bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreaticopericardial fistula: a rare complication of chronic pancreatitis
Authors: Nasa Mukesh , Patil Gaurav , Choudhary Narendra Singh , Puri Rajesh
Published: May 2016

Pancreaticopericardial fistula (PPF) is an extremely rare clinical problem encountered in patients with chronic pancreatitis. The diagnosis should be suspected if a patient presents with pericardial effusion on a background of chronic pancreatitis. Significantly raised amylase in the pericardial fluid offers an important clue for the diagnosis. CT is the initial imaging modality to look for pancreatic and pericardial changes. The therapeutic options include medical, endoscopic or surgical interventions. Medical and endoscopic therapies are the preferred modes of treatment while surgery is reserved for those who fail these measures.
Temporary leadless pacing in a patient with severe device infection
Authors: Kypta Alexander , Blessberger Hermann , Lichtenauer Michael , Steinwender Clemens
Published: May 2016

A 64-year-old patient underwent implantation of a transcatheter pacing systems (TPS) for severe lead endocarditis. The patient experienced fever after a dental procedure. On the transoesophageal echocardiogram (TEE), vegetations were attached to the leads. Because the patient was pacemaker dependent, a temporary pacing lead had to be placed. After removal, however, he did not improve. A second TEE showed new vegetations. Ventricular fibrillation occurred spontaneously; so isoprenalin had to be stopped and a new lead was implanted. Vegetations appeared soon after the new temporary lead was placed. We used a TPS as a bridging device, followed by implantation of a resynchronisation system, and explantation of the TPS. After the Micra TPS was implanted, the patient recovered noticeably. All inflammation parameters were negative and an additional18F-fluorodeoxyglucose-positron emission tomography/CT imaging also proved to be negative. So a CRT-D device was then implanted, and the TCP was removed.
Positional hoarseness: an unusual symptom in jugular foramen mass
Authors: Jaiswal Manish , Bhaskar Mukesh Kumar , Mittal Radhey Shyam , Ojha Balkrishna
Published: May 2016

We came across a case of jugular foramen mass causing positional hoarseness on turning the head left and disappearing on returning the head to a straight position. Hoarseness of voice due to vagus nerve involvement is seen in jugular foramen mass but positional hoarseness has never been seen before. We report this rarest presentation and discuss the pathophysiology behind it.
Comparing physical activity and sedentary time among overweight and nonoverweight preschoolers enrolled in early learning programs: a cross-sectional study
Authors: Tucker Patricia , Maltby Alana M. , Burke Shauna M. , Vanderloo Leigh M. , Irwin Jennifer D.
Published: May 2016

Establishing appropriate physical activity and sedentary behaviours during early childhood is important to ensure children accrue the many associated health benefits. While physical activity levels have been reported as low within early learning programs, little research has explored the physical activity and sedentary time of Canadian preschoolers classified as overweight within these facilities. The purpose of this study was to compare objectively measured physical activity and sedentary time among preschoolers classified as overweight and nonoverweight in early learning programs. Direct assessment of physical activity and sedentary time of 216 preschool-aged children was collected via Actical accelerometers during early learning hours, while body mass index percentile was calculated based on preschoolers’ objectively measured height and weight. Results of three 3-way ANOVAs suggest that rates of moderate to vigorous physical activity, total physical activity, and sedentary time (p > 0.05) did not significantly differ based on weight status, sex, and type of early learning facility. This study is one of few that has examined differences in overweight and nonoverweight preschoolers’ sedentary time, and adds to the limited research exploring physical activity levels among overweight and nonoverweight preschoolers during early learning hours. Given the high rates of sedentary time reported, programming within early learning facilities is necessary to support preschoolers, regardless of weight status, to achieve increased physical activity levels and decreased sedentary time.
Simple brane-world inflationary models — An update
Authors: Okada Nobuchika , Okada Satomi
Published: May 2016

In the light of the Planck 2015 results, we update simple inflationary models based on the quadratic, quartic, Higgs and Coleman–Weinberg potentials in the context of the Randall–Sundrum brane-world cosmology. Brane-world cosmological effect alters the inflationary predictions of the spectral index [Formula: see text] and the tensor-to-scalar ratio [Formula: see text] from those obtained in the standard cosmology. In particular, the tensor-to-scalar ratio is enhanced in the presence of the 5th dimension. In order to maintain the consistency with the Planck 2015 results for the inflationary predictions in the standard cosmology, we find a lower bound on the five-dimensional Planck mass [Formula: see text]. On the other hand, the inflationary predictions laying outside of the Planck allowed region can be pushed into the allowed region by the brane-world cosmological effect with a suitable choice of [Formula: see text].
Preparation of iron oxide nanoparticles by laser ablation in DMF under effect of external magnetic field
Authors: Ismail Raid A. , Sulaiman Ghassan M. , Abdulrahman Safa A.
Published: May 2016

