bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocols cure diseases, not patients: flaccid paresis in post-NSTEMI statin treatment
Authors: Rosada Javier , Rebelos Eleni , Petruccelli Stefania , Taddei Marco
Published: April 2015

An 82-year-old white woman presented at our Internal Medicine ward with flaccid tetraparesis. Two months earlier, she had suffered a non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) and stenting, and she had been prescribed the classical post-PCI therapy (β-blockers, statins and antiplatelet agents). At admission, she was haemodynamically stable and the physical examination revealed reduced reflexes in the four limbs. Urgent laboratory findings revealed mild hypokalaemia. Considering the high statin doses she was taking, we also performed an urgent creatine phosphokinase test, which indicated rhabdomyolysis. Statin therapy was immediately stopped and aggressive fluid treatment begun, supplemented with potassium for increased urinary potassium losses. The patient progressively regained muscle strength.
A new diagnosis of acute myeloid leukaemia complicated by peripancreatic tuberculous lymphadenitis
Authors: Harrington Patrick , Yeghen Tullie
Published: April 2015

A 29-year-old woman presented with neutropenic sepsis and was found to have a new diagnosis of acute myeloid leukaemia. Following initiation of induction chemotherapy the patient became increasingly unwell with ongoing sepsis despite broad-spectrum antibiotic treatment. An extensive septic screen failed to identify a source, other than the finding of a peripancreatic mass on imaging. Following the introduction of antituberculous treatment the patient showed signs of clinical improvement and a subsequent biopsy confirmed the mass to be tuberculous lymphadenitis. The patient completed three cycles of combination chemotherapy achieving a complete remission and also successfully completed 12 months of antituberculous treatment.
Results of Florida's Amyotrophic Lateral Sclerosis Surveillance Project, 2009–2011
Authors: Freer Cecilia , Hylton Tara , Jordan Heather M , Kaye Wendy E , Singh Sabrina , Huang Youjie
Published: April 2015

Objective

Studies to determine the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in defined geographic areas in the USA are needed. The Florida Department of Health received funding from the federal Agency for Toxic Substances and Disease Registry to implement a state-wide ALS Surveillance Project. The objectives of the project were to describe the demographic characteristics of ALS cases and to calculate the incidence and prevalence of ALS in Florida.

Setting/participants

All neurologists were asked to submit case reports for persons with ALS diagnosed and/or under their care during 1 January 2009 through 31 December 2011. A medical record verification form and an electromyogram (EMG) report were requested for a sample of cases and reviewed by an independent consulting neurologist to confirm ALS diagnosis. Death data were used to aid with case report collection.

Primary and secondary outcome measures

Demographics, relevant history and clinical characteristics, El Escorial classifications, time from symptom onset to diagnosis, crude annual incidence rates and 2009 period prevalence are presented.

Results

The 1450 reported ALS cases were more likely to be older, male, white and non-Hispanic. Slightly more than 4% of cases were reported as also having dementia, and 4.8% were reported to have an immediate family member diagnosed with ALS. Incidence rates ranged from 1.7 to 1.9 per 100 000 person-years during the project period and the 2009 period prevalence was 4.0 per 100 000 persons.

Conclusions

Project findings are generally consistent with findings of population-based studies in Europe, as well as geographically limited studies in the USA. Our findings add to the growing body of epidemiological literature about ALS in the USA. Future epidemiological studies in the USA should focus on identifying cases from minority groups and those that may have limited access to healthcare, and should consider conducting capture–recapture analysis to assess case ascertainment.
Emergence agitation during recovery from intracranial surgery under general anaesthesia: a protocol and statistical analysis plan for a prospective multicentre cohort study
Authors: Yan Li-Mei , Chen Han , Yu Rong-Guo , Wang Zhu-Heng , Zhou Guan-Hua , Wang Yong-Jin , Zhang Xia , Xu Ming , Chen Lu , Zhou Jian-Xin
Published: April 2015

Introduction

Emergence agitation after intracranial surgery is an important clinical issue during anaesthesia recovery. The aim of this multicentre cohort study is to investigate the incidence of emergence agitation, identify the risk factors and determine clinical outcomes in adult patients after intracranial surgery under general anaesthesia. Additionally, we will deliberately clarify the relationship between postoperative pneumocephalus and agitation.

