bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulomatous Cheilitis: Successful Treatment of Two Recalcitrant Cases with Combination Drug Therapy
Authors: Gupta Ambika , Singh Harneet
Published: October 2014

Granulomatous cheilitis is a rare, idiopathic, inflammatory disorder which usually affects young adults. It is characterized by persistent, diffuse, nontender, soft-to-firm swelling of one or both lips. Various treatment modalities have been suggested. In spite of the best treatment, recurrence of the disease is very common. We report two cases of granulomatous cheilitis treated with a combination of steroids, metronidazole, and minocycline with no signs of relapse at one-year follow-up.
Volatile Organic Silicon Compounds in Biogases: Development of Sampling and Analytical Methods for Total Silicon Quantification by ICP-OES
Authors: Chottier Claire , Chatain Vincent , Julien Jennifer , Dumont Nathalie , Lebouil David , Germain Patrick
Published: October 2014

Current waste management policies favor biogases (digester gases (DGs) and landfill gases (LFGs)) valorization as it becomes a way for energy politics. However, volatile organic silicon compounds (VOSiCs) contained into DGs/LFGs severely damage combustion engines and endanger the conversion into electricity by power plants, resulting in a high purification level requirement. Assessing treatment efficiency is still difficult. No consensus has been reached to provide a standardized sampling and quantification of VOSiCs into gases because of their diversity, their physicochemical properties, and the omnipresence of silicon in analytical chains. Usually, samplings are done by adsorption or absorption and quantification made by gas chromatography-mass spectrometry (GC-MS) or inductively coupled plasma-optical emission spectrometry (ICP-OES). In this objective, this paper presents and discusses the optimization of a patented method consisting in VOSiCs sampling by absorption of 100% ethanol and quantification of total Si by ICP-OES.
Water Mediated Synthesis ofN′-Arylmethylene-4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide Library
Authors: Savant Mahesh M. , Pansuriya Akshay M. , Bhuva Chirag V. , Kapuriya Naval , Naliapara Yogesh T.
Published: October 2014

A novel two-step synthesis of 4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide has been developed. The library ofN′-arylmethylene-4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide was generated by coupling of hydrazide to various aromatic and heterocyclic aldehydes in water media at ambient temperature with great flexibility regarding reaction time and yield.
A Statistical Analysis Based Probabilistic Routing for Resource-Constrained Delay Tolerant Networks
Authors: Xu Jixing , Li Jianbo , Jiang Shan , Dai Chenqu , You Lei
Published: October 2014

The nonexistence of end-to-end path between the sender and the receiver poses great challenges to the successful message transmission in delay tolerant networks. Probabilistic routing provides an efficient scheme to route messages, but most existing probabilistic routing protocols do not consider whether a message has enough time-to-live to reach its destination. In this paper, we propose an improved probabilistic routing algorithm that fully takes into account message's time-to-live when predicting the delivery probability. Based on statistical analysis, we compute and update the expected intermeeting times between nodes. And then the probability for a message to be delivered within its time-to-live is computed based on the assumed exponential distribution. We further propose an optimal message schedule policy, by modeling the buffer management problem as 0-1 knapsack, of which the maximum delivery probability sum can be achieved by resorting to the back track technique. Extensive simulations are conducted and the results show that the proposed algorithm can greatly enhance routing performance in terms of message delivery probability, overhead ratio, and average hop count.
Cerebral Arteriovenous Malformations: Evaluation and Management
Authors: Ajiboye Norman , Chalouhi Nohra , Starke Robert M. , Zanaty Mario , Bell Rodney
Published: October 2014

There has been increased detection of incidental AVMs as result of the frequent use of advanced imaging techniques. The natural history of AVM is poorly understood and its management is controversial. This review provides an overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management of AVMs. The authors discussed the imaging techniques available for detecting AVMs with regard to the advantages and disadvantages of each imaging modality. Furthermore, this review paper discusses the factors that must be considered for the most appropriate management strategy (based on the current evidence in the literature) and the risks and benefits of each management option.
Comparative Study on Electronic, Emission, Spontaneous Property of Porous Silicon in Different Solvents
Authors: Khan M. Naziruddin , Khan M. A. Majeed , Al Dwayyan A. S. , Labis J. Puzon
Published: October 2014

Luminescent porous silicon (Psi) fabricated by simple chemical etching technique in different organic solvents was studied. By quantifying the silicon wafer piece, optical properties of the Psi in solutions were investigated. Observation shows that no photoluminescence light of Psi in all solvents is emitted. Morphology of Psi in different solvents indicates that the structure and distribution of Psi are differently observed. Particles are uniformly dispersive with the sizes around more or less 5–8 nm. The crystallographic plane and high crystalline nature of Psi is observed by selected area diffraction (SED) and XRD. Electronic properties of Psi in solutions are influenced due to the variation of quantity of wafer and nature of solvent. Influence in band gaps of Psi calculated by Tauc’s method is obtained due to change of absorption edge of Psi in solvents. PL intensities are observed to be depending on quantity of silicon wafer, etched cross‐section area on wafer surface. Effects on emission peaks and bands of Psi under temperature annealing are observed. The spontaneous signals of Psi measured under high power Pico second laser 355 nm source are significant, influenced by the nature of solvent, pumped energy, and quantity of Si wafer piece used in etching process.
The Choice of the Iodinated Radiographic Contrast Media to Prevent Contrast-Induced Nephropathy
Authors: Andreucci Michele , Faga Teresa , Pisani Antonio , Sabbatini Massimo , Russo Domenico , Michael Ashour
Published: October 2014

