bluuebunny/crossref_metadata_2025 huggingface dataset:
Focal Adhesion Kinase and β‐Catenin Cooperate to Induce Hepatocellular Carcinoma
Authors: Shang Na , Wang Hao , Bank Thomas , Perera Aldeb , Joyce Cara , Kuffel Gina , Zilliox Michael J. , Cotler Scott J. , Ding Xianzhong , Dhanarajan Asha , Breslin Peter , Qiu Wei
Published: May 2019

There is an urgent need to understand the molecular signaling pathways that drive or mediate the development of hepatocellular carcinoma (HCC). The focal adhesion kinase (FAK) gene protein tyrosine kinase 2 is amplified in 16.4% of The Cancer Genome Atlas HCC specimens, and its amplification leads to increased FAK mRNA expression. It is not known whether the overexpression of FAK alone is sufficient to induce HCC or whether it must cooperate in some ways with other oncogenes. In this study, we found that 34.8% of human HCC samples with FAK amplification also show β‐catenin mutations, suggesting a co‐occurrence of FAK overexpression and β‐catenin mutations in HCC. We overexpressed FAK alone, constitutively active forms of β‐catenin (CAT) alone, or a combination of FAK and CAT in the livers of C57/BL6 mice. We found that overexpression of both FAK and CAT, but neither FAK nor CAT alone, in mouse livers was sufficient to lead to tumorigenesis. We further demonstrated that FAK’s kinase activity is required for FAK/CAT‐induced tumorigenesis. Furthermore, we performed RNA‐sequencing analysis to identify the genes/signaling pathways regulated by FAK, CAT, or FAK/CAT. We found that FAK overexpression dramatically enhances binding of β‐catenin to the promoter of androgen receptor (AR), which leads to increased expression of AR in mouse livers. Moreover, ASC‐J9, an AR degradation enhancer, suppressed FAK/CAT‐induced HCC formation. Conclusion: FAK overexpression and β‐catenin mutations often co‐occur in human HCC tissues. Co‐overexpression of FAK and CAT leads to HCC formation in mice through increased expression of AR; this mouse model may be useful for further studies of the molecular mechanisms in the pathogenesis of HCC and could lead to the identification of therapeutic targets.
The effects of the financial crisis on the general and dental health status of Greek citizens
Authors: Vlasiadis Konstantinos , Samaritaki Euaggelia , Koutsamani Maria , Konstantinidis Theocharis , Tzoutzas Ioannis G.
Published: May 2019

Purpose

To present the impact of the financial crisis on health status and dental health in Greece and compare it to the European Union and Finland and to identify any changes in health‐related expenditure focusing on pharmaceutical expenditure and generic medicines.

Design/methodology/approach

Databases as Scopus, Pubmed, Google Scholar, World Health Organization, Eurostat, and Elstat were used.

Findings

Indicators, such as mortality and life expectancy, show that there is no clear correlation between health deterioration and financial crisis while dental health has deteriorated. Out‐of‐pocket expenses were found to be catastrophic, and the use of generic medicines is still limited.

Practical implications

Proper prescribing of medicines, coverage of health care costs by the government, and cost savings from the use of generic medicines were implemented. As regards dental care, the state should focus on prevention as well as reinforcement of public dental care services.

Originality/value

The break through idea is to compare the impact of the financial crisis on health indexes in Greece with the European Union and Finland, to focus on pharmaceutical expenditure, generic medicines, and dental health.
Stimuli‐responsive poly(hydroxyethyl methacrylate) hydrogels from carboxylic acid‐functionalized crosslinkers
Authors: Bingol H. Betul , Agopcan‐Cinar Sesil , Bal Tugba , Oran D. Ceren , Kizilel Seda , Kayaman‐Apohan Nilhan , Avci Duygu
Published: May 2019

Tailoring hydrogel properties by modifications of the crosslinker structure is a good method for the design of hydrogels with a wide range of properties. In this study, two novel carboxylic acid‐functionalized dimethacrylate crosslinkers (1a and 2a) are synthesized by the reaction of poly(ethylene glycol) or 2‐hydroxyethyl disulfide with tert‐butyl α‐bromomethacrylate followed by cleavage of tert‐butyl groups using trifluoroacetic acid. Their copolymerization reactivity with 2‐hydroxyethyl methacrylate (HEMA) investigated by photopolymerization studies performed on photo‐differential scanning calorimetry shows higher reactivity of 2a compared to 1a. These crosslinkers are then used at different ratios for fabrication of pH‐ and redox‐responsive poly(2‐hydroxyethyl methacrylate)‐based hydrogels. The swelling behavior of the hydrogels is found to be dependent on the structure of the crosslinker, degree of crosslinking, pH, and CaCl2 concentration. The redox‐responsive behavior is demonstrated by degradation of the hydrogel upon exposure to 1,4‐dithiothreitol. The dye Rhodamine 6G and the drug resorcinol are used as models to demonstrate the pH and redox dependent release of loaded compounds from the hydrogels. The electrostatic interactions between the carboxylate groups and the positively charged R6G are found to govern the release profile in DTT and counteract the diffusion of dye molecules and significant amount of release (79% in 120 hr) occurs only at highly acidic conditions. The degradation mediated release in DTT is observed better in case of resorcinol (around 88% in 5 hr). Overall, these hydrogels can be regarded as good candidates for several applications, such as matrices for controlled release, tissue repair, and regeneration.
Employee disputes and CEO turnover: Evidence from labor lawsuits
Authors: Unsal Omer , Rayfield Blake
Published: May 2019

