bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Gap between Knowledge and Practices among Type 2 Diabetes Mellitus Patients at a Tertiary-Care Hospital in Bangladesh
Authors: Saleh Farzana , Ara Ferdous , Afnan Fadia
Published: March 2016

Newly diagnosed type 2 diabetes (T2 DM) patients who do not receive diabetes education (DE) have average knowledge on DM, and their practices about diabetes need to be improved. This prompted us to evaluate what happens when old diagnosed patients receive DE. The study therefore assessed the association between knowledge and practices in terms of Hemoglobin A1c (HbA1c), body mass index (BMI), and waist circumference (WC) among 500 diagnosed T2 DM using a cross-sectional design. An interviewer-administered questionnaire was used for assessing their knowledge. The mean knowledge score of the patients was 15.29 ± 3.6. A significant negative association was found between the knowledge score and the HbA1c level. Age was positively associated with HbA1c and WC. Duration of DM was positively and education was negatively associated with HbA1c. Gender was negatively associated with BMI while income was positively associated with BMI and WC. All the associations were significant. The diagnosed T2 DM patients are deficient of sufficient knowledge; the knowledge score and HbA1c have a significant negative relationship, not other actions. The risk factors for the patients’ outcome include old age, female gender, years of education, economic status, and duration of DM.
Products of Composition and Differentiation Operators from Bloch intoQKSpaces
Authors: Wang Shunlai , Zhang Taizhong
Published: March 2016

The boundedness and compactness of the product of differentiation and composition operators from Bloch spaces intoQKspaces are discussed in this paper.
Turn-Based War Chess Model and Its Search Algorithm per Turn
Authors: Nan Hai , Fang Bin , Wang Guixin , Yang Weibin , Sarah Carruthers Emily , Liu Yi
Published: March 2016

War chess gaming has so far received insufficient attention but is a significant component of turn-based strategy games (TBS) and is studied in this paper. First, a common game model is proposed through various existing war chess types. Based on the model, we propose a theory frame involving combinational optimization on the one hand and game tree search on the other hand. We also discuss a key problem, namely, that the number of the branching factors of each turn in the game tree is huge. Then, we propose two algorithms for searching in one turn to solve the problem: (1) enumeration by order; (2) enumeration by recursion. The main difference between these two is the permutation method used: the former uses the dictionary sequence method, while the latter uses the recursive permutation method. Finally, we prove that both of these algorithms are optimal, and we analyze the difference between their efficiencies. An important factor is the total time taken for the unit to expand until it achieves its reachable position. The factor, which is the total number of expansions that each unit makes in its reachable position, is set. The conclusion proposed is in terms of this factor: Enumeration by recursion is better than enumeration by order in all situations.
Benzene Removal by Iron Oxide Nanoparticles Decorated Carbon Nanotubes
Authors: Abbas Aamir , Abussaud Basim Ahmed , Ihsanullah  , Al-Baghli Nadhir A. H. , Khraisheh Marwan , Atieh Muataz Ali
Published: March 2016

In this paper, carbon nanotubes (CNTs) impregnated with iron oxide nanoparticles were employed for the removal of benzene from water. The adsorbents were characterized using scanning electron microscope, X-ray diffraction, BET surface area, and thermogravimetric analysis. Batch adsorption experiments were carried out to study the adsorptive removal of benzene and the effect of parameters such as pH, contact time, and adsorbent dosage. The maximum removal of benzene was 61% with iron oxide impregnated CNTs at an adsorbent dosage 100 mg, shaking speed 200 rpm, contact time 2 hours, initial concentration 1 ppm, and pH 6. However, raw CNTs showed only 53% removal under same experimental conditions. Pseudo-first-order kinetic model was found well to describe the obtained data on benzene removal from water. Initial concentration was varied from 1 to 200 mg/L for isotherms study. Langmuir isotherm model was observed to best describe the adsorption data. The maximum adsorption capacities were 987.58 mg/g and 517.27 mg/g for iron oxide impregnated CNTs and raw CNTs, respectively. Experimental results revealed that impregnation with iron oxide nanoparticles significantly increased the removal efficiency of CNTs.
Blood Lactate Is a Useful Indicator for the Medical Emergency Team
Authors: Schollin-Borg Maria , Nordin Pär , Zetterström Henrik , Johansson Joakim
Published: March 2016

