yang , Chen Jun , Bu Wenbo 
Published: May 2019

AbstractLong noncoding RNA CPS1‐IT1 is recently recognized as a tumor suppressor in several cancers. Here, we investigate the role of CPS1‐IT1 in human melanoma. Presently, our study reveals the low expression of CPS1‐IT1 in human melanoma tissues and cell lines, which is significantly associated with metastasis and tumor stage. Besides, the potential of CPS1‐IT1 as a prognosis‐predictor is strongly indicated. Functionally, CPS1‐IT1 overexpression inhibits cell migration, invasion, epithelial–mesenchymal transition, and angiogenesis in melanoma cells. CYR61, an angiogenic factor that participates in tumor metastasis as well as a recognized oncogene in melanoma, is shown to be confined under CPS1‐IT1 overexpression in melanoma cells. Furthermore, enforced expression of Cyr61 in CPS1‐IT1‐silenced melanoma cells dramatically normalized the protein level of Cyr61 and that of its downstream targets vascular endothelial growth factor and matrix metalloproteinase‐9, as well as the repressive effect of CPS1‐IT1 overexpression on melanoma cell metastasis. BRG1, a core component of SWI/SNF complex, is implied to interact with both CPS1‐IT1 and Cyr61 in melanoma cells. Moreover, CPS1‐IT1 negatively regulates Cyr61 expression by blocking the binding of BRG1 to Cyr61 promoter. Jointly, CPS1‐IT1 controls melanoma metastasis through impairing Cyr61 expression via competitively binding with BRG1, uncovering a novel potential therapeutic and prognostic biomarker for patients with melanoma.
CCL5 secreted by senescent theca‐interstitial cells inhibits preantral follicular development via granulosa cellular apoptosis
Authors: Shen Lu , Chen Yuan , Cheng Jing , Yuan Suzhen , Zhou Su , Yan Wei , Liu Junfeng , Luo Aiyue , Wang Shixuan 
Published: May 2019

AbstractAs a fundamental aging mechanism, cellular senescence causes chronic inflammation via the senescence‐associated secretory phenotype (SASP). Theca‐interstitial cells are an essential but little‐studied component of follicle development in the ovarian microenvironment. In the present study, we observed significant cellular senescence in theca‐interstitial cells and secretion of chemokine (C‐C motif) ligand 5 (CCL5) by these cells during aging. Furthermore, we aimed to investigate whether and how senescence‐associated secretory phenotype (SASP)‐associated CCL5 may be involved in follicle development. Increased levels of CCL5 in the microenvironment of follicles attenuated preantral follicle growth, survival, and estradiol secretion. Oocyte maturation and the expression of zona pellucida 3 and differentiation factor 9 (GDF9) were also inhibited by CCL5. Granulosa cell apoptosis in follicles was promoted by CCL5, accompanied by the phosphorylation of nuclear factor‐κB by CCL5 and inhibition of the PI3K/AKT pathway. These results suggest that SASP‐associated CCL5 produced by senescent theca‐interstitial cells may impair follicle development and maturation during ovarian aging by promoting granulosa cell apoptosis.
Deregulation of lncRNA‐AC078883.3 and microRNA‐19a is involved in the development of chemoresistance to cisplatin via modulating signaling pathway of PTEN/AKT
Authors: Xing Shijie , Qu Yue , Li Chaoyi , Huang Ai , Tong Song , Wu Chuangyan , Fan Kai 
Published: May 2019