In this study, we use a unique hand‐collected data set of employee lawsuits to understand the effect of litigation on CEO turnover. We gather 28,258 employee disputes (after initial court hearing) dating between the years 2000 and 2014 to test the relationship between executive turnover following employee allegations. We find increased turnover of CEOs following labor lawsuits. Additional analysis suggests that, following the lawsuits, CEO compensation decreases and becomes more sensitive to cash holding. Our results show that employee lawsuits have an impact on CEO turnover, regardless of the case outcome or motivation. Overall, we document the importance of employee treatment in the workplace. We conclude employee treatment may impact both the tenure and future job prospects of a CEO.
Some evidence on the impact of internal audit on external audit fees
Authors: Hazami‐Ammar Sourour
Published: May 2019

We examine responses of 2,160 internal auditors to a global survey of the internal auditing profession carried out by the Institute of Internal Auditors Research Foundation from 2009 to 2013. We found that when the internal audit function's (IAF's) quality is high, the external audit fees will be low. This result confirms the substitution effect. We also found that when internal audit hours work increase, audit fees will be high; indicating a complementary effect between these variables. The internal auditor can be the external audit assistant and fully engaged in specific monitoring and control tasks. Nevertheless, he also may be an independent partner of an external audit and fully engaged in corporate governance. If the external auditor apprehends that audit risk is low due to the quality of the IAF, he will require lower fees. If the IAF's work devoted to external audit is high, a signal of a great firm commitment in reinforcing corporate governance is transmitted. Such signal proves the company's willingness to invest more in improving the external audit quality and fees will be high.
Fair value, management discretion, and audit fees: An empirical analysis
Authors: Miah Muhammad Shahin
Published: May 2019

The main objective of this study is to investigate the impact of complexity resulting from fair value adoption on audit fees. Using a sample of 9,619 firm‐year observations from the United States, this study finds that auditors charge higher audit fees for firms exposed to higher level of complexity due to fair value adoption. More specifically, this study focuses on research and development expenditure, intangibles, goodwill, and property, plant and equipment to compute the intensity of complexity as these items are heavily affected by the fair value which is subject to management discretion. The results suggest that the greater level of complexity arising from the above sources increase auditors' efforts and risks level, thereby, results in higher audit fees. Further analysis, however, shows that auditors do not charge additional audit fees for complexity arising from goodwill if they have intangibles. It is because of economies of scale by auditors, they design their audit program which covers goodwill audit when they do audit for intangibles. Overall, the results support the proposition that judgmental or discretionary choice available for management increases audit risks, and auditors, to compensate higher risks, charge greater audit fees.
Role of microRNAs in osteogenesis of stem cells
Authors: Moghaddam Tayebe , Neshati Zeinab
Published: May 2019

Osteogenic differentiation is a controlled developmental process in which external and internal factors including cytokines, growth factors, transcription factors (TFs), signaling pathways and microRNAs (miRNAs) play important roles. Various stimulatory and inhibitory TFs contribute to osteogenic differentiation and are responsible for bone development. In addition, cross‐talk between several complex signaling pathways regulates the osteogenic differentiation of some stem cells. Although much is known about regulatory genes and signaling pathways in osteogenesis, the role of miRNAs in osteogenic differentiation still needs to be explored.

miRNAs are small, approximately 22 nucleotides, single‐stranded nonprotein coding RNAs which are abundant in many mammalian cell types. They paly significant regulated roles in various biological processes and serve as promising biomarkers for disease states. Recently, emerging evidence have shown that miRNAs are the key regulators of osteogenesis of stem cells. They may endogenously regulate osteogenic differentiation of stem cells through direct targeting of positive or negative directors of osteogenesis and depending on the target result in the promotion or inhibition of osteogenic differentiation.

This review aims to provide a general overview of miRNAs participating in osteogenic differentiation of stem cells and explain their regulatory effect based on the genes targeted with these miRNAs.
Improved bladder smooth muscle cell differentiation of the mesenchymal stem cells when grown on electrospun polyacrylonitrile/polyethylene oxide nanofibrous scaffold
Authors: Fakhrieh Maryam , Darvish Maryam , Ardeshirylajimi Abdolreza , Taheri Mohammad , Omrani Mir Davood
Published: May 2019

Reconstruction of the bladder wall plays an important role in improving its function in patients with urinary bladder dysfunction. Tissue engineering has been trying to introduce biocompatible nanofibers as scaffolds for bladder wall matrix substitutes. In this study a composite nanofibrous scaffold was fabricated from polyacrylonitrile (PAN) and polyethylene oxide (PEO) blend by electrospinning method and then its morphological and mechanical characteristics was evaluated by scanning electron microscopy (SEM), tensile, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays. Then smooth muscle cell (SMC) differentiation supportive capacity of PAN‐PEO nanofibers was investigated by culturing of human adipose tissue‐derived mesenchymal stem cells (AT‐MSCs) on this scaffold and then its differentiation potential in different groups was investigated using SMC‐related gene and protein markers. SEM and MTT results demonstrated that PAN‐PEO supported AT‐MSCs attachment, growth and proliferation, especially at early times after cell seeding. The obtained results from real‐time reverse transcription polymerase chain reaction revealed that collagen‐I‐α1, collagen‐III‐α1, α‐smooth muscle actin (α‐SMA), calponin1, SM22α, caldesmon1, elastin, and myosin heavy chain (MHC) genes were expressed in AT‐MSCs cultured on PAN‐PEO significantly higher than those stem cells that cultured on the culture plate as a control. In addition α‐SMA and MHC proteins were also expressed in AT‐MSCs cultured on PAN‐PEO significantly higher than control. According to the results PAN‐PEO nanofibrous scaffold showed a positive AT‐MSCs‐seeded PAN‐PEO has a great promising potential to use in bladder tissue engineering applications.
Elevation of circ‐PITX1 upregulates interleukin 17 receptor D expression via sponging miR‐518a‐5p and facilitates cell progression in glioma
Authors: Zhan Lan , Mu Zhuang , Yang Mingchun , Zhang Tianyu , Li Hui , Qian Lili
Published: May 2019

