bluuebunny/crossref_metadata_2025 huggingface dataset:
SU(2)N model of vector dark matter with a leptonic connection
Authors: Fraser Sean , Ma Ernest , Zakeri Mohammadreza
Published: January 2015

Models of fermion and scalar dark matter abound. Here we consider instead vector dark matter, from an SU(2)N extension of the standard model. It has a number of interesting properties, including a possible implementation of the inverse seesaw mechanism for neutrino mass. The annihilation of dark matter for calculating its relic abundance in this model is not dominated by its cross-section to standard-model particles, but rather to other new particles which are in thermal equilibrium with those of the standard model.
FLUID DYNAMIC CHARACTERISTICS OF SYSTOLIC BLOOD FLOW OF THE LEFT VENTRICLE
Authors: HUNG TIN-KAN , KHALAFVAND SEYED SAEID , NG EDDIE YIN-KWEE
Published: January 2015

Ejection of blood from the left ventricle to the aorta is studied using two-dimensional Navier–Stokes equations, the work-energy equation and the magnetic resonance imaging of a normal ventricular motion. Vortex shedding in the sinuses of Valsalva is dominated by the aortic jet, flow acceleration and valve motion. Momentums produced by ventricular contraction are in concert with vortices in the ventricle for blood ejection. Shear stresses and net pressures on the aortic valve are calculated during valve opening and closing. The rate of work done by shear and the energy dissipation in the ventricle are small. The Bernoulli energy flux delivered to blood from ventricular contraction is practically balanced by energy flux at the aortic root and the rate change of kinetic energy in the ventricle.
Magnetic susceptibility and geochemical characterization of an upper Mississippian cyclothemic section Polotnyanyi Zavod, (Moscow Basin, Russia)
Authors: Alekseev A. O. , Kabanov P. B. , Alekseeva T. V. , Kalinin P. I.
Published: January 2015

This case study provides insight into magnetic susceptibility (MS), iron and bulk-sample geochemistry patterns in an Upper Mississippian siliciclastic–carbonate cyclothemic section Polotnyanyi Zavod (Moscow Basin, Russia), with many subaerial disconformities and
Stigmaria
impressions. The goal of this paper is to test whether the MS and geochemical signals in this section are linked to any specific geological processes. The section is dominated by limestones but contains several siliciclastic units and numerous subaerial disconformities. This lithological heterogeneity is vividly expressed on MS and bulk geochemical logs. MS shows the strongest positive correlation to bulk iron and also strong correlations to Al
2
O
3
, MgO, K
2
O and TiO
2
, pointing to close association of iron with siliciclastic fines rich in detrital mica and clays. The correlation of iron and MS to siliciclastic fines or subaerial exposure horizons is not straightforward. The highest ferruginization with most intense MS excursions occurs in basal sooty silts and shales of three main siliciclastic units of the studied section. In addition, many other thin pedogenized shales are ferruginized and show a relative high magnetism, but some ferruginized shales are not palaeosols.
An Updated Meta-Analysis: Risk Conferred by Glutathione S-Transferases (GSTM1andGSTT1) Polymorphisms to Age-Related Cataract
Authors: Liao Rong-feng , Ye Min-jie , Liu Cai-yuan , Ye Dong-qing
Published: January 2015

Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC).Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included.Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057–1.429, andP=0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598–0.850, andP<0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137–1.830, andP=0.003) but not in Caucasians.Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.
Protein Complex Discovery by Interaction Filtering from Protein Interaction Networks Using Mutual Rank Coexpression and Sequence Similarity
Authors: Kazemi-Pour Ali , Goliaei Bahram , Pezeshk Hamid
Published: January 2015

The evaluation of the biological networks is considered the essential key to understanding the complex biological systems. Meanwhile, the graph clustering algorithms are mostly used in the protein-protein interaction (PPI) network analysis. The complexes introduced by the clustering algorithms include noise proteins. The error rate of the noise proteins in the PPI network researches is about 40–90%. However, only 30–40% of the existing interactions in the PPI databases depend on the specific biological function. It is essential to eliminate the noise proteins and the interactions from the complexes created via clustering methods. We have introduced new methods of weighting interactions in protein clusters and the splicing of noise interactions and proteins-based interactions on their weights. The coexpression and the sequence similarity of each pair of proteins are considered the edge weight of the proteins in the network. The results showed that the edge filtering based on the amount of coexpression acts similar to the node filtering via graph-based characteristics. Regarding the removal of the noise edges, the edge filtering has a significant advantage over the graph-based method. The edge filtering based on the amount of sequence similarity has the ability to remove the noise proteins and the noise interactions.
Nasal Dermoplasty for Recurrent Polyps in a Patient with Churg-Strauss Syndrome
Authors: Anastasopoulos George , Machas Theophanis , Kegioglou Sofia , Rapti Demetra
Published: January 2015

