bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between bronchopulmonary dysplasia and cerebral palsy in children: a meta-analysis
Authors: Gou Xiaoyun , Yang Lei , Pan Lingli , Xiao Dongqiong
Published: September 2018

Objective

To investigate the association between bronchopulmonary dysplasia (BPD) and the risk of cerebral palsy (CP) in children.

Data sources

We used EMBASE, PubMed and Web of Science to conduct a meta-analysis of studies published before 1 September 2017, written in English whose titles or abstracts discussed an association between BPD and CP.

Study selection

Observational studies, for example, case–control and cohort studies were included.

Data extraction and synthesis

All review stages were conducted by two reviewers independently. Data synthesis was undertaken via meta-analysis of available evidence.

Main outcomes and measures

The prevalence of developing CP was measured after exposure to BPD.

Results

Among 1234 initially identified studies, we selected those that addressed an association between BPD and CP according to our preselected inclusion criteria. Our meta-analysis included 11 studies. According to a random effect model, BPD was significantly associated with CP (ORs 2.10; 95% CI 1.57 to 2.82) in preterm infants. Factors explaining differences in the study results included study design, the definition of BPD, the time of diagnosis of CP and whether the studies adjusted for potential confounders.

Conclusion

This study suggests that BPD is a risk factor for CP. Further studies are required to confirm these results and to detect the influence of variables across studies.
Classic e-Delphi survey to provide national consensus and establish priorities with regards to the factors that promote the implementation and continued development of non-medical prescribing within health services in Wales
Authors: Courtenay Molly , Deslandes Rhian , Harries-Huntley Gail , Hodson Karen , Morris Gary
Published: September 2018

Objective

To provide national consensus and establish priorities with regards to the factors that promote the implementation and continued development of non-medical prescribing within health services.

Design

Classic e-Delphi survey.

Setting

National study in Wales.

Participants

Pharmacists, nurses and allied health professionals with the independent/supplementary prescribing qualification.

Results

A total of 55 non-medical prescribers agreed to become members of the expert panel of whom 42 (76%) completed the round 1 questionnaire, 40/42 (95%) completed round 2 and 34/40 (85%) responded to round 3. Twenty-one statements were developed, and consensus was achieved on nine factors representing those necessary for the successful implementation of non-medical prescribing and five representing actions required for its continued development. Strategic fit between non-medical prescribing and existing service provision, organisation preparedness, visible benefits, good managerial and team support, and a clear differentiation of roles were each important influences.

Conclusion

Given the high degree of consensus, this list of factors and actions should provide guidance to managers and commissioners of services wishing to initiate or extend non-medical prescribing. This information should be considered internationally by other countries outside of the UK wishing to implement prescribing by non-medical healthcare professionals.
Unusual perceptions at the end of life: limitations to the diagnosis of hallucinations in palliative medicine
Authors: Kellehear Allan
Published: September 2018

The diagnosis of hallucination for unusual perceptions such as deathbed visions, near-death experiences, or visions of the bereaved, is unhelpful in palliative medicine both academically and clinically. This paper reviews the broad prevalence data about unusual perceptions in the general population as background to identifying the more narrow epidemiological source from which the much smaller focus on hallucinations seem to emerge. Major debates and limitations of current hallucination research are reviewed to show that current academic and clinical certainties are largely confined to unusual perceptions that can be readily linked to psychopathology, quite specific organic disease states and psychoactive drug use. Current state-of-the-art in hallucination studies does not warrant broad or uncritical use of this type of diagnosis in end-of-life care. Conclusions from interdisciplinary (as opposed to single discipline) hallucination studies suggest that the way forward for clinical and research work in palliative medicine may lie in a more biographical and cultural approach to unusual perceptions at the end of life.
Assessing the long-term effectiveness of interferon-beta and glatiramer acetate in multiple sclerosis: final 10-year results from the UK multiple sclerosis risk-sharing scheme
Authors: Palace Jacqueline , Duddy Martin , Lawton Michael , Bregenzer Thomas , Zhu Feng , Boggild Mike , Piske Benjamin , Robertson Neil P , Oger Joel , Tremlett Helen , Tilling Kate , Ben-Shlomo Yoav , Lilford Richard , Dobson Charles
Published: September 2018

Background

Because multiple sclerosis (MS) is a chronic disease causing disability over decades, it is crucial to know if the short-term effects of disease-modifying therapies reported in randomised controlled trials reduce long-term disability. This 10-year prospective observational study of disability outcomes (Expanded Disability Status Scale (EDSS) and utility) was set up, in conjunction with a risk-sharing agreement between payers and producers, to investigate this issue.

Methods

The outcomes of the UK treated patients were compared with a modelled untreated control based on the British Columbia MS data set to assess the long-term effectiveness of these treatments. Two complementary analysis models were used: a multilevel model (MLM) and a continuous Markov model.

Results

4862 patients with MS were eligible for the primary analysis (mean and median follow-up times 8.7 and 10 years). EDSS worsening was reduced by 28% (MLM), 7% (Markov) and 24% time-adjusted Markov in the total cohort, and by 31% (MLM) and 14% (Markov) for relapsing remitting patients. The utility worsening was reduced by 23%–24% in the total cohort and by 24%–31% in the RR patients depending on the model used. All sensitivity analyses showed a treatment effect. There was a 4-year (CI 2.7 to 5.3) delay to EDSS 6.0. An apparent waning of treatment effect with time was seen. Subgroup analyses suggested better treatment effects in those treated earlier and with lower EDSS scores.

