bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferential Statistics from Black Hispanic Breast Cancer Survival Data
Authors: Khan Hafiz M. R. , Saxena Anshul , Ross Elizabeth , Ramamoorthy Venkataraghavan , Sheehan Diana
Published: February 2014

In this paper we test the statistical probability models for breast cancer survival data for race and ethnicity. Data was collected from breast cancer patients diagnosed in United States during the years 1973–2009. We selected a stratified random sample of Black Hispanic female patients from the Surveillance Epidemiology and End Results (SEER) database to derive the statistical probability models. We used three common model building criteria which include Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) to measure the goodness of fit tests and it was found that Black Hispanic female patients survival data better fit the exponentiated exponential probability model. A novel Bayesian method was used to derive the posterior density function for the model parameters as well as to derive the predictive inference for future response. We specifically focused on Black Hispanic race. Markov Chain Monte Carlo (MCMC) method was used for obtaining the summary results of posterior parameters. Additionally, we reported predictive intervals for future survival times. These findings would be of great significance in treatment planning and healthcare resource allocation.
Simple and Sensitive Analysis of Blonanserin and Blonanserin C in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry and Its Application
Authors: Zheng Yunliang , Hu Xingjiang , Liu Jian , Wu Guolan , Zhou Huili , Zhu Meixiang , Zhai You , Wu Lihua , ShenTu Jianzhong
Published: February 2014

A highly sensitive, simple, and rapid liquid chromatography tandem mass spectrometry method to simultaneously determine blonanserin and blonanserin C in human plasma with AD-5332 as internal standard (IS) was established. A simple direct protein precipitation method was used for the sample pretreatment, and chromatographic separation was performed on a Waters XBridge C8(4.6×150 mm, 3.5 μm) column. The mobile phase consists of a mixture of 10 mM ammonium formate and 0.1% formic acid in water (A) and 0.1% formic acid in methanol (B). To quantify blonanserin, blonanserin C, and IS, multiple reaction monitoring (MRM) was performed in positive ESI mode. The calibration curve was linear in the concentration range of 0.012–5.78 ng·mL−1for blonanserin and 0.023–11.57 ng·mL−1for blonanserin C (r2>0.9990). The intra- and interday precision of three quality control (QC) levels in plasma were less than 7.5%. Finally, the current simple, sensitive, and accurate LC-MS/MS method was successfully applied to investigate the pharmacokinetics of blonanserin and blonanserin C in healthy Chinese volunteers.
Screening of Indigenous Oxalate Degrading Lactic Acid Bacteria from Human Faeces and South Indian Fermented Foods: Assessment of Probiotic Potential
Authors: Gomathi Sivasamy , Sasikumar Ponnusamy , Anbazhagan Kolandaswamy , Sasikumar Sundaresan , Kavitha Murugan , Selvi M. S. , Selvam Govindan Sadasivam
Published: February 2014

Lactic acid bacteria (LAB) have the potential to degrade intestinal oxalate and this is increasingly being studied as a promising probiotic solution to manage kidney stone disease. In this study, oxalate degrading LAB were isolated from human faeces and south Indian fermented foods, subsequently assessed for potential probiotic propertyin vitroandin vivo. Based on preliminary characteristics, 251 out of 673 bacterial isolates were identified as LAB. A total of 17 strains were found to degrade oxalate significantly between 40.38% and 62.90% and were subjected to acid and bile tolerance test. Among them, nine strains exhibited considerable tolerance up to pH 3.0 and at 0.3% bile. These were identified asLactobacillus fermentumandLactobacillus salivariususing 16S rDNA sequencing. Three strains,Lactobacillus fermentumTY5,Lactobacillus fermentumAB1, andLactobacillus salivariusAB11, exhibited good adhesion to HT-29 cells and strong antimicrobial activity. They also conferred resistance to kanamycin, rifampicin, and ampicillin, but were sensitive to chloramphenicol and erythromycin. The faecal recovery rate of these strains was observed as 15.16% (TY5), 6.71% (AB1), and 9.3% (AB11) which indicates the colonization ability. In conclusion, three efficient oxalate degrading LAB were identified and their safety assessments suggest that they may serve as good probiotic candidates for preventing hyperoxaluria.
Pyoderma Gangrenosum in Two Successive Pregnancies Complicating Caesarean Wound
Authors: Amin Sapna Vinit , Bajapai Neha , Pai Ashwini , Bharatnur Sunanda , Hebbar Shripad
Published: February 2014

Pyoderma gangrenosum (PG) is a rare ulcerative cutaneous disorder with tendency to recur in the injured area. Though most of the time is associated with chronic systemic conditions, it can occur in isolation and can be a diagnostic dilemma. The aetiology is poorly understood. The diagnosis is based on clinical features and excluding other causes of skin ulcers, as it does not have characteristic histopathology or laboratory findings. Lesions can develop after surgery, after trauma or de novo. We are reporting a 32-year-old pregnant lady with two previous instances of pyoderma gangrenosum in the previous pregnancy, who in postoperative period following caesarean section developed the same condition for the third time. She responded well to local wound care, oral Prednisolone, and Dapsone and made a good recovery. Pregnancy being an immunologically altered status can play a role in development of pyoderma gangrenosum and one should always rule out its possibility when there is a delayed wound healing.
Macroblock Layer Rate Control Based on Structural Similarity and Mean Absolute Difference for H.264
Authors: Chen Xiao , Gu Dongjue
Published: February 2014