Nasal dermoplasty for recurrent polyps (NDRP) is a new technique for the surgical treatment of this condition. Churg-Strauss syndrome is characterized by the presence of nasal polyps with a great tendency for relapse after surgical or pharmaceutical treatment. It is the first time that we use NDRP to treat nasal polyps in a patient with Churg-Strauss syndrome. The patient was a 33-year-old female suffering from Churg-Strauss syndrome having had multiple operations in the past for recurrent polyps. NDRP was performed on the left nostril only. The mucosa of the left nasal vault was replaced by a split-thickness skin graft (modified dermoplasty). On the right nostril, polyps were removed and the ostia of the paranasal sinuses were enlarged as in typical endoscopic sinus surgery. The skin graft had a successful take and eight months after the operation no polyps are detected on the left side while polyps have recurred on the right nasal cavity. Applying the technique to a single nostril has several advantages, namely, the reduction of the operational time and therefore the risks for the patient from a prolonged general anaesthetic and the ability to judge the efficacy of the technique on the same patient.
Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling
Authors: Bao Yanju , Gao Yebo , Du Maobo , Hou Wei , Yang Liping , Kong Xiangying , Zheng Honggang , Li Weidong , Hua Baojin
Published: January 2015

To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere detected in the XZP-treated rats (P<0.05for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.
In Situ Thrombosis of Small Pulmonary Arteries in Pulmonary Hypertension Developing after Chemotherapy for Malignancy
Authors: Maeda Kay , Saiki Yoshikatsu , Yamaki Shigeo
Published: January 2015

A few reports have provided histopathological insight into pulmonary hypertension developing after antitumor chemotherapy. In general, plexogenic pulmonary arteriopathy is a commonly observed finding in patients with severe pulmonary hypertension. We herein report a novel pathological finding that may characterize the histopathological change occurring in patients with pulmonary hypertension after chemotherapy for malignancy. Lung biopsy or autopsy was performed in 7 patients with pulmonary hypertension that developed during or after chemotherapy between 2006 and 2013 to examine the pulmonary vascular changes or to determine the cause of death. Pathological findings included in situ thrombosis in the small pulmonary arteries in 4 of 7 patients. In 2 of 4 patients, pulmonary hypertension was controlled by anticoagulants and antithrombotic agents. One patient who had organized thrombi attained spontaneous remission with oxygen therapy. The other patient died of sudden cardiopulmonary arrest during chemotherapy. Autopsy showed complete occlusion of the peripheral small pulmonary arteries and veins by thrombi. These results demonstrate that in situ thrombosis in the small pulmonary arteries could cause pulmonary hypertension after chemotherapy.
Prevalence of Cardiovascular Disease and Associated Risk Factors among Adult Population in the Gulf Region: A Systematic Review
Authors: Aljefree Najlaa , Ahmed Faruk
Published: January 2015

Background. CVD is a principal cause of mortality and disability globally.Objective. To analyse the epidemiological data on CHD, strokes, and the associated risk factors among adult population in the Gulf countries.Methods. A systematic review of published articles between 1990 and 2014 was conducted.Results. The analysis included 62 relevant studies. The prevalence of CHD was reported to be 5.5% in Saudi Arabia. The annual incidence of strokes ranged from 27.6 to 57 per 100 000 in the Gulf countries with ischaemic stroke being the most common subtype and hypertension and diabetes being the most common risk factors among stroke and ACS patients. The prevalence of overweight and obesity ranged from 31.2% to 43.3% and 22% to 34.1% in males and from 28% to 34.3% and 26.1% to 44% in females, respectively. In males, the prevalence of hypertension and diabetes ranged from 26.0% to 50.7% and 9.3% to 46.8%, respectively; in females these ranged from 20.9% to 57.2% and 6% to 53.2%, respectively. The prevalence of inactivity was from 24.3% to 93.9% and 56.7% to 98.1% in males and females, respectively. Relatively more males (13.4% to 37.4%) than females (0.5% to 20.7%) were current smokers. Available data indicate poor dietary habits with high consumption of snacks, fatty foods, sugar, and fast food.Conclusion. Effective preventative strategies and education programs are crucial in the Gulf region to reduce the risk of CVD mortality and morbidity in the coming years.
Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum
Authors: Du Huan , Nie Shuke , Chen Guiqin , Ma Kai , Xu Yan , Zhang Zhentao , Papa Stella M. , Cao Xuebing
Published: January 2015

L-DOPA-induced dyskinesias (LID) remain a major problem of long-term therapy of Parkinson’s disease. Levetiracetam, a new antiepileptic drug, has been shown to reduce LID, but the mechanisms underlying its effects are unknown. In this study, we assessed the effect of levetiracetam on key mediators of LID in rats with 6-hydroxydopamine (6-OHDA) lesions. Following chronic administration of L-DOPA (12 mg/kg, twice daily for 14 days), rats developed abnormal involuntary movements (AIMs), but co-administration of levetiracetam (15, 30, and 60 mg/kg) with equivalent L-DOPA dosing significantly reduced AIMs scores in a dose dependent manner. The effects of levetiracetam were associated with changes in striatal expression ofΔFosB, phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and phosphorylated cAMP-regulated phosphoprotein of 32 kDa (p-DARPP-32). These data support that levetiracetam acts at multiple sites in the pathogenetic cascade of LID, and that further understanding of these actions of antiepileptics may contribute to developing new LID therapies.
Clostridium paraputrificumBacteremia Associated with Colonic Necrosis in a Patient with AIDS
Authors: Shinha Takashi , Hadi Christiane
Published: January 2015