We have studied the effect of applying an external magnetic field on the characteristics of iron oxide (IO) nanoparticles (NPs) synthesized by pulsed laser ablation in dimethylformamide (DMF). The NPs synthesized with and without applying of magnetic field were characterized by Fourier transformation infrared spectroscopy (FT-IR), UV–Vis absorption, scanning electron microscope (SEM), atomic force microscope (AFM), and X-ray diffraction (XRD). SEM results confirmed that the particle size was decreased after applying magnetic field.
Symmetric Structures Made of a Nonlocal Elastic Material
Authors: Fuschi P. , Pisano A. A.
Published: May 2016

The paper focuses on the analysis of symmetric structures in the context of nonlocal integral elasticity of Eringen-type. In particular, it highlights how the standard (local-type) concept of structural symmetry cannot be applied in a straightforward manner, but it has to be redefined involving an enlarged symmetric model of the structure. Such enlarged model is indeed able to take into account the nonlocal effects exerted on the (standard) symmetric portion of the structure chosen for the analysis by the portion neglected. The appropriate boundary conditions that have to be applied to the enlarged symmetric model for guaranteeing the exact matching between the mirrored symmetric solution and the complete one, are also discussed. Two numerical examples are solved by means of a nonlocal version of the finite element method and the results obtained are critically discussed.
MHD Peristaltic Pumping of a Jeffrey Fluid Between Two Deformable Coaxial Tubes with Different Wavelengths
Authors: Rachid H. , Ouazzani M. T.
Published: May 2016

The study of MHD peristaltic transport of a Jeffrey fluid through the gap between two deformable tubes has been investigated in this paper. The outer and the inner tubes have both sinusoidal waves travelling down their walls when the amplitudes and the wavelengths are different. The equations of motion are simplified under the assumption of long wavelengths and low Reynolds number approximations. Analytical solutions for the pressure rise and axial velocity has been obtained in the closed form. Effects of pertinent parameters on pressure gradient, pressure rise, axial velocity and mechanical efficiency have been discussed through graphs. The results show that we have two cases, the first one is [Formula: see text], i.e., the wavelength of the inner tube is smaller than that of the outer tube and the second case is the opposite one [Formula: see text]. It is found that an increase of [Formula: see text] causes a decrease of the pumping and the mechanical efficiency when [Formula: see text] while an opposite behavior for [Formula: see text] is observed. In addition and for the two cases, the pumping and the mechanical efficiency increase with increasing the amplitude ration of the outer tube or the radius ratio while they decrease with the increase in the Hartmann number, amplitude ration of the inner tube or in the ratio of relaxation to retardation times.
Blast Alleviation of Cellular Sacrificial Cladding: A Nonlinear Plastic Shock Model
Authors: Ding Yuanyuan , Wang Shilong , Zhao Kai , Zheng Zhijun , Yang Liming , Yu Jilin
Published: May 2016

The anti-blast behavior of cellular sacrificial cladding is investigated based on a continuum-based nonlinear plastic shock model. A rate-independent, rigid–plastic hardening (R-PH) model with two material parameters, namely the initial crushing stress and the strain hardening parameter, is employed to idealize the cellular material. The governing equation of the motion of cover plate is obtained and solved numerically with a fourth-order Runge–Kutta scheme. A comparison of the crushing percentage contours of sacrificial cladding based on the R-PH model and the rigid–perfectly plastic–locking (R-PP-L) model is carried out. Results transpire that the R-PP-L model is not accurate enough to evaluate the energy absorption. Dimensional analysis is employed to study the critical length of cellular sacrificial cladding and an empirical expression is determined by the controlling valuable method. An asymptotic solution is also obtained by applying the regular perturbation theory. Finally, the design criteria of cellular sacrificial cladding based on the R-PH shock model is verified by a cell-based finite element model.
Process Independent Design Methodology for the Active RC and Single-Inverter-Based Rail Clamp
Authors: Venkatasubramanian Ramachandran , Elio Robert , Ozev Sule
Published: May 2016

RC and single-inverter-based rail clamps are widely used in semiconductor products for electrostatic discharge (ESD) protection. We propose a technology-node-independent design methodology for these rail clamp circuits that takes process, voltage, and temperature variations into consideration. The methodology can be used as a cookbook by the designer or be used to automate the entire design process. Tradeoffs between various design metrics such as ESD performance (Human Body Model), leakage, and area are considered. Simplified circuit models for the rail clamp are presented to gain insights into its working and to size the circuit components. A rail clamp for core power domain is designed using the proposed approach in 40nm low-power process and performance results of the design are also presented. The effectiveness of the design methodology is proven in three different technology nodes by comparing the obtained design with the best design from among 250,000 designs obtained by randomly sampling from the design space.
A Four-Tier Annotated Urdu Handwritten Text Image Dataset for Multidisciplinary Research on Urdu Script
Authors: Choudhary Prakash , Nain Neeta
Published: May 2016