Lactate has been thoroughly studied and found useful for stratification of patients with sepsis, in the Intensive Care Unit, and trauma care. However, little is known about lactate as a risk-stratification marker in the Medical Emergency Team- (MET-) call setting. We aimed to determine whether the arterial blood lactate level at the time of a MET-call is associated with increased 30-day mortality. This is an observational study on a prospectively gathered cohort at a regional secondary referral hospital. All MET-calls during the two-year study period were eligible. Beside blood lactate, age and vital signs were registered at the call. Among the 211 calls included, there were 64 deaths (30.3%). Median lactate concentration at the time of the MET-call was 1.82 mmol/L (IQR 1.16–2.7). We found differences between survivors and nonsurvivors for lactate and oxygen saturation, a trend for age, but no significant correlations between mortality and systolic blood pressure, respiratory rate, and heart rate. As compared to normal lactate (<2.44 mmol/L), OR for 30-day mortality was 3.54 (p<0.0006) for lactate 2.44–5.0 mmol/L and 4.45 (p<0.0016) for lactate > 5.0 mmol/L. The present results support that immediate measurement of blood lactate in MET call patients is a useful tool in the judgment of illness severity.
TheGinkgo bilobaExtract Reverses the Renal Effects of Titanium Dioxide Nanoparticles in Adult Male Rats
Authors: Escárcega-González Carlos Enrique , Reynoso-Andeola Irma Guadalupe , Jaramillo-Juárez Fernando , Martínez-Ruvalcaba Haydée , Posadas del Rio Francisco A.
Published: March 2016

TheGinkgo bilobaextract (GbE) is a commercial product used as a nutraceutic herbal remedy in Europe and US. It contains 27% of the polyphenols isorhamnetin, kaempferol, and quercetin, as antioxidants. We used male adult Wistar rats (200–300 g), divided into four groups: control group (treated with 5.0 mg/kg of sodium chloride, intravenous), titanium dioxide nanoparticles (TiO2-NPs) group (5.0 mg/kg, intravenous), GbE group (10 mg/kg, intraperitoneal), and GbE + TiO2-NPs group (treated 24 h before with 10 mg/kg of GbE, intraperitoneal), followed, 24 h later, by 5.0 mg/kg of TiO2-NPs intravenously. The statistical analysis was performed using Student’st-test for grouped data with ANOVA posttest. The GbE protected renal cells against the effects of TiO2-NPs because it reversed the increased activity ofγ-glutamyltranspeptidase and the enzymatic activity of dipeptidylaminopeptidase IV at all times tested (0–5, 5–24, 24–48, and 48–72 h). Also it reversed the glucosuria, hypernatriuria, and urine osmolarity at three times tested (5–24, 24–48, and 48–72). Thus, we conclude that GbE has a beneficial activity in the cytoplasmic membranes of brush border cells on the renal tubules, against the adverse effects that can be produced by some xenobiotics in this case the TiO2-NPs, in experimental rats.
Fault Diagnosis of a High-Speed Cam-Driven Pin Assembly System
Authors: Cheng Chi-Cheng , Tseng Yih-Tun , Wu Cheng-Da , Wang Der-Lin
Published: March 2016

A cam-driven mechanical system applied for pin assembly of connectors of electrical devices is studied in this paper. Three cooperative cams are involved in the tasks of approaching, cutting, insertion, and restoring. In order to meet the demanded productivity growth, the operation speed tends to be elevated. However, high running speeds usually cause deficiencies of pin dropping and inaccurate positioning. Diagnosis is therefore conducted to explore their physical reasons so that modification of future mechanical design can be made. Frequency responses of experimental measurements show greater natural frequency and system stiffness caused by nonlinear dynamics for higher operation speed. It also appears that the clamping force is reduced and drift of the locked pin’s location is induced for higher running speed. In addition, separation of the fixture system induced by contact oscillation generates clearance larger than the thickness of the pin. Based on the mathematical models obtained from the technique of system identification, deeper insight of the mechanical system and future system improvement can be highly expected.
A Study on Mortality Profile among Fifty Plus- (50+-) Population (FPP) of India: A 5-Year Retrospective Study at New Delhi District
Authors: Chaudhary B. L. , Vidua Raghvendra K. , Kumar Arvind , Bajaj Amrita V.
Published: March 2016

Objectives. To find out the mortality profile vis-a-vis different epidemiological factors at the time of autopsy among the 50+-Population.Material and Method. A five-year retrospective evaluation of medicolegal records between 2006 and 2010 was done at Lady Hardinge Medical College, New Delhi.Results. A total of 493 (17.78%) cases belonged to 50+-Population age group out of total 2773 autopsies performed. The proportion of unidentified/unknown persons among this age group was 36.51%. The unnatural and natural causes constituted 44.62% and 55.38% cases, respectively. The unspecified pneumonitis (50.18%) was reported as the commonest cause followed by coronary artery disease and respiratory tuberculosis among natural ones and the transport accident (57.27%) followed by accidental and intentional self-poisoning and exposure to noxious substances and falls among the unnatural ones.Conclusion. The findings reveal that this age group most commonly dies of natural causes rather than the unnatural ones even in autopsy cases. They have definite cure with timely interventions. The study also points out the need to devise the road and home safety measures to reduce mortality among the study population.
Intelligent Model Building and GPC-PID Based Temperature Curve Control Strategy for Metallurgical Industry
Authors: Li Shuanghong , Li Xi , Yang Yupu
Published: March 2016

