bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiobjective Optimization Design and Experimental Investigation on the Axial Flow Pump with Orthogonal Test Approach
Authors: Zhang Yuquan , Xu Yanhe , Zheng Yuan , Fernandez-Rodriguez E. , Sun Aoran , Yang Chunxia , Wang Jue
Published: December 2019

A multiobjective optimization technique based on the computational fluid dynamics (CFD) simulations and the orthogonal test is proposed to reduce the pressure pulsation in this paper. Three levels of four well‐known performance factors L9 (34) were considered in the orthogonal test scheme: the number of blades, the blade setting angle, the hub ratio, and the distance between the blade and the guide vane. The evaluation indexes corresponded to the head, efficiency, shaft power, and pressure pulsation, respectively. An optimal configuration A2B1C2D3 was obtained by comprehensive frequency analysis method, after intuitive and range analysis. In comparison with the nonoptimized model, the new design’s head and efficiency increased by 17.8% and 4.26%, whilst the shaft power and the pressure pulsation coefficient reduced by 1.22% and 11%, respectively. Experiments conducted on the optimized pump were consistent with the CFD model. Six different rotational speed conditions in the optimal operating points were numerically calculated in order to explore the internal hydraulic characteristics of the optimized axial flow pump. It is verified that the comprehensive frequency analysis method based on the orthogonal test approach is effective for the multiobjective optimization of the axial flow pump.
4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells
Authors: Alshangiti Amnah M. , Tuboly Eszter , Hegarty Shane V. , McCarthy Cathal M. , Sullivan Aideen M. , O’Keeffe Gerard W.
Published: December 2019

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.
Seismic Acceleration Spectrum of Ground Surface under Urban Subway Tunnels with Circular Cross Sections in Soil Deposits Based on SSI
Authors: Fakhriyeh Hamed , Vahdani Reza , Gerami Mohsen
Published: December 2019

Underground tunnels with circular cross section nowadays have great application in the field of transportation. One of their most prominent uses is the subway, built with the help of tunnel boring machines (TBMs). The design of ground‐surface structures in the far field is related to the horizontal component of the peak ground of acceleration. Therefore, in this study, we tried to change the frequency of the soil‐tunnel system by changing the overburden depth, diameter, and lining thickness of the tunnel, as well as changes in the soil specification, and calculate the maximum acceleration of the ground’s surface in the presence of the tunnel. The relationship between the peak horizontal acceleration of the ground surface and the frequency of the soil‐tunnel system will result in the production of a horizontal acceleration spectrum. The results show that the amplification of ground surface depends on the period of the soil‐tunnel system, the characteristics of the model, and the status of the point studied at the ground surface relative to the tunnel. On the projection of the center of the tunnel on the surface of the ground, the presence of the tunnel, rarely, at a long period, is effective in amplifying the spectral acceleration. While moving away from the image of the center of the tunnel on the surface of the ground, the presence of the tunnel in many cases, in long periods, amplifies spectral acceleration. The presence of the tunnel amplifies the spectral acceleration on the ground surface above 11%, while the presence of a tunnel reduces the spectral acceleration on the ground surface by up to 15% (attenuation). Using Plaxis 2D and Ansys finite element software, the case study was conducted on a Delhi subway tunnel with horizontal components of acceleration records similar to the construction site.
Optimizing the Use of the Gamma-Glutamyl Transpeptidase-to-Platelet Ratio and Transient Elastography to Identify Liver Cirrhosis in Patients with Chronic Hepatitis B Concurrent with Nonalcoholic Fatty Liver Disease
Authors: Zhang Geng-lin , Xu Shi-cheng , Zeng Jie , Chen Zheng , Li Yi-Ping , Zhang Ting , Gao Zhi-liang
Published: December 2019

Background and Aim. Little information is available about the assessment and optimal use of the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and transient elastography (TE) in predicting liver cirrhosis in patients with chronic hepatitis B (CHB) and concurrent nonalcoholic fatty liver disease (NAFLD). This study is aimed at comparing their diagnostic performances and developing an optimal approach for predicting liver cirrhosis in CHB patients with NAFLD. Methods. Consecutive CHB patients with NAFLD were enrolled. The GPR was calculated, and TE was performed using liver biopsy as a reference standard. The accuracy of predicting liver cirrhosis using GPR and TE was assessed and compared, and an optimal approach was developed. Results. Both TE and GPR correlated significantly with the histological fibrosis stage. TE and GPR had excellent performance in predicting liver cirrhosis, and the comparison of areas under the receiver operating characteristic curves revealed that TE was superior to GPR (0.95 vs. 0.85, P=0.039). Moreover, the dual cutoffs established by the likelihood ratio showed that GPR had a similar misclassification but higher indeterminate rate than TE (54.5% vs. 11.7%, P<0.001). Additionally, a 2-step approach using GPR followed by TE had comparable performance to that of both GPR and TE tests for all patients (misclassification: 8.9% vs. 8.3%, P=0.866; indeterminate rate: 15.2% vs. 17.2%, P=0.750) but could reduce TE scans by approximately one-third. Conclusions. Both TE and GPR show excellent performance in predicting liver cirrhosis in CHB patients with NAFLD. The 2-step approach using GPR followed by TE may be optimal for the assessment of cirrhosis in CHB patients with NAFLD.
Pancreatic Inflammatory Pseudotumor-Like Follicular Dendritic Cell Tumor
Authors: Mograbi Madison , Stump Michael S. , Luyimbazi David T. , Shakhatreh Mohammad H. , Grider Douglas J.
Published: December 2019