Methods and analysis

The present study is a prospective multicentre cohort study. Five intensive care units (ICUs) in China will participate in the study. Consecutive adult patients admitted to the ICUs after intracranial surgery will be enrolled. Sedation-Agitation Scale (SAS) or Richmond Agitation-Sedation Scale (RASS) will be used to evaluate the patients 12 h after the enrolment. Agitation is defined as an SAS score of 5–7, or an RASS score of +2 to +4. According to the maximal SAS and RASS score, patients will be divided into two cohorts: the agitation group and the non-agitation group. Factors potentially related to emergence agitation will be collected at study entry, during anaesthesia and operation, during postoperative care. Univariate analyses between the agitation and the non-agitation groups will be performed. The stepwise backward logistic regression will be carried out to identify the independent predictors of agitation. Patients will be followed up for 72 h after the operation. Accidental self-extubation of the endotracheal tube and removal of other catheters will be documented. The use of sedatives and analgesics will be collected.

Ethics and dissemination

Ethics approval has been obtained from each of five participating hospitals. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

NCT02318199.
Non-infectious granulomatous conditions of the skin: a clinicopathological approach to diagnosis
Authors: Kamil Zaid Saeed , Chen Tiffany , Ghazarian Danny
Published: April 2015

Granulomatous disorders of the skin are diverse and include infectious and non-infectious conditions. They are a source of confusion to many dermatologists and pathologists, including even the most experienced dermatopathologists. Correlation with clinical picture, serology, microbiology and careful morphological examination is essential for accurate diagnosis. Most cases require ancillary histopathological studies to reach a final diagnosis. This review discusses important non-infectious granulomatous conditions of the skin and presents a practical approach when confronted with such entities.
Spherical "Top-Hat" collapse in a modified Chaplygin gas dominated universe
Authors: Karbasi S. , Razmi H.
Published: April 2015

Considering perturbation growth in spherical Top-Hat (STH) model of structure formation in a generalized Chaplygin gas (GCG) dominated universe, we want to study this scenario with modified Chaplygin gas (MCG) obeying an equation of state p = A - B/ρα model. Different parameters of this scenario for positive and negative values of A are computed. The evolution of background and collapsed region parameters are found for different cases. The stability of the model and the collapse time rate are considered in different cases. The turn-around redshifts for different values of α are computed; the results are in relatively good agreement with current observational data.
Semantically Enriched Task and Workflow Automation in Crowdsourcing for Linked Data Management
Authors: Basharat Amna , Arpinar I. Budak , Dastgheib Shima , Kursuncu Ugur , Kochut Krys , Dogdu Erdogan
Published: April 2015

Crowdsourcing is one of the new emerging paradigms to exploit the notion of human-computation for harvesting and processing complex heterogenous data to produce insight and actionable knowledge. Crowdsourcing is task-oriented, and hence specification and management of not only tasks, but also workflows should play a critical role. Crowdsourcing research can still be considered in its infancy. Significant need is felt for crowdsourcing applications to be equipped with well defined task and workflow specifications ranging from simple human-intelligent tasks to more sophisticated and cooperative tasks to handle data and control-flow among these tasks. Addressing this need, we have attempted to devise a generic, flexible and extensible task specification and workflow management mechanism in crowdsourcing. We have contextualized this problem to linked data management as our domain of interest. More specifically, we develop CrowdLink, which utilizes an architecture for automated task specification, generation, publishing and reviewing to engage crowdworkers for verification and creation of triples in the Linked Open Data (LOD) cloud. The LOD incorporates various core data sets in the semantic web, yet is not in full conformance with the guidelines for publishing high quality linked data on the web. Our approach is not only useful in efficiently processing the LOD management tasks, it can also help in enriching and improving quality of mission-critical links in the LOD. We demonstrate usefulness of our approach through various link creation and verification tasks, and workflows using Amazon Mechanical Turk. Experimental evaluation demonstrates promising results not only in terms of ease of task generation, publishing and reviewing, but also in terms of accuracy of the links created, and verified by the crowdworkers.
Safe Opponent Exploitation
Authors: Ganzfried Sam , Sandholm Tuomas
Published: April 2015

