bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in serum creatinine testing in Oxfordshire, UK, 1993–2013: a population-based cohort study
Authors: Oke Jason , Shine Brian , McFadden Emily , Stevens Richard , Lasserson Daniel , Perera Rafael
Published: December 2015

Objectives

To determine how many kidney function tests are done, on whom, how frequently they are performed and how they have changed over time.

Design

Retrospective study of all serum creatinine, urine albumin and urine creatinine tests.

Setting

Primary and secondary care in Oxfordshire from 1993 to 2013.

Participants

Unselected population of 1 220 447 people.

Main outcome measures

The total number of creatinine and urinary protein tests ordered from primary and secondary care and the number of tests per year stratified by categories of estimated glomerular filtration rate (eGFR). The frequency of testing in patients having their kidney function monitored.

Results

Creatinine requests from primary care increased steadily from 1997 and exceeded 220 000 requests in 2013. Tests corresponding to normal kidney function (eGFR >60/mL/min/1.73 m2) constituted 59% of all kidney function tests in 1993 and accounted for 83% of all tests in 2013. Test corresponding to chronic kidney disease (CKD) stages 3–5 declined after 2007. Reduced kidney function, albuminuria, male gender, diabetes and age were independently associated with more frequent monitoring. For a female patient between 61 and 80 years and with stage 3a CKD, the average number of serum creatinine tests (95% CI) was 3.23/year (3.19 to 3.26) and for a similar woman with diabetes, the average number of tests was 5.50 (5.44 to 5.56) tests per year.

Conclusions

There has been a large increase in the number of kidney function tests over the past two decades. However, we found little evidence that this increase is detecting more CKD. Tests are becoming more frequent in people with and without evidence of renal impairment. Future work using a richer data source could help unravel the underlying reasons for the increased testing and determine how much is necessary and useful.
Prolonged seizure‐like phenomena in an English springer spaniel after total intravenous anaesthesia with propofol
Authors: Monticelli Paolo , Seymour Christopher John
Published: December 2015

Propofol is an anaesthetic agent commonly used for both induction and maintenance of general anaesthesia and has been associated with seizure‐like phenomena (SLP) in both veterinary and human medicine. This case report describes an English springer spaniel with no previous history of neurological symptoms, which exhibited SLP after propofol anaesthesia for bronchoscopy. The SLP were refractory to treatment for 13 hours, but steadily improved after administration of phenobarbital and levetiracetam. To the authors’ knowledge, this is the first report of their use to manage SLP.
Investigation of severe coughing and ill thrift in adult hill sheep associated with Mycoplasma ovipneumoniae
Authors: Nicholas Robin A J , Ayling Roger D , Rosales Ruben Santana , Myerscough Christopher
Published: December 2015

Mycoplasma ovipneumoniae has long been associated with respiratory disease in young sheep and goats. Here, the authors present evidence that it may be a cause of a coughing syndrome and ill thrift in young and, unusually, older Swaledale ewes on a hill farm in northern England. M. ovipneumoniae was detected in nasal swabs of a majority of affected lambs and ewes, many of which were also seropositive. Postmortem examination of a severely affected seropositive ewe revealed gross and histopathological lesions suggestive of mycoplasma infection, from which M. ovipneumoniae was isolated as well as secondary bacterial pathogens.
Second‐year student diary
Authors: Perrett Rosie
Published: December 2015

Despite having lots to learn – and lots to organise for Christmas and her dad's retirement – Rosie Perrett recently enjoyed a weekend break with her friends from her previous degree course.
Histopathological, oxidative damage, biochemical, and genotoxicity alterations in hepatic rats exposed to deltamethrin: modulatory effects of garlic (Allium sativum)
Authors: Ncir Marwa , Ben Salah Ghada , Kamoun Hassen , Makni Ayadi Fatma , Khabir Abdelmajid , El Feki Abdelfattah , Saoudi Mongi
Published: December 2015

Deltamethrin is a pesticide widely used as a synthetic pyrethroid. The aim of this study was undertaken to investigate the effects of deltamethrin to induce oxidative stress and changes in biochemical parameters, hepatotoxicity and genotoxicity in female rats following a short-term (30 days) oral exposure and attenuation of these effects by Allium sativum extract. Indeed, Allium sativum is known to be a good antioxidant food resource which helps destroy free radical particles. Our results showed that deltamethrin treatment caused an increase in liver enzyme activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH); and hepatic lipid peroxidation (LPO) level. However, it induced a decrease in activities of hepatic catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (p < 0.01). Allium sativum extract normalized significantly (p < 0.01) the mentioned parameters in deltamethrin-treated rats. For genotoxic evaluation, deltamethrin treatment showed a significant increase in frequencies of micronucleus in bone-marrow cells. Micronucleus formation is an indicator of chromosomal damage which has been increasingly used to detect the genotoxic potential of environmental pests. The present study showed that Allium sativum diminished the adverse effects induced by this synthetic pyrethroid insecticide.
Berry phase and anomalous velocity of Weyl fermions and Maxwell photons
Authors: Stone Michael
Published: December 2015

