bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Relative Navigation Control Strategy Based on Relation Space Method for Autonomous Underground Articulated Vehicles
Authors: Dou Fengqian , Meng Yu , Liu Li , Gu Qing
Published: October 2016

This paper proposes a novel relative navigation control strategy based on the relation space method (RSM) for articulated underground trackless vehicles. In the RSM, a self-organizing, competitive neural network is used to identify the space around the vehicle, and the spatial geometric relationships of the identified space are used to determine the vehicle’s optimal driving direction. For driving control, the trajectories of the articulated vehicles are analyzed, and data-based steering and speed control modules are developed to reduce modeling complexity. Simulation shows that the proposed RSM can choose the correct directions for articulated vehicles in different tunnels. The effectiveness and feasibility of the resulting novel relative navigation control strategy are validated through experiments.
Deposition of Ibuprofen Crystals on Hydroxypropyl Cellulose/Polyacrylamide Gel: Experimental and Mathematic Modeling Releasing
Authors: Castillo-Miranda Claudia Alicia , Beatriz Morales-Cepeda Ana , Castro-Guerrero Carlos Fernando , Salas-Papayanopolos Homero , Velasco-Ocejo Hugo Alberto , González-Sánchez Jorge Alberto , Paramo-Garcia Ulises , De Alva-Salazar Hugo
Published: October 2016

The crystallization of nonsteroidal anti-inflammatory drug [2-(4-isobutyl-phenyl) propionic acid] ibuprofen (IBP) on a hydroxypropyl cellulose (HPC) and polyacrylamide (PAAm) gel was studied as well as the release kinetics of the drug. The IBP was crystallized on the gel surface of HPC/PAAm. It had a prismatic shape and the growth was made in an aqueous medium; the crystallinity grade of the gels HPC/PAAm and HPC/PAAm-IBU increased to 68% and to 58%, respectively. The release of IBP is performed by two means: by a non-Fickian diffusion process and by relaxation of the chains of the gel; without regard to temperature and the diffusion media, this correlates with the lower critical solution temperature (LCST) of the proposed gel. This polymer matrix provides an option for releasing nonsteroidal anti-inflammatory drugs in a temperature range of 35–39°C. Korsmeyer and Peppas mathematical model was simulated for data releases, statistically significant at 95% confidence level.
Splenic Involvement in Hereditary Hemorrhagic Telangiectasia
Authors: Takamatsu Susumu , Sato Kota , Kato Shunsuke , Nagano Hiroto , Ohtsukasa Shunro , Kawachi Yasuyuki
Published: October 2016

A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.
Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus
Authors: Mrozinska Sandra , Radkowski Piotr , Gosiewski Tomasz , Szopa Magdalena , Bulanda Malgorzata , Ludwig-Galezowska Agnieszka H. , Morawska Iwona , Sroka-Oleksiak Agnieszka , Matejko Bartlomiej , Kapusta Przemyslaw , Salamon Dominika , Malecki Maciej T. , Wolkow Pawel , Klupa Tomasz
Published: October 2016

Background. Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY).Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed.Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher (p=0.0006) and the amount of Bacteroidetes was lower (p=0.0005) in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (p=0.0143). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group.Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.
The Association of Retinopathy and Plasma Glucose and HbA1c: A Validation of Diabetes Diagnostic Criteria in a Chinese Population
Authors: Zhang Rui , Li Yufeng , Zhang Simin , Cai Xiaoling , Zhou Xianghai , Ji Linong
Published: October 2016

Aims. This study aimed to evaluate the associations of diabetic retinopathy (DR) with fasting plasma glucose (FPG), 2-hour postload plasma glucose (2hPG), and glycated hemoglobin A1c (HbA1c) in a Chinese population.Materials and Methods. A total of 3124 participants, identified from a population-based survey in Pinggu district, were examined by retinal photography (45°). DR was classified according to the Early Treatment Diabetic Retinopathy Study scale. FPG, 2hPG, and HbA1c were tested and categorized by deciles, with the prevalence of DR calculated in each decile.Results. The prevalence of DR increased sharply in the 10th deciles, when FPG exceeded 7.03 mmol/L and HbA1c exceeded 6.4%. Analysis of the receiver operating characteristic curves showed that the optimal cutoffs for detecting DR were 6.52 mmol/L and 5.9% for FPG and HbA1c, respectively. The World Health Organization (WHO) criteria for diagnosing diabetes showed high specificity (90.5–99.5%) and low sensitivity (35.3–65.0%). Further, 6 individuals with retinopathy had normal plasma glucose; however, their characteristics did not differ from those without retinopathy.Conclusions. Thresholds of FPG and HbA1c for detecting DR were observed, and the WHO criteria of diagnosing diabetes were shown to have high specificity and low sensitivity in this population.
Oxidative Stress and Salvia miltiorrhiza in Aging‐Associated Cardiovascular Diseases
Authors: Chang Cheng-Chieh , Chang Yu-Chun , Hu Wen-Long , Hung Yu-Chiang
Published: October 2016

