bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multiple Criteria Decision Analysis Method for Alternative Assessment Results Obeying a Particular Distribution and Application
Authors: He-Hua Wang , Jian-Jun Zhu , Xiao-Yan Gu , Ye Chen
Published: May 2018

A multiple criteria decision analysis (MCDA) problem is studied in this paper, for which the evaluation results obey a particular distribution. First, when solving a multiple criteria decision analysis (MCDA) problem, a grey target decision analysis framework is proposed to determine uncertain parameters and criteria weights. A measurement for comprehensive off-target distance is defined, which includes the undetermined parameters. Second, to satisfy the requirements of a specific distribution (such as a normal distribution) in the assessment results, an optimization model that incorporates the off-target distance constraints is proposed by considering the skewness and kurtosis test method. Third, a particle swarm optimization (PSO) algorithm is extended to solve the proposed model by seeking the appropriate parameters and weights. Fourth, a numerical example is applied to demonstrate the feasibility and application of the proposed method. In the end, the proposed model is extended to other distribution requirements.
March1 E3 Ubiquitin Ligase Modulates Features of Allergic Asthma in an Ovalbumin-Induced Mouse Model of Lung Inflammation
Authors: Kishta Osama A. , Sabourin Antoine , Simon Leora , McGovern Toby , Raymond Maxime , Galbas Tristan , Majdoubi Abdelilah , Ishido Satoshi , Martin James G. , Thibodeau Jacques
Published: May 2018

Membrane-associated RING-CH-1 (March1) is a member of the March family of E3 ubiquitin ligases. March1 downregulates cell surface expression of MHC II and CD86 by targeting them to lysosomal degradation. Given the key roles of MHC class II and CD86 in T cell activation and to get further insights into the development of allergic inflammation, we asked whether March1 deficiency exacerbates or attenuates features of allergic asthma in mice. Herein, we used an acute model of allergy to compare the asthmatic phenotype of March1-deficient and -sufficient mice immunized with ovalbumin (OVA) and later challenged by intranasal instillation of OVA in the lungs. We found that eosinophilic inflammation in airways and lung tissue was similar between WT and March1−/− allergic mice, whereas neutrophilic inflammation was significant only in March1−/− mice. Airway hyperresponsiveness as well as levels of IFN-γ, IL-13, IL-6, and IL-10 was lower in the lungs of asthmatic March1−/− mice compared to WT, whereas lung levels of TNF-α, IL-4, and IL-5 were not significantly different. Interestingly, in the serum, levels of total and ova-specific IgE were reduced in March1-deficient mice as compared to WT mice. Taken together, our results demonstrate a role of March1 E3 ubiquitin ligase in modulating allergic responses.
Location‐Dependent Prediction of Dynamic Stability Limit for Peripheral Milling of Surfaces with Variable Curvatures
Authors: Wang Baosheng , Hao Hongyan , Wang Mulan , Hou Junming
Published: May 2018

The stability limit may change with the cutter’s location due to effect of curvature during the milling of a complex surface. The method for calculating the actual radial cutting depth is presented by accounting for the effects of curvature on the actual cutting parameters. The computed radial cutting depth is in turn used to determine the entrance/exit angles. Moreover, a milling system dynamic model is established based on the instantaneous milling force coefficients, and the stability limit is determined by means of the time‐domain semidiscretization method. In addition, a location‐dependent method for predicting the stability associated with the peripheral milling of a complex surface is put forward and simulation is carried out to generate a stability limit diagram. The effectiveness of the proposed method is verified through milling tests.
Periampullary Variceal Bleeding: An Atypical Complication of Portal Hypertension
Authors: Farkas Zahava C. , Chugh Priyanka , Frager Shalom , Haq Khwaja F. , Khan Muhammad Ali , Solanki Shantanu , Esses Edward , Veillette Gregory , Bodin Roxana
Published: May 2018

Variceal bleeding remains a fatal complication of portal hypertension. Periampullary varices are rare and, due to their location, are difficult to diagnose and treat. Similar to esophagogastric varices, they are the result of high portosystemic pressures secondary to intrahepatic causes such as cirrhosis and extrahepatic causes such as portal or splenic vein thrombosis. We report a case of a periampullary varix resulting in hemobilia during endoscopic retrograde cholangiopancreatography (ERCP).
Research on Acoustic Emission and Electromagnetic Emission Characteristics of Rock Fragmentation at Different Loading Rates
Authors: Zhao Fujun , Li Yu , Ye Zhouyuan , Fan Yong , Zhang Siping , Wang Haifan , Liu Yonghong
Published: May 2018

The relationships among the generation of acoustic emission, electromagnetic emission, and the fracture stress of rock grain are investigated, which are based on the mechanism of acoustic emission and electromagnetic emission produced in the process of indenting rock. Based on the relationships, the influence of loading rate on the characteristics of acoustic emission and electromagnetic emission of rock fragmentation is further discussed. Experiment on rock braking was carried out with three loading rates of 0.001 mm/s, 0.01 mm/s, and 0.1 mm/s. The results show that the phenomenon of acoustic emission and electromagnetic emission is produced during the process of loading and breaking rock. The wave forms of the two signals and the curve of the cutter indenting load show jumping characteristics. Both curves have good agreement with each other. With the increase of loading rate, the acoustic emission and electromagnetic emission signals are enhanced. Through analysis, it is found that the peak count rate, the energy rate of acoustic emission, the peak intensity, the number of pulses of the electromagnetic emission, and the loading rate have a positive correlation with each other. The experimental results agree with the theoretical analysis. The proposed studies can lead to an in‐depth understanding of the rock fragmentation mechanism and help to prevent rock dynamic disasters.
Evaluation of Alkali-Pretreated Soybean Straw for Lignocellulosic Bioethanol Production
Authors: Kim Seonghun
Published: May 2018