In patients with preexisting renal impairment, particularly those who are diabetic, the iodinated radiographic contrast media may cause contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI), that is, an acute renal failure (ARF), usually nonoliguric and asymptomatic, occurring 24 to 72 hours after their intravascular injection in the absence of an alternative aetiology. Radiographic contrast media have different osmolalities and viscosities. They have also a different nephrotoxicity. In order to prevent CIN, the least nephrotoxic contrast media should be chosen, at the lowest dosage possible. Other prevention measures should include discontinuation of potentially nephrotoxic drugs, adequate hydration with i.v. infusion of either normal saline or bicarbonate solution, and eventually use of antioxidants, such as N-acetylcysteine, and statins.
36-Year-Old Female with Catastrophic Antiphospholipid Syndrome Treated with Eculizumab: A Case Report and Review of Literature
Authors: Strakhan Marianna , Hurtado-Sbordoni Mariana , Galeas Nahun , Bakirhan Kamila , Alexis Karenza , Elrafei Tarek
Published: October 2014

Catastrophic antiphospholipid syndrome (CAPS) is a rare but potentially life-threatening condition characterized by diffuse vascular thrombosis, leading to multiple organ failure developing over a short period of time in the presence of positive antiphospholipid antibodies (aPL). CAPS is a severe form of antiphospholipid syndrome, developing in about 1% of cases of classic antiphospholipid syndrome, manifesting as microangiopathy, affecting small vessels of multiple organs. It is acute in onset, with majority of cases developing thrombocytopenia and less frequently hemolytic anemia and disseminated intravascular coagulation. Lupus anticoagulant and anticardiolipin antibodies have been reported as predominant antibodies associated with CAPS. Treatment options often utilized in CAPS include anticoagulation, steroids, plasma exchange, cyclophosphamide therapy, and intravenous immunoglobulin therapy. Even though the reported incidence of this condition is considered to be low, the mortality rate is approaching 50%. The high rate of mortality should warrant greater awareness among clinicians for timely diagnosis and treatment of this life-threatening condition. Studies have shown that complement activation plays a key role in the pathogenesis of aPL mediated thrombosis in CAPS. We report a case of a 36-year-old female admitted with clinical and laboratory findings consistent with CAPS successfully treated with eculizumab, a terminal complement inhibitor.
Prevalence of and Risk Factors for Dry Eye Symptom in Mainland China: A Systematic Review and Meta-Analysis
Authors: Liu Ning-ning , Liu Lei , Li Jun , Sun Yi-zhou
Published: October 2014

Purpose. To evaluate the pooled prevalence rate and risk factors of dry eye symptoms (DES) in mainland China.Methods. All the published population-based studies investigating the prevalence of DES in China were searched and evaluated against inclusion criteria. A systematic review and meta-analysis were performed.Results. Twelve out of the 119 identified studies were included in the meta-analysis. The pooled prevalence of DES in China was 17.0%. Female individuals, subjects living in the Northern and Western China, and over 60 years of age had significantly higher prevalent rates (21.6%, 17.9%, 31.3%, and 34.4%, resp.) compared with their counterparts. Patients with diabetes were also found to be more vulnerable to DES.Conclusions. The pooled prevalence rate of DES in mainland China was lower than that in other Asian regions and countries. A remarkable discrepancy in the prevalence in different geographic regions was noted. Aging, female gender, and diabetes were found to be risk factors for DES in China.
On aq-Analogue of the Elzaki Transform Called Mangontarumq-Transform
Authors: Mangontarum Mahid M.
Published: October 2014

Twoq-analogues of the Elzaki transform, called Mangontarumq-transforms, are introduced in this paper. Properties such as the transforms ofq-trigonometric functions, transform ofq-derivatives, duality relation, convolution identity,q-derivative of transforms, and transform of the Heaviside function are derived and presented. Moreover, we will consider applications of the Mangontarumq-transform of the first kind to some ordinaryq-differential equations with initial values.
A Premature Termination of Human Epidermal Growth Factor Receptor Transcription inEscherichia coli
Authors: Elloumi-Mseddi Jihene , Jellali Karim , Villalobo Antonio , Aifa Sami
Published: October 2014

Our success in producing an active epidermal growth factor receptor (EGFR) tyrosine kinase inEscherichia coliencouraged us to express the full-length receptor in the same host. Despite its large size, we were successful at producing the full-length EGFR protein fused to glutathione S-transferase (GST) that was detected by Western blot analysis. Moreover, we obtained a majoritarian truncated GST-EGFR form detectable by gel electrophoresis and Western blot. This truncated protein was purified and confirmed by MALDI-TOF/TOF analysis to belong to the N-terminal extracellular region of the EGFR fused to GST. Northern blot analysis showed two transcripts suggesting the occurrence of a transcriptional arrest.
Optimal Variational Asymptotic Method for Nonlinear Fractional Partial Differential Equations
Authors: Baranwal Vipul K. , Pandey Ram K. , Singh Om P.
Published: October 2014