This article introduces a large handwritten text document image corpus dataset for Urdu script named CALAM (Cursive And Language Adaptive Methodologies). The database contains unconstrained handwritten sentences along with their structural annotations for the offline handwritten text images with their XML representation. Urdu is the fourth most frequently used language in the world, but due to its complex cursive writing script and low resources, it is still a thrust area for document image analysis. Here, a unified approach is applied in the development of an Urdu corpus by collecting printed texts, handwritten texts, and demographic information of writers on a single form. CALAM contains 1,200 handwritten text images, 3,043 lines, 46,664 words, and 101,181 ligatures. For capturing maximum variance among the words and handwritten styles, data collection is distributed among six categories and 14 subcategories. Handwritten forms were filled out by 725 different writers belonging to different geographical regions, ages, and genders with diverse educational backgrounds. A structure has been designed to annotate handwritten Urdu script images at line, word, and ligature levels with an XML standard to provide a ground truth of each image at different levels of annotation. This corpus would be very useful for linguistic research in benchmarking and providing a testbed for evaluation of handwritten text recognition techniques for Urdu script, signature verification, writer identification, digital forensics, classification of printed and handwritten text, categorization of texts as per use, and so on. The experimental results of some recently developed handwritten text line segmentation techniques experimented on the proposed dataset are also presented in the article for asserting its viability and usability.
News from the SIGs
Authors: Walker Ellen , Rodger Susan H. , Zilora Steve , Kasper George M.
Published: May 2016

Welcome once again to reports highlighting trends within the computing education community. In this issue, we have information from the chairs of SIGCSE, SIGITE and SIGMIS. First, Susan Rodger of SIGCSE updates us on the ITiCSE conference, elections, awards, and upcoming events. Next, Steve Zilora of SIGITE discusses a new framework for Information Technology curricula and the increased involvement of a new "generation" of active members in the SIGITE community. Finally, George Kasper of SIGMIS highlights the best IS Doctoral Dissertations of 2015.
G* studio
Authors: Labouseur Alan , Crumlish Shane , Graves Cassandra , Iori Melissa J. , Miller Gregory , Wojnar Thomas J.
Published: May 2016

The e-mail from the department chair was urgent. There were several graduate students with no classes to take. "Would somebody please run an independent study?" she asked. The semester was already a few days old. Alan had to strike fast. "I'm in," he wrote, "I'll put them to work on my graph database research." With that, Alan and his new team, which would become known as the G-stars, began a two-semester adventure in graph databases, distributed systems, and software development that resulted in more than 8,000 lines of code over 520 Git commits. This is their story.
A multi-institutional study of peer instruction in introductory computing
Authors: Porter Leo , Bouvier Dennis , Cutts Quintin , Grissom Scott , Lee Cynthia , McCartney Robert , Zingaro Daniel , Simon Beth
Published: May 2016

Peer Instruction (PI) is a student-centric pedagogy in which students move from the role of passive listeners to active participants in the classroom. Over the past five years, there have been a number of research articles regarding the value of PI in computer science. The present work adds to this body of knowledge by examining outcomes from seven introductory programming instructors: three novices to PI and four with a range of PI experience. Through common measurements of student perceptions, we provide evidence that introductory computing instructors can successfully implement PI in their classrooms. We find encouraging minimum (74%) and average (92%) levels of success as measured through student valuation of PI for their learning. This work also documents and hypothesizes reasons for comparatively poor survey results in one course, highlighting the importance of the choice of grading policy (participation vs. correctness) for new PI adopters.
ASIC1-mediated calcium entry stimulates NFATc3 nuclear translocation via PICK1 coupling in pulmonary arterial smooth muscle cells
Authors: Gonzalez Bosc Laura V. , Plomaritas Danielle R. , Herbert Lindsay M. , Giermakowska Wieslawa , Browning Carly , Jernigan Nikki L.
Published: May 2016