Clostridiumspecies are anaerobic Gram-positive rods that can cause a broad range of invasive infections in humans, including myonecrosis and bacteremia. Importantly, clostridial bacteremia is frequently associated with underlying medical conditions, such as colonic malignancy. CharacterizingClostridiumspp. and understanding their associated clinical disease spectrum are paramount to provide optimal treatment, thereby decreasing morbidity and mortality especially in those with underlying debilitating comorbidities.Clostridium paraputrificumis an infrequently isolatedClostridiumspecies and its clinical significance has not been well described. We herein report a case of bacteremia due toC. paraputrificumin a 65-year-old man with AIDS who developed acute colonic necrosis complicated by septic shock. We then review other cases of bacteremia associated withC. paraputrificumin the literature in addition to discussing the clinical significance of anaerobic bacteremia in general. To our knowledge, our report is the second case ofC. paraputrificumbacteremia in a patient with AIDS.
Lunasin Inhibits Cell Proliferation via Apoptosis and Reduces the Production of Proinflammatory Cytokines in Cultured Rheumatoid Arthritis Synovial Fibroblasts
Authors: Jia Shaohui , Zhang Shufang , Yuan Hong , Chen Ning
Published: January 2015

Lunasin, a peptide with 43 amino acid residues and initially isolated and identified in soybean cotyledon, has gained extensive attention due to its anti-inflammatory and anticancer properties. However, its treatment efficacy on rheumatoid arthritis (RA) and corresponding mechanisms have not been reported. Herein, the synovial fibroblasts harvested and isolated from patients with RA were treated with lunasin at various concentrations to examine the proliferation, apoptosis status, and corresponding cell cycle of cultured RA synovial fibroblasts. Meanwhile, the underlying mechanisms of lunasin for RA treatment are explored through Western blot, real-time PCR, ELISA, and luciferase reporter assays. Lunasin significantly inhibited the proliferation and induced the apoptosis of cultured RA synovial fibroblasts. In addition, lunasin reduced the production of interleukin-6 (IL-6), IL-8, and matrix metalloproteinase-3 (MMP-3) and suppressed the activation of NF-κB in cultured RA synovial fibroblasts but did not reveal obvious modulation on the secretion and gene expression of MMP-1. Therefore, lunasin will have promising potential as a novel nutritional supplement or drug candidate for RA due to its potency of suppressing synovial cell proliferation and decreasing the production of proinflammatory cytokines and MMPs in synovial cells.
Analytical Solutions of the Balance Equation for the Scalar Variance in One-Dimensional Turbulent Flows under Stationary Conditions
Authors: Amicarelli Andrea , Di Bernardino Annalisa , Catalano Franco , Leuzzi Giovanni , Monti Paolo
Published: January 2015

This study presents 1D analytical solutions for the ensemble variance of reactive scalars in one-dimensional turbulent flows, in case of stationary conditions, homogeneous mean scalar gradient and turbulence, Dirichlet boundary conditions, and first order kinetics reactions. Simplified solutions and sensitivity analysis are also discussed. These solutions represent both analytical tools for preliminary estimations of the concentration variance and upwind spatial reconstruction schemes for CFD (Computational Fluid Dynamics)—RANS (Reynolds-Averaged Navier-Stokes) codes, which estimate the turbulent fluctuations of reactive scalars.
A New Mutation in Blau Syndrome
Authors: Zeybek Cengiz , Basbozkurt Gokalp , Gul Davut , Demirkaya Erkan , Gok Faysal
Published: January 2015

Blau syndrome is a rare, autosomal dominant, granulomatous autoinflammatory disease. The classic triad of the disease includes recurrent uveitis, granulomatous dermatitis, and symmetrical arthritis. Blau syndrome is related to mutations located at the 16q12.2–13 gene locus. To date, 11 NOD2 gene mutations causing Blau syndrome have been described. Here, we describe a 5-year-old male patient who presented with Blau syndrome associated with a novel sporadic gene mutation that has not been reported previously.
Comparison of Two Reconstructive Techniques in the Surgical Management of Four-Level Cervical Spondylotic Myelopathy
Authors: Li FengNing , Li ZhongHai , Huang Xuan , Chen Zhi , Zhang Fan , Shen HongXing , Kang YiFan , Zhang YinQuan , Cai Bin , Hou TieSheng
Published: January 2015

To compare the clinical efficacy and radiological outcome of treating 4-level cervical spondylotic myelopathy (CSM) with either anterior cervical discectomy and fusion (ACDF) or “skip” corpectomy and fusion, 48 patients with 4-level CSM who had undergone ACDF or SCF at our hospital were analyzed retrospectively between January 2008 and June 2011. Twenty-seven patients received ACDF (Group A) and 21 patients received SCF. Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI) score, and Cobb’s angles of the fused segments and C2-7 segments were compared in the two groups. The minimum patient follow-up was 2 years. No significant differences between the groups were found in demographic and baseline disease characteristics, duration of surgery, or follow-up time. Our study demonstrates that there was no significant difference in the clinical efficacy of ACDF and SCF, but ACDF involves less intraoperative blood loss, better cervical spine alignment, and fewer postoperative complications than SCF.
On Better Estimating and Normalizing the Relationship between Clinical Parameters: Comparing Respiratory Modulations in the Photoplethysmogram and Blood Pressure Signal (DPOP versus PPV)
Authors: Addison Paul S. , Wang Rui , Uribe Alberto A. , Bergese Sergio D.
Published: January 2015

