bluuebunny/crossref_metadata_2025 huggingface dataset:
A Double Hit CD10-Negative B-Cell Lymphoma with t(3;8)(q27;q24) Leading to Juxtaposition of theBCL6andMYCLoci Associated with Good Clinical Outcome
Authors: Sanders Lucinda , Jayne Sandrine , Kennedy Ben , Miall Fiona , Aukema Sietse M. , Siebert Reiner , Wagner Simon D. , Dyer Martin J. S.
Published: October 2014

The WHO classification of lymphomas allows for a group of diseases that have features intermediate between those of Burkitt lymphoma and diffuse large B-cell lymphoma. These are a diverse group of diseases whose genetics and clinical course are yet to be fully described. We report an unusual case of high grade B-cell lymphoma, intermediate between DLBCL and BL, lacking CD10 expression in which the chromosomal translocation t(3;8)(q27;q24) was found to be the sole chromosomal abnormality. FISH analysis demonstrated juxtaposition of theBCL6andMYCloci without obvious involvement of theIGHlocus, suggesting constitutiveMYCexpression due to promoter substitution. The patient responded to intensive chemotherapy and remains in remission two years after finishing therapy.
Efficacy of Optical Internal Urethrotomy and Intralesional Injection of Vatsala-Santosh PGI Tri-Inject (Triamcinolone, Mitomycin C, and Hyaluronidase) in the Treatment of Anterior Urethral Stricture
Authors: Kumar Santosh , Garg Nitin , Singh Shrawan Kumar , Mandal Arup Kumar
Published: October 2014

Purpose. To study the efficacy of optical internal urethrotomy with intralesional injection of Vatsala-Santosh PGI tri-inject (triamcinolone, mitomycin C, and hyaluronidase) in the treatment of anterior urethral stricture.Material and Methods. A total of 103 patients with symptomatic anterior urethral stricture were evaluated on the basis of clinical history, physical examination, uroflowmetry, and retrograde urethrogram preoperatively. All patients were treated with optical internal urethrotomy followed by injection of tri-inject at the urethrotomy site. Tri-inject was prepared by diluting the combination of triamcinolone 40 mg, mitomycin C 2 mg, and hyaluronidase 3000 in 5–10 mL of saline according to length of stricture. An indwelling 18 Fr silicone catheter was left in place for a period of 7–21 days. All patients were followed up for 6–18 months postoperatively on the basis of history, uroflowmetry, and, if required, retrograde urethrogram and micturating urethrogram every 3 months.Results. The overall recurrence rate after first OIU is 19.4% (20 out of 103 patients), that is, a success rate of 80.6%. Overall recurrence rate after second procedure was 5.8% (6 out of 103 patients), that is, a success rate of 94.2%.Conclusion. Optical internal urethrotomy with intralesional injection of Vatsala-Santosh PGI tri-inject (triamcinolone, mitomycin C, and hyaluronidase) is a safe and effective minimally invasive therapeutic modality for short segment anterior urethral strictures.
Evaluation of a Smoking Cessation Program for HIV Infected Individuals in an Urban HIV Clinic: Challenges and Lessons Learned
Authors: Chew Debra , Steinberg Michael B. , Thomas Polly , Swaminathan Shobha , Hodder Sally L.
Published: October 2014

Introduction.HIV infected persons have high prevalence of smoking and tobacco-associated health risks. Few studies describe smoking cessation programs targeting this population. The Infectious Disease Practice (IDP) in Newark, New Jersey, initiated a smoking cessation program (SCP) for HIV infected smokers. We report participation, abstinence rates, and predictors of abstinence.Methods.This is a prospective cohort study, comparing participants to non-SCP smokers, during April 1, 2011, to October 31, 2012. Intervention included one individualized counseling session with an offer of pharmacotherapy. Univariate and multivariate analyses were performed with self-reported seven-day point prevalence abstinence at six months as primary outcome measure.Results.Among 1545 IDP patients, 774 (51%) were current smokers of whom 123 (16%) participated in the SCP. Mean six-month abstinence rate amongst SCP participants was 16%. A history of cocaine or heroin use was predictive of continued smoking (odds ratio [OR] adjusted 0.20, 95% confidence interval [CI] 0.07–0.55) while smokers in the preparation stage of change were more likely abstinent at six months (OR adjusted 8.26, 95% CI 1.02–66.67).Conclusions.A low-intensity smoking cessation intervention in an HIV treatment setting is effective in a minority of participants. Further research is needed to better address barriers to smoking cessation such as substance use.
Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma
Authors: Eivaz-Mohammadi Sahar , Gonzalez-Ibarra Fernando , Abdul Waheed , Tarar Omer , Malik Khurram , Syed Amer K.
Published: October 2014

A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0–5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma.
Neurocognitive and Seizure Outcomes of Selective Amygdalohippocampectomy versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy
Authors: Mansouri Alireza , Fallah Aria , McAndrews Mary Pat , Cohn Melanie , Mayor Diana , Andrade Danielle , Carlen Peter , del Campo Jose M. , Tai Peter , Wennberg Richard A. , Valiante Taufik A.
Published: October 2014