The development of chronic hypoxia (CH)-induced pulmonary hypertension is associated with increased pulmonary arterial smooth muscle cell (PASMC) Ca2+ influx through acid-sensing ion channel-1 (ASIC1) and activation of the Ca2+/calcineurin-dependent transcription factor known as nuclear factor of activated T-cells isoform c3 (NFATc3). Whether Ca2+ influx through ASIC1 contributes to NFATc3 activation in the pulmonary vasculature is unknown. Furthermore, both ASIC1 and calcineurin have been shown to interact with the scaffolding protein known as protein interacting with C kinase-1 (PICK1). In the present study, we tested the hypothesis that ASIC1 contributes to NFATc3 nuclear translocation in PASMC in a PICK1-dependent manner. Using both ASIC1 knockout (ASIC1−/−) mice and pharmacological inhibition of ASIC1, we demonstrate that ASIC1 contributes to CH-induced (1 wk at 380 mmHg) and endothelin-1 (ET-1)-induced (10−7 M) Ca2+ responses and NFATc3 nuclear import in PASMC. The interaction between ASIC1/PICK1/calcineurin was shown using a Duolink in situ Proximity Ligation Assay. Inhibition of PICK1 by using FSC231 abolished ET-1-induced and ionomycin-induced NFATc3 nuclear import, but it did not alter ET-1-mediated Ca2+ responses, suggesting that PICK1 acts downstream of Ca2+ influx. The key findings of the present work are that 1) Ca2+ influx through ASIC1 mediates CH- and ET-1-induced NFATc3 nuclear import and 2) the scaffolding protein PICK1 is necessary for NFATc3 nuclear import. Together, these data provide an essential link between CH-induced ASIC1-mediated Ca2+ influx and activation of the NFATc3 transcription factor. Identification of this ASIC1/PICK1/NFATc3 signaling complex increases our understanding of the mechanisms contributing to the vascular remodeling and increased vascular contractility that are associated with CH-induced pulmonary hypertension.
Macrophage migration inhibitory factor, a role in COPD
Authors: Husebø Gunnar R. , Bakke Per S. , Grønseth Rune , Hardie Jon A. , Ueland Thor , Aukrust Pål , Eagan Tomas M.L.
Published: May 2016

Macrophage migration inhibitor factor (MIF) is a pluripotent cytokine associated with several different inflammatory conditions, but its role within lung inflammation and chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to examine MIF in both stable COPD and during acute exacerbations (AECOPD). The study included 433 patients with COPD aged 41–76 and 325 individuals from the Bergen COPD cohort study who served as controls. All patients had an FEV1 of <80% predicted, FEV1/FVC ratio of <0.7, and a smoking history >10 pack-years. Serum levels of MIF were compared between the two groups at baseline, and for 149 patients, measurements were also carried out during AECOPD. Linear regression models were fitted with MIF as the outcome variable and adjusted for sex, age, body composition, smoking, and Charlson Comorbidity Score (CCS). Median MIF (interquartile range) in patients with COPD was 20.1 ng/ml (13.5–30.9) compared with 14.9 ng/ml (11.1–21.6) in controls ( P < 0.01). MIF was bivariately associated with sex, body composition, and CCS ( P < 0.05 for all). In the regression analyses, MIF was significantly higher in patients with COPD, coefficient 1.32 ( P < 0.01) and 1.30 ( P < 0.01) unadjusted and adjusted, respectively. In addition, in 149 patients during episodes of AECOPD, MIF was significantly elevated, with a median of 23.2 ng/ml (14.1–42.3) compared with measurements at stable disease of 19.3 ng/ml (12.4–31.3, P < 0.01). Serum levels of MIF were significantly higher in patients with COPD compared with controls. We also identified an additional increase in MIF levels during episodes of AECOPD.
Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology
Authors: Silverberg Mark S , Satsangi Jack , Ahmad Tariq , Arnott Ian DR , Bernstein Charles N , Brant Steven R , Caprilli Renzo , Colombel Jean-Frédéric , Gasche Christoph , Geboes Karel , Jewell Derek P , Karban Amir , Loftus Edward V , Peña A Salvador , Riddell Robert H , Sachar David B , Schreiber Stefan , Steinhart A Hillary , Targan Stephan R , Vermeire Severine , Warren Bryan F
Published: May 2016

The discovery of a series of genetic and serological markers associated
with disease susceptibility and phenotype in inflammatory bowel disease
has led to the prospect of an integrated classification system
involving clinical, serological and genetic parameters. The Working
Party has reviewed current clinical classification systems in Crohn’s
disease, ulcerative colitis and indeterminate colitis, and provided recommendations
for clinical classification in practice. Progress with
respect to integrating serological and genetic markers has been examined
in detail, and the implications are discussed. While an integrated
system is not proposed for clinical use at present, the introduction of a
widely acceptable clinical subclassification is strongly advocated,
which would allow detailed correlations among serotype, genotype and
clinical phenotype to be examined and confirmed in independent
cohorts of patients and, thereby, provide a vital foundation for future
work.
Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease? The Potential Role of Zolpidem in the Treatment of Parkinson’s Disease
Authors: Daniele Antonio , Panza Francesco , Greco Antonio , Logroscino Giancarlo , Seripa Davide
Published: May 2016