Follicular dendritic cell sarcoma (FDCS) is a rare and underdiagnosed malignant neoplasm which characteristically presents as a solitary, slow-growing mass with no discrete symptoms. Histologically, lymphocytes and spindle cells featuring large nucleoli in a whorled pattern are usually seen. FDCS is classically found in cervical and axillary lymph nodes, with occasional involvement of extranodal sites. Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDCT) is an uncommon subcategory of this neoplasm, demonstratively linked to the Epstein-Barr virus (EBV). This neoplasm can present similarly to FDCS, but systemic symptoms may be seen. Although, often found in the spleen and occasionally the liver, IPT-like FDCT has not previously been described within the pancreas. Presented, is an IPT-like FDCT of the pancreas and spleen of a 70 years old woman. Histologic features include variably sized geographic suppurative granulomas with chronic inflammatory cells and an atypical spindle cell proliferation with prominent nucleoli. Positivity for CD45 and CD68 in the larger spindled cells points to an inflammatory pseudotumor subtype and co-expression of CD21, CD23, and CD35 were indicative of follicular dendritic differentiation. The pseudotumor additionally demonstrated EBV-encoded RNA (EBER) positivity typical of IPT-like FDCT. Differentiation between inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) is additionally discussed.
A Network Coding-Based Braided Multipath Routing Protocol for Wireless Sensor Networks
Authors: Li Zhihua , Xu Minda , Liu Tingxu , Yu Lei
Published: December 2019

In wireless sensor networks (WSNs), energy efficiency can simultaneously guarantee robustness to link loss and node failure and is a key design goal of routing protocols because WSNs are strongly constrained in terms of transmission reliability, transmission delay, and energy consumption. Braided multipath routing has become a powerful tool for tolerating node failures and link losses, with high reliability and efficient data transmission rates. In this paper, we propose a novel network coding-based braided multipath routing called NC-BMR protocol. It integrates a data compression-based network coding method with the construction of hierarchical multiparent nodes (HMPNs) topology for the routing with coordinated data forwarding manner and a multipackets-based time scheduler strategy (MTSS). Its perfect transmission efficiency is achieved by only attaching a little control information with data packets. We validated NC-BMR based on the TOSSIM platform and compared it to several previous methods. Theoretical analysis and simulation results demonstrate its performance improvement in terms of the transmission reliability, delay, and overhead.
Thyroid Embryonic Anomalies Involving the Medial and Lateral Anlagen: Two Surgical Case Reports
Authors: Rico Ferdinand , Lung John
Published: December 2019

Introduction. An ectopic anomalous accessory thyroid is extremely rare. We present two related case reports. Case. A 43-year-old morbidly obese female presented with a palpable left thyroid mass. Initial impression after preoperative workup was a diffuse bilateral multinodular goiter with a left nodule suspicious for malignancy. She underwent a total thyroidectomy. On further palpation after initial excision, two masses on the left neck area were noted, dissected, and excised. In the second case, a 65-year-old female presented with a substernal exophytic mass displacing the trachea to the right after a left thyroid lobectomy 4 years ago. Cytology revealed a retained substernal thyroid. She is scheduled for a substernal thyroidectomy through a median sternotomy. Discussion. In all partial or complete thyroidectomy cases, care should be taken to palpate or to use intraoperative ultrasound (IOUS) for any extra thyroid mass. An intuitive surgical approach is needed to evaluate for possible embryologic anomalies of the thyroid. There are two thyroid anlagen that can explain ectopic aberrant anomalies: the median anlage-thyroid rest and the lateral anlage from the ultimobranchial body of the fourth pharyngeal pouch. Surgeons should keep in mind that multiple ectopic thyroid glands could be present in any thyroidectomy procedure.
Classification of Wheezing Children in Rural Bangladesh by Intensity of Ascaris Infection, Total and Specific IgE Levels, History of Pneumonia, and Other Risk Factors
Authors: Takeuchi Haruko , Khan Md Alfazal , Zaman Khalequz , Takanashi Sayaka , Hasan S. M. Tafsir , Yunus Mohammad , Iwata Tsutomu
Published: December 2019