AbstractNon‐small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum‐based chemotherapeutic drug, cisplatin has been used in the NSCLC treatment for over 30 years, and its effects are impaired by drug resistance. This study aimed to investigate the potential role of lncRNA‐AC078883.3 in the development of chemoresistance against cisplatin. Real‐time PCR, Western blot analysis, Immunohistochemistry (IHC) assay, bioinformatic analysis, and luciferase assay were collaboratively used to establish the lncRNA‐AC078883.3/miR‐19a/PTEN/AKT pathway. Also, the effect of cisplatin on cell proliferation was observed via an MTT assay. Furthermore, Cox regression and Kaplan–Meier analyses were used to study whether lncRNA‐AC078883.3 is involved in the survival of NSCLC. Compared with the Cisplatin‐Sensitive group, the Cisplatin‐Resistance group exhibited lower levels of lncRNA‐AC078883.3 and PTEN and higher levels of miR‐19a and p‐Akt. The growth rate of A549 and H460 cells and the IC
50 of DPP in the Cisplatin‐Resistance group were higher than those in the Cisplatin‐S group. miR‐19a contains a putative binding site of lncRNA‐AC078883.3, which enabled the luciferase activity of wild‐type lncRNA‐AC078883.3 to be reduced by miR‐19a. In addition, by directly targeting PTEN 3′‐untranslated region (UTR), miR‐19a repressed the luciferase activity of wild‐type PTEN 3′‐UTR. The median OS of patients with reduced lncRNA‐AC078883.3 expression was longer than that of patients with higher lncRNA‐AC078883.3 expression. Finally, compared with low lncRNA‐AC078883.3‐expression patients, the high lncRNA‐AC078883.3‐expression patients were associated with lower miR‐19a expression and higher PTEN expression. Therefore, we suggested for the first time that the low expression of lncRNA‐AC078883.3 contributed to the development of chemoresistance against cisplatin.
Is Moxifloxacin a Treatment Option for Pancreatic Infections? A Pharmacometric Analysis of Serum and Pancreatic Juice
Authors: Wicha Sebastian G. , Mundkowski Ralf G. , Klock Andrea , Hopt Ulrich T. , Drewelow Bernd , Kloft Charlotte , Wellner Ulrich F. , Keck Tobias , Wittel Uwe A. 
Published: May 2019

AbstractPostoperative local infection is a major complication after pancreatic surgery. The aim of this prospective clinical trial was to assess the potential of moxifloxacin (MXF) to treat pancreatic infections from a pharmacokinetic (PK)/pharmacodynamic (PD) perspective. The PK of MXF in serum and pancreatic juice, via an inserted tube in the pancreatic duct, was determined in 19 patients up to day 7 after pancreatoduodenectomy. PK data in both specimens was analyzed with NONMEM 7.3. Intraoperative swipes were performed for microbiological examination. PK/PD target attainment was assessed in both matrices using unbound area under the plasma concentration–time curve/minimum inhibitory concentration (MIC) targets of ≥30 and ≥100, for gram‐positive and gram‐negative pathogens, respectively. A 2‐compartment population PK model in which the measurements in pancreatic juice were assigned to a scaled peripheral compartment best described the PK in both specimens simultaneously. Median (10th–90th percentile) area under the plasma concentration–time curve values after the third dose were 28.9 mg · h/L (18.6–42.0) in serum and 55.8 mg · h/L (23.7–81.4) in pancreatic juice. Target attainment rate for the intraoperatively isolated bacterial strains was ≥0.88 after the third MXF dose. For gram‐negatives, high probability of target attainment ≥0.84 was observed in serum for MIC ≤ 0.125 mg/L and in pancreatic juice for MIC ≤ 0.25 mg/L. For gram‐positives, the probability of target attainment was 0.84–1 in serum for MIC ≤ 0.5 mg/L and in pancreatic juice for MIC ≤ 1 mg/L. In conclusion, penetration of MXF into pancreatic juice was substantial. The PK/PD analysis indicated that treatment of pancreatic infections by isolates with MIC ≤ 0.25 mg/L (gram‐negative) and ≤1 mg/L (gram‐positive) should be evaluated in further studies.
Going the distance: The biomechanics of gap‐crossing behaviors
Authors: Graham Mal , Socha John J. 
Published: May 2019

AbstractThe discontinuity of the canopy habitat is one of the principle differences between the terrestrial and arboreal environments. An animal's ability to cross gaps—to move from one support to another across an empty space—is influenced by both the physical structure of the gap and the animal's locomotor capabilities. In this review, we discuss the range of behaviors animals use to cross gaps. Focusing on the biomechanics of these behaviors, we suggest broad categorizations that facilitate comparisons between taxa. We also discuss the importance of gap distance in determining crossing behavior, and suggest several mechanical characteristics that may influence behavior choice, including the degree to which a behavior is dynamic, and whether or not the behavior is airborne. Overall, gap crossing is an important aspect of arboreal locomotion that deserves further in‐depth attention, particularly given the ubiquity of gaps in the arboreal habitat.
Assessing effects of scanner upgrades for clinical studies
Authors: Keenan Kathryn E. , Gimbutas Zydrunas , Dienstfrey Andrew , Stupic Karl F. 
Published: May 2019

