bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural learning in feedforward and feedback control
Authors: Yousif Nada , Diedrichsen Jörn
Published: August 2012

For smooth and efficient motor control, the brain needs to make fast corrections during the movement to resist possible perturbations. It also needs to adapt subsequent movements to improve future performance. It is important that both feedback corrections and feedforward adaptation need to be made based on noisy and often ambiguous sensory data. Therefore, the initial response of the motor system, both for online corrections and adaptive responses, is guided by prior assumptions about the likely structure of perturbations. In the context of correcting and adapting movements perturbed by a force field, we asked whether these priors are hard wired or whether they can be modified through repeated exposure to differently shaped force fields. We found that both feedback corrections to unexpected perturbations and feedforward adaptation to a new force field changed, such that they were appropriate to counteract the type of force field that participants had experienced previously. We then investigated whether these changes were driven by a common mechanism or by two separate mechanisms. Participants experienced force fields that were either temporally consistent, causing sustained adaptation, or temporally inconsistent, causing little overall adaptation. We found that the consistent force fields modified both feedback and feedforward responses. In contrast, the inconsistent force field modified the temporal shape of feedback corrections but not of the feedforward adaptive response. These results indicate that responses to force perturbations can be modified in a structural manner and that these modifications are at least partly dissociable for feedback and feedforward control.
Tar Barreler’s Hump: An Unusual Presentation of a Posttraumatic Pseudolipoma
Authors: Olubaniyi Babajide Olusola , Sidhu Harbir , Long Alex , de-Sousa Nigel , Redfern Andrew
Published: August 2012

This is an interesting paper of a 4 cm posttraumatic pseudolipoma on the back of the neck of an adult man who has participated in “tar barrel rolling” since adolescence. To the best of our knowledge, this is the first case of a pseudolipoma to be reported in the literature in association with tar barreling.
Mitochondrial Dynamics and Mitophagy in the 6-Hydroxydopamine Preclinical Model of Parkinson's Disease
Authors: Galindo Maria F. , Solesio Maria E. , Atienzar-Aroca Sandra , Zamora Maria J. , Jordán Bueso Joaquín
Published: August 2012

We discuss the participation of mitochondrial dynamics and autophagy in the 6-hydroxidopamine-induced Parkinson’s disease model. The regulation of dynamic mitochondrial processes such as fusion, fission, and mitophagy has been shown to be an important mechanism controlling cellular fate. An imbalance in mitochondrial dynamics may contribute to both familial and sporadic neurodegenerative diseases including Parkinson’s disease. With special attention we address the role of second messengers as the role of reactive oxygen species and the mitochondria as the headquarters of cell death. The role of molecular signaling pathways, for instance, the participation of Dynamin-related protein 1(Drp1), will also be addressed. Furthermore evidence demonstrates the therapeutic potential of small-molecule inhibitors of mitochondrial division in Parkinson’s disease. For instance, pharmacological inhibition of Drp1, through treatment with the mitochondrial division inhibitor-1, results in the abrogation of mitochondrial fission and in a decrease of the number of autophagic cells. Deciphering the signaling cascades that underlie mitophagy triggered by 6-OHDA, as well as the mechanisms that determine the selectivity of this response, will help to better understand this process and may have impact on human treatment strategies of Parkinson’s disease.
Congenital Tongue Base Cyst Presenting with Laryngeal Stridor in Youth: A Case Report
Authors: Zaki Zouheir , Ouattassi Naouar , Alami Noureddine
Published: August 2012

Introduction. Tongue base cyst is an uncommon but potentially dangerous cause of stridor in neonates and infants.Case Presentation. We report a case of a 2-month-old Arabic male infant with a congenital tongue base cyst revealed by inspiratory stridor and recurrent respiratory distress. Diagnosis of cyst was suspected at endoscopy and confirmed by MRI imaging. The cyst was marsupialized with CO2laser. One year later, the child remains asymptomatic without recurrence of the mass.Conclusion. Tongue base cysts should be considered in differential diagnosis in new borns with stridor, respiratory difficulties, or swallowing problems. Definitive therapy requires large marsupialization under general anesthesia.
New Nonlinear Conditions and Inequalities for the Existence of Coincidence Points and Fixed Points
Authors: Du Wei-Shih , Zheng Shao-Xuan
Published: August 2012

Some new fixed point theorems for nonlinear maps are established. By using these results, we can obtain some new coincidence point theorems. Our results are quite different in the literature and references therein.
Hypertrophic Cardiomyopathy Mimicking Acute Anterior Myocardial Infarction Associated with Sudden Cardiac Death
Authors: Daralammouri Y. , El Garhy M. , Same K. , Lauer B.
Published: August 2012

Hypertrophic cardiomyopathy is the most common genetic disease of the heart. We report a rare case of hypertrophic obstructive cardiomyopathy mimicking an acute anterior myocardial infarction associated with sudden cardiac death. The patient presented with acute ST elevation myocardial infarction and significant elevation of cardiac enzymes. Cardiac catheterization showed some atherosclerotic coronary artery disease, without significant stenosis. Echocardiography showed left ventricular hypertrophy with a left ventricular outflow tract obstruction; the pressure gradient at rest was 20 mmHg and became severe with the Valsalva maneuver (100 mmHg). There was no family history of sudden cardiac death. Six days later, the patient suffered a syncope on his way to magnetic resonance imaging. He was successfully resuscitated by ventricular fibrillation.
Mulberry Fruit Extract Protects against Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia
Authors: Kaewkaen Pratchaya , Tong-un Terdthai , Wattanathorn Jintanaporn , Muchimapura Supaporn , Kaewrueng Wiroje , Wongcharoenwanakit Sathaporn
Published: August 2012