Glioma (GM) is one of the major global health problems across the world. Circular RNAs (circRNAs) have been increasingly identified and characterized in almost every aspect of biology, especially in cancer biology. This study desires to investigate the mechanism of circ‐PITX1 on regulating GM development. Quantitative reverse‐transcription polymerase chain reaction was carried out to measure the expression of circ‐PITX1, which was upregulated in matched cancerous tissues and adjacent noncancerous tissues from 52 patients and four cell lines of GM. Fisher's exact indicated the upregulation of circ‐PITX1 was associated with patients' tumor size and World Health Organization grade. Gain and loss‐of‐function assays demonstrated that circ‐PITX1 could facilitate the growth, migration, and invasion and inhibit cell apoptosis in GM cell lines. What's more, circ‐PITX1 sponges miR‐518a‐5p to release its repression on 3′‐untranslated region (3′UTR) of interleukin 17 receptor D (IL17RD) messenger RNA to exert its oncogenic functions in GM cells proved by dual‐luciferase reporter and rescue assays. Taken together, circ‐PITX1 may play a critical role in GM and may be used as a therapeutic target for GM.
lncRNA DILC is downregulated in osteoarthritis and regulates IL‐6 expression in chondrocytes
Authors: Huang Junfeng , Liu Lijun , Yang Jinxing , Ding Jinglun , Xu Xu
Published: May 2019

Excessive production of interleukin 6 (IL‐6) is involved in the pathogenesis of osteoarthritis. It has been reported that long noncoding RNA (lncRNA) DILC inhibited IL‐6 to regulate liver cancer stem cells. Therefore, lncRNA DILC may also participate in osteoarthritis. We found that lncRNA DILC was downregulated, while IL‐6 was upregulated in plasma of osteoarthritis patients comparing to the control group. Levels of plasma lncRNA DILC and IL‐6 were significantly and inversely correlated only in patients with osteoarthritis. Downregulation of lncRNA DILC effectively distinguished patients with osteoarthritis from the control group. Overexpression of lncRNA DILC resulted in inhibited IL‐6 expression in chondrocytes, while treatment with exogenous IL‐6 did not affect lncRNA DILC expression. However, lncRNA DILC overexpression did not affect the proliferation and apoptosis of chondrocytes. Therefore, lncRNA DILC is downregulated in osteoarthritis and regulates IL‐6 expression in chondrocytes.
A conserved asparagine in a ubiquitin‐conjugating enzyme positions the substrate for nucleophilic attack
Authors: Jones Walker M. , Davis Aaron G. , Wilson R. Hunter , Elliott Katherine L. , Sumner Isaiah
Published: May 2019

The mechanism used by the ubiquitin‐conjugating enzyme, Ubc13, to catalyze ubiquitination is probed with three computational techniques: Born–Oppenheimer molecular dynamics, single point quantum mechanics/molecular mechanics energies, and classical molecular dynamics. These simulations support a long‐held hypothesis and show that Ubc13‐catalyzed ubiquitination uses a stepwise, nucleophilic attack mechanism. Furthermore, they show that the first step—the formation of a tetrahedral, zwitterionic intermediate—is rate limiting. However, these simulations contradict another popular hypothesis that supposes that the negative charge on the intermediate is stabilized by a highly conserved asparagine (Asn79 in Ubc13). Instead, calculated reaction profiles of the N79A mutant illustrate how charge stabilization actually increases the barrier to product formation. Finally, an alternate role for Asn79 is suggested by simulations of wild‐type, N79A, N79D, and H77A Ubc13: it stabilizes the motion of the electrophile prior to the reaction, positioning it for nucleophilic attack. © 2019 Wiley Periodicals, Inc.
Diagnostic biomarker and therapeutic target applications of miR‐326 in cancers: A systematic review
Authors: Jadideslam Golamreza , Ansarin Khalil , Sakhinia Ebrahim , Babaloo Zohreh , Abhari Alireza , Ghahremanzadeh Kazem , Khalili Mohamadreza , Radmehr Rahman , Kabbazi Alireza
Published: May 2019

MicroRNAs (miRNAs) are endogenous mediators of RNA interference and have key roles in the modulation of gene expression under healthy, inflamed, stimulated, carcinogenic, or other cells, and tissues of a pathological state. Many studies have proved the association between miRNAs and cancer. The role of miR‐326 as a tumor suppressor miRNA in much human cancer confirmed. We will explain the history and the role of miRNAs changes, especially miR‐326 in cancers and other pathological conditions. Attuned with these facts, this review highlights recent preclinical and clinical research performed on miRNAs as novel promising diagnostic biomarkers of patients at early stages, prediction of prognosis, and monitoring of the patients in response to treatment. All related publications retrieved from the PubMed database, with keywords such as epigenetic, miRNA, microRNA, miR‐326, cancer, diagnostic biomarker, and therapeutic target similar terms from 1899 to 2018 with limitations in the English language. Recently, researchers have focused on the impacts of miRNAs and their association in inflammatory, autoinflammatory, and cancerous conditions. Recent studies have suggested a major pathogenic role in cancers and autoinflammatory diseases. Investigations have explained the role of miRNAs in cancers, autoimmunity, and autoinflammatory diseases, and so on. The miRNA‐326 expression has an important role in cancer conditions and other diseases.
Citrulline stimulates muscle protein synthesis, by reallocating ATP consumption to muscle protein synthesis
Authors: Goron Arthur , Lamarche Frédéric , Blanchet Sandrine , Delangle Pascale , Schlattner Uwe , Fontaine Eric , Moinard Christophe
Published: May 2019

Background

Animal studies and clinical data support the interest of citrulline as a promising therapeutic for sarcopenia. Citrulline is known to stimulate muscle protein synthesis, but how it affects energy metabolism to support the highly energy‐dependent protein synthesis machinery is poorly understood.

