bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized multifactor dimensionality reduction approaches to identification of genetic interactions underlying ordinal traits
Authors: Hou Ting‐Ting , Lin Feng , Bai Shasha , Cleves Mario A. , Xu Hai‐Ming , Lou Xiang‐Yang
Published: November 2018

The manifestation of complex traits is influenced by gene–gene and gene–environment interactions, and the identification of multifactor interactions is an important but challenging undertaking for genetic studies. Many complex phenotypes such as disease severity are measured on an ordinal scale with more than two categories. A proportional odds model can improve statistical power for these outcomes, when compared to a logit model either collapsing the categories into two mutually exclusive groups or limiting the analysis to pairs of categories. In this study, we propose a proportional odds model‐based generalized multifactor dimensionality reduction (GMDR) method for detection of interactions underlying polytomous ordinal phenotypes. Computer simulations demonstrated that this new GMDR method has a higher power and more accurate predictive ability than the GMDR methods based on a logit model and a multinomial logit model. We applied this new method to the genetic analysis of low‐density lipoprotein (LDL) cholesterol, a causal risk factor for coronary artery disease, in the Multi‐Ethnic Study of Atherosclerosis, and identified a significant joint action of theCELSR2, SERPINA12, HPGD,andAPOBgenes. This finding provides new information to advance the limited knowledge about genetic regulation and gene interactions in metabolic pathways of LDL cholesterol. In conclusion, the proportional odds model‐based GMDR is a useful tool that can boost statistical power and prediction accuracy in studying multifactor interactions underlying ordinal traits.
The conceptual introduction of the “demyelinating Schwann cell” in peripheral demyelinating neuropathies
Authors: Park Hwan Tae , Kim Jong Kuk , Tricaud Nicolas
Published: October 2018

Myelinating Schwann cells undergo irreversible demyelination in many demyelinating neuropathies that show complete demyelination of the internode. Dedifferentiation, reprogramming, and myelin clearance processes—which are specifically discussed in this article—appear to be shared by various demyelinating peripheral conditions, such as Wallerian degeneration, immune‐mediated, and toxic demyelinating diseases. We propose to introduce the concept of the “demyelinating Schwann cell (DSC)” as a novel cell phenotype, which has specific properties required for myelin sheath clearance. We anticipate that the introduction of the DSC concept will provide a significant advance in understanding the pathophysiological mechanisms of demyelinating peripheral neuropathies.
A choice experiment to identify the most important elements of a successful cancer screening program according to those who research and manage such programs
Authors: Priaulx Jennifer , Csanádi Marcell , de Koning Harry J. , McKee Martin
Published: October 2018

Purpose

The relationship between cancer screening activities in Europe and the health systems in which they are embedded varies, with some screening programs organized largely separately and others using existing health service staff and facilities. Whatever the precise arrangements, the opportunity for screening to achieve health gain depends on many elements interacting within and beyond the health system, from an accurate register identifying the target population to a means to ensure and monitor follow‐up.

Method

A conjoint analysis was undertaken with 66 cancer screening experts from 31 countries taking part in EU‐TOPIA (towards improved screening for breast, cervical and colorectal cancer in all of Europe) to identify priorities for an effective screening program, taking a whole system perspective. Ten attributes, each with two levels, were derived from a review of the literature and consultation with experts in cancer screening. Statistical software generated 12 profiles that were ranked by respondents and analyzed using standard conjoint analysis.

Findings and conclusion

The most important attributes were having up‐to‐date and evidence‐based guidelines, followed by mechanisms for systematic monitoring of screening uptake, having a population register covering all of the eligible population and monitoring long‐term outcomes. In discussions about the results, participants argued that quality assurance and adherence to guidelines were important, even though they generated low scores in the experiment. This difference may be due some attributes being interrelated, more wide‐ranging or the sequential nature of establishing an effective screening program, with guidelines being the first stage of the process.
Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives
Authors: Dey Prasanta , Kundu Amit , Chakraborty Hirak Jyoti , Kar Babli , Choi Wahn Soo , Lee Byung Mu , Bhakta Tejendra , Atanasov Atanas G. , Kim Hyung Sik
Published: November 2018

Discovery and development of new potentially selective anticancer agents are necessary to prevent a global cancer health crisis. Currently, alternative medicinal agents derived from plants have been extensively investigated to develop anticancer drugs with fewer adverse effects. Among them, steroidal alkaloids are conventional secondary metabolites that comprise an important class of natural products found in plants, marine organisms and invertebrates, and constitute a judicious choice as potential anti‐cancer leads. Traditional medicine and modern science have shown that representatives from this compound group possess potential antimicrobial, analgesic, anticancer and anti‐inflammatory effects. Therefore, systematic and recapitulated information about the bioactivity of these compounds, with special emphasis on the molecular or cellular mechanisms, is of high interest. In this review, we methodically discuss thein vitroandin vivopotential of the anticancer activity of natural steroidal alkaloids and their synthetic and semi‐synthetic derivatives. This review focuses on cumulative and comprehensive molecular mechanisms, which will help researchers understand the molecular pathways involving steroid alkaloids to generate a selective and safe new lead compound with improved therapeutic applications for cancer prevention and therapy.In vitroandin vivostudies provide evidence about the promising therapeutic potential of steroidal alkaloids in various cancer cell lines, but advanced pharmacokinetic and clinical experiments are required to develop more selective and safe drugs for cancer treatment.
What Can Parents Tell Us About Poverty and Literacy Learning? Listening to Parents Over Time
Authors: Compton‐Lilly Catherine , Delbridge Anne
Published: October 2018