Nowadays, the preventive strategy of vascular dementia, one of the challenge problems of elderly, has received attention due to the limitation of therapeutic efficacy. In this study, we aimed to determine the protective effect and possible mechanism of action of mulberry fruit extract on memory impairment and brain damage in animal model of vascular dementia. Male Wistar rats, weighing 300–350?g, were orally given mulberry extract at doses of 2, 10 and 50?mg/kg at a period of 7 days before and 21 days after the occlusion of right middle cerebral artery (Rt.MCAO). It was found that rats subjected to mulberry fruits plus Rt.MCAO showed the enhanced memory, the increased densities of neuron, cholinergic neuron, Bcl-2-immunopositive neuron together with the decreased oxidative stress in hippocampus. Taken all data together, the cognitive enhancing effect of mulberry fruit extract observed in this study might be partly associated with the increased cholinergic function and its neuroprotective effect in turn occurs partly via the decreased oxidative stress and apoptosis. Therefore, mulberry fruit is the potential natural cognitive enhancer and neuroprotectant. However, further researches are essential to elucidate the possible active ingredient.
A New Numerical Solution of Maxwell Fluid over a Shrinking Sheet in the Region of a Stagnation Point
Authors: Motsa S. S. , Khan Y. , Shateyi S.
Published: August 2012

The mathematical model for the incompressible two‐dimensional stagnation flow of a
Maxwell fluid towards a shrinking sheet is proposed. The developed equations are used to discuss the
problem of being two dimensional in the region of stagnation point over a shrinking sheet. The nonlinear partial
differential equations are transformed to ordinary differential equations by first‐taking boundary‐layer
approximations into account and then using the similarity transformations. The obtained equations are
then solved by using a successive linearisation method. The influence of the pertinent fluid parameters
on the velocity is discussed through the help of graphs.
Investigating the Impacts of Intraregional Trade and Aid on Per Capita Income in Africa: Case Study of the ECOWAS
Authors: Adom Assandé Désiré
Published: August 2012

In the past 50 years, a striking stylized fact has been the downward—or flat—trend of intra-African trade as a share of Africa’s total trade, while official development assistance (ODA) has experienced a noticeable expansion. During the same period, economic growth performances have not been consistent and robust enough to put a dent in the poverty level across the African continent in general and the Economic Community of West African States (ECOWAS) in particular. Using a two-stage least square (TSLS) estimation technique, this paper finds out that intra-ECOWAS trade stimulates per capita income growth substantially more than foreign aid, which rather constitutes an impediment to that growth in most specifications. Additionally, comparable results are obtained when the scope of the study is expanded to include trade of ECOWAS members with the rest of the world. As a result, it becomes appropriate to suggest policy recommendations encouraging increased cooperation among member states in an attempt to (i) expand and build new cross-states infrastructures, aimed at boosting communications and telecommunications networks, (ii) accelerate the trade facilitation process by addressing administrative red tapes that balloon both transaction costs and delays in the flows of goods across borders, seaports, and airports, and (iii) develop and diversify the industrial base in member states.
Automatic Generation of Optimized and Synthesizable Hardware Implementation from High‐Level Dataflow Programs
Authors: Jerbi Khaled , Raulet Mickaël , Déforges Olivier , Abid Mohamed
Published: August 2012

In this paper, we introduce the Reconfigurable Video Coding (RVC) standard based on the idea that video processing algorithms can be defined as a library of components that can be updated and standardized separately. MPEG RVC framework aims at providing a unified high‐level specification of current MPEG coding technologies using a dataflow language called Cal Actor Language (CAL). CAL is associated with a set of tools to design dataflow applications and to generate hardware and software implementations. Before this work, the existing CAL hardware compilers did not support high‐level features of the CAL. After presenting the main notions of the RVC standard, this paper introduces an automatic transformation process that analyses the non‐compliant features and makes the required changes in the intermediate representation of the compiler while keeping the same behavior. Finally, the implementation results of the transformation on video and still image decoders are summarized. We show that the obtained results can largely satisfy the real time constraints for an embedded design on FPGA as we obtain a throughput of 73 FPS for MPEG 4 decoder and 34 FPS for coding and decoding process of the LAR coder using a video of CIF image size. This work resolves the main limitation of hardware generation from CAL designs.
Influence of Annealing and UV Irradiation on Hydrophilicity of Ag‐TiO2 Nanostructured Thin Films
Authors: Meng Fanming , Sun Zhaoqi , Song Xueping
Published: August 2012