Methods

Here, we used myotubes derived from primary culture of mouse myoblasts to study the effect of citrulline on both energy metabolism and protein synthesis under different limiting conditions.

Results

When serum/amino acid deficiency or energy stress (mild uncoupling) were applied, citrulline stimulated muscle protein synthesis by +22% and +11%, respectively. Importantly, this increase was not associated with enhanced energy status (ATP/ADP ratio) or mitochondrial respiration. We further analysed the share of mitochondrial respiration and thus of generated ATP allocated to different metabolic pathways by using specific inhibitors. Our results indicate that addition of citrulline allocated an increased share of mitochondrially generated ATP to the protein synthesis machinery under conditions of both serum/amino acid deficiency (+28%) and energy stress (+21%). This reallocation was not because of reduced ATP supply to DNA synthesis or activities of sodium and calcium cycling ion pumps.

Conclusions

Under certain stress conditions, citrulline increases muscle protein synthesis by specifically reallocating mitochondrial fuel to the protein synthesis machinery. Because ATP/ADP ratios and thus Gibbs free energy of ATP hydrolysis remained globally constant, this reallocation may be linked to decreased activation energies of one or several ATP (and GTP)‐consuming reactions involved in muscle protein synthesis.
Comparative analysis of transcriptomes between apical pulp‐derived cells from deciduous teeth and permanent teeth or dental pulp cells from exfoliated deciduous teeth
Authors: Xiong Hua‐cui , Chen Ke
Published: May 2019

Background

The present study aimed to explore the differences between apical pulp‐derived cells of deciduous teeth (De‐APDCs) and apical pulp‐derived cells of permanent teeth (P‐APDCs)/dental pulp cells from exfoliated deciduous teeth (De‐DPCs).

Methods

Three types of cells (De‐DPCs, P‐APDCs and De‐APDCs) were cultured by the tissue explant method. Transcriptome sequencing for the three types of cells was conducted and the differentially expressed genes (DEGs) between groups were selected. The potential biological functions and pathways enriched by the DEGs were analyzed.

Results

There were 35 up‐ and 21 down‐regulated DEGs in P‐APDC versus the De‐APDC comparison group, and 328 up‐ and 976 down‐regulated DEGs in De‐APDC versus De‐DPC. The DEGs in the P‐APDC versus De‐APDC group were significantly enriched in biological process terms associated with extracellular matrix organization, and regulation of cell proliferation and the pathway of cell adhesion molecules. Additionally, the DEGs between De‐APDC and De‐DPC were involved in functions related to extracellular matrix organization and the regulation of bone remodeling, as well as the pathway of extracellular matrix‐receptor interaction.

Conclusions

There were fewer differences between P‐APDC and De‐APDC compared to between De‐APDC and De‐DPC in view of the total number of DEGs. Differences in function existed relating to extracellular matrix organization among the three cells. P‐APDCs and De‐APDC had different functions on cell proliferation and adhesion. De‐APDCs may also act as a unique stem cell resource for tissue engineering.
Trade Openness, Economic Growth and the Global Financial Crisis of 2007–2009 in Latin America
Authors: Benita Francisco
Published: May 2019

This paper examines the relationship between bilateral trade openness and per capita gross domestic product for 15 Latin American countries during the financial crisis of 2008. It is employed an augmented gravity model of trade for the pre‐crisis, during‐crisis and post‐crisis periods (2004–2006, 2007–2009 and 2010–2012, respectively). Geographical characteristics and democracy rates of countries are used to instrument for average bilateral trade volumes. Different measures of trade openness are tested, and mixed results are identified. First, a slightly positive relationship between trade openness and growth is found when considering only Latin American countries. Second, after removing outliers and considering all importer countries, a negative relationship between the variables is found. © 2019 John Wiley & Sons, Ltd.
Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection
Authors: Matteucci Kely C , Pereira Gustavo J S , Weinlich Ricardo , Bortoluci Karina R
Published: May 2019

Autophagy and inflammasome activation are cell-autonomous and cross-regulated processes involved in host resistance against infections. Our group previously described that NLRP3 inflammasome is required for the control of Trypanosoma cruzi, the causative agent of Chagas disease. However, the involvement of autophagy in this process was unclear. Here, we demonstrated that T. cruzi was able to induce an increase in LC3-II expression as well as autophagosome and autolysosome formation in peritoneal macrophages (PMs) from C57BL/6 wild-type mice. Moreover, the pharmacologic inhibition of autophagic machinery impaired the ability of PMs to control T. cruzi replication. Importantly, NLRP3 was required for the induction of a regular autophagic flux in response to T. cruzi, an effect mediated by its participation in the autolysosomes formation. Together, these results indicate autophagy as an effector mechanism mediated by NLRP3 to control T. cruzi infection.
Bispecific radioligands targeting prostate‐specific membrane antigen and gastrin‐releasing peptide receptors on the surface of prostate cancer cells
Authors: Liolios Christos , Sachpekidis Christos , Schäfer Martin , Kopka Klaus
Published: May 2019