In this article, the authors use Bourdieu's conceptualization of capital and data from two longitudinal case studies to explore how financial challenges impacted learning opportunities for two children in a high‐poverty urban community. Interview data collected from two African American families over a 10‐year period were analyzed with attention to the role of economic academic capital (resources and experiences that require financial investment and translate to school success) in children's school trajectories. Findings revealed that the families’ homes, schools, and community lacked economic academic capital and that this dearth had dire consequences for the children's academic careers. However, the families could access other forms of capital, namely, embodied academic capital and social academic capital. These findings point to the important role that teachers can play when they act as advocates for students from low‐income backgrounds and their parents when they encounter educational and economic barriers.
Association of TNF‐308 G>A polymorphism located in tumor necrosis factor a with the risk of developing cervical cancer and results of pap smear
Authors: Babapour Nooshin , Mehramiz Mehrane , Rastgar Moghadam Azam , Behboodi Negin , Yousefi Zohre , Maftouh Mona , Talebian Sahar , Khazaei Majid , Jafarian Amirhosein , Sharifi‐Sistani Noorieh , Avan Amir , Hasanzadeh Malihe
Published: November 2018

Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF‐308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®‐probes‐based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval [CI]: 1.57‐4.83, <0.001) and OR of 7.27 (95%CI: 2.5‐20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF‐308 G>A located on TNF‐a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.
Performance of density functional theory for describing hetero‐metallic active‐site motifs for methane‐to‐methanol conversion in metal‐exchanged zeolites
Authors: Dandu Naveen K. , Adeyiga Olajumoke , Panthi Dipak , Bird Shaina A. , Odoh Samuel O.
Published: October 2018

Methane‐to‐methanol conversion (MMC) can be facilitated with high methanol selectivities by copper‐exchanged zeolites. There are however two open questions regarding the use of these zeolites to facilitate the MMC process. The first concerns the possibility of operating the three cycles in the stepwise MMC process by these zeolites in an isothermal fashion. The second concerns the possibility of improving the methanol yields by systematic substitution of some copper centers in these active sites with other earth‐abundant transition metals. Quantum‐mechanical computations can be used to compare methane activation by copper oxide species and analogous mixed‐metal systems. To carry out such screening, it is important that we use theoretical methods that are accurate and computationally affordable for describing the properties of the hetero‐metallic catalytic species. We have examined the performance of 47 exchange‐correlation density functionals for predicting the relative spin‐state energies and chemical reactivities of six hetero‐metallic [M‐O‐Cu]2+ and [M‐O2‐Cu]2+, (where MCo, Fe, and Ni), species by comparison with coupled cluster theory including iterative single, double excitations as well as perturbative treatment of triple excitations, CCSD(T). We also performed multireference calculations on some of these systems. We considered two types of reactions (hydrogen addition and oxygen addition) that are relevant to MMC. We recommend the use of τ‐HCTH and OLYP to determine the spin‐state energy splittings in the hetero‐metallic motifs. ωB97, ωB97X, ωB97X‐D3, and MN15 performed best for predicting the energies of the hydrogen and oxygen addition reactions. In contrast, local, and semilocal functionals do poorly for chemical reactivity. Using [Fe‐O‐Cu]2+ as a test, we see that the nonlocal functionals perform well for the methane CH activation barrier. In contrast, the semilocal functionals perform rather poorly. © 2018 Wiley Periodicals, Inc.
Decellularized breast matrix as bioactive microenvironment for in vitro three‐dimensional cancer culture
Authors: Jin Qin , Liu Gang , Li Shubin , Yuan Haihan , Yun Zhizhong , Zhang Wenqi , Zhang Shu , Dai Yanfeng , Ma Yuzhen
Published: November 2018

Breast cancer (BC) is a leading cause of cancer‐related death in women with unsatisfactory survival rates. Advances in the understanding of the genetic basis of BC provide the opportunity to develop gene‐based medicines capable of treating metastatic diseases. Here, we first demonstrated efficient tissue engineering approaches applied to normal breast and BC extracellular matrix (ECM) starting from decellularized human biopsies to generate a three‐dimensional (3D) bioactive model with the sodium lauryl ether sulfate solution. The decellularized tissues maximized the genetic component removal from tissues and minimally injured ECM structures and native compositions by histology and ECM compositions analyses. Importantly, we proved that the 3D ECM retained tissues biological properties. We demonstrated that after 30 days of recellularization with MCF‐7 cell (human breast adenocarcinoma cell line), the 3D cancer ECM induced an overexpression of epithelial–mesenchymal transition (EMT) and cancer proliferation. Meanwhile, normal ECM from the breast inhibited EMT and cell growth with the inducement of apoptosis. Given the biological activity preserved in the ECM after decellularization, we believe these approaches are powerful tools for future preclinical research for BC and breast development.
A six‐microRNA risk score model predicts prognosis in esophageal squamous cell carcinoma
Authors: Mao Yu , Fu Zhanzhao , Zhang Yunjie , Dong Lixin , Zhang Yanqiu , Zhang Qiang , Li Xin , Wang Chao
Published: November 2018