Ag‐TiO2 nanostructured thin films with silver content of 5 vol% have been deposited on silicon, glass, and quartz substrates by RF magnetron sputtering and annealed in ambient air at 900°C for 15, 30, 60, 90, and 120 min. Their crystal structure, surface morphology, and hydrophilicity have been characterized by X‐ray diffractometer, atomic force microscope, and water contact angle apparatus, respectively. The influence of annealing time and UV irradiation time on hydrophilic property of Ag‐TiO2 thin films have been studied in detail. It is shown that annealing time influences crystal structure of Ag‐TiO2 thin films. The unannealed film is amorphous and shows poor hydrophilicity. With the increase of annealing time from 15 to 120 min, the grain‐size slowly increases and tends to uniformity. A suitable annealing time can significantly enhance the hydrophilic behavior of Ag‐TiO2 films. Water contact angle decreases with the increase of irradiation time. The mechanism of hydrophilicity has been proposed and can be attributed to the increase of oxygen anion radicals and reactive center of surface Ti3+.
Mullerian Adenosaroma of the Cervix with Sarcomatous Overgrowth and Heterologous Elements Presenting as a Recurrent Cervical Polyp
Authors: Charfi Slim , Kallel Rim , Mnif Hela , Ellouze Sameh , Dhouib Mohamed , Guermazi Mohamed , Khabir Abdelmajid , Sellami-Boudawara Tahya
Published: August 2012

Mullerian adenosarcoma of the cervix is a rare tumor composed of benign epithelial and malignant stromal components. Sarcomatous overgrowth and heterologous elements in cervical adenosarcoma are extremely infrequent. We report the case of a 26-year-old woman admitted at the gynaecology department for a painless mass protruding from her vagina. The initial pathological exam concluded to endocervical polyp. Six months later, the patient was readmitted with a recurrence of the polyp. The pathological exam demonstrated interlacing fascicles of elongated spindle cells with few mitotic activity and no glandular formation. After reviewing of the initial polyp the diagnosis of mullerian adenosarcoma was suggested. A second recurrence of the polyp was noted one month later. Histopathological exam of the recurrent polyp confirmed the diagnosis of adenosarcoma with sarcomatous overgrowth and heterologous elements. The patient was lost for follow-up. Cervical adenosarcoma with sarcomatous overgrowth and heterologous element is a rare tumor that occurs in younger age in contrast to endometrium/corpus uterin mullerian adenosarcoma. In young women with recurrent cervical polyp, mullerian adenosarcoma must be considered and should be excluded by careful histopathological exam. Sarcomatous overgrowth and myometrial invasion are the most important prognostic factors. Treatment strategy is still unclear.
Vitiligo in a Patient Treated with Interferon Alpha-2a for Behçet’s Disease
Authors: Guney Esra , Akcali Gulunay , Akcay Betul Ilkay , Unlu Cihan , Erdogan Gurkan , Bozkurt Tahir Kansu , Bayramlar Huseyin
Published: August 2012

Behçet’s disease (BD) and vitiligo are diseases of unknown etiology. Interferon (IFN) alpha therapy is commonly used in Behçet uveitis. Interferon treatment in various diseases have also been observed causing certain autoimmune diseases such as vitiligo because of its immunomodulatory activity. The association between IFN therapy and vitiligo has been reported in the literature. We report a 21-year-old man with BD in whom vitiligo occurred during IFN treatment. To the best of our knowledge, this is the first reported case of such an association.
Tuboovarian Abscess due to Colonic Diverticulitis in a Virgin Patient with Morbid Obesity: A Case Report
Authors: Tuncer Zafer Selçuk , Boyraz Gokhan , Yücel Senem Özge , Selçuk İlker , Yazicioğlu Aslıhan
Published: August 2012

Since tuboovarian abscess is almost always a complication of pelvic inflammatory disease, it is rarely observed in virgins. A 30-year-old virgin patient presented with pelvic pain, fever, and vaginal spotting for the previous three weeks. Her abdominopelvic computed tomography scan revealed bilateral multiseptated cystic masses with prominent air-fluid levels suggesting tuboovarian abscesses. The sigmoid colon was lying between two tuboovarian masses, and its borders could not be distinguished from the ovaries. The patient was presumed to have bilateral tuboovarian abscesses which developed as a complication of the sigmoid diverticulitis. She was administered intravenous antibiotic therapy followed by percutaneous drainage under ultrasonographic guidance. She was discharged on the twenty second day with prominent clinical and radiological improvement. Diverticulitis may be a reason for development of tuboovarian abscess in a virgin patient. Early recognition of the condition with percutaneous drainage in addition to antibiotic therapy helps to have an uncomplicated recovery.
An Interdisciplinary Approach for Rehabilitating a Patient with Amelogenesis Imperfecta: A Case Report
Authors: Khodaeian Niloufar , Sabouhi Mahmoud , Ataei Ebrahim
Published: August 2012

Amelogenesis imperfecta (AI) has been defined as a group of hereditary enamel defects. It can be characterized by enamel hypoplasia, hypomaturation, or hypocalcification of the teeth. AI may be associated with some other dental and skeletal developmental defects. Restoration for patients with this condition should be oriented toward the functional and esthetic rehabilitation. This clinical report describes the oral rehabilitation of a young patient diagnosed with the hypoplastic type of AI in posterior teeth and hypomatured type of AI in anterior teeth.
Redox Regulation of Protein Function via Cysteine S-Nitrosylation and Its Relevance to Neurodegenerative Diseases
Authors: Akhtar Mohd Waseem , Sunico Carmen R. , Nakamura Tomohiro , Lipton Stuart A.
Published: August 2012

