bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Tradeoff between Stability and Fit
Authors: Cohen Edith , Cormode Graham , Duffield Nick , Lund Carsten
Published: September 2016

In computing, as in many aspects of life, changes incur cost. Many optimization problems are formulated as a one-time instance starting from scratch. However, a common case that arises is when we already have a set of prior assignments and must decide how to respond to a new set of constraints, given that each change from the current assignment comes at a price. That is, we would like to maximize the fitness or efficiency of our system, but we need to balance it with the changeout cost from the previous state.

We provide a precise formulation for this tradeoff and analyze the resulting
stable extensions
of some fundamental problems in measurement and analytics. Our main technical contribution is a stable extension of Probability Proportional to Size (PPS) weighted random sampling, with applications to monitoring and anomaly detection problems. We also provide a general framework that applies to top-
k
, minimum spanning tree, and assignment. In both cases, we are able to provide exact solutions and discuss efficient incremental algorithms that can find new solutions as the input changes.
One thousand interviews
Authors: Peek Geerten , Taspinar Ahmet
Published: September 2016

How customer insights keep one company agile, and challenge these data scientist to stay ahead in an ever-changing world.
Establishing quantum advantage
Authors: Bouland Adam
Published: September 2016

What are quantum computers good for? This essay reviews the progress toward proving a quantum advantage over classical computing.
Undecidability of the spectral gap
Authors: Bausch Johannes
Published: September 2016

What happens to undecidability in the quantum computing paradigm?
Cholinergic and β-adrenergic control of cardiovascular reflex responses to brief repeated asphyxia in term-equivalent fetal sheep
Authors: Galinsky Robert , Lear Christopher A. , Yamaguchi Kyohei , Wassink Guido , Westgate Jennifer A. , Bennet Laura , Gunn Alistair J.
Published: September 2016

The role of cholinergic and β-adrenergic activity in mediating fetal cardiovascular recovery from brief repeated episodes of asphyxia, consistent with established labor, remains unclear. In this study, we tested the effect of cholinergic and β-adrenergic blockade on the fetal chemoreflex and fetal heart rate (FHR) overshoot responses during brief repeated asphyxia at rates consistent with early or active labor. Chronically instrumented fetal sheep at 0.85 of gestation received either intravenous atropine sulfate (cholinergic blockade; n = 7) or vehicle ( n = 8) followed by 3 × 1-min umbilical cord occlusions repeated every 5 min (1:5; consistent with early labor), or intravenous propranolol hydrochloride (β-adrenergic blockade; n = 8) or vehicle ( n = 6) followed by 3 × 2-min occlusions repeated every 5 min (2:5; consistent with active labor). In vehicle controls, 1:5 occlusions were associated with rapid and sustained FHR decelerations followed by rapid return of FHR to baseline values after release of the occlusion. Cholinergic blockade abolished FHR decelerations during occlusions and caused FHR overshoot after release of the occlusion ( P < 0.05 vs. control 1:5). In vehicle controls, 2:5 occlusions caused rapid and sustained FHR decelerations followed by FHR overshoot after release of the occlusion. β-adrenergic blockade was associated with greater reduction in FHR during occlusions and attenuated FHR overshoot ( P < 0.05 vs. control 2:5). These data demonstrate that the FHR overshoot pattern after asphyxia is mediated by a combination of attenuated parasympathetic activity and increased β-adrenergic stimulation of the fetal heart.
Sex-dependent expression of TRPV1 in bladder arterioles
Authors: Phan Thieu X. , Ton Hoai T. , Chen Yue , Basha Maureen E. , Ahern Gerard P.
Published: September 2016

Transient receptor potential vanilloid type 1 (TRPV1) is a major nociceptive ion channel implicated in bladder physiology and/or pathophysiology. However, the precise expression of TRPV1 in neuronal vs. nonneuronal bladder cells is uncertain. Here we used reporter mouse lines (TRPV1-Cre:tdTomato and TRPV1PLAP-nlacZ) to map expression of TRPV1 in postnatal bladder. TRPV1 was not detected in the urothelium, however, we found marked expression of TRPV1 lineage in sensory nerves, and surprisingly, in arterial/arteriolar smooth muscle (ASM) cells. Tomato fluorescence was prominent in the vesical arteries and in small-diameter (15–40 μm) arterioles located in the suburothelial layer with a near equal distribution in bladder dome and base. Notably, arteriolar TRPV1 expression was greater in females than in males and increased in both sexes after 90 days of age, suggesting sex hormone and age dependency. Analysis of whole bladder and vesical artery TRPV1 mRNA revealed a similar sex and developmental dependence. Pharmacological experiments confirmed functional TRPV1 protein expression; capsaicin increased intracellular Ca2+ in ∼15% of ASM cells from wild-type female bladders, but we observed no responses to capsaicin in bladder arterioles isolated from TRPV1-null mice. Furthermore, capsaicin triggered arteriole constriction that was rapidly reversed by the TRPV1 antagonist, BCTC. These data show that predominantly in postpubertal female mice, bladder ASM cells express functional TRPV1 channels that may act to constrict arterioles. TRPV1 may therefore play an important role in regulating the microcirculation of the female bladder, and this effect may be of significance during inflammatory conditions.
Dissociable roles of preSMA in motor sequence chunking and hand switching—a TMS study
Authors: Muessgens Diana , Thirugnanasambandam Nivethida , Shitara Hitoshi , Popa Traian , Hallett Mark
Published: September 2016

