bluuebunny/crossref_metadata_2025 huggingface dataset:
Key Technology of Real-Time Road Navigation Method Based on Intelligent Data Research
Authors: Tang Haijing , Liang Yu , Huang Zhongnan , Wang Taoyi , He Lin , Du Yicong , Yang Xu , Ding Gangyi
Published: October 2016

The effect of traffic flow prediction plays an important role in routing selection. Traditional traffic flow forecasting methods mainly include linear, nonlinear, neural network, and Time Series Analysis method. However, all of them have some shortcomings. This paper analyzes the existing algorithms on traffic flow prediction and characteristics of city traffic flow and proposes a road traffic flow prediction method based on transfer probability. This method first analyzes the transfer probability of upstream of the target road and then makes the prediction of the traffic flow at the next time by using the traffic flow equation. Newton Interior-Point Method is used to obtain the optimal value of parameters. Finally, it uses the proposed model to predict the traffic flow at the next time. By comparing the existing prediction methods, the proposed model has proven to have good performance. It can fast get the optimal value of parameters faster and has higher prediction accuracy, which can be used to make real-time traffic flow prediction.
Synchronous Malignant Peripheral Nerve Sheath Tumor and Adenocarcinoma of the Prostate: Case Report and Literature Review
Authors: Ferakis Nikolaos , Katsimantas Antonios , Bouropoulos Konstantinos , Farmakis Antonios
Published: October 2016

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) of the prostate are extremely rare. A very unusual case of simultaneous adenocarcinoma and MPNST of the prostate is reported. A 60-year-old Caucasian male presented for annual urologic examination. Digital rectal examination revealed a painless, toughish, and asymmetrically enlarged prostate. Serum prostate-specific antigen was 1 ng/mL. Radiologic examinations demonstrated a large mass, which was arising from the left peripheral lobe of the prostate. The patient underwent transrectal ultrasound-guided biopsy of the prostate which revealed a smooth muscle tumor of uncertain malignant potential. Radical retropubic prostatectomy with en bloc removal of the mass and the seminal vesicles was performed and histology demonstrated low-grade MPNST and adenocarcinoma of the prostate. To the best of our knowledge, this is the first report of simultaneous prostatic adenocarcinoma and MPNST in the English literature.
Investigations of the Gas-Liquid Multiphase System Involving Macro-Instability in a Baffled Stirred Tank Reactor
Authors: Zhang Shuo , Talaga Jan , Müller David , Dylag Michal , Wozny Günter
Published: October 2016

Bubble Sauter Mean Diameter (SMD) in gas-liquid multiphase system is of particular interest and the quantification of gas characteristics is still a challenge today. In this contribution, multiphase Computational Fluid Dynamic (CFD) simulations are combined with Population Balance Model (PBM) to investigate the bubble SMD in baffled stirred tank reactor (STR). Hereby, special attention is given to the phenomenon known as the fluid macro-instability (MI), which is a large-scale low-frequency fluid velocity variation in baffled STRs, since the fluid MIs have a dominating influence on the bubble breakage and coalescence processes. The simulations, regarding the fluid velocity, are validated with Laser Doppler Anemometry (LDA) experiments, in which the instant radial velocity is analyzed through Fast Fourier Transform (FFT) spectrum. The frequency peaks of the fluid MIs are found both in the simulation and in the experiment with a high degree of accuracy. After the validation, quantitative predictions of overall bubble SMD with and without MIs are carried out. Due to the accurate prediction of the fluid field, the influence of the fluid MI to bubble SMD is presented. This result provides more adequate information for engineers working in the field of estimating bubble SMDs in baffled STRs.
Sports Nutrition Knowledge among Mid-Major Division I University Student-Athletes
Authors: Andrews Ashley , Wojcik Janet R. , Boyd Joni M. , Bowers Charles J.
Published: October 2016

Competitive athletes have goals to optimize performance and to maintain healthy body composition. Sports nutrition is a component of training programs often overlooked by student-athletes and their coaches. The purpose of this study was to examine student-athletes’ sports nutrition knowledge across sex, class level, team, and completion of prior nutrition coursework. Participants included 123 mid-major Division I university student-athletes (47 females and 76 males) from baseball, softball, men’s soccer, track and field, and tennis. The student-athletes completed a survey questionnaire to determine adequate sports nutrition knowledge (mean ≥ 75%). The overall mean sports nutrition knowledge score for the student-athletes was 56.9% which was considered inadequate sports nutrition knowledge (mean < 75%). Only 12 student-athletes achieved adequate sports nutrition knowledge score of 75% or higher. There were no differences by sex, class level, team, and completion of prior nutrition coursework. Student-athletes’ inadequate sports nutrition knowledge may place them at nutrition risk, lead to impaired performance, and affect their lean body mass and energy levels. Athletics personnel should not assume student-athletes have adequate sports nutrition knowledge. Athletic departments may make available a board certified Sports Dietitian or Registered Dietitian and offer classroom or online courses facilitating student-athletes to optimize nutrition knowledge and behaviors.
Solvability of (k,n-k) Conjugate Boundary Value Problems with Integral Boundary Conditions at Resonance
Authors: Sun Qiao , Cui Yujun
Published: October 2016