Debilitating neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), can be attributed to neuronal cell damage in specific brain regions. An important hallmark of these diseases is increased oxidative and nitrosative stress that occurs via overproduction of highly reactive free radicals known as reactive oxygen species (ROS) and reactive nitrogen species (RNS). These molecules are normally removed by cellular antioxidant systems. Under physiological conditions, ROS/RNS are present at low levels, mediating several neurotrophic and neuroprotective signaling pathways. In contrast, under pathological conditions, there is a pronounced increase in ROS/RNS generation, impairing normal neurological function. Nitric oxide (NO) is one such molecule that functions as a signaling agent under physiological conditions but causes nitrosative stress under pathological conditions due to its enhanced production. As first reported by our group and colleagues, the toxic effects of NO can be in part attributed to thiol S-nitrosylation, a posttranslational modification of cysteine residues on specific proteins. Here, we review several reports appearing over the past decade showing that S-nitrosylation of an increasing number of proteins compromises important cellular functions, including mitochondrial dynamics, endoplasmic reticulum (ER) protein folding, and signal transduction, thereby promoting synaptic damage, cell death, and neurodegeneration.
Reaction of N‐alkylisatins with 4‐(2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)thiosemicarbazide
Authors: Dinh Thanh Nguyen , Giang Nguyen Thi Kim
Published: August 2012

Some N‐alkylisatins were converted to corresponding thiosemicarbazones by reaction with 4‐(2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)thiosemicarbazide using microwave‐assisted heating method. The structure of products have been confirmed by IR, NMR, and mass spectra.
Investigation of the Orientation of CTA+ Ions in the Interlayer of CTAB Pillared Montmorillonite
Authors: Karaca Semra , Gürses Ahmet , Ejder Korucu Mehtap
Published: August 2012

The orientation of CTA+ in the interlayer of organic pillared montmorillonite prepared by adding different amounts of surfactant corresponding to the CEC of the pristine clay mineral has been studied using X‐ray diffraction (XRD), Fourier Transform Infrared (FTIR) spectra. Morphology of the samples was examined by scanning electron microscopy (SEM). The results are supported by the measurements of zeta potentials and contact angles of pristine clay and organoclay samples. From the XRD results, a series of arrangement models of CTA+ in the interlayer of montmorillonite have been proposed as lateral‐bilayer, pseudotrilayer, paraffin‐type‐monolayer and pseudotrilayer, paraffin‐type‐bilayer and pseudotrilayer for 0.5, 1, 1.5, and 2.0 CEC, respectively. FTIR spectrum and contact angle measurements of pristine montmorillonite and organoclays indicated the incorporation of surfactant and the changing of hydrophility in the different OMts. This study demonstrates that not only the arrangement model of surfactant, but also the morphology of organoclay strongly depends on the surfactant packing density within the montmorillonite interlayer space. In addition, it can be also proposed that, the magnitude of surface charge or its distribution on clay mineral might be an important factor for expansion characteristics of organoclay.
Poly‐β‐hydroxybutyrate (PHB) Depolymerase from Fusarium solani Thom
Authors: Shivakumar Srividya
Published: August 2012

Fusarium solani Thom produced maximum PHB depolymerase by 48 h when grown in BHM containing 0.2%, w/v PHB, pH 8.0 at 25°C. Statistical optimization studies using Plackett Burman design of PHB depolymerase production yielded maximum PHB depolymerase activity after 2 days as against 4 days in the unoptimized conditions with a 2‐fold increase in activity. Partial purification of the extracellular poly‐β‐hydroxybutyrate (PHB) depolymerase PHAZFus from F. solani Thom by two steps using ammonium sulphate (80% saturation) and affinity chromatography using concanavalin‐A yielded 162.3‐fold purity and 63% recovery of protein. The enzyme composed of a single polypeptide chain of 85 KDa, as determined by SDS‐PAGE. The enzyme stained positive for glycoprotein by PAS staining. Optimum enzyme activity was detected at pH 7.0 and 55°C. The enzyme was stable at pH 7.0 and 55°C for 24 h with a residual activity of almost 85%. Paper chromatography revealed β‐hydroxybutyrate monomer as the major end product of PHB hydrolysis. Complete inhibition of the enzyme by 1 mM HgCl2 (100%) indicated the importance of essential disulfide bonds (cystine residues) for enzyme activity or probably for maintaining the native enzyme structure.
Clusterin Mediates TGF-β–Induced Epithelial–Mesenchymal Transition and Metastasis via Twist1 in Prostate Cancer Cells
Authors: Shiota Masaki , Zardan Anousheh , Takeuchi Ario , Kumano Masafumi , Beraldi Eliana , Naito Seiji , Zoubeidi Amina , Gleave Martin E.
Published: August 2012