Objective. To report our institutional seizure and neuropsychological outcomes for a series of patients with mesial temporal lobe epilepsy (mTLE) undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SelAH) between 2004 and 2011. Methods. A retrospective study of patients with mTLE was conducted. Seizure outcome was reported using time-to-event analysis. Cognitive outcome was reported using the change principal in component factor scores, one each, for intellectual abilities, visuospatial memory, and verbal memory. The Boston Naming Test was used for naming assessment. Language dominant and nondominant resections were compared separately. Student’s t-test was used to assess statistical significance. Results. Ninety-six patients (75 ATL, 21 SelAH) were included; fifty-four had complete neuropsychological follow-up. Median follow-up was 40.5 months. There was no statistically significant difference in seizure freedom or any of the neuropsychological outcomes, although there was a trend toward greater postoperative decline in naming in the dominant hemisphere group following ATL. Conclusion. Seizure and neuropsychological outcomes did not differ for the two surgical approaches which is similar to most prior studies. Given the theoretical possibility of SelAH sparing language function in patients with epilepsy secondary to mesial temporal sclerosis and the limited high-quality evidence creating equipoise, a multicenter randomized clinical trial is warranted.
A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of Manipur, India
Authors: Singh Huidrom Suraj , Salam Kabita , Saraswathy Kallur Nava
Published: October 2014

Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (P>0.05). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (P>0.05). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41–5.01, P>0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers.
Extraction of Artemisinin, an Active Antimalarial Phytopharmaceutical from Dried Leaves of Artemisia annua L., Using Microwaves and a Validated HPTLC-Visible Method for Its Quantitative Determination
Authors: Misra Himanshu , Mehta Darshana , Mehta Bhupendra Kumar , Jain Dharam Chand
Published: October 2014

A simple, rapid, precise, and accurate high-performance thin-layer chromatographic method coupled with visible densitometric detection of artemisinin is developed and validated. Samples of the dried Artemisia annua leaves were extracted via microwaves using different solvents. This method shows the advantage of shorter extraction time of artemisinin from leaves under the influence of electromagnetic radiations. Results obtained from microwave-assisted extraction (MAE) were compared with hot soxhlet extraction. Chromatographic separation of artemisinin from plant extract was performed over silica gel 60 F254 HPTLC plate using n-hexane : ethyl acetate as mobile phase in the ratio of 75 : 25, v/v. The plate was developed at room temperature 25 ± 2.0°C. Artemisinin separation over thin-layer plate was visualized after postchromatographic derivatization with anisaldehyde-sulphuric acid reagent. HPTLC plate was scanned in a CAMAG’s TLC scanner 3 at 540 nm. Artemisinin responses were found to be linear over a range of 400–2800 ng spot−1 with a correlation coefficient 0.99754. Limits of detection and quantification were 40 and 80 ng spot−1, respectively. The HPTLC method was validated in terms of system suitability, precision, accuracy, sensitivity (LOD and LOQ), and robustness. Additionally, calculation of plate efficiency and flow constant were included as components of validation. Extracts prepared from different parts of the plant (leaves, branches, main stem, and roots) were analyzed for artemisinin content, in which, artemisinin content was found higher in the leaf extract with respect to branches and main stem extracts; however, no artemisinin was detected in root extract. The developed HPTLC-visible method of artemisinin determination will be very useful for pharmaceutical industries, which are involved in monitoring of artemisinin content during different growth stages (in vitro and in vivo) of A. annua for qualitative and quantitative assessment of final produce prior to commercial-scale processing for assessment of cost-benefit ratio.
Comparison of Two Mechanistic Microbial Growth Models to Estimate Shelf Life of Perishable Food Package under Dynamic Temperature Conditions
Authors: Lee Dong Sun
Published: October 2014

Two mechanistic microbial growth models (Huang’s model and model of Baranyi and Roberts) given in differential and integrated equation forms were compared in predicting the microbial growth and shelf life under dynamic temperature storage and distribution conditions. Literatures consistently reporting the microbial growth data under constant and changing temperature conditions were selected to obtain the primary model parameters, set up the secondary models, and apply them to predict the microbial growth and shelf life under fluctuating temperatures. When evaluated by general estimation behavior, bias factor, accuracy factor, and root‐mean‐square error, Huang’s model was comparable to Baranyi and Roberts’ model in the capability to estimate microbial growth under dynamic temperature conditions. Its simple form of single differential equation incorporating directly the growth rate and lag time may work as an advantage to be used in online shelf life estimation by using the electronic device.
Overview of the WEEE Directive and Its Implementation in the Nordic Countries: National Realisations and Best Practices
Authors: Ylä-Mella Jenni , Poikela Kari , Lehtinen Ulla , Tanskanen Pia , Román Elisabeth , Keiski Riitta L. , Pongrácz Eva
Published: October 2014