We investigate a (k,n-k) conjugate boundary value problem with integral boundary conditions. By using Mawhin continuation theorem, we study the solvability of this boundary value problem at resonance. It is shown that the boundary value problem (-1)n-kφ(n)(x)=fx,φx,φ′x,…,φ(n-1)(x), x∈[0,1], φ(i)(0)=φ(j)(1)=0, 1≤i≤k-1, 0≤j≤n-k-1, φ(0)=∫01φ(x)dA(x) has at least one solution under some suitable conditions.
Projection of Korean Probable Maximum Precipitation under Future Climate Change Scenarios
Authors: Lee Okjeong , Park Yoonkyung , Kim Eung Seok , Kim Sangdan
Published: October 2016

According to the IPCC Fifth Assessment Report, air temperature and humidity of the future are expected to gradually increase over the current. In this study, future PMPs are estimated by using future dew point temperature projection data which are obtained from RCM data provided by the Korea Meteorological Administration. First, bias included in future dew point temperature projection data which is provided on a daily basis is corrected through a quantile-mapping method. Next, using a scale-invariance technique, 12-hour duration 100-year return period dew point temperatures which are essential input data for PMPs estimation are estimated from bias-corrected future dew point temperature data. After estimating future PMPs, it can be shown that PMPs in all future climate change scenarios (AR5 RCP2.6, RCP 4.5, RCP 6.0, and RCP 8.5) are very likely to increase.
Rosai-Dorfman Disease Involving Multiple Organs: An Unusual Case with Poor Prognosis
Authors: Sendrasoa Fandresena Arilala , Ranaivo Irina Mamisoa , Raharolahy Onivola , Andrianarison Malalaniaina , Razanakoto Naina Harinjara , Ramarozatovo Lala Soavina , Rapelanoro Rabenja Fahafahantsoa
Published: October 2016

Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder that usually affects the lymph nodes. Although extranodal involvement has been reported in diverse sites, manifestation in the cardiovascular system is extremely rare. Specifically, cardiac involvement in Rosai-Dorfman disease is an extraordinarily infrequent event. We describe a case of a 36-year-old female who presented Rosai-Dorfman disease of multiple organs including the heart, with poor prognosis.
Fast Coprecipitation of Calcium Phosphate Nanoparticles inside Gelatin Nanofibers by Tricoaxial Electrospinning
Authors: Panzavolta Silvia , Gualandi Chiara , Fiorani Andrea , Bracci Barbara , Focarete Maria Letizia , Bigi Adriana
Published: October 2016

We present an effective method for fabricating electrospun gelatin nanofibers containing well-dispersed inorganic nanoparticles. The new method encompasses the use of a special triaxial needle where mixing calcium and phosphate aqueous solutions in an intermediate needle yield calcium phosphate (CaP) nanoparticles that immediately after precipitation are dragged by the outer polymeric solution and incorporated directly in the electrospinning jet, before nanofiber formation. Gelatin electrospun mats containing different amounts of CaP nanoparticles were prepared and characterized by SEM, TEM, TGA, and stress-strain measurements. The results demonstrate that CaP particles having diameter of few tens of nanometers were successfully introduced in the gelatin nanofibers during the electrospinning process and that they were well dispersed throughout the fiber length. In addition, the use of the special triaxial needle enabled modulating the CaP amount in the nanofibers.
A Case of Secondary Epiretinal Membrane Spontaneous Release
Authors: Andreev Andrey N. , Bushuev Alexey V. , Svetozarskiy Sergey N.
Published: October 2016

Purpose. To report a rare case of secondary epiretinal membrane (ERM) spontaneous separation with subsequent visual restoration. Case Summary. We are reporting a case with the history of branch retinal vein occlusion, peripheral retinal neovascularization, and retinal photocoagulation. Our examination revealed secondary ERM associated with relatively high visual acuity (0.6), and a watchful waiting strategy was chosen. During the follow-up, slight visual deterioration, progressive deformation of the retinal profile, and an increase in diffuse retinal edema were observed. No surgical or laser treatment was performed. On the next visit, the spontaneous ERM separation with residual parapapillary fixation, the increase in visual acuity (0.9), and the decrease in retinal thickness were revealed. Conclusion. Such cases present additional evidence to a deferral surgical strategy for the management of patients with ERM and relatively high visual acuity.
An Uncommon Feature of Chronic Granulomatous Disease in a Neonate
Authors: Afrough Razieh , Mohseni Sayyed Shahabeddin , Sagheb Setareh
Published: October 2016

Chronic Granulomatous Disease (CGD) represents recurrent life-threatening bacterial and fungal infections and granuloma formation with a high mortality rate. CGD’s sign and symptoms usually appear in infancy and children before the age of five; therefore, its presentation in neonatal period with some uncommon features may be easily overlooked. Here we describe a case of CGD in a 24-day-old boy, presenting with a diffuse purulent vesiculopustular rash and multiple osteomyelitis.
Concomitant Laparoscopic Burch Urethropexy and Combined Vaginal-Laparoscopic Mesh Sling Removal (x2) for Pain and Persistent Stress Urinary Incontinence
Authors: Huber Sarah A. , Dunlap-Wright LaChanda , Miklos John R. , Moore Robert D.
Published: October 2016