TGF-β promotes epithelial–mesenchymal transition (EMT) and induces clusterin (CLU) expression, linking these genes to cancer metastasis. CLU is a pleiotropic molecular chaperone that confers survival and proliferative advantage to cancer cells. However, the molecular mechanisms by which TGF-β regulates CLU expression and CLU affects metastasis remain unknown. In this study, we report that the transcription factor Twist1 mediates TGF-β–induced CLU expression. By binding to E-boxes in the distal promoter region of CLU gene, Twist1 regulated basal and TGF-β–induced CLU transcription. In addition, CLU reduction reduced TGF-β induction of the mesenchymal markers, N-cadherin and fibronectin, thereby inhibiting the migratory and invasive properties induced by TGF-β. Targeted inhibition of CLU also suppressed metastasis in an in vivo model. Taken together, our findings indicate that CLU is an important mediator of TGF-β–induced EMT, and suggest that CLU suppression may represent a promising therapeutic option for suppressing prostate cancer metastatic progression. Cancer Res; 72(20); 5261–72. ©2012 AACR.
Vaccination with mRNA-Electroporated Dendritic Cells Induces Robust Tumor Antigen-Specific CD4+ and CD8+ T Cells Responses in Stage III and IV Melanoma Patients
Authors: Aarntzen Erik H. J. G. , Schreibelt Gerty , Bol Kalijn , Lesterhuis W. Joost , Croockewit Alexandra J. , de Wilt Johannes H. W. , van Rossum Michelle M. , Blokx Willeke A. M. , Jacobs Joannes F. M. , Duiveman-de Boer Tjitske , Schuurhuis Danita H. , Mus Roel , Thielemans Kris , de Vries I. Jolanda M. , Figdor Carl G. , Punt Cornelis J. A. , Adema Gosse J.
Published: August 2012

Purpose: Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) has multiple advantages compared to peptide loading. We investigated the immunologic and clinical responses to vaccination with mRNA-electroporated DC in stage III and IV melanoma patients.

Experimental design: Twenty-six stage III HLA*02:01 melanoma patients scheduled for radical lymph node dissection (stage III) and 19 melanoma patients with irresectable locoregional or distant metastatic disease (referred to as stage IV) were included. Monocyte-derived DC, electroporated with mRNA encoding gp100 and tyrosinase, were pulsed with keyhole limpet hemocyanin and administered intranodally. TAA-specific T-cell responses were monitored in blood and skin-test infiltrating lymphocyte (SKIL) cultures.

Results: Comparable numbers of vaccine-induced CD8+ and/or CD4+ TAA-specific T-cell responses were detected in SKIL cultures; 17/26 stage III patients and 11/19 stage IV patients. Strikingly, in this population, TAA-specific CD8+ T cells that recognize multiple epitopes and produce elevated levels of IFNγ upon antigenic challenge in vitro, were significantly more often observed in stage III patients; 15/17 versus 3/11 stage IV patients, P = 0.0033. In stage IV patients, one mixed and one partial response were documented. The presence or absence of IFNγ-producing TAA-specific CD8+ T cells in stage IV patients was associated with marked difference in median overall survival of 24.1 months versus 11.0 months, respectively.

Conclusion: Vaccination with mRNA-electroporated DC induces a broad repertoire of IFNγ producing TAA-specific CD8+ and CD4+ T-cell responses, particularly in stage III melanoma patients. Clin Cancer Res; 18(19); 5460–70. ©2012 AACR.
Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma
Authors: Bauer Daniel E. , Mitchell Chelsey M. , Strait Kelly M. , Lathan Christopher S. , Stelow Edward B. , Lüer Sonja C. , Muhammed Somala , Evans Andrew G. , Sholl Lynette M. , Rosai Juan , Giraldi Eugenia , Oakley Richard P. , Rodriguez-Galindo Carlos , London Wendy B. , Sallan Stephen E. , Bradner James E. , French Christopher A.
Published: August 2012

Purpose: NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.

Experimental Design: A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses.

Results: The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% [1-year PFS 15% (5–24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%–31% (1-year OS: 30% (27–34%)]. Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome.

Conclusions: NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival. Clin Cancer Res; 18(20); 5773–9. ©2012 AACR.
Response to Erlotinib in Patients with EGFR Mutant Advanced Non–Small Cell Lung Cancers with a Squamous or Squamous-like Component
Authors: Paik Paul K. , Varghese Anna M. , Sima Camelia S. , Moreira Andre L. , Ladanyi Marc , Kris Mark G. , Rekhtman Natasha
Published: August 2012

We previously reported that although EGFR mutations are not a feature of pure squamous cell carcinomas (SCC) of the lung, these mutations do occur in adenosquamous carcinomas (AD-SCC) and in rare solid adenocarcinomas, both of which can mimic SCC in small samples. Here we present an expanded series of these cases with a focus on sensitivity to erlotinib. The study included 13 patients with EGFR mutant lung carcinomas, which after detailed pathologic review were classified as AD-SCC (n = 11) or solid adenocarcinoma (n = 2). The majority received a diagnosis of SCC in at least 1 sample. All patients were treated with erlotinib. Eight of 11 patients with AD-SCC were evaluable for response. Their overall response rate was 88% (7/8; 95% CI, 47% to 99%). One of 2 solid adenocarcinoma patients responded to erlotinib. As a group, median progression-free survival was 12 months (95% CI, 8 to not reached); median overall survival was 29 months (95% CI, 27 to not reached). In conclusion, EGFR mutant AD-SCC and solid adenocarcinoma show a response to erlotinib that is comparable to that seen in patients with conventional adenocarcinoma. These tumors can mimic SCC in small samples. We propose an approach to increase the capture of these rare histology patients for EGFR mutation testing. Mol Cancer Ther; 11(11); 2535–40. ©2012 AACR.
Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies
Authors: Musrap Natasha , Diamandis Eleftherios P.
Published: August 2012