Aging‐associated cardiovascular diseases (CVDs) have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM) has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging‐associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti‐inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low‐density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood‐brain barrier, and promotes self‐renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well‐designed and randomized control trials will be necessary to confirm the efficacy of SM in aging‐associated CVDs.
Parents Support Implementation of HIV Testing and Counseling at School: Cross-Sectional Study with Parents of Adolescent Attending High School in Gauteng and North West Provinces, South Africa
Authors: Madiba Sphiwe , Mokgatle Mathildah
Published: October 2016

Background. A formative assessment of the implementation of HIV testing and counseling (HTC) at school showed high acceptability and willingness to test among learners. However, the success of the proposed HTC depends on the support and acceptability of key stakeholders, including the parents. The aim of the study was to assess the opinions and acceptability of the implementation of HTC at school among parents of adolescents in high school.Methods. This was a cross-sectional household survey conducted with parents of adolescents attending high schools in educational districts in North West and Gauteng provinces, South Africa.Results. A total of 804 parents participated, and 548 (68.3%) were biological mothers, 85 (10.6%) were fathers, and the remaining were other relatives including grandmothers. Almost all (n=742, 92.9%) parents were in support of implementation and provision of HTC at school, 701 (87.7%) would allow their children to be tested at school, 365 (46%) felt that parental consent was not needed to test at school, and 39.4% preferred to receive the HIV test results with their children.Conclusion. Parents accept the roll-out of an HTC program at school and have a role to play in supporting children who test positive for HIV.
Optimal Uncertainty Decision of Innovation Products Output Based on Return Collection
Authors: Su Yi , Sun Wei , Lin Zhouzhou
Published: October 2016

As the length of time between product renewals decreases, the enterprises that make innovative products face new challenges. The production cost structure of innovative products can be changed by collecting product returns, which can be economically valuable for enterprises. Enterprises face both production and demand randomness; hence, it is important to improve the traditional optimal production decision-making model that considers the randomness of demand only. This paper divides innovative products into structural innovation products and improved innovation products. The paper studies the optimal single-period production decision between reused parts and conventional new parts in complementary and substitute relationships. It further gives the analytical expressions for satisfying the optimal production and provides some numerical examples. The research results indicate that when producing innovative products, whether based on structural or improved innovation, with the variance of the quantity of the recycled parts increasing, the optimal purchase quantity of the conventional parts will increase but the expected profits for the innovative products will decrease. With integrated substitution and complementation based on improved innovation, enhancing the fluctuation in the number of recycled parts has a greater impact on the optimal purchase quantity of the substitute conventional parts than that of the complementary parts.
A Novel Mobile Video Community Discovery Scheme Using Ontology-Based Semantical Interest Capture
Authors: Zhang Ruiling , Xiong Shengwu
Published: October 2016

Leveraging network virtualization technologies, the community-based video systems rely on the measurement of common interests to define and steady relationship between community members, which promotes video sharing performance and improves scalability community structure. In this paper, we propose a novel mobile Video Community discovery scheme using ontology-based semantical interest capture (VCOSI). An ontology-based semantical extension approach is proposed, which describes video content and measures video similarity according to video key word selection methods. In order to reduce the calculation load of video similarity, VCOSI designs a prefix-filtering-based estimation algorithm to decrease energy consumption of mobile nodes. VCOSI further proposes a member relationship estimate method to construct scalable and resilient node communities, which promotes video sharing capacity of video systems with the flexible and economic community maintenance. Extensive tests show how VCOSI obtains better performance results in comparison with other state-of-the-art solutions.
Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants
Authors: Lopes Rui , Alves José Carlos , Rego Raquel Garcia
Published: October 2016

Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice.
A Case of Tuberculous Meningitis with Paradoxical Response in a 14-Year-Old Boy
Authors: Özer Murat , Özsürekci Yasemin , Cengiz Ali Bülent , Emiralioğlu Nagehan , Doğru Deniz , Oğuz Kader Karlı , Akça Onur , Özkayar Özgür
Published: October 2016

A clinical or radiological worsening of already existing lesions or an emergence of new lesions after beginning treatment in patients with tuberculosis (TB) is referred to as the paradoxical response. This has aroused suspicion regarding the accuracy of diagnosis, the possibilities of treatment failure, or the presence of another underlying disease, and thus it is an important topic for clinicians to understand. In this article, the development of a paradox reaction in a 14-year-old male patient diagnosed with and treated for tuberculosis meningitis is reported. This pediatric patient with a healthy immune system is treated with steroids successfully and reported to elucidate the importance of managing the paradox of TB progression in spite of the appropriate anti-TB medications.
Colorimetric Analysis Using Scene-Adaptive Color Conversion Matrix of Calibrated CIS
Authors: Lee Sung-Hak
Published: October 2016