Ascaris lumbricoides is the most common soil-transmitted helminth and infects 447 million people in impoverished areas worldwide. It causes serious morbidity including wheezing and influences various aspects of human immunity, such as type 2 innate lymphoid cells, regulatory T cell function, and acquired immunity. Thus, it is crucial to elucidate its influence on human immunity. We aimed to classify wheezing children based on their Ascaris infection intensity and other risk factors using hierarchical cluster analysis to determine the mechanisms of and the degree to which Ascaris contributes to childhood wheezing in rural Bangladesh. We analyzed relevant data collected in 2001. The participants included 219 5-year-old wheezing children who were randomly selected from 1705 children living in the Matlab Health and Demographic Surveillance area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Hierarchical cluster analysis was conducted using variables of history of pneumonia, total and specific immunoglobulin E levels, Ascaris infection intensity, and parental asthma. Three distinct wheezing groups were identified. Children in Cluster 1 (n=50) had the highest titers of the total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anticockroach IgEs and experienced the fewest episodes of pneumonia. Cluster 2 (n=114), the largest group, experienced few episodes of pneumonia and had the lowest titers of the total, anti-Ascaris, anti-Dp, and anticockroach IgEs. Cluster 3 (n=32) consisted of participants with the most episodes of pneumonia and lower titers of the total and specific IgEs. The extremely high prevalence of Ascaris infection found in Clusters 1-3 was 78%, 77%, and 72%, respectively. Childhood wheezing in rural Bangladesh could be divided into three groups, with 26% of wheezing attributable to anti-Ascaris IgE and 16% to history of pneumonia during early childhood, and 58% might have been due to Ascaris infection without elevated anti-Ascaris IgE.
Salivary Antioxidant Barrier, Redox Status, and Oxidative Damage to Proteins and Lipids in Healthy Children, Adults, and the Elderly
Authors: Maciejczyk Mateusz , Zalewska Anna , Ładny Jerzy Robert
Published: December 2019

Despite the proven role of oxidative stress in numerous systemic diseases and in the process of aging, little is still known about the salivary redox balance of healthy children, adults, and the elderly. Our study was the first to assess the antioxidant barrier, redox status, and oxidative damage in nonstimulated (NWS) and stimulated (SWS) saliva as well as blood samples of healthy individuals at different ages. We divided 90 generally healthy people into three equally numbered groups based on age: 2–14 (children and adolescents), 25–45 (adults), and 65–85 (elderly people). Antioxidant enzymes (salivary peroxidase (Px), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase-1 (SOD)), nonenzymatic antioxidants (reduced glutathione (GSH) and uric acid (UA)), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), and malondialdehyde (MDA)) were evaluated in NWS and SWS as well as in erythrocyte/plasma samples. We demonstrated that salivary and blood antioxidant defense is most effective in people aged 25–45. In the elderly, we observed a progressive decrease in the efficiency of central antioxidant systems (↓GPx, ↓SOD, ↓GSH, and ↓TAC in erythrocytes and plasma vs. adults) as well as in NWS (↓Px, ↓UA, and ↓TAC vs. adults) and SWS (↓TAC vs. adults). Both local and systemic antioxidant systems were less efficient in children and adolescents than in the group of middle-aged people, which indicates age-related immaturity of antioxidant mechanisms. Oxidative damage to proteins (↑AGE, ↑AOPP) and lipids (↑MDA) was significantly higher in saliva and plasma of elderly people in comparison with adults and children/adolescents. Of all the evaluated biomarkers, only salivary oxidative damage products generally reflected their content in blood plasma. The level of salivary redox biomarkers did not vary based on gender.
Tensile Properties of Three Selected Collagen Membranes
Authors: Raz Perry , Brosh Tamar , Ronen Guy , Tal Haim
Published: December 2019

Background. Biological barriers are commonly used to treat alveolar bone defects and guide tissue regeneration. Understanding the biological and mechanical properties of the available membranes is crucial for selecting the one that is optimal for enhancing clinical outcomes.Purpose. To evaluate the mechanical behavior of three different collagen membranes to increasing tensile force in dry and wet conditions.Materials and Methods. Three commercially collagen membranes were selected for analysis: Bio-Gide® (Geistlich Biomaterials, Baden-Baden, Germany), Remaix™ (RX; Matricel GmbH, Herzogenrath, Germany), and Ossix Plus® (Datum Dental Biotech, Lod, Israel). Increasing tensile forces were applied on 10 dry and wet membranes of standard size via a loading machine. Force and extension values were acquired up to maximum load before failure, and maximum stress, maximum extension, and amount of energy needed for membrane tearing were analyzed. Membranes’ densities were also calculated.Results. The Remaix membrane exhibited the highest values of maximum load tensile strength, maximum extension, and maximum energy required for membrane tearing, followed by Bio-Gide. Ossix Plus had the lowest scores in all these parameters. Dry membranes had the highest scores for all parameters except extension. Membrane density was directly and significantly correlated with all tested parameters.Conclusions. The study was undertaken to provide clinicians with data upon which to base the selection of collagen membranes in order to achieve optimal clinical results. It emerged that the mechanical properties of dry and wet collagen membranes were significantly different from one another. Among the 3 tested membranes, Remaix exhibited higher performance results in all the mechanical tests. Collagen membrane density seems to have a significant influence upon mechanical resistance. These findings may also guide manufacturers in improving the quality of their product.
Ohmic Contact Mechanism for Ni/C-Faced 4H-n-SiC Substrate
Authors: Kim Seongjun , Kim Hong-Ki , Lim Minwho , Jeong Seonghoon , Kang Min-Jae , Kang Min-Sik , Lee Nam-Suk , Cuong Tran Viet , Kim Hyunsoo , Erlbacher Tobias , Bauer Anton , Shin Hoon-Kyu
Published: December 2019