Conclusions

This study supports a beneficial effect on long-term disability with first-line MS disease-modifying treatments, which is clinically meaningful. However the waning effect noted requires further study.
Eimeria species in cattle with diarrhoea in the Republic of Korea regarding age, season and nature of diarrhoea
Authors: Lee Seung‐Hun , Kim Ha‐Young , Lee Haeseung , Kim Jong Wan , Lee Yu‐Ran , Chae Myeong Ju , Oh Sang‐Ik , Kim Jong Ho , Rhee Man Hee , Kwon Oh‐Deog , Goo Youn‐Kyoung , Kim Tae‐Hwan , Geraldino Paul John L , Kwak Dongmi
Published: September 2018

This study evaluated the prevalence of Eimeria species, particularly E bovis, E zuernii and E auburnensis that are pathogenic to cattle, in faecal samples collected from cattle with diarrhoea reared in the Republic of Korea by using microscopy and PCR. In addition, the prevalence of Eimeria species was analysed according to age, type of cattle, region, season and nature of diarrhoea. Overall, Eimeria species were identified in 279 of the 1261 (22.1 per cent) faecal samples through microscopy, and statistical analysis revealed a lower prevalence in calves aged than three weeks or less and higher prevalence in cattle with haemorrhagic diarrhoea. Of the 279 microscopy‐positive samples, E bovis, E zuernii and E auburnensis were identified in 100 (7.9 per cent), 83 (6.6 per cent) and 27 (2.1 per cent) faecal samples, respectively, by using PCR. To the authors' knowledge, this study is the first to apply PCR for epizootiology of bovine coccidiosis.
Reliability of equine visual lameness classification as a function of expertise, lameness severity and rater confidence
Authors: Starke Sandra Dorothee , Oosterlinck Maarten
Published: September 2018

Visual equine lameness assessment is often unreliable, yet the full understanding of this issue is missing. Here, we investigate visual lameness assessment using near‐realistic, three‐dimensional horse animations presenting with 0–60 per cent movement asymmetry. Animations were scored at an equine veterinary seminar by attendees with various expertise levels. Results showed that years of experience and exposure to a low, medium or high case load had no significant effect on correct assessment of lame (P>0.149) or sound horses (P≥0.412), with the exception of a significant effect of case load exposure on forelimb lameness assessment at 60 per cent asymmetry (P=0.014). The correct classification of sound horses as sound was significantly (P<0.001) higher for forelimb (average 72 per cent correct) than for hindlimb lameness assessment (average 28 per cent correct): participants often saw hindlimb lameness where there was none. For subtle lameness, errors often resulted from not noticing forelimb lameness and from classifying the incorrect limb as lame for hindlimb lameness. Diagnostic accuracy was at or below chance level for some metrics. Rater confidence was not associated with performance. Visual gait assessment may overall be unlikely to reliably differentiate between sound and mildly lame horses irrespective of an assessor's background.
The exact closed solution in the analysis of a natural convection porous fin with temperature-dependent thermal conductivity and internal heat generation
Authors: Abbasbandy S. , Shivanian E.
Published: September 2018

In the current work, thermal behaviour analysis of a natural convection porous fin with internal heat generation and temperature-dependent thermal conductivity is studied. The developed symbolic heat transfer models are for the purpose of the investigation of the effects of various parameters on the thermal behaviour of the porous fin. It is shown that its governing nonlinear differential with proper boundary conditions is exactly solvable. To this aim, we reduce the order of differential equations first and then convert into a total differential equation by multiplying a convenient integrating factor. A full discussion and exact analytical solution in the implicit form is given for further physical interpretation and it is proved that a solution to the problem may not exist or the solution is mathematically unique depending on the values of the parameters of the model.
Measuring low-altitude wind gusts using the unmanned aerial vehicle GustAV
Authors: Yeung Alton , Bramesfeld Goetz , Chung Joon , Foster Stephen
Published: September 2018

A small unmanned aerial vehicle (SUAV) was developed with the specific objective to explore atmospheric wind gusts at low altitudes below 500 m. These gusts have significant impact on the flight characteristics and performance of SUAVs. The SUAV carried an advanced air-data system that includes a five-hole probe, which was adapted for this specific application. In several flight tests the entire test system was qualified and gust data were recorded. The subsequent experimentally derived gust data were post-processed and compared with turbulence spectra of the MIL-HDBK-1797 von Kármán turbulence model. On the day of the flight test, the experimental results did not fully match the prediction of the von Kármán model. Meanwhile, the wind measuring apparatus were proven to be able to measure gust during flight. Therefore, a broader sampling will be required to generalize the gust measurements and be compared with the existing models.
What are the wild waves saying? Yet another meditation on the predictions, searches for, and detections of gravitational waves
Authors: Trimble Virginia
Published: September 2018