We consider two systems of wave equations whose wave packet solutions have trajectories that are altered by the “anomalous velocity” effect of a Berry curvature. The first is the matrix Weyl equation describing cyclotron motion of a charged massless fermion. The second is Maxwell equations for the whispering-gallery modes of light in a cylindrical waveguide. In the case of the massless fermion, the anomalous velocity is obscured by the contribution from the magnetic moment. In the whispering-gallery modes, the anomalous velocity causes the circumferential light ray to creep up the cylinder at the rate of one wavelength per orbit, and can be identified as a continuous version of the Imbert–Federov effect.
Research on sintering behavior and microwave dielectric property of (Mg0.95Ca0.05)TiO3 ceramics for cross coupling filter
Authors: Luo Chunya , Ma Zhichao , Hu Laisheng , Hu Mingzhe , Huang Xiaomin
Published: December 2015

The microwave dielectric properties of [Formula: see text]–[Formula: see text] (abbreviated as 95MCT hereafter) ceramics have been studied for application in dielectric cross coupling filters. [Formula: see text] and [Formula: see text] were selected as liquid sintering aids to lower the sintering temperature and enhance the Qf value of 95MCT and simultaneously we varied the mole ratio of [Formula: see text] to tune the microwave dielectric properties of 95MCT. When the [Formula: see text] mole ratio was 1.5 and the co-doping content was 0.25 wt.%, the optimal sintering temperature of 95MCT ceramic could be lowered from [Formula: see text] to [Formula: see text] and the Qf value could be improved by about 7.7%. The optimal microwave dielectric properties obtained under this condition were Qf = 72730 GHz (6.8 GHz), [Formula: see text] and [Formula: see text], which demonstrated great potential usage in ceramic industry. High values of Qf ceramic were used to design the dielectric cross coupling filter. The dielectric filter measured at 2.35 GHz exhibited a 6.7% bandwidth (insert loss [Formula: see text] dB) of center frequency.
1/f noise from the nonlinear transformations of the variables
Authors: Kaulakys Bronislovas , Alaburda Miglius , Ruseckas Julius
Published: December 2015

The origin of the low-frequency noise with power spectrum [Formula: see text] (also known as [Formula: see text] fluctuations or flicker noise) remains a challenge. Recently, the nonlinear stochastic differential equations for modeling [Formula: see text] noise have been proposed and analyzed. Here, we use the self-similarity properties of this model with respect to the nonlinear transformations of the variables of these equations and show that [Formula: see text] noise of the observable may yield from the power-law transformations of well-known standard processes, like the Brownian motion, Bessel and similar stochastic processes. Analytical and numerical investigations of such techniques for modeling processes with [Formula: see text] fluctuations is presented.
Computational Acceleration of Real-Time Kernel-Based Tracking System
Authors: Pandey Manoj , Ubhi J. S. , Raju Kota Solomon
Published: December 2015

Object tracking in real-time is one of the applications of video processing, where the required computational cost is high due to intensive high data processing. In order to solve these problems, this paper presents an embedded solution, where the Hardware/Software (HW/SW) co-design architecture is used for the implementation of well-known kernel-based tracking system. In this algorithm, the target is searched in consecutive frame by maximizing the statistical match with similarity estimation of color distribution. The whole tracking system is implemented on low cost Field Programmable Gate Array (FPGA) device with image resolution of 1280[Formula: see text]720 pixels and target window size of 160[Formula: see text]80 pixels. The HW/SW co-design architecture is proposed to accelerate the computational speed of the system. The performance of the system is evaluated in terms of execution speed and frame rate compared with software based implementation. The hardware cost of design is also compared with other existing methods. The proposed design achieves 22 times computational speed and maximum 60 Frames Per Second (FPS) compared with software based design.
Halogenated tetraphenyl porphyrin; iodosylbenzene an efficient catalytic system for olefin epoxidation
Authors: Aggrawal Dau D. , Bhat Daisy
Published: December 2015

Olefin epoxidation using o-phenyl and [Formula: see text]-pyrrole substituted tetraphenyl porphyrin complexes of Fe(III) and Mn(III) as catalysts and [Formula: see text]Iodosylbenzene as oxidant was studied. Excellent yields of epoxide and secondary oxidation products were observed. Effect of pyridine, imadizole, sodium lauryl sulphate, and solvent variation was also studied. Effect of substituents on catalytic activity of the porphyrin complex is also explained. o-phenyl substituted complexes gave better yield of epoxide as compared to [Formula: see text]-pyrrole substituted complexes.
The vertebrate-bearing Late Triassic Fleming Fjord Formation of central East Greenland revisited: stratigraphy, palaeoclimate and new palaeontological data
Authors: Clemmensen Lars B. , Milàn Jesper , Adolfssen Jan Schulz , Estrup Eliza Jarl , Frobøse Nicolai , Klein Nicole , Mateus Octávio , Wings Oliver
Published: December 2015