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in North American women. Given that EOC encompasses a broad class of tumors consisting of a variety of different histologic and molecular subtypes, which generates genetically and etiologically distinct tumors, several challenges arise during treatment of patients with this disease. Overlaying this complexity is the contribution of supporting cells, particularly stromal components such as fibroblasts and immune infiltrates that collectively create a microenvironment that promotes and enhances cancer progression. A notable example is the induction of angiogenesis, which occurs through the secretion of pro-angiogenic factors by both tumor and tumor-associated cells. The recent development of angiogenic inhibitors targeting tumor vasculature, which have been shown to improve patient outcome when combined with standard therapy, has launched a paradigm shift on how cancer patients should be treated. It is evident that future clinical practices will focus on the incorporation of therapies that antagonize the protumoral effects of such microenvironment contributors. Herein, an overview of the varying tumor–host interactions that influence tumor behavior will be discussed, in addition to the recent efforts undertaken to target these interactions and their potential to revolutionize EOC patient care. Mol Cancer Res; 10(10); 1254–64. ©2012 AACR.
Identification of Luminal Breast Cancers That Establish a Tumor-Supportive Macroenvironment Defined by Proangiogenic Platelets and Bone Marrow–Derived Cells
Authors: Kuznetsov Hanna S. , Marsh Timothy , Markens Beth A. , Castaño Zafira , Greene-Colozzi April , Hay Samantha A. , Brown Victoria E. , Richardson Andrea L. , Signoretti Sabina , Battinelli Elisabeth M. , McAllister Sandra S.
Published: August 2012

Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC “instigators”) establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors (“responders”). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2+ tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically.

Significance: Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which cancer patients are likely to relapse. Our findings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from adjuvant therapy. Cancer Discov; 2(12); 1150–65. ©2012 AACR.

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Conditioned Medium from Bone Marrow Mesenchymal Stem Cells Transiently Retards Osteoblast Differentiation by Downregulating Runx2
Authors: Sun Jing , Zhou Huifang , Deng Yuan , Zhang Yidan , Gu Ping , Ge Shengfang , Fan Xianqun
Published: August 2012

Mesenchymal stem cells (MSCs) are attractive candidates for cell therapy and regenerative medicine because of their potential for proliferation and multilineage differentiation. MSCs secrete various cytokines, acting as trophic mediators to regulate neighboring cells. Osteoblasts are the cells directly responsible for forming new bone, and they are the final target of many osteogenic regulators. However, the induction effect of MSCs on osteoblasts is still unknown. In this study, we isolated osteoblasts from rat calvariae and investigated their proliferation and differentiation under induction of varied concentrations of MSC-conditioned medium (MSC-CM). Cells in the MSC-CM groups showed a reduction in cell proliferation at 3–6 days, and a decrease in the expression of osteocalcin and osteopontin at 3 days, with low levels of alkaline phosphatase activity. The expression of osteogenic markers went back to normal at 7 days. In order to evaluate the molecular mechanisms underlying this suppression, levels of two osteoblastic transcription factors, runt-related transcription factor 2 (Runx2) and osterix (Osx), were detected at both mRNA and protein levels. The results indicated that MSC-CM significantly inhibited Runx2 expression in a concentration-dependent manner. However, the effect was not due to the inhibition of Osx, for Osx was not significantly altered. This work demonstrates that MSCs may suppress osteoblast proliferation and transiently retard osteoblast differentiation by downregulating Runx2. These results highlight the need to take into account the paracrine effect of MSCs when using them in regenerative medicine for the repair of bone defects.
A Prospective Analysis of Efficacy and Long-Term Outcome of Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Okada Hiroyuki , Takemoto Mitshuhiro , Kawahara Yoshiro , Nasu Junichiro , Takenaka Ryuta , Kawano Seiji , Inoue Masafumi , Ichimura Koichi , Tanaka Takehiro , Shinagawa Katsushi , Yoshino Tadashi , Yamamoto Kazuhide
Published: August 2012

Background/Aims: Few studies exist on the efficacy and long-term outcome of radiation therapy (RT) for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: Twenty-two patients with stage I or stage II1 disease were prospectively evaluated, including 14 patients without Helicobacter pylori(H. pylori) infection and 8 patients with persistent lymphoma after H. pylori eradication. RT dose was 30 Gy in daily fractions of 1.5 Gy. All patients underwent endoscopic and histological follow-up regularly. Results: The study included 22 patients with a mean age of 63 years. The t(11;18)(q21;q21) translocation occurred in 8 of the 22 cases. All patients showed complete remission without any serious toxicity. At a median follow-up evaluation 74 months (range 27–159) after completion of RT, the overall and relapse-free survival rates after 5 years were 91 and 84%, respectively. Although no patient showed local recurrence of lymphoma, distant recurrence was detected in 3 patients, all of whom were H. pylori negative; MALT lymphoma relapsed in two patients with the t(11;18)(q21;q21) translocation, and diffuse large-cell lymphoma developed in one patient without the translocation. Conclusion: RT provides excellent local control of the gastric MALT lymphoma. However, continuous follow-up is mandatory as relapse may occur in other sites.
Chikungunya Virus Induces a More Moderate Cytopathic Effect in Mosquito Cells than in Mammalian Cells
Authors: Li Yong-Gang , Siripanyaphinyo Uamporn , Tumkosit Uranan , Noranate Nitchakarn , A-nuegoonpipat Atchareeya , Tao Ran , Kurosu Takeshi , Ikuta Kazuyoshi , Takeda Naokazu , Anantapreecha Surapee
Published: August 2012