Soybean straw is a renewable resource in agricultural residues that can be used for lignocellulosic bioethanol production. To enhance enzymatic digestibility and fermentability, the biomass was prepared with an alkali-thermal pretreatment (sodium hydroxide, 121°C, 60 min). The delignification yield was 34.1~53%, in proportion to the amount of sodium hydroxide, from 0.5 to 3.0 M. The lignin and hemicellulose contents of the pretreated biomass were reduced by the pretreatment process, whereas the proportion of cellulose was increased. Under optimal condition, the pretreated biomass consisted of 74.0±0.1% cellulose, 10.3±0.1% hemicellulose, and 10.1±0.6% lignin. During enzymatic saccharification using Cellic® CTec2 cellulase, 10% (w/v) of pretreated soybean straw was hydrolyzed completely and converted to 67.3±2.1 g/L glucose and 9.4±0.5 g/L xylose with a 90.9% yield efficiency. Simultaneous saccharification and fermentation of the pretreated biomass by Saccharomyces cerevisiae W303-1A produced 30.5±1.2 g/L ethanol in 0.5 L fermented medium containing 10% (w/v) pretreated biomass after 72 h. The ethanol productivity was 0.305 g ethanol/g dry biomass and 0.45 g ethanol/g glucose after fermentation, with a low concentration of organic acid metabolites. Also, 82% of fermentable sugar was used by the yeast for ethanol fermentation. These results show that the combination of alkaline pretreatment and biomass hydrolysate is useful for enhancing bioethanol productivity using delignified soybean straw.
Fetal Midgut Volvulus with Meconium Peritonitis Detected on Prenatal Ultrasound
Authors: Best Emanuelle J. , O’Brien Cecelia M. , Carseldine Wendy , Deshpande Aniruddh , Glover Rebecca , Park Felicity
Published: May 2018

Background. Fetal volvulus is a rare, yet life-threatening condition that requires skilful diagnosis and management. Volvulus occurs when bowel loops become twisted and the twisting of the mesenteric artery leads to congestion, impaired venous return, and bowel necrosis. Case Description. We present a case of fetal ileal volvulus suspected on third trimester ultrasound, complicated by premature labour, small bowel necrosis, and meconium peritonitis. Progressive dilatation and decreased peristalsis of echogenic bowel were noted in the early part of the third trimester. Daily surveillance ultrasound was performed and spontaneous labour occurred at 32 weeks’ gestation. A proactive postnatal approach guided by prenatal sonographic findings allowed prompt treatment and an urgent laparotomy was performed for an ileal volvulus with necrosis and meconium peritonitis. A segment of small bowel volvulus was resected and an end-to-end anastomosis was performed with uneventful recovery. Discussion. Clinically signs of fetal midgut volvulus are not pathognomonic, such as intestinal dilatation, abdominal mass, ascites, peritoneal calcifications, or polyhydramnios; thus, the diagnosis is often challenging. Complications reported in the literature include perforation and haemorrhagic ascites, which may lead to anaemia, hypovolemia, heart failure, and fetal demise. Conclusion. This case highlights the importance of assessing the fetal bowel as a part of routine third trimester ultrasound. The case describes the complexity of diagnosis in the fetus, important considerations along with multidisciplinary team approach to management.
PIK3CA and p53 Mutations by Next Generation Sequencing in Lymphoepithelioma-Like Carcinoma of the Endometrium
Authors: Bienfait Lucie , D’Haene Nicky , Catteau Xavier , Noël Jean-Christophe
Published: May 2018

Lymphoepithelioma-like carcinoma of the endometrium is a very rare variant of endometrial carcinoma characterized by syncytial nests of pleomorphic epithelial cells and heavy infiltration of the stroma by lymphocytes (in particular CD8 cytotoxic T-lymphocytes) and plasma cells. Until now, only five cases have been characterized in this location. This report describes the clinicopathological and the molecular features of this unusual tumor. In particular, using the next generation sequencing (NGS) technique, we have demonstrated that this tumor could be associated with PIK3CA and p53 gene mutations. These data have not been reported to date and suggest that lymphoepithelioma-like carcinoma of the endometrium shares common molecular features with high grade endometrioid and serous-like endometrial carcinoma which are associated with poor outcome. Nevertheless, in endometrial lymphoepithelioma-like carcinoma, the alterations on cell cycle, apoptosis, and/or senescence secondary to p53 mutations could potentially be counterbalanced by the antitumoral response induced by CD8 cytotoxic T-lymphocytes numerous in these tumors.
The Role of Osteocalcin and Alkaline Phosphatase Immunohistochemistry in Osteosarcoma Diagnosis
Authors: Agustina Hasrayati , Asyifa Ita , Aziz Afiati , Hernowo Bethy S.
Published: May 2018