Although midurethral mesh tape slings are considered the standard of care in the treatment of female stress urinary incontinence (SUI), complications such as pain, dyspareunia, or erosion are known to occur in addition to persistent incontinence. The management of these types of mesh sling complications can be very complex, especially when the pain is not just isolated to the vagina but extends into other areas, such as the abdomen which requires a much more extensive dissection. Additionally, if a mesh sling needs to be removed, the patient will most likely have a return of her SUI that often necessitates subsequent treatment. Vaginal and/or laparoscopic removal or revision of mesh tape slings should be considered in patients presenting with complications such as vaginal pain, abdominal pain, dyspareunia, or urinary obstructive symptoms. In those patients who demonstrate persistent SUI, concomitant laparoscopic Burch urethropexy can be considered and can safely be performed at the time mesh removal. In this case report we present a patient who required a dual-approach removal of two painful midurethral slings in addition to concomitant treatment of persistent SUI with a laparoscopic Burch urethropexy procedure.
Route Choice of the Shortest Travel Time Based on Floating Car Data
Authors: Shen Jingwei , Ban Yifang
Published: October 2016

Finding a route with shortest travel time according to the traffic condition can help travelers to make better route choice decisions. In this paper, the shortest travel time based on FCD (floating car data) which is used to assess overall traffic conditions is proposed. To better fit FCD and road map, a new map matching algorithm which fully considers distance factor, direction factor, and accessibility factor is designed to map all GPS (Global Positioning System) points to roads. A mixed graph structure is constructed and a route analysis algorithm of shortest travel time which considers the dynamic edge weight is designed. By comparing with other map matching algorithms, the proposed method has a higher accuracy. The comparison results show that the shortest travel time path is longer than the shortest distance path, but it costs less traveling time. The implementation of the route choice based on the shortest travel time method can be used to guide people’s travel by selecting the space-time dependent optimal path.
Tranexamic Acid: An Exceedingly Rare Cause of Anaphylaxis during Anaesthesia
Authors: Bansal R. A. , Nicholas A. , Bansal A. S.
Published: October 2016

Tranexamic acid (TXA) allergy is extremely rare. An 80-year-old woman without prior exposure to TXA underwent elective knee replacement. Shortly after induction of anaesthesia and intravenous TXA, she developed hypotension, tachycardia, and facial erythema accompanied by a raised serum tryptase. Later, skin prick and intradermal testing confirmed positive responses to TXA in high dilution and with negative results to the other drugs used. While neuromuscular blocking agents, opiates, and antibiotics remain the most frequent cause of anaphylaxis during anaesthesia, allergy to TXA should always be borne in mind and requires skin testing for confirmation as there are presently no blood tests available.
Antimalarial Properties of Aqueous Crude Extracts ofGynostemma pentaphyllumandMoringa oleiferaLeaves in Combination with Artesunate inPlasmodium berghei-Infected Mice
Authors: Somsak Voravuth , Borkaew Preeyanuch , Klubsri Chokdee , Dondee Kittiyaporn , Bootprom Panatda , Saiphet Butsarat
Published: October 2016

Due to the emergence and spread of malaria parasite with resistance to antimalarial drugs, discovery and development of new, safe, and affordable antimalarial are urgently needed. In this respect, medicinal plant extracts are targets to optimize antimalarial actions and restore efficacy of standard antimalarial drugs. The present study was aimed at determining the antimalarial activities ofGynostemma pentaphyllumandMoringa oleiferaleaf extracts in combination with artesunate againstPlasmodium berghei-infected mice.P. bergheiANKA maintained by serial passage in ICR mice were used based on intraperitoneal injection of 1 × 107parasitized erythrocytes and subsequent development of parasitemia. These infected mice were used to investigate the antimalarial activity of artesunate (6 mg/kg) in combination with 500, 1,000, and 2,000 mg/kg ofG. pentaphyllumandM. oleiferaleaf extracts using 4-day suppressive test. It was found that these extracts showed significant (P<0.05) antimalarial activity in dose-dependent manner with percentage of suppression of 45, 50, and 55% forG. pentaphyllumleaf extract and 35, 40, and 50% forM. oleiferaleaf extract. Additionally, artesunate combined with these extracts presented higher antimalarial activity, compared to extract treated alone with percentage of suppression of 78, 91, and 96% forG. pentaphyllumleaf extract and 73, 82, and 91% forM. oleiferaleaf extract. The results indicated that combination treatment ofG. pentaphyllumorM. oleiferaleaf extracts with artesunate was able to increase the antimalarial activity by using low dose of artesunate. Hence, these results justified the combination of these extracts and artesunate in antimalarial herbal remedies.
Changes in Anterior Segment Morphology of Iris Bombe before and after Laser Peripheral Iridotomy in Patients with Uveitic Secondary Glaucoma
Authors: Ikegawa Wakako , Suzuki Takashi , Namiguchi Koji , Mizoue Shiro , Shiraishi Atsushi , Ohashi Yuichi
Published: October 2016