DPOP (ΔPOP or Delta-POP) is a noninvasive parameter which measures the strength of respiratory modulations present in the pulse oximeter waveform. It has been proposed as a noninvasive alternative to pulse pressure variation (PPV) used in the prediction of the response to volume expansion in hypovolemic patients. We considered a number of simple techniques for better determining the underlying relationship between the two parameters. It was shown numerically that baseline-induced signal errors were asymmetric in nature, which corresponded to observation, and we proposed a method which combines a least-median-of-squares estimator with the requirement that the relationship passes through the origin (the LMSO method). We further developed a method of normalization of the parameters through rescaling DPOP using the inverse gradient of the linear fitted relationship. We propose that this normalization method (LMSO-N) is applicable to the matching of a wide range of clinical parameters. It is also generally applicable to the self-normalizing of parameters whose behaviour may change slightly due to algorithmic improvements.
Relative Entropies and Jensen Divergences in the Classical Limit
Authors: Kowalski A. M. , Plastino A.
Published: January 2015

Metrics and distances in probability spaces have shown to be useful tools for physical purposes. Here we use this idea, with emphasis on Jensen Divergences and relative entropies, to investigate features of the road towards the classical limit. A well-known semiclassical model is used and recourse is made to numerical techniques, via the well-known Bandt and Pompe methodology, to extract probability distributions from the pertinent time-series associated with dynamical data.
Modulation of Extracellular ATP Content of Mast Cells and DRG Neurons by Irradiation: Studies on Underlying Mechanism of Low‐Level‐Laser Therapy
Authors: Wang Lina , Hu Lei , Grygorczyk Ryszard , Shen Xueyong , Schwarz Wolfgang
Published: January 2015

Low‐level‐laser therapy (LLLT) is an effective complementary treatment, especially for anti‐inflammation and wound healing in which dermis or mucus mast cells (MCs) are involved. In periphery, MCs crosstalk with neurons via purinergic signals and participate in various physiological and pathophysiological processes. Whether extracellular ATP, an important purine in purinergic signaling, of MCs and neurons could be modulated by irradiation remains unknown. In this study, effects of red‐laser irradiation on extracellular ATP content of MCs and dorsal root ganglia (DRG) neurons were investigated and underlying mechanisms were explored in vitro. Our results show that irradiation led to elevation of extracellular ATP level in the human mast cell line HMC‐1 in a dose‐dependent manner, which was accompanied by elevation of intracellular ATP content, an indicator for ATP synthesis, together with [Ca2+]i elevation, a trigger signal for exocytotic ATP release. In contrast to MCs, irradiation attenuated the extracellular ATP content of neurons, which could be abolished by ARL 67156, a nonspecific ecto‐ATPases inhibitor. Our results suggest that irradiation potentiates extracellular ATP of MCs by promoting ATP synthesis and release and attenuates extracellular ATP of neurons by upregulating ecto‐ATPase activity. The opposite responses of these two cell types indicate complex mechanisms underlying LLLT.
Computational Approach in Formulating Mechanical Characteristics of 3D Star Honeycomb Auxetic Structure
Authors: Shokri Rad Mozafar , Ahmad Zaini , Alias Amran
Published: January 2015

Auxetic materials exhibit a unique characteristic due to the altered microstructure. Different structures have been used to model these materials. This paper treats a development of finite element model and theoretical formulation of 3D star honeycomb structure of these materials. Various shape parameters of the structural cell were evaluated with respect to the basic mechanical properties of the cell. Finite element and analytical approach for various geometrical parameters were numerically used to formulate the characteristics of the material. The study aims at quantifying mechanical properties for any domain in which auxetic material is of interest for variations in geometrical parameters. It is evident that mechanical properties of the material could be controlled by changing the base wall angle of the configuration. The primary outcome of the study is a design guideline for the use of 3D star honeycomb auxetic cellular structure in structural applications.
Development of a Loop-Mediated Isothermal Amplification Assay for Rapid Detection ofTrichosporon asahiiin Experimental and Clinical Samples
Authors: Zhou Jianfeng , Liao Yong , Li Haitao , Lu Xuelian , Han Xiufeng , Tian Yanli , Chen Shanshan , Yang Rongya
Published: January 2015