Electronic devices and mobile applications have become a part of everyday life. Fast technological progress and rapid product obsolescence have led to the rapid growth of waste electrical and electronic equipment (WEEE). Due to hazardous substances and also substantial amounts of valuable materials contained in electrical and electronic equipment, the European Union has implemented Directives related to WEEE, in order to reduce negative environmental and health impacts and to improve material recovery of valuable substances from WEEE. This paper provides an overview of the WEEE Directive and its implementation to national legislations in Finland, Sweden, and Norway and, further, describes how the nationwide WEEE recovery infrastructures in the Nordic countries have been built. The Nordic WEEE management systems are evaluated from the point of resource efficiency and best practices. Evidently, the WEEE management systems as established in the Nordic countries have advantages because the WEEE collection rates in 2012 were 12 kg/inhab./year, in Finland, 16 kg/inhab./year, in Sweden, and 27 kg/ inhab./year, in Norway, despite their sparsely populated nature. The Swedish and Norwegian experiences, especially, with long history of WEEE recovery indicate that increasing consumer awareness leads to more environmentally sound behaviour and improves recovery efficiency.
Mobile Imaging and Computing for Intelligent Structural Damage Inspection
Authors: Chen ZhiQiang , Chen Jianfei
Published: October 2014

Optical imaging is a commonly used technique in civil engineering for aiding the archival of damage scenes and more recently for image analysis-based damage quantification. However, the limitations are evident when applying optical imaging in the field. The most significant one is the lacking of computing and processing capability in the real time. The advancement of mobile imaging and computing technologies provides a promising opportunity to change this norm. This paper first provides a timely introduction of the state-of-the-art mobile imaging and computing technologies for the purpose of engineering application development. Further we propose a mobile imaging and computing (MIC) framework for conducting intelligent condition assessment for constructed objects, which features in situ imaging and real-time damage analysis. This framework synthesizes advanced mobile technologies with three innovative features: (i) context-enabled image collection, (ii) interactive image preprocessing, and (iii) real-time image analysis and analytics. Through performance evaluation and field experiments, this paper demonstrates the feasibility and efficiency of the proposed framework.
Comparative Evaluation of the Inhibitory Effect of Some Essential Oils with Antibiotics against Pseudomonas aeruginosa
Authors: El-Hosseiny Lobna , El-Shenawy Moustafa , Haroun Medhat , Abdullah Fadhil
Published: October 2014

Gas chromatography/mass spectroscopy analysis was performed to identify the chemical components of three extracted essential oils including thyme, marjoram, and sage. The antibacterial activity of the extracted essential oils against Pseudomonas aeruginosa (ATCC 9027) was investigated using disc diffusion assay, either alone or in combination with standard antibiotics (piperacillin, cefepime, meropenem, gentamicin, and norfloxacin). Results showed that the studied oils exhibited a variety of activities against the tested bacterium. Thyme oil was the most active followed by marjoram oil, whereas sage displayed no activity towards the tested organism. Thyme oil enhanced the antibacterial activity of cell wall targeting antibiotics (piperacillin, cefepime, and meropenem) by more than twofold. Marjoram oil potentiated the activity of all the tested antibiotics except norfloxacin. Sage, despite its inactivity against pseudomonas, synergistically enhanced the activity of piperacillin, meropenem, and gentamicin. Thyme essential oil, containing thymol as a major component (33.6%), exhibited higher activity alone or in combination with antibiotics than marjoram which contained alcoholic terpenes or sage essential oil that contained 1,8-cineole as its major component (29%). The investigated oils, as natural bioactive agents, may be used to enhance the activity of antibiotics towards pseudomonas.
Mathematical Modeling of Multienzyme Biosensor System
Authors: Ganesan SP. , Saravanakumar K. , Rajendran L.
Published: October 2014

A mathematical model of hybrid inhibitor biosensor system is discussed. This model consists of five nonlinear partial differential equations for bisubstrate sensitive amperometric system. Simple and closed form of analytical expressions for concentration of glucose-6-phosphate (substrate), potassium dihydrogen phosphate (inhibitor), oxygen (co-substrate), glucose (product 1), and hydrogen peroxide (product 3) is obtained in terms of rate constant using modified Adomian decomposition method (MADM). In this study, behavior of biokinetic parameters is analyzed using this theoretical result. The obtained analytical results (concentrations) are compared with the numerical results and are found to be in satisfactory agreement.
Angiotensin Converting Enzyme Activity in Alopecia Areata
Authors: Namazi Mohammad Reza , Ashraf Armaghan , Handjani Farhad , Eftekhar Ebrahim , Kalafi Amir
Published: October 2014

Background. Alopecia areata (AA) is a chronic inflammatory disease of the hair follicle. The exact pathogenesis of AA remains unknown, although recent studies support a T-cell mediated autoimmune process. On the other hand, some studies have proposed that the renin-angiotensin-aldosterone system (RAAS) may play a role in autoimmunity. Therefore, we assessed serum activity of angiotensin converting enzyme (ACE), a component of this system, in AA.Methods. ACE activity was measured in the sera of 19 patients with AA and 16 healthy control subjects. In addition, the relationship between severity and duration of the disease and ACE activity was evaluated.Results. Serum ACE activity was higher in the patient group (55.81 U/L) compared to the control group (46.41 U/L), but the difference was not statistically significant (P=0.085). Also, there was no correlation between ACE activity and severity (P=0.13) and duration of disease (P=0.25) in the patient group.Conclusion. The increased serum ACE activity found in this study may demonstrate local involvement of the RAAS in the pathogenesis of AA. Assessment of ACE in a study with a larger sample size as well as in tissue samples is recommended in order to further evaluate the possible role of RAAS in AA.
Ethical and Clinical Aspects of Intensive Care Unit Admission in Patients with Hematological Malignancies: Guidelines of the Ethics Commission of the French Society of Hematology
Authors: Malak Sandra , Sotto Jean-Jacques , Ceccaldi Joël , Colombat Philippe , Casassus Philippe , Jaulmes Dominique , Rochant Henri , Cheminant Morgane , Beaussant Yvan , Zittoun Robert , Bordessoule Dominique
Published: October 2014