A large majority of the physics and astronomy communities are now sure that gravitational waves exist, can be looked for, and can be studied via their effects on laboratory apparatus as well as on astronomical objects. So far, everything found out has agreed with the predictions of general relativity, but hopes are high for new information about the universe and its contents and perhaps for hints of a better theory of gravity than general relativity (which even Einstein expected to come eventually). This is one version of the story, from 1905 to the present, told from an unusual point of view, because the author was, for 28.5 years, married to Joseph Weber, who built the first detectors starting in the early 1960s and operated one or more until his death on 30 September 2000.
On the entropy numbers between the anisotropic spaces and the spaces of functions with mixed smoothness
Authors: Wang Kai , Wang Yali , Zhou Yinying
Published: September 2018

We study the entropy numbers of the anisotropic classes in the spaces of functions with mixed smoothness and those of the classes of functions with mixed smoothness in the anisotropic spaces. Exact orders of the corresponding entropy numbers are obtained.
Sarcasm Detection Algorithms
Authors: Yavanoglu Uraz , Ibisoglu Taha Yasin , Wıcana Setra Genyang
Published: September 2018

In this paper, we want to review one of the challenging problems for the opinion mining task, which is sarcasm detection. To be able to do that, many researchers tried to explore such properties in sarcasm like theories of sarcasm, syntactical properties, psycholinguistic of sarcasm, lexical feature, semantic properties, etc. Studies conducted within last 15 years have not only made progress in semantic features but have also shown increasing amounts of methods of analysis using a machine-learning approach to process data. Therefore, this paper will try to explain the most currently used methods to detect sarcasm. Lastly, we will present a result of our finding, which might help other researchers to gain a better result in the future.
Spontaneous pulmonary hypertension in genetic mouse models of natural killer cell deficiency
Authors: Rätsep Matthew T. , Moore Stephen D. , Jafri Salema , Mitchell Melissa , Brady Hugh J. M. , Mandelboim Ofer , Southwood Mark , Morrell Nicholas W. , Colucci Francesco , Ormiston Mark L.
Published: September 2018

Natural killer (NK) cells are cytotoxic innate lymphoid cells with an established role in the regulation of vascular structure in pregnancy and cancer. Impaired NK cell function has been identified in patients with pulmonary arterial hypertension (PAH), a disease of obstructive vascular remodeling in the lungs, as well as in multiple rodent models of disease. However, the precise contribution of NK cell impairment to the initiation and progression of PAH remains unknown. Here, we report the development of spontaneous pulmonary hypertension in two independent genetic models of NK cell dysfunction, including Nfil3−/− mice, which are deficient in NK cells due to the absence of the NFIL3 transcription factor, and Ncr1-Gfp mice, which lack the NK activating receptor NKp46. Mouse models of NK insufficiency exhibited increased right ventricular systolic pressure and muscularization of the pulmonary arteries in the absence of elevated left ventricular end-diastolic pressure, indicating that the development of pulmonary hypertension was not secondary to left heart dysfunction. In cases of severe NK cell impairment or loss, a subset of mice failed to develop pulmonary hypertension and instead exhibited reduced systemic blood pressure, demonstrating an extension of vascular abnormalities beyond the pulmonary circulation into the systemic vasculature. In both mouse models, the development of PAH was linked to elevated interleukin-23 production, whereas systemic hypotension in Ncr1-Gfp mice was accompanied by a loss of angiopoietin-2. Together, these results support an important role for NK cells in the regulation of pulmonary and systemic vascular function and the pathogenesis of PAH.
Comparative genomic analysis of the human and nematodeCaenorhabditis elegansuncovers potential reproductive genes and disease associations in humans
Authors: Kim Yongsoon , Park YoungJoon , Hwang JoonYeon , Kwack KyuBum
Published: September 2018

Reproduction is an important biological process. However, studies of human reproduction at the molecular level are limited due to the difficulty of performing in vivo studies. Hence, a mechanistic understanding of human reproduction remains still poor. Thus, it is important to use an alternative model organism for mechanistic studies of human reproduction. In this study, we used the nematode Caenorhabditis elegans as a model for studying human reproduction and identified 61 human and 535 worm reproductive genes through a combination of comparative genomic and Gene Ontology (GO) analyses. Interestingly, in terms of sex specificity, the number of male-specific genes was greater than the number of female-specific genes. Gene enrichment analysis identified biologically significant processes such as protein localization to cajal bodies/telomeres/nuclear bodies/chromosomes, helicase activity, pyrimidine biosynthesis, and determination of adult lifespan. Regarding the analysis of human reproductive diseases among the identified genes, 10 and 12 genes were identified in the human- and C. elegans-based analyses, respectively. In addition, RNA interference knockdown of a newly identified F52H2.6/DHCR24 gene increased brood size and ovulation/egg-laying rate in C. elegans. Therefore, gene identification, disease associations, and a proof-of-concept experiment using C. elegans will not only provide insights into mechanistic study of human reproduction, but also demonstrate the utility in studying human reproduction.
The Dynamical Modeling Analysis of the Spreading of Passive Worms in P2P Networks
Authors: Zhang Shujuan , Jin Zhen , Zhang Juan
Published: September 2018