At present, patients with advanced Parkinson’s disease (PD) are unsatisfactorily controlled by currently used anti-Parkinsonian dopaminergic drugs. Various studies suggest that therapeutic strategies based on nondopaminergic drugs might be helpful in PD. Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only forGABAAreceptors containing theα-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation ofGABAAreceptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable) effects on motor symptoms even after single doses and may also improve dyskinesias. Since a high density of zolpidem binding sites is in the two main output structures of the basal ganglia which are abnormally overactive in PD (internal globus pallidus, GPi, and substantia nigra pars reticulata, SNr), it was hypothesized that in PD patients zolpidem may induce throughGABAAreceptors an inhibition of GPi and SNr (and, possibly, of the subthalamic nucleus also), resulting in an increased activity of motor cortical areas (such as supplementary motor area), which may give rise to improvement of motor symptoms of PD. Randomized clinical trials are needed in order to assess the efficacy, safety, and tolerability of zolpidem in treating motor symptoms of PD.
The Application of Recurrence Quantification Analysis in Detection of Abrupt Climate Change
Authors: Zhang Wen , Feng Guoling , Liu Qunqun
Published: May 2016

This paper explores the possible application of recurrence quantification analysis in the detection of abrupt change of the dynamic structure of the climate system. It is discovered in the recurrence quantification analysis of the typical chaotic system-logistic model that the method may well distinguish the state of logistic model with different parameters, demonstrating its potential value in identifying the dynamic change of the system. When recurrence quantification analysis is later applied to the detection of abrupt change of average daily precipitation of all regions in China, the result indicates that the abrupt change of the dynamic structure corresponding to the precipitation of China in recent 50 years occurred in the late 1970s and the early 1980s. It is in agreement with the Chinese commonly recognized years of abruption; therefore the effectiveness is further demonstrated regarding the recognition of complexity of dynamical system.
Complex Odontoma: A Case Report with Micro-Computed Tomography Findings
Authors: Santos L. A. N. , Lopes L. J. , Roque-Torres G. D. , Oliveira V. F. , Freitas D. Q.
Published: May 2016

Odontomas are the most common benign tumors of odontogenic origin. They are normally diagnosed on routine radiographs, due to the absence of symptoms. Histopathologic evaluation confirms the diagnosis especially in cases of complex odontoma, which may be confused during radiographic examination with an osteoma or other highly calcified bone lesions. The micro-CT is a new technology that enables three-dimensional analysis with better spatial resolution compared with cone beam computed tomography. Another great advantage of this technology is that the sample does not need special preparation or destruction in the sectioned area as in histopathologic evaluation. An odontoma with CBCT and microtomography images is presented in a 26-year-old man. It was first observed on panoramic radiographs and then by CBCT. The lesion and the impacted third molar were surgically excised using a modified Neumann approach. After removal, it was evaluated by histopathology and microtomography to confirm the diagnostic hypothesis. According to the results, micro-CT enabled the assessment of the sample similar to histopathology, without destruction of the sample. With further development, micro-CT could be a powerful diagnostic tool in future research.
Identification and Quantitation of Melamine in Milk by Near-Infrared Spectroscopy and Chemometrics
Authors: Wu Tong , Chen Hui , Lin Zan , Tan Chao
Published: May 2016

Melamine is a nitrogen-rich substance and has been illegally used to increase the apparent protein content in food products such as milk. Therefore, it is imperative to develop sensitive and reliable analytical methods to determine melamine in human foods. Current analytical methods for melamine are mainly chromatography-based methods, which are time-consuming and expensive and require complex pretreatment and well-trained technicians. The present paper investigated the feasibility of using near-infrared (NIR) spectroscopy and chemometrics for identifying and quantifying melamine in liquor milk. A total of 75 samples were prepared. Uninformative variable elimination-partial least square (UVE-PLS) and partial least squares-discriminant analysis (PLS-DA) were used to construct quantitative and qualitative models, respectively. Based on the ratio of performance to standard deviate (RPD), UVE-PLS model with 3 components resulted in a better solution. The PLS-DA model achieved an accuracy of 100% and outperformed the optimal reference model of soft independent modeling of class analogy (SIMCA). Such a method can serve as a potential tool for rapid screening of melamine in milk products.
Update on Nonsurgical Lung Volume Reduction Procedures
Authors: Neder J. Alberto , O’Donnell Denis E.
Published: May 2016