Admission of patients with hematological malignancies to intensive care unit (ICU) raises recurrent ethical issues for both hematological and intensivist teams. The decision of transfer to ICU has major consequences for end of life care for patients and their relatives. It also impacts organizational human and economic aspects for the ICU and global health policy. In light of the recent advances in hematology and critical care medicine, a wide multidisciplinary debate has been conducted resulting in guidelines approved by consensus by both disciplines. The main aspects developed were (i) clarification of the clinical situations that could lead to a transfer to ICU taking into account the severity criteria of both hematological malignancy and clinical distress, (ii) understanding the process of decision-making in a context of regular interdisciplinary concertation involving the patient and his relatives, (iii) organization of a collegial concertation at the time of the initial decision of transfer to ICU and throughout and beyond the stay in ICU. The aim of this work is to propose suggestions to strengthen the collaboration between the different teams involved, to facilitate the daily decision-making process, and to allow improvement of clinical practice.
Conjugate Heat Transfer Study at Interior Surface of NGV Leading Edge with Combined Shower Head and Impingement Cooling
Authors: Pujari Arun Kumar , Prasad B. V. S. S. S. , Sitaram N.
Published: October 2014

A computational study on conjugate heat transfer is carried out to present the behavior of nondimensional temperature and heat transfer coefficient of a Nozzle Guide Vane (NGV) leading edge. Reynolds number of both mainstream flow and coolant impinging jets are varied. The NGV has five rows of film cooling holes arranged in shower head manner and four rows of impingement holes arranged in staggered manner. The results are presented by considering materials of different thermal conductivity. The results show that the mainstream flow affects the temperature distribution on the interior side of the vane leading edge for high conductivity material whereas it has negligible effects for low conductivity material. The effect of changing blowing ratio on internal heat transfer coefficient and internal surface temperature is also presented.
Catalytic Behaviour of Mesoporous Cobalt-Aluminum Oxides for CO Oxidation
Authors: Bordoloi Ankur , Sanchez Miguel , Noei Heshmat , Kaluza Stefan , Großmann Dennis , Wang Yuemin , Grünert Wolfgang , Muhler Martin
Published: October 2014

Ordered mesoporous materials are promising catalyst supports due to their uniform pore size distribution, high specific surface area and pore volume, tunable pore sizes, and long-range ordering of the pore packing. The evaporation-induced self-assembly (EISA) process was applied to synthesize mesoporous mixed oxides, which consist of cobalt ions highly dispersed in an alumina matrix. The characterization of the mesoporous mixed cobalt-aluminum oxides with cobalt loadings in the range from 5 to 15 wt% and calcination temperatures of 673, 973, and 1073 K indicates that Co2+ is homogeneously distributed in the mesoporous alumina matrix. As a function of the Co loading, different phases are present comprising poorly crystalline alumina and mixed cobalt aluminum oxides of the spinel type. The mixed cobalt-aluminum oxides were applied as catalysts in CO oxidation and turned out to be highly active.
Some Condition for Scalar and Vector Measure Games to Be Lipschitz
Authors: Centrone F. , Martellotti A.
Published: October 2014

We provide a characterization for vector measure gamesν=f∘μinpNA∞, withμvector of nonatomic probability measures, analogous to the one of Tauman for games inpNA, and also provide a necessary and sufficient condition for a particular class of vector measure games to belong toAC∞.
Ecotope-Based Entomological Surveillance and Molecular Xenomonitoring of Multidrug Resistant Malaria Parasites inAnophelesVectors
Authors: Sorosjinda-Nunthawarasilp Prapa , Bhumiratana Adisak
Published: October 2014

The emergence and spread of multidrug resistant (MDR) malaria caused byPlasmodium falciparumorPlasmodium vivaxhave become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decreasein vitroandin vivosusceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites inAnophelesvectors is proposed to monitor infection pockets in transmission control areas of forest and forest fringe-related malaria, so as to bridge malaria landscape ecology (ecotope and ecotone) and epidemiology. Malaria ecotope and ecotone are confined to a malaria transmission area geographically associated with the infestation ofAnophelesvectors and particular environments to which human activities are related. This enables the EES to encompass mosquito collection and identification, salivary gland DNA extraction,Plasmodium-and species-specific identification, molecular marker-based PCR detection methods for putative drug resistance genes, and data management. The EES establishes strong evidence ofAnophelesvectors carrying MDRP. vivaxin infection pockets epidemiologically linked with other data obtained during which a course of follow-up treatment of the notifiedP. vivaxpatients receiving the first-line treatment was conducted. For regional and global perspectives, the EES would augment the epidemiological surveillance and monitoring of MDR falciparum and vivax malaria parasites in hotspots or suspected areas established in most endemic GMS countries implementing the National Malaria Control Programs, in addition to what is guided by the World Health Organization.
Androgen Receptor Is the Key Transcriptional Mediator of the Tumor Suppressor SPOP in Prostate Cancer
Authors: Geng Chuandong , Rajapakshe Kimal , Shah Shrijal S. , Shou John , Eedunuri Vijay Kumar , Foley Christopher , Fiskus Warren , Rajendran Mahitha , Chew Sue Anne , Zimmermann Martin , Bond Richard , He Bin , Coarfa Cristian , Mitsiades Nicholas
Published: October 2014