Metastases of prostate cancer usually show highly heterogeneous or partly lost prostate‐specific membrane antigen (PSMA) expression. In order to image and treat both PSMA positive and negative tissues, the extension of PSMA tracer specificity to other receptors, also highly expressed on the surface of prostate cancer cells, has been suggested. Prostate cancer cells usually express both PSMA and gastrin‐releasing peptide (GRP) receptors; thus, bispecific heterodimeric molecules, addressing both targets at the same time, may significantly improve prostate cancer imaging and therapy. This article summarizes preclinical data regarding low‐molecular weight molecules targeting PSMA and GRP receptors.
Accuracy of breast cancer lesion classification using intravoxel incoherent motion diffusion‐weighted imaging is improved by the inclusion of global or local prior knowledge with bayesian methods
Authors: Vidić Igor , Jerome Neil P. , Bathen Tone F. , Goa Pål E. , While Peter T.
Published: May 2019

Background

Diffusion‐weighted MRI (DWI) has potential to noninvasively characterize breast cancer lesions; models such as intravoxel incoherent motion (IVIM) provide pseudodiffusion parameters that reflect tissue perfusion, but are dependent on the details of acquisition and analysis strategy.

Purpose

To examine the effect of fitting algorithms, including conventional least‐squares (LSQ) and segmented (SEG) methods as well as Bayesian methods with global shrinkage (BSP) and local spatial (FBM) priors, on the power of IVIM parameters to differentiate benign and malignant breast lesions.

Study Type

Prospective patient study.

Subjects

61 patients with confirmed breast lesions.

Field Strength/Sequence

DWI (bipolar SE‐EPI, 13 b values) was included in a clinical MR protocol including T2‐weighted and dynamic contrast‐enhanced MRI on a 3T scanner.

Assessment

The IVIM model was fitted voxelwise in lesion regions of interest (ROIs), and derived parameters were compared across methods within benign and malignant subgroups (correlation, coefficients of variation). Area under receiver operator characteristic curves (ROC AUCs) were calculated to determine discriminatory power of parameter combinations from all fitting methods.

Statistical Tests

Kruskal–Wallis, Mann–Whitney, Pearson correlation.

Results

All methods provided useful IVIM parameters; D was well‐correlated across all methods (r > 0.8), with a wider range for f and D* (0.3–0.7). Fitting methods gave detectable differences in parameters, but all showed increased f and decreased D in malign lesions. D was the most discriminatory single parameter, with LSQ performing least well (AUC 0.83). In general, ROC AUCs were maximized by the inclusion of pseudodiffusion parameters, and by the use of Bayesian methods incorporating prior information (maximum AUC of 0.92 for BSP).

Data Conclusion

DWI performs well at classifying breast lesions, but careful consideration of analysis procedure can improve performance. D is the most discriminatory single parameter, but including pseudodiffusion parameters (f and D*) increases ROC AUC. Bayesian methods outperformed conventional least‐squares and segmented fitting methods for breast lesion classification.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1478–1488.
Impact of land use on soil organic carbon stocks in the humid tropics of NE Tanzania
Authors: Kirsten Maximilian , Kimaro Didas N. , Feger Karl-Heinz , Kalbitz Karsten
Published: May 2019

The conversion of tropical forests to agricultural land use is considered as a major cause for a decline in soil organic carbon (SOC) stocks. However, the extent and impact of different land uses on SOC stock development is highly uncertain, especially for tropical Africa due to a lack of reliable data. Interactions of SOC with the soil mineral phase can modify the susceptibility of SOC to become mineralized. Pedogenic Fe‐, Al‐oxides and clay potentially affect SOC stabilization in highly weathered soils typically found in the humid tropics. The aim of our study was to determine the impact of different land uses on SOC stock on such soils. For that purpose, 10 pedologically similar, deeply weathered acidic soils (Acrisols, Alisols) in the Eastern Usambara Mountains (Amani Nature Reserve, NE Tanzania) under contrasting land use were sampled to a depth of 100 cm. The calculated mean SOC stocks were 17.5 kg C m−2, 16.8 kg C m−2, 16.9 kg C m−2, and 20.0 kg C m−2 for the four forests, two tea plantations, three croplands, and one homegarden, respectively. A significant difference in mean SOC stock of 1.3 kg C m−2 was detected between forest and cropland land use for the 0–10 cm depth increment. No further significant impacts of land use on SOC stocks were observed. All soils have a clearly clay‐dominated texture. They are characterized by high content of pedogenic oxides with 29 to 47 g kg−1 measured for the topsoils and 36 to 65 g kg−1 for the subsoils. No positive significant relationship was found between SOC and clay content. Statistically significant positive relationships existed between oxalate‐extractable Fe, Al, and SOC content for cropland soils only. Compared to data published in literature the SOC stocks determined in our study were generally high independent of the established land use. It appears that efficient SOC stabilization mechanisms are counteracting the higher disturbance regime under agricultural land use in these highly weathered tropical soils.
Simulating pH‐dependent surface‐enhanced Raman spectra by density functional theory calculations
Authors: Xiang Shi‐Qin , Zhang Li , Gao Shu‐Ting , Zhao Liu‐Bin
Published: May 2019