Esophageal cancer ranks the eighth most common cancer and the sixth most common cause of cancer death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate a wide variety of cancer‐related cellular processes. In the current study, a series of previously published gene expression microarray data from Gene Expression Ominus and The Cancer Genome Atlas were downloaded and further divided into training, internal, and external validation sets. Least absolute shrinkage and selectionator operator Cox regression model along with 10‐fold cross‐validation was performed to select the miRNAs associated with the prognosis of esophageal squamous cell carcinoma (ESCC) and constructed a six‐miRNA signature. Then the prediction accuracy of this signature was assessed in validation and test set using Kaplan–Meier analysis, time‐dependent receiver operating characteristic (ROC) curves and dynamic area under the ROC curve. According to the result, the prediction accuracy of miRNA signature was much better than that of tumor–node–metastasis (TNM) stage in all the three sets. Stratified analysis also demonstrated that the predict ability of this signature was independent of TNM stage. Finally, function experiments including apoptosis and colony formation assay were performed to further reveal the regulatory role of miRNAs in ESCC. Our study demonstrated the promising potential application of this novel six‐miRNA signature as an independent biomarker for survival prediction of ESCC patients.
Toll‐like receptor 3 agonist poly I:C reinforces the potency of cytotoxic chemotherapy via the TLR3‐UNC93B1‐IFN‐β signaling axis in paclitaxel‐resistant colon cancer
Authors: Zhao Jiaojiao , Xue Yaxian , Pan Yuchen , Yao Anran , Wang Guoqun , Li Dan , Wang Tingting , Zhao Shuli , Hou Yayi
Published: November 2018

Type I interferon (IFN) signaling in neoplastic cells has a chemo‐sensitizing effect in cancer therapy. Toll‐like receptor 3 (TLR3) activation promotes IFN‐β production, which induces apoptosis and impairs proliferation in some cancer cells. Herein, we tested whether the TLR3 agonist polyinosinic: polycytidylic acid (poly I:C) can improve chemotherapeutic efficacy in paclitaxel (PTX) resistant cell lines. Human colon cancer cell lines HCT116, SW620, HCT‐8 (sensitive to PTX), and HCT‐8/PTX (resistant to PTX) were treated with poly I:C and the cell viability was measured. Results showed that poly I:C specifically impaired the cell viability of HCT‐8/PTX by simultaneously promoting cell apoptosis and inhibiting cell proliferation. In addition, when TLR3 was overexpressed in HCT‐8/PTX cells, we found that TLR3 contributed to the production of IFN‐β that reduced cell viability, and poly I:C preferentially activated the TLR3‐UNC93B1 signaling pathway to mediate this effect. Moreover, cotreatment of poly I:C and PTX acted synergistically to induce cell apoptosis of HCT‐8/PTX via upregulating the expression of TLR3 and its molecular chaperone UNC93B1, assisting in the secretion of IFN‐β. Notably, a combination of poly I:C and PTX synergistically inhibited the PTX‐resistant tumor growth in vivo without side effects. In conclusion, our studies demonstrate that poly I:C reinforces the potency of cytotoxic chemotherapeutics in PTX‐resistant cell line through the TLR3‐UNC93B1‐IFN‐β signaling pathway, which supplies a novel mechanism of poly I:C for the chemotherapy sensitizing effect in a PTX‐resistant tumor.
Gene expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation
Authors: Jiang He , Hong Tao , Wang Tao , Wang Xinping , Cao Lingling , Xu Xiaoyuan , Zheng Meirong
Published: October 2018

Objective

Osteogenesis is a multiple‐step process through which osteoblasts are derived from bone marrow mesenchymal stem cells (MSCs) with multilineage differentiation potential. This study aimed to analyze gene expression profiling during osteogenic differentiation of MSCs.

Materials and Methods

Human MSCs were isolated and induced for differentiation in osteogenic medium. Full‐genome gene expression microarrays and gene ontology analysis were performed.

Results

A total of 1,680 differentially expressed genes in differentiated MSCs were identified including 430 upregulated and 1,250 downregulated. Moreover, pathway‐act‐network analysis showed that cell cycle, p53 signaling pathway and focal adhesion, had high degree (>5). The ribonucleotide reductase M1, thymidine kinase 1 and histone cluster 1 H3e also showed high degree (>10). Polymerase chain reaction analysis confirmed the differential expression of insulin‐like growth factor binding protein 3, SMAD family member 3, transforming growth factor beta 2, and fibroblast growth factor 14 in differentiated MSCs.

Conclusions

Gene expression profiling provides a foundation to reveal the mechanisms that regulate osteogenic differentiation of MSCs.
Identification of intracellular peptides associated with thermogenesis in human brown adipocytes
Authors: Li Yun , Wang Xing , Wang Fei , You Lianghui , Xu Pengfei , Cao Yan , Chen Ling , Wen Juan , Guo Xirong , Cui Xianwei , Ji Chenbo
Published: November 2018

Objectives

Currently, brown adipose tissue (BAT) is a therapeutic target in obesity and diabetes, but the mechanism of BAT activation remains unclear. Because increasing emphasis has been placed on the role of intracellular peptides in biological processes, we conducted a study to gain insight into the mechanism of BAT activation by using a peptidomic approach and then attempted to identify peptides that are capable of activating BAT.