In Late Triassic (Norian–Rhaetian) times, the Jameson Land Basin lay at 40° N on the northern part of the supercontinent Pangaea. This position placed the basin in a transition zone between the relatively dry interior of the supercontinent and its more humid periphery. Sedimentation in the Jameson Land Basin took place in a lake–mudflat system and was controlled by orbitally forced variations in precipitation. Vertebrate fossils have consistently been found in these lake deposits (Fleming Fjord Formation), and include fishes, dinosaurs, amphibians, turtles, aetosaurs and pterosaurs. Furthermore, the fauna includes mammaliaform teeth and skeletal material. New vertebrate fossils were found during a joint vertebrate palaeontological and sedimentological expedition to Jameson Land in 2012. These new finds include phytosaurs, a second stem testudinatan specimen and new material of sauropodomorph dinosaurs, including osteologically immature individuals. Phytosaurs are a group of predators common in the Late Triassic, but previously unreported from Greenland. The finding includes well-preserved partial skeletons that show the occurrence of four individuals of three size classes. The new finds support a late Norian–early Rhaetian age for the Fleming Fjord Formation, and add new information on the palaeogeographical and palaeolatitudinal distribution of Late Triassic faunal provinces.
Enhancement of postsynaptic GABAA and extrasynaptic NMDA receptor-mediated responses in the barrel cortex of Mecp2-null mice
Authors: Lo Fu-Sun , Blue Mary E. , Erzurumlu Reha S.
Published: December 2015

Rett syndrome (RTT) is a neurodevelopmental disorder that results from mutations in the X-linked gene for methyl-CpG-binding protein 2 ( MECP2). The underlying cellular mechanism for the sensory deficits in patients with RTT is largely unknown. This study used the Bird mouse model of RTT to investigate sensory thalamocortical synaptic transmission in the barrel cortex of Mecp2-null mice. Electrophysiological results showed an excitation/inhibition imbalance, biased toward inhibition, due to an increase in efficacy of postsynaptic GABAA receptors rather than alterations in inhibitory network and presynaptic release properties. Enhanced inhibition impaired the transmission of tonic sensory signals from the thalamus to the somatosensory cortex. Previous morphological studies showed an upregulation of NMDA receptors in the neocortex of both RTT patients and Mecp2-null mice at early ages [Blue ME, Naidu S, Johnston MV. Ann Neurol 45: 541–545, 1999; Blue ME, Kaufmann WE, Bressler J, Eyring C, O'Driscoll C, Naidu S, Johnston MV. Anat Rec (Hoboken) 294: 1624–1634, 2011]. Although AMPA and NMDA receptor-mediated excitatory synaptic transmission was not altered in the barrel cortex of Mecp2-null mice, extrasynaptic NMDA receptor-mediated responses increased markedly. These responses were blocked by memantine, suggesting that extrasynaptic NMDA receptors play an important role in the pathogenesis of RTT. The results suggest that enhancement of postsynaptic GABAA and extrasynaptic NMDA receptor-mediated responses may underlie impaired somatosensation and that pharmacological blockade of extrasynaptic NMDA receptors may have therapeutic value for RTT.
Impact of Strong Raman Self-Frequency Shift on Bound State of Dissipative Solitons
Authors: Xu Cong
Published: December 2015

Bound dissipative solitons are numerically studied by implementing strong Raman self-frequency shift (RSFS) in an all-normal-dispersion (ANDi) Yb-doped fiber laser. Results demonstrated that overstrong RSFS had no filter-like effect in the ANDi fiber laser when a bandpass filter was present in the intracavity. However, overstrong RSFS could cause the bandpass filter to destabilize the ANDi fiber laser. For the first time in the field, we have demonstrated that strong RSFS could destabilize bound DS pulses and generate noise-like bound pulses. Furthermore, the generation mechanism of destabilized noise-like bound pulses in the fiber laser with intracavity filter is different from the noise-like pulses in the fiber lasers without a bandpass filter.
Electric Load Forecast Using Combined Models with HP Filter-SARIMA and ARMAX Optimized by Regression Analysis Algorithm
Authors: Herui Cui , Xu Peng , Yupei Mu
Published: December 2015

Electric load in summer has a significant cyclical trend with temperature effects. In general, the parameters of the SARIMA and the SMA turn out to be nonsignificant in most cases. To address this issue, the hybrid time series model is utilized to extract the spectrum sequences with different frequencies. The original electric load series are first decomposed into the trend sequence “G” and the cycle sequence “C.” After that, a revised ARMAX model is proposed to deal with the two divided sequences. Finally, the combined models are tested by case study. The case study on electric load forecast in one city from China shows that the proposed model outperforms other four comparative models in terms of prediction accuracy. It proves that the combined model proposed by the authors is more accurate than those based on a single forecasting method.
An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy
Authors: Talavera Jesús , Giraldo Alejandro , Fernández-Del-Palacio María Josefa , García-Nicolás Obdulio , Seva Juan , Brooks Gavin , Moraleda Jose M.
Published: December 2015

Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality.
A Biomedical Surface Enhanced Raman Scattering Substrate: Functionalized Three-Dimensional Porous Membrane Decorated with Silver Nanoparticles
Authors: Yuan Li , Fang Jinghuai , Jin Yonglong , Wang Chaonan , Xu Tian
Published: December 2015

We fabricated a simple, cheap, and functional surface enhanced Raman scattering substrate for biomedical application. Hot spots between two close silver nanoparticles distributed in the skeleton of a three-dimensional porous membrane, especially in the pores, were formed. The dual poles of micropores in the membrane were discussed. The pores could protect the silver nanoparticles in the pores from being oxidized, which makes the membrane effective for a longer period of time. In addition,Staphylococcus aureuscells could be trapped by the micropores and then the Raman signal became stronger, indicating that the functional surface enhanced Raman scattering substrate is reliable.
Prevalence of Self-Reported Food Allergy in Lebanon: A Middle-Eastern Taste
Authors: Irani C. , Maalouly G.
Published: December 2015

Background. Food allergy (FA) is an important health problem in Western countries but there is limited data on the prevalence of food allergy in the Middle East. The main objective of our study is to assess the prevalence of self-reported food allergy in Lebanon. Methods. The survey was conducted by Telephone Calls questionnaire through random selection of landline phone numbers from the white pages all over Lebanon. A study questionnaire addressing the main objectives of the study was filled during the telephone call conversation. Results. Food allergy prevalence is estimated to be 4.1% in infants and children and 3.2% in adults. 65% of patients suffering from food allergy are females and 35% are males. Skin reactions are the most common symptoms among food allergy sufferers, reported in 86% of the cases. Signs of anaphylaxis appeared in 10.8% of cases. Fruits were the most common allergens at 35%, followed by eggs (19%) and nuts (16%). Cow’s milk and spices ranked fourth (14%). Only half of food allergy sufferers sought medical advice. Allergists, dermatologists, gastroenterologists, or GPs (general practitioners) were consulted. Blood testing for specific IgE was the main diagnostic tool used by physicians. Conclusion. This is a pilot study of self-reported food allergy prevalence in Lebanon based on telephone survey. General prevalence is estimated to be 4.1% in infants and children and 3.2% in adults. Our study may improve awareness for proper diagnosis, food elimination, and acquisition of epinephrine autoinjectors in this part of the world.
Study on Seismic Performance of a Stiffened Steel Plate Shear Wall with Slits
Authors: Lu Jin-yu , Yan Lu-nan , Tang Yi , Wang Heng-hua
Published: December 2015

To determine the force mechanism for the steel plate shear wall with slits, the pushover analysis method was used in this study. An estimated equation for the lateral bearing capacity which considered the effect of edge stiffener was proposed. A simplified elastic-plastic analytical model for the stiffened steel slit wall composed of beam elements was presented, where the effects of edge stiffeners were taken into account. The wall-frame analysis model was established, and the geometric parameters were defined. Pushover analysis of two specimens was carried out, and the analysis was validated by comparing the results from the experiment, the shell element model, and a simplified model. The simplified model provided a good prediction of the lateral stiffness and the strength of the steel slit wall, with less than 10% error compared with the experimental results. The mutual effects of the bearing wall and the frame were also predicted correctly. In the end, the seismic performance evaluation of a steel slit wall-frame structure was presented. The results showed that the steel slit wall could prevent the beams and columns from being damaged by an earthquake and that the steel slit wall was an efficient energy dissipation component.
The Role of FGFR1 Gene Amplification as a Poor Prognostic Factor in Squamous Cell Lung Cancer: A Meta-Analysis of Published Data
Authors: Wang Yang , Gao Wen , Xu Jiali , Chen Xiaojun , Yang Yang , Zhu Yizhi , Yin Yongmei , Guo Renhua , Liu Ping , Shu Yongqian , Liu Lingxiang
Published: December 2015

Objectives. The prognostic factors of the fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) remain controversial.Methods. We conducted a meta-analysis of published studies from 1974 to February 2015. In absence of quality difference between studies of reporting significant and nonsignificant results, the relationship between FGFR1 amplification and clinicopathological parameters in NSCLC was analyzed. And also the combined hazard ratio (HR) and their corresponding 95% confidence interval (CI) were calculated in terms of overall survival.Results. 3178 patients (12 studies) were included in the analysis. It was shown that FGFR1 amplification was significantly more prevalent among male patients (RR 2.03, 95% CI 1.57–2.63) with squamous cell lung cancer (SQCC) (RR 3.49, 95% CI 2.62–4.64) and current smokers (RR 2.63, 95% CI 1.92–3.60). The pooled data also showed that the FGFR1 amplification was a poor prognostic factor in SQCC (HR 1.38, 95% CI 1.07–1.78), Asian patients (HR 1.78, 95% CI 1.22–2.60), and fluorescence in situ hybridization (FISH) method (HR 1.30, 95% CI 1.06–1.58).Conclusions. This meta-analysis strongly suggests that FGFR1 amplification occurs more frequently in male, SQCC and smokers, and it is a risk factor for poor prognosis among Asian patients with SQCC.
Short-Term Load Forecasting Based on Wavelet Transform and Least Squares Support Vector Machine Optimized by Fruit Fly Optimization Algorithm
Authors: Sun Wei , Ye Minquan
Published: December 2015