Motor chunking, the grouping of individual movements into larger units, is crucial for sequential motor performance. The presupplementary motor area (preSMA) is involved in chunking and other related processes such as task switching, response selection, and response inhibition that are crucial for organizing sequential movements. However, previous studies have not systematically differentiated the role of preSMA in motor chunking and hand switching, thus leaving its relative contribution to each of these processes unclear. The aim of this study is to demonstrate the differential role of preSMA in motor chunking and hand switching. We designed motor sequences in which different kinds of hand switches (switching toward the right or left hand or continuing with the right hand) were counterbalanced across between- and within-chunk sequence points. Eighteen healthy, right-handed participants practiced four short subsequences (chunks) of key presses. In a subsequent task, these chunks had to be concatenated into one long sequence. We applied double-pulse transcranial magnetic stimulation (TMS) over left preSMA or left M1 areas at sequence initiation, between chunks, or within chunks. TMS over the left preSMA significantly slowed the next response when stimulation was given between chunks, but only if a hand switch toward the contralateral (right) hand was required. PreSMA stimulation within chunks did not interfere with responses. TMS over the left M1 area delayed responses with the contralateral hand, both within and between chunks. Both preSMA and M1 stimulation decreased response times at sequence initiation. These results suggest that left preSMA is not necessary for chunking per se, but rather for organizing complex movements that require chunking and hand switching simultaneously.
Neurofibromatosis Type 2 Presenting with Oculomotor Ophthalmoplegia and Distal Myopathy
Authors: Tevaraj Jessica Mani Penny , Li Min Evelyn Tai , Mohd Noor Raja Azmi , Yaakub Azhany , Wan Hitam Wan Hazabbah
Published: September 2016

Neurofibromatosis type 2 usually presents with bilateral acoustic schwannomas. We highlight the rare presentation of neurofibromatosis initially involving third nerve. A 23-year-old Malay female presented with left eye drooping of the upper lid and limitation of upward movement for 8 years. It was associated with right-sided body weakness, change in voice, and hearing disturbance in the right ear for the past 2 years. On examination, there was mild ptosis and limitation of movement superiorly in the left eye. Both eyes had posterior subcapsular cataract. Fundoscopy showed generalised optic disc swelling in both eyes. She also had palsy of the right vocal cord, as well as the third and eighth nerve. There was wasting of the distal muscles of her right hand, with right-sided decreased muscle power. Pedunculated cutaneous lesions were noted over her body and scalp. MRI revealed bilateral acoustic and trigeminal schwannomas with multiple extra-axial lesions and intradural extramedullary nodules. Patient was diagnosed with neurofibromatosis type 2 and planned for craniotomy and tumour debulking, but she declined treatment. Neurofibromatosis type 2 may uncommonly present with isolated ophthalmoplegia, so a thorough physical examination and a high index of suspicion are required to avoid missing this condition.
Cost-Sensitive Radial Basis Function Neural Network Classifier for Software Defect Prediction
Authors: Kumudha P. , Venkatesan R.
Published: September 2016

Effective prediction of software modules, those that are prone to defects, will enable software developers to achieve efficient allocation of resources and to concentrate on quality assurance activities. The process of software development life cycle basically includes design, analysis, implementation, testing, and release phases. Generally, software testing is a critical task in the software development process wherein it is to save time and budget by detecting defects at the earliest and deliver a product without defects to the customers. This testing phase should be carefully operated in an effective manner to release a defect-free (bug-free) software product to the customers. In order to improve the software testing process, fault prediction methods identify the software parts that are more noted to be defect-prone. This paper proposes a prediction approach based on conventional radial basis function neural network (RBFNN) and the novel adaptive dimensional biogeography based optimization (ADBBO) model. The developed ADBBO based RBFNN model is tested with five publicly available datasets from the NASA data program repository. The computed results prove the effectiveness of the proposed ADBBO-RBFNN classifier approach with respect to the considered metrics in comparison with that of the early predictors available in the literature for the same datasets.
Bilateral Lacrimal Gland Lymphoma in Sjögren Syndrome
Authors: Palamar Melis , Ozsan Nazan , Sahin Fahri
Published: September 2016

A 31-year-old female with Primary Sjögren Syndrome (pSS) presented with bilateral puffiness around the eye for 3 years. The lacrimal glands were hypertrophic and edematous bilaterally. Schirmer 1 score was 2 and 1 mm and tear-film break-up time was 3 and 4 seconds, in the right and the left eyes, respectively. An incisional biopsy from the left lacrimal gland revealed diffuse and intense CD20, CD5, and bcl-2 positivity with negative cyclin D1 and CD23 which supported lymphoma. Upon haematology consultation extranodal marginal zone lymphoma diagnosis was made. CHOP (cyclophosphamide, doxorubicin, vincristine, and methyl prednisolone) treatment was initiated. In conclusion, pSS is a well known autoimmune disease in which increased rate of lymphoma is present. Early detection with histopathologic confirmation and multidisciplinary approach with ophthalmology, rheumatology, and haematology are mandatory in these patients.
Meta‐Analysis of the Clinical Effectiveness and Safety of Ligustrazine in Cerebral Infarction
Authors: Yu Tian , Guo Xiaoheng , Zhang Zhen , Liu Rong , Zou Liang , Fu Jia , Shi Zheng
Published: September 2016