We propose optimal variational asymptotic method to solve time fractional nonlinear partial differential equations. In the proposed method, an arbitrary number of auxiliary parameters γ0,γ1,γ2,… and auxiliary functions H0(x),H1(x),H2(x),… are introduced in the correction functional of the standard variational iteration method. The optimal values of these parameters are obtained by minimizing the square residual error. To test the method, we apply it to solve two important classes of nonlinear partial differential equations: (1) the fractional advection-diffusion equation with nonlinear source term and (2) the fractional Swift-Hohenberg equation. Only few iterations are required to achieve fairly accurate solutions of both the first and second problems.
Study on Optimizing Operation of Preheating Commissioning for Waxy Crude Oil Pipelines
Authors: Zhang Jian , Wang Yi , Wang Xinran , Dong Handu , Huang Jinping , Yu Bo
Published: October 2014

A mathematical model is established for the preheating commissioning process of waxy crude oil pipelines. The governing equations are solved by the finite volume method and the finite difference method. Accordingly, numerical computations are made for the Niger crude oil pipeline and the Daqing-Tieling 3rd pipeline. The computational results agree well with the field test data. On this basis, fluid temperature in the process of the preheating commissioning is studied for single station-to-station pipeline. By comparing different preheating modes, it is found that the effect of forward preheating is the best. Under different preheating commissioning conditions, the optimal combination of outlet temperature and flow rate is given.
Second Atom-Bond Connectivity Index of Special Chemical Molecular Structures
Authors: Gao Wei , Wang Weifan
Published: October 2014

In theoretical chemistry, the second atom-bond connectivity index was introduced to measure the stability of alkanes and the strain energy of cycloalkanes. In this paper, we determine the second atom-bond connectivity index of unilateral polyomino chain and unilateral hexagonal chain. Furthermore, the secondABCindices of V-phenylenic nanotubes and nanotori are presented.
Traveling Wave Solutions of the Benjamin-Bona-Mahony Water Wave Equations
Authors: Seadawy A. R. , Sayed A.
Published: October 2014

The modeling of unidirectional propagation of long water waves in dispersive media is presented. The Korteweg-de Vries (KdV) and Benjamin-Bona-Mahony (BBM) equations are derived from water waves models. New traveling solutions of the KdV and BBM equations are obtained by implementing the extended direct algebraic and extended sech-tanh methods. The stability of the obtained traveling solutions is analyzed and discussed.
Dietary Conjugated Linoleic Acid Alters Oxidative Stability and Alleviates Plasma Cholesterol Content in Meat of Broiler Chickens
Authors: Kumari Ramiah Suriya , Meng Goh Yong , Ebrahimi Mahdi
Published: October 2014

This study was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) on fatty acid composition, lipoprotein content, lipid peroxidation, and meat colour of broiler chickens. A total of 180 broiler chickens were allocated to 3 dietary treatments (0, 2.5, and 5% Lutrell) and given a standard broiler starter diet and finisher diet. Body weight of chickens and feed intake were recorded weekly. After slaughter, the breast meat was aged at 4°C for 0, 3, and 6 days. The fatty acid composition was measured in the breast meat. Body weight (BW) and feed efficiency were decreased by dietary CLA level (P<0.05). Chicken fed with 2.5% Lutrell had the highest feed intake compared to the control (CON) group. The total CLA increased significantly (P<0.05) in breast meat from birds supplemented with CLA. Propensity for lipid peroxidation was significantly higher after 6 days of meat storage (P<0.05) and the redness in chicken breast meat was lower in CLA-fed birds (P<0.05). It is also notable that a 5% Lutrell supplementation decreased the plasma total cholesterol (TC), low density protein (LDL), and HDL (high-density lipoprotein)/LDL ratio in chickens (P<0.05).
Structure Design and Numerical Simulation of a High Performance Slit in Soft X-Ray Interference Lithography Beamline at SSRF
Authors: Gong Xuepeng , Lu Qipeng , Peng Zhongqi
Published: October 2014

A high precision slit in ultra-high vacuum is designed to develop a good performance soft X-ray interference lithography (XIL) beamline at Shanghai Synchrotron Radiation Facility (SSRF). In order to define the secondary source and enhance the performance of the beamline, many technical difficulties need resolving to design the precision slit. Therefore, to obtain reasonable design scheme, it is necessary to analyze the structural characteristics, the movement situation, the force state, the thermal load state, and the cooling state of the precision slit deeply by numerical simulation. The simulation results and the testing results demonstrate that the mechanical precision of the slit is at a high level and satisfies the requirements of the beamline.
Overdetection of Recurrence after Radical Prostatectomy: Estimates Based on Patient and Tumor Characteristics
Authors: Xia Jing , Trock Bruce J. , Gulati Roman , Mallinger Leslie , Cooperberg Matthew R. , Carroll Peter R. , Carter H. Ballentine , Etzioni Ruth
Published: October 2014

Purpose: Prostate-specific antigen recurrence (PSA-R) after radical prostatectomy (RP) can occur years before metastasis. This study estimates the chance that an untreated PSA-R would not progress to clinical metastasis within the patient's lifetime, that is, that recurrence is overdetected.