Electric power is a kind of unstorable energy concerning the national welfare and the people’s livelihood, the stability of which is attracting more and more attention. Because the short-term power load is always interfered by various external factors with the characteristics like high volatility and instability, a single model is not suitable for short-term load forecasting due to low accuracy. In order to solve this problem, this paper proposes a new model based on wavelet transform and the least squares support vector machine (LSSVM) which is optimized by fruit fly algorithm (FOA) for short-term load forecasting. Wavelet transform is used to remove error points and enhance the stability of the data. Fruit fly algorithm is applied to optimize the parameters of LSSVM, avoiding the randomness and inaccuracy to parameters setting. The result of implementation of short-term load forecasting demonstrates that the hybrid model can be used in the short-term forecasting of the power system.
Arsenic and Mercury Containing Traditional Chinese Medicine (Realgar and Cinnabar) Strongly Inhibit Organic Anion Transporters, Oat1 and Oat3,In Vivoin Mice
Authors: Yu Wen-Hao , Zhang Na , Qi Jin-Feng , Sun Chen , Wang Yong-Hui , Lin Mei
Published: December 2015

Toxic heavy metals, including mercury (Hg) and arsenic (As), accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3,in vivoin mice kidney. Mice (n=10) were orally treated with investigational samples. After last administration, all mice were i.v.p-aminohippuric acid (PAH), and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (p<0.05), PAH accumulations in the kidney tissues were significantly higher (p<0.05), PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar) probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3).
Amplify-and-Forward Distributed Beamforming with Local CSI in the Presence of Interferences
Authors: Kim Jung-Bin , Choi Ji-Woong , Choi Hyuk , Cioffi John M.
Published: December 2015

This paper introduces an optimum amplify-and-forward (AF) distributed beamforming (DBF) in the presence of cochannel interference (CCI) when only local channel-state information (CSI) is available at each relay. It is shown that the proposed DBF closely achieves the performance obtained with global CSI when interference power toward relays is small or there are a large number of interferers but greatly reduces the complexity and overhead. The proposed DBF provides significant improvements over the conventional DBF designed without considering CCI at the cost of slightly increased complexity and overhead and achieves the capacity scaling of1/2log⁡KthroughKrelays, where1/2log⁡Kcorresponds to the maximal capacity scaling when there is no CCI.
Not Just Painless Bleeding: Meckel’s Diverticulum as a Cause of Small Bowel Obstruction in Children—Two Cases and a Review of the Literature
Authors: Itriyeva Khalida , Harris Matthew , Rocker Joshua , Gochman Robert
Published: December 2015

Physicians are educated with the classical teaching that symptomatic patients with Meckel’s diverticulum (MD) most often present with painless rectal bleeding. However, a review of the literature reveals that young patients with MD will most commonly present with signs of intestinal obstruction, an etiology not frequency considered in patients presenting to the emergency department with obstruction. We present two cases of intestinal obstruction diagnosed in our emergency department, with Meckel’s diverticulum being the etiology.
Ameliorative Effects of Antioxidants on the Hippocampal Accumulation of Pathologic Tau in a Rat Model of Blast‐Induced Traumatic Brain Injury
Authors: Du Xiaoping , West Matthew B. , Cheng Weihua , Ewert Donald L. , Li Wei , Saunders Debra , Towner Rheal A. , Floyd Robert A. , Kopke Richard D.
Published: December 2015

Traumatic brain injury (TBI) can lead to early onset dementia and other related neurodegenerative diseases. We previously demonstrated that damage to the central auditory pathway resulting from blast‐induced TBI (bTBI) could be significantly attenuated by a combinatorial antioxidant treatment regimen. In the current study, we examined the localization patterns of normal Tau and the potential blast‐induced accumulation of neurotoxic variants of this microtubule‐associated protein that are believed to potentiate the neurodegenerative effects associated with synaptic dysfunction in the hippocampus following three successive blast overpressure exposures in nontransgenic rats. We observed a marked increase in the number of both hyperphosphorylated and oligomeric Tau‐positive hilar mossy cells and somatic accumulation of endogenous Tau in oligodendrocytes in the hippocampus. Remarkably, a combinatorial regimen of 2,4‐disulfonyl α‐phenyl tertiary butyl nitrone (HPN‐07) and N‐acetylcysteine (NAC) resulted in striking reductions in the numbers of both mossy cells and oligodendrocytes positively labeled for these pathological Tau immunoreactivity patterns in response to bTBI. This treatment strategy represents a promising therapeutic approach for simultaneously reducing or eliminating both primary auditory injury and nonauditory changes associated with bTBI‐induced hippocampal neurodegeneration.
Inhospital Mortality in Patients with Type 2 Diabetes Mellitus: A Prospective Cohort Study in Lima, Peru
Authors: Zelada Henry , Bernabe-Ortiz Antonio , Manrique Helard
Published: December 2015