We consider the problem of playing a repeated two-player zero-sum game safety: that is, guaranteeing at least the value of the game per period in expectation regardless of the strategy used by the opponent. Playing a stage-game equilibrium strategy at each time step clearly guarantees safety, and prior work has (incorrectly) stated that it is impossible to simultaneously deviate from a stage-game equilibrium (in hope of exploiting a suboptimal opponent) and to guarantee safety. We show that such profitable deviations are indeed possible specifically in games where certain types of “gift” strategies exist, which we define formally. We show that the set of strategies constituting such gifts can be strictly larger than the set of iteratively weakly-dominated strategies; this disproves another recent assertion which states that all noniteratively weakly dominated strategies are best responses to each equilibrium strategy of the other player. We present a full characterization of safe strategies, and develop efficient algorithms for exploiting suboptimal opponents while guaranteeing safety. We also provide analogous results for extensive-form games of perfect and imperfect information, and present safe exploitation algorithms and full characterizations of safe strategies for those settings as well. We present experimental results in Kuhn poker, a canonical test problem for game-theoretic algorithms. Our experiments show that (1) aggressive safe exploitation strategies significantly outperform adjusting the exploitation within stage-game equilibrium strategies only and (2) all the safe exploitation strategies significantly outperform a (nonsafe) best response strategy against strong dynamic opponents.
Ohmage
Authors: Tangmunarunkit H. , Hsieh C. K. , Longstaff B. , Nolen S. , Jenkins J. , Ketcham C. , Selsky J. , Alquaddoomi F. , George D. , Kang J. , Khalapyan Z. , Ooms J. , Ramanathan N. , Estrin D.
Published: April 2015

Participatory sensing (PS) is a distributed data collection and analysis approach where individuals, acting alone or in groups, use their personal mobile devices to systematically explore interesting aspects of their lives and communities [Burke et al. 2006]. These mobile devices can be used to capture diverse spatiotemporal data through both intermittent self-report and continuous recording from on-board sensors and applications.

Ohmage (http://ohmage.org) is a modular and extensible open-source, mobile to Web PS platform that records, stores, analyzes, and visualizes data from both prompted self-report and continuous data streams. These data streams are authorable and can dynamically be deployed in diverse settings. Feedback from hundreds of behavioral and technology researchers, focus group participants, and end users has been integrated into ohmage through an iterative participatory design process. Ohmage has been used as an enabling platform in more than 20 independent projects in many disciplines. We summarize the PS requirements, challenges and key design objectives learned through our design process, and ohmage system architecture to achieve those objectives. The flexibility, modularity, and extensibility of ohmage in supporting diverse deployment settings are presented through three distinct case studies in education, health, and clinical research.
Practical Lattice-Based Digital Signature Schemes
Authors: Howe James , Pöppelmann Thomas , O'neill Máire , O'sullivan Elizabeth , Güneysu Tim
Published: April 2015

Digital signatures are an important primitive for building secure systems and are used in most real-world security protocols. However, almost all popular signature schemes are either based on the factoring assumption (RSA) or the hardness of the discrete logarithm problem (DSA/ECDSA). In the case of classical cryptanalytic advances or progress on the development of quantum computers, the hardness of these closely related problems might be seriously weakened. A potential alternative approach is the construction of signature schemes based on the hardness of certain lattice problems that are assumed to be intractable by quantum computers. Due to significant research advancements in recent years, lattice-based schemes have now become practical and appear to be a very viable alternative to number-theoretic cryptography. In this article, we focus on recent developments and the current state of the art in lattice-based digital signatures and provide a comprehensive survey discussing signature schemes with respect to practicality. Additionally, we discuss future research areas that are essential for the continued development of lattice-based cryptography.
Bounds for the Quantifier Depth in Finite-Variable Logics
Authors: Berkholz Christoph , Krebs Andreas , Verbitsky Oleg
Published: April 2015

Given two structures
G
and
H
distinguishable in FO

k

(first-order logic with
k
variables), let A

k

(
G
,
H
) denote the minimum alternation depth of a FO

k

formula distinguishing
G
from
H
. Let A

k

(
n
) be the maximum value of A

k

(
G
,
H
) over
n
-element structures. We prove the strictness of the quantifier alternation hierarchy of FO
2
in a strong quantitative form, namely A
2
(
n
) >
n
/8 − 2, which is tight up to a constant factor. For each
k
⩾ 2, it holds that A

k

(
n
) > log 

k
+ 1

n
− 2 even over colored trees, which is also tight up to a constant factor if
k
⩾ 3. For
k
⩾ 3, the last lower bound holds also over uncolored trees, whereas the alternation hierarchy of FO
2
collapses even over all uncolored graphs. We also show examples of colored graphs
G
and
H
on
n
vertices that can be distinguished in FO
2
much more succinctly if the alternation number is increased just by one: Whereas in Σ

i

it is possible to distinguish
G
from
H
with bounded quantifier depth, in Π

i

this requires quantifier depth Ω(
n
2
). The quadratic lower bound is best possible here because, if
G
and
H
can be distinguished in FO

k

with
i
quantifier alternations, this can be done with quantifier depth
n

2
k
− 2

+ 1 and the same number of alternations.
A Novel Memristor-Based Hardware Security Primitive
Authors: Mathew Jimson , Chakraborty Rajat Subhra , Sahoo Durga Prasad , Yang Yuanfan , Pradhan Dhiraj K.
Published: April 2015