Objectives. To evaluate the efficacy and safety of ligustrazine in the treatment of cerebral infarction. Methods. A systematic literature search was conducted in 6 databases until 30 June 2016 to identify randomized controlled trials (RCTs) of ligustrazine in the treatment of cerebral infarction. The quality of all the included studies was evaluated. All data were analyzed by Review Manager 5.1 Software. Results. 19 RCTs totally involving 1969 patients were included. The primary outcome measures were Neurological Deficit Score (NDS) and clinical effective rate. The secondary outcome measure was adverse events. Meta‐analysis showed that ligustrazine could improve clinical efficacy and NDS of cerebral infarction with [OR = 3.60, 95% CI (2.72, 4.78), P < 0.00001] and [WMD = −3.87, 95% CI (−4.78, −2.95), P < 0.00001]. Moreover, ligustrazine in treatment group exerted better clinical effects in improving the Blood Rheology Index (BRI) in patients compared with control group. Ten trials contained safety assessments and stated that no obvious side effects were found. Conclusions. Ligustrazine demonstrated definite clinical efficacy for cerebral infarction, and it can also improve NDS in patients without obvious adverse events. However, due to the existing low‐quality research, more large‐scale and multicentric RCTs are required to provide clear evidence for its clinical efficacy in the near future.
Pancreatic Neuroendocrine Tumor in the Setting of Dorsal Agenesis of the Pancreas
Authors: Nassif Samih , Ponchiardi Cecilia , Sachs Teviah
Published: September 2016

Dorsal agenesis of the pancreas (DAP) is an uncommon embryological abnormality where there is absence of the distal pancreas. DAP is mostly asymptomatic, but common presenting symptoms include diabetes mellitus, abdominal pain, pancreatitis, enlarged pancreatic head, and, in a few cases, polysplenia. MRCP and ERCP are the gold standard imaging techniques to demonstrate the absence of the dorsal pancreatic duct. The literature on the association of pancreatic neoplasia and DAP is limited. We present the case of a pancreatic neuroendocrine tumor in a patient with dorsal agenesis of the pancreas, with a review of the related literature.
The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis
Authors: Ruiz-Padilla A. J. , Gamez-Nava J. I. , Saldaña-Cruz A. M. , Murillo-Vazquez J. D. , Vazquez-Villegas M. L. , Zavaleta-Muñiz S. A. , Martín-Márquez B. T. , Ponce-Guarneros J. M. , Rodriguez Jimenez N. A. , Flores-Chavez A. , Sandoval-Garcia F. , Vasquez-Jimenez J. C. , Cardona-Muñoz E. G. , Totsuka-Sutto S. E. , Gonzalez-Lopez L.
Published: September 2016

Objective. To evaluate the association of -174G/CIL-6polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped forIL-6-174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2).Results. Patients with MTX or LEF had significant decrement in DAS-28 (p<0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07–1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05–2.3;p=0.003), or CC (RR = 1.83; 95% CI = 1.07–3.14;p=0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03–1.72;p=0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded thatIL-6-174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.
Fractional Mathematical Operators and Their Computational Approximation
Authors: Crespo José , Montáns Francisco Javier
Published: September 2016

Usual applied mathematics employs three fundamental arithmetical operators: addition, multiplication, and exponentiation. However, for example, transcendental numbers are said not to be attainable via algebraic combination with these fundamental operators. At the same time, simulation and modelling frequently have to rely on expensive numerical approximations of the exact solution. The main purpose of this article is to analyze new fractional arithmetical operators, explore some of their properties, and devise ways of computing them. These new operators may bring new possibilities, for example, in approximation theory and in obtaining closed forms of those approximations and solutions. We show some simple demonstrative examples.
Long Noncoding RNA H19 in Digestive System Cancers: A Meta-Analysis of Its Association with Pathological Features
Authors: Lin Yang , Xu Lijian , Wei Wei , Zhang Xiaohui , Ying Rongchao
Published: September 2016

Long noncoding RNA (lncRNA) H19 has been reported to be upregulated in malignant digestive tumors, but its clinical relevance is not yet established. The meta-analysis was to investigate the association between H19 expression and pathological features of digestive system cancers. The databases of PubMed, EMBase, Web of Science, CNKI, and WanFang were searched for the related studies. A total of 478 patients from 6 studies were finally included. The meta-analysis showed that the patient group of high H19 expression had a higher risk of poorly differentiated grade, deep tumor invasion (T2 stage or more), lymph node metastasis, and advanced TNM stage than the group of low H19 expression, although there was no difference between them in terms of distant metastasis. Therefore, the high expression of lncRNA H19 might predict poor oncological outcomes of patients with digestive system cancers.
MMSE-NP-RISIC-Based Channel Equalization for MIMO-SC-FDE Troposcatter Communication Systems
Authors: Xie Zedong , Chen Xihong , Liu Xiaopeng , Zhao Yu
Published: September 2016