TheRGBsignals of different CISs (color image sensors) do not register the same values for the same viewing scene owing to their different spectral sensitivity and white balance mechanisms. Thus, CISs must be characterized based on CIE standard observation for colorimetric purposes. One general method for characterizing CISs is least square polynomial modeling to derive the colorimetric transfer matrix betweenRGBoutputs and CIEXYZtristimulus inputs. However, the transfer matrix that is obtained under the standard CIE illumination is unable to estimate various conditions of a CIS that is operated under various illuminations with varying chromaticity and luminance. Therefore, repeated experiments are necessary to obtain accurate colorimetric analysis results. This paper presents a scene-adaptive colorimetric analysis method using images captured by a general consumer camera under various environments.
Nonuniform Oxidation on the Surface of Fuel Element in HTR
Authors: Liu Peng , Zheng Yanhua , Xu Wei , Shi Lei
Published: October 2016

The graphite oxidation of fuel element has obtained high attention in air ingress accident analysis of high temperature gas-cooled reactor (HTR). The shape function, defined as the relationship between the maximum and the average of the oxidation, is an important factor to estimate the consequence of the accident. There are no detailed studies on the shape function currently except two experiments several decades ago. With the development of computer technology, CFD method is used in the numerical experiment about graphite oxidation in pebble bed of HTR in this paper. Structured packed beds are used in the calculation instead of random packed beds. The result shows the nonuniform distribution of oxidation on the sphere surface and the shape function in the condition of air ingress accident. Furthermore, the sensitive factors of shape function, such as temperature and Re number, are discussed in detail and the relationship between the shape function and sensitive factors is explained. According to the results in this paper, the shape function ranges from 1.05 to 4.7 under the condition of temperature varying from 600°C to 1200°C and Re varying from 16 to 1600.
Atomistic Study on Size Effects in Thermally Induced Martensitic Phase Transformation of NiTi
Authors: Gur Sourav , Frantziskonis George N.
Published: October 2016

The atomistic study shows strong size effects in thermally induced martensitic phase transformation evolution kinetics of equiatomic NiTi shape memory alloys (SMAs). It is shown that size effects are closely related to the presence of free surfaces; thus, NiTi thin films and nanopillars are studied. Quasi-static molecular dynamics simulations for several cell sizes at various (constant) temperatures are performed by employing well-established interatomic potentials for NiTi. The study shows that size plays a crucial role in the evolution of martensite phase fraction and, importantly, can significantly change the phase transformation temperatures, which can be used for the design of NiTi based sensors, actuators, or devices at nano- to microscales. Interestingly, it is found that, at the nanometer scale, Richard’s equation describes very well the martensite phase fraction evolution in NiTi thin films and nanopillars as a function of temperature.
Adaptive Finite Volume Method for the Shallow Water Equations on Triangular Grids
Authors: Mungkasi Sudi
Published: October 2016

This paper presents a numerical entropy production (NEP) scheme for two-dimensional shallow water equations on unstructured triangular grids. We implement NEP as the error indicator for adaptive mesh refinement or coarsening in solving the shallow water equations using a finite volume method. Numerical simulations show that NEP is successful to be a refinement/coarsening indicator in the adaptive mesh finite volume method, as the method refines the mesh or grids around nonsmooth regions and coarsens them around smooth regions.
miR-940 Suppresses Tumor Cell Invasion and Migration via Regulation of CXCR2 in Hepatocellular Carcinoma
Authors: Ding Dong , Zhang Yaodong , Yang Renjie , Wang Xing , Ji Guwei , Huo Liqun , Shao Zicheng , Li Xiangcheng
Published: October 2016

Aim. To investigate the expression of miR-940 in the hepatocellular carcinoma (HCC) and its impact on function and biological mechanism in the HCC cells.Methods. Quantitative RT-PCR analysis was used to quantify miR-940 expression in 46 cases of tissues and cells. Transfection of HCC cell lines was performed by miR-940 mimics; the abilities of invasion and migration were assessed through Transwell array. Western blot represents the alteration in expression of CXCR2 by miR-940 mimics.Results. miR-940 expression was decreased significantly in the HCC tissues and the relevant cell lines. miR-940 upregulation suppressed the invasion and migration of HCC cells in vitro. Furthermore, the CXCR2 was downregulated to suppress invasion and migration after miR-940 mimics. Moreover, decreased miR-940 expression was negatively correlated with Edmondson grade (P=0.008), tumor microsatellite or multiple tumors (P=0.04), vascular invasion (P=0.035), and recurrence and metastasis (P=0.038). Kaplan-Meier analysis demonstrated that decreased miR-940 expression contributed to poor overall survival (P<0.05).Conclusions. Our findings present that miR-940 acts as a pivotal adaptor of CXCR2 and its transcription downregulated CXCR2 expression to decrease HCC invasion and migration in vitro. Our study suggests that miR-940 may be a novel poor prognostic biomarker for HCC.
A 12-Week Assessment of the Treatment of White Spot Lesions with CPP-ACP Paste and/or Fluoride Varnish
Authors: Güçlü Zeynep Aslı , Alaçam Alev , Coleman Nichola Jayne
Published: October 2016