Experimental Design: Times from PSA-R to metastasis were estimated from patients with RP treated at Johns Hopkins University (Baltimore, MD) who did not receive salvage treatment (n = 441) at PSA-R. Times to other-cause death were based on U.S. life tables adjusted to reflect other-cause survival among RP cases in the Surveillance, Epidemiology, and End Results (SEER) registry. We used competing risks simulation to estimate lower bounds on the chance that other-cause death would precede clinical metastasis for patients with disease characteristics at diagnosis based on the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database (n = 4,455).

Results: Cumulative incidence of PSA-R in CaPSURE was 13.6% at 5 years and 19.9% at 10 years. The risk of other-cause death among patients with RP in SEER was 60% lower than the age-matched U.S. population. At least 9.1% of patients with PSA-R <5 years after RP and at least 15.6% of patients with PSA-R 5 to 10 years after RP were overdetected. At least 31.4% of patients over the age of 70 years at diagnosis, who recurred <10 years of diagnosis, were overdetected.

Conclusions: This analysis indicates that PSA-R after RP may be overdetected, with risk depending on patient age and tumor characteristics. The potential for overdetection of recurrence confirms the need for approaches to determine whether and when to initiate salvage therapies. Clin Cancer Res; 20(20); 5302–10. ©2014 AACR.
Precision Treatment of Distinct Molecular Subtypes of Diffuse Large B-cell Lymphoma: Ascribing Treatment Based on the Molecular Phenotype
Authors: Dunleavy Kieron , Roschewski Mark , Wilson Wyndham H.
Published: October 2014

Although diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma, was once considered to be a single disease, novel insights into its biology have revealed that it is molecularly heterogeneous. Technologies such as gene expression profiling have revealed that DLBCL consists of at least three distinct molecular diseases that have disparate outcomes following standard therapy. These subtypes arise from different stages of B-cell differentiation and are characterized by distinct oncogenic activation mechanisms. This knowledge has led to the investigation of strategies and novel agents that have selective activity within molecular subtypes and sets the stage for an era of precision medicine in DLBCL therapeutics, where therapy can be ascribed based on molecular phenotype. This work offers the chance of improving the curability of DLBCL, particularly in the activated B-cell subtype, where standard approaches are inadequate for a high proportion of patients.

See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”

Clin Cancer Res; 20(20); 5182–93. ©2014 AACR.
Human T-cell Lymphotropic Virus Type I–Associated Adult T-cell Leukemia–Lymphoma: New Directions in Clinical Research
Authors: Tsukasaki Kunihiro , Tobinai Kensei
Published: October 2014

Adult T-cell leukemia–lymphoma (ATL) is a distinct malignancy of regulatory T cell (Treg)/TH2 cells caused by human T-cell lymphotropic virus type I (HTLV-1), with a high frequency of expression of CD3/CD4/CD25/CCR4 and FoxP3 in about half of the cells. However, in primary ATL cells, although expression of the virus, including the Tax oncoprotein, appears just after an in vitro culture, integration sites of the provirus into the host genome are random, and chromosomal/genetic abnormalities are complex. ATL is thus a single disease entity that is caused by HTLV-1 and possesses diverse molecular features. The clinical features and prognosis of ATL vary, and this has led to subtypes classified into four categories: acute, lymphomatous, chronic, and smoldering types, based on lactate dehydrogenase and calcium values and organ involvement. Approximately 15 to 20 million individuals are infected with HTLV-1 worldwide, 1.1 million of whom reside in Japan, and the annual incidence of ATL has been estimated to be approximately 1,000. HTLV-1 infection early in life, mainly from breast feeding, is crucial for the development of ATL. The age-specific occurrence of ATL and complex genome abnormalities that accumulate with disease progression suggest a multistep carcinogenesis model following HTLV-1 infection. Various treatment options are available for ATL and consist of watchful waiting for indolent ATL, intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation for aggressive ATL, and a combination of IFNα and zidovudine for ATL with leukemic manifestation. Several promising new agents, including an anti-CCR4 antibody, are currently undergoing clinical trials associated with translational research.

See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”

Clin Cancer Res; 20(20); 5217–25. ©2014 AACR.
Genomic Classification of Serous Ovarian Cancer with Adjacent Borderline Differentiates RAS Pathway and TP53-Mutant Tumors and Identifies NRAS as an Oncogenic Driver
Authors: Emmanuel Catherine , Chiew Yoke-Eng , George Joshy , Etemadmoghadam Dariush , Anglesio Michael S. , Sharma Raghwa , Russell Peter , Kennedy Catherine , Fereday Sian , Hung Jillian , Galletta Laura , Hogg Russell , Wain Gerard V. , Brand Alison , Balleine Rosemary , MacConaill Laura , Palescandolo Emanuele , Hunter Sally M. , Campbell Ian , Dobrovic Alexander , Wong Stephen Q. , Do Hongdo , Clarke Christine L. , Harnett Paul R. , Bowtell David D.L. , deFazio Anna
Published: October 2014

Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies.

Experimental Design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling.

Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC.

Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. Clin Cancer Res; 20(24); 6618–30. ©2014 AACR.
New Strategies in Ovarian Cancer: Translating the Molecular Complexity of Ovarian Cancer into Treatment Advances
Authors: Liu Joyce , Matulonis Ursula A.
Published: October 2014

An improved understanding of the genomics of ovarian cancer and the separation of ovarian cancer into histologically and molecularly defined subgroups have affected drug development and clinical trial design in ovarian cancer. Active therapies that have been tested in ovarian cancer include agents that inhibit angiogenesis and poly (ADP-ribose) polymerase inhibitors (PARPi). However, no FDA drug approvals for ovarian cancer have been granted since 2006, and overall survival improvements have been difficult to achieve with new agents. The genomic complexity of ovarian cancer and modest single-agent activity of many biologic agents in this disease have led to testing of biologic agent combinations. In this article, we review recent advances in the understanding of the molecular diversity of ovarian cancer as well as emerging therapeutic strategies such as new agents and biologic combinations that attempt to target multiple aberrant pathways in this cancer. Clin Cancer Res; 20(20); 5150–6. ©2014 AACR.
The Novel, Small-Molecule DNA Methylation Inhibitor SGI-110 as an Ovarian Cancer Chemosensitizer
Authors: Fang Fang , Munck Joanne , Tang Jessica , Taverna Pietro , Wang Yinu , Miller David F.B. , Pilrose Jay , Choy Gavin , Azab Mohammad , Pawelczak Katherine S. , VanderVere-Carozza Pamela , Wagner Michael , Lyons John , Matei Daniela , Turchi John J. , Nephew Kenneth P.
Published: October 2014

Purpose: To investigate SGI-110 as a “chemosensitizer” in ovarian cancer and to assess its effects on tumor suppressor genes (TSG) and chemoresponsiveness-associated genes silenced by DNA methylation in ovarian cancer.

Experimental Design: Several ovarian cancer cell lines were used for in vitro and in vivo platinum resensitization studies. Changes in DNA methylation and expression levels of TSG and other cancer-related genes in response to SGI-110 were measured by pyrosequencing and RT-PCR.

Results: We demonstrate in vitro that SGI-110 resensitized a range of platinum-resistant ovarian cancer cells to cisplatin (CDDP) and induced significant demethylation and reexpression of TSG, differentiation-associated genes, and putative drivers of ovarian cancer cisplatin resistance. In vivo, SGI-110 alone or in combination with CDDP was well tolerated and induced antitumor effects in ovarian cancer xenografts. Pyrosequencing analyses confirmed that SGI-110 caused both global (LINE1) and gene-specific hypomethylation in vivo, including TSGs (RASSF1A), proposed drivers of ovarian cancer cisplatin resistance (MLH1 and ZIC1), differentiation-associated genes (HOXA10 and HOXA11), and transcription factors (STAT5B). Furthermore, DNA damage induced by CDDP in ovarian cancer cells was increased by SGI-110, as measured by inductively coupled plasma-mass spectrometry analysis of DNA adduct formation and repair of cisplatin-induced DNA damage.

Conclusions: These results strongly support further investigation of hypomethylating strategies in platinum-resistant ovarian cancer. Specifically, SGI-110 in combination with conventional and/or targeted therapeutics warrants further development in this setting. Clin Cancer Res; 20(24); 6504–16. ©2014 AACR.
Correlation of Preoperative Retinal Pigment Epithelium Status with Foveal Microstructure in Repaired Macular Holes
Authors: Reibaldi Michele , Avitabile Teresio , Longo Antonio , Uva Maurizio Giacinto , Bonfiglio Vincenza , Russo Andrea , Toro Mario D. , Stella Santo , Giovannini Alfonso , Viti Francesca , Nicolai Michele , Saitta Andrea , Cennamo Gilda , Gagliano Caterina , Mariotti Cesare
Published: October 2014

Purpose: To investigate, with spectral-domain optical coherence tomography, if the preoperative status of the retinal pigment epithelium (RPE) affects the postoperative foveal morphology and visual outcomes in eyes with surgically closed macular holes (MHs). Methods: In 52 eyes with surgically closed MHs, preoperative RPE morphology was evaluated and graded based on the measurement of the largest hyperreflective protrusions above the RPE line. Foveal microstructural features and best-corrected visual acuity (BCVA) were evaluated 12 months after surgery. Results: At 12 months, a significant correlation was found between postoperative degree of integrity of the photoreceptors with preoperative RPE morphology, and base diameter of the hole (p = 0.003 and p = 0.028, respectively); mean BCVA at 12 months in eyes with diffuse RPE alteration was significantly lower than in eyes with small or no RPE alteration (p < 0.05). Conclusions: Preoperative RPE integrity may be indicative of good photoreceptor restoration and visual recovery in patients with surgically closed MHs.
Non-Alcoholic Fatty Liver and Metabolic Syndrome in Children: A Vicious Circle
Authors: Alterio Arianna , Alisi Anna , Liccardo Daniela , Nobili Valerio
Published: October 2014

