bluuebunny/crossref_metadata_2025 huggingface dataset:
Wavelet-Based Frequency Response Function: Comparative Study of Input Excitation
Authors: Dziedziech K. , Staszewski W. J. , Uhl T.
Published: June 2014

Time-variant systems can be found in many areas of engineering. It is widely accepted that the classical Fourier-based methods are not suitable for the analysis and identification of such systems. The time-variant frequency response function—based on the continuous wavelet transform—is used in this paper for the analysis of time-variant systems. The focus is on the comparative study of various broadband input excitations. The performance of the method is tested using simulated data from a simple MDOF system and experimental data from a frame-like structure.
Silence of NLRP3 Suppresses Atherosclerosis and Stabilizes Plaques in Apolipoprotein E-Deficient Mice
Authors: Zheng Fei , Xing Shanshan , Gong Zushun , Mu Wei , Xing Qichong
Published: June 2014

Objectives. The role of the NLRP3 inflammasome in atherosclerosis remains controversial. The aim of this study was to determine whether inhibition of NLRP3 signaling by lentivirus-mediated RNA interference could reduce atherosclerosis and stabilizes plaques. We also tried to explore the mechanisms of the impact of NLRP3 inflammasome on atherosclerosis.Methods. Apolipoprotein E-deficient mice aged 8 weeks were fed a high-fat diet and were injected with NLRP3 interfering or mock viral suspension after 4 weeks. Lentivirus transfer was repeated in 2 weeks. Four weeks after the first lentivirus injection, we evaluated the effects of NLRP3 gene silencing on plaque composition and stability and on cholesterol efflux and collagen metabolism, by histopathologic analyses and real-time PCR.Results. Gene silence of NLRP3 prevented plaques progression and inhibited inductions of proinflammatory cytokines. Moreover, this RNA interference reduced plaque content of macrophages and lipid, and increased plaque content of smooth muscle cells and collagen, leading to the stabilizing of atherosclerotic plaques.Conclusions. NLRP3 inflammasomes may play a vital role in atherosclerosis, and lentivirus-mediated NLRP3 silencing would be a new strategy to inhibit plaques progression and to reduce local inflammation.
Jejunal Perforation: A Rare Presentation of Burkitt’s Lymphoma—Successful Management
Authors: Nayak Samir Ranjan , Rao Ganni Bhaskara , Yerraguntla Subramanya Sarma , Bodepudi Sisir
Published: June 2014

Malignant tumors of the small bowel presenting as acute abdomen are a rare occurrence. Burkitt’s lymphoma presenting as a surgical emergency needing emergency laparotomy is an uncommon presentation of this tumor. We present an interesting case of jejunal perforation as a first manifestation of Burkitt’s lymphoma which was successfully managed with surgical resection, high dose chemotherapy, and good supportive care.
Smart Bolts Monitoring Using Wireless Sensor Network: Implementation and Performance Evaluation
Authors: Baroudi Uthman , Al-Roubaiey Anas , Mekid Samir , Bouhraoua Abdelhafid , Garba Yau
Published: June 2014

Structural and industrial environments use hundreds to thousands of bolts to hold parts together. For most mechanical systems, the bolts are critical components because they are subject to axial tension triggering various failures; for example, compromised screw threadsand/or vibration caused untightening. Severe damages can result injury of personnel, equipment damage, and even loss of life. Typically, monitoring mechanical tension of the bolts is visually performed with red dot bolts or manually inspected, but this process is expensive in terms of effort, time, and money; additionally, perhaps the accessibility of the bolt itself is very difficult. Changing this tedious monitoring process to automated, quick, and precise process is our concern in this work. Nowadays, wireless sensor networks (WSN) have wide range of applications especially in surveillance and monitoring systems. In this paper, we propose an efficient and power-aware technique to monitor bolted joints using wireless sensor networks. Also, due to the randomization placement of bolts in real world, our proposed mechanisms have been studied with different deployment node distributions (grid, uniform, normal, and exponential). Furthermore, we have investigated different scenarios with different probability of bolt failures to explore their effect on power consumption and network lifetime.
Differential Diagnostics of Pain in the Course of Trigeminal Neuralgia and Temporomandibular Joint Dysfunction
Authors: Pihut M. , Szuta M. , Ferendiuk E. , Zeńczak-Więckiewicz D.
Published: June 2014

Chronic oral and facial pain syndromes are an indication for intervention of physicians of numerous medical specialties, while the complex nature of these complaints warrants interdisciplinary diagnostic and therapeutic approach. Oftentimes, lack of proper differentiation of pain associated with pathological changes of the surrounding tissues, neurogenic pain, vascular pain, or radiating pain from idiopathic facial pain leads to improper treatment.The objective of the paperis to provide detailed characterization of pain developing in the natural history of trigeminal neuralgia and temporomandibular joint dysfunction, with particular focus on similarities accounting for the difficulties in diagnosis and treatment as well as on differences between both types of pain. It might seem that trigeminal neuralgia can be easily differentiated from temporomandibular joint dysfunction due to the acute, piercing, and stabbing nature of neuralgic pain occurring at a single facial location to spread along the course of the nerve on one side, sometimes a dozen or so times a day, without forewarning periods. Both forms differ significantly in the character and intensity of pain. The exact analysis of the nature, intensity, and duration of pain may be crucial for the differential diagnostics of the disorders of our interest.
Effects of a Fluctuating Carrying Capacity on the Generalized Malthus-Verhulst Model
Authors: Calisto Héctor , Chandía Kristopher J. , Bologna Mauro
Published: June 2014