The pH‐dependent surface‐enhanced Raman spectra of two typical surface sensor molecules p‐mercaptobenzoic acid (PMBA) and p‐mercaptopyridine (PMPY) were simulated by density functional theory calculations. First, the acid dissociation constants and individual surface Raman spectra of PMBA and PMPY were computed and compared with experimental results. It was found that acid dissociation constants calculated by the hybrid implicit‐explicit model and surface‐enhanced Raman scattering (SERS) spectra simulated by the explicit model most closely coincide with experimental results. Then, the pH‐dependent SERS spectra of PMBA and PMPY were obtained by overlaying the SERS of individual acid species and base species multiplied by their molar fractions, which were calculated from the acid dissociation constants. During the deprotonation process of PMBA, the Raman intensity from COOH stretching decreases and the Raman intensity from COO− stretching increases. During the protonation process of PMPY, the ν8a mode undergoes a significant blueshift and the relative Raman intensity of ν7a mode decreases. At last, pH calibration curves of PMBA and PMPY were obtained according to the simulated pH‐dependent Raman spectra, in which the logarithmic value of relative Raman intensity of characteristic peaks varies almost linearly with solution pH.
Synergistically Toughening Polyoxymethylene by Methyl Methacrylate–Butadiene–Styrene Copolymer and Thermoplastic Polyurethane
Authors: Yang Jing , Yang Wenqing , Wang Xuanlun , Dong Mengyao , Liu Hu , Wujcik Evan K. , Shao Qian , Wu Shide , Ding Tao , Guo Zhanhu
Published: May 2019

Ternary polyoxymethylene (POM) blends comprising methacrylate‐butadiene‐styrene (MBS) copolymer and thermoplastic polyurethanes (TPU) in different weight percentages are prepared by a two‐step melt extrusion technique. The synergistic toughening effect of polyoxymethylene by MBS as the impact modifier and TPU as the compatibilizer is investigated. The thermal behaviors of the prepared POM/MBS/TPU blends are analyzed. The notched impact resistance of the modified POM (POM/MBS/TPU 80 wt%/15 wt%/10 wt%) reached 40.83 kJ m−2. The enhanced toughness of the POM/MBS blends with the incorporation of TPU indicates the significance of TPU as a compatibilizer. Although the TPU compatibilizer enhances the interfacial adhesion between POM and MBS and decreases the size of MBS particles, serious agglomeration phenomenon is observed at higher TPU contents (more than 10 wt%) and caused slightly reduced tensile strength and the elongation at break for the sample with both loadings of MBS and TPU at 15 wt%. Instead, further increase of the notched impact strength is noted resulting from the compatibilizer TPU and an effective impact modifier MBS on the POM blend system to achieve a “super‐tough” effect. These “super‐tough” polyoxymethylene blends can be applied as the host matrix for preparing various multifunctional nanocomposites.
Backbone‐Hydrolyzable Poly(oligo(ethylene glycol) bis(glycidyl ether)‐alt‐ketoglutaric acid) with Tunable LCST Behavior
Authors: Chao Huan , Li Guo , Yu Jiabao , Liu Zhaotie , Liu Zhong‐Wen , Jiang Jinqiang
Published: May 2019

A novel class of backbone‐hydrolyzable LCST‐type polyesters of poly(oligo(ethylene glycol) bis(glycidyl ether)‐alt‐ketoglutaric acid)s (PEmKs) with numerous reactive sites is presented in this study. The target polyesters are prepared with commercially available hexa(ethylene glycol) bis(glycidyl ether) (E6BG), ethylene glycol bis(glycidyl ether) (E1BG), and 2‐ketoglutaric acid (KGA). By varying the initial feed ratio of E6BG and E1BG and the polymer concentration, a tunable thermal responsiveness with excellent repeatability is achieved.
Responsive Polypseudorotaxane Hydrogels Triggered by a Compatible Stimulus of CO2
Authors: Yan Diwei , Liu Sa , Jia Yong‐Guang , Mo Lina , Qi Dawei , Wang Jin , Chen Yunhua , Ren Li
Published: May 2019

Realizing the reversible transformation of the supramolecular hydrogels is essential for their application as smart materials. The reversible sol‐gel transition of the polypseudorotaxane (PPR) hydrogels is achieved through adding a CO2‐switchable guest molecule into the PPR hydrogel of poly(ethylene glycol) (PEG) and α‐cyclodextrins (α‐CDs). Alternating treatments with CO2 and heating drive such reversible transition due to the competitive complexation as evidenced by 2D NOESY 1H NMR and isothermal titration calorimetry as well as X‐ray diffraction. The present work describes a straightforward way to obtain switchable PPR hydrogels triggered by a compatible stimulus of CO2. These stimuli‐responsive PPR hydrogels have potential applications as biomaterials.
Azobenzene‐Containing Triblock Copolymer Adhesive Based on Light‐Induced Solid–Liquid Phase Transition: Application to Bonding for Various Substrates
Authors: Ito Shotaro , Akiyama Haruhisa , Mori Miyuki , Yoshida Masaru , Kihara Hideyuki
Published: May 2019