Invasive trichosporonosis is a deep mycosis found mainly in immunocompromised hosts, and the major pathogen isTrichosporon asahii. We detected the species-specific intergenic spacers (IGS) of rRNA gene ofT. asahiiusing a loop-mediated isothermal amplification (LAMP) assay in 15 isolates with 3 different visualization methods, including SYBR green detection, gel electrophoresis, and turbidimetric methods. The LAMP assay displayed superior rapidity to other traditional methods in the detection time; that is, only 1 h was needed for detection and identification of the pathogen DNA. Furthermore, the detection limit of the LAMP assay was more sensitive than the PCR assay. We also successfully detect the presence ofT. asahiiin samples from experimentally infected mice and samples from patients with invasive trichosporonosis caused byT. asahii, suggesting that this method may become useful in clinical applications in the near future.
Some Properties of Fuzzy Soft Proximity Spaces
Authors: Demir İzzettin , Özbakır Oya Bedre
Published: January 2015

We study the fuzzy soft proximity spaces in Katsaras’s sense. First, we show how a fuzzy soft topology is derived from a fuzzy soft proximity. Also, we define the notion of fuzzy soft δ‐neighborhood in the fuzzy soft proximity space which offers an alternative approach to the study of fuzzy soft proximity spaces. Later, we obtain the initial fuzzy soft proximity determined by a family of fuzzy soft proximities. Finally, we investigate relationship between fuzzy soft proximities and proximities.
Comparison of Cloud Base Height Derived from a Ground-Based Infrared Cloud Measurement and Two Ceilometers
Authors: Liu Lei , Sun Xue-jin , Liu Xi-chuan , Gao Tai-chang , Zhao Shi-jun
Published: January 2015

The cloud base height (CBH) derived from the whole-sky infrared cloud-measuring system (WSIRCMS) and two ceilometers (Vaisala CL31 and CL51) from November 1, 2011, to June 12, 2012, at the Chinese Meteorological Administration (CMA) Beijing Observatory Station are analysed. Significant differences can be found by comparing the measurements of different instruments. More exactly, the cloud occurrence retrieved from CL31 is 3.8% higher than that from CL51, while WSIRCMS data shows 3.6% higher than ceilometers. More than 75.5% of the two ceilometers’ differences are within ±200 m and about 89.5% within ±500 m, while only 30.7% of the differences between WSIRCMS and ceilometers are within ±500 m and about 55.2% within ±1000 m. These differences may be caused by the measurement principles and CBH retrieval algorithm. A combination of a laser ceilometer and an infrared cloud instrument is recommended to improve the capability for determining cloud occurrence and retrieving CBHs.
Carbonic Anhydrase IX Promotes Myeloid-Derived Suppressor Cell Mobilization and Establishment of a Metastatic Niche by Stimulating G-CSF Production
Authors: Chafe Shawn C. , Lou Yuanmei , Sceneay Jaclyn , Vallejo Marylou , Hamilton Melisa J. , McDonald Paul C. , Bennewith Kevin L. , Möller Andreas , Dedhar Shoukat
Published: January 2015

The mobilization of bone marrow–derived cells (BMDC) to distant tissues before the arrival of disseminated tumor cells has been shown preclinically to facilitate metastasis through the establishment of metastatic niches. Primary tumor hypoxia has been demonstrated to play a pivotal role in the production of chemokines and cytokines responsible for the mobilization of these BMDCs, especially in breast cancer. Carbonic anhydrase IX (CAIX, CA9) expression is highly upregulated in hypoxic breast cancer cells through the action of hypoxia-inducible factor-1 (HIF1). Preclinical evidence has demonstrated that CAIX is required for breast tumor growth and metastasis; however, the mechanism by which CAIX exerts its prometastatic function is not well understood. Here, we show that CAIX is indispensable for the production of granulocyte colony-stimulating factor (G-CSF) by hypoxic breast cancer cells and tumors in an orthotopic model. Furthermore, we demonstrate that tumor-expressed CAIX is required for the G-CSF–driven mobilization of granulocytic myeloid-derived suppressor cells (MDSC) to the breast cancer lung metastatic niche. We also determined that CAIX expression is required for the activation of NF-κB in hypoxic breast cancer cells and constitutive activation of the NF-κB pathway in CAIX-depleted cells restored G-CSF secretion. Together, these findings identify a novel hypoxia-induced CAIX–NF-κB–G-CSF cellular signaling axis culminating in the mobilization of granulocytic MDSCs to the breast cancer lung metastatic niche. Cancer Res; 75(6); 996–1008. ©2015 AACR.
Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer: A Pooled Analysis
Authors: Lang Kuhs Krystle A. , Anantharaman Devasena , Waterboer Tim , Johansson Mattias , Brennan Paul , Michel Angelika , Willhauck-Fleckenstein Martina , Purdue Mark P. , Holcátová Ivana , Ahrens Wolfgang , Lagiou Pagona , Polesel Jerry , Simonato Lorenzo , Merletti Franco , Healy Claire M. , Kjaerheim Kristina , Conway David I. , Macfarlane Tatiana V. , Thomson Peter , Castellsagué Xavier , Znaor Ariana , Black Amanda , Huang Wen-Yi , Krogh Vittorio , Trichopoulou Antonia , Bueno-de-Mesquita H. B(as). , Clavel-Chapelon Françoise , Weiderpass Elisabete , Ekström Johanna , Riboli Elio , Tjønneland Anne , Sánchez María-José , Travis Ruth C. , Hildesheim Allan , Pawlita Michael , Kreimer Aimée R.
Published: January 2015

Background: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted.

Methods: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated.