Objective. To estimate cause of death and to identify factors associated with risk of inhospital mortality among patients with T2D.Methods. Prospective cohort study performed in a referral public hospital in Lima, Peru. The outcome was time until event, elapsed from hospital admission to discharge or death, and the exposure was the cause of hospital admission. Cox regression was used to evaluate associations of interest reporting Hazard Ratios (HR) and 95% confidence intervals.Results. 499 patients were enrolled. Main causes of death were exacerbation of chronic renal failure (38.1%), respiratory infections (35.7%), and stroke (16.7%). During hospital stay, 42 (8.4%) patients died. In multivariable models, respiratory infections (HR = 6.55,p<0.001), stroke (HR = 7.05,p=0.003), and acute renal failure (HR = 16.9,p=0.001) increased the risk of death. In addition, having 2+ (HR = 7.75,p<0.001) and 3+ (HR = 21.1,p<0.001) conditions increased the risk of dying.Conclusion. Respiratory infections, stroke, and acute renal disease increased the risk of inhospital mortality among hospitalized patients with T2D. Infections are not the only cause of inhospital mortality. Certain causes of hospitalization require standardized and aggressive management to decrease mortality.
Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function
Authors: Park Min Chul , Jeong Hyobin , Son Sung Hwa , Kim YounHa , Han Daeyoung , Goughnour Peter C. , Kang Taehee , Kwon Nam Hoon , Moon Hyo Eun , Paek Sun Ha , Hwang Daehee , Seol Ho Jun , Nam Do-Hyun , Kim Sunghoon
Published: December 2015

Tumor permeability is a critical determinant of drug delivery and sensitivity, but systematic methods to identify factors that perform permeability barrier functions in the tumor microenvironment are not yet available. Multicellular tumor spheroids have become tractable in vitro models to study the impact of a three-dimensional (3D) environment on cellular behavior. In this study, we characterized the spheroid-forming potential of cancer cells and correlated the resulting spheroid morphologies with genetic information to identify conserved cellular processes associated with spheroid structure. Spheroids generated from 100 different cancer cell lines were classified into four distinct groups based on morphology. In particular, round and compact spheroids exhibited highly hypoxic inner cores and permeability barriers against anticancer drugs. Through systematic and correlative analysis, we reveal JAK–STAT signaling as one of the signature pathways activated in round spheroids. Accordingly, STAT3 inhibition in spheroids generated from the established cancer cells and primary glioblastoma patient–derived cells altered the rounded morphology and increased drug sensitivity. Furthermore, combined administration of the STAT3 inhibitor and 5-fluorouracil to a mouse xenograft model markedly reduced tumor growth compared with monotherapy. Collectively, our findings demonstrate the ability to integrate 3D culture and genetic profiling to determine the factors underlying the integrity of the permeability barrier in the tumor microenvironment, and may help to identify and exploit novel mechanisms of drug resistance. Cancer Res; 76(5); 1044–54. ©2015 AACR.
Balancing Protein Stability and Activity in Cancer: A New Approach for Identifying Driver Mutations Affecting CBL Ubiquitin Ligase Activation
Authors: Li Minghui , Kales Stephen C. , Ma Ke , Shoemaker Benjamin A. , Crespo-Barreto Juan , Cangelosi Andrew L. , Lipkowitz Stanley , Panchenko Anna R.
Published: December 2015

Oncogenic mutations in the monomeric Casitas B-lineage lymphoma (Cbl) gene have been found in many tumors, but their significance remains largely unknown. Several human c-Cbl (CBL) structures have recently been solved, depicting the protein at different stages of its activation cycle and thus providing mechanistic insight underlying how stability—activity tradeoffs in cancer-related proteins—may influence disease onset and progression. In this study, we computationally modeled the effects of missense cancer mutations on structures representing four stages of the CBL activation cycle to identify driver mutations that affect CBL stability, binding, and activity. We found that recurrent, homozygous, and leukemia-specific mutations had greater destabilizing effects on CBL states than random noncancer mutations. We further tested the ability of these computational models, assessing the changes in CBL stability and its binding to ubiquitin-conjugating enzyme E2, by performing blind CBL-mediated EGFR ubiquitination assays in cells. Experimental CBL ubiquitin ligase activity was in agreement with the predicted changes in CBL stability and, to a lesser extent, with CBL-E2 binding affinity. Two thirds of all experimentally tested mutations affected the ubiquitin ligase activity by either destabilizing CBL or disrupting CBL-E2 binding, whereas about one-third of tested mutations were found to be neutral. Collectively, our findings demonstrate that computational methods incorporating multiple protein conformations and stability and binding affinity evaluations can successfully predict the functional consequences of cancer mutations on protein activity, and provide a proof of concept for mutations in CBL. Cancer Res; 76(3); 561–71. ©2015 AACR.
Injury-Driven Stiffening of the Dermis Expedites Skin Carcinoma Progression
Authors: Mittapalli Venugopal R. , Madl Josef , Löffek Stefanie , Kiritsi Dimitra , Kern Johannes S. , Römer Winfried , Nyström Alexander , Bruckner-Tuderman Leena
Published: December 2015