Laminar cooling process is a large-scale, nonlinear system, so the temperature control of such system is a difficult and complex problem. In this paper, a novel modeling method and a GPC-PID based control strategy for laminar cooling process are proposed to control the global temperature curve to produce high quality steel. First, based on the analysis of the cooling process of laminar flow, a new TS fuzzy model which possesses intelligence and self-learning ability is established to improve the temperature prediction accuracy. Second, the target temperature curve can be divided into several subgoals and each subgoal can be described by a CARIMA type of model. Then, by the decentralized predictive control method, GPC-PID based control strategy is introduced to guarantee the laminar cooling process to achieve subtargets, respectively; in that way the steel plate temperature will drop along the optimal temperature curve. Moreover, by employing the dSPACE control board into the process control system, the matrix process ability is added to the production line without large-scale reconstruction. Finally, the effectiveness and performance of the proposed modeling and control strategy are demonstrated by the industrial data and metallography detection in one steel company.
Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy
Authors: Wagner Kay-Dietrich , Vukolic Ana , Baudouy Delphine , Michiels Jean-François , Wagner Nicole
Published: March 2016

Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δactivation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δin the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δoverexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δinduces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δactivation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease.
The Dynamic Evolution of Firms’ Pollution Control Strategy under Graded Reward-Penalty Mechanism
Authors: Chen Li Ming , Wang Wen Ping
Published: March 2016

The externality of pollution problem makes firms lack enough incentive to reduce pollution emission. Therefore, it is necessary to design a reasonable environmental regulation mechanism so as to effectively urge firms to control pollution. In order to inspire firms to control pollution, we divide firms into different grades according to their pollution level and construct an evolutionary game model to analyze the interaction between government’s regulation and firms’ pollution control under graded reward-penalty mechanism. Then, we discuss stability of firms’ pollution control strategy and derive the condition of inspiring firms to control pollution. Our findings indicate that firms tend to control pollution after long-term repeated games if government’s excitation level and monitoring frequency meet some conditions. Otherwise, firms tend to discharge pollution that exceeds the stipulated standards. As a result, in order to effectively control pollution, a government should adjust its excitation level and monitoring frequency reasonably.
A Randomized Case-Series Study Comparing the Stability of Implant with Two Different Surfaces Placed in Fresh Extraction Sockets and Immediately Loaded
Authors: Vanden Bogaerde Leonardo , Sennerby Lars
Published: March 2016

Background. Hydrophilic and moderately rough implant surfaces have been proposed to enhance the osseointegration response.Aim. The aim of this study was to compare early changes of stability for two implants with identical macrodesign but with different surface topographies.Materials and Methods. In 11 patients, a total of 22 implants (11 bimodal (minimally rough, control) and 11 proactive (moderately rough and hydrophilic, test), Neoss Ltd., Harrogate, UK) were immediately placed into fresh extraction sockets and immediately loaded. The peak insertion torque (IT) was measured in Ncm at placement. Resonance Frequency Analysis (RFA) measurements were made at baseline and 2, 4, 6, and 12 weeks after surgery.Results. The two implant types showed similar IT and RFA values at placement (NS). A dip of RFA values after 2 weeks followed by an increase was observed, where the test implant showed a less pronounced decrease and a more rapid recovery than the control implant. The test implants were significantly more stable than the control ones after 12 weeks.Conclusions. The results from the present study indicated that the hydrophilic and rougher test implant was more resistant to immediate loading and showed a significantly higher stability than the smoother control implant after 12 weeks.
Attitude Optimal Backstepping Controller Based Quaternion for a UAV
Authors: Djamel Kaddouri , Abdellah Mokhtari , Benallegue Abdelaziz
Published: March 2016

A hierarchical controller design based on nonlinearH∞theory and backstepping technique is developed for a nonlinear and coupled dynamic attitude system using conventional quaternion based method. The derived controller combines the attractive features ofH∞optimal controller and the advantages of the backstepping technique leading to a control law which avoids winding phenomena. Performance issues of the controller are illustrated in a simulation study made for a four-rotor vertical take-off and landing (VTOL) aerial robot prototype known as the quadrotor aircraft.
Gel Based Sunscreen Containing Surface Modified TiO2Obtained by Sol-Gel Process: Proposal for a Transparent UV Inorganic Filter
Authors: Abuçafy Marina Paiva , Manaia Eloísa Berbel , Kaminski Renata Cristina Kiatkoski , Sarmento Victor Hugo , Chiavacci Leila Aparecida
Published: March 2016