The impact of intersymbol interference (ISI) on single-carrier frequency-domain equalization with multiple input multiple output (MIMO-SC-FDE) troposcatter communication systems is severe. Most of the channel equalization methods fail to solve it completely. In this paper, given the disadvantages of the noise-predictive (NP) MMSE-based and the residual intersymbol interference cancellation (RISIC) equalization in the single input single output (SISO) system, we focus on the combination of both equalization schemes mentioned above. After extending both of them into MIMO system for the first time, we introduce a novel MMSE-NP-RISIC equalization method for MIMO-SC-FDE troposcatter communication systems. Analysis and simulation results validate the performance of the proposed method in time-varying frequency-selective troposcatter channel at an acceptable computational complexity cost.
Hybrid Vibration Control under Broadband Excitation and Variable Temperature Using Viscoelastic Neutralizer and Adaptive Feedforward Approach
Authors: Marra João C. O. , Lopes Eduardo M. O. , Espíndola José João de , Gontijo Walter Antônio
Published: September 2016

Vibratory phenomena have always surrounded human life. The need for more knowledge and domain of such phenomena increases more and more, especially in the modern society where the human-machine integration becomes closer day after day. In that context, this work deals with the development and practical implementation of a hybrid (passive-active/adaptive) vibration control system over a metallic beam excited by a broadband signal and under variable temperature, between 5 and 35°C. Since temperature variations affect directly and considerably the performance of the passive control system, composed of a viscoelastic dynamic vibration neutralizer (also called a viscoelastic dynamic vibration absorber), the associative strategy of using an active-adaptive vibration control system (based on a feedforward approach with the use of the FXLMS algorithm) working together with the passive one has shown to be a good option to compensate the neutralizer loss of performance and generally maintain the extended overall level of vibration control. As an additional gain, the association of both vibration control systems (passive and active-adaptive) has improved the attenuation of vibration levels. Some key steps matured over years of research on this experimental setup are presented in this paper.
Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma
Authors: Lin Pei-cheng , He Jun-yan , Le Yu-yin , Du Kai-xin , Zhu Wei-feng , Peng Qing-qin , Dong Ya-ping , Li Jin-luan , Wu Jun-xin
Published: September 2016

Purpose.This study aimed to evaluate the characteristics of the HVGGSSV peptide, exploring radiation-guided delivery in a mouse model of nasopharyngeal carcinoma.Methods.Mice with CNE-1 nasopharyngeal carcinoma were assigned to two different groups treated with Cy7-NHS and Cy7-HVGGSSV, respectively. Meanwhile, each mouse received a single dose of 3 Gy radiation. Biological distribution of the recombinant peptide was assessed on anin vivosmall animal imaging system.Results.The experimental group showed maximum fluorescence intensity in irradiated tumors treated with Cy7-labeled HVGGSSV, while untreated (0 Gy) control tumors showed lower intensity levels. Fluorescence intensities of tumors in the right hind limbs of experimental animals were7.84×107±1.13×107,1.35×108±2.66×107,4.05×108±1.75×107,5.57×108±3.47×107, and9.26×107±1.73×107photons/s/cm2higher compared with left hind limb values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence intensities of tumor in the right hind limbs of the experimental group were1.66×108±1.71×107,1.51×108±3.23×107,5.38×108±1.96×107,5.89×108±3.57×107, and1.62×108±1.69×107photons/s/cm2higher compared with control group values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence was not specifically distributed in the control group. Compared with low fluorescence intensity in the heart, lungs, and tumors, high fluorescence distribution was found in the liver and kidney at 48 h.Conclusions.HVGGSSV was selectively bound to irradiated nasopharyngeal carcinoma, acting as a targeting transport carrier for radiation-guided drugs that are mainly metabolized in the kidney and liver.
Melanocortin-4 Receptor Deficiency Phenotype with an Interstitial 18q Deletion: A Case Report of Severe Childhood Obesity and Tall Stature
Authors: Abdullah Sarah , Reginold William , Kiss Courtney , Harrison Karen J. , MacKenzie Jennifer J.
Published: September 2016

Childhood obesity is a growing health concern, associated with significant physical and psychological morbidity. Childhood obesity is known to have a strong genetic component, with mutations in themelanocortin-4 receptor(MC4R) gene being the most common monogenetic cause of obesity. Over 166 differentMC4Rmutations have been identified in persons with hyperphagia, severe childhood obesity, and increased linear growth. However, it is unclear whether the MC4-R deficiency phenotype is due to haploinsufficiency or dominant-negative effects by the mutant receptor. We report the case of a four-and-a-half-year-old boy with an interstitial deletion involving the long arm of chromosome 18 (46,XY,del(18)(q21.32q22.1)) encompassing theMC4Rgene. This patient presented with tall stature and hyperphagia within his first 18 months of life leading to significant obesity. This case supports haploinsufficiency of MC4-R as it describes a MC4-R deficiency phenotype in a patient heterozygous for a fullMC4Rgene deletion. The intact functional allele with MC4-R haploinsufficiency has the potential to favor a therapeutic response to gastric surgery. Currently, small molecule MC4-R agonists are under development for pharmacologic therapy.
Shear Bond Strength of Three Orthodontic Bonding Systems on Enamel and Restorative Materials
Authors: Hellak Andreas , Ebeling Jennifer , Schauseil Michael , Stein Steffen , Roggendorf Matthias , Korbmacher-Steiner Heike
Published: September 2016