We consider a generalized Malthus-Verhulst model with a fluctuating carrying capacity and we study its effects on population growth. The carrying capacity fluctuations are described by a Poissonian process with an exponential correlation function. We will find an analytical expression for the average of a number of individuals and show that even in presence of a fluctuating carrying capacity the average tends asymptotically to a constant quantity.
Cost-Sensitive Learning for Emotion Robust Speaker Recognition
Authors: Li Dongdong , Yang Yingchun , Dai Weihui
Published: June 2014

In the field of information security, voice is one of the most important parts in biometrics. Especially, with the development of voice communication through the Internet or telephone system, huge voice data resources are accessed. In speaker recognition, voiceprint can be applied as the unique password for the user to prove his/her identity. However, speech with various emotions can cause an unacceptably high error rate and aggravate the performance of speaker recognition system. This paper deals with this problem by introducing a cost-sensitive learning technology to reweight the probability of test affective utterances in the pitch envelop level, which can enhance the robustness in emotion-dependent speaker recognition effectively. Based on that technology, a new architecture of recognition system as well as its components is proposed in this paper. The experiment conducted on the Mandarin Affective Speech Corpus shows that an improvement of 8% identification rate over the traditional speaker recognition is achieved.
Potential ofPleurotus ostreatusMycelium for Selenium Absorption
Authors: Milovanović Ivan , Brčeski Ilija , Stajić Mirjana , Korać Aleksandra , Vukojević Jelena , Knežević Aleksandar
Published: June 2014

The aim of this study was to evaluate the effect of high selenium (Se) concentrations on morphophysiological and ultrastructural properties ofPleurotus ostreatus. Mycelium growth was good in media enriched with 5.0, 10.0, and 20.0 mg L−1of Se, concentration of 500.0 mg L−1strongly inhibited growth, and 1000.0 mg L−1was the minimum inhibitory concentration. Contrary to thin-walled, hyaline, branched, and anastomized hyphae with clamp-connections in the control, at Se concentrations of 100.0 and 500.0 mg L−1, they were noticeably short, frequently septed and branched, with a more intensive extracellular matrix, and without clamp-connections. At high Se concentrations, hyphae with intact membrane, without cellular contents, with a high level of vacuolization, and with numerous proteinaceous bodies were observed. Biomass yield ranged between 11.8 g L−1, in the control, and 6.8 g L−1, at an Se concentration of 100.0 mg L−1, while no production was detected at a concentration of 500.0 mg L−1. Se content in the mycelia reached a peak (938.9 μg g−1) after cultivation in the medium enriched with Se at the concentration of 20.0 mg L−1, while the highest absorption level (53.25%) was found in the medium enriched with 5.0 mg L−1Se.
Diazepam Potentiates the Antidiabetic, Antistress and Anxiolytic Activities of Metformin in Type-2 Diabetes Mellitus with Cooccurring Stress in Experimental Animals
Authors: Garabadu Debapriya , Krishnamurthy Sairam
Published: June 2014

Psychological stress is considered as one of the limiting factors in the management of type-2 diabetes mellitus (T2DM). Therefore, the basic objective of the present study was to evaluate the antidiabetic effect of metformin, diazepam, and their combination in cooccurring T2DM and stress condition (DMS). T2DM was induced in the male rats by administering streptozotocin (45 mg/kg,i.p.) and nicotinamide (110 mg/kg,i.p.) with time lag of 15 min. Rats were subjected to two sessions of cold restraint stress paradigm for one hour on the sixth and seventh day after streptozotocin injection. Administration of metformin (25 mg/kg,p.o.) and diazepam (1 mg/kg,p.o.) in combination from the seventh to thirteenth day after streptozotocin injection showed better improvement in glucose tolerance and insulin sensitivity compared to monotherapy of either drug. In addition, the combination significantly attenuated DMS-induced hyperglycemia, hypertriglyceridaemia, hypercorticosteronemia, anxiety-like behavior, and insulin resistance through modulating insulin signaling pathway in the liver compared to monotherapy. Further, improvement of mitochondrial function, integrity, and oxidative stress in hippocampus, hypothalamus, prefrontal cortex, striatum, amygdala, and nucleus accumbens was observed with the combination. Therefore, metformin in combination with diazepam may be a better therapeutic option in the management of T2DM with cooccurring stress condition.
Gunshot Wound in Lumbar Spine with Intradural Location of a Bullet
Authors: Bordon G. , Burguet Girona S.
Published: June 2014

The presence of a migratory bullet in the spinal canal after a gunshot injury is a rare finding, specially without causing permanent neurologic damage. We present the case of a patient who suffered a gunshot wound with an entry point in the posterior arc of L2-L3 and a migratory bullet detected at the level of L5-S1 in the CT scan. The patient complained about intense headache, dizziness, and variable sensitive impairment in lower legs apparently depending on the patient’s position in bed. We decided to remove the bullet in order to prevent the delayed neurological damage and lead toxicity. We discuss technical details of this surgery.
Damage Detection of Bridges Using Vibration Data by Adjoint Variable Method
Authors: Mirzaee Akbar , Shayanfar Mohsenali , Abbasnia Reza
Published: June 2014