Purpose. To quantify changes in anterior segment (AS) parameters after laser peripheral iridotomy (LPI) using AS-optical coherence tomography (OCT) of iris bombe. Method. AS images of eight eyes were captured before and after iris bombe and more than 2 weeks after LPI (post-LPI) using AS-OCT. We compared the following AS parameters: anterior chamber depth (ACD), anterior chamber volume (ACV), iris curvature (IC), iris thickness at 500 μm from the scleral spur (IT-1) in the middle between the iris root and pupillary margin (IT-2) and 500 μm from the pupillary margin (IT-3) to the anterior chamber angle (ACA) (angle opening distance [AOD750]), and trabecular iris space area. Results. Mean IT-1 and IT-3, but not IT-2, were lower after iris bombe (IT-1, P=0.001; IT-2, P=0.081; and IT-3, P=0.001). There were no significant differences between ACD at pre-LPI and before iris bombe (P=0.096). The mean ACV and AOD750 of iris bombe increased at post-LPI (ACV, P<0.01, and AOD750, P<0.05). The mean IT-1, IT-2, and IT-3 increased at post-LPI (all, P≤0.01). IC decreased at post-LPI (P<0.001), and ACD at post-LPI did not change. Conclusions. The iris extends and becomes thinner during iris bombe. LPI during bombe decreases the IC and increases the ACV and ACA.
Angiosarcoma Arising in Ovarian Mucinous Tumor: A Challenge in Intraoperative Frozen Section Diagnosis
Authors: Khunamornpong Surapan , Settakorn Jongkolnee , Sukpan Kornkanok , Pongsuvareeyakul Tip , Siriaunkgul Sumalee
Published: October 2016

Angiosarcoma of the ovary is rare but represents an aggressive type of malignant ovarian neoplasms. The purpose of this report is to describe the features of angiosarcoma arising in mucinous tumor that was misinterpreted as a benign vascular proliferation during the intraoperative consultation. A 45-year-old woman presented with an abdominal mass for 1 month. Exploratory laparotomy was performed. A 35 cm right ovarian mass submitted for intraoperative consultation was a multicystic mucinous tumor with an 8 cm area of hemorrhagic lesion between cystic locules. The frozen section diagnosis was at least mucinous borderline tumor. The hemorrhagic area, which was intraoperatively interpreted as organizing vessels associated with previous hemorrhage, represented angiosarcoma in permanent sections. Angiosarcoma may present a challenge in intraoperative frozen section diagnosis of an ovarian mass. The presence of ectatic anastomosing vessels with dissecting growth appears to be the clue to a suspicion of angiosarcoma. The presence of endothelial atypia provides further support for the diagnosis. A macroscopic hemorrhagic area in an ovarian mucinous tumor should be evaluated with care, and the possibility of angiosarcoma should be borne in mind.
An Ecofriendly Initiative for the Corrosion Inhibition of Mild Steel in 1 M HCl UsingTecoma capensisFlower Extract
Authors: Prithiba A. , Rajalakshmi R.
Published: October 2016

Corrosion inhibition of mild steel in 1 M HCl in the presence ofTecoma capensisflower extract was carried out by means of mass loss, potentiodynamic polarisation, and electrochemical impedance techniques. The inhibition efficiency varied with concentration of the inhibitor, immersion time, and temperature. The adsorption of the inhibitor on mild steel surface obeys Langmuir’s adsorption isotherm. Thermodynamic parameters reveal that the adsorption process is spontaneous. Electrochemical studies reflect that the inhibitor acts as a mixed-type inhibitor. Surface analytical techniques ascertain the inhibitive nature of the studied inhibitor.
Porcine Pancreatic Lipase Inhibitory Agent Isolated from Medicinal Herb and Inhibition Kinetics of Extracts from Eleusine indica (L.) Gaertner
Authors: Ong Siew Ling , Mah Siau Hui , Lai How Yee
Published: October 2016

Eleusine indica (Linnaeus) Gaertner is a traditional herb known to be depurative, febrifuge, and diuretic and has been reported with the highest inhibitory activity against porcine pancreatic lipase (PPL) among thirty two plants screened in an earlier study. This study aims to isolate and identify the active components that may possess high potential as an antiobesity agent. Of the screened solvent fractions of E. indica, hexane fraction showed the highest inhibitory activity of 27.01±5.68% at 100 μg/mL. Bioactivity-guided isolation afforded three compounds from the hexane fraction of E. indica, namely, β-sitosterol, stigmasterol, and lutein. The structures of these compounds were elucidated using spectral techniques. Lutein showed an outstanding inhibitory activity against PPL (55.98±1.04%), with activity 60% higher than that of the reference drug Orlistat. The other compounds isolated and identified were β-sitosterol (2.99±0.80%) and stigmasterol (2.68±0.38%). The enzyme kinetics of E. indica crude methanolic extract on PPL showed mixed inhibition mechanism.
Unstable Modes and Order Parameters of Bistable Signaling Pathways at Saddle-Node Bifurcations: A Theoretical Study Based on Synergetics
Authors: Frank Till D.
Published: October 2016

Mathematical modeling has become an indispensable part of systems biology which is a discipline that has become increasingly popular in recent years. In this context, our understanding of bistable signaling pathways in terms of mathematical modeling is of particular importance because such bistable components perform crucial functions in living cells. Bistable signaling pathways can act as switches or memory functions and can determine cell fate. In the present study, properties of mathematical models of bistable signaling pathways are examined from the perspective of synergetics, a theory of self-organization and pattern formation founded by Hermann Haken. At the heart of synergetics is the concept of so-called unstable modes or order parameters that determine the behavior of systems as a whole close to bifurcation points. How to determine these order parameters for bistable signaling pathways at saddle-node bifurcation points is shown. The procedure is outlined in general and an explicit example is worked out in detail.
Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication
Authors: Roda E. , Giampreti A. , Vecchio S. , Apostoli P. , Coccini T.
Published: October 2016