Results: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2–51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3–15.4); E2 (OR, 7.7; 95% CI, 1.4–29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6–119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9–81.8). No associations were observed with moderate HPV16 E6 seroreactivity.

Conclusions: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors.

Impact: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Cancer Epidemiol Biomarkers Prev; 24(4); 683–9. ©2015 AACR.
Very Long-term Survival Following Resection for Pancreatic Cancer Is Not Explained by Commonly Mutated Genes: Results of Whole-Exome Sequencing Analysis
Authors: Dal Molin Marco , Zhang Ming , de Wilde Roeland F. , Ottenhof Niki A. , Rezaee Neda , Wolfgang Christopher L. , Blackford Amanda , Vogelstein Bert , Kinzler Kenneth W. , Papadopoulos Nickolas , Hruban Ralph H. , Maitra Anirban , Wood Laura D.
Published: January 2015

Purpose: The median survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC) is currently <20 months. However, survival ≥10 years is achieved by a small subset of patients who are defined as very long-term survivors (VLTS). The goal of this study was to determine whether specific genetic alterations in resected PDACs determined very long-term survival.

Experimental Design: We sequenced the exomes of eight PDACs from patients who survived ≥10 years. On the basis of the results of the exomic analysis, targeted sequencing of selected genes was performed in a series of 27 additional PDACs from VLTSs.

Results: KRAS mutations were identified in 33 of 35 cancers (94%) from VLTSs and represented the most prevalent alteration in our cohort. TP53, SMAD4, and CDKN2A mutations occurred in 69%, 26%, and 17%, respectively. Mutations in RNF43, which have been previously associated with intraductal papillary mucinous neoplasms, were identified in four of the 35 cancers (11%). Taken together, our data show no difference in somatic mutations in carcinomas from VLTSs compared with available data from PDACs unselected for survival. Comparison of clinicopathologic features between VLTSs and a matching control group demonstrated that younger age, earlier stage, well/moderate grade of differentiation, and negative resection margins were associated with VLTS. However, more advanced stage, poor grade, or nodal disease did not preclude long-term survival.

Conclusions: Our results suggest that in most patients, somatic mutations in commonly mutated genes are unlikely to be the primary determinant of very long-term survival following surgical resection of PDAC. Clin Cancer Res; 21(8); 1944–50. ©2015 AACR.
Id1 Deficiency Protects against Tumor Formation in ApcMin/+ Mice but Not in a Mouse Model of Colitis-Associated Colon Cancer
Authors: Zhang Ning , Subbaramaiah Kotha , Yantiss Rhonda K. , Zhou Xi Kathy , Chin Yvette , Benezra Robert , Dannenberg Andrew J.
Published: January 2015

Different mechanisms contribute to the development of sporadic, hereditary and colitis-associated colorectal cancer. Inhibitor of DNA binding/differentiation (Id) proteins act as dominant-negative antagonists of basic helix–loop–helix transcription factors. Id1 is a promising target for cancer therapy, but little is known about its role in the development of colon cancer. We used immunohistochemistry to demonstrate that Id1 is overexpressed in human colorectal adenomas and carcinomas, whether sporadic or syndromic. Furthermore, elevated Id1 levels were found in dysplasia and colon cancer arising in patients with inflammatory bowel disease. Because levels of PGE2 are also elevated in both colitis and colorectal neoplasia, we determined whether PGE2 could induce Id1. PGE2 via EP4 stimulated protein kinase A activity resulting in enhanced pCREB-mediated Id1 transcription in human colonocytes. To determine the role of Id1 in carcinogenesis, two mouse models were used. Consistent with the findings in humans, Id1 was overexpressed in tumors arising in both ApcMin/+ mice, a model of familial adenomatous polyposis, and in experimental colitis-associated colorectal neoplasia. Id1 deficiency led to significant decrease in the number of intestinal tumors in ApcMin/+ mice and prolonged survival. In contrast, Id1 deficiency did not affect the number or size of tumors in the model of colitis-associated colorectal neoplasia, likely due to exacerbation of colitis associated with Id1 loss. Collectively, these results suggest that Id1 plays a role in gastrointestinal carcinogenesis. Our findings also highlight the need for different strategies to reduce the risk of colitis-associated colorectal cancer compared with sporadic or hereditary colorectal cancer. Cancer Prev Res; 8(4); 303–11. ©2015 AACR.
Induced PD-L1 Expression Mediates Acquired Resistance to Agonistic Anti-CD40 Treatment
Authors: Zippelius Alfred , Schreiner Jens , Herzig Petra , Müller Philipp
Published: January 2015