This research entails a theoretical and numerical study on a new damage detection method for bridges, using response sensitivity in time domain. This method, referred to as “adjoint variable method,” is a finite element model updating sensitivity based method. Governing equation of the bridge-vehicle system is established based on finite element formulation. In the inverse analysis, the new approach is presented to identify elemental flexural rigidity of the structure from acceleration responses of several measurement points. The computational cost of sensitivity matrix is the main concern associated with damage detection by these methods. The main advantage of the proposed method is the inclusion of an analytical method to augment the accuracy and speed of the solution. The reliable performance of the method to precisely identify the location and intensity of all types of predetermined single, multiple, and random damages over the whole domain of moving vehicle speed is shown. A comparison study is also carried out to demonstrate the relative effectiveness and upgraded performance of the proposed method in comparison to the similar ordinary sensitivity analysis methods. Moreover, various sources of errors including the effects of noise and primary errors on the numerical stability of the proposed method are discussed.
Suspected Transfusion Related Acute Lung Injury Improving following Administration of Tranexamic Acid: A Case Report
Authors: Ryniak Stan , Harbut Piotr , Östlund Anders , Mysiak Andrzej , Jakobsson Jan G.
Published: June 2014

A 16-year-old woman with craniofacial injury developed severe acute respiratory failure under the primary reconstructive surgical procedure requiring several units of blood and plasma. A transfusion related acute lung injury (TRALI) was suspected and supportive treatment was initiated. Because of the severity of symptoms, acute extracorporeal membrane oxygenation (ECMO) was planned. During preparation for ECMO, a single intravenous dose, 1 g of tranexamic acid, was administered and a remarkable improvement was observed shortly thereafter. The patient was placed on ECMO for 16 hours. The further course was uncomplicated and the patient was discharged from ICU on the 6th day after admission fully and she recovered. A clinical improvement was observed in a timely fashion following the administration of tranexamic acid. The handling of a suspected TRALI and potential benefit from administration of tranexamic acid are discussed in this case report.
A Disturbance Rejection Framework for the Study of Traditional Chinese Medicine
Authors: Zhang Han , Sun Yan , Gao Zhiqiang , Wang Yueqi
Published: June 2014

The traditional Chinese medicine (TCM) is explained in the language of engineering cybernetics (EC), an engineering science with the tradition of rigor and long history of practice. The inherent connection is articulated between EC, as a science of interrelations, and the Chinese conception of Wuxing. The combined cybernetic model of Wuxing seems to have significant explaining power for the TCM and could potentially facilitate better communications of the insights of the TCM to the West. In disturbance rejection, an engineering concept, a great metaphor, is found to show how the TCM is practiced, using the liver cancer pathogenesis and treatment as a case study. The results from a series of experimental studies seem to lend support to the cybernetic model of Wuxing and the principles of disturbance rejection.
Biomechanical Evaluation of Ascending Aortic Aneurysms
Authors: Avanzini Andrea , Battini Davide , Bagozzi Lorenzo , Bisleri Gianluigi
Published: June 2014

The biomechanical properties of ascending aortic aneurysms were investigated only in the last decade in a limited number of studies. Indeed, in recent years, there has been a growing interest in this field in order to identify new predictive parameters of risk of dissection, which may have clinical relevance. The researches performed so far have been conducted according to the methods used in the study of abdominal aortic aneurysms. In most cases, uniaxial or biaxial tensile tests were used, while in a smaller number of studies other methods, such as opening angle, bulge inflation, and inflation-extension tests, were used. However, parameters and protocols of these tests are at present very heterogeneous in the studies reported in the literature, and, therefore, the results are not comparable and are sometimes conflicting. The purpose of this review then thence to provide a comprehensive analysis of the experimental methodology for determination of biomechanical properties in the specific field of aneurysms of the ascending aorta to allow for better comparison and understanding of the results.
2D Geoelectric Imaging of the Uneme-Nekhua Fracture Zone
Authors: Aminu Muslim B. , Akande Tunde M. , Ishola Olubukola A.
Published: June 2014

We have employed 2D geoelectric imaging to reveal the geometry and nature of a fracture zone in Uneme-Nekhua, southwestern Nigeria. The fracture zone is discernable from an outcropping rock scarp and appears to define the course of a seasonal stream. Data were acquired using the dipole-dipole survey array configuration with electrode separation of 6 m and a maximum dipole length of 60 m. Three traverses with lengths varying between 72 m and 120 m were laid orthogonal to the course of the seasonal stream. 2D geoelectric images of the subsurface along the profiles imaged a north-south trending fracture zone. This fracture zone appears to consist of two vertical fractures with more intense definition downstream. The eastern fracture is buried by recent sediment, while the western fracture appears to have experienced more recent tectonic activity as it appears to penetrate through the near surface. Perhaps at some point, deformation ceased on the eastern fracture and further strain was transferred to the western fracture. The fracture zone generally defines the course of the north-south seasonal stream with the exception of the downstream end where the fracture appears to have died out entirely. Two associated basement trenches lying parallel to and east of the fracture zone are also imaged.
The Domain Landscape of Virus-Host Interactomes
Authors: Zheng Lu-Lu , Li Chunyan , Ping Jie , Zhou Yanhong , Li Yixue , Hao Pei
Published: June 2014