Inorganic UV filters, as titanium dioxide (TiO2), have become attractive because of their role in protecting the skin against the damage caused by the continuous exposure to the sun. However, their high refractive index, responsible for a white residue when applied on the skin, has led to the development of alternative inorganic materials, such as TiO2nanoparticles. Thus, the aim of this study was the development of transparent and stable gel formulations containing surface modified TiO2nanoparticles for application in sunscreens. Also, the physical and chemical properties of formulations containing TiO2nanoparticles were evaluated. The UV absorption spectroscopy analyses indicated that the formulations containing TiO2nanoparticles had a broad protection spectrum. The diffuse reflectance spectroscopy revealed that the use of PTSH surface modified TiO2nanoparticles improved the transparency of the sunscreen formulations compared to that containing commercial ones. The rheology analyses showed that the amount of nanoparticles incorporated in the formulations influences the gel-like or liquid-like behavior. The results showed that the surface modified TiO2nanoparticles are a promising innovative UV filter and the formulations containing these nanoparticles are interesting candidates for being used as sunscreen.
Monitoring of Distillation Column Based on Indiscernibility Dynamic Kernel PCA
Authors: Gao Qiang , Chang Yong , Xiao Zhen , Yu Xiao
Published: March 2016

Aiming at complicated faults detection of distillation column industrial process, it has faced a grave challenge. In this paper, a new indiscernibility dynamic kernel principal component analysis (I-DKPCA) method is presented and applied to distillation column. Compared with traditional statistical techniques, I-DKPCA not only can capture nonlinear property and dynamic characteristic of processes but also can extract relevant variables from all the variables. Applying this new method to distillation column process (a hardware-in-the-loop simulation system), the results prove the proposed method has great advantages, that is, lower missing rate and higher detection rate for the faults, compared with KPCA and DPCA.
FGFR1 Is a Potential Prognostic Biomarker and Therapeutic Target in Head and Neck Squamous Cell Carcinoma
Authors: Koole Koos , Brunen Diede , van Kempen Pauline M.W. , Noorlag Rob , de Bree Remco , Lieftink Cor , van Es Robert J.J. , Bernards René , Willems Stefan M.
Published: March 2016

Purpose: FGFR1 is a promising therapeutic target in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). FGFR inhibitors have shown great therapeutic value in preclinical models. However, resistance remains a major setback. In this study, we have investigated the prognostic value of FGFR1 expression in HNSCC, the therapeutic relevance of targeting FGFR with AZD4547, and potential resistant mechanisms.

Experimental Design: IHC and FISH were applied on tissue microarrays to investigate FGFR1 protein expression and FGFR1 gene copy numbers in 452 HNSCCs. The sensitivity of HNSCC cell lines to AZD4547, either as single or combination treatment with the EGFR inhibitor gefitinib, was assessed using long-term colony formation assays, short-term viability assays, and biochemical analysis.

Results: FGFR1 protein overexpression occurred in 82% (36/44) of human papillomavirus (HPV)–positive HNSCC and 75% (294/392) of HPV-negative HNSCC and relates with poor overall survival and disease-free survival in HPV-negative HNSCC [HR, 3.07; 95% confidence interval (CI), 1.74–6.90; P = 0.001 and HR, 1.53; 95% CI, 1.04–2.39; P = 0.033]. Moreover, the FGFR1 gene was amplified in 3% (3/110) of HPV-negative HNSCC. Treatment of the high FGFR1-expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Two FGFR-amplified cell lines, SCC147 and BICR16, were resistant to AZD4547 treatment due to EGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited the proliferation of resistant cell lines.

Conclusions: Here, we identify high FGFR1 expression as a candidate prognostic biomarker in HPV-negative HNSCC. Furthermore, we provide a rationale for treating FGFR1-expressing HNSCC with the FGFR inhibitor AZD4547 and for combining AZD4547 and gefitinib in FGFR inhibitor–resistant HNSCC patients. Clin Cancer Res; 22(15); 3884–93. ©2016 AACR.
Methionine and Kynurenine Activate Oncogenic Kinases in Glioblastoma, and Methionine Deprivation Compromises Proliferation
Authors: Palanichamy Kamalakannan , Thirumoorthy Krishnan , Kanji Suman , Gordon Nicolaus , Singh Rajbir , Jacob John R. , Sebastian Nikhil , Litzenberg Kevin T. , Patel Disha , Bassett Emily , Ramasubramanian Brinda , Lautenschlaeger Tim , Fischer Steven M. , Ray-Chaudhury Abhik , Chakravarti Arnab
Published: March 2016

Purpose: We employed a metabolomics-based approach with the goal to better understand the molecular signatures of glioblastoma cells and tissues, with an aim toward identifying potential targetable biomarkers for developing more effective and novel therapies.

Experimental Design: We used liquid chromatography coupled with mass spectrometry (LC-MS/Q-TOF and LC-MS/QQQ) for the discovery and validation of metabolites from primary and established glioblastoma cells, glioblastoma tissues, and normal human astrocytes.