Somatic missense mutations in the substrate-binding pocket of the E3 ubiquitin ligase adaptor SPOP are present in up to 15% of human prostate adenocarcinomas, but are rare in other malignancies, suggesting a prostate-specific mechanism of action. SPOP promotes ubiquitination and degradation of several protein substrates, including the androgen receptor (AR) coactivator SRC-3. However, the relative contributions that SPOP substrates may make to the pathophysiology of SPOP-mutant (mt) prostate adenocarcinomas are unknown. Using an unbiased bioinformatics approach, we determined that the gene expression profile of prostate adenocarcinoma cells engineered to express mt-SPOP overlaps greatly with the gene signature of both SRC-3 and AR transcriptional output, with a stronger similarity to AR than SRC-3. This finding suggests that in addition to its SRC-3–mediated effects, SPOP also exerts SRC-3–independent effects that are AR-mediated. Indeed, we found that wild-type (wt) but not prostate adenocarcinoma–associated mutants of SPOP promoted AR ubiquitination and degradation, acting directly through a SPOP-binding motif in the hinge region of AR. In support of these results, tumor xenografts composed of prostate adenocarcinoma cells expressing mt-SPOP exhibited higher AR protein levels and grew faster than tumors composed of prostate adenocarcinoma cells expressing wt-SPOP. Furthermore, genetic ablation of SPOP was sufficient to increase AR protein levels in mouse prostate. Examination of public human prostate adenocarcinoma datasets confirmed a strong link between transcriptomic profiles of mt-SPOP and AR. Overall, our studies highlight the AR axis as the key transcriptional output of SPOP in prostate adenocarcinoma and provide an explanation for the prostate-specific tumor suppressor role of wt-SPOP. Cancer Res; 74(19); 5631–43. ©2014 AACR.
MPHOSPH1: A Potential Therapeutic Target for Hepatocellular Carcinoma
Authors: Liu Xinran , Zhou Yafan , Liu Xinyuan , Peng Anlin , Gong Hao , Huang Lizi , Ji Kaige , Petersen Robert B. , Zheng Ling , Huang Kun
Published: October 2014

MPHOSPH1 is a critical kinesin protein that functions in cytokinesis. Here, we show that MPHOSPH1 is overexpressed in hepatocellular carcinoma (HCC) cells, where it is essential for proliferation. Attenuating MPHOSPH1 expression with a tumor-selective shRNA-expressing adenovirus (Ad-shMPP1) was sufficient to arrest HCC cell proliferation in a manner associated with an accumulation of multinucleated polyploid cells, induction of postmitotic apoptosis, and increased sensitivity to taxol cytotoxicity. Mechanistic investigations showed that attenuation of MPHOSPH1 stabilized p53, blocked STAT3 phosphorylation, and prolonged mitotic arrest. In a mouse subcutaneous xenograft model of HCC, tumoral injection of Ad-shMPP1 inhibited MPHOSPH1 expression and tumor growth in a manner correlated with induction of apoptosis. Combining Ad-shMPP1 injection with taxol administration enhanced antitumor efficacy relative to taxol alone. Furthermore, Ad-shMPP1 tail vein injection suppressed formation of orthotopic liver nodules and prevented hepatic dysfunction. Taken together, our results identify MPHOSPH1 as an oncogenic driver and candidate therapeutic target in HCC. Cancer Res; 74(22); 6623–34. ©2014 AACR.
Systemic Immune-Inflammation Index Predicts Prognosis of Patients after Curative Resection for Hepatocellular Carcinoma
Authors: Hu Bo , Yang Xin-Rong , Xu Yang , Sun Yun-Fan , Sun Chao , Guo Wei , Zhang Xin , Wang Wei-Min , Qiu Shuang-Jian , Zhou Jian , Fan Jia
Published: October 2014

Purpose: We developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts and explored its prognostic value in hepatocellular carcinoma (HCC).

Experimental Design: The SII was developed based on a retrospective study of 133 patients with HCC undergoing resection between 2005 and 2006, and validated in a prospective study of 123 patients enrolled from 2010 to 2011. The circulating tumor cell (CTC) level in the validation cohort was measured using the CellSearch system. Prediction accuracy was evaluated with area under the receiver operating characteristic curve (AUC).