This 12-week clinical study evaluated the impact of 10% CPP-ACP and 5% sodium fluoride varnish regimes on the regression of nonorthodontic white spot lesions (WSLs). The study included 21 children with 101 WSLs who were randomised into four treatment regimes: weekly clinical applications of fluoride varnish for the first month (FV); twice daily self-applications of CPP-ACP paste (CPP-ACP); weekly applications of fluoride varnish for the first month and twice daily self-applications of CPP-ACP paste (CPP-ACP-FV); and no intervention (control). All groups undertook a standard oral hygiene protocol and weekly consultation. Visual appraisals and laser fluorescence (LF) measurements were made in weeks one and twelve. The majority of WSLs in the control and FV groups exhibited no shift in appearance, whereas, in the CPP-ACP and CPP-ACP-FV groups, the lesions predominantly regressed. The visual and LF assessments indicated that the extent of remineralisation afforded by the treatments was of the following order: control ~ FV < CPP-ACP ~ CPP-ACP-FV. Self-applications of CPP-ACP paste as an adjunct to standard oral hygiene significantly improved the appearance and remineralisation of WSLs. No advantage was observed for the use of fluoride varnish as a supplement to either the standard or CPP-ACP-enhanced oral hygiene regimes.
A New Hybrid BFOA-PSO Optimization Technique for Decoupling and Robust Control of Two-Coupled Distillation Column Process
Authors: Abdelkarim Noha , Mohamed Amr E. , El-Garhy Ahmed M. , Dorrah Hassen T.
Published: October 2016

The two-coupled distillation column process is a physically complicated system in many aspects. Specifically, the nested interrelationship between system inputs and outputs constitutes one of the significant challenges in system control design. Mostly, such a process is to be decoupled into several input/output pairings (loops), so that a single controller can be assigned for each loop. In the frame of this research, the Brain Emotional Learning Based Intelligent Controller (BELBIC) forms the control structure for each decoupled loop. The paper’s main objective is to develop a parameterization technique for decoupling and control schemes, which ensures robust control behavior. In this regard, the novel optimization technique Bacterial Swarm Optimization (BSO) is utilized for the minimization of summation of the integral time-weighted squared errors (ITSEs) for all control loops. This optimization technique constitutes a hybrid between two techniques, which are the Particle Swarm and Bacterial Foraging algorithms. According to the simulation results, this hybridized technique ensures low mathematical burdens and high decoupling and control accuracy. Moreover, the behavior analysis of the proposed BELBIC shows a remarkable improvement in the time domain behavior and robustness over the conventional PID controller.
A High Protein Diet Has No Harmful Effects: A One-Year Crossover Study in Resistance-Trained Males
Authors: Antonio Jose , Ellerbroek Anya , Silver Tobin , Vargas Leonel , Tamayo Armando , Buehn Richard , Peacock Corey A.
Published: October 2016

The purpose of this investigation was to determine the effects of a high protein diet over a one-year period. Fourteen healthy resistance-trained men completed the study (mean ± SD; age26.3±3.9 yr; height178.5±8.4 cm; and average years of training8.9±3.4 yr). In a randomized crossover design, subjects consumed their habitual or normal diet for 2 months and 4 months and alternated that with a higher protein diet (>3 g/kg/d) for 2 months and 4 months. Thus, on average, each subject was on their normal diet for 6 months and a higher protein diet for 6 months. Body composition was assessed via the Bod Pod®. Each subject provided approximately 100–168 daily dietary self-reports. During the subjects’ normal eating phase, they consumed (mean ± SD)29.94±5.65 kcals/kg/day and2.51±0.69 g/kg/day of protein. This significantly increased (p<0.05) during the high protein phase to34.37±5.88 kcals/kg/day and3.32±0.87 g/kg/day of protein. Our investigation discovered that, in resistance-trained men that consumed a high protein diet (~2.51–3.32 g/kg/d) for one year, there were no harmful effects on measures of blood lipids as well as liver and kidney function. In addition, despite the total increase in energy intake during the high protein phase, subjects did not experience an increase in fat mass.
Anticerebral Ischemia-Reperfusion Injury Activity of Synthesized Puerarin Derivatives
Authors: Ji Yubin , Jiang Pei , Yan Xinjia
Published: October 2016