Viral infections result in millions of deaths in the world today. A thorough analysis of virus-host interactomes may reveal insights into viral infection and pathogenic strategies. In this study, we presented a landscape of virus-host interactomes based on protein domain interaction. Compared to the analysis at protein level, this domain-domain interactome provided a unique abstraction of protein-protein interactome. Through comparisons among DNA, RNA, and retrotranscribing viruses, we identified a core of human domains, that viruses used to hijack the cellular machinery and evade the immune system, which might be promising antiviral drug targets. We showed that viruses preferentially interacted with host hub and bottleneck domains, and the degree and betweenness centrality among three categories of viruses are significantly different. Further analysis at functional level highlighted that different viruses perturbed the host cellular molecular network by common and unique strategies. Most importantly, we creatively proposed a viral disease network among viral domains, human domains and the corresponding diseases, which uncovered several unknown virus-disease relationships that needed further verification. Overall, it is expected that the findings will help to deeply understand the viral infection and contribute to the development of antiviral therapy.
1-1-12 One-Step Wash-In Scheme for Desflurane-Nitrous Oxide Low-Flow Anesthesia: Rapid and Predictable Induction
Authors: Sathitkarnmanee Thepakorn , Tribuddharat Sirirat , Suttinarakorn Chakthip , Nonlhaopol Duangthida , Thananun Maneerat , Somdee Wilawan , Theerapongpakdee Sunchai
Published: June 2014

Background. We propose a 1-1-12 wash-in scheme for desflurane-nitrous oxide (N2O) low-flow anesthesia. The objective of our study was to determine the time to achieve alveolar concentration of desflurane (FAD) at 1, 2, 3, 4, 5, and 6%.Methods. We enrolled 106 patients scheduled for elective surgery under general anesthesia. After induction and intubation, wash-in was started with a fresh gas flow (FGF) of N2O : O21 : 1 L min−1and vaporizer concentration of desflurane (FD) of 12%. Ventilation was controlled to maintainPACO2at 30–35 mmHg.Results. TheFADrose rapidly from 0 to 4% in 2 min in a linear manner in 0.5 min increments. AnFADof 6% was achieved in 4 min in a linear fashion fromFADof 4% but in 1 min increments. AnFADof 1 to 6% occurred at 0.6, 1, 1.5, 2, 3, and 4 min. Heart rate during wash-in showed a statistically, albeit not clinically, significant pattern of increase. By contrast, blood pressure slightly decreased during this period.Conclusions. We developed a 1-1-12 wash-in scheme using a FGF of N2O : O21 : 1 L min−1and FD of 12% for desflurane-nitrous oxide low-flow anesthesia. A respectiveFADof 1, 2, 3, 4, 5, and 6% can be expected at 0.6, 1, 1.5, 2, 3, and 4 min.
Expression of Myeloid Antigen in Neoplastic Plasma Cells Is Related to Adverse Prognosis in Patients with Multiple Myeloma
Authors: Shim Hyoeun , Ha Joo Hee , Lee Hyewon , Sohn Ji Yeon , Kim Hyun Ju , Eom Hyeon-Seok , Kong Sun-Young
Published: June 2014

We evaluated the association between the expression of myeloid antigens on neoplastic plasma cells and patient prognosis. The expression status of CD13, CD19, CD20, CD33, CD38, CD56, and CD117 was analyzed on myeloma cells from 55 newly diagnosed patients, including 36 men (65%), of median age 61 years (range: 38–78). Analyzed clinical characteristics and laboratory parameters were as follows: serumβ2-microglobulin, lactate dehydrogenase, calcium, albumin, hemoglobin, serum creatinine concentrations, bone marrow histology, and cytogenetic findings. CD13+ and CD33+ were detected in 53% and 18%, respectively. Serum calcium (P=0.049) and LDH (P=0.018) concentrations were significantly higher and morphologic subtype of immature or plasmablastic was more frequent in CD33+ than in CD33− patients (P=0.022). CD33 and CD13 expression demonstrate a potential prognostic impact and were associated with lower overall survival (OS;P=0.001andP=0.025) in Kaplan-Meier analysis. Multivariate analysis showed that CD33 was independently prognostic of shorter progression free survival (PFS;P=0.037) and OS (P=0.001) with correction of clinical prognostic factors. This study showed that CD13 and CD33 expression associated with poor prognosis in patients with MM implicating the need of analysis of these markers in MM diagnosis.
Joint Paediatric and Psychiatric Follow-Up for Families following Paediatric Intensive Care Unit Admission: An Exploratory Study
Authors: Gledhill Julia , Tareen Amina , Cooper Mehrengise , Nadel Simon , Garralda M. Elena
Published: June 2014

Psychopathology in parents and children is increased after Paediatric Intensive Care Unit (PICU) admission; few studies have evaluated interventions to reduce this. Objective. Evaluation of the feasibility of setting up a joint paediatric and psychiatric follow-up clinic for families after PICU discharge. Design. Feasibility study offering joint follow-up with a consultant paediatric intensivist and child and adolescent psychiatrist. Setting. Paediatric outpatient clinic in a university teaching hospital with a PICU. Patients. Children and their families discharged from PICU. Interventions. Outpatient appointment focussing on physical and psychological health; psychoeducation about emotional and behavioural difficulties occurring after PICU discharge, advice for parents about supporting their child’s psychological recovery, screening for more severe psychiatric disorders, and provision of a leaflet outlining possible difficulties and management strategies. Measurements. Attendance, content of discussion, psychiatric questionnaires, and family feedback. Main Results. It proved feasible to set up follow-up appointments to address physical and psychological health concerns; 4/12(33%) eligible families attended. Children and mothers who attended all reported child difficulties including sleep disturbance, increased anxiety, and PTSD symptoms in children and parents. Conclusions. Follow-up clinics after PICU discharge are feasible to set up; take-up is poor but families attending report psychopathology which may be addressed through the intervention.
Exploring Perceptions and Experiences of Food Allergy among New Canadians from Asia
Authors: Lu Stephanie K. , Elliott Susan J. , Clarke Ann E.
Published: June 2014