Results: An optimal cutoff point for the SII of 330 × 109 stratified the patients with HCC into high (≥330) and low SII (<330) groups in the training cohort. Univariate and multivariate analyses revealed the SII was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative α-fetoprotein and Barcelona Clinic Liver Cancer stage 0+A. The AUCs of the SII for survival and recurrence were higher than other conventional clinical indices. An SII ≥ 330 was significantly associated with vascular invasion, large tumors, and early recurrence. CTC levels were significantly higher in the SII ≥ 330 group (1.71 ± 0.34 vs. 4.37 ± 1.04, P = 0.029). In patients with detectable CTCs, those with SII ≥ 330 had higher recurrence rates and shorter survival time than patients with SII < 330.

Conclusion: The SII was a powerful prognostic indicator of poor outcome in patients with HCC and is a promising tool for HCC treatment strategy decisions. The dismal outcome in patients with high SII scores might be related to higher CTC levels. Clin Cancer Res; 20(23); 6212–22. ©2014 AACR.
The Prostate Cancer Susceptibility Variant rs2735839 Near KLK3 Gene Is Associated with Aggressive Prostate Cancer and Can Stratify Gleason Score 7 Patients
Authors: He Yonggang , Gu Jian , Strom Sara , Logothetis Christopher J. , Kim Jeri , Wu Xifeng
Published: October 2014

Purpose: Gleason score (GS) 7 prostate cancer is a heterogeneous disease with different clinical behavior. We sought to identify genetic biomarkers that may predict the aggressiveness of GS 7 diseases.

Experimental Design: We genotyped 72 prostate cancer susceptibility SNPs identified in genome-wide association studies in 1,827 white men with histologically confirmed prostate adenocarcinoma. SNPs associated with disease aggressiveness were identified by comparing high-aggressive (GS ≥8) and low-aggressive (GS ≤6) cases. The significant SNPs were then tested to see whether they could further stratify GS 7 prostate cancer.

Results: Three SNPs—rs2735839, rs10486567, and rs103294—were associated with biopsy-proven high-aggressive (GS ≥8) prostate cancer (P < 0.05). Furthermore, the frequency of the variant allele (A) at rs2735839 was significantly higher in patients with biopsy-proven GS 4+3 disease than in those with GS 3 + 4 disease (P = 0.003). In multivariate logistic regression analysis, patients carrying the A allele at rs2735839 exhibited a 1.85-fold (95% confidence interval, 1.31–2.61) increased risk of being GS 4 + 3 compared with those with GS 3 + 4. The rs2735839 is located 600 base pair downstream of the KLK3 gene (encoding PSA) on 19q13.33 and has been shown to modulate PSA level, providing strong biologic plausibility for its association with prostate cancer aggressiveness.

Conclusions: We confirmed the association of the rs2735839 with high-aggressive prostate cancer (GS ≥8). Moreover, we reported for the first time that rs2735839 can stratify GS 7 patients, which would be clinically important for more accurately assessing the clinical behavior of the intermediate-grade prostate cancer and for tailoring personalized treatment and posttreatment management. Clin Cancer Res; 20(19); 5133–9. ©2014 AACR.
Global Increase of p16INK4a in APC-Deficient Mouse Liver Drives Clonal Growth of p16INK4a-Negative Tumors
Authors: Ueberham Elke , Glöckner Pia , Göhler Claudia , Straub Beate K. , Teupser Daniel , Schönig Kai , Braeuning Albert , Höhn Anne Kathrin , Jerchow Boris , Birchmeier Walter , Gaunitz Frank , Arendt Thomas , Sansom Owen , Gebhardt Rolf , Ueberham Uwe
Published: October 2014

Reduction of β-catenin (CTNNB1) destroying complex components, for example, adenomatous polyposis coli (APC), induces β-catenin signaling and subsequently triggers activation of genes involved in proliferation and tumorigenesis. Though diminished expression of APC has organ-specific and threshold-dependent influence on the development of liver tumors in mice, the molecular basis is poorly understood. Therefore, a detailed investigation was conducted to determine the underlying mechanism in the development of liver tumors under reduced APC levels. Mouse liver at different developmental stages was analyzed in terms of β-catenin target genes including Cyp2e1, Glul, and Ihh using real-time RT-PCR, reporter gene assays, and immunohistologic methods with consideration of liver zonation. Data from human livers with mutations in APC derived from patients with familial adenomatous polyposis (FAP) were also included. Hepatocyte senescence was investigated by determining p16INK4a expression level, presence of senescence-associated β-galactosidase activity, and assessing ploidy. A β-catenin activation of hepatocytes does not always result in β-catenin positive but unexpectedly also in mixed and β-catenin–negative tumors. In summary, a senescence-inducing program was found in hepatocytes with increased β-catenin levels and a positive selection of hepatocytes lacking p16INK4a, by epigenetic silencing, drives the development of liver tumors in mice with reduced APC expression (Apc580S mice). The lack of p16INK4a was also detected in liver tumors of mice with triggers other than APC reduction.