In this work, the ohmic contact mechanism of Ni electrodes on C-faced 4H-n-SiC was investigated by evaluating the electrical and microstructural properties in the contact interface as a function of annealing temperatures ranging from 950 to 1100°C. We determined that Ni-silicide, especially the NiSi phase, plays a key role in the formation of ohmic contacts rather than an increase in carbon vacancies in the C-faced SiC substrate. A vertically oriented NiSi phase was observed in the thermally annealed sample at the optimized temperature that behaves as a current path. A further increase in annealing temperature leads to the degradation of ohmic behavior due to the formation of horizontal-type NiSi in the Ni-rich Ni-silicide/NiSi/SiC structure.
Detection by Flow Cytometry of Anti-DNA Autoantibodies and Circulating DNA Immune Complexes in Lupus Erythematosus
Authors: Abuaf Nisen , Desgruelles Chantal , Moumaris Mohamed , Boussa-Khettab Faïza , Rostane Hidayeth , Bellec Emilie , Frances Camille
Published: December 2019

A new method for the detection by flow cytometry of anti-double-stranded DNA antibodies and of circulating immune complexes (IC) containing endogenous DNA (IC-eDNA) is described. From each serum sample, two samples were taken, one was used to detect IC-eDNA. The other to detect anti-DNA antibodies was incubated with calf thymus DNA. ICs were isolated by polyethylene glycol precipitation or by cryoprecipitation, after which immunoglobulins were labeled with FITC-conjugated anti-human globulin. Serum samples from 63 systemic lupus erythematosus (SLE) patients, 32 incomplete lupus, and 87 control patients were tested. Detection of anti-dsDNA antibodies by flow cytometry had a diagnostic sensitivity and specificity almost comparable to routine tests, the fluorescent enzyme immunoassay EliA™-dsDNA test, and the ultrasensitive Crithidia luciliae indirect immunofluorescence test. In 21 (33%) out of 63 SLE serum samples, IC-eDNA was detected. In these samples, free anti-dsDNA antibodies were hardly detectable or undetectable by flow cytometry or by routine tests. When anti-DNA antibodies are neutralized by endogenous DNA and can no longer be detected by routine tests, the serologic diagnosis and the follow-up of relapses in patients with SLE is compromised. To overcome this obstacle, we propose an accessible solution: the detection of circulating IC-eDNA by flow cytometry.
Physicochemical and Morphological Properties of Extruded Adlay (Coix lachryma-jobi L) Flour
Authors: Zhang Gaopeng , Ding Yangyue , Ni Chunlei , Ban Qingfeng , Xu Li , Guo Liandong , Cheng Jianjun
Published: December 2019

The effects of extrusion treatment on the structure and properties of adlay (Job’s tears) were investigated. Adlay flour was extruded through a twin-screw extruder with different parameters, including barrel temperature (80–160°C), moisture content (19–27%), and screw speed (170–330 rpm). The results showed that although the expansion index increased with increasing temperature, an increase in moisture content significantly decreased the EI (p<0.05). Extrusion improved the water solubility index and water absorption index of adlay flour (p<0.05). Furthermore, analysis of the gelating properties revealed that the structure and function of adlay flour had radically changed. After extrusion, the viscosity of the adlay flour decreased (peak viscosity decreased by more than 1000 cP), and its fluidity increased. The rheological data were modeled by the Herschel–Bulkley model. X-ray diffraction experiments showed that extrusion contributed to a decrease in relative crystallinity. Scanning electron microscopy revealed that extrusion damaged the basic structure of adlay flour, causing holes and pits on the extrudate surface. Compared to the native adlay flour, the extrusion resulted in significantly changing the pasting, gelating, thermal, rheological, and morphological properties of adlay flour. In conclusion, the extrusion can alter adlay characteristics, but it is necessary to choose appropriate conditions to attain the desired properties.
Innovation Efficiency of China’s High‐End Manufacturing Industry: Evidence from Super‐SBM Model and Malmquist Index
Authors: Li Qiaochu , Liu TingLi
Published: December 2019

Technological innovation is an important engine to support the development of China from a big manufacturing country to a powerful manufacturing country. With the support of government policies, China’s high‐end manufacturing industry urgently needs to solve the problems of insufficient technological innovation and weak core competitiveness. This paper uses the super‐SBM model to measure the impact of incentive policies related to high‐end manufacturing industry on innovation efficiency of China’s high‐end manufacturing industry in 2012–2017. The DEA Malmquist model is used to analyse the dynamic change trend of efficiency. The results show that the innovation efficiency of China’s high‐end manufacturing industry shows a trend of gradual optimization, stepping into the middle and high‐end levels, but there are large differences in innovation efficiency among industries, and the optimization process is not stable; at the same time, China’s high‐end industry is not stable. Manufacturing industry needs to improve its pure technical efficiency as soon as possible and solve the problems of low efficiency of system and management level. Accordingly, this paper puts forward a series of policy suggestions, such as increasing financial and talent support, encouraging technological innovation, and promoting industrial synergy.
Evaluation of Implanted Stent Occlusion Status Based on Neointimal Tissue Bioimpedance Simulations
Authors: Portillo-Anaya J. M. , Pérez P. , Olmo A. , Huertas G. , Yúfera A.
Published: December 2019