In the process of the H.264 video coding, special attention should be paid to the subjective quality of the image. This paper applies the structural similarity (SSIM) based subjective evaluation to the rate control in the H.264 coding and proposes to combine the SSIM and the mean absolute difference (MAD) to perform the macroblock layer bit allocation instead of the MAD. Experimental results show that the proposed method is correlating better with the human visual system and thus achieves better subjective image quality.
Cyclosporine A Loaded PLGA Nanoparticles for Dry Eye Disease:In VitroCharacterization Studies
Authors: Wagh Vijay D. , Apar Dipak U.
Published: February 2014

Dry eye disease is a common disease of the tear film caused by decreased tear production or increased evaporation. The objective of this study was to develop and evaluate poly (dl-lactide-co-glycolide) (PLGA) nanoparticles for CsA (CsA) ophthalmic delivery, for the treatment of dry eye disease. Topical CsA is currently the only and safe pharmacologic treatment of severe dry eye symptoms. Nanoparticles (NPs) were prepared by W/O solvent evaporation technique followed by probe sonicator and characterized for various properties such as particle size, entrapment efficiency, zeta potential,in vitrodrug release,in vitropermeation studies by Franz diffusion cells, XRD, DSC, SEM, and stability studies. The developed nanosuspension showed a mean particle size in the range from 128 to 253.50 nm before freeze drying and after freeze drying 145.60 to 260.0 nm. The drug entrapment efficiency was from 58.35 to 95.69% and production yield was found between52.29±2.4and85.30±2.1% in all preparations. The zeta potential of the Eudragit RL containing nanoparticles was positive, that is, 20.3 mV to 34.5 mV. The NPs formulations exhibited a biphasic drug release with initial burst followed by a very slow drug release and total cumulative release up to 24 h ranged from 69.83 to 91.92%. Kinetically, the release profiles of CsA from NPs appeared to fit best with the Higuchi model. The change of surface characteristics of NPs represents a useful approach for improvement of ocular retention and drug availability.
A New Double Sequence Space m2(F,ϕ,p) Defined by a Double Sequence of Modulus Functions
Authors: Sağır Birsen , Duyar Cenap , Oğur Oğuz
Published: February 2014

In this work we introduce new spaces m2(F,ϕ,p) of double sequences defined by a double sequence of modulus functions, and we study some properties of this space.
Intracranial Rosai-Dorfman Disease
Authors: Arun Kumar Yadav , Yi Peng Peng , Chen Chen Xia
Published: February 2014

Rosai-Dorfman disease (RDD) is a rare, benign pseudolymphomatous condition, predominantly involving lymph nodes. Rosai-Dorfman disease (RDD) (sinus histiocytes with massive lymphadenopathy) rarely affects the intracranial region without involvement of other sites. It is a rare and idiopathic histoproliferation disorder characterized by painless lymphadenopathy. We report a case of 43-year-old male who presented with unconsciousness; MRI was done and right temporofrontal mass was found. Excision was done, and on histopathology it confirmed RDD.
An Improved Metric Learning Approach for Degraded Face Recognition
Authors: Zou Guofeng , Zhang Yuanyuan , Wang Kejun , Jiang Shuming , Wan Huisong , Fu Guixia
Published: February 2014

To solve the matching problem of the elements in different data collections, an improved coupled metric learning approach is proposed. First, we improved the supervised locality preserving projection algorithm and added the within‐class and between‐class information of the improved algorithm to coupled metric learning, so a novel coupled metric learning method is proposed. Furthermore, we extended this algorithm to nonlinear space, and the kernel coupled metric learning method based on supervised locality preserving projection is proposed. In kernel coupled metric learning approach, two elements of different collections are mapped to the unified high dimensional feature space by kernel function, and then generalized metric learning is performed in this space. Experiments based on Yale and CAS‐PEAL‐R1 face databases demonstrate that the proposed kernel coupled approach performs better in low‐resolution and fuzzy face recognition and can reduce the computing time; it is an effective metric method.
Some Connections between the Spherical and Parabolic Bases on the Cone Expressed in terms of the Macdonald Function
Authors: Shilin I. A. , Choi Junesang
Published: February 2014

Computing the matrix elements of the linear operator, which transforms the spherical basis ofSO(3,1)-representation space into the hyperbolic basis, very recently, Shilin and Choi (2013) presented an integral formula involving the product of two Legendre functions of the first kind expressed in terms of 4F3-hypergeometric function and, using the general Mehler-Fock transform, another integral formula for the Legendre function of the first kind. In the sequel, we investigate the pairwise connections between the spherical, hyperbolic, and parabolic bases. Using the above connections, we give an interesting series involving the Gauss hypergeometric functions expressed in terms of the Macdonald function.
Comparative Biomechanical and Microstructural Analysis of Native versus Peracetic Acid-Ethanol Treated Cancellous Bone Graft
Authors: Rauh Juliane , Despang Florian , Baas Jorgen , Liebers Cornelia , Pruss Axel , Gelinsky Michael , Günther Klaus-Peter , Stiehler Maik
Published: February 2014

Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at −20°C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young’s modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG.
Antioxidant Capacity and Total Phenolic Content in Fruit Tissues from Accessions ofCapsicum chinenseJacq. (Habanero Pepper) at Different Stages of Ripening
Authors: Castro-Concha Lizbeth A. , Tuyub-Che Jemina , Moo-Mukul Angel , Vazquez-Flota Felipe A. , Miranda-Ham Maria L.
Published: February 2014