Objective.The aim of this in vitro study was to determine the shear bond strength (SBS) and adhesive remnant index (ARI) score of two self-etching no-mix adhesives (iBond™and Scotchbond™) on different prosthetic surfaces and enamel, in comparison with the commonly used total etch system Transbond XT™.Materials and Methods. A total of 270 surfaces (1 enamel and 8 restorative surfaces,n=30) were randomly divided into three adhesive groups. In group 1 (control) brackets were bonded with Transbond XT primer. In the experimental groups iBond adhesive (group 2) and Scotchbond Universal adhesive (group 3) were used. The SBS was measured using a Zwicki 1120™testing machine. The ARI and SBS were compared statistically using the Kruskal–Wallis test (P≤0.05).Results. Significant differences in SBS and ARI were found between the control group and experimental groups.Conclusions. Transbond XT showed the highest SBS on human enamel. Scotchbond Universal on average provides the best bonding on all other types of surface (metal, composite, and porcelain), with no need for additional primers. It might therefore be helpful for simplifying bonding in orthodontic procedures on restorative materials in patients. If metal brackets have to be bonded to a metal surface, the use of a dual-curing resin is recommended.
Self‐Care for Common Colds by Primary Care Patients: A European Multicenter Survey on the Prevalence and Patterns of Practices—The COCO Study
Authors: Thielmann Anika , Gerasimovska-Kitanovska Biljana , Buczkowski Krzysztof , Koskela Tuomas H. , Mevsim Vildan , Czachowski Slawomir , Petrazzuoli Ferdinando , Petek-Šter Marija , Lingner Heidrun , Hoffman Robert D. , Tekiner Selda , Chambe Juliette , Edirne Tamer , Hoffmann Kathryn , Pirrotta Enzo , Uludağ Ayşegül , Yikilkan Hülya , Kreitmayer Pestic Sanda , Zielinski Andrzej , Guede Fernández Clara , Weltermann Birgitta
Published: September 2016

Background. Patients use self‐care to relieve symptoms of common colds, yet little is known about the prevalence and patterns across Europe. Methods/Design. In a cross‐sectional study 27 primary care practices from 14 countries distributed 120 questionnaires to consecutive patients (≥18 years, any reason for consultation). A 27‐item questionnaire asked for patients’ self‐care for their last common cold. Results. 3,074 patients from 27 European sites participated. Their mean age was 46.7 years, and 62.5% were females. 99% of the participants used ≥1 self‐care practice. In total, 527 different practices were reported; the age‐standardized mean was 11.5 (±SD 6.0) per participant. The most frequent self‐care categories were foodstuffs (95%), extras at home (81%), preparations for intestinal absorption (81%), and intranasal applications (53%). Patterns were similar across all sites, while the number of practices varied between and within countries. The most frequent single practices were water (43%), honey (42%), paracetamol (38%), oranges/orange juice (38%), and staying in bed (38%). Participants used 9 times more nonpharmaceutical items than pharmaceutical items. The majority (69%) combined self‐care with and without proof of evidence, while ≤1% used only evidence‐based items. Discussion. This first cross‐national study on self‐care for common colds showed a similar pattern across sites but quantitative differences.
Massive Preperitoneal Hematoma after a Subcutaneous Injection
Authors: Katagiri Hideki , Yoshikawa Kentaro , Lefor Alan Kawarai , Kubota Tadao , Mizokami Ken
Published: September 2016

Preperitoneal hematomas are rare and can develop after surgery or trauma. A 74-year-old woman, receiving systemic anticoagulation, developed a massive preperitoneal hematoma after a subcutaneous injection of teriparatide using a 32-gauge, 4 mm needle. In this patient, there were two factors, the subcutaneous injection of teriparatide and systemic anticoagulation, associated with development of the hematoma. These two factors are especially significant, because they are widely used clinically. Although extremely rare, physicians must consider this potentially life-threatening complication after subcutaneous injections, especially in patients receiving anticoagulation.
Hyers-Ulam Stability of Fractional Nabla Difference Equations
Authors: Jonnalagadda Jagan Mohan
Published: September 2016

We investigate the Hyers-Ulam stability, the generalized Hyers-Ulam stability, and the Fα-Hyers-Ulam stability of a linear fractional nabla difference equation using discrete Laplace transform. We provide a few examples to illustrate the applicability of established results.
Putative Key Role of Inositol Messengers in Endothelial Cells in Preeclampsia
Authors: Kunjara Sirilaksana , McLean Patricia , Rademacher Laurens , Rademacher Thomas W. , Fascilla Fabiana , Bettocchi Stefano , Scioscia Marco
Published: September 2016

Immunological alterations, endothelial dysfunction, and insulin resistance characterize preeclampsia. Endothelial cells hold the key role in the pathogenesis of this disease. The signaling pathways mediating these biological abnormalities converge on PKB/Akt, an intracellular kinase regulating cell survival, proliferation, and metabolism. Inositol second messengers are involved in metabolic and cell signaling pathways and are highly expressed during preeclampsia. Intracellular action of these molecules is deeply affected by zinc, manganese, and calcium. To evaluate the pathophysiological significance, we present the response of the intracellular pathways of inositol phosphoglycans involved in cellular metabolism and propose a link with the disease.
Hyperammonemia: What Urea-lly Need to Know: Case Report of Severe Noncirrhotic Hyperammonemic Encephalopathy and Review of the Literature
Authors: Upadhyay Ruby , Bleck Thomas P. , Busl Katharina M.
Published: September 2016