This paper describes the characterization of the light hole, also known as the lumen, in implanted stents affected by restenosis processes using bioimpedance (BI) as a biomarker. The presented approach will enable real-time monitoring of lumens in implanted stents. The basis of the work hereby reported is the fact that neointimal tissues involved in restenosis can be detected and measured through their impedance properties, namely, conductivity and permittivity. To exploit these properties, a 4-electrode setup for BI measurement is proposed. This setup allows study of the influence of the various tissues involved in restenosis fat, muscle, fibre, and endothelium, together with the blood, on the BI value at several frequencies. In addition, BI simulation tests were performed using the electric physics module available in COMSOL Multiphysics®. Interestingly, fat constitutes the most influential layer on the value of impedance (measured in kΩ/μm—magnitude change per micrometre of lumen occlusion). A case study using a standard stent is also presented. In this study, where the involved tissues and blood were simultaneously considered, we conducted an analysis for stable and vulnerable plaques in restenosis test situations. In this regard, the proposed method is useful to test the stent obstruction and detect potential dangerous cases due to nonstable fat accumulation.
Numerical Simulations of the Hall–Petch Relationship in Aluminium Using Gradient‐Enhanced Plasticity Model
Authors: Song Yooseob , Yeon Jaeheum , Na Byoungjoon
Published: December 2019

The Hall‐Petch relation in aluminium is discussed based on the strain gradient plasticity framework. The thermodynamically consistent gradient‐enhanced flow rules for bulk and grain boundaries are developed using the concepts of thermal activation energy and dislocation interaction mechanisms. It is assumed that the thermodynamic microstresses for bulk and grain boundaries have dissipative and energetic contributions, and in turn, both dissipative and energetic material length scale parameters are existent. Accordingly, two‐dimensional finite element simulations are performed to analyse characteristics of the Hall–Petch strengthening and the Hall–Petch constants. The proposed flow rules for the grain boundary are validated using the existing experimental data from literatures. An excellent agreement between the numerical results and the experimental measurements is obtained in the Hall–Petch plot. In addition, it is observed that the Hall–Petch constants do not remain unchanged but vary depending on the strain level.
Attachment and Mentalizing Abilities in Patients with Inflammatory Bowel Disease
Authors: Agostini Alessandro , Scaioli Eleonora , Belluzzi Andrea , Campieri Massimo
Published: December 2019

Background. Inflammatory bowel diseases (IBD) are associated with stress, poor quality of life, and attachment insecurity. Mentalization is the human ability to perceive and reason about feelings and psychological dispositions of one’s self and others. The chronic disorders are believed to affect patients’ mentalizing abilities and to determine a shift towards attachment insecurity in patients affected. In this study, the attachment dimensions and mentalization were assessed in IBD patients and healthy controls. Further knowledge about the interplay among IBD, mentalization, and attachment might shed more light into the psychopathological mechanisms leading to insecurity and vulnerability to stress in IBD. Methods. A group of 96 IBD patients and 102 healthy controls completed the attachment style questionnaire (ASQ), the reflective functioning questionnaire (RFQ), and the Eyes test, a performance-based measure of mentalization. Results. Compared to controls, IBD patients have shown more pronounced attachment anxiety and lower scores in the Eyes test. Disease activity was negatively correlated with the Eyes test scores. Conclusion. These findings have suggested a plausible impact of IBD on mentalization abilities and have provided new insights into the interplay between IBD, deficits in mentalization, and attachment insecurity. IBD patients are highly vulnerable to disease-related stress that may promote impairments in mentalization. Low mentalization might play a central role in the development of attachment insecurity and emotional disturbances in IBD. The present study’s results might open new scenarios for psychodynamic approaches to the treatment of the emotional disturbances in IBD based on attachment and mentalization theory.
The Protective Effect of Bosentan against Atherosclerosis in Apolipoprotein E-Deficient Mice Is Mediated by miRNA-21
Authors: Xu Xiaona , Zhao Zhiqiang , Li Guangping
Published: December 2019

Vascular calcification is an independent risk factor for plaque instability and is associated with endothelial cell function. Here, we investigated the role of endothelial cell function in the calcification of atherosclerotic plaques. We hypothesized that atherosclerosis would be associated with endothelial dysfunction and that bosentan (Tracleer®), a dual endothelin-receptor antagonist, would preserve endothelial cell function in an apolipoprotein E-deficient (ApoE−/−) mouse model of atherosclerosis. Accordingly, 4–6-week-old ApoE−/− mice were fed a high-fat diet and treated with bosentan, and the effects of this treatment on body weight and blood lipid concentrations was evaluated. Endothelial damage in the aortic arch was assessed immunohistochemically to detect the proapoptotic proteins PDCD4, caspase-3, and Bax and the antiapoptotic protein Bcl-2. Notably, bosentan treatment was associated with decreased concentrations of these proteins and of blood lipids in ApoE−/− mice. Consistent with these findings, we observed increased concentrations of miRNA-21 and PDCD4 mRNA expression in the aortic arch endothelium after bosentan treatment. We conclude that bosentan can prevent endothelial cell death and protect against atherosclerosis in ApoE-deficient mice by upregulating miRNA-21.
Radar Coherent Detection for Maneuvering Target Based on Product-Scaled Integrated Cubic Phase Function
Authors: Chen Jinyang , Jin Ke , Yu Shangjiang , Lai Tao , Zhao Yongjun
Published: December 2019