Background. The diagnosis of Osteosarcoma (OSA) is not always straightforward. OSA may resemble Other Primary Bone Tumours (OPBT). The diagnosis of osteosarcoma is sometimes difficult especially in a very small specimen. Immunohistochemistry is one of ancillary testing types that can help the diagnosis of many tumours. The aim of this study was to evaluate the validity of Osteocalcin (OCN) and Alkaline Phosphatase (ALP) immunohistochemistry in discriminating OSA from OPBT. Method. This study included 50 selected human primary bone tumours, 25 cases of OSA and 25 cases of OPBT. Immunohistochemical evaluation of OCN and ALP was done for all cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Result. The mean age of OSA and OPBT patients was 19.6±13.6 and 40.0±16.3 years, respectively. Osteocalcin was positive in 17/25 (68%) cases of OSA and 16/25 (64%) cases of OPBT (p=0.061). Alkaline Phosphatase was positive in 24/25 (96%) cases of OSA and 5/25 (20%) cases of OPBT (p<0.001). The sensitivity of OCN in OSA diagnosis was 68%, with specificity, PPV, NPV, and overall accuracy being 36%, 52%, 53%, and 52%, respectively. The sensitivity of ALP in OSA diagnosis was 96%, with specificity, PPV, NPV, and overall accuracy being 80%, 82.7%, 95.2%, and 88%, respectively. Conclusion. ALP immunohistochemistry is useful in discriminating OSA from OPBT. ALP is superior to OCN in OSA diagnosis. OCN cannot be used to differentiate between OSA and OPBT.
Utilization Status and Satisfaction with Medical Services in Nonresidential Foreign Medical Tourists Visiting a Korean Medicine Hospital
Authors: Shin Jaekwon , Lee Yoon Jae , Shin Joon-Shik , Lee Jinho , Kim Haneul , Kim Me-riong , Ha In-Hyuk
Published: May 2018

Medical tourism refers to international patient travel with the intent of receiving medical care. Recently, South Korea, armed with a dual medical system of conventional and traditional Korean medicine, has been gaining international standing in this industry. This study examined the characteristics, medical service use, and satisfaction of foreign patients who visited a spine‐specialty Korean medicine hospital as musculoskeletal disorders are the highest frequency category of medical conditions treated using Korean medicine. The electronic medical records of 1,733 foreign patients who had first visited an integrative Korean medicine hospital in 2012–2015 were analyzed, and a satisfaction survey was conducted by e‐mail along with phone calls and interviews. Female patients in their 40s with low back or neck pain comprised the most prevalent patient group. The most frequently used visiting channels were agencies, followed by recommendation by friends or family. Patients received an average of 5.25 sessions, and, based on analysis of 134 survey results, the highest satisfaction rates were associated with acupuncture and pharmacopuncture of provided treatments, high physician expertise, and reliability among medical services and coordinating and translating services among nonmedical factors. Overall, 90.2% replied that they were satisfied and 76.9% that their perception of Korean medicine had improved following treatment. Nonresidential foreigners who received integrative medicine treatment expressed high satisfaction, but visiting and promotion channels were shown to be limited, which connotes both the potential of Korean medicine in propelling Korea forward in the global medical tourism industry and the need for more systematic promotion of Korean medicine medical tourism.
Danshen-Honghua Ameliorates Stress-Induced Menopausal Depression in Rats
Authors: Gu Simeng , Ma Yao , Ge Kemin , Nie Ruifang , Wu Erxi , Li Yang
Published: May 2018

Objective. Previously, we have shown that Danshen-Honghua (DSHH) for cognitive deficits after ischemia induced impairments of the hippocampus. Here, we investigate the effects of DSHH on stress-induced depression in menopausal rats. Methods. A rat model with menopausal depression was established with bilateral ovariectomies in female SD rats followed by chronic mild stress treatment for 21 days. 40 rats were randomly divided into the sham surgery group (sham surgery and no stress treatment), surgery group (surgery with no stress treatment), surgery/stress group (surgery and stress treatment), fluoxetine group (2.4 mg·kg−1, with surgery and stress treatment), and DSHH group (35 g·kg−1, with surgery and stress treatment). The rats in the last two groups were treated with stresses together with intragastric drug administration for three weeks after the surgery. Then open-field locomotor scores and sucrose intake were tested for behavior changes. Also, the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and cortisone were determined by high-performance liquid chromatography (HPLC). Serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined by radioimmunoassay. Results. The results of open-field locomotor scores, sucrose intake in both the fluoxetine group and DSHH group, were significantly higher than those of the surgery/stress group (P<0.01). Serum LH, FSH, and cortisone levels in both the DSHH group and fluoxetine group were significantly lower than those in the surgery/stress group (P<0.01). Serum E2 levels in these groups were slightly increased in these medicine groups (P<0.01). The monoamine levels in the DSHH group were much higher than those in the surgery/stress group (P<0.01). Conclusion. DSHH can ameliorate stress-induced depressed syndromes in the surgery/stressed rats via regulating LH and FSH levels as well as monoamine levels.
On Generalized Moduli of Quasi-Banach Space
Authors: Kwun Young Chel , Ahmad Qadri Hussain Minhaj Uddin , Nazeer Waqas , Haq Absar Ul , Kang Shin Min
Published: May 2018