Methods

In the present study, we generated the peptidomic profile of the intracellular peptides in brown adipocytes treated with forskolin (FSK) using a peptidomic approach. Then, the differentially expressed peptides were evaluated via Gene Ontology (GO) enrichment, KEGG pathway, and protein–protein interaction (PPI) network analysis. Finally, we selected candidate peptides for further validation via assessing the expression levels of UCP‐1 and PGC‐1α in brown adipocytes exposed to the peptides.

Results

A total of 4,370 peptides were identified, of which 951 were upregulated and 379 were downregulated after FSK treatment. Bioinformatic analysis demonstrated that the ECM‐receptor interaction GO term was the most enriched and that collagen alpha‐related proteins exhibited the highest degree of PPI. Four peptides separately derived from TSC22 domain family protein 1 (T22D1), bromodomain and WD repeat‐containing protein 1 (BRWD1), protein piccolo (PCLO), and collagen alpha‐1 (III) chain (CO3A1) increased the expression levels of UCP‐1 and PGC‐1α.

Conclusions

ECM‐receptor interaction may play an important role in the process of FSK‐stimulated BAT activation, and the pT22D1tide, pBRWD1tide, pPCLOtide, and pCO3A1tide peptides potentially promote BAT thermogenesis.
Unloading of intercellular tension induces the directional translocation of PKCα
Authors: Sera Toshihiro , Arai Masataka , Cui Zhonghua , Onose Koichi , Karimi Alireza , Kudo Susumu
Published: November 2018

The migration of endothelial cells (ECs) is closely associated with a Ca2+‐dependent protein, protein kinase Cα (PKCα). The disruption of intercellular adhesion by single‐cell wounding has been shown to induce the directional translocation of PKCα. We hypothesized that this translocation of PKCα is induced by mechanical stress, such as unloading of intercellular tension, or by intercellular communication, such as gap junction‐mediated and paracrine signaling. In the current study, we found that the disruption of intercellular adhesion induced the directional translocation of PKCα even when gap junction‐mediated and paracrine signaling were inhibited. Conversely, it did not occur when the mechanosensitive channel was inhibited. In addition, the strain field of substrate attributable to the disruption of intercellular adhesion tended to be larger at the areas corresponding with PKCα translocation. Recently, we found that a direct mechanical stimulus induced the accumulation of PKCα at the stimulus area, involving Ca
2+ influx from extracellular space. These results indicated that the unloading of intercellular tension induced directional translocation of PKCα, which required Ca
2+ influx from extracellular space. The results of this study indicate the involvement of PKCα in the Ca
2+ signaling pathway in response to mechanical stress in ECs.
HDAC3 inhibition disrupts the assembly of meiotic apparatus during porcine oocyte maturation
Authors: Gu Ling , Li Xiaoyan , Liu Xiaohui , Gao Min , He Yongfu , Xiong Bo , Liu Honglin
Published: October 2018

Histone deacetylases (HDACs) are involved in a wide array of biological processes. However, the role of HDAC3 in porcine oocytes remains unclear. In the current study, we examine the effects of HDAC3 inhibition on porcine oocyte maturation using RGFP966, a selective HDAC3 inhibitor. We find that suppression of HDAC3 activity prevents not only the expansion of cumulus cells but also the meiotic progression of oocytes. It is interesting to note that HDAC3 displays a spindle‐like distribution pattern as the porcine oocytes enter meiosis. In line with this, confocal microscopy reveals the high frequency of spindle defects and chromosomal congression failure in metaphase oocytes exposed to RGFP966. Moreover, HDAC3 inhibition results in the hyperacetylation of α‐tubulin during oocyte meiosis. These findings indicate that HDAC3 activity might control the microtubule stability via the deacetylation of tubulin, which is critical for maintaining the proper spindle assembly, accurate chromosome separation, and orderly meiotic progression during porcine oocyte maturation.
miR‐21 and miR‐19b delivered by hMSC‐derived EVs regulate the apoptosis and differentiation of neurons in patients with spinal cord injury
Authors: Xu Guanghui , Ao Rongguang , Zhi Zhongzheng , Jia Jianbo , Yu Baoqing
Published: November 2018

Background

In this study, we aimed to evaluate the therapeutic effects of extracellular vesicles (EVs), which were collected from differentiated PC12 cells and mesenchymal cells (MSCs), on the treatment of spinal cord injury (SCI). In addition, we aimed to identify miRNAs related to the inhibitory effect of EVs against cell apoptosis.

Methods

Electron microscopy was used to observe the distributions of EVs in the samples. Real‐time PCR, western blot, thiazolyl blue tetrazolium bromide (MTT) assay, and flow cytometry were performed to establish the molecular signaling pathway underlying the effect of EVs in SCI. In addition, a Basso–Beattie–Bresnahan (BBB) score system, Nissl staining, immunohistochemistry assay, and TdT‐mediated dUTP nick‐end labeling (TUNEL) assay were conducted to validate the molecular signaling pathway established above.

Results

The expression of miR‐21 and miR‐19b was upregulated in EVs isolated from induced PC12 cells and MSCs, along with decreased expression of phosphatase and tensin homolog (PTEN) messenger RNA (mRNA)/protein and a lower level of cell apoptosis. The transfection of miR‐21/miR‐19b precursors into the cells also exhibited an inhibitory effect on cell apoptosis. In addition, in‐silicon analysis and luciferase assays validated the role of PTEN as a virtual target of miR‐21/miR‐19b. Finally, the BBB scores and Nissl staining also validated the therapeutic effects of EVs derived from differentiated P12 cells/MSCs in SCI rats. Accordingly, the negative correlations between miR‐21/miR‐19b and PTEN mRNA/protein were implicated in the post‐SCI recovery.