Introduction. Chronic poisoning may result in home setting after mercury (Hg) vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg) monitoring were performed from admission (t0), until 1 year later (t2), paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs). At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1–4.5; UHg 0.1–4.5), associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0–16.0). At t1 (two days after DMSA-mobilization test), BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes). At t2 (eight months after two cycles of DMSA chelating therapy ending), gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp.) and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes). Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.
Phospholipase D1 Acts through Akt/TopBP1 and RB1 to Regulate the E2F1-Dependent Apoptotic Program in Cancer Cells
Authors: Kang Dong Woo , Lee Shin Wha , Hwang Won Chan , Lee Bo Hui , Choi Yong-Seok , Suh Young-Ah , Choi Kang-Yell , Min Do Sik
Published: October 2016

The RB1/E2F1 signaling pathway is frequently deregulated in colorectal cancer and has been suggested to intersect with Wnt/β-catenin and PI3K/Akt pathways, but molecular evidence for this link is lacking. In this study, we demonstrate that phospholipase D1 (PLD1), a transcriptional target of β-catenin/TCF4, orchestrates functional interactions between these pathways during intestinal tumor development. Overexpression of PLD1 in intestinal epithelial cells protected cells from apoptosis induced by PLD1 ablation in the Apcmin/+ mouse model of intestinal tumorigenesis. Mechanistic investigations revealed that genetic and pharmacologic targeting of PLD1 promote the E2F1-dependent apoptotic program via both miR-192/4465–mediated downregulation of RB1 and inhibition of Akt–TopBP1 pathways. Moreover, the miRNA–RB1 axis and Akt pathway also contributed to the PLD1-mediated self-renewal capacity of colon cancer–initiating cells. Finally, PLD1-driven E2F1 target gene expression positively correlated with tumor stage in patients with colorectal cancer. Overall, our findings suggest that PLD1 mediates cross-talk between multiple major signaling pathways to promote the survival and malignancy of colon cancer cells and may therefore represent an ideal signaling node for therapeutic targeting. Cancer Res; 77(1); 142–52. ©2016 AACR.
Enhanced Detection of Cancer Biomarkers in Blood-Borne Extracellular Vesicles Using Nanodroplets and Focused Ultrasound
Authors: Paproski Robert J. , Jovel Juan , Wong Gane Ka-Shu , Lewis John D. , Zemp Roger J.
Published: October 2016

The feasibility of personalized medicine approaches will be greatly improved by the development of noninvasive methods to interrogate tumor biology. Extracellular vesicles shed by solid tumors into the bloodstream have been under recent investigation as a source of tumor-derived biomarkers such as proteins and nucleic acids. We report here an approach using submicrometer perfluorobutane nanodroplets and focused ultrasound to enhance the release of extracellular vesicles from specific locations in tumors into the blood. The released extracellular vesicles were enumerated and characterized using micro flow cytometry. Only in the presence of nanodroplets could ultrasound release appreciable levels of tumor-derived vesicles into the blood. Sonication of HT1080-GFP tumors did not increase the number of circulating tumor cells or the metastatic burden in the tumor-bearing embryos. A variety of biological molecules were successfully detected in tumor-derived extracellular vesicles, including cancer-associated proteins, mRNAs, and miRNAs. Sonication of xenograft HT1080 fibrosarcoma tumors released extracellular vesicles that contained detectable RAC1 mRNA with the highly tumorigenic N92I mutation known to exist in HT1080 cells. Deep sequencing serum samples of embryos with sonicated tumors allowed the identification of an additional 13 known heterozygous mutations in HT1080 cells. Applying ultrasound to HT1080 tumors increased tumor-derived DNA in the serum by two orders of magnitude. This work is the first demonstration of enhanced extracellular vesicle release by ultrasound stimulation and suggests that nanodroplets/ultrasound offers promise for genetic profiling of tumor phenotype and aggressiveness by stimulating the release of extracellular vesicles. Cancer Res; 77(1); 3–13. ©2016 AACR.
DNA Repair Capacity in Multiple Pathways Predicts Chemoresistance in Glioblastoma Multiforme
Authors: Nagel Zachary D. , Kitange Gaspar J. , Gupta Shiv K. , Joughin Brian A. , Chaim Isaac A. , Mazzucato Patrizia , Lauffenburger Douglas A. , Sarkaria Jann N. , Samson Leona D.
Published: October 2016

Cancer cells can resist the effects of DNA-damaging therapeutic agents via utilization of DNA repair pathways, suggesting that DNA repair capacity (DRC) measurements in cancer cells could be used to identify patients most likely to respond to treatment. However, the limitations of available technologies have so far precluded adoption of this approach in the clinic. We recently developed fluorescence-based multiplexed host cell reactivation (FM-HCR) assays to measure DRC in multiple pathways. Here we apply a mathematical model that uses DRC in multiple pathways to predict cellular resistance to killing by DNA-damaging agents. This model, developed using FM-HCR and drug sensitivity measurements in 24 human lymphoblastoid cell lines, was applied to a panel of 12 patient-derived xenograft (PDX) models of glioblastoma to predict glioblastoma response to treatment with the chemotherapeutic DNA-damaging agent temozolomide. This work showed that, in addition to changes in O6-methylguanine DNA methyltransferase (MGMT) activity, small changes in mismatch repair (MMR), nucleotide excision repair (NER), and homologous recombination (HR) capacity contributed to acquired temozolomide resistance in PDX models and led to reduced relative survival prolongation following temozolomide treatment of orthotopic mouse models in vivo. Our data indicate that measuring the combined status of MMR, HR, NER, and MGMT provided a more robust prediction of temozolomide resistance than assessments of MGMT activity alone. Cancer Res; 77(1); 198–206. ©2016 AACR.
Effect of Neutrophils on Gallbladder Interstitial Cajal-Like Cells in Guinea Pig Model of Acute Cholecystitis
Authors: Huang Zhen-peng , Qiu Hu , Yang Yan , Yu Bao-ping
Published: October 2016