We shall discuss three generalized moduli such as generalized modulus of convexity, modulus of smoothness, and modulus of Zou-Cui of quasi-Banach spaces and give some important properties of these moduli. Furthermore, we establish relationships of these generalized moduli with each other.
Efficacy and Renal Safety of Dapagliflozin in Patients with Type 2 Diabetes Mellitus Also Receiving Metformin: A Real-Life Experience
Authors: Scorsone Alessandro , Saura Gabriella , Fleres Mattia , Spano Lucia , Aiello Vito , Brancato Davide , Di Noto Anna , Provenzano Francesca , Provenzano Vincenzo
Published: May 2018

Introduction. This study aimed at evaluating the efficacy and safety of dapagliflozin in patients with type 2 diabetes (T2D) who also received metformin in clinical practice in Italy. Methods. This was a retrospective observational study and it included data from patients who received dapagliflozin 10 mg once daily in conjunction with metformin for 12 months (DAPA + MET). In those with inadequate glycemic control, insulin or glimepiride was added after 30 days (DAPA + MET + other glucose-lowering drugs). Efficacy assessments included glycosylated hemoglobin (HbA1c) levels at 6 and 12 months, as well as body mass index (BMI) and lipid parameters at 12 months. Safety was also assessed. Results. Data on 66 patients were included. In both groups, HbA1c was significantly reduced at 6 and 12 months compared with baseline and significant reductions in HbA1c were observed at 12 months compared with 6 months. Over the 12-month treatment period, dapagliflozin significantly reduced BMI in both groups. No significant changes in lipid parameters were observed in either group and no detrimental effects on renal function were detected. Conclusions. Dapagliflozin is effective and safe in patients with T2D also receiving metformin. Glycemic control was already achieved with dapagliflozin + metformin, and add-on therapy was not associated with further improvements.
Successful Management of Cervical Ectopic Pregnancy with Bilateral Uterine Artery Embolization and Methotrexate
Authors: Takeda Keitaroh , Mackay John , Watts Susan
Published: May 2018

Cervical ectopic pregnancy (CEP) is a rare form of ectopic pregnancy. Cases diagnosed early in pregnancy can be managed medically, but more advanced pregnancies often require hysterectomy. Uterine artery embolization (UAE) is a novel approach to CEP for those who wish to preserve fertility. Here we present the case of a 44-year-old female with a 2-week history of vaginal bleeding and abdominal pain who was diagnosed with CEP and successfully treated with bilateral UAE (BUAE) in combination with methotrexate. A 44-year-old female presented to the emergency department with a 2-week history of vaginal bleeding. Serum beta-hCG was 71,964 mIU/ml. The transvaginal ultrasound confirmed CEP. The patient was referred to obstetrics and interventional radiology and ultimately treated with BUAE and methotrexate. Symptoms resolved quickly and she was discharged after 3 days.
Analysis of Metal Flow Behavior and Residual Stress Formation of Complex Functional Profiles under High‐Speed Cold Roll‐Beating
Authors: Cui Fengkui , Su Yongxiang , Xie Kege , Xiaoqiang Wang , Ruan Xiaolin , Liu Fei
Published: May 2018

To obtain a good surface layer performance of the complex functional profile during the high‐speed cold roll‐beating forming process, this paper analyzed the metal plastic flow and residual stress‐formed mechanism by using a theoretical model of the metal flow and residual stress generation. By using simulation software, the cold roll‐beating forming process of a spline shaft was simulated and analyzed. The metal flow and residual stress formation law in the motion were researched. In a practical experiment, the changes in the grains in the spline tooth profile section and the residual stress distribution on the tooth profile were studied. A microcorrespondence relationship was established between the metal plastic flow and the residual stress generation. The conclusions indicate that the rate at which the metal flow decreases changes gradually at different metal layers. The residual stress value is directly related to the plastic flow difference. As the roll‐beating speed increases, the uneven degree of plastic deformation at the workpiece surface increases, and the residual stress in the tooth profile is generally greater. At the same roll‐beating speed, the rate change trend of the metal flow decreases gradually from the surface to the inner layer and from the dedendum to the addendum. The residual stress distribution on the surface of the tooth profile decreases from the dedendum to the addendum. These findings provide a basis and guidance for the controlled use of residual stress, obtaining better surface layer quality in the high‐speed cold roll‐beating process of the complex functional profile.
Changes in Body Compositions and Basal Metabolic Rates during Treatment of Graves’ Disease
Authors: Kim Min Joo , Cho Sun Wook , Choi Sumin , Ju Dal Lae , Park Do Joon , Park Young Joo
Published: May 2018