In the past few years, there has been a renewed interest in studying a wide variety of food products that show beneficial effects on human health.Capsicumis an important agricultural crop, not only because its economic importance, but also for the nutritional values of its pods, mainly due to the fact that they are an excellent source of antioxidant compounds, and also of specific constituents such as the pungent capsaicinoids localized in the placental tissue. This current study was designed to evaluate the antioxidant capacity and total phenolic contents from fruits tissues of twoCapsicum chinenseaccessions, namely, Chak k’an-iik (orange) and MR8H (red), at contrasting maturation stages. Results showed that red immature placental tissue, with a Trolox equivalent antioxidant capacity (TEAC) value of 55.59 μmols TE g−1 FW, exhibited the strongest total antioxidant capacity using both the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the CUPRAC methods. Placental tissue also had the highest total phenolic content (27 g GAE 100 g−1 FW). The antioxidant capacity ofCapsicumwas directly related to the total amount of phenolic compounds detected. In particular, placentas had high levels of capsaicinoids, which might be the principal responsible for their strong antioxidant activities.
In VitroWhole Blood Clot Lysis for Fibrinolytic Activity Study Using D-Dimer and Confocal Microscopy
Authors: Elnager Abuzar , Abdullah Wan Zaidah , Hassan Rosline , Idris Zamzuri , Wan Arfah Nadiah , Sulaiman S. A. , Mustafa Zulkifli
Published: February 2014

This study aimed to evaluatein vitrowhole blood (WB) clot lysis method for the assessment of fibrinolytic activity. Standardized unresected (uncut) retracted WB clot was incubated in pool platelet poor plasma (PPP) for varying incubation times and in streptokinase (SK) at different concentrations. The fibrinolytic activity was assessed by D-dimer (DD), confocal microscopy, and clot weight. DD was measured photometrically by immunoturbidimetric method. There was a significant difference in mean DD levels according to SK concentrations (P=0.007). The meanDD±SDaccording to the SK concentrations of 5, 30, 50, and 100 IU/mL was:0.69±0.12,0.78±0.14,1.04±0.14and2.40±1.09 μg/mL. There were no significant changes of clot weight at different SK concentrations. Gradual loss and increased branching of fibrin in both PPP and SK were observed. Quantitation of DD and morphology of fibrin loss as observed by the imaging features are in keeping with fibrinolytic activity. Combination of DD levels and confocal microscopic features was successfully applied to evaluate thein vitroWB clot lysis method described here.
Dividend Problems in the Diffusion Model with Interest and Exponentially Distributed Observation Time
Authors: Wang Cuilian , Liu Xiao
Published: February 2014

Consider dividend problems in the diffusion model with interest and exponentially distributed observation time where dividends are paid according to a barrier strategy. Assume that dividends can only be paid with a certain probability at each point of time; that is, on each observation, if the surplus exceeds the barrier level, the excess is paid as dividend. In this paper, integrodifferential equations for the moment-generating function, thenth moment function, and the Laplace transform of ruin time are derived; explicit expressions for the expected discounted dividends paid until ruin and the Laplace transform of ruin time are also obtained.
Spectral Characterization and 3D Molecular Modeling Studies of Metal Complexes Involving the O, N-Donor Environment of Quinazoline-4(3H)-one Schiff Base and Their Biological Studies
Authors: Siddappa Kuruba , Mane Sunilkumar B. , Manikprabhu Deene
Published: February 2014

A simple condensation of 3-amino-2-methylquinazoline-4-one with 2-hydroxy-1-naphthaldehyde produced new tridentate ONO donor Schiff base ligand with efficient yield. The structural characterization of ligand and its Cu(II), Ni(II), Co(II), Mn(II), Zn(II), and Cd(II) complexes were achieved by the aid of elemental analysis, spectral characterization such as (UV-visible, IR, NMR, mass, and ESR), and magnetic data. The analytical and spectroscopic studies suggest the octahedral geometries of Cu(II), Co(II), Ni(II) and Mn(II) complexes and tetrahedral geometry of Zn(II) and Cd(II) complexes with the tridentate ONO Schiff base ligand. Furthermore, the conclusions drawn from these studies afford further support to the mode of bonding discussed on the basis of their 3D molecular modeling studies by considering different bond lengths, bond angles, and bond distance. The ligand and its metal complexes evaluated for their antimicrobial activity againstStaphylococcus aureus(MTCC number 7443),Bacillus subtilis(MTCC number 9878),Escherichia coli(MTCC number 1698),Aspergillus niger(MTCC number 281), andAspergillus flavus(MTCC number 277). The MIC of these compounds was found to be most active at 10 μg/mL concentration in inhibiting the growth of the tested organisms. The DNA cleavage activity of all the complexes was studied by gel electrophoresis method.
Characteristics of Metachronous Gastric Tumors after Endoscopic Submucosal Dissection for Gastric Intraepithelial Neoplasms
Authors: Boda Tomoyuki , Ito Masanori , Oka Shiro , Kitamura Yoko , Numata Norifumi , Sanomura Yoji , Matsuo Taiji , Tanaka Shinji , Yoshihara Masaharu , Arihiro Koji , Chayama Kazuaki
Published: February 2014