Purpose. A 66-year-old man who presented with coma was found to have isolated severe hyperammonemia and diagnosed with a late-onset urea-cycle disorder. He was treated successfully and had full recovery.Methods. We report a novel case of noncirrhotic hyperammonemia and review the literature on this topic. Selected literature for review included English-language articles concerning hyperammonemia using the search terms “hyperammonemic encephalopathy”, “non-cirrhotic encephalopathy”, “hepatic encephalopathy”, “urea-cycle disorders”, “ornithine transcarbamylase (OTC) deficiency”, and “fulminant hepatic failure”.Results. A unique case of isolated hyperammonemia diagnosed as late-onset OTC deficiency is presented. Existing evidence about hyperammonemia is organized to address pathophysiology, clinical presentation, diagnosis, and treatment. The case report is discussed in context of the reviewed literature.Conclusion. Late-onset OTC deficiency presenting with severe hyperammonemic encephalopathy and extensive imaging correlate can be fully reversible if recognized promptly and treated aggressively.
The Evolution of Temporal and Spatial Patterns of Carbon Monoxide Concentrations in the Metropolitan Area of Sao Paulo, Brazil
Authors: Ribeiro Flavia Noronha Dutra , Salinas Delhi Teresa Paiva , Soares Jacyra , de Oliveira Amauri Pereira , de Miranda Regina Maura , Souza Luana Antunes Tolentino
Published: September 2016

The Environmental Agency of Sao Paulo has a large dataset of carbon monoxide measurements: 20 years of records in 18 automatic stations inside the metropolitan area. However, a thorough investigation on the time evolution of CO concentration tendency and cycles also considering spatial variability is lacking. The investigation consists of a trend line analysis, a periodogram analysis, a correlation between CO concentration and meteorological variables, and spatial distribution of CO concentration. Local and federal policies helped in decreasing CO concentrations and the highest decreasing rate was 0.7% per month. This tendency is lately stabilizing, since the vehicles fleet is increasing. CO most relevant cycles are annual and diurnal and a few series indicate a weekly cycle. Diurnal cycle shows two peaks, morning and evening rush hours, 1.2 and 1.1 ppm, respectively, in 2012. However, lately there is an extended evening peak (20 h to 23 h), related to changes in emission patterns. The spatial analysis showed that CO concentration has high spatial variability and is influenced by proximity to heavy traffic and vegetated areas. The present work indicates that several processes affect CO concentration and these results form a valuable basis for other studies involving air quality modeling, mitigation, and urban planning.
Heuristics for the Economic Production Quantity Problem under Restrictions on Production and Maintenance Time
Authors: Xu Qi , Xu Jianteng
Published: September 2016

This paper proposes an economic production quantity problem with the maximal production run time and minimal preventive maintenance time over a finite planning horizon. The objective is to find the efficient production and maintenance policy to minimize the total cost composed of production, maintenance, shortages, and holding costs under the restriction on the production run time and the preventive maintenance time. The production and maintenance decisions include the production and maintenance frequencies and the production run and the maintenance time. The variability and the boundedness of the production run and maintenance time make the problem difficult to solve. Two heuristic algorithms are developed using different techniques based on the optimal properties of the relaxed problem. The performance comparison between the two algorithms is illustrated by numerical examples. The numerical results show that, for the most part, there exists a heuristic algorithm which is more effective than the other.
Distribution of Helminth Parasites in Intestines and Their Seasonal Rate of Infestation in Three Freshwater Fishes of Kashmir
Authors: Wali Asifa , Balkhi Masood-ul Hassan , Maqbool Rafia , Darzi Mohammed Maqbool , Shah Feroz Ahmad , Bhat Farooz Ahmad , Bhat Bilal Ahmad
Published: September 2016

The present study was undertaken to determine the incidence of helminth parasites in fishes with special reference to water quality parameters in Dal Lake and River Jhelum and correlate the observations. Water, fish, and parasite samples were collected during different seasons from various sites and processed. Three fish species, namely,Schizothorax nigerHeckel 1838,Schizothorax esocinusHeckel 1838, andSchizothorax curvifronsHeckel 1838, were recovered from these water bodies. The physicochemical parameters temperature, dissolved oxygen, pH, and free carbon dioxide showed variation vis-à-vis the season and location of the stations in water bodies. Acanthocephalan parasitePomphorhynchus kashmirensisKaw 1941 (27.47%) and two intestinal cestodesBothriocephalus acheilognathiYamaguti 1934 (30.63%) andAdenoscolex oreiniFotedar 1958 (32.43%) were recovered from all the three species ofSchizothorax. All the three parasites showed higher prevalence during summer and the least prevalence during winter. Parasitic infections were prevalent more in male fishes compared to females. The presence of the parasites had reduced the condition coefficient of the infected fishes in both water bodies. The study also showed that some of the physicochemical features showed a significant positive correlation with the prevalence.
Blast Protection of Unreinforced Masonry Walls: A State-of-the-Art Review
Authors: Lantz Lucas , Maynez Joshua , Cook Wesley , Wilson Claudia Mara Dias
Published: September 2016