Objectives. Because thyroid hormone is an important determinant of body weight and basal metabolic rate, we investigated the changes in the basal metabolic rate and body composition sequentially after treatment for Graves’ disease. Methods. A prospective cohort study was performed with six women newly diagnosed with Graves’ disease. During a 52-week treatment of methimazole, body composition, resting respiratory expenditure (REE), and handgrip strength were measured consecutively. Results. After methimazole treatment, body weight was initially increased (0–8 weeks), subsequently plateaued (8–24 weeks), and gradually decreased in the later period (24–52 weeks) despite the decreased food intake. The measured REE was 40% higher than the predicted REE at baseline, and it gradually decreased after treatment. REE positively correlated with thyroid hormone levels, peripheral deiodinase activity, and thyroid’s secretory capacity. Body compositional analyses showed that the fat mass increased during an earlier period (4–12 weeks), while the lean mass increased significantly during the later period (26–52 weeks). Consistent with the lean mass changes, muscle strength also significantly increased during the later period. Conclusions. Treatment of Graves’ disease increased body weight and fat mass transiently with decreased REE. However, long-term compositional changes moved in a beneficial direction increasing lean mass and reinforcing muscle strength, following decreasing fat percentages.
Functional Disconnectivity during Inter-Task Resting State in Dementia with Lewy Bodies
Authors: Chabran Eléna , Roquet Daniel , Gounot Daniel , Sourty Marion , Armspach Jean-Paul , Blanc Frédéric
Published: May 2018

Aims: Limited research has been done on the functional connectivity in visuoperceptual regions in dementia with Lewy bodies (DLB) patients. This study aimed to investigate the functional connectivity differences between a task condition and an inter-task resting state condition within a visuoperceptual paradigm, in DLB patients compared with Alzheimer disease (AD) patients and healthy elderly control subjects. Methods: Twenty-six DLB, 29 AD, and 22 healthy subjects underwent a detailed clinical and neuropsychological examination along with a functional MRI during the different conditions of a visuoperceptual paradigm. Functional images were analyzed using group-level spatial independent component analysis and seed-based connectivity analyses. Results: While the DLB patients scored well and did not differ from the control and AD groups in terms of functional activity and connectivity during the task conditions, they showed decreased functional connectivity in visuoperceptual regions during the resting state condition, along with a temporal impairment of the default-mode network activity. Functional connectivity disturbances were also found within two attentional-executive networks and between these networks and visuoperceptual regions. Conclusion: We found a specific functional profile in the switching between task and resting state conditions in DLB patients. This result could help better characterize functional impairments in DLB and their contribution to several core symptoms of this pathology such as visual hallucinations and cognitive fluctuations.
Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients
Authors: Zai Clement C. , Tiwari Arun K. , Zai Gwyneth C. , de Luca Vincenzo , Shaikh Sajid A. , King Nicole , Strauss John , Kennedy James L. , Vincent John B.
Published: May 2018

Background: A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide. Methods: We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder (N = 219). We analyzed these variants for a possible association with the suicide severity score (ranging from suicidal ideation/plan to serious suicide attempt) from the Schedule for Clinical Assessment in Neuropsychiatry. We conducted tests of individual variants and gene-based tests. Results: We found a number of DNA variants in the transforming growth factor beta receptor 1 gene (TGFBR1) to be suggestively associated with suicide severity scores (p < 0.005). The gene-based tests also pointed to TGFBR1 to be associated with suicide severity (p = 0.0001). However, these findings were not replicated in an independent bipolar disorder sample. Conclusions: We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.
Impact of Caries Severity/Activity and Psychological Aspects of Caregivers on Oral Health-Related Quality of Life among 5-Year-Old Children
Authors: Granville-Garcia Ana Flávia , Gomes Monalisa Cesarino , Perazzo Matheus França , Martins Carolina Castro , Abreu Mauro Henrique Nogueira Guimarães , Paiva Saul Martins
Published: May 2018

The aim of the present study was to evaluate the influence of the severity/activity of dental caries as well as sense of coherence (SOC) and locus of control (LOC) on oral health-related quality of life (OHRQoL) among 5-year-old children. A cross-sectional study was conducted involving 769 children at schools in a city in northeast Brazil. Parents/caregivers answered validated questionnaires addressing SOC and LOC. The children and parents/caregivers answered their respective modules of the Brazilian version of the Scale of Oral Health Outcomes for 5-year-old children (SOHO-5). Data were also collected on sociodemographic characteristics, visits to the dentist, and the occurrence of toothache. Clinical examinations were performed by 2 trained examiners. A directed acyclic graph was used to select covariates for statistical adjustment, and logistic regression for complex samples was used to test associations between the dependent and independent variables (α = 5%). For parents/caregivers, the variables associated with a negative impact on OHRQoL were the occurrence of toothache (odds ratio, OR: 10.53; 95% confidence interval, CI: 6.34–17.51; p < 0.001) and a low SOC (OR: 2.17; 95% CI: 1.37–3.43; p = 0.001). According to the children’s perceptions, the following variables were associated with a negative impact on OHRQoL: toothache (OR: 3.58; 95% CI: 2.30–5.55; p < 0.001), caries activity (OR: 1.97; 95% CI: 1.07–3.62; p = 0.028), and traumatic dental injury (OR: 1.71; 95% CI: 1.15–2.53; p = 0.007). Among parents/caregivers, a low SOC led to poorer OHRQoL. For the children, however, neither psychological aspect affected OHRQoL. In the perception of both the parents/caregivers and children, toothache was the oral condition that exerted a negative impact on OHRQoL.
Prognostic Factors Associated with Postprogression Survival in Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib Not Eligible for Second-Line Regorafenib Treatment
Authors: Kuzuya Teiji , Ishigami Masatoshi , Ishizu Yoji , Honda Takashi , Hayashi Kazuhiko , Ishikawa Tetsuya , Nakano Isao , Hirooka Yoshiki , Goto Hidemi
Published: May 2018