Background.Recently, endoscopic submucosal dissection (ESD) has become a standard treatment method for early gastric cancer and concurrent stomach preservation. However, metachronous recurrences have become a major problem. We evaluated the incidence and clinicopathologic features of and examined the risk factors for metachronous gastric tumors.Methods.A total of 357 patients who underwent ESD for gastric tumors (245 early gastric cancers and 112 adenomas) and were followed up for more than 12 months without recurrence within the first 12 months were enrolled. We investigated the incidence and clinicopathologic features of metachronous tumors after ESD. We also analyzed the potential risk factors for metachronous tumors using the Kaplan-Meier method and Cox’s proportional hazards model.Results.The annual incidence of metachronous tumors after ESD was 2.4%. The median period until discovery after initial ESD was 26.0 months, and the median observation period was 52.6 months. Male patients developed metachronous tumors more frequently (P=0.04), and the hazard ratio of female to male patients was 0.36 (95% confidence interval: 0.11–0.89).Conclusions.Patients with a previous history of gastric tumors have a high risk of subsequent gastric tumor development and male patients should be carefully followed up after ESD for gastric tumor.
Counting Extended Irreducible Goppa Codes
Authors: Ryan John A.
Published: February 2014

We produce an upper bound on the number of extended irreducible Goppa codes over any
finite field.
Investigation of the Effects of Curcumin on Serum Cytokines in Obese Individuals: A Randomized Controlled Trial
Authors: Ganjali Shiva , Sahebkar Amirhossein , Mahdipour Elahe , Jamialahmadi Khadijeh , Torabi Sepideh , Akhlaghi Saeed , Ferns Gordon , Parizadeh Seyed Mohammad Reza , Ghayour-Mobarhan Majid
Published: February 2014

Background. Obesity is a disorder often accompanied by a heightened state of systemic inflammation and immunoactivation. The present randomized crossover trial aimed to investigate the efficacy of curcumin, a bioactive polyphenol with established anti-inflammatory and immunomodulatory effects, on the serum levels of a panel of cytokines and mediators in obese individuals.Methods. Thirty obese individuals were randomized to receive curcumin at a daily dose of 1 g or a matched placebo for 4 weeks. Following a 2-week wash-out period, each group was assigned to the alternate treatment regimen for another 4 weeks. Serum samples were collected at the start and end of each study period. Serum levels of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFNγ, EGF, MCP-1, and TNFαwere measured using a multiplex Biochip Array Technology based method.Results. Mean serum IL-1β(P=0.042), IL-4 (P=0.008), and VEGF (P=0.01) were found to be significantly reduced by curcumin therapy. In contrast, no significant difference was observed in the concentrations of IL-2, IL-6, IL-8, IL-10, IFNγ, EGF, and MCP-1.Conclusions. The findings of the present trial suggested that curcumin may exert immunomodulatory effects via altering the circulating concentrations of IL-1β, IL-4, and VEGF.
The Relationship between Stasis‐Stagnation Constitution and Peripheral Arterial Disease in Patients with Type 2 Diabetes
Authors: Huang Kuo-Chin , Chen Ching-Chu , Su Yi-Chang , Lin Jui-Shan , Chang Chwen-Tzuei , Wang Tzu-Yuan , Chen Rong-Hsing , Tsai Fuu-Jen
Published: February 2014

Objectives. In traditional Chinese medicine, Yu‐Zhi (YZ, indicating stasis and stagnation) constitution describes a body that tends to express abnormal circulatory conditions. This study identified the linkage between YZ constitution and peripheral arterial disease (PAD) in patients with type 2 diabetes. Methods. Patients over 20 years of age who had had type 2 diabetes for 5 years or longer were recruited. PAD was diagnosed if the ankle‐brachial index score was ≤0.9 in either leg. Level of YZ constitution was accessed by an YZ Constitution Questionnaire. Results. A total of 712 patients (354 men and 358 women) with a mean age of 61.5 ± 10.6 years and diabetes duration of 13.1 ± 6.7 years were recruited. The prevalence of PAD among our patients was 7.2%. Multivariate logistic regression revealed significant correlations between PAD and, respectively, YZ score, age, diabetes duration, current smoking, and hs‐CRP. Conclusion. In addition to traditional risk factors, YZ constitution was statistically associated with PAD in patients with type 2 diabetes. This result invites further research into the effectiveness of traditional Chinese medicine to treat YZ constitution.
An Email Survey of Physician and Licensed Midwife Vaccination Practices in Washington State in 2011
Authors: D’Angeli Marisa Anne , Eckert Linda O’Neal
Published: February 2014

Despite proven benefit to mothers and infants, influenza and Tdap vaccination for pregnant women remain suboptimal. We conducted an email survey for physicians (MDs) and licensed midwives (LMs) in Washington to assess vaccination practices. The Washington State Department of Health and University of Washington, Department of Obstetrics and Gynecology, created an electronic survey and sent it to 644 providers. We used chi-square statistic for comparisons, with Fisher’s exact test for cell size smaller than 5. We received responses from 121 (19%), 106 of whom provided prenatal or obstetric care: 81 MDs and 25 LMs. MDs were more likely than LMs to ask whether pregnant patients are current on vaccinations for influenza and pertussis (96% versus 56% and 84% versus 40%, resp.,P<0.001) and to recommend influenza and pertussis vaccine during pregnancy (100% versus 20% and 86% versus 24%, resp.,P<0.001). Significantly more MDs received influenza vaccine in the most recent season than did LMs (99% versus 20%,P<0.001). In this study, LMs were less likely to inquire about immunization status, recommend influenza and pertussis vaccines, or be vaccinated against influenza than MDs. Enhancing educational communication with LMs deserves further study and may provide an opportunity to improve immunization rates in pregnant women.
A Block‐Based Regularized Approach for Image Interpolation
Authors: Chen Li , Huang Xiaotong , Tian Jing
Published: February 2014