Introduction. In Canada, perceived prevalence of food allergy surpasses systematic estimates. Canadian immigrants have been found more likely to rate the risk of food allergy as “high” compared to nonimmigrants. Methods. Qualitative interviews were conducted with 3 key informants and 18 allergic individuals of East and Southeast Asian descent in order to capture their lived experience with food allergies. Results. Participants found food allergies to be more common in Canada than in Asia. Participants also agreed that having a food allergy is more manageable in Canada as a result of the policy environment (e.g., food labelling and school policies). In addition, participants had dealt with skepticism and disbelief about their food allergy in Asia, resulting in social exclusion and impacting quality of life. Discussion. Findings demonstrate the need to recognize the varied impacts and experiences of food allergy among new Canadians, given that immigrants represent a large and growing proportion of the Canadian population.
A Functional Variant in NKX3.1 Associated with Prostate Cancer Risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Authors: Martinez Erin E. , Darke Amy K. , Tangen Catherine M. , Goodman Phyllis J. , Fowke Jay H. , Klein Eric A. , Abdulkadir Sarki A.
Published: June 2014

NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knockout mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting that our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case–cohort substudy (1,866 cases; 3,135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared with placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk [HR, 1.676; 95% confidence interval (CI), 1.011–2.777; P = 0.045] and low-grade prostate cancer risk (HR, 1.811; 95% CI, 1.016–3.228; P = 0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR, 1.450; 95% CI, 1.117–1.882; P = 0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents. Cancer Prev Res; 7(9); 950–7. ©2014 AACR.
EGFR Variant Heterogeneity in Glioblastoma Resolved through Single-Nucleus Sequencing
Authors: Francis Joshua M. , Zhang Cheng-Zhong , Maire Cecile L. , Jung Joonil , Manzo Veronica E. , Adalsteinsson Viktor A. , Homer Heather , Haidar Sam , Blumenstiel Brendan , Pedamallu Chandra Sekhar , Ligon Azra H. , Love J. Christopher , Meyerson Matthew , Ligon Keith L.
Published: June 2014

Glioblastomas (GBM) with EGFR amplification represent approximately 50% of newly diagnosed cases, and recent studies have revealed frequent coexistence of multiple EGFR aberrations within the same tumor, which has implications for mutation cooperation and treatment resistance. However, bulk tumor sequencing studies cannot resolve the patterns of how the multiple EGFR aberrations coexist with other mutations within single tumor cells. Here, we applied a population-based single-cell whole-genome sequencing methodology to characterize genomic heterogeneity in EGFR-amplified glioblastomas. Our analysis effectively identified clonal events, including a novel translocation of a super enhancer to the TERT promoter, as well as subclonal LOH and multiple EGFR mutational variants within tumors. Correlating the EGFR mutations onto the cellular hierarchy revealed that EGFR truncation variants (EGFRvII and EGFR carboxyl-terminal deletions) identified in the bulk tumor segregate into nonoverlapping subclonal populations. In vitro and in vivo functional studies show that EGFRvII is oncogenic and sensitive to EGFR inhibitors currently in clinical trials. Thus, the association between diverse activating mutations in EGFR and other subclonal mutations within a single tumor supports an intrinsic mechanism for proliferative and clonal diversification with broad implications in resistance to treatment.

Significance: We developed a novel single-cell sequencing methodology capable of identifying unique, nonoverlapping subclonal alterations from archived frozen clinical specimens. Using GBM as an example, we validated our method to successfully define tumor cell subpopulations containing distinct genetic and treatment resistance profiles and potentially mutually cooperative combinations of alterations in EGFR and other genes. Cancer Discov; 4(8); 956–71. ©2014 AACR.

See related commentary by Gini and Mischel, p. 876

This article is highlighted in the In This Issue feature, p. 855
Synaptosomal Lactate Dehydrogenase Isoenzyme Composition Is Shifted toward Aerobic Forms in Primate Brain Evolution
Authors: Duka Tetyana , Anderson Sarah M. , Collins Zachary , Raghanti Mary Ann , Ely John J. , Hof Patrick R. , Wildman Derek E. , Goodman Morris , Grossman Lawrence I. , Sherwood Chet C.
Published: June 2014

With the evolution of a relatively large brain size in haplorhine primates (i.e. tarsiers, monkeys, apes, and humans), there have been associated changes in the molecular machinery that delivers energy to the neocortex. Here we investigated variation in lactate dehydrogenase (LDH) expression and isoenzyme composition of the neocortex and striatum in primates using quantitative Western blotting and isoenzyme analysis of total homogenates and synaptosomal fractions. Analysis of isoform expression revealed that LDH in synaptosomal fractions from both forebrain regions shifted towards a predominance of the heart-type, aerobic isoform LDH-B among haplorhines as compared to strepsirrhines (i.e. lorises and lemurs), while in the total homogenate of the neocortex and striatum there was no significant difference in LDH isoenzyme composition between the primate suborders. The largest increase occurred in synapse-associated LDH-B expression in the neocortex, with an especially remarkable elevation in the ratio of LDH-B/LDH-A in humans. The phylogenetic variation in the ratio of LDH-B/LDH-A was correlated with species-typical brain mass but not the encephalization quotient. A significant LDH-B increase in the subneuronal fraction from haplorhine neocortex and striatum suggests a relatively higher rate of aerobic glycolysis that is linked to synaptosomal mitochondrial metabolism. Our results indicate that there is a differential composition of LDH isoenzymes and metabolism in synaptic terminals that evolved in primates to meet increased energy requirements in association with brain enlargement.
Prospective Evaluation of the Routine Use of a Nasopharyngeal Airway (Wendl Tube) during Endoscopic Propofol-Based Sedation
Authors: Müller Michaela , Wehrmann Till , Eckardt Alexander J.
Published: June 2014