Azobenzene‐containing block copolymers have been previously developed as light‐induced reworkable adhesives that can undergo repeatable bonding/debonding on demand, based on photoisomerization of the azobenzene moiety and concomitant softening/hardening of the azo polymer block. For practical use, the applicability of such adhesives to various types of substrates is important and is thus studied as one of their most fundamental properties in this work. Ultraviolet (UV)‐transparent acrylic resin as well as non‐transparent polycarbonate resin, polyethylene ones, and metallic aluminum substrates are utilized as substrates. UV‐transparent acrylic resin is used as one of two substrates to investigate the photoisomerization process. The bonding/debonding process is successful for these substrates, and single lap shear tests show typical adhesion strengths of 1.5–2.0 MPa for the substrates investigated. UV irradiation induced a decrease in the adhesion strength to 0.03 MPa irrespective of the substrate type, indicating that the mechanism of the detachability is flow of the softened adhesive. Facile removal of the residual adhesive on the substrate is successfully demonstrated after detachment without any damage to the substrates by wiping the substrate with laboratory‐grade disposable wipes wet with ethanol.
An Injectable ROS‐Responsive Self‐Healing Hydrogel Based on tetra‐poly(ethylene glycol)‐b‐oligo(l‐methionine)
Authors: Zhao Dinglei , Zhou Qiang , Yang Kaixiang , Yang Haiyang , Tang Quan , Zhang Xingyuan
Published: May 2019

Abnormal physiological conditions provide an ideal stimulus for the design of responsive hydrogels which function as controlled and site‐specific release of drugs. Here, an injectable reactive oxygen species (ROS) responsive self‐healing hydrogel based on tetra‐poly(ethylene glycol)‐b‐oligo (l‐methionine) (t‐PEG56‐b‐OMethn) synthesized by a novel and facile method is reported. The hydrophobic interactions between the side chains of l‐methionine make the polymer chains crosslinked and lead to the formation of hydrogels which can be injected and self‐healed, meanwhile, the cross‐linker also provides a hydrophobic domain to encapsulate Dox. In presence of ROS, the side chain of l‐methionine can be oxidized to methionine sulfoxide. The side chain of l‐methionine is changed accordingly from hydrophobic to hydrophilic. As a result, both the hydrophobic domain and the hydrogel itself are destroyed. The controlled release of Dox by ROS at site‐specific is realized. The excellent biocompatibility of hydrogel based on t‐PEG56‐b‐OMethn indicates the door of the potential application in controlled release of drug in a truly physiological environment.
Numerical simulation of reinforced concrete structures under impact loading
Authors: Živaljić N. , Nikolić Ž. , Smoljanović H. , Munjiza A.
Published: May 2019

This study presents the performance of a combined finite‐discrete element method for prediction of the structural response of reinforced concrete beams under impact loading. A combination of finite and discrete element methods enables the modelling of the concrete and the reinforcement before the concrete cracking, as well as a discontinuous nature of the concrete caused by fracture and fragmentation under high impact loading. Discretization of the concrete with triangular finite elements is coupled with one‐dimensional reinforcing bars embedded inside the concrete finite elements. The cracking in the concrete activates the joint elements used to simulate the non‐linear behavior of both concrete and reinforcement. Numerical analysis based on experimental test data has been carried out to simulate the main features of the reinforced concrete beams impacted by free‐falling drop‐weights. A high level of accuracy was demonstrated in various comparisons between the experimental tests and the analysis results, including peak displacement, crack pattern, damage level and failure modes of reinforced concrete beams.
Shear effect on seismic behaviour of masonry walls
Authors: Smilović M. , Radnić J. , Harapin A.
Published: May 2019

Firstly, a finite element numerical model for nonlinear dynamic analysis of masonry walls is briefly presented. The model can simulate the main nonlinear effects of masonry and reinforced concrete. It is simple and intended to the engineering application. A macro model of masonry is adopted for simulation its behaviour in compression and for cracks modelling in tension. Two constitutive models are implemented to describe the shear resistance of the masonry wall: One that does not take the effect of the shear failure of masonry (Model 1), and second which takes into account shear failure of masonry (Model 2). By using the numerical model, the shear effect of masonry on the behaviour of two‐storey unreinforced and confined masonry walls exposed to harmonic base acceleration was investigated. The height to length ratio of the walls and the quality of masonry are varied. Analysis results for Model 1 and Model 2 are significantly different. Model 1 gives a significantly higher load bearing capacities of masonry. It was concluded that the shear effect of masonry significantly depends on the type of the masonry walls (unreinforced, confined), the quality of the masonry and height to length ratio of masonry walls.
Sound quality analysis of slide adjuster for automotive power seat using stepwise regression
Authors: Kim S.Y. , Oh J.S. , Kim K.S.
Published: May 2019

This study has analyzed the effect of noise sources of power seat slide adjuster on sound quality and human sensitivity through statistical methods. First, sound quality analysis using sound quality metrics was performed to analyze objective data. Next, the subjective evaluation of sound quality was performed by a jury test. There were two types of sound sources used for the jury test; one was two original sounds measured in the operating test and the other one was eight virtual sound sources that were produced by amplifying a specific frequency of original sounds. It was designed to derive the causal relationship between each noise source and human sensitivity. Thirdly, we analyzed the correlation between the sound quality metrics and the sound pressure level of the noise source through the factor analysis. As a result, four independent variables were derived. Lastly, stepwise regression analysis was performed using four independent variables and the results of the jury test. The derived regression models had considerable explanatory power. From this, it was possible to understand the influence of the noise source of the seat slide adjuster on the sound quality and human sensitivity.
Targeted fetal cell‐free DNA screening for aneuploidies in 4,594 pregnancies: Single center study
Authors: Koc Altug , Ozer Kaya Ozge , Ozyilmaz Berk , Kutbay Yasar B. , Kirbiyik Ozgur , Ozdemir Taha R. , Erdogan Kadri M. , Saka Guvenc Merve , Oztekin Deniz C. , Ozeren Mehmet , Pala Halil G. , Ekin Atalay , Gezer Cenk , Sahingoz Yildirim Alkim G. , Konuralp Atakul Bahar , Kurtulmus Secil , Turhan Ugur , Taner Cuneyt E.
Published: May 2019

Background

Next‐generation sequencing (NGS) and discovery of fetal cell‐free DNA (cfDNA) in the maternal circulation render possible prenatal screening for trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and sex chromosome aneuploidies. The approach is called “fetal cfDNA screening” and in contrast to noninvasive conventional serum screening, it provides the identification of 98%–99% of fetuses with Down syndrome.