This paper presents a new efficient algorithm for image interpolation based on regularization theory. To render a high-resolution (HR) image from a low-resolution (LR) image, classical interpolation techniques estimate the missing pixels from the surrounding pixels based on a pixel‐by‐pixel basis. In contrast, the proposed approach formulates the interpolation problem into the optimization of a cost function. The proposed cost function consists of a data fidelity term and regularization functional. The closed‐form solution to the optimization problem is derived using the framework of constrained least squares minimization, by incorporating Kronecker product and singular value decomposition (SVD) to reduce the computational cost of the algorithm. The effect of regularization on the interpolation results is analyzed, and an adaptive strategy is proposed for selecting the regularization parameter. Experimental results show that the proposed approach is able to reconstruct high‐fidelity HR images, while suppressing artifacts such as edge distortion and blurring, to produce superior interpolation results to that of conventional image interpolation techniques.
Identification of Family Specific Fingerprints inβ-Lactamase Families
Authors: Srivastava Abhishikha , Singhal Neelja , Goel Manisha , Virdi Jugsharan Singh , Kumar Manish
Published: February 2014

Beta-lactamases are a superfamily of enzymes which degrade theβ-lactam class of antibiotics. They are produced endogenously by the bacterial cells, which when exposed to theβ-lactam class of antibiotics inactivate them by cleaving theβ-lactam ring. Based on the presence or absence of metallic ligand,β-lactamases have been divided into two broad functional classes.β-Lactamases are a constitutively evolving and expanding superfamily of enzymes, which could be further subdivided on the basis of presence/absence of conserved motifs. In the present study we have used the MEME/MAST suit to identify the patterns/motifs which are specific to a particular family or subfamily ofβ-lactamases. The family specific patterns/motifs can be also useful in recognizing and assigning newly discoveredβ-lactamases to one or the other family or subfamily. Cross-validation showed that the proposed method is highly sensitive and specific. We have also designed a webserver, LactFP, for this purpose.
Light In and Sound Out: Emerging Translational Strategies for Photoacoustic Imaging
Authors: Zackrisson S. , van de Ven S.M.W.Y. , Gambhir S.S.
Published: February 2014

Photoacoustic imaging (PAI) has the potential for real-time molecular imaging at high resolution and deep inside the tissue, using nonionizing radiation and not necessarily depending on exogenous imaging agents, making this technique very promising for a range of clinical applications. The fact that PAI systems can be made portable and compatible with existing imaging technologies favors clinical translation even more. The breadth of clinical applications in which photoacoustics could play a valuable role include: noninvasive imaging of the breast, sentinel lymph nodes, skin, thyroid, eye, prostate (transrectal), and ovaries (transvaginal); minimally invasive endoscopic imaging of gastrointestinal tract, bladder, and circulating tumor cells (in vivo flow cytometry); and intraoperative imaging for assessment of tumor margins and (lymph node) metastases. In this review, we describe the basics of PAI and its recent advances in biomedical research, followed by a discussion of strategies for clinical translation of the technique. Cancer Res; 74(4); 979–1004. ©2014 AACR.
Recurrent Prostate Cancer Genomic Alterations Predict Response to Brachytherapy Treatment
Authors: Fontugne Jacqueline , Lee Daniel , Cantaloni Chiara , Barbieri Christopher E. , Caffo Orazio , Hanspeter Esther , Mazzoleni Guido , Palma Paolo Dalla , Rubin Mark A. , Fellin Giovanni , Mosquera Juan Miguel , Barbareschi Mattia , Demichelis Francesca
Published: February 2014

Background: This study aimed to evaluate the association of recurrent molecular alterations in prostate cancer, such as ERG rearrangements and phosphatase and tensin homolog gene (PTEN) deletions, with oncologic outcomes in patients with prostate cancer treated with brachytherapy.

Methods: Ninety-two men underwent I-125 brachytherapy with a 145 Gy delivered dose between 2000 and 2008. Pretreatment prostate biopsies were analyzed by immunohistochemistry (IHC) and FISH for ERG rearrangement and overexpression, PTEN deletion, and expression loss. Univariable and multivariable Cox-regression analyses evaluated association of ERG and PTEN status with biochemical recurrence (BCR).

Results: Within a median follow-up of 73 months, 11% of patients experienced BCR. Of 80 samples with both IHC and FISH performed for ERG, 46 (57.8%) demonstrated rearrangement by FISH and 45 (56.3%) by IHC. Of 77 samples with both IHC and FISH for PTEN, 14 (18.2%) had PTEN deletion by FISH and 22 (28.6%) by IHC. No significant associations were found between ERG, PTEN status, and clinicopathologic features. Patients with concurrent ERG rearrangement and PTEN deletion demonstrated significantly worse relapse-free survival rates compared with those with ERG or PTEN wild type (P < 0.01). In multivariable Cox regression analysis adjusted for the effects of standard clinicopathologic features, combined ERG rearranged and PTEN deletion was independently associated with BCR (HR = 2.6; P = 0.02).

Conclusions: Concurrent ERG rearrangement and PTEN loss was independently associated with time to BCR in patients undergoing brachytherapy. Future studies are needed to validate prostate cancer molecular subtyping for risk stratification.

Impact: Identifying patients in the ERG-rearranged/PTEN-deleted molecular subclass may improve treatment personalization. Cancer Epidemiol Biomarkers Prev; 23(4); 594–600. ©2014 AACR.
Reduced Expression of miRNA-27a Modulates Cisplatin Resistance in Bladder Cancer by Targeting the Cystine/Glutamate Exchanger SLC7A11
Authors: Drayton Ross M. , Dudziec Ewa , Peter Stefan , Bertz Simone , Hartmann Arndt , Bryant Helen E. , Catto James WF.
Published: February 2014

Purpose: Resistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs (miRNA) that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug-resistant phenotype, and how this resistance might be overcome.