There has been a surge of interest in endoscopic lung volume reduction (ELVR) strategies for advanced COPD. Valve implants, coil implants, biological LVR (BioLVR), bronchial thermal vapour ablation, and airway stents are used to induce lung deflation with the ultimate goal of improving respiratory mechanics and chronic dyspnea. Patients presenting with severe air trapping (e.g., inspiratory capacity/total lung capacity (TLC) < 25%, residual volume > 225% predicted) and thoracic hyperinflation (TLC > 150% predicted) have the greatest potential to derive benefit from ELVR procedures. Pre-LVRS or ELVR assessment should ideally include cardiological evaluation, high resolution CT scan, ventilation and perfusion scintigraphy, full pulmonary function tests, and cardiopulmonary exercise testing. ELVR procedures are currently available in selected Canadian research centers as part of ethically approved clinical trials. If a decision is made to offer an ELVR procedure, one-way valves are the first option in the presence of complete lobar exclusion and no significant collateral ventilation. When the fissure is not complete, when collateral ventilation is evident in heterogeneous emphysema or when emphysema is homogeneous, coil implants or BioLVR (in that order) are the next logical alternatives.
Comparison of 6 Diode and 6 Transistor Mixers Based on Analysis and Measurement
Authors: Ladvánszky J. , Osbáth K. M.
Published: May 2016

Our goal is to overview semiconductor mixers designed for good large signal performance. Twelve different mixers were compared utilizing pn diodes, bipolar transistors, and/or junction field effect transistors. The main aspect of comparison is the third-order intercept point (IP3), and both circuit analysis and measurement results have been considered. IP3 has been analyzed by the program AWR (NI AWR Design Environment) and measured by two-tone test (Keysight Technologies). We provide three ways of improvement of large signal performance: application of a diplexer at the RF port, reduction of DC currents, and exploiting a region of RF input power with infinite IP3. In addition to that, our contributions are several modifications of existing mixers and a new mixer circuit (as illustrated in the figures). It is widely believed that the slope of the third-order intermodulation product versus input power is always greater than that of the first-order product. However, measurement and analysis revealed (as illustrated in the figures) that the two lines may be parallel over a broad range of input power, thus resulting in infinite IP3. Mixer knowledge may be useful for a wide range of readers because almost every radio contains at least one mixer.
Psychometric Properties of the Persian Version of the Short Beck Depression Inventory with Iranian Psychiatric Outpatients
Authors: Dadfar Mahboubeh , Kalibatseva Zornitsa
Published: May 2016

The short form of the Beck Depression Inventory (BDI-13) is useful for the screening and assessment of depression in clinical and research settings. The aim of the present study was to investigate the psychometric properties of the Persian (Farsi) version of BDI-13 in an Iranian clinical sample. The sample consisted of 52 Iranian psychiatric outpatients who received services at psychiatric and psychological clinics at the School of Behavioral Sciences & Mental Health-Tehran Institute of Psychiatry, Iran University of Medical Sciences (IUMS) in Tehran, Iran. The study examined the reliability, construct validity, and factor structure of the instrument. The instrument indicated good reliability with Cronbach’s alpha of .85 and strong construct validity based on moderate to strong positive correlations with other measures of mental health issues. Using a Principal Component Analysis and Varimax Rotation with Kaiser Normalization, three factors were identified and labeled Affective (F1), Somatic/Vegetative (F2), and Cognitive/Loss of Functioning (F3). The current factor structure suggests that depression is a multidimensional construct in an Iranian clinical sample. This study provides further evidence that the Persian version of the BDI-13 is a psychometrically sound instrument that can be used for clinical and research purposes in Iran.
Angelica acutilobaKitagawa Extract Attenuates DSS-Induced Murine Colitis
Authors: Jang Jong-Chan , Lee Kang Min , Ko Seong-Gyu
Published: May 2016

We examined the protective effects ofAngelica acutilobaKitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis.
A Rare Cause of Acute Kidney Injury in a Female Patient with Breast Cancer Presenting as Renal Colic
Authors: Jurubita Roxana , Obrisca Bogdan , Ismail Gener
Published: May 2016

Renal infarction is a rare cause of acute kidney injury which could lead to permanent loss of renal function. A prompt diagnosis is necessary in order to achieve a successful revascularization of the occluded artery. Given the rarity of the disease and the paucity of the reported cases in the previous literature a high index of suspicion must be maintained not only in the classical cardiac sources of systemic emboli (atrial fibrillation, dilated cardiomyopathy, or endocarditis), but also in the situations when a hypercoagulable state is presumed. The unspecific presenting symptoms often mask the true etiology of the patient’s complaints. We present here a rare case of renal infarction that occurred in the setting of a hypercoagulable state, in a female patient with a history of breast cancer and documented hepatic metastases.
Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab
Authors: Weide Benjamin , Martens Alexander , Hassel Jessica C. , Berking Carola , Postow Michael A. , Bisschop Kees , Simeone Ester , Mangana Johanna , Schilling Bastian , Di Giacomo Anna Maria , Brenner Nicole , Kähler Katharina , Heinzerling Lucie , Gutzmer Ralf , Bender Armin , Gebhardt Christoffer , Romano Emanuela , Meier Friedegund , Martus Peter , Maio Michele , Blank Christian , Schadendorf Dirk , Dummer Reinhard , Ascierto Paolo A. , Hospers Geke , Garbe Claus , Wolchok Jedd D.
Published: May 2016

Purpose: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients.