Methods

Retrospective analysis of targeted noninvasive prenatal testing (NIPT) (Clarigo Test) pregnancies with moderate risk, which we have reported between 2016 and 2018 years is presented. Two separate laboratory workflows and NGS platforms are used for the same targeted NIPT analysis.

Results

In total, 4,594 pregnant women were investigated. Initial 3,594 cases are studied by MiSeq platform, the last 1,000 cases by NextSeq. Failure rate for MiSeq platform is 10.9% and for NextSeq is 8.7%. Automatically reported cases constitute 75% of the MiSeq group and 87% of the NextSeq group.

Conclusions

Targeted NIPT results suggest that MiSeq platform could be used for NIPT which would be an essential option particularly for laboratories with low sample flow. And, the NextSeq platform has easier wet lab process and also increased success rate in automatic reporting which is suitable for centers with high number of NIPT cases.
The influence of ACYP2 polymorphisms on gastrointestinal cancer susceptibility in the Chinese Han population
Authors: Duan Xianglong , Hong Jiajing , Wang Fuchun , Wei Kun , Wang Pengyuan , Hou Feng , Zhang Min , Liu Dengfeng , Yuan Dongya , Liu Sida
Published: May 2019

Background

Gastrointestinal cancer (GI cancer) is a type of cancer that has a high death rate. It has been reported that ACYP2 gene was associated with the development of gastric cancer and colorectal cancer, but it is not clear that the relationship between ACYP2 gene and GI cancer in Chinese Han population. This study aimed to investigate the association between polymorphisms of ACYP2 and GI cancer in the Chinese Han population.

Methods

We used Agena MassARRAY to determine the genotypes of 1,160 GI cancer patients and 495 healthy controls. The correlation between ACYP2 variants and GI cancer risk was examined by logistic regression analysis.

Results

We identified that rs6713088 (OR = 1.17, 95% CI: 1.00–1.36, p = 0.047), rs843711 (OR = 1.17, 95 CI: 1.01–1.36, p = 0.035), and rs11896604 (OR = 1.20, 95% CI: 1.00–1.45, p = 0.048) were correlated with an increased risk of GI cancer under allele model. Rs11125529 under the recessive model (OR = 2.05, 95% CI: 1.00–4.23, p = 0.038), rs843711 in recessive model (OR = 1.37, 95% CI: 1.04–1.82, p = 0.026), and rs11896604 under log‐additive model (OR = 1.23, 95% CI: 1.01–1.51, p = 0.042) were associated with an increased risk of GI cancer.

Conclusion

Our study suggested that polymorphisms of ACYP2 gene might be associated with susceptibility to GI cancer.
A mutation in Site‐1 Protease is associated with a complex phenotype that includes episodic hyperCKemia and focal myoedema
Authors: Schweitzer George G. , Gan Connie , Bucelli Robert C. , Wegner Daniel , Schmidt Robert E. , Shinawi Marwan , Finck Brian N. , Brookheart Rita T.
Published: May 2019

Background

Site‐1 Protease (S1P) is a Golgi‐resident protein required for the activation of regulatory proteins that drive key cellular functions, including, the unfolded protein response (UPR) and lipid and cholesterol biosynthesis. While disruptions in S1P function have been widely characterized in animal models, to date, the implications of disrupted S1P function in human disease states are not completely known.

Methods

The patient and both parents underwent whole exome and mitochondrial DNA sequencing, and Sanger sequencing was used to confirm the mutation. Western blotting and immunofluorescence studies were performed on either proband‐derived fibroblasts or on an established cell line to assess protein expression and cellular localization of the mutated S1P protein. Quantitative real‐time PCR and luciferase reporter assays were used to examine activation of S1P target pathways in the context of the S1P mutation.

Results

We describe a female patient with a de novo heterozygous missense mutation in the transmembrane domain of S1P (p. Pro1003Ser). The patient presented to our neuromuscular clinic with episodic, activity‐induced, focal myoedema and myalgias with hyperCKemia. Her clinical phenotype was complex and included gastrointestinal hypomotility, ocular migraines, and polycystic ovary syndrome. Molecular analysis using proband‐derived fibroblasts and cell lines harboring the Pro1003Ser mutation demonstrated increased activation of UPR and lipid and cholesterol regulatory pathways and localization of S1P Pro1003Ser in the Golgi.

Conclusion

These findings suggest a critical function for S1P in several human organ systems and implicate an important role for S1P in various human disease states.
Predicting pKa for Small Molecules on Public and In‐house Datasets Using Fast Prediction Methods Combined with Data Fusion
Authors: Kalliokoski Tuomo , Sinervo Kai
Published: May 2019

Data fusion approach was investigated in the context of pKa prediction for 391 small molecules derived from a public data source as well as for 681 compounds from an internal corporate database. Four different pKa prediction methods (Simulations Plus ADMET‐Predictor S+pKa, ACD/Labs Percepta Classic, ACD/Labs Percepta GALAS and Epik) were used to predict the most acidic or basic pKa for each of the compounds. By using data fusion, the median absolute error for the internal compounds was reduced from the best performing single model's value of 0.69 down to 0.50. In addition to the improved accuracy, data fusion also enabled predictions for all of the compounds in the dataset as individual methods failed on some of the molecules.