During the last decade, paediatricians have observed a dramatic increase of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in children. Furthermore, several lines of evidence have reported that a large part of children with NAFLD presents one or more traits of MS making plausible that, in the coming years, these subjects may present a rapid course of disease towards more severe cirrhosis and cardiovascular disease. Genetic susceptibility and the pressure of intrauterine environment and lifestyle are all crucial to activate molecular machinery that leads to development of NAFLD and MS in childhood. In this scenario, central obesity and consequent adipose tissue inflammation are critical to promote both MS-associated metabolic dysfunctions and NAFLD-related hepatic damage. An excessive dietary intake may in fact cause a specific lipid partitioning and induce metabolic stressors, which in turn promote insulin resistance and the release of several circulating factors. These molecules, on the one hand, trigger steatosis and the inflammatory response that characterize liver damage in NAFLD, and on the other hand contribute to the onset of other features of MS. This review provides an overview of current genetic, pathogenetic and clinical evidence of the vicious circle created by NAFLD and MS in children.
Prevalence of Mutations in Basal Core Promoter and Precore Region of Hepatitis B Virus in Vaccinated and Nonvaccinated Individuals of the Aboriginal Nicobarese Tribe of Car Nicobar Island, India
Authors: Bhattacharya Haimanti , Bhattacharya Debdutta , Nagarajan Muruganandam , Reesu Rajesh , Roy Subarna , Attayur Purushottaman Sugunan
Published: October 2014

The aim of this study was to explore the prevalence of basal core promoter (BCP) and precore gene (PC) mutations in hepatitis B virus (HBV) isolates among the Nicobarese tribe and their relationship with genotypes and HBeAg status. A total of 726 blood samples were collected from two villages of the Car Nicobar Island where mass vaccination was performed in the year 2000. HBV DNA was isolated and the BCP and PC regions were amplified and sequenced directly. The samples positive for HBV DNA were tested for HBsAg, HBeAg and anti-HBe. Among the 211 and 515 samples collected from vaccinated and nonvaccinated persons, 16 and 82 were positive for HBV DNA, respectively. Among the vaccinated individuals, only 1 had a mutation in both the BCP and PC gene. Among the nonvaccinated subjects, 3 (4.5%) had an A1762T mutation, 8 (12.1%) had a G1764A mutation, 11 (16.7%) had a G1896A mutation and 4 (6.1%) had a G1899A mutation. The HBeAg-negative subjects had a significantly higher frequency of BCP and PC mutations than the HBeAg-positive subjects. The prevalence of a PC mutation was higher than that of a BCP mutation. The present study stresses the need for the continuous surveillance of subjects with BCP and PC mutations, as the mutations may contribute to the progression of liver disease.
Can HTLV-1 Infection Be a Potential Risk Factor for Atherosclerosis?
Authors: Layegh Parvaneh , Shoeibi Ali , Nikkhah Karim , Ghabeli Juibary Ali , Raftari Samaheh , Darbarpanah Sahar , Boroumand Reza , Azarpazhooh Mahmoudreza
Published: October 2014

Introduction: Chronic inflammations including infectious disorders such as HIV infection are now considered as risk factors for atherosclerosis. In this study, conducted for the first time on human subjects, human T-lymphotropic virus type 1 (HTLV-1) infection was examined as a potential risk factor for atherosclerosis. Materials and Methods: This is a matched-pair cross-sectional study on 58 HTLV-1-infected cases and 55 healthy control subjects. The subjects did not have any major cerebrovascular risk factors. Carotid intima-media thickness (IMT) was measured for each patient using the standard protocol of the Atherosclerosis Risk in Communities (ARIC) Study. Results: The mean age of the subjects was 42.9 ± 10.52 years, and males made up 33% of the population. The difference between the mean IMT of the infected case group and that of the healthy control group was significant (p < 0.05). Discussion: This study indicated that the HTLV-infected individuals showed a greater carotid IMT than the age- and sex-matched control subjects. Observing no other known risk factor for atherosclerosis, we concluded that this significant difference in IMT might support the hypothesis that HTLV-1 infection is an independent risk factor for atherogenesis.
Expression of Reactive Oxygen Species-Related Proteins according to Androgen and HER-2 Status in Estrogen Receptor-Negative Breast Cancer
Authors: Kim Ji-Ye , Jung Woo Hee , Koo Ja Seung
Published: October 2014

Objective: The purpose of the current study is to understand the clinicopathological implications of redox proteins in association with androgen receptor (AR) and HER-2 status in estrogen receptor (ER)-negative breast cancers through evaluation of the expression patterns of redox proteins, such as catalase, thioredoxin reductase (TxNR), glutathione S-transferase π (GSTπ), thioredoxin interacting protein (TxNIP), and manganese superoxide dismutase (MnSOD). Methods: Two hundred cases of ER-negative breast cancer samples were collected as a tissue microarray. Immunohistochemical staining was done for redox-related proteins, after which the resulting data set was organized by AR and HER-2 status. Results: The redox proteins that had a significant association with AR and HER-2 status were tumoral catalase (p < 0.001) and stromal GSTπ (p < 0.001). Tumoral catalase was least expressed in the AR-/HER-2- group, while stromal GSTπ was least expressed in both the AR+/HER-2- and the AR-/HER-2- groups. Stromal GSTπ was highly expressed in HER-2 positive groups (p < 0.001). Stromal GSTπ negativity and tumoral MnSOD positivity were associated with a shorter disease-free survival (p = 0.041 and p = 0.007, respectively) in univariate analysis. Conclusion: ER-negative breast cancers showed different expressions of redox-related proteins according to AR and HER-2 status. Catalase expression was high in AR-negative groups, while stromal GSTπ expression was high in HER-2-positive groups.
Very Old Patients on Hemodialysis: How They Start and Can We Predict Survival?
Authors: Gubensek Jakob , Ponikvar Rafael , Ekart Robert , Buturovic-Ponikvar Jadranka
Published: October 2014