Conclusions

The increased levels of miR‐21/miR‐19b in the EVs derived from differentiated PC12 cells and MSCs suppresses the apoptosis of neuron cells by downregulating the expression of PTEN.
Thymoquinone‐induced antitumor and apoptosis in human lung adenocarcinoma cells
Authors: Samarghandian Saeed , Azimi‐Nezhad Mohsen , Farkhondeh Tahereh
Published: November 2018

Background

Lung cancer has been associated with the highest cancer‐associated mortality rate in the world. Chemotherapeutic management of cancer necessitates introducing new promising agents. Plants represent a rich source of new antineoplastic and chemotherapeutic agents. Thymoquinone (TQ), the main constituent of Nigella sativa (black seed or black cumin), has shown potent antioxidant and anti‐inflammatory activities so far. The purpose of the current study was to evaluate the antineoplastic potential of TQ and their underlying mechanisms in A549 cells (human lung cancer cell line).

Method

The A549 cells were treated with the different concentrations of TQ for three following days. Cell viability was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Necrosis and apoptosis were assessed by fluorescence‐activated cell sorter analysis through propidium iodide and annexin V staining and also by assessing caspase‐3 and ‐9 activation. DNA fragmentation was monitored by gel electrophoresis.

Results

TQ decreased the viability and increased apoptotic cell death in A549 human lung tumor cells. TQ treatment significantly elevated the Bax/
Bcl‐2 ratio in the lung cancer cells. TQ also upregulated p53 expression, another apoptotic modulator in A549 cancer cells. TQ also activated caspase‐dependent apoptosis by the activation of caspases‐3 and ‐9.

Conclusion

Our results proposed that TQ may be a potential new therapeutic agent for the management of lung cancer. TQ promoted apoptosis in A546 lung cancer cells by the activation of p53 and caspase cascade dependent pathways.
Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass
Authors: Chen Huang‐Jen , Wang Ching‐Chia , Chan Ding‐Cheng , Chiu Chen‐Yuan , Yang Rong‐Sen , Liu Shing‐Hwa
Published: October 2018

Background

Acrolein is an extremely electrophilic aldehyde. Increased urinary acrolein adducts have been found in type 2 diabetic patients and people with a smoking habit. The increased blood acrolein was shown in patients who received the cancer drug cyclophosphamide. Both diabetes and smoking are risk factors for skeletal muscle wasting or atrophy. Acrolein has been found to induce myotube atrophy in vitro. The in vitro and in vivo effects and mechanisms of acrolein on myogenesis and the in vivo effect of acrolein on muscle wasting still remain unclear.

Methods

C2C12 myoblasts were used to assess the effects of low‐dose acrolein (0.125–1 μM) on myogenesis in vitro. Mice were exposed daily to acrolein in distilled water by oral administration (2.5 and 5 mg/kg) for 4 weeks with or without glycerol‐induced muscle injury to investigate the effects of acrolein on muscle wasting and regeneration.

Results

Non‐cytotoxic‐concentration acrolein dose dependently inhibited myogenic differentiation in myoblasts (myotube formation inhibition: 0.5 and 1 μM, 66.25% and 46.25% control, respectively, n = 4, P < 0.05). The protein expression for myogenesis‐related signalling molecules (myogenin and phosphorylated Akt: 0.5 and 1 μM, 85.15% and 51.52% control and 62.63% and 56.57% control, respectively, n = 4, P < 0.05) and myosin heavy chain (MHC: 0.5 and 1 μM, 63.64% and 52.53% control, n = 4, P < 0.05) were decreased in acrolein‐treated myoblasts. Over‐expression of the constitutively active form of Akt in myoblasts during differentiation prevented the inhibitory effects of acrolein (1 μM) on myogenesis (MHC and myogenin protein expression: acrolein with or without constitutively active Akt, 64.65% and 105.21% control and 69.14% and 102.02% control, respectively, n = 5, P < 0.05). Oral administration of acrolein for 4 weeks reduced muscle weights (5 mg/kg/day: 65.52% control, n = 6, P < 0.05) and cross‐sectional area of myofibers in soleus muscles (5 mg/kg/day: 79.92% control, n = 6, P < 0.05) with an up‐regulation of atrogin‐1 and a down‐regulation of phosphorylated Akt protein expressions. Acrolein retarded soleus muscle regeneration in a glycerol‐induced muscle regeneration mouse model (5 mg/kg/day: 49.29% control, n = 4, P < 0.05). Acrolein exposure reduced muscle endurance during rotarod fatigue performance in mice with or without glycerol‐induced muscle injury (5 mg/kg/day without glycerol: 30.43% control, n = 4, P < 0.05). Accumulation of acrolein protein adducts could be detected in the soleus muscles of acrolein‐treated mice.