Objectives: The aim of this study was to investigate the prognostic factors associated with postprogression survival (PPS) in advanced hepatocellular carcinoma (HCC) patients treated with sorafenib, who were not eligible for second-line treatment with regorafenib. Methods: A total of 103 patients with radiological confirmation of progressive disease (PD) were enrolled. Results: The median PPS (n = 67) was 6.1 months. Significant and independent prognostic factors at initial radiological PD associated with good PPS were an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0, the absence of macrovascular invasion (MVI), and time to progression (TTP) ≥4 months. Upon scoring these three variables as good PPS factors, the median PPS in the good PPS score of 3 or 2 group (n = 38) was significantly longer than that in the good PPS score of 1 or 0 group (n = 29) (16.6 vs. 2.9 months; p < 0.0001, respectively). Conclusions: An ECOG-PS score of 0, the absence of MVI, and TTP ≥4 months at first radiological confirmation of PD may be useful for predicting good PPS in patients with advanced HCC who do not meet the eligibility criteria for the RESORCE trial.
Transvenous Embolization of Dural Arteriovenous Fistulas of the Hypoglossal Canal: Report of Three Cases and Review of the Literature
Authors: Santillan Alejandro , Schwarz Justin , Patsalides Athos
Published: May 2018

In this article, we report three cases of dural arteriovenous fistulas of the hypoglossal canal treated via transvenous approach. We also perform a review of the literature on the endovascular management of this type of lesions with particular attention to the dangerous extracranial-intracranial anastomoses that can occur at this level.
Dioleoylphosphoethanolamine Retains Cell Surface GLUT4 by Inhibiting PKCα-Driven Internalization
Authors: Nishizaki Tomoyuki
Published: May 2018

Background/Aims: Phosphatidylethanolamine, a component of the plasma membrane, regulates diverse cellular processes. The present study investigated the role of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in the trafficking of the glucose transporter GLUT4 and the glucose homeostasis. Methods: Monitoring of GLUT4 trafficking, GLUT4 internalization assay, and glucose uptake assay were carried out using differentiated 3T3-L1-GLUT4myc adipocytes. Akt1/2 and PKC isozymes were knocked-down by transfecting each siRNA. Cell-free PKC assay and in situ PKCα assay with a FRET probe were carried out. Oral glucose tolerance test (OGTT) was performed using BKS.Cg-+Lepdb/+Lebdb/Jcl mice, an animal model of type 2 diabetes mellitus (DM). Results: DOPE increased cell surface localization of the glucose transporter GLUT4 in differentiated 3T3-L1-GLUT4myc adipocytes, regardless of Akt activation. Likewise, PKCα deficiency increased cell surface localization of GLUT4, that occludes the effect of DOPE. DOPE clearly suppressed phorbol 12-myristate 13-acetate-induced PKCα activation in the cell-free and in situ PKC assay. DOPE and PKCα deficiency cancelled endocytic internalization of GLUT4 localized on the plasma membrane after insulin stimulation. DOPE significantly enhanced glucose uptake into cells. A similar effect was obtained by knocking-down PKCα, that occludes the effect of DOPE. In OGTT, oral administration with DOPE effectively restricted an increase in the blood glucose levels after glucose loading in type 2 DM model mice. Conclusion: The results of the present study show that DOPE retains cell surface GLUT4 by suppressing PKCα-driven endocytic internalization of GLUT4, to enhance glucose uptake into cells and restrict an increase in the blood glucose levels after glucose loading in type 2 DM.
Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells
Authors: Xu Kui , Liu Xiu-fen , Ke Zhi-qiang , Yao Qing , Guo Shuang , Liu Chao
Published: May 2018

Background/Aims: Diabetic cardiomyopathy is associated with increased apoptosis and suppressed autophagy in cardiac cells. The polyphenol resveratrol has shown beneficial effects in various cardiovascular diseases. This study investigated if resveratrol protected cardiac cells by modulating apoptosis and autophagy in the context of diabetes. Methods: H9c2 cardiac myoblast cells were exposed to high glucose combined with palmitate. Autophagy was evaluated by estimating LC3-II/I ratio, P62 protein levels, and LC3 fluorescent puncta. Apoptosis was assessed by using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), flow cytometry, and analysis of the protein expression of apoptotic markers (cleavage of caspase-3 and PARP). Results: High glucose and palmitate suppressed autophagic activity and exacerbated apoptotic cell death in cardiac myoblast cells. Resveratrol restored autophagy and attenuated apoptosis in cells upon diabetic stimuli. Moreover, resveratrol activated AMPK and JNK1, thereby suppressing mTOR and its downstream effectors p70S6K1 and 4EBP1, as well as disrupting the Beclin1–Bcl-2 complex. Conclusion: Resveratrol protects cardiac cells by regulating the switch between autophagy and apoptotic machinery under diabetic conditions, which is attributed by AMPK-mediated phosphorylation of mTORC1/p70S6K1/4EBP1 and JNK-mediated dissociation of Beclin1-Bcl-2. Our study suggests that autophagy may be an important target for resveratrol in the treatment of diabetic cardiomyopathy.
Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats
Authors: Zheng Long , Li Long , Qi Guisheng , Hu Mushuang , Hu Chao , Wang Shuo , Li Jiawei , Zhang Mingnan , Zhang Weitao , Zeng Yigang , Zhang Yi , Li Liping , Wang Xuanchuan , Lin Miao , Zhu Tongyu , Rong Ruiming
Published: May 2018