Background: We describe circumstances of dialysis initiation, dialysis prescription and factors affecting survival in elderly patients. Methods: We included all incident patients ≥80 years old from a National Registry for which clinical and laboratory data at dialysis initiation could retrospectively be obtained. Results: Of 170 patients included, 24% had diabetes, 30% ischemic heart disease, 13% peripheral arterial disease, 15% active malignancy and 60% prior nephrology care. Mean creatinine was 672 ± 225 µmol/l, eGFR 7.3 ± 3.7 ml/min/1.73 m2, 81% started dialysis in hospital and 78% with a catheter. 32% had <2 sessions/week and 29% had single-needle dialysis. One-year survival was 74% (median 26 months). In multivariate analysis only age (HR 1.10) and prior nephrology care (HR 0.48) were significant predictors of survival. Conclusions: The majority of elderly patients started dialysis with a catheter and in hospital setting. We estimate observed survival as good. Only age and prior nephrology care were independent predictors of survival. Video Journal Club ‘Cappuccino with Claudio Ronco' at www.karger.com/?doi=367681.
Menstrual Cycle Recovery in Patients with Anorexia Nervosa: The Importance of Insulin-Like Growth Factor 1
Authors: Cominato Louise , da Silva Mariana Moraes Xavier , Steinmetz Leandra , Pinzon Vanessa , Fleitlich-Bilyk Bacy , Damiani Durval
Published: October 2014

Background: Follow-up visits of patients recovering from anorexia nervosa (AN) have shown that some patients do not resume menstrual cycles despite returning to the normal weight for their age and height. Aim: To verify whether leptin, insulin-like growth factor 1 (IGF-1) or another hormonal marker could be a good predictor of the return of menses. Patients and Methods: This prospective study included female adolescents diagnosed with AN or eating disorders not otherwise specified (EDNOS) and who were being treated in an ambulatory care unit during nutritional recovery. Body mass index and leptin, luteinizing hormone, estradiol and IGF-1 levels of these patients were evaluated. Blood samples were collected in the 1st (T1), 5th (T2), 10th (T3), 15th (T4) and 20th (T5) weeks of treatment. The hormone levels during nutritional recovery and at the time of the resumption of menses were analyzed. Results: The hormonal profiles improved after nutritional recovery, with IGF-1 correlating the most with the resumption of menses and nutritional recovery (p = 0.0001). At the resumption of menstruation, the patients showed IGF-1 levels >342.8 ng/ml. Conclusion: IGF-1 was the best predictor of the return of menses in female adolescents with AN or EDNOS.
Rac1 Signaling Is Critical to Cardiomyocyte Polarity and Embryonic Heart Development
Authors: Leung Carmen , Lu Xiangru , Liu Murong , Feng Qingping
Published: October 2014

Background

Defects in cardiac septation are the most common form of congenital heart disease, but the mechanisms underlying these defects are still poorly understood. The small
GTP
ase Rac1 is implicated in planar cell polarity of epithelial cells in
Drosophila
; however, its role in mammalian cardiomyocyte polarity is not clear. We tested the hypothesis that Rac1 signaling in the second heart field regulates cardiomyocyte polarity, chamber septation, and right ventricle development during embryonic heart development.

Methods and Results

Mice with second heart field–specific deficiency of
Rac1
(
Rac1

SHF

) exhibited ventricular and atrial septal defects, a thinner right ventricle myocardium, and a bifid cardiac apex. Fate‐mapping analysis showed that second heart field contribution to the interventricular septum and right ventricle was deficient in
Rac1

SHF

hearts. Notably, cardiomyocytes had a spherical shape with disrupted F‐actin filaments in
Rac1

SHF

compared with elongated and well‐aligned cardiomyocytes in littermate controls. Expression of Scrib, a core protein in planar cell polarity, was lost in
Rac1

SHF

hearts with decreased expression of

WAVE

and
Arp2/3
, leading to decreased migratory ability. In addition, Rac1‐deficient neonatal cardiomyocytes displayed defects in cell projections, lamellipodia formation, and cell elongation. Furthermore, apoptosis was increased and the expression of
Gata4
,
Tbx5
,
Nkx2.5
, and
Hand2
transcription factors was decreased in the
Rac1

SHF

right ventricle myocardium.

Conclusions

Deficiency of Rac1 in the second heart field impairs elongation and cytoskeleton organization of cardiomyocytes and results in congenital septal defects, thin right ventricle myocardium, and a bifid cardiac apex. Our study suggests that Rac1 signaling is critical to cardiomyocyte polarity and embryonic heart development.
Use of Coumarin Anticoagulants and Cerebral Microbleeds in the General Population
Authors: Akoudad Saloua , Darweesh Sirwan K.L. , Leening Maarten J.G. , Koudstaal Peter J. , Hofman Albert , van der Lugt Aad , Stricker Bruno H. , Ikram M. Arfan , Vernooij Meike W.
Published: October 2014

Background and Purpose—

It remains undetermined whether the use of coumarin anticoagulants associates with cerebral microbleeds in the general population. We investigated whether (1) coumarin use relates to higher prevalence and incidence of microbleeds, (2) microbleeds are more frequent in people with higher maximum international normalized ratios (INRs), and (3) among coumarin users, variability in INR associates with microbleed presence.