Conclusions

Low‐dose acrolein significantly inhibited myogenic differentiation in vitro, which might be through inhibition of Akt signalling. Acrolein induced muscle wasting and retarded muscle regeneration in mice. These results suggest that acrolein may be a risk factor for myogenesis and disease‐related myopathy.
Multinodular fatty change in the liver in three patients with chronic hepatic porphyria: Contribution of sonography to the diagnosis
Authors: Naganuma Hiroko , Ishida Hideaki , Yoshida Makoto , Funaoka Masato , Ito Shuichi , Ohyama Yoko
Published: October 2018

We present three cases of chronic hepatic porphyria (CHP) in alcoholic patients, in which grayscale ultrasound (US) revealed multiple echogenic masses in the liver, mimicking multinodular hepatocellular carcinoma on alcoholic liver injury. In all cases, contrast‐enhanced US (CEUS) showed iso‐enhancement of the mass lesions throughout all vascular phases. Additionally, two‐dimensional shear wave elastography (2DSWE) (performed in two cases) revealed the mass to have almost the same SWE value as the surrounding parenchyma. When encountering alcoholic patients with multiple echogenic masses in the liver, CHP must be included in the differential diagnosis. CEUS and 2DSWE allow us to increase our diagnostic confidence of CHP.
High‐resolution GC/MS studies of a light crude oil fraction
Authors: Kondyli Aikaterini , Schrader Wolfgang
Published: October 2018

The continuous development in analytical instrumentation has brought the newly developed Orbitrap‐based gas chromatography / mass spectrometry (GC/MS) instrument into the forefront for the analysis of complex mixtures such as crude oil. Traditional instrumentation usually requires a choice to be made between mass resolving power or an efficient chromatographic separation, which ideally enables the distinction of structural isomers that is not possible by mass spectrometry alone. Now, these features can be combined, thus enabling a deeper understanding of the constituents of volatile samples on a molecular level. Although electron ionization is the most popular ionization method employed in GC/MS analysis, the need for softer ionization methods has led to the utilization of atmospheric pressure ionization sources. The last arrival to this family is the atmospheric pressure photoionization (APPI), which was originally developed for liquid chromatography / mass spectrometry (LC/MS). With a newly developed commercial GC‐APPI interface, it is possible to extend the characterization of unknown compounds. Here, first results about the capabilities of the GC/MS instrument under high or low energy EI or APPI are reported on a volatile gas condensate. The use of different ionization energies helps matching the low abundant molecular ions to the structurally important fragment ions. A broad range of compounds from polar to medium polar were successfully detected and complementary information regarding the analyte was obtained.
The strategic configurations as a contingency factor in the success of operational risk measures
Authors: Amedzro St‐Hilaire Walter
Published: October 2018

The loan loss provisions and risk measures may be needed to examine the repercussions on the advancing approach profitability. The more loan loss provision, capital adequacy ratio, and risks measures are accurate, the more banks can enhance their profitability and cater the need of their target audience. Loan loss provisions are increasing in the tax rate for countries that permit general provision tax deductibility. They have a negative relationship with profitability of financial institution.
Synergistic Influence of pH and Temperature on Rheological Behavior of Adhesive Emulsions Stabilized with Micelle Dispersion of an Anionic Surfactant
Authors: Kundu Partha , Kumar Vimal , Scales Peter J. , Mishra Indra Mani
Published: October 2018

The influence of emulsion pH and temperature on the rheological behavior of adhesive oil‐in‐water (o/w) emulsions stabilized with an anionic surfactant (sodium dodecyl benzene sulfonate, SDBS) was studied. The flow properties of emulsions as a complex fluid were investigated using steady and dynamic rheometry for characterization of non‐Newtonian behavior. Emulsion pH was varied from 2 to 12 and temperature was varied from 20 to 50 °C, respectively. The influences of the above‐mentioned variables on the rheology of o/w emulsion were studied using steady‐shear and dynamic oscillatory experiments. Various viscosity models (2, 3, and 4 parameter rheological model) were used to predict the rheological parameters. An increase in the pH of the emulsion led to an increase in the emulsion stability, viscosity, and viscoelastic properties (
G′,
G″,
η*, and tan δ), and a decrease in the mean droplet size of the emulsion. A decrease in the temperature yields higher values of steady‐shear viscosity and viscoelastic properties upon a decrease in droplet size. Emulsions were characterized as flocculated structured liquid exhibiting a characteristic crossover frequency (
ω*) within the range of angular frequency studied in oscillatory measurements. Overall, emulsions exhibited non‐Newtonian shear‐thinning behavior and the synergy of pH and temperature significantly influences the emulsion rheology.
Randomized controlled trial comparing short‐term outcomes of laparoscopic and open spleen‐preserving splenic hilar lymphadenectomy for advanced proximal gastric cancer: An interim report
Authors: Guo Xin , Peng Zheng , Lv Xiaohui , Cui Jianxin , Zhang Kecheng , Li Jiyang , Jin Naizhong , Xi Hongqi , Wei Bo , Chen Lin
Published: October 2018

Background and Objectives

We compared the clinical outcomes of laparoscopic and open spleen‐preserving splenic hilar lymphadenectomy (LSPL and OSPL) for gastric cancer.

Methods

We performed a single‐center, randomized, controlled trial to compare the short‐term surgical outcomes between LSPL and OSPL. The study was registered in ClinicalTrials.gov (NCT02980861).