Background/Aims: Insertion of a nasopharyngeal airway (NPA) during endoscopic sedation is only recommended in the event of respiratory problems. We evaluated the safety and efficacy of routine insertion of an NPA during sedation in gastrointestinal (GI) endoscopy. Methods: Between July 2009 and April 2012, patients with colonoscopy or expected longer-lasting or therapeutic upper GI endoscopy were pseudo-randomized in a weekly alternating fashion to perform sedation (midazolam in combination with propofol) with or without NPA insertion. The primary outcome measure was respiratory depression (oxygen saturation <90%). Secondary measures included hypotension (systolic blood pressure <90 mm Hg), bradycardia (heart rate <40 beats/min) or nasopharyngeal damage after NPA insertion. Results: 216 (106 females, mean age 60.7 ± 9.65 years) were enrolled. Colonoscopy was performed in 131 patients and upper endoscopy in 85 patients. In 105 patients an NPA was used (intervention group). Five (4.7%) of those patients showed minor nasopharyngeal injury. Respiratory depression (13.5 vs. 1.9%, p = 0.002) and hypotension (11 vs. 5%, p = 0.09) occurred more frequently in the control than in the intervention group. Conclusion: The routine placement of an NPA can reduce the frequency of hypoxemic events during endoscopic sedation with minor risks for nasopharyngeal injury.
Urinary Podocyte Excretion and Proteinuria in Patients Treated with Antivascular Endothelial Growth Factor Therapy for Solid Tumor Malignancies
Authors: Hayman Suzanne R. , Calle Juan C. , Jatoi Aminah , Craici Iasmina M. , Wagner Steven J. , Weaver Amy L. , Greene Eddie L. , Grande Joseph P. , Garovic Vesna D.
Published: June 2014

Background: Urinary podocyte excretion (podocyturia) may function as a more specific marker of ongoing glomerular damage. This study sought to analyze the relationship between proteinuria and podocyturia in cancer patients treated with antivascular endothelial growth factor (anti-VEGF) agents. Methods: Thirty-seven patients treated with anti-VEGF medications were analyzed in a single-institution, cross-sectional study. Podocyte cultures were performed on random urine collections (50-100 ml), and podocytes were identified by positive podocin staining. The corresponding urine samples were analyzed for protein and creatinine (Cr) measurements. Results: Proteinuria ≥0.5 g/g Cr was found in 30% of the patients (median, 0.12; interquartile range, 0.04-0.86), and 62% had podocyturia. There was a significant difference in the amount of podocyturia between patients with proteinuria ≥0.5 g/g Cr and those with a value <0.5 g/g Cr (median podocyturia, 1.08 cells/mg Cr, range, 0-14.55 vs. 0.03 cells/mg Cr, range, 0-1.64, respectively; p < 0.001). A statistically significant correlation was observed between the cumulative dose of bevacizumab and both proteinuria (r = 0.48, p = 0.004) and podocyturia (r = 0.34, p = 0.045) as well as between proteinuria and podocyturia (r = 0.63, p < 0.001), suggesting that these are mechanistically related. Discussion: Ongoing podocyte loss may be mechanistically related to the onset and severity of proteinuria in patients treated with anti-VEGF agents.
Hyperhomocysteinemia and Methylenetetrahydrofolate Reductase Polymorphism in Cervical Artery Dissection: A Meta-Analysis
Authors: Luo Hongzhi , Liu Bo , Hu Jing , Wang Xian , Zhan Siyan , Kong Wei
Published: June 2014

Background: Cervical artery dissection (CAD) is a recognized cause of ischemic stroke. Hyperhomocysteinemia (HHcy), i.e. an elevated concentration of plasma homocysteine, is identified as an independent risk factor for stroke prevalence. However, an association between HHcy and CAD has so far remained unknown. Methods: A meta-analysis was performed to analyze the association between HHcy and CAD as well as the relevance of the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), the key enzyme in homocysteine metabolism during CAD. We searched PubMed and Embase for studies reporting homocysteine concentrations or MTHFR genotype frequencies in CAD patients from 1990 to 2013. Outcomes were extracted from studies meeting the inclusion criteria and were subjected to a meta-analysis by the random-effect model. Heterogeneity was assessed by the I2 test. Results: Eight case-control studies with 2,146 individuals fulfilled the required criteria and were included in the meta-analysis. HHcy was found to be significantly associated with CAD (pooled standardized mean difference: 0.96; 95% confidence interval, CI: 0.42-1.49; p < 0.01). We also found a significantly increased risk of CAD in individuals with the MTHFR C677T polymorphism by both the recessive model (TT vs. CT+CC; odds ratio, OR = 1.81; 95% CI: 1.22-2.67; p = 0.003) and the dominant model (TT+CT vs. CC; OR = 1.47; 95% CI: 1.08-1.99; p = 0.014). Conclusion: Our data suggest positive correlations between HHcy and CAD and between the C677T polymorphism of MTHFR and CAD.
Secondary or Second Primary Malignancy in the Thyroid? Metastatic Tumors Suggested Clinically: A Differential Diagnostic Task
Authors: Dušková Jaroslava , Rosa Pavel , Přeučil Pavel , Svobodová Eva , Lukáš Jindřich
Published: June 2014