Results: We identified tryptophan, methionine, kynurenine, and 5-methylthioadenosine as differentially regulated metabolites (DRM) in glioblastoma cells compared with normal human astrocytes (NHAs). Unlike NHAs, glioblastoma cells depend on dietary methionine for proliferation, colony formation, survival, and to maintain a deregulated methylome (SAM:SAH ratio). In methylthioadenosine phosphorylase (MTAP)-deficient glioblastoma cells, expression of MTAP transgene did not alter methionine dependency, but compromised tumor growth in vivo. We discovered that a lack of the kynurenine-metabolizing enzymes kynurenine monooxygenase and/or kynureninase promotes the accumulation of kynurenine, which triggers immune evasion in glioblastoma cells. In silico analysis of the identified DRMs mapped the activation of key oncogenic kinases that promotes tumorigenesis in glioblastoma. We validated this result by demonstrating that the exogenous addition of DRMs to glioblastoma cells in vitro results in oncogene activation as well as the simultaneous downregulation of Ser/Thr phosphatase PP2A.

Conclusions: We have connected a four-metabolite signature, implicated in the methionine and kynurenine pathways, to the promotion and maintenance of glioblastoma. Together, our data suggest that these metabolites and their respective metabolic pathways serve as potential therapeutic targets for glioblastoma. Clin Cancer Res; 22(14); 3513–23. ©2016 AACR.
ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer
Authors: Gao Shuai , Ye Huihui , Gerrin Sean , Wang Hongyun , Sharma Ankur , Chen Sen , Patnaik Akash , Sowalsky Adam G. , Voznesensky Olga , Han Wanting , Yu Ziyang , Mostaghel Elahe A. , Nelson Peter S. , Taplin Mary-Ellen , Balk Steven P. , Cai Changmeng
Published: March 2016

Purpose: ErbB2 signaling appears to be increased and may enhance androgen receptor (AR) activity in a subset of patients with castration-resistant prostate cancer (CRPC), but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer and to determine whether it may contribute to AR signaling in these tumors.

Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model.

Results: We found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Furthermore, concomitantly treating CRPC cells with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression.

Conclusions: ErbB2 signaling is elevated in a subset of patients with abiraterone-resistant prostate cancer and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity. Clin Cancer Res; 22(14); 3672–82. ©2016 AACR.
Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma
Authors: Cottereau Anne-Ségolène , Lanic Hélène , Mareschal Sylvain , Meignan Michel , Vera Pierre , Tilly Hervé , Jardin Fabrice , Becker Stéphanie
Published: March 2016

Purpose: The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment 18F-FDG PET/CT and its added value to molecular characteristics was investigated in patients with diffuse large B-cell lymphoma (DLBCL).

Experimental Design: For 81 newly diagnosed patients with DLBCL treated with rituximab and CHOP/CHOP-like regimen, TMTV was computed using the 41% SUVmax thresholding method. According to the gene expression profile, determined using DASL (cDNA-mediated Annealing, Selection, Ligation and extension) technology, a subset of 57 patients was classified in germinal center B (GCB) or activated B-cell (ABC) subtypes and MYC or BCL2 overexpressed.

Results: Median follow-up was 64 months. Five-year progression-free survival (PFS) and overall survival (OS) were 60% and 63% in the whole population. Median pretherapy TMTV was 320 cm3 (25th–75th percentiles 106–668 cm3). With a 300 cm3 cutoff, patients with high TMTV (n = 43) had a 5-year PFS and OS of 43% and 46% compared with 76% and 78% for patients with a low TMTV (P = 0.0023, P = 0.0047). ABC status, MYC, or BCL2 overexpression and both overexpression (“dual expressor,” DE) were significantly associated with a worse PFS and OS. TMTV combined with molecular data allowed a significant better risk substratification of ABC/GCB patients, on PFS and OS. High TMTV individualized in molecular-low-risk patients a group with a poor outcome (MYC, PFS=51%, OS=55% BCL2, PFS=49%, OS=49% or DE PFS=50%, OS=50%) and a group with a good outcome (MYC, PFS=93%, OS=93% BCL2, PFS=86%, OS=86%, or DE PFS=81%, OS=81%).

Conclusions: The combination of molecular and imaging characteristics at diagnosis could lead to a more accurate selection of patients, to increase tailor therapy. Clin Cancer Res; 22(15); 3801–9. ©2016 AACR.
Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses
Authors: Piyathilake Chandrika J. , Ollberding Nicholas J. , Kumar Ranjit , Macaluso Maurizio , Alvarez Ronald D. , Morrow Casey D.
Published: March 2016