Passive worms are prone to spreading through Peer-to-Peer networks, and they pose a great threat to the security of the network. In this paper, considering network heterogeneity and the number of hops a search can reach, we propose a novel mathematical model to study the dynamics of the propagation of passive worms. For the proposed model, the basic reproduction number R0 is derived by employing the existence of the positive equilibrium. And the stabilities of the worm-free equilibrium and positive equilibrium are analyzed. Moreover, we verify the rationality of the model established by comparing the stochastic simulation with the numerical simulation. Finally, we examine the effect of the number of hops on the spread of passive worms and discuss the various immunization strategies. We find that if R0>1, the propagation speed of passive worms is accelerated with the increase of hop count d; if R0<1, the number of infected peers decreases rapidly with the increase of the value of d and drops to zero eventually. Results show that the network topology and the number of hops can affect the spread of passive worms.
An Incremental Two-Dimensional Principal Component Analysis for Object Recognition
Authors: Ge Weimin , Sun Mingyue , Wang Xiaofeng
Published: September 2018

Two-dimensional principal component analysis algorithm (2DPCA) can be performed in the batch mode and can not meet the real-time requirements of the video stream. To overcome these limitations, the incremental learning of the candid covariance-free incremental PCA (CCIPCA) is innovated to the existing 2DPCA, and the called incremental 2DPCA (I2DPCA) is firstly presented to incrementally compute the principal components of a sequence of samples directly on the 2D image matrices without estimating the covariance matrices. Therefore, the I2DPCA can improve the feature extraction speed and reduce the required memory. However, the variations between the column direction, generally neglected, are also useful for the high-accuracy object recognition. Thus, another incremental sequential row-column 2DPCA algorithm (IRC2DPCA), based on the proposed I2DPCA algorithm, is also proposed. The IRC2DPCA can compress the image matrices in the row and column direction, and the feature matrices extracted by the IRC2DPCA are with less dimensions than the I2DPCA. The substantial experimental results show that the IRC2DPCA, compared with the other three algorithms, can improve the convergence rates and the recognition rates, compress the dimensions of the feature matrices, and reduce the feature extraction time and the classification time.
Disparities in Intimate Partner Violence among Currently Married Women from Food Secure and Insecure Urban Households in South Ethiopia: A Community Based Comparative Cross-Sectional Study
Authors: Andarge Eshetu , Shiferaw Yohannes
Published: September 2018

Intimate partner violence (IPV) against women and food insecurity are an ever growing public health concerns in Ethiopia. However, the connection between the two is not yet well investigated. Therefore, this study compares IPV by household food security status and examines the association between IPV and food insecurity and among currently married women in childbearing age in Arba Minch town, South Ethiopia. A community based comparative cross-sectional study was conducted among 696 currently married women (15-49). A quantitative data was collected using a pretested and structured questionnaire on randomly selected women. Logistic regression was done using IBM SPSS version 20. Statistical significance was declared at p-value of less than 0.05 and odds ratio with its 95% confidence interval was used to show the degree of association. Lifetime and current IPV were 62.4% and 50%, respectively. Sixty-three (23.6%) and 285 (66.4%) women who experienced current IPV were from food secured and insecure households, respectively (P-value<0.001). The odds of experiencing current IPV were higher among women from food insecure households (AOR=6.59,95% CI(4.54,9.57)) and who were in the age range of 30-39 (AOR=2.16, 95% CI(1.34,3.56)) and it was lower among women with 10 and more years age difference with their husband (AOR=0.52, 95% CI (0.31,0.88)) and with high decision-making power (AOR=0.61, 95% CI (0.38.0.96)) than their reference groups. The prevalence of current IPV was significantly higher among women from food insecure households as compared to their counterparts. The odds of experiencing current IPV were higher among women from food insecure households. Policy makers and programme planners should consider improving urban women’s household food security status in order to improve gender inequality and empower women. Multisectorial effort is needed to improve women education and other behavioral factors.
Dynamic Operation Management of a Renewable Microgrid including Battery Energy Storage
Authors: Jin Shaozhen , Mao Zhizhong , Li Hongru , Qi Wenhai
Published: September 2018

In this paper, a novel dynamic programming technique is presented for optimal operation of a typical renewable microgrid including battery energy storage. The main idea is to use the scenarios analysis technique to proceed the uncertainties related to the available output power of wind and photovoltaic units and dynamic programming technique to obtain the optimal control strategy for a renewable microgrid system in a finite time period. First, to properly model the system, a mathematical model including power losses of the renewable microgrid is established, where the uncertainties due to the fluctuating generation from renewable energy sources are considered. Next, considering the dynamic power constraints of the battery, a new performance index function is established, where the Lagrange multipliers and interior point method will be presented for the equality and inequality operation constraints. Then, a feedback control scheme based on the dynamic programming is proposed to solve the model and obtain the optimal solution. Finally, simulation and comparison results are given to illustrate the performance of the presented method.
Particle Swarm Optimization-Based Support Vector Regression for Tourist Arrivals Forecasting
Authors: Liu Hsiou-Hsiang , Chang Lung-Cheng , Li Chien-Wei , Yang Cheng-Hong
Published: September 2018