When cerebral ischemia-reperfusion injury happened in patients, multiple pathological processes occur, such as leukocyte infiltration, platelet, and complement activation, which would result in cognitive dysfunction and inflammation. Puerarin has shown protective effect on injury of neural cell. In order to enhance this protective effect of puerarin, puerarin derivatives with differentlog⁡Pvalues were designed and synthesized. The original phenolic hydroxyl in the puerarin molecules was substituted in order to change the blood-brain barrier permeability and thus enhance the efficacy for preventing cerebral ischemia/reperfusion injury. And the structure of the newly synthesized molecules was confirmed by 1H NMR spectroscopy and mass spectrometry. The mouse model of cerebral artery ischemia/reperfusion injury was established to test the anticerebral ischemia-reperfusion injury activity of the puerarin derivatives. The assays of the water maze, Y maze, brain cortex Ca2+-Mg2+-ATP enzyme, and iNOS enzyme activity were performed in this mouse model. The results showed that puerarin derivative P1-EA and P2-EA were resulting in an increased lipophilicity that enabled the derivatives to pass more efficiently through the blood-brain barrier, thus, improving the protective effects against cerebral ischemia/reperfusion injury. Therefore, derivatives of puerarin may serve as promising approach to improve neuron function in ischemia-reperfusion brain injury-related disorders.
Large-scale Radiomic Profiling of Recurrent Glioblastoma Identifies an Imaging Predictor for Stratifying Anti-Angiogenic Treatment Response
Authors: Kickingereder Philipp , Götz Michael , Muschelli John , Wick Antje , Neuberger Ulf , Shinohara Russell T. , Sill Martin , Nowosielski Martha , Schlemmer Heinz-Peter , Radbruch Alexander , Wick Wolfgang , Bendszus Martin , Maier-Hein Klaus H. , Bonekamp David
Published: October 2016

Purpose: Antiangiogenic treatment with bevacizumab, a mAb to the VEGF, is the single most widely used therapeutic agent for patients with recurrent glioblastoma. A major challenge is that there are currently no validated biomarkers that can predict treatment outcome. Here we analyze the potential of radiomics, an emerging field of research that aims to utilize the full potential of medical imaging.

Experimental Design: A total of 4,842 quantitative MRI features were automatically extracted and analyzed from the multiparametric tumor of 172 patients (allocated to a discovery and validation set with a 2:1 ratio) with recurrent glioblastoma prior to bevacizumab treatment. Leveraging a high-throughput approach, radiomic features of patients in the discovery set were subjected to a supervised principal component (superpc) analysis to generate a prediction model for stratifying treatment outcome to antiangiogenic therapy by means of both progression-free and overall survival (PFS and OS).

Results: The superpc predictor stratified patients in the discovery set into a low or high risk group for PFS (HR = 1.60; P = 0.017) and OS (HR = 2.14; P < 0.001) and was successfully validated for patients in the validation set (HR = 1.85, P = 0.030 for PFS; HR = 2.60, P = 0.001 for OS).

Conclusions: Our radiomic-based superpc signature emerges as a putative imaging biomarker for the identification of patients who may derive the most benefit from antiangiogenic therapy, advances the knowledge in the noninvasive characterization of brain tumors, and stresses the role of radiomics as a novel tool for improving decision support in cancer treatment at low cost. Clin Cancer Res; 22(23); 5765–71. ©2016 AACR.
TGFβR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells
Authors: Tran Hung C. , Wan Zesheng , Sheard Michael A. , Sun Jianping , Jackson Jeremy R. , Malvar Jemily , Xu Yibing , Wang Larry , Sposto Richard , Kim Eugene S. , Asgharzadeh Shahab , Seeger Robert C.
Published: October 2016

Purpose: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma.

Experimental Design: TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis. The ability of galunisertib to inhibit SMAD activity induced by neuroblastoma patient blood and bone marrow plasmas in neuroblastoma cells was tested. The impact of galunisertib on TGFβ1-induced inhibition of aNK cytotoxicity and ADCC in vitro and on anti-neuroblastoma activity in NOD-scid gamma (NSG) mice was determined.

Results: Neuroblastomas express TGFB1 and TGFBR1 mRNA. Galunisertib suppressed SMAD activation in neuroblastoma cells induced by exogenous TGFβ1 or by patient blood and bone marrow plasma, and suppressed SMAD2 phosphorylation in human neuroblastoma cells growing in NSG mice. In NK cells treated in vitro with exogenous TGFβ1, galunisertib suppressed SMAD2 phosphorylation and restored the expression of DNAM-1, NKp30, and NKG2D cytotoxicity receptors and the TRAIL death ligand, the release of perforin and granzyme A, and the direct cytotoxicity and ADCC of aNK cells against neuroblastoma cells. Addition of galunisertib to adoptive cell therapy with aNK cells plus dinutuximab reduced tumor growth and increased survival of mice injected with two neuroblastoma cell lines or a patient-derived xenograft.

Conclusions: Galunisertib suppresses activation of SMAD2 in neuroblastomas and aNK cells, restores NK cytotoxic mechanisms, and increases the efficacy of dinutuximab with aNK cells against neuroblastoma tumors. Clin Cancer Res; 23(3); 804–13. ©2016 AACR.

See related commentary by Zenarruzabeitia et al., p. 615
Therapeutics for Brain Metastases, v3
Authors: Steeg Patricia S. , Zimmer Alexandra , Gril Brunilde
Published: October 2016

The role of blood–brain barrier (BBB) permeability in the efficacy of brain metastasis therapeutics is debated. Both BBB-permeable and BBB-impermeable compounds were compared in a melanoma brain metastasis model using imaging through a cranial window. Only the BBB-permeable compound inhibited both the ∼30% permeable metastases and the ∼70% impermeable metastases. Clin Cancer Res; 22(24); 5953–5. ©2016 AACR.