Results

A total of 222 patients were enrolled (114 in the LSPL group and 108 in the OSPL group). There were no significant differences between the two groups in operative time (P = 0.152), a number of harvested lymph nodes (P = 0.669) including no. 10 lymph nodes (2.1 ± 1.4 vs 2.3 ± 1.2,P = 0.713). The time taken for no. 10 lymph node dissection was similar in both groups (13.9 ± 10.4 vs 15.2 ± 9.4 minutes,P = 0.217); however, the LSPL group experienced less total blood loss (P < 0.001) and less blood loss during no. 10 lymph node dissection compared with the OSPL group (15.3 ± 37.8 vs 29.5 ± 36.4 mL,P < 0.001). The postoperative complication rates of LSPL and OSPL were 18.3% and 16.1%, respectively (P = 0.331).

Conclusion

LSPL is a safe and feasible surgical procedure in no. 10 LN dissection for patients with advanced proximal gastric cancer. Thus, this prospective trial is continuing.
Impact of delayed care on surgical management of patients with gastric cancer in a low‐resource setting
Authors: Martin Allison N. , Silverstein Allison , Ssebuufu Robinson , Lule Joseph , Mugenzi Pacifique , Fehr Alexandra , Mpunga Tharcisse , Shulman Lawrence N. , Park Paul H. , Costas‐Chavarri Ainhoa
Published: October 2018

Background

Gastric cancer is the fifth most common cancer in Eastern Africa. Diagnostic delays in low‐resource countries result in advanced disease presentation. We describe perioperative management of gastric cancer in Rwanda.

Methods

A retrospective review of records at three hospitals was performed to identify gastric adenocarcinoma cases from January 2012 to June 2016. Multiple perioperative and tumor‐related variables were collected. Descriptive and bivariate analyses were performed.

Results

The final analysis included 229 patients with gastric cancer. Median age was 58 years (interquartile range [IQR] 49‐65) and 49.6% were female (n = 114). Patients reported symptoms (ie, weight loss, epigastric pain) for a median time of 12 months (IQR 7.5‐24). On presentation, 18.8% (
n = 43) had gastric outlet obstruction; 13.5% (
n = 31) had a palpable mass. Fifty‐one percent (
n = 117) underwent an operation; of these, 74% (
n = 86) received gastrojejunostomy or were inoperable; and 29% (
n = 34) underwent curative resection. Palliative care referrals were made for 9% (
n = 20). Pathology reports were available for 190 patients (83.0%). Only 11.3% (
n = 26) had
Helicobacter pylori (
H. pylori) testing of which 65.4% tested positive (
n = 17).

Conclusions

A majority of patients presented with advanced disease. Very few patients had a curative resection. Significant advances in diagnosis and treatment are needed to improve the care of gastric cancer patients in Rwanda.
Effect of Hepatic Artery Spasm on a Rat Model of Hepatic Ischemia‐Reperfusion Injury
Authors: Tang Hui , Qu En‐ze , Li Kun , Ye Lin‐sen , Zhang Qi , Yang Yang , Chen Gui‐hua , Zhang Ying‐cai
Published: October 2018

Objectives

To investigate hemodynamic changes in the hepatic artery after hepatic ischemia‐reperfusion injury (IRI) in rats via ultrasound (US) imaging and to discuss the protective effect of phentolamine (PHT) pretreatment on hepatic IRI.

Methods

Fifty rats were randomly divided into 3 groups: a sham operation group (n = 10), a control ischemia‐reperfusion group (n = 20), and a PHT pretreatment group (n = 20). Color Doppler flow imaging and contrast‐enhanced US examinations were performed in each group at 30 minutes (n = 10) and 90 minutes (n = 10) after reperfusion. Blood samples were obtained to analyze serum alanine aminotransferase and aspartate aminotransferase levels, and liver tissue specimens were collected for pathologic analysis.

Results

Using US, we found that hepatic artery resistance at 30 minutes after reperfusion in the control group was higher than that in the sham group (mean resistive index [RI] ± SD, 0.65 ± 0.09 versus 0.50 ± 0.09; P < .01), which was higher at 30 than 90 minutes (RI, 0.65 ± 0.09 versus 0.50 ± 0.08; P < .01) after reperfusion in the control group. However, the hepatic artery resistance and liver microcirculation in the PHT group were better than those in the control group at 30 minutes after reperfusion (RI, 0.54 ± 0.09 versus 0.65 ± 0.09; P < .05; time to peak, 31.94 ± 2.02 versus 48.34 ± 4.74 seconds; P < .01). Compared to the control group, the aspartate aminotransferase and alanine aminotransferase levels were significantly lower at 30 minutes after reperfusion in the PHT group (P < .05). A pathologic examination revealed a smaller hepatic artery diameter and a depressed vessel wall in the control group.