Implications: Epigenetic silencing of p16Ink4a in selected liver cells bypassing senescence is a general principle for development of liver tumors with β-catenin involvement in mice independent of the initial stimulus. Mol Cancer Res; 13(2); 239–49. ©2014 AACR.
Serial Diffusion Tensor Images during Infancy and Their Relationship to Neuromotor Outcomes in Preterm Infants
Authors: Shim So-Yeon , Jeong Hye-Jin , Son Dong Woo , Chung Mira , Park Sukyoung , Cho Zang-Hee
Published: October 2014

Background: Even preterm infants with normal magnetic resonance imaging (MRI) results are at greater risk for neuromotor dysfunction. Objectives: Our aim was to compare serial diffusion tensor imaging (DTI) data from preterm infants without apparent brain abnormalities on magnetic resonance imaging with those from term controls and to investigate the white matter (WM) region associated with neuromotor outcomes. Methods: We obtained serial DTIs from 21 preterm infants at term-equivalent age (TEA) and 1 year of corrected age. As controls, 15 term neonates and 20 newly recruited term infants aged 1 year underwent DTI. Preterm and term infants at 1 year of age were assessed with the Bayley Scales of Infant Development, second edition. Tract-based spatial statistics and regions of interest were used for analysis. Results: At TEA, the entire WM development was delayed in the preterm infants compared with the term controls, but at 1 year of age, the WM development, except for that of the corpus callosum (CC), had reached the development level of the term controls. The psychomotor developmental index was positively correlated with the fractional anisotropy (FA) in the CC (particularly in the body and splenium) at 1 year of age after correcting for gestational age, chronic lung disease, and postnatal infection. Conclusions: The CC of the preterm infants was consistently underdeveloped compared with that of the term controls. The FA in the CC, particularly in the body and splenium at 1 year of age, well reflected the degree of motor function in infants without apparent brain abnormalities.
Achievement of NKF/K-DOQI Recommended Target Values for Bone and Mineral Metabolism in Incident Hemodialysis Patients: Results of the FARO-2 Cohort
Authors: Cozzolino Mario , Messa Piergiorgio , Brancaccio Diego , Cannella Giuseppe , Bolasco Piergiorgio , Di Luca Marina , Costanzo Anna Maria , di Luzio Paparatti Umberto , Festa Vincenzo , Gualberti Giuliana , Mazzaferro Sandro ,   on behalf of the FARO Study Group
Published: October 2014

Background: Mineral Bone Disorders (MBD) is prevalent in hemodialysis (HD) patients and associated with increased cardiovascular mortality. The FARO-2 study evaluated the achievement of the NKF/K-DOQI guidelines on recommended target values for serum calcium (Ca), phosphorous (P) and intact parathyroid hormone (PTH) levels on survival in incident HD patients. Methods: Data were collected by questionnaire from 568 incident HD patients followed prospectively over a 3-year period from 26 Italian dialysis units. The cumulative probability of time-to-death for CKD-MBD treatment characteristics was determined by the Kaplan-Meier curves. Results: Serum PTH levels (median values at 6 months vs. 36 months; 225 vs. 254 pg/ml), Ca (8.8 vs. 8.9 g/dl) and P (5.1 vs. 4.8 mg/dl) were not significantly different at 6 months versus follow-up. The majority of incident HD patients (60-70%) who were followed up for 36 months did not achieve the NKF/K-DOQI recommended target values. Survival rates were higher in patients on target for three parameters versus patients off target (survival at 24 months: at target 95.7% (95% CI: 84.0-98.9) versus not on target 71.1% (95% CI: 66.3-75.4, p < 0.01)). The 30.1% of patients on target for three MBD parameters at least once during the follow-up period had better survival rates compared to those not reaching these targets (survival at 24 months: at least once 88.0% (95% CI: 81.9-92.1); 67.7% (95% CI: 61.9-72.8, p < 0.01)). Conclusion: Our findings indicate that incident HD patients who achieved target levels (for three MBD parameters) for at least one visit have a lower risk of mortality.
Novel α-Spectrin Mutation in Trans with α-SpectrinLEPRA Causing Severe Neonatal Jaundice from Hereditary Spherocytosis
Authors: Nussenzveig Roberto H. , Christensen Robert D. , Prchal Josef T. , Yaish Hassan M. , Agarwal Archana M.
Published: October 2014

We evaluated a neonate with severe jaundice but a negative family history. Spherocytes were present and suspected hereditary spherocytosis was confirmed by osmotic fragility and eosin-5-maleimide erythrocyte staining. We found he was a compound heterozygote for two pathogenic mutations in the gene encoding α-spectrin: a previously reported αLEPRA inherited from his asymptomatic mother, and a novel α-spectrin mutation in intron 45 +1 disrupting the consensus splice site, from his asymptomatic father.
Dissemination of ESBL-Producing Escherichia coli of Chicken Origin to the Nearby River Water
Authors: Gao Lili , Hu Jiaqing , Zhang Xiaodan , Ma Ruihua , Gao Jing , Li Song , Zhao Miaoqing , Miao Zengmin , Chai Tongjie
Published: October 2014