Background: Acute cholecystitis is a common condition in gallbladder motility disorder. Interstitial Cajal-like cells (ICLCs) in the gallbladder are known as one of the players in the complex motility mechanisms affecting gallbladder motility. Aim: This study explored morphological symptoms and molecular mechanisms underlying gallbladder ICLC changes induced by acute cholecystitis. Materials and Methods: Fifteen adult guinea pigs were randomly divided into 3 groups: sham-operated group (healthy controls) and 2 experimental groups wherein these guinea pigs were subjected to common bile duct ligation to induce acute cholecystitis. Neutrophils were isolated from the peripheral blood of sham-operated animals and from the experimental animals at 24 and 48 h after surgery, and co-cultured with gallbladder ICLCs. The morphology of gallbladder ICLCs was examined by laser confocal immunofluorescence microscopy, TUNEL assay was used to detect apoptosis, and western blot and real-time PCR were performed to detect stem cell factor (SCF) and c-kit protein and mRNA expression, respectively. Results: No morphological differences in the gallbladder ICLCs were observed between single-culture and co-culture with healthy control neutrophil groups. However, the ICLCs in all co-culture groups with acute inflammation were impaired. In the co-culture groups, the rate of ICLC apoptosis was significantly higher than that in the single-culture group. SCF and c-kit protein and mRNA expression levels decreased in all co-culture groups as well. Conclusion: We demonstrated that the neutrophils are involved in gallbladder ICLC injury in acute cholecystitis cases and associated with gallbladder motility disorder.
Inhibition of MDM2 Re-Sensitizes Rapamycin Resistant Renal Cancer Cells via the Activation of p53
Authors: Tian Xin , Dai Shundong , Sun Jing , Jiang Shenyi , Sui Chengguang , Meng Fandong , Li Yan , Fu Liye , Jiang Tao , Wang Yang , Su Jia , Jiang Youhong
Published: October 2016

Background/Aims: Rapamycin is a potential anti-cancer agent, which modulates the activity of mTOR, a key regulator of cell growth and proliferation. However, several types of cancer cells are resistant to the anti-proliferative effects of rapamycin. In this study, we report a MDM2/p53-mediated rapamycin resistance in human renal cancer cells. Methods: Trypan blue exclusion tests were used to determine the cell viability. Changes in mRNA and protein expression were measured using real-time PCR and western blot, respectively. Xenograft models were established to evaluate the in vivo effects of rapamycin combined with a MDM2 inhibitor. Results: Rapamycin treatment suppresses the expression of MDM2 and exogenous overexpression of MDM2 in A498 cells contributes to rapamycin resistance. By establishing a rapamycin resistant cell line, we observed that MDM2 was significantly upregulated in rapamycin resistant cells than that in rapamycin sensitive cells. Importantly, the rapamycin resistant cells demonstrated attenuated accumulation of p53 in the nucleus in response to rapamycin treatment. Moreover, the inhibition of MDM2 by siMDM2 sensitizes A498 cells to rapamycin through the activation of p53. In both in vitro and in vivo models, the combination of rapamycin with the MDM2 inhibitor, MI-319, demonstrated a synergistic inhibitory effect on rapamycin resistant cells. Conclusion: Our study reports a novel mechanism for rapamycin resistance in human renal cancer and provides a new perspective for the development of anti-cancer drugs.
Bevacizumab in Ovarian Cancer: State of the Art and Unanswered Questions
Authors: Musella Angela , Vertechy Laura , Romito Alessia , Marchetti Claudia , Giannini Andrea , Sciuga Valentina , Bracchi Carlotta , Tomao Federica , Di Donato Violante , De Felice Francesca , Monti Marco , Muzii Ludovico , Benedetti Panici Pierluigi
Published: October 2016

Ovarian cancer is a most lethal gynecologic tumor. The mainstay treatment is cytoreductive surgery followed by platinum-based chemotherapy. However, a high percentage of patients recur, thus needing multiple treatments with a frequently poor prognosis. In the last two decades, research has focused on the potential of target therapies to improve the survival of patients affected by ovarian cancer. Bevacizumab is one of the most studied target therapies, and it is approved for first- and second-line treatment of advanced epithelial ovarian, fallopian tube, and primary peritoneal tumors. Despite its widespread use with favorable results, controversy regarding patient selection and the best schedule, dosage, and timing of bevacizumab still exists. This review summarizes the state of the art on the use of bevacizumab for ovarian cancer in front-line, recurrence, and neoadjuvant settings. This study focuses on the results of pivotal trials, emerging data, ongoing research, and still unanswered questions about the most adequate dosage of bevacizumab and its potential activity after disease progression or rechallenge in previously treated patients.
Aberrant Splicing in Cancer: Mediators of Malignant Progression through an Imperfect Splice Program Shift
Authors: Luz Felipe Andrés Cordero , Brígido Paula Cristina , Moraes Alberto Silva , Silva Marcelo José Barbosa
Published: October 2016