BackgroundScanner upgrades due to software and hardware changes are an inevitable part of MR research and, without quality assurance protocols, can jeopardize studies.PurposeTo evaluate changes in T1 relaxation time by inversion recovery (IR) and variable flip angle (VFA) measurements on a 3T system that underwent an "everything but the magnet" upgrade.Study TypeLongitudinal.PhantomAn International Society of Magnetic Resonance in Medicine / National Institute of Standards and Technology (ISMRM/NIST) system phantom with repeated measurements across multiple (n = 3) days.Field Strength/SequenceT1 IR, VFA at 3T.AssessmentThe T1 measurements by IR and VFA were compared with the nuclear magnetic resonance (NMR) measurements, which constitute the known values for the ISMRM/NIST system phantom, to determine the measurement error.Statistical TestsDescriptive.ResultsThe T1 VFA measurement errors were distributed around zero (–15% to +10%) on the original system and then the errors were distributed entirely above zero post‐upgrade (+5% to 30%). The T1 IR results had a dramatic increase in error distribution (±5% original, ±20% post‐upgrade) prior to the identification of signal saturation as an issue. Once the signal saturation was accounted for, the T1 IR errors decreased to ±10% post‐upgrade.Data ConclusionThe T1 VFA measurement differences between the original and post‐upgrade systems can be entirely attributed to contributions from B1. The T1 IR measurements demonstrate the need for quantitative quality assurance (QA) processes. The site under study passed the QA protocols in place, which did not identify the increased T1 error, nor the signal saturation issue. To improve on this study, we would make systematic, quantitative measurements at intervals less than a year and following any hardware or software upgrade.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2019;50:1948–1954.
High frame rate cardiac cine MRI for the evaluation of diastolic function and its direct correlation with echocardiography
Authors: Zhang Jiming , Chen Jie , Cheong Benjamin , Pednekar Amol , Muthupillai Raja 
Published: May 2019

BackgroundBreath‐hold cine MR is the method of choice for evaluating left ventricular (LV) systolic function; however, the evaluation of diastolic function remains in the domain of high frame rate echocardiography. Thus, a cine MR technique for simultaneously evaluating LV systolic and diastolic function would be clinically valuable.PurposeTo test the feasibility of extracting indices that characterize LV diastolic function from high frame rate cine MR.Study TypeSingle center, prospective.PopulationAsymptomatic volunteers (N = 24; age 45.8 ± 12.3 years).Field Strength/SequenceHigh frame rate (70 fps) cine MR and phase‐contrast MR during free breathing were acquired at 1.5T.AssessmentThe following MR‐based LV filling metrics were extracted from LV volume changes during the cardiac cycle: 1) the volume–rate ratio, REFP/RLFP (ratio of the peak LV filling rate during the early filling period [EFP] to that during the late filling period [LFP]); and 2) the volume ratio, VEFP/VLFP (the ratio of cumulative LV volume change between the EFP and LFP). These metrics were then compared with traditional transmitral blood flow‐based MR and echocardiographic indices. The effect of temporal resolution on these metrics was also evaluated.Statistical TestsBland–Altman and linear regression analyses were used to evaluate the performance of the proposed metrics against traditional indices of diastolic function.ResultsThe REFP/RLFP and VEFP/VLFP correlated well with E/AQ‐flow (r
2 = 0.66 and 0.54, respectively) and E/Aecho (r
2 = 0.58 and 0.49, respectively). Systolic indices remained robust (<3% error) for frame rates ≥20 fps. Although the proposed VEFP/VLFP was robust (<5% error) up to 25 fps, the proposed volume–rate diastolic function metrics were less reliable (>8% error) for frame rates below 35 fps.Data ConclusionIn asymptomatic volunteers, cardiac cine MR images acquired at frame rates >35 fps can be used to extract LV diastolic function indices from the temporal changes in LV volume.Level of Evidence: 1Technical Efficacy Stage: 1J. Magn. Reson. Imaging 2019;50:1571–1582.