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin fragility disorder characterized by injury-driven blister formation, progressive soft-tissue fibrosis, and a highly elevated risk of early-onset aggressive cutaneous squamous cell carcinoma (cSCC). However, the mechanisms underlying the unusually rapid progression of RDEB to cSCC are unknown. In this study, we investigated the contribution of injury-induced skin alterations to cSCC development by using a genetic model of RDEB and organotypic skin cultures. Analysis of RDEB patient samples suggested that premalignant changes to the dermal microenvironment drive tumor progression, which led us to subject a collagen VII hypomorphic mouse model of RDEB to chemical carcinogenesis. Carcinogen-treated RDEB mice developed invasive tumors phenocopying human RDEB-cSCC, whereas wild-type mice formed papillomas, indicating that the aggressiveness of RDEB-cSCC is mutation-independent. The inherent structural instability of the RDEB dermis, combined with repeated injury, increased the bioavailability of TGFβ, which promoted extracellular matrix production, cross-linking, thickening of dermal fibrils, and tissue stiffening. The biophysically altered dermis increased myofibroblast activity and integrin β1/pFAK/pAKT mechanosignaling in tumor cells, further demonstrating that cSCC progression is governed by pre-existing injury-driven changes in the RDEB tissue microenvironment. Treatment of three-dimensional organotypic RDEB skin cultures with inhibitors of TGFβ signaling, lysyl oxidase, or integrin β1–mediated mechanosignaling reduced or bypassed tissue stiffness and limited tumor cell invasion. Collectively, these findings provide a new mechanism by which RDEB tissue becomes malignant and offer new druggable therapeutic targets to prevent cSCC onset. Cancer Res; 76(4); 940–51. ©2015 AACR.
SSBP1 Suppresses TGFβ-Driven Epithelial-to-Mesenchymal Transition and Metastasis in Triple-Negative Breast Cancer by Regulating Mitochondrial Retrograde Signaling
Authors: Jiang Hong-Lin , Sun He-Fen , Gao Shui-Ping , Li Liang-Dong , Huang Sheng , Hu Xin , Liu Sheng , Wu Jiong , Shao Zhi-Ming , Jin Wei
Published: December 2015

Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Mitochondrial function is dysregulated frequently in cancer cells to allow for adaptation to a harsh tumor microenvironment. Targeting mitochondrial biogenesis and bioenergetics is, therefore, an attractive therapeutic strategy. In this study, we performed quantitative proteomic analyses in human parental and metastatic breast cancer cell lines to identify mitochondrial proteins involved in TNBC metastasis. We found that single-strand DNA-binding protein 1 (SSBP1) was downregulated in highly metastatic breast cancer cells. Moreover, SSBP1 downregulation promoted TNBC cell metastasis in vitro and in vivo. Mechanistically, SSBP1 loss decreased mitochondrial DNA copy number, thereby potentiating calcineurin-mediated mitochondrial retrograde signaling that induced c-Rel/p50 nuclear localization, activated TGFβ promoter activity, and TGFβ-driven epithelial-to-mesenchymal transition. Low SSBP1 expression correlated with tumor progression and poor prognosis in patients. Collectively, our findings identified SSBP1 as a novel metastasis suppressor and elucidated the mechanisms by which dysregulated mitochondrial signaling contributes to metastatic potential, providing potential new prognostic indicators for patients with TNBC. Cancer Res; 76(4); 952–64. ©2015 AACR.
Variants in 6q25.1 Are Associated with Mammographic Density in Malaysian Chinese Women
Authors: Mariapun Shivaani , Ho Weang Kee , Kang Peter Choon Eng , Li Jingmei , Lindström Sara , Yip Cheng Har , Teo Soo Hwang
Published: December 2015

Background: Mammographic density is an established risk factor for breast cancer and has a strong heritable component. Genome-wide association studies (GWAS) for mammographic density conducted in women of European descent have identified several genetic associations, but none of the studies have been tested in Asians. We sought to investigate whether these genetic loci, and loci associated with breast cancer risk and breast size, are associated with mammographic density in an Asian cohort.

Methods: We conducted genotyping by mass spectrometry in 1,189 women (865 Chinese, 187 Indian, and 137 Malay). Quantitative measurements of mammographic density were performed using ImageJ, a fully automated thresholding technique. The associations of SNPs to densities were analyzed using linear regression models.