Memristor is an exciting new addition to the repertoire of fundamental circuit elements. Alternatives to many security protocols originally employing traditional mathematical cryptography involve novel hardware security primitives, such as Physically Unclonable Functions (PUFs). In this article, we propose a novel hybrid memristor-CMOS PUF circuit and demonstrate its suitability through extensive simulations of environmental and process variation effects. The proposed PUF circuit has substantially less hardware overhead than previously proposed memristor-based PUF circuits while being inherently resistant to machine learning-based modeling attacks because of challenge-dependent delays of the memristor stages. The proposed PUF can be conveniently used in many security applications and protocols based on hardware-intrinsic security.
Traffic Shaping to Optimize Ad Delivery
Authors: Chakrabarti Deepayan , Vee Erik
Published: April 2015

Web publishers must balance two objectives: how to keep users engaged by directing them to relevant content, and how to properly monetize this user traffic. The standard approach is to solve each problem in isolation, for example, by displaying content that is tailored to the user’s interests so as to maximize
clickthrough
rates
(CTR), and also by building a standalone ad serving system that displays ads depending on the user’s characteristics, the article being viewed by the user, and advertiser-specified constraints. However, showing the user only those articles with highest expected CTR precludes the display of some ads; if the publisher had previously guaranteed the delivery of a certain volume of impressions to such ads, then
underdelivery
penalties might have to be paid. We propose a joint optimization of article selection and ad serving that minimizes underdelivery by
shaping
some of the incoming traffic to pages where underperforming ads can be displayed, while incurring only minor drops in CTR. In addition to formulating the problem, we design an online optimization algorithm that can find the optimal traffic shaping probabilities for each new user using only a cache of one number per ad contract. Experiments on a large real-world ad-serving Web portal demonstrate significant advantages over the standalone approach: a threefold reduction in underdelivery with only 10% drop in CTR, or a 2.6-fold reduction with a 4% CTR drop, and similar results over a wide range.
A stringent validation of mouse adipose tissue identity markers
Authors: de Jong Jasper M. A. , Larsson Ola , Cannon Barbara , Nedergaard Jan
Published: April 2015

The nature of brown adipose tissue in humans is presently debated: whether it is classical brown or of brite/beige nature. The dissimilar developmental origins and proposed distinct functions of the brown and brite/beige tissues make it essential to ascertain the identity of human depots with the perspective of recruiting and activating them for the treatment of obesity and type 2 diabetes. For identification of the tissues, a number of marker genes have been proposed, but the validity of the markers has not been well documented. We used established brown (interscapular), brite (inguinal), and white (epididymal) mouse adipose tissues and corresponding primary cell cultures as validators and examined the informative value of a series of suggested markers earlier used in the discussion considering the nature of human brown adipose tissue. Most of these markers unexpectedly turned out to be noninformative concerning tissue classification ( Car4, Cited1, Ebf3, Eva1, Fbxo31, Fgf21, Lhx8, Hoxc8, and Hoxc9). Only Zic1 (brown), Cd137, Epsti1, Tbx1, Tmem26 (brite), and Tcf21 (white) proved to be informative in these three tissues. However, the expression of the brite markers was not maintained in cell culture. In a more extensive set of adipose depots, these validated markers provide new information about depot identity. Principal component analysis supported our single-gene conclusions. Furthermore, Zic1, Hoxc8, Hoxc9, and Tcf21 displayed anteroposterior expression patterns, indicating a relationship between anatomic localization and adipose tissue identity (and possibly function). Together, the observed expression patterns of these validated marker genes necessitates reconsideration of adipose depot identity in mice and humans.
The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia
Authors: Gillis Ellen E. , Williams Jan M. , Garrett Michael R. , Mooney Jennifer N. , Sasser Jennifer M.
Published: April 2015