The tourism industry has become one of the most important economic sectors for governments worldwide. Accurately forecasting tourism demand is crucial because it provides useful information to related industries and governments, enabling stakeholders to adjust plans and policies. To develop a forecasting tool for the tourism industry, this study proposes a method that combines feature selection (FS) and support vector regression (SVR) with particle swarm optimization (PSO), named FS–PSOSVR. To ensure high forecast accuracy, FS and a PSO algorithm are employed to, respectively, select reliable input variables and to identify the optimal initial parameters of SVR. The proposed method was tested using a data set of monthly tourist arrivals to Taiwan from January 2006 to December 2016. The results reveal that the errors obtained using FS–PSOSVR are comparatively smaller than those obtained using other methods, indicating that FS–PSOSVR is an effective method for forecasting tourism demand.
An r‐Order Finite‐Time State Observer for Reaction‐Diffusion Genetic Regulatory Networks with Time‐Varying Delays
Authors: Fan Xiaofei , Wang Yantao , Wu Ligang , Zhang Xian
Published: September 2018

It will be settled out for the open problem of designing an r‐order finite‐time (F‐T) state observer for reaction‐diffusion genetic regulatory networks (RDGRNs) with time‐varying delays. By assuming the Dirichlet boundary conditions, aiming to estimate the mRNA and protein concentrations via available network measurements. Firstly, sufficient F‐T stability conditions for the filtering error system have been investigated via constructing an appropriate Lyapunov–Krasovskii functional (LKF) and using several integral inequalities and (reciprocally) convex technique simultaneously. These conditions are delay‐dependent and reaction‐diffusion‐dependent and can be checked by MATLAB toolbox. Furthermore, a method is proposed to design an r‐order F‐T state observer, and the explicit expressions of observer gains are given. Finally, a numerical example is presented to illustrate the effectiveness of the proposed method.
Characterizations of Certain Types of Type 2 Soft Graphs
Authors: Hayat Khizar , Cao Bing-Yuan , Ali Muhammad Irfan , Karaaslan Faruk , Qin Zejian
Published: September 2018

The vertex-neighbors correspondence has an essential role in the structure of a graph. The type 2 soft set is also based on the correspondence of initial parameters and underlying parameters. Recently, type 2 soft graphs have been introduced. Structurally, it is a very efficient model of uncertainty to deal with graph neighbors and applicable in applied intelligence, computational analysis, and decision-making. The present paper characterizes type 2 soft graphs on underlying subgraphs (regular subgraphs, irregular subgraphs, cycles, and trees) of a simple graph. We present regular type 2 soft graphs, irregular type 2 soft graphs, and type 2 soft trees. Moreover, we introduce type 2 soft cycles, type 2 soft cut-nodes, and type 2 soft bridges. Finally, we present some operations on type 2 soft trees by presenting several examples to demonstrate these new concepts.
Simultaneous Determination of Columbianadin and Its Metabolite Columbianetin in Rat Plasma by LC‐MS/MS: Application to Pharmacokinetics of Columbianadin after Oral Administration
Authors: Li Jin , Li Zhen , Luo Qian , Wang Chun-Peng , He Jun , Pang Xiaoli , Teye Azietaku John , Chang Yan-xu
Published: September 2018

Columbianadin and its metabolite columbianetin exhibited the anti‐inflammatory, analgesic, calcium channel blocking and antitumor activities. To compare the differences between pharmacokinetics of columbianadin and its metabolite columbianetin after oral administration of pure columbianadin and Angelicae Pubescentis Radix (APR) extract, a simple and sensitive liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method was established and validated to simultaneously determine columbianadin and columbianetin in rat plasma. Two analytes and an internal standard (warfarin) were well separated and determined after liquid‐liquid extraction with ethyl acetate. Ammonium acetate aqueous solution (1 mmol/L) and acetonitrile were used as the mobile phase and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) was 0.1 ng/mL for columbianetin and 0.5 ng/mL for columbianadin, respectively. There were significant differences between some pharmacokinetic parameters and bioavailability of columbianadin after oral administration of pure columbianadin and APR extract. The studies on comparative pharmacokinetics of columbianadin were of great use for facilitating the clinical application of columbianadin and were also highly meaningful for the potential development of APR.
HBV-DNA Load-Related Peritumoral Inflammation and ALBI Scores Predict HBV Associated Hepatocellular Carcinoma Prognosis after Curative Resection
Authors: Liao Rui , Du Cheng-You , Gong Jian-Ping , Luo Fang
Published: September 2018

Background. Both persistent inflammatory activity and liver function damage contribute to a poor prognosis of hepatocellular carcinoma (HCC). This study aimed to develop nomograms that incorporate hepatitis virus B (HBV)-related peritumoral inflammation score (PIS) and liver function based on ALBI score to predict postoperative outcomes of HCC.Methods.The prognostic roles of HBV-related preoperative PIS and ALBI scores in HCC recurrence were examined, and then two nomograms were constructed. The predictive accuracy and discriminative ability of the nomograms were compared with AJCC and BCLC staging systems of HCC.Results.PIS (HBV-PIS) and ALBI scores (HBV-ALBI) with different HBV-DNA loads had association with overall survival (OS) and/or recurrence-free survival (RFS) of HCC. The independent predictors of OS and RFS were incorporated into the corresponding nomograms. In the training cohort, the C-indexes of OS and RFS nomograms were 0.751 and 0.736, respectively. ROC analyses showed that both OS and RFS nomograms had larger AUC (0.775 and 0.739, respectively) than AJCC and BCLC staging systems. These results were verified by the internal and external validation cohorts.Conclusion. The proposed nomograms, including HBV-DNA load-related PIS and ALBI scores, were accurate in predicting survival for HCC after curative resection.
Polymorphisms in the Chicken Growth Differentiation Factor 9 Gene Associated with Reproductive Traits
Authors: Liu Lingbin , Cui Zhifu , Xiao Qihai , Zhang Haihan , Zhao Xiaoling , Wang Yan , Yin Huadong , Li Diyan , Zhu Qing
Published: September 2018