Experimental Design: Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab treatment. Kaplan–Meier analysis and Cox regression were applied for survival analysis.

Results: Relative eosinophil count (REC) ≥1.5%, relative lymphocyte count (RLC) ≥17.5%, ≤2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n = 177) and the confirmation (n = 182) cohort and had independent positive impact (all P < 0.001). Their independent role was subsequently confirmed in the validation cohort (n = 257; all P < 0.01). The number of favorable factors was strongly associated with prognosis. One-year OS probabilities of 83.9% versus 14.7% and response rates of 58.3% versus 3.3% were observed in patients with four of four compared to those with none of four favorable baseline factors present, respectively.

Conclusions: High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated. Clin Cancer Res; 22(22); 5487–96. ©2016 AACR.
Use of Liquid Biopsies in Clinical Oncology: Pilot Experience in 168 Patients
Authors: Schwaederle Maria , Husain Hatim , Fanta Paul T. , Piccioni David E. , Kesari Santosh , Schwab Richard B. , Patel Sandip P. , Harismendy Olivier , Ikeda Megumi , Parker Barbara A. , Kurzrock Razelle
Published: May 2016

Purpose: There is a growing interest in using circulating tumor DNA (ctDNA) testing in patients with cancer.

Experimental Design: A total of 168 patients with diverse cancers were analyzed. Patients had digital next-generation sequencing (54 cancer-related gene panel including amplifications in ERBB2, EGFR, and MET) performed on their plasma. Type of genomic alterations, potential actionability, concordance with tissue testing, and patient outcome were examined.

Results: Fifty-eight percent of patients (98/168) had ≥1 ctDNA alteration(s). Of the 98 patients with alterations, 71.4% had ≥ 1 alteration potentially actionable by an FDA-approved drug. The median time interval between the tissue biopsy and the blood draw was 2.7 months for patients with ≥ 1 alteration in common compared with 14.4 months (P = 0.006) for the patients in whom no common alterations were identified in the tissue and plasma. Overall concordance rates for tissue and ctDNA were 70.3% for TP53 and EGFR, 88.1% for PIK3CA, and 93.1% for ERBB2 alterations. There was a significant correlation between the cases with ≥ 1 alteration with ctDNA ≥ 5% and shorter survival (median = 4.03 months vs. not reached at median follow-up of 6.1 months; P < 0.001). Finally, 5 of the 12 evaluable patients (42%) matched to a treatment targeting an alteration(s) detected in their ctDNA test achieved stable disease ≥ 6 months/partial remission compared with 2 of 28 patients (7.1%) for the unmatched patients, P = 0.02.

Conclusions: Our initial study demonstrates that ctDNA tests provide information complementary to that in tissue biopsies and may be useful in determining prognosis and treatment. Clin Cancer Res; 22(22); 5497–505. ©2016 AACR.
Dual mTORC1/2 Inhibition as a Novel Strategy for the Resensitization and Treatment of Platinum-Resistant Ovarian Cancer
Authors: Musa Fernanda , Alard Amandine , David-West Gizelka , Curtin John P. , Blank Stephanie V. , Schneider Robert J.
Published: May 2016

There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue culture and in animal tumor models of serous ovarian cancer. Cell survival, tumor growth, PI3K–AKT–mTOR pathway signaling, DNA damage and repair response (DDR) gene expression, and translational control were all investigated. We show that platinum-resistant OVCAR-3 ovarian cancer cells are resensitized to low levels of carboplatin in culture by mTOR inhibition, demonstrating reduced survival after treatment with either mTORC1 inhibitor everolimus or mTORC1/2 inhibitor PP242. Platinum resistance is shown to be associated with activating phosphorylation of AKT and CHK1, inactivating phosphorylation of 4E-BP1, the negative regulator of eIF4E, which promotes increased cap-dependent mRNA translation and increased levels of CHK1 and BRCA1 proteins. Animals with platinum-resistant OVCAR-3 tumors treated with carboplatin plus mTORC1/2 inhibition had significantly longer median survival and strikingly reduced metastasis compared with animals treated with carboplatin plus everolimus, which inhibits only mTORC1. Reduced tumor growth, metastasis, and increased survival by mTORC1/2 inhibition with carboplatin treatment was associated with reduced AKT-activating phosphorylation and increased 4E-BP1 hypophosphorylation (activation). We conclude that mTORC1/2 inhibition is superior to mTORC1 inhibition in reversing platinum resistance in tumors and strongly impairs AKT activation, DNA repair responses, and translation, promoting improved survival in the background of platinum resistance. Mol Cancer Ther; 15(7); 1557–67. ©2016 AACR.
Circulating Neutrophil Extracellular Trap Levels in Well-Controlled Type 2 Diabetes and Pathway Involved in Their Formation Induced by High-Dose Glucose
Authors: Miyoshi Arina , Yamada Mai , Shida Haruki , Nakazawa Daigo , Kusunoki Yoshihiro , Nakamura Akinobu , Miyoshi Hideaki , Tomaru Utano , Atsumi Tatsuya , Ishizu Akihiro
Published: May 2016