See related article by Osswald et al., p. 6078
Fetal and Neonatal Alloimmune Thrombocytopenia: Management and Outcome of a Large International Retrospective Cohort
Authors: Kamphuis Marije M. , Tiller Heidi , van den Akker E.S. , Westgren Magnus , Tiblad Eleonor , Oepkes Dick
Published: October 2016

Objective: To evaluate the management and outcome of a large international cohort of cases of pregnancies complicated by fetal and neonatal alloimmune thrombocytopenia (FNAIT). Methods: This was an observational prospective and retrospective cohort study of all cases of FNAIT entered into the international multicentre No IntraCranial Haemorrhage (NOICH) registry during the period of 2001-2010. We evaluated human platelet antigen (HPA) specificity, the antenatal and postnatal interventions performed, and clinical outcome. Results: A total of 615 pregnancies complicated by FNAIT from 10 countries were included. Anti-HPA-1a was the most commonly implicated antibody. Antenatal treatment was administered in 273 pregnancies (44%), varying from intrauterine platelet transfusion to maternal administration of immunoglobulins, steroids, or a combination of those. Intracranial haemorrhage was diagnosed in 23 fetuses or neonates (3.7%). Overall perinatal mortality was 1.14% (n = 7). Conclusion: This study presents the largest cohort of cases of FNAIT published. Our data show that antenatal treatment for FNAIT results in favourable perinatal outcome. Over time, in most centres, treatment for FNAIT changed from an invasive to a complete non-invasive procedure.
High Rate of Early Posterior Capsule Opacification following Femtosecond Laser-Assisted Cataract Surgery
Authors: Rostami Benjamin , Tian Jack , Jackson Nicholas , Karanjia Rustum , Lu Kenneth
Published: October 2016

Purpose: To compare the rates of rapid posterior capsule opacification (PCO) formation in the first 3 months following femtosecond laser-assisted cataract surgery (FLACS) to manual anterior capsulorhexis. Methods: Retrospective review of 29 cases of FLACS, comparing the rates of PCO in the first 3 months following surgery to 50 consecutive cases of manual anterior capsulorhexis. Results: Seven of the 29 FLACS cases developed PCO requiring capsulotomy at 3 months, while none of the control cases required a capsulotomy over the same time period (p < 0.05). Conclusion: There is an increased incidence of early-onset PCO following the use of femtosecond laser in cataract surgery that is otherwise unfounded in manual capsulorhexis. This suggests that the use of a femtosecond laser could increase the risk of this novel postoperative complication.
Use and Selection of Sleeping Sites by Proboscis Monkeys, Nasalis larvatus, along the Kinabatangan River, Sabah, Malaysia
Authors: Thiry Valentine , Stark Danica J. , Goossens Benoît , Slachmuylder Jean-Louis , Drubbel Régine Vercauteren , Vercauteren Martine
Published: October 2016

The choice of a sleeping site is crucial for primates and may influence their survival. In this study, we investigated several tree characteristics influencing the sleeping site selection by proboscis monkeys (Nasalis larvatus) along Kinabatangan River, in Sabah, Malaysia. We identified 81 sleeping trees used by one-male and all-male social groups from November 2011 to January 2012. We recorded 15 variables for each tree. Within sleeping sites, sleeping trees were taller, had a larger trunk, with larger and higher first branches than surrounding trees. The crown contained more mature leaves, ripe and unripe fruits but had vines less often than surrounding trees. In addition, in this study, we also focused on a larger scale, considering sleeping and non-sleeping sites. Multivariate analyses highlighted a combination of 6 variables that revealed the significance of sleeping trees as well as surrounding trees in the selection process. During our boat surveys, we observed that adult females and young individuals stayed higher in the canopy than adult males. This pattern may be driven by their increased vulnerability to predation. Finally, we suggest that the selection of particular sleeping tree features (i.e. tall, high first branch) by proboscis monkeys is mostly influenced by antipredation strategies.
Pharmacogenetic Analysis of Functional Glutamate System Gene Variants and Clinical Response to Clozapine
Authors: Taylor Danielle L. , Tiwari Arun K. , Lieberman Jeffrey A. , Potkin Steven G. , Meltzer Herbert Y. , Knight Joanne , Remington Gary , Müller Daniel J. , Kennedy James L.
Published: October 2016