The aim of the study was to investigateGDF9gene polymorphisms and their association with reproductive traits in chicken using DNA sequencing. A total of 279 Dongxiang blue-shelled (DX) chickens and 232 Luhua (LH) chickens were used for validation. We detected 15 single nucleotide polymorphisms (SNPs): nine SNPs were previously unreported in chicken, two were missense mutations, and only three exhibited significant associations with reproductive traits. G.17156387C>T was significantly associated with age at first egg (AFE) and weight of first egg (WFE) in both breeds. Birds carrying the CC genotype exhibited higher AFE and WFE values than those with the TT genotype. The SNP g.17156427A>G exhibited an association with egg weight at 300 days of age (EWTA) in DX but not in LH chickens. The SNP g.17156703A>C affected the AFE and EN (total number of eggs at 300 days of age) in DX chickens. In addition, certain diplotypes significantly affected AFE, BWTA (body weight at 300 days of age), and EN in both breeds. RT-PCR results showed that theGDF9gene was highly expressed in stroma with cortical follicles (STR) and prehierarchal follicles. These results provided further evidence that theGDF9gene is involved in determining reproductive traits in chicken.
Androgen Receptor Inhibitor Enhances the Antitumor Effect of PARP Inhibitor in Breast Cancer Cells by Modulating DNA Damage Response
Authors: Min Ahrum , Jang Hyemin , Kim Seongyeong , Lee Kyung-Hun , Kim Debora Keunyoung , Suh Koung Jin , Yang Yaewon , Elvin Paul , O'Connor Mark J. , Im Seock-Ah
Published: September 2018

The androgen receptor (AR) is expressed in 60%–70% of breast cancers regardless of estrogen receptor status, and has been proposed as a therapeutic target in breast cancers that retain AR. In this study, the authors aimed to investigate a new treatment strategy using a novel AR inhibitor AZD3514 in breast cancer. AZD3514 alone had a minimal antiproliferative effect on most breast cancer cell lines irrespective of AR expression level, but it downregulated the expressions of DNA damage response (DDR) molecules, including ATM and chk2, which resulted in the accumulation of damaged DNA in some breast cancer cells. Furthermore, AZD3514 enhanced cellular sensitivity to a PARP inhibitor olaparib by blocking the DDR pathway in breast cancer cells. Furthermore, the downregulation of NKX3.1 expression in MDA-MB-468 cells by AZD3514 occurred in parallel with the suppression of ATM–chk2 axis activation, and the suppression of NKX3.1 by AZD3514 was found to result from AZD3514-induced TOPORS upregulation and a resultant increase in NKX3.1 degradation. The study shows posttranslational regulation of NKX3.1 via TOPORS upregulation by AZD3514-induced ATM inactivation–increased olaparib sensitivity in AR-positive and TOPORS-expressing breast cancer cells, and suggests the antitumor effect of AZD3514/olaparib cotreatment is caused by compromised DDR activity in breast cancer cell lines and in a xenograft model. These results provide a rationale for future clinical trials of olaparib/AR inhibitor combination treatment in breast cancer.
Histone Deacetylase Inhibitors Synergize with Catalytic Inhibitors of EZH2 to Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Authors: Wang Yemin , Chen Shary Yuting , Colborne Shane , Lambert Galen , Shin Chae Young , Santos Nancy Dos , Orlando Krystal A. , Lang Jessica D. , Hendricks William P.D. , Bally Marcel B. , Karnezis Anthony N. , Hass Ralf , Underhill T. Michael , Morin Gregg B. , Trent Jeffrey M. , Weissman Bernard E. , Huntsman David G.
Published: September 2018

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but extremely lethal malignancy that mainly impacts young women. SCCOHT is characterized by a diploid genome with loss of SMARCA4 and lack of SMARCA2 expression, two mutually exclusive ATPases of the SWI/SNF chromatin-remodeling complex. We and others have identified the histone methyltransferase EZH2 as a promising therapeutic target for SCCOHT, suggesting that SCCOHT cells depend on the alternation of epigenetic pathways for survival. In this study, we found that SCCOHT cells were more sensitive to pan-HDAC inhibitors compared with other ovarian cancer lines or immortalized cell lines tested. Pan-HDAC inhibitors, such as quisinostat, reversed the expression of a group of proteins that were deregulated in SCCOHT cells due to SMARCA4 loss, leading to growth arrest, apoptosis, and differentiation in vitro and suppressed tumor growth of xenografted tumors of SCCOHT cells. Moreover, combined treatment of HDAC inhibitors and EZH2 inhibitors at sublethal doses synergistically induced histone H3K27 acetylation and target gene expression, leading to rapid induction of apoptosis and growth suppression of SCCOHT cells and xenografted tumors. Therefore, our preclinical study highlighted the therapeutic potential of combined treatment of HDAC inhibitors with EZH2 catalytic inhibitors to treat SCCOHT.
Targeted Delivery of Cytotoxic NAMPT Inhibitors Using Antibody–Drug Conjugates
Authors: Neumann Christopher S. , Olivas Kathleen C. , Anderson Martha E. , Cochran Julia H. , Jin Steven , Li Fu , Loftus Luke V. , Meyer David W. , Neale Jason , Nix Jay C. , Pittman Paul G. , Simmons Jessica K. , Ulrich Michelle L. , Waight Andrew B. , Wong Abbie , Zaval Margo C. , Zeng Weiping , Lyon Robert P. , Senter Peter D.
Published: September 2018