Objectives: Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose. Methods: Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well-controlled T2D patients and 13 healthy volunteers were determined by enzyme-linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors. Results: Serum MPO-DNA complex levels were significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose. Conclusions: Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose.
Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma
Authors: Wang Lu , Yang Lei , Lu Ying , Chen Yingzhun , Liu Tianhua , Peng Yanli , Zhou Yuhong , Cao Yang , Bi Zhenggang , Liu Tianyi , Liu Zhenhong , Shan Hongli
Published: May 2016

Background/Aims: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. Methods: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. Results: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. Conclusion: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.
The Emerging Role and Promise of Long Noncoding RNAs in Lung Cancer Treatment
Authors: Chen Ying , Li Chen , Pan Yan , Han Siqi , Feng Bing , Gao Yanping , Chen Jing , Zhang Kai , Wang Rui , Chen Longbang
Published: May 2016

Lung cancer is the leading cause of cancer death around the world. The advanced discovery of numerous long noncoding RNAs (lncRNAs) has dramatically changed the understanding of biology of human cancers, including lung cancer. LncRNAs are a group of noncoding RNAs (ncRNAs) with a length greater than 200 nucleotides with limited or no protein-coding capacity. Increasing evidence has shown that specific lncRNAs may be implicated in the process of tumorigenesis. Because of their roles in the regulation of multiple molecular pathways associated with changes in gene expression, lncRNAs can serve as potential diagnostic biomarkers or therapeutic targets in lung cancer. Importantly, dysregulated lncRNAs is reported to be correlated with the sensitivity of lung cancer cells to anticancer therapies, including chemotherapy, molecular-targeted therapy, etc. Herein, we review the recent progress of lncRNAs in lung cancer, with a particular focus on the multiple molecular roles of regulatory lncRNAs on the molecular signaling pathways involved in tumorigenesis and the resistance to such therapies.
Effects of 1, 25-Dihydroxyvitamin D3 on Experimental Autoimmune Myocarditis in Mice
Authors: Hu Fen , Yan Lianhua , Lu Shuai , Ma Wenhan , Wang Ya , Wei Yuzhen , Yan Xiaofei , Zhao Xin , Chen Zhijian , Wang Zhaohui , Cheng Bo
Published: May 2016

Background/Aims: Myocarditis is an important inflammatory disease of the heart which causes life-threatening conditions. 1, 25(OH)2 D3 has effects on multiple systems and diseases. The present study was aimed to investigate the effect of 1, 25(OH)2 D3 on experimental autoimmune myocarditis (EAM), and explored the underlying mechanisms involved. Methods: EAM was induced by immunizing BALB/c mice with cardiac α-myosin heavy chain peptides (MyHC-α). 1, 25(OH)2 D3 (1,000 ng/kg once) or vehicle was administered intraperitoneally every other day during the entire experiment. On day 21, transthoracic echocardiography was performed and cardiac inflammatory infiltration was detected by hematoxylin and eosin (HE). The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, and Western blots for the expression of protein caspase-3 and cleaved-caspase3 were used to evaluate apoptosis. Transmission electron microscopy and Western blots for the expression of protein Beclin-1, LC3B, and P62 were used to evaluate autophagy. Results: The ratio of heart weight/body weight was significantly reduced in 1, 25(OH)2 D3 -treated EAM mice, compared with vehicle -treated ones. 1, 25(OH)2 D3 treatment improved cardiac function, diminished cell infiltration in cardiac, suppressed myocardial apoptosis, decreased the number of autophagosomes, and decreased the protein expression of Beclin-1, LC3-II and p62. Conclusions: The present results demonstrated that administration of 1, 25(OH)2 D3 decreased EAM severity. 1, 25(OH)2 D3 treatment may be a feasible therapeutic approach for EAM.