Although the efforts to understand the genetic basis of cancer allowed advances in diagnosis and therapy, little is known about other molecular bases. Splicing is a key event in gene expression, controlling the excision of introns decoded inside genes and being responsible for 80% of the proteome amplification through events of alternative splicing. Growing data from the last decade point to deregulation of splicing events as crucial in carcinogenesis and tumor progression. Several alterations in splicing events were observed in cancer, caused by either missexpression of or detrimental mutations in some splicing factors, and appear to be critical in carcinogenesis and key events during tumor progression. Notwithstanding, it is difficult to determine whether it is a cause or consequence of cancer and/or tumorigenesis. Most reviews focus on the generated isoforms of deregulated splicing pattern, while others mainly summarize deregulated splicing factors observed in cancer. In this review, events associated with carcinogenesis and tumor progression mainly, and epithelial-to-mesenchymal transition, which is also implicated in alternative splicing regulation, will be progressively discussed in the light of a new perspective, suggesting that splicing deregulation mediates cell reprogramming in tumor progression by an imperfect shift of the splice program.
Cognitive Impairment in Advanced Chronic Kidney Disease: The Canadian Frailty Observation and Interventions Trial
Authors: Foster Rukhsana , Walker Simon , Brar Ranveer , Hiebert Brett , Komenda Paul , Rigatto Claudio , Storsley Leroy , Prasad Bhanu , Bohm Clara , Tangri Navdeep
Published: October 2016

Background: Chronic kidney disease (CKD) affects more than one third of older adults, and is a strong risk factor for vascular disease and cognitive impairment. Cognitive impairment can have detrimental effects on the quality of life through decreased treatment adherence and poor nutrition and results in increased costs of care and early mortality. Though widely studied in hemodialysis populations, little is known about cognitive impairment in patients with pre-dialysis CKD. Methods: Multicenter, cross-sectional, prospective cohort study including 385 patients with CKD stages G4-G5. Cognitive function was measured with a validated tool called the Montreal Cognitive Assessment (MoCA) as part of a comprehensive frailty assessment in the Canadian Frailty Observation and Interventions Trial. Cognitive impairment was defined as a MoCA score of ≤24. We determined the prevalence and risk factors for cognitive impairment in patients with CKD stages G4-G5, not on dialysis. Results: Two hundred and thirty seven participants (61%) with CKD stages G4-G5 had cognitive impairment at baseline assessment. When compared to a control group, this population scored lower in all domains of cognition, with the most pronounced deficits observed in recall, attention, and visual/executive function (p < 0.01 for all comparisons). Older age, recent history of falls and history of stroke were independently associated with cognitive impairment. Conclusions: Our study uncovered a high rate of unrecognized cognitive impairment in an advanced CKD population. This impairment is global, affecting all aspects of cognition and is likely vascular in nature. The longitudinal trajectory of cognitive function and its effect on dialysis decision-making and outcomes deserves further study.
Comparison between Three Methods of Fetal Weight Estimation during the Active Stage of Labor Performed by Residents: A Prospective Cohort Study
Authors: Weiner Eran , Mizrachi Yossi , Fainstein Nataly , Elyashiv Osnat , Mevorach-Zussman Noa , Bar Jacob , Kovo Michal
Published: October 2016

Objective: To compare the accuracy of ultrasonographic, calculated, and clinical methods for the estimation of fetal weight (EFW) performed during active labor by residents. Methods: Parturients in active labor underwent prospectively EFW by 3 methods: ultrasonographic, clinical, and calculated (extrapolating EFW from a previous scan). Three different blinded residents evaluated each woman. Background variables were examined for their effect on the accuracy of each method. Comparison of the methods for the detection of macrosomia and small for gestational age (SGA) was also performed. Results: Among the 405 women recruited, the rates of accuracy of ultrasonographic, clinical, and calculated EFW (within ±10%) was 72.5, 74.3, and 71.1%, respectively. The correlation coefficient between the methods and actual birth weight (ABW) were 0.702-0.611 (using 7 Hadlock formulas), 0.649, and 0.622, respectively (all p < 0.001). By logistic regression, epidural analgesia was associated with higher and second stage of labor with lower accuracy of ultrasonographic EFW. For the detection of macrosomia, clinical (p < 0.001) and calculated EFWs (p = 0.035) were superior to ultrasonographic EFW. For the detection of SGA, ultrasonographic EFW was superior to calculated (p < 0.001) and clinical (p < 0.001) EFWs. Conclusion: All 3 methods performed by residents during labor correlated well with ABW. Clinical and calculated EFWs were superior for macrosomia detection, whereas ultrasonographic EFW was superior for SGA detection.
Recurrent Orbital Solitary Fibrous Tumor in a 12-Year-Old
Authors: Vu Alexander F. , Chundury Rao V. , Blandford Alexander D. , Perry Julian D.
Published: October 2016