Antibody–drug conjugates (ADCs) are a therapeutic modality that enables the targeted delivery of cytotoxic drugs to cancer cells. Identification of active payloads with unique mechanisms of action is a key aim of research efforts in the field. Herein, we report the development of inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) as a novel payload for ADC technology. NAMPT is a component of a salvage biosynthetic pathway for NAD, and inhibition of this enzyme results in disruption of primary cellular metabolism leading to cell death. Through derivatization of the prototypical NAMPT inhibitor FK-866, we identified potent analogues with chemical functionality that enables the synthesis of hydrophilic enzyme-cleavable drug linkers. The resulting ADCs displayed NAD depletion in both cell-based assays and tumor xenografts. Antitumor efficacy is demonstrated in five mouse xenograft models using ADCs directed to indication-specific antigens. In rat toxicology models, a nonbinding control ADC was tolerated at >10-fold the typical efficacious dose used in xenografts. Moderate, reversible hematologic effects were observed with ADCs in rats, but there was no evidence for the retinal and cardiac toxicities reported for small-molecule inhibitors. These findings introduce NAMPT inhibitors as active and well-tolerated payloads for ADCs with promise to improve the therapeutic window of NAMPT inhibition and enable application in clinical settings.
Targeting TAZ-Driven Human Breast Cancer by Inhibiting a SKP2-p27 Signaling Axis
Authors: Shen He , Yang Nuo , Truskinovsky Alexander , Chen Yanmin , Mussell Ashley L. , Nowak Norma J. , Kobzik Lester , Frangou Costa , Zhang Jianmin
Published: September 2018

Deregulated expression of the transcriptional coactivator with PDZ-binding motif (WWTR1/TAZ) is a common feature of basal-like breast cancer (BLBC). Yet, how oncogenic TAZ regulates cell-cycle progression and proliferation in breast cancer remains poorly understood, and whether TAZ is required for tumor maintenance has not been established. Here, using an integrative oncogenomic approach, TAZ-dependent cellular programs essential for tumor growth and progression were identified. Significantly, TAZ-driven tumor cells required sustained TAZ expression, given that its withdrawal impaired both genesis and maintenance of solid tumors. Moreover, temporal inhibition of TAZ diminished the metastatic burden in established macroscopic pulmonary metastases. Mechanistic investigation revealed that TAZ controls distinct gene profiles that determine cancer cell fate through cell-cycle networks, including a specific, causal role for S-phase kinase–associated protein 2 (SKP2) in mediating the neoplastic state. Together, this study elucidates the molecular events that underpin the role of TAZ in BLBC and link to SKP2, a convergent communication node for multiple cancer signaling pathways, as a key downstream effector molecule.

Implications:

Understanding the molecular role of TAZ and its link to SKP2, a signaling convergent point and key regulator in BLBC, represents an important step toward the identification of novel therapeutic targets for TAZ-dependent breast cancer.
Efficacy of Dexamethasone Implants in Uveitic Macular Edema in Cases with Behçet Disease
Authors: Yalcinbayir Ozgur , Caliskan Enver , Ucan Gunduz Gamze , Gelisken Oner , Kaderli Berkant , Yucel Ahmet Ali
Published: September 2018

Purpose: Investigation of the efficacy of intravitreal dexamethasone implants (0.7 mg) in patients with Behçet disease (BD) who had cystoid macular edema (CME) despite immunomodulatory treatment. Materials and Methods: Twenty-seven eyes of 20 patients who had intravitreal dexameth­asone implant injections and follow-up for more than 6 months were included in this study. Best corrected visual acuities (BCVA), intraocular pressures (IOP), and central macular thicknesses (CMT) were recorded. Systemic immunomodulatory treatment was noted. Injection-related complications and the need for recurrent injections were recorded. Results: Statistically significant anatomical and functional success was achieved with a single injection. BCVA increased from 0.85 ± 0.72 to 0.45 ± 0.52 logMAR, while the mean CMT decreased from 406 ± 190 to 243 ± 101 µm at the sixth month. The peak of visual acuity gain was reached within the first 2 months and a substantial proportion of the patients gained 3 or more lines. There was no complication other than transient IOP elevation in 4 eyes and cataract surgery in 2 eyes. Conclusion: Adjuvant intravitreal dexamethasone implant injections offer promising results in cases of BD with CME. It is effective in preserving the macular anatomy and vision particularly in transition to biological agents.
Holmium Laser Enucleation of the Prostate Provides Similar Incidental Prostate Cancer Detection Rates as Open Prostatectomy: A Matched Pair Analysis
Authors: Rosenhammer Bernd , Lausenmeyer Eva Maria , Mayr Roman , Burger Maximilian , Eichelberg Christian
Published: September 2018