The recent rise of terrorist attacks has reinforced the need for mitigation of damage caused by blast loading on unreinforced masonry walls. The primary goal of the techniques is to prevent the loss of life while simultaneously preserving the integrity of the structure. This paper presents a compilation of recently available literature on blast protection of unreinforced masonry walls. It seeks to present the state of the art in this field, including mitigation techniques considered as well as testing methods selected. Fiber reinforced polymers and polyurea are the two dominant retrofitting techniques being assessed in the field. Other techniques include but are not limited to polyurethane, steel sheets, and aluminum foam. Since there is no widely implemented standard for blast loading test procedures, direct comparisons between the efficiencies of the mitigation techniques proposed are not always feasible. Although fragmentation is an indicator of the efficiency of retrofits, it is currently measured by subjective observation of postblast debris.
Activated Müller Cells Involved in ATP-Induced Upregulation of P2X7Receptor Expression and Retinal Ganglion Cell Death
Authors: Xue Ying , Xie Yuting , Xue Bo , Hu Nan , Zhang Guowei , Guan Huaijin , Ji Min
Published: September 2016

P2X7receptor (P2X7R), an ATP-gated ion channel, plays an important role in glaucomatous retinal ganglion cell (RGC) apoptotic death, in which activated retinal Müller glial cells may be involved by releasing ATP. In the present study, we investigated whether and how activated Müller cells may induce changes in P2X7R expression in RGCs by using immunohistochemistry and Western blot techniques. Intravitreal injection of DHPG, a group I metabotropic glutamate receptor (mGluR I) agonist, induced upregulation of GFAP expression, suggestive of Müller cell activation (gliosis), as we previously reported. Accompanying Müller cell activation, P2X7R protein expression was upregulated, especially in the cells of ganglion cell layer (GCL), which was reversed by coinjection of brilliant blue G (BBG), a P2X7R blocker. In addition, intravitreal injection of ATP also induced upregulation of P2X7R protein expression. Similar results were observed in cultured retinal neurons by ATP treatment. Moreover, both DHPG and ATP intravitreal injection induced a reduction in the number of fluorogold retrogradely labeled RGCs, and the DHPG effect was partially rescued by coinjection of BBG. All these results suggest that activated Müller cells may release ATP and, in turn, induce upregulation of P2X7R expression in the cells of GCL, thus contributing to RGC death.
Aberrant JMJD3 Expression Upregulates Slug to Promote Migration, Invasion, and Stem Cell–Like Behaviors in Hepatocellular Carcinoma
Authors: Tang Bo , Qi Guangying , Tang Fang , Yuan Shengguang , Wang Zhenran , Liang Xingsi , Li Bo , Yu Shuiping , Liu Jie , Huang Qi , Wei Yangchao , Zhai Run , Lei Biao , Yu Hongping , Tomlinson Stephen , He Songqing
Published: September 2016

The Jumonji domain–containing chromatin remodeling factor JMJD3 has important roles in development and cancer. Here, we report a pivotal role for JMJD3 in sustaining the phenotype of aggressive hepatocellular carcinomas. Expression levels of JMJD3 in clinical specimens of hepatocellular carcinoma correlated inversely with patient survival. In hepatocellular carcinoma cells, we found that enforcing its overexpression induced epithelial–mesenchymal transition (EMT), invasive migration, stem cell–like traits, and metastatic properties. Conversely, silencing JMJD3 in hepatocellular carcinoma cells overexpressing it inhibited these aggressive phenotypes. Mechanistically, JMJD3 modulated H3K27me3 in the SLUG gene promoter, a histone mark associated with active SLUG transcription. SLUG silencing blocked JMJD3-induced EMT, stemness, and metastasis. Furthermore, SLUG expression in hepatocellular carcinoma clinical specimens correlated positively with JMJD3 expression. Our results establish JMJD3 as a critical driver of hepatocellular carcinoma stem cell–like and metastatic behaviors, with implications for prognosis and treatment. Cancer Res; 76(22); 6520–32. ©2016 AACR.
LncRNA HOXA11-AS Promotes Proliferation and Invasion of Gastric Cancer by Scaffolding the Chromatin Modification Factors PRC2, LSD1, and DNMT1
Authors: Sun Ming , Nie Fengqi , Wang Yunfei , Zhang Zhihong , Hou Jiakai , He Dandan , Xie Min , Xu Lin , De Wei , Wang Zhaoxia , Wang Jun
Published: September 2016

Long noncoding RNAs (lncRNA) have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we investigated lncRNA alterations that contribute to gastric cancer through an analysis of The Cancer Genome Atlas RNA sequencing data and other publicly available microarray data. Here we report the gastric cancer–associated lncRNA HOXA11-AS as a key regulator of gastric cancer development and progression. Patients with high HOXA11-AS expression had a shorter survival and poorer prognosis. In vitro and in vivo assays of HOXA11-AS alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, and apoptosis. Strikingly, high-throughput sequencing analysis after HOXA11-AS silencing highlighted alterations in cell proliferation and cell–cell adhesion pathways. Mechanistically, EZH2 along with the histone demethylase LSD1 or DNMT1 were recruited by HOXA11-AS, which functioned as a scaffold. HOXA11-AS also functioned as a molecular sponge for miR-1297, antagonizing its ability to repress EZH2 protein translation. In addition, we found that E2F1 was involved in HOXA11-AS activation in gastric cancer cells. Taken together, our findings support a model in which the EZH2/HOXA11-AS/LSD1 complex and HOXA11-AS/miR-1297/EZH2 cross-talk serve as critical effectors in gastric cancer tumorigenesis and progression, suggesting new therapeutic directions in gastric cancer. Cancer Res; 76(21); 6299–310. ©2016 AACR.
Meat, Fish, Poultry, and Egg Intake at Diagnosis and Risk of Prostate Cancer Progression
Authors: Wilson Kathryn M. , Mucci Lorelei A. , Drake Bettina F. , Preston Mark A. , Stampfer Meir J. , Giovannucci Edward , Kibel Adam S.
Published: September 2016