The mechanisms of the pathogenesis of preeclampsia, a leading cause of maternal morbidity and death worldwide, are poorly understood in part due to a lack of spontaneous animal models of the disease. We hypothesized that the Dahl salt-sensitive (S) rat, a genetic model of hypertension and kidney disease, is a spontaneous model of superimposed preeclampsia. The Dahl S was compared with the Sprague-Dawley (SD) rat, a strain with a well-characterized normal pregnancy, and the spontaneously hypertensive rat (SHR), a genetic model of hypertension that does not experience a preeclamptic phenotype despite preexisting hypertension. Mean arterial pressure (MAP, measured via telemetry) was elevated in the Dahl S and SHR before pregnancy, but hypertension was exacerbated during pregnancy only in Dahl S. In contrast, SD and SHR exhibited significant reductions in MAP consistent with normal pregnancy. Dahl S rats exhibited a severe increase in urinary protein excretion, glomerulomegaly, increased placental hypoxia, increased plasma soluble fms-like tyrosine kinase-1 (sFlt-1), and increased placental production of tumor necrosis factor-α (TNF-α). The Dahl S did not exhibit the expected decrease in uterine artery resistance during late pregnancy in contrast to the SD and SHR. Dahl S pups and litter sizes were smaller than in the SD. The Dahl S phenotype is consistent with many of the characteristics observed in human superimposed preeclampsia, and we propose that the Dahl S should be considered further as a spontaneous model to improve our understanding of the pathogenesis of superimposed preeclampsia and to identify and test new therapeutic targets for its treatment.
Evaluation of voiding assays in mice: impact of genetic strains and sex
Authors: Bjorling Dale E. , Wang Zunyi , Vezina Chad M. , Ricke William A. , Keil Kimberly P. , Yu Weiqun , Guo Lianyu , Zeidel Mark L. , Hill Warren G.
Published: April 2015

Void spot assays (VSA) and cystometry are two of the most common tests performed in mice to assess lower urinary tract function. Assay protocols and methodology vary greatly among laboratories, and little is known about reproducibility of results generated by different laboratories. We performed VSA in four mouse strains, comparing males with females and comparing results between two independent laboratories. Unique aspects of the current study include direct comparison of results of VSA performed in a similar manner in two locations and comparison of cystometry performed using two different rates of infusion in these two laboratories. Both assays were performed in male and female 129S1/SvImJ, C57BL/6J, NOD/ShiLtJ, and CAST/EiJ mice, and cystometry was performed under urethane anesthesia (10/group). Assays were performed and results analyzed as previously described. Results obtained in female mice were compared with previously reported values. Results of lower urinary tract function testing in mice vary in a consistent manner with strain and sex. Variables in husbandry, testing techniques, and analysis of results can significantly affect conclusions, particularly those obtained by cystometry. Although VSA results were remarkably similar between the two laboratories, consistent methods for performing lower urinary tract function testing in mice are required to compare results among studies with confidence.
Automatic comparison of stimulus durations in the primate prefrontal cortex: the neural basis of across-task interference
Authors: Genovesio Aldo , Cirillo Rossella , Tsujimoto Satoshi , Mohammad Abdellatif Sara , Wise Steven P.
Published: April 2015

Rhesus monkeys performed two tasks, both requiring a choice between a red square and a blue circle. In the duration task, the two stimuli appeared sequentially on each trial, for varying durations, and, later, during the choice phase of the task, the monkeys needed to choose the one that had lasted longer. In the matching-to-sample task, one of the two stimuli appeared twice as a sample, with durations matching those in the duration task, and the monkey needed to choose that stimulus during the choice phase. Although stimulus duration was irrelevant in the matching-to-sample task, the monkeys made twice as many errors when the second stimulus was shorter. This across-task interference supports an order-dependent model of the monkeys' choice and reveals something about their strategy in the duration task. The monkeys tended to choose the second stimulus when its duration exceeded the first and to choose the alternative stimulus otherwise. For the duration task, this strategy obviated the need to store stimulus-duration conjunctions for both stimuli, but it generated errors on the matching-to-sample task. We examined duration coding in prefrontal neurons and confirmed that a population of cells encoded relative duration during the matching-to-sample task, as expected from the order-dependent errors.
ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents
Authors: Ferreira-Neto Hildebrando Candido , Antunes Vagner R. , Stern Javier E.
Published: April 2015

We have previously shown that ATP within the paraventricular nucleus (PVN) induces an increase in sympathetic activity, an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and assessed whether this receptor coupling contributed to osmotically driven sympathetic PVN neuronal activity. Whole-cell patch-clamp recordings obtained from PVN-rostral ventrolateral medulla neurons showed that ATP (100 μM, 1 min, bath applied) induced an increase in firing rate (89%), an effect blocked by kynurenic acid (1 mM) or 4-[[4-Formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 μM). Whereas ATP did not affect glutamate synaptic function, α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 μM, n = 13) were increased in magnitude by ATP (AMPA amplitude: 33%, AMPA area: 52%). ATP potentiation of AMPA currents was blocked by PPADS ( n = 12) and by chelation of intracellular Ca2+ (BAPTA, n = 10). Finally, a hyperosmotic stimulus (mannitol 1%, +55 mosM, n = 8) potentiated evoked AMPA currents (53%), an effect blocked by PPADS ( n = 6). Taken together, our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute hyperosmotic stimulus, which might contribute in turn to osmotically driven sympathoexcitatory responses by the PVN.
Applications of Fractionalq-Calculus to Certain Subclass of Analyticp-Valent Functions with Negative Coefficients
Authors: Wongsaijai Ben , Sukantamala Nattakorn
Published: April 2015