It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases, including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPV) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the presence of cervical cells positive for 8-hydroxy-2′-deoxyguanosine. The study included 340 women diagnosed with CIN 2+ (cases) and 90 diagnosed with CIN 1 (non-cases). Microbiota composition was determined by Illumina sequencing of the 16S rRNA gene amplified from DNA extracted from cervical mucus samples. Measures of alpha/beta-diversity were not associated with either CIN severity or oxidative DNA damage. However, a cervical mucosal community type (CT) dominated by L. iners and unclassified Lactobacillus spp. was associated with CIN 2+ (OR = 3.48; 95% CI, 1.27–9.55). Sequence reads mapping to Lactobacillaceae, Lactobacillus, L. reuteri, and several sub–genus level Lactobacillus operational taxonomic units were also associated with CIN 2+ when examined independently (effect size >2.0; P < 0.05). Our 16S rRNA sequencing results need confirmation in independent studies using whole-genome shotgun sequencing and that would allow sharpening the suggested associations at finer taxonomic levels. Our results provide little evidence that DNA oxidative damage mediates the effect of the microbiome on the natural history of HPV infection and CIN severity. Cancer Prev Res; 9(5); 357–66. ©2016 AACR.
Manual Lymphatic Drainage after Subepidermal Tracer Injection Optimizes Results of Sentinel Lymph Node Labeling in Primary Breast Cancer
Authors: Sillem Martin , Bromberger Urban , Heitzelmann Barbara , Brauer Wolfgang J. , Werner Martin , Timme Sylvia
Published: March 2016

Introduction: Our aim was to assess the practicability and reliability of a novel labeling regime for axillary sentinel lymph nodes (SLNs) in early breast cancer. Methods: 362 patients with early breast cancer (bilateral in 9 cases, giving a total of 371 cases) underwent intradermal radio tracer injection with simultaneous manual lymphatic drainage. SLN biopsy was performed within 24 h. For retrospective analysis, data were extracted from patient's records. Results: At least 1 SLN was detected intraoperatively in 369 cases (99.5%, range 1-9 nodes). This node was metastatic in 88 and unaffected in 281 cases. Coincidentally removed but unlabeled lymph nodes were affected in 3 cases in which the SLN was unaffected (3/153 = 2%). In all cases, on histological evaluation, tissue removed as SLN contained lymph nodes. After a period of 69.5 months (median 1.7-115.8 months), no axillary recurrences were observed in 213 patients. Conclusion: Manual lymphatic drainage is a simple technique that leads to an extremely high pick-up rate of axillary SLNs after subepidermal radio tracer injection. If unaffected, this node correctly predicts nodal-negative disease in 98% of cases studied.
Comparison of HER2 Expression in Primary Tumor and Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients
Authors: Rack Brigitte , Zombirt Ewa , Trapp Elisabeth , Jückstock Julia , Andergassen Ulrich , Neugebauer Julia , Kost Bernd , Weissenbacher Tobias , Jeschke Udo , Schindlbeck Christian , Janni Wolfgang , Alunni-Fabbroni Marianna
Published: March 2016

Objective: The aim of this study was to measure the human epidermal growth factor receptor 2 (HER2) status of disseminated tumor cells (DTCs) from bone marrow (BM) aspirates and to assess correspondence or discrepancy with the primary tumor. Methods: DTCs were isolated from the BM of 156 breast cancer patients. Cytokeratin-positive DTCs were further analyzed by the chromogenic in situ hybridization method to detect HER2 gene amplification. Results: A significant correlation (p = 0.021) was found between the HER2 status of DTCs and the primary tumors. Sixty-one (68.5%) patients had a corresponding status. However, a shift of phenotype between primary tumor and DTCs was found in the remaining patients. Conclusion: This study showed a significant grade of discordance of the HER2 status between primary tumors and DTCs in the BM of a relevant subgroup of patients. Detection of HER2 amplification on DTCs could therefore help to better stratify patients for a more tailored therapy, since they would benefit from a HER2-targeted therapy.
Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction
Authors: Wu Wenjing , Wang Hui , Yu Changan , Li Jiahui , Gao Yanxiang , Ke Yuannan , Wang Yong , Zhou Yifeng , Zheng Jingang
Published: March 2016

Background/Aims: High ADAMTS-7 levels are associated with acute myocardial infarction (AMI), although its involvement in ventricular remodeling is unclear. In this study, we investigated the association between ADAMTS-7 expression and cardiac function in a rat AMI model. Methods: Sprague-Dawley rats were randomized into AMI (n = 40) and sham (n = 20) groups. The left anterior descending artery was sutured to model AMI. Before surgery and 7, 14, 28, and 42 days post-surgery, ADAMTS-7 and brain natriuretic peptide (BNP), and cartilage oligomeric matrix protein (COMP) were assessed by ELISA, western blot, real-time RT-PCR, and/or immunohistochemistry. Cardiac functional and structural parameters were assessed by M-mode echocardiography. Results: After AMI, plasma ADAMTS-7 levels increased, peaking on day 28 (AMI: 13.2 ± 6.3 vs. sham: 3.4 ± 1.3 ng/ml, P < 0.05). Compared with the sham group, ADAMTS-7 expression was higher in the infarct zone at day 28. COMP present in normal myocardium was degraded by day 28 post-AMI. Plasma ADAMTS-7 correlated positively with BNP (r = 0.642, P = 0.025), left ventricular end-diastolic diameter (r = 0.695, P = 0.041), left ventricular end-systolic diameter (r = 0.710, P = 0.039), left ventricular ejection fraction (r = 0.695, P = 0.036), and left ventricular short-axis fractional shortening (r = 0.721, P = 0.024). Conclusions: ADAMTS-7 levels may reflect the degree of ventricular remodeling after AMI.
Function of Deubiquitinating Enzyme USP14 as Oncogene in Different Types of Cancer
Authors: Zhu Ying , Zhang Chaoxiong , Gu Changxin , Li Qiang , Wu Ning
Published: March 2016