CD40 stimulation on antigen-presenting cells (APC) allows direct activation of CD8+ cytotoxic T cells, independent of CD4+ T-cell help. Agonistic anti-CD40 antibodies have been demonstrated to induce beneficial antitumor T-cell responses in mouse models of cancer and early clinical trials. We report here that anti-CD40 treatment induces programmed death ligand-1 (PD-L1) upregulation on tumor-infiltrating monocytes and macrophages, which was strictly dependent on T cells and IFNγ. PD-L1 expression could be counteracted by coadministration of antibodies blocking the PD-1 (programmed death-1)/PD-L1 axis as shown for T cells from tumor models and human donors. The combined treatment was highly synergistic and induced complete tumor rejection in about 50% of mice bearing MC-38 colon and EMT-6 breast tumors. Mechanistically, this was reflected by a strong increase of IFNγ and granzyme-B production in intratumoral CD8+ T cells. Concomitant CTLA-4 blockade further improved rejection of established tumors in mice. This study uncovers a novel mechanism of acquired resistance upon agonistic CD40 stimulation and proposes that the concomitant blockade of the PD-1/PD-L1 axis is a viable therapeutic strategy to optimize clinical outcomes. Cancer Immunol Res; 3(3); 236–44. ©2015 AACR.
On the Relationship between the Rate of Salivary Flow and Salivary Fluoride Clearance
Authors: Duckworth Ralph M. , Jones S.
Published: January 2015

The amount of fluoride retained in the mouth following the application of dentifrices, mouthwashes, etc. may be important in determining their anticaries efficacy. In this study we investigated the relationship between the salivary flow rate and salivary fluoride clearance. Ten adults tested six mouthrinses, consisting of aqueous sodium fluoride solutions (0.013, 0.026 mol/l) with and without added sodium chloride (1.28 mol/l) or sucrose (0.44 mol/l), in a randomised order. Prior to each test, subjects swallowed, rinsed for 2 min with 2 ml water and then expectorated into a preweighed container to obtain a measure of initial saliva flow rate. Next, the procedure was repeated using one of the test rinses. Finally, samples of unstimulated whole saliva were collected for up to 3 h after each mouthrinse application and analysed for fluoride. Salivary fluoride concentrations were significantly lower after application of mouthrinses that contained either sucrose or NaCl, both of which compounds markedly enhanced salivary flow, than after the use of corresponding mouthrinses without any additive. Area under the salivary fluoride clearance curve (AUC) values were inversely correlated with salivary flow rate on an individual basis (p < 0.01). The observed behaviour could not be completely attributed to treatment dilution by saliva at the time of application.
Honokiol Decreases Intra-Abdominal Adhesion Formation in a Rat Model
Authors: Agacayak Elif , Tunc Senem Yaman , Icen Mehmet Sait , Alabalik Ulaş , Findik Fatih Mehmet , Yuksel Hatice , Gul Talip
Published: January 2015

Aim: The purpose of this study was to investigate the effectiveness of honokiol, a natural molecule that was shown to have antioxidant effects, in prevention of intra-abdominal adhesion formation in a rat model. Material and Method: This study was conducted on a total of 40 non-pregnant Sprague-Dawley rats, which were divided into 4 groups as follows: sham, control, saline, and honokiol groups. Both uterine horns of the rats in control, saline, and honokiol groups were exposed and a 2-cm segment of the anti-mesenteric surface of both uterine horns was traumatized by a scalpel. The saline group was administered 2 ml of saline/day intraperitoneally for 5 days after the operation. The honokiol group, on the other hand, was administered honokiol intraperitoneally at a dose of 1 mg/kg/day for 5 days after the operation. On postoperative day 14, 3 ml of intracardiac blood sample was taken from the rats for biochemical analyses, and the rats were sacrificed this way. Results: Adhesion and inflammation scores were significantly lower in the honokiol group compared with the saline and control groups (p < 0.008). Similarly, fibrosis score was significantly lower in the honokiol group compared with the saline group (p < 0.008). Conclusion: Honokiol was found to be effective in prevention of intra-abdominal adhesion formation in a rat model. However, larger studies are needed to shed light on the exact role of honokiol in intra-abdominal adhesion formation and to determine the molecular aspects of the promising results found in this study.
Monochorionic Monozygotic Twin Pregnancy Complicated with Twin-Twin Transfusion Syndrome Presenting with an Obvious Lambda Sign in the First Trimester
Authors: Yamashita Akiko , Ishii Keisuke , Hidaka Nobuhiro , Yonetani Naoto , Hayashi Shusaku , Takeuchi Makoto , Mitsuda Nobuaki
Published: January 2015

In this report, we present a case of twin-twin transfusion syndrome in the presence of the thick dividing wall of each sac in dichorionic twins. The dichorionic diagnosis was based on the presence of the lambda sign at the first-trimester ultrasound evaluation. In addition to fetoscopic and pathological investigation, DNA typing confirmed that the twin set was monochorionic and monozygotic. This case illustrates that although extremely uncommon, the presence of lambda sign does not exclude monochorionic pregnancy.
Single Incision Trans-Umbilical Total Hysterectomy: Robotic or Laparoscopic?
Authors: Akdemir Ali , Yildirim Nuri , Zeybek Burak , Karaman Semra , Sendag Fatih
Published: January 2015