Background/Aims: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. Methods: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days. The degree of renal damage and fibrosis was determined using histological assessment. The expression of collagen I, fibronectin, epithelial-mesenchymal transition markers, and Smad2/3 phosphorylation was examined by western blot analyses. Real-time PCR and enzyme-linked immunosorbent assay were performed in vivo to detect the levels of transforming growth factor (TGF)-β1 and various growth factors. Results: Telocytes attenuated renal fibrosis, as evidenced by reduced interstitial collagen accumulation, decreased expression of fibronectin and collagen I, upregulation of E-cadherin, and downregulation of α-smooth muscle actin. Furthermore, telocytes decreased serum TGF-β1 levels, suppressed Smad2/3 phosphorylation, and increased the expression of hepatocyte growth factor (HGF) in rat kidney tissue following UUO. Blockage of HGF counteracted the protective effect of telocytes on UUO-treated kidneys. Through the detection of HGF mRNA levels in vitro, we found that telocytes had no effect on HGF expression compared with renal fibroblasts. Conclusion: Telocytes attenuated UUO-induced renal fibrosis in rats, likely through enhancing the expression of HGF in an indirect manner.
Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model
Authors: Bin-Jaliah Ismaeel 
Published: May 2018

Background/Aims: Cancer cells in vivo develop resistance to many anti-tumor drugs. One known factor to influence such drug resistance is hypoxia, which is an important component of the tumor microenvironment. Standard cancer lines mostly do not exhibit a cellular hypoxic microenvironment and there is a paucity of information on the efficacy of lead molecules in both cellular- and environment-induced hypoxic conditions. Therefore, in the present study, we have evaluated the efficacy of the arylidene derivative MLT-401, a lead molecule showing activity against colorectal cancer model using the HCT 116 cell line and CCD-80-C control cells in normoxic and natural (marginal) hypoxic conditions, which is usually observed in high-altitude regions. Methods: The efficacy of MLT-401 on HCT 116 and CCD-80-C cells were tested in both normoxia and marginal hypoxia conditions. MTT assay was used to evaluate cell proliferation, Annexin V binding assay for apoptotic cell quantification and PI staining for cell cycle were done by flow cytometry. Induction of pro-apoptotic marker BAX and anti-apoptotic Bcl-2 were assessed by western blot. Bcl-2/BAX ratio was calculated based on protein expression by western blotting and bands were quantified by Image J software. Results: Analysis of cell proliferation showed an average 10-fold reduction in the inhibition of HCT 116 cells in hypoxic conditions with approximately 500 nM MLT-401, while there was no significant change noted in marginal hypoxic conditions. A proportionate increase in the number of apoptotic cells and large M4 fraction of 10.5% and 26.7% of HCT116 against 6.3% of control cells in cell cycle assessment with MLT-401 concentrations ranging from 250 to 500 nM respectively clearly demonstrated anti-cancer activity. A Bcl-2/BAX ratio of < 1 showed that the induction of apoptosis was the gross mechanism underlying the inhibition of HCT 116 cells by MLT-401. Conclusion: Collectively, these results show MLT-401 as an effective anti-colorectal cancer lead molecule irrespective of normoxia or natural hypoxia.
Genetic Analysis of TREM2 Variants in Tunisian Patients with Alzheimer's Disease
Authors: Landoulsi Zied , Ben Djebara Mouna , Kacem Imen , Sidhom Youssef , Kefi Rym , Abdelhak Sonia , Gargouri-Berrechid Amina , Gouider Riadh
Published: May 2018

Objective: Rare variants in the TREM2 gene have been reported to significantly increase the risk of Alzheimer’s disease in Caucasian populations. Hitherto, this association was not studied in North African populations. In this work, we aimed to study the association between TREM2 exon 2 variants and the risk of late-onset Alzheimer’s disease (LOAD) in a Tunisian population. Subjects and Methods: We sequenced exon 2 of TREM2 in a Tunisian cohort of 172 LOAD patients and 158 control subjects. We used the Fisher exact test to compare the distribution of allelic frequencies between the two groups. Results: We identified 4 previously reported nonsynonymous variants (p.Asp39Glu, p.Arg62His, p.Thr96Lys, and p.Val126Gly) and 1 novel synonymous variant (p.Gln109Gln), none of which was significantly associated with the risk of Alzheimer’s disease. Moreover, the rare TREM2 variant (p.Arg47His), which was considered to be a risk factor for Alzheimer’s disease in European descent populations, was not detected in our cohort. Conclusion: These findings do not support a major role for TREM2 in the pathogenesis of LOAD in the Tunisian population.
Temporal and Spatial Post-Transcriptional Regulation of Zebrafish
tie1
mRNA by Long Noncoding RNA During Brain Vascular Assembly
Authors: Chowdhury Tamjid A. , Koceja Chris , Eisa-Beygi Shahram , Kleinstiver Benjamin P. , Kumar Suresh N. , Lin Chien-Wei , Li Keguo , Prabhudesai Shubhangi , Joung J. Keith , Ramchandran Ramani
Published: May 2018

Objective—

Tie1 (tyrosine kinase containing immunoglobulin and epidermal growth factor homology 1), an endothelial and hematopoietic cell–specific receptor tyrosine kinase, is an important regulator of angiogenesis and critical for maintaining vascular integrity. The post-transcriptional regulation of
tie1
mRNA expression is not understood, but it might partly explain Tie1’s differential expression pattern in endothelium. Following up on our previous work that identified natural antisense transcripts from the
tie1
locus—
tie1 antisense
(
tie1AS
), which regulates
tie1
mRNA levels in zebrafish—we attempted to identify the mechanism of this regulation.