Introduction: Whereas the excellent functional outcomes after Holmium laser enucleation of the prostate (HoLEP) and its equivalency to open prostatectomy (OP) have been studied in detail in the past years, the oncological equivalency has yet to be investigated. Therefore, we conducted a matched pair analysis to evaluate and compare incidental prostate cancer detection rates after HoLEP and OP. Patients and methods: Preoperative patient age, total prostate-specific antigen (PSA), and prostate volume were used as primary matching criteria. Descriptive statistics were used to confirm matching quality. Statistical analyses were performed using Fisher´s exact test and T-test or Mann-Whitney U-test for dichotomous and continuous variables, respectively. Results: After the matching procedure, 72 out of 145 patients after HoLEP and 72 out of 477 patients after OP were included. Mean patient age (70 vs. 71 years), median prostate volume (106 vs. 107 mL), and median preoperative total PSA (4.32 vs. 4.36 ng/mL) were almost identical. The amount of removed tissue did not differ between HoLEP and OP. Incidental prostate cancer detection rate was similar with 9.7% after HoLEP and 8.3% after OP (p = 1.000). Conclusion: This first matched pair analysis shows that HoLEP does not have a disadvantage regarding cancer detection rate during desobstructive surgery for large prostates.
Pterostilbene Reduces Acetaminophen-Induced Liver Injury by Activating the Nrf2 Antioxidative Defense System via the AMPK/Akt/GSK3β Pathway
Authors: Fan Xiaoye , Wang Lidong , Huang Jingbo , Lv Hongming , Deng Xuming , Ci Xinxin
Published: September 2018

Background/Aims: Pterostilbene (Pts), a natural dimethylated analog of resveratrol from blueberries, exerts antioxidative and anti-apoptotic effects in various diseases. This study aims to investigate the protective effects and mechanism of Pts against acetaminophen (APAP)-induced hepatotoxicity in vivo. Methods: C57BL/6 mice were treated with APAP or APAP+Pts. HepG2 cells were used to further explore the underlying mechanisms in vitro. The effects of Pts on hepatotoxicity were measured by commercial kits, Hematoxylin and Eosin (H&E) straining, TUNEL assay, Western blot analysis, and Flow cytometry assay. Results: In vivo, Pts treatment effectively protected against APAP-induced severe liver injury by decreasing the lethality rate, the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, liver histological injury, liver malondialdehyde (MDA) formation and myeloperoxidase (MPO) levels and by increasing liver glutathione (GSH) and superoxide dismutase (SOD) levels. Moreover, in Pts-treated mice, the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway was activated; however, APAP-induced c-Jun NH2-terminal kinase (JNK) activation, mitochondrial Bcl-2 Associated X Protein (Bax) translocation, apoptosis-inducing factor (AIF) levels and cytochrome c release were attenuated. In vitro, Pts was found to reverse hydrogen peroxide (H2O2) -induced cytotoxicity, reactive oxygen species (ROS) production and apoptosis that depended on Nrf2 activation. Moreover, Pts induced a dose-dependent increase in the phosphorylation of AMP-activated protein kinase (AMPK), serine/threonine kinase (Akt), and glycogen synthase kinase 3β (GSK3β) in HepG2 cells. Moreover, Pts protect against APAP or H2O2-induced toxicity were effectively attenuated or abolished in HepG2 Nrf2-/- cells and Nrf2-/- mice. Conclusion: Our data suggest that Pts protects against APAP-induced toxicity by activating Nrf2 via the AMPK/Akt/GSK3β pathway.
Association of Serum Uric Acid with Arterial Stiffness in Peritoneal Dialysis Patients
Authors: Liu Xinhui , Wu Juan , Wu Haishan , Yi Chunyan , Huang Fengxian , Yu Xueqing , Yang Xiao
Published: September 2018

Background/Aims: Serum uric acid (SUA) has been proposed as a mediator associated with increased cardiovascular risk and arterial stiffness. However, evidence on the association between SUA and arterial stiffness in peritoneal dialysis (PD) patients is lacking. The aim of this study was to examine the relationship between SUA and arterial stiffness in PD patients. Methods: The patients who performed vascular profiler test from January 1, 2014 to October 31, 2016, and with SUA values were enrolled. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). The relationship between SUA and baPWV was tested by multiple linear regression models. Results: Of 645 PD patients, mean SUA was 6.80 (±1.29) mg/dL, mean baPWV was 1713 (±505) cm/s. In fully adjusted linear regression models, higher SUA was significantly associated with higher baPWV in young [standardized coefficients (β), 0.085; 95% confidence interval (95% CI), 0.013 to 0.130; P=0.02] but not in elderly (β, -0.194; 95% CI, -0.774 to 0.093; P=0.1) PD patients. In gender-stratified models of young patients, there was a significant association between SUA and baPWV in male (β, 0.115; 95% CI, 0.015 to 0.182; P=0.02) but not in female. Male in the highest gender-specific SUA quartile had a higher baPWV than those in the lowest quartile (β, 0.132; 95% CI, 0.011 to 0.209; P=0.03). This gender difference was reversed when selecting male patients with lower SUA levels (quartile 1 and 2) and female patients with higher SUA levels (quartile 3 and 4). Conclusion: SUA was positively associated with baPWV in young PD patients, and this association was significant in males but not in females, which is possibly explained by the higher SUA level in males than in females.