Altered glutamate neurotransmission is implicated in the etiology of schizophrenia (SCZ) and the pharmacogenetics of response to clozapine (CLZ), which is the drug of choice for treatment-resistant SCZ. Response to antipsychotic therapy is highly variable, although twin studies suggest a genetic component. We investigated the association of 10 glutamate system gene variants with CLZ response using standard genotyping procedures. GRM2 (rs4067 and rs2518461), SLC1A2 (rs4354668, rs4534557, and rs2901534), SLC6A9 (rs12037805, rs1978195, and rs16831558), GRIA1 (rs2195450), and GAD1 (rs3749034) were typed in 163 European SCZ/schizoaffective disorder patients deemed resistant or intolerant to previous pharmacotherapy. Response was assessed following 6 months of CLZ monotherapy using change in Brief Psychiatric Rating Scale (BPRS) scores. Categorical and continuous response variables were analyzed using χ2 tests and analysis of covariance, respectively. We report no significant associations following correction for multiple testing. Prior to correction, nominally significant associations were observed for SLC6A9, SLC1A2, GRM2, and GRIA1. Most notably, CC homozygotes of rs16831558 located in the glycine transporter 1 gene (SLC6A9) exhibited an allele dose-dependent improvement in positive symptoms compared to T allele carriers (puncorrected = 0.008, pcorrected = 0.08). To clarify the role of SLC6A9 in clinical response to antipsychotic medication, and CLZ in particular, this finding warrants further investigation in larger well-characterized samples.
Effects of Sulfate-Rich Mineral Water on Functional Constipation: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: Naumann Johannes , Sadaghiani Catharina , Alt Felix , Huber Roman
Published: October 2016

Background: Magnesium sulfate has a long tradition as a laxative. It osmotically prevents water absorption in the large bowel and thus leads to an acceleration of the intestinal transit and better stool consistency. We wanted to investigate the efficacy of a carbonated calcium/magnesium sulfate-rich natural mineral water in subjects with functional constipation (FC). Patients and Methods: In this double-blind, randomized, placebo-controlled study, subjects with FC (Rome III criteria) received 1 l/day (4 × 250 ml) of mineral water (Ensinger Schiller Quelle) or carbonated tap water (placebo) for 6 weeks. The primary endpoint was the change in the frequency of bowel movements per week between baseline and visit 4 (after 6 weeks). The prespecified main secondary endpoint was the change in the frequency of bowel movements per week between baseline and visit 3 (after 3 weeks). Results: Efficacy was analyzed in 100 subjects (intention-to-treat). After 6 weeks of treatment there was no statistical difference between the groups (p = 0.163). However, statistical significance was reached after 3 weeks, with an increase in the frequency of bowel movements per week of 2.02 ± 2.22 for the mineral water group compared to 0.88 ± 1.67 for the placebo group (p = 0.005). Conclusions: A 3-week treatment with 1 l/day of the sulfate-rich mineral water improved the frequency of bowel movements in subjects with FC compared with tap water; however, the difference was no longer significant after 6 weeks. Further evaluation in rigorously designed clinical studies will be necessary to validate the impact of sulfate-rich natural mineral water on FC.
Neutrophil Gelatinase-Associated Lipocalin, Fibroblast Growth Factor 23, and Soluble Klotho in Long-Term Kidney Donors
Authors: Thorsen Inga Strand , Bleskestad Inger Hjørdis , Jonsson Grete , Skadberg Øyvind , Gøransson Lasse Gunnar
Published: October 2016

Background: The best treatment for end-stage renal disease (ESRD) is kidney transplantation. Twenty-seven percent of transplantations in Norway are from living donors. Recent studies have shown an increased risk of ESRD and increased mortality in donors. The aim of this study was to determine if the levels of the new biomarkers neutrophil gelatinase-associated lipocalin (NGAL), soluble Klotho (sKlotho), and fibroblast growth factor 23 (FGF23) are changed in kidney donors with normal kidney function defined as an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 compared to patients with chronic kidney disease (CKD) stages 3-5 and healthy controls. Methods: This is a cross-sectional, observational, single-center study including 35 kidney donors with an eGFR ≥60 ml/min/1.73 m2 5 years after donation, 22 patients with CKD stage 3 (eGFR 30-59 ml/min/1.73 m2), 18 patients with CKD stage 4 (eGFR 15-29 ml/min/1.73 m2), 20 patients with CKD stage 5 (eGFR <15 ml/min/1.73 m2), and 35 controls comparing levels of biomarkers in long-term kidney donors with those in CKD patients and healthy controls. Results: The level of log NGAL was significantly higher in donors than in healthy controls (2.02 ± 0.10 vs. 1.89 ± 0.10 ng/ml; p < 0.001), and the level increased with declining kidney function. The log FGF23 level was nonsignificantly higher in donors than in controls, but it significantly increased with declining kidney function. The log sKlotho levels were significantly lower in patients with CKD stages 4 and 5 than in controls, but no difference was revealed between controls and donors. Conclusion: Kidney donors have significantly higher levels of NGAL than healthy controls after a median of 15 years (range 5-38). NGAL could be a valuable diagnostic marker in the future. FGF23 and sKlotho were not significantly different between donors and controls.
Successful Management in a Case of Traumatic Retinal Detachment due to Open Globe Injury Using Microincisional Vitrectomy
Authors: Lai Wei-Yu , Wu Tsung-Tien
Published: October 2016