Approach and Results—

Through in vitro and in vivo ribonucleoprotein binding studies, we demonstrated that
tie1AS
long noncoding RNA interacts with an RNA binding protein—embryonic lethal and abnormal vision Drosophila-like 1 (Elavl1)—that regulates
tie1
mRNA levels. When we disrupted the interaction between
tie1AS
and Elavl1 by using constitutively active antisense morpholino oligonucleotides or photoactivatable morpholino oligonucleotides,
tie1
mRNA levels increased between 26 and 31 hours post-fertilization, particularly in the head. This increase correlated with dilation of primordial midbrain channels, smaller eyes, and reduced ventricular space. We also observed these phenotypes when we used CRISPR (clustered regularly interspaced short palindromic repeats)–mediated CRISPRi (CRISPR-mediated interference) to knock down
tie1AS
. Treatment of the morpholino oligonucleotide–injected embryos with a small molecule that decreased
tie1
mRNA levels rescued all 3 abnormal phenotypes.

Conclusions—

We identified a novel mode of temporal and spatial post-transcriptional regulation of
tie1
mRNA. It involves long noncoding RNA,
tie1AS
, and Elavl1 (an interactor of
tie1AS
).
Myeloid β-Catenin Deficiency Exacerbates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Authors: Wang Fang , Liu Zun , Park Se-Hyung , Gwag Taesik , Lu Weiwei , Ma Murong , Sui Yipeng , Zhou Changcheng
Published: May 2018

Objective—

The Wnt/β-catenin signaling is an ancient and evolutionarily conserved pathway that regulates essential aspects of cell differentiation, proliferation, migration and polarity. Canonical Wnt/β-catenin signaling has also been implicated in the pathogenesis of atherosclerosis. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis, but the role of macrophage β-catenin in atherosclerosis remains elusive. This study aims to investigate the impact of β-catenin expression on macrophage functions and atherosclerosis development.

Approach and Results—

To investigate the role of macrophage canonical Wnt/β-catenin signaling in atherogenesis, we generated β-catenin
Δmye
LDLR
−/−
mice (low-density lipoprotein receptor–deficient mice with myeloid-specific β-catenin deficiency). As expected, deletion of β-catenin decreased macrophage adhesion and migration properties in vitro. However, deficiency of β-catenin significantly increased atherosclerotic lesion areas in the aortic root of LDLR
−/−
(low-density lipoprotein receptor–deficient) mice without affecting the plasma lipid levels and atherosclerotic plaque composition. Mechanistic studies revealed that β-catenin can regulate activation of STAT (signal transducer and activator of transcription) pathway in macrophages, and ablation of β-catenin resulted in STAT3 downregulation and STAT1 activation, leading to elevated macrophage inflammatory responses and increased atherosclerosis.

Conclusions—

This study demonstrates a critical role of myeloid β-catenin expression in atherosclerosis by modulating macrophage inflammatory responses.
Hypoxia and Ischemia Promote a Maladaptive Platelet Phenotype
Authors: Cameron Scott J. , Mix Doran S. , Ture Sara K. , Schmidt Rachel A. , Mohan Amy , Pariser Daphne , Stoner Michael C. , Shah Punit , Chen Lijun , Zhang Hui , Field David J. , Modjeski Kristina L. , Toth Sandra , Morrell Craig N.
Published: May 2018

Objective—

Reduced blood flow and tissue oxygen tension conditions result from thrombotic and vascular diseases such as myocardial infarction, stroke, and peripheral vascular disease. It is largely assumed that while platelet activation is increased by an acute vascular event, chronic vascular inflammation, and ischemia, the platelet activation pathways and responses are not themselves changed by the disease process. We, therefore, sought to determine whether the platelet phenotype is altered by hypoxic and ischemic conditions.

Approach and Results—

In a cohort of patients with metabolic and peripheral artery disease, platelet activity was enhanced, and inhibition with oral antiplatelet agents was impaired compared with platelets from control subjects, suggesting a difference in platelet phenotype caused by the disease. Isolated murine and human platelets exposed to reduced oxygen (hypoxia chamber, 5% O
2
) had increased expression of some proteins that augment platelet activation compared with platelets in normoxic conditions (21% O
2
). Using a murine model of critical limb ischemia, platelet activity was increased even 2 weeks postsurgery compared with sham surgery mice. This effect was partly inhibited in platelet-specific ERK5 (extracellular regulated protein kinase 5) knockout mice.

Conclusions—

These findings suggest that ischemic disease changes the platelet phenotype and alters platelet agonist responses because of changes in the expression of signal transduction pathway proteins. Platelet phenotype and function should, therefore, be better characterized in ischemic and hypoxic diseases to understand the benefits and limitations of antiplatelet therapy.