Purpose: To report the clinical features and pathology of orbital solitary fibrous tumors and present a case of a recurrence in a 12-year-old boy. Methods: Case Report. Results: A 12-year-old boy presented to our institution with double vision in upgaze for 6 months. Examination revealed 3 mm of left-sided proptosis, hypoglobus, and -3 impairment of supraduction. Magnetic resonance imaging of the orbits showed an avidly enhancing mass within the superolateral aspect of the orbit. Biopsy revealed a solitary fibrous tumor with STAT6 and CD34 positivity. Positron emission tomography-computed tomography was negative for metastatic disease. The tumor underwent excision. However, 4 months postoperatively, imaging revealed changes consistent with recurrence. A repeat lateral orbitotomy with orbital rim marginotomy was performed with complete gross excision of the tumor. The patient remains tumor-free 22 months after reoperation. Conclusion: Orbital solitary fibrous tumor rarely occurs in the pediatric population. Despite initial complete gross tumor excision, this case represents the youngest individual with a recurrence to the authors' knowledge. This case of rapid recurrence may have been due to tumor seeding at the time of initial biopsy or other factors. This case increases the known spectrum of orbital solitary fibrous tumors.
Effects of Distigmine on Electrical Field Stimulation-Induced Contraction of Mouse Urinary Bladder Smooth Muscles
Authors: Obara Keisuke , Kobayashi Yurina , Chino Daisuke , Tanaka Yoshio
Published: October 2016

Distigmine bromide (distigmine), a reversible carbamate cholinesterase inhibitor, is used in Japan for treating detrusor underactivity, myasthenia gravis, and glaucoma. Although there is clinical evidence about the effectiveness of distigmine in the treatment of detrusor underactivity, mechanisms by which distigmine restores impaired urinary bladder smooth muscle (UBSM) contractility have not been fully investigated. The aims of this study were to investigate the potentiating effects of distigmine on UBSM contractions in response to parasympathetic nerve stimulation induced by electrical field stimulation (EFS) in mice. In isolated mouse UBSM, EFS (1-16 Hz) produced tetrodotoxin-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely attenuated by atropine (10-6 mol/l). UBSM contractility that occurred in the presence of atropine was nearly eliminated by the addition of α,β-methylene adenosine triphosphate (α,β-mATP, 10-4 mol/l). Distigmine (3 × 10-7 mol/l) significantly potentiated EFS-induced contractile responses engendered in the presence of α,β-mATP (10-4 mol/l), but not atropine (10-6 mol/l). These findings indicate that distigmine powerfully potentiates UBSM contractions selectively induced by parasympathetic nerve-derived acetylcholine, thereby demonstrating a potential mechanism by which it stimulates detrusor contractile function.
Clinical Presentation, Magnetic Resonance Angiography, Ultrasound Findings, and Stroke Patterns in Patients with Vertebral Artery Dissection
Authors: Günther Albrecht , Witte Otto W. , Freesmeyer Martin , Drescher Robert
Published: October 2016

Background/Aims: Vertebral artery dissection (VAD) is an important cause of ischemic stroke. In this observational study, clinical data, magnetic resonance (MR) and ultrasound (US) imaging findings and ischemic patterns were analyzed. Methods: Forty-seven patients with a diagnosis of VAD underwent clinical examination, US, MR of the brain and neck and MR angiography (MRA) of the cervical arteries. Vascular abnormalities and ischemic brain lesions were noted. Data were evaluated separately and compared for spontaneous and traumatic VAD subgroups. Results: The most common overall clinical symptom was vertigo followed by neck pain. In the traumatic subgroup, vertigo was relatively rare (p = 0.022). Most common MRA findings were vessel irregularity and vessel occlusions. Ischemic lesions occurred significantly more frequently after spontaneous than after traumatic VAD (p = 0.009). Unilateral VAD was significantly more common in non-dominant vertebral arteries (p < 0.001). Mortality after trauma was not only due to VAD complications but also due to other trauma-related injuries. Conclusion: The variability of MR and US imaging findings in patients with VAD is illustrated. The algorithm of management should be based on a multimodality approach involving patient history and clinical neurological examination. Several types of vessel abnormalities and ischemic lesion in diverse locations may point to arterial dissection, and the differential diagnosis of VAD must be kept in mind.
Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study
Authors: Gaß Paul , Fasching Peter A. , Fehm Tanja , de Waal Johann , Rezai Mahdi , Baier Bernd , Baake Gerold , Kolberg Hans-Christian , Guggenberger Martin , Warm Mathias , Harbeck Nadia , Wuerstlein Rachel , Deuker Jörg-Uwe , Dall Peter , Richter Barbara , Wachsmann Grischa , Brucker Cosima , Siebers Jan W. , Fersis Nikos , Kuhn Thomas , Wolf Christopher , Vollert Hans-Walter , Breitbach Georg-Peter , Janni Wolfgang , Landthaler Robert , Kohls Andreas , Rezek Daniela , Noesselt Thomas , Fischer Gunnar , Henschen Stephan , Praetz Thomas , Heyl Volker , Kühn Thorsten , Krauss Thomas , Thomssen Christoph , Hohn Andre , Tesch Hans , Mundhenke Christoph , Hein Alexander , Rauh Claudia , Bayer Christian M. , Jacob Adib , Schmidt Katja , Belleville Erik , Hadji Peyman , Brucker Sara Y. , Beckmann Matthias W. , Wallwiener Diethelm , Kümmel Sherko , Löhberg Christian R.
Published: October 2016

Background: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.