Background: Retinal detachment (RD) following ocular trauma often results in guarded visual prognosis and sometimes leads to loss of the eye. With the advent of microincisional vitrectomy surgery and the development of surgical techniques, the management of ocular trauma has been transformed. Case Presentation: A 34-year-old man sustained an open globe injury from fragmented glass at work. He received primary repair and another follow-up surgery 9 days later, including vitrectomy, silicone oil tamponade, and lensectomy for RD and traumatic cataract at another medical center. However, his retina was totally detached and completely curled up in a roll with choroid on display when he was seen by us 1 month later. He was managed with vigilant and patient peeling and unfolding of the retina using a 23-gauge forceps and silicone oil tamponade, and achieved anatomical success and preservation of his eye at 6-month follow-up. Conclusions: This report demonstrates that even in cases which appear to be hopeless at presentation, the surgeon’s perseverance and surgical technique can salvage an eye that may otherwise be phthisical. It also encourages retinal surgeons to use microincisional vitrectomy to manage severe traumatic RD.
Nucleolar Dominance and Repression of 45S Ribosomal RNA Genes in Hybrids between Xenopus borealis and X. muelleri (2n = 36)
Authors: Maciak Sebastian , Michalak Katarzyna , Kale Shiv D. , Michalak Pawel
Published: October 2016

Nucleolar dominance is a dramatic disruption in the formation of nucleoli and the expression of ribosomal RNA (rRNA) genes, characteristic of some plant and animal hybrids. Here, we report that F1 hybrids produced from reciprocal crosses between 2 sister species of Xenopus clawed frogs, X. muelleri and X. borealis, undergo nucleolar dominance somewhat distinct from a pattern previously reported in hybrids between phylogenetically more distant Xenopus species. Patterns of nucleolar development, 45S rRNA expression, and gene copy inheritance were investigated using a combination of immunostaining, pyrosequencing, droplet digital PCR, flow cytometry, and epigenetic inhibition. In X. muelleri × X. borealis hybrids, typically only 1 nucleolus is formed, and 45S rRNA genes are predominantly expressed from 1 progenitor's alleles, X. muelleri, regardless of the cross-direction. These changes are accompanied by an extensive (∼80%) loss of rRNA gene copies in the hybrids relative to their parents, with the transcriptionally underdominant variant (X. borealis) being preferentially lost. Chemical treatment of hybrid larvae with a histone deacetylase inhibitor resulted in a partial derepression of the underdominant variant. Together, these observations shed light on the genetic and epigenetic basis of nucleolar dominance as an underappreciated manifestation of genetic conflicts within a hybrid genome.
Coincidence of Inflamed Conjunctival Carcinoma in situ and Primary Pterygium
Authors: Endo Hiroaki , Kase Satoru , Suzuki Yasuo , Kase Manabu
Published: October 2016

Background: We report a rare case of carcinoma in situ (CIS) in conjunction with a primary pterygium that exhibited characteristic angiographic and histopathological findings. Case: A 78-year-old man presented with a pterygium and a whitish tumor adjacent to the pterygium in his right eye. Indocyanine green angiography displayed that feeder vessels within the primary pterygium spread to the whitish tumor. The tumor and pterygial tissues were surgically removed. Histologically, the resected tissue contained CIS as well as squamous metaplasia. There was a marked inflammatory cell infiltration within the tumor and beneath the epithelium. Topical interferon alfa-2b was given 4 times per day for 2 months. The patient has been well without local recurrence of tumor or distal metastases to 54 follow-up months after surgery. Conclusions: Because CIS can occur adjacent to pterygial tissues, long-term follow-up is necessary in patients with pterygia.
Invasive Lobular Carcinoma of the Breast: Appearance on Digital Breast Tomosynthesis
Authors: Grubstein Ahuva , Rapson Yael , Morgenstern Sara , Gadiel Itai , Haboosheh Amit , Yerushalmi Rinat , Cohen Maya
Published: October 2016

Background: The aim of this study was to characterize the signs of invasive lobular carcinoma of the breast on digital breast tomosynthesis (DBT) imaging. Patients and Methods: The study group included 23 women with pathologically proven invasive lobular carcinoma of the breast for whom both digital mammography (DM) and DBT images were available. The images were read jointly by 2 experienced breast radiologists. Findings were recorded according to the descriptors in the Breast Imaging and Reporting Data System lexicon and correlated with the detailed pathology results. Results: In 21 of the 23 patients, the combination of DM and DBT yielded pathologic findings (91%). Architectural distortions or spiculations were demonstrated in 87% of cases. The addition of DBT to DM improved lesion detection by more clearly depicting both the lesion margins and architectural distortions. Only 2 lesions were occult by both DM and DBT, including 1 lesion in a peripheral location that was not incorporated in the standard mediolateral oblique and craniocaudal views. Conclusion: DBT improves the detection of invasive lobular carcinoma lesions by more clearly depicting architectural distortions and spiculations.