Experimental Design: miRNA expression in paired cisplatin-resistant and -sensitive cell lines was measured. Dysregulated miRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin-resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione (GSH). Candidate miRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and miRNA-27a were quantified in patient tumor material.

Results: A panel of miRNAs were found to be dysregulated in cisplatin-resistant cells. miRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of GSH biosynthesis. In patients, SLC7A11 expression was inversely related to miRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring miRNA-27a expression or reducing SLC7A11 activity with siRNA or with sulfasalazine.

Conclusion: Our findings indicate that miRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease. Clin Cancer Res; 20(7); 1990–2000. ©2014 AACR.
The Orphan Nuclear Receptor NR4A1 (Nur77) Regulates Oxidative and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells
Authors: Lee Syng-Ook , Jin Un-Ho , Kang Jeong Han , Kim Sang Bae , Guthrie Aaron S. , Sreevalsan Sandeep , Lee Ju-Seog , Safe Stephen
Published: February 2014

NR4A1 (Nur77, TR3) is an orphan nuclear receptor that is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity. RNA interference of NR4A1 expression in Panc-1 cells induced apoptosis and subsequent proteomic analysis revealed the induction of several markers of endoplasmic reticulum stress, including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), and activating transcription factor-4 (ATF-4). Treatment of pancreatic cancer cells with the NR4A1 antagonist 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) gave similar results. Moreover, both NR4A1 knockdown and DIM-C-pPhOH induced reactive oxygen species (ROS), and induction of ROS and endoplasmic reticulum stress by these agents was attenuated after cotreatment with antioxidants. Manipulation of NR4A1 expression coupled with gene expression profiling identified a number of ROS metabolism transcripts regulated by NR4A1. Knockdown of one of these transcripts, thioredoxin domain containing 5 (TXNDC5), recapitulated the elevated ROS and endoplasmic reticulum stress; thus, demonstrating that NR4A1 regulates levels of endoplasmic reticulum stress and ROS in pancreatic cancer cells to facilitate cell proliferation and survival. Finally, inactivation of NR4A1 by knockdown or DIM-C-pPhOH decreased TXNDC5, resulting in activation of the ROS/endoplasmic reticulum stress and proapoptotic pathways.

Implications: The NR4A1 receptor is pro-oncogenic, regulates the ROS/endoplasmic reticulum stress pathways, and inactivation of the receptor represents a novel pathway for inducing cell death in pancreatic cancer. Mol Cancer Res; 12(4); 527–38. ©2014 AACR.
Should We Measure Fetal Omphalocele Diameter for Prediction of Perinatal Outcome?
Authors: Kiyohara Marina Y. , Brizot Maria L. , Liao Adolfo W. , Francisco Rossana P.V. , Tannuri Ana C.A. , Krebs Vera L.J. , Zugaib Marcelo
Published: February 2014

Objective: To evaluate the fetal omphalocele diameter/abdominal circumference ratio (OD/AC) as a predictor of adverse perinatal outcome. Methods: Analysis involving 47 singleton pregnancies with fetal omphalocele, normal karyotype and absence of other major abnormalities. The OD/AC ratio was determined antenatally by ultrasound and the best cutoff for the prediction of neonatal death was determined by receiver operating characteristic curve analysis. Additional secondary outcomes included need for oral intubation in the first 24 h of life, two-step surgery or use of synthetic mesh, reoperation, parenteral feeding and need for respiratory assistance >21 days, time to first oral feed, and time to hospital discharge. Results: Fetal OD/AC did not change significantly with gestational age. Postnatal death occurred in 10 (21.3%) cases and the best cutoff for prediction was an OD/AC ratio ≥0.26. In pregnancies with the first ultrasound evaluation performed before 31 weeks' gestation and an OD/AC ≥0.26, the likelihood ratio for needing intubation in the first 24 h of life was 2.6 (95% CI: 1.2-5.7), needing two-step surgery or use of mesh was 4.9 (95% CI: 1.9-14.4), and postnatal death was 4 (95% CI: 1.9-7.5). Conclusion: A fetal ultrasound OD/AC ratio ≥0.26 is associated with increased postnatal morbidity and mortality.
Noninvasive Fetal RhD Status Determination in Early Pregnancy
Authors: Manzanares Sebastian , Entrala Carmen , Sánchez-Gila Mar , Fernández-Rosado Francisco , Cobo Davinia , Martinez Esther , Molina Luis , Reche Rosa , Pineda Alicia , Gallo José Luis
Published: February 2014