This paper considers the long-time coherent detection problem for maneuvering targets with jerk motion. A novel method based on product-scaled integrated cubic phase function (PSICPF) is proposed. The main strategy of PSICPF is to estimate target’s motion parameters along the slow time for each range frequency cell. In order to eliminate the coupling terms between range frequency and slow time, the scaled nonuniform fast Fourier transform (SNUFFT) is newly defined in the integrated cubic phase function (ICPF). Then, the product operation is employed to coherently synthesize the estimation results, improve the antinoise performance, and suppress the cross terms. Finally, coherent integration is achieved via keystone transform (KT) and fold factor searching. Analysis demonstrates that the SNUFFT has the same computational complexity with nonuniform fast Fourier transform (NUFFT), and thus the PSICPF could be efficiently implemented via complex multiplications, the fast Fourier transform (FFT), and NUFFT. Detailed comparisons with other representative methods in computational cost, motion parameter estimation performance, and detection ability indicate that the PSICPF could achieve a good balance between the computational cost and detection ability. Simulations and real data processing results are presented to verify the effectiveness of the proposed method.
Prediction of Response of Existing Building Piles to Adjacent Deep Excavation in Soft Clay
Authors: Liang Yao-Ying , Liu Nian-Wu , Yu Feng , Gong Xiao-Nan , Chen Yi-Tian
Published: December 2019

This study investigates building settlements near excavations in soft clay. A simplified theoretical method is proposed to predict the additional settlements and axial forces of excavation‐adjacent existing building floating piles in soft clay. The soil displacement is simplified as a line or broken line along the depth direction, depending on the distance from the excavation. A hyperbolic model is applied to calculate the skin friction and tip resistance induced by the vertical soil displacement. The parameters of the hyperbolic model are corrected to fit data from in‐service piles. Based on the load‐transfer curve method, the additional settlements and axial forces are determined. The measured data of 17 floating piles from two excavation cases in Hangzhou, China, show good agreement with the calculated values. The results show that the position of the neutral point of the loaded pile varies with the soil settlement. Because of the upper structure, the theoretical settlements for piles near the excavation are larger than those obtained from the measured values; for distant piles, this relationship is reversed. The proposed prediction methodology is expected to guide the design of practical excavations.
Murine Oviductal High-Grade Serous Carcinomas Mirror the Genomic Alterations, Gene Expression Profiles, and Immune Microenvironment of Their Human Counterparts
Authors: McCool Kevin W. , Freeman Zachary T. , Zhai Yali , Wu Rong , Hu Kevin , Liu Chia-Jen , Tomlins Scott A. , Fearon Eric R. , Magnuson Brian , Kuick Rork , Cho Kathleen R.
Published: December 2019

Robust preclinical models of ovarian high-grade serous carcinoma (HGSC) are needed to advance our understanding of HGSC pathogenesis and to test novel strategies aimed at improving clinical outcomes for women with the disease. Genetically engineered mouse models of HGSC recapitulating the likely cell of origin (fallopian tube), underlying genetic defects, histology, and biologic behavior of human HGSCs have been developed. However, the degree to which the mouse tumors acquire the somatic genomic changes, gene expression profiles, and immune microenvironment that characterize human HGSCs remains unclear. We used integrated molecular characterization of oviductal HGSCs arising in the context of Brca1, Trp53, Rb1, and Nf1 (BPRN) inactivation to determine whether the mouse tumors recapitulate human HGSCs across multiple domains of molecular features. Targeted DNA sequencing showed the mouse BPRN tumors, but not endometrioid carcinoma-like tumors based on different genetic defects (e.g., Apc and Pten), acquire somatic mutations and widespread copy number alterations similar to those observed in human HGSCs. RNA sequencing showed the mouse HGSCs most closely resemble the so-called immunoreactive and mesenchymal subsets of human HGSCs. A combined immuno-genomic analysis demonstrated the immune microenvironment of BPRN tumors models key aspects of tumor-immune dynamics in the immunoreactive and mesenchymal subtypes of human HGSC, with enrichment of immunosuppressive cell subsets such as myeloid-derived suppressor cells and regulatory T cells. The findings further validate the BPRN model as a robust preclinical experimental platform to address current barriers to improved prevention, diagnosis, and treatment of this often lethal cancer.

Significance:

The acquired gene mutations, broad genomic alterations, and gene expression and immune cell–tumor axis changes in a mouse model of oviductal serous carcinoma closely mirror those of human tubo-ovarian high-grade serous carcinoma.
Tryptophan 2,3-Dioxygenase Expression Identified in Human Hepatocellular Carcinoma Cells and in Intratumoral Pericytes of Most Cancers
Authors: Hoffmann Delia , Dvorakova Tereza , Stroobant Vincent , Bouzin Caroline , Daumerie Aurélie , Solvay Marie , Klaessens Simon , Letellier Marie-Claire , Renauld Jean-Christophe , van Baren Nicolas , Lelotte Julie , Marbaix Etienne , Van den Eynde Benoit J.
Published: December 2019