Background/Aims: Non-small cell lung cancer (NSCLC) tissues overexpress USP14, which promotes tumor cell proliferation and is associated with shorter overall survival time. Methods: The expression of USP14 was assayed in many types of cancers. USP14 was up-and down-regulated using appropriate plasmid or lentiviral vector constructs and its effects on proliferation, cell colony number, and apoptosis rate were measured. A human NSCLC cell line was inoculated into nude mice and the survival rates were recorded. Results: We found USP14 amplification and overexpression in many different cancers. The overexpression of USP14 in USP14 low-expression cell lines promoted cell proliferation and migration, whereas USP14 downregulation suppressed tumor cell proliferation, decreased tumor cell colony number, increased apoptosis rate, and decreased cell migration and invasion. Conclusion: USP14 plays an oncogenic role in various types of cancer, and may thus represent a new cancer therapy target.
Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer
Authors: Zhu Aiyu , Li Yan , Song Wei , Xu Yumei , Yang Fang , Zhang Wenwen , Yin Yongmei , Guan Xiaoxiang
Published: March 2016

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.
MicroRNA-3666 Regulates Thyroid Carcinoma Cell Proliferation via MET
Authors: Wang Gang , Cai Chengzhong , Chen Lei
Published: March 2016

Background/Aims: Thyroid carcinoma (TC) is a highly lethal malignant cancer and its carcinogenesis remains undetermined. Dysregulation of microRNAs (miRNAs) is well known to be involved in the development of various cancers, including TC, whereas a role of miR-3666 in the pathogenesis of TC has not been appreciated. Methods: We analyzed the levels of MET and miR-3666 in TC tissue and the relationship of miR-3666 levels with patients' prognosis. We then overexpressed miR-3666 by miRNA mimics transfection and inhibited miR-3666 by miRNA antisense transfection in TC cells. Cell survival and growth were analyzed by CCK-8 assay and MTT assay, respectively. Cell apoptosis and proliferation were analyzed by flow cytometry. Bioinformatics analyses were applied to predict miR-3666 targets, which was then confirmed using luciferase reporter assay. Results: We detected significantly higher levels of MET, and significantly lower levels of miR-3666 in TC tissue, compared to the adjacent non-tumor tissue. Moreover, the low miR-3666 levels were associated with poor survival of the patients. Overexpression of miR-3666 significantly inhibited cell growth, while depletion of miR-3666 increased cell growth in TC cells. Moreover, the effects of miR-3666 on cell growth appeared to result from alteration in cell proliferation, rather than changes in cell apoptosis. MiR-3666 was found to bind to the 3'-UTR of MET mRNA to inhibit its translation in TC cells. Conclusion: Reduced miR-3666 levels in TC tissue may promotes TC growth, possibly through MET-mediated cell proliferation.
Protective Effect of Whole and Fat-Free Fluoridated Milk, Applied before or after Acid Challenge, against Dental Erosion
Authors: Cassiano Luiza P.S. , Charone Senda , Souza Juliana G. , Leizico Ligia C. , Pessan Juliano P. , Magalhães Ana Carolina , Buzalaf Marília Afonso Rabelo
Published: March 2016

This study analysed in vitro the effect of milk against dental erosion, considering three factors: the type of milk (bovine whole/fat-free), the presence of different fluoride concentrations and the time of application (before/after erosive challenge). Bovine enamel (n = 15/group) and root dentine (n = 12/group) specimens were submitted to the following treatments: after the first erosive challenge - 0.9% NaCl solution (negative control), whole milk with 0, 2.5, 5.0 and 10.0 ppm F, fat-free milk with 0, 2.5, 5.0 and 10.0 ppm F, and 0.05% NaF solution (positive control); before the first erosive challenge - whole milk with 0, 2.5, 5.0 and 10.0 ppm F, fat-free milk with 0, 2.5, 5.0 and 10.0 ppm F, and 0.05% NaF solution (positive control). Specimens were submitted to demineralisation-remineralisation regimes 4 times/day for 5 days. The response variables were enamel and dentine loss (in micrometres). Data were analysed using Kruskal-Wallis/Dunn's test (p < 0.05). For enamel, whole milk containing 10 ppm F, applied before the erosive challenge, was the most protective treatment, but with no significant difference compared with the same treatment carried out after the erosive challenge. For dentine, whole fluoridated milk (all concentrations, after), fat-free 10 ppm F milk (after, before) and whole milk with or without F (except 2.5 ppm F, all before) significantly reduced dentine erosion. It seems that the presence of fluoride, especially at 10 ppm, is the most important factor in reducing dental erosion.
Differentiation between Melanin-Laden Macrophages and Melanoma Cells in Vitreous Aspirates
Authors: Iakovlev Ernest , Ghorab Zeina , Krema Hatem , Iakovlev Vladimir , Kertes Peter , Yucel Yeni
Published: March 2016