The dissemination of drug-resistant bacteria from animal farms to aquatic environments can pose a potential threat to public health. In this study, antimicrobial resistance, resistance genes, and genetic similarity of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli of different origins (chicken feces and upstream and downstream river waters) were analyzed to track the spread of drug-resistant bacteria of animals. The results showed that a total of 29 ESBL-producing E. coli were obtained from 258 samples, and isolation rates of the ESBL-producing E. coli from chicken feces and upstream and downstream waters were 10.7% (16/150), 3.7% (1/27), and 14.8% (12/81), respectively. The ESBL-producing E. coli from upstream water was resistant to 7 antibiotics, but isolates from feces and downstream water had a higher resistance rate. In 29 ESBL-producing E. coli, the most common gene was CTX-M and the SHV gene was not detected. Five ESBL-producing isolates from downstream water showed >90% similarity with the fecal isolates, while the only one isolate from upstream water had <70% similarity with fecal isolates. The results suggest that animal farms' effluent, especially the untreated wastewater, could contribute to the spread of resistance genes.
Risk of Gastrointestinal Bleeding with Dabigatran: A Head-to-Head Comparative Study with Rivaroxaban
Authors: Sherid Muhammed , Sifuentes Humberto , Sulaiman Samian , Samo Salih , Husein Husein , Tupper Ruth , Thiruvaiyaru Dharma , Spurr Charles , Sridhar Subbaramiah
Published: October 2014

Introduction: The risk of gastrointestinal (GI) bleeding of dabigatran and rivaroxaban is relatively unexplored. The aim of our study was to compare this risk in both drugs. Methods: We examined the medical records of patients on either dabigatran or rivaroxaban from October 2010 to April 2013 in two hospitals. Results: A total of 374 patients (147 rivaroxaban vs. 227 dabigatran) were identified. GI bleeding occurred in 5.3% in the dabigatran when compared to 4.8% in the rivaroxaban group (p = 0.8215). Multivariate analysis showed that the odds of GI bleeding while on dabigatran for ≤40 days when compared to ≥40 days was 8.3 (p < 0.0001). In the rivaroxaban group, patients who were on the drug for ≤40 days had a higher incidence of bleeding when compared to those >40 days (OR = 2.8, p = 0.023). Concomitant use of antiplatelets (single or dual) or non-steroidal anti-inflammatory drugs was not associated with increased bleeding in the dabigatran group; however, the use of dual antiplatelet agents with rivaroxaban was associated with an increased risk of GI bleeding (OR = 7.4, p = 0.0378). Prior GI bleeding had a higher risk of bleeding in the rivaroxaban group (OR = 15.5, p = 0.0002). Conclusion: Dabigatran was not associated with a higher incidence of GI bleeding. Both drugs had a higher bleeding risk in the first 40 days.
Rats Fed Diets with Different Energy Contribution from Fat Do Not Differ in Adiposity
Authors: Miras Alexander D. , Seyfried Florian , Phinikaridou Alkystis , Andia Marcelo E. , Christakis Ioannis , Spector Alan C. , Botnar René M. , le Roux Carel W.
Published: October 2014

Objective: To determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition. Methods: In experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin. Results: In experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments. Conclusions: We conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it.
The Great Canadian Slump, 1990–92
Authors: McCormack Geoffrey
Published: October 2014

After examining the character of the downturn and existing explanations for it, the article provides an alternative classical Marxian account based upon the methodological and theoretical framework developed by Henryk Grossman. This article investigates the long- and short-run dynamics of capital accumulation in Canada leading up to and culminating in the economic downturn of 1990–2.
Gramsci without the Prince
Authors: Thomas Martin
Published: October 2014

Peter Thomas, inThe Gramscian Moment, explains well how Gramsci strove to re-educate the communist movement in an expansive spirit, around the united front. He makes clear that the united-front approach advocated by Gramsci, based on working-class mobilisation and accompanied by clear communist criticism, was distinct from the policy of bourgeois alliances to be advocated by the Stalinist parties after 1935 under the name ‘popular front’. He demystifies the concept in Gramsci of working-class ‘hegemony’, from which so many speculations are spun, showing that it meant nothing other than working-class political leadership, achieved through sound use of united-front tactics. Yet Thomas makes the formula of ‘united front’ do too much, or bundles into it more than it can rationally contain. Meanwhile, the question of the revolutionary working-class political party is almost entirely absent in Thomas’s discussion.
Towards a Theory of the Integral State
Authors: Bosteels Bruno
Published: October 2014

This review assesses the strengths and weaknesses of Peter Thomas’s long-awaited study ofThe Prison Notebooks, based on his extensive research and philological reconstruction of the critical edition. I distinguish three senses in which the ‘moment’ in the book’s title can be understood: as the historical moment around 1932 in which Gramsci proposed the outline of his distinct brand of the philosophy of praxis; as the moment or momentum that still lies in wait for a future research programme in Marxist philosophy; and as a methodological principle for understanding the dialectic as a theory in which entities such as state and civil society, but also coercion and consent, far from allowing the kind of Eurocommunist or post-Marxist instrumentalisations in which they are seen as part of a chain of binaries, are actually moments of a unified larger structure that in Gramsci’s work comes to be associated with the idea of the integral state. This impressive reconstruction of Gramsci’s notebooks, however, also reveals some major lacunae, above all, in terms of the lack of attention given to Gramscian developments in the non-European world, in places such as India or Latin America. This omission is all the more surprising given the longstanding tradition, particularly in Latin America, of viewing Gramsci as a theorist of the integral state more so than of hegemony.