Results: We successfully evaluated the associations of 36 SNPs with mammographic densities. After adjusting for age, body mass index, parity, and menopausal status, we found that in our cohort of 865 Malaysian Chinese, three SNPs in the 6q25.1 region near ESR1 (rs2046210, rs12173570, and rs10484919) that were associated with mammographic density, breast cancer risk, or breast size in previous GWAS were significantly associated with both percentage density and absolute dense area. We could not replicate the most significant association found previously in European women (rs10995190, ZNF365 gene) because the minor allele was absent for Asian women.

Conclusion: We found that the directions of genetic associations were similar to those reported in Caucasian women.

Impact: Our results show that even in Asian women with lower population risk to breast cancer, there is shared heritability between mammographic density and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 25(2); 327–33. ©2015 AACR.
Imaging Diagnosis of Hepatocellular Carcinoma: Recent Advances of Contrast-Enhanced Ultrasonography with SonoVue®
Authors: Salvatore Veronica , Gianstefani Alice , Negrini Giulia , Allegretti Giulia , Galassi Marzia , Piscaglia Fabio
Published: December 2015

Due to the ability to detect the typical contrast-imaging pattern for hepatocellular carcinoma (HCC), that is hyperenhancement in the arterial phase and hypoenhancement in the late phase on a cirrhotic background, contrast-enhanced ultrasonography (CEUS) was included in the American diagnostic algorithm for HCC in 2005. However, its role has been questioned because of the possibility of misdiagnosis of cholangiocarcinoma. The present review aims to describe the advantages and disadvantages of CEUS applications using Sonovue® for HCC. In particular there is focus on the accuracy of CEUS in detecting the typical HCC pattern, the CEUS patterns of intrahepatic cholangiocarcinoma (ICC), the risk of misdiagnosis with HCC, the diagnostic use of CEUS in cases of locoregional and systemic treatments, and the evaluation of response to antiangiogenic treatment using dedicated software.
Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI
Authors: Joo Ijin , Lee Jeong Min
Published: December 2015

Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain.
Occlusion Location of Middle Cerebral Artery Stroke and Outcome after Endovascular Treatment
Authors: Arnold Marcel , Slezak Agnieszka , El-Koussy Marwan , Lüdi Rudolf , Findling Oliver , Mono Marie-Luise , Heldner Mirjam Rachel , Fischer Urs , Mordasini Pasquale , Schroth Gerhard , Mattle Heinrich P. , Gralla Jan , Jung Simon
Published: December 2015

Background: The aim of this study was to analyze the influence of the location of middle cerebral artery (MCA) occlusion on recanalization, complications and outcome after endovascular therapy. Methods: Four-hundred sixty-four patients with acute MCA occlusions were treated with endovascular therapy. Results: Two-hundred ninety-three patients had M1 occlusions, 116 had M2, and 55 had M3/4 occlusions. Partial or complete recanalization was more frequently achieved in M1 (76.8%) than in M2 (59.1%) or M3/4 (47.3%, p < 0.001) occlusions, but favorable outcome (modified Rankin Scale 0-2) was less frequent in M1 (50.9%) than M2 (63.7%) or M3/4 (72.7%, p = 0.018) occlusions. Symptomatic intracerebral hemorrhage (ICH) did not differ between occlusion sites, but asymptomatic ICH was more common in M1 (22.6%) than in M2 occlusions (8.6%, p = 0.003). Recanalization was associated with favorable outcome in M1 (p < 0.001) and proximal M2 (p = 0.003) but not in distal M2 or M3/4 occlusions. Conclusions: Recanalization with endovascular therapy was more frequently achieved in patients with proximal than distal MCA occlusions, but recanalization was associated with favorable outcome only in M1 and proximal M2 occlusions. Outcome was better with distal than proximal occlusions. This study shows that recanalization can be used as a surrogate marker for clinical outcome only in patients with proximal occlusions.
IL12B (p40) Gene Polymorphisms Contribute to Ustekinumab Response Prediction in Psoriasis
Authors: Galluzzo Marco , Boca Andreea Nicoleta , Botti Elisabetta , Potenza Concetta , Malara Giovanna , Malagoli Piergiorgio , Vesa Stefan , Chimenti Sergio , Buzoianu Anca Dana , Talamonti Marina , Costanzo Antonio
Published: December 2015

Background: Psoriasis is characterized by multiple genetic variations. Some of these variations, such as the presence of HLA-Cw6 or TNFAIP3 single-nucleotide polymorphisms (SNPs), have been correlated to the response to biologic treatments. Objective: The aim of our study was to evaluate the effects of IL12B and IL6 SNPs on the response to ustekinumab. Methods: We retrospectively analyzed the genotypes of 64 patients who had been treated with ustekinumab for up to 1 year. Efficacy data were evaluated using ‘intention to treat-last observation carried forward' analysis. Results: We confirmed the positive role of HLA-Cw6 as a predictor of the response to ustekinumab and discovered that presence of the GG genotype on the IL12B rs6887695 SNP and absence of the AA genotype on the IL12B rs3212227 SNP significantly increase the probability of therapeutic success in HLA-Cw6 positive patients. Conclusions: The availability of pharmacogenetic data will influence therapeutic decisions in the clinical management of psoriatic patients.