By making use of the concept of fractionalq-calculus, we firstly defineq-extension of the generalization of the generalized Al-Oboudi differential operator. Then, we introduce new class ofq-analogue ofp-valently closed-to-convex function, and, consequently, new class by means of this new general differential operator. Our main purpose is to determine the general properties on such class and geometric properties for functions belonging to this class with negative coefficient. Further, theq-extension of interesting properties, such as distortion inequalities, inclusion relations, extreme points, radii of generalized starlikeness, convexity and close-to-convexity, quasi-Hadamard properties, and invariant properties, is obtained. Finally, we briefly indicate the relevant connections of our presented results to the former results.
Aggressive Angiomyxoma of the Vulva: A Bizarre Perineal Lesion
Authors: Zizi-Sermpetzoglou Adamantia , Myoteri Despoina , Koulia Kalliroi , Kontostolis Vassilios , Moschouris Hippokratis , Dellaportas Dionysios
Published: April 2015

Introduction. Aggressive angiomyxoma is a rare, slowly growing, and benign tumour of mesenchymal origin, which affects women of reproductive age and is associated with a high risk of local recurrence.Case Presentation. A case of a 47-year-old white female is presented herein, with a large polypoid, gelatinous mass on the right labia majora, measuring 26 × 21 × 6 cm. Histopathologically, the lesion was composed of spindle and stellate-shaped cells embedded in a myxoid matrix. Another specific feature was the presence of variable-sized thin-walled capillaries and thick-walled vascular channels. The patient underwent wide local excision of the tumour with clear margins and developed local recurrence 18 months later.Discussion. Aggressive angiomyxoma of the vulva needs to be distinguished from benign myxoid tumors with a low risk of local recurrence as well as from malignant myxoid neoplasms. Usually wide local excision with tumour-free margins and occasionally hormonal manipulation is the treatment of choice.
Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and HepG2 Cells
Authors: Go Hiroe , Ryuk Jin Ah , Lee Hye Won , Park In Sil , Kil Ki-Jung , Park Sunmin , Kim Dong il , Ko Byoung Seob
Published: April 2015

The present study was conducted to investigate the effect of Sagunja-tang on the lipid related disease in a rat model of menopausal hyperlipidemia and lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells. Inin vivostudy using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media thickness, and nonalcoholic steatohepatitis score, when compared to menopausal hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased the lipid accumulation, total cholesterol levels, and low-density/very-low-density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-β-cyclodextrin-induced decrease in the protein levels of critical molecule involved in cholesterol synthesis, sterol regulatory element binding protein-2, and low-density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of AMP-activated protein kinase was stimulated by Sagunja-tang. These results suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation through regulation of cholesterol synthesis and AMPK activityin vitro. These observations support the idea that Sagunja-tang is bioavailable bothin vivoandin vitroand could be developed as a preventive and therapeutic agent of hyperlipidemia in postmenopausal females.
Dioscorea bulbifera Mediated Synthesis of Novel AucoreAgshell Nanoparticles with Potent Antibiofilm and Antileishmanial Activity
Authors: Ghosh Sougata , Jagtap Soham , More Piyush , Shete Usha J. , Maheshwari Neeraj O. , Rao Shilpa J. , Kitture Rohini , Kale Sangeeta , Bellare Jayesh , Patil Shivprasad , Pal Jayanta K. , Chopade Balu A.
Published: April 2015

Dioscorea bulbifera is a potent medicinal plant used in both Indian and Chinese traditional medicine owing to its rich phytochemical diversity. Herein, we report the rapid synthesis of novel AucoreAgshell nanoparticles by D. bulbifera tuber extract (DBTE). AucoreAgshell NPs synthesis was completed within 5 h showing a prominent peak at 540 nm. HRTEM analysis revealed 9 nm inner core of elemental gold covered by a silver shell giving a total particle diameter upto 15 nm. AucoreAgshellNPs were comprised of 57.34 ± 1.01% gold and 42.66 ± 0.97% silver of the total mass. AucoreAgshellNPs showed highest biofilm inhibition upto 83.68 ± 0.09% against A. baumannii. Biofilms of P. aeruginosa, E. coli, and S. aureus were inhibited up to 18.93 ± 1.94%, 22.33 ± 0.56%, and 30.70 ± 1.33%, respectively. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) confirmed unregulated cellular efflux through pore formation leading to cell death. Potent antileishmanial activity of AucoreAgshellNPs (MIC = 32 µg/mL) was confirmed by MTT assay. Further SEM micrographs showed pronounced deformity in the spindle shaped cellular morphology changing to spherical. This is the first report of synthesis, characterization, antibiofilm, and antileishmanial activity of AucoreAgshellNPs synthesized by D. bulbifera.
Bifurcation Analysis for Nonlinear Recurrence Relations with Threshold Control and2k-Periodic Coefficients
Authors: Dou Liping , Hou Chengmin , Cheng Sui Sun
Published: April 2015