Conclusions

The hepatic artery can undergo a transient spasm during the hepatic IRI process, which can exacerbate liver damage. Phentolamine treatment can alleviate hepatic artery spasms, improve liver perfusion, and reduce liver injury by ameliorating the hepatic microcirculation.
Propagation Imaging in the Demonstration of Common Shear Wave Artifacts
Authors: Dubinsky Theodore J. , Shah Hardik U. , Erpelding Todd N. , Sannananja Bhagya , Sonneborn Rachelle , Zhang Man
Published: October 2018

In this article, we describe our experience with shear wave propagation imaging (SWPI) as an adjunct to 2‐dimensional (2D) shear wave elastography (SWE) in a cohort of patients being evaluated for diffuse liver disease. Two‐dimensional SWE has been extensively studied in previous publications; however, 2D SWE using propagation images has not been widely described in the literature to date. We observed that when certain artifacts occurred on the color elastograms, highly characteristic changes to shear wave propagation contours were seen, which can help clarify the cause of the artifacts. To our knowledge, the use of SWPI to explain the etiology of artifacts has never been published before. The artifacts described in this article include the capsule reverberation artifact, penetration limitation or dropout artifact, artifact due to blood vessels, shadowing artifact, tissue motion artifact, and near‐field distortion/precompression artifact. Hence, the purpose of this article is to show examples of common artifacts seen on 2D SWE as depicted on corresponding SWPI to demonstrate that both types of image displays are complementary to each other.
Assessment of Liver Graft Steatosis: Where Do We Stand?
Authors: Cesaretti Manuela , Addeo Pietro , Schiavo Luigi , Anty Rodolphe , Iannelli Antonio
Published: October 2018

The growing number of patients on waiting lists for liver transplantation and the shortage of organs have forced many centers to adopt extended criteria for graft selection, moving the limit of acceptance for marginal livers. Steatotic grafts that were, in the past, considered strictly unacceptable for transplantation because of the high risk of early nonfunction are now considered as a potential resource for organ implementation. Several methods to diagnose, measure, classify, and stage steatosis exist, but none can be considered qualitatively and quantitatively “the ideal method” to date. Clinical, biological, and imaging data can be very helpful to estimate graft steatosis, but histology still remains the gold standard. There is an increasing need for rapid and reliable tools to assess graft steatosis. Herein, we present a comprehensive review of the approaches that are currently used to quantify steatosis in liver grafts.
The effects of promotional package frames and price strategies on inaction inertia
Authors: Liu Hsin‐Hsien , Chou Hsuan‐Yi
Published: October 2018

Inaction inertia is the phenomenon in which people are less likely to accept a less attractive opportunity after having missed a relatively more attractive one. Previous studies have mainly explored the inaction inertia effect on single products or services, whereas this study explored how the promotional frames of sales packages influence inaction inertia toward the individual items within the sales packages and the inaction inertia effect of the target product under different price strategies. On the basis of the cost assignments of mental accounting and comparisons of the current inferior promotion with missed superior promotion, this study found evidence that when consumers encounter a freebie (bundle) condition, they assign a higher cost to the focal (supplementary) product and a lower cost to the supplementary (focal) product. Therefore, consumers who have missed a freebie (bundle) promotion exhibit lower (higher) inaction inertia toward the focal product, but higher (lower) inaction inertia toward the supplementary product. Applying a similar internal mechanism to pricing strategies, the findings also show that when consumers encounter a two‐component sales package with a surcharge promotion using a partitioned price (vs. a price discount promotion using an all‐inclusive price), they assign a higher cost to the base product and a lower cost to the surcharge. So, consumers who have missed the surcharge (vs. price discount) promotion show higher inaction inertia when the surcharge of the current inferior opportunity is salient, but show less inaction inertia when it is not salient. Moreover, the percent of a surcharge as a part of the total package value moderates the impact of promotional price strategy frames on inaction inertia. These findings have significant implications for both theoreticians and practitioners interested in inaction inertia, promotional frames, and price strategies.
Synthesis of Functional Polymer Particles from Morita–Baylis–Hillman Polymerization
Authors: Ramakers Gijs , D'Incal Claudio , Gagliardi Mick , Molin Daniël G. M. , Junkers Tanja
Published: November 2018

Functional synthetic polymers are frequently explored for their use in the biomedical field. To fulfill the stringent demands of biodegradability and compatibility, the materials need to be versatile and tunable. Post‐modification is often considered challenging for well‐known degradable materials like poly(lactic acid) because of their chemical inertness. In this work a procedure is proposed to produce densely functionalized polymer particles using oligomeric precursors synthesized via the Morita–Baylis–Hillman reaction. This allows for a variety of post‐modification reactions to serve bio‐conjugation or tuning of the material properties. The particles are subjected to basic media and found to be degradable. Furthermore, cytotoxicity tests confirm good biocompatibility. Finally, as a proof of concept to demonstrate the versatility of the particles, post‐modification reactions are carried out through the formation of imines.
Environmentally Adaptable and Temperature‐Selective Self‐Healing Polymers
Authors: Ju Sung Hwan , Kim Jin Chul , Noh Seung Man , Cheong In Woo
Published: November 2018

Development of polymeric materials capable of self‐healing at low temperatures is an important issue since their mechanical strength and self‐healing performance are often in conflict with each other. Herein, random copolymers with self‐healing capability in a wide temperature range prepared from 2‐(dimethylamino)ethyl methacrylate (DMAEMA), glyceryl monomethacrylate (GlyMA), and butyl methacrylate monomers via free‐radical polymerization and subsequent cross‐linking with hexamethylene diisocyanate are reported. Wound closure is facilitated by swelling below the lower critical solution temperature or by heating above the glass transition temperature (T

g) of the polymer. GlyMA units form metal–ligand coordination complexes with dibutyltin dilaurate, leading to the formation of new carbonate bonds under ambient CO2 and H2O conditions. Although swelling/heating reduces the polymer's mechanical strength, it is fully restored following chemical re‐bonding/drying at room temperature. The swelling and degree of scratch healing are affected by pH, temperature, and the DMAEMA content.