Objectives: Chikungunya virus (CHIKV) is an alphavirus belonging to the Togaviridae family. Alphaviruses cause a chronic non-cytopathic infection in mosquito cells, while they develop a highly cytopathic infection in cells originating from various vertebrates. In this study, we compared the cytopathic effect (CPE) induced by CHIKV in Vero cells and a mosquito cell line, C6/36 cells. Methods: CPE and the virus titers were compared between the CHIKV-infected C6/36 and Vero cells. Apoptosis was measured by TUNEL assay, and the differences between the C6/36 and Vero cells were compared. Results: CHIKV infection induced strong CPE and apoptosis in the Vero cells, but light CPE in the C6/36 cells. The virus titers produced in the C6/36 cells were much higher than those produced in the Vero cells. Conclusions: The reason CHIKV induced strong CPE is that this virus triggers strong apoptosis in Vero cells compared with C6/36 cells. CHIKV established a persistent infection in C6/36 cells after being passaged 20 times. CHIKV infection in mosquito cells was distinct from that in Vero cells. The cell and species specificity of CHIKV-induced cell death implies that the cellular and viral regulators involved in apoptosis may play an important role in determining the outcome of CHIKV infection.
A Novel Method for Three-Dimensional Analysis of Endoscopic Spatial Relationships of Pterygopalatine Fossa Structures and Associated Regions
Authors: Feng Guo-dong , Gao Zhi-qiang , Jiang Hong , Zha Yang , Shen Peng , Lv Wei
Published: August 2012

Background: The spatial orientation rules of the important skull base structures are essential for performing endoscopic surgery. However, there is no satisfactory three-dimensional (3-D) anatomy study available to the surgeon at present. The aims of this study are to construct a new method to learn the spatial orientation of anatomical features under endoscopy and to help the surgeon establish a 3-D image of skull base structures in his mind. Methods: A modified MicronTracker navigation system was used to measure the pitch angle, direction angle and distance from the reference points to various anatomical landmarks of the pterygopalatine fossa and related structures (PPFRS) at the skull base in 10 fresh cadavers (20 sides). Results: The location data of the positions of the major landmarks were acquired and a digital model of the anatomical structures of the PPFRS was built, which can be moved, whirled or demonstrated easily. Conclusion: It is practical to measure the positions of the anatomical structures of the PPFRS with a modified binocular vision-based MicronTracker navigation system. It is a valuable exploration tool to help the surgeon establish the orientation of surgical landmarks in his mind by the 3-D parameters and model.
Radiographic and Laser Fluorescence Methods Have No Benefits for Detecting Caries in Primary Teeth
Authors: Mendes F.M. , Novaes T.F. , Matos R. , Bittar D.G. , Piovesan C. , Gimenez T. , Imparato J.C.P. , Raggio D.P. , Braga M.M.
Published: August 2012

Clinical guidelines advise that dentists take radiographs in children to detect caries lesions missed by visual inspection; however, due to the current low caries prevalence in most countries, we hypothesized that the adjunct methods of caries detection would not significantly improve the detection of primary molar lesions in comparison to visual inspection alone. We evaluated the performance of visual inspection, alone or in combination with radiographic and laser fluorescence pen (LFpen) methods, in detecting occlusal and approximal caries lesions in primary molars. Two examiners evaluated children who had sought dental treatment with these diagnostic strategies. The reference standard involved the temporary separation of approximal and operative interventions for occlusal surfaces. The sensitivity, specificity, accuracy and utility of diagnostic strategies were calculated. Simultaneous combined strategies increased sensitivities but decreased specificities. Furthermore, no differences were observed in accuracy and utility, parameters more influenced by caries prevalence. In conclusion, adjunct radiographic and laser fluorescence methods offer no benefits to the detection of caries in primary teeth in comparison to visual inspection alone; hence, present clinical guidelines should be re-evaluated.
Taxanes for Ovarian Cancer during Pregnancy: A Systematic Review
Authors: Zagouri Flora , Sergentanis Theodoros N. , Chrysikos Dimosthenis , Filipits Martin , Bartsch Rupert
Published: August 2012