Introduction: The aim of this study was to examine if noninvasive fetal RhD genotyping from maternal blood cell-free fetal DNA performed in the first trimester of pregnancy is accurate enough to propose its routine application to replace usual immunoprophylaxis. Material and Methods: We carried out a prospective study analyzing fetal RhD genotype in 149 nonimmunized RhD-negative women with single pregnancies between 8 and 13 weeks of gestation. Fetal RhD genotype was detected by quantitative PCR targeting exons 5 and 7. The results were compared with postnatal cord blood phenotype, and discrepancy rates were calculated. Results: The concordance of fetal RhD genotypes in maternal plasma and newborn D phenotypes at delivery was 98.2%, including 1 false-positive and 1 false-negative result. The specificity and sensitivity of the assay were 97.5% (95% CI 87.1-99.9) and 98.6% (95% CI 92.7-99.9), respectively, and 6.5% of the results were inconclusive. The application of this test in early pregnancy would avoid unnecessary antenatal prophylaxis in about 27% (40/143) of nonsensitized RhD-negative women. Discussion: Determination of the fetal RhD status from cell-free fetal DNA in maternal plasma in the first trimester of pregnancy is feasible and highly accurate, thus allowing consideration of replacing general routine immunoprophylaxis in the cases of mothers with Rh-negative fetuses.
Prospective Clinical and Epidemiologic Study of Vulvar Lichen Sclerosus: Analysis of Prevalence and Severity of Clinical Features, together with Historical and Demographic Associations
Authors: Virgili Annarosa , Borghi Alessandro , Toni Giulia , Minghetti Sara , Corazza Monica
Published: February 2014

Background: Few reports have addressed the associations between clinical, demographic and historical variables of vulvar lichen sclerosus (VLS). Objective: To elaborate the prevalence and severity of signs and symptoms and to identify potential factors predicting the severity and course of VLS. Methods: A prospective cohort of 225 patients affected by VLS was included. Data were collected by direct interview and clinical examination. Results: 98% of patients complained of symptoms, principally itching. Pallor and scarring-sclerosis-atrophy were the most frequent and severe signs. The severity of VLS signs was not associated with age at onset and duration of the disease. About 70% of the patients had previously undergone treatment. Conclusions: VLS-related symptoms were not associated with the clinical features which resulted less severe. Personal history of autoimmune diseases and familial history of VLS did not influence the age at onset and the severity of VLS. A considerable part of patients had previously received inappropriate treatment.
An Articulatory and Acoustic Study of the Fricative Clusters /sʃ/ and /ʃs/ in Catalan
Authors: Recasens Daniel , Mira Meritxell
Published: February 2014

Elect ropalatographic and acoustic data for the fricative clusters /sʃ/ and /ʃs/ and the single fricatives /s/ and /ʃ/ in Eastern Catalan reveal that, while /sʃ/ undergoes regressive assimilation, /ʃs/ blends into an intermediate fricative or exhibits a twotarget realization. On the other hand, acoustic data for /ʃs/ in Western Catalan show that /s/ may assimilate to preceding /ʃ/ or undergo blending or a two-target realization depending on speaker and prosodic condition (no data are available for /sʃ/ in this dialect). Duration values for the two fricative clusters suggest that the assimilated outcome of /sʃ/ shortens down to the length of /ʃ/. A production-based account of the two sequences /sʃ/ and /ʃs/ in Catalan and other languages is proposed.
Association between a Lumican Promoter Polymorphism and High Myopia in the Chinese Population: A Meta-Analysis of Case-Control Studies
Authors: Deng Zhu-Jun , Shi Ke-Qing , Song Yi-Jiang , Fang Yu-Xiao , Wu Jianmin , Li Guiling , Tang Kai-Fu , Qu Jia
Published: February 2014

Purpose: To evaluate the relationship between lumican polymorphisms and high myopia in Chinese populations. Methods: An electronic search was conducted in Pubmed, Embase, Cochrane Library and the China Biological Medicine Database for articles published prior to September 30, 2012. A meta-analysis was performed to assess heterogeneity, combine results and determine publication bias. Results: This meta-analysis, including 1,545 subjects from 5 studies, indicated that Chinese lumican rs3759223 C allele carriers had a decreased risk of high myopia in comparison to T allele carriers (odds ratio: 0.531; 95% confidence interval, CI: 0.304-0.925; p = 0.025). There was some heterogeneity between studies. A metaregression showed that the mean axial length of controls weakens the effect of rs3759223 on high myopia (slope: -0.914; 95% CI: -1.490 to 0.337; p = 0.002). Sensitivity analysis confirmed the reliability and stability of this meta-analysis. Conclusion: Chinese lumican rs3759223 C allele carriers may be at reduced risk of high myopia.
The Effects of Propidium Monoazide Treatment on the Measured Composition of Polymicrobial Biofilms after Treatment with Chlorhexidine
Authors: Exterkate R.A.M. , Zaura E. , Buijs M.J. , Koopman J. , Crielaard W. , ten Cate J.M.
Published: February 2014

Background: The treatment of polymicrobial biofilms with antimicrobial compounds results in not only an overall loss of viability, but also compositional shifts. While DNA-based technologies may be more appropriate for the assessment of bacterial composition than culturing, these techniques amplify DNA from both live and dead cells. Propidium monoazide (PMA) has been used to discriminate between live and dead cells by blocking the DNA from membrane-damaged cells from being amplified. Aim: This study evaluated the use of PMA in a saliva-derived polymicrobial biofilm model subjected to a single chlorhexidine (CHX) treatment. Materials and Methods: The effects of PMA on viable cells were tested using both untreated and PMA-treated saliva as an inoculum. Viability was determined by plate counts, metabolic activity was determined by lactic acid production, and biofilm composition was assessed by 16S rRNA gene amplicon sequencing. Results: Exposure to a 0.2% CHX rinse (meridol® perio) reduced the viability and metabolic activity of 48-hour biofilms. The shift in biofilm composition observed after the CHX exposure was enhanced after a post-rinse PMA treatment. PMA treatment had a small effect on the measured composition of water-rinsed biofilms. Treating saliva with PMA reduced bacterial viability and shifted the bacterial composition of saliva and saliva-derived biofilms. Conclusion: The removal of DNA from non-viable cells with PMA treatment was shown to elicit an improvement in the detection of shifts in in vitro polymicrobial biofilms after antimicrobial treatment. However, PMA also influenced the ability of cells to grow, indicating that PMA should be used with caution.
Growth Hormone Response to Standard Provocative Stimuli and Combined Tests in Very Young Children with Prader-Willi Syndrome
Authors: Di Giorgio Girolamo , Grugni Graziano , Fintini Danilo , Bocchini Sarah , Spera Sabrina , Cuttini Marina , Cappa Marco , Crinò Antonino
Published: February 2014