Objective: To describe the algorithms employed to explore the suggestion or consideration of metastatic malignancy in the thyroid. Study Design: Thirty-seven cases with a history of malignancy (n = 21) and/or uncommon fine-needle aspiration biopsy (FNAB) findings (n = 37) were reviewed and reclassified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Results: The group was heterogeneous in terms of the final histopathology results: the suggested metastasis was confirmed in only half of the cases (11/21; 52.4%). Primary thyroid malignancies were mostly nondifferentiated, medullary, or rare. However, 3 papillary carcinomas (the less common variants) were also found. Finally, 5 out of 37 cases were surprisingly benign upon histopathological investigation (uncommon repair and fibrotizing Hashimoto thyroiditis). Conclusions: The metastatic nature of thyroid gland nodule(s) must be considered in cases of generalization of malignancy and/or uncommon FNAB findings. We must be as open-minded as possible from the outset. Additional techniques are helpful if available - cytoblock and immunocytochemistry can contribute substantially. Morphological comparisons with the previous malignancy are recommended whenever possible. To avoid overtreatment, cases without precise typing should not be classified as TBSRTC diagnostic category VI - malignant, but should remain in TBSRTC diagnostic category V - suspicious for malignancy. Repeated FNAB to enable additional techniques may be suggested.
Outcome Disparities among Ethnic Subgroups of Waldenström's Macroglobulinemia: A Population-Based Study
Authors: Ailawadhi Sikander , Kardosh Adel , Yang Dongyun , Cozen Wendy , Patel Gaurav , Alamgir Mohammad A. , Chanan-Khan Asher A.
Published: June 2014

Background: Ethnic disparities in cancers are associated with variability in clinical outcomes. We present a Surveillance Epidemiology and End Results (SEER)-based outcome analysis of multiethnic Waldenström's macroglobulinemia (WM) patients. Methods: Adult WM patients diagnosed in 1992 or later (n = 3,175) were analyzed. Median overall survival (OS) was compared across different ethnicities stratified by year of diagnosis, registry identification, age at diagnosis, sex, and marital status. Results: African-Americans (AA) had the youngest median age at diagnosis (63 years) and Whites had the oldest (73 years) (p < 0.001). Female gender, a younger age at diagnosis, and a recent year of diagnosis were associated with an improved OS. Hispanics had the worst (5.6 years) while Whites had the best (6.8 years) median OS. A significant interaction existed between median OS, gender, and race (p = 0.007). Among males, AA had the worst (4.3 years) and Asians had the best (7.3 years) median OS. A significant interaction was also noted between median OS, age at diagnosis, and race (p = 0.033). The worst median OS was seen in Hispanics among patients aged >75 years, and in AA among those aged <65 years. Conclusions: These disparities among WM patients may be multifactorial but need to be explored systematically to better understand the disease biology and for optimal triaging of health care resources.
Chromosome Banding in Amphibia. XXXI. The Neotropical Anuran Families Centrolenidae and Allophrynidae
Authors: Schmid Michael , Steinlein Claus , Feichtinger Wolfgang , Bogart James P.
Published: June 2014

The mitotic chromosomes of 11 species from the anuran families Centrolenidae and Allophrynidae were analyzed by means of conventional staining, banding techniques, and in situ hybridization. The amount, location, and fluorochrome affinities of constitutive heterochromatin, the number and positions of nucleolus organizer regions, and the patterns of telomeric DNA sequences were determined for most of the species. The karyotypes were found to be highly conserved with a low diploid chromosome number of 2n = 20 and morphologically similar chromosomes. The sister group relationship between the Centrolenidae and Allophrynidae (unranked taxon Allocentroleniae) is clearly corroborated by the cytogenetic data. The existence of heteromorphic XY♂/XX♀ sex chromosomes in an initial stage of morphological differentiation was confirmed in Vitreorana antisthenesi. The genome sizes of 4 centrolenid species were determined using flow cytometry. For completeness and for comparative purposes, all previously published cytogenetic data on centrolenids are included.
Higher Working Memory Predicts Slower Functional Decline in Autopsy-Confirmed Alzheimer's Disease
Authors: Pillai Jagan A. , Bonner-Jackson Aaron , Walker Esteban , Mourany Lyla , Cummings Jeffrey L.
Published: June 2014