Methods—

From the population-based Rotterdam Study, 4945 participants aged ≥45 years were included in the cross-sectional analysis, and 3069 participants had follow-up brain MRI. Information on coumarin use was obtained from automated pharmacy records. Coumarin users were monitored, and INR values were measured in consecutive visits. Presence and location of microbleeds were rated on brain MRI. We investigated the association of coumarin use with microbleeds using multivariable logistic regression.

Results—

Overall, 8.6% had used coumarin anticoagulants before the first MRI and 5.9% before follow-up MRI. The prevalence of microbleeds was 19.4%, and the incidence was 6.9% during a mean follow-up of 3.9 years (SD, 0.5). Compared with never users, coumarin users had a higher prevalence of deep or infratentorial microbleeds and a higher incidence of any microbleeds, although statistical significance was not reached in the latter. A higher maximum INR was associated with deep or infratentorial microbleeds. Among coumarin users, a greater variability in INR was associated with a higher prevalence of microbleeds.

Conclusions—

Coumarin use is associated with microbleeds. Associations were strongest for people with greater variability in INR.
Group size, contest competition, and social structure in Cayo Santiago rhesus macaques
Authors: Balasubramaniam K.N. , Dunayer E.S. , Gilhooly L.J. , Rosenfield K.A. , Berman C.M.
Published: October 2014

In non-human primate systems, the Ecological Model of Female Social Relationships (EMFSR) views variation in female social structure as adaptations to variation in recent past and/or current ecological conditions. Group size may be a major additional demographic factor affecting social structure through its effects on resource competition. In particular, in Resident Nepotistic Despotic (RND) societies, when resources are uniformly clumped, larger groups are expected to face higher levels of within-group contest competition (WGC) than smaller groups and to respond by showing more highly despotic social relationships than smaller groups. On the other hand, smaller groups are expected to face higher levels of between-group contest competition (BGC) and hence, show greater levels of intragroup tolerance (or lower despotism). While formal models do not explicitly predict this kind of variation within species, many researchers have investigated such intraspecific variation. Thus, we tested these predictions across three groups of free-ranging rhesus macaques (Macaca mulatta) of varying sizes on Cayo Santiago, Puerto Rico, where we were able to control for variation in resource-patch contestability and predation risk. Subjects were adult females. For each group, we collected data on (1) exposure and (2) behavioural reactions to WGC and BGC at two independent sets of clumped resources (feeding corrals and drinking stations) and (3) agonistic and affiliative social behaviour, using focal animal, all occurrences, and ad-libitum sampling methods. As predicted, our largest group showed the greatest levels of exposure and behavioural responses to WGC contexts. Likewise, our smallest group showed greatest levels of exposure and responses to BGC contexts. However, aspects of social structure did not vary across groups in directions predicted by the EMFSR. These findings are broadly consistent with several previous comparative tests of the model on other primate taxa that found strong links between group size, ecological factors and contest competitive regimes, but little or no evidence of links with social structure. Our study adds strength to these conclusions given our unique ability to control for several variables on Cayo Santiago. We suggest that our findings may be generalizable to several wild rhesus populations in North India, given that they have lived in similarly dense populations and have been frequently provisioned by humans for thousands of years.
An experimental study measuring the effects of a tarsus-mounted tracking device on the behaviour of a small pursuit-diving seabird
Authors: Robinson Jill L. , Jones Ian Lawrence
Published: October 2014

Miniaturized tracking devices are taking a rapidly increasing role in studies measuring animal movement and other aspects of behaviour, especially for wide-ranging species such as seabirds that are difficult to observe otherwise. A crucial, but questionable criterion of such migration research is assuming that effects of tracking devices on animal behaviour are negligible, to ensure results of tracking studies are biologically relevant. To address this concern, we experimentally quantified effects of a 2 g (ca. 1.1% of body mass) geolocation device on crested auklet (Aethia cristatella) behaviour, including return rate, activity on the colony surface, and measures of reproductive performance in a two-year, two-part field study. In experiment 1, we fitted tracking devices (or identical dummy devices) to one mate of a breeding pair in nesting crevices, to quantify effects on reproductive performance and nest fidelity. In experiment 2, we assigned dummy devices to birds captured at the colony site surface, to quantify effects on social activity, return rate and provisioning behaviour. For birds tagged in crevices, we detected no effect on fledging success, or chick growth rate (mass and wing length). However, mass at fledging age of chicks provisioned with one tagged parent was significantly lower than control, and low nest site fidelity (compared to control birds) was observed for tagged birds. Individuals tagged on the colony surface showed significantly reduced colony surface activity, return rates and provisioning behaviour. This study shows strong ‘observer effects’ of an attached device well below the recommended size limit for wildlife tagging. Future studies should both quantify effects of attached devices and consider the biological relevance of measures of the behaviour of interest.