Background: In Prader-Willi syndrome (PWS) a reduced growth hormone (GH) response to several stimulators has been documented in many studies, but none have focused on very young children. We evaluated the pattern of GH secretion in very young PWS patients. Patients and Methods: Twenty-seven genetically confirmed PWS children (10 females, aged 0.4-5 years, mean: 2.2 ± 1.4 years) were included. All subjects underwent standard provocative tests (clonidine, CLO; and arginine, ARG) and one combined test [growth hormone-releasing hormone (GHRH) plus pyridostigmine (13 patients) or GHRH plus arginine (14 patients)]. Insulin-like growth factor-1 (IGF-1) levels were also measured. Results: While standard tests (CLO and ARG) showed low GH peak in 85.2 and 70.4% of the patients, respectively, the combined test was found to be normal in 85.2%. IGF-1 was low in 66.7% of patients. Out of 27 patients, 3 (11%) showed a normal GH peak with both standard tests (group A), 6 (22%) to one of the standard tests (group B) and 18 (67%) presented a low response to both standard tests (group C). Four subjects showed low response to both the combined and standard tests and reduced IGF-1. Conclusion: Our data suggest that very young PWS children seem to have impaired hypothalamic GHRH secretion with a normal GH pituitary reserve.
Synergistic Restoring Effects of Isoproterenol and Magnesium on KCNQ1-Inhibited Bradycardia Cell Models Cultured in Microelectrode Array
Authors: Kim Sook Kyoung , Pak Hui-Nam , Park Yongdoo
Published: February 2014

Objectives: Bradycardia is caused by loss-of-function mutations in potassium channels that regulate phase 3 repolarization of the cardiac action potential. The purpose of this study is to monitor the effects of potassium channel (KCNQ1) inhibition and to evaluate the effects of isoproterenol (ISO) and MgSO4 in restoring sinus rhythm in atrial cells. Methods: Microelectrode array was used to analyze conduction velocity, voltage amplitude and cycle length of atrial cells (HL-1). A combination of ISO and MgSO4 was used to restore sinus rhythm in these cells. Results: mRNA expression levels of KCNQ1 (42.2 vs. 100%, p < 0.0001), connexin 43 (29.6 vs. 100%, p = 0.0033), atrial natriuretic peptide (31.0 vs. 100%, p = 0.0030), cardiac actin (38.2 vs. 100%, p < 0.0001) and α-myosin heavy chain (31.2 vs. 100%, p = 0.00254) were significantly lower in the KCNQ1 gene-inhibited group compared to the control group. When treated with MgSO4 (1 mM) and ISO (10 μM), conduction velocity (0.0208 ± 0.0036 vs. 0.0086 ± 0.0014 m/s, p = 0.0004) and voltage amplitude (1,210.78 ± 65.81 vs. 124.1 ± 13.30 μV, p < 0.0001) were higher, and cycle length (431.55 ± 2.05 vs. 1,015.15 ± 4.31 ms, p < 0.0001) was shorter than in the gene-inhibited group. Conclusion: Inhibition of sinus rhythm in the bradycardia cell model was recovered by treatment with ISO and MgSO4, demonstrating the potency of combination therapy in the treatment of bradycardia.
Decompressive Craniectomy in Patients with Aneurysmal Subarachnoid Hemorrhage: A Single-Center Matched-Pair Analysis
Authors: Uozumi Yoichi , Sakowitz Oliver , Orakcioglu Berk , Santos Edgar , Kentar Modar , Haux Daniel , Unterberg Andreas
Published: February 2014

Background: The role of decompressive craniectomy (DC) in aneurysmal subarachnoid hemorrhage (aSAH) patients is still controversial. In this study we evaluated the effect of DC for aSAH patients. Methods: A matched-pair analysis was performed to compare the outcomes of patients with DC to those of patients without DC. Among 295 consecutive aSAH patients, 56 required DC. Of the remaining group, 56 matched controls were found. The match was conducted on the basis of epidemiological and potential prognostic factors, such as age, gender, World Federation of Neurosurgical Societies (WFNS) grade, Fisher group and occurrence of vasospasm. Results: Fifty-four of 56 (96.4%) patients with DC were dependent or dead at 1 month, compared with 49 of 56 (87.5%) without DC. There was no significant difference between the groups (p = 0.16). One-year outcomes were available for 108 patients (96.4%). Thirty-nine of 54 (72.2%) patients treated with DC were dependent or dead at 1 year, compared with 30 of 54 (55.6%) patients in the control group. There was no significant difference between the groups (p = 0.11). This result was unaffected by age, sex and WFNS grade. Subgroup analyses whether DC was performed primarily or delayed, and whether DC was performed due to spasm, hematoma or vessel occlusion failed to detect any significant difference. Conclusion: There was no significant advantage for patients treated with DC, but more than 25% achieved a good long-term outcome. While the value of DC is deemed uncertain, it may be effective for a very specific subset of aSAH patients. Further comparative studies are needed to resolve this matter.