Little information exists on diet and prostate cancer progression. We examined the association between intakes of total red meat, processed and unprocessed red meat, poultry, fish, and eggs and prostate cancer recurrence. We conducted a prospective study of 971 men treated with radical prostatectomy for prostate cancer between 2003 and 2010. Men completed a food frequency questionnaire at diagnosis. We used logistic regression to study the association between diet and high-grade or advanced-stage disease. We used Cox models to study the risk of progression [N = 94 events, mainly prostate-specific antigen (PSA) recurrence]. Total red meat intake was marginally associated with risk of high-grade disease [Gleason ≥ 4+3; adjusted OR top vs. bottom quartile: 1.66; 95% confidence interval (CI), 0.93–2.97; Ptrend = 0.05], as was very high intake of eggs (OR top decile vs. bottom quartile: 1.98; 95% CI, 1.08–3.63, Ptrend = 0.08). Well-done red meat was associated with advanced disease (≥pT3; OR top vs. bottom quartile: 1.74, 95% CI, 1.05–2.90; Ptrend = 0.01). Intakes of red meat, fish, and eggs were not associated with progression. Very high poultry intake was inversely associated with progression (HR top decile vs. bottom quartile: 0.19; 95% CI, 0.06–0.63; Ptrend = 0.02). Substituting 30 g/d of poultry or fish for total or unprocessed red meat was associated with significantly lower risk of recurrence. Lower intakes of red meat and well-done red meat and higher intakes of poultry and fish are associated with lower risk of high grade and advanced prostate cancer and reduced recurrence risk, independent of stage and grade. Cancer Prev Res; 9(12); 933–41. ©2016 AACR.
Long-Range Chromatin Interactions Drive Mutant TERT Promoter Activation
Authors: Akıncılar Semih Can , Khattar Ekta , Boon Priscilla Li Shan , Unal Bilal , Fullwood Melissa Jane , Tergaonkar Vinay
Published: September 2016

Cancer-specific TERT promoter mutations (-146C>T and -124C>T) have been linked to reactivation of the epigenetically silenced telomerase reverse transcriptase gene (TERT). Understanding how these single-nucleotide alterations drive TERT reactivation is a fundamental unanswered question and is key for making successful therapeutics. We show that unlike wild-type promoters, recruitment of the transcription factor GABPA specifically to mutant TERT promoters mediates long-range chromatin interaction and enrichment of active histone marks, and hence drives TERT transcription. CRISPR-mediated reversal of mutant TERT promoters, or deletion of its long-range interacting chromatin, abrogates GABPA binding and long-range interactions, leading to depletion of active histone marks, loss of POL2 recruitment, and suppression of TERT transcription. In contrast, de novo introduction of a TERT promoter mutation enables GABPA binding and upregulation of TERT via long-range interactions, acquisition of active histone marks, and subsequent POL2 recruitment. This study provides a unifying mechanistic insight into activation of mutant TERT promoters across various human cancers.

Significance: This study identifies a key mechanism by which cancer-specific mutant TERT promoters cause reactivation of TERT. Because the mechanism uncovered here is not utilized by promoters that drive TERT in normal cells, this mechanism could be exploited to make inhibitors which have the potential to block telomerase function and hence the progression of up to 90% of human cancers. Cancer Discov; 6(11); 1276–91. ©2016 AACR.

See related commentary by Min and Shay, p. 1212.

This article is highlighted in the In This Issue feature, p. 1197
Prenatal Echocardiographic Assessment of Foramen Ovale Appearance in Fetuses with D-Transposition of the Great Arteries and Impact on Neonatal Outcome
Authors: Tuo Giulia , Paladini Dario , Montobbio Giovanni , Volpe Paolo , Cheli Martino , Calevo Maria Grazia , Marasini Maurizio
Published: September 2016

Introduction: Neonates with D-transposition of the great arteries (dTGA) may die at birth because of the inadequate intracardiac mixing due to a misdiagnosed restrictive foramen ovale. We reviewed our experience in echocardiographic assessment and perinatal management of fetuses with dTGA searching for new features that may predict the need for urgent balloon atrial septostomy (BAS) immediately after birth. Patients and Methods: We included fetuses diagnosed with dTGA between January 2000 and December 2014. We assessed pre- and postnatal appearance of the foramen ovale, ductus arteriosus and pulmonary veins. Both the diagnostic findings at the time of last prenatal echocardiogram and those findings deriving from a retrospective reevaluation of stored videos were considered. BAS was defined as urgent if performed in neonates with restrictive foramen ovale and severe hypoxemia. Results: We reviewed 40 fetuses with dTGA. 20/40 fetuses received urgent BAS at birth. Not only the restrictive but also the hypermobile and the redundant appearance of the foramen ovale was significantly associated with urgent BAS (p < 0.0001, p = 0.002 and p = 0.0001, respectively). Conclusions: Prenatal evaluation of the foramen ovale appearance in fetuses with dTGA is still challenging. Based on our experience, also the redundant foramen ovale appearance may need urgent BAS at birth.