Background: There is heterogeneity in the pattern of early cognitive deficits in Alzheimer's disease (AD). However, whether the severity of initial cognitive deficits relates to different clinical trajectories of AD progression is unclear. Objective: To determine if deficits in specific cognitive domains at the initial visit relate to the rate of progression in clinical trajectories of AD dementia. Methods: 68 subjects from the National Alzheimer's Coordinating Center database who had autopsy-confirmed AD as the primary diagnosis and at least 3 serial assessments a year apart, with a Mini-Mental State Examination (MMSE) score >15 and a Clinical Dementia Rating Scale-Global (CDR-G) score ≤1 at the initial visit were included. A mixed regression model was used to examine the association between initial neuropsychological performance and rate of change on the MMSE and CDR Sum of Boxes. Results: Preservation of working memory, but not episodic memory, in the mild cognitive impairment and early dementia stages of AD relates to slower rate of functional decline. Discussion: These findings are relevant for estimating the rate of decline in AD clinical trials and in counseling patients and families. Improving working memory performance as a possible avenue to decrease the rate of functional decline in AD dementia warrants closer investigation.
Treatment and Prognostic Factors in Primary Peritoneal Carcinoma: A Multicenter Study of the Anatolian Society of Medical Oncology (ASMO)
Authors: Unal Olcun U. , Oztop İlhan , Yazici Ozan , Ozatli Tahsin , İnal Ali , Günaydın Yusuf , Alici Suleyman , Demirci Umut , Cinkir Havva Y. , Aktas Bilge , Aslan Kubra , Uncu Dogan , Yilmaz Ahmet U. , Oksuzoglu Berna , Buyukberber Suleyman
Published: June 2014

Background: In this study, we aimed to evaluate the clinicopathological characteristics and prognosis of patients with primary peritoneal carcinoma (PPC), and the effectiveness and toxicity of first-line platinum/taxane combination therapy. Patients and Methods: We retrospectively evaluated 79 patients with PPC, who were treated and followed up between December 2001 and August 2012 at 10 medical oncology clinics. Results: All patients were female, with a median age of 63 years (range 34-79 years). Histopathological diagnoses included primary peritoneal serous carcinoma (PPSC) (n = 69) and mixed epithelial carcinoma of the peritoneum (MEC) (n = 10). Patients received first-line treatment with carboplatin/paclitaxel (n = 67) or cisplatin/paclitaxel (n = 12) combination therapy. Overall response rate, median progression-free survival, and median survival time in the paclitaxel/carboplatin group and the paclitaxel/cisplatin group were 74.6 vs. 75%, 15.6 vs. 37.8 months, and 41 vs. 70.3 months, respectively. In multivariate analysis, favorable prognostic factors were: ECOG performance status 0 (p < 0.001) and optimal cytoreduction (p = 0.03). Conclusion: PPC is a rare, heterogeneous disease. ECOG performance status and optimal cytoreduction are important prognostic factors regarding survival rates. Platinum/taxane combination therapy is an effective and tolerable regimen in this patient group.
Immunoglobulin G Values before Treatment Are Correlated With the Responsiveness to Initial Intravenous Immunoglobulin Therapy for Kawasaki Disease
Authors: Yanagimoto Kosuke , Nomura Yuichi , Masuda Kiminori , Hirabayashi Masako , Morita Yasuko , Yoshishige Michiko , Ueno Kentaro , Eguchi Taisuke , Kawano Yoshifumi
Published: June 2014

Background: Low levels of serum immunoglobulin G (IgG) before intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD) have been reported as one of the risk factors for coronary artery abnormalities (CAAs). This risk factor needs to be re-evaluated because the dosage of IVIG has changed from 0.2-0.4 g/kg/day for 5 days to a single high dose of 2 g/kg. Methods: We reviewed the clinical records of KD patients admitted to our hospital from January 2001 to August 2011. Patients who were given a single high dose of IVIG within 7 days of illness, and who had blood collected for serum immunoglobulin values before treatment, were selected. The serum immunoglobulin levels and coronary artery diameters measured by echocardiogram were transformed to z-scores. Results: The subjects were 197 KD patients, including 22 IVIG nonresponders and 16 patients with CAAs. Of these, 150 (76%) had a z-score for IgG (IgGz) of ≤0. There were no differences in IgGz values between patients with CAAs and those without CAAs. However, nonresponders had higher IgGz values than responders (median, 25th percentile and 75th percentile: −0.26, −0.83 and 0.34 vs. −0.79, −1.40 and −0.03; p = 0.020). Logistic regression analysis showed that the IgGz value was an independent risk factor for resistance to IVIG (OR 1.36, 95% CI 1.002-1.849; p = 0.048). Conclusions: Low IgGz values were not a risk factor for CAAs in this study. However, KD patients with relatively high IgGz values before treatment may have an increased risk of resistance to initial IVIG therapy.
Association Between Perceived Health Care Stigmatization and BMI Change
Authors: Hansson Lena M. , Rasmussen Finn
Published: June 2014

Background/Aims: This study examined the association between experiences of health care stigmatization and BMI changes in men and women with normal weight and obesity in Sweden. Methods: The participants were drawn from a population-based survey in Sweden (1996-2006), and data on their perceived health care stigmatization were measured in 2008. They were categorized in individuals with normal weight (n = 1,064), moderate obesity (n = 1,273), and severe obesity (n = 291). The main outcome measure was change in BMI. Results: Individuals with severe obesity experiencing any health care stigmatization showed a BMI increase by 1.5 kg/m2 more than individuals with severe obesity with no such experience. For individuals with moderate obesity, insulting treatment by a physician and avoidance of health care were associated with a relative BMI increase of 0.40 and 0.75 kg/m2, respectively, compared with their counterparts who did not experience stigmatization in these areas. No difference in experience of any form of health care stigmatizing associated BMI change was observed for men and women with normal weight. Conclusion: In this large, population-based study, perceived health care stigmatization was associated with an increased relative BMI in individuals with severe obesity. For moderate obesity, the evidence of an association was inconclusive.