Tryptophan catabolism is used by tumors to resist immune attack. It can be catalyzed by indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO). IDO1 is frequently expressed in tumors and has been widely studied as a potential therapeutic target to reduce resistance to cancer immunotherapy. In contrast, TDO expression in tumors is not well characterized. Several human tumor cell lines constitutively express enzymatically active TDO. In human tumor samples, TDO expression has previously been detected by transcriptomics, but the lack of validated antibodies has precluded detection of the TDO protein and identification of TDO-expressing cells. Here, we developed novel TDO-specific monoclonal antibodies and confirmed by immunohistochemistry the expression of TDO in the majority of human cancers. In all hepatocarcinomas (10/10), TDO was expressed by most tumor cells. Some glioblastomas (10/39) and kidney carcinomas (1/10) also expressed TDO in tumor cells themselves but only in focal tumor areas. In addition, all cancers tested contained foci of nontumoral TDO-expressing cells, which were identified as pericytes by their expression of PDGFRβ and their location in vascular structures. These TDO-expressing pericytes belonged to morphologically abnormal tumor vessels and were found in high-grade tumors in the vicinity of necrotic or hemorrhagic areas, which were characterized by neoangiogenesis. We observed similar TDO-expressing pericytes in inflammatory pulmonary lesions containing granulation tissue, and in chorionic villi, two tissue types that also feature neoangiogenesis. Our results confirm TDO as a relevant immunotherapeutic target in hepatocellular carcinoma and suggest a proangiogenic role of TDO in other cancer types.

See article by Schramme et al., p. 32
Variation on the CRH Gene Determines the Different Performance of Opioid Addicts and Healthy Controls in the IOWA Gambling Task
Authors: Seeliger Christian , Lippold Julia V. , Reuter Martin
Published: December 2019

Background: The hypothalamus-pituitary-adrenal (HPA) axis, the biological substrate of stress reactivity, and related genetic variations play a crucial role in the initiation and maintenance of drug addiction. On the behavioral level, substance abusers are characterized by impulsivity and the inability to pursue long-term goals. The neural substrate of these behaviors is assumed to be related to the ventromedial prefrontal cortex (VMPFC). One of the most established paradigms to assess VMPFC deficiency is the IOWA gambling task (IGT). Aims: The aim of this study was to investigate the interplay between the HPA axis-related genetic variation on corticotropin-releasing hormone (CRH; secreted from the hypothalamus and constituting the starting point of the HPA axis) gene and opioid addiction, with respect to IGT performance. There is some evidence that stress and pathological HPA axis hyperactivity, in the same way as drug addiction, is related to a poorer IGT performance. Methods: In total, 138 long-term opioid addicts (mean age 38.63 years [SD 9.15]) and 160 healthy controls (mean age 22.57 years [SD 5.86]) performed the IGT and were genotyped for 6 SNPs covering the CRH gene and adjacent regions (rs3176921, rs6999780, rs7816410, rs1870393, rs1814583, and rs11996294). The first 5 of these 6 SNPs build a haplotype block spanning 15 kb on the CRH gene. Results: We found a significant group difference in the total IGT score, with higher scores in controls than in opioids. Most interestingly, there was a 3-way interaction, group × haplotype × block. Carriers homozygous for the TGTAA-haplotype differed in IGT performance dependent on group. In the control group, carriers homozygous for the TGTAA-haplotype showed a linear learning curve across blocks of trials, which was not observed in participants without this homozygosity. There were diametric effects in opioid addicts. Controlling for age and gender did not change the findings. Conclusion: This study provides genetic evidence for the interplay between stress, decision-making, and opioid addiction.
Inhibition of NLRP3 Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by NF-κB Signaling
Authors: Zou Yuanyuan , Cui Bingjie , Liang Pei , Tian Xiaoyu , Ma Yiming , Zhao Shaozhen
Published: December 2019

Backgrounds/Aims: To explore whether NLRP3 is involved in the development of cataract and to study the effect of NLRP3 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells. Methods: Oxidative stress-induced apoptosis model was constructed by treating HLEB3 cells with 50 µM H2O2 at different times (6 h, 12 h) and was confirmed by flow cytometry and Western blot. HLEB3 were divided into NC, NC+H2O2, shNLRP3, and shNLRP3+H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, DCFH-DA to measure reactive oxygen species production, and Annexin V-FITC/PI staining to determine cell apoptosis. Results: NLRP3 expression significantly increased in H2O2-induced HLEB3 cells. shRNA interference of NLRP3 inflammasome protects HLEB3 cells against oxidative stress-induced apoptosis by decreasing the expression levels of caspase-3 and Bax and increasing Bcl-2 expression. shNLRP3 was able to effectively suppress H2O2-induced apoptosis via inhibition of NF-κB signaling. Conclusion: NLRP3 might be involved in the apoptosis of lens epithelial cells. The inhibition of NLRP3 obviously attenuated H2O2-induced oxidative stress injury of human lens epithelial cells via NF-κB signaling.
The Current Practice of Lynch Syndrome Diagnosis and Management in Italy: A Qualitative Assessment
Authors: Tognetto Alessia , Pastorino Roberta , Castorina Sergio , Condorelli Daniele Filippo , DeCensi Andrea , De Vito Corrado , Magnano Antonio , Scaldaferri Franco , Villari Paolo , Genuardi Maurizio , Boccia Stefania
Published: December 2019