Objective: The differential diagnosis between retinal detachment and melanoma metastatic to the vitreous can be challenging, both clinically and cytologically. We demonstrate the diagnostic features and pitfalls of the cytological assessment. Study Design: A case of a metastatic melanoma to the vitreous is compared to a case of retinal detachment initially suspected as melanoma metastasis. Case 1 was a 54-year-old patient with a vague history of pigmented lesions 20 years previously and a current presentation of a visual defect. Case 2 was a 68-year-old patient with a history of melanoma and a presentation of floaters and flashing lights. Results: The vitreous fluid of case 1 contained atypical, pigment-laden cells positive for HMB-45 and assessed as melanoma. On enucleation, a melanoma metastatic to the vitreous was diagnosed. The vitreous fluid of case 2 revealed atypical cells containing pigment granules. The cells were negative for melanocytic markers, while the granules stained positive for melanin. Macrophage marker CD163 was positive in all cells. The interpretation was one of macrophages reactive to the retinal detachment. Conclusion: Melanin-laden macrophages can mimic melanoma cells. This needs to be considered in the differential diagnosis. Additional stains can help the distinction.
Characteristics of Patients with Lymphangioleiomyomatosis and Pleural Effusion: A Systematic Review
Authors: Lama Adriana , Ferreiro Lucía , Golpe Antonio , Gude Francisco , Álvarez-Dobaño José M. , González-Barcala Francisco J. , Toubes María E. , San José Esther , Rodríguez-Núñez Nuria , Valdés Luis
Published: March 2016

The characteristics of patients with lymphangioleiomyomatosis (LAM) are poorly defined, as they may present with or without pleural effusion (PE). We performed a systematic review across four electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of LAM. Case descriptions and retrospective studies were included, unrestricted by year of publication. The review consisted of 94 studies (199 patients) spanning a period of nearly 55 years. The median age was 38 years (range: 1 month to 69 years), and 79.7% were between 21 and 50 years old. All cases had dyspnea, 95% had a cough, and 87.5% had chest pain. PE was exudative chylothorax, usually unilateral (76%) and right-sided, predominantly lymphocytic, and with proportionately higher levels of proteins than lactate dehydrogenase. Sirolimus was effective in all cases, completely in 87%, and partially in 13%, although the number of patients receiving sirolimus was small. The present study confirmed that LAM and PE mainly occur in women of childbearing age (third to fifth decade of life). PE was usually unilateral and presented as a lymphocyte-predominant chylous exudate. The most effective treatment for PE seems to be sirolimus, although studies with larger series are needed to confirm this.
Advances in the Pathogenesis, Diagnosis and Treatment of Bow Hunter's Syndrome: A Comprehensive Review of the Literature
Authors: Duan Guangxin , Xu Jiaping , Shi Jijun , Cao Yongjun
Published: March 2016

Bow hunter's syndrome (BHS), also known as rotational vertebral artery (VA) occlusion syndrome, is a rare yet treatable type of symptomatic vertebrobasilar insufficiency resulting from mechanical occlusion or stenosis of the VA during head and neck rotation or extension. The symptoms of BHS range from transient vertigo to posterior circulation stroke. The underlying pathology is dynamic stenosis or compression of the VA by abnormal bony structures with neck rotation or extension in many cases, such as osteophyte, disc herniation, cervical spondylosis, tendinous bands or tumors. Imaging approaches, such as Doppler sonography, computed tomography and angiography, as well as magnetic resonance imaging and angiography, are widely used in the diagnosis and evaluation of this syndrome. Digital subtraction angiography with head rotation remains the gold standard diagnostic method. Conservative management, surgery and endovascular procedures are the three major treatment methods for BHS, whereas some symptomatic patients may need operative treatment including surgery and endovascular procedures when conservative management is not adequate.
The Role of Protein Kinase A in Anxiety Behaviors
Authors: Keil Margaret F. , Briassoulis George , Stratakis Constantine A.
Published: March 2016

This review focuses on the genetic and other evidence supporting the notion that the cyclic AMP (cAMP) signaling pathway and its mediator, the protein kinase A (PKA) enzyme, which respond to environmental stressors and regulate stress responses, are central to the pathogenesis of disorders related to anxiety. We describe the PKA pathway and review in vitro animal studies (mouse) and other evidence that support the importance of PKA in regulating behaviors that lead to anxiety. Since cAMP signaling and PKA have been pharmacologically exploited since the 1940s (even before the identification of cAMP as a second messenger with PKA as its mediator) for a number of disorders from asthma to cardiovascular diseases, there is ample opportunity to develop therapies using this new knowledge about cAMP, PKA, and anxiety disorders.