Objective: Ovarian cancer in pregnancy is uncommon; however, this diagnosis adds complexity to cancer treatment recommendations. This is the first systematic review to synthesize all available data and evaluate the efficacy and safety of taxanes during pregnancy in ovarian cancer. Methods: This systematic review was performed in accordance with PRISMA guidelines. All studies that examined the efficacy and safety of taxanes administered during pregnancy in ovarian cancer, regardless of sample size, were considered eligible. Results: Overall, 8 articles (11 pregnancies, 12 newborns) were retrieved for paclitaxel and 1 for docetaxel (1 pregnancy, 1 newborn). In 92.31% of cases a healthy child was born, with a median follow-up of 20 months. The mean weight of the babies at delivery was 2,381 g. One study providing follow-up until the 11th year of age reported a case of attention deficit disorder. In 6 out of 8 case reports providing survival data, the mother was alive and disease free at the end of follow-up (ranging from 9.75 to 45 months). Conclusion: Taxanes may play a significant role in the treatment of ovarian cancer patients during the 2nd and 3rd trimesters. Before that, the risk of abortion or congenital anomalies is increased.
Tibial Lymphoplasmacytic Plaque: A New, Illustrative Case of a Recently and Poorly Recognized Benign Lesion in Children
Authors: Moulonguet Isabelle , Hadj-Rabia Smaïl , Gounod Nicolas , Bodemer Christine , Fraitag Sylvie
Published: August 2012

Tibial lymphoplasmacytic plaque (TLP) is a recently recognized clinicopathological entity affecting children and is characterized by a linear, reddish brown plaque on the leg with a dense dermal lymphoplasmacytic infiltrate. No effective treatments are available for this lesion of unknown etiology and its course is chronic. We report a new case in which, for the first time, a causative factor (insect bite) is strongly suspected. The clinical and pathological features of TLP may be misleading for the uninformed dermatologist or pathologist. Therefore, we would like to draw attention to this very distinctive clinicopathological presentation in order to help them recognize it easily and prevent it from being misdiagnosed as an infectious disease or, above all, a cutaneous lymphoma. We will discuss the relationship between TLP and linear acral pseudolymphomatous angiokeratoma of children, a variant of pseudolymphoma localized on acral sites in children which may share some of TLP’s histopathological features.
High Frequency of Hypertrichosis after Cast Application
Authors: Akoglu Gulsen , Emre Selma , Metin Ahmet , Bozkurt Murat
Published: August 2012

Background: Hypertrichosis following cast application is commonly observed after removing casts, due to an unknown mechanism. Objective: To determine the frequency and associated demographic and clinical risk factors of postcast hypertrichosis in patients who underwent cast application for bone fractures. Methods: The study included 117 patients (50 females, 67 males, age range: 3–91 years). Demographic information of each patient (age, gender, fracture localization, type of cast, cast duration and pruritus) was recorded. After removing the cast, the presence of hypertrichosis, contact dermatitis and lymphedema of the cast area was evaluated. Demographic and clinical features of the patients were analyzed to determine the risk factors for postcast hypertrichosis. Results: Postcast hypertrichosis was detected in 34.2% of patients. Patients with hypertrichosis were younger than those without hypertrichosis (p = 0.015). Duration of cast application, session of cast application, presence of lymphedema, contact dermatitis and pruritus between patients with hypertrichosis and without hypertrichosis were similar (p > 0.05). Age was the only parameter independently associated with developing postcast hypertrichosis (OR: 0.97, 95% CI: 0.95–0.99; p = 0.008). The frequency of hypertrichosis peaked significantly between 12 and 25 years (p = 0.026). Conclusion: A significant number of patients with cast application developed hypertrichosis. Patient age was closely associated with postcast hypertrichosis.
Male Breast Cancer: Immunohistochemical Subtypes and Clinical Outcome Characterization
Authors: Sánchez-Muñoz Alfonso , Román-Jobacho Alicia , Pérez-Villa Lidia , Sánchez-Rovira Pedro , Miramón José , Pérez Diego , Sáez Maria-Isabel , de Luque Vanesa , Medina Laura , Ramírez-Tortosa César Luis , Vicioso Luis , Medina José Antonio , Ribelles Nuria , Alba Emilio
Published: August 2012

Aim: The aim of this study was to assess the molecular subtype profiles of male breast cancer (MBC) and subsequent clinical outcome using a validated 6-marker immunohistochemical panel. Methods: A total of 43 cases of MBC were examined retrospectively using a semiquantitative immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (Her2), epidermal growth factor receptor and cytokeratin 5/6. Patients were classified into the following categories: luminal A, luminal B, Her2-positive or basal-like subtypes. Results: The median age of patients was 63 years (r: 32–89). The predominant histology was invasive ductal carcinoma (91%). Only 1 patient had advanced breast cancer at diagnosis. Ninety-three percent were ER-positive and 84% were PR-positive. Two patients had tumors that were ER- and PR-negative. The distribution of tumor molecular subtypes was 19 (44%) luminal A, 22 (51%) luminal B and 2 (5%) basal-like. The Her2-positive tumor subtype was not identified. The clinicopathological characteristics did not differ significantly between tumor subtypes A and B. There were no significant differences in 6-year disease-free survival (74 vs. 82%, p = 0.77) or overall survival (74 vs. 82%, p = 0.69) between luminal A and luminal B subtypes, respectively. Conclusion: The most common subtypes in our cohort of MBC were luminal B followed by luminal A, and no differences were found between both tumor subtypes in terms of clinicopathologic characteristics and patient outcome.