A nonlinear recurrence involving a piecewise constant McCulloch-Pitts function and2k-periodic coefficient sequences is investigated. By allowing the threshold parameter to vary from 0 to∞, we work out a complete bifurcation analysis for the asymptotic behaviors of the corresponding solutions. Among other things, we show that each solution tends towards one of four different limits. Furthermore, the accompanying initial regions for each type of solutions can be determined. It is hoped that our analysis will provide motivation for further results for recurrent McCulloch-Pitts type neural networks.
Metabolomics Profiling to Investigate the Pharmacologic Mechanisms of Berberine for the Treatment of High-Fat Diet-Induced Nonalcoholic Steatohepatitis
Authors: Li Jian , Liu Zezhou , Guo Mingxing , Xu Kejia , Jiang Miao , Lu Aiping , Gao Xiaoyan
Published: April 2015

Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH), which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques.Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group): (i) normal control group; (ii) high-fat diet- (HFD-) induced NASH model group; and (iii) HFD berberine-treated group (i.d. 200 mg/kg). The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH.Key Findings. (i) According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii) Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM), phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE), eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine.Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH.
Quantification of Nonenhancing Tumor Burden in Gliomas Using Effective T2 Maps Derived from Dual-Echo Turbo Spin-Echo MRI
Authors: Ellingson Benjamin M. , Lai Albert , Nguyen Huytram N. , Nghiemphu Phioanh L. , Pope Whitney B. , Cloughesy Timothy F.
Published: April 2015

Purpose: Evaluation of nonenhancing tumor (NET) burden is an important yet challenging part of brain tumor response assessment. This study focuses on using dual-echo turbo spin-echo MRI as a means of quickly estimating tissue T2, which can be used to objectively define NET burden.

Experimental Design: A series of experiments were performed to establish the use of T2 maps for defining NET burden. First, variation in T2 was determined using the American College of Radiology (ACR) water phantoms in 16 scanners evaluated over 3 years. Next, the sensitivity and specificity of T2 maps for delineating NET from other tissues were examined. Then, T2-defined NET was used to predict survival in separate subsets of patients with glioblastoma treated with radiotherapy, concurrent radiation, and chemotherapy, or bevacizumab at recurrence.

Results: Variability in T2 in the ACR phantom was 3% to 5%. In training data, ROC analysis suggested that 125 ms < T2 < 250 ms could delineate NET with a sensitivity of >90% and specificity of >65%. Using this criterion, NET burden after completion of radiotherapy alone, or concurrent radiotherapy, and chemotherapy was shown to be predictive of survival (Cox, P < 0.05), and the change in NET volume before and after bevacizumab therapy in recurrent glioblastoma was also a predictive of survival (P < 0.05).

Conclusions: T2 maps using dual-echo data are feasible, stable, and can be used to objectively define NET burden for use in brain tumor characterization, prognosis, and response assessment. The use of effective T2 maps for defining NET burden should be validated in a randomized, clinical trial. Clin Cancer Res; 21(19); 4373–83. ©2015 AACR.
CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer
Authors: Svensson Susanne , Abrahamsson Annelie , Rodriguez Gabriela Vazquez , Olsson Anna-Karin , Jensen Lasse , Cao Yihai , Dabrosin Charlotta
Published: April 2015

Purpose: Novel therapeutic targets of estrogen receptor (ER)–positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models.

Experimental Design: For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish.

Results: ER+ cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment.