Objective: The aim of this study was to compare the early surgical outcomes in patients who underwent total hysterectomy with laparoendoscopic single-site surgery (LESS-TH) versus robotic single-site total hysterectomy (RSS-TH). Methods: Twenty-four patients who underwent RSS-​TH and thirty-four patients who underwent LESS-TH were retrospectively evaluated. Patient characteristics, operation time, intraoperative data (conversions, complications, estimated blood loss, etc.) and postoperative pain scores were compared. Results: The total operation time was significantly longer in the robotic surgery group, with a time of 98.5 vs. 86 min (p = 0.013), while vaginal closure time was significantly higher in the laparoscopic surgery group (p = 0.011). Intraoperative outcomes and postoperative pain scores were similar in the two groups. Conclusion: RSS-TH helps surgeons to overcome the technical disadvantages of LESS-TH, particularly vaginal cuff closure, ergonomics and instrument crowding and clashing. Early surgical outcomes are comparable in the two groups, and both techniques are safe and feasible.
Utility of DOG1 Immunomarker in Fine Needle Aspirates of Gastrointestinal Stromal Tumor
Authors: Kakkar Aanchal , Mathur Sandeep R. , Jain Deepali , Iyer Venkateswaran K. , Nalwa Aasma , Sharma Mehar C.
Published: January 2015

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. DOG1 is a sensitive and specific immunohistochemical marker for the diagnosis of GIST. To date, no study has reported the utility of DOG1 immunocytochemistry on aspirate smears. Methods: Aspirates with a cytological diagnosis of GIST were retrieved. DOG1 immunocytochemistry was performed on aspirates with adequate material. Results: 23 cases were included (11 primary, 2 recurrent, 10 metastatic). Primary tumors were most frequently located in the stomach; most metastatic tumors were in the liver. Tumor cells were arranged in cohesive clusters with high cellularity. Cells were spindled, had a low N:C ratio, and a moderate amount of cytoplasm, which was elongated and tapering. Characteristic nuclear features included elongated nuclei with blunt or tapering ends, fine chromatin, mild anisonucleosis, and longitudinal grooves. The mitotic count was low, including in metastatic tumors. DOG1 immunopositivity was noted in 57% of the cases examined. Histopathology was available in 5 cases, all diagnosed as GIST. Conclusion: Cytology is a sensitive investigative modality for the preoperative diagnosis and confirmation of metastasis of GISTs. In ambiguous cases, DOG1 immunocytochemistry can serve as a valuable adjunct. Cytologic assessment, however, cannot predict malignant potential of GISTs as even metastatic tumors display bland nuclear features.
Serum Metabolomic Characteristics of Patients with Liver Cirrhotic Ascites
Authors: Yang Tao , Zheng Xiyuan , Xing Feng , Zhuo Hua , Liu Chenghai
Published: January 2015

Chronic hepatitis B is a common and frequently encountered disease in our country, the final outcome of which develops into liver cirrhosis and primary liver cancer. It was the aim of this study to provide a theoretical basis for the early diagnosis and treatment of liver cirrhosis. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) is used to analyze endogenous bioactive substance change in healthy controls and patients with liver cirrhotic ascites. A metabolic fingerprint spectrum was established for the analysis. The results show that metabolic profiling of the serum indicates significant differences between the controls and the patients. Except for the tyrosine content which was decreased in the serum, the other 12 amino acids and 8 conjugated bile acids were significantly increased compared to controls (p < 0.01). Additionally, the 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) of serum were significantly decreased in the patients with liver cirrhotic ascites. In conclusion, the lysophosphatidylcholines C18:0, C18:2 and C16:1 are potential biomarkers. Moreover, the bile acid metabolism, amino acid metabolism and 5-HT as well as 5-HIAA metabolites are significantly changed in patients with cirrhotic ascites. These endogenous metabolites are potential biomarkers used for the diagnosis and treatment of liver fibrosis and cirrhosis.
A Case of Childhood Vitrectomy Performed for Dense Vitreous Hemorrhage Secondary to Leukemia Therapy and Tumor Lysis Syndrome
Authors: Kudo Takashi , Suzuki Yukihiko , Metoki Tomomi , Nakazawa Mitsuru
Published: January 2015

Purpose: To report a case of vitrectomy performed in a child with dense massive vitreous hemorrhage due to secondary acute myelogenous leukemia (AML) and tumor lysis syndrome. Case: A 4-year-old boy with clear-cell renal cell carcinoma was successfully treated with chemotherapy in 2011. However, in May 2012, he developed secondary AML. Although he was treated with combined chemotherapy and radiation, tumor lysis syndrome occurred with renal and heart failure complications. After an ultrasound examination by pediatricians found bilateral subretinal protrusions, he was referred to our clinic. Fundus examinations confirmed that the protrusions were bilateral subretinal or choroidal hemorrhages. A few weeks later, dense vitreous hemorrhages occurred bilaterally, and he completely lost vision in both eyes. Electroretinograms were extinguished in both eyes. After improvement of his general condition, we performed a 25-gauge vitrectomy combined with lens extraction in his left eye in December 2012. After removal of the vitreous hemorrhage, we found the subretinal hemorrhage had already been absorbed, leaving a mottled fundus color. However, the optic disc was not pale. Nine months after the surgery, his best-corrected visual acuity finally improved to 0.1. Conclusion: We successfully treated a case of severe vitreous hemorrhage secondary to leukemia therapy and tumor lysis syndrome using 25-gauge vitrectomy. This procedure may be safe and effective to perform, even in children with complications.