Background: Lynch syndrome (LS) is the most frequent form of hereditary colorectal cancer (CRC; up to 3–5% of the total CRC burden) and predisposes to the development of other cancers. Multidisciplinary diagnostic strategies are relevant both to the index cases and to their at-risk relatives, but their implementation is still limited. Our study aimed to explore LS testing practices in Italy. Methods: In order to ascertain the current practice of LS diagnosis and management, we conducted a qualitative assessment by sending a questionnaire to health care professionals at 4 Italian hospitals selected as “models” representing different hospital settings. Based on the surveys, we reconstructed the management pathways for CRC patients in terms of diagnostic strategies and health professionals involved. Results: Seven of the 8 invited professionals filled in the questionnaire. Noncompliance with the latest guidelines was reported, as no tumor “screening” was performed on CRC cases. The lack of a structured multidisciplinary team who manages CRC patients from risk assessment to diagnosis and follow-up was reported. The availability of professionals and laboratory technologies differ widely between hospitals. As for cascade testing of at-risk relatives, a systematic and active approach was absent in all the considered hospitals. Conclusions: Our study shows that no structured and standardized pathways for the diagnosis and management of LS patients are currently in place in Italy. We envisage that by extending our research to further experiences and countries, an increasing awareness of the topic can be translated into a health gain for hereditary CRC patients and their at-risk relatives.
Siglec-14 Enhances NLRP3-Inflammasome Activation in Macrophages
Authors: Tsai Chih-Ming , Riestra Angelica M. , Ali Syed Raza , Fong Jerry J. , Liu Janet Z. , Hughes Gillian , Varki Ajit , Nizet Victor
Published: December 2019

Pathogenic microorganisms are sensed by the inflammasome, resulting in the release of the pro-immune and proinflammatory cytokine interleukin-1β (IL-1β). In humans, the paired sialic acid-binding Ig-like lectin receptors Siglec-5 (inhibitory) and Siglec-14 (activating) have been shown to have reciprocal roles in regulating macrophage immune responses, but their interaction with IL-1β signaling and the inflammasome has not been characterized. Here we show that in response to known inflammasome activators (ATP, nigericin) or the sialic acid-expressing human bacterial pathogen group B Streptococcus (GBS), the presence of Siglec-14 enhances, whereas Siglec-5 reduces, inflammasome activation and macrophage IL-1β release. Human THP-1 macrophages stably transfected with Siglec-14 exhibited increased caspase-1 activation, IL-1β release and pyroptosis after GBS infection, in a manner blocked by a specific inhibitor of nucleotide-binding domain leucine-rich repeat protein 3 (NLRP3), a protein involved in inflammasome assembly. Another leading pathogen, Streptococcus pneumoniae, lacks sialic acid but rather prominently expresses a sialidase, which cleaves sialic acid from macrophages, eliminating cis- interactions with the lectin receptor, thus attenuating Siglec-14 induced IL-1β secretion. Vimentin, a cytoskeletal protein released during macrophage inflammatory activation is known to induce the inflammasome. We found that vimentin has increased interaction with Siglec-14 compared to Siglec-5, and this interaction heightened IL-1β production by Siglec-14-expressing cells. Siglec-14 is absent from some humans because of a SIGLEC5/14 fusion polymorphism, and we found increased IL-1β expression in primary macrophages from SIGLEC14+/+ individuals compared to those with the SIGLEC14–/+ and SIGLEC14–/– genotypes. Collectively, our results identify a new immunoregulatory role of Siglec-14 as a positive regulator of NLRP3 inflammasome activation.
Dynamic Changes in the Localization of Neuronatin-Positive Cells during Neurogenesis in the Embryonic Rat Brain
Authors: Kanno Naoko , Fujiwara Ken , Yoshida Saishu , Kato Takako , Kato Yukio
Published: December 2019

Neuronatin (NNAT) was first identified as a gene selectively and abundantly expressed in the cytoplasm of the newborn mouse brain, and involved in neonatal neurogenesis. However, the particular roles of NNAT in the developing prenatal brain have not been identified, especially in mid to late stages. In this study, we performed immunohistochemical analyses of NNAT and SOX2 proteins, a nuclear transcription factor and neural stem/progenitor marker, in the rat brain on embryonic days 13.5, E16.5, and E20.5. NNAT signals were broadly observed across the developing brain on E13.5 and gradually more localized in later stages, eventually concentrated in the alar and basal parts of the terminal hypothalamus, the alar plate of prosomere 2 of the thalamus, and the choroid plexus in the lateral and fourth ventricles on E20.5. In particular, the mammillary body in the basal part of the terminal hypothalamus, a region with a high number of SOX2-positive cells, evidenced intense NNAT signals on E20.5. The intracellular localization of NNAT showed diverse profiles, suggesting that NNAT was involved in various cellular functions, such as cell differentiation and functional maintenance, during prenatal neurogenesis in the rat brain. Thus, the present observations suggested diverse and active roles of the NNAT protein in neurogenesis. Determining the function of this molecule may assist in the elucidation of the mechanisms involved in brain development.