Conclusions: Our findings shed new light on the mechanisms underlying the progression of ER+ breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways. Clin Cancer Res; 21(16); 3794–805. ©2015 AACR.
Accelerating the Delivery of Patient-Centered, High-Quality Cancer Care
Authors: Abrahams Edward , Foti Margaret , Kean Marcia A.
Published: April 2015

Significant progress has been made in the past 50 years across the field of oncology, and, as a result, the number of cancer survivors in the United States is more than 14.5 million. In fact, the number of cancer survivors continues to grow on an annual basis, which is due in part to improved treatments that help people with cancer live longer, and improvements in early detection that allow doctors to find cancer earlier when the disease is easier to treat. However, in spite of this progress, innovation in cancer research and care is at risk as the rise in health care spending is leading to significant pressure to contain costs. As the oncology community seeks to ensure that innovation in cancer research and care continues, it is imperative that stakeholders focus their attention on the value that the research and care continuum provides. Over the past several years, the Turning the Tide Against Cancer initiative has worked with the cancer community to accelerate the delivery of patient-centered, high-quality cancer research and care, while addressing value and cost. This article highlights policy recommendations that resulted from the convening of an expert working group comprising leaders from across the oncology field. Of the recommendations, the co-conveners have identified several issue areas that merit particular focus in 2015: Support FDA's efforts to modernize its framework for bringing new medicines to patients, through facilitating and implementing innovative approaches to drug development and regulatory review.Ensure that cancer clinical pathways or similar decision-support tools are transparent; developed through a physician-driven process that includes patient input; and meet minimum standards for clinical appropriateness, timeliness, and patient centeredness.Support oncology decision-support tools that are timely, clinically appropriate, and patient centered.Build on existing efforts to convene a multistakeholder committee and develop a report on ways to define and measure value in oncology care, taking into account many of the complex dynamics associated with measuring value, including the interests and needs of patients, as well as the importance of committed and ongoing support for innovative research.These policy options are intended to further the national dialogue and represent meaningful and actionable steps toward supporting cancer research and care that is innovative, efficient, and focused on the patient. Clin Cancer Res; 21(10); 2263–7. ©2015 AACR.
Pathogenic Microorganisms and Pancreatic Cancer
Authors: Wang Chunsaier , Li Jingnan
Published: April 2015

Background: Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist, and available treatment modalities do not effectively treat the disease. Established risk factors for pancreatic cancer, including smoking, chronic pancreatitis, obesity and type 2 diabetes mellitus, collectively account for less than half of all pancreatic cancer cases. Accumulating reports have demonstrated that there is an association between pathogenic microorganisms and pancreatic cancer. Summary: A substantial amount of preclinical and clinical evidence suggests that microbiota are likely to influence pancreatic carcinogenesis. This review summarizes the literature on studies examining infections that have been linked to pancreatic cancer. Key Message:Helicobacter pylori infection may be a risk factor for pancreatic cancer; chronic hepatitis virus and oral microbiota may also play a role in pancreatic carcinogenesis. Practical Implications: Considering the worldwide burden of the disease, the association between microbiota and pancreatic cancer in this review may provide new ideas to prevent and treat pancreatic cancer more efficiently. Further studies in this direction are urgently needed.
Viruses, Other Pathogenic Microorganisms and Esophageal Cancer
Authors: Xu Wenjia , Liu Zhongshun , Bao Qunchao , Qian Zhikang
Published: April 2015

Background: Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. Summary: Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. Key Message: Among the above-mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. Practical Implications: Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti-infection measures to prevent EC.
Tissue Transglutaminase, Not Lysyl Oxidase, Dominates Early Calcium-Dependent Remodeling of Fibroblast-Populated Collagen Lattices
Authors: Simon D.D. , Niklason L.E. , Humphrey J.D.
Published: April 2015

Cell-populated collagen gels have provided significant insight into the cellular contractile mechanisms and cell-matrix interactions that are necessary for compacting and remodeling extant matrix. Nevertheless, little research has been devoted towards determining how cells entrench these deformations that contribute to establishing a preferred mechanical state. To this end, we examined the roles of two covalent matrix cross-linkers, i.e. tissue transglutaminase and lysyl oxidase, during global remodeling of the free-floating fibroblast-populated collagen lattice. Inhibition of tissue transglutaminase resulted in a reduced rate of compaction compared to controls during early remodeling (up to 2 days). In contrast, inhibition of lysyl oxidase did not alter the early compaction of these lattices, but it reduced the compaction after 2 days of culture. Acute inhibition of different contractile mechanisms suggested further that calcium-dependent contractility may have dominated during the initial remodeling of the collagen lattice before giving way to calcium-independent contractility at later times. In summary, these findings suggest that early remodeling of the free-floating collagen lattice is facilitated by calcium-dependent cell contraction while entrenchment is dominated by a tissue transglutaminase-mediated cross-linking of the extant matrix. As remodeling continues, however, lysyl oxidase increases its contribution, perhaps by consolidating de novo collagen fibrils into fibers to continue the remodeling while the cells transition to a more sustained, calcium-independent contractility. These results promise to influence future tissue engineering studies as well as computational simulations aimed at understanding matrix remodeling in complex in vivo situations.